Vol XVIII No 13 9 December 1967

Journal of the Society of Cosmetic Chemists

ContentsPage

SOCIETY NEWSSt. Louis Chapter...................................................................... 753Martin M. Rieger Honored......................................................... 754I.F.F. Award.............................................................................. 754

REVIEW PAPERMeasuring the meaning of fragrance

J . S tephan J e l l in e k ............................................................. 755ORIGINAL PAPERS

Hand degerming evaluation utilizing a split-use method Ja m e s B row n , J r . , Ron a ld J . E r ik s so n , Frank Yackov ich ,

and D avid T a b e r................................................................. 769The color of red hair

P e te r F le sch , E liza b e th J . E so d a , and S id n e y A . K a tz .............. 777Use of electronic data processing in anti-dandruff clinical research

M artin G re if and H arry J . P r o k o p .......................................... 785Pseudomonads in cosmetics

S a u l T e n e n b a u m .................................................................. 797A statistical approach to the evaluation of cutaneous responses

to irritantsW. M . W ooding and D. L . O p d yke ............................................ 809

DEPARTMENTSSynopses for card indexes................ xviiLiterature survey........................................................................ xxiBook reviews............................................................................ 831Index to Volume XVIII................................................................ 835Index to advertisers................................................................... xlii

J^)eauty qfjmgmnce.......

made-to-measurejoryour success!Fragrance of outstanding beauty adds the distinctive char­acter— the individuality — that can bring success to a perfume or cosmetic . . . or a complete line!

Givaudan s demonstrated creative shill, its unusual variety of fragrant materials, its world wide affiliations and its market know-how are all coordinated to bring you fragrances o( unique new beauty and originality — made-to- measure for your success.

G I V A U D A N '•C O R P O R A T I O N

V A U D A N321 West 44th Street, New York, N.Y., 10036

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

I f , _ a * '

.. ^

EVANSTESfED AND APPROVED FORCOLD WAVE LOTIONS AND DEPILATORIES

THIOVANIC A(Evans’ brand of vac distilled thioglycolic acid.

AMMONIUMTHIOGLYCOLATEM ade w ith vacuum distilled th iog lycolic afcid.

CALCIUMTHIOGLYCOLATEHigh purity fo r depilatories.

l A | 1AND all o ther derivatives of Thioglycolic Acid.

'l l# , - Jt&r/ .

A\ %̂ \ y

? f r

p\ &

W rite fo r sam ples and data sheets.E V A N S

Æ e v a n s ^ ^

V 250 EAST 43rd STREET NEW YORK, N.250 EAST 43rd STREET PHONE 212-683-0071

NEW YORK, N.Y. 10017 TWX 212-867-4286

Journal of the Society of Cosmetic Chemists

VOLUME XVIII • NUMBER 13

Published by The Society of Cosm etic Chem ists, Inc.

Publication Office: 20th and Northampton Streets, Easton, Pa. 183-12

Editor:

Associate Editors:

Business Manager:

Editorial Assistant:

Literature Survey:

British Editorial Office:

German Editorial Office:

Publication Committee:

President:

President-Elect:

Secretary:

Treasurer:

Karl Laden, 6220 Kansas Ave., N. E., Washington, D. C. 20011

Martin M. Rieger, 170 Tabor Road, Morris Plains, N. J. 07950

Gabriel Barnett, 145 Paterson Ave., Little Falls, N. J. 07424

George King, 505 Hamilton Road, Merion Station, Pa. 19066

Mariam C. McGillivray, 761 North Valley Chase Road, Bloomfield Hills, Mich. 48013

Joseph H. Kratochvil, 100 Jefferson Road, Parsippany, N. J. 07054

Society of Cosmetic Chemists of Great Britain, Ashbourne House, Alberon Gardens, London N.W. 11, Great Britain

Gesellschaft Deutscher Kosmetik-Chemiker, e. V., Beselerstrasse Hamburg-Grossflottbek, Germany

Karl Laden, Chairman, Martin M. Rieger, Gabriel Barnett,Ruth R. Bien, Jean F. Caul, Maison G. deNavarre,Paul Finkelstein, Sol Gershon, E. J. Karolyi, Paul G. I. Lauffer

OFFICERS FOR 1967

Henry F. Maso, 210 Lawrence St., New Brunswick, N. J. 08902

Jesse Starkman, 505 Kingston Terrace, Deerfield, III. 60015

Harry Isacoff, 43-23 Forty-second St., Long Island City, N. Y. 11104

Kenneth Hartley, 75 Ninth Ave., New York, N. Y. 10011

Su bscrip tio n : JO U R N A L OF THE SOCIETY OF COSMETIC CHEM ISTS is p ub lis h e d six t im e s per year, in February, M arch, May, A u g us t, S e p te m be r, and D ecem ber, in th e U. S. A., w ith a d d itio n a l issues p u b lish e d in E urope. Y early s u b s c r ip tio n p rice is $34.00 pos t-p a id in N orth A m erica and U. S. possess ions and $35.30 in a ll o th e r c o u n tr ie s . The s u b s c r ip ­tio n ra te to m e m b e rs o f th e S ocie ty is $13.00 and is in c lu d e d in th e m e m b e rs h ip dues.

© C op y righ t 1967 by T h e S ocie ty o f C osm etic C he m is ts , Inc.

M issing N um b ers: B ecause o f u n ce rta in and haza rd o us co n d itio n s , c la im s fo r m iss in g n u m b e rs can be e n te rta in e d on ly fro m s u b ­sc ribe rs in th e c o u n try o f o rig in o f th e p a r t ic u ­la r issue and m u s t be m ade w ith in JO days fro m date o f issue.

Chang e of A d d ress : M e m be rs and su bsc rib e rs are urged to g ive n o tice o f change o f a d ­d ress to th e E d ito ria l A s s is ta n t and th e o ffice o f th e Society.

R espo nsib ility for S tatem ents P ub lish ed : TheS ocie ty o f C osm e tic C he m is ts , th e C om m itte e

on P u b lica tion s , and th e Board o f D irec to rs a s ­su m e no re s p o n s ib ility fo r s ta te m e n ts or o p in io n s a dvanced by c o n tr ib u to rs to th is Jo u rn a l.

Ed ito rs and P u b lish e rs : A b s tra c ts o r d ig e s t o f a rtic le s n o t e xcee d ing 400 w ords m ay be p u b ­lish e d , d u ly c re d ite d to th e a u th o r and JO U R ­NAL OF TH E SOCIETY OF COSM ETIC C H E M ­ISTS. R e p rin t in g or m ore ex te n s ive co py in g (w ho le pages or a rtic le s ) are fo rb id d e n , e xcep t by spec ia l p e rm is s io n , in w rit in g , fro m th e C ha irm an of th e P u b lica tion C o m m itte e .

Authors: W hen u s ing illu s tra tio n s or q u o ta tio n s ta ke n fro m c o py rig h te d p u b lic a tio n s , a u th o rs m u s t g e t w r it te n p e rm iss ion fro m th e co p y ­r ig h t h o ld e r to re p ro d u ce th e sam e.

M anuscript: M a n u s c rip ts sh ou ld be p repa red in accordance w ith th e “ D ire c tio ns fo r th e P re p ­a ra tio n o f M a n u s c r ip ts ," cop ies o f w h ich are a va ila b le fro m Dr. Karl Laden , 6220 K ansas A ve n ue N. E., W a sh in g to n , D. C. 20011

S econd-c lass p os ta ge pa id a t E aston, P e n n sy l­van ia .

w M fU R n i u w t n r t w t* ' . n f 3 Cl ‘»£11

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

HalbV 11111

¡1

are BEST for YOUR formulations

Uniform Q uality—Exceeds T.G.A. Standards Prompt Delivery

AMMONIUM and MONOETHANOLAMINE

THIOGLYCOLATES THIOGLYCOLIC ACID

S m lS k

Write fo r technical in form ation.

■

1Ì/T, 2WS\\v\i

HALBY PRODUCTS CO., INC.WILMINGTON, DEL. 19899

'Phone: (302) OL 6-5428Thiogly colic & Thiodipropionic Acids & Derivatives

2SCD

-*KC

CZ3«OCc 5

axe

«gco d

sEo

Specify A m erchol lanolin derivatives fo r u n i f o r m q u a l i t y in y o u r p r o d u c t s throughout the w orld.

A C E T U L A N ®A M E R C H O L ®A M E R L A T E ®C H O L E S T E R O LM O D U L A N ®P O L Y L A N RR I C I L A N -S O L U L A N ®V I S C O L A N ®W A X O L A N ®

Write for theAmerchol brochure listing our world wide distributors.

Acetylated Lanolin Alcohols M ulti-stero l Extracts Lanolin Fatty Acid Derivatives USP quality Acetylated Lanolin Essential Polyunsaturate Lanolin Alcohol Ricinoleates Ethoxylated Lanolin Derivatives Lanolin Oil Lanolin Wax

SPAIN SWEDE!

~ T ± 5

”“C2

CD

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

For nearly h a lf a ce n tu ry . . . u npa ra lle led crea tive a rtis try . . . in the deve lopm en t and to ta l expression of the frag rance concep t and its in f in ite nuances . . . has been the ded ica ted role o f A lb e rt Verley & Company.

In the e vo lu tio n of a p rom is ing essence from w hich b e a u tifu l frag rances are conce ived . . . Verley ins is ts upon ing re d ie n ts o f the h ighest q u a lity . . . u tiliz e s the fin e s t labo ra to ry fa c ilit ie s e m p lo y in g the m ost advanced of s c ie n tif ic te ch n iq u es . and possesses, th rough extensive and c o n tin u in g research, a com prehensive know ledge o f consum er requ irem en ts . The m a te ria ls used in the c re a tio n and p rod u c tio n are c a re fu lly screened

. . the re su ltin g com pounds p rec ise ly checked and per­fo rm ance tested in co n tro l and a p p lica tio n labora to ries. O b jective eva lu a tion of a frag rance th ro u gh re liab le panel p rocedures assures a m arket a c c e p ta b ility of Verley com pounds.

Add to th is unp a ra lle le d heritage the endless search fo r un ique and p rovoca tive frag rances . . . the ca p tu re . . . then the su b tle b le n d in g o f rare and e lus ive q u a litie s th a t em body the p erfum e long rem em bered and cherished. Each scent . . . deve loped so le ly to perfo rm and fu l f i l l the fu n c tio n fo r w h ich it was crea ted . . . in su ring the fu ll a rom a tic expression and acceptance of your p roduct.

for unparalleled fragrance . . . for the expression .. for your product. . .check with the man from VERLEY

A l b e r t V e r l e y & C O M P A N Y124 CA SE DRIVE . SOUTH PLA IN FIELD , NEW JE R S E Y 07080

N.J.: 201-754-2222 N.Y.: 212: MU 3-38813804 W EST NORTH A VEN U E . STONE PARK, ILL IN O IS 60165

10325 LOW ER AZUSA ROAD . T EM P LE C ITY, CALIFORN IA 91780 A R O M ESCEN CE INC.

10 R U E P E R G O L ES E . PARIS 16, FRAN CE

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

CALLON

WHITTAKERF O R . . .

T A L C+

K A O L IN+

O T T A S E P T ®+

S T E A R A T E S+

C O S M E T IC C O L O R S+

M I N E R A L C O L L O ID S+

T IT A N IU M D IO X ID E T G A

Whittaker, Clark & Daniels, Inc. 100 Church St., New York, N. Y.

It’s all of these things because it's based on BRIJ 97 — one of three new BRIJ ethoxylated oleyl ethers with desirable properties for cos­metic formulations: “super ele­gance,” freedom from odor and color, and a new low look in costs.

Using technique based on this new gel, Atlas Product Develop­ment Laboratories have made a clear gel hairdressing that stays clear and stable through freeze- thaw cycling and prolonged storage

at above-room temperatures. The unique clarity and stability made possible by this new Atlas gel tech­nique are readily adaptable to many other types of gels—for topi­cal pharmaceutical preparations as well as cosmetics.

For first-hand experience with the new clear gel technology, send for Atlas Cosmetic Bulletin LD-11, “Clear Gel Hairdressing,” and ask for samples and prices on BRIJ 93, 97 and 99 (polyoxyethylene 2, 10

and 20 respectivelyj for complete oil-water solubility range.

Clear ringing gels that stay clear are another example of how you get something extra from

OH EM ICAL INDUSTRIES, .no

WILMINGTON, DELAWARE 19899t he le a d e r in s o r b i to l - s u r fa c ta n t t e c h n o lo g y

Where the aromatics action is.The action is here in our research tower where hundreds of chemists are developing new ideas to enhance the aromatics we offer you, as well as developing new fragrances.It’s in the toxicological and skin irritation studies we prepare and make available to the industry

on every one of our products.And it continues in our plant where we synthesize all our aromatics from readily available domestic materials so you don't have to worry about nature’s uncertainties.It’s right up to the point of

departure, where a Roche action

quality control team checks ever drum of aromatics before shipnnIt makes sense to go where the aromatics action is. Contact Aromatics Dept., Roche Chemic Division, Hoffmann- La Roche Inc., NutleyX ROCHE New Jersey 07110.

A V A IL A B L E F O R E V A L U A T IO N :

Cosmetic Grades of UCON^ Fluids and Propellants. Write Dept. WHK, 31st Floor, Union Carbide Corporation, 270 Park Avenue, New York, N.Y. 10017

JOURNAL OF THE SOCIETY OF COSMETIC CFIEMISTS

A word about Sonneborn

First.That’s the word.Because Sonneborn was

the first (1915) to produce white oils and a great many com m ercially available petrolatums.

And Sonneborn has been

first ever since.Frankly, we don't know

of any white oil or petrola­tum problem we can’t solve.

But if there is one, we’d like to find out about it. And solve it. Because solving problems is the only way

we can stay the way we are.No. 1 in white oils and

petrolatums.Call (212-826-1000) or

write Witco Chemical, Son­neborn Division, Depart­ment SCC, 277 Park Ave., New York, N. Y. 10017.

F irs t!

which says . a lotaboutWitco Chemical

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS xi

Pa rm avertFLORAL GREEN NOTE NON-IRRITATING STABLE IN ALKALIES EXTREMELY POWERFUL

Parmavert is a new, extremely powerful, long lasting aromatic chemical of high purity which fills the need for a subtle green and floral- fresh note so essential to total naturalness. Especia lly e ffec tive in bouquets o f f lo ra l c o m p o s itio n and m odern com pounds.

Parmavert is a new acetal, developed in our laboratories, stable in soaps as well as in cosmetics and perfumes. It is non- rritating, and can be used as a replacement for Heptin Carbonate esters.

COMPAGNIE PARENTOCroton-on-Hudson, New York

INC.

New York Office: 507 Fifth Avenue, MU 7-5133 / Detroit: 14812 Alma Avenue, LA 7-5018 / Chicago: 2141 West Touhy Avenue, 764-8668 / Compagnie Parento, Limited. 70 Mack Avenue, Scarborough, Ontario, Canada. 694-1123

Only you know what makes her hair so soft.But we know a way to make her reach for yonr product again and again.We offer the low-odor anhydrous ethanol that helps you create aerosols with extended shelf-life. The reliability of our ethanol starts with our integrated raw material resources. Quality comes from three decades of experience in ethanol refining, controlled by 32 exacting in-process tests. And its aerosol performance and aging are checked in our laboratory studies.Shouldn’t you be giving your product the appeal of an ethanol with reliability, purity, and quality?

@ Call Enjay’s cosmetic specialists at 212-974-6318. Enjay Chemical

Company, 60 West 49th Street,

Dept. C-119M, N. Y„ N.Y. 10020.

XIV JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

■ffsasEI" '

o n ly R.I.T.A.AMONG ALL LANOLIN REFINERS OFFERSDETAILED, INDEPENDENT LABORATORY DOCUMENTATION ON THE SAFETY AND EFFICACY OF ALL R.I.T.A.COSMETIC AND PHARMACEUTICAL LANOLIN AND LANOLIN BASED PRODUCTSR.I.T.A. Furnishes This Test Data:• Oral Toxicity• Eye and Skin Irritation• Potential Guinea Pig

Sensitization• Sub-Acute Dermal Toxicity

A partial list of R .I.T .A . products includes: R ITALAN 100% Pure Lano­lin Oil . . . FORLAN Series of Chlo- resterol Absorption Bases . . . LANETO Ethoxylated Water Soluble Hydrophyllic Lanolin . . . RITACHOL Liquid Lanolin-Sterols Emulsifiers... SUPER-SAT Hydrogenated and Hy- drogenated-Ethoxylated Lanolins.

/I I

» n 4 /

«

Il IIR.I.T.A. Lanolin Emollients and Conditioning Agents are Stable, Non-Allergenic and Non-Irritating—Oil-in Water or Water-in-Oil Emulsion Systems

• R.I.T.A. Super-Sat Hydrogenated Lanolinis a superb ameloriant when added to shampoo, soap and detergent formulations (less than 1%) decreases eye and dermal irritancy associated with ail surface-active agents. Imparts an unusual silky after-feet to skin and hair. . . excellent for all skin and hair products.

• R.I.T.A. Super-Sat AWS Alcohol and Water Soluble Ethoxylated and Hydrogenated Lanolin acts as an auxiliary emulsifier, pil solublizer, and gel former. . . particularly suited foreye makeup, facial cleansers, washable cold creams, etc.

• R.I.T.A. Laneto Ethoxylated, Water-Soluble, Hydrophyllic Lanolin provides excellent surface- active properties for gels, soaps, aerosols, shaving creams, lotions, deodorants, bath oils and hair sprays.

R .l.T .A .’s research and product consultation service are yours for the asking. Samples and formulations sent on request.

R . I . T . A . Chemical Corporation 612 North Michigan Ave. Chicago, 111. 60611 Telephone 312-787-00S1

America's Largest Supplier of Wool Grease and Lanolin Products

REPRESENTATIVESBRAZIL COMPANHIA QUIMICA NOVOBRAS, P.O. Box 722«. Sao Paulo 2-SP, Brazil-Telephone No.

37-9743ENGLAND JACOBSON VAN DEN BERG & CO. (UK) LTD.. Market House. Richbell Place. LondonW.C. 1 -

Telephone No. Holborn 9113-9FRANCE GATTEFOSSE SFPA, IS Rue Constant, Lyon. Rhone, France—Telephone Noe. (78) 84-90-56

AND ITALY and 84-56-39GERMANY H. ERHARD WAGNER, 282 Bremen-Lesum, Poatfach 112, Bremen, Germany—Telephone No.

(0421) 63-30*68TAKASAGO PERFUMERY CO., LTD., P.O. Box #1033, Tokyo Central, Japan-Telephone No. 551-6351

JAPAN

SPAIN

SWEOEN

COMMERCIAL OUIMICA MASSO SA, Valencia 320, 2° 2°. Barcelona. Spain-Telephone No. 257-54-00F. af PETERSENS. LoddekopmQe, Sweden—Telephone No. 046-394 66

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS x v

MIRANOL AMPHOTERIC SURFACTANTS FAMOUS FOR MILDNESS AND SAFETY...

The Surface Active Agents that N ot Only M eet the DRAIZE T E S T , but EXCEED its requirem ents . . .NO irritation at any tim e!NOT ONLY THE “ DRAIZE TEST", MIRANOLS PASS THE “ BABY TEST" THOUSANDS OF TIMES EVERY DAY...

Miranols do not cause irritation to eyes . . . have no unpleasant odor and feature unexcelled chemical stability.

Miranols come through where conventional surfactants cannot deliver the performance, solving product prob­lems that other surface active agents can't solve. Only the Miranol ionic balance in AMPHOTERIC SURFAC­TANTS is the recognized, respected and accepted standard for complete application versatility.

MIRANOL AMPHOTERIC SURFACTANTS ARE IN A CLASS BY THEMSELVES!

Wr'te for Technical and Product Development Data Book

272 COIT STREET • IRVINGTON, N. d. Phone: Area Code 201 • 374-2500

Agents in Principal Cities Throughout the World

X V I JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

ETHYL A N \ . . the most effective liquid lanolinadditive for hair sprays provides

S I X F U N C T I O N A L A D V A N T A G E S

j Increases plasticity — reduces hygroscopicity of PVP films - reduces theii sensitivity to weather conditions — eliminates flaking during dry weather and stickness in wet weather.

2 Forms stable solutions with PVP/alcohol concentrates.

3 Compatible with all aersol propellents.4 Can be incorporated at room temperature by simple mixing.

5 Prevents valve clogging due to crystallization and sedimentation of suspended solid ingredients.

6 Imparts sheen.For details see our Product Bulletin 53

ROBINSON WAGNER CO., INC.L E A D E R S I N L A N O L I N R E S E A R C H A N D D E V E L O P M E N T

628 WAVERLY AVENUE • MAMARONECK, NEW YORK

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS X V II

SYNOPSES FOR CARD INDEXES

The following synopses can be cut out and mounted on 3 X 5 in. index cards for refer­ence, without mutilating the pages of the Journal.

Measuring the meaning of fragrance: J. Stephan Jellinek. Journal of the Society of Cosmetic Chemists 18, 755 (Dec. 9, 1967)

Synopsis—Three different techniques for measuring the meaning of fragrar.ces are reviewed. Profiling, Semantic Differential, and Multidimensional Scaling are dis­cussed with special emphasis on the last. The application of these techniques by perfumers and in consumer testing is described.

Hand degerming evaluation utilizing a split-use method: James Brown, Jr.,Ronald J. Eriksson, Frank Yackovich, and David Taber. Journal of the Society of Cosmetic Chemists 18, 769 (Dec. 9, 1967)

Synopsis—Utilizing a modified split-use method, two bacteriostatic soaps were evaluated for their utility in degerming the hands. One soap contained 0.75% (by weight) of hexachlorophene and 0.75%, of 3,4,4'-trichlorocarbanilide; the other con­sisted of equal parts by weight of 3,5-di- and 3,4',5-tribromosalicylanilides, 4,4'- dichloro-3-(trifluoromethyl)carbanilide, and 3,4,4'-triehlorocarbanilide for a total concentration of 2%. A significant reduction in bacterial counts was achieved by both soaps as compared to a nonmedicated soap. It is emphasized that rigorous handling of data requires that the confidence interval be identified when per cent reduction is used as a basis for describing degerming efficiency.

The color of red hair: Peter Flesch, Elizabeth J. Esoda, and Sidney A. Katz.Journal of the Society of Cosmetic Chemists 18, 777 (Dec. 9, 1967)Synopsis—The iron pigments extracted with boiling acids from human red hair and chicken feathers are closely related and are possibly identical. Evidence is presented that these unique substances arc well-defined chemical entities and not artifacts of keratin hydrolysis. The iron pigment is probably the major pigment of human red hair. Its limited extractability from red hair is due to its destruction during ex­traction and not to the small amount present in the hair. In all of its forms the iron pigment has been proved to be a metallo-protein. It can be broken down to a compound with a relatively small molecular size which retains all the essential properties of the originally extracted pigment. Synthesis of an iron-protein in melanocytes raises many questions which cannot be answered at present.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS xix

Use of electronic data processing in anti-dandruff clinical research: Martin Greifand Harry J. Prokop. Journal of the Society of Cosmetic Chemists 18, 785 (Dec. 9, 1967)

Synopsis—Fifteen different compositions were studied in a pilot clinical program in terms of their ability to control the symptoms of dandruff. The clinical protocol is discussed briefly. Electronic data processing of the double-blind monadic clin­ical study is described in some detail. For comparison purposes, the data were analyzed both by EDP and manual means. The relative economics are discussed.

Pseudomonads in cosmetics : Saul Tenenbaum. Journal of the Society of Cosmetic Chemists 18, 797 (Dec. 9, 1967)

Synopsis—Pseudomonads are bacterial organisms found in soil, water, air, food, in and on the body. They break emulsions, and produce foul odors and slime while decomposing cosmetics and pharmaceuticals. The organisms have the capacity to develop resistance to agents inimical to other microorganisms.

Preparations are placed on preservation study to determine the ability of a product to withstand consumer use and abuse. Some materials can inactivate the preservatives used to protect the product. The only effective way of knowing whether a product is protected is to inoculate the formulation with organisms and examine for viability.

The ability of pseudomonads to adapt to and proliferate in preparations is such that maintenance of the inoculum is insufficient for adequate preservation status. The only properly preserved preparation is one that is essentially self-sterilizing. A self-sterilizing preparation can be achieved, in most cosmetic products, without an increase in costs or loss of marketability.

A statistical approach to the evaluation of cutaneous responses to irritants: W. M.Wooding and D. L. Opdyke. Journal of the Society of Cosmetic Chemists 18, 809 (Dec. 9, 1967)Synopsis—This study was done to test the application of certain common statistical experimental designs to the field of human patch testing where they do not appear to have been used previously, and to investigate certain variables affecting irritation test results. Sodium lauryl sulfate, a typical irritant of general interest, was used. Two experiments are described in which several factors thought to affect irritation results were tested; these included irritant concentration, certain time factors, and types of patch used. Irritation was basically scored on a five-point scale. Results showed that experimental and subject-to-subject variation could be greatly reduced by adequate experimental design, that several factors of interest were influential in the system, and that the error of measurement (estimation by a judge scoring the patch sites) was much smaller than had been expected. One of the significant effects of considerable interest was the finding that the degree of observable irrita­tion was a function of the interval between removal of a patch and the time the site was scored.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS xxi

LITERATURE SURVEY*

Analytical

Thin-Layer Chromatographic Identification of Lipstick Dyes. Dcshusses, J., and Des- baumes, P., Mitt. Gebiete Lebensm. Hyg., 57, 373-76 (1906).

Application of Differential Scanning Colorimetry in Pharmaceutical Analysis. Rcubke, R., and Mollica, J. A., Jr., J. Pharm. Set., 56, 822-25 (July, 1967).

Identification and Differentiation of Organic Medicinal Agents. V. Quaternary Ammonium Compounds. Chatten, L. G., etal., Ibid., 834-27.

Chromatographic Analysis of Polyglycerols and Their Fatty Acid Esters. Saharabudhe, M. R., J. Am. Oil Chemists' Soc., 44, 376-78 (July, 1967).

Gas-Liquid Chromatographic Analysis of Mono and Diglyceridcs. Saharabudhe, M. R., and Legari, J. J,, Ibid., 379-80.

The Differential Thermal Analysis of Edible Fats. Moran, D. P. J., Proc. Soc. Anal. Chem., 3, 170-71(1966).

Antioxidants for the Chromatography of Lipids. Neudocrffcr, T. S., and Lea, C. H., J. Chromatog., 21, 130-40 (1966).

Quantitative Determination of Cholesterol in Autooxidation Mixtures by Thin-Layer Chromatography. Horvath, C., Ibid.. 22, 52-59 (1966).

Determining the Water Content of Emulsions of the First Order of the Type Oil-in-Water and Water-in-Oil. Jily, O. A., Textil-Praxis, 22, 271-72 (April, 1967) (German).

Derivatography. New Thermoanalytical Method. Wein, '1'.. Pharm. Dell. Epistem. Ekdosis, 6, 96-113 (1966).Tests on Anodized Aluminums. Class, M., and Class, E., Aluminium, 43, 98-100 (February, 1967) (German).

Acid-Base Titration and Distribution Curves. Waser, J., J. Chem. Educ., 44, 274-76 (May, 1967).Modern Electroanalytical Methods. Almargo, V., Inform. Quint. Anal. (Madrid), 20, 170-83 (1966) (Spanish).Nuclear Magnetic Resonance Determination of Bacteriostats. Dietrich, M. W.. and Keller, R. E., J. Am. Oil Chemists' Soc., 44, 491-93 (August, 1967).Thin-Layer Chromatography; Application to Analysis of Fats. Grynberg, H., Tluszcze i SrodkiPiorace, Kosmet., 10, 119-30(1966) (Polish).Determination of the Complete Structure of Natural Lecithins. Kuksis, A., and Marai, L., Lipids, 2, 217-24 (March, 1967).Detergent Intermediates Analysis. Carasik, W., et al., Soap. Chem. Specialties, 43, 106-08 (May, 1967).Automating the Analytical Chemistry Lab. Scientific Res., 2, 87-88 (August, 1967).

Prepared by J. H. Kratochvil and H. Feinberg.

X X l l JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Analytical Chemistry in the Cosmetics Industry. Fairchild, C. M., Anal. Chem., 39, 22A- 34A (August. 1967).

Thin-Layer Chromatography in the Wax Analysis: The Identification of Wax Alcohols andAcids. Scholz, G. H., Fette, Seifen, Anstrichmittel, 69, 333-35 (May, 1967) (German).

Determination of Certain Complex Dosage Forms by Differentiating Non-Aqueous Titration. Lin, S., Dissertation Abstr., 27, Part B : 3052B (March, 1967).New Methods Detect Titration End Points. Chem. Eng. News, 45, 40-42 (July 10, 1967).

Submicro Methods for the Analysis of Organic Compounds. The Determination of Hy­droxyl Groups. Belcher, R., et al., Anal. Chim. Acta, 38, 435-45 (July, 1967).

Chromatographic Analysis of Optical Brighteners. Theidel, H., and Schmitz, G., J. Chroma- tog., 27, 413-22 (April, 1967) (German).

Fractionation of Hydrocarbons of Human Hair Lipids by Chromatographic and Thermal Diffusion Methods. Gershbein, L. L., et al., Ibid., 431-49.

Differential Analysis of the Scleroprotein Lysers Used in Cosmetics, by Thin-Layer Chroma­tography. Bonadeo, I., Parfum., Cosmet., Savons, 10, 206-15 (May, 1967) (French).

The Determination of Some Aromatic Diamines Used in Hair Dyes by Thin-Layer Chroma­tography. Pinter, I., and Kramer, M., Ibid., 257-60 (June, 1967) (French).

Potentiometric Determination of Dissociation Constants. Benet, L. Z., and Goyan, J. E., J. Pharm. Sci., 56, 665-80 (June, 1967).

Spectroscopy in Chemistry. Daltrozzo, E., et al., Seifen-Ole-Fette-Wachse, 93, 443-48 (June, 1967) (German).

Separation, Determination, and Identification of Antipyrine and Benzocaine in Glycerol and Propylene Glycol Bases. Krause, R. T., J. Assoc. OJJic. Anal. Chemists, 50, 685-88 (June, 1967).

Bacteriology

Preservatives. In: Pharmaceutical Sciences—1966. A Literature Review. Polli, G. P.,and Ravin, L. J., J. Pharm. Sci., 56, 782 (July, 1967).

Comparative Evaluation of Antibacterial Soaps. Jungermann, E., et al., J. Am. Oil Chemists’, Soc., 44, 232-34 (1967).

Comparison of a Short-time Preservation Test at High Temperature and Storage under Normal Conditions. Lukesch, H., Parfum., Cosmet., Savons, 10, 298-302 (July, 1967).

Antimicrobial Substances for Cosmetic Preparations with Special Considerations of Bisphe- nols. Treuhoff, I., Parfuem. Kosmetik, 47, 355-58 (December, 1966) (German).

The Role of the American Medical Association in Product Evaluation. Jerome, J. B., J. Am. Oil Chemists' Soc., 44, 470-72 (August, 1967).

The Microbiological Availability of Soap Bacteriostats. Taber, D., et al., Ibid., 473-75.

Use of Bacteriostats in Soaps and Household Cleansing Agents. Vinson, L., Ibid., 476-77.

In Vitro Evaluation of Tissue Substantivity of Selected Antibacterial Agents. McNamara. T. F., and Steinbach, M., Ibid., 478-80.

Method for Determining the Distribution of Bacteria in the Skin. LTpdegraff, D. M., Ibid., 481-83.

New Preservatives for Ointments and Creams. Neuwald, F., Fette. Seif en, A nstrichmittel, 69, 361-65 (May, 1967) (German).

Quantitative Measurement of Bacterial Growth by the Reduction of Tétrazolium Salts. Tengerdy, R. P., etal., Appl. Microbiol., 15, 954-55 (1967).

The Preservation of Pharmaceutical and Cosmetic Preparations Against Microbial Spoilage, Parker, M. S., and Barnes, M., School Sci. Rev., 48, 386-93 (1967).

S,B,-Dihalodiethylammoniutn Thiosulfonates. U. S. Patent 3,305,581. Filed October 28, 1963. Patented February 21, 1967. Granted to The Dow Chemical Co.

Method for Study of Saliva and Bacteria in Dental Enamel Décalcification. Sylvester, C. J., and Green, G. E., J. Dental Res., 46, 584-94 (May-June, 1967).

Disinfectants. Walters, A. H., Mfg. Chemist Sf Aerosol News, 38, 44-46 (June, 1967).

Computer Simulation of Fermentation Systems. Koga, S., et al., Appl. Microbiol., 15, 683-89 (July, 1967).

Antifungal Activity of Isothiocyanates and Related Compounds. I. Naturally Occurring Isothiocyanates and Their Analogs. Drobnica, L., et al., Ibid., 701-09.

Antifungal Activity of Isothiocyanates and Related Compounds. II. Mononuclear Aromatic Isothiocyanates. Drobnica, L., etal., Ibid., 710-17.

Effect of High Oxygen Concentration on Virulence of Staphylococcus Aureus. Schmidt, J. P., and Ball, R. J., Ibid., 757-58.Effect of Continued and Interrupted Radiation on Microorganisms. Borick, P. M., and Fogarty, M. G., Ibid., 785-89.

Chemistry and BiologyTransesterification of Lecithin on Silicic Acid Columns. Camejo, G., J. Chromatog., 21,6-12 (1966).Detection of Rearrangement Reaction of Natural Glycerides by Chromatography. Chakra- baty, M. M., et ah, Ibid., 84-89.Polyhedral Emulsion Particles. Graves, M. J., and Freshwater, D. C., J. Pharm. Pharmacol., 19, 193-94 (March, 1967).Stability of Paraffin Oil Emulsions. Petricic, V., Farm. Glasnik, 22, 81-87 (1966) (Serbo- croat).Theory of Gel Formation. I. Ligand Field of the Gegenions. Thiels, H., and Cordes, J., Kolloid-Z.Z. Polym., 216/217, 361-70 ( 1967) (German).Particle Size in Cosmetic Pigments. Hadert, H., Riechstoffe, Aromen, Koerperpfiegem., 17, 32-95 (March, 1967) (German).Measuring the Contact Angles of Powder-Liquid Systems. Heertjis, P. M., and Kossen, X. W. F., Powder Technoh, 1,33-42 (January, 1967).Rheology of Gels. Blatt, J. H., and Allan, B. D., U. S. Govt. Res. Develop. Rept., 41, 133 (1966).

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS xxiii

X X I V JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Will Controversial DMSO Become Solvent Once More? Med. World News, 8, 36-37 (June 16, 1967).Use and Dosage Ratios of Sorbitol in Cosmetics. Bergwein, K., Seifen-Ole-Fette-Wackse, 93, 357-58 (May, 1967) (German).

The Synthesis of Keratin. Walker, G. T., Ibid., 531-32 (July, 1967) (German).

The Chemistry and Applications of Organotin Compounds. Chalmers, L., Mfg. Chemist & Aerosol News, 38, 37-41 (June, 1967).

Emulsion Technology and HLB-Value. Bergwein, K., Fette, Seifen, Anstrichmittel, 69, 353-55 (May, 1967) (German).

The Flow Properties of Emulsions. Fluckiger, W., Ibid., 449-52 (June, 1967) (German).

The Composition of Organic Films Formed on Human Teeth. Armstrong, W. G., Caries Res., 1,89-103(1967).

Determination of the Thixotropy of Ointment Vehicles. Delonca, H., et al., Ann. Phann. Franc., 25, 225-35 (March, 1967) (French).

The Rheology of Some Oil-in-Water Emulsions Stabilized by Condensed Complex Films. Talinan, F. A. J., et al., J. Pharmacol, 19, 417-25(1967).

Some Legal, Chemical and Physical Aspects of Permitted Color Additives. Koch, L., Am.Perfumer Cosmetics, 82, 35-40 (July, 1967).

Rheologic Research on Cream Bases as a Function of Temperature. Neuwald, F., and Scheel, D., Parfum., Cosmet., Savons, 10, 216-20 (May, 1967) (French).

Progress in the Field of Pyridine Oxidation Dyes Used in Hair Tints. Lange, F. W., Ibid., 261-66 (June, 1967) (French).

High Molecular Weight Alcohols of Human Hair Lipids. Singh, E. J., and Gershbein, L. L.,J. Chromatog., 29, 229-31 (July, 1967).

The Acidities of Weak Acids in Dimethyl Sulfoxide (DMSO) Solutions. III. Comments on the H-Acidity Scales. Steiner, E. C., and Starkey, J. D., J. Am. Chem. Soc., 89, 2751-52(May 24, 1967).Acidity in Nonaqueous Solvents. Y. Acidity Scales in Dimethyl Sulfoxide Solution. Ritchie, C. D., and Uschold, R. E., Ibid., 2752-53.

Effect of Preparation Parameters on the Initial Size Distribution Function in Oil-in-Water Emulsions. Beeher, P., J. Colloid Interface Sci., 24, 91-96 (May 1967).

Changes in the Rheological Properties of Emulsions on Aging. II. Viscosity Changes in W/O Emulsions at Rates of Shear From 0.133 sec.-1 to 10.77 sec.-1. Sherman, P., Ibid., 97-106.Rheological Changes in Emulsions on Aging. III. At Very Low Rates of Shear. Sherman. P., Ibid., 107-14.Process for Forming Optically Active Menthol. U. S. Patent 3,308,169. Filed October 17. 1963. Patented March 7, 1967. Granted to Colgate-Palmolive Co.Method of Selecting Emulsions Intended for the Preparation of Cosmetics and Skin Products. U. S. Pat. 3,300,386. Filed July 3, 1962. Patented January 24, 1967. Granted to A. F. R. Peyron.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS X X V

The Metal Chelates of Thio Derivatives of B-Diketones. Yokoyama, A., ct al., Chew. I1 harm. Bull. (Tokyo), 15 (April, 1967).

Consumer ProductsSome Recent Developments in Cosmetic Systems. Chester, J. F. L., Soap, Perfumery Cosmetics, 40, 393-98 (June, 1967).

Suntan Preparations. Consumer Rrpts., 32, 364-67 (July, 1967).

Dow Corning Silicones. Specialties, 3, 30 (May, 1967).

Makeup in the Soviet Union. Lozzi, C., Parfnm., Cosmet., Savons, 10, 221-32 (May, 1967) (French).

Cosmetic Compounding. Kalish, J., Drug Cosmetic Ind., 100, 147-48 (June, 1967).

Hair Dyes for Men. Cook, M., Ibid., 40-41, 170-72 (August, 1967).

Cleaning Products for Wigs and Hairpieces. Shansky, A., Am. Perfumer Cosmetics, 82, 43-45 (July, 1967).

The Art of Pogonotomy. The Saga of Shaving Traces the History of Man and the Develop­ment of an Industry. Stoller, L., Givandanian, 3-6 (June, 1967).

Odoriferous Compounds in Hair Tonics Containing Isopropyl Alcohol. Bergwein, K., Seifen-Ole-Fette-Wachse, 93, 317 (May, 1967) (German).

Hair Dyeing. Walker. G. T., Ibid.,319-20.

Aerosol Mouth Fresheners Might Spark New Aerosol Product Category. Aerosol Age, 12, 21. 108 (June, 1967).

Union Carbide Restudies Hair Spray Use Patterns. Ibid., 37, 40 (July, 1967).

Cyclohexylcyclohexanone in Mercapto-Acetate Hair-Treating Compositions. U. S. Patent 3,331,743. Filed April 28, 1964. Patented July 18, 1967. Granted to Allied Chemical Corp.Green Walnut Shell Extract Used with Methyl Salicylate and Anthranilate in Sunscreen Products. Rovesti, P., Soap, Perfumery Cosmetics, 40, 408 (June, 1967).

Preparation of a Hair Conditioner Containing an Alcohol. Netherlands Appl. 6,607,794. Published December 20, 1966. Granted to Firtna Hans Schwarzkopf.

Depilatories. Netherlands Appl. 6,508,984. Published January 13, 1967. Granted to Chemway Corp.Agents for the Protection of Hair from Damage Upon Bleaching and Dyeing. Canadian Patent 761,905. Published June 27, 1967. Granted to Theraehcmie chemisch thera- peutische Gesellschaft.Aminodihydroxynaphthalene Hair Dyes. Canadian Patent 761,906. Published June 27, 1967. Granted to Therachemis chemisch therapeutische Gesellschaft.

New Eye Makeup. French Patent 1,484,652. Published June 16, 1967. Granted to Harriet Hubbard Ayer.Composition for the Treatment of the Skin, Particularly in the Form of a Mask. French Patent 1,484,662. Published June 16, 1967. Granted to Metzingcr. (Mine).

X X V I JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Fixatives for the Hair. French Patent 1,484,730. Published June 16, 1967. Granted to R. A. Yerhovert.

Dentifrice Composition. French Patent 1,484,762. Published June 16, 1967. Granted to Colgate-Palmolive Co.

Hair Treating Agent. French Patent 1,484,804. Published June 16, 1967. Granted to The Realistic Co.

New Colored Resins for Hair Lacquers and Lotions. French Patent 1,484,836. Published June 16, 1967. Granted to L'Oreal.

