Dicopper oxide - ECHA

Regulation (EU) No 528/2012

concerning the making available on the

market and use of biocidal products

Evaluation of active substance

Assessment Report

Dicopper oxide

Product-type 21

January 2016

France

Dicopper oxide PT 21 Product-type 21 January 2016

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TABLE OF CONTENT

1 STATEMENT OF SUBJECT MATTER AND PURPOSE ......................................... 3

1.1 Principle of evaluation and procedure followed ...................................... 3 1.2 Purpose of the assessment ..................................................................... 4 1.3 Applicant ................................................................................................ 4

2 OVERALL SUMMARY AND CONCLUSIONS ..................................................... 5

2.1 Presentation of the active substance and biocidal product ..................... 5 Identity, physico-chemical properties and methods of analysis of active substance . 5

2.1.1.1 Identity........................................................................................ 5 2.1.1.2 Purity/Impurities, additives ............................................................ 5 2.1.1.3 Physico-chemical properties ........................................................... 5 2.1.1.4 Analytical methods for determination and identification ...................... 6 2.1.1.5 Identity........................................................................................ 6 2.1.1.6 Physico-chemical properties ........................................................... 7 2.1.1.7 Analytical methods for determination and identification ...................... 8

2.2 Intended uses and efficacy .................................................................... 9 Field of use/function ........................................................................................ 9 Object to be protected, target organisms ........................................................... 9 Efficacy ......................................................................................................... 9 Mode of action ................................................................................................ 9 Resistance ................................................................................................... 10

2.3 Classification and labelling ................................................................... 10 Current classification of active substance ......................................................... 10

2.3.1.1 Current classification proposed by the applicant .............................. 10 2.3.1.2 Proposed classification by the RMS ................................................ 10

Classification of biocidal product ..................................................................... 11 2.3.1.3 Proposed classification of the representative biocidal product

INTERSMOOTH 360 SPC by the RMS ............................................................ 11 2.3.1.4 Proposed classification of the representative biocidal product HEMPEL’S

ANTIFOULING OLYMPIC 86951 by the RMS ................................................... 11 2.4 Summary of the risk assessment .......................................................... 12

Summary of human health risk assessment ..................................................... 12 2.4.1.1 Hazard identification of active substance ........................................ 12 2.4.1.2 Hazard identification of product .................................................... 18 2.4.1.3 Summary of exposure assessment and risk characterization ............. 18

Summary of environmental risk assessment ..................................................... 29 2.4.1.4 Fate and distribution in the environment ........................................ 29 2.4.1.5 Effects assessment on environmental organisms (active substance) .. 30 2.4.1.6 Environmental effect assessment (product) .................................... 35 2.4.1.7 Environmental exposure assessment and risk characterisation .......... 35

2.5 Overall conclusions .............................................................................. 59 2.6 Requirement for further information related to the product ................. 62

APPENDIX 1: LIST OF ENDPOINTS.................................................................... 63

APPENDIX 2: LIST(S) OF ABBREVATIONS ........................................................ 80

APPENDIX 3: LIST OF STUDIES ........................................................................ 87


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1 STATEMENT OF SUBJECT MATTER AND PURPOSE

1.1 Principle of evaluation and procedure followed This assessment report has been established as a result of the evaluation of the active

substance of cuprous oxide or dicopper oxide CAS n° 1317-39-1, as product-type 21

(Antifouling), carried out in the context of the work programme for the review of existing

active substances provided for in Article 16(2) of Directive 98/8/EC concerning the

placing of biocidal products on the market1, with the original view to the possible

inclusion of this substance into Annex I or IA to that Directive, then carried out in the

context of Regulation (EU) No 528/20122, with a view to the possible approval of this

active substance.

The evaluation has therefore been conducted to determine whether it may be expected,

in light of the common principles laid down in Annex VI to Directive 98/8/EC, that there

are products in product-type 21 containing cuprous oxide that will fulfil the requirements

laid down in Article 5(1) b), c) and d) of that Directive.

Cuprous oxide (CAS-no: 1317-39-1) was notified as an existing active substance, by the

EU Antifouling Copper Task Force (EUACTF) for product-type 21. Data on representative

biocidal products were submitted by the two biocidal product manufacturers International

paint Ltd and Hempel.

Data submitted were collected to compile a complete dossier on the hazard assessment

of the active substance. Therefore, there will be references to the data submitted by both

manufacturers and EUACTF in this report.

Commission Regulation (EC) No 1451/2007 of the 4th of December 20073 lays down the

detailed rules for the evaluation of dossiers and for the decision-making process in order

to include or not an existing active substance into the Annex I or IA of the Directive.

In accordance with the provisions of Article 3 paragraph 2 of that Regulation, France was

designated as Rapporteur Member State to carry out the assessment of cuprous oxide on

the basis of the dossier submitted by the applicant. The deadline for submission of a

complete dossier for cuprous oxide as an active substance in product-type 21 was the 30

th Avril 2006, in accordance with Article 9 paragraph 2 of Regulation (EC) No 1451/2007.

The hazard assessment of cuprous oxide was conducted in line with the assessment of

copper compounds dossiers for PT8 for which the active substances have already been

included into the annex I of Directive 98/8/EC. It has to be noted that the EUACTF has a

letter of access for the PT8 copper compounds dossiers, which permit to use several

agreed endpoints for PT8 copper compounds in the assessment of cuprous oxide as PT21.

On the 28th April 2006, the French competent authority received a dossier from EU

Antifouling Copper Task Force (EUACTF) and from the biocidal product manufacturers

International paint Ltd and Hempel. The Rapporteur Member State accepted the dossier

as complete for the purpose of the evaluation, taking into account the supported uses,

and confirmed the acceptance of this dossier on the 9th March 2007.

1 Directive 98/8/EC of the European Parliament and of the Council of 16 February 1998 concerning the placing

biocidal products on the market, OJ L 123, 24.4.98, p.1 2 Regulation (EU n° 528/2012 of the European Parliament and of the council o 22 May 2012 concerning the

making available on the market and use of biocidal products. 3 Regulation EC n° 1451/2007 of december 2007 on the second phase of 10-year work programme referred

to in article 16(2) of Directive 98/8/EC of the European Parliament and of the Council concerning the placing

biocidal products on the market OJ L 325, 11.12.2007, p. 3.


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In order to review the competent authority report and the comments received on it,

consultations of technical experts from all Member States (peer review) were organised

by the Agency. Revisions agreed upon were presented at the Biocidal Products

Committee and its Working Groups meetings and the competent authority report was

amended accordingly.

1.2 Purpose of the assessment

The aim of the assessment report is to support a decision on the approval of coated

cuprous oxide for product-type 21, and should it be approved, to facilitate the

authorisation of individual biocidal products in product-type 21 that contain cuprous

oxide. In the evaluation of applications for product-authorisation, the provisions of

Regulation (EU) No 528/2012 shall be applied, in particular the provisions of Chapter IV,

as well as the common principles laid down in Annex VI.

The conclusions of this report were reached within the framework of the uses that were

proposed and supported by the applicant (see Appendix II). For the implementation of

the common principles of Annex VI, the content and conclusions of this assessment

report shall be taken into account.

However, where conclusions of this assessment report are based on data protected under

the provisions of Regulation (EU) No 528/2012, such conclusions may not be used to the

benefit of another applicant, unless access to these data has been granted.

1.3 Applicant

Name: EU Antifouling Copper Task Force

Address:

Regulatory Compliance Limited

Bilston Glen Business Centre

Loanhead

Edinburgh, UK

EH20 9LZ


2 OVERALL SUMMARY AND CONCLUSIONS

2.1 Presentation of the active substance and biocidal product

Identity, physico-chemical properties and methods of analysis of active substance

2.1.1.1 Identity

Ta ble 0-1: Ide ntification of Cuprous oxide

CAS-No. 1317- 39-1

EINECS-No. 215-270-7

Other No. {CIPAC, ELINCS CI PAC 8084

IUPAC Name Copper (I) oxide

Common name, synonyms Cuprous oxide, d icopper oxide

Molecular formu la Cu20

Structura l formula

Cu I

Cu-0

Molecu lar weight (g/mol) 143.09

The active substance is currently named cuprous oxide in the CAR however the EC name is dicopper oxide (or the I UPAC name is copper (I) oxide).

2.1.1.2 Purity/I mpurities. add it ives

The active substance as manufactured is cuprous oxide and reacts on fou ling organisms as cupric ion Cu2+.

The specifications of cuprous oxide of each applicant are presented in the confidential doc IIIA2 of the Competant Authority Report . Cuprous oxide as manufactured contains four relevant impurities: arsen ic, cadmium, nickel and lead.

The specifications of the active substance cuprous oxide have been assessed according to what has been agreed as reference specifications of copper compounds PT8 already included into annex I of Directive 98/8/EC. The assessment of data submitted conducted to conclude that the th ree sources are acceptable for the approval of the active substance cuprous oxide as their specifications are covered by the batches used in the toxicological and ecotoxycological studies.

2.1.1.3 Physico-chemical properties

Cuprous oxide is an orange, fi ne and odorless powder. It has a density of 5 .87. The measure of vapour pressure is not necessary as the melting point is above 300 °C. Cuprous oxide is not soluble in water (0.639 mg/Lat pH 6.5 and 20°C). The solubilisation

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results of the oxido-reduction reaction of the copper (I) oxide into ionic copper. Cu+

rapidly gives Cu2+ predominantly. At low pH, the reaction is promoted.

Cuprous oxide is slightly soluble in toluene (14mg/L), DCM (10mg/L), n-hexane and ethyl

acetate (12mg/L), in acetone (13mg/L) and in methanol (9.3 mg/L). The partition

coefficient n-octano/water is not relevant for the ecotoxicological risk assessment due to

the specific absorption mechanism of copper.

Cuprous oxide is not oxidizing and not explosive. Further data should be provided for the

flammability and auto-flammability.

As the active substance is a solid, particle size distribution should be provided. Active

substance in form of nanomaterial is not considered in this assessment.

2.1.1.4 Analytical methods for determination and identification

The content of the active ingredient copper (I) in cuprous oxide technical was determined

by conversion of the test substance batches with iron (III) chloride solution and

potentiometric back-titration with cerium (IV) sulfate solution. The determined reducing

power allows to obtained cuprous oxide content by calculation after the determination of

copper metal content.

Analytical method is validated for Spiess Urania. Further validation data would be

required for American Chemet and Nordox for the approval of the active substance.

Relevant trace metals can be determined by HPLC –AES (Atomic Emission Spectroscopy),

ICP-AES (Inductively Coupled Plasma – Atomic Emission Spectroscopy) or by AAS, the

samples are previously digested in dilute nitric acid. Complete validation data are missing

for Nordox and American Chemet and would be required for the approval of the active

substance. Validated analytical methods have been provided by Spiess Urania for the

determination of other impurities. Analytical methods and validation data are missing for

Nordox and American Chemet and would be required for the approval of the active

substance.

The analyses of copper in environmental matrices and body fluids and tissues are

routinely performed in many laboratories. As these methods were collaborately validated

and are very widely used, limited validation data were accepted. Moreover, the EUACTF

has a letter of access for the PT8 copper dossiers where the methods are described.

Allthough no method is required for dicopper oxide in food and feedings stuff, a method

has been provided for the determination of copper in fresh fish by ICP-AES.

Identity, physic-chemical properties and methods of analysis of biocidal

products

2.1.1.5 Identity

There are two representative biocidal products in the cuprous oxide dossier; Intersmooth

360 SPC (International paint) and Olympic 86951 (Hempel).


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Table 0-1: identity of Intersmooth 360 SPC

Trade name Intersmooth 360 SPC

Manufacturer’s development

code No(s)

BEA 368

Ingredient of preparation Function Content

Cuprous oxide Active substance 42.56%

Zinc pyrithione Active substance 4.00%

Other formulants Details of the product composition and

information on the co-formulants are

confidential and are presented in the

confidential part of the dossier IIIB.2

Physical state of preparation Liquid wet paint

42.56% of cuprous oxide is equivalent to 37.8 % of copper in the product.

Table 0-2: Identity of Hempel’s Antifouling Olympic 86951

Trade name Hempel’s Antifouling Olympic 86951

Manufacturer's

development code

number(s)

86951-60700

Ingredient of

preparation

Function Content

Cuprous oxide Active substance 37.46%

Other formulants Details of the product composition and information on the

co-formulants are confidential and are presented in the

confidential part of the dossier IIIB.2

Physical state of

preparation

Viscous liquid solvent borne paint

37.46% of cuprous oxide is equivalent to 33.3% of copper in the product.

2.1.1.6 Physico-chemical properties

2.1.1.6.1 Intersmooth 360 SPC

Intersmooth 360 SPC is a dark brown liquid paint with a typical aromatic solvent odour.

Its pH is neutral (pH = 6.0 at 1% dispersion). It has a density of 1.551.

Intersmooth360 SPC is classified as flammable; R10. However it is not possible to

conclude on the flammability of the product under the CLP. As the flash-point is below 23

°C, the boiling point is necessary to classified H226 cat 1 or 2. It has neither oxidizing

nor explosive properties.

It is not possible to conclude on the stability of the product during 56 days at 40°C, the

zinc pyrithione content increases of 6.7%, moreover the long term storage stability study

(2 years) has not been provided. The study is required at the product authorization stage

to set the shelf life of the product. Moreover no data has been provided on the effect of

light.

The stability of the product at 0°C and the surface tension of the pure product should be

provided at the product authorization stage.

Due to the presence of lumps during storage, a recommendation should be set on the

label: shake well before use.


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Residues exceeds 5% limit, however the product is not diluted, therefore a study to

determine true residue level in container after use or a management of the packaging in

a specialized processing dedicated circuit is required.

2.1.1.6.2 Hempel’s Antifouling Olympic 86951

Hempel’s Antifouling Olympic 86951is a red liquid paint. Ist odour is assumed to

ressemble of the sweet odour of xylene. It has a density of 1.8112 and is classified as

flammable R10 and H226 cat.3. However as the flash-point is an estimated value closed

to 21 °C and 23 °C which are the limit values for classification R11 and H225 or H224, a

full flash point test according to relevant standard will be necessary at the product

authorisation stage. Moreover if the flash-point is below 23°C the boiling point of the

product will be required for the classification H224 or H225. It has neither oxidizing nor

explosive properties.

It is not possible to conclude on the stability of the product. A full accelerated storage

stability study conducted under GLP (14 days at 54°C) and a long term storage stability

study (2 years) are required at the product authorisation stage. Moreover no data has

been provided on the effect of light and the compatibility of the packaging.

The stability of the product at 0°C, the surface tension of the pure product and a full

pourability test according to CIPAC MT 148 should be provided at the product

authorization stage.

2.1.1.7 Analytical methods for determination and identification

2.1.1.7.1 Intersmooth 360 SPC

The analytical method for the determination of copper in the product Intersmooth 360

SPC is not acceptable and a validated analytical method for the identification and

determination of cuprous oxide in the product Intersmooth 360 SPC should be provided

at the product authorization stage.

The method for the determination of Zinc pyrithione in the product Intersmooth 360 SPC

is not fully validated. Further data on specificity should be provided at the product

authorization stage in order to show that there are no interference with the co-

formulants of Intersmooth 360 SPC.

2.1.1.7.2 Hempel’s Antifouling Olympic 86951

The analytical method for the determination of copper in the product Hempel’s

Antifouling Olympic 86951is not acceptable and a validated analytical method for the

identification and determination of cuprous oxide in the product Olympic should be


2.1.1.7.3 Residues analytical methods

For residue analysis of cuprous oxide please refer to data given in active substance part

(see 2.1.1.4 in the document). For the the product Intersmooth 360 SPC, no analytical

methods for zinc pyrithione and/or residues of zinc pyrithione have been provided in the

dossier.


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2.2 Intended uses and efficacy

The assessment of the biocidal activity of the active substance demonstrates that it has a

sufficient level of efficacy against the target organism(s) and the evaluation of the

summary data provided in support of the efficacy of the accompanying product,

establishes that the product may be expected to be efficacious.

In addition, in order to facilitate the work of Member States in granting or reviewing

authorisations, the intended uses of the substance, as identified during the evaluation

process, are listed in Appendix II.

Field of use/function

Main group: 4 – Other biocidal products

Product type 21–Antifouling products

Cuprous oxide as Cu2+ is used in the control of fouling organisms in marine and

freshwater environments.

Object to be protected, target organisms

Cuprous oxide is intended to be used for the protection against fouling of both mobile

(including but not limited to marine and freshwater vessels) and stationary (including but

not limited to buoys, aquaculture nets, immersed structures) objects.

Efficacy

Cuprous oxyde is used on vessels which potentially cover large geographical ranges; they

are potentially exposed to multiple marine biotypes. The number of fouling organisms to

which a vessel may be exposed is therefore large; there are over 4000 fouling species

with representatives from a variety of phyla, for example:

- slime, diatoms species e.g. Achnanthes and Amphora species,aquatic plants such

as Green and red algae spores e.g. Enteromorpha spp, Polysiphonia, animal,

barnacles, mussels, tubeworms e.g Serpulids, sponges.

Efficacy of the product Intersmooth 360 SPC (42.56 % w/w Cu2O and 4.00 % Zinc

pyrithione) has been proved in European sea waters during 19 months and in tropical sea

waters during 12 months, with a dry film thickness of 200 µm. No efficacy data has been

provided neither for fresh water nor for static objects.

Efficacy of Cuprous oxide has been proved in European sea waters during 103 weeks and

in tropical sea waters during 32 weeks, with a dry film thickness of 100 µm, in field tests

performed with the product Hempel’s Antifouling Olympic 86951 (37.5 % w/w Cu2O).

Efficacy Cuprous oxide in combination with Zinc oxide has been proved in European sea

waters during 19 months and in tropical sea waters during 12 months, with a dry film

thickness of 200 µm, in field test performed with the product Intersmooth 360 SPC

(42.56 % w/w Cu2O and 4.00 % Zinc pyrithione).

Mode of action

When copper from metallic copper, copper thiocyanate or cuprous oxide leaches into

marine water in presence of oxygen, the predominant form of the copper is the active

substance, the cupric ion, Cu2+. The cupric ion acts to retard settlement of the


microscopic larvae of fouling organisms with in a m icrolayer of water at t he pa int surface via two mechanisms:

( 1) the ion ret ards organism's vital processes by inactivating enzymes; (2) the ion acts more directly by precipitating cytoplasmic proteins as met all ic proteinates.

Resistance

There have never been any recorded cases of resistance in populations of fou ling organisms th rough the use of Copper based anti-fou ling paints in the literature up to now. However, some studies, in the literature, showed some impacts of copper pollution on marine life and indicate that some hull -fou ling species have copper tolerance.

2.3 Classification and labelling

Current classification of active substance

2.3.1.1 Current classification proposed by the applicant

None

2.3.1.2 Proposed classification by the RMS

No harmonised classification according to Regu lation (EC) No 1272/ 2008 (CLP Regulation) of active substance is available. However the RAC opinion4 adopted in December 2014 contains the following classification :

Table 0-1 : Proposed classification according to regulation 1272/2008

Classification accordina to the CLP Reaulation Hazard Class and Acute tox. 4, H302 Category Codes Acute tox. 4, H332

Eye dam 1, H318 Aquatic Acute 1, H400 Aquatic chronic l , H4 10

Labellina Pictoarams GHSOS, GHS07 GHS09 Signal Word Danger Hazard Statement Codes H302: Harmful if swallowed

H332 Harmful if inhaled H318: Causes serious eye damage. H410: very toxic to aquatic life with long lasting effects

Specific Concentration Aquatic Acute 1: M- factor = 100 limits, M-Factors Aquatic chronic 1: M-factor = 100

4 Opinion proposing harmonised classificat ion and labelling at EU level of Copper(II) oxide EC number : 215-269-1, CAS number : 1317-38-0, CLH- 0 -0000001412-86-45/ F- Adopted 04 December 2014

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The American Chemet, Spiess Urania and Nordox sources of cuprous oxide shou ld be classified for Skin Sens. 1 H317 since they contain nickel as an impurity above the classification limit for skin sensitisation (SCL in Skin Sens. for nickel is :2:0.0 1 % w/w).

Classification of biocidal product

2.3.1.3 Proposed classification of the representative biocidal product INTERSMOOTH 360 SPC by the RMS

According to the available studies and to CLP regu lation, the classification is:

Classification accordina to the CLP Reaulation Hazard Class and Acute tox.,H332 Category Codes Acute tox. 4, H302

Eye irritant of category 2, H319 Skin irritant of category 2, H315 Aquatic Acute 1, H400 Aauatic chronic 1 H4 10

Labellina Pictoarams GHS07, GHS09 Signal Word Warning Hazard Statement Codes H332 : Harmful if inhaled

H302 : Harmful if swallowed H319 : Causes serious eye irritation H315: Causes skin irritation . H410: very toxic to aquatic life with long lasting effects

Based on the ava ilable data, it is not possible to conclude on the CLP classification for the flammabi lity properties.

2.3.1 .4 Proposed classification of the representative biocidal product HEMPEL'S ANTI FOULING OLYMPIC 86951 by the RMS

According to the available studies and to CLP regu lation, the classification is:

Classification accordina to the CLP Reaulation Hazard Class and Flam. Liq. 3, H226 Category Codes Acute tox. 4, H332

Skin sensit isation 1, H317 Aquatic Acute 1, H400 Aquatic chronic 1, H410

Labellina Pictograms GHS02,GHS07,GHS09 Siana! Word Warnina Hazard Statement Codes H226 Flammable liquid and vapour

H332: Harmful if inhaled. H317 : May cause an allergic skin reaction H410: very toxic to aquatic life with long lasting effects

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2.4 Summary of the risk assessment

Summary of human health risk assessment

2.4.1.1 Hazard identification of active substance

Foreword

Copper is a micronutrient. It is essential for life and necessary for all living cells. It is

used in many enzyme systems, particularly in energy transfer where the property of

electron transfer is exploited in photosynthesis and catabolism. It is involved in the

reactions and functions of many enzymes (e.g. amine oxidase, ceruloplasmin,

cytochrome-c oxidase...) and in addition, copper is involved in angiogenesis,

neurohormoneangiogenesis, neuro-hormone release, oxygen transport and regulation of

genetic expression. Copper is present in almost all foods, and some products. Most

human diets naturally include between 1 and 2 mg/person/day of copper, with some

containing up to 4 mg/person/day.

The copper transport mechanisms in the organism form part of the system of

homeostasis: the body is able to maintain a balance of dietary copper intake and

excretion that allows normal physiological processes to take place. The relationship

between copper concentration and observed effects show a flattened ‘U’-shaped dose-

response curve. The left side of the ‘U’ curve represents deficiency, where intake of

copper is less than required. This can lead to lethality, especially in children, where

copper is essential for growth. Copper deficiency is associated with growth retardation,

anemia, skin lesions, impaired immunity, intestinal atrophy, impaired cardiac function,

reproductive disturbance, neurological defects and skeletal lesions. Copper is essential

for normal physiological function such as cellular respiration, free radical defence,

synthesis of melanin, connective tissue, iron metabolism, regulation of gene expression,

and normal function of the heart, brain and immune system.

Figure 1: Dose-response curve for copper (adapted from Ralph and McArdle,

2001).

The central near-horizontal part of the ‘U’ curve represents homeostasis, where intake

and excretion are balanced and copper level is in a normal range. The right-hand part of

the ‘U’ represents toxicity or excess copper disease. Chronic copper toxicity is extremely

rare, and the upper limit of homeostasis has never been strictly defined.

The active substance released from cuprous oxide is the cupric ion.


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Although a full guideline ADME study has not been performed for copper, the knowledge

of copper in the human body at the level of the organism, organ, cell and gene is

sufficient to meet the requirements of the Regulation. Extensive information is available

relating to the toxicokinetics and toxicodynamics of the copper ion within the human

body. The cupric ion is an inorganic charged species that cannot exist in an un-solvated,

un-associated state and so cannot be prepared in a pure form. Submission of toxicology

data for Cu2+ is therefore not possible or relevant. Under these circumstances,

information relating to copper sulfate pentahydrate is provided instead and where data

for the copper sulfate pentahydrate is not available, information has been supplied with

other forms of copper which have been demonstrated to all produce cupric ion in a

bioequivalence study.

2.4.1.1.1 Metabolism

Absorption

Oral administration:

The proportion absorbed in a clinical study over 90 days varied between 56 % for

subjects receiving 0.8 mg Cu/day, 36 % for individuals receiving 1.7 mg Cu/day and 12

% for individuals receiving 7.5 mg Cu/day (A6.2/01).

To determine the systemic NOAEL, as stated in Technical Meeting (TM)III08,

consistencely with the EU RAR5, the percentage of the administered copper sulfate

pentahydrate retained to be available for absorption following administration in the diet

for rats is 25 % whereas 36 % will be used as the oral absorption value in humans.

Dermal administration:

For the active substance, in order to harmonize BPR dossier and EU RAR, the dermal

delivery of copper compound (in solution) retained in TMIII08 was 5 %.

This value will be used in the risk assessment for general situation of exposure to Cu2O.

However, it is recognized that a strong matrix effect of paint on the dermal absorption of

substances exists.

For the product intersmooth 360 SPC,a study with formulation close to Intersmooth

360 SPC was provided in the PT 21 dossier leading to a value of 0.14% for copper

contained in Intersmooth 360.

For the product Hempel’s Antifouling Olympic 86951, a dermal penetration study

on a formulation close to Hempel’s Antifouling Olympic 86951was provided in the PT

21 dossier leading to a value of 0.34 % for copper contained in Hempel’s Antifouling

Olympic 86951.

It should be noted that these studies present some methodological deviations. However,

at this stage it would not be reasonable to require new dermal absorption studies.

Nevertheless, for the purpose of this dossier of substance approval, RMS proposes to use

these values of 0.14% and 0.34% for copper dermal absorption as they are much more

realistic than the default value of 5%. It was agreed at WG IV-2015 that these values

would only apply for active substance approval. Hence, studies of better reliability should

absolutely be provided at the product authorization level. In the absence of news studies,

the value of 5% will be used.

5 Voluntary risk assessment reports (VRAR) submitted to ECHA based on industry initiative to follow the risk

assessment procedures of Existing Substance Regulation (EEC) No 793/93 June 2008


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It is also important to note that the rinse of the skin with water and soap is inefficient.

Consequently, paint stays in the skin and in the stratum corneum. As the stratum

corneum was removed from skin at the end of the study (24 hours) by stripping and

exluded to determination of dermal absorption, an efficient removal of residual paint on

the skin by professional and non professional should be performed after the use of

paints.

Inhalation administration:

No animal or human studies were available to supply an inhalation absorption level.

Thus, the default absorption value of 100 % is used in risk characterisation as worst-case

value of copper salts penetration.

Distribution

Once absorbed by oral route, copper is bound to albumin and transcuprein and then

rapidly transported to the liver where it is incorporated to ceruloplasmin, a transport

protein that circulates in the organism and deliver the copper to other organs. It should

be however noted that a minor fraction of the absorbed dose can directly be distributed

to peripheral organs. In both humans and animals, copper is tightly regulated at a

cellular level, involving metallothionein and metallochaperones. These regulating

molecules prevent from the accumulation of potentially toxic, free copper ions within the

cell. In addition to the liver, the brain is another organ which contains relatively high

concentrations of copper.

Elimination

Biliary excretion, with subsequent elimination in the faeces, represents the main route of

excretion for copper in animals (rats) and humans, with an excretion rate approximately

of 1.7 mg Cu/day in humans. Available data show that copper is excreted in the bile in a

relatively inabsorbable form. Consequently, little enterohepatic absorption takes place.

Biliary excretion of copper and elimination in the faeces is recognised to be essential to

the homeostatic regulation of copper in animals and humans.

A small amount of copper is also excreted in urine and sweat.

2.4.1.1.2 Acute toxicity

Based on the results of the acute oral toxicity studies, Cu2O is classified as “Harmful “

according to the classification criteria as given in Annex VI of Commission directive

2001/59/EC, with the risk phrase R22 “Harmful if swallowed” (LD50 = 1340 mg/kg bw).

Based on the CLP criteria, a classification Acute Tox.4-H302 is proposed.

Cu2O is not hazardous or classified by the dermal route.

Based on the results of the acute inhalation toxicity studies, cuprous oxide requires the

classification Xn, R20 “harmful by inhalation” (3/5 males and 3/5 females died on day 1

after exposure of 5.78 mg/L during 4 hours), indeed LC50 was lower than 5.78 mg/L and

approximately 5 mg/l, which is the limit value used in classification. Moreover, the clinical

signs observed in different studies are moderately severe (haemorrhagic appearance of

lungs, hunched appearance, apathy, difficult respiration).

Moreover, classifications R20 for copper (I) oxide is proposed on the peer review of

copper compounds of EFSA based on one study not available in this dossier.


15

Besides, a classification Acute Tox.4-H332 is proposed based on the CLP criteria.

2.4.1.1.3 Skin and eye irritation

Cuprous oxide is not hazardous or classified as a skin irritant.

A classification Eye Dam. 1-H318 was proposed in RAC opinion of December 2014.

2.4.1.1.4 Skin sensitization

Cuprous oxide is not hazardous or classified as a skin sensitising.

For systemic effect after repeated exposure, the most toxic form of any copper salt is the

Cu2+ ion. The copper compound which releases more Cu2+ is the most soluble salt:

copper sulphate. In this context, to avoid repeating assay in animals, it was decided at

TM III 08 to extrapolate data from copper sulphate to the other copper compounds when

no other data is available.

This read across between copper compounds and copper sulphate for repeated toxicity

and CMR endpoints was adopted by TM for previous PT8 and PT2 copper dossiers. This

approach was also presented in the CLH report for the classification and labelling of

copper compounds.

2.4.1.1.5 Oral repeated toxicity

With regard to oral repeated dose toxicity, the 90-day dietary study was considered to be

the pivotal study for Cu2+ presented as copper sulphate pentahydrate. Based on kidney

damages, consisting in an increase of cytoplasmic protein droplets, a NOAEL of 1000 ppm

in rats (16.3 and 17.3 mgCu/kg bw/day in male and female rats respectively) was

determined. Other findings such as liver inflammation and lesions of the forestomach

were also reported at 2000 ppm and above (corresponding to doses from 34 mgCu/kg

bw/day).The NOAEL of 16.3 mg/kg bw/d was used for the risk characterisation.

Mice equally displayed forestomach lesions when exposed through diet to copper

sulphate for 92 days but this occurred at a much higher dose (4000 ppm, corresponding

to 187 and 267 mgCu/kg bw/day in males and females, respectively). No other damage

was observed in mice

Subchronic and chronic studies in the dog can be waived, as the dog is an unsuitable

animal model for studying copper toxicity in relation to man. Indeed, dogs have a

different form of albumin compared to rats and humans, and cannot excrete copper in

the bile as readily as most other species. The dog is not a good animal model for human

risk assessment of copper.

2.4.1.1.6 Dermal repeated toxicity

There were no dermal repeated dose toxicity studies. However, these studies are not

required considering the ability to read-across from the above oral study. Moreover, due

to the lack of toxicity observed in the acute dermal toxicity and the weak rate of dermal

penetration, a toxic effect is not expected.

2.4.1.1.7 Inhalation repeated toxicity


16

A study performed on cuprous oxide was provided for the antifouling copper compound

dossier.

Cuprous oxide was administered via whole body as 6 hours to male and female Sprague

Dawley rats for 1, 2, 3 or 4 weeks (5 days/week) at 0.2, 0.4, 0.8 and 2 mg/m3. Effects

observed are essentially local effect (LDH and protein increase in the bronchoalveaolar

lavage fluid, minimal inflammation and the decrease in wet/dry lung weight ratio),

reversible in 13-week recovery period except the decrease the effects on the lung weight.

2.4.1.1.8 Genotoxicity

In vitro tests

There was no evidence of mutagenic activity in Salmonella typhimurium strains in the

presence or absence of the metabolic activation system when tested with copper

sulphate pentahydrate.

Although limited, these in vitro data were deemed sufficient and no further in vitro

assays were required, considering the results of the in vivo tests.

In vivo tests

In vivo studies, conducted with copper sulphate pentahydrate, induced neither

micronuclei in the polychromatic erythrocytes from the bone marrow of mice, nor DNA

damage in a rat hepatocyte UDS assay.

Equivocal results of additional in vivo genotoxicity studies from the public domain

(Bhunya and Pati, 1987; Agarwal et al., 1990; Tinwell and Ashby, 1990) are observed

but these studies do not meet the higher reliability criteria (1 or 2) under the regulation.

Copper is therefore considered as non genotoxic

2.4.1.1.9 Chronic toxicity and carcinogenicity

No carcinogenic potential of copper sulphate was detected in rats and mice. However, all

available data are of limited value to evaluate the carcinogenic potential of copper

compounds. Study durations are in particular too short (<2 years) and group sizes are

small for drawing formal conclusions. However, based on the available data, human data

and due to the lack of genotoxicity there is no need to conduct new carcinogenicity

studies.

2.4.1.1.10 Reproductive toxicity

Developmental toxicity

A developmental study in mice was submitted but suffers from major methodological

deficiencies including no information on maternal toxicity and is neither adequate for

classification and labelling nor for risk assessment.

Subsequent to the original submission, the EU Antifouling Copper Task Force submitted

another study, that conforms to Annex V and OECD methods for a teratogenicity test

(Annex V method B.31; OECD method 414). This study provides the most reliable

animal data concerning the developmental toxicity of copper.

Technical copper hydroxide was given by gavage to groups of mated female rabbit during

days 7 to 28 of pregnancy at three different doses (6, 9 and 18 mg Cu/kg bw/d).

Administration of copper to pregnant rabbits at 18 and 9 mg Cu /kg bw/d was associated

with marked initial bodyweight loss, inappetance, abortion and death.


17

Pups in litters from surviving dams showed slightly lower mean foetal weight and slightly

increased incidence of retarded ossification of skull and pelvic bones at 18 mg Cu/kg

bw/d.

Therefore, the maternal no observed effect level was 6 mg/kg bw/d and the foetal no

observed effect level was 9 mg/kg bw/d.

Fertility

According to the two-generation oral reproduction study in rats administered with copper

sulphate pentahydrate, the NOAEL for reproductive toxicity for parental males was 1500

ppm (the highest concentration tested corresponding to 23.6 mg/kg bw/d), The NOAEL

for parental females was only 1000 ppm (15.2-35.2 mg/kg bw/d), based on the reduced

spleen weight at 1500 ppm. This reduction also occurred in F1 and F2 generations at the

same dose level in both males and females. However the reduced spleen weights were

not considered a reproductive endpoint as it did not affect growth and fertility.

Therefore as the results of this study do not indicate specific reproductive toxicity at the

highest dose level tested, it is proposed that copper sulphate and cuprous oxide (by read

across) should not be classified as reprotoxic compounds.

2.4.1.1.11 Neurotoxicity

From a neurotoxicological point of view, copper has been recently suspected to be

involved in the pathogenesis of the Alzheimer's disease and other prion-mediated

encephalopathies. Although no valid neurotoxicity study was submitted, no evidence of a

neurotoxic potential of copper is suspected from the available studies in animals up to

now. No further study was therefore deemed necessary.

2.4.1.1.12 AEL derivation

The key health effect to consider in the risk characterization is kidney and forestomach

damages observed in the 90-day dietary study, which determined a NOAEL of 1000 ppm

(16.3 and 17.3 mgCu/kg bw/day in male and female respectively) in rats. This NOAEL is

considered to be the most appropriate in the risk characterization for short-term and

chronic exposures (carcinogenicity studies considered unnecessary).

To determine the systemic NOAEL, as stated in TMIII08, in order to harmonize BPD

dossier and EU RAR, the percentage of the administered copper sulphate pentahydrate

retained to be available for absorption following administration in the diet for rats is 25%.

Therefore, the systemic NOAEL, based on the NOAEL of 16.3 mgCu/Kg bw/d and the oral

absorption of 25% for animals is:

dbwkgmgCuNOAELmicNOAELsyste /1.425.0* 1

To derive the AEL from the NOAEL, the NOAEL is first converted to a systemic NOAEL

then then it is divided by the assessment factors taking into account uncertainties and

extrapolations. The assessment factors were discussed during the TM IV08 and TMI09 for

TP 8 copper substances and we will use the same way in these assessments.

Acute-term AEL

The acute-term AEL is the NOAEL (16.3 mg Cu/kg bw/day) times 25%, the absorption

factor, divided by the 50-fold safety factor, corresponding to the MOEref (5 for inter-

species variation and 10 for intra-species variation). An acute-term AEL of 0.082 mg

Cu/kg/d is proposed.


18

Medium-term AEL

The medium-term AEL is the NOAEL (16.3 mg Cu/kg bw/day) times 25%, the absorption


species variation and 10 for intra-species variation). A medium-term AEL of 0.082 mg

Cu/kg/d is proposed.

Long-term AEL

The long-term AEL is the NOAEL (16.3 mg Cu/kg bw/day) times 25%, the absorption


species variation, 10 for intra-species variation and 2 for the duration of exposure from

sub-chronic to chronic). A long-term AEL of 0.041 mg Cu/kg/d is proposed.

Generally AEL long-term is used to characterize the risk for professional. However, it has

been agreed among MS (TM III 2011), the medium-term AEL should be used for risk

characterization of professional applying or removing antifouling product, given the

expected periodic uses of antifouling agents.

The acute-term AEL value is also used to characterize the risk for non professional.

2.4.1.2 Hazard identification of product

INTERSMOOTH 360 SPC

The acute toxity studies for oral and inhalation routes, eye irritation and sensitisation

were considered not acceptable. In this context, the toxicity for these endpoints was

determined by calculation according to Directive 99/45/CE and CLP regulation.

No death was observed in the acute dermal toxicity study. However, irritation of skin was

observed in the appropriate study.

Hempel’s Antifouling Olympic 86951

The product has low toxicity by oral and dermal routes. It is not irritant for skin and eyes

but it is a skin sensitiser.

No study was provided for inhalation route. In this context, the toxicity for this endpoint

was determined by calculation according to Directive 99/45/CE and CLP Regulation.

2.4.1.3 Summary of exposure assessment and risk characterization Two representative products are proposed for this active substance. Hence the risk

assessment will be assessed for each product.

These two products are ready to use paints, intended to be used by professionals as well

as non professionals.

Four steps during the antifouling use could lead to exposure to humans:

Mixing and loading

Paint application

Post-application cleaning

Paint removal

For professional use, different actors are potentially exposed:


19

Potman (on the floor) who mixes and loads the antifoulant paint from supply

container to high pressure pump reservoir ensuring continuous supply to the

spray gun. After application, potman cleans the spray equipment.

Professional who applies paint to the surface:

o By spraying (mainly). Sprayer works from a manoeuvrable platform

which is operated either by himself or by an ancillary worker

He can also clean the spray equipment.

o By brush and roller (to recover any mistakes)

Ancillary worker, keeping paint lines free, manoeuvring mobile spray platforms as

well as other tasks intended to aid the sprayer’s job

Blast worker who performs a total or partial removal of the expired coating from

the ship hull using abrasive grit or high-pressure water

Grit filler who assists the blast worker in regularly filling the mixing kettle with grit

and monitoring the grit and water supply to the kettle and air to the tower wagon.

The non professional can apply the product by brushing/roller. He can also remove old

paint, washing the boat with a power washer and the scrubbing loose or blistered parts of

the paint in order to remove the leached layer of paint giving a good surface to apply a

new coat paint.

Secondary exposure can occur in connection to non-professional application of paint:

toddler touching wet and dry paint with subsequent hand-to-mouth transfer.

Several models (TNsG or Links study) were available to determine the exposure during

the different tasks. However, in order to harmonise the approach, an opinion of HEEG

was endorsed during the TM IV 2012: HEEG opinion on the paper by links at al. 2007 on

occupational exposure during application and removal of antifouling paints. This dossier

will follow these recommandations.

