Dose-response genotoxicity of triclosan in mice: an estimate of acceptable daily intake based on organ toxicity.

Triclosan (TCS) is widely used and it bioaccumulates in humans. We found that TCS induced DNA damage in TK6 cell in our previous work. Herein, we performed a pilot assay of the TK6 cell/TK gene (TK+/-) mutation assay without metabolic activation for 24 h and found that TCS significantly induced mutation frequency. We further investigated the dose-response toxicity and genotoxicity of TCS. We combined the newly developed Pig-a gene mutation assay with bone marrow micronucleus (MN) test in a 19-day short-term study. ICR mice were administered orally with TCS at six dose levels from 0 to1000 mg/kg/day. We quantitatively assessed the dose-response relationships for the Pig-a assay, MN test, and organ coefficient data for possible points of departure (PoDs) by estimating the benchmark dose using PROAST software. We did not observe elevated Pig-a mutant frequency or MN frequency in TCS-treated mice. But a dose-dependent and statistically significant increase in liver organ coefficient data was observed. The PoD and acceptable daily intake based on organ toxicity were further developed and no greater than 1.82 and 0.00182 mg/kg/day, respectively, indicating that the toxicity of TCS may has been underestimated in previous studies and greater attention should be paid to low-level TCS exposure.