Antiperspirant (Anticholinergic). Canadian Patent 761,413. Published June 20. 1967. Granted to The Procter & Gamble Co.

False Eyelash Container and Curler. U. S. Patent 3,333,593. Filed October 3 1966. Patented August 1, 1967. Granted to Barbara J. McGivern.

Camouflage of Blemishes and Scars. Thorne, N., Brit. J. Clin. Pract., 20, 593-96 (1966).

Transparent Soaps. Whalley, G. R., Perfumery Essent. Oil Record, 58, 465-68 (July, 1967).

Hair Treating Compositions. Netherlands Appl. 6,609,031. Published January 3, 1987. Granted to Dr. Karl Thomae.

Hair Treating Compositions. Netherlands Appl. 6,610,296. Published January 30, 1967. Granted to Oreal S. A.

Universal Hair Cosmetic. Netherlands Appl. 6,608,470. Published January 30, 1967. Granted to Oreal S. A.

A New Quaternary Ammonium Compound Hair Conditioning Agent. Egan, R. R., and Hoffman, B. J., Paper presented at the AOCS Annual Meeting, Chicago, October, 1967.

Alcohol Ether Sulfates in Shampoos. Watanabe, H., and Groves, W. L., Ibid.

The Effect of Structural Differences of Amine Oxides on the Foaming Properties of Simple Shampoo Formulations. Goodell, R. N., Ibid.

Fatty Glycols and Isostearyl Alcohol as Lipstick Components. Egan, R. R., and Hoffman, B. J ..Ibid.

A Clinical Evaluation of Sunscreens. Owens, D. W., and Freeman, R. G., Clin. Med., 74, 45-46 (August, 1967).

Improvements in or Relating to the Treatment of Keratinie Fibres (Permanent Wave). British Patent 1,067,065. Published May 3, 1967. Granted to L’Oreal.

Hair Setting Compositions. British Patent 1,070,304. Published June 1, 1967. Granted to Schwarzkopf Yerwaltung.

Dyeing Keratin with Reactive Dyes. British Patent 1,070,730. Published June 1, 1987. Granted to Sandoz Patents Ltd.

Nail Strengthening Compositions. British Patent 1,071,807. Published June 14, 1967. Granted to Recherches Pharmaceutiques et Scientifiques.

Stabilized Dyeing Compositions. Canadian Patent 763,406. Published July 18, 1967. Granted to Clairol, Inc.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS X X V l l

Hair Dye. German DAS 1,242,323. Published June 15, 1967. Granted to Hans Schwarz­kopf.

New- Compositions for the Care of the Nails. French Patent 1,485,602. Published June 23, 1967. Granted to J. V. Morelle.

Depilatory Composition. British Patent 1,064,388. Published April 5, 1967. Granted to Chemrvay Corp.

Coloring Agents for the Hair. French Patent 1,488,169. Published July 7, 1967. Granted to Therachemie Chemisch Therapeutische Ges.

Theatrical Makeup. Bergwein, K., Seifen-Ole-Fette-Wachse, 93, 533 (July, 1967).

Aluminum Organic Complex and Antiperspirant Compositions Containing the Same. U. S. Patent Reissue 26,250. Filed Tune 11, 1963. Patented August 15, 1967. Granted to Helene Curtis (Orig. No. 3,030,274).

Method for Applying Artificial Nails. Canadian Patent 764,743. Published August 8, 1967. Granted to Maxwell M. Lappe.

Face Masks. Bergwein, K., Seifen-Ôle-Fette-Wachse, 93, 555-57 (August 2, 1967).

Mascara Preparations, Ibid., 560.

Some Specialty Soaps. Whalley, G. R., Am. Perfumer Cosmetics, 82, 47-49 (August, 1967).

Compositions for Dyeing Keratinic Fibres. Canadian Patent 765,380. Published August 15, 1967. Granted to L’Oreal.

Compositions for Inhibiting Body Odours. British Patent 1,077,289. Published July 26, 1967. Granted to R. T. Vanderbilt Co.

Cosmetic Devices (Lipstick and Eyebrow Brushes). British Patent 1,078,584 Published August 9, 1967. Granted to Joseph Aversa.

Improvements in or Relating to Bath Oils. British Patent 1,077,016. Published July 26, 1967. Granted to Martin Fuld Emory.

Compositions for Dyeing Keratinic Fibres. British Patent 1,079,553. Published August 16, 1967. Granted to L’Oreal.

Dyeing and Permanent Waving of Keratinous Substances. British Patent 1,077,758. Published August 2, 1967. Granted to Hoyu Kabushiki Kaisha.

Hair Dye Compositions. British Patent 1,076,127. Published July 19, 1967. Granted to Monsieur Robert Aktiebolag.Hair Treating Composition (Permanent Wave; Hair Straightener). British Patent 1,076,420. Published July 19, 1967. Granted to The Gillette Co.Oral Preparations Containing an Antimicrobial Agent. British Patent 1,076,613. Published Junel, 1967. Granted to Sandoz Patents Ltd.Product for Masking Visible Skin Defects. French Patent 1,489,041. Published July 21, 1967. Granted to Filmove Studie Bar-Randov.Hormone Cosmetics. Alexander, P., Am. Perfumer Cosmetics, 82, 31-38 (September, 1967).

Review of Pediatric Products and Markets. Faust, R. E., Ibid., 57-60.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTSxxviii

Synthetic Gum Dispersions. U. S. Patent 3,325,416. Filed October 1, 1963. Patented June 13, 1967. Granted to Colgate-Palmolive Co. (Clear liquid gel shampoo).

Eyebrow Curler. U. S. Patent 3,339,561. Filed June 15, 1964. Patented September 5, 1967. Granted to Lilian L. Brickner.

Process and Compositions for Mending Fingernails. U. S. Patent 3,342,686. Filed June 11, 1962. Patented September 19, 1967. Granted to Max Factor & Co.

Self-Heating Shaving Preparation Composition. U. S. Patent 3,341,418. Filed March 3, 1965. Patented September 12, 1967. Granted to The Gillette Co.

Sun-Screening Compositions. U. S. Patent 3,341,419. Filed June 30, 1965. Patented September 12, 1967. Granted toShulton, Inc.

Shampoo Composition. U. S. Patent 3,341,460. Filed October 21, 1965. PatentedSeptember 12, 1967. Granted to Colgate-Palmolive Co.

Hair Colourants. British Patent 1,080,154. Published August 23, 1967. Granted to LTnilever Ltd.

Anthraquinone Dyes and their use in the Dyeing of Keratinie Fibres. British PatentI, 080,264. Published August 23, 1967. Granted to L'Oreal.

Topical Compositions for Inhibiting Perspiration. British Patent 1,080,960. Published August 31, 1967. Granted to A. H. Robins Co.

Scopolamine Esters and Acid Addition Salts Thereof Useful as Anti-Perspirant Agents. British Patent 1,081,577. Published August 31, 1967. Granted to The Procter & Gamble Co.

Hair Bleaching Composition. British Patent 1,083,007. Published September 13, 1967. Granted to Rayette-Faberge, Inc.

Method of Dyeing Hair and Compositions for LTse in the Method. Canadian Patent 767,081. Published September 12, 1967. Granted to L'Oreal.

Waving of Human Hair. Canadian Patent 766,735. Published September 5, 1967. Granted to Olin Mathieson Chem. Corp.

Fats and Oils

Influence of Cellular Structure on Some Technological Properties of Certain Oleaginous Raw Materials. Rac, M., Rev. Franc. Corps Gras, 14, 223-28 (April, 1967) (French).

Physical Properties of Triglycerides. IV. Dielectric Constant. Gouw, T. H., and Vlugter,J. C., Fette, Seifen, Anstrichmittel, 69, 223-26 (April, 1967).

The Influence of Glyceride Structure on the Rate of Autooxidation. Raghuveer, K. G., andHammond, E. G., J. Am. Oil Chemists’ Soc., 44, 239-43 (April, 1967).

Crystal Morphology in Hydrocarbon Systems. Chichakli, M., and Jessen, F. W., hid. Eng. Chem., 59, 86-98 (May, 1967).

Oleochemicals. Natural Fatty Acids as Base Materials for Technical Products. Osteroth,D., Seifen-Öle-Fette- Wachse, 92, 251-56 (1966) (German).

Non-Volatile Alpha-Branched Chain Fatty Esters. Ault, W. C. et al., J. Am. Oil Chemists’ Soc., 44, 506-08 (August, 1967).

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS X X IX

The Glassy Form of Hydrogenated Fat. Nikonov, I. V., Izv. Vysshikh Uchebn. Zavedenii, Pishchevaya Teckhnol., 1967, 131-33 (February, 1967) (Russian).

Glyceride Isomerizations in Lipid Chemistry. Serdarevich, B., J. Am. Oil Chemists' Soc., 44,381-93 (July, 1967).

Recent Developments in the Chemistry of Fatty Acids. Ansell, M. F., ./. Oil Colour Chem­ists’ Assoc., 49,884-93 (1966).

Quality and Defects of Soap. Bardella, E., Corriere Farm., 21,413-15 (1966) (Italian).

Composition of Coconut Oil. Augustin, P., Oléagineux, 22, 99-102 (February, 1967) (French).

Polymorphism of Lipids. Luzzati, V., and Spegt, P. A., Nature, 215, 701-04 (August 12, 1967).

The Monoene and other Wax Alcohols of Human Skin Surface Lipid and Their Relation to the Fatty Acids of This Lipid. Nicolaides, N., Lipids, 2, 266-75 (May, 1967).

ManufacturingApparatus for Evacuation of Viscous Liquids. Czechoslovakian Patent 119,315. Published July 15, 1966. Granted to R. Markea and M. Korejci.

Research in Nondestructive Testing. Sharpe, R. S., Brit. J. Non-Destruct. Test., 9, 10-15 (January, 1967).Flow Characteristics of Complex Soap Systems. White, A., Nature, 214, 585-86 (^5088 1967).Pulverizing and Drying Apparatus. U. S. Patent 3,317,415. Filed January 2, 1964. Patented May 2, 1967. Granted to Fluid Energy—Processing and Equipment Co.

Colorimeter Employing Tristimulus Valves. U. S. Patent 3,314,327. Filed December 13, 1961. Patented April 18, 1967. Granted to Honeywell, Inc.The Mixing of Powders and Pastes: Some Basic Concepts. Valentin, F. H H., Chem.Eng. {London), 208, 99-104, 106 (1967).

Hysteresis in the Flow Through an Orifice. Deckker, B. E. L., Nature, 214, 904 (¡¿5091 1967).Particle Reduction to Micron Size. Smith, E. A., Mfg. Chemist & Aerosol News, 38, 31, 36 (July, 1967).Selection of Filling Equipment. Soap Chem. Specialties, 43, 109-10 (June, 1967).

Technical Processes and Apparatus for the Continuous Manufacturing of Toilet Soaps. Sievers, L., Seifen-Ole-Fette-Wachse, 93, 433-37 (June, 1967) (German).

Tabletting Today. Mallee, J. P., Drug Cosmetic Ind., 101,98-102, 147-50 (July, 1967).

Analysis and Apparatus for Surface Rheological Measurements. Burton, R. A., and Mann- heimer, R. J., Advan. Chem. Soc., 63, 315-28 (1967).Improved Granulating Equipment. French Patent 1,456,886. Published October 28, 1966. Granted to Potasse & Engrais Chimiques.Powders Compression. Vergnon, P., Rev. Intern. Hautes Teny. Refract., 3, 399-408 (1966) (French).

X X X JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Six Tips on Processing Dry Chemicals. Bullock, H. L., Chem. Eng., 74, 186, 188 (April 24,1967).Principles of Powder Drying. Stockburger, D., Staub, Reinbaltung Luft, 27, 61-63 (February, 1967) (German).

Drying Systems and Equipment. Sloan, C. E., Chem. Eng., 74, 169-70 (June 19, 1967).

Air-Suspended Systems. Ibid... 171-84.Drying Theory and Calculations. Tsao, G. T., and Wheelock, T. D., Ibid., 201-14.

Method of Granulating Materials for Subsequent Forming into Tablets. U. S. Patent 3,308,217. Filed February 9, 1965. Patented March 7, 1967. Granted to L. Lowy & W. O. Wurtz.

PackagingPermeability of Plastics. Problems in Drug Packaging. Berger, H., Sci. Pharm., 35, 31-39 (January, 1967) (German).Fluid Develops New Plastic Pack. Aerosol Age, 12, 19 (August, 1967).

The Sepro Can. Irland, L. F., and Kinnavy, J. W., Drug Cosmetic Ind.. 101, 42-43, 164-67 (August, 1967).Aerosol Packaging/Marketing. Detergent Age, 4, 35-36 (July, 1967).

Solid Cardboard as a Packaging Material. Herwig, G. P., Soap, Perfumery Cosmetics, 40, 426, 428, 432 (June, 1967).

Aerosols: New Ways to Grow. Mod. Packaging, 40, 116-21 (August, 1967).

A New A.B.C. Guide of Packaging Papers—Part V. Day, F. T., Perfumery Essenl. Oil Record, 58, 327-30 (May, 1967).Plastics Packages for Cosmetics. Greber, W., Ilid., 382-84 (June, 1967).

Packaging Panorama. Day, F. T., Ibid., 403-05.

Packaging. In: Pharmaceutical Sciences—1966. A Literature Review. Polli, G. P., andRavin, L. J., J. Pharm. Sri., 56, 790 (July, 1967).

Packaging in the Perfumery and Allied Trades. LXXV. A New A.B.C. Guide of Packaging Papers—Part VI. Day, F. T., Perfumery Essenl. Oil Record, 58, 406-10 (June, 1967).

Flexible Plastic Producer-Dispenser of Foam. U. S. Patent 3,308,993. Filed March 16, 1966. Patented March 14, 1967. Granted to Victor M. Bruno.

Plastic Containers Revived. Aerosol Age, 12, 27-31, 99 (August, 1967).

Poly Vinyl Fluoride. Something New for Container Linings. R. W. Miller, Package Eng., 12,94-100(1967).Glass and Plastic Container Interactions with Contents. Am. Perfumer Cosmetics, 82, 25-30 (August, 1967).AMA Packaging Seminar. Drug. Cosmetic. Ind., 101,47 (September, 1967).

Perfumery and Essential OilsThe Perfumer’s Newsletter. Billot, M., Parfum., Cosmet., Savons, 10, 246-49 (June, 1967) (French).

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS X X X I

Citrus Essential Oils from Israel. Basker, H. B., Am. Perfumer Cosmetics, 82, 33-34 (July, 1967).

Absorption and Permeability of a Flavor in Plastic Containers as Determined by Head-Space Gas Chromatography. Donato, S. J., J. Pharm. Sci., 56, 759-60 (June, 1967).

Photoallergy to Sandalwood Oil. Starke, J. C., Arch. Dermatol., 96, 62-63 (July, 1967).

Compact Makeup and Their Perfumes. Specialties, 3, 31-33 (May, 1967).

Fragrance Yearbook 1967: Index of Fragrance Products; Index of Manufacturers. BeautyFashion, 52, 44-105 (June, 1967).

Perfumes as Insect Attractants and Repellents. Naarden News, 18, 2-3, 6-7 (May, 1967).

What’s Happening to Synthetic Flavors. Eiserle, R. J., Candy Ind. and Confectioners J., 128, 5, 58-59 (May 30, 1967).

Absorption and Elimination of Balsamic Compounds and Some Essential Oils. Le Nouene, J., Rev. Pathol. Comp., 3(10), 613-40 (1966).

The Applications of Infrared Spectroscopy to the Study of Essential Oils and Their Terpenic and Aromatic Components. Vernin, G., France Parfums, 10 (2), 35-54 (1967).

Essential Oils from Chrysanthemum Morifolium Leaves. Bahadur, R., and Gupta, G. N.,Riechstoffe, Aromen, Koerperpflegem., 17(2), 55-58 (1967).

The Presence of »-Hexyl Butanoate in Lavender and in Lavandin Essential Oils. Peyron,L., and Benezet, L., France Parfums, 10(2), 55-58 (1967).

( + )-i-Methyl-7-vinylbutyrolactone, a New Component of Lavender and Lavandin Oils. Klein, E., and Rojahn, W., Dragoco Rep. (Ger. Ed.), 14(1), 3—4 (1967).Octahydro-1,3a,6-trimethyl-lH-1,6a-ethanopentaleno-(l,2-C)-furan. French Pat. 1,484,429. Published June 9, 1967. Granted to International Flavors and Fragrances, Inc.

Flavor, Aroma, and Color. In: Pharmaceutical Sciences—1966. A Literature Review.Polli, G. P., and Ravin, L. J., J. Pharm. Sci., 56, 782 (July, 1967).

Oil of Bergamot; Speculation and Sophistication. Muller, P. A., Perfumery Essent. Oil Record, 58, 368-71 (June, 1967).Chemical Structure and Odour (V). Hoinologues and Structural Analogues of Cyclamen- aldehyde. Berends, W., and Linde, L. M., vd., Ibid., 372-78.

Odorant for Perfumery. Polish Patent 50,868. Published April 5, 1966. Granted to Warszawska Fabryka Syntetykow Zapachowych.New Perfume and Procedure for Its Preparation. French Patent 1,490,341. Published July 28, 1967. Granted to Universal Oil Products Co.

The Forsythia and Related Fragrances. A Study of the Golden Ball or Golden Bell. Per­fumery Essent. Oil Record, 58, 445-46, 501 (July, 1967).

Odorant Compositions. French Patent 1,489,241. Published July 21, 1967. Granted to N.V. Chemische Fabriel “ Naarden.”

Perfume Composition. German Patent 1,234,900. Published August 10, 967. Granted to Schering Akt.

XXX11 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

High Resolution Gas Chromatography in Aroma Research. Teranishi, R., Am. Perfumer Cosmetics, 82, 43-51 (September, 1987).

PharmacologyPharmaceutical Sciences—1966. A Literature Review. Polli, G. P., and Ravin. L. J., J. Pharm. Sci., 56, 781-803 (July, 1967).

Determination of Toxicity of Surface-Active Agents and Related Products. Pascual, J. O., Afinidad, 23, 507-18 (1966) (Spanish).

Eye Burns Caused by Modern Cosmetics. Eckermann, M., and Gessner, L., Z. Arztl. Fortbild., 60(10), 612-15 (1966).

Pharmacologically Active Cosmetics. Opdyke, D. L., Feinberg, H., and Burnett. C. M., Drug Cosmetic Ind., 101, 40 (September, 1967).

Effectiveness of Sodium Fluoride Dentifrices. Groen, P., and Brudevold, F., J. Dent. Children, 34, 122-27 (February, 1967).

Role of Starch in the Mechanism of Tablet Disintegration. Bonzunov, E. E., and Shev­chenko, S. M., Farmatsevt. Zh., 22, 45-48 (February, 1967) (Ukrainian).

Interaction of Sodium and Calcium Salicylates with Cationic Surfactants. Wan, L. S. C., J. Pharm. Sci., 56, 743—47 (June, 1967).

Compression Characteristics of Some Pharmaceutical Materials. Leigh, S., et al., Ibid., 888-92 (July, 1967).Current Concepts in Periodontal Disease. Stallard, R. E., J. Dent. Children, 34, 204-10 (May, 1967).The Effect of an Automatic Toothbrush on Periodontitis. Lobene R. R., J. Oral Therap. Pharma., 3, 284-90 (January, 1967).

Comparison of Ultrasonic and Hand Instruments for the Removal of Calculus. Stewart, J. L., et al., J. Am. Dental Assoc., 75, 153-57 (July, 1937).

Influence of Particle Size Upon Effectiveness of Pharmaceutical Aerosols. Sciarra, J. J., Aerosol Age, 12, 40, 95, 97 (August, 1967).

Effect of Food on Aspirin Absorption. Wood, J. H., Lancet, 2, 212 (July 22, 1967).

Allergy to Fluoride. Shea, J. J., et al., Ann. Allergy, 25, 388-91 (July, 1967).

Resistivity of Human Enamel and Dentine. Mumford, J. M., Arch. Oral Biol., 12, 925-27 (July, 1967).Comments on Comparative Patterns of Drug Metabolism. Gillette, J. R., Federation Proc., 26, 1040-43 (July-August 1967).Comparative Toxicity of Drugs. Darborn, E. H., Ibid., 1075-77.

Effect of Some Nonionic Surfactants on the Rate of Release of Drugs from Suppositories. Plaxco, J. M., Jr., et al., J. Pharm. Sci., 56, 809-14 (July, 1967).

Placebos. Stevenard, M., and Mauvernay, R. Y., Pharmacien France, 1967, 39-49 (February, 1967) (French).Latency of Cough Response on a Measure of Antitussive Agents. Glesnick, B., and Christen­sen, J. A., Clin. Pharmacol. Therap., 8, 374-80 (March, 1967).

Skin and Physiology

Urocanic Acid Content of the Epidermis in Africans and Europeans. Krai J. A., and Zenisek, A., Parfuem. Kosmetik 48, 193-95 (July, 1967).

Contact Sensitivity to Para-Hydroxybenzoate Esters. Rudner, E. J., and Cronin, E., Am..Perfumer Cosmetics 82, 31-32 (August 1967).

Fingernail Necrosis from Nail Hardener Formula. Van de Erve, J., J. .S'. Carolina Med. Assoc.., 63(1) (1967).

Synthesis of Nucleic Acids in Hair. Sims, R. T., Nature, 213 (5074) 387-88 (1967).

Use of Fluorescent and Phosphorescent Substances to Protect Skin from Sun or Artificial Light Rays. French Patent 1,458,223. Published November 10, 1966. Granted to Charles Risler.

Onycholysis Due to Nail Hardener. Donsky, N. J., Can. Med. Assoc. J., 96, 1375-6 (May 20, 1967).

Correlation of Tissue Mucopolysaccharides with the Hair Cycle. Moretti, G., et al., J. Invest. Dermatol., 48, 498-503 (June, 1987).

Measurement of the Total Normal Emissivity of Skin Without the Need for Measuring Skin Temperature. Mitchell, D., et al., Phys. Med. Biol., 12, 359-66 (July, 1967).

Differentiation of Epidermis & Epidermal Derivatives. Wessells, N. K., New Engl. J. Med., 277, 21-33 (July 6, 1967).

Chemical Substances and Skin Allergies. Halpern, M., Arch. Biochim. Cosmetol., 10, 9-27 (May, 1967) (French).

Action of Ultra-Violet Light on Soluble Collagens. Consden, R., and Kirrane, J. A., Nature, 215, 165-66 (July 8, 1967).

The Scaliness of Human Skin. Prall, J. K., Specialties, 3, 15-18, 20, 22-24 (May, 1967).

The Ability of the Skin to Change Its Insensible Perspiration. Spruit, D., and Herweyer, N. E., Dermatologica, 134, 364-70 (1967).

Studies on the Human Dandruff Allergen. IV. Immunochemical Analysis of a Purified Allergen Preparation. Berrens, L., Ibid., 432-48.

Phototoxicity and Photosensitivity. Edelson, E., et al, Drug Cosmetic Ini., 100, 43-45, 175 (June, 1967).Acne and Surface Lipids and Sebum. Idson, B., Ibid., 101, 42-44, 155-56 (July, 1967).Substances which Influence the Activity of Sebaceous Glands. Schimmel Briefs, No. 387 (June, 1967).Desquamation of the Human Horny Layer. Goldschmidt, H., and Kligman, A. M., Arch. Dermatol., 95, 583-86 (June, 1967).Allergic Contact Dermatitis to Methyl and Propyl Paraben. Schamberg, I. L., Ibid., 626-28.

Enzymatic and Histological Effects of a Standard Stimulus to the Skin of Normals and the Clinically Normal Skin of Psoriatics. Reid, J., and Jarrett, A., Ibid., 632-41.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS xxxiii

Adrenergic Focal Sweating. Dutta, A. K., Ibid., 642-44.

X X X I V JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

The Topical Effect of Hormones on Hair Growth. Herzberg, J. J., Fette-Seifen-Anstrich- mittel, 69, 355-57 (May, 1967) (German).

Occupational Medical Problems and Skin Protection from Acne Caused by Synthetic Waxes. Weichardt, H., Ibid.., 358-61.

Surface Activity

New Application of Gel Filtration. Sosaki. T., Yukagaku, 16, 49-55 (February, 1967) (Japanese).

Stable Alkali Soluble Surfactants. U. S. Patent 3,312,624. Filed May 18, 1962 and March 12, 1965. Patented April 4, 1967. Granted to Rohm and Haas Co.

Wetting of Powder. Kuno, H., Funtai Oyobi Funmatsuyakin, 13, 67-72 (1966) (Japanese).

Rheological Properties of Concentrated Hydroxyls of Gelatin. Watase, M., and Arakawa,K., Nippon Kagaku Zasshi, 88, 317—20 (March, 1967) (Japanese).

The Efficiency of Emulsifying Agents. I. The General Characteristics of Emulsions. Kajl,M., and Wilinska, E., Tluszczei Srodki Piorace, Kosmet., 10, 181-89 (1966) (Polish).

Hysteresis Experiment in Rheology. Harris, J., Nature, 214, 796-97 (#5090 1967).

Ampholytic Surface Active Agents, Their Properties and Uses. Chalmers, L., Specialties, 3, 3, 5-10 (May, 1967).

Literature Survey of the Effect of Surfactants on the Skin. Gotte, E., Tenside, 4, 209-17 (July, 1967) (German).

Micellar and Phase Properties of Dimethyldodecylphosphine Oxide in Ethanol/Water Sol­vent. Herrmann, K. W., and Benjamin, L., J. Colloid Interface Sci., 23, 478-86 (April, 1967).

Measurement of Surface Tensions of Surfactant Solutions. Boucher, E. A., et at., Ibid., 600-03.

Solubilization of Polymers in Aqueous Cationic Surfactant Solution. Saito, S., and Mizuta, Y., Ibid., 604-05.

Phenyloctadecanol and Surface-Active Derivatives. Smith, F. D., et at., ./. Am. Oil Chemists' Soc., 44, 413-15 (July, 1967).

Anionic Surfactants: Their Preparation and Properties. Solvat, J. L., Afinidad, 23, 489-97 (1966) (Spanish).

Rheological Investigation of Surfactant Systems. Goblke, F. J., and Hoffmann, H., Ibid., 519-25.

Use of Surfactants in Adhesives. Hodert, H., Seifen-Ole-Fette-Wachse, 93, 139-43 (May, 1967 (German).

General

Evaluating a Company’s Research Program. Engles, E. F., Res. Manag., 10, 147-56 (May, 1967).

Measuring the Profits from Research. Roche, A. F., Ibid.. 157-68.

Essential Elements of Research in Industry. Redmond, J. C., Ibid., 175-86.

JOURNAL OF THU SOCIETY OF COSMETIC CHEMISTS X X X V

Variables Affecting Supply and Demand of Scientists and Engineers—The User’s Viewpoint. McDonald, J. R., Ibid., 195-210.

Patent Equity and the Scientist in Pharmaceutical Research. Suter, C. M., Ibid., 10, 263-73 (July, 1967).

When to Terminate a Research and Development Project. Buell, C. k., Ibid., 275-84.

Evaluation of Research Expenditures Using Triangular Distribution Functions and Monte Carlo Methods. Sprovv, F\ B,, Ind. Eng. Chem., 59, 35-38 (July, 1967).

Need Oriented Joint Venture Research and Development. A New Approach to Greater R & D Productivity. Michaels, A, S., and Jacobs, N. A., Ibid., 39-45.

CPM for New Product Introductions. Dusenbury, W., Harvard Bus. Rev., 45, 124-39 (July-August, 1967).

The Cosmetic Industry—A Status Report. Mandakos, L., Drug Cosmetic Ind.. 100, 38-39, 164-70 (June, 1967).

The Makeup of a Cosmetic Chemist. Goldemberg, R. L., Ibid., 46-47, 49, 51, 160, 162-64.

Fundamentals of Planning a Clinical Trial. II. Ozick, J., J. Oral Therap. Pharmacol.. 3, 300-07 (January, 1967).

Perspiration—Everybody’s Problem. Lederer, M., Today's Health, 45, 12-14 (August, 1967).

The Review and Processing of New Drug Applications. Hodges R., FDA Papers, 1, 27-30 (July-August, 1967).

Creative Tensions in the Research and Development Climate. Pelz, D. C., Science, 157, 160-5 (July 14, 1967).

Using the Profit-and-Loss Statement. Teplitzky, G., Chem. Eng.. 74, 215-20 (June 19, 1967).

Consumer Attitudes Toward Shaving Creams. Detergent Age, 4, 40, 42-43 (June, 1967).

Emulsionano Power of a Third Solvent. Rimlinger, G., Arch Biochim. Cosmetol., 9, 103-12 (1966).Purification of Organic Dyes, Particularly of the Anthraquinone Series. Egerton, G. S., et al., J. Chromatog., 26, 62-71 (1967).

A Breaking Phenomenon of an Oil/Water Emulsion. Duyfjes, I. W., Sor. Chem. Ind., 21, 89-96 (1966).Emulsions. In: Pharmaceutical Sciences—1966. A Literature Review. Polli, G. P., and Ravin, L. J., J. Pharm. Sci., 56, 787-88 (July, 1967).

Pressurized Emulsion Quick Breaking Foam Compositions. U. S. Patent 3,330,730. Filed August 3, 1962. Patented July 11, 1967. Granted to Colgate-Palmolive Co.Water-Oil Emulsion of Copolymer of an Olefinically-Unsaturated Carboxylic Acid and Poly­alkenyl Polyether of a Polyhydric Alcohol, and Polyoxyalkylene Ester of Coconut Fatty Acids. U. S. Patent 3,330,731. Filed August 3, 1962. Patented July 11, 1967. Granted to Colgate-Palmolive Co.Recent Developments in Organic Pigments. Shah, X. V. J. Soc. Dyers Colourists, 83, 220-26 (June, 1967).

X X X V I JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Water for Cosmetics Manufacture, James, G. V., Soap Perfumery Cosmetics, 40, 405-US (June, 1967).Seaweed Extracts and Their Uses. Aberdein, C., Am. Perfumer Cosmetics, 82, 45-46 (August, 1967).Methyl Glucoside Esters in Cosmetics. Libman, O. E., and Packer, H., Paper presented at the AOCS Annual Meeting, Chicago, October, 1967.

Reduced Lanolins: The Synthesis, Properties and Cosmetic Applications. Siegel, F. P., et al., Ibid.

Microencapsulation. Sirine, G., Drug Cosmetic Ind., 101, 56 (September, 1967).

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 753

St. Louis Chapter of SCC Is Organized

Henry Maso (4th from left), president of the Society of Cosmetic Chemists, presents the charter for the newly formed St. Louis Chapter of the S.C.C. to Warren Hintz (3rd from left), Chairman of the St. Louis Chapter. Also pictured are (left to right) Hubert Merrell, treas­urer; Jesse Starkman, president elect of the S.C.C.; Warren Hintz; Henry Maso; Ray­mond Auer, Chairman elect; and Chris Christensen, secretary.

754 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

MARTIN M. RIEGER HONORED BY SCC Dr. M. M. Rieger honored. Dr. M. M. Rieger (left) was honored by the Society of Cosmetic Chemists for his five years of distinguished service as Editor of the J o u r n a l o f t h e S o c iet y o f C o sm et ic C h e m is t s . Mr. Henry Maso, President of the Society of Cosmetic Chemists is shown presenting the plaque.

I.F.F. AWARD 1966The 1966 I.F.F. Award of $1,000 was presented to Dr. Christopher M. Papa (left) by Henry Maso, President of the Society of Cosmetic Chemists. Dr. Papa’s paper, "The Action of Antiperspirants,” was judged to be the best paper published in the J o u r n a l o f t h e S o c ie t y o f C o sm et ic C h e m is t s during 1966.

J. Soc. Cosmetic Chemists, 18, 755-768 (Dec. 9, 1967)

Measuring the Meaning of Fragrance

J. STEPHAN JELLINEK, Ph.D.*

Presented September 20-21, 1966, Seminar, New York City

Synopsis —Three different techniques for measuring the meaning of fragrances are reviewed. Profiling, Semantic Differential, and Multidimensional Scaling are discussed with special emphasis on the last. The application of these techniques by perfumers and in consumer testing is described.

I ntrodu ction

The title of this paper may be a little mystifying; we do not usually think of fragrance as having a meaning, nor of meaning as being something measurable. The phrase “the measurement of meaning,” was borrowed from Osgood, who described the uses of a new linguistic technique, the semantic differential, in a book by this title (1). We shall have more to say about the semantic differential and its use in measuring meaning later on.

But what about the meaning of fragrance? It is quite obvious to anyone who has worked with fragrance that it would be highly inap­propriate to use a Tabu-type fragrance in a dishwashing detergent or an insecticide spray, just as it would be a hopeless undertaking to launch, under a sophisticated name and with a romantic advertising story, a perfume that smells like lemons and lavender. That quality of the Tabu fragrance which clashes with the concept of a detergent or an insecticide is what may be called its meaning. It is the message which

* General Foods Corporation, 250 North St., White Plains, N. Y. 10602.755

'56 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

the fragrance conveys to the consumer, the connotations and asso­ciations which it evokes.

In this sense, the meaning of a fragrance is its most important quality ; it is its reason for being. The function of a fragrance is always to convey a message about the woman (or man) who wears it or about the product in which it is used. If it succeeds in conveying the right message forcefully, the fragrance will be successful (2). If we accept this to be true, it becomes obvious that a perfumer, no matter whether his job is to create fragrances or to select them, must have a good under­standing of their meaning and of the message they convey. To be more exact, since the product with which he is involved will have to be sold to a specific public, he must understand the meaning which his fra­grances hold for that public. Understanding the meaning of a fragrance is very closely related to that most valuable gift a perfumer can have : the gift to predict what will sell.

To get this understanding, the perfumer traditionally has had to rely on three sources of information : introspection (what message does this fragrance convey to me?), observation of market performance (what kinds of fragrances are successful in what products?), and an understand­ing of certain chemical relationships (phenolic odorants occur in smoke and hence connote danger; citrus oils smell refreshing since they are associated with sour fruits; fatty aldehydes and indol are related to components of bodily excretions and hence have erogenous meanings (2). All of these approaches are indirect, and all have their pitfalls. Intro­spection fails if the perfumer is not completely in tune with his public; market performance depends on many things other than the fragrance ; and the effect of chemical relationships on meaning has been largely in the realm of speculation and could not be proven. The direct approach—to go to a consumer or to a group of consumers and ask: What does this fragrance mean to you?—has not been considered feasible in the past.

There are several reasons for this. Every perfumer has had bad experiences with the layman’s ability to identify odors or to react to them in any consistent way. He has repeatedly run into normal, intelligent people who fail to recognize the odors of the most familiar flowers or even of their own perfume, or who on Monday definitely prefer fragrance A over B only to reverse their judgment, with equal conviction, on Tuesday. After a few of these encounters, a perfumer tends to get discouraged about using laymen’s judgments for guidance (3). Also, if you give people a fragrance and ask them to describe it, you usually

MEASURING THE MEANING OF FRAGRANCE 757

don’t get much that is useful. Most respondents will tell you that it is “very nice” or “fragrant” or maybe that “I don’t like it much” ; and if you are lucky, you get some more specific descriptions, such as “smells like something you eat,” “like my grandmother’s garden” or “like a drugstore.” If, as is the case, every respondent who says anything at all says something different, how can you combine and interpret the comments ?

There are, then, real difficulties. Still, if fragrance is, in essence, a message, it is highly important to search for techniques which will re­liably measure the meaning of this message to the consumer. And it is a milestone in perfumery that such techniques have recently been devel­oped and are beginning to get used.

O d o r P r o f i l e s a n d t h e S e m a n t ic D i f f e r e n t i a l

In 1960, Paukner (4) obtained from respondents unschooled in perfumery descriptions of the odorants, citral, p-methyl quinoline, eugenol, geraniol, menthone, and hexenyl formate, which were very interesting since they partly confirmed but also partly conflicted with the meanings which these materials hold for professional perfumers. More important, these descriptions could be said to have statistical reliability. There are several noteworthy features about Paukner’s approach. For one thing, he did not use just a handful of people in his test; he used 287 respondents. In tests of this type, there is real value in large numbers. People disagree about such questions as “To what extent is the odor of citral stimulating?”, but if you take a sufficiently large group, the opinions of those who find the odor extremely stimulating will be counterbalanced by a group of people who hardly find it stimulating at all. Averaging all the votes, you arrive at a value which is valid in the sense that a very similar value can be obtained by posing the same question about citral to a different group of respondents.

Poffenberger, in 1932, conducted an experiment which, although it does not deal with odor, nicely illustrates this point (5). He presented his test subjects with ten different shapes and asked them to rank these in order of decreasing area (Fig. 1). Poffenberger then scored each indi­vidual’s performance by calculating the rank correlation coefficient be­tween the actual order and the order guessed by the subject. Lining up the shapes in perfectly correct order would result in a coefficient of + 1.00, doing it all wrong (reverse order) would give a coefficient of —1.00, and guessing at random would usually give values between +0.40 a n d —0.40. Judging the area of these complex shapes is not easy. When

758 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

« + « 4B C D E

G H I J

Figure 1. S h a p e s o f d i f f e r e n t a r e a s ( a f t e r P o f f e n b e r g e r )

seven people were asked to rank the shapes their scores ranged from — 0.03 to +0.67, with an average score of +0.36. The interesting point is that when the judgments of these seven people were combined by addition, a ranking was obtained which scored +0.79, which is not only very much better than the average score of the respondents but is even distinctly better than the score of the best judge. When a ranking was obtained by combining the judgment of 20 individuals it scored +0.92, which is remarkably close to perfect. There was nothing unique about this experiment and about the results obtained. It has been repeated many times and you can repeat it at home, if you wish. You always find that the judgment of the group will be closer to the truth than that of the individual judges. The reason is that the mistakes of different judges tend to go in different directions. Among our seven judges there may have been three who underestimated the size of shape A, two who over­estimated it, and two who judged it correctly. When all the answers were combined, the negative and the positive errors largely canceled one another, so that the group answer was close to the truth. In ex­periments where you can’t establish objectively how correct an answer is, you will find that the average judgments of larger groups are generally in better agreement with one another than the opinions of individuals. This is the reason why Paukner worked with 287 respondents.

Another important feature of his experiment was that he did notallow his respondents to choose freely the words with which to describe the odors. If 287 people start associating freely with drugstores, grand­mother’s gardens, things they eat, etc., it becomes impossible to combine their votes. He used a questionnaire in which the respondents were given words such as delicate, bitter, cold; the instructions were to indicate on a clearly defined scale (0 = not at all appropriate, 4 = completely appropriate) the extent to which each word fits each odor.* With such

* In s im i la r e x p e r im e n t s , m a n y in v e s t ig a t o r s p r e fe r t o u s e w o r d p a ir s (delicate-rough., cold- w arm ) r a t h e r t h a n s in g le w o r d s ; e a c h p r o c e d u r e h a s c e r t a in a d v a n t a g e s .

MEASURING T H E M EA N IN G OF FRAGRANCE 759

a highly structured questionnaire it becomes easy to arrive at a group judgment simply by adding individual votes.

The technique of providing the respondent with words rather than letting him choose his own carries with it the danger of losing infor­mation; a respondent will not be able to express the meaning an odor has for him if you don’t provide him with the words with which to ex­press it. It is, therefore, important to use a well-chosen list of words and to make it long enough to include all aspects of odors that might be relevant. Paukner worked with a list of 66 adjectives. Actually, an extensive list may make the respondent more articulate than a free “ open end” questionnaire by reminding him of ways to describe an odor which are meaningful to him but which he would not have thought of had he been left to his own devices; however, we have to admit that there is a danger of “ leading the witness” in this procedure. There is yet another advantage inherent in long lists: if they contain words that are either similar or nearly opposite in meaning, the results can be checked for consistency. An odor for which the word strong is rated as highly appropriate should probably have low ratings for delicate and mild. If it doesn’t, it may be worth checking whether the respondents have understood the instructions and whether no mistakes were made in the tabulating or processing of the data. Often, where a single piece of information is not meaningful or statistically significant, a pattern of responses such as may be obtained in a longer questionnaire can convey valuable information. Naturally, there are practical limits to the length of a list of words: the longer it is, the more time-consuming and costly the interview and subsequent data processing and interpretation become. After having used his questionnaire in several large-scale tests the experimenter learns which adjectives are the most important and relevant for his particular kind of problems and which ones he can omit without losing much information. Using his lengthy questionnaire, asking 287 respondents to describe six odors and calculating the averages of their responses, what did Paukner achieve? He obtained profiles of odorants in terms of adjectives which give the perfumer, for the first time, a reliable, direct indication how these odorants strike his public, what kind of meaning they convey to nonperfumers (Fig. 2). This is certainly important, but it is only a first step. A very natural next step is to apply the same technique of questioning to complete perfume com­pounds rather than single ingredients. Thus Paukner (6) took a simple lavender composition and proceeded to add increasing amounts of an ambermuskcivet complex to it. According to the perfumer (2) this

760 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

Degree of Appropriateness

1 2 3 A 5 6 7

Figure 2. P a r t ia l p r o f i le o f a m b e r ( a f t e r P a u k n e r )

should make the composition increasingly sexy; but does the public agree? Paukner tested it and found it to be so. In these tests, he used a mathematical extension of the profile generation technique: He applied a factor analysis to his scores and thus obtained a semantic differential (1).