2.4.1.3.1 Primary exposure

2.4.1.3.1.1 Professional exposure

For professional exposure assessment, the following parameters and models were used:

Model Duration

min

Exposure

Spraying

Potman – mixing

and loading

TNsG 2002 Model 6: Loading liquid

antifoulant into reservoir for airless

spray application (user guidance)

180 Dermal and

inhalation

Potman/sprayer-

cleaning of

equipment

BEAT model: Delago study

10 Dermal

Sprayer- spraying TNsG 2002 Model 3: Airless spraying

viscous solvent-based liquids at > 100

bar pressure, overhead and forwards

180 Dermal and

inhalation

Ancillary worker Covered by assessment of sprayer, considering that ancillary

worker wears the same PPEs.

Brushing/roller

Mixing and loading Links study 90 Dermal and

inhalation Application

Cleaning of brush Model proposed by HEEG: “primary

exposure scenario - washing out of a

brush which has been used to apply

Not

relevant

Dermal


20

paint”

Other

Blast worker Links study 180 Dermal and

inhalation

Grit filler Links study 180 Dermal and

inhalation

Two steps assessments were performed:

Tier I: no PPE are worn. Gloves can be included at this step when no

exposure without gloves is available in the models

Tier II: PPE/RPE are worn

INTERSMOOTH 360 SPC

Table 0-1: The exposures compared to AEL medium term:

Task PPE

Total

systemic

exposure

mg

Cu/kg/d

AEL

mg

Cu/kg/d

Exposure

% AEL Risk

Potman

Mixing and

loading of paint

in pump

reservoir

No PPE 2.39 E-01 8.2E-02 291% Unacceptable

Gloves and

impermeable

coverall

6.52 E-02 8.2E-02 80% Acceptable

Cleaning spray

equipment No PPE

1.51E-02 8.2E-02 18% Acceptable

Combined

exposure: M&L

and cleaning

No PPE 2.54E-01

8.2E-02 309% Unacceptable

M&L of paint in

pump reservoir:

gloves and

impermeable

coverall

Cleaning: no PPE

8.03E-02

8.2E-02 98%

Acceptable

Application by spraying

Spraying

Gloves 8.09 E-01 8.2E-02 986% Unacceptable

Coated coverall,

gloves and mask

APF 40

5.31 E-02 8.2E-02 65% Acceptable

Cleaning spray

equipment

No PPE 1.51E-02 8.2E-02 18% Acceptable

Combined

exposure:

Spraying phase

and cleaning

Spraying: gloves

Cleaning: no PPE

8.24E-01 8.2E-02 1005% Unacceptable

Spraying: coated

coverall, gloves

and mask APF 40

Cleaning: no PPE

6.82E-02

8.2E-02 83% Acceptable

Application by brush/roller

Brushing No PPE 1.35E-01 8.2E-02 165% Unacceptable


21

Task PPE

Total

systemic

exposure

mg

Cu/kg/d

AEL

mg

Cu/kg/d

Exposure

% AEL Risk

Gloves and tyvek 3.66E-03 8.2E-02 4% Acceptable

Cleaning of

brush No PPE 1.8E-03 8.2E-02 2% Acceptable

Combined

exposure:

mixing and

loading,

application by

brush/roller and

cleaning

No PPE 1.37E-01 8.2E-02 167% Unacceptable

Tyvek coverall

and gloves during

M&L and brushing

and no PPE

during and

cleaning

5.46E-03 8.2E-02 7% Acceptable

Sand blasting

Paint removal


Protective water-

proof overalls, an

airstream helmet

with rubber flaps

that covered a

large part of their

upper body and

strong protective

gloves and mask

APF 10

5.72E-02 8.2E-02 70% Acceptable

Grit filling

Grit filling

No PPE 1.40 8.2E-02 1704% Unacceptable

Coated coverall,

gloves, mask APF

40

5.79 E-02 8.2E-02 71% Acceptable

A risk for potman during mixing and loading exists when no PPE are worn. However,

when gloves and impermeable coverall are worn, the risk becomes acceptable. No PPE is

required for cleaning.

A risk for sprayer during application under the conditions specified above (with gloves but

without coverall and mask) exists. However, when gloves, coated coverall and mask APF

40 are worn the risk becomes acceptable. The combined risk with cleaning of spray

equipment if gloves, coated coverall and mask APF 40 are worn during spraying is also

acceptable. No PPE are required for cleaning task.

The combined risk is acceptable for brusher when an equivalent Tyvek coverall and

gloves are worn during mixing and loading of paint into trail and application of the paint.

A risk for sand blaster without PPE exists. However, when protective water-proof

overalls, an airstream helmet with rubber flaps that covered a large part of their upper

body, strong protective gloves and and mask APF 10 are worn the risk becomes

acceptable.

A risk for grit filler exists without PPE. However, when coated coverall, gloves and mask

APF 40 are worn the risk becomes acceptable.



22

Table 0-2: The exposures compared to AEL medium term

Task PPE

Total

systemic

exposure

mg Cu/kg/d

AEL

mg

Cu/kg/d

Exposure

% AEL Risk

Potman

Mixing and

loading of paint

in pump reservoir


Gloves,

impermeable

coverall and

mask APF 10

4.74 E-02 8.2E-02 58% Acceptable

Cleaning spray

equipment

Tier I: No PPE 3.77E-02 8.2E-02 46% Acceptable

Tier II: gloves 1.56E-02 8.2E-02 19% Acceptable

Combined

exposure: M&L

and cleaning

No PPE


M&L of paint in

pump reservoir:

gloves,

impermeable

coverall and

mask APF 10

Cleaning: gloves

6.31E-02


Application by spraying

Spraying

Gloves 1.22 8.2E-02 1483% Unacceptable

Impermable

coverall, gloves

and mask APF

40

5.84 E-02 8.2E-02 71% Acceptable

Cleaning spray

equipment

Tier I: No PPE 3.77E-02 8.2E-02 46% Acceptable

Tier II: gloves 1.56E-02 8.2E-02 19% Acceptable

Combined

exposure:

Spraying phase

and cleaning

Spraying:

gloves

Cleaning: no

PPE

1.25 8.2E-02 1529% Unacceptable

Spraying:

impermeable

coverall, gloves

and mask APF

40

Cleaning: gloves

7.40 E-02


Application by brush/roller

Brushing


Gloves and

tyvek 3.66E-03 8.2E-02 4% Acceptable

Cleaning of brush No PPE 4.50E-03 8.2E-02 5% Acceptable

Combined

exposure: mixing

and loading,

application by

brush/roller and

cleaning


Tyvek coverall

and gloves

during M&L and

brushing and no

PPE during and

cleaning

8.16E-03 8.2E-02 10% Acceptable


23

Task PPE

Total

systemic

exposure

mg Cu/kg/d

AEL

mg

Cu/kg/d

Exposure

% AEL Risk

Sand blasting

Paint removal


Protective

water-proof

overalls, an

airstream

helmet with

rubber flaps that

covered a large

part of their

upper body and

strong

protective

gloves and mask

APF 10

5.27E-02 8.2E-02 64% Acceptable

Grit filling

Grit filling

No PPE 1.34 8.2E-02 1633% Unacceptable

Coated coverall,

gloves, mask

APF 40

7.42 E-02 8.2E-02 91% Acceptable

A risk for potman during mixing and loading exists when no PPE are worn. However,

when gloves, impermeable coverall and mask APF 10 are worn, the risk becomes

acceptable. To take into consideration the combined risk with cleaning task, although the

risk is acceptable without PPE for the cleaning task alone, gloves are required for this

task.

A risk for sprayer during application under the conditions specified above (with gloves but

without coverall and mask) exists. However, when gloves, impermeable coverall and

mask APF 40 are worn the risk becomes acceptable.

To take into consideration the combined risk with cleaning task, although the risk is

acceptable without PPE for the cleaning task alone, gloves are required for this task.

The combined risk is acceptable for brusher when an equivalent Tyvek coverall and

gloves are worn during mixing and loading of paint into trail and application of the paint.

A risk for sand blaster without PPE exists. However, when PPEs equivalent to protective

water-proof overalls, an airstream helmet with rubber flaps that covered a large part of

their upper body, strong protective gloves and and mask APF 10 are worn the risk

becomes acceptable.

A risk for grit filler exists without PPE. However, when coated coverall, gloves and mask

APF 40 are worn the risk becomes acceptable.


24

2.4.1.3.1.2 Non-Professional exposure

For non-professional exposure assessment, the following parameters and models were

used:

Model Duration

min

Exposure

Brushing/roller

Mixing and loading

application

TNsG 2002: model 4 – non professionals

brush and roller painting of antifoulant

on the underside of small boats (user

guidance)

90 Dermal and

inhalation

Cleaning Model proposed by HEEG: « primary

exposure scenario - washing out of a

brush which has been used to apply

paint »

Not

relevant

Dermal

No relevant model is available to assess the exposure of non professional during the

removal of paint. . However, it was considered that this scenario will be covered by the

scenario“application of the paint“.

The use of gloves by non professional is usually not accepted, several discussions

occured on the use of PPE by non-professionals at the previous TMs (TM I 2011 and TM

III 2011) and some documents provided (i.e. TMI 2011: Agenda point 3a. "Feasibility for

non-professional users of antifouling to wear gloves"). TMIII 2011 agreed that all PT 21

CARs having non-professional applications should include two exposure/risk

assessments; one assessment where no gloves are worn and a second assessment where

gloves are worn.

In this context, assessments for these products were performed also with gloves for non-

professional.

INTERSMOOTH 360 SPC

Table 0-3: the exposures compared to AEL acute term

Task PPE

Total systemic

exposure

b(dermal)

mg Cu/kg/d

AEL

mg Cu/kg/d

Exposure

% AEL Risk

Mixing and loading application

Brushing*

No PPE 8.58E-02 8.2E-02 105% Unacceptab

le

Gloves 3.96E-02 8.2E-02 48% Acceptable

Cleaning

Cleaning of brush No PPE 1.8E-03 8.2E-02 2% Acceptable

Combined exposure

Combined

exposure: mixing

and loading of

No PPE

8.76E-02 8.2E-02 107% Unacceptab

le


25

Task PPE

Total systemic

exposure

b(dermal)

mg Cu/kg/d

AEL

mg Cu/kg/d

Exposure

% AEL Risk

paint, application

and cleaning brush

Househ

old

gloves

during

mixing

and

loading

and

applica

tion

No PPE

during

cleanin

g

4.14E-02 8.2E-02 51%

Acceptable

Note*: In the study used to determine exposure of non professional during brushing, the

brushing was performed outdoor.

The risk for combined exposure is unacceptable for non professional without household

gloves. The risk would be acceptable only if appropriate PPE were worn.

In consequence, according to the guidance document CA-March14-Doc.4.2-Final-

“Antifouling (PT21): Way forward for the management of active substances and the

authorisation of biocidal products”, persons making products containing copper flakes

(coated with aliphatic acid) available on the market for non-professional users shall make

sure that the products are supplied with appropriate gloves.

This measure is however without prejudice to the provisions of paragraph 63 of Annex VI

to BPR, whereby Member States shall normally not authorise antifoulings to the general

public if the wearing of personnel protective equipment (PPE), such as gloves, is the only

risk mitigation measure to reduce exposure to acceptable levels.


Table 0-4: the exposures compared to AEL acute term

Task PPE

Total systemic

exposure

b(dermal)

mg Cu/kg/d

AEL

mg Cu/kg/d

Exposure

% AEL Risk

Mixing and loading application

Brushing*

No PPE


Gloves


Cleaning

Cleaning of

brush No PPE

4.50E-03 8.2E-02 5% Acceptable

Combined exposure


26

Task PPE

Total systemic

exposure

b(dermal)

mg Cu/kg/d

AEL

mg Cu/kg/d

Exposure

% AEL Risk

Combined

exposure:

mixing and

loading of

paint,

application

and cleaning

brush


Household

gloves

during

mixing and

loading and

application

No PPE

during

cleaning


Note*: In the study used to determine exposure of non professional during brushing, the

brushing was performed outdoor.

The risk for combined exposure is unacceptable for non professional brusher (even if

household gloves are worn during application). In this context, the use for non

professional cannot be authorized.

2.4.1.3.2 Secondary exposure

For professional uses, secondary exposure could occur to bystanders if individuals

working in the dock yard were to pass by or stop to watch a spraying or blasting

operation. However, it was decided at TM III2011 that no quantitative risk assessment

should be performed for this group but that the product should be labelled with the

phrases “unprotected persons be kept out of treatment areas”. If a person is in an area

where he/she could be exposed then that person would need to suitably attire

him/herself with the relevant PPE/RPE.

For non professional uses, secondary exposure could occur in connection to non-

professional application of paint, when toddlers (as a worst case) touch wet or dry paint

with subsequent hand-to-mouth transfer. The exposure level was compared to AEL acute

term.

Exposure to the by-stander is covered by the exposure of the non-professional who

applies the paint.

Intersmooth 360 SPC

As the non professional use cannot be authorized (see above), these assessments are

presented for information.

Scenario Exposure

mg Cu/kg/d

AEL

mg

Cu/kg/d

Exposure

% AEL Risk

Systemic

exposure –

toddler touching

wet treated

surface

1.14 8.2E-02 1392% Unacceptable

Systemic

exposure –

toddler touching

1.51 E-01 8.2E-02 184% Unacceptable


27

dry treated

surface

Systemic

exposure –

toddler touching

dry treated

surface

(refined)

2.11E-02 8.2E-02 26% Acceptable

An unacceptable risk is identified (from dermal and hand-to-mouth exposure, % of AEL is

>100) for a toddler touching wet paint on the boat. However, the risk is acceptable for a

toddler touching dry paint. Therefore, it is considered that this potential risk to children

can be mitigated by suitable labelling of products containing copper flakes intended for

non-professional use indicating that unprotected persons should be kept away from

treated surfaces until they are dry. This measure to manage potential risks to children is

proposed in the document of European Commission: “Antifouling (PT21),: way forward

for the management of active substances and the authorisation of biocidal products”,

adopted during the Competant Authorities meeting of March 2014.


As the non professional use cannot be authorized (see above), this assessment is

presented only for information.

Scenario Exposure

mg Cu/kg/d

AEL

mg

Cu/kg/d

Exposure

% AEL

Risk

Systemic

exposure –

toddler touching

wet treated

surface

3.90 8.2E-02 4757 % Unacceptable

Systemic

exposure –

toddler touching

dried treated

surface

4.91 E-01 8.2E-02 599% Unacceptable

Systemic

exposure –

toddler touching

dried treated

surface

(refinement)

2.03 E-02 8.2E-02 25% Acceptable

An unacceptable risk is identified (from dermal and hand-to-mouth exposure, % of AEL is

>100) for a toddler touching wet paint on the boat. However, the risk is acceptable for a

toddler touching dry paint. Therefore, it is considered that this potential risk to children

can be mitigated by suitable labelling of products containing copper flakes intended for

non-professional use indicating that unprotected persons should be kept away from

treated surfaces until they are dry. This measure to manage potential risks to children is

proposed in the document of European Commission: “Antifouling (PT21),: way forward

for the management of active substances and the authorisation of biocidal products”,

adopted during the Competant Authorities meeting of March 2014.


28

2.4.1.3.2.1 Secondary exposure via food contamination

It is stated in the last MOTA6 that “in specific cases for PT 21, where it can be

demonstrated that there residues of the a.s. in fish and shellfish are not to be expected,

even in cases of misuse, the monitoring method is not required. A specific justification

has to be presented, together with the sound proof that there would be no residue also in

cases of misuse“.

As stated in the toxicological foreword, the case of copper is rather particular since this

element is naturally present in the environment and also at stake and essential for many

metabolic functions and reactions for both plants and animals. Copper is also used as

fungicide in plants for phytopharmaceutical purposes and for veterinary purposes7.

Copper is authorized as a feed additive under EU Reg. 479/20068 in nutrition of livestock

including fish and shellfish (involved in PT21) with a maximum content in the complete

feedingstuffs of 25 mg/kg for fish and 50 mg/kg for crustaceans. It is also present in

many food supplements, according to Directive 2002/46/EC9.

There is currently no harmonized methodology to assess the level in foodstuff of a

substance involved in PT21. The most relevant methodology currently available to

estimate level in fish and shellfish is based on a rough calculation with highest Predicted

Environmental Concentration (PEC) calculated from the marine environment and the Bio

Concentration Factor (BCF). Based on the particular case of copper (ionic form) and its

properties (high solubility/dilution in sea water, complexation, low bio-accumulation,

natural occurrence and physiological needs), at the state of the art, this approach is not

deemed relevant.

Indeed, because of the homeostasis of metals, BCF values are not indicative of the

potential bioaccumulation. There is therefore limited evidence of accumulation and

secondary poisoning of inorganic forms of metals. In addition, an in-depth literature

search showed the absence of copper biomagnification across the trophic chain in the

aquatic and terrestrial food chains. Differences in sensitivity among species were not

related to the level in the trophic chain but to the capability of internal homeostasis and

detoxification. Field evidence had further provided no indications of secondary

poisoning.Hence no PECoral, predator was assessed for this product. Consequently an

assessment of the risk to food consumers due to contamination of fish/shellfish is not

deemed relevant in this case.

Additionally, copper is already significantly involved for phytopharmaceutical purposes

under EU Reg. 396/2005 with rather significant rates (in the order of kg/ha/year)

covered by MRLs under the EU regulation Reg. (EC) N°149/200810 (in the order of 2-

6 Manual of Technical Agreements of the Biocides Technical Meeting (MOTA) V.6 last version n°6 of 2013, p.

1-60 : http://echa.europa.eu/documents/10162/19680902/mota v6 en.pdf

7 The European Agency for the Evaluation of Medicinal Products (EMEA), Veterinary Medicines Evaluation Unit, EMEA/MRL/431/98-Final, May 1998, Committee for Veterinary Medicinal Products – Copper Chloride, Copper Gluconate, Copper Heptanoate, Copper Oxide, Copper Methionate, Copper Sulphate and Dicopper Oxyde – summary report, p.1-4 : http://www.ema.europa.eu/docs/en GB/document library/Maximum Residue Limits -Report/2009/11/WC500013010.pdf

8 COMMISSION REGULATION (EC) No 479/2006 of 23 March 2006 as regards the authorization of certain additives belonging to the group compounds of trace elements, OJ L 86 24/03/2006, p. 4-7 : http://eur-lex.europa.eu/legal-

content/EN/TXT/PDF/?uri=CELEX:32006R0479&qid=1399886943661&from=EN 9 DIRECTIVE 2002/46/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 10 June 2002 on the

approximation of the laws of the Member States relating to food supplements, OJ L 183, 12.7.2002, p. 1-16 http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:02002L0046-

20111205&qid=1399993783567&from=EN

10 Commission Regulation (EC) No 149/2008 of 29 January 2008 amending Regulation (EC) No 396/2005 of

the European Parliament and of the Council by establishing Annexes II, III and IV setting maximum residue

levels for products covered by Annex I thereto (Text with EEA relevance), OJ L 58, 01/03/2008, p. 1–398 :

http://eur-lex.europa.eu/legal-

content/EN/TXT/PDF/?uri=CELEX:32008R0149&qid=1399895764828&from=EN


29

1000 mg/kg). There is currently no EU MRL for fish and shellfish under this regulation or

associated with veterinary purposes and consequently no risk of additive exposures

which would induce MRLs to be revised accordingly.

An acceptable risk is identified for potential exposure via food contamination. This is

based on available knowledge about the natural occurrence of copper, physiological

needs, physico-chemical properties and regulations already in force. Exposure via food

contamination may need to be reassessed when a uniform methodology to assess dietary

exposure induced by an antifouling application is available.

2.4.1.3.2.2 Overall conclusion for human health

With regard to human health exposures and effects, safe use of dicopper oxide

antifouling based product is identified if both professional and non-professional operators

wear appropriate personal protective equipment.

Summary of environmental risk assessment

2.4.1.4 Fate and distribution in the environment

As a result of the unique fate of copper in water, soil, sediment and sludge, many of the

data requirements listed in Section A7 of the Technical notes for Guidance are not

applicable for inorganic compounds and metals; in particular e.g. hydrolysis,

photodegradation and biodegradation. It is not applicable to discuss copper in terms of

degradation half-lives or possible routes of degradation. Subsequently, dicopper oxyde,

which is an inorganic salt, cannot be transformed into related degradation products other

than copper ions (Cu2+) and water in solution.

As with all metals, copper becomes complexed to organic and inorganic matter in waters,

soil and sediments and this affects copper speciation, bioavailability and thus toxicity,

which mainly depends of the abundance of the copper ion .

An important parameter determining the distribution of copper in the aquatic and soil

environment is the adsorption onto solid materials and therefore partitioning coefficients.

For an organic compound, solid-liquid/solution partitioning is related to its hydrophobic

properties, as determined using octanol-water partitioning coefficient Kow and organic

carbon partitioning coefficient Koc. Since metals do not have the hydrophobic or lipophilic

characteristics of organic compounds, the concept of Kow and Koc is not applicable. The

distribution of metals is not only controlled by pure adsorption/desorption mechanisms.

The distribution of metals between aqueous phase and soil/sediment/suspended matter

should preferentially be described on the basis of measured soil/water, sediment/water

and suspended matter/water equilibrium distribution coefficient (TECHNICAL GUIDANCE

DOCUMENT on Risk Assessment Part II Appendix VIII, 2003; TECHNICAL GUIDANCE

DOCUMENT Annex 4-VIII Environmental risk assessment for metals and metal

compounds (RIP 3.2-2).

From the literature overview, the following partitioning coefficients have thus been

derived for Cu metal and Cu compounds:

Partition coefficient in freshwater suspended matter

- Kpsusp = 30,246 l/kg (log Kp (pm/w) = 4.48) (50th percentile)

- (Heijerick et al, 2005)

Partition coefficient in freshwater sediment

- Kpsed = 24,409 l/kg (log Kp(sed/w) = 4.39) (50th percentile)

- -(Heijerick et al., 2005)

Partition coefficient in soil


30

- Kd = 2120 l/kg (log Kp = 3.33) (50th percentile)

- (Sauvé et al. 2000)

Partition coefficient in marine suspended matter

- Kpsusp = 131826 l/kg (log Kp (pm/w) = 5.12) (50th percentile)

- (Heijerick and van Sprang 2008)

Partition coefficient in estuarine suspended matter

- Kpsusp = 56234 l/kg (log Kp (pm/w) = 4.45) (50th percentile)

- (Heijerick and van Sprang 2008)

The 50th percentile value of the distribution function represents a typical suspended

matter/sediment partition coefficient for EU waters and will be used for the derivation of

local and typical regional PECs.

As all metals, copper becomes complexed to organic and inorganic matter in waters, soil

and sediments and this affects copper speciation, bioavailability and toxicity.

Because of the homeostasis of metals, BCF values are not indicative of the potential

bioaccumulation. There is therefore limited evidence of accumulation and secondary

poisoning of inorganic forms of metals, and biomagnification in food webs.

2.4.1.5 Effects assessment on environmental organisms (active substance)

2.4.1.5.1 Aquatic compartment (including water, sediment and STP)

2.4.1.5.1.1 PNEC for aquatic organisms

Information on the mode of action of copper exposure indicated that the target tissue for

copper toxicity were the water/organism interface with cell wall and gill-like surfaces

acting as target biotic ligands in all species investigated.

Freshwater pelagic compartment

For the freshwater pelagic compartment, 139 individual NOEC/EC10 values resulting in

27 different species-specific NOEC values, covering different trophic levels (fish,

invertebrates and algae) were used for the PNEC derivation. The large intra-species

variabilities in the reported single species NOECs were related to the influence of test

media characteristics (e.g., pH, dissolved organic carbon, hardness) on the bioavailability

and thus toxicity of copper. Species-specific NOECs were therefore calculated after

normalizing the NOECs towards a series of realistic environmental conditions in Europe

(typical EU scenario’s, with welldefinedpH, hardness and DOC). Such normalization was

done by using chronic copper bioavailability models (Biotic Ligand Models), developed

and validated for three taxonomic groups (fish, invertebrates and algae) and additional

demonstration of the applicability of the models to a range of other species. The species-

specific BLM-normalized NOECs were used for the derivation of log-normal Species

Sensitivity Distributions (SSD) and HC5-50 values (the median fifth percentile of the

SSD), using statistical extrapolation methods.

The HC5-50 values of the typical EU scenarios ranged between 7.8 to 22.1 μg Cu/L.

Additional BLM scenario calculations for a wide range of surface waters across Europe

further demonstrated that the HC5-50 of 7.8 μg Cu/L, is protective for 90% of the EU

surface waters and can thus be considered as a reasonable worst case for Europe in a

generic context.

Copper threshold values were also derived for three high quality mesocosm studies,

representing lentic and lotic systems. The mesocosm studies included the assessment of


31

direct and indirect effects to large variety of taxonomic group and integrate potential

effects from uptake from water as well as from food.

BLM-calculated HC5-50 values (Assessment Factor (AF) = 1) were used as PNEC for the

risk characterisation.

The AF = 1 has been chosen due to the uncertainty concerning

1) the mechanism of action;

2) the overall evaluation of the database;

3) the robustness of the HC5-50 values;

4) corrections for bioavailability (reducing uncertainty);

5) the sensitivity analysis with regards to DOC and read-across assumptions;

6) the factor of conservatism “built in into” the data and assessment (such as no

acclimation of the test organisms and no pre equilibration of test media);

7) results from multi-species mesocosm studies ;

8) comparison with natural backgrounds and optimal concentration ranges for copper, an

essential metal.

The choice of the AF of 1 has been challenged during the WG-IV 2015 and it was stated,

with a slight majority of MSs, that the AF of 1 should be kept to derive the PNECwater.

However, it was also concluded that the conditions for using an AF of 1 in general should

be re-discussed in the frame of the revision of Vol. IV Part B of the guidance document.

And therefore, this AF should be re-discussed at the renewal stage of the first copper

substances (in PT8) in case the revision of the guidance or new data available show the

need of a revised AF.

The HC5-50, with an AF=1, was used to derive a PNECfreshwater of 7.8 µg Cu/l for

Europe in a generic context in absence of site-specific information on

bioavailability parameters (pH, DOC, hardness).

Marine compartment

For the marine PNEC derivation, 56 high-quality chronic NOEC/EC10 values, resulting in

24 different species-specific NOEC values covering different trophic levels (fish,

invertebrates, algae), were retained for the PNEC derivation. NOEC values were related

to the DOC concentrations of the marine test media. Species-specific NOECs were

therefore calculated after DOC normalizing of the NOECs. These species-specific NOECs

were used for the derivation of species sensitivity distributions (SSD) and HC5-50 values,

using statistical extrapolation methods. Considering that the log-normal distribution had

a poor data fit according to goodness of fit tests, HC5-50 values, obtained by using the

best-fitting parametric distribution, were considered for the PNEC derivation. The organic

carbon normalisation was carried out at a DOC level typical for harbours and marinas (2

mg/l), for surrounding waters (0.5 mg/l) and sea (0.2 mg/l) and resulted in an HC5-50

value of 5.2 µg Cu/L for harbours and marinas, 2.3 µg Cu/L for surrounding waters and

1.3 µg Cu/L for sea. Additionally a semi-parametric statistical analysis of the NOECs

distribution was performed and a HC5-50 derived. Because the differences between the

HC5-50 by either approach were similar, the HC5-50 derived by the parametric curve

fitting (using the fit function that fitted best) was used. The evaluations of lower-quality

NOECs and EC50s from single species and multi-species marine studies added weight to

the HC5-50 value derived from the best-fitting distribution.

No reliable mesocosm or semi-field study was available for the marine compartment at

the time of the final version of the effects assessments of copper and its compounds on

the marine organisms of the EU-RAR (2008). This was underlined by the SCHER in its

opinion in 2009. TC NES agreed that, considering the large amount of information

available, the assessment factor used in the derivation of the PNEC (AF=2) could be

reduced in future if the HC5-50 could be validated with reliable, representative and


32

comprehensive mesocosm data (TC NES opinion 2008). The SCHER also “agreed with the

logic of this approach” (Scher opinion 2009).

Therefore, the applicant has submitted a marine mesocosm which is of high quality. This

study revealed a marine NOEC of 5.7 µg Cu/L which validates the HC5-50 of 5.2 µg Cu/L

derived from the Q1 database.

However, this mesocosm study was not considered sufficient to lower the assessment

factor, in the light of the higher variability of the marine ecosystem during the discussion

at the WG IV-2015. Therefore, an assessment factor of 2 was still applied to the HC5-50

derived from the different marine environments.

The HC5-50 (AF=2) of 2.6 µg Cu/L for harbours and marinas, 1.15 µg Cu/L for

surrounding waters and 0.65 µg Cu/L for sea was used as PNEC to the risk

characterisation.

2.4.1.5.1.2 PNEC for STP micro-organisms

For the STP compartment, high-quality NOECs from respiration or nitrification inhibition

studies, relevant to the functioning of a Sewage Treatment Plant (STP), resulted from

biodegradation/removal studies and NOECs for ciliated protozoa were used to derive the

PNEC for STP micro-organisms.

The lowest reliable observed NOEC value was noted for the inhibition of

respiration (AF=1) of 0.23 mg/l expressed as dissolved copper and carried

forward as PNEC to the risk characterisation.

2.4.1.5.1.3 PNEC for sediment

Freshwater sediment

The sediment PNEC included using a weight of evidence approach considering different

sources and tiered approaches of information: (1) sediment ecotoxicity data, (2) pelagic

ecotoxicity data in combination with Kd values derived through different approaches, (3)

soil ecotoxicity data and soil bioavailability models and (4) mesocosm/field ecotoxicity.

High-quality chronic benthic NOECs for six benthic species, representing 62 NOEC values

were retained for the PNEC derivation. NOEC values were related to sediment

characteristics (e.g., Organic Carbon (OC) and Acid Volatile Sulphides (AVS)), influencing

the bioavailability and thus toxicity of copper to benthic organisms. The derivation of the

freshwater HC5-50sediment for copper was therefore based on the OC-normalized

dataset, containing only low-AVS sediments. Using the log-normal species sensitivity

distribution a freshwater HC5-50sediment of 1741 mg Cu/kg OC was derived through the

statistical extrapolation method.

Using the equilibrium partitioning (EqP) approach, the derived HC5-50sediment (EP)

values were comparable or higher than the HC5-50 derived from whole sediment tests.

The comparison between the sensitivity of soil and benthic organisms added weight to

the HC5-50 from whole sediment tests. The same did sediment threshold values and

benthic NOECs that were obtained from four mesocosm studies and one field cohort

study.

The AF of 1 has been chosen due to the uncertainty concerning 1) weight of evidence

provided; 2) the overall quality of the database; 3) the robustness of the HC5-50 values;


33

4) corrections for bioavailability (reducing uncertainty); 5) the conservative factor built

into the system (no acclimation of the test organisms and only low AVS sediments

retained); 6) validations from multi-species mesocosm studies and field studies and 7)

comparison with natural backgrounds and optimal concentration ranges.

As for the PNECwater derivation, the choice of the AF of 1 has been challenged during the

WG-IV 2015 and it was stated, that the AF of 1 should be kept to derive the

PNECsediment. However, this AF should be re-discussed at the renewal stage of the first

copper substances (in PT8) in case the revision of the guidance document or new data

available show the need of a revised AF.

In case of natural sediments both the amount of AVS and organic carbon present in the

sediment has dictated the observed effect levels for copper and were used for the risk

characterisation. In absence of AVS data, a default AVS value of 0.77 μmol/kg dry weight

was used. This value corresponded to the 10th percentile of the AVS obtained from a

wide Flemish monitoring database and additional AVS data from other European

countries.

The HC5-50, with an AF=1, was used to estimate a PNECsediment of 1741 mg

Cu/kg OC, for Europe in a generic context. This corresponding to 87 mg Cu/kg

dry weight for a sediment with 5 % O.C. (TGD default value).

Marine compartment

As no reliable toxicity data are available for the marine sediment compartment, the

PNECmarine sediment was calculated according to the equilibrium partitioning concept based

on a PNECwater using the 10th percentile of the Kd value for marine sediment according to

the Guidance for environmental risk assessment for metals and metal compounds

(Appendix R.7.13-2).

The PNECmarine sediment of 98.8 mg Cu/kg dw sediment (corresponding to 21.48

mg Cu/kg ww sediment) is carried forward to the risk characterization.

2.4.1.5.1.4 Terrestrial compartment

A high-quality dataset of 252 individual chronic NOEC/EC10 values from 28 different

species and processes representing different trophic levels (i.e., decomposers, primary

producers, primary consumers) has been retained for the PNEC derivation. The observed

intra-species differences in toxicity data were related to differences in bioavailability, the

latter related to differences in soil properties and to differences in ageing and application

mode and rate.

The soil property best explaining the variability in toxicity for most of the endpoints was

the eCEC (effective Cation Exchange Capacity).

For the normalisation of the ecotoxicity data, the respective Cu background

concentrations were added on all NOEC/EC10 values which were subsequently

normalised to representative EU soils using the relevant regression (bio)availability

models, generating so soil-type specific HC5-50 values.

Species Sensitivity Distributions were constructed using the normalised NOEC/EC10 data.

HC5-50 values from log-normal distributions ranging between 13.2 and 94.4 mg Cu/kg

dry weight were obtained. A total of eight single species studies were available in which

the toxicity of Cu to microorganisms, invertebrates and plants in field-contaminated aged

soils was investigated for a wide range of European soil types (peaty, sandy, clay). A

total of five multi-species studies were available, three of which studied the effects of

copper in freshly spiked soils and 2 in field contaminated aged soils. Invertebrates, plants


34

and micro-organisms were studied. Single species and multi-species field studies indicate

that effects did not occur at an exposure level at the HC5-50-value.

Normalized HC5-50 values (AF=1) were used as PNEC for the risk characterisation.

The uncertainty analysis that provides arguments for the AF=1 was based on: 1) the

overall quality of the database and the end-points covered; 2) the diversity and

representativeness of the taxonomic groups covered by the database; 3) corrections for

differences in bioavailability (soil properties); 4) the statistical uncertainties around the

5th percentile estimate; 5) NOEC values below the HC5-50 and 6) field and mesocosm

studies and comparisons of their results with the HC5-50.

To account for the observed difference between lab-spiked soils and field-contaminated

soils, a conservative leaching-ageing factor of 2 was agreed based on test data from the

mechanistic research on ageing and ionic strength (leaching) effects.

For the PT21 biocidal product dossier, unlikely to the VRA, a leaching ageing

“L/A” factor of 2 was not used to derive the PNECsoil but it was taken into

account in the assessment of the PEC soil (PEC divided by 2).

As for the PNECwater derivation, the choice of the AF of 1 has been challenged during the

WG-IV 2015 and it was stated, that the AF of 1 should be kept to derive the PNECsoil.

However, this AF should be re-discussed at the renewal stage of the first copper

substances (in PT8) in case the revision of the guidance document or new data available

show the need of a revised AF.

The HC5-50, with an AF=1, was used to derive a PNECsoil of 45.6 mg Cu/kg dry

weight for Europe in absence of site-specific information on soil properties.

2.4.1.5.1.5 Non compartment specific effects relevant to the food chain

(secondary poisoning)

An in-depth literature search showed the absence of copper biomagnification across

the trophic chain in the aquatic and terrestrial food chains. Differences in

sensitivity among species were not related to the level in the trophic chain but to the

capability of internal homeostasis and detoxification. Field evidence had further provided

no indications of secondary poisoning.

2.4.1.5.1.6 Summary of PNEC values

Table 0-1: Summary of the selected PNEC values used for the risk

characterisation

ENVIRONMENTAL COMPARTMENT PNEC Unit

PNECSTP 0.23 mg Cu/L

PNECsurface water 7.8 µg Cu/L

PNECmarine water

- Harbour – Marinas

- Surrounding waters

- Sea

2.6

1.15

0.65

µg Cu/L

PNECsediment freshwater 87 mg Cu/ kgdwt


35

equivalent to 18.9 mg Cu/ kgwwt

PNECsediment marinewater 98.8

equivalent to 21.48

mg Cu/ kgdwt

mg Cu/ kgwwt

PNECsoil 45.6

Equivalent to 40.20

µg Cu/kgdwt

µg Cu/ kgwwt

2.4.1.6 Environmental effect assessment (product)

No data were provided for the representative product.

2.4.1.7 Environmental exposure assessment and risk characterisation

2.4.1.7.1 Environmental exposure

Biocides from antifouling paints enter the marine environment as a result of direct

leaching from the paint while a treated vessel is in service. A second route of

environmental exposure is associated with vessel maintenance and construction. The

OECD ESD presents default scenarios for application, removal and in service phases of

antifouling products (for commercial harbours, marina and shipping lanes when

relevant). Therefore the two main situations identified in the ESD leading to potential

emissions of biocides from antifouling paint applied on ship hulls to the environment are:

New Building, Maintenance and Repair (M&R) of ships

During these phases, the antifouling paint is applied or removed. There are potential

emissions of antifouling paint droplets, and thus biocide, to surface water, soil and STP

(Sewage Treatment Plant). For these scenarios, the OECD ESD for PT21 distinguishes

commercial vessels and pleasure crafts but also professional and non-professional users.

Service-life of ships

During service-life, the antifouling paint leaches into water, preventing organisms to

attach to the ship hulls. For this emission phase, the OECD ESD for PT21 distinguishes

different environments of release: marinas, commercial harbours (and their adjacent

areas) and shipping lanes (open sea).

The OECD ESD scenarios propose releases to the marine compartment only. In fact,

direct emissions to the freshwater environment have not been assessed due to the lack

of a harmonized scenario and should be considered during product assessment, if

appropriate.

The antifouling products Intersmooth 360 SPC and Olympic 86951 used to support the

approval of cuprous oxide is a paint applied by professional and non-professional users

for the following field of uses:

- professional applications on commercial, Navy and Government vessels, super-yachts

and pleasure crafts;

- non-professional applications on pleasure crafts only.

The exposure assessment for the different compartments of interest were conducted

according to the equations of the Emission Scenario Document (ESD) for Antifouling

Products (Product Type 21) in OECD’s countries (OECD, 2004), considering the

amendments from European consultations and papers. Direct releases to the marine


36

compartments were also covered by MAMPEC 2.5 modelling for their assessment

(service-life phase) and refinement (new-building, maintenance and repair and

cumulative assessment).

For every scenario, a ‘typical case’ (TC) and a ‘realistic worst case’ were defined. For the

‘typical case’, more realistic control measures preventing the releases to the environment

are applied. The considered mitigation measures are different for each scenarios and

detailed in the exposure assessment.

The following scenarios were developed to cover all the situations of exposure:

Table 0-2: Proposed scenarios for the exposure assessment

Boat type User Exposure Environment

New Building –Application of paint

Commercial

vessels

Professional Direct exposure Aquatic compartment

(harbour)

Pleasure crafts Professional Direct exposure Soil and STP (Sewage

Treatment Plant)

Indirect exposure

via the STP

Aquatic (freshwater and

marina) and soil

compartments

Maintenance and repair – Removal of paint

Commercial

vessels


(harbour)

Pleasure crafts Professional Direct exposure Aquatic (marina) and soil

compartments, STP

(Sewage Treatment Plant)

Indirect exposure

via the STP


marina) and soil

compartments

Pleasure crafts Non -

professional

Direct exposure Aquatic (marina) and soil

compartments, STP

(Sewage Treatment Plant)

Indirect exposure

via the STP


marina) and soil

compartments

Maintenance and repair – Application of paint

Commercial

vessels


(harbour)

Pleasure crafts Professional Direct exposure Soil and STP (Sewage

Treatment Plant)

Indirect exposure

via the STP


marina) and soil

compartments

Pleasure crafts Non -

professional

Direct exposure Soil and STP (Sewage

Treatment Plant)

Indirect exposure

via the STP


marina) and soil

compartments

Service-life of ships

All types - Direct exposure Marine aquatic

compartment (harbour,

marina, shipping lane)


For each d irect release scenario, the exposure assessment considering the ESD equations was based in Tier 1 on daily releases and on cumulated releases over the year at once. For the aquatic compartment, a Tier 2 using MAMPEC modelling was proposed for the cumulat ive assessment.

