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AR226-2948 Performing Laboratory Haskell E. I. du P< it de Nemours and iCempany, Inc. Laboratory 'or Toxicology ^industrial Medicine P. . Box $Q, ginon W^id Newark, Delaware 19714 Laboratory Project 10 Haskell (laboratory Report No. 180-90 ! Page 1 of 6 r 'mpany SanKized. Does nofconfam TSCA CBf Du Pent HLR 180-90 <ERAl INFORMATION Material Tested; Medical Research Ho.; Haskell No.: Haskell Test Code: Physical Form; Purity: Composition; 18.267 ^Ambedrispersion Synonym; Stability: Sponsor; The test materi?"' was assumed to be stable under the conditions of administration. Chemicals and Pigments Department E. I. du Font de Nemours and Company, MIlBilngton, Delaware Ir.c. Material Submitted By: Chemicals and Pigments Department E. I. du Pont de Nemours and Company, Jackson Laboratory Deepwater, New Jersey Inc. Study Initiated - Completed: 2/16/90 - 5/2/90 In-Life Phase Inl t1 ated - Coropieted; 3/6/90 - 3/20/90 Notebook; There are 6 pages In this report. Distribution: 2 - Company Sanitized. Does not contain TSCA CK Du Pont HLR 180-90 '(at^t Intact skin of 2 male rs. Under the 0 9/kg of body wel9ot. imately 24 hours after ^affeF frr 14 days. This .....D greater than sifclti of male rabbits. work by ^^^^m^Hahn Technician Study Director? ^aA^\ t^3. Jonn w. sarver Technologist i Approved by[ ^ d ^ E ^ < Boleres^. Malek. Ph.D. Resiearch Toxicologist Acute and Developmental Toxicology Division i ( \ Reviewed and ! fl Approved for Issue]: "/^}tds-0nn ] C"' \ <' (^.<^L^^ M. sarver Study Director &---/Q^t^ Acknowledgments: Craig Lightctop, Teresa Bishel. and Maureen Godwin also participated in the conduct of this study. JWS:a1r:HLR41.8 - 3 Company Sanitized. Does nol contain TSCA CB1 'w^1 '"^Ip?"^;^;'^^^ Font WW 180-90 STUDY; Ht 18,267 I^NI Approxiaatt Sktn Absorption ALD) by in Rabbits AUDITS: Items Audited In-life Observations STSPS, Records and Final Report Audit Dates 3/7/90 4/12,16/90 SHORT-TERM AUDIT REPORT DATE FINDINGS REPORTED TO MANAGEMENTAND STUDY DIRECTOR: 4/16/90 Reported by: ^Wc -H5im------ Qualiitty Assssuu;rance Auditor t ^ 0 'Date 4 - Company SanTHzed. Does nol contain TSCA CB1 Du Pont HLR 180-90 The purpose of this (ALD) by skin absorption of the test material admNis within 14 days of exposure* applicable EPA Good Laboratory are documented In the study records. significantly affected the vaTtWty of ti^, proximate lethal dose 'fined as the lowest dose th of a test animal I according to the Areas of noncompilance existed that ER1ALSANPMETH0PS A. Animal Husbandry Young adult male New Zealand White r. "awere received from re^ Hare Marland. Hewltt. New 3ersey, We ri Hwere. housed singly In suspended, stainless steel, wire-mesh cag^?, l|ach rabbit was assigned a unique Identification number which was | on a card affixed to the cage. Purlna Certified Rabbit ChoW #53^a, ^ater were available ad llbltum. Rabbits were quarantined, we1ghelr,1 observed for general health for approximately 2 weeks, Animdl * were maintained on a timer-controlled. 12-hour 1lght/12-nour dai^^cle. Environmental conditions of the rooms were targeted for a temperature of 20'*C ^ 2C and relative humidity of 501 t 1(. Any excurstot? outside these ranges were of small magnitude and/or"brief duration arid did not adversely affect the validity of the study. B. Protocol On the day prior to s ;udy Initiation, the hair of each rabbit was closely clipped to expose the back from the scapular to the lumbar region. The rabbits were then fitted with pN^tic collars to prevent ingest!on of the test material or disruption Of the wrappings. The test material was applied to the -tntffct skin of 2 male rabbits. The rabbits were dosed atjSOOOmg/kg. the maxllmum feasible dose. The test material was spread rvenly over the entire exposed skin of each animal. The rabbits' bod,f weights ranged from 2884 - 2897 grams on the day of dosing. After application of the test material, sterile gauze pads (9" x 3") were applied to the treated site. The rabbits were then wrapped with successive layers of plastic film, stretch gaaze bandage and elastic adhesive bandage. After Wrapping, the rabbits were returned to their cages. Company Sanitized. Does not corilain TSCA CB1 Du Font HLR 180-90 Approximately 24 hours ifter t|pNtij;9i fl^the test material. the rabbits were removed froi ' ie1r ^a|es and ^he ^ were removed. f^^he fWi1 Excess test material was ww<ahed back with warm water and the skin dried with a |iiper ((iwyl. were welshed, WittWs observed for clinical signs of texltlty and returned to their cages. Observations for clinical s Igns were Bade if^ximately 24 hours after application and then dally thereafter for W days (excluding weekends). Observations for mortal 1ties were made dally throughout the study. The animals were weighed on days 1, 7 and 14 following treatment. C. Records Retention | All raw data and the f1|na1 report win be stored In the archives of Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Company, Newark,Delaware or In the Du Pont Records Management Center, wnmingtfon, Delaware. RESULTS A. Dosage and Mortality Two rabbits were previously treated with this test material; however, because the test sites were not occluded, the test was considered Invalid and the! data Is not Included In this report. Two additional rabbits were treated. The dosage regimen and the mortality resulting over the 14-day t^est period are detailed below. Dosage (mg/kg) DOS? (mLl Initial Body Height (g) Mortality 50QO 13.2 2884 No 5000 13.2 2897 No B. Clinical Signs No clinical signs of toxiclty were observed during the study. CONCLUSION for^fftwas Under the conditions of this study, the ALD greater than 5000 ing/kg of body weight. This material is considered to have very low toxicity (ALD greater than 5000 nig/kg) when applied to the clipped, intact skin of male rabbits. Company Sanitized. Does not contain TSCA CBI