We are here getting into territory that may seem obscure to the nonpsychologist and the nonstatistician; the underlying ideas, however, are fairly simple. If we take a number of odors, each of which is described in terms of the appropriateness of a series of adjectives, we can, by carefully looking at the data, discover certain patterns. Odors which are described as fresh, warm, or cheerful, are likely also to have high ratings on the adjectives pleasing and harmonious and to have low ratings on poor or artificial. This is because the words fresh, warm, and cheerful have overtones of goodness and pleasantness which are also inherent in pleasing and harmonious but not in poor and artificial. This underlying notion of pleasantness, which will tend to make the ratings on adjectives such as fresh, warm, cheerful, and harmonious move together as we pass from one fragrance to another, is, in a mathematical sense, a factor which can account for a certain proportion of the dif­ference between different odors. In a psychological sense, it is one of the basic dimensions in terms of which odors are perceived. Certainly, pleasantness is usually a very important factor, but it is by no means the

MEASURING T H E M EA N IN G OF FRAGRANCE 7G1

I ACTIVITY- I

Figure 3. O d o r d e s c r i p t i o n s p a c e ( a f t e r P a u k n e r )

only one. Two fragrances may be about equally pleasant, but one has a high rating on fresh, stimulating, and spicy while the other may have low ratings on these adjectives but be very calming, soft, and mild. The underlying dimension in which these two fragrances differ might be described as activity. The important thing about these dimensions is that they are not speculative contructs of the investigator’s imagina­tion but actual patterns and regularities underlying the respondent’s reactions to the fragrances, isolated by rigorous mathematical tech­niques and labeled only afterwards by the investigator. It is not naive or presumptuous to say that these are true, meaningful dimen­sions of people’s responses to odors.

It is common to extract five or six factors (or uncover five or six basic dimensions) in a semantic differential on odors. One of the basic features of factor analysis is that the factors are always extracted in order of decreasing importance: the first factor explains most of the differences between the responses, the second factor a smaller portion, etc. Thus it is usually legitimate to disregard the factors beyond the third or fourth one. There is a tendency among workers in the field to use three factors for this makes possible a visual representation in three dimensions. The three factors are represented by mutually orthogonal axes and the things judged by points. An odor which is rated high in pleasantness will be represented by a point close to the positive end of the “ pleasantness axis” ; an unpleasant odor will lie close to the other end. Odors represented by points which lie close together are perceived by the respondents to be similar in the message they convey, although they may be, as fragrances, distinctly different (Fig. 3).

Thus, the semantic differential technique provides a very elegant way of uncovering, describing, and graphically representing the meaning of different fragrances to the consumer. It makes it possible for the perfumer to assess whether a certain change he has made in a fragrance actually moves it in the desired direction, as far as the public is con­cerned. It also makes possible a new and truly creative type of imita­tion of successful perfumes. If a soap manufacturer brings out a highly successful toilet soap with a novel type of fragrance, we can use this fragrance as a model, not as we have always done by trying to make one that smells just like it, but by finding out just how the consumer de­scribes this fragrance and then developing one which may smell quite different to the perfumer but which is described by the consumer as being similar to the model in terms of the basic dimensions important to him! Better yet, we will try to make a fragrance which the consumer sees as being similar to the model in all relevant respects but which he likes just a little better. This new fragrance, although different, will be equally appropriate to toilet soap and should at least be equally successful* if one of the basic hypotheses of linguistics is true, namely, that “ an individual will behave toward a new object or event in a manner that is similar to the way he behaves toward objects and events that he encodes in the same way” (7). To be good at this new type of imitation, the perfumer has to have a thorough understanding of what it is about a fragrance that will make the consumer describe it in a cer­tain way. It certainly is not easy to acquire this kind of understanding; but running exactly the kind of test which Paukner and several others have been conducting during the past few years can be of great help.

The semantic differential opens another intriguing possibility. It is quite feasible to have respondents describe, in terms of the adjectives of the questionnaire, not only different fragrances but also such concepts as “ the ideal erogenous fragrance” or “ a very masculine after-shave lo­tion.” After running through the factor analysis, these concepts can then be represented by points in the semantic space, along with the points representing actual fragrances. By determining in what way the actual fragrances differ from the concepts and then making the adjust­ments necessary to bring them close (this may sound simple, but it re­quires all the art and understanding of a master perfumer) new fra­grances can be created. If the semantic differential truly and fully de-

* N a t u r a l ly , i f t h is n e w f r a g r a n c e is i n c o r p o r a t e d in a n e w t o i l e t s o a p , t h is s o a p w il l b e a s s u c c e s s fu l a s i t s m o d e l o n l y i f e v e r y t h i n g e ls e a b o u t it , s o a p q u a l i t y , n a m e , p r ic e , p a c k a g in g , e t c . , is a ls o r ig h t .

762 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

MEASURING T H E M EA N IN G OF FRAGRANCE 763

scribed the respondents’ feelings, if the respondents were representative of the population for whom the new fragrance is intended, and if it is true that people act similarly toward things they describe similarly, the new fragrance thus developed should be highly successful.

Let us now take another close look at the semantic differential. What are the basic dimensions it uncovers? Are they always the same? In principle, the dimensions emerging will depend both on the odors or other stimuli tested and on the adjectives used in the questionnaire. If the range of adjectives is sufficiently broad and diverse so that the re­spondent can clearly express through them any and all feelings he has about odors, then the adjectives should not place any limitation on the factors emerging. But what odors (or other things) are tested does make a difference. Paukner found that his first three dimensions were characterized, respectively, by the adjectives beautiful/harmonious, spicy/ alert/strong, and fresh/hard/aggressive. He labeled the first dimen­sion evaluation, the second activity and the third intensity.* Rande- brock, in a similar study, found that his first dimension was characterized by the contrasting word pairs elated-depressed, and uplifting-depressing; the second one by the word pairs, ferocious-gentle and stern-mild; and the third dimension by bracing-insipid and full-empty (8). These di­mensions are similar to Paukner’s, but they are not identical. In some of our own studies on foods and flavors we found wholesome-risky and everyday-party emerging as important dimensions.

O d o r C l a s s i f i c a t i o n a n d M u l t i d i m e n s i o n a l S c a l i n g

Recently there has been a resurgence of interest in the old question: Are there any basic odor types in terms of which all odors can be de­scribed (9) ? A great deal is known about the four basic tastes, about the primary colors, and about the physical foundation of acoustics, but odor has always defied meaningful, objective, verifiable classification. Couldn’t the new techniques of uncovering the basic dimensions of fragrance lead us to a recognition of the “ primary odors,” if such exist? Most of the investigators who have worked in this area have not used the semantic differential to construct their “ odor space” but have used a technique which, starting from different premises, leads to a similar representation of odors as points in a space. This is the technique of multidimensional scaling (10). In this technique the respondents are

* T h e s e t h r e e d im e n s io n s , w i t h t h e t h ir d o n e u s u a l ly la b e le d potency , a r e a ls o t h e m a in o n e s w h ic h O s g o o d o b t a in e d w h e n e x a m in in g a ll k in d s o f c o n c e p t s a n d t h in g s o t h e r th a n

o d o r s , u s in g ( h e s e m a n t i c d i f fe r e n t ia l ,

764 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

presented not with single odorants but with pairs. They are asked to indicate simply how similar to one another or how different they find the members of a pair to be. If there are a total of three odors to be studied, this would make three pairs and three “distances” between odors (A-B, B-C, and A-C). If there are 25 odors, there are 300 dis­tances to be determined. There are various ways of getting estimates of magnitude of difference from respondents. Whatever method is used, judging these differences or distances is a difficult task, not unlike the lining up of different shapes in order of area which was discussed before. Again, we have to take a fairly large number of judges and calculate average judgments if we want to get reproducible results.

By the time we complete the interviews and calculations on, say, 25 odorants, we will have 300 figures representing the pair-wise distances between 25 points (the odorants). Two points and a given distance be­tween them can be represented on a (one-dimensional) straight line; three points, with three pair-wise distances between them, can be ac­curately represented by a triangle in a (two-dimensional) plane; four points, with six interpoint distances, will be represented by a pyramid in a three-dimensional space. To represent 25 points accurately, when the 300 pair-wise distances between them are given, takes a 24-dimen­sional space. In multidimensional analysis we actually start out with such a space, but through mathematical techniques, too complex to de­scribe here but similar in principle to the techniques a cartographer uses in depicting a three-dimensional reality on a two-dimensional map, we simplify it down to a space with maybe four or five dimensions. In this process we inevitably introduce some distortion but we make our infor­mation much easier to understand and to handle. By the time we get down to three dimensions, we may have introduced some fairly severe distortions but we have something we can look at.

Such a three-dimensional representation is, in many ways, similar to the “ odor-space” we discussed before, the end-result of the semantic differential. There is one important difference: while the meaning of the dimensions of the space obtained in the semantic differential can be understood by reference to the adjectives or word pairs that are closely related to these dimensions, the space model obtained by multidimen­sional scaling has dimensions which are unlabeled and which may have no meaning. In a way this limits its usefulness; but in another way, it is the direct result of a fundamental advantage which the multidi­mensional scaling technique has over the semantic differential. In the semantic differential, the respondent has to give his answers in terms

MEASURING T H E M EA NIN G OF FRAGRANCE 765

of the adjectives the experimenter has provided. The experimenter will make every effort to select adjectives which will cover all aspects and all dimensions of the odor which may be relevant to the respondent, but he can never be sure that he has succeeded in this. Also, the adjectives or word-pairs used in the questionnaire may introduce distortions by in­fluencing the respondent, e.g., by suggesting that certain things are rele­vant which are actually of no importance to him. In the multidimen­sional scaling technique, the respondent is given no words. He judges differences and similarities between odors along dimensions which he may not even consciously formulate but which are, ipso facto, the most relevant to him. It is for this reason that those who have set out to ex­plore olfaction without preconceived ideas, in search of primary odor qualities, have preferred to use multidimensional scaling. *

Woskow (11) used odorants and described them in a nine-dimensional space of which the first three dimensions were the most important. Al­though the dimensions are not labeled, their meaning can be interpreted by looking at what odorants lie close to the ends of the space along each of the dimensions. Woskow’s first and mathematically most important dimension (it accounted for a large portion of the differences between the odorants) was clearly an evaluative one. It had vanillin, safrol, methyl salicylate, and benzaldehyde at one end and butyric acid, pyri­dine, and scatol at the other. The second dimension has camphor, guaiacol, and menthol at one end and aliphatic alcohols (C2-C 9) and vanillin at the other. Woskow suggests the label cooling, woodsy for this axis; but prickling-medicinal vs. soothing-unctuous might be prefer­able. The third and following dimensions are difficult to interpret. In fact, in interpreting a multidimensional model, a good case can be made for not assigning any meaning to dimensions but only to interpoint dis­tances.

Schütz, also trying to uncover primary odors, measured the quality of 30 odorants using both a semantic differential technique and multidi­mensional scaling (12). From the multidimensional scaling experiment he derived nine main factors which he labeled: fragrant, etherish, sweet, burnt, rancid, oily, metallic, spicy, and sulfurous or goaty.

On the basis of this work, Schütz proposed a nonverbal method of describing odors: choose some standard odors which are distinctly dif­ferent from one another; for each odor to be described, have respondents

* E v e n u s in g th is t e c h n iq u e t h e e x p e r im e n t e r c a n n o t h e lp in f lu e n c in g t h e o u t c o m e o f h is e x p e r im e n t : h e is t h e o n e w h o s e le c ts t h e o d o r a n t s t o b e t e s t e d , a n d h e h a s t o in t e r p r e t th e

r e s u lts .

766 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

judge the pair-wise distances (degrees of difference) between this odor and each of the standard odors; use a group of respondents and average their judgments to get reproducible values. The set of average distance judgments of the new odor with respect to the standard odor describes, and in a sense, defines the new odor. Schütz used nine odorants, one for each of his factors, as standards, but other standards may also be used with this method which Schütz called the "matching standards method.” Amoore (13) has applied the matching standards method to test his own theory about primary odors.

Yoshida (14) also examined a divergent group of odorants by the multidimensional scaling technique in an attempt to ascertain whether earlier proposed schemes for odor classification had any objective basis. He also investigated a group of modern luxury perfumes and a group of spices and herbs by the same technique. In each case, he extracted four or five factors, of which the evaluative one was the most important one.

So far, then, attempts to find primary odors as the underlying dimen­sions in a multidimensional space model of odor have only been moder­ately successful. They have, however, shown that multidimensional scaling can be used to construct space models of odors. We can then use these models for different purposes, i.e., to measure how consumers at large react to given fragrances, in what way and in what direction a change in a fragrance affects the consumers’ perception of it, or to get guidance in the development of new fragrances for a specific purpose.* True, the lack of words in the model to guide us can become a handicap, but there are ways of overcoming this difficulty. A research group at General Foods is currently using a modified multidimensional scaling technique in flavor work with very promising results.

P r o d u c t T e s t i n g

The new techniques for measuring the relations between, and the meaning of things and concepts in general, and of fragrances in particu­lar, can be of real value not only to the perfumer, but also to those in the perfumery and cosmetic industry who are concerned with the con­sumer testing of new or improved products. As Randebrock (8) pointed out, the use of a questionnaire containing many different scales (2!) in his case), rather than only questions about degree of liking or preference has the advantage of yielding stable, reproducible results with panels of as few as 30 respondents; whereas the traditional tests require several

* A n o v e l t e c h n iq u e o f n e w p r o d u c t d e v e l o p m e n t w h ic h m a k e s e x t e n s iv e u s e o f m u l t i ­d im e n s io n a l s c a l in g is d e s c r ib e d b y B a r n e t t ( 1 5 ) .

MEASURING T H E M EA NIN G OF FRAGRANCE 767

hundred respondents to give stable findings. That is a practical ad­vantage. A more significant, fundamental difference lies in the fact that the traditional tests, by centering only on the questions, “ How much do you like this sample?” or “Which do you prefer?” , have, in effect, assumed that the evaluative dimension, the question of pleasing­ness, is the only relevant one, the only one which determines consumer behavior toward the product. We know that this is not true. One cannot help wondering how far beer, cigarettes or coffee would have gone in the marketplace if at their first exposure to the consuming public they would have been accompanied by a questionnaire asking, “ How much do you like this new product?” Since aspects other than pleasant­ness do influence consumer acceptance of a product, new techniques to measure these other aspects can and will lead to important advances in acceptance prediction.

C o n c l u s i o n

The techniques for measuring the meaning of fragrance discussed in this paper, namely, profiling, the semantic differential, and multidimen­sional scaling, are new and we still have to learn a lot about how to use them. We have to learn, among other things, how to choose those ad­jectives for our questionnaires which will give the most useful informa­tion ; how best to select the samples or concepts to be included in a test (for what we learn about one sample depends on what other samples are tested alongside with it) ; and how to interpret the space models ob­tained in multidimensional scaling. We shall learn these things, and in so doing we shall be forging powerful tools for the perfumer and for the marketing expert.

To the perfumer, these techniques will provide a more direct and clear means of communication with the consumer than he has had up to now. By setting up, through the kinds of tests we have discussed, a feedback system and a continuing dialogue with his public, the perfumer will learn more and more precisely what it is about a fragrance that makes the public perceive it as sexy, as refreshing, as dull, or as masculine. If the marketing group has determined that the new baby powder that is being developed should be perceived by the public as being more cool, gentle, and wholesome than those currently available, the perfumer can use his dialogue with the public to guide him towards a fragrance which is cool, gentle, wholesome, and baby-like. Also, the dialogue makes possible a creative rather than slavish imitation of competitors’ successful prod­ucts. To the marketing expert, these testing methods will provide

768 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

better, more subtle, and more reliable means of predicting consumer ac­ceptance of new products and new fragrances. The tests will be the more valuable the more different the new product is from existing, fa­miliar ones.

Finally, and maybe most importantly: if both the laboratories and marketing groups start using these tests and adopt the relationship to the consumer which the tests imply, a better understanding and closer cooperation between the two groups will be the inevitable outcome. No one can deny that this would be a good thing.

(Received March 20, 1907)

R e f e r e n c e s

( 1 ) O s g o o d , C . E , , S u c i , G . J . , a n d T a n n e n b a u m , P . H . , The M easurement of M eaning, U n i ­v e r s i t y o f I l l in o is P re s s , U r b a n a , 111., 1 9 5 7 .

( 2 ) J e l l in e k , P ., Die psychologischen Gmndlagen der Parfumerie, 2 n d e d . , H u t h i g V e r la g , H e id e lb e r g , 1 96 5 .

( 3 ) P a u k n e r , E . , Parfuem. Kosmetik, 3 9 , 7 5 0 (1 9 5 8 ) .( 4 ) P a u k n e r , E ., J . Soc. Cosmetic Chemists, 1 1 , 5 1 7 ( 1 9 6 0 ) ; e f . A m . Perfumer, 7 9 ( 2 ) , 3 7

(1 9 6 4 ) .

( 5 ) P o f fe n b e r g e r , A . T . , Psychology of Advertising, N e w Y o r k , 1 9 3 2 .( 6 ) P a u k n e r , E . , J . Soc. Cosmetic Chemists, 1 6 , 5 1 5 (1 9 6 5 ) .( 7 ) S te f f lr e , V . , A m . Behavioral Scientist, 8 (9 ) , 12 (1 9 6 5 ) .( 8 ) R a n d e b r o c k , R . , J . Soc. Cosmetic Chemists, 1 6 , 6 5 3 (1 9 6 5 ) .( 9 ) W e n z e l , B . M . , a n d S ie c k , M . H . , A n n . Rev. Physiol., 2 8 , 3 8 1 (1 9 6 6 ) .

( 1 0 ) T o r g e r s o n , W . S ., Theory and methods o f scaling, J o h n W i l e y & S o n s , I n c . , N e w Y o r k , 1 95 8 .

( 1 1 ) W o s k o w , M . IT ., M ultidim ensional Scaling of Odors, P h .D . th e s is , U n iv . o f C a l i f . , L o s A n g e le s , 1 9 6 4 ; U n i v e r s i t y M i c r o f i l m s , A n n A r b o r , M i c h . # 6 4 -6 1 9 8 .

( 1 2 ) S c h ü t z , H . G . , A n n . N . Y. Acad. Sci., 1 16 ( 2 ) , 5 1 7 (1 9 6 4 ) .( 1 3 ) Y o s h i d a , M . , Japan. Psychol. J ., 6 ( 3 ) , 1 1 5 (1 9 6 4 ) .( 1 4 ) A m o o r e , J . E . , a n d V e n s t r o m , D . , J . Food Sci., 3 1 , 1 1 8 (1 9 6 6 ) .( 1 5 ) B a r n e t t , N . L . , M a r k e t s t r u c t u r e a n a ly s is : A n e x p l o r a t o r y a p p l i c a t i o n t o t h e m a r k e t

f o r m a r k e t r e s e a r c h t e c h n iq u e s a n d s e r v ic e s , P h .D . th e s is , H a r v a r d U n iv e r s i t y , C h a p ­t e r 2 (1 9 6 6 ) .

J . Soc. C osm etic C h e m ists , 18, 769-775 (Dec. 9, 1967)

H and Degerm ing Evaluation U tilizing A Split-Use M ethod

JAMES BROWN, JR., M.S., RONALD J. ERIKSSON, B.S., FRANK YACKOVICH, Ph.D., and DAVID TABER, Ph.D.*

Presented November 30, 1966, New York City

S y n o p s i s — U t i l i z in g a m o d if i e d s p l i t -u s e m e t h o d , t w o b a c t e r io s t a t i c s o a p s w e r e e v a lu a t e d fo r t h e ir u t i l i t y in d e g e r m in g t h e h a n d s . O n e s o a p c o n t a i n e d 0 . 7 5 % ( b y w e i g h t ) o f h e x a c h lo r o - p h e n e a n d 0 .7 5 , o f 3 ,4 ,4 '- t r i c h lo r o c a r b a n i l i d e ; t h e o t h e r c o n s is t e d o f e q u a l p a r t s b y w e ig h t

o f 3 ,5 - d i - a n d 3 ,4 ',5 - t r i b r o m o s a l i e y l a n i l id e s , 4 ,4 '- d i c h lo r o - 3 - ( t r i f l u o r o m e t h y l ) c a r b a n i l i d e , a n d 3 ,4 ,4 '- t r i c h lo r o c a r b a n i l i d e f o r a t o t a l c o n c e n t r a t io n o f 2 % . A s ig n i f i c a n t r e d u c t i o n in b a c ­t e r ia l c o u n t s w a s a c h ie v e d b y b o t h s o a p s a s c o m p a r e d t o a n o n m e d ie a t e d s o a p . I t is e m p h a ­s iz e d t h a t r ig o r o u s h a n d l in g o f d a t a r e q u ir e s t h a t t h e c o n f id e n c e in t e r v a l b e id e n t i f ie d w h e n p e r c e n t r e d u c t i o n is u s e d a s a b a s is f o r d e s c r i b in g d e g e r m in g e f f i c ie n c y .

I n t r o d u c t i o n

To investigators in the field of soap germicides, many techniques are available for evaluating skin degerming after use of an antibacterial soap. Among these are clinical observations, tape strippings, swab methods, contact plate methods, and plate counts obtained from hand­washings. Four of these methods involve counting bacterial colonies, while clinical trials involve observations of the progress of bacterial dis­eases of the skin.

The moderation or the prevention of skin diseases is one of the at­tributes of an effective bacteriostatic soap. However, for the initial evaluation of a new bacteriostatic system in soap, the length of time needed for a meaningful clinical study makes this tool of questionable value.

* A r m o u r G r o c e r y P r o d u c t s C o m p a n y , 3 1 1 5 S . B e n s o n S t . , C h ic a g o , 111. 6 0 6 0 9 .

769

770 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

Tape stripping as used by Updegraff (1) involves applying an ad­hesive tape to the skin surface then removing the tape with an adhering layer of skin containing colonies of bacteria. This method allows one to determine the distribution of bacterial colonies in relation to area and depth of the epidermal layers.

Skin swabbing (2) is performed with cotton or calcium alginate swabs. The swabs are placed in water or hexametaphosphate solution, the suspension is shaken thoroughly to distribute the organisms, and an aliquot is plated baeteriologically. Variations in bacterial counts can occur because of nonreproducibility in the pressure used in applying the swabs to the skin and because the number of bacteria removed from the swabs may vary with the efficiency of the shaking.

A more reproducible swabbing technique is utilized by Pachtman, et al. (3). An aliquot of a 0.1% aqueous solution of Triton X-100®* is pipetted into a glass cylinder 23 mm in diameter pressed firmly against the skin. The skin is abraded gently with a glass rod or Teflon police­man for two minutes, then the solution is removed, diluted, and plated baeteriologically.

Contact plates are made by adding liquefied nutrient agar to a Rodac platef or small container, allowing the agar to harden, then pressing the plate with uniform pressure to the skin area to be tested. Plates are incubated at 37 °C for 48 hours, whereupon colonies are counted. Ulrich(2) stated that the method is reproducible for the first five plates taken sequentially from the same area of skin. Only bacteria on the surface of the skin are enumerated by this method.

This paper deals primarily with handwashing as a technique for eval­uating skin degerming.

Price (4) developed a procedure whereby bacteria are removed from the hands and forearms by scrubbing with a surgical scrub brush in a series of basins containing a standard volume of water. Bacteria are removed at a decreasing rate as determined by counting the bacteria in each basin, plotting a curve which can be used to calculate the total bacterial flora on the area tested. Counts are taken on ten to fourteen basins.

If an antibacterial soap is used, the reduction in bacterial count as compared to the number obtained when a nonmedicated soap is used gives a measure of the effectiveness of the antibacterial product.

* I s o - o c t y l p h e n o x y p o l y e t h o x v e t h a n o l . R e g is t e r e d t r a d e m a r k o f R o h m & H a a s C o . , P h i la d e lp h ia , P a .

t D is t r ib u t e d b y B a l t im o r e B io lo g ic a l L a b o r a t o r i e s , I n c . , B a l t im o r e , M d . 2 1 2 1 8 .

HAND D E G E R M IN G EVALUATION' 771

Cade (5), also utilizing a multiple basin technique, determined that degerming could be evaluated after one to two weeks of test soap applica­tion. By counting the bacteria in the first, fourth, and fifth basins of a series, a curve was developed from the data obtained. Since bacterial removal beyond the fifth basin was constant when an effective bacterio­static soap was employed, it was considered unnecessary to go beyond five basins (5). Per cent reduction was calculated by comparing counts obtained with a bacteriostatic soap to those obtained with a control (nonmedicated) soap.

The multiple-basin procedure was further modified by Roman, et al.(6) who used a baseline control of 1,580,000 bacteria per fifth basin for all participants on the panel and evaluated the degerming efficiency of a bacteriostatic soap in five days. This number was obtained from non­medicated soap washings. Similarly, Kooistra, et al. (7) used a control reference figure of 1,300,000 bacteria for the fifth basin, a value derived from more than 500 individual fifth basin handwashings. The assump­tion behind this method is that participants in any experiment have essentially the same number of bacteria on their hands at the outset. However, this hypothesis is not confirmed by the second basin data for control soaps presented in their paper.

In the four handwashing tests mentioned the underlying assumption is that the bacterial counts from the hands of the individual or the group would have remained constant during the entire test period if a non­medicated soap had been used exclusively.

Unlike the handwashing techniques just described, the procedure of Quinn, et al. (8) allows each participant to serve as his own control dur­ing the five-day evaluation period. This is accomplished by requiring the panelist to wash one of his hands, generally the left, with nonmedi­cated soap, reserving the other hand for the bacteriostatic soap. When either hand is being washed, the other is covered with a neoprene glove. Results are obtained by comparing counts from the hand using non­medicated soap with those from the one on which bacteriostatic soap is applied.

Prior to the evaluation period, nonmedicated soap is used on both hands for seven days. Neoprene gloves are used by panelists when per­forming such chores as dishwashing, scrubbing, shampooing, etc.

The Quinn procedure (8) has been used by the authors to evaluate skin degerming. Results obtained with two antibacterial soaps by means of this split-use method are described here.

JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

E x p e r i m e n t a l

The procedure provides for two types of washing sessions: applica­tion and sampling. Application washing sessions are those in which both the medicated and nonmedicated soaps are applied to the hands. These sessions make certain that panelists are exposed to the test soaps several times each day. Sampling washing sessions are identical to ap­plication sessions except that nonmedicated soap is applied to both hands and the basin water from each hand is plated and cultured for bacteria.

The daily application is as follows: 1500 ml of tap water are addedto each of two basins. Each subject covers his right hand with a sterile neoprene glove and wets both the gloved and ungloved hands. Twenty milliliters of a 10% solution of nonmedicated soap are poured into the cupped hands which the subject then washes up to the wrists. After 20 seconds of washing, additional water is taken up and the washing con­tinued for another 75 seconds. Hands are then rinsed in the wash basin for 20 seconds and the water is allowed to drain into the basin for 20 seconds. The procedure is repeated, but this time the left hand is covered with a sterile glove and a 10% solution of bacteriostatic soap is used.

During the sampling periods, both hands are washed individually with nonmedicated soap solution only.

The panelist is instructed to follow the same washing procedure at home, which includes the use of neoprene gloves with medicated and nonmedicated soap bars. Soap solutions are used in the laboratory be­cause quantitative dispensing and lathering are made easier.

For colony counting, aliquots of wash water are added to Tryptic Soy Agar* containing 0.07% lecithin and 0.5% Tween-80®, f both of which are used as bacteriostat neutralizers. Plates are run in duplicate and incubated for 48 hours at 37 °C before counting.

Basin sampling sessions for bacterial counts are conducted on Mon­day, Wednesday, and Friday noons. The schedule of washing and sampling is shown in Table I.

For the experiments reported here, a nonmedicated soapj was used as the control. Two medicated soaps were evaluated, the first (Soap A)

* D i f c o L a b o r a t o r i e s I n c o r p o r a t e d , D e t r o i t , M i c h .f P o l y o x y e t h y le n e ( 2 0 ) s o r b i t a n m o n o - o l e a t e . R e g is t e r e d t r a d e m a r k o f A t l a s C h e m ic a l

I n d u s t r ie s , W i lm i n g t o n , D e l . 1 9 8 9 9 .+ I v o r y ® , P r o c t e r & G a m b le , C in c in n a t i , O h io .

HAND D E G E R M IN G EVALUATION 773

T a b l e 1

S p l i t -U s e W a s h i n g a n d B a c t e r ia l S a m p l in g S c h e d u le

D a y T i m e L e f t h a n d R ig h t h a n d

M o n d a y a m I v o r y I v o r yN o o n I v o r y ( c o u n t ) I v o r y ( c o u n t )p m I v o r y T e s t s o a p

T u e s d a y a m I v o r y T e s t s o a pN o o n I v o r y T e s t s o a pp m I v o r y T e s t s o a p

W e d n e s d a y a m I v o r y T e s t s o a pN o o n " I v o r y ( c o u n t ) I v o r y ( c o u n t ) ; t e s t s o a pp m I v o r y T e s t s o a p

T h u r s d a y a m I v o r y T e s t s o a pN o o n I v o r y T e s t s o a pp m I v o r y T e s t s o a p

F r i d a y a m I v o r y T e s t s o a pN o o n I v o r y ( c o u n t ) I v o r y ( c o u n t )

“ A f t e r c o u n t w a s h o n W e d n e s d a y , r ig h t h a n d w a s h e d w ith t e s t s o a p .

containing 0.75% hexachlorophene and 0.75% 3,4,4'-trichlorocarbani- lide, a synergistic bacteriostatic system. The second bacteriostatic soap (Soap B) contains equal parts by weight of 3,5-di and 3,4',5-tribro- mosalieylanilides, 4,4'-diehloro-3-(trifluoromethyl)carbanilide, and 3,4, 4'-trichlorocarbanilide for a total of 2%.

R e s u l t s a n d D i s c u s s i o n

A total of twenty-four men and women of various occupations were divided into four panels for the experiment. Two methods of analyzing the data were used to determine degerming efficiency of the two medi­cated soap bars: per cent reduction and an analysis of variance. Be­fore analyzing the data by an analysis of variance, logarithms of the bacterial counts were taken.

In Table II are presented the results of the analysis. A statistically significant difference was found between the degerming properties of the two bacteriostatic soaps as compared to the nonmedicated soap. For this test to show a statistical difference between medicated and non­medicated soaps, the probability that a difference does not exist should be less than or equal to 0.05.

The analysis also showed that there was no significant variation among panelists for all four tests. This indicates that in these panels

774 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

T a b le II

S u m m a r y o f A n a ly s i s o f V a r ia n c e o f Q u in n ( B a c t e r io s t a t i c s o a p s A & B v s . n o n -

T e s t ( F i f t h D a y D a t a ) m e d ic a t e d s o a p " )

S o a p A S o a p B

V a r ia t io n V a r ia t io n

T e s t V a r ia t io n a m o n g T e s t V a r ia t io n a m o n g

n o . b e t w e e n s o a p p a n e l is t s n o . b e t w e e n s o a p p a n e l is t s

i P < 0 .0 1 N .S . ' ’ 3 P < 0 .0 1 N .S .2 0 . 0 2 5 < P < 0 . 0 5 N .S . 4 0 0 5 < P < 0 . 1 N .S .

P o o le d P < 0 .0 1 N .S . P o o le d P < 0 .0 1 N .S .

“ X o n m e d i c a t e d s o a p : I v o r y ” , P r o c t e r & G a m b le , C in c in n a t i , O h io .

S o a p A : A c t i v e in g r e d ie n t s : 0.75% 3 ,4 ,4 '- t r i c h lo r o c a r b a n i l i d e , 0 . 7 5 % h e x a c h lo r o -p h e n e .

S o a p B : A c t i v e in g r e d ie n t s : 0 . 6 7 % 3 ,5 - d i - a n d 3 ,4 ',5 - t r i b r o m o s a I i c y l a n i l i d e s , 0 .6 7 % 4 ,4 '- d i c h lo r o - 3 - ( t r i f l u o r o m e t h y l ) c a r b a n i l i d e , 0 .6 7 % , 3 ,4 ,4 '- t r i c h lo r o c a r b a n i - Iid e .

h N . S . : N o t s ig n if ic a n t .

T a b l e I I I

R a n g e o f D e g e r m in g E f f ic ie n c ie s in P e r C e n t R e d u c t i o n s ( F i f t h D a y D a t a )

S o a p A S o a p B

T e s t n o . 9 5 % c o n f id e n c e l im it s T e s t n o . 9 5 % c o n f id e n c e l im it s

i 8 8 . 5 - 9 8 . 5 3 8 4 . 5 - 9 9 . 42 8 3 . 0 - 9 1 . 5 4 8 6 . 5 - 9 7 . 5

P o o le d 8 7 . 4 - 9 6 . 2 P o o le d 8 7 . 7 - 9 8 . 9

S o a p A : A c t i v e in g r e d ie n t s : 0 . 7 5 % 3 ,4 ,4 '- t r i c h l o r o c a r b a n i l i d e , 0 . 7 5 % h e x a c h lo r o p h e n e . S o a p B : A c t iv e in g r e d ie n t s : 0 .6 7 % 3 ,5 - d i - a n d 3 ,4 ', 5 - t r i b r o m o s a l i c y l a n i l i d e s , 0 .6 7 % 4 ,4 '-

d i c h l o r o - 3 - ( t r i f lu o r o i n e t h y l ) c a r b a n i l i d e , 0 . 6 7 % 3 , 4 , 4 '- t r i c h lo r o c a r b a n i l id e .

the pairing, or using an individual as his own control, was not absolutely necessary. Contrary to what might be expected, the number of tran­sient bacteria present on the hands of the subjects did not significantly influence the variation among panelists. Resident as well as transient bacteria were removed because of the extended period of handwashing.

To obtain a meaningful comparison of degerming ability between two test soaps using per cent reduction as the method of analysis, a con­fidence range or interval should be used in place of a single average value to avoid making false conclusions based on apparent differences between average values. This minimizes the possibility of making the assump­tion that a real difference exists between two soaps when the observed differences may be due merely to random biological variations.

HAND D E G E R M IN G EVALUATION

Results of the tests are summarized in Table III using per cent re­duction as the method of analysis. Only the 95% confidence limits are shown so as to emphasize the importance of using a range in the inter­pretation of per cent reduction calculations.

(Received April 12, 1967)

R e f e r e n c e s

( 1 ) U p d e g r a f f , D . M . , A c u lt u r a l m e t h o d o f q u a n t i t a t i v e l y s t u d y i n g t h e m ic r o o r g a n is m s in t h e s k in , J . Invest. Dermatol., 4 3 , 1 2 9 - 1 3 7 (A u g u s t 1 9 6 4 ) .

( 2 ) U lr ic h , J . A . , T e c h n i c s o f s k in s a m p l in g f o r m ic r o b ia l c o n t a m in a n t s , Hosp. Topics, 4 3 , 1 2 1 - 1 23 ( M a r c h 1 9 6 5 ) .

( 3 ) P a c h t m a n , E . A . , V ic h e r , E . E . , a n d B r u n n e r , M . J . , T h e b a c t e r io l o g i c f lo r a in s e b o r r h e ic d e r m a t i t is , J . Invest. Dermatol., 2 2 , 3 8 9 - 3 9 6 ( M a y 1 9 5 4 ) .

( 4 ) P r ic e , P . B . , T h e b a c t e r io l o g y o f n o r m a l s k in ; a n e w q u a n t i t a t i v e t e s t a p p l ie d t o a s t u d y o f t h e b a c t e r ia l f lo r a a n d t h e d i s in f e c t a n t a c t io n o f m e c h a n ic a l c le a n s in g , J . Infect. D is­eases, 6 3 , N o . 3 , 3 0 1 - 3 1 8 (1 9 3 8 ) .

( 5 ) C a d e , A . R , , A n t i s e p t i c s o a p s : a s im p l i f ie d in vivo m e t h o d f o r d e t e r m in in g t h e ir d e g e r m - in g e f f i c i e n c y , Soap Sanit. Chemicals, 2 6 , 3 5 - 3 8 a n d 73 ( J u ly 1 9 5 0 ) .

( 6 ) R o m a n , D . P . , B a r n e t t , E . H . , a n d B a ls k e , R . J . , C u t a n e o u s a n t i s e p t ic a c t i v i t y o f 3 ,4 ,4 '- t r i c h lo r o c a r b a n i l id e , Proc. Sci. Sect., Toilet Goods Assoc., N o . 2 8 , 1 2 - 1 3 ( D e c e m b e r 1 9 5 7 ) .

( 7 ) K o o i s t r a , J . A . , B a n n a n , E . A . , a n d C a r te r , R . O . , U s e o f h u m a n s u b je c t s f o r p r o d u c t e v a l u a t i o n : a n e v a lu a t io n o f a n t ib a c t e r ia l s o a p b a r s , J . Soc. Cosmetic Chemists, 1 7 , 3 4 3 -

3 5 3 ( M a y 1 9 6 6 ) .( 8 ) Q u in n , I T , V o s s , J . G . , a n d W h i t e h o u s e , H . S ., A m e t h o d f o r t h e in vivo e v a lu a t io n o f s k in

s a n it iz in g s o a p s , A ppl. Microbiol., 2 , 2 0 2 - 2 0 4 ( J u l y 1 9 5 4 ) .

77G JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

“Pleaac/idutic

CHANGE OF ADDRESS(1) Allow 6 weeks to make the

change.

(2) Send change to Editorial Assistant, 761 North Valley Chase Rd., Bloomfield Hills, Michigan 4801 3.

(3) Print name and new ad­dress— including postal zone number. Give old address— if possible re­turn addressed portion of the envelope in which your last Journal was mailed.

J . Soc . C osm etic C h e m ists , 18, 777-784 (Dec. 9, 1907)

The Color of Red Hair"

PETER FLESCH, M.D., Ph.D., ELIZABETH J. ESODA, M.D.,and SIDNEY A. KATZ, Ph.D.f

S y n o p s i s — T h e ir o n p ig m e n t s e x t r a c t e d w i t h b o i l in g a c id s f r o m h u m a n re d h a ir a n d c h ic k e n fe a th e r s a r e c l o s e ly r e la t e d a n d a re p o s s i b ly id e n t ic a l . E v i d e n c e is p r e s e n t e d t h a t t h e s e u n iq u e s u b s t a n c e s a re w e l l -d e f in e d c h e m ic a l e n t i t ie s a n d n o t a r t i f a c t s o f k e r a t in h y d r o ly s i s . T h e i r o n p ig m e n t is p r o b a b l y t h e m a j o r p ig m e n t o f h u m a n r e d h a ir . I t s l im i t e d e x t r a c t a - b i l i t y f r o m r e d h a ir is d u e t o it s d e s t r u c t io n d u r in g e x t r a c t i o n a n d n o t t o t h e s m a ll a m o u n t p r e s e n t in t h e h a ir . In a ll o f i t s f o r m s t h e ir o n p ig m e n t h a s b e e n p r o v e d t o b e a m e t a l l o - p r o - t e in . I t c a n b e b r o k e n d o w n t o a c o m p o u n d w ith a r e l a t i v e l y s m a ll m o le c u la r s iz e w h ic h r e ­t a in s a ll t h e e s s e n t ia l p r o p e r t ie s o f t h e o r i g in a l l y e x t r a c t e d p ig m e n t . S y n t h e s is o f a n i r o n - p r o t e in in m e la n o c y t e s r a is e s m a n y q u e s t io n s w h ic h c a n n o t b e a n s w e r e d a t p r e s e n t .

I n t r o d u c t i o n

Why is red hair red ? What is the chemical difference between the pigments of blonde and black hair? These natural variations in hair color usually extend to all epidermal pigment cells. For this reason, while ultraviolet light turns the skin of brunettes dark brown, it imparts a copper color to blondes, and burns red individuals. Yet we know very little about the chemistry of these basic types of human pigmentation.

Recent chemical studies have led to the conclusion that it will be a most difficult, possibly insurmountable, task to unravel the structure of the black and brown melanins, also called eumelanins, because of the variable course that polymerization may take during pigment formation(1). At least the precursors of eumelanins and the nature of the building stones aggregating to form the black pigment are known. In the case of

* I n v e s t ig a t io n s u p p o r t e d b y P u b l i c H e a lt h S e r v i c e R e s e a r c h G r a n t N o . A M 1 0 0 4 6 fr o m

t h e D i v is i o n o f R e s e a r c h G r a n t s , N a t io n a l I n s t i t u t e s o f H e a lt h .t D e p a r t m e n t o f D e r m a t o l o g y , S c h o o l o f M e d i c i n e , U n iv e r s i t y o f P e n n s y lv a n ia , P h ila ­

d e lp h ia , P a . 1 9 1 0 4 .

/ 1i

778 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

the yellow-red pigments (pheomelanins) * not even the chemistry of the mother substance has been clarified. Tryptophane has been suggested as a candidate, but there is no evidence that it has any such role except in lower species (2). Studies to test whether it gives rise to pheomelanins in man have led to negative results (3).