A cumulative assessment using MAMPEC was also conducted considering the potential simultaneous releases from the d ifferent phases of emissions to harbour and marina . The following situations have been considered :

commercial shipping in harbour area : direct releases during New Build ing and M & R (daily emission from New Building as a worst case) + service-life, professional pleasure craft in marina : direct releases during M&R (Removal) + indirect releases during New Building (Application) + service-life, non professional pleasure craft in marina: during M&R (Removal) + indirect releases during M&R (Removal) + service- life.

Exposure assessment based on total Cu concentrations

The risk assessment was carried out on the basis of tota l concentrations of copper in the environment. The PEC values issued from the ESD equations, in itially calculated as "added va lues" were corrected in order to integrate the background concentrations in copper. Concerning MAMPEC modelling, the concentrations were derived in integrating or not the background directly in the model. The worst case value was considered for the risk assessment (without the integration of the background for surface water and with the integration of the background for sediment). Total copper concentrations were calcu lated in taking into account of the regiona l copper background concentrations only (as agreed under the Council Regulation (EEC) 793/93 on Existing Substances - EU-RAR). These background concentrations are presented in the table below. For the risk assessment, tota l concentrations considering the regiona l backgrounds are always considered.

Table 0-3: Regional Background background concentratio Natural/ pristine concentration ns used for background Unit the exposure concentration assessmentC ompartment

1.1 (coastal waters, harbours, marinas)

Marine surface [µg. L-1] -water 0 .50 (open sea)

Marine 16 .1 [mg.kgdwt-1] -sediment 3.5 [mg.kgwwt-1]

Freshwater 0 .88 2.9 [µg .L-1]

Freshwater 21 67.5 [mg .kgdwt-1] Sediment 4 .56 14 .7 [mg.kgwwt-1]

Soi l 12 24 .4 [ mg .kgdwt-1]

10.6 21.6 [mg.kgwwt-1]

Ground water 0 .88 2.9 [µg. L-1]

37


38

Leaching rate for in-service exposure

A specific leaching rate calculated with the CEPE method and based on the intended

application rate was set to 44.00 µg/cm2/day for the product Intersmooth 360 SPC and

42.42 µg/cm2/day for the product Olympic 86951. Additional information on the leaching

rate of copper in antifouling paints is available in the ESD for antifouling products (ESD

PT21, 2004). A default value of 50 µg/cm2/day was determined by the CEPE Antifouling

Working Group and can be used in the MAMPEC model. This value is based on literature

data and an expertise available within the CEPE Antifouling Working Group (MAMPEC

v1.4 main report, van Hattum et al. 2002, Report number E-02-04 / Z 3117). As the

specific leaching rates for Intersmooth 360 SPC and Olympic 86951 were comparable to

the default value from the literature, the generic leaching rate of 50 µg/cm2/d for copper

was only used to evaluate the exposure from ship hull service-life as a worst case.

The leaching rate correction factor of 2.9 for vessels at berth was not applied for copper

based paints.

2.4.1.7.2 Risk characterisation

2.4.1.7.2.1 Sewage treatment plant

The PEC values for copper and the corresponding PEC/PNEC ratios for the sewage

treatment plant (STP) resulting from the use of Intersmooth 360 SPC product and

Olympic 86951 product as antifouling are presented below for new building and

maintenance & repair phases of pleasure crafts by professionals and non-professionals.

Table 0-4: INTERSMOOTH 360 SPC - PEC/PNEC ratios for the STP for Copper in

Intersmooth 360 SPC on pleasure crafts by professionals and non-professionals

Exposure Scenario

PEC (mg/L) PEC/PNEC

PNECmicro-organisms = 0.23 mg/L

WC TC WC TC

New building, pleasure craft,

professional 3.67E-03 1.60E-02

M&R removal, pleasure craft,

professional

2.81E-

03

2.81E-

04

1.22E-

02 1.22E-03

M&R application, pleasure craft,

professional

1.69E-

03

7.03E-

04

7.33E-

03 3.06E-03

M&R removal, pleasure craft, non-

professional

3.93E-

03

5.05E-

04

1.71E-

02 2.19E-03

M&R application, pleasure craft,

non-professional 1.40E-04 6.10E-04

WC: worst case / TC: typical case / M&R = Maintenance and repair

Table 0-5: OLYMPIC 86951 - PEC/PNEC ratios for the STP for Copper in Olympic

86951 on pleasure crafts by professionals and non-professionals

Exposure Scenario

PEC (mg/L) PEC/PNEC

PNECmicro-organisms = 0.23 mg/L

WC TC WC TC

New building, pleasure craft,

professional 3.78E-03 1.64E-02


professional 2.89E-03 2.89E-04 1.26E-02 1.26E-03

M&R application, pleasure 1.74E-03 7.23E-04 7.55E-03 3.14E-03


39

craft, professional


non-professional 4.04E-03 5.19E-04 1.76E-02 2.26E-03

M&R application, pleasure

craft, non-professional 1.44E-04 6.27E-04

WC: worst case / TC: typical case / M&R = Maintenance and repair

These results indicate acceptable risks to the STP, with PEC/PNEC ratios < 1, during the

application and removal of paint for pleasure crafts by professional and non-professional

users, whatever the scenario applied (realistic worst case or typical case) for both

products Intersmooth 360 SPC and Olympic 86951.

2.4.1.7.2.2 Aquatic compartment (including sediment)

Marine Compartment - Direct releases to the aquatic compartment

The PEC values for copper and the corresponding PEC/PNEC ratios for the marine aquatic

environment (surface water and sediment) resulting from the use of Intersmooth 360

SPC product and Olympic 86951 product as antifouling are presented below for new

building, maintenance & repair phases and service-life of commercial vessels and

pleasure crafts, leading to direct releases to harbour and marinas.

Tables below present the values for marine surface water in Tier 1 and Tier 2 (refined

with MAMPEC when relevant) respectively.


Table 0-6: INTERSMOOTH 360 SPC - PEC/PNEC ratios for marine surface water after direct releases to the environment - TIER 1 - Average dissolved concentrations considering the background (not integrated in the model for service-life)

Exposure Scenario PEC (µg/ L) PEC/ PNEC

PNECmarinas, harbours = 2.6 µg/L PNECsurrounding waters= 1.15 µg/L PNECsea = 0.65 µg/L = Shipping lane scenario

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR {M8tR) SCENARIOS Commercial vessels - Harbour New building

1.82 1.25 0.70 0.48 Daily emission

New building 2.54 1.41 0.98 0.54 Cumulat ive emission

M&R, Removal 1.59 1.17 0.61 0.45 Daily emission

M&R, Removal 3.37 1.30 Cumulat ive emission M&R, Application Daily

1.82 1.25 0.70 0.48 emission M&R, Application - 29.88 7.27 11.49 2.79 Cumulative emission

Pleasure crafts - Marina - Professionals M&R, Removal - Daily

1.27 1.12 0.49 0.43 emission

M&R, Removal - 32.14 4 .20 12.36 1.62 Cumulative emission Pleasure crafts - Marina - Non-professionals M&R, Removal - Daily 1.34 1.13 0.51 0.43 emission

M&R, Removal - 22.66 3.87 8.71 1.49 Cumulat ive emission

SERVICE LIFE SCENARIOS {Generic leaching rate of 50 µg/cm2 /day)

OECD Shipping Lane 0.50 0.77 OECD Commercial

1.35 0.52 Harbour Surroundings of OECD

1.11 0.96 Commercial Harbour OECD Marina 2.02 0.78 Surroundings of OECD

1.11 0.96 Marina WC: worst case I TC: typical case I M&R = Maintenance and repair

40


Table 0-7: INTERSMOOTH 360 SPC - PEC/PNEC ratios for marine surface water after direct releases to the environment - TIER 2 - MAMPEC modelling for New building and Maintenance 8t Repair - Average dissolved concentration considering the background (not integrated in the model for service life)

Exposure Scenario PEC (µg/L) PEC/PNEC

PNECmarinas, harbours = 2.6 µg/L PNECsurroundinq waters= 1.15 µg/L

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR) SCENARIOS MAMPEC Modelling Commercial vessels - Harbour

1.86 1.26 0.72 0.49 ( New bu ilding as a worst case) Commercial vessels -Surrounding area of Harbour 1.12 1.11 0.98 0.96 (New buildino as worst case) Professionals - Marina

1.11 1.10 0.43 0.42 (M&R Removal as worst case) Professionals - Surrounding area of Marina (M&R, Removal as 1.10 1.10 0.96 0.96 worst case) Non-professionals - Marina

1.11 1.10 0.43 0.42 (M&R, Removal as worst case) Non-professionals - Surrounding area of Marina (M&R, Removal as 1.10 1.10 0.96 0.96 worst case)

WC: worst case I TC: typical case I M&R = Maintenance and repair

Table 0-8: OLYMPIC 86951 - PEC/PNEC ratios for marine surface water after direct releases to the environment - TIER 1 - Average dissolved concentrations considering the background (not integrated in the model for service-life)


PNECmarinas, harbours = 2.6 µg/L PNECsurrounding waters= 1.15 µg/L PNECsea = 0.65 µg/L = Shipping lane scenario

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR) SCENARIOS Commercial vessels - Harbour New bu ilding

1.63 1.21 0.63 0.47 Daily emission

New bu ilding 2.15 1.33 0.83 0.51 Cumulative emission

M&R, Removal 1.46 1.15 0.56 0.44

Daily emission

M&R, Removal 2.76 1.06

Cumulat ive emission

M&R, Application Daily 1.63 1.21 0.63 0.47

emission

41


Exposure Scenario PEC (µg/L} PEC/PNEC M&R, Appl icat ion - 22.15 5.61 8.52 2.16 Cumulat ive emission

Pleasure crafts - Marina - Professionals M&R, Removal - Daily

1.27 1.12 0.49 0.43 em ission

M&R, Removal - 33.04 4.29 12.71 1.65 Cumulative emission Pleasure crafts - Marina - Non-professionals M&R, Removal - Daily

1.34 1.13 0.52 0.44 emission

M&R, Removal - 23.28 3.95 8.95 1.52 Cumulat ive emission

SERVICE LIFE SCENARIOS (Generic leaching rate of SO pg/cm2 /day}

OECD Shipping Lane 0.50 0.77 OECD Commercial

1.35 0.52 Harbour Surroundings of OECD

1.11 0.96 Commercial Harbour OECD Marina 2.02 0.78 Surroundings of OECD

1.11 0.96 Marina


Table 0-9: OLYMPIC 86951 - PEC/PNEC ratios for marine surface water after direct releases to the environment - TIER 2 - MAMPEC modelling for New building and Maintenance St Repair - Average dissolved concentration considering the background (not integrated in the model for service life}

Exposure Scenario PEC (µg/L} PEC/PNEC

PNECmarina, harbours = 5.2 µg/L PNECcoastal waters surroundinas of harbours and marinas= 2.3 µg/L

WC TC WC TC

NEW BUILDING - MAINTENANCE AND REPAIR (M&R} SCENARIOS MAMPEC Modelling Commercial vessels - Harbour

1.66 1.22 0.64 0.47 ( New buildino as a worst case) Commercial vessels -Surrounding area of Harbour 1.12 1.10 0.97 0.96 ( New buildina as worst case) Professionals - Marina

1.11 1.10 0.43 0.42 ( M&R, Removal as worst case) Professionals - Surrounding area of Marina (M&R, Removal as 1.10 1.10 0.96 0.96 worst case) Non-professionals - Marina

1.11 1.10 0.43 0.42 ( M&R, Removal as worst case) Non-professionals - Surrounding area of Marina (M&R, Removal as 1.10 1.10 0.96 0.96 worst case)

42



As presented in tables above, for both products Intersmooth 360 SPC and Olympic 86951, considering a one-day emission, the results indicate acceptable risks to the marine surface water, with PEC/PNEC ratios < 1, during the application and removal of paint for commercial vessels and pleasure crafts by professional a non- professional users, whatever the scenario applied (real istic worst case or typical case). The risks are also deemed acceptable for the service-life of sh ip hulls in considering a generic leaching rate for copper of 50 µg/cm2/day.

The Tier 1 cumulative assessments considering the releases over the year lead to unacceptable risks for the application and remova l phases of M&R for commercial vessels and for the removal phase of M&R for pleasure crafts. Nevertheless, the Tier 1 approach seems to be unrealistic as it does not consider complex transport and exchange processes in marine environments. Therefore a Tier 2 approach based on MAMPEC modelling is proposed to refine the risk assessment for direct releases (Table 0-7) and shows acceptable risk for all the scenarios and for both products Int ersmooth 360 SPC and Olympic 86951.

Tables below contain va lues for marine sediment in Tier 1 and Tier 2 respectively.

Table 0-10: INTERSMOOTH 360 SPC - PEC/PNEC ratios for marine sediment after direct releases to the environment (TIER 1) - Concentration on suspended matter considering the background (integrated in the model for service-life)

Exposure PEC (mg/kg wwt) PEC/PNEC Scenario PNECmarinesediment = 21.48 mg/kg wwt

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (MltR} SCENARIOS Commercial vessels - Harbour New building

64.88 16.65 3.02 0.78 Daily emission New bui lding Cumulat ive 126.27 29.81 5.88 1.39 emission M&R, Removal

45.59 9.60 2.12 0.45 Dailv emission M&R, Removal Cumulat ive 197.54 9.20 emission M&R, Application

64.88 16.65 3.02 0.78 Daily emission M&R, Application -Cumulative 2458.86 529.65 114.47 24.66 emission Pleasure crafts - Marina - Professionals M&R, Removal - 17.97 4.95 0.84 0.23 Daily emission M&R, Removal -Cumulative 2652.34 268.38 123.48 12.49 emission Pleasure crafts - Marina - Non-professionals

43


Exposure PEC (mg/kg wwt) PEC/PNEC Scenario

M&R, Removal - 23.71 6. 10 1.10 0.28 Daily emission M&R, Removal -Cumulative 1842.97 16.49 85.80 0.77 emission SERVICE LIFE SCENARIOS (Generic leaching rate of 50 µg/cm2 /day) OECD Shipping

8.67 0.40 Lane OECD Commercial

12.09 0.56 Harbour Surroundings of OECD Commercial 5.80 0.27 Harbour OECD Marina 31.96 1 .49 Surroundings of

5.83 0.27 OECD Marina WC: worst case I TC: typical case I M&R = Maintenance and repair

Table 0-11: INTERSMOOTH 360 SPC - PEC/PNEC ratios for marine sediment after direct releases to the environment - TIER 2 - MAMPEC modelling for New building and Maintenance 8t Repair - Average concentration on suspended solids considering the background (integrated in the model)

Exposure Scenario PEC (mg/kg wwt) PEC/PNEC

PNECmarine sediment = 21.48 mg/kg wwt

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (MStR} SCENARIOS MAMPEC Modelling Commercial vessels - Harbour

26.74 9.70 1.24 0.45 (New buildino as a worst case) Commercial vessels -Surrounding area of Harbour 6.28 5.74 0.29 0.27 (New bu ilding as worst case) Professionals - Marina

5.83 5.61 0.27 0.26 (M&R Removal as worst case) Professionals - Surrounding area of Marina (M&R, Removal as 5.61 5.61 0.26 0.26 worst case) Non-professionals - Marina

5.93 5.61 0.28 0.26 (M&R, Removal as worst case) Non-professionals - Surrounding area of Marina (M&R, Removal as 5.61 5.61 0.26 0.26 worst case)


Table 0-12: OLYMPIC 86951 - PEC/PNEC ratios for marine sediment after direct releases to the environment (TIER 1) - Concentration on suspended matter considering the background (integrated in the model for service-life)

44


Exposure PEC (mg/kg wwt) PEC/PNEC Scenario

PNECmarinesediment = 21.48 mg/ kg wwt

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (MltR} SCENARIOS

Commercial vessels - Harbour New bu ilding

48.41 13.12 2.25 0.61 Daily emission New bu ilding Cumulat ive 93.33 22.75 4.34 1.06 emission M&R, Removal

34.30 7.97 1.60 0.37 Dailv emission M&R, Removal Cumulative 145.48 6.77 em ission M&R, Appl ication

48.41 13.12 2.25 0.61 Daily emission M&R, Application -Cumulative 1800.08 388.48 83.80 18.09 emission Pleasure crafts - Marina - Professionals M&R, Removal - 18 .39 4.99 0.86 0.23 Daily emission M&R, Removal -Cumulat ive 2729.02 276.05 127.05 12.85 emission Pleasure crafts - Marina - Non-professionals M&R, Removal - 24.30 6. 17 1.13 0.29 Daily emission M&R, Removal -Cumulative 1896.22 16.87 88.28 0.79 emission SERVICE LIFE SCENARIOS (Generic leaching rate of 50 µg/cm2 /day) OECD Shipping

8.67 0.40 Lane OECD Commercia l

12.09 0.56 Harbour Surroundings of OECD Commercia l 5.80 0.27 Harbour OECD Marina 31.96 1.49 Surroundings of

5.83 0.27 OECD Marina WC: worst case I TC: typical case I M&R = Maintenance and repair

Table 0-13: OLYMPIC 86951 - PEC/PNEC ratios for marine sediment after direct releases to the environment - TIER 2 - MAMPEC modelling for New building and Maintenance 8t Repair - Average concentration on suspended solids considering the background (integrated in the model)

45


Exposure Scenario PEC (mg/ kg wwt) PEC/ PNEC PNECmarinesediment = 9.50 mg/ kg wwt

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (MltR) SCENARIOS MAMPEC Modelling Commercial vessels - Harbour

20.98 8.43 0.98 0.39 ( New building as a worst case) Commercial vessels -Surround ing area of Harbour 6.11 5.70 0.28 0.27 ( New buildino as worst case) Professionals - Marina

5.85 5.61 0.27 0.26 ( M&R, Removal as worst case) Professionals - Surrounding area of Marina (M&R, Removal as 5.61 5.61 0.26 0.26 worst case) Non-professionals - Mar ina

5.96 5.63 0.28 0.26 ( M&R, Removal as worst case) Non-professionals - Surrounding area of Marina (M&R, Removal as 5.61 5.61 0.26 0.26 worst case)


As presented in the tables above, for New bu ilding and M&R of commercia l vessels and pleasure crafts, r isks to sediment are unacceptable considering cumulative emissions in Tier 1, except for t he removal phase in typical case by non-professionals. Concern ing t he service-l ife of sh ip hulls, t he risks are deemed except inside the marinas considering a generic leach ing rate for copper of 50 µg/ cm 2/ day for both products.

The Tier 1 approach conducted for New building and M&R seems to be unrealistic as it does not consider complex t ransport and exchange processes in marine environments. Therefore a Tier 2 approach based on MAMPEC modelling is proposed to refine the r isk assessment for direct releases and shows acceptable risk for all the scenarios except inside commercial harbour for Intersmooth 360 SPC (realistic worst case).

Marine Comoartment - Indirect releases to the aquatic comoartment

The PEC values for copper and the corresponding PEC/ PNEC ratios for the marine aquatic environment (surface water and sediment) resu lting from the use of Intersmooth 360 SPC product and Olympic 86951 product as antifoul ing are presented below for new building, maintenance & repair phases of pleasure crafts, leading to indirect releases to marinas v ia t he STP. Tables below present the values for marine surface water and for marine sediment for both products. As a worst case for the mar ine compartment, the PNEC for coasta l waters and surroundings of marina has been considered instead of the PNEC for marina.

Table 0-14: INTERSMOOTH 360 SPC - PEC/ PNEC ratios for marine surface water after indirect re leases via the STP to the environment - Dissolved concentration considering the background

Exposure Scenario I PEC (µg/ L) IPEC/ PNEC PNECsurrounding waters = 1.15 µg/ L

lwc ITC lwc ITC NEW BUILDING - MAINTENANCE AND REPAIR (MltR) SCENARIOS Pleasure crafts - Professionals

46


New bu ilding - Daily emission 1.11 0.97

M&R, Removal - Dai ly emission 1.11 1.10 0.96 0.96

M&R, Appl ication - Daily emission 1.11 1.10 0.96 0.96

Pleasure crafts - Non-professionals


M&R, Appl ication - Daily emission 1.10 0.96


Table 0-15: OLYMPIC 86951 - PEC/PNEC ratios for marine surface water after indirect releases via the STP to the environment - Dissolved concentration considering the background

Exposure Scenario PEC (µg/L) PEC/PNEC PN ECsurrounding waters = 1.15 µg/L

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (MltR} SCENARIOS Pleasure crafts - Professionals


M&R, Removal - Dai ly em ission 1.11 1.10 0.96 0.96



M&R, Removal - Dai ly em ission 1.11 1.10 0.97 0.96



Table 0-16: INTERSMOOTH 360 SPC - PEC/PNEC ratios for marine sediment after indirect releases via the STP to the environment -Concentration on suspended matter considering the background


PNECmarinesediment = 21.48 mg/kg wwt WC TC WC TC

NEW BUILDING - MAINTENANCE AND REPAIR (MltR} SCENARIOS Pleasure crafts - Professionals

New bu ilding - Daily emission 3.85 0. 18

M&R, Removal - Dai ly emission 3.77 3.53 0. 18 0.16

M&R, Appl ication - Daily emission 3.66 3.57 0. 17 0.17


47



M&R, Application - Daily emission 3 .51 0. 16


Table 0-17: OLYMPIC 86951 - PEC/PNEC ratios for marine sediment after indirect releases via the STP to the environment - Concentration on suspended matter considering the background


PNECmarine sediment = 21.48 mg/kg wwt WC TC WC TC

NEW BUILDING - MAINTENANCE AND REPAIR (MltR) SCENARIOS Pleasure crafts - Professionals

New building - Dai ly emission 3 .86 0. 18


M&R, Application - Daily emission 3.67 3.57 0. 17 0 .17



M&R, Application - Daily emission 3.51 0. 16


These results indicate acceptable risks to the marine surface water and sediment for both products, with PEC/PNEC ratios < 1, during t he appl ication and removal of paint for pleasure crafts by professional and non-professional users, whatever the scenario applied (realistic worst case or typical case), for indirect contamination of the environment via the STP.

Cumulatjye assessment for djrect apd jpdjrect releases to the commercial harbour and marina

The following situat ions have been considered for a cumulat ive assessment using MAMPEC modelling and considering each environment (harbour and marina) and each activity sector (professional and non-professiona l users) :

commercial shipping in harbour area : direct releases during New Bui lding and M & R (daily emission from New Building as a worst case) +service-life, professional pleasure craft in marina : direct releases during M&R (Removal) + indirect releases during New Building (Application) + service-life, non professional pleasure craft in marina: during M&R (Removal) + indi rect releases during M&R (Removal) +service- life.

A gener ic leaching rate for copper of 50 µg/cm2/day for t he service-life of ship hulls was considered as a worst case for th is cumulative assessment.

48


Table 0-18: INTERSMOOTH 360 SPC - CUMULATIVE ASSESSMENT - PEC/ PNEC ratios for marine surface water after direct and indirect releases via the STP to the environment - Average dissolved concentrations considering the background (not integrated in the model)

Exposure Scenario PEC (µg/L) PEC/PNEC PNECmarinas, harbours = 2.6 µg/L PNECsurroundinn waters= 1.15 uq/L

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR} SCENARIOS MAMPEC Modelling

Commercial vessels - Harbour 2.11 1.51 0.81 0.58

Commercial vessels - Surrounding 1.13 1.11 0.98 0.97 area of Harbour

Professionals - Marina 2.03 2.02 0.78 0.78

Professionals - Surrounding area of 1.11 1.11 0.96 0.96

Marina

Non-professionals - Marina 2.03 2.02 0.78 0.78

Non-professionals -Surrounding of 1.11 1.11 0.96 0.96

marina

WC: worst case I TC: typical case I M&R = Maintenance and repai r

Table 0-19: OLYMPIC 86951 - CUMULATIVE ASSESSMENT - PEC/PNEC ratios for marine surface water after direct and indirect releases via the STP to the environment - Average dissolved concentrations considering the background (not integrated in the model)


PNECmarinas, harbours = 2.6 µg/L PNECsurroundina waters= 1.15 µg/L

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR} SCENARIOS MAMPEC Modelling




Professiona ls - Surrounding area of 1.11 1.11 0.96 0.96

Marina


Non- professionals -Surrounding of 1.11 1.11 0.96 0.96 marina


49


Table 0-20: INTERSMOOTH 360 SPC - CUMULATIVE ASSESSMENT - PEC/ PNEC ratios for marine sediment after direct and indirect releases via the STP to the environment - Average concentrations on suspended solids considering the background (integrated in the model)

Exposure Scenario PEC (mg/kg wwt) PEC/PNEC PN EC marine sediment = 21.48 mg/ kq wwt

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M•R) SCENARIOS MAMPEC Modelling


Commercial vessels - Surrounding 6.52 5.96 0.30 0.28

area of Harbour


Professionals - Surrounding area of 5.85 5.83 0.27 0.27 Marina


Non-professionals -Surrounding of 5.85 5.83 0.27 0.27

marina


Table 0-21: OLYMPIC 86951 - CUMULATIVE ASSESSMENT - PEC/PNEC ratios for marine sediment after direct and indirect releases via the STP to the environment - Average concentrations on suspended solids considering the background (integrated in the model)

Exposure Scenario PEC (mg/kg wwt) PEC/PNEC PNECmarinesediment = 21.48 mg/ kg wwt

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M•R) SCENARIOS MAMPEC Modelling




Professiona ls - Surrounding area of 5.85 5.83 0.27 0.27

Marina


Non- professionals -Surrounding of 5.85 5.83 0.27 0.27 marina


For both products, these resu lts indicate acceptable risks t o the marine surface water, with PEC/ PNEC ratios < 1, for a cumulative assessment in harbours and mar inas. For

so


marine sediment the risks are only acceptable for the surrounding areas of harbours and marinas, except for the commercial harbour in typical case. It worth noting that for marinas, the r isk is led by t he service-life of ship hulls. I n this case, direct or indirect releases for new building or maintenance & repair consist in negligible emissions compared to service- life.

I t has to be hignlighted t hat this cumulative risk assessment is based upon the approach outl ined in the "Transitional Guidance on mixture toxicity assessment for biocida l products for the environment" (May 2014).

Freshwater Compartment - Indirect releases to the aquatic compartment

The PEC values for copper and the correspond ing PEC/PNEC ratios for the fresh aquatic environment (surface water and sediment) result ing from the use of Intersmooth 360 SPC product and Olympic 86951 product as antifouling are present ed below for new building, maintenance & repa ir phases of pleasure crafts, lead ing to indirect releases to marinas via the STP. Tables below present the values for freshwater water and for fresh sediment for both products.

Table 0-22: INTERSMOOTH 360 SPC - PEC/PNEC ratios for freshwater after indirect releases via the STP to the environment - Dissolved concentration considering the background

Exposure Scenario PEC (1Jg/L) PEC/PNEC PNECtreshwater= 7.8 µg/L

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M•R) SCENARIOS Pleasure crafts - Professionals

New building - Dai ly emission 3.15 0.40


M&R, Application - Daily emission 3.02 2.95 0.39 0.38



M&R, Application - Daily emission 2.91 0.37


Table 0-23: OLYMPIC 86951 - PEC/PNEC ratios for freshwater after indirect releases via the STP to the environment - Dissolved concentration considering the background

Exposure Scenario PEC (1Jg/L) PEC/PNEC PNECtreshwater= 7 .8 µg/L

WC ITC WC ITC NEW BUILDING - MAINTENANCE AND REPAIR (M•R) SCENARIOS Pleasure crafts - Professionals

New building - Daily emission 3.16 0.41

51


Exposure Scenario PEC (µg/L} PEC/PNEC






WC: worst case/ TC: typical case I M&R = Maintenance and repair

Table 0-24: INTERSMOOTH 360 SPC - PEC/PNEC ratios for fresh sediment after indirect releases via the STP to the environment - Concentrations on suspended matter considering the background

Exposure Scenario PEC (mg/kg wwt} PEC/PNEC

PNECfresh sediment = 18. 90 mg/kg wwt WC TC WC TC

NEW BUILDING - MAINTENANCE AND REPAIR (M•R} SCENARIOS Pleasure crafts - Professionals





M&R, Removal - Dai ly emission 16.48 14 .93 0.87 0.79



Table 0-25: PEC/PNEC ratios for fresh sediment after indirect releases via the STP to the environment - Concentrations on suspended matter considering the background

Exposure Scenario PEC (mg/kg wwt} PEC/PNEC

PNECtresh sediment = 18.90 mg/kg wwt WC TC WC TC

NEW BUILDING - MAINTENANCE AND REPAIR (M•R} SCENARIOS Pleasure crafts - Professionals





52


M&R, Removal - Dai ly emission 16.53 I 14.93 0.87 l o.79



These results indicate acceptable risks to the freshwater and sed iment, with PEC/PNEC ratios < 1, during the application and remova l of paint for pleasure crafts by professional and non-professional users, whatever the scenario applied (realistic worst case or typical case), for indirect contamination of the environment via the STP for Intersmooth 360 SPC product and Olympic 86951 product.

2.4.1..7.2.3 Terrestrial compartment (including groundwater)

The proposed uses of copper oxide as antifouling are anticipated to result in direct and indirect (via the STP) exposure of the terrestrial environment ( including groundwater) and hence the risk has been assessed for these compartments.

According to the applicants, it should be considered that the majority of the soil emissions are from old pa int flakes and not soluble copper emissions directly to soil. It should be noted that, for amateur application and removal of paint, it is recommended that these activities should only be undertaken over a tarpaulin or simi lar impervious barrier in order to minimise pa int loss to the soi l. Once the task is completed (either amateur or professional), the remaining paint can be swept up and disposed of in accordance with local and national requ irements . This would further ensure that the exposure of bioavailable copper in soil would be minimal. However, typical and worstcase exposure values were calculated for the terrestria l compartment from the use of Intersmooth 360 SPC product and Olympic 86951 product and these are discussed below.

Direct releases to the terrestrial compartment

The PEC va lues for copper and the correspond ing PEC/PNEC ratios for the terrestrial environment (soil and groundwater) resulting from the use of Intersmooth 360 SPC product and Olympic 86951 product as antifouling are presented below for new building, maintenance & repair phases of pleasure crafts, lead ing to direct releases to soil. Tables below present the va lues for soil and groundwater for both products.

Table 0-26: INTERSMOOTH 360 SPC - PEC/PNEC ratios for soil after direct releases to the environment - Concentrations considering the background

Exposure Scenario PEC (mg/kg wwt) PEC/PNEC PNEC50;1 = 40.20 mg/kg wwt

WC ITC WC ITC NEW BUILDING - MAINTENANCE AND REPAIR (MltR) SCENARIOS Pleasure crafts - Professionals New building - Daily

28.88 0.72 emission New building - Cumulative 458.13 11.40 emission M&R, Removal - Daily 25.06 121.95 0.62 1 o.55 emission

53


Exposure Scenario PEC (mg/kg wwt) PEC/PNEC M&R, Remova l - Cumulative 654.96 84.94 16.29 2.11 emission M&R, Appl ication - Daily

23.68 22.47 0.59 0.56 emission M&R, Application - 401.62 179.94 9.99 4.48 Cumulative emission Pleasure crafts - Non-Professionals M&R, Removal - Daily

29.37 22.60 0.73 0.56 emission M&R, Remova l - Cumulative

60.46 26.60 1.50 0.66 emission M&R, Appl icat ion - Daily

21.88 0.54 emission M&R, Application - 22.99 0.57 Cumulative emission


Table 0-27: OLYMPIC 86951 - PEC/PNEC ratios for soil after direct releases to the environment - Concentrations considering the background

Exposure Scenario PEC (mg/kg wwt) PEC/PNEC PNECsoil = 40.20 mg/ kg wwt

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR) SCENARIOS Pleasure crafts - Professionals New building - Daily emission 29.09 0.72

New building - Cumulative emission 470.76 11.71

M&R, Removal - Daily 25.16 21.96 0.63 0.55 emission

M&R, Remova l - Cumulative 673.30 86.77 16.75 2.16 emission

M&R, Appl icat ion - Daily emission 23.74 22.49 0.59 0.56

M&R, Application - 412.62 184.52 10.26 4.59 Cumulative emission Pleasure crafts - Non-Professionals M&R, Removal - Daily emission 29.60 22.63 0.74 0.56

M&R, Remova l - Cumulative 61.59 26.74 1.53 0.67 emission M&R, Appl ication - Daily emission 21.89 0.54

M&R, Application - 23.03 0.57 Cumulative emission


Table 0-28: INTERSMOOTH 360 SPC - Risk assessment for groundwater after direct releases to the environment - Concentrations considering the background

54


Exposure Scenario PEC (µg/L} Risk characterization Acceptable concentration according to the drinking water di rect ive : 2000 µg/L

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR) SCENARIOS Pleasure crafts - Professionals New bu ilding - Daily

6.79 Acceptable emission New bu ilding - Cumulat ive

Acceptable emission

236.25

M&R, Removal - Daily 4.75 3.09 Acceptable Acceptable

emission M&R, Remova l - Cumulat ive

34 1.47 36.76 Acceptable Acceptable emission M&R, Appl ication - Daily

Acceptable Acceptable emission

4.01 3.36

M&R, Application - 206.04 87.54 Acceptable Acceptable Cumulat ive emission Pleasure crafts - Non-Professionals M&R, Removal - Daily

Acceptable Acceptable emission

7.06 3.43

M&R, Remova l - Cumulative 23.68 5.57 Acceptable Acceptable

emission M&R, Appl ication - Daily

Acceptable emission

3.05

M&R, Application - 3.64 Acceptable Cumulative emission


Table 0-29: OLYMPIC 86951 - Risk assessment for groundwater after direct releases to the environment - Concentrations considering the background

Exposure Scenario PEC (µg/L} Risk characterization Acceptable concentration according to the drinking water di rective : 2000 µg/L

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR) SCENARIOS Pleasure crafts - Professionals New bu ilding - Daily

6.90 Acceptable em ission New bu ilding - Cumulat ive

243.00 Acceptable em ission M&R, Removal - Daily

4.80 3.09 Acceptable Acceptable emission M&R, Remova l - Cumulat ive

351.27 37.74 Acceptable Acceptable em ission M&R, Appl ication - Daily

4.04 3.38 Acceptable Acceptable emission M&R, Application - 21 1.92 89.99 Acceptable Acceptable Cumulative emission Pleasure crafts - Non-Professionals M&R, Removal - Daily 7.18 3.45 Acceptable Acceptable em ission

SS


M&R, Remova l - Cumulative 24.28 15.65 Acceptable I Acceptable

emission M&R, Application - Daily

3.05 Acceptable emission M&R, Application - 3.66 Acceptable Cumulative emission


Results of the r isk assessment are similar for both products. Considering a one-day emission, the results indicate acceptable risks to the terrestrial compartment, with PEC/PNEC ratios < 1, during the appl ication and remova l of paint for pleasure crafts by professiona l and non-professional users, whatever the scenario applied (realistic worst case or typica l case) . Nevertheless the r isks are deemed unacceptable for professiona l users over the emission period when copper cumulate in soil after multiple applications. The risks are acceptable for non- professiona l users for a cumulative risk assessment over the emission period for the application phase of M&R and the remova l (typica l case only) . Concern ing groundwater, all the scenarios lead to acceptable level of contamination for Intersmooth 360 SPC product and Olympic 86951 product.

Labels and/ or safety data sheets of product s authorised for professional uses shall indicate that application must be conducted on impermeable hard standing to prevent direct losses to soil and water and that any losses must be collected for disposal.

Indirect releases to the terrestrial compartment

The PEC values for copper and the correspond ing PEC/PNEC ratios for the terrestrial environment (soil and groundwater) resulti ng from t he use of Intersmooth 360 SPC product and Olympic 86951 product as antifouling are presented below for new building, maintenance & repair phases of pleasure crafts, leading to indirect releases to soil v ia the spreading of STP sludge. Tables below present the values for soil and groundwater for both products. The concentrations in soil do not consider the ageing factor of 2.

Table 0-30: INTERSMOOTH 360 SPC - PEC/PNEC ratios for soil after indirect releases via the STP to the environment - Concentrations considering the background

Exposure Scenario PEC (mg/kg wwt) PEC/PNEC PNECsoil = 40.20 mg/kg wwt

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR) SCENARIOS Pleasure crafts - Professionals

New building - Daily emission 22.54 0.56






56



Table 0-31: OLYMPIC 86951 - PEC/PNEC ratios for soil after indirect releases via the STP to the environment - Concentrations considering the background

Exposure Scenario PEC (mg/kg wwt) PEC/PNEC PNECsoil = 40.20 mg/kg wwt









Table 0-32: INTERSMOOTH 360 SPC - Risk assessment for groundwater after direct releases to the environment - Concentrations considering the background

Exposure Scenario PEC (µg/L) Risk characterization

Acceptable concentration according to the drinking wat er direct ive : 2000 µg/L


New bu ilding - Daily emission 3.40 Acceptable

M&R, Removal - Dai ly emission 3.29 2.94 Acceptable Acceptable

M&R, Appl ication - Daily emission 3.13 3.00 Acceptable Acceptable



M&R, Appl ication - Daily emission 2.92 Acceptable


57


Table 0-33: OLYMPIC 86951 - Risk assessment for groundwater after direct releases to the environment - Concentrations considering the background

Exposure Scenario PEC (µg/L) Risk characterization Acceptable concentration according to the drinking water directive : 2000 µg/L

WC TC WC TC NEW BUILDING - MAINTENANCE AND REPAIR (M8tR} SCENARIOS Pleasure crafts - Professionals

New building - Daily emission 3.42 Acceptable


M&R, Application - Daily emission 3.14 3.00 Acceptable Acceptable


M&R, Removal - Dai ly em ission 3.45 2.97 Acceptable Acceptable

M&R, Application - Daily emission 2.92 Acceptable


These results indicate acceptable risks to soi l and groundwater, during the application and removal of pa int for pleasure crafts by professional and non-professional users, whatever t he scenario applied (realistic worst case or typica l case), for indirect contamination of the environment via the STP, for I ntersmooth 360 SPC product and Olympic 86951 product.

2.4.1..7.2.4 Non-compartmental specific effects relevant to the food chain (secondary poisoning)

An in-depth literature search showed the absence of copper biomagnification across the t roph ic chain in the aquatic and terrestrial food chains . Differences in sensitivity among species were not related to t he level in the trophic chain but to the capability of internal homeostasis and detoxification . Field evidence had further provided no indicat ions of secondary poisoning.

2.4.1..7.2.5 Atmospheric compartment

Emission to the air of copper in the I ntersmooth 360 SPC product may occur during the application and removal phases and through spray drift, HP water wash and abrasion and volati lization from paint during drying . However, cuprous oxideis an inorganic compound and as such has negligible volati lity. Hence, the amount emitted to air is expected to be very low and no risk assessment is carried out for the atmosphere compartment .

2.4.1..7.2.6 Overall conclusion for the environment

The marine aquat ic compartment can be exposed di rectly or indirect ly (via the STP) to the product during the phases of appl ication or removal of paint and directly during the service-l ife of ship hulls. The proposed scenarios led to acceptable risks for commercial vessels and pleasure crafts, when the wider mar ine environments were considered. In

58


59

fact, the risks were not deemed acceptable for the sediment inside commercial harbours

or marinas, but are acceptable for the whole aquatic compartment in the adjacent areas

of the harbours and marinas.

It was considered that the freshwater environment (including the sediment) can also be

exposed indirectly via the STP only, during the pleasure crafts application or removal

phases. Whatever the scenarios, the risks were considered acceptable for the STP and

the freshwater environment. Direct emissions to the freshwater environment have not

been assessed due to the lack of a harmonized scenario and should be considered during

product assessment, if appropriate.

