Review of BBP for Prioritization

Jay Xu, Ph.D.

Valtris Specialty Chemicals

Nov. 21, 2019

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Agenda

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Introduction

BBP Production and Sales in U.S. Over the Past 10 Years

BBP Applications, Then and Now

WWTP (waste water treatment plant) at Plant Making BBP

BBP Health and Tox Test Summary

Introduction

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BBP, commercially known as Santicizer 160, was introduced as a PVC stabilizer in 1950-60s.

Valtris Specialty Chemicals is the only manufacturer of BBP in U.S. It is made at a single site in Bridgeport, NJ.

It is a high solvating, fast fuser plasticizer for PVC• BBP is compatible with PVC• BBP helps PVC to dissolve and mix together quickly• Processing can be done at relatively lower temperature (saving energy).• If temperature is kept the same (as other plasticizers), processing time is shortened

(improve productivity)

Typical PVC Applications:• Rigid PVC – larger part of the PVC volume, contains no plasticizer

o PVC pipe, PVC siding, PVC fences, PVC window profile, etc.• Flexible PVC – 30~60 phr plasticizer (making PVC softer and also helps processing)

o PVC flooring (tiles), PVC roofing, IV bags, PVC coating and adhesives, etc.

History of Production & Sales in US

• EPA has done an excellent job of restricting BBP production and sales• Santicizer® S-160 (BBP) production in 2018 (<7 million lbs) was about 10% of the

production in 2010• Its sales was around 2.4 million lbs in 2018, only about 4% of its sales in 2008• From the production volume and sales of BBP in US, it is a low priority case

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How BBP Production Compared to Overall Phthalate Plasticizers

• BBP production is < 1% of total phthalate products in NA now

• It is used only in niche applications and has become a small volume player

• It is a low priority product from the volume point of view

Total Phthalate reference - IHS July 2015 Plasticizers report numbers converted to lbs.

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Applications in NA, Then & Now

Flooring Applications Ended around 2014

Flooring Applications Ended around 2014

RoofingAuto-

motive Sealants

FlooringRoofing

Automotive SealantsIndustrial Coatings

History, Applications Then Application Now

Bubble Size – Sales in 2008 Bubble Size – Sales in 2018~ 6% of 2008 Sales

• EPA has done an excellent job of restricting BBP production and sales – to industrial applications only.

• Roofing and automotive glass sealants are the leftover applications.

• BBP is a low priority substance. With today’s applications, there is virtually no human contact during the product use.

We had one single customer who bought 40 millions lbs of BBP in 2008. It was for consumer vinyl flooring. They bought 0 lbs since 2015

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Applications in NA, Now

PVC Roofing PVC Automotive Sealants

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WWTP at Bridgeport NJ Plant where BBP Is Produced

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Brief Explanation of Process Description:

The following treatment methods are used to remove or destroy wastewater contaminants: (1) Neutralization, (2) Equalization, (3) Biological Aeration, (4) Clarification, and (5) Filtration. Activated sludge from secondary clarification may be reused at Aeration Basins to allow microbes to be reused. Final sludge generated from treatment is further reduced by dewatering and then shipped out for disposal as a non-hazardous waste. Neutralization, equalization, and clarification are primary treatment. Aeration basins/activated sludge is secondary treatment along with the secondary clarification, and filtration is tertiary treatment.

WWTP at Bridgeport NJ Plant where BBP Is Produced

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YearBBP Influent Average

(ppm)BBP Effluent Average

(ppm)Removal

Rate2016 728 <0.03 >99%2017 7 <0.03 >99%2018 11 <0.03 >99%

The Bridgeport plant has monitored the concentration of BBP in the influent (weekly) and effluent (monthly) for several years and the yearly average data are included in the below table. The removal rate is above 99% for all three recent years (2016-2018), confirming that BBP is readily biodegradable and WWTP is very effective at removing it.

Review of BBP for prioritization

Raymond M. David, Ph.D., DABT

behalf of

Jay Xu, Ph.D.

Valtris Specialty Chemicals

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Overview

• Hazards and exposure

• Potential for effects on sensitive subpopulations

• Persistence and bioaccumulation

• Conclusion: BBP is a low priority substance

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Acute hazards

• BBP is not acutely toxic:– Oral LD50 = 2330 mg/kg in rats, higher in mice (NTP 1982)

– Dermal LD50 > 10 000 mg/kg in rabbits (Birch, 1976)

– Not irritating to the eyes or skin (Birch 1976)

– Not a dermal sensitizer (Little, 1983)

– Not a respiratory sensitizer (Butala et al., 2004; Dearman et al., 2009); not likely to act as an adjuvant (Kimber & Dearman, 2010)

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Repeated dose toxicity

• No chronic toxicity or carcinogenicity in mice exposed to >1000 mg/kg (NTP, 1982)

• MNCL in female rats exposed to 600 mg/kg for 24 months (NTP, 1982) that was not reproducible (NTP, 1997).

