Document ppDMRYr5ZjL1r485r9qozbBLB

AR226-3017 Study Titir Skin Irritation Test vith H-21095 in Rabbits Laboratory Project ID Baskell Laboratory Report Mo. 311-95 Author M. Scott Karr Study Completed On April 26, 1995 Performing Laboratory Haskell E. I. du Font de Nemours and Company Laboratory for Toxicology and Industrial Elkton Road, P. 0. Box 50 Newark, Delaware 197U Medicine Medical Research No- Company Sanitized ^ "^Ooeg ,, eon^ Page 1 of 8 Substance Tested; Synonyms/Codes; GENERAL INFORMATION DuPont HLR 311-95 Physical Form: Compos i t ion: Contaminants: Puri ty: CAS Registry No.: Sponsor: St udy In 1t i a t ed Comp1e t ed; In Life Phase Initiated -_ Completed: Transparent tan Uquid H-21095 contains: 0 None 302 None available DuPont Specialty Chemicals E. I. du Font de Nemours and Company Wi Islington. Delavare 3.2U/'?5 ^./26/95 3/21/95 - 3/2A/95 Ooteo 2 - ^^Cfil DuPont HLR 311-95 Skin Irritation Test with H-21095 in Rabbits SUMMARY H-21095 vas evaluated for acute -sVin irritation potential in 6 Bale Nev Zealand tfhite rabbits. A '-.5 iaL aiisuot of the test substance vas applied to the shaved, intact skin of each labbi't and covered vith a seal-occluslve g dressing. The rabbits were exposed for 4 hours after which the test substance vas removed. Approximately 1, 2k, 48, and 72 hours after roaoval of the test substance, the 'est sites vere evaluated for erythema, edema, and other evidence of dermal effects and vere scnred according to the Draize Scale. The adjacent areas '? untreated skin vere used for comparison. The test substance adhe:ed to th; skin of the labbits; however, the test sites could still be evalua-ed. Slight to moderate eryhena and no ede-- vere observed in the rabbit? by 1 hour after removal of the test substance. By 24 hours, slight or mild erythema and no to mild edema were observed. By 48 and 72 hours, the rabbi"; exhibited no or slight erythema and no edem. No clinical signs of toxic :-: vere observed during this study- Undei the conditions 'it .is st'irly. H-21095 vas a moderate skin irritant. york y; <>.^'^' / ' ^ < M. Scott Karr Toxicology Technician Revieved and Approved for Is' -: -.-. C_^< a-^^ C^rol. Fin^ay Study Director ^fUfi^ Acknowledgments: Bryan V. Crossley also,participated in the conduct of this study. CP/alv Company Sanifeed. Does ^ ^ ^ TSCA cm DuPont HLR 311-95 INTRODUCTION The purpose of this study vas to evaluate the skin Irritation potential of H-21095 when applied to the shaved, intact skin of Nev Zealand tfhi >. rabbits. MATERIAL?. AND HETHODS A. Animal Husbandly i' 'fou.ig adult ,nale :iM: (NZy)fBF. '.'e.' Zealand White rabbits vere received fro' Hare Mcirizni, He'-;:'-.. He'. Jeisey. The "abbits vcre housed singly in ,''rii.ied, stii .'"ss s;'?pl. .:. iriesh cages. Each rabbit was assigned a was recorded on a card affixed to the jniqrC cage. '. < i.^'^irc.' inibi.f uni.h The last 3 aig.is ui. the identification number were written on the inside of each rabbit's ear vith a vater insoluble maiker. The rabbits 125 gianis of Purina Ceitified High Fiber were offered approximately P.abM t rhov* #5325 r^i'" drring 'lie study. Vater was available ad. y< ;,.,. & . r oeriod vhile the animals vere in n ; . Haske""' ' aSnratoi . has an a!::- 1 hea'r,'i monitoiing prograni. This y ~'7. '''' '''" ="1 "!;;(' iijiiiin.; . (* Ly the I ahniritory Velerinar'"an. . i* .-i ...in.p-eh - t- ^ . . ,,.: a i.'.' .-, i r'"" ' : rntal bacterial counts and for the pit t-(.-e if ro\ i foin" i' id, -tiri o^r.i-'. i...)n::'ninants. cages and cage racks are Additionally, samples periodically analyzed ^iom iiei...... -?-?' to assure adequate sanitation by the cagevashers. Data from this program are maintained separately from study records. Animal feed is ceitified by the isanufacturer to Tieet specified nutritional reqOuniretrhaecna'sasi..is.id (fTO "'''.ee&e'reaenaolyf sea s,listht eoref sispencoifieevdidence "''intaininantssuggesting that conta-'.:;ant; -e:e uresent in the .! or water in amounts vh" ^ "nay have interfc;' -a vii''. the results of this studj . Rabbits rt-i.e qi. in...-1' .eig'ec, and 'Kiserved for general health for aiip^oximately / - .1,11':.,-1 rooms were maintained on a timer- controlled, I'-hoL, i:!,: 12 ..<.'-ii daric cycle. Environmental conditions rcr a temperature of ..0C * i' and -lative of tt.e rooms were hunldity of 50X s ta.,,t;iJ 10!!;. Excursions outside thesp '"ges weri 'udged to have been of insufficient macni'.ude and/oi durarir!' "i :iavv adversely affected the validity of the study. - 4 Company Sanitized. Does not eonfa?R TSCA CBf DoPoat E&R 311-95 B. Protocol On the day prior to creafent, the hair of 6 ale New Zealand Dhif rabbits was closely shaved to expose the Stkia froa the scapular to die luabar region of the back. The body weights of the rabbit* ranged froa 1930 to 2174 grams on the day of treatment. Each rabbit was placed into a stock which had been fitted with a piece of rubber sheeting, approximately 8" x 18". The rabbits remained in the