There is however in bright red human hair a characteristic entity, the “ possible pink constituent” of Sorby who discovered it almost 90 years ago. His classical description (4, 5) lists most of the unique properties of this pigment: its pink color when extracted from bright red human hairwith hot “ 20 times diluted sulfuric acid;” the color change and subse­quent precipitation upon addition of alkali to the solution; and its broad absorption band in the visible region of the spectrum. Sorby correctly suspected that the pink substance may be a degradation product and not the original form in which the pigment exists in the hair.

In 1943 unaware of this early account, Rothman and the senior author isolated this substance again by boiling red hair with 0.1 TV HC1 for 1-2 hours. The pink solution turned reversibly yellow above pH 2, precipitated at the neutral point, dissolved at an alkaline pH, had an ab­sorption band in acid solution with a maximum at about 535 my, and contained iron in the trivalent form. Very little information was ob­tained about its chemical composition. Because of its iron content, the material was named trichosiderin (6).

Trichosiderin met with a less than unprejudiced acceptance by the scientific world. An attempt was made to relegate it to the status of an artifact of keratin hydrolysis (7). No mention was made of the fact that the pink colored products in keratin hydrolysates turn yellow at pH 7 and can be obtained by boiling horny products (or other proteins with aromatic amino acids) for 4-6 hours with 40-60 times stronger acids than are required for the extraction of trichosiderin. Such procedures de­stroy the red hair pigment. Nevertheless this allegation found its way into the literature (2, 8) casting doubts on the existence of trichosiderin as a valid chemical entity.

The belief that trichosiderin was merely an incidental by-product of pigmentation in red hair was reinforced by the observation that after an apparently exhaustive extraction of trichosiderin, the color of red hair was not diminished noticeably. Also, the presence of iron in an epi­dermal pigment seemed incompatible with the copper enzyme-controlled synthesis of the eumelanins.

* T h e d i s t in c t io n b e tw e e n e u m e la n in s a n d p h e o m e la n in s is b a s e d o n c o l o r d i f fe r e n c e s , s o lu ­b i l i t y in a c id s a n d a lk a l ie s a n d n a t u r e o f p r e c u r s o r s (2 ) .

T H E COLOR OF RED HAIR 779

During the past 20 years, other investigators have extracted similar pigments from red chicken feathers (9, 10). These results suggested that red iron pigments were also present. More recently, Barnicot (11), ex­tracted from human red hair a yellow solution with weak alkali at room temperature. Upon boiling in weak acids for five minutes, this solution turned red and assumed the characteristic absorption spectrum of tri- chosiderin. Barnicot’s finding has provided further proof that tri- chosiderin is not an artifact of keratin hydrolysis.

The progress of the past 20 years in the isolation and purification of tissue components persuaded us to resume the study of this unique sub­stance. It was hoped that the pigment of red chicken feathers would prove sufficiently similar to trichosiderin to serve as an experimental model, thus overcoming the difficulty of obtaining sufficient quantities of red hair.

R e c e n t R e s e a r c h o n R e d H a i r P i g m e n t

The first aim of the work, the isolation of various forms of iron pig­ments from chicken feathers has been achieved (12). All these forms have absorption bands at about 280 m,u. This paper describes the over­all direction and some general aspects of these studies.

In all major respects the pigment of red chicken feathers behaved as its human counterpart. It had the same indicator properties in its “ siderin” form, precipitated at pH 7, had the same absorption spectrum, contained iron, and could be degraded to derivatives analogous to those of trichosiderin. This finding is of considerable biologic importance. It suggests not only that the iron pigment is phylogenetically very old, but also sheds new light on the relative importance of trichosiderin.

Considerably larger amounts of pigment could be extracted from feathers than from hair. Boiling for ten minutes with 0.1 iV HC1 yields 6-10 times more pigment than two hours of boiling of hair. This finding was not surprising, because on a macroscopic and molecular level feathers are looser structures than hair and would release their pigment more easily. However, feathers of Rhode Island Red chickens are not notice­ably redder than bright red hair. It appears that a large proportion of trichosiderin may be retained by the compact hair shafts. Conse­quently, during the prolonged extraction the pigment may be attacked by the extracting hot acid and made insoluble in the hair shaft.

This hypothesis was tested by prolonging the extraction of hair and feathers with boiling 0.177 HC1 for several hours. Although the solu­tions obtained in the later stages are pale yellow or virtually colorless,

780 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

F ig . 1. A b s o r p t i o n s p e c t r a o f t r i c h o s id e r in s in O . l iV H C I w it h in c r e a s in g le n g th o f e x t r a c t io n f r o m h a ir . A t a r r o w t h e c o n c e n t r a t io n o f t h e s o lu t io n s w a s d e c r e a s e d t o o b t a in r e a d in g s a t

s h o r t e r w a v e le n g t h

upon neutralization small amounts of pigment may be precipitated from them. These late precipitates are increasingly brown; their absorption bands at 535 m/r flatten and eventually disappear (Fig. 1), and their iron content steadily decreases (Table I). The organic portion of the pig­ment has no characteristic absorption bands and is complexed in acid solution through its combination with iron. Therefore it is likely that when the iron content drops below a certain level (about 0.1%), the pig­ment becomes insoluble and cannot be extracted anymore.

Indirect evidence for this view comes from Dutcher and Rothman’s iron determinations in hair of different colors (13). Black and blonde hairs were found to contain, on the average, 2.71 and 2.43 mg Fe/100 g, respectively; red hair, on the average, 9.78 mg/100 g i.e., about 7 mg more per 100 g hair than the other varieties. Assuming an iron content of about 0.5% in the original pigment in situ, 7 mg iron corresponds to 1400 mg pigment. Actually, red hair yields 40-60 mg trichosiderin per 100 g of hair; therefore only 3-5% of the total amount may be ex­tracted. As the iron content of the pigment in the hair itself is unknown,

T H E COLOR OF RED HAIR 7,SI

T a b le I

I r o n C o n t e n t o f H a ir a n d F e a t h e r P ig m e n t s a f t e r V a r y i n g L e n g t h s o f E x t r a c t i o n T im e

L e n g t h o f e x t r a c t i o n w ith b o i l i n g O . l iV H C 1 (h r ) H a ir p ig m e n t (F e % ) F e a t h e r p ig m e n t (F e

1 0 . 3 8 0 .5 12 0 . 2 4 0 . 1 73 0 . 1 5 0 . 1 5

this calculation may be faulty.* Yet the basic observation is correct that the pigment is destroyed gradually during extraction. The authors believe that the iron pigment is a major, possibly the major, pigment of bright red human hair.

In attempts to elucidate the chemical nature of trichosiderin, the re­search concentrated on the chromophore group which contains iron com- plexed with an organic moiety. The presence of iron in the molecule is responsible for its acid solubility, absorption band in the visible, indi­cator property, and neutral iso-electric point. The iron-free or iron-poor parts of the pigment have few characteristic features; they are insoluble in acids, dissolve with a yellow-brown color in alkalies, and have no ab­sorption band in the visible.

Trichosiderin proved to be a metallo-protein; preliminary analyses indicate that it is composed solely of iron, amino acids, and maybe some amines.| The protein nature is firmly established by a CHN ratio of 47.2-49.2, 6.8-7.3, 15.4-16.3 in all forms of the pigment, a positive Lowry reaction (14), typical infrared spectra, and amino acid analyses.

Before carrying out extensive amino acid analyses, efforts were di­rected at obtaining a chromophore of the smallest possible molecular weight which still retains all the specific properties of trichosiderin. The method is essentially one of repeated acid extraction. The chromophore is soluble in acids and highly resistant to them at room temperature. Acid extraction of the chromophore with successive removal of the iron- poor parts is carried out at different levels: first with boiling O.liV HC1during the extraction of trichosiderin or feather siderin; then with 5N HC1 or 10% KSCN which splits off large amounts of brown, iron-poor material. The resulting chromophore becomes dialyzable in O.liV HC1.

* D u t c h e r a n d R o t h m a n 's d a t a a re b a s e d o n a n ir o n c o n t e n t o f 1 0 % , a n u n r e a l is t i c f ig u r e . A t b e s t , s u c h a h ig h i r o n c o n t e n t c o u ld b e f o u n d in p u r i f ie d p r e p a r a t io n s o n l y (5 , 1 5 ) ; in th e p r e s e n t w o r k it w a s im p o s s ib le t o o b t a i n s u c h s a m p le s .

f I m p r o v e d a n a ly t i c a l m e t h o d s m a y a c c o u n t f o r t h e d i s c r e p a n c ie s b e t w e e n e a r l ie r r e p o r t e d d a t a (5 , 1 5 ) a n d t h o s e r e p o r t e d h e r e in .

782 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

With each successive step more and more of the brown, nondialyzable component is removed and the chromophore becomes increasingly purple with sharpened absorption bands and a threefold increase in iron content. The dialyzable chromophore passes through a Sephadex G-.;0 column as a single sharp band, and its ultraviolet and visible bands are in the same fractions. Present experiments suggest that further diminution of its molecular size may be achieved; the size already obtained is smaller than that of any heretofore described human epidermal pigment.

Amino acid analyses may reveal much about the nature of the chromophore. By comparing hair pigments with feather pigments and by analyzing the iron-free and iron-rich portions, it should be possible to single out those amino acids which combine with iron to form the chro­mophore group. Preliminary amino acid analyses already have revealed regularities in some of the split products.

B i o l o g i c a l I m p l i c a t i o n s

The synthetic pathway of this pigment raises many questions. If the iron pigment is elaborated by pigment cells, then the synthesis of an iron- protein by nucleic acids must follow a radically different course than the copper-catalyzed polymerization of eumelanin in the melanosomes. This view must be reconciled with everyday observations and clinical ex­perience which strongly suggest that these two pathways must coexist(2). Here only a few pertinent observations will be mentioned. There is a whole gamut of red shades, ranging from “ carrot-red” or “ orange” through Titian-red to red-brown (1(5). While these varieties could be explained with differences in the chromophore content of the iron pig­ment, it is conceivable that a varying admixture of eumelanin pigment also is present. The frequently observed gradual darkening of red (and blonde) individuals with advancing age favors the view that the two pig­mentary processes coexist. The strongest proof for this theory is the occasional irreversible conversion of red hair to brown after the adminis­tration of chloroquine (2).

Is it then the same pigment cell which produces a metallo-protein and a melanin? The answer is not known. Although red pigment cells in man and fowl appear to differ from the melanocytes synthesizing black melanins (17, 18), the data are too fragmentary to permit a definite con­clusion. It is also possible that macroscopic red color occasionally may be produced without iron. From time to time the authors have obtained specimens of bright red hair which did not yield any iron pigment A case in point also may be the reddening of the hair of infants suffering

T H E COLOR OF RED HAIR 783

from kwashiorkor, a severe nutritional deficiency (19). That redness does not necessarily presuppose an iron pigment is proved by the Irish setter whose red hair contains no tricliosiderin.

Although two pigmentary pathways must be postulated, there is no reason why these pathways must follow a common initial course, as sug­gested by Fitzpatrick et al. (2). All the available facts may be explained by assuming two coexisting but independent pathways for red and black pigments.

Another unsolved problem is presented by the “ missing links” be­tween chicken and man. Tricliosiderin may occur in other species as well, but as yet none has been found.

Red-haired individuals may be biologically inferior. The hair cover­ing the entire body of our ancestors regardless of its color, offered ade­quate protection against ultraviolet light. As hair became a rudimen­tary structure, the epidermis became exposed to sun against which the iron pigment apparently does not offer adequate protection. The pres­ent scarcity of red-haired people may be due to their suppression by the more viable dark-colored races.

Discovery of a previously unknown substance, such as the iron pig­ment of red hair, always raises more questions than can be answered. Most of these problems are accessible to experimental study. It is hoped that their solution will be attempted before another 25 years will elapse.

(Received February 3, 1997)

R e f e r e n c e s

( 1 ) W e r t z , J . E . , et al., Electron Sp in Resonance Studies of Autoxidation of 3 ,4-dihydroxy- phenylalanine, in B lo is , M . S ., J r . , el al., Free Radicals m Biological Systems, A c a d e m i c P re s s , N e w Y o r k , N . Y . , H if.il, p p . 1 8 3 -1 9 3 .

( 2 ) F i t z p a t r i c k , T . B ., et al., The Nature of H air Pigment, ill M o n t a g n a , W . , a n d E ll is , R . A ., Biology of H air Growth, A c a d e m i c P re s s , N e w Y o r k , N . Y . , 1 95 8 , p p . 2 5 5 - 3 0 1 .

( 3 ) F i t z p a t r i c k , T . B ., P e r s o n a l c o m m u n i c a t i o n .( 4 ) S o r b y , H . C ., O n t h e c o l o u r in g m a t t e r s f o u n d in h u m a n h a ir , J . Anthropol. Inst. Gt.

Brit., 8 , 1 - 1 4 ( J a n u a r y 1 8 7 8 ).( 5 ) F le s c h , P ., a n d R o t h m a n , S ., I s o la t io n o f a n ir o n p ig m e n t f r o m h u m a n r e d h a ir , J.

Invest. Dermatol., 6, 2 5 7 - 2 7 0 ( A u g u s t 1 9 4 5 ) .( 6 ) R o t h m a n , S ., a n d F le s c h , P . , I s o la t io n o f a n ir o n p ig m e n t f r o m h u m a n r e d h a ir , Troc.

Soc. Exptl. Biol. Med., 5 3 , 1 3 4 - 1 3 5 (J u n e 1 9 4 3 ) .( 7 ) H a n n a , B . L . , P r o d u c t i o n o f p ig m e n t s s im ila r t o t h o s e f r o m h a ir f r o m a m in o a c id a n d

k e r a t in i n t e r a c t io n , Ibid., 8 0 , 2 8 5 - 2 8 7 (J u n e 1 9 5 2 ) .( 8 ) R o t h m a n , S ., Physiology and Biochemistry of the Skin , T h e U n i v e r s i t y o f C h i c a g o P re s s ,

C h i c a g o , I I I , 1 9 5 4 , p p . 5 1 8 - 5 1 9 .( 9 ) N i c k e r s o n , N . , R e la t i o n b e t w e e n b la c k a n d r e d m e la n in p ig m e n t s in f e a th e r s , Physiol.

Znol., 1 9 , 6 6 - 7 7 ( J a n u a r y 1 9 4 6 ) .

784 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

( 1 0 ) S m y t h , J . R . , P o r t e r , J . W . , a n d B o h r e n , B . B . , A s t u d y o f p ig m e n t s f r o m re d , b r o w n a n d b u f f fe a th e r s a n d h a ir , Physiol. Zool., 2 4 , 2 0 5 - 2 1 6 ( J u ly 1 9 5 1 ) .

( 1 1 ) B a r n ic o t , N . A . , T h e p ig m e n t , t r i c h o s id e r in , f r o m h u m a n re d h a ir , Nature, 1 7 7 , 5 2 8 - 5 2 9 ( M a r . 17 . 1 9 5 6 ) .

( 1 2 ) F le s c h , P . , E s o d a , E . J . a n d K a t z , S- A . , T h e i r o n p ig m e n t o f r e d h a ir a n d fe a th e r s , J. Invest. Dermatol., 4 7 , 5 9 5 - 5 9 7 ( D e c e m b e r 1 9 6 6 ) .

( 1 3 ) D u t c h e r , T . F . , a n d R o t h m a n , S ., I r o n , c o p p e r , a n d a sh c o n t e n t o f h u m a n h a ir o f d i f ­f e r e n t c o lo r s , Ibid., 1 7 , 6 5 - 6 8 ( A u g . 1 9 5 1 ) .

( 1 4 ) L o w r y , O . H ., R o s e b r o u g h , N . J ., F a r r , A . L . , a n d R a n d a l l , R . J . , P r o t e in m e a s u r e m e n t w it h t h e F o l in p h e n o l r e a g e n t , J . Biol. Chem., 1 9 3 , 2 6 5 - 2 7 5 ( N o v e m b e r 1 9 5 1 ) .

( 1 5 ) R o t h m a n , S ., a n d F le s c h , P . , I s o la t io n o f a n i r o n p ig m e n t f r o m h u m a n r e d h a ir , Pror. Sor. Exptl. Biol. Med.. 5 3 , 1 3 4 - 1 3 5 ( M a y - J u n e 1 9 4 3 ) .

( 1 6 ) F o x , H . M . , a n d V e v e r s , G . , The Nature of A nim al Colours, S id g w ic k a n d J a c k s o n L t d . , L o n d o n , 1 9 6 0 , p . 3 3 .

( 1 7 ) B o h r e n , B . B ., C o n r a d , R . M . , a n d W a r r e n , D . C . , A c h e m ic a l a n d h is t o lo g ic a l s t u d y o f t h e f e a t h e r p ig m e n t s o f t h e d o m e s t i c f o w l , A m . Naturalist, 7 7 , 4 8 1 - 5 1 8 ( N o v e m b e r - D e c e m b e r 1 9 4 3 ).

( 1 8 ) B a r n ic o t , N . A . , a n d B ir b e c k , M . S . C . , The Electron Microscopy of H um an Melanocytes and M elanin Granules, in M o n t a g n a , W . , a n d E ll is , R . A . , Biology o f H air Growth, A c a d e m i c P re s s , N e w Y o r k , N . Y . , 1 9 5 8 , p p . 2 5 5 - 3 0 1 .

( 1 9 ) E l - H e f n a w i , H . , S h u k r i, A . S ., a n d R a s h e e d , A . , K w a s h io r k o r in t h e U n it e d A r a b R e ­p u b l i c , Brit. J . Dermatol., 7 7 , 1 3 7 -1 5 0 ( M a r c h 1 9 6 5 ) .

J . Soc. C osm etic C h em ists , 18, 785-796 (Dec. 9, 1967)

Use of Electronic D ata Processing in A nti-D andruff Clinical Research

MARTIN GREIF, B.S.,* and HARRY J. PROKOPf

Presented November 30, 1966, New York City

S y n o p s is - F i f t e e n d i f f e r e n t c o m p o s i t i o n s w e r e s t u d ie d in a p i l o t c l in i c a l p r o g r a m in t e r m s o f t h e ir a b i l i t y t o c o n t r o l t h e s y m p t o m s o f d a n d r u f f . T h e c l in i c a l p r o t o c o l is d is c u s s e d b r ie f ly . E le c t r o n i c d a t a p r o c e s s in g o f t h e d o u b l e - b l i n d m o n a d ic c l in i c a l s t u d y is d e s c r ib e d in s o m e d e t a i l . F o r c o m p a r i s o n p u r p o s e s , th e d a t a w e r e a n a ly z e d b o t h b y E D P a n d m a n u a l m e a n s T h e r e la t iv e e c o n o m i c s a r e d is c u s s e d .

I n t r o d u c t i o n

The etiology of dandruff and its treatment have been discussed in scores of technical communications during the past century. In an early scientific discussion of dandruff, Malassez (1) was the first to indict Pityrosporum ovale as the cause of dandruff. Over the years from 1874 to the present day, numerous authors have taken sides for or against this hypothesis. Each has presented evidence to support his contentions. The literature is replete with references (2-8) covering both sides of this controversy.

A systematic review of the literature discloses that numerous addi­tional theories on the cause of dandruff have been offered, and countless treatment procedures were reported as being effective. Thus there are theories relating to various microbial causes (9-14). Wallace (15) con­siders dandruff to be a manifestation of seborrhea or psoriasis bearing no

* C o n s u m e r P r o d u c t s D iv is io n , A m e r ic a n C y a n a m id C o m p a n y , W a y n e , N . J . 0 7 4 7 0 . j F i s h e r -S t e v e n s , C l i f t o n , N . J . 0 7 0 1 2

785

780 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

causal relationship to the microorganisms found on the scalp. He recom­mends the keratolytic approach. Van Abbe (16) suggests that an al­lergic mechanism plays a significant role in dandruff causation. Some investigators (17, 18) maintain that the condition is a disordered normal desquamating process often associated with excessive oil secretion on the scalp. Harry (3) cites several authors who attempted to show a relation­ship between digestive disorders and dandruff.

Considering the many hypothetical causes of dandruff symptom­atology, it is no surprise that treatment approaches include antimicrobial as well as keratolytic therapy; steroid; antihistaminic; antimitotic; special dietary; and recently, enzymatic (19, 20) approaches. It is widely agreed that the first consideration in effective treatment for dan­druff requires thorough cleansing of the scalp to remove both loose and adherent scale. The second phase generally involves the use of a suit­able agent to inhibit further production of scale. It is in the latter phase where most differences of opinion arise. Some investigators employ various biochemical means to inhibit scaling. Others prefer to incorpo­rate the therapeutic agent in a shampoo, while still others apply it as a post-shampoo rinse. Another school of thought recommends a pre­shampoo treatment.

This investigation was designed on the theory that topical post­shampoo rinse therapy is most easily controlled. A standard pre-treat­ment shampoo was used. The rinses were simple aqueous solutions or suspensions of different active ingredients supplemented with a condi­tioner. They were designed to place the therapeutic agents in intimate contact with the hair and scalp. Approximately 750 subjects entered and 717 completed the study.

Early in the planning stages it became apparent that more than one clinical trial with basically the same design would eventually be required. Masses of data would be generated, and these would undoubtedly be cumbersome and costly to process manually. A review of the protocol suggested that with properly designed record forms the study could be programmed for electronic data processing. Once the programming costs were amortized, subsequent data processing costs and time require­ments would be relatively small. If the program were flexible enough, it might be adaptable to other studies with other products. This paper will briefly discuss the clinical protocol and then consider the data pro­cessing in some detail. For comparison purposes the data were analyzed by both EDP and manual means. The relative economics will also be discussed.

DATA PROCESSING OF ANTI-D AN D RU FF RESEARCH 787

P r o c e d u r e

At the start of the study the subjects were divided into fifteen balanced groups with all groups using the same shampoo but each a different test rinse. At the initial visit the consulting dermatologist examined each subject and noted the severity of both loose and adherent dandruff. Using a scale of zero to four plus, only those subjects with three plus or four plus in both loose and adherent dandruff were admitted to the study. Additional information, such as scalp conditions, derma­toses, and presence of itching, was noted on the record forms. Once a subject was qualified to participate in the study, a dandruff history was prepared for that subject. The details of the actual clinical trial, which lasted eight weeks, are not germane to this discussion. However, the subjects were examined by a dermatologist five days after treatment during weeks Nos. 1, 2, 4, (i, and 8, and his observations were recorded. Upon completion of the trial, each participant was required to complete a questionnaire wherein he or she provided subjective responses to various questions. The completed forms were checked and then forwarded for key punching and data processing.

E l e c t r o n i c D a t a P r o c e s s i n g

Transmittal Forms

Three custom transmittal forms were designed to record the pertinent information for each subject in the study (Figs. 1, 2, and 3). The infor­mation from each transmittal sheet was key punched into an SO-column data card. For each subject there were three cards of punched data. The subjects were identified by name and number. Transmittals were designed to allow flexibility in the subjects’ entries and still provide meaningful data for computer processing. Encoded on the transmittals were numbers associated with answer boxes or comment entries which ranged from 1 to 80. These are the card columns in which the data were punched. Figure 4 shows a typical punched-in data card.

Dandruff History Form

This form contained the subject’s identification including name, number, address, phone number, vocation, sex, age, etc., and a brief history relating to scalp and hair. The history included information such as : years with dandruff, number of shampoos per month, the sub­ject’s own appraisal of his extent of hair loss from (a) combing and (b) shampooing, and the names of products used on the hair.

788 JOURNAL OF T H E SOCIETY OF COSMETIC CHEMISTS

DANDRUFF HISTORY FORM

n... •SfrtTu. m a r y ____________________ pk™ rsT-ta/a6l2l

Address V C , 6- A 0 ✓ Ê 5 7 . ̂ À S 'Y ^ H £ K £ , _______________________________________

Vocation f-)O C^p ^ 1 !~/3 22-39

Date 1 - O / 'C C

Subject GroupNo. No.

¡CCS / Ä1-3 4-5

Sex Age DandruffNo. SHAMPOOS

F vs* '3 S '40 41-42 43-44 45-46

S O A P S SHAMPOOS HAIR-DRESSINGS RINSES and DYES

1 - Comay2 - Cashmere Bouquet3 - Dial4 - Dove5 - Ivory6 - Lifebuoy7 - Lux Toilet8 - Palmolive9 - Safeguard

1 0 - Zest

1 - Alberto VO-52 - Breck3 - Chorles Antell4 - Conti5 - Enden6 - Holo7 - Head 8. Shoulders8 - Helene Curt.s

10- Prell

1 - Alberto VO-52 - Brylcreem3 - Commond4 - Groom & Clean5 - Nestle6 - Score7 - Top Brass8 - Vaseline Cream 8 - Vito lis

10 - Vitapointe

1 - Bright Idea2 - Color L ift3 - Color Up4 - Foam & Sparkle5 - Lady Clairol6 - Loving Care7 - Morchands8 - Nestle9 - Nice & Easy

10 - Roux Fonciful

> 2 - ----------- y r r n r T - ---------- 1 2 - --------- Is-pÉfcTé-vf---------- 12--------------tsp-e iFvi---------- 12 ------------- ,SP, , . FY,----------

a 1 c 1 / 1 1___ vl i 149-50 51-52 53-54 55-56 57-58 59-60 61-62 63-64 65-66 67-68 69-70 71-72 73-74

H A I R L O S S from

COMBING SHAMPOOING

a /47 48

SCALE FOR EVALUATIONS

0 - Absent

1 - Mild

2 - Moderate

3 - Moderate to Severe

4 - Severe

DERMATOLOGIST'S COMMENTS: 75-76

Figure 1. P a t ie n t h i s t o r y t r a n s m it t a l fo r m

Dandruff Record FormIn addition to the subject’s identification, this form contained the

dermatologist’s evaluation of the subject’s hair and scalp condition at each observation interval. Included in the evaluation were the extent of dandruff scaling (both loose and adherent) ; the condition of the scalp whether dry, oily, or normal ; and the degree of itching. The derma­tologist was also afforded a place to note the presence of supraorbital dermatoses, which are often associated with dandruff. If such derma­titis was reported, it was described under doctor’s comments. Six ob­servations were made by the dermatologist during the eight-week study.

Dandruff QuestionnaireThe Questionnaire posed key questions about the subject’s personal

response to the test product and a comparison to previously used prod­ucts. The subject was asked to note the extent of hair loss (if any) dur­ing the last week of the study.

DATA PROCESSING OF ANTI-D AN D RU FF RESEARCH 789

DANDRUFF RECORD FORM

Nam. M 1 T M . ¿A A J? Y ________________________________________________ PKon* No. ¿ g j j ; / S / ? Vocation H cU SC U* / A £

k i t . . , . ~7 C S 7 I A / v Y ^ H F R E V . S . A _________________________________________________________________

s T A R T 1st W E KSubject

No.Group

No. Lo o .. Adherent Dry Oily—Normal Itching Dermatitis Loos. Adherent Dry Oily Normal Itching Dermatiti!

F C ? / a ? £ o « 3 1̂ 21-3 4-5 6 7 8 9 10 12 13 14 15 16 17 18 19

2nd W E E K 4th W E

Loos. Adherent Dry Oily Normal Itching Dermatitis Loose Adherent Dry Oily Normal Itching Dermatitis

a a 1/ / 2. / / \ S <o O20 21 22 23 24 25 26 27 28 29 30 31 32 33

6th W E E K 8th W E

Loo*. Adherent Dry Oily Normal Itching Dermatitis Loose Adherent Dry Oily Normal Itching Dermatitis

/ > C> o o / Ö

34 35 36 37 38 39 40 41 42 43 45 46 47

SCALE FORWEEKLY EVALUATIONS D A T E D O C T O R S C O M M E N T S CODE

Start M.D. 48-9

1st Week M.D. 50-1

2nd Week 5 c./t L / M p & F Ë A F 5 A * -0 F c R E H F A P “ d . O f 52-3

4th Week M.D. 54-5

6th Week M D. 56-7

8th Week M.D. 58-1

Figure 2. P a t ie n t r e c o r d t r a n s m it t a l fo r m

Coding System

A coding method was established for tabulating entries on the trans­mittals in order to simplify key punching and to eliminate the need for a large volume of alphabetic information in core storage. It also simplified computer program logic and reduced machine processing time.

Each test product was assigned a two-digit number called group number. The subjects were assigned three-digit numbers called subject number. A scale for evaluations to record severity of each condition under study was included and is shown in Figs. 1, 2, and 3. Entries in spaces provided for doctor’s comments, previously used hair and scalp products, and the subject’s recorded likes and dislikes about the test product were all assigned two-digit numbers for coding. Through the use of this coding system, the printed reports were far more comprehens­ible in that they were not cluttered with verbose descriptions.

790 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

D A N D R U F F Q U E ST IO N N A IR E

S’ai ) T h ? A l j / ? y

y - g o - écy <¿9S u b je c t N o.

A d d re ss ~7 (c C r A O V f <S7~. , A M / U ht F. f i ß . Ç A S. A - G roup N o .___________________________J ̂ 4_5P ho ne N o . S ~ f T 5 " ! «L J ________ V o co tio n / / £? O* ^ ^ / F £ S e x Q M o le [ 0 F e ma le Age

_Z^_

How w ould you ra te the te s t p ro duct w h ic h you used the p ast 2 m onths? (C h e c k o n ly one).

O ne of the b e s t 1■v. tr ie d 0 ^G o o d , but not on e of the b e s t f- 1 2F a i r P 3P oor □ <

D uring the month befo re you sta rte d th is te s t , w h a t one p ro duct d id you u se m ost for tre a t in g do ndruff or w a sh in g yo ur hair.-

D------------------------------------; 7 - r e ----------------

How w ould you ra te the te s t p roduct you used the p a s t 2 m onths w ith the one lis te d im m ed iate ly abo ve . (C h e c k proper b o xes)T e s t P ro d u ct T e s t P ro d u ct T e s t P ro d uct

M O R E E F F E C T I V E AS E F F E C T I V E L E S S E F F E C T I V EC o m p ariso n of D A N D R U F F r e s u lt s

A . R e d u c tio n in am ount of dand ru ff ŒT □B . Len g th of tim e d a nd ru ff w a s reduced □ 0 " □ »

H a ir M O R E M A N A G E A B L E □ □ 105'H a ir F E E L S C L E A N E R 0 " □ □ 22

P le a s e w r ite down e ve ry th in g you can th in k o f tha t you L IK E D about th is t

D e d u c e d O a u d r o F P ____________________________

CODE

23-24S C A L p ____ F E Z l - S G- & & Û ClA 25-26

27-2829-30

P le a s e w r ite down e ve ry th in g you can th in k o f tha t you D IS L IK E D about th is

C A U S E D i T u H / ^ C _______________________ 2 2 . 31-3233-3435-3637-38

H A R D T o C o A A f t

U s in g the S c a le F o r E v a lu a t io n s e n te r the number in b o xes 39 and 40 w h ich b e s t d e s c r ib e s your e x p e r ie n c e w ith h a ir lo ss during the la s t w eek o f th e s tu d y .

H A IR L O S S from

C O M B IN G S H A M P O O IN G

/39 40

S C A L E F O R E V A L U A T IO N S

0 — A b se n t1 - M ild2 — M oderate3 - M oderate to S ev ere

SUBJECT'S SIGNATURE

Figure 3. P a t ie n t q u e s t io n n a ir e t r a n s m it t a l f o r m

DATA PROCESSING OF ANTI-DANDRUFF RESEARCH 701

Transmittal Processing

A ft e r th e s t u d y w a s c o m p le te d , t r a n s m itta ls w e re e d ite d fo r c o m ­p le te n e ss a n d a c c u r a c y . T h e d o c t o r ’s c o m m e n ts o n th e r e c o r d fo r m s a n d th e s u b je c t ’s r e c o r d e d lik e s a n d d is lik e s o n th e q u e s t io n n a ire s w ere c o d e d a t th is t im e u s in g m a ste r c o d e lists . N e x t , th e p e r t in e n t in fo r m a ­t io n w a s k e y p u n c h e d in t o 8 0 -c o lu m n d a ta ca rd s . T h e ca rd s w ere v e r i ­fie d t o in su re a c c u r a c y . B e c a u s e th e re are o n ly 80 co lu m n s p e r ca rd , a s e p a ra te ca rd w a s re q u ir e d fo r e a ch t r a n s m it ta l fo rm .

Unit Record M achine Processing

T h e k e y p u n c h e d ca rd s w e re s o r te d t o g r o u p n u m b e r a n d s u b je c t n u m b e r s e q u e n ce a n d s e p a ra te d in t o th re e ca rd ty p e s — 'h is to r y , re c o rd , a n d q u e s t io n n a ire — o n a h ig h -s p e e d ca rd so rte r . T h e n e a ch d e c k w a s l is te d o n a ta b u la t in g m a ch in e fo r th e p u r p o s e o f v is u a lly e d it in g th e k e y p u n c h d a ta . A ft e r n e ce s s a r y c o r r e c t io n s w e re m a d e , th e h is to r y d e c k w a s m a tc h e d a g a in s t th e r e c o r d a n d q u e s t io n n a ire d e ck s o n g r o u p a n d s u b je c t n u m b e r s t o in su re th a t a ll th re e ca rd s fo r e a ch p a t ie n t h a d b e e n k e y p u n c h e d fo r p r o c e ss in g . T h e c o m p u t e r w a s p r o g r a m m e d t o n o te in ­co n s is te n c ie s o r lo g ic e rrors in th e ra w d a ta . I f a ca rd fo r a p a t ie n t w a s m iss in g in a n y o f th e th re e d e c k s o r if an id e n t i fy in g n u m b e r w a s in c o r ­r e c t ly k e y p u n c h e d , th is w o u ld c o n s t itu te se le c te d u n m a tc h e d ca rd s . R e a s o n s fo r u n m a tc h e d ca rd s , o th e r th a n th e tw o m e n t io n e d a b o v e , c o u ld b e as f o l l o w s :

(a ) A s u b je c t v o lu n t a r i ly d r o p p e d o u t o f th e s tu d y .(b ) A s u b je c t fa i le d t o fo l lo w th e p r e s c r ib e d p r o t o c o l in s tr u c t io n s a n d

w a s d r o p p e d .(c ) A t r a n s m it ta l f o r m w a s in a d v e r t e n t ly n o t k e y p u n c h e d .

A ll u n m a t c h e d ca rd s e je c t e d in th e s o r t a n d m a tc h p r o c e ss w e re c h e c k e d a t th is t im e , a n d n e c e s s a r y c o r r e c t io n s w e re m a d e b e fo r e p ro c e s s in g c o u ld c o n t in u e (F ig . 5 ).

T h e n e x t p h a s e in u n it r e c o r d p ro c e s s in g w a s t o s e g m e n t th e h is to r y ca rd s in t o d e s ire d a ge g r o u p s a n d y e a r s w ith d a n d r u ff g r o u p s fo r c o r r e la ­t io n r e p o r ts . T h is w a s a c c o m p lis h e d b y s o r t in g th e h is t o r y ca rd s in to th e a g e o r y e a rs w ith d a n d r u ff s e q u e n c e a n d s e p a ra t in g th e ca rd s in t o th e d e s ire d g ro u p s . T h e n e a ch g r o u p w a s m a tc h e d a g a in s t th e r e c o r d ca rd s o n te s t p r o d u c t a n d s u b je c t n u m b e r in o r d e r t o s e p a ra te th e r e c o r d d e c k in to th e sa m e g ro u p s . T h e s e g m e n te d r e c o r d ca rd s w e re th e n c o d e d u s in g th e g a n g p u n c h in g m e th o d o n a r e p r o d u ce r . T h u s , th e a ss ig n ed c o d e s w e re u se d as c o n t r o l fa c t o r s in c o m p u t e r p ro c e s s in g ra th e r th a n th e

60 OR

80 INT

ERPR

ETING

-GENE

RAL

PURPO

SE

792 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

« S l Ê S m K . P i f - ï ^FC L 'SE l'IF r FIT f ? "771C? f 7 01 07

7«m i |s:| .| ' . IT ? s s o E o [ i | | »1 s ? ;■ 6 î ? î î s !» : ; : r| 1 1 s c s I | | | T|T T m lT îT iïiT ïT m îI ? 1 I 2 i I I 1 II IM I II U 15 K U II II ?S 71 27 21 74 72 71 71 71 7! Il II 77 71 74 77 21 II 71 77 41 II 4 7 4 7 4 4 47 II (I II I! It II 12 II 74 22 » I) Il 22 II il 17 11 14 12 il il il IS It II I' 77 14 >2 i II II 1! II

; I 1 1 1 I T I e : i 1 1 1 ] I 1 1 i 1 1 1 1 1 i l 1 1 I I M 1 1 1 1 1 1 : I ! I i I I 1 1 1 i : i i | i ; 1 1 ■ ; ■ |

1 1 ! ! ■ ■ 2 1 2 2 7 ! ! 2 2 2 ì ; ì 2 Ì 2 2 2 Ì | ! 2 2 2 2 2 2 2 i f } l 2 ! | 2 ! 7 1 1 1 ! ! | 2 . Ì :2 2 ! I 7 2 2 2 * 1 1 l 1 i 1 J Ì 2 2 1 l 1 1 ! 1 2 ! I1 7 7 I I I 1 I ! Il II 17 11 U II IS I) II It 21 71 72 77 71 72 It 71 21 71 » 71 77 77 74 72 U II 71 72 41 41 42 47 44 42 41 II II 4 1 21 21 27 27 24 22 It 21 21 It It It l? 17 14 |2 K il il It !| 71 17 17 74 12 It II II It II

3 3 3 3 3 3 3 3 1 3 1 3 3 3 3 3 3 3 3 3 3 3 3 S 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 a 3 3 3 1 3 3 3 3 3 3 3 2 3 3 3 3 3 3 3 3 3 3 3 3 m 3 2 3 3 3 3 3 3 3 3 3 3 3

I 4 < 4 4 4 I i i & 4 I - i i 4 4 4 4 4 4 4 4 | 4 « i 4 4 4 4 4 4 4 4 4 i 4 1 4 4 4 4 4 4 4 4 4 4 1 4 4 4 1 4 4 4 4 4 4 i i 4 4 4 4 4 4 4 4 4 4 4 i i l 4 i ( iI 7 7 I I I 1 I > Il IM I 17 II 11 II I) II It 21 71 77 77 74 72 21 I! 71 7Î 71 71 72 77 74 72 21 71 71 71 41 II 17 4] 44 42 II 11 II It 2t 21 27 21 24 22 21 21 21 21 M II 17 17 II 12 11 l ’ Il it 'I II 12 77 II 12 'I II II It It

; 5 5 5 5 5 5 5 5 5 : i i 5 5 5 5 5 5 5 5 5 5 5 5 j | i i D 5 | 5 5 â 5 5 5 5 j S f i D | 3 5 5 | 5 5 5 S Î 5 S b î : 5 5 S 5 5 2 5 D ! i ! i 5 2 | : :i 5 5 ï 5 5 3 5 i 5 5

S I 6 6 6 6 8 £ G 6 6 6 6 6 6 6 6 6 6 6 6 6 1 6 à E | 5 fl 6 6 c 6 6 6 è 6 6 G | E c 6 6 b 6 6 £ 6 6 6 6 G È S 6 6 | E 6 6 6 6 6 R 6 6 6 6 6 6 6 6 6 t 8 E 6 6 î1 2 7 I 2 I 1 I ! Il 1117 11 II 12 II 11 II II 21 71 77 77 71 72 71 71 71 71 71 11 77 11 14 72 71 71 71 7t II 41 11 17 44 4 2 41 II II 4 1 21 21 27 21 24 22 21 21 21 21 U 11 17 11 II 11 II II II It 11 II 17 11 11 12 U 11 II li II

7 7 7 7 I 7 7 7 7 7 7 7 7 ? 7 7 ? 7 7 7 ? T 7 7 7 7 7 7 7 7 7 »' 7 7 i 7 7 7 7 7 7 7 7 7 7 ’ 7 7 7 7 I | 7 7 ? ? 7 7 7 7 ? ? 7 7 7 7 7 7 7 7 / 7 7 7 7 ' 7 7 7 V

8 8 1 8 8 8 8 8 8 1 1 6 8 8 1 8 9 8 8 8 8 | 8 8 D 8 8 S 8 9 8 8 8 8 8 8 8 8 8 S 8 8 8 8 8 8 8 B 8 8 8 8 8 3 8 8 8 8 8 8 8 8 8 8 S 8 B ? S 8 E 8 S 8 i 8 S S fi SI 2 7 * 2 I 1 I ! Il II I! Il 14 12 II IM I 11 21 71 77 21 74 72 21 V 71 71 71 71 12 7 1 74 12 » 71 11 li II 41 47 41 44 42 II II II 11 21 27 21 24 2 2 21 il 21 21 K II il 11 14 li II II II il 11 II 11 17 II 12 H 11 II II II

9 3 9 9 9 9 9 1 8 8 9 S 9 1 9 9 3 9 3 S S S 9 9 9 9 9 I 9 9 9 3 9 9 9 9 9 9 8 9 9 9 9 8 § S 9 9 0 3 9 9 9 8 3 9 9 9 S 8 S ï S 8 9 3 3 9 S S S S 9 S 8 5 S 3 9 0PR1NTCO in u. » * U N I V A C P-2U480

Figure 4. P a t ie n t h i s t o r y d a t a c a r d

Figure 5. E d i t p h a s e o f u n it r e c o r d c a r d p r o c e s s in g

DATA PROCESSING OF ANTI-DANDRUFF RESEARCH 793

a c tu a l a g e o r y e a rs w ith d a n d r u ff fo r a p a t ie n t . A t y p ic a l e x a m p le f o l ­lo w s :

Age groups (years) Code Years / dandruff Code

2 9 a n d u n d e r 1 5 a n d u n d e r 13 0 t o 3 9 2 6 t o 10 24 0 a n d o v e r 3 11 t o 15 3

16 a n d o v e r 4

T h e la s t p h a s e o f c a r d p ro c e s s in g w a s t o s o r t th e ca rd s t o a r e p o r t s e ­q u e n c e f o r c o m p u t e r p ro ce ss in g .

