Metabolic Interactions of 1,3-Butadiene and Styrene in Male B6C3F1 Mice

Butadiene and styrene are a mixture of hazardous air pollutants found in the workplace of industries producing polymers such as styrene–butadiene rubber. Both butadiene and styrene require metabolic activation to exert their genotoxic effect; therefore metabolic interactions may influence their genotoxicity. Our objective was to quantitate potential metabolic interactions in mice exposed to a mixture of butadiene and styrene. The rate of metabolism of butadiene and styrene was estimated from the steady-state rate of uptake of the chemicals by male B6C3F1 mice exposed for 8 hr in a dynamic, whole-body inhalation system to 100 or 1000 ppm butadiene in combination with 0, 50, 100, or 250 ppm styrene. Styrene, styrene oxide, 1,2-epoxy-3-butene, and 1,2:3,4-diepoxybutane concentrations in blood were measured by gas chromatography–mass spectrometry at 2, 4, 6, and 8 hr of exposure. As the styrene concentration in the mixture increased, the rate of butadiene metabolism was inhibited up to 48%. 1,2-Epoxy-3-butene blood concentrations were increased by approximately 1.5-fold; however, 1,2:3,4-diepoxybutane blood concentrations were unaffected. Styrene uptake in the inhalation system was inhibited slightly by exposure with butadiene, but styrene blood concentrations increased significantly as the butadiene concentration in the mixture increased to 1000 ppm. Blood concentrations of styrene oxide increased approximately 1.6-fold for the 250-ppm styrene exposures when the butadiene concentration was increased from 0 to 1000 ppm. The data suggest that metabolic interactions occurred among the reactive metabolites (e.g., competition for detoxication pathways) as well as between butadiene and styrene in mice exposed to mixtures of butadiene and styrene. However, metabolic interactions were significant only at concentrations of butadiene and styrene higher than those typically observed in the workplace of industries producing polymers of butadiene and styrene.