stocks throughout the exposure period and during that ti-- did not have access to food or water. A 0.5 iL aliquot of H-21095 vas applied directly on the test site beneath a 2-inch gauze square that vas held in place vlth non-irritating tape. The rubber sheeting was then wrapped / around the animal and secured with clips to retard evaporation and to keep the test substance in contact with the skin without undue pressure. In the absence of visible evidence to the contrary, the test substance was assumed to be stable under the conditions of administration. Up to 3 other test substances were tested concurrently on separate, localised test sites on the backs of these rabbits. Approximately 4 hours after application of the test substance, the rubber sheeting was loosened, and the skin at the corners of the gauze squares was marked with a waterproof pen; wrappings and gauze squares were then removed. The test sites were gently washed with warm water to remove excess test substance. The skin was gently patted dry, and the aninials were returned to their cages. Approximately 1, 24, 48, and 72 hours after removal of the test substance, the test sites were evaluated for erythema, edeaa, and other "Uance of dermal effects and were scored according to the Draixa scale (Table I). The adjacent areas of the untreated skin were used for comparison. In addition, the rabbits were observed for clinical signs of toxic!ty at each observation. C. Records Retention All raw data and the final report will be stored in the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Font de Nenorrs and Company, Newark, Delaware or in the DuPont Records Management Center, tfilmingtcn, Delaware. RESULTS AND CONCLUSIONS The test substance adhered to the skin of the rabbits; however, the test sites could still be evaluated. H-21095 produced slight erythema in 4 rabbits, mild erytheaa in I rabbit, and moderate erythema in 1 rabbit by 1 hour after reaoval of the test substance. Ko edeaa was observed at 1 hur Company Sanitized. Does not contain TSCA CBI OuPont HU 311-95 By 24 hours, 3 rabbits exhibited slight erytheaa but no edea, and 3 exhibited ild eryth--a and no to mild edeaa. By 48 hours, 2 rabbits exhibited oo deraal irritation, and 4 exhibited alight erytluwa but BO d----. By 72 hours, 3 rabbits exhibited no denial irritation, and 3 exhibited light erytheaa but no edena. No clinical signs of toxicity were observed during this study. Individual skin irritation scores are presented in Table II. A su--ary of skin responses is presented in the following table. Summary of Skin Responses to H-21095 Response No Response Slight Mild Moderate 1 hr Eryt hema 24 hr 48 hr 72 hr 0/6 0/6 2/6 . 3/6 4/6 3/6 4/6 3/6 1/6 3/6 0/6 0/6 1/6 0/6 0/6 0/6 1 hr 6/6 Ede oa 24 hr 48 hr 4/6 6/6 It hr 6/6 0/6 1/6 0/6 0/6 0/6 1/6 0/6 0/6 0/6 0/6 0/6 0/6 Under the conditions of this study, H-21095 was a moderate skin irritant. If these test scores are to be used for EEC/OECD classification, according to the guide to the labeling of dangerous substance's .published in the Official Journal of European Communities (EEC Directive 9-3/21, Annex VI), H-21095 probably could be classified as a "HON-IRRITANT" until further data is available. Does not c^Wn TSCA CBI 6 - DuPont BLR 311-95 SKIN IRRITATION TEST VITH H-21095 TABLE I DRAIZE^ SCALE FOR SCORING PRIMART SKIN IRRITATION Evaluation of Skin Reactions Erytheu wad eschar foraation; No erythema Very slight erythema (barely perceptible) Well-defined erythema Moderate to severe eryhema Severe erythema (beet redness) to slight eschar foraation (injuries in depth) Edema format Ion: No edeu Very slight edema (barely perceptible) Slight edema (edges of area veil defined by definite raising) Moderate edema (raised approximately 1.0 oun) Severe edema (raised more than 1.0 mm extending beyond the area of exposure) Value 0 1 (Slight) 2 (Hild) 3 (Moderate) 4 (Severe) 1 (Slight) 2 (Mild) 3 (Moderate) 4 (Severe) Abbreviations of other A - Abraded I Intact T Thickening C - Eschar - - No Effect B - Blanching dermal effects are; F Fissuring N = Necrosis G = Pissuring with Bleeding S = Epidermal Scaling L Sloughing R Raw Areas X Compound Adhered to Skin SN Superficial Necrosis 1 Draize, J. H., "Deraal Toxicity." Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. The Editorial Commit tee of the Association of Food and Drug Officials of the United States, Austin. Texas, 1959, pp. 46-59. Company Sanitized. Does not contain TSCA CBI SKIM IIBIITATIOH TEST WITH H-21095 TABLE II INDIVIDUAL SKIN IRRITATION SCORES SKIN RESPONSES OBSERVED IS RABBITS OitPont OLR 311-5 Rabbit Number 29985 29986 2998 / 29994 29995 29996 1 hr 2X* IX" 1X 3X* IX* IX* Ery thema 24 hr A8 hr 2X IX* IX* IX* IX* OX* 2X IX* 2X IX" IX* OX* 7;' hr IX* OXOX* IX* IX* ox* 1 hr 0 Edenia 24 hr 48 hr 0 0 72 hr 0 0 0 0 0 0 0 0 0 0 2 0 0 0 1 0 0 0 0 0 0 Although the test substance adhered to the skin of the rabbits, the test sites could be evaluated. Company Sanitized. Does not contain TSCA CBI