Computer Processing

T h e c o m p u t e r p r o g r a m s w e re w r it te n t o a c c e p t m a g n e t ic ta p e as in ­p u t s in ce th e p ro c e s s in g ra te w ith ta p e is m u c h fa s te r th a n th a t w ith ca rd s . F u r th e r m o r e , u se o f ta p e m in im iz e d th e h a n d lin g o f b u lk y ca rd s . T h e c a r d im a g e s w e r e c a p tu r e d o n ta p e via a c a r d - t o - t a p e u t i l i t y p ro g r a m . F iv e in p u t ta p e s w e re p r o d u c e d . E a c h p a ss re q u ir e d r e s o r t in g th e ca rd s t o a n o th e r r e p o r t s e q u e n ce . T h e fin a l s e q u e n ce o f a ll r e p o r ts w a s b y te s t p r o d u c t g r o u p . U n d e r th e c o n t r o l o f th e p r o g r a m (s ) , c u m u la t iv e to ta ls , c o u n ts , a n d a v e ra g e s w e re p r in te d fo r e a ch o b s e r v a t io n b y te s t p r o d u c t , a n d a n im p r o v e m e n t fa c t o r w a s c a lc u la te d . I n a d d it io n t o p r in t in g th e s u b je c t ’s d a ta in d e ta il, s u m m a r y ta b le s w e r e a lso p r o d u c e d . T h e c o m ­p u te r w a s p r o g r a m m e d t o s ig n a l in co n s is te n c ie s in th is p h a se as in all o th e r p h a ses .

Generated Reports

N in e te e n r e p o r ts w e re p r in te d o n th e c o m p u te r in th e a n a ly s is o f e a ch o f 15 a n t id a n d r u ff p r o d u c t s . T h r e e r e p o r ts ( A , B , C ) s h o w e d th o s e s u b ­je c t s w h o s e c o n d it io n o f s ca lp a t s ta r t w a s e ith e r d r y , o i ly , o r n o rm a l a n d th e tr e n d e a ch fo l lo w e d t o th e e n d o f th e c lin ica l s t u d y ; th re e r e p o r ts (H , I, J ) s h o w e d th e c o r r e la t io n o f c o n d it io n o f s ca lp a t s ta r t t o th e d e g re e o f d a n d r u ff w ith th e tr e n d s t o c o n c lu s io n ; s ix r e p o r ts (D , E , F , G , K , Q ) s h o w e d th e tr e n d s fr o m s ta r t t o e ig h th w e e k u n d e r th e p a r a m e te r s “ d e g re e o f d a n d r u f f ,” “ d e g re e o f i t c h in g ,” “ d e r m a t it is ,” a n d “ o v e r a ll im p r o v e ­m e n t ” ; t w o r e p o r ts (O , P ) s h o w e d th e tr e n d s in r e d u c t io n o f d a n d r u ff vs.(a ) a ge g r o u p s a n d (b ) y e a rs w ith d a n d ru ff f r o m te s t p r o d u c t s e q u e n ce . T h e la s t f iv e r e p o r ts (L , M , N , R , S ) s h o w e d ta llie s o f re s p o n se s t o th e q u e s t io n n a ire f r o m th e te s t p r o d u c t s e q u e n c e (F ig . 6 ).

94 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Figure 6. C o m p u t e r s y s t e m f l o w c h a r t o f t h e d a n d r u f f p i l o t c l in i c a l p r o g r a m

DATA PROCESSING OF ANTI-DANDRUFF RESEARCH 7 9 5

L is te d b e lo w are th e g e n e r a te d r e p o r ts b y id e n t i f ic a t io n le t te r a n d title .

Item Title

A C o n d i t i o n o f s c a lp a t s ta r t — d r yB C o n d i t i o n o f s c a lp a t s ta r t — o i l yC C o n d i t i o n o f s c a lp a t s t a r t — n o r m a lH C o r r e la t io n o f c o n d i t i o n o f s c a lp a t s ta r t t o q u a n t i t y o f lo o s e d a n d r u f fI C o r r e la t io n o f c o n d i t i o n o f s c a lp a t s ta r t t o q u a n t i t y o f a d h e r e n t d a n d r u f fJ C o r r e la t io n o f c o n d i t i o n o f s c a lp a t s ta r t t o q u a n t i t y o f lo o s e a n d a d h e r e n t

c o m b in e dD Q u a n t i t y o f lo o s e d a n d r u f fE Q u a n t i t y o f a d h e r e n t d a n d r u f fF Q u a n t i t y o f lo o s e a n d a d h e r e n t d a n d r u f f c o m b in e dG D e g r e e o f i t c h in gK O v e r a l l im p r o v e m e n t r a t in gQ D e g r e e o f d e r m a t i t isO R e d u c t i o n o f d a n d r u f f vs a g e g r o u p sP R e d u c t i o n o f d a n d r u f f vs y e a r s w i t h d a n d r u f fL H a ir lo s s d u r in g c o m b i n g a n d s h a m p o o i n g ( S t a r t vs e ig h th w e e k )M T e s t p r o d u c t r a t in gN C o m p a r is o n o f d a n d r u f f r e s u lt sR R e c o r d e d l ik e s a b o u t t e s t p r o d u c tS R e c o r d e d d is l ik e s a b o u t t e s t p r o d u c t

C o m p a r i s o n : T i m e a n d C o s t

T h e e s t im a te s d e s c r ib e d b e lo w are b a s e d o n a d a n d ru ff c lin ica l s tu d y in v o lv in g 717 s u b je c ts . I t s h o u ld b e n o t e d th a t th e c o s t o f m a n u a lly c o m p i l in g a n d a n a ly z in g d a ta re m a in s c o n s ta n t fo r e a ch c l in ic a l s t u d y o f th e sa m e size a n d n a tu re , re g a rd le ss o f th e n u m b e r o f s tu d ie s c o n d u c te d . T h e n e t c o s t o f e a ch e le c t r o n ic c o m p i la t io n w o u ld b e th e a c tu a l ru n n in g c o s t p lu s a pro-rata sh are o f th e in it ia l p r o g r a m m in g co s t . T h is sh a re o f p r o g r a m m in g c o s t d im in is h e s as th e n u m b e r o f s tu d ie s in c re a se s a s s u m ­in g n o ch a n g e s in p r o g r a m m in g a re re q u ire d . T h e t im e re q u ir e m e n ts a n d d o lla r c o s ts p e r s tu d y (a s s u m in g f iv e s tu d ie s a re t o b e ru n ) are s h o w n b e l o w :

M anual method Electronic methodC o s t p e r s t u d y $ 2 5 0 0 $ 8 0 0

T i m e r e q u ir e m e n t p e r s t u d y 6 w e e k s 1 . 8 w e e k s

C o n c l u s i o n

W h a t h a s b e e n d e s c r ib e d h e re is p r o p e r ly re fe r re d t o as a " p i l o t p r o ­g r a m .” I t w a s in s t itu te d t o d e te r m in e fe a s ib il ity , co s ts , a n d t im e r e ­q u ire m e n ts . T h e c o m p u t e r p r o g r a m d id n o t in c lu d e te s ts o f s ta t is t ica l s ig n if ic a n ce o r p lo t t in g o f cu r v e s . S u ch a p r o g r a m ca n b e m o d if ie d to

796 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

in c lu d e all th e s ta t is t ic a l t r e a tm e n ts p r e v io u s ly d o n e m a n u a lly . I t lias b e e n s h o w n th a t c o m p u te r p ro c e s s in g ca n s ig n if ic a n t ly re d u c e th e a m o u n t o f t im e re q u ir e d t o c o m p le te a n a ly s is o f re su lts in a la rg e c l in ic a l tr ia l, e l im in a te h u m a n m e c h a n ic a l e rrors , a n d a t th e sa m e t im e s a v e a c o n s id e r a b le a m o u n t o f m o n e y . W h e n a p r o g r a m is u se d in m o r e th a n o n e tr ia l, th e s a v in g s in b o t h t im e a n d d o lla rs b e c o m e e v e n m o r e d r a ­m a t ic .

(R e c e iv e d M a y 22, 11)07)

R e f e r e n c e s

( 1 ) M a la s s e z , R . , f r o m V a n A b b e , N . J . , T h e in v e s t ig a t io n o f d a n d r u f f , J. Soc. Cosmetic Chemists, 1 5 , 6 0 9 - 3 0 (1 9 6 4 ) .

( 2 ) S a v i l l , A . , The H air and Scalp, T h i r d E d . , W i l l ia m s & W i lk in s , B a l t im o r e , M d . 1 9 4 4 , p p . 1 5 3 -6 8 .

( 3 ) H a r r y , R . G . , The Principles and Practice of Modern Cosmetics, Vol. I — Modern Cos- meticology, C h e m ic a l P u b l i s h in g C o m p a n y , N e w Y o r k , N . Y . , 1 9 6 2 , p p . 3 3 2 - 9 .

( 4 ) M a c K e e , G . M . , a n d L e w is , G . M . , D a n d r u f f a n d s e b o r r h e a . I. F lo r a o f “ n o r m a l ” a n d d is e a s e d s c a lp s , J . Invest. Dermatol., 1 , 1 3 1 - 9 (1 9 3 8 ) .

( 5 ) W r i g h t , C . S ., T h e s e b o r r h e ic s ta t e , i t s e t i o l o g y a n d c o n t r o l , Med. World, 5 9 , 4 3 1 - 3 (1 9 4 1 ) .

( 6 ) K e l l y , D . E . , a n d A r l o o k , T . D . , S e b o r r h e ic d e r m a t i t is , J . Indiana State Med. Soc., 43, 1 0 8 8 -9 1 (1 9 5 0 ) .

( 7 ) D o w l in g , G . B . , A e t i o l o g y o f s e b o r r h o e ic d e r m a t i t is , Brit. J . Dermatol., 5 1 , 1 - 7 (1 9 3 9 ) .( 8 ) M i t c h e l l - H e g g s , G . B ., S e b o r r h o e i c d e r m a t i t i s a n d a c n e v u lg a r is , Brit. Med. J ., 2 , 1 0 7 9 -

8 2 (1 9 5 1 ) .( 9 ) Y a n d e r W y k , R . W . , a n d R o ia , F . C ., T h e r e la t io n s h ip b e t w e e n d a n d r u f f a n d t h e m ic r o ­

b ia l f lo r a o f t h e h u m a n s c a lp , J . Soc. Cosmetic Chemists, 1 5 , 7 6 1 - 8 (1 9 6 4 ) .( 1 0 ) B a l l , F . I . , A n e w t r e a t m e n t f o r s e b o r r h o e i c d e r m a t i t is , Arch. Dermatol., 7 1 , 6 9 6 (1 9 5 5 ) .( 1 1 ) R e d d is h , G . F . , T h e e t io l o g y o f in f e c t i o u s d a n d r u f f , J . Soc. Cosmetic Chemists, 3, 9 0

(1 9 5 2 ) .

( 1 2 ) K la u d e r , J . Y . , M o d e r n c o n c e p t a n d t r e a t m e n t o f d a n d r u f f a n d s e b o r r h e ic e r u p t io n s , Ibid., 7 , 4 4 3 - 9 (1 9 5 6 ) .

( 1 3 ) L u b o w e , I. I ., A n t i - s e b o r r h e i c a g e n t s , Drug and Cosmetic Ind ., 81, 6 0 2 - 7 6 (1 9 5 7 ) .(1 4 ) S p o o r , H . J . , M i c r o b i o l o g i c a l a n d c l in ic a l s t u d y o f a n t i -d a n d r u f f a g e n ts , Prim. Sci.

Sect. Toilet Goods Assoc., N o . 23, 2 7 - 3 1 ( M a y 1 9 5 5 ) .( 1 5 ) W a l la c e , H. J ., D is e a s e s o f th e h a ir a n d s c a lp , The Practitioner, 188, 5 94 —8 0 8 ( 1 9 6 2 ) .(1 6 ) V a n A b b e , N . J . , T h e in v e s t ig a t io n o f d a n d r u f f , J . Soc. Cosmetic Chemists, 1 5 , 6 0 9 - 3 0

(1 9 6 4 ) .

(1 7 ) R o b i n s o n , R . C . Y . , a n d R o b e r t s , D . , A n e w m e d ic a t e d s h a m p o o f o r s e b o r r h e i c s c a lp c o n d i t i o n s , M aryland Med. J ., 1 2 , 2 2 3 - 5 (1 9 6 3 ) .

( 1 8 ) S p o o r , H . J . , C l in ic a l e v a lu a t io n o f a n t id a n d r u f f f o r m u la t io n s , J . Soc. Cosmetic Chemists, 14, 1 3 5 - 4 5 (1 9 6 3 ) ,

( 1 9 ) H o w a r d , K . L . , T h e u s e s o f e n z y m e s in c o s m e t i c s , Ibid., 13, 5 9 - 6 3 (1 9 6 2 ) .( 2 0 ) C a y le , T . , T h e p o t e n t ia l o f e n z y m e s f o r t o p ic a l a p p l i c a t io n , Ibid., 14, 2 4 9 - 5 9 (1 9 6 3 ) .

/ . Soc. C osm etic C h e m ists , 18, 797-807 (Dec. 9, 1967)

Pseudomonads in Cosmetics

S A U L T E N E N B A U M M .S .*

Presented before the N ew York Chapter, October 3, 1 9 6 6

S y n o p s i s — P s e u d o m o n a d s a r e b a c t e r ia l o r g a n is m s f o u n d in s o i l , w a t e r , a ir , a n d f o o d , in a n d o n t h e b o d y . T h e y b r e a k e m u ls io n s a n d p r o d u c e f o u l o d o r s a n d s lim e w h ile d e c o m p o s i n g c o s m e t i c s a n d p h a r m a c e u t i c a ls . T h e o r g a n is m s h a v e t h e c a p a c i t y t o d e v e l o p r e s is t a n c e t o a g e n t s i n im ic a l t o o t h e r m ic r o o r g a n is m s . P r e p a r a t io n s a r e p la c e d o n p r e s e r v a t i o n s t u d y t o d e t e r m in e t h e a b i l i t y o f a p r o d u c t t o w i t h s t a n d c o n s u m e r u s e a n d a b u s e . S o m e m a t e r ia ls c a n i n a c t i v a t e t h e p r e s e r v a t iv e s u s e d t o p r o t e c t t h e p r o d u c t . T h e o n l y e f f e c t i v e w a y o f k n o w in g w h e t h e r a p r o d u c t is p r o t e c t e d is t o i n o c u la t e t h e f o r m u l a t i o n w it h o r g a n is m s a n d e x a m in e f o r v i a b i l i t y . T h e a b i l i t y o f p s e u d o m o n a d s t o a d a p t t o a n d p r o l i f e r a t e in p r e p a r a ­t io n s is s u c h t h a t m a in t e n a n c e o f t h e in o c u lu m is in s u f f i c ie n t f o r a d e q u a t e p r e s e r v a t io n s ta tu s . T h e o n l y p r o p e r l y p r e s e r v e d p r e p a r a t io n is o n e t h a t is e s s e n t ia l ly s e l f - s t e r i l iz in g . A s e l f - s t e r i l iz in g p r e p a r a t io n c a n b e a c h i e v e d , in m o s t c o s m e t i c p r o d u c t s , w i t h o u t a n in c r e a s e in c o s t s o r lo s s o f m a r k e t a b i l i t y .

I n t r o d u c t i o n

P s e u d o m o n a d s a re b a c te r ia l o rg a n is m s fr e q u e n t ly re s p o n s ib le fo r d e t e r io r a t io n o f f o o d , p e tr o le u m p r o d u c ts , p h a rm a c e u t ic a ls , a n d c o s ­m e t ic s . T h e y p a r t ic ip a t e in th e d e g r a d a t io n o f p o ly s ty r e n e , d ib u t y l p h th a la te , p o ly v in y l c h lo r id e , f o r m a ld e h y d e res in s , c u t t in g o ils , j e t fu e l, k e ro s e n e , a n d in te r fe re in th e m a n u fa c tu r e o f p a p e r a n d p la s t ic s (1 ) . M i l i t a r y a n d re la te d c iv i lia n re s e a rc h in to c o n ta m in a te d je t fu e l h a v e d e m o n s tr a t e d t h a t p s e u d o m o n a d s a re a n im p o r t a n t m e m b e r o f th e c o n ­ta m in a t in g flo ra . T h e d e g re e o f c o n ta m in a t io n h as , o n o c c a s io n , b e e n s e v e re e n o u g h t o d e g r a d e th e fu e l a n d ca u s e o p e r a t in g p r o b le m s .

P s e u d o m o n a d s a re h e te r o t r o p h ie , a sp o r o g e n o u s , p o la r ly f la g e lla te d o rg a n ism s w ith o r w ith o u t s lim e , w ith o r w ith o u t p y o c y a n in e , w ith o r w it h o u t g r e e n -y e llo w is h f lu o re s c e n c e , a n d w ith o r w i t h o u t a y e l lo w - b r o w n c o lo n y . O n ly in a fe w ca se s c a n th e g e n u s b e e a s ily r e c o g n iz e d b y

* R e v l o n R e s e a r c h C e n t e r , 9 4 5 Z e r e g a A v e n u e , B r o n x , N . Y . 1 0 4 7 3 .

797

798 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

o n e o f its s tr ik in g p r o p e r t ie s s u ch as p ig m e n t fo r m a t io n . F r o m a n in ­d u s tr ia l p o in t o f v ie w pseudomonads can be considered, in a general sense, as motile, gram-negative rods giving a positive oxidase test. P s y c h r o - p h ilie p s e u d o m o n a d s are u b iq u it o u s a n d ca n b e is o la te d fr o m so il, fre s h a n d sa lt w a te r , f o o d , sk in , a n d fe ce s .

R e p o r t s o f p s e u d o m o n a d s in p h a r m a c e u t ic a ls a n d c o s m e t ic p r o d u c t s , w ith th e e x c e p t io n o f o p h t h a lm ic p re p a r a t io n s , h a v e b e e n s c a r c e ; a n d o n e w o u ld b e lie v e th a t p s e u d o m o n a l c o n ta m in a t io n o f p h a r m a c e u t ic a ls a n d , in p a r t ic u la r , c o s m e t ic s are in fr e q u e n t . T h e m o s t fr e q u e n t c o n ­ta m in a n t o f o p h t h a lm ic p r e p a r a t io n s a n d , as su ch , re s p o n s ib le fo r se r io u s e y e in ju r ie s a n d e v e n lo ss o f v is io n h a s b e e n Pseudom onas aeruginosa (2 , 3 ) . A c c o r d in g ly , n o n s te r ile p r e p a r a t io n s are n o w re g a r d e d as a d u l­te r a te d a n d m is b r a n d e d w ith in th e U . S . F o o d , D r u g , a n d C o s m e t ic A c t . F u r th e r , m u lt ip le d o s e o p h t h a lm ic p r o d u c t s m u s t c o n ta in a g e n ts th a t w ill in h ib it th e g r o w th o f m ic r o o r g a n is m s (4 ) .

D u r in g th e p a s t d e c a d e a n u m b e r o f p r e s e r v a t io n fa ilu re s in c o s m e t ic p r o d u c t s h a v e b e e n r e p o r te d . B r y c e a n d S m a rt (5 ) , fo r e x a m p le , fo u n d th a t c o n ta m in a te d h a ir p r o d u c t s , o f a ll v a r ie t ie s , in v a r ia b ly c o n ta in e d g r a m -n e g a t iv e o rg a n is m s s o m e o f w h ic h w e r e p s e u d o m o n a d s . T h is p e r io d c o in c id e s w ith th e p e r io d o f c h a n g e o v e r fr o m a n io n ic t o n o n io n ic em u ls ifie rs (6 ) . T h e s e n o n io n ic s u r fa c ta n ts , d e r iv e d fr o m f a t t y a c id s , are r e s p o n s ib le fo r th e s u p e r io r ity o f c u r r e n t c o s m e t ic a n d p h a r m a c e u t i ­ca l p r e p a r a t io n s as s ta b le , s m o o th , a p p e a lin g , a n d e f fe c t iv e fo r m u la t io n s c o m p a r e d t o th o s e o f 10 y e a rs a g o . B u t n o n io n ic s h a v e c h a n g e d m a n y p r e p a r a t io n s w h ic h c o u ld n o t s u p p o r t m ic r o o r g a n is m s in t o v e r ita b le c u l ­tu re m e d ia fo r g r o w th , a n d th e c o n ta m in a t io n o rg a n ism s fo u n d m o s t f r e ­q u e n t ly h a v e b e e n p s e u d o m o n a s .

A lth o u g h th e re h a v e b e e n r e la t iv e ly fe w p u b lis h e d r e p o r ts d e a lin g d ir e c t ly w ith p s e u d o m o n a s c o n ta m in a t io n , th e m a n y p u b l ic a t io n s c o n ­c e r n in g p r o b le m s in p r e s e r v a t io n w h ic h h a v e a p p e a r e d w ith in th is sa m e p e r io d , fr e q u e n t ly m e n t io n th is g e n u s . W it h in th e 1 9 5 7 -1 9 6 0 p e r io d , fo r e x a m p le , a d o z e n d if fe r e n t p s e u d o m o n a d s w e re is o la te d fr o m c o m m e r ­cia l a n d e x p e r im e n ta l fo r m u la t io n s a n d th is e x p e r ie n c e h a s o c c u r r e d in se v e ra l o th e r la b o r a to r ie s . T h u s , p s e u d o m o n ia s is h as b e e n a n d is a c o n ­t in u in g p r o b le m .

S u s c e p t i b l e P r e p a r a t i o n s a n d T h e i r C o n t a m i n a n t s

P s e u d o m o n a s g r o w th h as b e e n fo u n d in o r r e p o r te d as r e s p o n s ib le fo r th e d e g r a d a t io n o f s h a m p o o s , fa c ia l lo t io n s , su n p re p a r a t io n s , b a b y p r o d ­u cts , o p h t h a lm ic s o lu t io n s , m a k e -u p p r o d u c ts , c le a n s in g cre a m s , e m o l ­

PSEUDOMONADS IN COSMETICS 799

l ie n t cre a m s , c le a n s in g p a d s , c o s m e t ic e y e p re p a r a t io n s , “ w r in k le r e ­m o v e r ” s o lu t io n s , c le a n s in g s p o n g e s , p r o te in s o lu t io n s , p h a r m a c e u t ic a l a n d c o s m e t ic ge ls , h y d r o c a r b o n c le a n s in g o ils , a n d s o fo r th . T h e s e in ­c lu d e s im p le s o lu t io n s , O / W a n d W / O e m u ls io n s , t r ip h a s e s y s te m s , ge ls , a n d h y d r o c a r b o n o ils .

T h e p r e p a r a t io n s fr o m w h ic h p s e u d o m o n a d s are u s u a lly r e c o v e r e d are O / W e m u ls io n s a t a p H o f 7 .5 -8 .5 , w h ic h c o n ta in a s ig n if ica n t a m o u n t o f n o n io n ic s . T h is d o e s n o t m e a n th a t fo r m u la t io n s c o n ta in in g a n io n ic o r c a t io n ic e m u ls ifie rs a re n o t s u b je c t t o a t ta c k , b u t th e p re s e n ce o f n o n io n ic s h as b e e n fo u n d t o b e m o s t c o n d u c iv e t o p s e u d o m o n a s c o n ­ta m in a t io n . T h is m e n s tru u m is so fa v o r a b le , th a t p s e u d o m o n a s , b e ­ca u se o f its r e s is ta n c e t o b io s t a t ic a g e n ts , is th e u su a l c o n ta m in a n t a n d o n e th a t g r o w s in th e p r o d u c t as a p u r e c u ltu re . A t t im e s s t a p h y lo c o c c i , a e ro g e n e s , y e a s ts , a n d m o ld s h a v e b e e n is o la te d b u t n e v e r m ix e d w ith p s e u d o m o n a s . E x p e r ie n c e h a s in d ic a te d th a t a p o o r ly p r e s e r v e d p r o d ­u c t is n a tu r a l ly c o n ta m in a te d o n ly b y a s p e c if ic o rg a n ism , e .g ., a c re a m s u s c e p t ib le t o p s e u d o m o n a s is n o t s u s c e p t ib le t o s t a p h y lo c o c c i o r y e a s t , a lth o u g h a fu lm in a t in g p s e u d o m o n a s in fe c t io n m a y p a v e th e w a y fo r s u b s e q u e n t m o ld g r o w th . T h e c o n s e q u e n c e s t o th e p r o d u c t o f h e a v y g r o w th o f p s e u d o m o n a s are l ik e ly t o b e th e d e v e lo p m e n t o f a fo u l o d o r , f o r m a t io n o f a d e p o s it o r tu r b id ity , a c h a n g e in f lo w a n d b r e a k -d o w n o f th e e m u ls io n s b y e n z y m a t ic a c t iv i t y , d e c o lo r iz a t io n a n d /o r th e d e v e lo p ­m e n t o f a b r o w n c o lo r in th e p r e s e n c e o f h y d r o c a r b o n o ils .

A b a c te r ia l p o p u la t io n su ch as is e n c o u n te r e d in a O / W e m u ls io n is c o n t in u o u s ly ch a n g in g th r o u g h a d a p ta t io n o r m u ta t io n . I t is p o s s ib le , th e re fo r e , fo r o rg a n ism s t o e m e r g e w h ic h m a y d e v e lo p re s is ta n ce t o a p a r t ic u la r c o m b in a t io n o f in h ib ito r s a n d th e e m u ls io n w ill u lt im a te ly s p o il. T h e s p o ila g e m a y o c c u r a fte r th e p e a k o f th e m ic r o b ia l p o p u la ­t io n h as b e e n r e a c h e d a n d th e m ic r o b ia l c o u n t is d e c lin in g . O c c a s io n a l ly m a te r ia ls a re se e n c o n ta in in g as m a n y as 5 m ill io n o r g a n is m s /m l w ith o u t o b v io u s s ig n s o f d e te r io r a t io n . F e w w o u ld b e lie v e th a t su ch m a te r ia l is fit fo r sa le .

A p e ru sa l o f th e p u b lic a t io n s o n p s e u d o m o n a s g r o w th in c o s m e t ic a n d o th e r in d u s tr ia l p r o d u c t s r e v e a l th e c a p a b il it ie s o f th is g e n u s . T h e y b r e a k d o w n h y d r o c a r b o n s (7 ) in c lu d in g p e t r o la tu m (8 ) , r e m a in v ia b le fo r m o n th s in a ir c r a ft fu e l (9 ) , u t i liz e a lk a n e s su ch as h e x a n e , a n d a r o m a t ic s l ik e b e n z e n e (1 0 ) . T h e y fo r m in d u c ib le e n z y m e s t o b e n z o ic a n d a n - th ra n il ic a c id (1 1 ) , p r o d u c e lip a se s a n d o x id iz e f a t t y a c id s (1 2 . 1 3 ), m a l ­to se , la c to s e , c e l lo b io s e , a n d m e lib io s e (1 4 ) . T h e n th e ir e n z y m e s l iq u ify g e la t in , a t ta c k ca se in , p e r fo r m a m y lo ly s is (1 5 ) , a n d are m o s t a c t iv e a t

800 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

2 5 ° C a n d a t a p H o f 7 -8 . T h e y a re m ie r o -a e r o p h il ic a n d fe w o rg a n ism s h a v e th e ir c a p a c it y fo r g r o w th a t 0 ° C (1 6 ).

T h e s u s c e p t ib il ity o f s o m e fo r m u la t io n s t o p s e u d o m o n a s c o n t a m in a ­t io n m a y b e s p e c ific . A p s e u d o m o n a d iso la te d fr o m o n e p r e p a r a t io n m a y n o t r e a d ily g r o w in a n y o th e r . P s e u d o m o n a d s th a t h a v e b e e n i s o ­la te d fr o m a m a k e -u p p r o d u c t , fo r e x a m p le , w ill o n ly g r o w w ith in th e s p e c if ic p r o d u c t . P s e u d o m o n a d s is o la te d fr o m a cre a m c o u ld o n ly g r o w w ith in th a t cre a m . I t h as b e e n n e ce s s a r y o n o c c a s io n t o p re p a r e p r o d ­u c t -c o n t a in in g cu ltu re m e d ia t o a ch ie v e p r o fu s e g r o w th a n d a fte r a d a p t a ­t io n t o la b o r a t o r y m e d ia , th e p s e u d o m o n a d o rg a n ism m u s t f r e q u e n t ly b e in o c u la te d in to th e o r ig in a l c re a m t o m a in ta in th e r e s is ta n ce o f th e o r ­g a n is m . B e c a u s e o f th e se p r o p e r t ie s , it is a p r a c t ic e o f th e a u t h o r ’s la b ­o ra to r ie s t o n a m e is o la te d p s e u d o m o n a d s a c c o r d in g t o th e p r o d u c t o f o r ig in . F o r e x a m p le , th e re is a cu ltu re n a m e d Pseudom onas aquasolarus, a v a r ie t y o f a e ru g in o sa , w h o s e n a m e in d ic a te s th e o r ig in o f th e cu ltu re .

P S E U D O M O N I A S I S , A n I N D U S T R I A L D I S E A S E A N D I T S C O N T R O L

T h e g r o w th o f p s e u d o m o n a d s in a p r o d u c t b e c o m e s a n in fe c t io n a n d th e t e r m in a t io n o f w h ich is th e d e s tr u c t io n o f th e p r o d u c t . T h e m e c h a ­n ism s o f in d u s tr ia l c o n t r o l are s im ila r t o th o s e u se d b y a h e a lth d e p a r t ­m e n t in a c o m m u n ic a b le d ise a se p ro g r a m .

1. P r e s e r v a t iv e s in cre a se th e re s is ta n ce o f p r o d u c t s t o in fe c t io n .2. M a n u fa c tu r in g a t 1 8 0 ° F r e d u ce s o r e lim in a te s th e m ic r o b ia l c o n ­

t e n t o f th e in g re d ie n ts .3. S a n ita r y c o m p o u n d in g a n d fillin g m in im iz e s c o n ta m in a t io n o f th e

p re p a r a t io n .4 . H o u s e k e e p in g a n d s a n ita t io n is e n h a n c e d b y c o m p a n y issu e d sa n ­

ita r y r e g u la t io n s a n d p e r io d ic in s p e c t io n b y sa n ita r ia n s.5. E d u c a t io n o f m a n u fa c tu r in g p e rs o n n e l ca n h e lp a ch ie v e a h ig h

le v e l o f s e n s ib le , c le a n p r o d u c t io n m e th o d s . S u cc e s s fu l re su lts ca n m o s t r e a d ily b e o b ta in e d w h e n p la n t p e rs o n n e l u n d e r s ta n d th e re a s o n s fo r s a n ita t io n o f e q u ip m e n t a n d fo r c le a n m a n u fa c tu r e .

6. A n in v e s t ig a t iv e m ic r o b io lo g y p r o g r a m te s ts th e a d e q u a c y o f p r o d u c t p r e s e r v a t io n , c o n t r o ls th e m ic r o b io lo g ic a l q u a li t y o f p r o d u c t s a t th e t im e o f m a n u fa c tu r e , c o n d u c t s sh e lf s tu d ie s , a n d e x a m in e s p a r t ia lly u se d p r o d u c t s se cu re d fr o m co n s u m e rs .

In su m , th e m e c h a n is m s w h ic h in su re th e m ic r o b io lo g ic a l q u a li t y o f m a n u fa c tu r e d p r o d u c t s a r e :

1. M ic r o b io lo g ic a l c o n t r o l 3 . S a n ita ry in s p e c t io n2. S a n ita r y m a n u fa c tu r in g 4. P e rso n n e l e d u c a t io n

PSEUDOMONADS IN COSMETICS 801

Preservation

R e g a r d le s s o f s a n ita r y m a n u fa c tu r in g m e th o d s , a p o o r ly p r e s e rv e d p r e p a r a t io n p r o v id e s m a n y o p p o r tu n it ie s fo r m ic r o b ia l in fe c t io n . A s d e s c r ib e d e a r lie r a n O / 'W e m u ls io n a t a p H o f 7 - 8 c o n ta in in g n o n io n ic s p r o v id e s a p a r t ic u la r ly s u ita b le m e n s tru u m fo r p s e u d o m o n a s g r o w th . P r e s e rv a t iv e s u se d t o re s tra in g r o w th are th e w e ll k n o w n p h e n o lic s , p a r a b e n s , b is p h e n o ls , a n d o rg a n o -m e ta ls . O r g a n ic a c id s ca n b e e f fe c t iv e a t p H < 7 w h ile q u a te rn a r ie s te n d to b e in c o m p a t ib le w ith a n o n io n ic s lig h t ly a lk a lin e s y s te m . I t is n e c e s s a r y t o b e a r in m in d th a t fe w c o s m e t ic a l ly a c c e p ta b le b a c te r io c id e s are a c t iv e a g a in s t p s e u d o m o n a d s s p e c if ic a lly , e v e n in th e a b s e n c e o f s u r fa c ta n ts . A n io n ic s in g e n e ra l a p ­p e a r t o in h ib it s e le c t iv e ly th e m e ta b o l is m o f g r a m -p o s it iv e o rg a n ism s , a n d th o s e w h ic h are b a c te r io c id e s te n d t o h a v e a n a r ro w e r s p e c tr u m th a n c a t io n ic s . T h e b a c te r ia l a c t io n o f a n io n ic s is in flu e n c e d t o a g r e a te r e x ­t e n t b y ch a n g e s in p H .

S o m e n o n io n ic s a c tu a lly inactivate th e b a c te r io s t a t ic a c t io n o f b is p h e n o ls a n d T w e e n " 8 0 ,* fo r e x a m p le , is a m o r e e f fe c t iv e a n t id o te th a n b lo o d se ru m fo r n u ll ify in g th e a n t ib a c te r ia l p r o p e r t ie s o f th e se c o m ­p o u n d s (1 7 ) . H o w e v e r , T w e e n 80 in lo w c o n c e n tr a t io n s , su ch as 0 .0 2 % , re n d e r p s e u d o m o n a d s a c tu a lly m o r e s u s c e p t ib le t o a n t im ic r o b ia l a g e n ts . T h is e n h a n c in g e f fe c t a t lo w le v e ls is n o t e w o r t h y s in ce a t h ig h e r le v e ls th e s u r fa c ta n t w a s fo u n d b y K o h n et al. (1 8 ) t o b e an a n ta g o n is t t o th e v e r y sa m e b a c te r io s t a t ic a g e n ts . S tu d ie s h a v e s h o w n th a t Pseudom onas aeruginosa is c a p a b le o f g r o w th in s o lu t io n s a n d d is p e r s io n s o f n o n io n ic s u r fa c ta n ts o f th e T w e e n t y p e a n d ca n s p lit th e e s te r lin k a g e s o f th e se a g e n ts (1 9 ) . P r a c t ic a lly a ll th e n o n io n ic s o f e th y le n e o x id e o r p r o p y le n e o x id e c o n d e n s a te s o f f a t t y a c id s a n d a lc o h o ls in a c t iv a te m a n y p r e ­s e r v a t iv e s in c u r r e n t u se . I t w a s fo u n d , in a s tu d y o f 36 n o n io n ic s a n d 26 p r e s e r v a t iv e s , th a t th e n o n io n ic s u r fa c ta n ts r e d u c e d th e e f f ic ie n c y o f a ll p r e s e r v a t iv e s w h e n th e r a t io o f s u r fa c ta n t t o p r e s e r v a t iv e e x ­c e e d e d ce r ta in c r it ic a l v a lu e s (2 0 ) .

O f co u r se , o n e is n o w c o g n iz a n t th a t w ith t im e , in a c t iv a t io n o f m a n y b io s ta t s o c c u r s a n d w h a t a p p e a rs as a w e ll-p r e s e r v e d p r e p a r a t io n t o d a y c a n b e s p o ile d b y a n in o c u lu m 2 - 3 m o n th s a fte r m a n u fa c tu r e (2 1 ). E m u ls io n s o f th e w a te r - in -o i l t y p e are r e la t iv e ly r e s is ta n t to n a tu ra l p s e u d o m o n a s a t ta c k s in ce th e c o n t in u o u s o il p h a s e a c ts as a b a r r ie r to p e n e t r a t io n o f th e o rg a n ism in t o th e w a te r p h a se , a n d im p e d e s th e sp re a d o f g r o w th th r o u g h th e s y s te m . H o w e v e r , th e fe a tu r e s w h ich p re -

T w e e n 8 0 is a r e g is t e r e d t r a d e m a r k o f A t la s P o w d e r C o m p a n y , W i lm i n g t o n , D e l .

802 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

v e n t in v a s io n a lso re ta r d th e a n t im ic r o b ia l a c t iv i t y o f th e b io s ta ts , so th a t a W / O e m u ls io n w h ic h is m o r e d if f ic u lt t o in fe c t a lso a p p e a r s t o b e m o r e d if f ic u lt t o p re s e rv e . O th e r fa c to r s a ffe c t in g th e a c t iv i t y o f p r e ­s e r v a t iv e s in W / O s y s te m s a re th o s e c o n tr o ll in g th e a v a i la b il ity o f th e p r e s e r v a t iv e s in th e a q u e o u s p h a se , in p a r t ic u la r , th e O / W p a r t it io n c o ­e ffic ie n t o f th e p r e s e r v a t iv e , th e p h a s e -v o lu m e ra t io , a n d th e te m p e r a ­tu re . A n t im ic r o b ia l c o m p o u n d s w ith h ig h o i l-w a te r p a r t it io n c o e f f i ­c ie n ts c o n c e n tr a te in th e o il o f te n w ith in s u ffic ie n t q u a n t it ie s b e in g d is ­tr ib u te d in th e a q u e o u s p h a s e to in h ib it m ic r o b ia l g r o w th . T h e p a r t i ­t io n c o e f f ic ie n t o f m o s t b io s t a t ic a g e n ts w ill b e h ig h e r fo r v e g e ta b le o ils th a n fo r m in e ra l o ils , m a k in g v e g e ta b le o il c re a m s m o r e d if f icu lt t o p r e ­s e rv e th a n th o s e p re p a r e d fr o m m in e ra l o il. K n o w in g th e c o n c e n tr a t io n o f a b io s ta t , th e d is s o c ia t io n c o n s ta n t , th e c o n c e n t r a t io n o f n o n io n ic s a n d th e p a r t it io n co e f f ic ie n t , th e a m o u n t o f th e a g e n t d is s o lv e d in th e a q u e o u s a n d m ice lla r p h a se s a t a g iv e n p H ca n b e c a lc u la te d . E v a n s (2 2 ) fo u n d , fo r e x a m p le , th a t a 0 .5 % c o n c e n t r a t io n o f p -h y d r o x y b e n z o a te in an a q u e o u s (5 .0 % T w e e n s o lu t io n g a v e a c o n c e n t r a t io n e q u iv a le n t to 0 .1 % o f th e b e n z o a te in th e w a te r p h a se .

N o b le a n d S a v in (2 3 ) r e p o r te d a h o s p ita l p s e u d o m o n a s o u tb r e a k w h ic h illu s tra te s th e se c o n c e p t s . A w e ll p re s e rv e d s te ro id cre a m w a s d ilu te d w ith lip id s . T h e d ilu te d cre a m c o n ta in in g 0 .1 % c h lo r o c r e s o l w a s fo u n d c o n ta m in a te d w ith P . aeruginosa. A lth o u g h 0 .0 2 % e h lo r o - c r e s o l in a q u e o u s s o lu t io n w a s s u ffic ie n t t o p r e v e n t g r o w th o f o rg a n ism , th e c h lo r o c r e s o l m ig r a te d in to th e o il c o n s t itu e n ts o f th e c re a m le a v in g th e a q u e o u s p o r t io n w ith in s u ffic ie n t b io s ta t . E x a m in a t io n o f th e c l in i ­ca l r e c o r d s s u g g e s te d th a t th e c re a m h a d ca u se d m in o r in fe c t io n s o v e r a p e r io d o f s e v e ra l m o n th s . S im ila r ly d ilu te d cre a m s fr o m t w o o f e ig h t o th e r h o s p ita ls w e re a lso fo u n d c o n ta m in a te d w ith p s e u d o m o n a d s .

