Document 5bJ8ZoOOm1Jkkk0V6LnaDO6NJ

WPP "': AR226-2982 ft J',:-, ft Uri w ^ i fautt* -V Vj: Vi:  Ou Pent A 1 * ~ n mm IWHWff This study v m conducted iccordln* toifl n i l flood laboratory fraction Standards (40 CFK 70S). Any ,e w b o of opoeooplfoiieo aro doeuaontod In the study raeards. No deviations tiiot OffbctOd tho validity of tba study Subaittoti I. 1 du font do Honours and Coapany Sponsor flu font Chooieals 1 1. du font do Honours and coapany i ) Study Diractort Sarvor . a ' <Xi Toxicologist ' J : * 2 - jmpany Sanitized. Poes not contain TSCACB1 : ^ ^ - -...- 1 Subs tance Tested ? S1MERAL INFORMATION Du Pont HLR 28-93 Synonya/Codea> H-19913 Phyalcal Forai Colpositioni Purityi Submitter's Notebook Ho.i GSNCTAL ItfPOKHATIOH (COMT.) Du Pont HUt 28-9$ Sponsor Study Initiated - Conplatadi In Life Phase Initiated - Coapletedt Du Pont Cheaicals E. I. du Pont do Npaour* and Coapany wiinington, Dolavara 12/7/92 - 2/2/93 12/8/92 - 12/11/92 - 4Company Sanitized Does not contain TSCA PPJ Du Font LR 28-93 Skin Irritation Tot with 9-19913 in Rabblta SUMMARY 9-19913 vaa avaluatad for acuta akin irritation potantial in 6 faaale rabbita. Tha taat aubatanca produced alld or aodarata orythaaa and no or alight adoaa by 24 houra following application. By 48 houra alight to aodarata orythaaa and no to alld adaaa vara obaarvad. By 72 houra the rabbita exhibited alight or hild arythaaa and no or alld adaaa. Undar the conditiona of thia atudy, 9-19913 va~ a aodarata akin irritant. Vork by Ni Scott Karr Toxicology Technician Reviewed and Approved for laauai A /a/S3 ^ John V. &arver Study Director Acknovladgaaentai Tracy Filliben and Bryan Croaalay alao participated in tha conduct of thia atudy. JVS/alv "aopany Sanitized. Does not contain TSCA CBI Du Pont BLR 28-93 QUALITY A38URAHC1 DOCUHiWTATION (H-19913) Dato of Inaoouiont Conduct - 12/8/92 Record* Roport(o) - 1/26/93 Pete(a) Finding Reported to> rocStudy D1 tor - 1/26/93 HanafMant - 2/1/93 Reported a 11 " j"I Donna R. Holt Quality Aaaurance Auditor - 6Company Sanitized. Doss not contain TSCA CBi Du Pont HLR 28-93 INTRODUCTION Th* purpoa* of this atudy vaa to valuata tha akin irritation potantial of H-19913 vhan applied to the shaved, intact akin of Nav Zaaland Whit* rabbita. MATERIALS AND METHODS A. Animal Huabandry Young adult faaalt Nav Zaaland White rabbits vara racaivad froa Hara Marland, Hewitt, Nav Jersey or Hazleton Raaaarch Product*, Denver, Pannaylvania. Tha rabbit* vara housed singly in auapandad, stainless steal, vira-aaah cages. Each rabbit vaa assigned a unique identification number which vaa recorded on a card affixed to the cage. Th* rabbits vara offered approximately 129 grass of Purina Certified High Fiber Rabbit Chov* #5325 daily during th* atudy and vatar vaa available ad libitum except as noted under Protocol. Rabbits vere quarantined, vaighad, and observed for'general heat th for approximately 2 vaaka. Animal rooms vara maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of th* rooms vara targeted for a temperature of 20*C * 2*C and relative humidity of 50Z 10X. Any excursions outside these ranges vere of small magnitude and/or brief duration and did not adversely affect the validity of the study. B. Protocol On the day prior to treatment, the hair of 6 female Nev Zealand White rabbits vas closely shaved to expose the skin from tha scapular to the lumbar region of the baekf Th* body veights of the rabbits ranged from 2947 to 3320 grams on the day of treatment. Each rabbit vas placed into a stock vhich had been fitted vith a piece of rubber sheeting, approximately 8** x 18". Tha rabbits remained in the stocks throughout the exposure period and during that time did not have access to food or va^er. In the absence of visible evidence to tha contrary, the test substance vas assumed to be stable under the conditions of administration. Approximately 0.5 aL of H-19913 vas applied directly to a 2--itjich gauze square that vas then placed on the test site. The patch vas held in place vith non-irritating tape. The rubber sheeting vas then trapped around the animal and secured vith clips to retard evaporation and to keep the test substance in contact vith the skin vithout undue pressure. - 7 - ;ompany Sanitized. Poes noi couwuj 5 c m Ou Font RLU 21*93 Approxloatoly 24 hours afttr applicatin oi tho tot sbatenos, tho rubbor sheeting va* loosanad, id tito okin at tho crner* of tho (uto iquaroa vas arkad vith a vaterproof pon vrappings and (auto squares varo thon roaovod. 