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(n\~~__~'J L FINAL REPORT AMENDMENT ; ~ STUDY NAME Unscheduled DNA Synthesis in Rat Primary Hepatocytes STUDY NUMBER T5290.380 INITIATION DATE February 17, 1987 PART OF FINAL REPORT TO BE AMENDED (EXACT LOCATION) 1) Page 3 2) Page 9, paragraph 1, line 2 REASON FOR THE AMENDMENT 1) Correct typographical error 2) Correct typographical error AMENDMENT (ATTACH ADDITIONAL SHEETS AS NECESSARY) 1) Change "Date Sample Received: November 20, 1987" to "Date Sample Received: November 20, 1986" 2) Change "100 ug/ml" to "1000 ug/ml" See attached amended pages APPROVALS ~7 - /:) -C• -q_ ~ --- ~ -f1 - .-: _ .. _ DATE ST D DIRECTOR f /, '3 I ;i7 DATE QUALITY AS RANCE

UNSCHEDUIED IJNA SYNi'FIESIS IN RAT PRINIARY REPAZnCY`I'FS FIlNAL REFORT Test Article : A80 L,ot : OR133-87-4 MA Study No.: T5290.380 Test Article Description: Mzite powder storage Conditions: Refrigerated in an amber bottle Date Sample Received: Novembex 20, 1987 $(.. Initiation Date: Februazy 17, 1987 . Coupletion Date: June 5, 19 8 7 Sponsor: Sponsor's Investigator: Testing Facility: Study Director: Assistant Study Director: Laboratory Technician: laboratory Technician: Iaboratoxy Technician: hboratory Technician: Iorillard Research Center 420 Erxglish Street Greensboro, North Carolina 27420 J. Daniel Heck, Ph. D. 5221 River Road Bethesda, Maryland 2.Q816 MICROBIOIfJGICAL ASSOCIA'PES, INC. ~~ ~~ yal~fie B. A~a~and, B.$,/ Barbara J. , A.S. Drate `~c'4.('r" LJ a.I&LO (~ - y - F-1 Ka een Wallace, B.S. Date 3 .^ %..d 0 Da T° A -/ d v Han~"J ~' Da ~ MICROBIOLOGICAL ASSOCIATES INC.

Study No. T5290.380 RESULTS AND DISCUSSION The results of the preliminary cytotoxicity assay are shawn in Table 1. The relative toxicity was nearly 100% at doses of test article of 1000ug/ml and above, decreasing to 54%, 40% and 23% at doses of 300, 100 and 30 ug/ml respectively. All lawer doses were essentially non-toxic. Microscopic Pxamination of the cultures indicated toxicity at the six highest concentra- tions of test article, and slight toxicity at the seventh. The UDS assay was performed using nine doses of test article ranging from 0.1 to 1000 ug/ml. The results of the parallel cytotoxicity assay are reoorded in Table 2. Zhe values obtained indicated that concentrations of test article of 300 ug/ml and above were very toxic. Assays of culture fluid for lactic acid dehydrogenase activity yielded relative toxicities of 41%, 33%, 20%, 10% and 25% at concentrations of 100, 30, 10, 3 and 1 ug/ml. These dose levels were fully evaluated for Unscheduled WA Synthesis. Tlle results of the UDS assay are summarized in Table 3. Slides treated with A80 or IMBA were ccatpared to the appropriate negative control. According to the criteria set for evaluating the test results, both doses of the positive control ccacpcund, DMBA, induced a significant increase in the average net nuclear count of silver grains. None of the test article doses caused a significant increase in the mean net nuclear counts. All criteria for a valid test were met. ~ .~ 9 Ir N :!t ~ W .^ ;.. 0 MICROBIOLOGICAL ASSOCIATES INC.