title: Genotoxicity of styrene-acrylonitrile trimer in brain, liver, and blood cells of weanling F344 rats.
abstract: Styrene-acrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P < 0.0001) in MN-RET were measured in both male and female rats administered SAN Trimer. The RET population was reduced in high dose male rats, suggesting chemical-related bone marrow toxicity. Results of the Comet assay showed significant, dose-related increases in DNA damage in brain cells of male (P < 0.0074) and female (P < 0.0001) rats; increased levels of DNA damage were also measured in liver cells and leukocytes of treated rats. Chemical-related cytotoxicity was not indicated in any of the tissues examined for DNA damage. The results of this subacute MN/Comet assay indicate induction of significant genetic damage in multiple tissues of weanling F344 male and female rats after oral exposure to SAN Trimer.
authors.affiliation: Department of Genetic and Molecular Toxicology, Research Triangle Park, North Carolina 27709, USA. chobbs@ils-inc.com
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Hobbs
authors.forename: Rajendra S
authors.initials: RS
authors.lastname: Chhabra
authors.forename: Leslie
authors.initials: L
authors.lastname: Recio
authors.forename: Michael
authors.initials: M
authors.lastname: Streicker
authors.forename: Kristine L
authors.initials: KL
authors.lastname: Witt
mesh_terms: D000181:Acrylonitrile / Q000031:analogs & derivatives* / Q000633:toxicity*; D000818:Animals; D001773:Blood Cells / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D051381:Rats; D011916:Rats, Inbred F344; D020058:Styrene / Q000633:toxicity*; D013343:Styrenes / Q000633:toxicity*
chemical_list: D013343:Styrenes; D020058:Styrene; D000181:Acrylonitrile