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I, E, du Font de Neraours and Company Haskell Laboratory For Toxicology and Industrial Medicine AR226-2821 TEH-DOSE SUBACOTE ORAL TEST (RATS) The test material (H-3824) was administered dally by stomach tube to each of six young ad five t$iaes a week for two weeks, Groups of three test rats, along w Lth eont rols, weze sacri fleed foi aceer tlie last treatment. Results a a lw Indlvl dual LiMrer Weight (R> Aquftoua 4 Hours After 14 Days After 4 Hours Saspo Doae 10th Dose 10th I )ose 10th % (mg/kR/day) Mortality Toxic Signs Control Teat Control Test Contro- 5 220 0/6 Slight depression in rate 17.6 15,5 19.7 16.8 5.1 oanfdwreeicgohvt egryainpedriuordinsg test 16.7 15.3 17.0 16.0 5.0 16.1 18.8 16.3 17.8 4.8 0.5 22 0/5** Very slight depression in rate of weight gain during test period One animal accidentally killed with 8th dose. 17.6 14.7 19.7 16.0 5.1 16.7 14.5 17.0 16.3 5.0 16.1 16.3 18.4 4.8 & ACUTE ORAL TEST (RABBITS) Procedure: The test material (H-38-24) was administered as 3313% aqueous suspension by intragastric in albino rabbits in single doses. Survivors were killed i.0-l6 days later. Results; Dose (mR/kfO 5000 ,3,4n0n0 2250 1500 Mortality 0/1 ,,0/1, 0/1 0/1 Toxic Signs Weight losses for 12 and 8 days, respectively, at 5000 and 3400 ing/kg; decreased f.,od and water consumption at these doses; urine of a11 rabbits, first 24 hours, clear, foamy and brown Weight When Killed Body (e) Liver (e) 2189 135 2,,4,,86 3137 inion . 170 g Liver Wt Body Wt 6.2 41.-14 5.4 ACUTE SKIN ABSORPTION TEST (RABBITS) ^.fSSS^SS.6: The teat material (H-3825), aa rppplwri, vaa flppllo^ In n1ng1a rfnnoa fn ^-he finely clippe rabbits and rubbed in lightly with a glass rod. The animals were restrained In wooden stocks for 24 ^ skin was washed with warm water. Survivors were killed 14 days later. '5 Results: B> -------- ^ Dose*** (mn/ta^ 1' 3765 ^ 2250 | "OO Mortality 0/1 0/1 0/1 Toxic Sl^ns None WelRht When Killed Body (e) Liver (s) 2869 122 2657 167 2734 88 Liver Wt " ,- Body Wt ---- 4.2 6.3 3.2 0 ? TEH-DOSE SUBACUTE SKIN ABSORPTION TEST <RABBITS> ar ^ Procedure.: ^i^81'11for The test material (H-3825), as received, was two week8* After 6at^ exposure. Which lasted rubbed Into the clipped six hours, the material akin of six male alb was washed from the ^ Three teat and three control rabbits were sacrificed four hours and 14 days after the laat treatment a. ------------------. ^ g *** Based on active ingredient. - Reaulta: Dose**** (mg/kg/day^ 1500 Mortality 0/6 Toxic Signs None **** Based on active ingredient. Individual Liver Weights (g) 4 Hours After 14 Days After 10th Doae 10th Dose Control Teat Control Teat 131 103 86 105 82 110 124 180 108 140 139 157 Individual L 4 Hours Afte 10th Dose Control Tes 4.6 4.2 3.6 4.6 4.3 5.2 Summary: L^^^^^3ihibited low cumulative oral toxieity for the male rat when administered repeated 22 ing/kg/day or 220 ing/kg/day. Except for a very slight adverse effect upon weight gain, there were toxieity. The livers of these test animals Kereeraaimetrically and histologically within the range be contrasted with the results obtained vhea'flfffffuaa administered orally to rate at a rate of. 22 of these animals were extremely heavy and histologically abnormalC|^^H^IIHI^HHHHHI^B 7|J'--1^------^--^|Iias Low acute oral toxieity and low acute dermal toxieity for the male rabbit, the Doses (ALD'e) being greater than 5000 mg/kg and greater than 3765 ing/kg, ^respectively. Vl--------H'as for the male rabbit when administered repeatedly via the dermal route at a dose of 1500mg7kg7d8y. L body weight ratios were considered normal for all the rabbits examined; moreover, the livers did not e which could be attributed to the administration of the test material. o The difference between the response of the rat and that of the rabbit to acute oral doses to liver weight suggests a species difference. Organs other than liver were not studied histologica / ^\U^f ^ HS/mfa Date; May 6. 1964