A pharmacokinetic/mechanism-based analysis of the carcinogenic risk of butadiene.
Center for Technology, Policy and Industrial Development, Massachusetts Institute of Technology, Cambridge, Massachusetts, Report CTPID 87-3, 1987 Nov; :1-122
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. Use of results from the mouse study in making an assessment of human risk was considered. A comparison was made of the results of the current study and those obtained for similar pharmacokinetic model studies for perchloroethylene and ethylene-oxide. 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.
NIOSH-Cooperative-Agreement; Cooperative-Agreement-U60-CCU-100929; Cancer-rates; Carcinogens; Synthetic-rubber-manufacturing; Synthetic-rubbers; Laboratory-animals; Risk-analysis; Mortality-rates; Pharmacodynamics; Models; Kinetics
Final Cooperative Agreement Report
NTIS Accession No.
Center for Technology, Policy and Industrial Development, Massachusetts Institute of Technology, Cambridge, Massachusetts, Report CTPID 87-3, 122 pages, 41 references