Document yrnRaaB35oGapx0JLq3ZE91eD

REVISED REPORT AR226-2875 Copies to: E. I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine HASKELL LABORATORY REPORT NO. 721-78 Material Tested* Haskell No. 12,398 Other Codes Sample Ready for Testing 7-6-78 Submitted by ^ ___ FCD&P Department, Jabkson Lab., Chambers Works Procedure: The test material, as an aqueous solution, was administered by intragastric intubation to a g rup of ten young adult ChR--CD male rats, five times a week for two weeks, at a repeated dosage level of 3,400 mg/kg/day; an additional group of ten rats served as controls and was intubated with distilled water. Five control and five test rats were sacrificed approximately two-four hours after the last dose. The remaining five control and five test rats were sacrificed 14 days after the last dose. Results : Dose (mg/kq/day) 3.400 No. of Doses 10 Mortality 0/10 ' Clinical Signs First Week: Sporadic weight loss. Second Week: Sporadic we iaht loss. Recovery Period: None. ^ .. . . pathologic Changes;** Gross and microscopic compound-related changes were observed in arstaVe<hii \i;ats e * ftm,ned on the last day of dosing. The mean absolute liver weight of test rats was40% " .r that * 'ths control group. The liver weight of test rats examined after a 14-day recovery period was 26% greater than the control group. Histologically, liver hypertrophy was observed in test a s. These changes appeared to be reversible although not completely during the 14-day recovery Company Sanitized. Does not contain T SCA CBl Company S " * TQ r'ft r m Z- administered orally to young adult ChR-CD male rats at a repeated dose leve) of J.9UU mg/kg/day for ten days over a two-week period. The compound-related patholoaical effect was hypertrophy of the liver. The changes observed would be expected to be comoletelv reversible if given a longer recovery period. r* ** Tissues examined histologically b; l,iver, kidney.s, lun.gs,, brain, adre,na,ls, heart, spleen, __ ____________ included: sternal bone mSrrowT^eyes^upper and lower gastrointestinal tracts, epididymides, testes, thyroid, lymph'nodes and trachea............................... .......... parathyroid - .. ....' pancreas, 'thymus, Date Date Issued: Revised: December 1, December 2 219, 781978 Report b y : 7^ _________ T. Q. Dilworth Technician Approved by: Cj. -v A. Michael Kaplan Chief, Acute Investigations :ction Company Sanitized. Does not contain T SC A CBl f Copies to: ? 13 3 -------------- 3 2 Material Tested H ma O o 3 O O a 3 E. 1. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine HASKELL LABORATORY REPORT MO. 52-79 Haskell No. 12,402 Other Codes TEH-DOSE Sample Ready for Testing 7/6/78 Material Submitted by Chemicals, Dyes & Pigments Dept. Jackson Laboratory Chambers forks H?:- COO' > Procedure; The test material, as a 50Z suspension in a cetone/com oil 15:85 or 7.5:92.5, vas administered by intrsgastric intubation to a group of 10 young adult ChR-CD male rats at a repeated dosage level of 3,400 mg/kg/day; an additional o group of 10 rats served as controls and was intubated with acetone/cora o i l 15:85 or 7.5:92.5. Bight test rata died before the fifth dose and the remaining two test rats fore sacrificed the dey after the fourth dose. Two control rats were sacrificed after the fourth dose. Four of the remaining eight controls were sacrificed after the tenth dose and the f remaining four were sacrificed after a 14-day recovery period.** The test material, as an 18Z suspension in acetone/cora oil 15:85, was administered by intragastric intubation to a 13 group of 10 young adult ChR-CD male rats at a repeated dosage level of 1,700 mg/kg/day; an additional group of 10 rats 0 served as controls and was Intubated with acetone/cora oil 15:85. Ten test rats died before the sixth dose. Tw o control rats were, sacrificed after the seventh dose and the remaining eight controls were sacrificed rlthout pathology.*** w The test material, as a 7Z suspension in a c e t o n e / c o m oil 15:85, was administered by intragastric intubation to a N group of 10 young adult ChR-CD male rats at s repeated dosage level of 850 mg/kg/day; an additional group of 10 rats 0a. served as controls and was intubated with acetone/cora oil 15:85. Four test rats died before the tenth dose and three O of the remaining six test rats were sacrificed approximately four hours after the tenth dose, en d three after e 14-day o aC3P recovery period. Five control rats were sacrificed after the tenth dose and ths remaining five controls were sacrificed after a 14-day recovery period. 0 0 P 3 H CO o Company Sanitized. Does not contain TSCA CBS > Result Dose (mg/kg/day) 3,400 1,700 850 No. of Doses 2-4 3-5 3-10 Mortality 8/10 10/10 4/10 First Week: Clinical Signs Stained and wet perineal area, stained face, diarrhea, lacrimation, prostration, and weight loss. First Week: Diarrhea, hu m p e d posture, congestion stained face, stained and wet perineal area, weakness, and weight loss. First Week: Stained and wet perineal area, stained face, diarrhea, lacrimation, weakness, humped posture, and weight loss. Second Week: Piloerection, unkempt fur, humped posture, weakness, stained and wet perineal area, stained face, eyes half-dosed, and weight loss. -- Recovery Period: Hone Pathologic Changesi**** See Appendix (Pathology Report Ho. 2-79).+ Summary? administered orally to groups of young adult ChR-CD male rats at repeated dose levels of either 3,400 mg/kg/day (2 to 4 days), 1,700 mg/kg/day (2 to 5 days) or 850 ag/kg/day (3 to 1 0 days). Severe weight loss and mortalities were observed In all 3 groups. Histopathologic changes involving the lungs, gastrointestinal tract, liver, spleen, thymus, sternal bone marrow, epididymis, testes, renal tubules, heart, and hematopoietic cells were observed in the treated rats. Following a 14-day recovery period, histopathologic changes among rats in the 850 mg/kg group were confined to the liver (with 1 rat also showing atrophic testes). " * These animals served as a common control group for H-12,402 and H-12,403. *** These animals served as a common control group for H-12,402 and II-12,396. **** Tissues examined histologically by Included: lungs, gastrointestinal tract, exterior body s u r f a c a ^ l l v e r ^ T e e r ^ ^ j p l e e n , thymus, sternal bone marrow, epididymis, testes, renal tubules, hematopoietic system, kidneys, brain adranalo, thyroid, parathyroid, eyes, trachea, stomach, duodenum, pancreas, cecum, colon, esophagus, and lymph n odes. t There will be a supplemental pathology report for the 3,400 mg/kg/day dose level animals when histology is coaplete. Company Sanitized. Does not contain TSCA Company Sanitized. Does not contain T SCA CBI ) Company Sanitized. Does not contain TSCA CBt Report by: Approved by: LH:vlm Pate Issued: March 16, 1979 sport Ho. 52-79 V  A r ttocir Lonnie Hinckle Technician r, M ______________ Gerald*^. Kennedy Chief, Acute Investigations