• Pancreatic cell acinar adenomas in rats exposed to 500 mg/kg (NTP, 1997).

• Macrocytic anemia, hypospermia and atrophy of seminiferous tubules in male rats exposed to >1000 mg/kg (NTP, 1997) over 26 weeks.

• Testicular atrophy in male rats exposed to 480 mg/kg for 4 days (Lake et al., 1978).

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Reproductive/Developmental

• Reproductive NOEL of 250 mg/kg based on fertility in a 2-generation study (Tyl et al., 2004).

• Developmental NOEL of 50 mg/kg based on AGD in 2-generation study (Tyl et al., 2004). NOEL of 420 mg/kg based on visceral and skeletal anomalies (Field, 1989).

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Neurotoxicity

• No evidence of neurotoxicity in rats or hens at >1000 mg/kg (Bischoff, 1983; Branch, 1982; Robinson, 1991).

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Exposure

• According to NHANES, exposure to BBP, which was already 2-10 times lower than for other phthalates, has decreased over the past 20 years (Zota et al, 2014; CDC, 2019).

• Using an average of the last 3 NHANES values, exposure to BBP is 0.5 – 1.2 μg/kg/day for 95th percentile (75 kg person) - ~ 10 times lower than DEHP. 0

10

20

30

40

50

60

70

2000 2005 2010 2015

MBzP (μg/g creat)*

* = 95th percentile16

Exposure

• Vinyl flooring is associated with higher BBP exposure (Just et al, 2015), although BBP contributes little to total exposure (Beko et al, 2013).

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Susceptible subpopulations

• CPSC convened a Chronic Hazard Advisory Panel to review potential effects of susceptible subpopulations exposed to phthalates.– Established an ADI of 1 mg/kg/d based on all concerns

– NHANES indicates that exposures are ~1000 lower than ADI

• Association of exposure with respiratory effects in children (CPSC, 2014), yet experimental evidence does not support causation (Butala et al, 2004) and BBP use in vinyl flooring (typically used in households with children that have respiratory issues) contributes to exposure (Just et al, 2015).

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Susceptible subpopulations

• No association of BBP exposure with risk of Diabetes (Radke et al, 2019)

• Slight evidence of developmental effects on male reproductive tract (Radke et al, 2018)

• Moderate evidence of impact on semen quality (Radke et al, 2018)

• Indeterminate and inconsistent evidence of effect on testosterone (Radke et al, 2018)

• Indeterminate association of exposure with pregnancy outcome (Radke et al, 2019)

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Susceptible subpopulations

From Radke et al, 2019

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Persistence/Bioaccumulation

• BBP is biodegradable (readily biodegradable, CITI Japan, 1992; inherently biodegradable, Saeger and Tucker, 1976).– Supported by measurement of wastewater treatment

showing 62% degradation (Clara et al, 2010).

• BBP has a low potential for bioaccumulation in fish (BCF of 12.4-225 based on experimental design, Carr et al, 1997).

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Summary

Production and sales of BBP has declined more than 90% in the past 10 years. It is a small volume plasticizer now.

BBP has low hazard potential based on NOEL values of ≥ 100 mg/kg.

Exposure to BBP is ~ 1 μg/kg/day for 95% of population based on average of last 3 NHANES.

BBP has low potential for effects on sensitive subpopulations.

BBP is biodegradable and is not bioaccumulative.

At the BBP production site, WWTP removes >99%.

BBP should be a low priority for further action.

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References

• Bekö G, Weschler CJ, Langer S, Callesen M, Toftum J, Clausen G. Children’s phthalate intakes and resultant cumulative exposures estimated from urine compared with estimates from dust ingestion, inhalation and dermal absorption in their homes and daycare centers. PloS one. Apr 23;8(4):e62442, 2013

• Birch MD, Acute Dermal Toxicity of Santicizer 160, Monsanto unpublished report, Report Y-76-54, 1976.

• Birch MD, Primary Skin Irritation, Acute Eye Irritation of Santicizer 160, Monsanto unpublished report, Report Y-76-54, 1976.

• Bischoff M. Six week study of Santicizer(R) 160 plasticizer administered in the feed to Sprague Dawley rats: neuropathological study, Monsanto unpublished report, 1983.

