Chronic Toxicity and Oncogenicity Study with Vinyl Acetate in the Rat: In Utero Exposure in Drinking Water |
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| Authors: | BOGDANFFY M S; TYLER T R; VINEGAR M B; RICKARD R W; CARPANINI F M B; CASCIERI T C |
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| Institution: | *Haskell Laboratory for Toxicology and Industrial Medicine, E. I. du Pont de Nemours and Co., Inc. P. O. Box 50, Newark, Delware 19714
 Union Carbide Chemicals and Plastics Company, Inc. Danbury, Connecticut
 Quantum Chemical Corporation Cincinnati, Ohio
 BP International Limited Sundbury on Thaines, England
¶Hoechst Celanese Corporation Somerville, New Jersey
Received August 25, 1993;
accepted March 3, 1994 |
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| Abstract: | The purpose of this study was to evaluate vinyl acetate forpotential chronic toxicity and oncogenicity when given to ratsin drinking water from the time of gestation. Target concentrationswere 0, 200, 1000, and 5000 ppm (v/v). Drinking water solutionswere prepared daily and analyzed at approximately 4-week intervals.F0 rats were given solutions of vinyl acetate for 10 weeks andthen mated. Offspring (F1 rats) were culled to equal group sizesof 60 main study rats and 30 rats for satellite groups. F1 ratswere treated for up to 104 weeks with interim kills of satellitegroups at 52 and 78 weeks. Body weights and clinical signs oftoxicity were monitored in F0 and F1 rats. Food and water consumptionwere measured in F1 rats. At Weeks 52 and 78 of the test, clinicalpathology and urine analysis examinations were conducted on10 rats per group from satellite animals. A complete gross andhistopathological examination of F1 rats was conducted at theinterim kills and on main study rats at Week 104. Average vinylacetate consumption over the course of the study in male ratsof the 200, 1000, and 5000 ppm groups was 10, 47, and 202 mg/kg/day,respectively. Female rats consumed an average of 16, 76, and302 mg/kg/day, respectively. Compound-related effects observedduring the study included a concentration-related decrease inwater consumption among rats of the 1000 and 5000 ppm groupsand a decrease in food consumption among rats of the 5000 ppmgroups. Concurrent body weight decrement was observed only inthe 5000 ppm groups. There were no compound-related effectson clinical chemical, hematological, or urinalysis parameters.The pathological evaluations revealed no compound-related effectson organ weight, nonneoplastic lesions, or neoplastic lesions.The no-observable-effect level was 200 ppm while the no-observable-adverse-effectlevel was 1000 ppm. Under the conditions of this study, vinylacetate showed no evidence of systemic target organ toxicityand was not oncogenic when administered to rats in the drinkingwater. |
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