In p r e s e rv in g a p r o d u c t o n e f r e q u e n t ly o v e r lo o k s th e n u tr it iv e q u a l­i t y o f th e p r e p a r a t io n . C o s m e t ic a n d p h a r m a c e u t ic a l fo r m u la t io n s o f t e n ra n g e fr o m w a te r s o lu t io n s t o h ig h p r o te in so u p s . T h e g r o w th p o ­te n t ia l o f th e p r o d u c t itse lf is a p r im e a g e n t in flu e n c in g th e e a se o r d if f i ­c u lt y o f p r e s e r v a t io n , fo r a n u tr ie n t -fr e e p r e p a r a t io n is ea sier to p re s e rv e th a n o n e co n ta in in g n u tr ile s . T h e “ m a g ic in g r e d ie n ts ’ ’ n o w c u r re n t in m a n y fo r m u la t io n s ca n o n o c c a s io n b e n u tr ie n ts , s t im u la t in g th e g r o w th o f o rg a n ism s a n d o b s t r u c t in g th e a c t io n o f p r e s e rv a t iv e s .

E x is t in g s cre e n in g te s ts in a g a r o r b r o t h w h ic h d e te rm in e a c o m ­p o u n d ’s in h e re n t a n t im ic r o b ia l a c t iv i t y are h e lp fu l o n ly in e l im in a t in g c o m p le te ly in a c t iv e m a te r ia ls . T h e y w ill n o t p r e d ic t , w ith a n y r e lia b il ­ity , p e r fo r m a n c e in th e a c tu a l c o s m e t ic o r p h a r m a c e u t ic a l e m u ls io n .

PSEUDOMONADS IN COSMETICS 803

T h e p r e s e r v a t io n o f fo r m u la t io n s d e p e n d o n m a n y fa c to r s a n d the only reliable w ay to determine the resistance o f a product to organism growth is to inoculate and test the product itself.

I n th e a u t h o r ’s la b o r a to r ie s a m in im u m in c u b a t io n p e r io d o f 13 w e e k s is u t i liz e d t o d e te r m in e th e p o s s ib le lo ss o f p r e s e r v a t io n p o t e n c y w ith t im e . R e - in o c u la t io n o f th e sa m p le s d u r in g in c u b a t io n o f t e n d e m o n ­s tra te s d e c lin in g e f fe c t iv e n e s s o f th e p r e s e r v a t io n s y s te m . O n o n e o c c a ­s io n d u r in g a p r o lo n g e d p r o d u c t in o c u la t io n te s t th e p r e s e r v a t iv e r e ­p re s se d th e in o c u lu m fo r 17 w e e k s , b u t s h o r t ly th e r e a fte r v ig o r o u s g r o w th a n d d e te r io r a t io n o f th e p r e p a r a t io n e n su e d . A d a p t a t io n o f p s e u d o m o n a d s c a n ta k e p la c e q u ic k ly , o r v e r y s lo w ly o v e r se v e ra l w e e k s , a n d i t is th e la t te r w h ic h o n e h a s t o w a t c h (6 ) . T h is m a y a c c o u n t f o r th e s p o r a d ic s p o ila g e r e p o r te d in th e fie ld w h e n c o n t r o l sa m p le s o n sh e lv e s are in p e r fe c t c o n d it io n (1 9 ).

P r e s e r v a t io n is in te r p r e te d b y s o m e as p r e v e n t in g th e g r o w th o f m ic r o -o r g a n is m s . D o e s th a t d e fin it io n fu l ly p r o t e c t th e c o n s u m e r ? W h e n p s e u d o m o n a d s in t r o d u c e d in t o a p r o d u c t s u rv iv e , b u t d o n o t m u lt ip ly , ca n o n e r e a l ly sa y , f r o m w h a t is k n o w n o f th e o rg a n ism , th a t th e p r e p a r a t io n is a d e q u a te ly p r e s e r v e d ? K o h n et al. (2 4 ) , c o n s id e r a p r e s e r v a t iv e t o o s lo w -a c t in g t o b e u se d in o p h t h a lm ic s o lu t io n s i f it c o u ld n o t s te r iliz e a g iv e n p s e u d o m o n a s su sp e n s io n w ith in o n e h o u r . P r e p a r a t io n s a re p la c e d o n p r e s e r v a t io n s tu d y t o d e te r m in e th e a b i l i t y o f th e p r o d u c t t o w ith s ta n d c o n s u m e r u se a n d a b u se . T h e n u m b e r s o f p s e u d o m o n a d s o n e fin d s in a p r o d u c t m a y h a v e b e e n in t r o d u c e d as in c r e ­m e n ts d u r in g u se o r d e v e lo p e d a s a re s u lt o f g r o w th . R e g a r d le s s o f th e o r ig in , th e p r e s e n c e o f a la rg e n u m b e r o f p s e u d o m o n a d s o v e r a s ig n if ica n t p e r io d o f t im e p r e d ic a te s a q u a lity , h e a lth , a n d le g a l h a z a rd . A sm a ll n u m b e r o f o rg a n ism s s u r v iv in g w ith in a p r e p a r a t io n m a y in t im e a d a p t t o a n d p r o l i fe r a te in th e p r o d u c t . I t th e r e fo r e fo l lo w s th a t th e o n ly a d e ­q u a te ly p r e s e r v e d p r e p a r a t io n is o n e th a t is e s se n t ia lly s e lf-s te r iliz in g . T h e s te r iliz in g t im e h o w e v e r n e e d n o t b e m e a su re d in h o u rs b u t in d a y s o r e v e n w e e k s .

T h e te s t o rg a n ism s w h ic h th e a u th o r e m p lo y s h a v e b e e n ta k e n fro m w o r k in g fo r m u la t io n s w h ic h w e r e a t o n e t im e c o n ta m in a te d , so th a t th e s cre e n c o n ta in s s tra in s a d a p te d t o a n d e n c o u n te r e d b y th e la b o r a t o r y ’s p re p a r a t io n s . S c re e n in g m e th o d s s h o u ld n o t b e fix e d s in ce n e w stra in s o f p s e u d o m o n a d s c o n t in u a l ly a re is o la te d fr o m d o m e s t ic a n d fo r e ig n so u rce s .

I t m u s t b e a c c e p t e d th a t u n fo r e s e e n a n d e x c e p t io n a l o rg a n ism s or c o n d it io n s m a y tu rn u p d u r in g r o u t in e m a n u fa c tu r e t o in a c t iv a te a

804 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

p r e s e r v a t io n s y s te m . I t is th e a u t h o r ’ s v ie w th a t th e p re s e r v a t io n a b i l i t y o f a p r o d u c t s h o u ld b e w e ll in e x ce ss o f th e m in im u m n e c e s s a r y to in h ib it th e a n t ic ip a te d flo ra , a n d id e a lly o n e a im s a t a p r o d u c t th a t is s e lf-s te r iliz in g . I n th e a u t h o r ’ s e x p e r ie n ce , a s e lf -s te r iliz in g p r e p a r a t io n ca n b e a c h ie v e d in m o s t c o s m e t ic a n d p h a r m a c e u t ic a l p r o d u c ts , w it h o u t a n y s ig n if ic a n t in c re a se in c o s t o r lo ss o f m a r k e ta b i li ty .

Sanitation

P r e s e r v a t io n s h o u ld n o t b e e x p e c te d t o c o m p e n s a te fo r in s a n ita ry o r ca re le ss m a n u fa c tu r in g o r p a c k a g in g . A s e p t ic p r o d u c t io n , w ith th e e x ­c e p t io n o f e y e p re p a r a t io n s , is n e ith e r e c o n o m ic a l n o r n e ce s s a ry . T h e p r o d u c t w ill th e re fo r e b e m ic r o b io lo g ie a l ly c h a lle n g e d , th e m a g n itu d e a n d q u a lity o f w h ic h w ill v a r y w ith th e in g re d ie n ts , w a te r s u p p ly , c le a n li­n ess, a n d se a so n . T h is c h a lle n g e m a y b e m o s t s e v e re fo r i t is h e re th a t c o n t in u in g a d a p ta t io n o f th e p s e u d o m o n a d s t o th e fo r m u la t io n s ta k e s p la ce . T h e n u m b e r o f o rg a n ism s fr o m th e se s o u rce s h as a b e a r in g o n th e ir s u b s e q u e n t a b i l i t y t o p r o life r a te w ith in th e p r e p a r a t io n . V e r y sm a ll in o c u la h a v e l it t le o p p o r t u n it y t o m u lt ip ly . L a rg e in o c u la in ­cre a s e th e a ss a u lt o n th e p r e s e r v a t io n s y s te m a n d in cre a se th e p r o b ­a b i l i t y th a t a d a p t iv e r e s is ta n t p s e u d o m o n a d s w ill b e in t r o d u c e d in to th e p r o d u c t .

In g r e d ie n ts th e m s e lv e s ca n b e a p o t e n t s o u rce o f c o n ta m in a t io n . In t im e th e tr o u b le m a k e r s are fo u n d , a n d m ic r o b ia l s p e c if ic a t io n s are th e n a d d e d t o fu tu r e p u r c h a s e c o n tr a c ts . A n io n ic d e te rg e n ts h a v e fr e q u e n t ly b e e n a p a r t ic u la r p r o b le m . C o n ta in e r s are ra re ly a p r o b le m b u t c lo su re s a re . A lin e r m a y s u p p o r t g r o w th or, b y a b s o r b in g m o is tu r e fr o m s p a t- te r in g s o f th e p r o d u c t o n th e su r fa ce , a lte r th e p o t e n c y o f th e p r e s e r v a ­t iv e s . P s e u d o m o n a d s w ith b o r d e r lin e re s is ta n ce ca n d e v e lo p th e re , a n d o n c e e n h a n c e d , in fe c t a n d m u lt ip ly w ith in th e p r e p a r a t io n itse lf.

W a t e r s u p p ly is a p a r t ic u la r ly im p o r ta n t s o u rce o f Pseudom onas. T h e d if f ic u lty o f e r a d ic a t in g th is o rg a n ism fr o m w a te r is u n d e r s c o r e d b y th e w o r k o f B e liu m a n d K o s h i (2 5 ) , w h o fo u n d th a t th e re s is ta n ce o f Pseudom onas t o ch lo r in e r a n g e d fr o m 4 5 -1 5 0 p p m . W a t e r s u p p ly s y s ­te m s s h o u ld b e m o n ito r e d m ic r o b io lo g ie a lly , fr o m th e m a in t o th e m a n u ­fa c tu r in g ta n k in le t . A t t e n t io n s h o u ld b e p a id t o th e s ta te o f p ip e w o r k , v a lv e s , h o se s , lo o p s , a n d o th e r s ites o f w a te r s ta g n a t io n . T h e w a te r s u p p ly o f t e n c o n ta in s a sm a ll n u m b e r o f o rg a n ism s b u t w ith o u t a d e q u a te c o n tr o l , w a te r c a n issu e fr o m a ta p o r h o s e w ith th o u s a n d s o f p s e u d o m o ­n a d s a n d o th e r g r a m -n e g a t iv e s /m l. A d e m in e r a liz e r m a y b e a f r e q u e n t s o u rce o f th is d e v e lo p m e n t . I t p r o v id e s a g o o d m e d iu m fo r m u lt ip lic a -

PSEUDOMONADS IN COSMETICS 805

t io n a n d d u r in g w a rm w e a th e r ca n d is ch a rg e c o u n ts o f 1 0 0 ,0 0 0 o r m o r e g r a m -n e g a t iv e s . T h e b e s t w a te r c o n t r o l s y s te m th e a u th o r h as d e v is e d h as b e e n th e in s ta lla t io n o f a h o t w a te r s to r a g e ta n k a n d m a n u fa c tu r in g p r o c e s s e s h a v e b e e n re v is e d t o u se h o t w a te r w h e r e v e r p o ss ib le .

T h e m a n u fa c tu r e r m u s t ta k e s te p s t o e n su re th a t n o b u i ld -u p o f r e ­s is ta n t o rg a n ism s o c c u r s in th e p r o d u c t io n a n d d is t r ib u t in g s y s te m s . T h is c a n b e e f fe c te d b y fa c t o r y h y g ie n e u s in g h o t w a te r , d e te r g e n t a n d fo r m a lin t r e a tm e n t o f fillin g m a ch in e s , ta n k s , p u m p s , filters , m ills , p ip e s , e t c ., im m e d ia te ly a fte r u se . M ic r o b io lo g ic a l te s ts o n e q u ip m e n t s h o u ld b e m a d e t o in su re th e e f fe c t iv e n e s s o f th e c le a n s in g o p e r a t io n . T h e p r e s e n c e o f th o u s a n d s o r h u n d r e d s o f o r g a n is m s /s w a b o r m l ca lls f o r im ­m e d ia te a c t io n . T e n s m a y b e u n a v o id a b le a lth o u g h z e ro c o u n ts c a n b e o b ta in e d fr o m a rea s w h o s e c le a n lin e ss is d e e m e d cru c ia l.

A y l i f fe et al. (2 6 ) d e s c r ib e d a n o u tb r e a k o f m e n in g it is in 14 n e u r o s u r ­g e r y p a t ie n ts . T h e in fe c t io u s a g e n t w a s Pseudom onas aeruginosa. A n e x a m in a t io n o f th e e n v ir o n m e n t r e v e a le d th e e p id e m ic s tra in in a s h a v in g b ru s h u se d fo r p r e p a r a t io n o f th e s ca lp a n d o n th e f lo o r o f a r o o m o c ­c u p ie d b y a n in fe c t e d p a t ie n t . T w e n t y o th e r s tra in s w e r e is o la te d f r o m h a n d c re a m s , s in k s , f lo o rs , s o a p tr a y s , s in k c lo th s , a n d th e c a p o f a b o t t le o f a n t is e p t ic .

G o o d g e n e ra l c le a n lin e ss is im p o r t a n t in c o n t r o ll in g p s e u d o m o n a s c o n ­ta m in a t io n . A n d b y g e n e ra l c le a n lin e ss is m e a n t th a t o f sh e lv e s , b in s , ta b le s , b e n e a th ta b le s , th e u n d e r s id e o f sh e lv e s , e tc . A t th e s e p o in ts s p illa g e o f p r o d u c t s m ix e d w ith d u s t , d ir t a n d m o is tu r e p r o v id e a m e n ­s tru u m fo r th e d e v e lo p m e n t o f re s is ta n t p s e u d o m o n a d stra in s .

T w o in c id e n ts i llu s tr a te th e d il ig e n c e n e ce s s a r y in m e e t in g a p s e u ­d o m o n a s p r o b le m w ith in a p la n t .

1. A s tra in o f p s e u d o m o n a s h a d a d a p te d t o a p h a r m a c e u t ic a l s te r io d c r e a m . T h e m ic r o b ia l c o n t e n t w a s m o n ito r e d th r o u g h th e m ix in g k e t ­tle , f ilte r , p u m p , h o m o g e n iz e r , a g in g ta n k , p ip e lin e s , a n d fillin g m a ch in e s . E a c h e le m e n t in th e p r o c e s s w a s s c r u p u lo u s ly c le a n e d a n d s te r iliz e d , a n d y e t th e v e r y n e x t b a t c h h a d t o b e r e je c t e d . T h e n u m b e r o f o rg a n is m s in th e p r o d u c t w a s so la rg e th a t i t c o u ld o n ly h a v e b e e n in t r o d u c e d b y a m a s s iv e in o c u la t io n . T h e o n ly e le m e n t in th e c h a in th a t h a d n o t b e e n d is m a n t le d h a d b e e n a n in -p la c e p ip e d e liv e r in g th e e m u ls io n f r o m ta n k t o filler . T h e lin e , h o w e v e r , h a d b e e n c le a n e d a n d fo rm a lin -s te r il iz e d a n d z e r o p la te c o u n ts w e re o b ta in e d fr o m th e e fflu e n t t o p r o v e it . I t w a s fo u n d , o n b r e a k in g in to th e p ip e , th a t th e w a te r h a d c le a n e d th e b o t t o m o v a l o f th e p ip e , w h ile th e t o p o v a l, b e c a u s e o f th e lo w p it c h , c o n ­ta in e d a la y e r o f c re a m . R e c o v e r y o f v ia b le o rg a n ism s c o u ld n o t b e

806 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

m a d e im m e d ia te ly a fte r th e s te r iliz in g tr e a tm e n t , b u t w ith in a s h o r t t im e th e in fe c t io n r e e s ta b lis h e d itse lf w ith in th e t o p o v a l, a n d a w a te r w a sh th e re a fte r c o n ta in e d th o u s a n d s o f p s e u d o in o n a d s / 'm l. S c o u r in g th e p ip e e lim in a te d th e p r o b le m a n d th e n e x t b a t c h w h ich w a s c o n ta m in a te d a g a in h a d t o b e r e je c t e d . M ic r o b ia l e x a m in a t io n o f th e e n tire p r o c e s s fa ile d t o r e v e a l a n y s o u rce o f in o c u la t io n . A g im le t -e y e d c h e m is t s o lv e d th e p r o b le m . H e fo u n d a n e c o n o m y -m in d e d , f illin g -lin e s u p e r v is o r h a d u t iliz e d , as a lu b r ic a n t f o r th e c a p o f th e v ia l , r e je c t e d m a te r ia l w h ich h a d e s ca p e d d e s tr u c t io n . T h is m a te r ia l, w h ic h s h o u ld h a v e b e e n d is p o s e d o f w e e k s ea rlier , c o n ta in e d h u n d r e d s o f th o u s a n d s o f o r g a n is m s /m l. T h e r e a fte r , th e re w e re n o p ro b le m s .

2. T h e la b o r a t o r y r e p o r te d a s ig n if ic a n t m ic r o o r g a n is m c o n t e n t in a n e x p e r im e n ta l m a k e -u p p r o d u c t . T h e p r e p a r a t io n in t im e k ille d th e p s e u d o m o n a d w h ic h h a d a n id e n t ifia b le ch a ra c te r is t ic . T h e s o u rce p r o v e d e lu s iv e . T w o b o t t le s c o n ta in in g a s u sp e n s io n o f a n in g re d ie n t u se d in th e p r e p a r a t io n w e r e fo u n d tu c k e d a w a y in a r a r e ly u s e d p a r t o f th e s to c k r o o m . T h e b o t t le s w e re c o a te d w ith a m ix tu r e o f sp illa g e a n d d u s t . T h e c o n te n ts w e r e s te r ile b u t a s w a b o f th e sp illa g e y ie ld e d th o u s a n d s o f th e p a r t ic u la r p s e u d o m o n a d /s q u a r e ce n t im e te r . I t is p r o b a b le th a t w ith t im e th e s e o rg a n ism s , i f n o t e lim in a te d , w o u ld h a v e c o m p le t e ly a d a p te d t o th e p re p a r a t io n .

C o n c l u s i o n

T h is p a p e r r e p r e se n ts th e e x p e r ie n c e o f a m ic r o b io lo g y la b o r a t o r y in d e a lin g w ith in d u s tr ia l p s e u d o m o n ia s is o v e r m o r e th a n a d e c a d e . D u r ­in g th is p e r io d , r e s p e c t fo r p s e u d o m o n a d s as a d a p t iv e o rg a n ism s h as c o n t in u e d to g r o w . T h e le s s o n t o b e le a rn e d is th a t e te rn a l v ig i la n c e is th e p r ice o f q u a li t y a n d , o c c a s io n a l ly , e v e n o f s a fe ty .

(R e c e iv e d A p r il 12, 1967)

R e f e r e n c e s

( 1 ) B e ju c k i , W . , P s e u d o m o n a s ; i t s u b i q u i t y a n d r o le s in in d u s t r ia l m ic r o b i o lo g i c a l t e s t p r o c e d u r e s , personal communication ( 1 9 6 5 ) .

( 2 ) H u g o , W . B . , a n d F o s t e r , J . H . S ., B a c t e r io c id a l e f f e c t u p o n Pseudomonas aeruginosa o f c h e m ic a l a g e n t s f o r u s e in o p h t h a l m i c s o lu t io n , J. Pharm . Pharmacol. 1 6 , Suppl. 1 2 4 T - 1 2 6 T ( 1 9 6 4 ) .

( 3 ) B r o w n , M . R . W . , a n d N o r t o n , D . A . , T h e p r e s e r v a t io n o f o p h t h a l m i c p r e p a r a t io n s , J. Soc. Cosmetic Chemists, 1 6 , 3 6 9 - 3 9 3 ( 1 9 6 5 ) .

( 4 ) U . S . F e d e r a l R e g is t e r , 2 9 F .R . 1 2 4 5 8 , S e p t e m b e r 1, 1 9 6 4 .( 5 ) B r y c e , D . M . , a n d S m a r t , R . , T h e p r e s e r v a t io n o f s h a m p o o s , J . .Voc. Cosmetic Chemists,

1 6 , 1 8 7 -2 0 1 ( 1 9 6 5 ) .

PSEUDOMONADS IN COSMETICS 807

( 6 ) B e a n , H . S ., H e m a n - A c k e h , M . , a n d T h o m a s , J . , T h e a c t i v i t y o f a n t ib a c t e r ia l s in t w o - p h a s e s y s te m s , Ibid., 1 6 , 1 5 - 3 0 ( 1 9 6 5 ) .

( 7 ) R o g o f f , M . H . , C h e m is t r y o f o x i d a t io n o f p o l y c y c l i c a r o m a t i c h y d r o c a r b o n s b y s o il p s e u d o m o n a d s , J. Bacteriol., 8 3 , 9 9 8 - 1 0 0 4 ( 1 9 6 2 ) .

( 8 ) S o la r i , A . A . , D a t o , A . A . , H e r r e r o , M . M . , d e C r e in a s c h i , M . S ., d e R e id , M . I . , S a ig a d o ,L . P . , a n d P a in c e ir a , M . T . , U s e o f a s e le c t iv e e n r ic h m e n t m e d iu m f o r t h e is o la t io n o f Pseudomonas aeruginosa f r o m f e c e s , J. Bacteriol., 8 4 , 1 9 0 ( 1 9 6 2 ) .

( 9 ) H e d r i c h , H . G . , C a r r o l l , N . T . , O w e n , H . P . , a n d P r i t c h a r d D . J . V i a b i l i t y o f s e le c t e d m ic r o o r g a n is m s in h y d r o c a r b o n fu e ls , A ppl. Microbiol., 1 1 , 4 7 2 - 4 7 5 ( 1 9 6 3 ) .

( 1 0 ) T r a x le r , R . W . , M i c r o b i a l d e g r a d a t io n o f a s p h a lt , Biotechnol. Bioeng., 4 , 3 6 9 - 3 7 6 ( 1 9 6 2 ) .( 1 1 ) D u r h a m , N . N . , a n d M c P h e r s o n , D . L . , I n f lu e n c e o f e x t r a n e o u s c a r b o n s o u r c e s o n b i o ­

s y n t h e s i s d e n o v o o f b a c t e r ia l e n z y m e s , J. Bacteriol., 8 0 , 7 - 1 3 ( 1 9 6 0 ) .( 1 2 ) A l f o r d , J . A . , a n d P ie r c e , D . A . , P r o d u c t i o n o f l ip a s e b y Pseudomonas frag i in a s y n t h e t i c

m e d iu m , Ib id ., 8 6 , 2 4 - 2 9 ( 1 9 6 3 ) .( 1 3 ) S u lt z e r , B . M . , O x i d a t i v e a c t i v i t y o f p s y c h r o p h i l i c a n d m e s o p h i l i c b a c t e r ia o n s a t u r a t e d

f a t t y a c id s , Ib id ., 8 2 , 4 9 2 - 4 9 7 ( 1 9 6 1 ) .( 1 4 ) B e n t ly , R . , a n d S le c h t a , L . , O x id a t io n o f m o n o a n d d is a c c h a r id e s t o a l c o n i c a c id s b y

Pseudomonas s p e c ie s , Ibid., 79, 3 4 6 - 3 5 5 ( 1 9 6 0 ) .( 1 5 ) P e t e r s o n , A . C ., a n d G u n d e r s o n M . F . , S o m e c h a r a c t e r is t ic s o f p r o t e o l y t i c e n z y m e s f o r

Pseudomonas fluorescens, A ppl. Microbiol., 8 , 9 8 - 1 0 4 ( 1 9 6 0 ) .( 1 6 ) I n g r a h a m , J . L . , a n d S to k e s , J . L . , P s y c h r o p h i l i c b a c t e r ia , Bacteriol. Rev., 2 3 , 9 7 - 1 0 8

( 1 9 5 9 ) .( 1 7 ) M a n o w it z , M . , P r e s e r v a t io n o f c o s m e t i c e m u ls io n s , Developments in Industria l M icro­

biology, 2 , 6 5 - 9 1 ( 1 9 6 1 ) .( 1 8 ) K o h n , S . R . , G e r s h e n fe ld , L . , a n d B a r r , M . , T h e e f f e c t iv e n e s s o f c e r t a in a n t ib a c t e r ia l

a g e n t s in o p h t h a l m i c s o lu t io n s a g a in s t Pseudomonas aeruginosa. J . P harm . Sci., 5 2 , 9 6 7 - 9 7 4 ( 1 9 6 3 ) .

( 1 9 ) T i c e , L . F . , a n d B a r r , M . , F a c t o r s t o b e c o n s id e r e d in t h e p r e s e r v a t io n o f c o s m e t i c e m u ls io n s , / . Soc. Cosmetic Chemists, 9, 1 7 1 - 1 8 0 ( 1 9 5 8 ) .

( 2 0 ) W e d d e r b u r n , D . L . , P r e s e r v a t io n o f t o i l e t p r e p a r a t io n s c o n t a i n i n g n o n io n ic s , Ib id ., 9

2 1 0 - 2 2 8 ( 1 9 5 8 ) .( 2 1 ) B a r r , M . , a n d T i c e , L . F . , T h e p r e s e r v a t io n o f a q u e o u s p r e p a r a t io n s c o n t a i n i n g n o n ­

i o n i c s u r fa c t a n t s I . , J. A m . Pharm . Assoc. Sci. Ed., 4 6 , 4 4 2 - 4 4 5 ( 1 9 5 7 ) .( 2 2 ) E v a n s , W . P . , T h e s o lu b i l i z a t io n a n d in a c t i v a t i o n o f p r e s e r v a t iv e s b y n o n io n ic d e t e r ­

g e n ts , J . Pharm . Pharmacol., 1 6 , 3 2 3 - 3 3 1 ( 1 9 6 4 ) .( 2 3 ) N o b le , W . C . , a n d S a v in , J . A . , S t e r o id c r e a m c o n t a m in a t e d w i t h Pseudomonas aeru­

ginosa, Lancet, 1 , 3 4 7 - 3 4 9 ( 1 9 6 6 ) .( 2 4 ) K o h n , S . R . , G e r s h e n fe ld , L . , a n d B a r r , M . , A n t ib a c t e r ia l a g e n t s n o t p r e s e n t ly e m p lo y e d

a s p r e s e r v a t iv e s in o p h t h a l m i c p r e p a r a t io n s f o u n d e f f e c t i v e a g a in s t Pseudomonas aeru­ginosa, J . Pharm.. Sciences, 5 2 , 1 1 2 6 - 1 1 2 9 ( 1 9 6 3 ) .

( 2 5 ) B e lo ia n , A . , a n d K o s k i , T . , R e s i s t a n c e o f Pseudomonas t o v a r io u s c h e m ic a l g e r m ic id e s , J . Assoc. Agr. Chem., 47, 8 0 4 - 8 0 7 ( 1 9 6 4 ) .

( 2 6 ) A y l i f f e , G . A . J ., L o w b e r y , E . J . L . , H a m i l t o n , J . G . , S m a ll , J . M . , A s h e s h o v , R . A . , a n d P a r k e r , M . T . , H o s p i t a l in fe c t i o n w i t h Pseudomonas aeruginosa in n e u r o s u r g e r y , Lancet, 1 1 , 3 6 5 - 3 6 9 ( 1 9 6 5 ) .

808 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Society of Cosmetic Chemists

Journal Advertising

takes your

message straight

to the

Chemists

of the

Cosmetic Industry

For information address:

Editorial Assistant

Society of Cosmetic Chemists761 North Valley Chase Road

Bloomfield Hills, Michigan 48013

J. Soc. Cosmetic Chemists, 18, 809-829 (Dec. 9, 1967)

A Statistical Approach to the Evaluation of Cutaneous Responses to Irritants

W . M . W O O D I N G , B .C h .E .* a n d D . L . O P D Y K E , P h .D . f

S y n o p s i s — T h is s t u d y w a s d o n e t o t e s t t h e a p p l i c a t i o n o f c e r t a in c o m m o n s ta t is t i c a l e x p e r i ­m e n t a l d e s ig n s t o t h e f ie ld o f h u m a n p a t c h t e s t in g w h e r e t h e y d o n o t a p p e a r t o h a v e b e e n u s e d p r e v io u s ly , a n d t o in v e s t ig a t e c e r t a in v a r ia b le s a f f e c t in g i r r i t a t io n t e s t r e s u lt s . S o d iu m la u r y l s u l fa te , a t y p i c a l i r r i t a n t o f g e n e r a l in t e r e s t , w a s u s e d . T w o e x p e r im e n t s a r e d e ­s c r ib e d in w h ic h s e v e r a l f a c t o r s t h o u g h t t o a f f e c t i r r i t a t io n r e s u lt s w e r e t e s t e d ; th e s e in c lu d e d ir r i t a n t c o n c e n t r a t io n , c e r t a in t im e fa c t o r s , a n d t y p e s o f p a t c h u s e d . I r r i t a t io n w a s b a s i c a l ly s c o r e d o n a f i v e - p o i n t s c a le . R e s u lt s s h o w e d t h a t e x p e r im e n t a l a n d s u b je c t - t o - s u b j e c t v a r i a t io n c o u ld b e g r e a t l y r e d u c e d b y a d e q u a t e e x p e r im e n t a l d e s ig n , t h a t s e v e r a l f a c t o r s o f in t e r e s t w e r e in f lu e n t ia l in th e s y s t e m , a n d t h a t t h e e r r o r o f m e a s u r e m e n t ( e s t im a t io n b y a j u d g e s c o r in g t h e p a t c h s it e s ) w a s m u c h s m a l le r t h a n h a d b e e n e x p e c t e d . O n e o f t h e s ig n i f ­i c a n t e f f e c t s o f c o n s id e r a b le in t e r e s t w a s t h e f in d in g t h a t t h e d e g r e e o f o b s e r v a b l e i r r i t a t io n w a s a f u n c t io n o f th e in t e r v a l b e t w e e n r e m o v a l o f a p a t c h a n d th e t im e th e s it e w a s s c o r e d .

I n t r o d u c t i o n

I t is w e ll k n o w n th a t th e u se o f p a t c h te s t in g f o r th e d e t e c t io n o f p r im a r y ir r ita t io n o r s e n s it iz a t io n o f h u m a n sk in t o v a r io u s su b s ta n ce s , as u s u a lly p r a c t ic e d , is s u b je c t t o s e v e re l im ita t io n s o f n u m b e r s (1 ) . F o r e x a m p le , it m a y r e a d ily b e s h o w n b y e le m e n ta r y p r o b a b i l i t y c a l ­c u la t io n s th a t th e u se o f th e u su a l p a tc h te s t in g te c h n iq u e s , e v e n w e re se v e ra l th o u s a n d s u b je c t s t o b e u se d , m ig h t e a s ily fa il t o p r e d ic t a s e r io u s p r o p o r t io n o f r e a c to r s in th e p o p u la t io n .

T h is p r o b le m h a s n o t b e e n s o lv e d b y t h e te c h n iq u e s t o b e d e s c r ib e d in th is p a p e r , b u t it is h o p e d th a t it m a y h a v e b e e n a m e lio ra te d . T h e

* C a r t e r P r o d u c t s R e s e a r c h , C a r t e r - W a l la c e , I n c . , H a lf A c r e R o a d , C r a n b u r y , X . J . 0 8 5 1 2 . t R e v l o n R e s e a r c h C e n t e r , I n c . , 9 4 5 Z e r e g a A v e n u e , B r o n x , X . Y . 1 0 4 7 3 .

809

810 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

a u th o r s h a v e fe lt fo r s o m e t im e th a t u t i liz a t io n o f m o d e r n m e th o d s o f e x p e r im e n ta l d e s ig n a n d d a ta a n a ly s is ca n b e o f g r e a t v a lu e in sk in re se a rch as w e ll as in p r a c t ic a l te s t in g . S u rp r is in g ly , v e r y l it t le h as b e e n d o n e w ith th e se te c h n iq u e s in th is a rea , d e sp ite th e r e la t iv e ly h e a v y u se o f s ta t is t ic s in re la te d b io lo g ic a l f ie ld s .*

M a n y ir r ita n ts h a v e b e e n p a t c h te s te d a n d m a n y in v e s t ig a to r s h a v e s u g g e s te d te s t m e th o d s . T h e r e are n o w a lm o s t as m a n y m e th o d s as th e re h a v e b e e n in v e s t ig a to r s . P io n e e rs h a v e in c lu d e d S c h w a r tz(2 ) , S h e la n sk i (3 ) , D r a iz e (4 ) , V o s s (5 ) , a n d R o s t e n b e r g (G), all o f w h o m h a v e m a d e im p o r ta n t c o n tr ib u t io n s . H o w e v e r , th e re re m a in s a n e e d fo r a s ta n d a rd , e a s ily m a n a g e d , a n d s ta t is t ic a lly v a lid p r o c e d u r e f o r th e a ss a y o f ir r ita t io n p o te n t ia l, o n e w h ic h w ill g iv e u n ifo r m a n d r e p r o d u c ib le re su lts w ith in a s h o r t t im e .

T h e p u r p o s e s o f th is in v e s t ig a t io n w e r e :1. T o s t u d y th e a d v a n ta g e s o f u s in g ce r ta in w e l l-k n o w n e x p e r i ­

m e n ta l d e s ig n s a n d s u b s e q u e n t s ta t is t ica l a n a ly se s w h ich d o n o t a p p e a r t o h a v e b e e n p r e v io u s ly u se d in sk in te s t in g .

2. T o d e s c r ib e c e r ta in m in o r m o d if ic a t io n s o f c u r re n t h u m a n p a t c h te s t in g te c h n iq u e s w h ic h th e a u th o r s fe e l m a y im p r o v e e x p e r i­m e n ta l r e l ia b il ity a n d q u a n t ita t io n .

3. T o in v e s t ig a te c e r ta in v a r ia b le s w h ic h a p p e a r t o o p e r a te in a p a r t ic u la r ir r ita n t s y s te m , p r in c ip a lly as a n e x a m p le t o d e m o n s tr a te th e e x p e r im e n ta l t e c h n iq u e s a n d s ta t is t ic a l a n a ly s is .

P r e l i m i n a r y E x p e r i m e n t s

Irritant-

T o a c c o m p lis h th e a b o v e o b je c t iv e s , p a r t ic u la r ly th e fir s t {viz., t o d e m o n s tr a te th e e f f ic ie n c y o f fo r m a l e x p e r im e n ta l d e s ig n a n d a n a ly s is ), i t w a s b e lie v e d a d v is a b le t o u se a s p e c if ic s in g le irr ita n t. S o d iu m la u ry l s u l fa t e f w a s c h o s e n b e c a u s e o f its c o m m o n u se in m a n y h o u s e ­h o ld p r o d u c t s a n d to ile tr ie s , b e c a u s e it is b e lie v e d t o h a v e n o im p o r ta n t s e n s it iz a t io n e f fe c ts , a n d b e c a u s e it is w e l l-k n o w n t o d e r m a to lo g ic a l in v e s t ig a to r s .

Scoring

A g a in , in o r d e r t o u se a fa m ilia r s y s te m , it w a s fe lt d e s ira b le to h a v e a n u m e r ica l s ca le o f m e a s u r e m e n t s im ila r t o th o s e u se d in th e p a s t .

* R e c e n t l y , a n o t h e r a p p r o a c h t o q u a n t i f y i n g s k in t e s t in g h a s b e e n d e s c r ib e d , a n d w i l l b e p u b l i s h e d s o o n ( 1 6 ) .

f D u p o n o l C '“ '— E . I . d u P o n t d e N e m o u r s a n d C o . , T n c ., W i lm in g t o n , D e l . 1 9 8 9 8 .

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 811

I t w a s b e lie v e d , h o w e v e r , th a t th e d e g re e o f ir r ita t io n c o u ld b e ju d g e d v is u a lly m u c h m o r e p r e c is e ly th a n h a s p r e v io u s ly b e e n s u p p o s e d , a n d th e sca le s h o w n in F ig . 1 w a s th e r e fo r e a d o p te d .

I n u s in g th is sca le , th e o b s e r v e r w a s r e q u ir e d t o e s t im a te th e d e g re e o f ir r ita t io n o n th e t r e a te d s ite c o m p a r e d t o u n tr e a te d s u rro u n d in g

f T~ I ~T~ 1 —r~ T" T " ’j » 'T— ■— T » I « }

Figure 1. I r r i t a t io n s c o r i n g s c a le

sk in . D u r in g th e r e a d in g o f a n y s ite , o th e r t r e a te d s ite s w e re c o v e r e d w ith tissu e t o e l im in a te d ir e c t c o m p a r is o n s . The estimates were always made to the nearest 0 .2 5 unit on the scale o f Fig. 1. ( I t w a s s h o w n la te r th a t th is d e g r e e o f p r e c is io n w a s re a s o n a b le .)

I n p la n n in g p r e lim in a r y w o r k in o r d e r t o i d e n t i fy p o s s ib le rea l v a r ia b le s a ffe c t in g ir r ita t io n w ith s o d iu m la u ry l su lfa te , th e fo l lo w in g fa c to r s w e re c o n s id e r e d :

S ize o f p a tc hT y p e o f c o v e r in g (o c c lu s io n ) N a tu r e o f p a t c h Q u a n t ity o f t e s t s o lu t io n C o n c e n t r a t io n o f ir r ita n t

P a tc h c o n t a c t t im e O b s e r v a t io n t im e (e la p s e d t im e

a fte r r e m o v a l o f p a t c h ) T ig h tn e s s o f p a t c h N a tu r e o f s u b je c t s ’ sk in A c t i v i t y o f s u b je c t s

I t w a s in te n d e d th a t m a n y o f th e p o te n t ia l v a r ia b le s b e h e ld c o n ­s ta n t s o th a t th e e x p o s it io n o f th e s ta t is t ic a l p r o c e d u r e w o u ld n o t b e c o n fu s e d b e c a u s e o f u n d u e c o m p le x it y . I t is t o b e u n d e r s to o d th a t in a n y rea l s y s te m u n d e r in v e s t ig a t io n i t m a y b e p r a c t ic a l a n d f r e q u e n t ly n e c e s s a r y t o te s t m o r e s o u rce s o f v a r ia t io n th a n th e n u m b e r in c lu d e d in th is ca se . T h e e x p e r im e n ta l d e s ig n s th e n u se d w o u ld s im p ly b e e x te n ­s io n s o r m o d if ic a t io n s o f th o s e s h o w n h e re .* I n th e p r e s e n t ca se , s o m e p r e lim in a r y w o r k w a s d o n e in o r d e r t o t r y t o s e le c t a sm a ll n u m b e r o f im p o r ta n t fa c t o r s fr o m th e a b o v e list. T h is w o r k is t r e a te d b r ie f ly b e lo w .

Development o f T yp e o f Patch

S o m e in it ia l w o r k w a s d o n e w ith o v a l-s h a p e d o p e n p a tc h e s , su ch as a re u se d o f t e n in r o u t in e p a t c h te s t in g . T h e s e w e re a p p lie d o v e r 14 in .

* T h e r e a r e m a n y m o d i f i c a t io n s o f f a c t o r ia l d e s ig n s , a s w e l l a s c e r t a in n o n f a c t o r ia l a r ­r a n g e m e n t s a v a i la b le w h ic h d o n o t r e q u ir e e x t r e m e ly la r g e e x p e r im e n t s w h e n m a n y v a r ia b le s a r e t o b e e v a lu a t e d .

812 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Figure 2. " R e g u l a r ” p a t c h

p ie c e s o f b lo t t in g p a p e r t o w h ich a c o n s ta n t q u a n t it y o f ir r ita n t s o lu ­t io n (4 d r o p s ) w a s a p p lie d . T h e sk in w a s s w a b b e d th o r o u g h ly w ith a c e to n e ju s t p r io r to p a tc h in g . S e v e ra l d if fe r e n t a rea s o f th e b o d y w e re u se d . T h e s e p a tc h e s w e re fo u n d u n s a t is fa c to r y fo r re a so n s w h ic h in c lu d e d th e fo l lo w in g :

1. I n m a n y ca se s th e s o lu t io n e v a p o r a t e d o r s o a k e d in to th e g a u z e b a c k in g a fte r a fe w h o u rs .

2. T h e r e w a s m u c h a p p a r e n t v a r ia t io n in p re ssu re e x e r te d o n th e b lo t t in g p a p e r d u e t o th e sh a p e o f th e p a t c h a n d a t e n d e n c y fo r th e a d h e s iv e t o c re e p .

