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Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Butadiene,

PB88202817

Publication Date	1987
Personal Author	Hattis, D.; Wasson, J.
Page Count	146
Abstract	Rats and mice were exposed to butadiene (106990) for 6 hours/day, 5 days/week, in an effort to establish a pharmacokinetic model for this compound. Direct projections of human risks from models incorporating different blood/air partition coefficients were compared. Predictions were also given of different rat and mouse models for the overall production of butadiene epoxides in the rat and mouse bioassays. After corrections for pharmacokinetic differences, there were wide differences in the apparent carcinogenic susceptibility between the two species. All three compounds, even at the lowest currently proposed (1 part per million) standard levels, should be expected to produce appreciable cancer risks if the exposures are maintained over an entire working lifetime. The authors suggest that future research should include direct measurements of the relevant blood/air and tissue/air partition coefficients. Also, existing occupational cohorts of butadiene exposed workers should be followed to add to the mortality experience data.
Keywords	Butadienes Toxicity Rats Humans Laboratory animals Metabolism Exposure Concentration(Composition) Pharmacokinetics Pharmacodynamics Carcinogenesis
Source Agency	National Institute for Occupational Safety and Health
NTIS Subject Category	57Y - Toxicology 57Q - Pharmacology & Pharmacological Chemistry
Corporate Authors	Massachusetts Inst. of Tech., Cambridge. Center for Technology, Policy and Industrial Development.; National Inst. for Occupational Safety and Health, Rockville, MD.
Supplemental Notes	See also PB88-163209. Sponsored by National Inst. for Occupational Safety and Health, Rockville, MD.
Document Type	Technical Report
NTIS Issue Number	198817

Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Butadiene,

Pharmacokinetic/Mechanism-Based Analysis of the Carcinogenic Risk of Butadiene,
PB88202817

Publication Date	1987
Personal Author	Hattis, D.; Wasson, J.
Page Count	146
Abstract	Rats and mice were exposed to butadiene (106990) for 6 hours/day, 5 days/week, in an effort to establish a pharmacokinetic model for this compound. Direct projections of human risks from models incorporating different blood/air partition coefficients were compared. Predictions were also given of different rat and mouse models for the overall production of butadiene epoxides in the rat and mouse bioassays. After corrections for pharmacokinetic differences, there were wide differences in the apparent carcinogenic susceptibility between the two species. All three compounds, even at the lowest currently proposed (1 part per million) standard levels, should be expected to produce appreciable cancer risks if the exposures are maintained over an entire working lifetime. The authors suggest that future research should include direct measurements of the relevant blood/air and tissue/air partition coefficients. Also, existing occupational cohorts of butadiene exposed workers should be followed to add to the mortality experience data.
Keywords	Butadienes Toxicity Rats Humans Laboratory animals Metabolism Exposure Concentration(Composition) Pharmacokinetics Pharmacodynamics Carcinogenesis
Source Agency	National Institute for Occupational Safety and Health
NTIS Subject Category	57Y - Toxicology 57Q - Pharmacology & Pharmacological Chemistry
Corporate Authors	Massachusetts Inst. of Tech., Cambridge. Center for Technology, Policy and Industrial Development.; National Inst. for Occupational Safety and Health, Rockville, MD.
Supplemental Notes	See also PB88-163209. Sponsored by National Inst. for Occupational Safety and Health, Rockville, MD.
Document Type	Technical Report
NTIS Issue Number	198817