The terrestrial compartment (including groundwater) can be exposed directly or indirectly

via the STP during the pleasure craft application or removal of paint by professionals or

non-professionals. The risks for the soil and groundwater were considered acceptable for

non-professional activities (leading to direct or indirect soil emission). On the other hand,

the releases during application and removal of paint by professionals working on pleasure

crafts led to unacceptable risks for soil when a direct exposure of the terrestrial

compartment is foreseen. In this case the risk remained acceptable for groundwater or

when releases were directed to a STP. Labels and/ or safety data sheets of products

authorised for professional uses shall indicate that application must be conducted on

impermeable hard standing to prevent direct losses to soil and water and that any losses

must be collected for disposal.

The regional copper background concentrations were added to the calculated

concentrations of copper issuing from cuprous oxide antifouling paint application, for all

the environmental compartments. This has been done to cover all the other possible uses

of copper in the calculation of the risk ratios, and in consequence in the assessment of

the risk for environment.

2.5 Overall conclusions

The outcome of the assessment for cuprous oxide in product-type 21 is specified in the

BPC opinion following discussions at the 13rd meeting of the Biocidal Products Committee

(BPC). The BPC opinion is available from the ECHA web-site.

Dicopper oxide PT 21 Product - type 21 January 2016

Intersmooth 360 SPC SPC

Human primary exposure Hu man secondary Aquatic compartment exposure Terrest r ial Gr oundwat Secondar

SCENARIO Professiona

No n Gener al

STP Surface

compartme Air y professio na Wo rker Sediment nt er poisoning

I I pu blic wat er

APPLICATION Appl icatio

Com m e rd a n and Acceptable NR Accepta NR4 NR Acceptable1 Acceptable2 NR NR NR NR I vessel rem oval ble5

of oaint Direct

Pleasure Appl icatio releases: Non

cr afts - n and Acceptable NR Accepta NR4 Acceptable Acceptable1 Acceptable2 accept able Acceptable NR NR Profession r em oval ble5

a ls of paint I ndirect releases: acceotable

Pleasure Appl icat io

crafts - Acceptable Acceptabl Non- n and NR only with NR ea Acceptable Acceptable1 Acceptable2 Acceptable Acceptable NR NR rem oval Profession of paint PPE6

als Shipping Service- NR NR NR NR NR Acceptable1

Acceptable1 NR NR NR NR lane life Commercia Service- NR NR NR NR NR Acceptable1

Acceptable2 NR NR NR NR I Harbour life

Marina Service- NR NR NR NR NR Acceptable1

Acceptable2 NR NR NR NR life

NR: not relevant 1 Acceptable with MAMPEC modelling 2 Acceptable with MAMPEC modelling, for surrounding areas only 3 Unacceptable but labels and where provided instructions for use shall indicate that children sha ll be kept away unt il t reated surface are dry. 4 To protect byst anders in the ship yard the area where painting is performed should be labelled with "Unprotected persons should be kept out of t reatment areas" 5Safe operational procedures and appropriate organizational measures shall be established. Where exposure cannot be reduced to an acceptable level by other means, products shall be used with appropriate personal protective equipment. 6The r isk for non-professionals is acceptable only when gloves are worn .

60


H empe I' A t"f r s n I OU m 01 IVffiPIC 86951

Human primary exposure Human secondary Aquatic compartment exoosure Terrestrial Secondar SCENARIO Non STP compartme Groundwat Air y

Professiona professiona Worker General Surface Sediment nt er poisoning I I

public water

APPLICATION Applicatio

Commercia n and Acceptable NR Accepta NR3 NR Acceptable 1 Acceptable2 NR NR NR NR I vessel removal ble3 A

of oaint Direct

Pleasu re Applicatio releases: Non crafts - n and Acceptable NR Accepta NR3 Acceptable Acceptable 1 Acceptable2 accept able Acceptable NR NR Profession removal ble3A

als of paint I ndirect releases: acceotable

Pleasure Applicatio crafts - Unaccept Non- n and NR Acceptable NR able6 Acceptable Acceptable1 Acceptable2 Acceptable Acceptable NR NR Profession removal only with PPE5

als of paint

Shipping Service- NR NR NR NR NR Acceptable 1

Acceptable1 NR NR NR NR lane life Commercia Service- NR NR NR NR NR Acceptable 1

Acceptable2 NR NR NR NR I Harbour life

Marina Service- NR NR NR NR NR Acceptable 1

Acceptable2 NR NR NR NR life NR: not relevant 1 Acceptable with MAMPEC modelling 2 Accept able w ith MAMPEC modell ing, for surrounding areas only 3 To protect bystanders in the ship yard the area where painting is performed should be labelled with "Unprotected persons shou ld be kept out of t reatment areas" 4 Safe operational procedures and appropriate organ izational measures shall be established. Where exposure cannot be reduced to an acceptable level by other means, products shall be used with appropriate personal protective equipment. 5The r isk for non-professionals is acceptable on ly when gloves are worn 6 Unacceptable but labels and where provided instructions for use shall indicate t hat children sha ll be kept away until treated surface are dry.

61


62

2.6 Requirement for further information related to the product

Further data on products containing cuprous oxide shall be required as detailed below:

Intersmooth 360 SC:

- The stability at 0°C of the product, the surface tension of the pure product, the flash-

point, a long term storage stability study (2 years) with the effect of light, a study to

determine true residue level in container after use or a management of the

packaging in a specialized processing dedicated circuit, a validated analytical method

for the identification and determination of cuprous oxide in the product Intersmooth

360 and further data on specificity for the analytical method for the determination of

zinc pyrithione in the product should be provided at the product authorization stage.

- With regard to human health assessment, following information should be provided:

A dermal absorption study will be required at product authorisation stage to refine

the risk assessment: Because of deficiencies in the available dermal absorption

studies, new studies would be needed at product authorisation. However, at this

point it would not be reasonable to require new dermal absorption studies before

harmonised guidance for PT 21 dermal absorption studies is developed. It was

agreed to set a provisional absorption value for each copper compound based on the

products tested, and these values would only apply for active substance approval).

Hempel’s Antifouling Olympic 86951:

- The stability at 0°C of the product, the surface tension of the pure product, an

accelerated storage stability study14 days at 54°C, a long term storage stability

study (2 years) with the effect of light, a pourability test, the flash point (and if

necessary the boiling point of the product) and a validated analytical method for the

identification and determination of cuprous oxide in the product Olympic should be


- With regard to human health assessment, following information should be provided:

A dermal absorption study will be required at product authorisation stage to refine

the risk assessment: Because of deficiencies in the available dermal absorption

studies, new studies would be needed at product authorisation. However, at this

point it would not be reasonable to require new dermal absorption studies before

harmonised guidance for PT 21 dermal absorption studies is developed. It was

agreed to set a provisional absorption value for each copper compound based on the

products tested, and these values would only apply for active substance approval).

- With regard to physico-chemical properties, labelling of the product should indicate

‘shake well before use’.


APPENDIX 1: LIST OF ENDPOINTS

Chapter 1: Identity, Physical and Chemical Properties, Details of Uses, Further Information, and Proposed Classification and Labelling

Active substance (ISO Common Name) Function (e.g. fung icide)

Rapporteur Member State

Identity (Annex IIA, point II.)

Chemical name (IUPAC) Chemical name (CA) CAS No EC No Other substance No. Minimum purity of the active substance as manufactured (g/ kg or g/ I) Ident ity of relevant impurities and additives (substances of concern) in the active substance as manufactured (g/ kg)

Molecular formu la Molecular mass Structural formula

Cuorous oxide Prevention of foul ina bv settlina oraanisms.

I France.

Coooer ( I) oxide Cuorous oxide, dicoooer oxide 1317-39-1 215-270-7 CIPAC 8084 942g/ kg as cuprous oxide 837g/ kg as cooper ( I) There are four relevant impurities: Arsenic (max 0.009Sg/ kg) Cadmium (max 0.04g/ kg) Lead ( max 1.2g/ kg) Nickel (max 0.3a/ ka) Cu?O 143.09 a/ mol

Cu I

Cu- 0

63


64

Physical and chemical properties (Annex IIA, point III., unless otherwise indicated)

Melting point (state purity) >346 °C

Purity: 97%

Boiling point (state purity) Not necessary as boiling point will occur at

temperatures greater than 360 SPC°C based

on the melting point

Temperature of decomposition >346ºC

Appearance (state purity) Easily compactable orange powder.

Purity: 97%

Relative density (state purity) 5.87

Purity: 97%

Surface tension Not applicable due to the low water solubility

of cuprous oxide (< 1mg/L)

Vapour pressure (in Pa, state

temperature)

Not necessary as the melting point is above

300°C.

Henry’s law constant (Pa m3 mol -1) Not relevant

Solubility in water (g/l or mg/l, state

temperature)

pH 4.0: at least 28.6 g/L at 20°C

pH 6.5 to 6.6: 0.639 mg/L at 20°C

pH 9.7: < LOQ (0.539 mg/L) at 20°C

Solubility in organic solvents (in g/l or

mg/l, state temperature) (Annex IIIA,

point III.1)

Toluene <1.4 × 10-2 g/L

DCM <1.0 × 10-2 g/L

n-Hexane <1.2 × 10-2 g/L

Ethyl acetate <1.2 × 10-2 g/L

Methanol <9.8 × 10-3 g/L

Acetone <1.3 × 10-2 g/L

Stability in organic solvents used in

biocidal products including relevant

breakdown products (IIIA, point III.2)

Not required. The active substance as

manufactured does not include any organic

solvents.

If biocidal products (i.e. antifouling paints) are formulated with organic

solvents, the compatibility between dicopper oxide and solvents and the stability of the products will be reported

in the product dossier Partition coefficient (log POW) (state

temperature)

Not relevant for the ecotoxicological risk

assessement, due to the specific absorption

mechanism of copper.

Hydrolytic stability (DT50) (state pH and

temperature) (point VII.7.6.2.1)

pH______:

pH______:

pH______:

Not applicable for metal compounds.

Dissociation constant (not stated in

Annex IIA or IIIA; additional data

requirement from TNsG)

Not relevant, cuprous oxide oxide is slightly

soluble in water and the solubilisation results

of oxido-reduction reaction of the cuprous

oxide into ionic copper. Any addition of acid

would result in reaction with cuprous oxide

UV/VIS absorption (max.) (if absorption

> 290 nm state at wavelength)

Maximal absorption at :

260 nm (marginal) for neutral solution

206 nm for alkaline solution

225 nm for acidic solution

Photostability (DT50) (aqueous, sunlight,

state pH)

(point VII.7.6.2.2)

Not applicable.


65

Quantum yield of direct

phototransformation in water at > 290

nm (point VII.7.6.2.2)

Not applicable.

Flammability Not highly flammable

Explosive properties Not explosive


66

Summary of validated intended uses

Object

and/or situation (a)

Member

State or Country

Product

name

Organisms

controlled (c)

Formulation Application Applied amount per treatment

Remarks:

(m)

Type

(d-f)

Conc.

of as

(i)

method

kind

(f-h)

number

min max

(k)

interval

between

applications (min)

g as/L

min

max

water

L/m2 min

max

g

as/m2

min max

Objects to be protected include

hulls of commercial, naval and other government

vessels, pleasure

craft and man-made structures and objects..

EU Antifouling Product 1 – see

confidential file

Fouling organisms in marine ans

freshwater environments

Antifouli ng paint.

42.56% w/w wet paint 37.5 %

w/w wet paint

42.56% w/w wet

paint

Airless spray, brush, roller.

Minimum one coat. Multiple coats may

be applied to achieve required

film thickness

dependent on in-

service lifetime.

Reapplication times will

depend on maintenance schedule

of treated

vessels.

Not applicabl e

Not applicable

Depends on required film thickness

Antifouling product 1 should be regarded as a representative formulation for the

purpose of supporting an application for cuprous oxide approval.

(a) e.g. biting and suckling insects, fungi, molds; (b) e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR)

(c) GCPF Codes - GIFAP Technical Monograph No 2, 1989 ISBN 3-8263-3152-4); (d) All abbreviations used must be explained (e) g/kg or g/l;(f) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench; (g) Kind, e.g. overall, broadcast, aerial spraying, row, bait, crack and crevice equipment used must be indicated; (h) Indicate the minimum and maximum number of application possible under practical conditions of use; (i) Remarks may include: Extent of use/economic importance/restrictions


67

Classification and proposed labelling (Annex IIA, point IX.)

with regard to physical/chemical data Not classified

with regard to toxicological data Acute Tox 4 H302: Harmful if swallowed

Acute Tox 4 H332 Harmful if inhaled

Eye dam. 1 H318: Causes serious eye

damage.

with regard to fate and behaviour data R53, May casue long-term adverse effects in

the aquatic environment.

with regard to ecotoxicological data R50, Very toxic to aquatic organisms

Chapter 2: Methods of Analysis

Analytical methods for the active substance

Technical active substance (principle of

method) (Annex IIA, point 4.1)

Determination by conversion of the test

substance batches with iron(III) chloride

solution and potentiometric back-titration

with cerium(IV) sulfate solution. The

determined reducing power allows to

obtained cuprous oxide content by

calculation after the determination of copper

metal content.

Analytical method is validated for Spiess

Urania and Nordox. Further validation data

would be required for American Chemet for

the approval of the active substance

Impurities in technical active substance

(principle of method) (Annex IIA, point

4.1)

Relevant trace metals can be determined by

HPLC –AES (Atomic Emission Spectroscopy),

ICP-AES (Inductively Coupled Plasma –

Atomic Emission Spectroscopy) or by AAS,

the samples are previously digested in dilute

acid.

Complete validation data are missing for

Nordox and American Chemet and would be

required for the approval of the active

substance.

Validated analytical methods have been

provided by Spiess Urania for the

determination of other impurities. Analytical

methods and validation data are missing for

Nordox and American Chemet and would be

required for the approval of the active

substance

Analytical methods for residues

Soil (principle of method and LOQ)

(Annex IIA, point 4.2)

Residues of copper may be determined in

soils using ICP-AES methods (e.g. AOAC

official method 990.8). The estimated

instrumental limit of determination (LOD) is


68

6 µg Cu/l. Another suitable method is AAS

(e.g. US EPA method 7210), with an LOD of

20 µg Cu/l. For both methods of analysis,

the sample must first be digested.

Air (principle of method and LOQ)


Residues of copper may be determined in air

using Flame-AAS or ICP-AES methods (e.g.

NIOSH methods 7029 or 7300 respectively).

The estimated instrumental limits of

determination (LOD) are 0.05 and 0.07 µg

Cu/filter (LOQ not determined).

Water (principle of method and LOQ)


In water, trace elements may be

determined by Inductively Coupled Plasma

– Atomic Emission Spectrometric (ICPAES)

(e.g. US EPA method 220.7). The LOD for

this method was estimated at 3 µg Cu/l and

the LOQ was determined at 20 µg Cu/l.

Other suitable methods include AAS with

direct aspiration (LOD 20 µg/l, LOQ 200

µg/l) (e.g. US EPA method 220.1) and AAS

with graphite furnace (LOD 1 µg/l, LOQ 5

µg/l) (e.g. US EPA method 220.2). For all

three methods of analysis, the sample must

first be digested.

Sea water analysis can be performed by a

voltammetry method such as Differential

Pulse Anodic Stripping Voltammetry at a

Hanging Mercury Drop Electrode (DPASV

HMDE). The detection limit is dependant on

the deposition time. For a typical 300 second

deposition time, 0.1 µg/l is achievable.

Body fluids and tissues (principle of

method and LOQ) (Annex IIA, point 4.2)

ICP-AES may also be used for analysing

elements in body fluids and tissues following

acid digestion of the sample. LOQs are 10

µg/100 g blood, 2 µg/g tissue (e.g. NIOSH

method 8005) and 0.1 µ/sample of urine

(NIOSH method 8310).

Nevertheless no analytical method is

required as the active substance is not

classified T or T+.

Food/feed of plant origin (principle of

method and LOQ for methods for

monitoring purposes) (Annex IIIA, point

IV.1)

Not applicable for antifouling applications

Food/feed of animal origin (principle of

method and LOQ for methods for

monitoring purposes) (Annex IIIA, point

IV.1)

ICP-AES may be used for analyzing copper in

fresh fish. LOQ is 2.5µg/g wet tissue (US EPA

200.11)


69

Chapter 3: Impact on Human Health

Absorption, distribution, metabolism and excretion in mammals (Annex IIA, point

6.2)

Rate and extent of oral absorption: It was agreed during the TMIII08 that

an oral absorption of 36% for humans

and 25% for animals have to be used.

Rate and extent of dermal absorption: By default, a dermal absorption of 5%

has to be used for copper compound in

solution.

For product, it has been agreed to set

provisional absorption values of 0.14%

for International paint product and

0.34% for Hempel product, based on the

products tested. This value would only

apply for active substance approval.

Dermal absorption study of copper in

formulated product should be provided

at the product authorization level.

Rate and extent of inhalative absorption: 100 % (default value)

Distribution: Once absorbed by oral route, copper is

bound to albumin and transcuprein and then

rapidly transported to the liver where it is

incorporated to ceruloplasmin, a transport

protein that circulates in the organism and

deliver the copper to other organs. The liver

is the main organ involved in copper

distribution and plays a crucial role in copper

homeostasis by regulating its release. It

should be however noted that a minor

fraction of the absorbed dose can directly be

distributed to peripheral organs. In both

humans and animals, copper is tightly

regulated at a cellular level, involving

metallothionein and metallochaperones.

These regulating molecules prevent from the

accumulation of potentially toxic, free copper

ions within the cell. In addition to the liver,

the brain is another organ which contains

relatively high concentrations of copper.

Potential for accumulation: Mammals have metabolic mechanisms that

maintain homeostasis (a balance between

metabolic requirements and prevention

against toxic accumulation). Because of this

regulation of body copper, indices of copper

status remain stable except under extreme

dietary conditions. This stability was

demonstrated in a study in which human

volunteers received a diet containing total

copper in the range 0.8 to 7.5 mg/d. Under

these conditions, there were no significant

changes in commonly used indices of copper

status, including plasma copper,

ceruloplasmin, erythrocyte superoxide

dismutase and urinary copper.

Rate and extent of excretion: Biliary excretion is quantitatively the most


70

important route, with a mean copper

excretion estimated to be in the order of 1.7

mg Cu/day (24.6 12.8 µg Cu/kg

bodyweight). A small amount of copper is

also lost in urine and in sweat. Excretion of

endogenous copper is influenced by dietary

copper intake. When the copper intake is

low, turnover is slow and little endogenous

copper is excreted and vice versa. Faecal

copper losses reflect dietary copper intake

with some delay as intake changes and

copper balance is achieved. Urinary losses do

not contribute to the regulation of copper

stores and contribute very little to the overall

balance.

Toxicologically significant metabolite None

Acute toxicity (Annex IIA, point 6.1)

Rat LD50 oral 1340 mg/kg

Rat LD50 dermal >2000 mg/kg

Rat LC50 inhalation < 5 mg/l

Skin irritation Negative; not classified as irritating to skin.

Eye irritation Positive; classified as an eye irritant.

Skin sensitization (test method used and

result)

Negative; not classified as a skin sensitiser.

Repeated dose toxicity (Annex IIA, point 6.3)

Species/ target / critical effect The test substance used the following study

was copper (II) sulphate.

Rat/ liver/ inflammation

Rat/ kidney/ cytoplasmic droplets

Rat, mouse/ forestomach/ minimal to

moderate hyperplasia of the squamous

mucosa

Lowest relevant oral NOAEL / LOAEL 16.3 mgCu/mg kg/d

Lowest relevant dermal NOAEL / LOAEL Not available

Lowest relevant inhalation NOAEL /

LOAEL

0.2 mgCu/m3

Genotoxicity (Annex IIA, point 6.6)

The test substance used in each of the

following studies was copper (II) sulphate

pentahydrate.

1. Ames test in Salmonella typhimurium -

negative in both the presence and absence of

S9 mix.

2. Bone marrow micronucleus study in the

mouse – negative at a dose of 447 mg/kg

bw.

3. In vivo/in vitro unscheduled DNA

synthesis study in the livers of orally dosed

male rats – negative, following treatment

with doses of 632.5 or 2000 mg/kg bw.

These studies demonstrate that copper is not

mutagenic in the in vitro and in vivo test


71

systems used.

Carcinogenicity (Annex IIA, point 6.4)

Species/type of tumour Available studies of the carcinogenicity of

copper compounds in rats and mice,

although not fully reliable, have given no

indication that copper salts are carcinogenic.

lowest dose with tumours Not applicable.

Reproductive toxicity (Annex IIA, point 6.8)

Species/ Reproduction target / critical

effect

The test substance used in the following

study was copper (II) sulphate pentahydrate.

Rat/Two-generation study/No evidence of

effects on the fertility potential of either male

or female rats.

Lowest relevant reproductive NOAEL /

LOAEL

Copper sulphate cannot be regarded as

having adverse effects on fertility in the

animals tested.

1500 ppm NOAEL in rat two-generation

study = 23.6-43.8 mgCu/kg bw/d (maximal

dose tested)

Species/Developmental target / critical

effect

Mouse/ Developmental toxicity/

malformations (study with major

methodological deficiencies)

Lowest relevant developmental NOAEL /

LOAEL

6 mg Cu/kg bw/d

(NOAEL maternal toxicity = 6 mg Cu/kg

bw/d)

However rat two-generation study with

copper sulphate pentahydrate does not raise

any particular teratogenic concern.

Neurotoxicity / Delayed neurotoxicity (Annex IIIA, point VI.1)

Species/ target/critical effect Rat/ CNS/ locomotor activity, learning ability,

relearning capacity and memory

Lowest relevant developmental NOAEL /

LOAEL.

No adverse effects for these endpoints.

Other toxicological studies (Annex IIIA, VI/XI)

.........................................................

......................

None

Medical data (Annex IIA, point 6.9)

Direct observation, eg clinical cases,

poisoning incidents if available; data

point 6.12.2.

Acute symptoms resulted in metallic taste,

salivation, epigastric pain, nausea, vomiting

and diarrhoea. Anatomo-pathological

examinations after self-poisoning (ingestion

varying between 1 and 100 g of copper

dissolved in water) revealed ulcerations of

gastro-intestinal mucosa, hepatic damages

(dilatation of central vein, cell necrosis and

bile thrombi) and kidney lesions (congestion

of glomeruli, swelling or necrosis of tubular

cells and sometimes haemoglobin casts).

Chronic symptoms, occurred in a voluntary

intoxication by daily ingestion of 30 mg of


72

copper for 2 years and 60 mg during the

third year, were malaise, jaundice,

hepatomegaly and splenomegaly. Liver

examination revealed micronodular cirrhosis.

In the particular case of vineyard sprayers

intoxication by the Bordeaux mixture

(unknown doses), lung lesions with focal

distribution were observed: alveoli filled with

desquamated macrophages, granuloma in

the alveoli septa and fibro-hyaline nodules.


73

Summary (Annex IIA, point 6.10) Value Study Safety factor

ADI (if residues in food or feed) 0.15

mgCu/kg

bw/day

EFSA (2008) Not

applicable.

Acute-term AEL 0.082 mg/kg

bw/d 90d in rats

MOE ref =

50

Medium-term AEL 0.082 mg/kg

bw/d 90d in rats

MOE ref =

50

Long-term AEL 0.041 mg/kg

bw/d 90d in rats

MOE ref =

100

Drinking water limit Not applicable

ARfD (acute reference dose) Not applicable

Acceptable exposure scenarios (including method of calculation)

Professional users Acceptable, if professionals wear the

following PPE/RPE: (most conservative

PPE/RPE):

Potman: impermeable coverall, gloves and

mask APF 10 during mixing and loading

phase,

Sprayer: impermeable coverall, gloves and

mask APF 40 during application,

Worker who applies product by roller

and brush: an equivalent Tyvek coverall

and gloves during mixing and loading of

paint into trail and brushing,

Sand blaster: protective protections

equivalent to water-proof overalls, an

airstream helmet with rubber flaps that

covered a large part of their upper body,

strong protective gloves and mask APF 10,

Grit filler: coated coverall, gloves and mask

APF 40.

Non-professional users Unacceptable

Indirect exposure as a result of use Acceptable under conditions mentioned

below:

Due to application by professionals, no

quantitative risk was performed to assess

exposure of bystander but the product

should be labelled with the phrases

“unprotected persons be kept out of

treatment areas”

Due to application by non professionals,

labels and where provided instructions for

use shall indicate that children shall be kept

away until treated surface are dry.

Concerning secondary exposure via food

contamination, pending uniform methodology

to assess dietary exposure induced by an

antifouling treatment, available knowledge


74

about the natural occurrence of copper,

physiological needs, physico-chemical

properties and regulations already in force

constitute appreciable information to

consider as negligible its influence on the

consumer.

Chapter 4: Fate and Behaviour in the Environment

Route and rate of degradation in water (Annex IIA, point 7.6, IIIA, point XII.2.1, 2.2)

Hydrolysis of active substance and

relevant metabolites (DT50) (state pH

and temperature)

pH______: Not applicable to metals.

pH______:

pH______:

Photolytic / photo-oxidative degradation

of active substance and resulting

relevant metabolites

Not applicable to metals.

Readily biodegradable (yes/no) No.

Biodegradation in seawater Not applicable to metals.

Non-extractable residues Not applicable to metals.

Distribution in water / sediment systems

(active substance)

The distribution of metals between

aqueous phase and

soil/sediment/suspended matter should

preferentially be described on the basis

of measured soil/water,

sediment/water and suspended

matter/water equilibrium distribution

coefficient (TECHNICAL GUIDANCE

DOCUMENT on Risk Assessment Part II

Appendix VIII, 2003; TECHNICAL

GUIDANCE DOCUMENT Annex 4-VIII

Environmental risk assessment for

metals and metal compounds (RIP 3.2-

2).

From the literature overview, the following

partitioning coefficients have thus been


Partition coefficient in suspended

matter

Kpsusp = 30,246 l/kg (log Kp (pm/w) = 4.48)

(50th percentile) (Heijerick et al, 2005)

Partition coefficient in sediment

Kpsed = 24,409 l/kg (log Kp(sed/w) = 4.39)

(50th percentile) (Heijerick et al., 2005)

Distribution in water / sediment systems

(metabolites)


Route and rate of degradation in soil (Annex IIIA, point VII.4, XII.1.1, XII.1.4;

Annex VI, para. 85)


75

Mineralization (aerobic) Not applicable to metals.

Laboratory studies (range or median,

with number of measurements, with

regression coefficient)

DT50lab (20C, aerobic): Not applicable to

metals.


metals.


metals.

DT50lab (20C, anaerobic): Not applicable to

metals.

degradation in the saturated zone: Not

applicable to metals.

Field studies (state location, range or

median with number of measurements)

DT50f: Not applicable to metals.

DT90f: Not applicable to metals.

Anaerobic degradation Not applicable to metals.

Soil photolysis Not applicable to metals.

Non-extractable residues Not applicable to metals.

Relevant metabolites - name and/or

code, % of applied a.i. (range and

maximum)


Soil accumulation and plateau

concentration

Although unable to degrade, the affect of

ageing on the distribution of copper in soil

results in increased immobilisation by long

term adsorption and complexation reactions

in the soil.

Adsorption/desorption (Annex IIA, point XII.7.7; Annex IIIA, point XII.1.2)

Ka , Kd

Kaoc , Kdoc

pH dependence (yes / no) (if yes type of

dependence)

The distribution of metals between aqueous

phase and soil/sediment/suspended matter

should preferentially be described on the

basis of measured soil/water,

sediment/water and suspended matter/water

equilibrium distribution coefficient

(TECHNICAL GUIDANCE DOCUMENT on Risk

Assessment Part II Appendix VIII, 2003;

TECHNICAL GUIDANCE DOCUMENT Annex 4-

VIII Environmental risk assessment for

metals and metal compounds (RIP 3.2-2).

From the literature overview, the following

partitioning coefficients have thus been


Partition coefficient in soil

Kd = 2120 l/kg (log Kp = 3.33) (50th

percentile)

(Sauvé et al. 2000)

Fate and behaviour in air (Annex IIIA, point VII.3, VII.5)

Direct photolysis in air Not applicable to metals.

Quantum yield of direct photolysis Not applicable to metals.


76

Photo-oxidative degradation in air Latitude: ............. Season:

................. DT50 ..............


Volatilization The potential for volatilisation of copper

under environmentally relevant conditions is

considered not to be significant.

Monitoring data, if available (Annex VI, para. 44)

Soil (indicate location and type of study) No data available relating to the use of

copper in antifouling paints..

Surface water (indicate location and type

of study)

Two monitoring studies have been conducted

in the UK and Finland and have investigated

the speciation of copper in the marine

environment. The monitoring data of

commercial harbours and estuaries in the UK

(which did not show any elevated copper

concentrations at these sites) also confirm

the modelled output data from MAMPEC.

The measured water results from marinas

compare identically with the modelling data

from MAMPEC with values within the marina

and as with the modelled data, show that the

average concentrations in the marina are

within the normal background levels of

copper in the marine environment. Samples,

taken just outside the marina shows that the

copper levels fall even further indicating that

if increased copper levels are observed, they

are a very localised effect to the actual

marina itself.

The results of the Finnish monitoring data

showed that the boating activity and

associated release of Cu2+ from the pleasure

craft and no significant effect on the copper

levels in the water when comparing the

samples taken in the marina and those taken

at the entrance and further downstream of

the marina.

Ground water (indicate location and type

of study)

No data available relating to the use of

copper in antifouling paints.

Air (indicate location and type of study) No data available relating to the use of

copper in antifouling paints


77

Chapter 5: Effects on Non-target Species

Toxicity data for aquatic species (most sensitive species of each group)

(Annex IIA, Point 8.2, Annex IIIA, Point 10.2)

Acute toxicity to aquatic

organisms

No acute toxicity data are presented as the toxicity

was evaluated using a SSD based on chronic

toxicity data.

Chronic toxicity to

aquatic organisms in the

FRESHWATER COMPARTMENT

SSD result from 139 individual NOEC/EC10

values: HC5-50 = 7.8 µg Cu / l as reasonable

worst case

Freshwater algae and higher plants:

Lowest NOEC used in the SSD = 15.7 µg Cu /L

(growth of Pseudokirchneriella subcapitata)

Highest NOEC used in the SSD = 510.2 µg Cu /L

(growth of Chlorella vulgaris)

Freshwater Invertebrates:

Lowest NOEC used in the SSD = 4 µg Cu /L

(mortality and reproduction of Ceriodaphnia dubia)

Highest NOEC used in the SSD = 181 µg Cu /L

(reproduction of Daphnia magna)

Freshwater Fishes:

Lowest NOEC used in the SSD = 2.2 µg Cu /L

(growth of Oncorhynchus mykiss)

Highest NOEC used in the SSD = 188 µg Cu /L

(mortality of Perca fluviatilis)

Chronic toxicity to


FRESHWATER SEDIMENT

COMPARTMENT

SSD result from 62 individual NOEC values:

HC5-50 = 1741 mg Cu/kg OC, corresponding to

87 mg Cu/kg dry weight for a sediment with 5

% O.C.(TGD default value)

Sediment organisms:

Lowest NOEC used in the SSD = 18.3 mg Cu /kg

d.w. (growth and reproduction of Tubifex tubifex)

Highest NOEC used in the SSD = 580.9 mg Cu /kg

d.w. (survival of Tubifex tubifex )

Chronic toxicity to

Sewage microorganisms

The lowest reliable observed NOEC value was

noted for the inhibition of respiration = 0.23 mg/l

Chronic toxicity to


MARINE WATER

COMPARTMENT

SSD result from 56 individual NOEC/EC10 values:

HC5-50 = 5.2 µg Cu / 2 for DOC level

typical for harbours and marinas (2 mg/L)


typical for surrounding waters (0.5 mg/L)


typical for sea (0.2 mg/L)

Marine water algae and higher plants:

Non normalized lowest NOEC = 2.9 µg Cu /L

(growth of Phaeodactylum tricornutum)

Non normalized highest NOEC = 50.1 µg Cu /L

(germination of Macrocystis pyrifera)


78

Marine water Invertebrates:

Non normalized lowest NOEC = 5.9 µg Cu /L

(development of Mytilus galloprovincialis)

Non normalized highest NOEC = 145 µg Cu /L

(growth of Penaeus monodon)

Marine water Fishes:

Non normalized lowest NOEC = 55 µg Cu /L (length

and weight of Atherinops affinis)

Non normalized highest NOEC = 123 µg Cu /L

(hatchability and survival of Atherinops affinis)

Effects on earthworms or other soil non-target organisms

Acute toxicity to soil

organisms

(Annex IIIA, point XIII.3.2)

No acute toxicity data are presented as the toxicity

was evaluated using a SSD based on chronic

toxicity data.

Chronic toxicity to

soil organisms in the

TERRESTRIAL COMPARTMENT

SSD result from 252 individual chronic

NOEC/EC10 values: HC5-50 = 45.6 mg Cu/kg

dry weight was used as reasonable worst

case value for Europe in absence of site-

specific information on soil properties.

Terrestrial higher plants:

Lowest NOEC used in the SSD = 18 mg Cu /kg d.w.

(Hordeum vulgare)

Highest NOEC used in the SSD = 698 mg Cu /kg

d.w. (Lycopersicon esculentum)

Terrestrial Invertebrates:

Lowest NOEC used in the SSD = 8.4 mg Cu /kg

d.w. (cocoon production of Eisenia andrei)


d.w. (reproduction of Falsomia candida)

Soil micro-organisms:

Lowest NOEC used in the SSD = 30 mg Cu /kg d.w.

(glucose respiration)


d.w. (maize respiration)

Effects on terrestrial vertebrates

Acute toxicity to mammals


Not applicable to active substances used in

antifouling products

Acute toxicity to birds




Dietary toxicity to birds




Reproductive toxicity to birds





79

Effects on honeybees (Annex IIIA, point XIII.3.1)

Acute oral toxicity Not applicable to active substances used in


Acute contact toxicity Not applicable to active substances used in


Effects on other beneficial arthropods (Annex IIIA, point XIII.3.1)

Acute oral toxicity Not applicable to active substances used in


Acute contact toxicity Not applicable to active substances used in


Acute toxicity to



Bioconcentration (Annex IIA, point 7.5)

Bioconcentration factor (BCF) For the naturally occurring substances such

as essential metals as copper,

bioaccumulation is complex, and many

processes are available to modulate both

accumulation and potential toxic impact.

Biota regulates their internal concentrations

of essential metals through homeostatic

control mechanisms (i.e. active regulation,

storage). As a result of these processes, at

low metal concentrations, organisms

accumulate essential metals more actively in

order to meet their metabolic requirements

than when they are being exposed at higher

metal concentrations.

As a consequence of homeostatic processes,

and unlike many organic substances, the

BCF/BAF is not independent of exposure

concentrations for metals and it is inversely

related to exposure concentrations. Thus, the

use of ratios Cbiota/Cwater or

Cbiota/Csediments as an overall approach for

estimating copper bioconcentration factors is

thus not appropriate.

Depration time (DT50)

(DT90)

Not applicable for metals.

Level of metabolites (%) in organisms

accounting for > 10 % of residues

Not applicable for metals.

Chapter 6: Other End Points

None required


80

APPENDIX 2: LIST(S) OF ABBREVATIONS

List of standard terms and abbreviations (adapted from: (i) Guidelines and criteria

for the preparation of PPP dossiers11; (ii) TNsG on Data Requirements12).

