Mutagenicity evaluation of phthalic acid esters and metabolites in salmonella typhimurium cultures

Abstract

The mutagenic potential of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), and di‐2‐ethylhexyl phthalate (DEPH), as well as metabolites of DEHP‐i.e., mono‐2‐ethylhexyl phthalate (MEHP), 2‐ethylhexanol (2‐EH), and phthalic acid (PA)—were tested in Salmonella typhimurium cultures using the Ames test procedure. The compounds were tested on strains TA98, TA100, TA 1535, TA 1537, TA 1538, and TA2637 for base‐pair substitution or frameshift‐type mutations. Spot tests yielded negative responses for all compounds with the strains tested. Each compound was tested for a dose‐effect relationship in the TA98, TA100, TA1535, and TA 1538 systems. DEP and DBP exhibited a mildly positive response in both TA 100 and TA 1535 cultures, and DMP showed a similar response in TA 1535. Normalization of the data for cytotoxicity of DMP suggests TA 100 has a mildly positive effect. The higher doses of these compounds exhibited some cytotoxic effects. The mutagenic effects were apparently abolished by the addition of S9 fraction in TA 100 and TA 1535 cultures, while no effect, other than cytotoxicity, was observed in the TA98 and TA 1538 systems. DEHP, MEHP, 2‐EH, and PA exhibited no mutagenicity in any of the strains of Salmonella typhimurium tested, with or without S9 metabolic activation. MEHP and 2‐EH, however, exhibited a moderate cytotoxic effect in most cultures.