'na tqst titos varo gsntly vathod vith Ivory* toap and vara vatar to raaova axcasa taat sub*tanca. Tho tkin vas gently pattad dry, and tho enlacia varo raturnad to thair cagas Approxiaataly 24, 48, and 72 houra altar applicatin of tho tost subatanca, tho tost sitas vara avaluatad for arythsaa, adaaa, and othar evidanca o dorsal effects and vara acorad aecording to tha Draita scala (Tabla I). Tha adjacent airaos of tha unUaatad akin varo usad Cor coapariaon. No othar taat subatancas vara tastad on thasa rabbits. C. Records Retention All rav data and tha linai raport vili ba storad in tha archivas of Haskall Laboratory for Toxicology and Industrial Nadicina, E. 1. du Pont da Naaours and Company, Nsjvark, Dolavara or in tha Du Pont Racords Managaaant Cantor, Vllalnijton, Dalavara. muto m M W M W f H-19913 producad slid orytjhana vith no adana in 5 rabbits and nodarata arythaaa vith slight adaaa in 1 rabbit by 24 hours folloving application. By 48 hours slight arythaaa vith no adaaa vaa obsarvad in 1 rabbit, aild arythaaa vith no or alight adaaa vaa obsarvad in 3 rabbits, and aodarata arythaaa vith slight or aild adaaa vas obsarvad in 2 rabbits. By 72 hours 2 rabbits axhibltad alight arythaaa vith no adaaa and 4 rabbits oxhibitad aild arythaaa vith no or aild adaaa. Individual akin irritation scores ara prasontad in Tabla II. A auaaary of skin rasponaas is prasantad in tha folloving tabla. Sunaary of Skin Rasponaas to H-19913 Response No Response Slight Hild Nodarata Imhaaa 24 hr 4o nr 0/4 0/6 0/6 1/6 5/6 3/6 1/6 2/6 JThr 0/6 2/6 4/6 0/6 24 hr 5/6 1/6 0/6 0/6 Rdoaa 48 hr 3/6 2/6 1/6 0/6 "7F'fir 5/6 0/6 1/6 0/6 Under tha conditions of this study, 8*19913 vas a moderate skin irritant. - 8 * 'ompany Sanitized. Does not coma,n i s c a c m  .i . ` . Du Vont O * S M S i ' 11 ' 1 . ' ; If tboso tost scoros oro to bo used fer SBC/4SCD cUiflestion nccordinf to 83/4?, Atho Official thft cuido to tho Isboliwj of M ^ u s ubsUneo Joiiriol of luroposn Coostoitl<l|| Diroctlv publisjhiemdxin 8-19913 boVI), probably should classified as an "IMITANT" until further data is available. O n i; \' j I hi 5 'U s lr 9 - Jony>MSanitized. Does noi coruam TSCABI Du Pont HUt 28-93 TABU I DRAIZB1 SCALE FOR SCORING PRIMARY SKIN IRRITATION Evaluation of Skin Reactions Erythoaa and atchar formation* No tryt h e m Very slight erythema (barely perceptible) Well-defined erythema Moderate to severe erythep* Severe erythema (beet redness) to slight eschar formtion (injuries in depth) Valut 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Edam formtion i No edema Very slight edema (barely perceptible) Slight edema (edges of arpa veil defined by definite raising) Moderate e d e m (raised approximately 1.0 mm) Severe e d e m (raised more than 1.0 am extending beyond the area of exposure) 0 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other dermi effects arei A - Abraded P Pissuring I - Intact N Necrosis T - Thickening G - Pissuring vith C Eschar bleeding - - No Bffect S Epidermal B - Blanching Scaling L Sloughing R Rev Areas X Compound Adhered to Skin SN Superficial Necrosis 1 Dralse, J. H., "Denial Toxicity." Appraisal of the Safety of Chemicals in Poods, Drugs and Cosmetics. The Editorial Committee of the Association of Pooil and brug Officials Of the United States, Austin, Texas, 1959, pp. 46-59. - io - Sanitized. Does not contain TSCA CBi Du Pent BLR 28-93 TABLE II INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IN TEST RABBITS FOLLOWING TOPICAL EXPOSURE TO H-19913 Rftbblt Nuiiber 27558 27659 27662 27663 27664 27665 1Srytheae 24 hr ijp.hr 7 by 232 232 222 322 221 211 Eden M hr 48 hr 72 hr 0 20 0 10 000 112 000 000 - 11 - .Company Sanitized, uoe$ tun comatu $