Stand. Term/ abbreviation

Explanation Stand. Term/ abbreviation

Explanation

A ampere Bt Bacillus thuringiensis

ACh acetylcholine Bti Bacillus thuringiensis israelensis

AChE acetylcholinesterase Btk Bacillus thuringiensis kurstaki

ADI acceptable daily intake Btt Bacillus thuringiensis tenebrionis

ADME administration distribution metabolism and excretion

BUN blood urea nitrogen

ADP adenosine diphosphate bw body weight

AE acid equivalent c centi- (x 10 –2 )

AF assessment factor °C degrees Celsius (centigrade)

AFID alkali flame-ionisation detector or detection

CA controlled atmosphere

A/G albumin/globulin ratio CAD computer aided design

ai active ingredient CADDY computer aided dossier and data supply (an electronic dossier interchange and archiving format)

ALT alanine aminotransferase (SGPT)

cd candela

Ann. Annex CDA controlled drop(let) application

AEC acceptable concentration level

cDNA complementary DANN

AEL acceptable exposure level CEC cation exchange capacity

AMD automatic multiple development

cf confer, compare to

AMD automatic multiple development

CFU colony forming units

ANOVA analysis of variance ChE cholinesterase

AP alkaline phosphatase CI confidence interval

approx approximate CL confidence limits

ARfD acute reference dose cm centimetre

as active substance CNS central nervous system

AST aspartate aminotransferase (SGOT)

COD chemical oxygen demand

ASV air saturation value CPK creatinine phosphatase

ATP adenosine triphosphate cv coefficient of variation

BAF bioaccumulation factor Cv ceiling value

BCF bioconcentration factor d day(s)

bfa body fluid assay DCA Dichloroacetaldehyde

BOD biological oxygen demand DDVP Dimethyl Dichloro Vinyl Phosphate

bp boiling point DIS draft international standard (ISO)

BPD Biocidal Products Directive DMSO dimethylsulfoxide

BSAF biota-sediment accumulation

factor

DNA deoxyribonucleic acid

BSP bromosulfophthalein dna designated national authority

11 EU (1998a): European Commission: Guidelines and criteria for the preparation of complete

dossiers and of summary dossiers for the inclusion of active substances in Annex I of Directive

91/414/EC (Article 5.3 and 8,2). Document 1663/VI/94 Rev 8, 22 April 1998 12 European Chemicals Bureau, ECB (1996) Technical Guidance Documents in support of the

Commission Directive 93/67/EEC on risk assessment for new notified substances and the

Commission Regulation (EC) 1488/94 for existing substances


81



Explanation

DO dissolved oxygen FOB functional observation battery

DOC dissolved organic carbon foc organic carbon factor (compartment dependent)

dpi days post inoculation fp freezing point

DRP detailed review paper (OECD)

FPD flame photometric detector

DT50(lab) period required for 50 percent dissipation (under laboratory conditions) (define method of estimation)

FPLC fast protein liquid chromatography

DT90(field) period required for 90 percent dissipation (under field conditions) (define method of estimation)

g gram(s)

dw dry weight GC gas chromatography

decadic molar extinction coefficient

GC-EC gas chromatography with electron capture detector

EC50 median effective concentration

GC-FID gas chromatography with flame ionisation detector

ECD electron capture detector GC-MS gas chromatography-mass spectrometry

ED50 median effective dose GC-MSD gas chromatography with mass-selective detection

EINECS European inventory of existing commercial substances

GEP good experimental practice

ELINCS European list of notified chemical substances

GFP good field practice

ELISA enzyme linked immunosorbent assay

GGT gamma glutamyl transferase

e-mail electronic mail GI gastro-intestinal

EMDI estimated maximum daily intake

GIT gastro-intestinal tract

EN European norm GL guideline level

EPMA electron probe micro-analysis

GLC gas liquid chromatography

ERL extraneous residue limit GLP good laboratory practice

ESPE46/51 evaluation system for pesticides

GM geometric mean

EUSES European Union system for the evaluation of substances

GMO genetically modified organism

F field GMM genetically modified micro-organism

F0 parental generation GPC gel-permeation chromatography

F1 filial generation, first GPMT guinea pig maximisation test

F2 filial generation, second GPS global positioning system

FBS full base set GSH glutathione

FELS fish early-life stage GV granulosevirus

FIA fluorescence immuno-assay h hour(s)

FID flame ionisation detector H Henry’s Law constant (calculated as a unitless value)

Fmol fractional equivalent of the metabolite´s molecular weight compared to the active substance

ha hectare(s)


82



Explanation

Hb haemoglobin ISBN international standard book number

HC5 concentration which will be harmless to at least 95 % of the species present with a given level of confidence (usually 95

%)

ISSN international standard serial number

HCG human chorionic gonadotropin IUCLID International Uniform Chemical Information Database

Hct haematocrit iv intravenous

HDT highest dose tested IVF in vitro fertilisation

hL hectolitre k (in combination)

kilo

HEED high energy electron diffraction k rate constant for biodegradation

HID helium ionisation detector K Kelvin

HPAEC high performance anion exchange chromatography

Ka acid dissociation constant

HPLC high pressure liquid chromatography or high performance liquid chromatography

Kb base dissociation constant

HPLC-MS high pressure liquid chromatography - mass spectrometry

Kads adsorption constant

HPPLC high pressure planar liquid chromatography

Kdes apparent desorption coefficient

HPTLC high performance thin layer chromatography

kg kilogram

HRGC high resolution gas chromatography

KH Henry´s Law constant (in atmosphere per cubic metre per mole)

HS Shannon-Weaver index Koc organic carbon adsorption coefficient

Ht haematocrit Kom organic matter adsorption

coefficient

HUSS human and use safety standard Kow octanol-water partition coefficient

I indoor Kp solid-water partition coefficient

I50 inhibitory dose, 50% kPa kilopascal(s)

IC50 median immobilisation concentration or median inhibitory concentration 1

l, L litre

ICM integrated crop management LAN local area network

ID ionisation detector LASER light amplification by stimulated emission of radiation

IEDI international estimated daily intake

LBC loosely bound capacity

IGR insect growth regulator LC liquid chromatography

im intramuscular LC-MS liquid chromatography- mass spectrometry

inh inhalation LC50 lethal concentration, median

INT 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazoliumchloride testing method

LCA life cycle analysis

ip intraperitoneal LC-MS-MS liquid chromatography with tandem mass spectrometry

IPM integrated pest management LD50 lethal dose, median; dosis letalis media

IR infrared LDH lactate dehydrogenase

IRAC Insecticide resistance action committee

ln natural logarithm


83



Explanation

LOAEC lowest observable adverse effect concentration

MLD minimum lethal dose

LOAEL lowest observable adverse effect level mm millimetre

LOD limit of detection MMAD mass median aerodynamic diameter

LOEC lowest observable effect concentration mo month(s)

LOEL lowest observable effect level MOE margin of exposure

log logarithm to the base 10 mol mole(s)

LOQ limit of quantification (determination) mp melting point

LPLC low pressure liquid chromatography MRE maximum residue expected

LSC liquid scintillation counting or counter MRL maximum residue level or limit

LSD least squared denominator multiple range test

mRNA messenger ribonucleic acid

LSS liquid scintillation spectrometry MS mass spectrometry

LT lethal threshold MSDS material safety data sheet

m metre MTD maximum tolerated dose

M molar MT material test

µm micrometre (micron) MW molecular weight

MAC maximum allowable concentration n.a. not applicable

MAK maximum allowable concentration n- normal (defining isomeric configuration)

MC moisture content MT material test

MCH mean corpuscular haemoglobin MW molecular weight

MCHC mean corpuscular haemoglobin concentration

n.a. not applicable

MCV mean corpuscular volume n number of observations

MDL method detection limit NAEL no adverse effect level

MFO mixed function oxidase nd not detected

µg microgram NEDI national estimated daily intake

mg milligram NEL no effect level

MHC moisture holding capacity NERL no effect residue level

MIC minimum inhibitory concentration ng nanogram

min minute(s) nm nanometre

MKC minimum killing concentration NMR nuclear magnetic resonance

mL millilitre no, n° number

MLT median lethal time NOAEC no observed adverse effect concentration



Explanation

NOAEL no observed adverse effect level PIC prior informed consent

NOEC no observed effect concentration pic phage inhibitory capacity

NOED no observed effect dose PIXE proton induced X-ray emission

NOEL no observed effect level pKa negative logarithm (to the base 10) of the acid dissociation constant

NOIS notice of intent to suspend pKb negative logarithm (to the base 10) of the base dissociation constant

NPD nitrogen-phosphorus detector or detection

PND post natal day

NPV nuclear polyhedrosis virus PNEC predicted no effect

concentration (compartment to be added as subscript)

NR not reported po by mouth

NTE neurotoxic target esterase POP persistent organic pollutants

OC organic carbon content ppb parts per billion (10 -9 )

OCR optical character recognition PPE personal protective equipment

ODP ozone-depleting potential ppm parts per million (10 -6 )

ODS ozone-depleting substances PPP plant protection product


84

OH hydroxide ppq parts per quadrillion (10 -24 )

OJ Official Journal ppt parts per trillion (10 -12 )

OM organic matter content PSP phenolsulfophthalein

OP Organophosphate PrT prothrombin time

Pa pascal PRL practical residue limit

PAD pulsed amperometric detection PT product type

2-PAM 2-pralidoxime PT(CEN) project team CEN

pc paper chromatography PTT partial thromboplastin time

PC personal computer QA quality assurance

PCV haematocrit (packed corpuscular volume)

QAU quality assurance unit

PEC predicted environmental concentration (Q)SAR quantitative structure-activity relationship

PECA predicted environmental concentration in air

r correlation coefficient

PECS predicted environmental concentration in soil

r 2 coefficient of determination

PECSW predicted environmental concentration in surface water

RA risk assessment

PECGW predicted environmental concentration in ground water

RBC red blood cell

PED plasma-emissions-detector REI restricted entry interval

pH pH-value RENI Registry Nomenclature Information System

PHED pesticide handler’s exposure data Rf retardation factor


85



Explanation

RfD reference dose SPE solid phase extraction

RH relative humidity SPF specific pathogen free

RL50 median residual lifetime spp subspecies

RNA ribonucleic acid SSD sulphur specific detector

RP reversed phase SSMS spark source mass spectrometry

rpm revolutions per minute STER smallest toxicity exposure ratio (TER)

rRNA ribosomal ribonucleic acid STMR supervised trials median residue

RRT relative retention time STP sewage treatment plant

RSD relative standard deviation t tonne(s) (metric ton)

s second t½ half-life (define method of estimation)

S solubility T3 tri-iodothyroxine

SAC strong adsorption capacity T4 thyroxine

SAP serum alkaline phosphatase T25 tumorigenic dose that causes tumours in 25 % of the test animals

SAR structure/activity relationship TADI temporary acceptable daily intake

SBLC shallow bed liquid chromatography

TBC tightly bound capacity

sc subcutaneous TCD thermal conductivity detector

sce sister chromatid exchange TG technical guideline, technical group

SCAS semi-continous activated sludge TGD Technical guidance document

SCTER smallest chronic toxicity exposure ratio (TER)

TID thermionic detector, alkali flame detector

SD standard deviation TDR time domain reflectrometry

se standard error TER toxicity exposure ratio

SEM standard error of the mean TERI toxicity exposure ratio for initial exposure

SEP standard evaluation procedure TERST toxicity exposure ratio following repeated exposure

SF safety factor TERLT toxicity exposure ratio following chronic exposure

SFC supercritical fluid chromatography

tert tertiary (in a chemical name)

SFE supercritical fluid extraction TEP typical end-use product

SIMS secondary ion mass spectroscopy

TGGE temperature gradient gel electrophoresis

S/L short term to long term ratio TIFF tag image file format

SMEs small and medium sized enterprises

TLC thin layer chromatography

SOP standard operating procedures Tlm median tolerance limit

sp species (only after a generic name)

TLV threshold limit value


Explanation

TMDI theoretical maximum daily intake

TMRC theoretical maximum residue contribution

TMRL temporary maximum residue limit

TNsG technical notes for guidance

TOC total organic carbon

Tremcard transport emergency card

tRNA transfer ribonucleic acid

TSH thyroid stimulating hormone


86

(thyrotropin)

TTC 2,3,5-triphenylterazoliumchloride

testing method

TWA time weighted average

UDS unscheduled DNA synthesis

UF uncertainty factor (safety factor)

ULV ultra low volume

UR unit risk

UV ultraviolet

UVC unknown or variable composition, complex reaction products

UVCB undefined or variable composition, complex reaction products in biological material

v/v volume ratio (volume per volume)

vis visible

WBC white blood cell

wk week

wt weight

w/v weight per volume

ww wet weight

w/w weight per weight

XRFA X-ray fluorescence analysis

yr year

< less than

less than or equal to

> greater than

greater than or equal to


APPENDIX 3: LIST OF STUDIES

Reference list of st udies submitted and validated by Section number for the active substance:

TNG AUTHOR(S) YEAR TITLE SOURCE ( WHERE DIFFERENT FOR COMPANY) COMPANY, DATA OWNER Essential Essential SECTION REPORT NO. PROTECT studies for studies for

CLAIMED evaluat ion evaluation ( Yes/ Nol Yes No

A 3.1.1 O'Connor, B.J., Mullee, D.M. 2003 Nordox Copper Oxide : Determination of general physico-chemical properties. Yes Nord ox i:gJ SafePharm Laboratories. SPL Report No. 1515/003; GLP; Unpublished


A 3.3. 1 O'Connor, B.J., Mullee, D.M. 2003 Nordox Copper Oxide : Determination of general physico-chemical properties. Yes Nord ox i:gJ SafePharm Laboratories. SPL Report No. 1515/003; GLP; Unpublished

A 3.3.2 O'Connor, B.J., Mullee, D.M. 2003 Nordox Copper Oxide: Determinat ion of general physico-chemical properties. Yes Nord ox i:gJ SafePharm Laboratories. SPL Report No. 1515/003; GLP; Unpublished

A 3.3.3 O'Connor, B.J., Mullee, D.M. 2003 Nordox Copper Oxide: Determinat ion of general physico-chemical properties. Yes Nord ox 18:1 SafePharm Laboratories. SPL Report No. 1515/003; GLP; Unpublished

A 3.4.1 Xu, L., Chen, X., Wu, Y., Chen, c., 2006 Solution-phase synthesis of single-crystal hollow Cu20 spheres with No Public 18:1 Li, W., Pan, W., Wang, Y. nanoholes. Nanotechnology 17; 1501- 1505; Not GLP; Published domain

A 3.4.1 Messerschmidt , s. 2006 UV/VIS absorption spectrum of cuprous oxide; study code 20051363/01- Yes Nord ox i:gJ PCSD


A 3.5 O'Connor, B.J., Mullee, D.M. 2003 Nordox Copper Oxide: Determinat ion of general physico-chemical properties. Yes Nord ox 18:1 SafePharm Laboratories. SPL Report No. 1515/003; GLP; Unpublished

A 3.7 Messerschmidt, s . 2006 Solubility of Cuprous oxide in organic solvents; GAB Biotechnologie GmbH & Yes EU 18:1 GAB Analytik GmbH. Report No. 20051363/01-PSBO; GLP; Unpubl ished Antifou li

ng Task Force

A 3.7 O'Connor, B.J., Mullee, D.M. 2003 Nordox Copper Oxide : Determination of general physico-chemical properties. Yes Nord ox 18:1 SafePharm Laboratories. SPL Report No. 1515/003; GLP; Unpublished

A 3.8 Messerschmidt, s . 2006 UV/VIS Absorption Spectrum of Cuprous oxide; GAB Biotechnologie GmbH & Yes EU ~ GAB Analytik GmbH. Report No. 20051363/01-PCSD; GLP; Unpublished Antifou li

ng Task Force

A 3.8 O'Connor, B.J., Mullee, D.M. 2003 Nordox Copper Oxide: Determinat ion of general physico-chemical properties. Yes Nord ox ~ SafePharm Laboratories. SPL Report No. 1515/003; GLP; Unpublished

A4.l Blossom, N. 2006 Copper { I ) oxide : Determinat ion of Purity of Five Technical Batches. Yes America 18:1 American Chemet Corportat ion, Helena, USA Report No. 42406; April 2006; n GLP; Unpublished Chem et

A4.1 Blossom, N. 2012 Copper {I ) oxide: Determination of Purity of Ten Technical Batches. American Yes America 18:1 Chemet Corportation, Helena, USA; February 2012; Not GLP; Unpublished n

Chem et A4.l CIPAC - CI PAC method for tota l copper 44/TC/M/3.2. Volumetric thiosulphate No Public 18:1

method. CIPAC E, Pace 44. Not GLP, oublished. domain

8 7


TNG AUTHOR(S) YEAR TITLE SOURCE ( WHERE DIFFERENT FOR COMPA NY) COMPANY, DATA OWNER Essent ial Essential SECTION REPORT NO. PROTECT studies for studies for

CLAIMED evaluat ion evaluation (Yes/ Nol Yes No

A4.1 CIPAC - CIPAC method for total copper 44/TC/M/3.1. Electrolytic method (Referee No Public ~ method). CIPAC E, Paae 42. Not GLP, oublished. domain

A4.1 Kiefer, R. 2004 Cuprous oxide: Determination of Purity of Five Technical Batches. GAB Yes Spiess- ~ Biotechnologie GmbH Report No.20021079/ 01-UCA; September 2004; GLP; Urania Unoublished

A4.1 Kreuscher, T 2012 Cuprous oxide technical : Determination of Purity of Five Technical Batches. Yes Spiess- ~ Aurubis AG Report; February 2012; Not GLP; Unpublished Urania

A4.1 O'Connor, B.J., Mullee, D.M. 2003 Copper I Oxide: Analytical method validation. SafePharm Laboratories. SPL Yes Nord ox ~ Reoort No. 1515/002· GLP· Unoublished

A4.1 O'Connor, B.J., Mullee, D.M. 2003 Copper I Oxide: Analytical profi le of batches. SafePharm Laboratories. SPL Yes Nord ox ~ Reoort No. 1515/001 · GLP· Unoubl ished

A4.1 Stromberg, A 2012 5-batch Analysis - Qualitative and Quantitative Profi le of the test substance Yes Nord ox ~ NORDOX Cuprous Oxide; Nordox AS Report; Not GLP; Unpublished

A4.2 AOAC 1993 AOAC Official Method 990.08,. Metals in Solid Wastes; I nductively Coupled No Public ~ Plasma Atomic Emission Method. AOAC Official Methods of Analysis; Metals domain and Other Elements Chanter 9 oaae 31. Not GLP oublished.

A4.2 EPA 1983 Methods for Chemical Analysis of Water and Wastes. Method 220.2 (Copper. No Public ~ Atomic Absorpt ion, furnace technique). Washington, DC; U.S. Environmental domain Protection Aaencv. Not GLP oublished.

A4.2 EPA 1983 Inductively Coupled Plasma - Atomic Emission Spectrometric Method for No Public ~ Trace Element Analysis of Water and Wastes - Method 200.7. Washington, domain DC· U.S. Environmental Protection Aaencv. Not GLP oublished.

A4.2 EPA 1986 Test Methods for Evaluating Solid Waste, Physical/Chemical Methods (SW- No Public ~ 846). Method 7210 (Copper. Atomic Absorpt ion, direct aspiration) . domain Washington, DC; U.S. Environmental Protection Agency. Not GLP, published. And appended : EPA, 1986. Test Methods for Evaluating Solid Waste, Physical/Chemical Methods (SW-846). Method 3050B (Acid digestion of sediments, sludges and soils). Washington, DC; U.S. Environmental Protect ion Aaencv. (published).

A4.2 EPA 1986 Methods for Chemical Analysis of Water and Wastes. Method 220.1 (Copper. No Public ~ Atomic Absorption, direct aspiration). Washington, DC; U.S. Environmental domain Protection Aaencv. Not GLP, published.

A4.2 NIOSH 1987 Method 8005. NIOSH Manual of Analytical Methods, Fourth Edit ion, 8/ 15/94. No Public ~ Not GLP, oublished. domain

A4.2 NIOSH 1987 Method 8310. NIOSH Manual of Analytical Methods, Fourth Edition, 8/ 15/ 94. No Public ~ Not GLP, published. domain

A4.2 NIOSH N/A Method 7029. NIOSH Manual of Analytical Methods, Fourth Edition, 8/ 15/ 94. No Public ~ No GLP, oublished. domain

A 4.3 Martin TD, Martin ER, Lobring LB 1991 US EPA Method 200.11, Revision 2.1. Determination of Metals in Fish Tissue No Public ~ and McKee GD. by Inductively Coupled Plasma-Atomic Emission Spectrometry. EPN600/ 4- domain

91-010, nn 177-209; Not GLP; Published A 6.1.1 1984a OECD Acute Oral Toxicity Test: Determination of the Acute Oral Medial Lethal Yes Nord ox ~

Dose (LOSO) of Cuprous Oxide in the Rat. Reoort No. 296/8404

A 6.1.1 Hixson, O.F. 1973 Determination of the Oral Toxicity and Skin Irritat ion Potential of Purple Copp Yes America ~ 97. Rosner Hixson Laboratories. Laboratory No. PT73-40. 27 March 1973 n lunoublishedl. Chem et

88



CLAIMED evaluat ion evaluation (Yes/ No l Yes No

A 6 .1.1 1991a Purple Copp 97N Cuprous Oxide: Acute Oral LOSO in Rats. Yes America ~ Report No. 91048- 2 n

Chem et A 6.1.2 Kuku linski, M. 1976 Acute Dermal Toxicity/ Eye Irritation. Rosner, Hixson Laboratories. Report Yes America ~

No. PT76-298 n Chem et

A 6 .1.2 1991b Purple Copp 97N Cuprous Oxide: Acute Dermal Toxicity in Rabbits. Yes America ~ Report No. 91048-1 n

Chem et A 6.1.2 1988 Akute Derma le Toxizitat an Ratten m it. -- Yes Spiess- ~

Reoort No. 1-4-1602-BB Urania A 6.1.3 1988a Acute Toxicolog ical Study of Kupfer-1-0xid After I nhalation by the Rat. Yes Spiess- ~

Report No. 1-4-40-88 Urania

A 6 .1.3 1991 Acute Inhalat ion Toxicit y in the Rat Single Level Limit Test Purple Copp Yes America ~ 97N Cuprous Oxide. -· Study No. n 131.003 Chem et

A 6 .1.3 1985 Cuprous Oxide, Acute Inhalation Toxicity Study in Rats (Lim it Test). Yes Nord ox ~ Reoort No. 3401

A 6 .1.3 1985 Cuprous Oxide, Acute I nhalation Toxicity Study in Rats. Yes Bardyke ~ Reoort No. 3398; GLP; Unoublished

A 6 .1.3 1973 Purple Copp 97 : Acute Inhalation Toxicity in Rats. -- Yes America ~ Report No. PT73-40A n

Chem et A 6.1.4 1984b OECD Skin Irritation Test : Determination of the Degree of Primary Cutaneous Yes Nord ox ~

Irritation Caused by Cuprous Oxide in the Rabbit . Reoort No. 237/8404

A 6 .1.4 1984c OECD Eye Irritation Test : Determination of the Degree of Ocular Irritation Yes Nord ox ~ Caused by Cuprous Oxide in the Rabbit. Report No. 105/8404

A 6.1.4 1988b Irritant Effects of Kupfer-1-0xid on Rabbit Skin Acc. To Draize. Yes Spiess- ~ Reoort No. 1-3-42-88 Urania

A 6.1.4 Dickhaus, s . & Heisler, E. 1988c Eye Irritation Test with Kupfer-I -Oxide Acc. To Draize and OECD Guidelines Yes Spiess- ~ No. 405. Beratung und Forschung GmbH. Report No. 1- 3-4 1-88. Urania

A 6 .1.4 Hixson, O.F. 1973 To Determine the Oral Toxicity and Skin Irritation Potential for Purple Copp Yes America ~ 97. Rosner Hixson Laboratories. Laboratory No. PT73-40. 27 March 1973 n lunoublished). Chem et

A 6.1.4 1994 Primary Eye Irritation Study in Rabbits . Report No. 0634- Yes America ~ 93 n

Chem et A 6 .1.4 Kuku linski, M. 1980 Low Tint Purple Copp 97N: Eye I rritation. Rosner, Hixson Laboratories. Yes America ~

Report No. TM 80-373 n Chem et

A 6.1.4 Kuku linski, M. 1976 Acute Dermal Toxicity and Eye Irritation. Rosner, Hixson Laboratories. Yes America ~ Report No. PT76-298 n

Chem et A 6 .1.5 - 1993 Guinea Pig Maximisat ion Test of Skin Sensitisat ion with 'URA 17030'. Yes Spiess- ~

Report No. 10-05-1961/00-92 Urania

89




A 6.1.5 1986 Dermal Sensitization Study in Guinea Pigs with Purple Copp 97N Cuprous Yes America 18] Oxide. Study No. 480-2833 n

Chem et A 6.12.2 Chuttani HK, Gupta PS, Gulati S, 1965 Acute Copper Sulfate Poisoning. Am J Med, 39 : 849-854; Not GLP; published No Public 18]

Gupta DN. domain A 6.12.2 O'Donohue JW, Reid MA, Varghese 1993 Micronodular cirrhosis and acute liver failure due to chronic copper self- No Public 18]

A, Partmann B, Will iams R intoxication. Eur. J. Gastroenterol. 5:561-562; Not GLP; published domain

A 6.12.2 O'Connor, J.M., Bonham, M.P., 2003 Copper supplementation has no effect on markers of DNA damage and liver No Public ~ Turley, E., McKeown, A., function in healthy adults (FOODCUE Project). Ann Nutr Metab, 47: 201- domain McKelvey-Martin, V.J., Gilmore, 206. Not GLP, Published w.s. and Strain, J.J.

A 6.12.2 Pimentel JC, Marques F 1969 Vineyard sprayer's lung - A new occupational disease. Thorax, 24, 678-688; No Public 18] Not GLP; oublished domain

A 6.12.2 Pimentel JC, Menezes AP. 1977 Liver disease in vineyard sprayers. Gastroenterology 72:275-283; Not GLP; No Public 18] published domain

A 6.12.2 Pimentel JC, Menezes AP. 1975 Liver granulomas containing copper in vineyard sprayer's lung - A new No Public ~ Etiology of Hepatic Granulomatosis. Am. Rev. Respir. Dis. 111:189-195; Not domain GLP; published

A 6.12.2 Pratt, W.B., Omdahl, J.L. and 1985 Lack of Effects of Copper Gluconate Supplementat ion. The American Journal No Public ~ Sorenson, R.J., of Clinical Nutrition, 42: 681 - 682. Not GLP, Published domain

A 6.12.2 Rock, E., Mazur, A., O'Connor, 2000 The Effect of Copper Supplementation on Red Blood Cell Oxidizability and No Public 18] J.M., Bonham, M.P., Rayssiguier, Plasma Ant ioxidants in Middle-Aged Healthy Volunteers. Free Radica l Biology domain Y. & Strain, J .J and Medicine. 28 (3); 324-329. Not GLP, Published

A 6.12.2 Tanner MS, Partmann B, Mowat 1979 Increased hepatic copper concentration in Indian Childhood Cirrhosis. Lancet No Public 18] AP, Will iams R, Pandit AN, Mills 1 :1203-5; Not GLP; published domain CF, Bremner I.

A 6.12.2 Turley, E., McKeown, A., Bonham, 2000 Copper supplementation in Humans Does Not Affect the Susceptibility of Low No Public 18] M.P., O'Connor, J.M, Chopra, M., Density Upoprotein to In Vitro Induced Oxidation (Foodcue Project). Free domain Harvey, L.J., Majsak-Newman, G., Radical Biology & Medicine, 29: (11); 1129-1134. Not GLP, Published Fairweather-Tait, S.J., Bugel, s., Sandstrom, B. Rock, E., Mazur, A., Tavssiauier Y. & Strain J.J.

A 6.12.4 Plamenac P, Santic z, Nikulin A, 1985 Cytologic changes of the respiratory tract in vineyard spraying workers. Eur No Public 18] Serdarevic H. J Respir Dis, 67 : 50-55; Not GLP; published domain

A 6.12.4 Scheinberg IH, Sternlieb I. 1994 Is non- Indian childhood cirrhosis caused by excess dietary copper? Lancet, No Public 18] 344: 1002-1004 ' Not GLP· oublished domain

A 6.12.4 Tanner MS, Kantarjian AH, Bhave 1983 Early introduction of copper-contaminated animal milk feeds as a possible No Public 18] SA, Pandit AN. cause of Indian Childhood Cirrhosis. Lancet 2: 992-995; Not GLP; published domain

A 6.12.5 Internationa I Programme on 1990 Poisons Informat ion Monograph (PIM G002) : Copper and copper salts; Not No Public ~ Chemical Safety GLP; Published domain

A 6.12.7 Internationa I Programme on 1990 Poisons Information Monograph (PIM G002) : Copper and copper salts; Not No Public 18] Chemical Safety GLP; Published domain

A 6.12.8 Internationa I Programme on 1990 Poisons Informat ion Monograph (PIM G002) : Copper and copper salts; Not No Public 18] Chemical Safety GLP; Published domain

90




A 6.2 Allen, M.M., Barber, R.S., Braude, 1961 Further studies on various aspects of the use of high-copper supplements for No Public ~ R. and Mitchell, K.G. growing pigs. Brit. J. Nutr., 15: 507 - 522, Not GLP Published domain

A6.2 Amaravadi, R., Glerum, D.M. and 1997 Isolation of a cDNA encoding the human homolog of COX17, a yeast gene No Public ~ Tzagoloff, A. essent ial for mitochondrial copper recruitment . Hum Genet. 99: 329-333. domain

Not GLP, Published. A 6.2 Aoyagi, s. and Baker, D.H. 1993 Bioavailabilit y of Copper in Analytical-Grade and Feed Grade Inorganic No Public ~

Copper Sources when Fed to Provide Copper at Levels Below the Chick's domain Reauirement. Poultrv Science. 72 : 1075-1083. Not GLP Published

A 6.2 Baker, D.H., Odle, J., Funk, M.A. 1991 Research Note: Bioavailability of Copper in Cupric Oxide, Cuprous Oxide, No Public ~ and Wieland, T.M. and in a Copper-Lysine Complex. Poultry Science. 70 : 177-179. Not GLP, domain

Published A 6.2 Buescher, R.G., Griffin, S.A. and 1961 Copper Availability to Swine from Cu64 Labelled Inorganic Compounds. No Public ~

Bell, M.C. Journal of Animal Science, 20: 529-531. Not GLP, Published domain A 6.2 Bunch, R.J., Speer, V.C., Hays, 1963 Effects of High Levels of Copper and Chlortetracycline on Performance of No Public ~

v.w. and Mccall, J.T. Pigs. J. An imal Sci. 22: 56-60. Not GLP, Published domain A 6.2 Bunch, R.J., Speer, v.c., Hays, 1961 Effects of copper Sulfate, Copper oxide and Chlortetracycline on Baby Pig No Public ~

V.W., Hawbaker, J.H. and Catron, Performance. J. Animal Sci. 20 : 723-726. Not GLP, Published domain D.V.

A 6.2 campbell, C.H., Brown, R. and 1981 Circulating Ceruloplasmin is an Important Source of Copper for Normal and No Public ~ Linder, M.C. Malignant Animal Cells. Biochim. Biophys. Acta. 678: 27-38. Not GLP, domain

Published. A 6.2 Cromwell, G.L., Stahly, T.S. and 1989 Effects of Source and Level of Copper on Performance and Liver Copper No Public ~

Monegue, H.J. Stores in Weanling Pigs. J. Animal Sci. 67: 2996-3002. Not GLP, Published domain A6.2 Culotta, V.C., Klomp, J.S., 1997 The Copper Chaperone for Superoxide Dismutase. The Journal of Biological No Public ~

casareno, R.L.B., Krems, B. And chemistry. 272 (38) : 23469 - 23472. Not GLP, Published domain Gitlin, J.D

A 6.2 Darwish, H.M., Cheney, J.C., 1984 Mobilisat ion of copper (II) from plasma components and mechanism of No Public ~ Schmitt, R.C. and Ettinger, M.J. hepatic copper transport. Am. J. Physiol., 246 (9):G72-G79. Not GLP, domain

Published. A6.2 Gunshin, H., Mackenzie, B, Berger, 1997 Cloning and Characterisation of a Mammalian Proton-Coupled Metal-Ion No Public ~

u.v., Gunshin, Y., Romero, M.F., t ransporter. Nature. 388:482-488. Not GLP, Published. domain Boron, W.F., Nussberger, s., Golian, J.L. & Hediger, M.A.

A6.2 Kegley, E.B. and Spears, J.W. 1994 Bioavailability of feed-grade copper sources (oxide, sulfate, or lysine) in No Public ~ growing cattle. J. Animal Sci. 72: 2728-2734. Not GLP, Published domain

A 6.2 Klomp, L.W.J., Lin, S.J., Yuan, 1997 Identification and Functional Expression of HAHl, a Novel Human Gene No Public ~ D.S., Klausner, R.D., Culotta, V.C. Involved in Copper Homeostasis. The Journal of Biological Chemistry domain and Gitlin, J.D. 272(14): 9221-9226. Not GLP, Published.

A 6.2 Lee S.H., Lancey R., Montaser A., 1993 Ceruloplasmin and copper transport during the latter part of gestation in the No Public ~ Madani N., Under M.C. rat. Proc Soc Exp Biol Med 203 : 428-39. Not GLP, Published. domain

A 6.2 Linder M.C., Weiss K.C. and Hai, 1987 Structure and function of transcuprein in transport of copper by mammalian No Public ~ V.M. blood plasma. In: Hurley L.C., Keen C.L., Lonnerdal, B. and Rucker, R.B. domain

(eds). Trace Elements in Man and Animals (TEMA-6). New York: Plenum, 141- 144. Not GLP Published.

9 1




A 6.2 McArdle, H.J., Gross S.M., Danks 1990 Role of Albumin's Copper Binding Site in Copper Uptake by Mouse No Public ~ D.M. & Wedd, A.G. Hepatocytes. Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21}: 988-991. domain

Not GLP, Published. A 6.2 McArdle, H.J., Gross, S.M. and 1988 Uptake of Copper by Mouse Hepatocytes. Journal of Cellular Physiology, No Public ~

Danks, D.M. 136: 373-378. Not GLP, Published. domain A 6.2 Norvell, M.J., Gable, D.A. and 1975 Effects of feeding high levels of various copper salts to broiler ch ickens. I n No Public ~

Thomas, M.C., Trace Substances in Environments! Health - 9, (Hemphill, D.D., Ed}. domain Universitv of Missouri, Columbia, MO. Not GLP, Published

A 6.2 Pirot , F., Millet, J., Ka lia, Y.N. & 1996 In vitro Study of Percutaneous Absorption, Cutaneous Bioavailability and No Public ~ Humbert, P Bioequivalence of Zinc and Copper from Five Topica l Formulations. Skin domain

Pharmacol. 9 : 259-269. Not GLP, Published. A 6.2 Pirot, F., Panisset, F., Agache, P. & 1996 Simultaneous Absorption of Copper and Zinc through Human Skin in vitro. No Public ~

Humbert, P. Skin Pharmacol. 9: 43-52. Not GLP, Published. domain

A6.2 Rojas, L.X., McDowell, L R., 1996 Interaction of different organic and inorganic zinc and copper sources fed to No Public ~ Cousins, R.J., Martin, F.G., rats. J. Trace Elements Med. Biol. 10: 139-144. Not GLP, Published domain Wilkinson, N.S., Johnson, A.B. and Velasquez, J.B.

A 6.2 Scott, K.C. & Turnlund, J.R., 1994 Compartment Model of Copper Metabolism in Adult Men. J. Nutr. Biochem. No Public ~ 5: 342-350. Not GLP, Published. domain

A 6.2 Turnlund, J.R., Keen, C.L. and 1990 Copper status and urinary and salivary copper in young men at three levels No Public ~ Smith, R.G. of dietary copper. Am. J. Clin. Nutr. 51 : 658-64.Not GIP, Published. domain

A 6.2 Turnlund, J.R., Ketes, W.R., 1998 Copper absorption, excretion and retention by young men consuming low No Public ~ Peiffer, G.L. and Scott, K.C dietary copper determined using the stable isotope 65Cu. Am. J. Clin. Nutr., domain

67: 1219 - 1225. Not GLP, Published A6.2 Turnlund, J.R., Keyes, W.R., 1989 Copper absorpt ion and retention in young men at three levels of dietary No Public ~

Anderson, H.L and Acord, LL. copper by use of the stable isotope 65Cu. Am. J. Clin. Nutr. 49:870-878.Not domain GLP, Published.

A 6.2 Turnlund, J.R., Wada, L., King, 1988 Copper Absorpt ion in Young Men Fed Adequate and Low Zinc Diets. No Public ~ J.C., Keyes, W.R. and Lorra, L.A Biological and Trace Element Research, 17 : 31 - 41. Not GLP, Published domain

A 6.2 van Berge Henegouwen, G.P., 1977 Biliary Secretion of Copper in Healthy Man. Quantitation by an intestinal No Public ~ Tangedahl, T.N., Hofmann, A.F., perfusion technique. Gastroenterology, 72: 1228-1231. Not Published. domain Northfield, T.C. La Russo, N.F. and Mccall, J.T.,

A 6.2 Van den Berg, G.J., Van Wouwe, 1990 Ascorbic Acid Supplementation and Copper Status in Rats. Biological Trace No Public ~ J.P and Beynen, A.C., Element Research, 23 : 165-172. Not GLP, Published domain

A6.2 Walker, R.W. 1982 The Result of a Copper Bracelet Clinical Trial and Subsequent Studies. p 469 No Public ~ - 478. In: J. R. J. Sorenson (ed) Inflammatory Diseases and Copper: The domain Metabolic and Therapeutic Roles of Copper and Other Essential Metal loelements in Humans; Humana Press; Clifton N.J .. USA. Not GLP, Published.

A 6.2 Weiss K.C. & Linder M.C. 1985 Copper transport in rats involving a new plasma protein. Am. J. Physiol. No Public ~ 249: E77-88. Not GLP, Published. domain

A 6.2 Whitaker, P. & McArdle, H.J. 1997 Iron Inhibits Copper Uptake by Rat Hepatocytes by Down-Regulating the No Public ~ Plasma Membrane NADH Oxidase. In. Fisher, P.W., L'Abbe, M.R., Cockell, domain K.A. et al. (Eds}. Trace Elements in Man and Animals. (TEMA9}. NRC Research Press Ottowa nn 237-239

92



CLAIMED evaluat ion evaluation (Yes/Nol Yes No

A 6.2 Wirth, W.L. and Under, M.M. 1985 Distribution of Copper Among Components of Human Serum. JNCI. 75: 277- No Public ~ 284. Not GLP, Published. domain

A 6.2 Xin, Z., Waterman, D.F., Hemken, 1991 Effects of copper sources and dietary cation-anion balance on copper No Public ~ R.W., Harmon, R.J. and Jackson, availability and acid-base status in dietary calves. J. Dairy Sci. 74: 3167- domain J.A 3173. Not GLP, Published

A 6.2 Zhou, B. & Gitschier, J. 1997 hCTRl; A Human Gene for Copper Uptake Identified by Complementation in No Public ~ Yeast. Proc. Natl. Acad. Sci USA. 94:7481-7486. Not GLP, Published. domain

A 6.4.1 Hebert, C.D., 1993 NTP Technical Report on toxicity studies of cupric sulphate {CAS No. 7758- No Public ~ 99-8) administered in drinking water and feed to F344/N rats and B6C3Fl domain mice. National Toxicology Program, Toxicity Report Series No. 29, United States Department of Health and Human Services {NIH Publication 93-3352). GLP Published

A 6.4.1 Hebert, C.D., 1993 NTP Technical Report on toxicity studies of cupric sulphate {CAS No. 7758- No Public ~ 99-8) administered in drinking water and feed to F344/N rats and B6C3Fl domain mice. National Toxicology Program, Toxicity Report Series No. 29, United States Department of Health and Human Services {NIH Publication 93-3352). GLP Published

A 6.5 Burki, H.R. and Okita, G.T. 1969 Effect of oral copper sulfate on 7, 12-dimethylbenz( a )anthracene No Public ~ carcinogenesis in mice. Br. J. cancer Sep; 23{3) : 591-596. Not GLP, domain Published.

A6.5 carlton, W.W. and Price, P.S. 1973 Dietary Copper and the Induction of Neoplasms in the Rat by No Public ~ Acetylaminofluorene and Dimethylnitrosamine. Fd Cosmet. Toxicol. 11: 827- domain 840 foublished\ .

A 6.5 De Vries, D.J., Sewell, R.B. and 1986 Effects of Copper on Dopaminergic Function in the Rat Corpus Striatum. No Public [81 Beart P.M. Experimental Neurology, 91 : 546-558. Not GLP, Published domain

A 6.5 Hall, E.M. and Butt, E.M 1928 Experimental Pigment Cirrhosis Due to Copper Poisoning. It's Relation to No Public ~ Hemochromatosis. Archives of Pathology, 6 : 1-25. Not GLP, Published domain

A6.5 Hall, E.M. and Mackay, E.M. 1931 Experimental Hepatic Pigmentation and Cirrhosis. I. Does Copper Poisoning No Public ~ Produce Pigmentation and Cirrhosis of the Liver? The American Journal of domain Patholoov, 7: 327-342. Not GLP, Published

A 6.5 Harrison, J.W.E., Levin, S.E. and 1954 The Safety and Fate of Potassium Sodium Copper Chlorophyll in and Other No Public ~ Trabin, B. Copper Compounds. Journal of the American Pharmaceutical Association, domain

43(12): 722-737. Not GLP, Published. A6.5 Haywood, S. 1980 The Effect of Excess Dietary Copper on the Liver and Kidney of the Male Rat. No Public ~

Journal of Comparative Pathology, 90: 217-232. Not GLP, Published domain

A6.5 Haywood, S. 1985 Copper Toxicosis and Tolerance in the Rat. I - Changes in Copper Content of No Public [81 the Liver and Kidney. Journal of Pathology, 145: 149-158. Not GLP, domain Published

A 6.5 Haywood, S. and Comerford, B. 1980 The Effect of Excess Dietary Copper on Plasma Enzyme Activity and on the No Public [81 Copper Content of the Blood of the Male Rat. Journal of Comparative domain Patholonv 90: 233-238. Not GLP Published

A6.5 Haywood, S. and Loughran, M. 1985 Copper Toxicosis and Tolerance in the Rat. II. Tolerance - a Liver Protective No Public [81 Adaotation. Liver 5: 267-275. Not GLP Published domain

A 6.5 Haywood, s . and Loughran, M. 1985 Copper Toxicosis and Tolerance in the Rat. II. Tolerance - a Liver Protective No Public [81 Adaotation. Liver 5: 267-275. Not GLP Published domain

A 6.5 Liu, c .-C.F. and Medeiros, D.M. 1986 Excess Diet Copper Increases Systolic Blood Pressure in Rats. Biological No Public [81 Trace Element Research 9 : 15-24. Not GLP Published domain

93




A 6.5 Tachibana, K. 1952 Pathological Transition and Functional Vicissitude of liver During Formation No Public ~ of Cirrhosis by Copper. The Nagoya Journal of Medical Science, 15 : 108-114. domain Not GLP, Published

A 6.5 Wiederanders, M.D. and Wasdahl, 1968 Acute and Chronic Copper Poisoning in the Rat. The Journal-Lancet, Minneap, No Public ~ W.W. 88: 286-291. Not GLP, Published domain

A 6.6.4 Agarwal, K., Sharma, A. and 1990 Clastogenic effects of copper sulphate on the bone marrow chromosomes of No Public ~ Talukder, G., mice in vivo. Mutation Research, 243 :1-6. Not GLP, Published domain

A 6.6.4 Bhunya, S.P. & Pati, P.C. 1987 Genotoxicity of an Inorganic Pesticide, Copper Sulpahte in Mouse in vivo Test No Public ~ svstem. Cvtoloaia. 52: 801-808. Not GLP Published. domain

A 6.6.4 Tinwell, H. & Ashby, J. 1990 Inactivity of Copper Sulphate in a Bone-Marrow Micronucleus Assay. Mutat. No Public ~ Res. 245 : 223-226. Not GLP Published. domain

A 6.7 Burki, H.R. and Okita, G.T. 1969 Effect of oral copper sulfate on 7, 12-dimethylbenz{ a )anthracene No Public ~ carcinogenesis in mice. Br. J. Cancer Sep; 23{3) : 591-596. Not GLP, domain Published

A 6.7 carlton, W.W. and Price, P.S., 1973 Dietary Copper and the Induction of Neoplasms in the Rat by No Public ~ Acetylaminofluorene and Dimethylnitrosamine. Fd Cosmet. Toxicol. 11: 827- domain 840. Not GLP Published.

