An assessment of the (anti)androgenic properties of hexachloronaphthalene (HxCN) in male rats

The persistent organic pollutants (POPs) defined by the Stockholm Convention include polychlorinated naphthalenes (PCNs); of these, the most toxic, persistent, abundant, dioxin-like congeners found in human tissues are the hexachloronaphthalenes (HxCNs). Recent research also indicates that PCNs may disrupt hormonal homeostasis. The aim of this study was to evaluate the (anti)androgenic action of HxCN. Immature, castrated male Wistar rats were exposed per os to HxCN in corn oil at daily doses ranging from 0.3-3.0 mg kg-1 for 10 days. According to the OECD 441 protocol (Hershberger Bioassay), the anti-androgenic assay groups were co-exposed with testosterone propionate (TP), while the androgenic groups were not. TP was used as the reference androgen (subcutaneous daily doses of 0.4 mg kg-1), and flutamide (FLU) as the reference antiandrogen (per os daily doses of 3.0 mg kg-1). Five assessor sex tissues (ASTs) were weighed: ventral prostate, seminal vesicles, levator ani-bulbocavernosus muscle (LABC), Cowper’s glands and glans penis. HxCN + TP significantly decreased the weight of the ventral prostate and seminal vesicle indicating an anti-androgenic action via 5α-reductase inhibition. These weight changes were also accompanied by abnormalities in cell morphology and hormonal disturbances: lowered levels of the testosterone and thyroid hormones thyroxine and triiodothyronine. Disturbances were also noted in the lipid profile, viz. total cholesterol, triglycerides and high-density lipoprotein and non-HDL fraction content. However, the direction of these changes differed depending on the size of the HxCN dose. No dose-effect relationship was noted for most of the obtained results; as such, exposure to even small HxCN doses run the risk of anti-androgenic effects in the general population, especially when encountered in combination with other POPs and endocrine-disrupting chemicals in the environment.