Triazines

Abstract

The chemical class chloro-s-triazines herbicides includes atrazine, simazine, propazine, and terbuthylazine. Atrazine and simazine are more commonly used, more so for atrazine. This discussion is focused on atrazine and simazine and their metabolites desethyl-s-atrazine, desisopropyl-s-atrazine (DIA), and diaminochlorotriazine. For this group of chemicals, US Environmental Protection Agency (EPA) has conducted a cumulative risk assessment based on neuroendocrine effects as the common mechanism of toxicity. Current interest is focused on potential carcinogenicity and other potential neuroendocrine effects. Chronic studies on atrazine, simazine, and their metabolites showed an elevated incidence of mammary tumors in female Sprague–Dawley (SD) rats, but not in Fischer rats or mice. The underlying mechanism involves a reduction in the release of gonadotropin releasing hormone from the hypothalamic–pituitary–gonadal axis in the rats. This is followed by attenuation of the afternoon pituitary luteinizing hormone (LH) surge, leading to a lengthening of the estrus cycle that increases estrogen levels that, in turn, is associated with an increased incidence of mammary tumors in this rat model. Epidemiological studies did not show evidence of carcinogenicity. The US EPA and the European Union determined a rat-specific hormonal mechanism for mammary tumors that is not relevant to humans. International Agency for Research on Cancer has placed atrazine into Group 3: not classifiable as to its carcinogenicity in humans. The US EPA Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Science Advisory Panel did not agree that a lack of strong evidence justifies a conclusion that atrazine is not likely to be a human carcinogen. The Agency noted that reproductive effects are the most sensitive effects observed in atrazine toxicity studies, and the registration review of atrazine is scheduled to begin in 2013. A consideration is whether the chemicals' effects on endocrine responses have an impact on reproduction, development, and the brain related or unrelated to carcinogenesis. Although, the mechanism for mammary tumor induction in female SD rats is believed not to occur in humans, the reduction of LH may occur and produce other effects. Data deficiencies exist and the effects on the endocrine, neurotoxicity, immunotoxicity, and developmental and reproductive effects continue to be a subject of discussion and research.