• Branch DK. Six week study of Santicizer(R) 160 plasticizer administered in feed to Sprague-Dawley rats, Monsanto unpublished report, 1982.

• Butala JH, David RM, Gans G, McKee RH, Guo TL, Peachee VL, White Jr KL. Phthalate treatment does not influence levels of IgE or Th2 cytokines in B6C3F1 mice. Toxicology. 201, 77-85, 2004.

• Carr KH, Coyle GT, Kimerle RA. Bioconcentration of [14C] butyl benzyl phthalate in bluegill sunfish (Lepomis Macrochirus), Environmental Toxicology and Chemistry: An International Journal, 16, 2200-3, 1997.

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References

• Centers for Disease Control, Fourth National Report on Human Exposure to Environmental Chemicals Updated Tables, January 2019, Volume One, https://www.cdc.gov/exposurereport/index.html, 2019.

• Chemicals Inspection and Testing Institute, Biodegradation and bioaccumulation data of existing chemicals based on the CSCL JAPAN, Published by Japan Chemical Industry Ecology-Toxicology & Information Center, 1992.

• Clara M, Windhofer G, Hartl W, Braun K, Simon M, Gans O, Scheffknecht C, Chovanec A. Occurrence of phthalates in surface runoff, untreated and treated wastewater and fate during wastewater treatment. Chemosphere, 78, 1078-84, 2010.

• Consumer Product Safety Commission, Toxicity Review of Butyl Benzyl Phthalate, 2014.

• Dearman RJ, Betts CJ, Beresford L, Bailey L, Caddick HT, Kimber I. Butyl benzyl phthalate: effects on immune responses to ovalbumin in mice. Journal of Applied Toxicology. 29, 118-25, 2009 .

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References

• Field EA. Final report: Developmental toxicity evaluation of butyl benzyl phthalate (CAS No. 85-68-7) administered in feed to CD rats on gestational days 6 to 15, NTP-89-246, 1989.

• Just AC, Miller RL, Perzanowski MS, Rundle AG, Chen Q, Jung KH, Hoepner L, Camann DE, Calafat AM, Perera FP, Whyatt RM. Vinyl flooring in the home is associated with children’s airborne butylbenzyl phthalate and urinary metabolite concentrations. Journal of Exposure Science and Environmental Epidemiology, 25, 574, 2015.

• Kimber I, Dearman RJ. An assessment of the ability of phthalates to influence immune and allergic responses. Toxicology. 271, 73-82, 2010.

• Lake BG, Harris RA, Grasso P, Gangolli SD. Studies on the Metabolism and Biological Effects of n-Butyl Benzyl Phthalate in the Rat, CMA unpublished report 232-78, 1978.

• Little JR, Investigation of Santicizer 160 (Butyl Benzyl Phthalate) as a Potential Allergen, Monsanto unpublished report, 1983.

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References

• National Toxicology Program, Carcinogenensis Bioassay of Butyl Benzyl Phthalate in F344/N Rats and B6C3F1 Mice, TR-213, NTP-80-25, NIH Publication No. 82-1769, 1982.

• National Toxicology Program, Toxicology and Carcinogenesis Studies of Butyl Benzyl Phthalate in F344/N Rats, NTP TR-458, NIH Publication No. 97-3374, 1997.

• Radke EG, Braun JM, Meeker JD, Cooper GS. Phthalate exposure and male reproductive outcomes: a systematic review of the human epidemiological evidence. Environment international, 121, 764-93, 2018.

• Radke EG, Galizia A, Thayer KA, Cooper GS. Phthalate exposure and metabolic effects: a systemaic review of the human epidemiological evidence. Environ Int. Jun 10:104768, 2019.

• Radke EG, Glenn BS, Braun JM, Cooper GS. Phthalate exposure and female reproductive and developmental outcomes: a systematic review of the human epidemiological evidence. Environment International, 130, p.104580, 2019.

• Robinson EC. Lack of neuropathological changes in rats after exposure to butyl benzyl phthalate. Journal of Toxicology and Environmental Health, Part A Current Issues, 32(3):345-7, 1991.

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References

• Saeger VW, Tucker ES. Biodegradation of phthalic acid esters in river water and activated sludge. Appl. Environ. Microbiol. 31, 29-34, 1976.

• Tyl RW, Myers CB, Marr MC, Fail PA, Seely JC, Brine DR, Barter RA, Butala JH. Reproductive toxicity evaluation of dietary butyl benzyl phthalate (BBP) in rats. Reproductivetoxicology, 18, 241-64, 2004.

• Zota AR, Calafat AM, Woodruff TJ. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001–2010. Environmental Health Perspectives, 122, 235-41, 2014.

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