Bacterial mutagenicity testing of urine from rats dosed with 2-ethylhexanol derived plasticizers

• Published in: Toxicology (Amsterdam) Vol. 34; no. 3; p. 247
• Main Authors: DiVincenzo, G D, Hamilton, M L, Mueller, K R, Donish, W H, Barber, E D
• Format: Journal Article
• Language: English
• Published: Ireland 15.03.1985
• Subjects: Animals; Hexanols - toxicity; Hexanols - urine; Male; Mutagenicity Tests; Mutagens - urine; Plasticizers - toxicity; Plasticizers - urine; Rats; Rats, Inbred Strains; Salmonella typhimurium - genetics
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/0300-483X(85)90175-1

Di-(2-ethylhexyl)phthalate (DEHP) produced hepatocellular carcinomas in rodents at high doses in a NTP/NCI bioassay. DEHP has not shown evidence of genotoxic activity in in vitro mutagenicity tests. We extended these studies by examining the mutagenicity of urine from rats dosed with DEHP, 2-ethylhexanol (2-EH), and several other 2-EH derived plasticizers, i.e. di-(2-ethylhexyl)adipate (DEHA), di-(2-ethylhexyl)terephthalate (DEHT) and tri-(2-ethylhexyl)trimellitate (TEHT). A modified Ames Salmonella/microsome assay was used to determine mutagenicity. Urine was pooled from male Sprague--Dawley rats dosed daily for 15 days with 2000 mg/kg of each test substance with the exception of 2-EH which was given at 1000 mg/kg. Direct plating procedures were used to determine the presence of mutagens in urine. Urine from rats dosed with 8-hydroxyquinoline was used as a positive control. There was no evidence that mutagenic substances were excreted in the urine by rats dosed with either DEHP, DEHA, DEHT, TEHT or 2-EH as determined in the presence or absence of rat liver microsomes, and with or without treatment with beta-glucuronidase/aryl sulfatase. Our findings indicate that the above test compounds were not converted to urinary metabolites that were mutagenic. These observations provide no evidence for a genotoxic mechanism for DEHP carcinogenicity in rodents.