Genetic toxicity of 1,3-butadiene and styrene. 1993

H Norppa, and M Sorsa
Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.

1,3-Butadiene and styrene (vinyl benzene) are indirect genotoxins, which require metabolic activation to an epoxide form in order to bind covalently to DNA. Styrene 7,8-oxide, the active metabolite of styrene, is a carcinogen in rodents and has been shown to be genotoxic in most in-vitro test systems and at various genetic endpoints. The few studies available on the genotoxicity of styrene 7,8-oxide in vivo have yielded negative or (in mice) weakly positive results. Styrene is not usually genotoxic in vitro in assays employing a microsomal preparation from rat liver for metabolic activation, but positive effects have been obtained when other sources of metabolic activation, such as human erythrocytes, were provided. In vivo, styrene has been found repeatedly to be weakly genotoxic in the assay for sister chromatid exchange, especially in mice. Cytogenetic damage (usually chromosomal aberrations) has been reported in many studies of workers, mainly from the reinforced plastics industry where ambient concentrations of styrene may be high (50-100 ppm), while most negative findings are associated with exposure to lower levels. Butadiene is metabolized to two reactive forms, 1,2-epoxy-3-butene and further to 1,2:3,4-diepoxybutane, both of which are genotoxic in various test systems in vitro. The lowest effective dose of the latter is 1-2 orders of magnitude higher than that of the respective monoepoxide. Butadiene itself has not been tested extensively for genotoxicity in vitro. A species-specific difference in the responses of mice and rats at various cytogenetic end-points is seen in vivo, the lowest effective concentrations in rats being clearly higher than those in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D002070 Butadienes Four carbon unsaturated hydrocarbons containing two double bonds. Butadiene Derivative,Butadiene Derivatives,Derivative, Butadiene,Derivatives, Butadiene
D002869 Chromosome Aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS. Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D004784 Environmental Monitoring The monitoring of the level of toxins, chemical pollutants, microbial contaminants, or other harmful substances in the environment (soil, air, and water), workplace, or in the bodies of people and animals present in that environment. Monitoring, Environmental,Environmental Surveillance,Surveillance, Environmental
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012854 Sister Chromatid Exchange An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME. Chromatid Exchange, Sister,Chromatid Exchanges, Sister,Exchange, Sister Chromatid,Exchanges, Sister Chromatid,Sister Chromatid Exchanges
D013343 Styrenes Derivatives and polymers of styrene. They are used in the manufacturing of synthetic rubber, plastics, and resins. Some of the polymers form the skeletal structures for ion exchange resin beads.
D020058 Styrene A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. Styrene Monomer,Styrol,Vinylbenzene,Monomer, Styrene

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