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AR226-2820 Material Tested: Submitted by: E. I. du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine HASKELL LABORATORY REPORT NO. 11-64 ganic Chemicals Department, Jackson Laboratory Haskell No Other Code ACOTE ORAL TEST Procedure; The material was administered, as received, by stomach tube to young adult Call-CD male rats Survivors were sacrificed 14-15 daya later. Result 8; Dose* fa>B^) 11,000 1,500 5,000 2,250 Mortality** S - 15 d. S - 15 d. S - 14 d. S - 14 d. Toxic Signs Slight initial weight loaa Weight When Killed Body (an) Liver (gm) 345 23.2 334 18.9 314 15.3 305 15.7 ^y" wt- Body Wt. x 100 -- 6.7 5.7 4.9 5.1 * ** Baaed S- ( o ) n a d. c = t i ve Sa ci nri gfi cree dd i e( n)th, i]a_y_s_ ____ after ______ dosing TEN-DOSE SUBACuTE ORAL TEST Procedure; The test material, as received, was administered daily by stomach tube to each of six youn rats, five times a week for one or two weeks. Where animals survived, groups of three teat rats, along sacrificed four hours and 14 days after the last treatment. ^conta Comp^S^28'-30857 Results: Dose* fmgyke/day) 5,000 2,250 Mortally 6/6 0/6 Toxic Signs Death after 3-5 doses, weight loss, diarrhea, discoloration of perineal area. First Week: slight weight loss Second Week; slightly depressed rate of weight gain. Reeovegy Period; none; weight gain parallel that of. controls * Based on active ingredient 2 - Individual Liver Weights (a) 4 hours after 14 days after 10th dogse 10th doge Control Teat Cootrol Test 13.9 16.6 17.4 29.8 35.2 30.2 16.8 16.6 18.6 24.2 25.0 23.9 Individual Liv 4 hours after 10th doae Control Test 4.5 11.5 5.0 11.6 5.0 11.8 r i L male rac, its Appuxiiate Lethal Doee (ALD) being greater thanTT,000 mg/kg of bodywiight, based on The compound produced an increase in the liver weight of the animal doaed at 11,000 ing/kg, and possib 'Bosed at 7,500 mg/kg. \ji^f^SIhouB high cumulative oral toxic&ty. When administered to each of six rats at a d day, all1. died after thaving received three to five doses. Two of the animals examined hietologically terminal lung damage, in addition, their stomach contents were in the form of a firm core that waaBO the digestive tract in a normal Bander., When administered to rats at a dose of 2,250 mg/kg/day,|||||^ extremely heavy livers in animals sacrificed after the tenth dose, with evidence of some recovery' me sacrificed after a 14-day recovery period. Microscopically, the heavy livers contained some enlarged enlarged nuclei which had prominent nucleoli or an uneven distribution of chromatin material. The le were not those usually indicative of deg<aerative changes. o ;sn' .Sa^^00" ^ - 3 - oJ||B|BIHHHHIBHHBgupon Because of the effect the liver of rats after high le their use as a component of food wrappi'-" "tterlal would require (a) that studies be conducted to determ if any, to which they migrate from wrappiu\ " foods and (b) that additional feeding studies of longer ated to determine a "no-effect'" level as ? r- Liminary to securing Food and Drug Administration approva Report by: Approved by: enry Sherm Toxicologis .^/- ^z . D. B. Hood Chief, Toxicology HS/ujd Oste: February 3. 19f4 nocs Co^3^5'