A 6.7 Harrison, J. W.E., Levin, S.E. and 1954 The Safety and Fate of Potassium Sodium Copper Chlorophyllin and Other No Public ~ Trabin, B., Copper Compounds. Journal of the American Pharmaceutical Association, domain

43112): 722-737. Not GLP Published A 6.8.1 Aulerich, R.J., Ringer, R.K., 1982 Effects of Supplemental Dietary Copper on Growth, Reproductive No Public ~

Bleavins, M.R. and Napolitano, A. Performance and Kit Survival of Standard Dark Mink and the Acute Toxicity domain of Conner to Mink 5512\: 337 - 343. Not GLP Published

A 6.8.1 Barash, A., Shoham {Schwartz), 1990 Development of Human Embryos in the Presence of a Copper Intrauterine No Public ~ z., Borenstein, R. and Nebel, L. Device. Gynecol. Obstet. Invest., 29:203-206. Not GLP, Published domain

A6.8.1 Barlow, S.M., Knight, A.F. and 1981 Intrauterine exposure to copper IUDs and prenatal development in the rat. No Public ~ House, I. J. Reo. Fert. , 62 : 123 - 130 domain

A 6.8.1 Chang, c.c. And Tatum, H.J. 1973 Absence of teratogenicity of intrauterine copper wire in rats, hamsters and No Public ~ rabbits . Contraceotion, 7(5): 413 - 434 domain

A 6.8.1 Dicarlo, F.J 1980 Syndromes of Cardiovascular Malformations Induced by Copper Citrate in No Public ~ Hamsters. Teratoloav 21: 89-101. Not GLP, Published domain

A 6.8.1 Ferm, V.H. and Hanlon, D.P. 1974 Toxicity of Copper Salts in Hamster Embryonic Development. Biology of No Public ~ Reoroduction, 11 : 97-101. Not GLP, Published domain

A 6.8.1 Haddad, D.S., Al-Alousi, L.A. and 1991 The Effect of Copper Loading on Pregnant Rats and Their Offspring. No Public ~ Kantarjian, A.H. Functional and Developmental Morphology 1{3): 17-22. Not GLP, Published domain

A 6.8.1 Kasama, T. and Tanaka, H 1988 Effects of copper administration on fetal and neonatal mice. J. Nutr. Sci. No Public ~ Vitaminol. 34 : 595-605. Not GLP Published domain

A 6.8.1 Lecyk, M. 1980 Toxicity of CuS04 in mice embryonic development. Zoologica Poloniae, No Public ~ 28(2): 101-105. Not GLP Published domain

A 6.8.2 Aulerich, R.J., Ringer, R.K., 1982 Effects of Supplemental Dietary Copper on Growth, Reproductive No Public ~ Bleavins, M.R. and Napolitano, A. Performance and Kit Survival of Standard Dark Mink and the Acute Toxicity domain

of Conner to Mink 55(2): 337 - 343. Not GLP Published A 6.8.2 Chang, c.c. And Tatum, H.J. 1973 Absence of teratogenicity of intrauterine copper wire in rats, hamsters and No Public ~

rabbits . Contraceotion 715): 413 - 434 domain A6.8.2 Cromwell, G.L., Monegue, H.J. and 1993 Long-term effects of feeding a high copper diet to sows during gestation and No Public ~

Stahly, T.S. lactation. J. Anim. Sci. 71: 2996-3002. Not GLP, Published domain

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A 6.8.2 Hebert, c.o., 1993 NTP Technical Report on toxicity studies of cupric sulphate (CAS No. 7758- No Public ~ 99-8) administered in drinking water and feed to F344/N rats and B6C3Fl domain mice. National Toxicology Program, Toxicity Report Series No. 29, United States Department of Health and Human Services (NIH Publication 93-3352). GLP, Published

A6.8.2 Hebert, c.o., 1993 NTP Technical Report on toxicity studies of cupric sulphate (CAS No. 7758- No Public ~ 99-8) administered in drinking water and feed to F344/N rats and B6C3Fl domain mice. National Toxicology Program, Toxicity Report Series No. 29, United States Department of Health and Human Services (NIH Publication 93-3352). GLP, Published

A 6.8.2 Lecyk, M. 1980 Toxicity of CuS04 in mice embryonic development . Zoologica Poloniae, No Public ~ 28(2): 101-105. Not GLP, Published domain

A 6.8.2 Llewellyn, G.C., Floyd, E.A., Hoke, 1985 Influence of dietary aflatoxin, zinc and copper on bone size, organ weight, No Public ~ G.D., Weekley, L.B. and and body weight in hamsters and rats. Bull . Environ. Contam. Toxicol., 35: domain Kimbrouah T.D. 149-156. Not GLP Published

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A 6.9 Murthy, R.C., Lal, s., Saxena, - Effect of Manganese and Copper Interaction on Behaviour and Biogenic No Public ~ D.K., Shukla, G.S., Mohd Ali, M Amines in Rats Fed a 10% Casein Diet. Chem. Biol. Interactions, 37: 299 - domain and Chandra S.V. 308. Not GLP Published

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A 7.1.4 Comber sow, Gunn AM, Whalley 1995 Comparison of the partitioning of t race metals in the Humber and Mersey No Public ~ c, Estuaries. Marine Pollution Bulletin 30, 12, 851-860. domain

A 7.1.4 Helmers E, 1996 Trace metals in suspended particu late matter of Atlantic Ocean surface water No Public ~ (40°N to 20°S). Marine Chemistrv 53, 51-67. domain

A 7.1.4 Lin, C-F., Houng, L-M., Lo, K.S., 1994 Kinetics of copper complexation with dissolved organic matter using stopped- No Public ~ Lee, D-Y. flow fluorescence technique; Toxicological and Environmental Chemistry, Vol. domain

43 nn. 1-12· Not GLP· Published A 7.1.4 McManus JP, Prandle D, 1996 Determination of source concentrations of dissolved and particu late t race No Public ~

metals in the southern North Sea. Marine Pollution Bulletin 32, 504-512. domain A 7.1.4 Munksgaard NC, Parry DL, 2001 Trace metals, arsenic and lead isotopes in dissolved and particulate phases of No Public ~

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A 7.1.4 Owens RE, Balls PW, Price NB, 1997 Physicochemical processes and their effects on the composition of suspended No Public ~ particulate material in estuaries : implications for monitoring and modelling. domain Marine Pollution Bulletin 34, 51-60.

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A 7.1.4 Pohl C, Hennings U, 1999 The effect of redox processes on the partitioning of Cd, Pb, Cu and Mn No Public ~ between dissolved and particulate phases in the Baltic Sea. Marine Chemistry domain 65, 41-53.

A 7.1.4 Safiudo-Wilhelmy SA, Rivera- 1996 Distribution of colloidal trace metals in the San Francisco Bay estuary. No Public ~ Duarte I, Flegal AR, Geochimica et Cosmochimica Acta 60, 4933-4944. domain

A 7.1.4 Tappin AD, Millward GE, Statham 1995 Trace metals in the Central and Southern North Sea. Estuarine, Coastal and No Public ~ PJ, Burton JD, Morris AW, Shelf Science 41, 275-323. domain

A 7.1.4 Vasconcelos MTSD, Leal MFC, 1997 Speciation of Cu, Pb, Cd and Hg in waters of the Oporto coast in Portugal, No Public ~ using pre-concentration in a Chelamine resin column. Analytica Chimica Acta domain 353 189-198

A 7.1.4 Zhou JL, Liu VP, Abrahams PW, 2003 Trace metal behaviour in the Conwy estuary, North Wales. Chemosphere 51, No Public ~ 429-440. domain

A 7.4.1.1 Buhl, P.C., & Steven, J.H. 1990 Comparative toxicity of inorganic contaminants released by placer mining to No Public ~ early life stages of salmonids. Ecotoxicol . Environ. Saf. Vol. 20, 325-342. domain Not GLP Published

A 7.4.1.1 Howarth, R. S. & Sprague, J. B. 1978 Copper lethality to rainbow trout in waters of various hardness and pH. No Public ~ Water Res. Vol . 12 455-462. Not GLP Published domain

A 7.4.1.1 1973 To determine the toxicity of Chem Copp Spray Grade 75 (EPA #26883) to Yes America ~ bluegill; II I I Report No. 040260; Not n GLP; Unpublished Chem et

A 7.4.1.1 1991 Acute toxicity of purple copp 97N to the sheepshead minnow (cyprinodon Yes America ~ variegatus); II I I Project ID ESE No. 3913022- n 0200-3140; GLP; Unpublished Chem et

A 7.4.1.2 Baird, D. J. et al. 1991 A comparative study of genotype sensitivity to acute toxic stress using clones No Public ~ of Daphnia magna. Ecotoxicol Envrion. Saf. Vol. 21, 257-265. Not GLP, domain Published

A 7.4.1.2 Dave, G. 1984 Effects of copper on growth, reproduction, survival and haemoglobin in No Public ~ Daphnia magna. Comp. Biochem. Physiol. Vol. 78C (2) 439-443. Not GLP, domain Published

A 7.4.1.2 Le Blanc, G. A. 1982 Laboratory investigation into the development of resistance of Daphnia No Public ~ magna to environmental pollutants. Environ. Poll. Vol. A27, 309-322. Not domain GLP, Publ ished

A 7.4.1.2 Noack, M. 1993 Acute immobilisation test (48 hour) to Daphnia magna Straus according to Yes Spiess- ~ OECD 202 I of URA-17030; Dr U Noack-Laboratorium fur angewandte Urania biologie, Proiect No. 921027NH, Study No. DAI33241; GLP; Unpublished

A 7.4.1.2 Oikari, A. et al. 1992 Acute toxicities of chemicals to Daphnia magna in humic waters. Sci. Total. No Public ~ Environ. Vol. 117/118, 367-377. Not GLP, Published domain

A 7.4.1.2 Wade, B. A. 1991 Acute toxicity of purple copp 97N to the mysid shrimp (mysidopsis bahia); Yes America ~ ESE Laboratories, Gainesville, FL, Project ID ESE No. 3913022-0600-3140; n GLP; Unoublished Chem et

A 7.4.1.3 De Schamphelaere KAC, Janssen 2005 A unified bioavailability model for predicting copper toxicity to freshwater No Public ~ CR green micro-algae; University of Gent; Draft report - not yet published; not domain

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A 7.4.1.3 Dickhaus, s . & Heisler, E. 1988 Algal growth inhibition test with copper-I-oxide (OECD guideline 201); Yes Spiess- ~ Pharmatox Gmbh reoort No. 1-7-44-88; GLP; unoublished Urania

A 7.4.1.3 Garvey, J.E. et al.* 1991 Toxicity of C-Opper to the Green Alga Chlamydomonas reinhardt ii No Public ~ (Chlorophyceae) as Affected by Humic Substances of Terrestria l and domain Freshwater Oriain. Aauatic Toxicoloav. Vol. 19 89-96. Not GLP Published

A 7.4.1.3 Ghent University.* 2002 Chronic algae testing of copper with Chlamydomonas reinhardtii and No Public ~ Chlorella vulaaris. Unoublished data domain

A 7.4.1.3 Heijerick D., Bossuyt B. and 2001 EURO-ECOLE Assessment of the Bioavailability and Potent ial Ecological No Europea ~ Janssen c. Effects of Copper in European Surface Waters - Subproject 4 :Evaluation and n

improvement of the ecological relevance of laboratory generated toxicity Copper data· no reoort number· not GLP· Unoublished Inst itute

A 7.4.1.3 Heijerick* 2002 Heijerick DG, Bossuyt BTA, Indeherberg M, Mingazinni M, Janssen CR, 2002. No Public ~ Effects of varying physico-chemistry of European surface waters on the domain copper toxicity to the green algae Pseudokirchneriel la subcapitata. Not GLP, Not Published I submitted) .

A 7.4.1.3 Nyholm, N. * 1990 Expression of results from growth inhibition toxicity tests with algae. Arch. No Public ~ Environ Contam. Toxicol. Vol 19 (4) 518- 522. Not GLP, Published domain

A 7.4.1.3 Schafer, H. et al.* 1994 Biotests using unicellular algae and ciliates for predicting long-term effects of No Public ~ toxicant. Ecotoxicol. Enviorn. Safe. Vol. 27, 64-81. Not GLP, Published domain

A 7.4.1.3 Simpson, s et al 2003 Effect of declining toxicant concentrations on algal bioassay endpoints; No Public ~ Environmental Toxicology and Chemistry, Vol. 22, No. 9, pp. 2073- 2079; domain Not GLP; Published

A 7.4.1.3 Smyth, D.V., Kent, s. 2006 Copper: toxicity to the marine alga Skeletonema costatum; BEL report no. Yes EU ~ BL8337/ B; GLP; Unpublished Antifouli

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A 7.4. 1.3 Smyth, D.V., Kent, s . 2006 Copper: toxicity to the marine alga Phaeodactylum t ricornutum; BEL report Yes EU ~ no. BL8338/B; GLP; Unpublished Antifou li

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A 7.4.1.3 Teisseire, H. et al.* 1998 Toxic Responses and Catalase Activity of Lemna minor Exposed to Folpet , No Public ~ Copper and their Combinat ion. Ecotoxicol. Environ. Saf. 40, 194-200. Not domain GLP, Published

A 7.4. 1.4 Cha, D.K., Allen, H.E. & Song, J.S. - Effect of C-Opper on Nitrifying and Heterotrophic Populations in Activated Yes Europea ~ Sludge. Department of Civil and Environmental Engineering, University of n Delaware, USA. Not GLP, Unpublished Copper

Inst itute A 7.4.1.4 Codina, J.C., Munoz, M.A., 1998 The Inhibition of Methanogenic Activity from Anaerobic Domestic Sludges as No Public ~

cazorla, F.M., Perez-Garcia, A., a Simple Toxicity Bioassay. Water Research. 32 (4) 1338-1342. Not GLP, domain Morifiigo, M.A. & De Vicente, A. Published

A 7.4.1.4 Madoni, P., Davole, D., Gorbim G. 1996 Toxic Effect of Heavy Metals on the Activated Sludge Protozoan Community. No Public ~ & Vescovi, L. Water Research. 30 (1) 135-141. Not GLP, Published domain

A 7.4.1.4 Madoni, P., Davoli, D. & Guglielmi, 1999 Response of Sour and Aur to Heavy Metal Contaminat ion in Activated Sludge. No Public ~ L. Water Research. 33 {10): 2459-2464. Not GLP, Published domain

9 7




A 7.4.2 Ahsanulla, M. & Williams, A.R. 1991 Sublethal Effects and Bioaccumulation of Cadmium, Chromium, Copper and No Public ~ Zinc in the Marine Amphipod, Allorchestes compressa. Mar. Biol. Not GLP, domain Published.

A 7.4.2 Amiard, J.C., Amiard-Triquet, C. & 1985 Experimental Study of Bioaccumulation, Toxicity and Regulation of Some No Public ~ Metayer, c. Trace Metals in Various Estuarine and Coastal Organisms. Symp. Biologica. domain

Huna. 29; 313-323 (published). A 7.4.2 Benoit, D .A. 1975 Chronic Effects of Copper on Survival, Growth and Reproduction of the No Public ~

Bluegill ( Lepomis macrochirus). Trans. Am. Fish. Soc. 104 (2). 353-358. Not domain GLP, Published.

A 7.4.2 Borgmann, u., Norwood, W.P. & 1993 Accumulation, Regulation and Toxicity of Copper, Zinc, Lead and Mercury in No Public ~ Clarke, c. Hyalella azteca. Hydrobiologica . 259: 79-89. Not GLP, Published. domain

A 7.4.2 Brown, B. E 1977 Uptake of Copper and Lead by a Metal Tolerant Isopod Asellus meridianus. No Public ~ Freshwater Biol. 7: 235-244. Not GLP Published. domain

A 7.4.2 Brungs, W. A. Leonard, E.N., 1973 Acute and Long Term Accumulation of Copper by the Brown Bullhead, No Public ~ McKim, J.M. Ictalurus nebulosus. J. Fish Res. Board. Can. 30 : 583-586. Not GLP, domain

Published. A 7.4.2 calabrese, A., Maci nnes, Nelson, 1984 Effects of Long-Term Exposure to Silver or Copper on Growth, No Public ~

D.A, Greig, R.A. & Yevich, P.P. Bioaccumulation and Histopathology in the Blue Mussel, Mytilus edulis. Mar. domain Environ. Res. 11 : 253-274. Not GLP Published.

A 7.4.2 canterford, G.S., Buchanan, A.S. 1978 Accumulation of Heavy Metals by the Marine Diatom Ditylum brightwell i No Public ~ & Ducker, s .c. {West) Grunow. Aust. J. Freshwater Res. 29: 613-22. Not GLP, Published domain

A 7.4.2 Djangmah, J.S. & Grove, D.J. 1970 Blood and Hepatopancreas Copper in Crangon vulgaris {Fabricius) . No Public ~ Comoarative Biochemistrv and Phvsioloav (oublished). domain

A 7.4.2 Engel, D.W. & Brouwer, M. 1985 Cadmium and Copper Metallothioneins in the American Lobster, Homarus No Public ~ americanus. Environ. Health. Perspect. 66; 87-92 (published). domain

A 7.4.2 George, S.G., Pirie, B.J.S., 1978 Detoxication of Metals by Marine Bivalves. An Ultrastrutural Study of the No Public ~ Cheyne, A.R., Coombs, T.L. & Compartmentation of Copper and Zinc in the Oyster Ostrea edulis. Marine domain Grant, P.T. Bioloav, 45; 147-156 <oublished).

A 7.4.2 Graney, R.L, Cherry, D.S. & Carins 1993 Heavy Metal Indicator Potential of the Asiatic Clam {Corbicula fluminea) in No Public ~ Jr., J. Artificial Stream Systems. Hydrobiological. 102: 81-88. Not GLP, Published. domain

A 7.4.2 Kaland, T. Andersen, T. & Hylland, 1993 Accumulation and Subcellular Distribution of Metals in the Marine Gastropod No Public ~ K. Nassarius reticulatus. p37-53. In : R. Dallinger and P.S. Rainbow (eds). domain

Ecotoxicology of Metals in Invertebrates Proceedings of the 1st SETAC European Conference. Lewis Publications; Boca Raton, Fl. USA 461, pp loublishedl.

A 7.4.2 Kraak, M. H. S., Lavy, D., Peeters, 1992 Chronic Ecotoxicity of Copper and Cadmium to the Zebra Mussel Dreissena No Public ~ W. H. M. & Davids, c. polymorpha. Arch. Envrion. Contam. Toxicol. 23: 363-369. Not GLP, domain

Published. A 7.4.2 Melusky, D.S. & Phillips, c. N. K. 1975 Some Effects of Copper on the Polychaete Phyllodoce maculata. Estuarine & No Public ~

Coastal Mar. Sci. 3: 103-108. Not GLP Published. domain A 7.4.2 Mersch, J., Morhain, E. & Mouvet, 1993 Laboratory Accumulation and Depuration of Copper and cadmium in the No Public ~

c. Freshwater Mussel Dreissena polymorpha and the Aquatic Moss domain Rhynchostegium riparioides. Chemosphere. 27 (8): 1475-1485. Not GLP, Published.

A 7.4.2 Millanovich, F.P., Spies, R., 1976 Uptake of Copper by the Polychaete Cirriformia spirabrancha in the Presence No Public ~ Guram, M.S. & Sykes, E.E. of Dissolved Yellow Organic Matter of Natural Origin. Estuarine and Coastal domain

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A 7.4.2 Pesch, C.E. & Morgan, D 1978 Influence of Sediment in Copper Toxicity Tests with the Polychaete Neanthes No Public 18] arenaceodentata. Water Research. 12: 747-751. Not GLP, Published domain

A 7.4.2 Phillips, D. J. H. 1976 The Common Mussel Mytilus edulis as an Indicator of Pollution by Zinc, No Public 18] Cadmium, Lead and Copper. I. Effects of Environmental Variables on Uptake domain of Metals. Mar. Biol. 38: 59-69. Not GLP, Published.

A 7.4.2 Rainbow, P.S. 1985 Acaimulation of Zn, Cu and Cd by Crabs and Barnacles. Estuarine, Coastal No Public 18] Shelf Science. 21 · 669-686 foublished). domain

A 7.4.2 Rainbow, P.S. & White, s. L 1989 Comparative Strategies of Heavy Metal Accumulation by Crustaceans: Zinc, No Public 18] Copper and Cadmium in a Decapod and Am phi pod and a Barnacle. domain Hvdrobioloaia 174· 245-262 foublishedl .

A 7.4.2 Rainbow, P.S. & White, S. L 1989 Comparative Strategies of Heavy Metal Accumulation by Crustaceans: Zinc, No Public 18] Copper and Cadmium in a Decapod and Amphipod and a Barnacle. domain Hvdrobioloaia 174· 245-262 foublishedl.

A 7.4.2 Rainbow, P.S. & White, s. L 1989 Comparative Strategies of Heavy Metal Accumulation by Crustaceans: Zinc, No Public 18] Copper and Cadmium in a Decapod and Amphipod and a Barnacle. domain Hvdrobioloaia 174· 245-262 foublishedl .

A 7.4.2 Rainbow, P.S., Scott, A.G., 1980 Effect of Chelating Agents on the Accumulation of Cadmium by the Barnacle No Public 18] Wiggins, E.S. & Jackson, R.W. Semibalanus balanoides, and Complexation of Soluble Cd, Zn and Cu. domain

Marine Ecoloav. 2· 143-152 foublishedl . A 7.4.2 Riley, J.P. & Roth, I. 1971 The Distribution of Trace Elements in Some Species of Phytoplankton Grown No Public 18]

in Culture. J. Mar. Biol. Ass. UK. 51: 63-72. Not GLP, Published domain A 7.4.2 Roesijadi, G 1980 Influence of Copper on the Clam Protothaca staminea: effects on Gills and No Public 18]

Occurrence of Copper Binding Proteins. Biol. Bull. 158: 233-247. Not GLP, domain Published.

A 7.4.2 Shuster, c. N. & B.H. Pringle 1969 Trace Metal Accumulation by the American Eastern Oyster, Crassostrea No Public ~ virg inica. Proc. Nat. Shellfish. Ass. 59: 91-103. Not GLP, Published. domain

A 7.4.2 Shuster, C.N and Pringle, B.H. 1969 Effects of Trace Metals on Estuarine Molluscs. Proceedings of the 1st Mid- No Public ~ Atlantic Industrial Waste Conference. November 13-15, 197. Not GLP, domain Published

A 7.4.2 Solbe, J.F. de LG. & Cooper, V.A. 1976 Studies on the Toxicity of Copper Sulphate to Stone Loach Neomacheilus No Public 18] Barbatulus (L.) in Hard Water. Wat. Res. 10: 523-527. Not GLP, Published. domain

A 7.4.2 Timmermans, K. R. & Walker, P.A. 1989 The Fate of Trace Metals During Metamorphosis of Chrionomids (Diptera, No Public 18] Chironomidae). Environmental Pollution. 62; 73-85 (published). domain

A 7.4.2 White, S.L. & Rainbow, P.S. 1982 Regulation and Accumulation of Copper, Zinc and cadmium by the Shrimp No Public 18] Palaemon elegans. Marine Ecology Progress Series. 8; 95-101 (published). domain

A 7.4.2 Winner, R.W. 1984 The Toxicity and Bioaccumulation of cadmium and Copper as Affected by No Public l8J Humic Acid. Aquatic Toxicology. 5: 267-274. Not GLP, Published. domain

A 7.4.2 Young, J.S., Buschbom, R.L., 1979 Effects of Copper on the Sabel lid Polychaete, Eudistylia vancouveri: I No Public 18] Gurtisen, J.M. & Joyce, S.P. Concentration Limits for Copper Accumulation. Archives of Environmental domain

Contamination and Toxicoloav. 8: 97-106. Not GLP. Published A 7.4.2 Zaroogian, G.E. & Johnston, M. 1983 Copper Accumulation in the Bay Scallop, Argopecten irradians. Arch. Environ. No Public 18]

Contam. Toxicol . 12: 127-133. Not GLP, Published. domain A 7.4.3 Foekema E.M., Kramer K.J.M., 2010 Determination of the biological effects and fate of dissolved copper in Yes EU ~

Kaag N.H.M.B., Sneekes A.C., outdoor marine mesocosms; !MARES Wageningen UR Report No. C105/ 10; Antifou li Hoornsman G., Lewis W.E., van Not GLP; Unpublished ng Task der Vlies E.M. Force

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A 7.4.3.1 Collvin, L.* 1984 The effect of copper on growth, food consumption and food conversion of No Public ~ perch Perea fluviatilis L. offered maximal food rations. Aquatic Toxicology domain (Amsterdam) 6 : 105-113. Not GLP, Publ ished

A 7.4.3.1 Scudder, B. c., J. L. carter and H. 1988 Effects of copper on development of the fathead minnow, Pimephales No Public ~ v. Leland* promelas Rafinesque. Aquatic Toxicology (Amsterdam) 12: 107-124. Not domain

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A 7.4.3.1/ Job, K.M., A.M. Askew and R.B. 1995 Development of a water-effect-ratio for copper, cadmium and lead for the No Public ~ 7.4.3.2 Foster.* Great Works River in Maine using Ceriodaphnia dubia and Salvelinus domain

fontinalis. Bulletin of Environmental Contamination and Toxicology. 54: 29-35. Not GLP, Published

A 7.4.3.1/ Mount, D. I.* 1968 Chronic toxicity of copper to fathead minnows {Pimephales promelas No Public ~ 7.4.3.2 Rafinesque) . Water Research 2 : 215-223. Not GLP, Published domain

A 7.4.3.1/ Spehar, R. L. and J. T. Fiandt* 1985 Acute and chronic effects of water quality criteria based metal mixtures on No Public ~ 7.4.3.2 three aquatic species. Project Summary EPN6000/S3-85/074. u. s . domain

Environmenta I Protection Agency, Environmental Research Laboratory, Duluth Minnesota. Not GLP Published

A 7.4.3.1/ Mount, D. I. and c. E. Stephan.* 1969 Chronic toxicity of copper to the fathead minnow {Pimephales promelas) in No Public ~ 7.4.3.2 soft water. Journal of the Fisheries Research Board of canada 26: 2449- domain

2457. Not GLP Publ ished A 7.4.3.1/ Mudge, J. E., N. T. E., G. s . Jeane, 1993 Effect of varying environmental conditions on the toxicity of copper to No Public ~ 7.4.3.2 W. Davis and J. L. Hickam* salmon. pp. 19-33. In : J. W. Gorsuch, F. J. Dwyer, C. G. Ingersoll and T. W. domain

L. Point (eds.). Environmental Toxicology and Risk Assessment: 2nd Volume, ASTM STP 1216. American Society for Testing Materials, Philadelphia, Pennsvlvania. Not GLP Published

A 7.4.3.1/ McKim, J.M. and D. A. Benoit.* 1971 Effects of long-term exposures to copper on survival, growth, and No Public ~ 7.4.3.2 reproduction of brook trout {Salvelinus fontina lis). Journal of the Fisheries domain

Research Board of Canada 28: 655-662. Not GLP Published A 7.4.3.1/ Horning, w. B. and T. w. 1979 Chronic effect of copper on the bluntnose minnow, Pimephales notatus No Public ~ 7.4.3.2 Neiheisel* {Rafinesque). Archives of Environmental Contamination and Toxicology 8: domain

545-552. Not GLP, Published A 7.4.3.1/ Sauter, s., K. s . Buxton, K. J. 1976 Effects of exposure to heavy metals on selected freshwater fish . Toxicity of No Public ~ 7.4.3.2 Macek ands. R. Petrocelli* copper, cadmium, chromium and lead to eggs and fry of seven fish species. domain

Ecologica l Reseach Series EPA-600/3-76-105. U.S. Environmental Protection Agency, Environmental Research Laboratory, Duluth, Minnesota. Not GLP, Published

A 7.4.3.2 Anderson, B.S., Middaugh, D.P., 1991 Copper toxicity to sperm, embryos, and larvae of topsmelt Atherinops affinis, No Public ~ Hunt, J.W., and Turpen, S.L. with notes on induced spawning. Mar. Environ. Res. 31 : 17-35 domain

A 7.4.3.2 Belanger, S. E. and D. S. Cherry.* 1990 Interacting effects of pH acclimation, pH, and heavy metals on acute and No Public ~ chronic toxicity to Ceriodaphnia dubia {Cladocera). Journal of Crustacean domain Bioloav 1012) : 225-235. Not GLP, Published

A 7.4.3.2 Brungs, w. A., J. R. Geekier and 1976 Acute and chronic toxicity of copper to the fathead minnow in a surface No Public ~ M. Gast.* water of variable quality. Water Research 10: 37-43. Not GLP, Published. domain

A 7.4.3.2 Collvin, L* 1985 The effects of copper on maximum respiration rate and growth rate of perch, No Public ~ Perea fluviatilis L. Water Research 18{2): 139-144. Not GLP, Published domain

100




A 7.4.3.2 2006 Copper: Determinat ion of the effects on the embryo larval development of Yes EU ~ the Sheepshead Minnow {Cyprinodon variegates). Report No. BL8353/ B Antifou li

ng Task Force

A 7.4.3.2 2006 Copper: Determinat ion of the effects on the embryo larval development of Yes EU ~ the Sheepshead Minnow {Cyprinodon variegates). Report No. BL8353/ B Antifou li

ng Task Force

A 7.4.3.2 Marr, J. c. A., J. Upton, D. cacela, 1996 Relationship between copper exposure durat ion, t issue copper concentration, No Public ~ J. A. Hansen, H. L. Bergman, J. s . and ra inbow trout growth. Aquatic Toxicology 36: 17-30. Not GLP, Published domain Meyer and c. Hogstrand. *

A 7.4.3.2 Pickering, Q., W. Brungs and M. 1977 Effect of exposure time and copper concentration on reproduction of the No Public ~ Gast.* fathead minnow {Pimephales promelas). Water Research 11{12) : 1079-1083. domain

Not GLP, Published A 7.4.3.2 Seim, W. K., L. R. Curtis, S. W. 1984 Growth and survival of developing steelhead trout {Sal mo gairdneri) No Public ~

Glenn and G. A. Chapman.* continuously or intermittent ly exposed to copper. Canadian Journal of domain Fisheries and Aauatic Sciences 4H3l: 433-438. Not GLP, Published

A 7.4.3.4 Ahsanullah, M., Ying, W. 1995 Toxic Effects of Dissolved Copper on Penaeus mergulensis and Penaeus No Public ~ monodon. Bull. Environ. Contain. Toxicol. {1995) 55 :81-88; Not GLP; domain Published

A 7.4.3.4 Arthur, J. W. and E. N. Leonard.* 1970 Effects of copper on Gammarus pseudolimnaeus, Physa integra, and No Public ~ Campeloma decisum in soft water. Journal of the Fisheries Research Board of domain Canada 27171: 1277-1283. Not GLP Published

A 7.4.3.4 Bechmann R.K. 1994 Use of life tables and LC50 tests to evaluate chronic and acute toxicity effects No Public ~ of copper on the marine copepod Tisbe furcata {Baird), Environmental domain Toxicoloav and Chemistrv Vol.13 No. 9 nn. 1509-1517.

A 7.4.3.4 Belanger, S. E., J. L. Fanris and D. 1989 Effects of diet, water hardness, and population source on acute and chronic No Public ~ S. Cherry* copper tox icity to Ceriodaphnia dubia. Arch ives of Environmental domain

Contamination and Toxicoloav 18: 601-611. Not GLP, oublished A 7.4.3.4 Brix, K.V. , Gerdes, R.M., Adams, 2006 Effects of Copper, Cadmium, and Zinc on the Hatching Success of Br ine No Public ~

W.J., Grosel, M Shrimp {Artemia franciscana) . Arch. Environ. Contam. Toxicol. 51, 580- 583; domain Not GLP· Published

A 7.4.3.4 Cerda, Band Olive, J.H. 1993 Effects of Diet on Seven-Day Ceriodaphnia dubia Toxicity Tests; Ohio J. Sci. No Public ~ 93 (3): 44-47, 1993; no report number; not GLP; Published domain

A 7.4.3.4 Deaver, E. and J. H. Rodgers, Jr.* 1996 Measuring bioavailable copper using anodic stripping voltammetry. No Public ~ Environmental Toxicology and Chemistry 15(11): 1925-1930. Not GLP, domain Unoublished

A 7.4.3.4 Gould E.,Thompson R. J., Buckley 1988 Uptake and effects of copper and cadmium in the gonad of the scallop No Public ~ L.J., Rusanowsky D., Sennefelder Placopecten magellanicus: concurrent metal exposure; Marine Biology {97) domain G.R. 212-233; Not GLP; Published

A 7.4.3.4 Hall, L W.Jr, Anderson, R.D., 1997 Acute and chronic toxicity of copper to the estuarine copepod eurytemora No Public ~ Kilian, J.V. affinis: influence of organic complexation and speciation. Chemosphere, Vol. domain

35 No. 7 nn. 1567-1597 A 7.4.3.4 Hatakeyama, s . and M. Yasuno.* 1981 A method for assessing chronic effects of toxic substances on the midge, No Public ~

Paratanytarsus parthenogenet icus-effects of copper. Archives of domain Environmental Contamination and Toxicoloav 10: 705-713. Not GLP,

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A 7.4.3.4 Heijerick D., Bossuyt B. and 2001 EURO-ECOLE Assessment of the Bioavailability and Potential Ecological No Europea ~ Janssen c . Effects of Copper in European Surface Waters - Subproject 4 :Evaluation and n

improvement of the ecological relevance of laboratory generated toxicity Copper data· no reoort number· not GLP· Unoublished Institute

A 7.4.3.4 Heijerick DG, Bossuyt BTA, 2002 Effects of varying physico-chemistry of European surface waters on the No Public ~ Indeherberg M, Mingazinni M, copper toxicity to the green algae Pseudokirchneriella subcapitata. Not GLP, domain Janssen CR,* Not Published (submitted).

A 7.4.3.4 Jop, K.M., A.M. Askew and R.B. 1995 Development of a water-effect-ratio for copper, cadmium and lead for the No Public ~ Foster.* Great Works River in Maine using Ceriodaphnia dubia and Salvelinus domain

fontinalis. Bulletin of Environmental Contaminat ion and Toxicology. 54: 29-35. Not GLP Published

A 7.4.3.4 LaBreche T.M.C., Dietrich A.M., 2002 Copper Toxicity to Larval Mercenaria mercenaria (hard clam), Environmental No Public ~ Gallagher D.L., Shepherd N. Toxicology and Chemistry, Vol. 21, No. 4, pp 760-766. domain

A 7.4.3.4 Maund S.J., E.J. Taylor and D. 1992 Population responses of the freshwater amphipod crustacean Gammarus No Public igJ Pascoe.* pulex to copper . Freshwater Biology 28: 29-36. Not GLP, Published domain

A 7.4.3.4 Nebeker, A. V., A. Stinchfield, c. 1986 1986; Effects of copper, nickel and zinc on three species of Oregon No Public ~ Savonen and G. A. Chapman freshwater snails; Environmental Toxicology and Chemistry 5(9) : 807-811; domain

not GLP· Publ ished A 7.4.3.4 Nebeker, A. V., c. Savonen, R. J. 1984 Effects of copper, nickel and zinc on the life cycle of the caddisfly Clistoronia No Public ~

Baker and J. K. Mccrady.* magnifica {Limnephilidae). Environmental Toxicology and Chemistry 3 : 645- domain 649. Not GLP Published

A 7.4.3.4 Reichelt-Brushett A. J., Michalek- 2005 Effects of Copper on the fertilisation success of the soft cora l Lobophytum No Public ~ Wagner, K compactum, Aquatic Toxicology 74 {2005) 280- 284. domain

A 7.4.3.4 Reichelt-Brushett A.J, Harrison 2000 The Effect of Copper on the Settlement Success of Larvae from the No Public ~ P.L. Scleractinian Coral Acropora tenuis, Marine Pollution Bulletin Vol. 41, Nos. domain

7±12, DD. 385±391. A 7.4.3.4 Reichelt-Brushett A.J, Harrison 2004 Development of a Sublethal Test to Determine the Effects of Copper and No Public ~

P.L. Lead on Scleractinian Coral Larvae, Arch. Environ. Contam. Toxicol. 47, 40- domain 55

A 7.4.3.4 Rosen G., Rivera-Duarte I., and 2004 Sinclair Inlet Toxicity Assessment: Puget Sound Naval Shipyard & No Public igJ Johnston, R.K. Intermediate Maintenance Facility Surface Water Copper Bioavailability and domain

Toxicity Study. Environmental Sciences & Applied Systems Branch, Code 2375 Space and Naval Warfare Systems Center, U.S. Navy San Diego, CA. Draft Report.

A 7.4.3.4 Spehar, R. L. and J. T. Fiandt* 1985 Acute and chronic effects of water quality criteria based metal mixtures on No Public ~ three aquatic species. Project Summary EPN6000/S3-85/074. u. s . domain Environmental Protection Agency, Environmental Research Laboratory, Duluth, Minnesota. Not GLP, Published

A 7.4.3.4 Taylor E.J., S.J. Maund and D. 1991 Evaluation of a chronic toxicity test using growth of the insect Chironomus No Public igJ Pascoe.* riparius Meigen. In : Bioindicators and Environmental Management . Eds. D.W. domain

Jeffrey and B. Madden. Academic Press, United Kingdom, pp. 343-352. Not GLP, Published

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A 7.4.3.4 Van Leeuwen, c. J., J. L. Buchner 1988 Intermittent flow system for population toxicity studies demonstrated with No Public ~ and H. Van Dijk.* Daphnia and copper. Bullet in of Environmental Contaminat ion and Toxicology domain

40(4): 496-502. Not GLP, Published A 7.4.3.4 Will iams, T.D., Hayfield, A.J. 2006 Copper: effects on the surviva l, development and reproduction of the marine Yes EU ~

copepod Tisbe battagliai; BEL report no. BL8295/B; GLP; Unpublished Antifou li ng Task

Force A 7.4.3.4 Will iams, T.D., Hayfield, A.J. 2006 Copper: effects on the surviva l, development and reproduction of the marine Yes EU ~

copepod Tisbe battagliai; BEL report no. BL8295/B; GLP; Unpublished Antifou li ng Task

Force A 7.4.3.4 Winner, R. W.* 1985 Bioaccumulation and toxicity of copper as affected by interactions between No Public ~

humic acid and water hardness. Water Research 19(4) : 449-455 . Not GLP, domain Published

A 7.4.3.4 Young, J.S., Gurtisen, J.M., Apts, 1979 The Relationship Between the Copper Complexing Capacity of Sea Water and No Public ~ c.w., Crecelius, E.A. Copper Toxicity in Shrimp Zoeae. Mar. Environ. Res. 2: 344-348 domain

A 7.4.3.4 Young, J.S., Gurtisen, J.M., Apts, 1979 The Relationship Between the Copper Complexing capacity of Sea Water and No Public ~ C.W., Crecelius, E.A. Copper Toxicity in Shrimp Zoeae. Mar. Environ. Res. 2: 344-348 domain

A 7.4.3.5 Belanger, S.E., Farris, J.L., Cherry, 1990 Validation of Corbicula f luminea Growth Reductions Induced by Copper in No Public ~ D.S., & cairns, Jr ., J. Artificia l Streams and River Systems. Can. J. Fish. Aquat. Sci. 47: 904-914. domain

Not GLP, Published A 7.4.3.5 Borgmann, u., Cover, R. & 1980 Effects of Metals on the Biomass Production Kinetics of Freshwater Copepods. No Public ~

Loveridge, c. Can. J. Fish. Aquat. Sci. 37: 567-575. Not GLP, Published . domain A 7.4.3.5 Brooks, s . 2006 The effects of dissolved organic carbon on the toxicity of Copper to the Yes EU ~

embryo of the pacific oyster . Cefas contract report C2548-1 Antifou li ng Task

Force A 7.4.3.5 Brooks, s . 2006 Copper speciation and toxicity to the development of the mussel embryo. Yes EU ~

Cefas contract report CEFAS/PRO/ C1921 Antifou li ng Task

Force A 7.4.3.5 Brooks, s . 2006 The effects of dissolved organic carbon on the toxicity of Copper to the Yes EU ~

embryo of the pacific oyster . Cefas contract report C2548-1 Antifou li ng Task

Force A 7.4.3.5 Clements, W.H., Cherry, D.S. & 1988 Structural Alterations in Aquat ic Insect Communities Exposed to Copper in No Public ~

cairns Jr., J. Laboratory Streams. Environ. Toxicol. Chem. 7: 715-722. Not GLP, Published domain

A 7.4.3.5 Clements, W.H., Cherry, D.S. & 1989b The Influence of Copper Exposure on Predator-Prey Interactions in Aquat ic No Public ~ cairns, Jr., J. Insect Communities. Freshwater Biology. 21 : 483-488. Not GLP, Published. domain

A 7.4.3.5 Clements, W.H., Farris, J.L. , 1989a The Influence of Water Quality on Macroinvertebrate Community Responses No Public ~ Cherry, D.S. & cairns Jr ., J. to Copper in Outdoor Experimental Streams. Aquat ic Toxicol. 14 : 249-262. domain

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A 7.4.3.5 Girling, A.E., Pascoe, s., Janssen, 2000 Development of Methods for Evaluating Toxicity in Freshwater Ecosystems. No Public ~ C.R., Peither, A. Wenzel, A., Ecotoxicol. Environ. Safe. 45, 148-176. Not GLP, Published domain Schafer, H., Neumeier, B., Mitchel l, G.C., Taylor, E.J., Maund, S.J., Lay, J.P., Juttner, I., Crossland, N.O., Stephenson, & Persoone, G.