F o l lo w in g th is , 34 in- sq . p la s t ic B a n d -A id s 8* w e re te s te d . T h e s e w e re m u c h m o r e s a t is fa c to r y fo r a d h e s io n a n d p re ssu re v a r ia t io n , b u t lo ss o f s o lu t io n b y e v a p o r a t io n o r a b s o r p t io n in to th e p a t c h w a s s till a p r o b le m . F in a lly , th e b lo t t in g p a p e r w a s o c c lu d e d b y th e a p p lic a t io n o f a 44 in . sq . o f S a r a n " f film u n d e r th e B a n d -A id , as s h o w n in F ig . 2. T h is a r ra n g e m e n t w a s a d o p te d as o n e o f th e fin a l tw o ty p e s o f p a tc h u se d , a n d a p p e a r e d t o s o lv e th e p r o b le m o f lo ss o f s o lu t io n ; b lo t te r s r e ­m a in e d m o is t e v e n a fte r 24 h o u rs . A lth o u g h th is d e g re e o f o c c lu s io n is n o t u s u a lly e m p lo y e d in p a t c h te s t in g , th e re su lts o f th is a n d s u b s e q u e n t w o r k h a v e in d ic a te d th a t th is a r ra n g e m e n t , u n d e r th e c o n d it io n s o f th e se e x p e r im e n ts , m a y b e g e n e r a lly su p e r io r t o th e c u s to m a r y ty p e .

T h e r e w a s s tro n g e v id e n c e th a t th e r e p r o d u c ib i l i t y o f r e a c t io n s t o th e n e w “ re g u la r ” p a t c h w a s s u p e r io r t o th a t o f th o s e p r e v io u s ly u sed . H y p o th e s iz in g th a t th is m a y h a v e re s u lte d fr o m m a in te n a n c e o f m o r e c o n s ta n t a n d in t im a te sk in c o n t a c t , it w a s d e c id e d t o t r y a fu r th e r m o d if ic a t io n d e s ig n e d t o h a v e a s lig h t ly in c re a s e d p re ssu re a g a in st th e sk in , a n d , it w a s h o p e d , a m u c h m o r e u n ifo r m d e g re e o f c o n ta c t . T h is

* B a n d - A i d s ® — J o h n s o n a n d J o h n s o n & C o . , N e w B r u n s w ic k , N . J . 0 8 9 0 3 . t S a r a n 1"’— T h e D o w C h e m ic a l C o . , M i d l a n d , M ic h . 8 4 6 4 1 .

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 813

“ p re s s u r e ” p a t c h c o n s is te d o f th e re g u la r p a t c h p lu s tw o g a u ze sq u a res , th e n a t a p e d -o n p la s t ic p o k e r ch ip (F ig . 3 ) . P r e lim in a ry e x p e r im e n ts in d ic a te d th a t s u b s ta n t ia lly d if fe r e n t re su lts m ig h t b e e x p e c te d fr o m th is a r ra n g e m e n t . S in c e th e p re ssu re d if fe r e n c e w a s b e lie v e d s lig h t, w e a t t r ib u te d th is t o th e p re s u m e d g r e a te r u n ifo r m ity o f c o n t a c t . T h e a u th o r s a re n o t n e ce s s a r ily r e c o m m e n d in g th is a r ra n g e m e n t fo r g e n e ra l use, o f co u r se , a n d are a w a re th a t th e u se o f a n y s u b s ta n tia l d e g re e o f p re ssu re is fr e q u e n t ly b e lie v e d u n d e s ira b le . H o w e v e r , it is fe lt th a t th is e x p e r ie n ce , e s p e c ia lly w h e n v ie w e d in th e l ig h t o f th e tw o fo r m a l e x p e r im e n ts t o b e d e s c r ib e d b e lo w , d e m o n s tr a te s th e im p o r ta n c e o f m a in ta in in g a c o n s ta n t c o n ta c t .

Selection o f Variables

P r e lim in a r y w o r k in d ic a te d th a t th e d e g re e o f ir r ita t io n w a s p r o b ­a b ly a ls o in flu e n c e d b y th e p e r io d o f t im e fo l lo w in g th e r e m o v a l o f th e p a tc h . I t w a s th e re fo r e p la n n e d t o u se th is fa c t o r as a n a d d it io n a l v a r ia b le . F u r th e r , c o n t a c t t im e a n d ir r ita n t c o n c e n t r a t io n w e re r e le v a n t fa c to r s , s in ce it w a s w e ll k n o w n th a t th e s e v a r ia b le s w o u ld a ffe c t th e s y s te m ; h o w e v e r , n o th in g w a s k n o w n t o th e a u th o r s o f th e ir in t e r a c t io n w ith e a ch o th e r a n d w ith th e o th e r t w o v a r ia b le s .

T o s u m m a r iz e , p r e lim in a r y e x p e r im e n ta l e v id e n c e s u g g e s te d u se o f th e fo l lo w in g fo u r v a r ia b le s in th e first fo r m a l e x p e r im e n t :

A . C o n c e n t r a t io n o f ir r ita n tB . T y p e o f p a tc hC . P a tc h c o n t a c t t im eD . O b s e r v a t io n t im e (a fte r r e m o v a l)

I n th is f ir s t fa c to r ia l e x p e r im e n t , th e fo l lo w in g p o te n t ia l v a r ia b le s w e re t o b e c a r e fu lly c o n t r o lle d a t as c o n s ta n t a le v e l as p o s s ib le fr o m ru n t o r u n :

1. S in g le ju d g e (s c o r e r )*2. T y p e o f ir r ita n t3 . P r e -t r e a tm e n t o f s ite (5 -s e c o n d s w a b b in g w ith fa c ia l tissu e w e t

w ith a c e to n e )4 . F o u r d r o p s o f s o lu t io n o n e a ch b lo t t e r sq u a re5 . A ll p a tc h e s a p p lie d in a s in g le sess ion

* A l l s c o r in g in t h e w o r k t o b e d e s c r ib e d w a s d o n e b y a n e x p e r ie n c e d p h a r m a c o l o g i s t , a l ­t h o u g h a s m a ll p r e l im in a r y s t u d y in d i c a t e d n o s ig n i f i c a n t d i f f e r e n c e , a n d v e r y h ig h c o r r e l a ­t io n ( o v e r 9 5 % ) b e t w e e n h is s c o r e s a n d t h o s e o f a t e c h n ic ia n w h o h a d b e e n in s t r u c t e d b y t h e p h a r m a c o l o g i s t a n d h a d h a d le s s th a n o n e d a y ’s p r a c t i c e .

814 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

6. S o lu t io n s o f ir r ita n t c a r e fu lly p re p a r e d in a n a n a ly t ic a l la b o r a to r y7. A ll te s ts d o n e a t sa m e t im e o f y e a r (w ith in a 2 -m o n t h p e r io d )8 . A ll te s ts d o n e o n s u b je c t s ’ b a c k s .9 . A ll s u b je c t s m a le

10. A ll s u b je c t s 18 t o 45 y e a rs o ld11. A ll s u b je c t s h e a lth y C a u ca s ia n s12. E x t r e m e ly h irsu te s u b je c t s e x c lu d e d13. A ll p a t c h ch a r a c te r is t ic s (d im e n s io n s , e t c ) h e ld t o c lo s e to le ra n ce s

fo r e a ch t y p e o f p a t c h14. A ll s u b je c t s la b o r a t o r y w o r k e r s15. A ll s u b je c t s o n o v e r n ig h t te s ts a sk e d t o k e e p p a tc h e s d r y16. A ll p a tc h e s a p p lie d b y o n e p e rs o n17. A ll s u b je c t s l im ite d t o e ig h t p a tc h e s fo r c o m fo r t

D e s i g n o f F i r s t E x p e r i m e n t

General

4 'h e s im p le s t p o s s ib le d e s ig n w h ic h w o u ld in c o r p o r a te th e fo u r s e le c te d v a r ia b le s a n d a llo w e lim in a t io n o f in t e r s u b je c t r e s p o n se d i f ­fe re n ce s w as p la n n e d . T h is g o a l, t o g e t h e r w ith th e e ig h t p a tc h e s p e r s u b je c t re s tr ic t io n , d e te rm in e d th e g e n e ra l o u t l in e o f th e d e s ig n u sed .

A ca re fu l s e a rch o f th e lite r a tu r e d id n o t d is c lo s e th e p r e v io u s u se o f d e s ig n t e c h n iq u e s s im ila r t o th o s e c o n te m p la te d . T h e a u th o r s th e r e ­fo r e fe lt it d o u b ly im p o r ta n t t o m a k e th e in it ia l tr ia ls w ith as s im p le a fa c to r ia l d e s ig n as p o s s ib le , w it h o u t s a c r ific in g th e m a jo r a d v a n ta g e s o f m u lt i - fa c t o r e x p e r im e n ta l d e s ig n s as c o m p a r e d t o c la ss ica l ( o n e - fa c to r - a t -a -t im e ) p ro c e d u re s .

Objects o f the Experim ent

T h e p r in c ip a l p u r p o s e s o f th is e x p e r im e n t , w h ich d e te rm in e d th e d e s ig n , w e r e :

1. T o m in im iz e e x p e r im e n ta l e rro r b y is o la t in g s u b je c t - t o -s u b je c t d iffe re n ce s .

2. T o d e te rm in e th e s u ita b i l i ty o f a n a ly s is o f v a r ia n c e te c h n iq u e s fo r h a n d lin g th e d a ta r e s u lt in g fr o m th e e x p e r im e n t .

3. T o d e te rm in e “ s ig n if ic a n c e ” (i.e ., p r o b a b i l i t y o f r e a l ity ) o f th e v a r ia b le s te s te d (a n d th e ir in te r a c t io n s ) .

O n ly a sm a ll n u m b e r o f s u b je c t s w e re t o b e u se d in th is in itia l fo rm a l d e s ig n , b e c a u s e it w a s im p o r ta n t t o d e te rm in e w h e th e r a n y o f th e s e le c te d fa c to r s c o u ld b e te s te d in a sm a ll e x p e r im e n t , a n d i t w a s d e s ir -

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 815

Figure 3. “ P r e s s u r e ” p a t c h

a b le t o m a k e fu tu r e c o m p a r is o n s w ith o th e r sm a ll g r o u p s as a m e a su r e o f th e v a r ia b i l i t y a m o n g s e p a ra te e x p e r im e n ts . T h e p r e lim in a r y w o r k h a d a lr e a d y s u g g e s te d th a t su ch v a r ia b i l i t y w o u ld b e sm a ll o n c e th e s u b je c t - t o -s u b je c t e f fe c t w a s r e m o v e d .

I s o la t io n o f s u b je c t d if fe r e n ce s ca lle d f o r th e u se o f “ b lo c k in g ” a n d “ c o n fo u n d in g ,” w h ic h a re w id e ly u se d in s ta t is t ic a l d e s ig n s in b io a s s a y a n d in c h e m ic a l a p p lic a t io n s re se a rch . E ss e n t ia lly , b lo c k in g is a te c h n iq u e w h e r e b y , in th e p r e s e n t ca se , th e in flu e n c e o f s u b je c t - t o - s u b je c t d if fe r e n ce s o n th e re su lts is is o la te d , s o th a t , i f s u cce s s fu l, i t h as l it t le o r n o e f fe c t u p o n th e d if fe r e n ce s o f in te re s t r e p r e s e n te d b y su ch fa c to r s as ir r ita n t c o n c e n t r a t io n , c o n t a c t t im e , e tc . C o n fo u n d in g is a te c h n iq u e o f “ m ix in g ” e ffe c ts o f m in o r in te re s t w ith b lo c k s o r s u b je c t s in o r d e r t o in c re a s e th e p r e c is io n o f m e a s u r e m e n t o f m o r e im p o r ta n t v a r ia b le s . I f i t is a ss u m e d b e fo r e a n e x p e r im e n t th a t in t e r s u b je c t d if fe r e n ce s are s u b s ta n t ia lly g r e a te r th a n in t r a s u b je c t v a r ia t io n , sm a lle r v a lu e s o f e x p e r im e n ta l e rro r ca n b e e x p e c te d w h e n th e se te c h n iq u e s are u s e d .* T h e re m a in in g in t r a s u b je c t error , o n c e th is m a jo r s o u rce is e l im in a te d is th a t l ik e ly t o re s u lt f r o m r e la t iv e ly sm a ll d if fe r e n ce s in lo c a t io n o n th e sk in , p a t c h a p p lic a t io n te c h n iq u e s , e s t im a t io n o f sco re s , e tc .

I t is n o t in te n d e d th a t th is p r e s e n ta t io n p r o v id e a c o m p le te “ c o o k ­b o o k ” d e s c r ip t io n o f th e e x p e r im e n ta l d e s ig n a n d s ta t is t ic a l a n a ly se s u s e d ; th e s e m a y b e o b ta in e d fr o m se v e ra l s o u rce s l is te d in th e b ib l i o g ­r a p h y ( 7 - 1 5 ) . T h e r e fo r e , th e e x p e r im e n ta l d e s ig n , fin a l a n a ly s is o f v a r ia n c e ta b le s , a n d c o n c lu s io n s are g iv e n , b u t th e s ta t is t ic a l c a lc u la ­t io n s a re o m it t e d

T h is e x p e r im e n t w a s t o in c lu d e th e a b o v e fo u r v a r ia b le s , e a ch t o b e te s te d a t t w o le v e ls in a fo u r v a r ia b le fa c to r ia l d e s ig n . T h e w h o le

* T h e s e n s i t iv i t y o f t h e e x p e r im e n t a l d e s ig n a n d a n a ly s is in t e s t in g t h e v a r io u s f a c t o r s f o r s ig n i f i c a n c e d e p e n d s : ( a ) u p o n t h e m a g n i t u d e o f t h e a p p a r e n t e f f e c t d u e t o c h a n g in g a f a c t o r f r o m o n e le v e l t o t h e n e x t , a n d ( b ) u p o n t h e m a g n i t u d e o f th e e x p e r im e n t a l e r r o r . T h e f o r m e r is c o n t r o l l a b le o n l y b y t h e s p a c in g s e t b e t w e e n t w o le v e l s o f t h e f a c t o r a n d u p o n i t s in h e r e n t a b i l i t y t o c a u s e v a r ia t io n , b u t t h e la t t e r d e p e n d s u p o n t h e d e s ig n c h a r a c t e r is t ic s .

816 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

d e s ig n w a s t o b e r e p e a te d (r e p lic a te d ) th re e t im e s , w ith tw o b lo c k s or s u b je c t s in e a ch re p lic a te , c o n fo u n d in g th e fo u r - fa c t o r in te r a c t io n b e tw e e n ea ch p a ir o f b lo c k s . T h e le v e ls o f th e fo u r v a r ia b le s w e r e :

A (Concentration of Irritant)

A i = 1 % D u p o n o l C A 3 = 4 % D u p o n o l C

B (T yp e o f Patch)B L = R e g u la r p a tc h ( c f . F ig . 2)B 3 = “ P r e s su r e ” p a tc h (c f . F ig . 3 )

C (Patch Contact Time)

C i = 6 h o u rs C 3 = 24 h o u rs

D (Observation Tim e)D i = 2 h o u rs a fte r r e m o v in g p a t c h Do = 18 h o u rs a fte r r e m o v in g p a tc h

T h e fa c to r ia l c o m b in a t io n o f th e a b o v e re s u lte d in 16 “ ru n s ” t o b e r e p e a te d in e a ch o f th e th re e re p lic a te s . E a c h r e p lic a te co n s is te d o f tw o “ b lo c k s ” o r s u b je c ts , w ith e ig h t ru n s a p p lie d t o e a ch . T h e q u a d ­ru p le in te r a c t io n , A B C D , w a s c o n fo u n d e d b e tw e e n e a ch p a ir o f b lo c k s ;i.e ., its e ffe c t , w h ic h w a s a ss u m e d a p r io r i t o b e o f n o in tr in s ic in te re s t , w a s “ m ix e d ” w ith t h a t o f th e s u b je c ts .

In th e d ia g ra m w h ich fo llo w s , s ta n d a r d t w o - le v e l fa c to r ia l n o ta t io n is u se d . T h u s , o n e o f th e s ix te e n ru n s w a s A i B ^ i D i ( 1 % D u p o n o l, re g u la r p a tc h , 6 h o u rs ' c o n t a c t t im e a n d 2 h o u r s ’ o b s e r v a t io n t im e ). A n o th e r , fo r e x a m p le , w a s A 2B 2C iD i ( 4 % D u p o n o l , p re ssu re p a tc h , 6 h o u rs , 2 h o u r s ). T h e s e tw o ru n s are d e s ig n a te d in s ta n d a r d n o ta t io n as ru n (1 ) a n d ru n a b , r e s p e c t iv e ly . T h is n o ta t io n in c lu d e s th e a p p r o ­p r ia te lo w e r ca s e le t te r i f th e fa c t o r re fe r re d t o is u s e d a t th e h ig h le v e l, a n d o m its th is le t te r if th e fa c t o r is u se d a t its lo w le v e l. T h u s , th e 16 ru n s in e a ch r e p lic a te w e r e :

1 (AJEhCiD,) a ( A 2B ,C iD ,) b (A jB a C .D ,) a b ( A 2B 2C \ D ,) c ( A 1B ,C ,D 1) a c ( A 2B |C 2D ,) b e ( A 1B .)C2D i)

d ( A ,B 1C 1D 2) a d ( A 2B iC i D 2) b d ( A ,B 2C ] D 2) a b d ( A 2B 2C iD 2) cd ( A jB jC jD o) a cd (A jB iC o D a ) b e d (A iB a C jD a )a b e d ( A 2B 2C 2D 2)a b c ( A 2B 2C 2D ])

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 817

Block' 1 (Sib j e c t 1)

Block 2 (S u b jec t 2)

ad abed c b

be ac a abc

cd bd bcc abd

( i ) ah c acd

i

R e p l i c a t e I

Bloc 3 Block 4(S u b jec t 3) LSu b j e c t 4)

ad ab c abc

d i be a d

ac cd bcc abc

bd abed b acd

R e p l i c a t e I I

Block 5 (S u b je c t 5)

~ c u ab

ac cd

ab be

abed bd

B lock 6 (S u b je c t b)

bed c

b abc

acd d

a abd

R e p l i c a t e I I I

Figure 4. F in a l e x p e r im e n t a l d e s ig n — fir s t e x p e r im e n t

F ig u r e 4 s h o w s th e fin a l d e s ig n . T h e o r d e r o f th e ru n s (i.e ., th e s e q u e n ce a n d p o s it io n u s e d in a p p ly in g th e p a tc h e s t o e a ch s u b je c t ) w a s r a n ­d o m iz e d , as w a s th e o r d e r o f th e t w o b lo c k s in e a ch r e p lic a te , b y u s in g a ta b le o f r a n d o m n u m b e r s . T h e r e c ta n g le s o f F ig . 4 r e p r e se n t th e b a c k s o f th e s u b je c t s ; fo u r p a tc h e s w e r e a p p lie d a lo n g e a ch s id e o f e a ch b a c k , b e lo w th e s ca p u la e .

D a t a a n d A n a l y s i s o f F i r s t E x p e r i m e n t

T h e e x p e r im e n t w a s p e r fo r m e d as s h o w n in F ig . 4 . T h e p a tc h e s w e r e a p p lie d in th e p o s it io n s s h o w n . E a c h a re a t o b e p a t c h e d w a s s w a b b e d w ith a c e to n e as d e s c r ib e d p r e v io u s ly , a n d fo u r d r o p s o f th e ir r ita n t s o lu t io n w e re p la c e d o n e a ch b lo t t in g p a p e r s q u a re ju s t b e fo r e p a tc h in g . O b s e r v a t io n s w e r e m a d e as s ch e d u le d b y V a r ia b le s C ( c o n ­

818 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

ta c t t im e ) a n d D (o b s e r v a t io n t im e ) . A ll s c o r in g w a s d o n e b y c o m p a r ­in g a p a t c h e d a rea w ith a n a d ja c e n t u n tre a te d a n d u n ta p e d sk in area . A ll p a tc h e s n o t b e in g re a d w e re d r a p e d t o r e d u c e s u b je c t iv it y . T h e o r d e r o f r e a d in g th e s ite s o n a g iv e n s u b je c t w a s n o t c o n tr o lle d .

T a b le I sh o w s th e s co r e s o b ta in e d . T h e s c o r in g s y s te m u se d w a s th a t o f F ig . 1.

A c o n v e n t io n a l a n a ly s is o f v a r ia n c e w a s ca rr ie d o u t o n th e d a ta o f T a b le I .* T a b le I I s u m m a r iz e s th e a n a ly s is . N o t e th a t th e m e a n sq u a re fo r e rro r w a s 0 .2 3 3 5 . T h is r e p r e se n ts a n e rro r s ta n d a r d d e v ia ­t io n o f a b o u t 0 .4 8 s c o r in g u n its , a n d a c c o u n ts fo r a ll s o u rce s o f v a r ia t io n n o t s p e c if ic a lly lis te d in T a b le I I ( s c o r in g errors , p o s it io n e ffe c ts , p a tc h t ig h tn e s s , e t c . ) . T h e r e fo r e , th e p o r t io n o f th is e rro r a t t r ib u ta b le to s c o r in g e rro r m u s t h a v e b e e n less th a n th is v a lu e u n less a ll o th e r s o u rce s o f v a r ia t io n w e r e ze ro . I t th u s a p p e a r e d th a t th e r e a d in g o f p a tc h e s t o th e n e a r e s t 0 .2 5 u n it w a s a re a s o n a b le p r o c e d u r e .

I t s h o u ld a lso b e n o t e d th a t th e t o t a l b lo c k s m e a n sq u a re w a s s u b ­s ta n t ia l, as e x p e c te d , s u g g e s t in g t h a t th e s e p a ra t io n o f th is e f fe c t (i.e ., s u b je c t - t o -s u b je c t d if fe r e n ce s ) f r o m th e e rro r b y th e b lo c k in g a n d c o n ­fo u n d in g te c h n iq u e s w a s im p o r ta n t .

I n d r a w in g c o n c lu s io n s fr o m th is e x p e r im e n t , it w a s d e c id e d n o t t o ig n o re a n y e f fe c ts s h o w in g s ig n if ic a n ce a t th e 8 5 % c o n f id e n c e le v e l o r b e t te r , s in ce th e o n ly c o n s e q u e n c e s o f fa ls e ly a ssu m in g an e f fe c t t o b e rea l w o u ld b e its in c lu s io n in fu r th e r w o r k .

T h e r e w a s a s tr o n g c o n t a c t t im e e ffe c t , as e x p e c te d , b u t th e o n ly in te r a c t io n in v o lv in g th is w a s th e tr ip le in te r a c t io n . S in ce s u ch in t e r ­a c t io n s a re ra re , th is w a s v ie w e d w ith s o m e s k e p t ic is m , b u t i t w a s n e v e r th e le s s in v e s t ig a te d fu r th e r (se e s e c o n d e x p e r im e n t b e lo w ) . T h e re m a in in g s ig n if ic a n t e ffe c ts w e re all in c lu d e d in th e sa m e tr ip le in t e r ­a c t io n , s o th a t th e m o s t in fo r m a t iv e in te r p r e ta t io n o f th e e x p e r im e n t w ith r e s p e c t t o th e s e e ffe c ts w a s d o n e b y e x a m in in g th is a lo n e . T o d o th is , a v e ra g e s o f a ll d a ta fo r e a ch c o m b in a t io n o f fa c to r s , A , B , a n d D w e re c o m p u te d a n d p lo t t e d . T h e a v e ra g e s a n d th e p lo t s a re s h o w n in F ig . 5.

A s s h o w n in F ig . 5, a t 2 h o u r s ’ o b s e r v a t io n t im e , in c re a s in g c o n ­c e n tr a t io n o f th e ir r ita n t p r o d u c e d a sh a rp in cre a se in ir r ita t io n w h e n th e p re ssu re p a t c h w a s u se d b u t a decrease w h e n th e re g u la r p a t c h w a s u se d . A ft e r 18 h o u rs , h o w e v e r , a lth o u g h th e re is a p o s s ib i l i t y o f a s lig h t ly

* T h e r e h a s b e e n h e s i ta t io n in t h e p a s t t o w a r d t h e u s e o f a n a ly s is o f v a r ia n c e w i t h s c o r e d d a t a ; h o w e v e r , i t h a s b e e n s h o w n t h a t t h e n o n - n o r m a l i t y o f s u c h d a t a d o e s n o t s e r io u s ly in t e r fe r e w i t h t h e v a l i d i t y o f c o n c lu s io n s d r a w n , a n d s u c h p r o c e d u r e s a r e n o w w i d e l y u s e d .

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 819

T3 Û, S O'

H OQ CO 15 lO :£> 15M ¿4u u _ o o C"”' a o C/Îc c c-1 0 c r-* c 0 u-1

o 5 3 g* 5 5 o 5 5 |■V h

820 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

T a b l e II

A n a ly s is o f V a r ia n c e

S o u r c e o f V a r ia t io n D F S S M S F ' S ig . ( ? ) '•

B e t w e e n c o n c e n t r a t io n s ( A ) 1 0 5 2 0 8 0 5 2 0 8 2 .2 3 ~ 0 15B e tw e e n t y p e s o f p a t c h ( B ) 1 0 0 4 6 9 0 0 4 6 9 < 1B e tw e e n c o n t a c t t im e s ( C ) 1 9 6 3 0 2 9 6 3 0 2 4 1 . 2 4 < 0 . 001

B e tw e e n o b s e r v a t i o n t im e s ( D ) 1 0 1 8 7 5 0 1 8 7 5 < 1C o n c e n t r a t i o n X p a t c h t y p e ( A B ) 1 0 7 5 0 0 0 7 5 0 0 3 .2 1 —11 0 8

C o n c e n t r a t i o n X c o n t a c t t im e ( A C ) 1 0 0 2 0 8 0 0 2 0 8 < 1C o n c e n t r a t i o n X o b s e r v a t i o n t im e ( A D ) 1 0 1 30 2 0 1 3 0 2 < 1P a t c h t y p e X c o n t a c t t im e ( B C ) 1 0 1 30 2 0 1 3 0 2 < 1P a t c h t y p e X o b s e r v a t i o n t im e ( B D ) 1 0 0 2 0 8 0 0 2 0 8 < 1C o n t a c t t im e X o b s e r v a t i o n t im e ( C D ) 1 0 1 8 7 5 0 1 8 7 5 < 1C o n c e n t r a t i o n X p r e s s u r e X c o n t a c t t im e

( A B C ) 1 0 0 2 0 8 0 0 2 0 8 < 1C o n c e n t r a t i o n X p r e s s u r e X o b s e r v a t i o n t im e

( A B D ) 1 0 6 3 0 2 0 6 3 0 2 2 . 7 0 ~ 0 12C o n c e n t r a t i o n X c o n t a c t t im e X o b s e r v a t i o n

t im e ( A C D ) 1 0 0 4 6 9 0 0 4 6 9 < 1P r e s s u r e X c o n t a c t t im e X o b s e r v a t i o n t im e

( B C D ) 1 0 0 0 0 0 0 0 0 0 0 < 1

14 12 3 2 2 8

A m o n g r e p l i c a t e s 2 8 0 0 2 6 4 0 0 1 3 2 .1 6A B C D ( w i t h in r e p l ic a t e s , b e t w e e n b l o c k s ) i 1 1 71 9 1 1 71 9 < 1B e t w e e n b l o c k d i f f e r e n c e s 2 3 7 1 0 9 1 8 5 5 5

T o t a l a m o n g b lo c k s 1 5li _ l 12 .8 8 5 4 2 5 77 1

R e s id u a l ( e r r o r ) 2 8 6 5 3 6 6 0 2 3 3 5

T o t a l 4 7 31 7 4 4 8

Notes: ( 1 ) A ll m a in e f f e c t s a n d in t e r a c t io n s e x c e p t A B C D t e s t e d a g a in s t r e s id u a l. ( 2 ) A B C D a n d r e p l i c a t e s t e s t e d a g a in s t t h e “ b e t w e e n b l o c k d i f f e r e n c e s M . S . ” ( 3 ) D e f in i t i o n s o fc o lu m n h e a d s y m b o l s : D F ' = d e g r e e s o f f r e e d o m , S S = s u m o f s q u a r e s o f d e v i a t io n s f r o m th e m e a n , M S = m e a n s q u a r e , F ' = v a lu e o b t a i n e d in F t e s t o f s ig n i f i c a n c e , a n d P = p r o b a b i l i t y o f t h e o b s e r v e d d i f f e r e n c e h a v in g o c c u r r e d b y c h a n c e .

“ T h i s c o l u m n s h o w s t h e p r o b a b i l i t y t h a t t h e g iv e n e f f e c t is not real. I f P ( p r o b a b i l i t y o f H o o r u n r e a l i t y ) w a s o v e r a b o u t 0 .1 5 , n o e n t r y w a s m a d e in t h is c o l u m n a n d t h e e f f e c t w a s c o n s id e r e d “ n o t s ig n i f i c a n t .”

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 821

2 .00 r 2 .00 r

Bg " P r e s s u r e " P o lc h XX

I 8 0 - Br, " P r e s s u r e " P a t c h /

1 .6 0 -

1 .4 0

/

® 1.20 1.20 —

o A t D, ( 2 h rs . Obs. T i m e ) At P2 ( I 8 h r s . Obs. T i m e )

l.OO 100 A,(1%)

Ir r it an t Cone , % I r r it an t Cone. , %

Figure 5 . T r i p l e in t e r a c t io n ( A B D ) . C o n c e n t r a t i o n X t y p e o f p a t c h X o b s . t im e

g r e a te r ir r ita t io n e f fe c t w ith th e p re ssu re p a tc h , th e d if fe r e n ce , i f a n y , b e tw e e n p re ssu re a n d re g u la r p a tc h e s is th e sa m e a t b o t h c o n c e n tr a t io n s .

T h e s e c o n d d e s ig n w a s w o r k e d o u t a n d ru n a fte r n o t in g a n d d is ­cu s s in g th e fin d in g s ju s t g iv e n . S e v e r a l im p o r ta n t d if fe r e n ce s w e r e to b e b u i lt in t o th is n e w e x p e r im e n t . F r o m th e b e g in n in g , it h a d b e e n fe lt d e s ira b le t o ru n a n e x p e r im e n t in w h ic h c o n c e n t r a t io n w a s u se d a t m o r e th a n t w o le v e ls , so th a t th e n a tu r e o f th e c o n c e n t r a t io n r e s p o n se (e .g ., c u r v e d o r lin e a r ) c o u ld b e s tu d ie d . S u ch a p r o c e d u r e ca rr ie s a d d it io n a l a d v a n ta g e s in t h a t i t is o f t e n p o s s ib le t o o b ta in g r e a te r s e n s it iv ity in th e a n a ly s is o f th e d a ta .

A d d it io n a l le v e ls o f c o n c e n t r a t io n w ere u s a b le o n ly i f o n e o r m o r e o f th e o r ig in a l fo u r v a r ia b le s w a s e lim in a te d a n d n o n e w o n e s a d d e d , o r i f th e n e w e x p e r im e n t w a s m a d e la rg er . F o r p r a c t ic a l re a so n s , th e la t te r w a s u n d e s ira b le . S in c e c o n t a c t t im e h a d b e e n fo u n d n o t to in te r a c t w ith a n y o f th e o th e r v a r ia b le s in th e fir s t e x p e r im e n t , it w a s p o s s ib le t o e l im in a te th is f a c t o r f r o m th e s e c o n d o n e , b e c a u s e a ll n e c e s ­sa ry in fo r m a t io n a b o u t its m a in e f fe c t r e s p o n se w a s a lr e a d y a v a ila b le .

D e s i g n o f S e c o n d E x p e r i m e n t

8 2 2 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

This left three variables for the new experiment, with contact time held constant at some fixed level (preferably close to one of those used in the first experiment). It was decided to use 24 hours, because the longer time gave higher irritation values compared to the shorter period, and thus took greater advantage of the range of the scale used. The three remaining variables to be used in this experiment, and the levels decided upon were:

(A) Concentration of Irritant (.Duponol C)A, = 0.5%A2 = 1%A3 = 2%A4 = 4%

(B ) Type of PatchB, = Regular B3 = Pressure

(C) Observation Time Ci = 2 hoursC2 = 2 4 hours

The spacing of the levels of concentration (each double the previous one) was adopted because: (a) it was believed that, like many chemicalconcentration and biological dosage effects, the increase in response might well become progressively smaller as concentration increased (this was also indicated by some of the preliminary work), and (b) this type of spacing made the data amenable to a particularly simple type of statistical analysis for the curvature effects.

The same system of blocking and replication as before was used;i.e., three repetitions of two blocks (two subjects) each. None of the subjects were the same as those used before.

The basic experimental design was that known as a “ split plot,” in which a main effect instead of an interaction is confounded between (“mixed with” ) blocks. Thus, it will be noted (Fig. 6) that only one of the two types of patch was used on a given subject in each pair. This procedure results in loss of sensitivity for the detection of the con­founded effect (but not complete loss of information, since there was replication). It was decided to use the patch type variable, B, for the splitting, because the previous experiment indicated that this main effect was of little value in interpretation of the other factors, and it had already been established as a strongly significant variable, so that there was little doubt of its reality and little need for further verification.

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 823

After randomizing the assignment of each run to each position on each subject’s back (i.e., each block), as well as the order of application of the patches, the experimental design was prepared and is shown in Fig. 6.

Block 1 Block 2

211 411 422 321

212 312 421 221

311 112 222 121

111 412 322 122

Block 3 Block 4

212 311 121 122

111 312 322 421

112 411 321 221

211 412 222 422

Block 5 Block 6

211 212 221 421

412 111 422 321

311 411 322 122

312 112 121 222

Subject 1!

Subject 2___I

Subj ect 3 Subject 4 Subject 5 Subject 6

Replicate 1 Replicate II Replicate III

Key to Identification of Runs:

First digit (A): 1 = 0.'5% 2 = 1% 3 = 2 % 4 = 4%

Second " (B): 1 = regular patch 2 = pressure patch

Third " (C): 1 = 2 hours 2 = 24 hours

The procedure for this experiment was analogous to that used previously with

the exception that the scoring system was changed for convenience. Since it had

been established to the authors' satisfaction that readings to the nearest 0.25 score

unit could be made, the scores for this experiment were recoded before analysis as

shown below:

Original Score New Score Original Score New Score

0.00 1 2.25 10

0.25 2 2.50 11

0.50 3 2.75 12

0.75 4 3.00 13

1.00 5 3.25 14

1.25 6 3.50 15

1.50 7 3.75 16

1.75 8 4.00 17

2.00 9

Figure 6. Experim ental design

Tab

le I

II

824 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

<

3«

<

a

3

co

aJajQ

_b/D*co

©

a3

PQ

a

PÌ

O ^ £

O £

o ^ £

o ^ £

~ _ u VJ Cl TT !_,o O. £

£

c-i0 <N

u c x

<N0 <N

- _L| VIo c £

y 'S ao a cuS

05 i 0 oq 00 o oq lo i> [CO © T—1 CO - t 1 oq r-i I w 1

; oo

^ M h y oo o&5 3

o o o* 3 3

n 1

h h ¿4 ¿4(-H U <J O Og*3 3r/. T

otal

s 13

7

8 13

12

12

6

19

17

10

7 20

15

23

13

10

21

7

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 825

R e s u l t s o f A n a l y s i s o f S e c o n d E x p e r i m e n t

DataThe second experiment was carried out as described, and resulted in

the raw data shown in Table III (after coding). All readings were made by a single experienced observer, as before.

AnalysisAn “ over-all” analysis of variance of the data shown in Table III was

done following the usual computational procedures. The sums of squares for the concentration effect and its interaction were then par­titioned into segments representing linear, quadratic, and cubic (cubic is equivalent to higher curvature and scatter) portions. This final analysis is shown in Table IV.

Discussion of Results(1) The partitioning of the concentration effect and its interaction

with the other two variables resulted in a very strong test of significance for the linear effect of concentration (probability 1% that effect was not real). None of the double interactions with concentration were signif­icant, however, and although the triple interaction gave a weak signif­icance test as before, the authors were less disposed to accept it, since the previous indication was not strongly reinforced despite the parti­tioning.

(2) The patch type-observation time interaction was significant, unlike results in the first experiment (if the triple interaction results for that experiment are ignored).

(3) The experimental error mean square was estimated as 4.02, as shown in the table. This is strikingly similar to that of the previous experiment (remembering that a new scoring scale was used here); the estimated standard deviation for error would be V4.02, or approxi­mately 2.0 units, corresponding to 0.50 original units, almost identical to the error found in the first experiment. Thus, again, the use of estimates to the nearest 34 of an original scale unit was demonstrated to be practical. Applying the same reasoning as before, this result in­dicates, as before, that the average error of measurement was less than about 0.5 original scale units, including the error of estimation.

Two of the effects showing considerable significance (linear concen­tration, A, and the patch type times observation time interaction, BC) are plotted in Figs. 7 and 8. The significant observation time effect

8 2 6 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

itself is not plotted, since this is better illustrated in the plot of its interaction.

It will be noted that Fig. 7 (which is a plot of means of the original data with a straight line visually fitted to them) bears out the conclusions as to linearity of the concentration effect suggested by the analysis of

T ab le IVA nalysis of V ariance

Source of V ariation D F SS M S F ' P

J1 A m o n g concen tra tion s (A)CJ<v L inear (Ai) 1 33 .00 33 .00 8 .2 8 < 0 .0 1

m Q uadratic (A„) 1 0 .02 0 .02 <1C C ubic (Ac) 1 0 .2 0 0 .2 0 <1oS B etw een p atch ty p es (confounded w ith blocks)

B etw een observation tim es (C ) 1 25.52 25 .52 6 .3 5 < 0 .0 3C oncentration linear X p a tch type

(AiB) 1 5.71 5.71 1.42C oncentration qu ad ratic X p a tch

fiO ty p e ( A qB) 1 0 .1 9 0 .19 <1O C oncentration cubic X p a tch ty p eaiu. (ACB) 1 0.51 0.51 <1* C oncentration linear X observation<V tim e (AiC) 1 5.11 5.11 1.27

fi C oncentration q u ad ra tic X observa-O

Q tion tim e (A qC) 1 4 .6 9 4 .69 1.17C oncentration cubic X observation

tim e (AcC) 1 0.81 0.81 <1P a tch type X observation tim e (B C ) 1 22 .69 22 .69 5.64 < 0 .0 5C oncentration linear X p a tch observa- 5

tion tim e (A iBC) 1 9 .20 9 .20 2 .2 9 ~ 0 . 1Ai ù ts ft ai o C oncentration quadratic X p a tch XU tn +-»h £ " observation tim e (A qBC) 1 9 .1 8 9 .1 8 2 .2 8 ~ 0 . 15

C oncentration cubic X p a tch Xobservation tim e (A cB C ) 1 1.63 1.63

14 118.46

Am ong replicates 2 129.54 64 .77 2 .83Betw een blocks (w ith in replicates) 1 3 .5 2 3 .5 2 <1W ith in blocks 2 45 .80 22 .90

T o ta l am ong blocks □ 178.86

R esidual (error) 28 112.66 4 .0 2

T o ta l 47 409 .98

N o tes : D efinitions of colum n head sym bols: D F = degrees of freedom , SS = sum of squares of deviations from th e m ean, M S = m ean square, F ' = value ob tained in F te s t of significance, and P = probability of th e observed difference having occurred by chance.

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 827

30 0 0 307

05 V.

Figure 7. V ariable A. P lo t of concen tra tion effect. (Log linear portion significant a t < 0 .01 level.) No significant cu rv a tu re

variance. Because of the significant linear effect and the nonsignif­icance of higher effects, the visual fitting with a straight line was justified. Note, however, that the “ linearity” is based upon logarithmic spacing of the four concentrations, with + 1 added to keep all values positive.

D i s c u s s i o n a n d C o n c l u s i o n s

These experiments demonstrate three points which the authors believe are of great importance in irritation testing, and perhaps for patch testing in general, in addition to the specifics connected with the particular variables used. These are the following:

(1) It appears possible with a properly designed experiment to obtain meaningful estimates of irritation on a scale of 0 to 4, to less than the nearest 0.50 scale unit.

(2) Differences among subjects and among repetitions of experi­ments have always been regarded as a source of difficulty in irritation testing. This work demonstrates that it is possible, by using very well- known and commonly-used statistical techniques, to isolate completely the first of these sources of variation and to prevent their interference with differences sought among various experimental conditions.

(3) The use of common multi-factor experimental techniques to­gether with appropriate statistical analyses appears practical and useful in studying patch test data.

828 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

60 i-

20 ---------- 1---------- 1-----------1---------- 1---------- 1---------- 10 1 8 12 ¡6 20 21

Elopsad Time Alter Removot of Patches, Hours

Figure 8. V ariable B X C. P lo t of observation tim e X p a tch = type in teraction . (Signi­ficant a t 0.05 level)

The more specific and less important conclusions to be drawn from this work are connected with the specific variables used. Discounting the first experiment except for the contact time variable, because of the relatively low significance levels obtained, and remembering that the analyses were of the kind known to statisticians as Type I (i.e., more or less limited to the particular levels of the variables and particular populations used), the folio wing conclusions were drawn:

(1) The increase of irritation with increasing concentration of sodium lauryl sulfate (within the range of concentrations tested) appears to be a logarithmic function, with the r a t e o f i n c r e a s e o f i r r i t a t i o n d e c r e a s ­

i n g a s c o n c e n t r a t i o n i n c r e a s e s .

