title: Mutagenicity of bisphenol A (4,4'-isopropylidenediphenol) in vitro: effects of nitrosylation.
abstract: Bisphenol A (4,4'-isopropylidenediphenol) is a common component of polycarbonate plastics and epoxy resins. Since bisphenol A-containing plastics and resins have found uses in food-contact items, its potential migration into foodstuffs and possible health consequences have been the focus of many recent studies. However, the potential mutagenic activation of bisphenol A by nitrosylation has received little attention. Incubation of bisphenol A with sodium nitrite under acidic conditions produced a yellow-brown product. When nitrosylated bisphenol A was tested in the Ames Salmonella/microsome assay at 100 ng to 1 mg/plate, dose-dependent increases in mutagenicity were found in both TA98 and TA100 Salmonella strains. These results indicated the presence of a direct-acting mutagenic activity causing both frameshift and base pair mutations, respectively. When compared to colony formation in untreated controls, the addition of rat liver S9 for metabolic activation had little influence on revertant colony formation. Unreacted bisphenol A dissolved in DMSO, acidic buffer, or inactivated nitrosylation solution showed negligible mutagenicity. When the nature of the mutagenic changes was examined using the Ames II trade mark Assay, a variety of base pair changes was found including T:A to A:T - S9, G:C to A:T +/- S9,C:G to A:T +/- S9 and C:G to G:C +/- S9. Bisphenol A also induced frameshift mutations at G:C sites. In addition, the presence of electrophiles was shown by the production of an intensely coloured orange-red product upon incubation of nitrosylated bisphenol A with the nucleophile 4-(4'-nitrobenzyl)pyridine. These findings suggest that migration of bisphenol A into nitrite containing foodstuffs, or its ingestion in the presence of nitrite, could lead to the formation of mutagenic compounds.
authors.affiliation: Toxicology Research Division, Food Directorate, Health Canada, Banting Research Centre,Tunney's Pasture, Ottawa, Ontario, Canada. Tim_Schrader@hc-sc.gc.ca
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Schrader
authors.forename: I
authors.initials: I
authors.lastname: Langlois
authors.forename: K
authors.initials: K
authors.lastname: Soper
authors.forename: W
authors.initials: W
authors.lastname: Cherry
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001559:Benzhydryl Compounds; D004247:DNA / Q000187:drug effects*; D016368:Frameshift Mutation; D007202:Indicators and Reagents / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008956:Models, Chemical; D009152:Mutagenicity Tests; D009153:Mutagens; D010636:Phenols / Q000633:toxicity*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012475:Salmonella / Q000187:drug effects / Q000235:genetics; D012977:Sodium Nitrite / Q000494:pharmacology; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D004247:DNA; D007202:Indicators and Reagents; D009153:Mutagens; D010636:Phenols; D011725:Pyridines; D012977:Sodium Nitrite; C008633:4-(4-nitrobenzyl)pyridine; C006780:bisphenol A; D000098826:Bisphenol A Compounds