title: Genotoxicity and cytotoxicity in male B6C3F1 mice following exposure to mixtures of 1,3-butadiene and styrene.
abstract: 1,3-Butadiene and styrene are oxidized, in part, by cytochrome P450 2E1 and have been shown to metabolically interact in rodents exposed by inhalation to mixtures of both compounds. Because the reactive metabolites of butadiene and styrene are thought to be responsible for the toxicity 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 genotoxicity and cytotoxicity in male B6C3F1 mice exposed to mixtures of butadiene and styrene. Male B6C3F1 mice were exposed to 6.25, 62.5, 200, or 625 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 assessed by quantitating the frequency of micronucleated polychromatic erythrocytes in bone marrow. Cytotoxicity was assessed by counting total spleen and thymus cells and by quantitating the frequency of polychromatic erythrocytes in the peripheral blood. Butadiene and mixtures of butadiene 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 frequency following exposure to butadiene alone. Styrene and mixtures of butadiene and styrene were cytotoxic in mice, as shown by significantly decreased number of spleen cells. Exposure to mixtures of butadiene and styrene with butadiene concentrations of 62.5 or 625 ppm significantly reduced the number of thymus cells. Exposure to 200 ppm or 625 ppm butadiene alone, or to mixtures of 200 ppm or 625 ppm butadiene and 50 ppm styrene, significantly reduced the frequency of polychromatic erythrocytes in the peripheral blood. The results of the study demonstrate that exposure to mixture of butadiene and styrene does not reduce the respective genotoxicity of butadiene or cytotoxicity of styrene.
authors.affiliation: Curriculum in Toxicology, University of North Carolina, Chapel Hill, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Leavens
authors.forename: G M
authors.initials: GM
authors.lastname: Farris
authors.forename: R A
authors.initials: RA
authors.lastname: James
authors.forename: R
authors.initials: R
authors.lastname: Shah
authors.forename: V A
authors.initials: VA
authors.lastname: Wong
authors.forename: M W
authors.initials: MW
authors.lastname: Marshall
authors.forename: J A
authors.initials: JA
authors.lastname: Bond
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002070:Butadienes / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D020058:Styrene; D013343:Styrenes / Q000378:metabolism / Q000633:toxicity*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D018675:Toxicity Tests
chemical_list: D002070:Butadienes; D002273:Carcinogens; D004852:Epoxy Compounds; D009153:Mutagens; D013343:Styrenes; D020058:Styrene; C024370:3,4-epoxy-1-butene; C007366:diepoxybutane; C013690:styrene oxide; C031763:1,3-butadiene