(2) The changes in observable irritation which occur a f t e r the patches are removed have not been emphasized in the literature. This work suggests that it is important to give the skin adequate time to develop a full irritation manifestation and to take this factor into account, especially in view of its interaction with the type of patch used.

(3) The use of the “ pressure” patch, as explained above, was meant not as a device to apply pressure p e r s e , but as an attempt to determine whether normal minor variations in pressure under a patch affect the results, so that if so, means for controlling it and thus mini­mizing variation could be arranged. As this work shows, a relatively small increase in pressure was apparently very important, especially at certain observation times. This suggests that more study and experi­

STATISTICAL EVALUATION OF CUTANEOUS IRRITANTS 829

mentation in the design of patches and the techniques used in applying them is desirable.

(4) It has frequently been felt that lack of uniformity in patch test responses is the result of a “ pressure effect.” This work has demonstrated that one of the greatest sources of variation is subject-to- subject variation, which is easily isolated by proper experimental designs, which in turn has the effect of sensitizing the experiment so that a given variable may be tested with a much smaller group of subjects than otherwise. Of course the use of small groups presupposes that they are a fair sample of the population to which the results are to be extrapolated.

(Received February 14, 1967)

R e f e r e n c e s

(1) Schneiderm an, M . A., Is it really bad? A proposal for the toxicity-testing of drugs, J . Soc. Cosmetic Chemists, 14, 227—232 (1963).

(2) Schw artz, L., D erm atitis from new synthetic resin fabric finishes, J. Invest. Dermatol.. 4, 459-470 (1941).

(3) Shelanski, H. A., and Shelanski, M . V., A new technique for hum an p a tch tests, Proc. Sci. Sect. Toilet Goods Assoc., 19, 46-49 (1953).

(4) Draize, J ., Procedures for the appraisal of chem icals in foods, drugs and cosm etics; V III D erm al Toxicity , Food Cosmetic Law J., 10, 722-732 (1955).

(5) Voss, J., Skin sensitization by m ercap tans of low m olecular weight, J. Invest. Dermatol., 31, 273-279 (1958).

(6) R ostenberg, A., C utaneous reactions from cosmetics, J. Soc. Cosmetic Chemists. 11, 170- 178 (1960).

(7) Davies, O. W. (E d ito r), Design and Analysis of Industrial Experiments, 2nd ed., H afner Publishing Co., Inc., New Y ork, N. Y., 1962.

(8) Cochran, W. G., and Cox, G. M ., Experimental Designs, 2nd ed., Jo h n W iley & Sons, Inc., New Y ork, N. Y., 1962.

(9) Goldstein, A., Biostatistics, T he M acM illan Co., New Y ork, N. Y., 1964.(10) Snedecor, G. W., Statistical Methods Applied to Experiments in Agriculture and Biology,

5th ed., T he Iow a S ta te LTniversity Press, Ames, la ., 1962.(11) Fisher, R. A., The Design of Experiments, 7th ed., H afner Publishing Co., New Y ork,

N. Y., 1960.(12) B ennett, C. A., and Franklin , N. L., Statistical Analysis in Chemistry and the Chemical

Industry, John W iley & Sons, Inc., New Y ork, N. Y., 1963.(13) Fisher, R. A., and "Yates, F ., Statistical Tables for Biological, Agricultural and Medical

Research, 6 th ed., H afner Publishing Co., Inc., New Y ork, N. Y ., 1963.(14) Cox, D. R ., Planning of Experiments, John W iley & Sons, Inc., New York, X. Y., 1958.(15) Sheffe, H ., The Analysis of Variance, John W iley & Sons, Inc., New Y ork, N. Y ., 1959.(16) K ligm an, A. M ., and W ooding, W. M ., A M ethod for th e M easurem ent and E valuation

of I r r ita n ts on H um an Skin, J. Invest. Dermatol, (publication expected in 1967).

830 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

STATEM ENT OF OWNERSHIP, MANAGEMENT AND CIRCU LATION (Act of October 23, 7962: section 4369. Title 39 United States Code)

1. Date of Filing October 1, 1967.2. Title of Publication T he Jo u r n a l o f th e So c ie t y of C osm etic C hemists.3. Frequency of Issue Six times per year.4. Location of Known Office of Publication (Street, city, county, stale, zip code) Twentieth and Northampton

Streets, Easton, Pennsylvania 18042.5. Location of the Headquarters or General Business Offices of the Publishers (Not printers) 2 East Sixty-

third Street, New York, New York 10021.6. Names and Addresses of Publisher, Editor and Managing Editor.

Publisher (Name and Address) The Society of Cosmetic Chemists, Inc., 2 East Sixty-third Street, New York, New York 10021.Editor (Name and address) Dr. Karl Laden, 6220 Kansas Avenue, N. E., Washington, D. C. 20011. Managing Editor (Name and address) None

7. Owner (If owned by a corporation, its name and address must be stated and also immediately thereunder the names and addresses of stockholders owning or holding 1 percent or more of total amount of stock. If not owned by a corporation, the names and addresses of the individual owners must be given. If owned by a partnership or other unincorporated firm, its name and address, as well as that of each individual must be given.) Name Society of Cosmetic Chemists, Inc. Address 2 East Sixty-third Street, New York, New York 10021.

8. Known Bondholders, Mortagees, and Other Security Holders Owning or Holding 1 Percent or more of Total Amount of Bonds, Mortgages or Other Securities (If there are none, so state) None

9. Paragraphs 7 and 8 include, in cases where the stockholder or security holder appears upon the books of the company as trustee or in any other fiduciary relation, the name of the person or corporation for whom such trustee is acting, also the statements in the two paragraphs show the affiant’s full knowledge and belief as to the circumstances and conditions under which stockholders and security holders who do not appear upon the books of the company as trustees, hold stock and securities in a capacity other than that of a bona fide owner. Names and addresses of individuals who are stock­holders of a corporation which itself is a stockholder or holder of bonds, mortgages or other securities of the publishing corporation have been included in paragraphs 7 and 8 when the interests of such in­dividuals are equivalent to 1 percent or more of the total amount of the stock or securities of the pub­lishing corporation.

10. This Item Must Be Completed for All Publications Except Those Which Do Not Carry Advertising Other Than the Publisher’s Own and Which Are Named in Sections 132.231, 132.232 and 132.233 Postal Manual (Sections 4355#, 43556, and 4356 of Title 39, United States Code)

Average No. Copies Single IssueEach Issue During Nearest to

Preceding 12 Months Filing DateA. Total No. Copies Printed (Net Press Run) 2800 SeptemberB. Paid Circulation

1. Sales Through Dealers and Carriers, Street Ven­ Nonedors and Counter Sales

2. Mail Subscriptions 2518C. Total Paid Circulation 2518D. Free Distribution (including samples) by Mail, Carrier 208

or Other MeansE. Total Distribution (Sum of C and D) 2726F. Office Use, Left-Over, Unaccounted, Spoiled After 74

PrintingG. Total (Sum of E & F—should equal net press run shown in A) 2800I certify that the statements made by me above are correct and complete.

(Signature of editor, publisher business manager or owner) Karl Laden (Signature of Editor)

Book Reviews

P h arm aceutical C h em istry , V ol­ume I: T heory and A pplication , edited by Leslie G. Chatten, Marcel Dekker, Inc., New York. 1966. 504 pages, indexed. Price $14.50.

The scope of this text can most ac­curately be described as analytical pharmaceutical chemistry. It is the first volume of a two-volume series which is intended as a text for senior undergraduate and graduate phar­macy students. It deals with theo­retical and practical considerations of gravimetric analysis, acid-base ti­trations and pH, precipitation and complex formation, acidimetry and alkalimetry, nonaqueous titrimetry, complexometric analysis, alkaloidal assay, miscellaneous methods, ion exchange, chromatography, and anal­ysis of fixed oils and volatile oils. Vol­ume II will cover the theory and ap­plication of instrumental techniques.

This book is composed of thirteen chapters, each of which has been writ­ten by a different contributing au­thor. The joint authorship has an international character with contrib­utors from the United States, Canada, and England. Each of the authors is a teacher of pharmaceutical chemis­try or a related discipline of phar­macy.

Considering this organizational ap­proach, the material within the book is surprisingly well presented and inte­grated. Only a slight tendency to­ward repetition is evident, and this is often justified for the sake of com­pleteness within each chapter. An ample number of references are listed at the end of each chapter for those interested in further pursuing a par­ticular topic.

The reviewer believes that this book provides a significant advance over some previously available under­graduate texts in analytical pharma­ceutical chemistry in that emphasis has been placed on basic theory and applications of specific methods rather than on official assay proced­ures in the official compendia. The text helps to give insights into the of­ficial United States Pharmacopoeia and British Pharmacopoeia assay methods, but only as examples of the basic methods which are described in length.

For individuals who have not been directly involved in analytical chem­istry, this book can serve as an excel­lent review and provides the opportu­nity to assimilate new methodology which has been added to the field in recent years.

831

832 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

This text is recommended as a gen­eral review and reference text for those interested in updating their knowledge of analytical chemistry and analytical pharmaceutical chem­istry.— P aul T h au— CIBA Pharma­ceutical Company.

O il , D etergents and M aintenance Spe cia lties . V olume 1: M ate ­rials and Processes, edited by Ben­jamin Levitt. Chemical Publishing Company, Inc., New York. 1967. 280 pages indexed. Price $13.75.

This is the first of two volumes deal­ing with all aspects of fats and oils in­cluding raw materials, manufacturing processes, test methods and applica­tions. This volume deals primarily with materials and manufacturing processes, although many formula­tions are included. Volume II will deal with additional applications.

After a brief introduction, this book is divided into eight chapters: ani­mal fats and oils; vegetable fats and oils; fatty acids and alcohols; sur­factants; production of fats and oils; soap manufacture; synthetic deter­gents and analysis of oils and deter­gents.

Since all of the topics covered in these chapters have already been the subjects of full length volumes, the author could include only a small frac­tion of the information available on each topic. Unfortunately very few references are listed, and many of the classic texts on oils and fatty acids are not mentioned at all.

Yet, there is much useful informa­tion in this book, and it should be of value to individuals who are not di­rectly involved with fats, oils and de­tergents but would like a handy refer­ence work on these subjects.—T. K aufm an— Drew Chemical Corp.

M athem atics and Statistics for T echnologists, by H. G. Cuming and C. J. Anson. Chemical Publish­ing Company, Inc., New York, N. Y. 1967. 490 Pages, indexed and illus­trated. Price $12.50.

This is a most unusual and valuable book for the industrial scientist, but it is not entirely what its title implies. A more appropriate name, which would describe over 75% of the con­tents (and, in my opinion, all of the more valuable material) might be, “ A Concise Review of College Mathe­matics for Technologists.”

The value of the book lies in the fact that most of the material (351 of the 490 pages) comprises a lucid and succinct presentation of nearly every important topic in college mathe­matics normally encountered by the undergraduate chemist or engineer, but aimed specifically toward the needs of the adult professional who may wish a relatively painless refresh­er course. I believe that any such person who has studied the topics cov­ered, even several decades ago, will find the book easy to study as well as an excellent reference work. Despite the brevity of most of the topics, all are treated with clarity and vigor, al­though with no attempt to develop

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 833

complete proofs in every case. The subjects covered range from elemen­tary algebra through analytic geome­try, trigonometry, intermediate alge­bra, differential and integral calculus with applications, and differential equations. Each topic includes a good supply of examples, and each chapter ends with a group of problems for practice, with answers given at the back of the book.

There are a few short chapters on elementary statistics, comprising a total of 114 pages, including an intro­ductory section and short chapters on probability, frequency distributions, control charts, sampling, significance tests, analysis of variance and simple linear regression. In sharp contrast to the above material, these give the impression of having been included as an afterthought. They are brief, in­complete and quite inexact. The adult reader would do better to ignore these chapters and, after covering the mathematical material, to consult some more expert text on applied statistics, such as Mandel’s “ The Statistical Analysis of Experimental Data” (Interscience, 1954).

A regrettable omission is the lack of a chapter on matrix algebra, a most important topic in modern applied statistics. Also, there is no material on solid analytical geometry. In spite of these omissions and the short­comings of the statistical section, however, this text is most highly rec­ommended to the audience for which it is intended.—W . M. W ooding— Carter-Wallace, Inc.

R esearch in Surface F orces. Vol. 2. Edited by B. V. Deryagin. Pp. viii X 320. 1966. ConsultantsBureau, New York. $27.50.

This is a compilation of the papers presented at the Second Conference on Surface Forces which was spon­sored by the Institute of Physical Chemistry of the Academy of Sciences of the USSR. Volume 1 contains the papers presented at the First Confer­ence on Surface Forces which was held in March of 1960 and which celebrated the 25th anniversary of the Laboratory of Surface Phenomena of the Institute of Physical Chemistry.

Academician B. V. Deryagin, in addition to being the editor, is the author of many of the papers. His lead article points out that the empha­sis in Volume 2 is on the three dimen­sional aspects of surface forces.

The volume is divided into five sec­tions of about eight papers each: “ Theoretical Problems in Sur­face Phenomena,” “ Electrosurface Forces,” “ Experimental Studies of the Properties of Thin Films,” “ Sur­face Phenomena in Dispersed and Porous Systems,” and “ Surface Phe­nomena in Adhesion and Friction.” Over half of the papers are from Deryagin’s laboratory at the Institute of Physical Chemistry: however,approximately ten additional labora­tories in the USSR are represented.

A wide variety of problems in both fundamental and applied Surface Chemistry formed the subjects of the papers in this volume. This reviewer

834 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

found that there were papers in al­most all of his specific current inter­ests. Further, he felt that in most cases important, new information was contained in the papers. In spite of

its high price, this must be considered a convenient source of very important literature in the field of Surface Chemistry.—A lfred H. Ellison—- Gillette Research Institute.

AUTHOR INDEX TO VOLUME XVIII

Alexander, D. J . Some aspects of labora­to ry planning, 41

Amoore, J . A, See Brasch, S. V.Anderson, R. A., and Chow, C. E . T h e dis­

trib u tio n and a c tiv ity of benzoic acid in some emulsified system s, 207

B axter, B. H. See P u ttn am , N. A. B eekm an, S. M ., H olbert, J . M ., and

Schm ank, H. W. Studies of new alum inum com pounds for antiperspi- ran t use, 105

Bellinger, H orst. T he preservation of cos­m etic products, 727

B erth , Peter, and Kaiser, W. J. N itro , azo, and an th raqu inone dyes w ith q u a te r­n a ry am m onium groups for hair dyeing,705

B ogaty, H erm an. T orsional p roperties of ha ir in relation to perm anen t waving and setting, 575

Bollert, Volker, and E ckert, L ieselotte. Q u an tita tiv e m onitoring of cosm etic trea tm e n ts of hair, 273

Brasch, S. V., and Amoore, J . A. T he effect of sham pooing on solvent extractab le m ateria l on hair, 31

Brasch, S. V., and Amoore, J . A. T he q u an tita tiv e estim ation of the de te r­gency and allied properties of sham poos in practice, 651

B reuer, M . M ., and Prichard , D. M . T he behavior of ha ir a t low p H values, 643

Brown, Jam es, J r ., Eriksson, R . J ., Yacko- vich, F rank , an d T aber, D avid. H and degerm ing evaluation utilizing a split- use m ethod, 769

Brown, J. C. T he chem istry of syn thetic dyes used in cosmetics, 225

B runner, M. J. P itfalls and problem s in predictive p a tch testing, 323

Bull, W. H. T he lab o ra to ry evaluation of p rophylactic dentifrices, 473

C alnan, C. D. R eactions to artificial color­ing m aterials, 215

Carsch, G ustav . An experim ental design for relating personality to perfum es, 521

Caul. J . F., and R aym ond, S. A. C om pari­son of local and national consum er p an ­els in a paired preference tes t. I. S ta ­tis tica l d a ta , 123

Cheshire, J . D ., and C orby, T . C. T he rap id assessm ent of color for routine storage testing , 3

Chow, C. E . See Anderson, R . A.

C layton, J . W ., Jr. F luorocarbon toxicity : past, present, fu tu re, 333

C orby, T . C. See Cheshire, J . D.Cronin, E. C on tac t derm atitis from cos­

m etics, 681D as G u p ta , V. E valuation of sunscreen

agents, 143Davies, R. E ., and H arper, K. H. T he

po ten tial irritan cy to th e ra b b it eye m ucosa of com m ercially available cream sham poos, 663

D ean, P. M . See Van Abbé, N , J.Dubow, E m anuel, W inter, Leo, J r . , and

E llickson, B. E . Clinical evaluation of bacteriosta tic soap in d iaper derm a­titis-prophylaxis, 161

E ckert, L ieselotte. See Bollert, Volker.Ellickson, B. E. See Dubow, Em anuel.Eriksson, R. J. See Brown, Jam es, Jr.Esoda, E . J . See Flesch, Peter.Flesch, Peter, Esoda, E. J ., and K a tz , S. A.

T h e color of red hair, 777G ershon, S. D. Acceptance of E igh teen th

M edal Award, 77G loxhuber, C hristian . Toxicological te s t­

ing of cosm etics, 737Golberg, L. T he toxicology of artificial

coloring m aterials, 421Greif, M artin , and Prokop, H. J . Use of

electronic d a ta processing in a n tid a n ­druff clinical research, 785

H arper, K. H. See Davies, R . E.H arris, M ilton. John B. Speakm an, eu­

logy, 503Hechem y, K . E. See V anderW yk, R . W.Hefferren, J. J. L ab o ra to ry analysis of

to o thpastes contain ing anticaries agents, 135

H olbert, J . M . See Beekm an, S. M .Idson, B ernard . A dsorption to skin and

hair, 91Jacobi, O. K. N a tu re of cosm etic films on

th e skin, 149Ja rre t t , A. T he m elanocyte system and

keratin ization, 413Jass, H. E. Effect of process variables on

the stab ility of some specific emulsions, 591

Jellinek, J . S. M easuring th e m eaning of fragrance, 755

Johnston , V. D. See M anow itz, M ilton.K aiser, W. J. See B erth , Peter.K arja la , S. A., K arler, A., and W illiam son,

J . E . T he effect of pH on the sorption

835

836 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

of collagen-derived peptides by hair, 599

K arler, A. See K arja la , S. A.K atz , S. A. See Flesch, Peter.Laden, K arl, and Spitzer, R obert. Iden­

tification of a n a tu ra l m oisturizing agen t in skin, 351

L evenstein, Irving. See W olven, Anne. M acD onald , P. T h e evaluation of place­

bos in clinical tria ls, 455 M anow itz, M ilton , and Johnston , V. D.

D eposition of hexachlorophene on the skin, 527

M cLaren, K. T he action of ligh t on color­ing m atters , 245

M iller, Aaron. T h e relationship between surface effects due to electro ly tes and emulsion stab ility , 169

M ueller, W . H. Annual report of the P res­ident, 61

Olson, S. W. T he application of m icro­biology to cosm etic testing , 191

O pdyke, D. L. See W ooding, W. M . O rentreich, N orm an, and Sharp, N. J.

K eratin replacem ent as an aging p a ­ram eter, 537

Papa, C. M . Effect of topical horm ones on aging hum an skin, 549

Parslow, M . W ., and Scott, B. A. H air colorants—a practical approach, 19

Peck, S. M ., and Vinson, L. J . Use of two prophetic p a tch tes ts for th e practical determ ination of photosensitization po­ten tia l of widely used deodoran t soaps, 361

Phillips, R. W. Sol G ershon— the p ro ­fessional m an, 72

Prichard , D. M . See Breuer, M. M. Prokop, H. J . See Greif, M artin .Proppe, Albin. Im p o rta n t criteria for the

m icrobial p u rity of external derm ato ­logical preparations, 715

P u ttn am , N. A., and B axter, B. H. Spec­troscopic studies of skin in situ by a tte n u a ted to ta l reflectance, 469

Raff, A. M . T ris tim ulus color m easure­m ents in fading studies and o ther color

changes of pharm aceutical dosage form s, 367

R au, K arl. D ental science and develop­m ent in the cosm etic industry , 303

R aym ond S. A. See Caul, J. F.R iethe, Peter. Effect of surface active m a­

terials on oral hygiene, 291 Schlossman, M . L., T hau , Paul, and Tricoli,

Em anuel. 1966 survey of professional background and achievem ent of scien­tis ts in the cosm etic industry , 515

Schtnank, H. W. See Beekm an, S. M. Scott, B. A. See Parslow, M. W.Sharp, N. J . See O rentreich, N orm an. Shaw, C. T ., and V anderW yk, R. W. T h e

hum an scalp as a h a b ita t for molds, 563 Speakm an, J . B. Acceptance of T h irteen th

L ite ra tu re Award, 506 Spitzer, R obert. See Laden, Karl. Stevenson, J. I. See W right, K. H. R. T aber, D avid. See Brown, Jam es, Jr. T enenbautn, Saul. Pseudom onads in cos­

metics, 797T h au , Paul. See Schlossman, M . L.Tricoli, E m anuel. See Schlossm an, M. L. Tucker, H. H. H air coloring w ith oxida­

tion dye interm ediates, 609 Van Abbé, N. J ., and Dean, P. M . T h e

clinical evaluation of an tidandru ff sham poos, 439

V anderW yk, R. W ., and Hechem y, K. E. A com parison of th e bacterial and yeast flora of th e hum an scalp and their effect upon dandruff production, 629

V anderW yk, R. W. See Shaw, C. T . Vinson, L. J . See Peck, S. M.W ebster, G. L. Sol G ershon—the m an, 67 W illiamson, J . E. See K arjala, S. A. W inter, Leo, J r . See Dubow, Em anuel. W olven, Anne, and Levenstein, Irving.

Techniques for evaluating derm al irri­ta tion , 199

W ooding, W. M ., and Opdyke, D. L. A sta tistica l approach to the evaluation of cutaneous responses to irritan ts , 809

W right, K. H. R ., and Stevenson, J . I T he m easurem ent and in te rp reta tio n of den­tifrice abrasiveness, 387

Yackovich, F rank . See Brown, Jam es, Jr.

SUBJECT INDEX TO VOLUME XVIII

Acidic solutions, effects on ha ir exposure, 643

Aging, hum an skin, effect of topical hor­mones, 549

keratin replacem ent as param eter, 537 A lum inum com pounds for an tip e rsp iran t

use, 105A nticaries agents, in too thpastes, labora­

to ry analysis, 135A ntiperspirants, new alum inum com pounds,

105B acterial flora com pared w ith yeast flora of

hum an scalp, 629Benzoic acid d istribu tion and ac tiv ity in

emulsified system s, 207 C hrom atography, th in layer, of solvent ex­

trac tab le m ateria l on hair, 31 Color, rap id assessm ent for rou tine storage

testing, 3 of red hair, 777tris tim u lus m easurem ents, 367

Colorants. See Dyes.Consum er panels, local and national, com ­

parison in paired preference test, 123 Cosm etic trea tm en ts , of hair, q u an tita tiv e

m onitoring, 273Cosm etics, chem istry of syn thetic dyes in,

225con tact d e rm atitis from, 681 films, on skin, n a tu re of, 149 m icrobial pu rity , 715 preservation , 727 pseudom onads in, 727 testing, application of microbiology, 191 toxicological testing, 737

D andruff, electronic d a ta processing of com ­positions for control of, 787

production, effect of bacterial and yeast flora, 629

Degerm ing of hands, evaluation of bacterio ­sta tic soaps, 771

Dentifrices, m easurem ent and in te rp re ta tio nof abrasiveness, 387

prophylactic , labo ra to ry evaluation , 473 D erm atitis, allergic, from artificial coloring

m aterials, 215 from cosmetics, 681diaper, b acterio sta tic soap in prophylaxis

of, 161Sulphan Blue in evaluation of, 199

D erm atological p reparations, m icrobial p u r­ity of, 715

D yes, action of ligh t on, 245artificial, allergic reactions to, 215 artificial, toxicology of, 421 nitro , azo, and an thraquinone, w ith q u a ­

te rn a ry am m onium com pounds, 705 oxidation in term ediates, 609 relevance of color and ra te of diffusion to

developm ent of, 19 syn thetic , chem istry of, 225

E lectro ly tes, and em ulsion s ta b il i ty , . rela­tionship betw een surface effects due to, 169

E lectronic d a ta processing in an tidandru ff clinical research, 785

Em ulsions, d istribu tion and a c tiv ity of ben ­zoic acid in, 207

effect of process variables on stab ility of, 591

stab ility , and re lationship of surface effects due to electrolytes, 169

Fingernail grow th ra te as aging param eter, 537

Fluorocarbons, toxicity , 333 Fragrances, m easuring th e m eaning of, 755

and personality relationship, 521 H air, adsorp tion effects on, 91

behavior a t low pH values, 643 colorants for, relevance of color and ra te

of diffusion, 19coloring of, w ith oxidation dye in te rm ed i­

ates, 609cosm etic trea tm en ts , q u a n tita tiv e m oni­

toring , 273dyeing of, study of nitro , azo, and a n th ra ­

quinone dyes w ith q u a te rn a ry am m o­nium com pounds, 705

effect of pH on sorption of collagen-de­rived peptides, 599

effect of sham pooing on solvent e x tra c t­able m ateria l on, 31

red, iron pigm ent in, 777 torsional properties, 575

Hexaehlorophene, deposition on skin, 527 Horm ones, effect on aging hum an skin, 549 Iron p igm ent in hum an red hair, 777 Irr itan ts , sta tistica l approach to evaluation

of cu taneous responses to, 809 K eratin , replacem ent as aging param eter,

537type determ ination and m elanocyte sys­

tem , 413L ab ora to ry planning, aspects of, 41

837

838 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

L ight, action on coloring m atte rs , 245 M elanocyte system and keratin ization , 413 M icrobiology, application to cosm etic te s t­

ing, 191M oisturizing agent, n a tu ra l, in skin, iden­

tification of, 351 M olds, on hum an scalp, 563 O bituary , Russell, K. L ., 573 Oral hygiene, effect of surface active m ate ri­

als on, 291evaluation of effectiveness of to o th cleans­

ing process, 303P a tch tests, in de term ination of photosensi­

tiza tion p o ten tia l of deodoran t soaps, 361

predictive, p itfalls and problem s, 323 sta tistica l approach to evaluation of, 809

Peptides, collagen-derived, effect of pH on sorption of, by hair, 599

Photosensitization, po ten tial, of deodorant soaps, 361

Placebos, evaluation in clinical trials, 455 Preservatives, for cosm etic products, 727

and stu d y of pseudom onads in cosmetics, 797

Pseudom onads, in cosmetics, 797 P u rity , m icrobial, of external derm atological

p reparations, 715R a b b it eye mucosa, po ten tial irritancy to,

of cream sham poos, 663 Scalp, com parison of bacteria l and yeast

flora, 629h a b ita t for molds, 563

Sham poos, antidandruff, clinical evalua­tion, 439

cream , irritancy to ra b b it eye mucosa, 663

detergency and allied properties, 651 effect of, on solvent ex tractab le m aterial

on hair, 31Skin, adsorption effects on, 91

color, m elanocyte system and keratin iza­tion, 413

hexachlorophene deposition, 527 hum an, aging, effect of topical horm ones,

549identification of n a tu ra l m oisturizing

agen t in, 351n a tu re of cosm etic films on, 149

spectroscopic studies, 469 Soap, bacteriosta tic , clinical evaluation of,

in d iaper derm atitis-prophylaxis, 161

bacteriosta tic , evaluation for degerm ing hands, 769

deodorant, determ ination of photosensiti­zation poten tial, 361

Society of Cosm etic C hem ists, G rea t B ri­tain , A nnual M eeting, 499

A nnual R eport, 499 D inner and Dance, 271 D iplom a Course, 58 H ib b o tt M em orial Prize, 58 Officers and Council 1966-7, 1 Program , 58, 271, 500 Sem inar, 59, 272 Sym posia, 58, 59, 272, 500

Society of Cosm etic C hem ists, U .S.A., Annual R eport, 61

California C hapter, 82 I.F .F . Award, 754 L ite ra tu re Award, 502 M edal Award, 65 M eetings, 104, 148, 366, 548, 590 M id-A tlan tic C hapter, 83 M idw est C hapter, 84 M iner, E . T ., honored, 514 New E ngland C hapter, 86 New Y ork C hapter, 88 Plechner, Sophie, honored, 514 Rieger, M artin , aw ard, 754 St. Louis C hapter, 753

Spectroscopy, I.R ., a tte n u a ted to ta l reflec­tance, skin studies, 469

S ta tistica l approach to evaluation of cu tan e­ous responses to irritan ts , 809

Storage testing , rapid assessm ent of color for, 3

Sulphan Blue, use in evaluating derm al irrita tion , 199

Sunscreen agents, evaluation of, 143 Surface active m aterials, effect on oral

hygiene, 291T oothpaste , contain ing anticaries agents,

labo ra to ry analysis, 135 evaluation of effectiveness, 303 as te s t p roduct in com parison of local and

national consum er panels, 123 Toxicology, of artificial coloring m aterials,

421testing of cosm etics, 737

U ltravio let, use in evaluation of sunscreen agents, 143

Y east flora, com pared w ith bacterial flora of hum an scalp, 629

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS X X X V I I

4

Y o u ’re now using th e m , , . but d o n ’t re a lize how m uch m o re W ash ine has to o ffer.

Who knows more about parabens than Washine

We are probably in the best position to help you with yourpreservation problems. Washine has long been active in

problem-solving and has pioneered in the development of new applications for p-hydroxybenzoates (methyl, propyl.

butyl and ethyl; U.S.P., pure and technical grades).As truly basic producers, we continue to probe

for new and expanded applications.Write or phone our product manager, Mr. Zwicker,

for samples, information and technical service.

'astine WASHINE CHEMICAL CORPORATION

xxxviii JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

xl JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Topically Speaking—Why Not ROBANIZE Your Product?

R O B A N E ®c 3„h 62

Purified Hexamethyltetracosane, Squalane

Liquid vehicle NATURAL to skin and sebum

A truly NATURAL adjunct to the Cosmeto-Dermatological field.

And Emulsify it with—

C A R O L A T E ®CETYL PALMITIC ALKY LOLAMI DE

Self-Emulsifying Spermaceti-Amide

The satiny feel

The most desirable properties and structure of Spermaceti and Cetyl Alcohol combined in an emulsifiable form.

Emulsions incorporating CAROLATE as the emulsifier can he conveniently and economically formed.

ROBECO CHEMICALS, INC.51 Madison Avenue New York, N. Y. 10010

212-683-7500©Reg. U. S. Pat. Off. Pat. Pend.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS x l i

reflectionsLeijecfiouaSo it isn’t every dressing table that carries a big jar of P o la w a x . But chances are it's there all right - more than likely holding together a famous creamor lotion.........or poised for action in a quickbreak foam.Today’stop O/W emulsifier- P o la w a x . Write for new formulary and sample.

i . I f New York LondonI VI Milan Dusseldo-I

Croda Inc.51 Madison Ave.New York. N.Y. 10010 MU 3-3089CABLES- CRODAFAS N EW YORK

x l i i JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

LEADING SOURCE SINCE 1883FOR Sesame Oil USP

Peanut Oil USP Corn Oil USP Coconut Oils Edible Safflower Oil Cottonseed Oil USP Animal Fatty Acids Vegetable Fatty Acids

WELCH, HOLME & CLARK CO., INC.One Hudson Street • NewYork, N. Y. 10013 • (212) BA 7'4465

INDEX TO ADVERTISERS

American Cholesterol Products,Inc..............................................

Atlas Chemical Industries, Inc..Cosmetic Laboratories, Inc.......Croda, Inc...................................

IVvii

xlili xli

Dodge & Olcott, Inc.......Inside Back CoverEnjay Chemical Co........................... xii-xiliEvans Chemetlcs, Inc...................... iFleuroma........................................... xlvFritzsche Brothers, Inc.................... xlvilGlvaudan Corp...............Inside Front CoverGoldschmidt Chemical Corp......... IHalby Products Co., Inc................... iiHoffmann-LaRoche, Inc.................. viiInternational Flavors & Fragrances

Miranol Chemical Co. Norda........................

xlixXV

Noville Essential Oil Co., Inc.Parento, Compagnie, Inc.......Pennsylvania Refining Co__Rehels Chemical Co..............R.l.T.A. Chemical Corp...........Robeco Chemicals, Inc.........Robinson Wagner Co., In c ....

xlii xl

xliv Hi

xiv xl

xviUnion Carbide Corp........................... lx, xlvlVanderbilt, R. T., and Co., Inc....... xlviliVanD yk& C o.................................... xxxlxVerley, Albert & Co........................... vWashine Chemical Corp.................. xxxvilWelch, Holme & Clark Co., Inc....... xliiWhittaker, Clark & Daniels, In c .. . . vi Witco Chemical, Sonneborn Div.. . . x Will and Baumer Candle Co., Inc.

.................................. Outside Back Cover

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS xliii

COSMETICSSPECIALISTS TO THE PRIVATE LABEL TRADE

* Formulating* Manufacturing* Styling* Packaging

Our experienced staff offers a com­plete service for Distributors in the Atlantic and Central States.

COSMETIC LABORATORIES, INCORPORATED

2272 East Jefferson Avenue Detroit, Michigan 48207

SPECIAL EDITIONS OF THE JOURNAL

OF THE SOCIETY OF COSMETIC CHEMISTS

T h e following special ed itions are available

Ten-V olum e Index, 1947-1959

Price $2.50

Sem inar on P ercu taneous A bsorption

Price $3.00

P rep a id orders m ay be sen t to :

Editorial Assistant761 N o rth Valley Chase R oadBloomfield Hills, M ichigan 48013

Panelists are panel-testing, surplus dollars need investing,

hush-hush product needs a scent.

Call the guys who can invent: Call Noville.

e s s e n t i a l o i l c o i n cNORTH BERGEN, N. J.

ASSOCIATED COMPANY NICKSTADT-MOELLER, INC.

Ridgefield, N. J.

chem gsnuity put the Boogaloo in the lab!Why not a Boogaloo victory dance

after weeks of exhaustive research! You had to come up with a novel for­mulation containing a white mineral oil as the principal ingredient. But time was running out...patience, too.

That's when you turned to Penn- Drake. Their technologists went to work. Used skill, experience and un­limited ingenuity (we call it C hem - G e n u ity ) .J h e y found the answer. You never had a sweeter victory!

Maybe Penn-Drake C he m -G en u ity won't spark the “ boogaloo" in y o u r .

lab next week. It may not even trig­ger a two-step. But when you have a tough problem - where either a white mineral oil or petrolatum could get you off the hook-you can de­pend on P enn-D rake to solve it. Our customers represent a w id e ra n g e of industries — cosmetics, pharmaceu­ticals, textiles, plastics, and many more. May we show you w hy they depend on Penn-Drake year-\n ,

y e a r-o u \'!

Write for our new comprehensive guide to prop­erties and applications for white oils and petro­latums. No obligation. PENNSYLVANIA REFINING COMPANY, Dept. 37-4, Butler, Pa. 16001 Phone 412/287-2781

penn-drakeWHITE MINERAL OILS

PETROLATUMS

penn-drake

This graceful racing sloop, skillfully manned by crewmen who are masters of the sailing arts, is an example of truly outstanding performance. At Fleuroma, the highly specialized skills and imagi­native talents of world-renowned perfumers,

combined with the finest technical and chemical facilities available, create exciting fragrances that make your products unique . . . desirable . . . memorable. Fleuroma, 43-23 37th Avenue, Long Island City, New York 11101.

FLELmDMABtp

thesecret

ofsuccess

inf a . e e !c r e a m !

I

76 NINTH AVENUE, NEW YORK, N. Y. 10011

xlviii JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

Em ulsion stab ilizer? Suspending agent?

Gum m odifier?VEEGUM® is all o f th ese— and m ore!

Veegum is a binder, disintegrating agent, viscosity modifier and thickener, it imparts thixotropy, improves spreadability and adds cosmetic elegance to for­mulations. Do you have a specific emulsion, suspension, tableting or other formulating problem Veegum can help you solve? Write us on your company ietterhead and we will send you our 32-page Technical Bulletin #44F containing 35 formulas illustrating the use of Veegum. Samples for experimental work on request. R. T. VANDERBILT Company, Inc.,Specialties Department , 230 ParkAve. New York, New York 10017.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS xlix

Joinusinthepursuitofexcellence

I N T E R N A T I O N A L F L A V O R S & F R A G R A N C E S I N C .521 West 57th Street. New York. N.Y. 10019ARGENTINA AUSTRALIA BELGIUM BRAZIL CANADA DENMARK ENGLAND FRANCE GERMANY HOLLAND IRELAND ITALY JAPAN MALAYSIA MEXICO NORWAY PORTUGAL S. AFRICA SPAIN SWEDEN SWITZERLAND U.S.A.

1 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

o o o

the only standard that guides our hand. For more than forty years, creating scents and flavors of time-honored reputation.

NORDA, 475 Tenth Avenue, New York, N. Y. 10018 Telephone: 594-3232 • Cable Address "NORDOIL,” New York EXCLUSIVE BASIC MATERIALS for Scented Products: W rite or wire for specific information Offices in Chicago, Dallas, Los Angeles, San Francisco, Sydney, Toronto, Montreal, London, Paris, Grasse, Mexico City and other worldwide offices through Norda/Schimmel International (U.S.A.) and Norda/Schimmel International Ltd., Slough. Bucks (England).

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS l i

VI TEGIN The ESTER-BALANCED-¿-'■s.; Self-emulsifying glyceryl monosteara+e

for anionic, neutral or alkaline systems.

TEGACID REGULARThis unique ESTER-BALANCED self-emul­sifying glyceryl monostearate for cationic systems, produces emulsions having prime cosmetic elegance.

TEGIN P The ESTER-BALANCED self-emulsifying propylene glycol monostearate for anionic, neutral or alkaline systems.

TEGACID SPECIALThe ESTER-BALANCED self-emulsifying g ly­ceryl monostearate for anionic, neutral, acid or alkaline systems.

TEGIN 515 The ESTER-BALANCEDnon-self-emulsifying glyceryl monostearate for use with auxiliary emulsifiers and as a thickener and stabilizer.

TEGOSEPTS The universally used Parabens and'other esters of P-Hydroxybenzoic acid. USP and Technical. Methyl,. Ethyl, Propyl, Butyl.

Ask about our new customer service facilities• Technical laboratory service • Formulations assistance

• Pilot run lab testsDEPEND ON GOLDSCHMIDT FOR TRIED AND TESTED PRODUCTS

Write For Data and Samples

GOLDSCHMIDT CHEMICALA D IV IS IO N O F W IL S O N PHARMACEUTICAL & CHEMICAL CORP.

147-153 Waverly Place • New York, N. Y. 10014 • CHelsea 3-4792

lii J O U R N A L O F T H E S O C IE T Y O F C O S M E T IC C H E M IS T S

Most leading brands of antiperspirants are formulated with Reheis Chlorhydrol. Why? For well over fifteen years, Chlorhydrol has proved to be unmatched for efficacy and pH values that are safe for skin and fabric. Chlorhydrol exhibits none of the corrosive characteristics of other metallic salts which have been tried as the active antiperspirant ingredient.

Chlorhydrol is easiest to incorporate into specific formulations because of the wide range of forms in which it is supplied. It is offered in liquid or powder form for lotions, gels, creams and roll-ons and also as Rehydrol A5C for aerosol formulations.

Only Reheis offers you such a broad line of uniformly high-quality aluminum chlorhydroxides in bulk quantities. And only Reheis can offer technical services backed by over 25 years of experience in light metal chemical technology.

FLAVORS AND FRAGRANCES FOR OVER A CENTURY AND A HALF

* * * * * ESSENTIAL OILS • FLAVOR BASES

' PERFUME BASES • AROMATIC1 W > CHEMICALS • CERTIFIED

COLORS • SPRAY DRIED PRODUCTS

DODGE &OLCOTT INC.,SEVENTY FIVE 9 th AVE., NEW YORK, N.Y.

★ ★

- ' s h e d

Refined and sun-bleached from the world's finest Crude Beeswaxes,B E E H IV E B R A N D B E E S W A Xundergoes rigorous chemical and physical tests to assure:

1. U n i f o r m P u r i t y2 . U n i f o r m T e x t u r e

3 . U n i f o r m W h i t e n e s s

Behind it is the reputation and integrity of a concern with more than a century of experi­ence in blending beeswax formulae to special requirements. The guaranteed purity and uni­form texture and whiteness of Beehive Brand Beeswax will simplify your laboratory work and assure more saleable quality in your finished products.

W IL L & B A U M E R C a n d l e C o . , I n c . , D e p t . J S C , S y r a c u s e , N . Y .

Consultation Service• The experimental data and practical manufacturing experience of more than 100 years' specialization in beeswax and beeswax compounds are at your service without cost or obligation.

Write us about your beeswax problems.BEEHIVE BRAND

/3 j Zj Zs3s IV T ?U ^C NEW YORK 10010 300 Park Ave. So.CHICAGO 60606

162 N. Franklin St.

BOSTON 02109 71 Broad St.

LOS ANGELES 90015 952-4 S. Flower St.

I * r.'u. I V I