Estrogenic activities of two synthetic pyrethroids and their metabolites

Synthetic pyrethroids (SPs) are among the most common pesticides in current use, and so far, several SPs have been assessed for their potential estrogenicities by various methods. Previous studies have shown that the estrogenicities partly come from their metabolites. Although considerable information is available with respect to the metabolism and environmental degradation of SPs, little is known about the estrogenicities of the metabolites. In this study, permethrin (PM) and β-cypermethrin (CP), as well as their metabolites (3-phenoxybenzoic alcohol (PBCOH), 3-phenoxybenzaldehyde (PBCHO) and 3-phenoxybenzoic acid (PBCOOH) were evaluated for their estrogenic activities in the MCF-7 human breast carcinoma cell line. In the MCF-7 cell proliferation assay, PM and CP exhibited significant estrogenic activities at 10⁻⁷ mol/L, comparable to 17β-estradiol (E₂) of 10⁻⁹ mol/L, with the relative proliferative effect ratios of 55.4% and 56.3%, respectively. The real-time quantitative polymerase chain reaction (qRT-PCR) results confirmed the estrogenicities of PM and CP with significant alteration of pS2 and ERα mRNA levels observed at 10⁻⁶ mol/L. For the three major metabolites, PBCOH and PBCOOH exhibited estrogenic activities in all assays, while no significant estrogenic responses was observed for PBCHO compared to the vehicle control. In particular, PBCOH had even slightly stronger estrogenic activity than its parent compounds, indicating that metabolism may be one of the reasons for the estrogenicities of the SPs. Given the widespread use of SPs, the toxicological effects of parent compounds and their metabolites should be taken into consideration in the risk assessment of SPs.