A 7.4.3.5 Hart, B.T., Currey, N.A. & Jones, 1992 Biogeochemistry and Effects of Copper, Manganese and Zinc Added to No Public ~ M.J. Endosures in Island Billa bong, Magela Creek, Northern Australia. domain

Hvdrobioloaica. 230: 93-134. Not GLP, Published A 7.4.3.5 Havens, K. E 1994b Structural and Functional Responses of Freshwater Plankton Community to No Public ~

Acute Copper Stress. Environmental Pollution. 86 (3); 259-266. Not GLP, domain Published

A 7.4.3.5 Havens, K.E. 1994a An Experimental Comparison of the Effects of Two Chemica l Stressor on a No Public ~ Freshwater Zooplankton Assemblage. Environmental Pollut ion. 84: 245-251. domain Not GLP, Published

A 7.4.3.5 Hedtke, s. F. 1984 Structure and Function of Copper-Stressed Aquatic Microcosms. Aquatic No Public ~ Toxicoloav. 5: 227-244. Not GLP, Published domain

A 7.4.3.5 Hurd, K. 2006 Copper: Determination of the toxicity to the larvae of the Sea Urchin Yes EU ~ (Paracentrotus lividus). Report No. BL8354/B Antifou li

ng Task Force

A 7.4.3.5 Hurd, K. 2006 Copper: Determination of the toxicity to the larvae of the Sea Urchin Yes EU ~ (Paracentrotus lividus). Report No. BL8354/B Antifou li

ng Task Force

A 7.4.3.5 Leland, H.V. & Carter, J.L 1985 Effects of Copper on Production of Periphyton, Nitrogen Fixation and No Public ~ Processing of Leaf Litter Sierra Nevada california, Stream. Freshwater domain Bioloav. 15 : 155-173. Not GLP Published

A 7.4.3.5 Leland, H.V. & Garter, J.L 1984 Effects of copper on Species Composit ion of Periphyton in a Sierra Nevada, No Public ~ California, Stream. Freshwater Biology. 14: 281-296. Not GLP, Published domain

A 7.4.3.5 Leland, H.V. & Kent, E. 1981 Effects of Copper on Microfaunal Species Composition in a Sierra Nevada, No Public ~ California Stream. Verh. Internat. Verein. Liminol. 21 : 819-829. Not GLP, domain Published

A 7.4.3.5 Leland, H.V., Fend, s.v., Dudley, 1989 Effects of Copper on Species Composit ion of Benthic Insects in a Sierra No Public ~ T.L & Carter, J.L Nevada, California Stream. Freshwater Biology. 21: 163-179. Not GLP, domain

Published A 7.4.3.5 Lorenzo, J.I., Nieto, o., Beiras, R. 2006 Anodic stripping voltammetry measures copper bioavailability for sea urchin No Public ~

larvae in the presence of fu lvic acids. Environmenta I Toxicology and domain Chemistrv. Volume 25 Number 1

A 7.4.3.5 Moore, M.V. & Winner, R.W 1989 Relative Sensitivity of Cerodaphnia dubia Laboratory Tests and Pond No Public ~ Communities of Zooplankton and Benthos to Chronic Copper Stress. Aquatic domain Toxicoloav. 15 : 311-330. Not GLP Published

A 7.4.3.5 Pesch c. E., Schauer, P.S., 1986 Effect of diet on copper toxicity to Neanthes arenaceodentata.NTIS PB 87- No Public ~ Balboni, M.A. 167128. pp. 369-383. In : T.M. Poston and R. Purdy (eds.) . ASTM Special domain

Technical Publication N°921 : Aquat ic Toxicology and Environmental Fate, Vol. 9. A Symposium Amer. Soc. Test. Mater . Philadelphia, PA, USA, 530 p.

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A 7.4.3.5 Redpath, K. J. 1985 Growth Inhibition and Recovery in Mussels (Mytilus edulis) Exposed to Low No Public ~ Copper Concentrations. Journal of the Marine Biological Association of the domain United Kinadom, 65(2) :421-31; Not GLP; Published

A 7.4.3.5 Roesijadi, G. 1980 Influence of copper on the clam Protothaca staminea: effects on gills and No Public ~ occurrence of copper-binding proteins. Biol. Bull ., 158: 233-247 domain

A 7.4.3.5 Roesijadi, G. 1980 Influence of copper on the clam Protothaca staminea: effects on gills and No Public ~ occurrence of copper-binding proteins. Biol. Bull., 158: 233-247 domain

A 7.4.3.5 Schafers, c. 2003 Community Level Study with Copper in Aquatic Microcosms. Fraunhofer Yes Europea ~ Institute for Molecular Biology and Applied Ecology {IME}. Fraunhofer Study n Number EECU 01. Not GLP, Unpublished Copper

Institute A 7.4.3.5 Taub, F.B., Kindig, A.C., Meador, 1991 Effects of 'Seasonal Succession' and Grazing on Copper Toxicity in Aquatic No Public ~

J.P. & Swartzman, G.L. Microcosms. Verh. Internat. Verein. Limnol. 24: 2205-2214. domain A 7.4.3.5 Winner, R.W. & Owen, H.A. 1991 Seasonal Variability in the Sensitivity of Freshwater Phytoplankton No Public ~

Communities to a Chronic Copper Stress. Aquatic. Toxicol. 19: 73-88. Not domain GLP, Published.

A 7.4.3.5 Winner, R.W., Owen, H.A. & 1990 Seasonal Variability in the Sensitivity of Freshwater Lentic Communities to a No Public ~ Moore, M.V. Chronic Copper Stress. Aquatic Toxicology. 17: 75-92. Not GLP, Publ ished domain

A 7.4.3.5 Winner, R.W., Van Dyke, J.S., 1975 Response of the Macroinvertebrate Fauna to a Copper Gradient in an No Public ~ Garis, N. & Farrel, M.P. Experimentally Polluted Stream. Verh. I nternat . Verein. Liminol. 19: 2121- domain

2127. Not GLP, Published A 7.4.3.5.1 Torp, U.M. 1994 Assessment of sediment-phase toxicity to the sediment reworker Corophium Yes Nord ox ~

volutator (Pallas); TERRA Milj0-laboratorium NS Report No. 60169.sft\tm.003; GLP; Unpublished

A 7.4.3.5.2 Anderson, B.S., Hunt, J.W., 1990 Copper toxicity to microscopic stages of giant kelp Macrocystis pyrifera: No Public ~ Turpen, S.L., Coulon, A.R., Martin, interpopulation comparisons and temporal variability. Mar. Ecol. Prog. Ser. domain M. 68: 147 - 156

A 7.4.3.5.2 Brooks, s . 2006 The effects of dissolved organic carbon on the toxicity of Copper to the Yes EU ~ marine macroalgae Fucus vesiculosus. Cefas contract report C2548-2 Antifou li

ng Task Force

A 7.4.3.5.2 Brooks, s . 2006 The effects of dissolved organic carbon on the toxicity of Copper to the Yes EU ~ marine macroalgae Fucus vesiculosus. Cefas contract report C2548-2 Antifou li

ng Task Force

A Ahsanullah, M., Ying, w. 1995 Toxic Effects of Dissolved Copper on Penaeus mergulensis and Penaeus No Public ~ 7.4.3.5.2{2} monodon. Bull. Environ. Contain. Toxicol. {1995} 55:81-88; Not GLP; domain

Published A 7.4.3.6 De Schamphelaere K., Roman, 2004 Bioavailabilit y and ecotoxicity of copper in sediments. Ghent University Yes Europea ~

Y.E., Nguyen, L.H. and Janssen, Report prepared for ECI. Report Ref. PRP ENV-05-59; not GLP; Unpublished. n C.R. Copper

Inst itute A 7.4.3.6 Milani D., T.B. Reynoldson, u. 2003 The relative sensit ivity of four benthic invertebrates to metals in spiked No Public ~

Borgmann and J. Kolasa. sediment exposures and applicat ion to contaminated field sediment. Env. Tox domain and Chem 22 4 845-854· not GLP· Published.

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A 7.4.3.6 Vecchi M., T.B. Reynoldson, A. 1999 Toxicity of Copper Spiked Sediments to Tubifex tubifex : Comparison of the No Public ~ Pasteris and D. Bonomi. 28-day reproductive bioassay with an early life stage bioassay. Env. Tox and domain

Chem, 18, 6, 1173-1179; not GLP; Published A 7.5.1.1 Arshad, M. & Frankenberger, 1991 Effects of Soil Properties and Trace Elements on Ethylene Product ion in Soils. No Public ~

W.T.* Soil Science. 151, 5 : 377-386. Not GLP, Published domain A 7.5.1.1 Arshad, M. & Frankenberger, 1991 Effects of Soil Properties and Trace Elements on Ethylene Production in Soils. No Public ~

W.T.* Soil Science. 151, 5: 377-386. Not GLP, Published domain A 7.5.1.1 Bogomolov, D.M., Chen, S.K., 1996 An Ecosystem Approach to Soil Toxicity Testing: A Study of Copper No Public ~

Parmalee, R.W, Subler, s . & Contaminat ion in Laboratory Soil Microcosms. Applied Soil Ecology. 4 : 95- domain Edwards C.A. * 105. Not GLP Published

A 7.5.1.1 Bogomolov, D.M., Chen, S.K., 1996 An Ecosystem Approach to Soil Toxicity Test ing : A Study of Copper No Public ~ Parmalee, R.W, Subler, s . & Contamination in Laboratory Soil Microcosms. Applied Soil Ecology. 4: 95- domain Edwards C.A. * 105. Not GLP Published

A 7.5.1.1 Bollag, J-M, Barabasz, W.* 1979 Effect of Heavy Metals on the Denitrification Process in Soi l. J. Environ. Qual. No Public ~ 8: (2) · 196-201. Not GLP Published domain

A 7.5.1.1 Bollag, J-M, Barabasz, W.* 1979 Effect of Heavy Metals on the Denit rification Process in Soi l. J. Environ. Qual. No Public ~ 8 : (2) · 196-201. Not GLP Published domain

A 7.5.1.1 Chang, F-H. & Broadbent, F.E* 1981 Influence of Trace Metals on Carbon Dioxide Evolution from a Yolo Soil . Soil No Public ~ Science. 132: 6· 416-421. Not GLP Published. domain

A 7.5.1.1 Chang, F-H. & Broadbent, F.E* 1981 Influence of Trace Metals on carbon Dioxide Evolution from a Yolo Soil. Soil No Public ~ Science. 132: 6· 416-421. Not GLP Published. domain

A 7.5.1.1 Chang, F-H. & Broadbent, F.E* 1982 Influence of Trace Metals on Some Soil Nit rogen Transformations. J. Environ. No Public ~ oual. 11: 1 · 1-4. Not GLP Published. domain

A 7.5.1.1 Chang, F-H. & Broadbent, F.E* 1982 Influence of Trace Metals on Some Soil Nitrogen Transformations. J. Environ. No Public ~ oual. 11: 1; 1-4 . Not GLP, Publ ished. domain

A 7.5.1.1 Doelman, P. & Haanstra, L* 1984 Short Term and Long Term Effects of cadmium, Chromium, Copper, Nickel, No Public ~ Lead and Zinc on Soil Microbial Respiration in Relation to Abiotic Soil Factors. domain Plant and Soil. 79; 317-327. Not GLP, Publ ished.

A 7.5.1.1 Doelman, P. & Haanstra, L* 1984 Short Term and Long Term Effects of cadmium, Chromium, Copper, Nickel, No Public ~ Lead and Zinc on Soil Microbial Respiration in Relation to Abiotic Soil Factors. domain Plant and Soil. 79; 317-327. Not GLP, Published.

A 7.5.1.1 Doelman, P. & Haanstra, L* 1986 Short and Long Term Effects of Heavy Metals on Urease Activity in Soils. No Public ~ Biol. Fertil. Soils. 2; 213-218. Not GLP, Published. domain

A 7.5.1.1 Doelman, P. & Haanstra, L* 1986 Short and Long Term Effects of Heavy Metals on Urease Activity in Soils. No Public ~ Biol. Fertil. Soils. 2; 213-218. Not GLP, Published. domain

A 7.5.1.1 Doelman, P. & Haanstra, L.* 1989 Short and Long Term Effects of Heavy Metals on Phosphatase Activity in No Public ~ Soils: An Ecologica l Dose-Response Model Approach. Biol. Fertil. Soils. 8; domain 235-241.Not GLP, Published.

A 7.5.1.1 Doelman, P. & Haanstra, L.* 1989 Short and Long Term Effects of Heavy Metals on Phosphatase Activity in No Public ~ Soils: An Ecologica l Dose-Response Model Approach. Biol. Fertil. Soils. 8; domain 235-241.Not GLP, Published.

A 7.5.1.1 E. Smolders, Oorts, K 2004 Development of a predicitive model of bioavailability and toxicity of copper in Yes Europea ~ soils: microbial toxicity; Laboratory of Soil and Water Management, n Katholieke Universiteit Leuven; No report number; not GLP; Unpublished Copper

Inst itute

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A 7.5.1.1 Frostegard, A, Tunlid, A. & Baath, 1993 Phospholipid Fatty Acid Composition, Biomass and Activity of Microbial No Public ~ E.* Communities from Two Different Soil Types Experimentally Exposed to domain

Different Heavy Metals. App. Environ. Microbiol. 59 (11) : 3605- 3617. Not GLP, Publ ished

A 7.5.1.1 Frostegard, A, Tunlid, A. & Baath, 1993 Phospholipid Fatty Acid Composition, Biomass and Activity of Microbial No Public ~ E.* Communities from Two Different Soil Types Experimentally Exposed to domain

Different Heavy Metals. App. Environ. Microbiol. 59 (11): 3605- 3617. Not GLP, Publ ished

A 7.5.1.1 Haanstra, L. & Doelman, P.* 1984 Glutamic Acid Decomposition as a Sensitive Measure of Heavy Metal Pollution No Public ~ in Soil. Soil Biol. Biochem. 16; 595-600. Not GLP, Publ ished. domain

A 7.5.1.1 Haanstra, L. & Doelman, P. * 1984 Glutamic Acid Decomposition as a Sensitive Measure of Heavy Metal Pollution No Public ~ in Soil . Soil Biol. Biochem. 16; 595-600. Not GLP, Published. domain

A 7 .5.1.1 Haanstra, L. & Doelman, P. * 1991 An Ecological Dose-Response Model Approach to Short and Long Term Effects No Public l8J of Heavy Metals on Arylsulphatase Activity in Soil. Biol. Fert. Soils. 11; 18- domain 23. Not GLP Published.

A 7 .5.1.1 Haanstra, L. & Doelman, P.* 1991 An Ecological Dose-Response Model Approach to Short and Long Term Effects No Public l8J of Heavy Metals on Arylsulphatase Activity in Soil. Biol. Fert. Soils. 11; 18- domain 23. Not GLP Published.

A 7 .5.1.1 Hemida, S.K., Omar, S.A. & Abdel- 1995 Microbial Populations and Enzyme Activity in Soil Treated with Heavy Metals. No Public l8J Mallek, A.Y.* Water, Air. Soil Poll. 95: 13-22. Not GLP, Published . domain

A 7.5.1.1 Hemida, S.K., Omar, S.A. & Abdel- 1995 Microbial Populations and Enzyme Activity in Soil Treated with Heavy Metals. No Public ~ Mallek, A.Y.* Water, Air. Soil Poll. 95: 13-22. Not GLP, Published. domain

A 7 .5.1.1 Khan, M. and Scullion, J. 2002 Effects of metal (Cd, Cu, Ni, Pb or Zn) enrichment of sewage-sludge on soil No Public ~ micro-organisms and their activities. Applied Soil Ecology, 20, 145-155; not domain GLP; Published

A 7 .5.1.1 Maliszewska, w., Dec, s ., 1985 The Influence of Various Heavy Metal Compounds on the Development and No Public ~ Wierzbicka, H. & Wozniakowska, Activity of Soil Micro-Organisms. Environ. Poll. (Series A). 37; 195-215. Not domain A.* GLP, Publ ished

A 7 .5.1.1 Maliszewska, W., Dec, s ., 1985 The Influence of Various Heavy Metal Compounds on the Development and No Public ~ Wierzbicka, H. & Wozniakowska, Activity of Soil Micro-Organisms. Environ. Poll. (Series A). 37; 195-215. Not domain A.* GLP, Publ ished

A 7 .5.1.1 Premi, P.R. & Cornfield, A.H.* 1969 Effects of Addition of Copper, Manganese, Zinc and Chromium Compounds on No Public ~ Ammonification and Nitrification During Incubation of Soil. Plant and Soil. domain 31 : 12) ' 345-352. Not GLP Published.

A 7.5.1.1 Premi, P.R. & Cornfield, A.H.* 1969 Effects of Addition of Copper, Manganese, Zinc and Chromium Compounds on No Public l8J Ammonification and Nitrificat ion During Incubation of Soil. Plant and Soil. domain 31 : 12) ' 345-352. Not GLP Published.

A 7.5.1.1 Quraishi, M.S.I & Cornfield, A.H.* 1973 Incubation Study of Nitrogen Mineralisation and Nitrification in Relation to No Public l8J Soil pH and Level of Copper (II) Addition. Environ. Poll. 4; 159-163. Not GLP, domain Published.

A 7.5.1.1 Quraishi, M.S.I & Cornfield, A.H.* 1973 Incubation Study of Nitrogen Mineralisation and Nitrification in Relation to No Public l8J Soil pH and Level of Copper (II) Addition. Environ. Poll . 4; 159-163. Not GLP, domain Publ ished.

A 7.5.1.1 Saviozzi, A., Levi-Minzi, R., 1997 The Influence of Heavy Metals on Carbon Dioxide Evolution from A Typic No Public l8J cardelli, R. & Riffaldi, R* Xerochrept Soi l. Water, Air Soil Poll . 93: 409-417 (published) . domain

A 7.5.1.1 Saviozzi, A., Levi-Minzi, R., 1997 The Influence of Heavy Metals on Carbon Dioxide Evolution from A Typic No Public l8J cardelli, R. & Riffaldi, R* Xerochrept Soil. Water, Air Soil Poll . 93: 409-417 (published). domain

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A 7.5.1.1 Skujins, J., Nohrstedt, H-0., Oden, 1986 Development of a Sensitive Biological Method for the Determination of a No Public ~ S.* Low-Level Toxic Contamination in Soils. Swedish J. Agric. Res. 16; 113- domain

118.Not GLP, Published A 7.5.1.1 Skujins, J., Nohrstedt, H-0., Oden, 1986 Development of a Sensitive Biological Method for the Determination of a No Public ~

S.* Low-Level Toxic Contamination in Soils. Swedish J. Agric. Res. 16; 113- domain 118.Not GLP, Published

A 7.5.1.1 Speir, T.W., Kettles, H.A., Percival, 1999 Is Soil Acidification the Cause of Biochemical Response when Soils are No Public ~ H.J. & Parshotam, A* Amended with Heavy Metal Salts? Soil Biology and Biochemist ry. 31: 1953- domain

1961. Not GLP, Published A 7.5. 1.1 Speir, T.W., Kettles, H.A., Percival, 1999 Is Soil Acidificat ion the Cause of Biochemical Response when Soils are No Public ~

H.J. & Parshotam, A* Amended with Heavy Metal Salts? Soi l Biology and Biochemistry. 31: 1953- domain 1961. Not GLP, Published

A 7.5.1.2/ van Gestel, C.A.M., van Dis, W.A., 1991 Influence of Cadmium, Copper and Pentachlorophenol on Growth and Sexual No Public ~ 7.5.6 Dirven-van Breeman, E.M., Development of Eisenia andrei {Oligochaeta; Annelida). Biology and Fertility domain

Sparenburg, P.M. & Baerselman, of Soils. 12; 117-121. Not GLP, Published. R.*

A 7.5.1.2/ van Gestel, C.A.M., van Dis, W.A., 1991 Influence of Cadmium, Copper and Pentachlorophenol on Growth and Sexual No Public ~ 7.5.6 Dirven-van Breeman, E.M., Development of Eisenia andrei {Oligochaeta; Annelida). Biology and Fertility domain

Sparenburg, P.M. & Baerselman, of Soils. 12; 117-121. Not GLP, Published. R.*

A 7 .5.1.2/ Spurgeon, D.J. & Hopkin, S.P.* 1995 Extrapolation of the Laboratory-Based OECD Earthworm Toxicity Test to No Public ~ 7.5.6/ Metal-Contaminated Field Sites. Ecotoxicity. 4; 190-205 domain 7.5.2.1 A 7 .5.1.2/ Spurgeon, D.J. & Hopkin, S.P.* 1995 Extrapolation of the Laboratory-Based OECD Earthworm Toxicity Test to No Public ~ 7.5.6/ Metal-Contaminated Field Sites. Ecotoxicity. 4; 190-205 domain 7.5.2.1 A 7 .5.1.2/ Svendsen, C. & Weeks, J.M* 1997a Relevance and Applicability of a Simple Earthworm Biomarker of Copper No Public ~ 7.5.6 Exposure. I. Links to Ecological Effects in a Laboratory Study with Eisenia domain

andrei. Ecotoxicolonv and Environmental Safetv. 36' 72-79 A 7 .5.1.2/ Svendsen, c. & Weeks, J.M* 1997a Relevance and Applicability of a Simple Earthworm Biomarker of Copper No Public ~ 7.5.6 Exposure. I. Links to Ecological Effects in a Laboratory Study with Eisenia domain

andrei. Ecotoxicolonv and Environmental Safetv. 36' 72-79 A 7 .5.1.2/ Martin, N.A.,* 1986 Toxicit y of Pesticides to Allolobophora caliginosa {Oligochaeta: Lumbricidae) . No Public ~ 7.5.2.1 New Zealand Journal of Agricultural Research. 29; 699-706. Not GLP, domain

Published. A 7 .5.1.2/ Martin, N.A.,* 1986 Toxicity of Pesticides to Allolobophora ca liginosa {Oligochaeta: Lumbricidae) . No Public ~ 7.5.2.1 New Zealand Journal of Agricultura l Research. 29; 699-706. Not GLP, domain

Published. A 7.5.2.1 Herbert IN, Svendsen C, Hankard 2004 Comparison of instantaneous rate of population increase and critical -effect No Public ~

PK and Spurgeon DJ estimates in Folsomia candida exposed to four toxicants. Ecotox. Environ. domain Safetv 57 :175-183 ' not GLP· Published

A 7.5.2.1 Kammenga, J.E., Van Koe rt, 1996 A Toxicity Test in Artificial Soil based on the Life History Strategy of the No Public ~ P.H.G., Riksen, J.A.G., Korthals, Nematode Plectus acuminatus. Environmental Toxicology and Chemistry. domain G.W. & Bakker, J.* 15; 722-727. Not GLP, Published.

A 7.5.2.1 Kammenga, J.E., Van Koe rt, 1996 A Toxicity Test in Artificia l Soil based on the Life History Strategy of the No Public ~ P.H.G., Riksen, J.A.G., Kortha ls, Nematode Plectus acuminatus. Environmental Toxicology and Chemistry. domain G.W. & Bakker, J.* 15; 722-727. Not GLP, Published.

108




A 7.5.2.1 Lock, K., Janssen, C.R. 2001 Test designs to assess the influence of Soil Characteristics on the Toxicity of No Public ~ Copper and Lead to the Oligochaete Enchytraeus albidus; Ecotoxicology, 10, domain 137-144; not GLP; Published

A 7.5.2.1 Ma, W-C.,* 1988 Toxicity of Copper to Lumbricid Earthworms in Sandy Agricultural Soils No Public ~ Amended with cu-Enriched Organic Waste Materials. Ecological Bulletins. 39; domain 53-56. Not GLP, Published.

A 7.5.2.1 Ma, W-C.,* 1988 Toxicity of Copper to Lumbricid Earthworms in Sandy Agricultural Soils No Public ~ Amended with cu-Enriched Organic Waste Materials. Ecological Bulletins. 39; domain 53-56. Not GLP, Published.

A 7.5.2.1 P. Criel, K.A.C. De Schamphelaere 2005 Development of a predictive model of bioavailability and toxicity of copper in Yes Europea ~ and C. R. Janssen soils Invertebrate toxicity; Laboratory of Environmental Toxicology and n

Aquatic Ecology, Ghent University; No Report number; not GLP; Unpublished Copper Institute

A 7.5.2.1 Pedersen, M. B., van Gestel, 2001 Toxicity of copper to the collembolan Folsomia fimetaria in relation to the age No Public ~ C.A.M. of soil contamination; Ecotoxicology and Environmental Safety, 49, 54-59; domain

not GLP· Published A 7.5.2.1 Pedersen, M. B., van Gestel, 2000 Effects of copper on reproduction of two collembolan species exposed No Public ~

C.A.M., Elmegaard, N. through soil, food and water. Environmental Toxicology and Chemistry, 19, domain 10 2579-2588' not GLP· Published

A 7.5.2.1 Rundgren s . & Van Gestel, C.A.M. 1988 Comparison of Species Sensitivity. In : Handbook of Soil Invertebrate No Public ~ Toxicity Tests. pp 41-55 Ed. H. Lokke and C.A.M. Van Gestel. J. Wiley and domain Sons Ltd Chichester UK· not GLP· Published.

A 7.5.2.1 Sandifer, R.D & Hopkin, S.P. 1997 Effects of Temperature on the Relative Toxicities of Cd, Cu, Pb and Zn to No Public ~ Folsomia candida (Col lembola). Ecotoxicology and Environmental Safety. 37; domain 125-130 ' not GLP· Published

A 7.5.2.1 Spurgeon DJ, Svendsen C, Kille P, 2004 Responses of earthworms {Lumbricus rubellus) to copper and cadmium as No Public ~ Morgan AJ, Weeks JM. determined by measurement of juvenile traits in a specifically designed test domain

svstem. Ecotoxicol Environ Saf. 57 fl) 54-64' not GLP· Published A 7.5.2.1 van Dis, W.A., Van Gestel, C.A.M., 1988 Ontwikkeling van een toets ter bepaling van sublethale effecten van No Public ~

and Sparenburg, P.M. chemische stoffen op regenwormen; RIVM expert report 718480002; not domain GLP· Published

A 7.5.2.1 Van Gestel, C.A.M. & Doornekamp, 1998 Tests of the Oribatid mite Playnothrus peltifer. In Handbook of Soil No Public ~ A.* Invertebrate Toxicity Tests. Ed. H. Lokke and C.A.M. Van Gestel. J. Wiley and domain

Sons Ltd Chichester UK. Not GLP Published. A 7.5.2.1 Van Gestel, C.A.M. & Doornekamp, 1998 Tests of the Oribatid mite Playnothrus peltifer. In Handbook of Soil No Public ~

A.* Invertebrate Toxicity Tests. Ed. H. Lokke and C.A.M. Van Gestel. J. Wiley and domain Sons Ltd, Chichester, UK. Not GLP, Published.

A 7.5.2.1 van Gestel, C.A.M., Van Dis, W.A., 1989 Development of a Standardised Reproduction Toxicity Test with the No Public 18] Breemen, E.M. & Sparenburg, P.M. Earthworm Species Eisenia fetida andrei Using Copper, Pentachlorophenol domain

and 2, 4-Dichloroaniline. Ecotoxicol. Environ. Safety. 18: 305-312; not GLP; Published.

A 7.5.2.1 Van Gestel, C.A.M., Van Dis, W.A., 1989 Development of a Standardised Reproduction Toxicity Test with the No Public ~ Breemen, E.M. & Sparenburg, Earthworm Species Eisenia fetida andrei Using Copper, Pentachlorophenol domain P.M.* and 2, 4-Dichloroanil ine. Ecotoxicol. Environ. Safety. 18: 305-312. Not GLP,

Published. A 7.5.2.1 Van Gestel, C.A.M., Van Dis, W.A., 1989 Development of a Standardised Reproduction Toxicity Test with the No Public 18]

Breemen, E.M. & Sparenburg, Earthworm Species Eisenia fetida andrei Using Copper, Pentachlorophenol domain P.M.* and 2, 4-Dichloroaniline. Ecotoxicol. Environ. Safety. 18: 305-312. Not GLP,

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Published.

A 7.5.2.2 Ali, N. A., Ater, M., Sunahara, G., 2004 Phytotoxicity and bioaccumulation of copper and chromium using barley No Public ~ Robidoux, P.Y. (Hordeum vulgare L.) in spiked artificial and natural forest soils. domain

Ecotoxicology and Environmental Safety Volume 57, Issue 3 , March 2004, Paaes 363-374· not GLP· Published

A 7.5.2.2 Alva, A.K., Graham, J.H. & Tucker, 1993 Role of Calcium in Amelioration of Copper Phytotoxicity for Citrus. Soil No Public ~ D.P.H.* Science. 155· 3· 211-218. Not GLP Published. domain

A 7.5.2.2 Belanger, A., Levesque, M.P. & 1987 The Influence of Variation in Soil Copper on the Yei ld and Nutrition of No Public ~ Mathur, S.P.* Radishes Grown in Microplots on Two Peat Soils. International Peat Journal. domain

2; 65-73.Not GLP, Published. A 7.5.2.2 Belanger, A., Levesque, M.P., 1987 The influence of variation in soil copper on the yield and nutrition of rad ishes No Public ~

Mathur, S.P. grown in microplots on two peat soils. International Peat Journal, 2, 65-73; domain not GLP· Publ ished

A 7.5.2.2 Brun LA, Le Corff J, Maillet J. 2003 Effects of elevated soil copper on phenology, growth and reproduction of five No Public ~ ruderal p lant species. Environ Pollut. 2003;122(3): 361-8; not GLP; Published domain

A 7.5.2.2 Chhibba, I. M. Nayyar, V.K. & 1994 Upper Critical Level of Copper in Wheat (Triticum aestivum) Raised on Typic No Public ~ Takkar, P.N.* Ustipsamment Soil. Indian Journal of Agricultural Sciences. 64 (5); 285-289 domain

Not GLP, Published. A 7.5.2.2 de Haan, s ., Rethfeld, H. & van 1985 Acceptable Levels of Heavy Metals (Cd, Cr, Cu, Ni, Pb, Zn) in Soils, No Public ~

Oriel, w. Depending on their Clay and Human Content and Cation-Exchange Capacity. domain Instituut Voor Bodemvruchtbaarheid Haren-Gr. Report No. 0434-6793 (published).

A 7.5.2.2 de Haan, s ., Rethfeld, H. & van 1985 Acceptable Levels of Heavy Metals (Cd, Cr, Cu, Ni, Pb, Zn) in Soils, No Public ~ Oriel, W.* Depending on their Clay and Human Content and Cation-Exchange Capacity. domain

Instituut Voor Bodemvruchtbaarheid Haren-Gr. Report No. 0434-6793. Not GLP, Publ ished

A 7.5.2.2 Jarvis, S.C. 1978 Copper Uptake and Accumulation by Perennial Ryegrass Grown in Soil and No Public ~ Solution Culture. J. Sci. Fd. Aoric. 29 : 12-18 (published). domain

A 7.5.2.2 Jarvis, s.c. * 1978 Copper Uptake and Accumulation by Perennial Ryegrass Growth in Soil and No Public ~ Solution culture. J. Sci. Food. Agric. 29: 12-18. Not GLP, Published . domain

A 7.5.2.2 Kalyanaraman, S.B. & 1993 Effect of cadmium, Copper and Zinc on the Growth of Blackgram. Journal of No Public ~ Sivaaurunathan P. * Plant Nutrition. 16 110) 2029-2042. Not GLP Published. domain

A 7.5.2.2 Kjcer, c. & Elmegaard. N. 1996 Effects of Copper Sulphate on Black Bindweed (Polygonum convolvulus L.) No Public ~ Ectoxicology and Environmental Safety. 33; 110-117 (published). domain

A 7.5.2.2 Kjcer, C. & Elmegaard. N.* 1996 Effects of Copper Sulphate on Black Bindweed (Polygonum convolvulus L.) No Public ~ Ectoxicology and Environmental Safety. 33; 110-117. Not GLP, Published domain

A 7.5.2.2 Korthals, G.W., Alexiev, A.D., 1996a Long Term Effects of Copper and pH on the Nematode Community in an No Public ~ Lexmond, T.M., Kammenga, J.E. & Agrosystem. Environ. Toxicol. Chem. 15 (6) : 979-985. Not GLP, Published. domain Bongers, T.*

A 7.5.2.2 Lexmond, T. M.* 1980 The Effect of Soil pH on Copper Toxicity to Forage Maize Grown Under Field No Public ~ Conditions. Neth. J. Agric. Sci. 28: 164-183. Not GLP, Published. domain

A 7.5.2.2 Lexmond, T.M. 1980 The effect of soil pH on copper toxicity to forage maize grown under field No Public ~ conditions. Neth. J. Agric . Science 28, 164-183; not GLP; Published domain

A 7.5.2.2 McBride, M.B.* 2001 Cupric Ion Activity in Peat Soil as a Toxicity Indicator for Maize. Journal of No Public ~

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A 7.5.2.2 Pedersen, M. B., Kjcer, c. 2000 Toxicity and Bioaccumulat ion of Copper to Black Bindweed (Fallopia No Public 18] Elmegaard, N. convolvulus) in Relation to Bioavailability and the Age of Soil Contamination. domain

Archives of Environmenta l Contamination and Toxicology. 39; 431 -439 loublishedl.

A 7.5.2.2 Pedersen, M. B., Kjcer, c. 2000 Toxicity and Bioaccumulat ion of Copper to Black Bindweed (Fallopia No Public 181 Elmegaard, N.* convolvulus) in Relat ion to Bioavailability and the Age of Soil Contamination. domain

Archives of Environmental Contamination and Toxicology. 39; 431-439. Not GLP, Published.

A 7.5.2.2 Rhoads, F.M., Barnett, R.D. & 1992 Copper Toxicity and Phosphorus Concentration in 'Florida 502' Oats. Soil No Public 181 Olson, S.M.* Crop Science Society Florida Proceedings. 51; 18-20. Not GLP, Published. domain

A 7.5.2.2 Rhoads, F.M., Barnett, R.D., 1992 Copper toxicity and phosphorous concentration in "Florida 502" oats. Soil and No Public 181 Olson, S.M Crop Science of Florida, 51 :18-20; not GLP; Published domain

A 7.5.2.2 Rooney, C.P, McGrath, S.P, Zhao, 2004 Development of a predicit ive model of bioavailability and toxicity of copper in Yes Europea 18] F.J., Davis, M.R.H., Zhang, H. soils: biological endpoints: Plant toxicity and effects of shock on microbial n

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A 7.5.2.2 Roth, J.A., Wallihan, E.F. & 1971 Uptake by Oats and Soybeans of Copper and Nickel Added to a Peat Soil. Soil No Public 18] Sharpless, R.G* Science. 112; 5; 338-342. Not GLP, Published domain

A 7.5.2/ Sandifer, R.D. & Hopkin, s . P.* 1996 Effects of pH on the Toxicity of Cadmium, Copper, Lead and Zinc to Folsomia No Public 18] 7.5.2.1 candida Willem, 1902 (Collembola) in a Standard Laboratory Test System. domain

Chemosohere. 33: 12; 2475-2486. Not GLP, Published. A 7.5.2/ Sandifer, R.D. & Hopkin, s . P. * 1996 Effects of pH on the Toxicity of Cadmium, Copper, Lead and Zinc to Folsomia No Public ~ 7.5.2.1 candida Willem, 1902 (Collembola) in a Standard Laboratory Test System. domain

Chemosohere. 33: 12; 2475-2486. Not GLP, Published. A 7.5.3.1.1 Dickhaus, s . 1988 Acute Toxicolog ica l Study of Kupfer- I-Oxid After Oral Application to the Yes Spiess- ~

Quail; Pharmatox GmbH, project no. 1-8-43-88; GLP; Unpublished Urania

A 7.5.4.1 Hoxter, K.A., Lynn, S.P. 1991 Cuprous oxide - Agro grade: An acute contact toxicity study with the honey Yes Nord ox 18] bee; Wild life International Ltd. Project No. 303- lOl B; GLP; Unpublished

A 7.5.6 Augustsson, A. K., & Rundgren, S* 1998 The Enchytraeid Cognettia sphagnetorum in Risk Assessment: Advantages No Public 181 and Disadvantages. Ambio. 27; 62-69. Not GLP, Published. domain

A 7.5.6 Bogomolov, D.M., Chen, S.K., 1996 An Ecosystem Approach to Soil Toxicity Testing: A Study of Copper No Public 181 Parmalee, R.W, Subler, s. & Contamination in Laboratory Soil Microcosms. Applied Soil Ecology. 4; 95- domain Edwards C.A. * 105. Not GLP Published.

A 7.5.6 Jaggy, A. & Streit, B. * 1982 Toxic Effects of Soluble Copper on Octolasium cyaneum sav. ( lumbricidae). No Public 18] Rev. Suisse De Zoologie. 89; 4: 881-889. Not GLP, Published. domain

A 7.5.6 Kah ii , M.A., Abdel-Lateif, H.M., 1996b Effects of Metals and Metal Mixtures on Survival and Cocoon Production of No Public 18] Bayoumi, B.M, van Straalen, N.M. the Earthworm Aporrectodea ca lig inosa. Pedobiology. 40; 548-556 .Not GLP, domain & van Gestel, C.A.M.* Published.

A 7.5.6 Khalil, M.A., Abdel-Lateif, H.M., 1996a Analysis of Separate and Combined Effects of Heavy Metals on the Growth of No Public 18] Bayou mi, B. M. & van Straalen, Aporrectodea calig inosa (Oligochaeta; Annelida), Using the Toxic Unit domain N.M.* Annroach. Annlied Soil Ecoloav. 4 ' 213-219.Not GLP Published.

