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Among polychlorinated naphthalenes (PCNs), listed by the Stockholm convention as Persistent Organic Pollutants (POPs), hexachloronaphthalenes are considered the most toxic and raise the highest concern. Of these, 1,2,3,5,6,7-hexachloronaphthalanene (PCN67) is considered the main congener affecting human health due to its hepatotoxicity and its ability to disturb the reproductive, endocrine, and hematological systems. It is also prevalent in human serum/plasma, milk, and adipose tissue. However, little is known about its neurotoxicity, despite the fact that anorectic effects have been observed in workers occupationally exposed to PCNs and in animal research on PCN67. Since dopamine is involved in many aspects of food intake, the aim of this study was to confirm whether PCN67 affects dopamine synthesis in differentiated PC12 cells, a widely used model of neurosecretion. Our results show that exposure to PCN67 resulted in diminished dopamine content and release. Moreover, PCN67 also affected the expression of tyrosine hydroxylase and lowered the expression of vesicular monoamine transporter 1 (VMAT1). In addition, significantly lower expression of antioxidant enzymes, including catalase, glutathione peroxidase and copper/zinc superoxide dismutase, was observed in comparison to the vehicle. In conclusion, PCN67 appears to disturb dopaminergic transmission by altering tyrosine hydroxylation, reducing VMAT1 expression and impairing antioxidant protection. Our study provides a potential mechanism for how PCN67 may cause dopamine deficiency and contribute to neuronal death by affecting cellular antioxidant potency; however, this conclusion requires further research.

Many persistent organic pollutants (POPs) exhibit endocrine disrupting activity but studies on some POPs, e.g., polychlorinated naphthalenes (PCNs), are very scarce. The present study investigates the (anti)estrogenic and (anti)androgenic activities of 1,2,3,5,6,7-hexachloronaphthalane (PCN67) and 1,3,5,8-tetrachloronaphthalene (PCN43) using the yeast estrogen and androgen reporter bioassays. Among the tested substances, antiestrogenic response was only shown by PCN67. The strongest inhibition of estrogenic activity (up to 17.4%) was observed in the low concentration ranges (5 pM - 0.5 nM) in the presence of 1.5 nM 17β-estradiol. Both tested compounds showed partial estrogenic activity with a hormetic-type response. However, both studied chemicals showed strong antiandrogenic effects: their potency in the presence of 100 nM 17β-testosterone for PCN43 (IC50 = 2.59 μM) and PCN67 (IC50 = 3.14 μM) was approximately twice that of the reference antiandrogen flutamide (IC50 = 6.14 μM). It cannot be excluded that exposure to PCNs, together with other endocrine disrupting chemicals (EDCs), may contribute to the deregulation of sex steroid hormone signaling.

Although Persistent Organic Pollutants (POPs) are some of the most dangerous environmental toxicants, data on their impact on hemostasis are virtually limited. 1,2,3,5,6,7-hexachloronaphthalene (PCN67) seems to be one of the most toxic congeners of polychlorinated naphthalenes (PCNs), which have recently been listed as POPs. The toxic effects of PCNs are similar to other chlorinated aromatics, e.g. polychlorinated dibenzo-p-dioxins (PCDDs), so an impact on hemostasis could not be excluded. Therefore, this study examines, for the first time, if short-term (two and four weeks) exposure of a mixture of hexachloronaphthalene congeners with a PCN67 as a predominant component to female Wistar rats may have an impact on selected hemostasis parameters, such as overall potential and kinetic parameters of clot formation and fibrinolysis; hematology and basic coagulology parameters. It also examines the influence of PCN67 on the stability of erythrocyte membranes. Obtained results indicate that PCN67 may be an important disturbing factor regarding both coagulation and fibrinolysis processes, as well as platelet count. Exposure to PCN67 significantly affected clot formation and lysis processes and diminished fibrinogen concentration after both administration periods. After two weeks of administration, an increased activated partial thromboplastin time (APTT) was noted; after four weeks - decreased platelet count with concomitant increased in mean platelet volume. Moreover, PCN67 may exert adverse effects on the red blood cells membrane stability, which were manifested by a statistically significant increase of red blood cells lysis.