The endocrine-disrupting potential of four chlorophenols by in vitro and in silico assay.

Chlorophenols (CPs) have mainly been used as a biocide, wood treatment agent and a byproduct of bleaching in paper mills. They have been a topic of concern due to their wide spread and potential effects on human and wildlife. However, data on the thresholds and effects of the number of chlorine atoms on the endocrine-disrupting potential of CPs remain scarce. In this study, we adopted two in vitro models (reporter gene assays and H295R cell line) to investigate the endocrine-disrupting effects of four CPs (pentachlorophenol (PCP), 2,4,6-trichlorophenol (2,4,6-TCP), 2,4-dichlorophenol (2,4-DCP) and 2-chlorophenol (2-CP)). The molecular docking platform was adopted to further confirm the results of the in vitro assessment. Our results revealed that PCP exhibited oestrogen receptor alpha (ERα) agonistic activity at the concentration of 10 M and the value of REC was 1.9 × 10 M. PCP and 2, 4, 6-TCP showed anti-oestrogenic activities with a RIC value of 2.8 × 10and 2.9 × 10 M, respectively. Notably, only PCP exhibited thyroid hormone receptor beta (TRβ) antagonistic activity occurred at the concentration of 10 M, with a RIC value of 1.3 × 10 M. The oestrogenic and thyroid hormone effects of CPs may be dependent on the number of chlorine atoms. A higher number of chlorine atoms indicated the higher effect of four CPs. The results of molecular docking were consistent with the reporter gene assay. For H295R cell line assay, PCP induced the StAR upregulation, while CYP17 was downregulated in a concentration-dependent manner by PCP and 2, 4, 6-TCP.