GENOTOXICITY AND CYTOTOXICITY IN MALE B6C3F1 MICE FOLLOWING EXPOSURE TO MIXTURES OF 1,3-BUTADIENE AND STYRENE

1,3-Butadiene and styrene are oxidized, in part, by cytochrome P450 2E 1 and have been shown to metabolically interact in rodents exposed by inhalation to mixtures of both compounds. Because the reactive metabol ites of butadiene and styrene are thought to be responsible for the to xicity of each compound, metabolic interactions may alter the response in animals exposed to mixtures of butadiene and styrene compared with the response in animals exposed to butadiene alone or styrene alone. The purpose of this study was to quantitate alterations in genotoxicit y and cytotoxicity in male B6C3F1 mice exposed to mixtures of butadien e and styrene. Mole B6C3F1 mice were exposed to 6.25, 62.5, 200, or 62 5 ppm butadiene alone, 50 ppm styrene alone, or mixtures of 6.25, 62.5 , 200, or 625 ppm butadiene and 50 ppm styrene. Genotoxicity was asses sed by quantitating the Frequency of micronucleated polychromatic eryt hrocytes in bone marrow. Cytotoxicity was assessed by counting total s pleen and thymus cells and by quantitating the frequency of polychroma tic erythrocytes in the peripheral blood. Butadiene and mixtures of bu tadiene and styrene were genotoxic in mice, as shown by a significant increase in the Frequency of micronucleated polychromatic erythrocytes . The increased frequency following exposure to mixtures of butadiene and styrene was not significantly different compared with the frequenc y Following exposure to butadiene alone. Styrene and mixtures of butad iene and styrene were cytotoxic in mice, as shown by significantly dec reased number of spleen cells. Exposure to mixtures of butadiene and s tyrene with butadiene concentrations of 62.5 or 625 ppm significantly reduced the number of thymus cells. Exposure to 200 ppm or 625 ppm but adiene alone, or to mixtures of 200 ppm or 625 ppm butadiene and 50 pp m styrene, significantly reduced the frequency of polychromatic erythr ocytes in the peripheral blood. The results of the study demonstrate t hat exposure to mixtures of butadiene and styrene does not reduce the respective genotoxicity of butadiene or cytotoxicity of styrene. (C) 1 997 Wiley-Liss, Inc.