A 7.5.6 Korthals, G.W, Van de Ende, A., 1996b Short-Term Effects of Cadmium, Copper, Nickel and Zinc on Soil Nematodes No Public 18] Van Megen, H., Lexmond, T.M., from Different Feeding and Life-History Strategy Groups. App. Soil. Ecology. domain Kammenga, J.E. & Bongers, T. 4, 107-117. GLP, published

111




A 7.5.6 Korthals, G.W., Alexiev, A.O., 1996a Long Term Effects of Copper and pH on the Nematode Community in an No Public ~ Lexmond, T.M., Kammenga, J.E. & Agrosystem. Environ. Toxicol. Chem. 15 (6) : 979-985. Not GLP, Published. domain Bongers, T.*

A 7.5.6 Korthals, G.W., van de Ende, A., 1996 Short-Term Effects of cadmium, Copper, Nickel and Zinc on Soil Nemat odes No Public ~ van Megen, H., Lexmond, T.M., from Different Feeding and Life History Strategy Groups. Applied Soil. domain Kammenga, J. & Bongers, T. * Ecology. 4; 107- 117. Not GLP, Published.

A 7.5.6 Ma, W.C. * 1982 The Influence of Soi l Properties and Worm Related Factors on the No Public ~ Concentration of Heavy Metals in Earthworms. Pedobiologica. 24; 109-119. domain Not GLP, Published.

A 7.5.6 Parmalee, R. w., Wentsel, R.S., 1993 Soil Microcosm for Testing the Effects of Chemical Pollutants on Soil Fauna No Public ~ Phill ips, C.T., Simini, M. & Checkai, Communities and Trophic Structure. Environ. Toxicol. Chem. 12; 1477- domain R.T.* 1486. Not GLP, Published.

A 7.5.6 Scott-Fordsmand, J.J., Krogh P.H. 1997 Sublethal Toxicity of Copper to a Soil-Dwelling Springtail {Folsomia fimetaria) No Public ~ & Weeks, J.M.* {Collembola: Isotomidae). Environmental Toxicology and Chemistry, 16: 12; domain

2538-2542.Not GLP, Published. A 7.5.6 Svendsen, C. & Weeks, J. M.* 1997b Relevance and Applicability of a Simple Earthworm Biomarker of Copper No Public ~

Exposure. II Validation and Applicability Under Field Conditions in a domain Mesocosm Experiment with Lumbricus rubellus. Ecotoxicol . Environ. Saf. 36, 80-88. Not GLP, Published.

A 7.5.6/ Kula, H. & Larink, O.* 1997 Development and Standardisation of Test Methods for the Prediction of No Public ~ 7.5.2.1 Sublethal Effects of Chemicals on Earthworms. Soil Biology and Biochemistry. domain

29: 3/ 4; 635-639. Not GLP, Published. A 7.5.6/ Spurgeon, D.J., Hopkin, S.P. & 1994 Effects of Cadmium, Copper, Lead and Zinc on Growth, Reproduction and No Public ~ 7.5.2.1 Jones, D.T.* Survival of the Earthworm Eisenia fetida {Savigny) : Assessing the domain

Environmental Impact of Point-Source Metal Contamination in Terrestria l Ecosystems. Environmental Pollution. 84; 123-130. Not GLP, Published.

A 7.5.6/ Bengtsson G., Gunnarsson, T. & 1986 Effects of Metal Pollution on the Earthworm Dendrobaena rubida {Sav) in No Public ~ 7.5.2.1 Rundgren, S. * Acified Soils. Water, Air and Soil Pollution. 28; 361-383 domain

A 7.5.6/ Krogh, P.H. & Axelsen, J.A.* 1998 Test on the Predatory Mite Hypoaspis aculeifer Preying on the Collembolan No Public ~ 7.5.2.1 Folsomia fimetaria. In: Handbook of Soil I nvertebrate Toxicity Tests. pp domain

239-251. Ed. H. Lokke and C.A.M. Van Gestel. J. Wiley and Sons Ltd, Chichester UK. Not GLP Published.

A 7.5.6/ Rundgren S. & Van Gestel, C.A.M 1998 Comparison of Species Sensitivity. I n : Handbook of Soil Invertebrate No Public ~ 7.5.2.1 Toxicity Tests. pp 95-112 Ed. H. Lokke and C.A.M. Van Gestel. J. Wiley and domain

Sons Ltd Chichester UK. Not GLP. <oublished). A 7.5.6/ Rundgren s . & Van Gestel, 1998 Comparison of Species Sensitivity. I n : Handbook of Soil Invertebrate No Public ~ 7.5.2.1 C.A.M.* Toxicity Tests. pp 41-55. Ed. H. Lokke and C.A.M. Van Gestel. J. Wiley and domain

Sons Ltd Chichester UK. Not GLP Published. A 7.5.6/ Ku la, H. & Larink, O.* 1998 Tests of the Earthworms Eisenia fetida and Aporrectodea caliginosa. In : No Public ~ 7.5.2.1 Handbook of Soil I nvertebrate Toxicity Tests. pp 95- 112 Ed. H. Lokke and domain

C.A.M. Van Gest el. J. Wiley and Sons Ltd, Chichester, UK. Not GLP, Published.

A 7.5.6/ Sandifer, R.D & Hopkin, S.P.* 1997 Effects of Temperature on the Relative Toxicit ies of Cd, Cu, Pb and Zn to No Public ~ 7.5.2.1 Folsomia candida {Collembola). Ecotoxicology and Environmental Safety. 37; domain

125-130. Not GLP Published.

112




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Riemsdijk, W.H., Tipping, E. substances. Environ. Sci. Technol. 37 (5),958- 971. Cited in Hiemstra 2006 domain

IIA Milne, C.J., Kinniburgh, D.G., Van 2003 Generic NICA- Donnan model parameters for metal-ion binding by humic No Public ~ Riemsdijk, W.H., Tipping, E. substances. Environ. Sci. Technol. 37 (5),958- 971. Cited in Hiemstra 2006 domain

IIA Mitchelmore, C.L. et al. 2003 Differential accumulation of heavy metals in the sea anemone Anthopleura No Public ~ elegantissima as a function of symbiotic state. Aquatic Toxicology 64 {2003) domain 317 /329

IIA Mitchelmore, C.L. et al. 2003 Differential accumulat ion of heavy metals in the sea anemone Anthopleura No Public ~ elegantissima as a function of symbiotic state. Aquatic Toxicology 64 {2003) domain 317 /329

IIA Moffett, J. W. and L E. Brand 1996 Production of strong, extracellular Cu chelators by marine cyanobacteria in No Public ~ response to cu stress. Umnology and Oceanography 41(3) : 388-395. domain

IIA Moffett, J. W., L. E. Brand, et al. 1997 Cu speciation and cyanobacteria l d istribution in harbors subject to No Public ~ anthropogenic Cu inputs. Limnology and Oceanography 42(5): 789-799. domain

IIA Monteny F, Elskens M, Baeyens W, 1993 The behaviour of copper and zinc in the Scheidt Estuary. No Public ~ Nertherl.J.Aqua .Ecol. 27, 279-286. domain

IIA Morel, F.M.M., Price, N.M. 2003 The Biogeochemical Cycles of Trace Metals in the Oceans. Science 9 May No Public ~ 2003: 944 domain

IIA Mouneyrac, c., Mastain, 0 ., 2003 Trace-metal detoxification and tolerance of the estuarine worm Hediste No Public ~ Amiard, J.C., Amiard-Triquet, C., diversicolor chronically exposed in their environment . Marine Biology 143, domain Beaunier, P., Jeantet, A.Y., Smith, 731-744. B.D., and Rainbow, P.S.

IIA Mwanuzi F, De Smedt F, 1999 Heavy metal d istribut ion model under estuarine mixing. Hydro!. Process. 13, No Public ~ 789-804. domain

IIA Negri A. P. Heyward A. J 2001 Inhibit ion of cora l fertilisation and larval metamorphosis by tributyltin and No Public ~ copper . Marine Environmental Research 51 {2001) 17-27 domain

IIA Nell J.A., Holliday, J.E 1986 Effects of potassium and copper on the settling rate of Sydney rock oyster No Public ~ (Saccostrea commercialis) . Aauaculture, 58:263-267. domain

IIA Nelson D.A.,Miller, J.E., Galabrese, 1988 Effect of heavy metals on bay scallops, surf clams and blue mussels in acute No Public ~ A. and long-term exposures. Arch. Environ. Contam. Toxicol., 17:595-600. domain

IIA Ng and Keough 2003 Delayed effects of larval exposure to Cu in the bryozoan Watersipora No Public ~ subtorquata. Mar Ecol Proo Ser 257: 77- 85, 2003 domain

IIA Noriki s, Ishimori N, Harada K, 1985 Removal of trace metals from seawater during a phytoplankton bloom as No Public ~ Tsunogai s, studied with sediment traps from seawater during a phytoplankton bloom as domain

studied with sediment t raps in Funka Bay, Japan. Marine Chemistry 17, 75-89.

120




IIA Nystrom M., Moberg, F. and 1997 Natural and anthropogenic disturbance on reef cora ls in the Inner Gulf of No Public ~ Tedengren, M. Thailand: Physiological effects of reduced salinity, copper, and siltation. domain

Chapter pp.: 1893-1898 In : Proceedings of the 8th International Coral Reef Svmoosium, Panama, June 24-29, 1996

IIA Nystrom, M., Nordemar, I., and 2001 Simultaneous and sequential stress from increased temperature and copper No Public ~ Tedengren, M. on the metabolism of the hermatypic coral Porites cylindrica. Marine Biology domain

138(6): 1225-1231 IIA Obernosterer, I., Herndl, G.J. 2000 Differences in the optical and biological reactivity of the humic and nonhumic No Public ~

dissolved organic carbon component in two contrasting coasta l mar ine domain environments. Umnol. Oceanoar., 45(5), 2000, 1120-1129

IIA Obernosterer, I., Herndl, G.J. 2000 Differences in the optical and biological reactivity of the humic and nonhumic No Public ~ dissolved organic carbon component in two contrasting coastal marine domain environments. Umnol. Oceanoar., 45(5), 2000, 1120-1129

IIA OECD 2002 Draft Revised Guidel ine 201 : Freshwater Alga and Cyanobacteria, Growth No Public ~ Inhibition Test. Guidelines for the testina of chemicals domain

IIA Ogle, R. S. 2008 Review of article by Stromgren and Nielsen {1991) on copper toxicity to No Public ~ Mvtilus edulis soawnina and larval survival and arowth. domain

IIA OSPAR 2001 Data Report on the Comprehensive Study of Riverine Inputs and Direct No Public ~ Discharaes (RID) in 2001 domain

IIA Paulsson M, Nystrom B, and 2000 Long-term toxicity of zinc to bacteria and algae in periphyton communities No Public ~ Blanck H. from the river Gota alv, based on a microcosm study. Aquat ic Toxicol domain

47 :243-57 IIA Peers, G., Price, N.M. 2006 Copper-containing plastocyanin used for electron transport by an oceanic No Public ~

diatom. Nature fLond.) 4417091 : 341-344 domain IIA Peers, G., Quesnel, S-A., Price, 2005 Copper requirements for iron acquisition and growth of coastal and oceanic No Public ~

N.M. diatoms. Umnol. Oceanoar . 50(4) 2005 1149- 1158 domain IIA Pempkowiak, J., Widrowski, M., 1984 Dissolved organic carbon and particulate carbon in the Southern Balt ic in No Public ~

Kulinski,W., September, 1983. Proceedings XIV Conference of Balt ic Oceanographers, domain IMGW Gdvnia 699-713. Cited in K&P 2008

IIA Pettine, M., Patrolecco, L, 1999 Seasonal variations of dissolved organic matter in the northern Adriatic Sea. No Public ~ Manganelli, M., Capri, s ., Farrace, Marine Chemistry, 64,1999, 153-169 domain M.G.

IIA Piola and Johnston 2006 Differential resistance to extended copper exposure in four introduced No Public ~ brvozoans. Mar Ecol Proa Ser 311 : 103- 114 2006 domain

IIA Piola and Johnston 2006 Different ial tolerance to metals among populations of the int roduced No Public ~ bryozoan Bugula neritina. Marine Biology {2006) 148: 997- 1010 domain

IIA Piola and Johnston 2006 Differential resistance to extended copper exposure in four introduced No Public ~ brvozoans. Mar Ecol Proa Ser 311 : 103- 114, 2006 domain

IIA Rainbow, P.S. 1985 Accumulation of Zn, Cu and Cd by Crabs and Barnacles. Estuarine, Coastal No Public ~ Shelf Science. 21; 669-686; Not GLP; Published domain

IIA Rainbow, P.S. 2002 Trace metal concentrations in aquatic invertebrates: why and so what ? No Public ~ Environmental Pollut ion 120, 497-507. domain

IIA Rainbow, P.S. & White, S. L 1989 Comparative Strategies of Heavy Metal Accumulation by Crustaceans: Zinc, No Public ~ Copper and Cadmium in a Decapod and Am phi pod and a Barnacle. domain Hvdrobioloaia 174; 245-262; Not GLP; Published

IIA Rao V.N.R., Latheef, G.M. 1989 Effect of Copper on Artemia salina Linn. and of Skeletonema costatum No Public ~ {Grev.) Cleve as Feed. Comp. Physiol. Ecol., 14(2) :41-48. domain

121




IIA Rao V.N.R., Latheef, G.M. 1989 Effect of Copper on Artemia salina Linn. and of Skeletonema costatum No Public ~ {Grev.) Cleve as Feed. Comp. Physiol. Ecol., 14(2) :41-48. domain

IIA Rayburn J.R., Fisher, w.s. 1999 Developmental toxicity of copper chloride, methylene ch loride and 6- No Public ~ aminonicotinamide to embryos of the grass shrimp Palaemonetes pugio. domain Environ. Toxicol. Chem., 18:950-957.

IIA Regnier P, Hoenig M, Chou L, 1990 Trace metals in the suspended matter collected in the mixing zone of the No Public ~ Wollast R Rhone estuarv. Water Pollut. Res.Rea. 20 385-396. domain

IIA Reichelt-Brushett 1999 The Efect of Copper, Zinc and cadmium on Fertilizat ion Success of Gametes No Public ~ from Scleractinian Reef Corals. Marine Pollution Bulletin Vol. 38, No. 3, pp. domain 182-187 1999

IIA Reish D.J., Martin, J.M., Piltz, F.M., 1976 The effect of heavy metals on laboratory populations of two polychaetes with No Public ~ Word, J.Q. comparisons to the water quality conditions and standards in southern domain

California marine waters. Water Research 10:299-302. IIA Reish, D.J., carr, R.S. 1978 The effect of heavy metals on the surviva l, reproduction, development and No Public ~

life cycles for two species of polychaetous annelids. Mar. Pollut. Bull., 9, 24- domain 27

IIA Ringwood AH 1992 Comparative sensitivity of gametes and early developmental stages of a sea No Public ~ urchin species {Echinometra mathaei) and a bivalve species {I sognomon domain californicum) during metal exposures. Arch Environ Contam Toxicol, 22: 288-295.

IIA Saifullah, S.M. 1978 Inhibitory Effects of Copper on Marine Dinoflagellates. Mar. Biol . Vol.44; 299. No Public ~ domain

IIA Scott 1992 Flexible Kernel Density Estimation reference No Public ~ domain

IIA Scott 1992 Flexible Kernel Density Estimation reference No Public ~ domain

IIA Scoullos, M., Plavsic, M., 2006 Partitioning and distribution of dissolved copper, cadmium and organic No Public ~ Karavoltsos, S., Sakellari, A., matter in Mediterranean marine coastal areas: The case of a mucilage event . domain

Estuarine, Coastal, and Shelf Science 67, 2006, 484-490 IIA Shcolnick, s., Keren, N. 2006 Metal Homeostasis in Cyanobacteria and Chloroplasts. Balancing Benefits and No Public ~

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IIA Silverman 1986 Flexible Kernel Density Estimation reference No Public ~ domain

IIA Silverman 1986 Flexible Kernel Density Estimation reference No Public ~ domain

IIA Skrabal, S.A. et al. 1997 Fluxes of Copper-Complexing ligands from Estuarine Sediments. limnol. No Public ~ Ocean. Vol. 42 (5) 992-996 domain

IIA Smith, s . D., DePalma, S.G.S., 2008 Natural Organic and Inorganic Matter Quality and Copper Toxicity to Mytilus No Public ~ Arnold W.R. galloprovincialis. Abstract and presentation at SETAC Europe Conference, domain

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122




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IIA Smyth, D.V., Kent, s. 2006 Copper: toxicity to the marine algae Skeletonema costatum; BEL report no. Yes EU ~ BL8243/B; GLP; Unpublished Antifou li

ng Task Force

IIA Soria-Dengg, s ., Reissbrodt, R., 2001 Siderophores in marine coastal waters and their relevance for iron uptake by No Public ~ Horstmann, U. phytoplankton : experiments with the diatom Phaeodactylum tricornutum. domain

Mar Ecol Proa Ser. Vol. 220: 73- 82, 2001 IIA Stagg, R.M., Shuttleworth, T.J. 1982 The accumulation of copper in Platichthys flesus L. and its effect on plasma No Public ~

electrolvte concentration. J. Flsh Biol. 20, 491-500. domain IIA Stagg, R.M., Shuttleworth, T.J. 1982 The effects of copper on ionic regulation by the gills of the seawater adapted No Public ~

flounder {Platichthys flesus L.). J. Comp. Physiol. 149: 83-90. domain

IIA Stark J.S. 1998 Effects of copper on macrobenthic assemblages in soft sediments: a No Public ~ laboratory experimental study. Ecotoxicology, 7, 163-171 domain

IIA Stark J.S. 1998 Effects of copper on macrobenthic assemblages in soft sediments: a No Public ~ laboratory experimental study. Ecotoxicology, 7, 163-171 domain

IIA Stebbing, A. 1976 The effects of low metal levels on a clonal hydroid. J. Mar . Biol. Ass. {U.K), No Public ~ 56:977-994. domain

IIA Stebbing, A., Pomroy, A. 1978 A sublethal technique for assessing the effects of contaminants using Hydra No Public ~ littoralis. Water Research, 12:631-635. domain

IIA Steele, c .w . 1983 Acute toxicity of copper to sea catfish. Mar . Pollut. Bull . 14 : 168-170. No Public ~ domain

IIA Steele, c .w. 1983 Comparison of the behavioural and acute toxicity of copper to sheepshead, No Public ~ Atlantic croacker and pinfish. Mar. Pollut. Bull. 14 : 425-428. domain

IIA Steele, c .w . 1983 Acute toxicity of copper to sea catfish. Mar . Pollut. Bull . 14 : 168-170. No Public ~ domain

IIA Steele, c .w . 1983 Comparison of the behavioural and acute toxicity of copper to sheepshead, No Public ~ Atlant ic croacker and pinfish. Mar. Pollut. Bull . 14: 425-428. domain

IIA Stephens M.A. 1982 Andersen-Darling test for goodness-of-fit. In Kots S. and N.L. Johnson, Eds. No Public ~ Encyclopedia of Statistical Sciences, Vol. 1, Wiley, New York. domain

IIA Stromgren T., Nielsen, M.V. 1991 Spawning frequency, growth and mortality of Mytilus edulus larvae, exposed No Public ~ to copper and diesel oil. Aquatic Toxiciology, 171-179. domain

IIA Stumm, W. and J.J. Morgan 1981 Aquatic Chemistry: An Introduction Emphasizing Chemica l Equilibra In No Public ~ Natural Waters. John Wiley & Sons, NY, 780 DD. domain

IIA Subrahmanyam 1990 Concentration of Mn, cu, Ni, Cd and Co and toxicity of Mn and Ni in No Public ~ zooplankton from Visakhapatnam harbour {Bay of Bengal). Indian j ournal of domain marine sciences 1990, vol. 19, no4, DD. 297-299

IIA Tipping E, Lofts S, Lawlor AJ, 1998 Modell ing the chemical speciation of trace metals in the surface waters of the No Public ~ Humber svstem. Sci.Total Environ. 210, 211, 63-77. domain

IIA Torres et al. 1987 Acute toxicity of copper to Mediterranean dogfish. Comp Biochem Physiol; No Public ~ 86C: 169-171 domain

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123




IIA Turner A, Millward GE, Schuchard 1992 Trace metal distribution coefficients in the Weser Estuary (Germany). No Public ~ B, Schirmer M, Prange A, Cont.Shelf Res. 12, 1277-1292. domain

IIA Valenta P, Duursma EK, Merks 1986 Distribution of Cd, Pb and Cu between the dissolved and particu late phases in No Public ~ AGA, rutzel H, Nurnberg HW, the Eastern and Western Scheidt estuary. Sci.Total Environ. 53, 41-76. domain

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24: 785- 797. IIA Vignudelli, s ., Santinelli, c., 2004 Distribution of dissolved organic carbon {DOC) and chromophoric dissolved No Public ~

Murru, E., Nannicini, L , Seritti A., organic matter {CDOM) in coastal waters of the northern Tyrrhenian Sea domain (lta lv) . Estuarine, Coastal and Shelf Science 60, 2004, 133-149

IIA Visviki I & Rachlin JW 1991 The toxic action and interactions of copper and cadmium to the marine alga No Public ~ Dunaliella minuta, in both acute and chronic exposure. Arch Environ Contam domain Toxicol, 20 : 271- 275.

IIA Visviki I & Rachlin JW 1994 Acute and chronic exposure of Dunaliella salina and Chlamydomonas No Public ~ bullosa to copper and cadmium: Effects on growth. Arch Environ Contam domain Toxicol, 26 : 149-153.

IIA Visviki I & Rachlin JW 1994 Acute and chronic exposure of Dunaliella salina and Chlamydomonas No Public ~ bullosa to copper and cadmium: Effects on ultrastructure. Arch Environ domain Contam Toxicol 26: 154-162.

IIA Wagner c., Lokke H. 1991 Estimation of ecotoxicological protection levels for NOEC toxicity data. Water No Public ~ Research 25: 1237-1242. domain

IIA Wang, W-X, and Flsher, N.S. 1998 Accumulation of trace elements in a marine copepod. Limnol Oceanogr. No Public ~ 1998 Vol 43 Issue 2 0273-283 domain

IIA Wangberg S-A, Heyman u, Blanck 1991 Long-term and short-term arsenate toxicity to freshwater phytoplankton and No Public ~ H. periphyton in limnocorrals. Can J Fish Aquat Sci 48 :173-82 domain

IIA Wangberg, S-A., Alexandersson, 1995 Rapport fran projektet : Batbottentargernas bidrag till kopparforekomsten I No Public ~ s., Hellgren, M. den akvatiska miljon. Uppfoljning av Keml's beslut om batbottenfarger, med domain

hjalp av en PICT-undersokning pa mikroalgsamhallen. Delprojekt 1 och 2. 95-01-10

IIA Webster, N.S, Webb, R.I., Ridd, 2001 The effects of copper on the microbial community of a coral reef sponge. No Public ~ M.J., Hil l, R.T, Negri, A.P. Environmenta l Microbiology {2001) 3(1), 19-31 domain

IIA Webster, N.S, Webb, R.I., Ridd, 2001 The effects of copper on the microbial community of a coral reef sponge. No Public ~ M.J., Hil l, R.T, Negri, A.P. Environmenta l Microbiology {2001) 3(1), 19-31 domain

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IIA Wheeler, J.R., Leung, K.M.Y., 2002 Freshwater to Saltwater toxicity extrapolation using Species Sensitivity No Public ~ Morritt, D., Sorokin, N., Rogers, Distribution,s Environmental Toxicology and Chemistry, Vol. 21, No. 11, pp. domain H., Toy, R., Holt, M., Whitehouse, 24 59- 2467 P., Crane, M.

IIA White, S.L. & Rainbow, P.S. 1982 Regulation and Accumulation of Copper, Zinc and cadmium by the Shrimp No Public ~ Palaemon elegans. Marine Ecology Progress Series. 8; 95-101; Not GLP; domain Published

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124




IIA Young, J.S., Buschbom, R.L , 1979 Effects of Copper on the Sabellid Polychaete, Eudistylia vancouveri: I No Public ~ Gurtisen, J.M. & Joyce, S.P. Concentration Limits for Copper Accumulation. Archives of Environmental domain

Contamination and Toxicoloav. 8 : 97- 106 IIA Zaroogian, G.E. & Johnston, M. 1983 Copper Accumulation in the Bay Scallop, Argopecten irradians. Arch. Environ. No Public ~

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125


Intersmooth 360 SPC

Reference list of stud ies submitted and validated by Section number for the representative product Intersmooth 360 SPC:

Section No / Reference Author (s) Year Ti tle Source (where different from company) Data Prot ection Owner Essential Essent ial No Company, Report No. GLP ( where r elevant) I Claim ed studies for studies for

(Un)Publ ished (Yes/ No) evaluation evaluat ion Yes No

Section 1 No study reports submitted ~ Section 2 No study reports submitted ~ Section 3 Greenwood J, Wright E 2002 Intersmooth 360 Ecoloflex Antifouling Paint: Evaluation Yes Internation [8J

of Physical Properties and Storage Stabil ity (New First) al Paint Covance Laboratories Ltd Report Number 1485-12-02149 GLP/Unoublished

Section 4 4.1/01 Wright E., Ristorcelli D 2001 Copper Compounds:Validation of the Analytical Method Yes Internation 1:8:1 for the Analysis in Antifouling Paints (New First) al Paint Covance Laboratories Ltd Report Number 1485/010-02149 GLP/Unoublished

Section 4 4.1/02 Wright E., Ristorcelli D 2001 Zinc Pyrithione:Validat ion of the Analytical Method for Yes Internation ~ the Analysis in Antifouling Paints (New First) al Paint Covance Laboratories Ltd Report Number 1485/009-02149 GLP/Unoublished

Section 5 5.1-5.11 Shilton c, Green G 2001 Antifouling Efficacy Report; I ntersmooth 360 Yes Internation [8J B5.10.2/0l (New First) al Paint Section 5 5.1-5.11 Callow ME 2005 Toxicity of Copper to Algae University of Yes Internation [8J B5.10.2/02 Birmingham Report number not (First New) al Paint

soecified Unoublished Section 5 5.1-5.11 Callow ME 2005 Toxicity of Zinc Pyrithione to Algae Yes Internation 1:8:1 B5.10.2/03 University of Birmingham Report (First New) al Paint

number not soecified Unoublished Section 5 5.1-5.11 Prowse, G. and 2006 Antifouling paint efficacy report, Intersmooth type zinc Yes Internation [8J B5.10.2/03 Solomon, T. pyrithione f ree formulation (First New) al Paint

International Paint Ltd Report number not soecified Unoublished

Section 5 5.1-5.11 Prowse G.M. 2009 The Efficacy of Copper in Antifouling Paints Yes Internation ~ B5.10.2/04 International Paint Ltd Report (First New) al Paint

number not soecified Unoublished Section 6 B6.1.1 2003 Intersmooth 360 Ecoloflex SPC Antifouling BEA368 Dark Yes Internation 181

Brown : Acute Oral Toxicity in Rats (New First) al Paint

1 leoo~ ~umber 7432-03 GLP/Unou~l 1s~e~

126


Section No I Reference Author (s) Year Title Source (where different from company) Data Pr ot ection Owner Essential Essent ial No Com pany, Report No. GLP ( w her e relevant ) I Claimed studies for studies for

{Un)Published {Yes/ No) evaluat io n evaluat ion Yes No

Section 6 B6.1.2 iiiiii 2001 Intersmooth 365 Ecoloflex {BEA363) Acute Dermal Yes Intemation IZI Toxicity {Limit) Test in Rats

Gl9,~npu~l1s~e~ {New First) al Paint

Report Number 17983 Section 6 B6.1.3 - 2003 Intersmooth 360 Ecoloflex SPC Antifouling BEA368 Dark Yes Intemation IZI

Brown : Acute Inhalation Toxicity Study in Rats {New First) al Paint

leoo~ ~umber 7433-03 GLP/Unoutil 1s~e~ Section 6 B6.2/0l 2001 Intersmooth 365 Ecoloflex {BEA363) Acute Dermal Yes Intemation IZI

Irritat ion Test in Rabbits Repo~ ~um~er H~H

{New First) al Paint

l!J1unpublished Section 6 B6.2/02 iiiiii 1997 Intersmooth 360 Ecoloflex Dermal I rritation Test in Yes Intemation IZI

Rabbits {New First) al Paint

1 ~um~er IHl6 Report GLP/Unoublished

Section 6 B6.2/03 1998 Intersmooth 460 Ecoloflex Primary Eye Yes Intemation IZI Irritat ion/Corrosion in Rabbits

Report Numberl {New First) al Paint

!1-HIUI !~9,~npublished Section 6 B6.3 liiiiiiiiiiiiii 1994 Ecoloflex Paint Buehler Sensitisation Test in Guinea Yes Intemation IZI

PigsTest in Rabbits {New First) al Paint Reoort Number 9979 GLP/Unout>lisheel

Section 6 B6.4/0l Roper c s, Sherratt R 2003 The In Vitro Percutaneous Absorption of Copper in Two Yes Intemation ~ Paint Preparations Through Human Skin {New First) al Paint Inveresk Research, UK. Reoort Number 23056 GLP/Unoublished

Section 6 B6.4/02 Roper cs 2005 The In Vitro Percutaneous Absorpt ion of Copper in Two Yes Intemation ~ Paint Preparations Through Human Skin - Dermal {New First) al Paint Delivery Inveresk Research, UK. Report Number 24740 GLP/Unoublished

Section 6 B6.4/03 Roper cs 2005 The In Vitro Percutaneous Absorption of Copper in Two Yes Intemation ~ Paint Preparations Through Human Skin - An Expert {New First) al Paint Report Inveresk Research, UK. Report Number 25631 GLP/Unoublished

Section B6.4/04 Roper cs 2002· The In Vitro Percutaneous Absorption of Radiolabelled Yes Intemation ~ Zinc Pyrithione in Two Antifouling Paint Test Preparations {New First) al Paint Through Human Skin Inveresk Research, UK. Report Number 20499 GLP/Unpublished

Section 6.4/ McGurk c 2014 Dermal Penetration of Copper Compounds from Biocidal Yes Inernationa IZI Supplimentary Antifouling Paints Product Type 21 {PT21) {New First) I Paint

International Paint Ltd Report number not soecified Unoublished

127


Section No I Reference Author(s) Year Title Source (where different from company) Data Protection Owner Essential Essential No Company, Report No. GLP ( where relevant ) I Claimed studies for studies for

{Un)Published {Yes/ No) evaluat ion evaluat ion Yes No

Section 6.4/ Roper cs, Sheratt R. 2003 The In Vitro Percutaneous Absorption of Copper in Two Yes Intemation IZI Supplimentary Paint Test Preparations Through Human Skin, Inveresk (New First) al Paint

Study number 203927, Inveresk Report Number 23056, Inveresk Research. GLP/Unoublished

Section 6.4/ Toner F. 2009 The In Vitro Percutaneous Absorption of Radiolabelled Yes Intemation IZI Supplimentary Zinc Pyrithione in an Antifouling Paint Through Human (New First) al Paint

Skin, Charles River Study number 785726, Report number 30556, Charles River. GLP/Unoublished

Section 6.4/ Roper C, 2006 The In Vitro Percutaneous Absorption of Radiolabelled Yes Intemation IZI Supplimentary Toner F, Biocide in a Single Solvent-Based Paint Formulat ion (New First) al Paint

Prowse G, Hunter ], through Human Skin. Charles River Laboratories Maddens. Preclinica l Services.

GLP/Published

Section 6.4/ Toner F. 2012 The In Vitro Assessment of Different Methods for Yes Intemation IZI Supplimentary Removal of Zinc Pyrith ione in Paint from Human Skin, (New First) al Paint

Charles River Study number 785380, Report Number 30557, Charles River Laboratories. GLP/Unoublished.

Section 6.4/ Toner F. 2008 The In Vitro Percutaneous Absorpt ion of Zinc Through Yes Intemation IZI Supplimentary Human Skin Following Application of Three Paints (New First) al Paint

Containing Zinc Oxide to Human Skin, Charles River Study Number 779529, Report number 28075, Charles River GLP/Unpublished.

Section 6.4/ Toner F, 2005 The In Vitro Percutaneous Absorption of Radiolabelled Yes Intemation [gJ Supplimentary Crow LF, Econ ea 028 in a Single Paint Formulation Through (New First) al Paint

Roper cs. Human Skin, Inveresk Study Number 775566, Inveresk Report Number 25468, Inveresk Research. GLP/Unoublished

Section 7 No study reports submitted




128


Hempel 's Antifouling Olympic 86951

Reference list of studies submitted and validated by Section number for the representative product Olympic 86951 :

Section No / Refer ence Author (s) Year Tit le Data protection Owner Essential Essential No. Source Claimed (Yes/ No) stud ies for studies for

Company evaluation evaluation Report No. Yes GLP No (Un )Published

62.2.2 Guldberg et al 2002 High-Alumina Low-Silica HT Stone Wool Flbres - A No - llSI Chemica l Composit iona I Range with High Biosolubility. Regulatory Toxicology and Pharmacology 35, pp 1-10. Published

62.2.2 HempelA/S 2005b Safety Data Sheet for Hempel's Ant ifouling Olympic No - llSI 86951. 26/07-2005 Published

63.1 Ramsay N 2005 Olympic 86951 Physico-Chemical testing of Olympic Yes Hempel A/S ~ 86951. (first) Inveresk Research, Tranent, Edinburgh, Inveresk Study No : 207298, Inveresk Report No : 24516 GLP Unpublished

63.4 Ramsay N 2005 Olympic 86951 Physico-Chemical testing of Olympic Yes Hempel A/S ~ 86951. (first) Inveresk Research, Tranent, Edinburgh, I nveresk Study No: 207298, Inveresk Report No : 24516 GLP Unpublished

63.6 Ramsay N 2005 Olympic 86951 Physico-Chemical testing of Olympic Yes Hempel A/S ~ 86951. (first) Inveresk Research, Tranent, Edinburgh, Inveresk Study No : 207298, Inveresk Report No: 24516 GLP Unpubl ished

63.7 Soria M 2003 Storage Stability Test: Hempel's Antifouling Olympic Yes Hempel A/S ~ 86951-50220 (first) Project number A2931PES. February 2003. Unpublished

129


Section No/ Reference Author(s) Year Title Data protection Owner Essential Essential No. Source Claimed ( Yes/No) studies for studies for

Company evaluation evaluation Report No. Yes GLP No ( Un )Published

B3.8 Soria M 2003 Storage Stability Test: Hempel's Ant ifouling Olympic Yes Hempel A/S ~ 86951-50220 (first) Project number A2931PES. February 2003. Unpublished

B3.8 PSD 2002 Pesticides Safety Directorate No - ~ Data requirements handbook Published

B3.10.2 Ramsay N 2005 Olympic 86951 Physico-Chemical testing of Oly mpic Yes Hempel A/S ~ 86951. (first) Inveresk Research, Tranent, Edinburgh, Inveresk Study No : 207298, Inveresk Report No : 24516 GLP Unoublished

84.1 Eng K 1999 Qualitative and Quantitative Determinat ion of Yes Hempel A/S ~ Cuprous Oxide in Antifouling Paints. Hempel's (first) Analytica l Laboratories. Report number A99044. February 1999 Unoublished

84.1 Lykke S E 1999 Quantitat ive Determination of Cuprous Oxide in Yes Hempel A/S ~ Antifouling Paints, Method Validation. AnalyTech (first) Milj0laboratorium ApS Unoublished

84.1 ASTM 1999 Standard Test Method for Chemical Analysis of No ~ Cuprous Oxide and Copper Pigments

B5.2 Hempel A/S 2005a Product data Sheet for Hempel's Antifou ling No - ~ Olympic 86950 Tin-free. February 2005

Published

B5.3 Hempel A/S 2005a Product data Sheet for Hempel's Antifou ling No - ~ Olympic 86950 Tin-free. February 2005

Published

B5.6.1 Little & DePalma 1988 Marine Biofouling No - ~ Treatise on Materials Science and Technology 28, pp 89-119.

Published

B5.10.2 Soria M 2006 Efficacy report for Hempel's Antifouling Olympic Yes Hempel A/S ~ 86951, Barcelona - Lab R&D, Report number (first) A1440RES, Project number PR99070A, March 2006 Unpublished

B5.10.2 Soria M 2008 Efficacy report of Hempel's Antifou ling Olympic Yes Hempel A/S ~ 86951, Barcelona - Lab R&D, Report number (first) A4050RES, Project number A7836PES, April 2008 Unoublished

130

Dicopper oxide PT 21

Section No/ Reference Author(s) No.

85.10.2 Willeboordse s

85.10.2 Wright R

86.1.1

86.1.2

86.1.3 Anderson B

86.2.1

86.2.2

86.3 Pritchard J D

Product-type 21 January 2016

Year

2008

2005

2005a

2005b

2002

2005c

2005d

2005e

Title Source Company Report No. GLP

Un Published Hempel Marine Maintenance Report, Project number NLSTW000008, March 2008 Un ublished Hempel's Ship Data, Sand Heron, Apri l 2005 Un ublished Hempel's Antifou ling Olympic 86951 Acute Oral Toxicity (Acute Toxic Class) Test in Rats.

MLJY Mo~epok Mo : ;41;215•• GLP

Unpublished

Hempel's Antifouling Olympic 86951 Acute Dermal Toxicity (Limit) Test in Rats

Stu y No : 506944,

GLP

unpublished

Report No :

Statement on acute inhalation test ing with paint mixes. Inveresk Research, Tranent, Edinburgh 07/05-2002 Un ublished Hempel's Antifouling Olympic 86951 Acute Dermal Skin Irritation Test in Rabbits.

24267 GLP

stuay No : 506970,

No : 506965,

Un ublished

Report No:

86951 Acute Eye

Report No:

Hempel's Antifouling Olympic 86951 Local Lymph Node Assay. Inveresk Research, Tranent, Edinburgh, Inveresk Study No : 506923, Inveresk Report No: 24264 GLP Un ublished

13 1

Data protection Owner Claimed ( Yes/ No)

Yes (first)

Yes first Yes

(first)

Yes (first)

Yes (first)

Yes (first)

Yes (first)

Yes (first)

Hempel A/S

Hempel A/S

Hempel A/S

Hempel A/S

Hempel A/S

Hempel A/S

Hempel A/S

Hempel A/S

Essentia l studies for evaluation

Yes

Essential studies for evaluation

No

Dicopper oxide PT 21

Section No / Refer ence Author(s) No.

66.4 Roper c s

67.7.2 OECD

69/ 01

69/ 02

69/ 03

69/ 04

69/ 05 Hempel NS

Product-type 21 January 2016

Year

2006

2004

2005a

2005b

2005c

2005d

2005b

Title Source Company Report No. GLP

Un Published The In Vitro Percutaneous Absorption of Copper in a Single Commercial Paint Formulation Through Human Skin. Inveresk Research, Tranent, Edinburgh, Inveresk Study No : 777359, Inveresk Report No: 25983 GLP Un ublished Harmonisat ion of Environmental Emission Scenarios. An Emission Scenario Document for Antifouling Products in OECD countries - ESD PT21. Project number 9M2892.0l. September - 2004 Published Hempel's Antifou ling Olympic 86951 Acute Oral Toxicity (Acute Toxic Class) Test in Rats.

MLJY Mo~epok Mo: ;41;215•• GLP

Unpublished

Hempel's Antifouling Olympic 86951 Acute Dermal Toxicity (Limit) Test in Rats

stuay No: 506944, Report No:

No : 506970, Report No:

86951 Acute Eye

No: 506965, Report No: 24267 GLP un ublished Safety Data Sheet for Hempel's Ant ifouling Olympic 86951. 26/07-2005 Published

132

Dat a protection Owner Claimed ( Yes/No)

Yes (first)

No

Yes (first)

Yes (first)

Yes (first)

Yes (first)

No

Hempel A/S

Hempel A/S

Hempel A/S

Hempel A/S

Hempel A/S

Essentia l studies for evaluatio n

Yes

Essential studies for evaluation

No

Dicopper oxide - ECHA

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