Should Atrazine and Related Chlorotriazines Be Considered Carcinogenic for Human Health Risk Assessment?

Abstract

Chloro-s-triazines have been a mainstay of preemergent pesticides for a number of decades and have generally been regarded as having low human toxicity. Atrazine, the major pesticide in this class, has been extensively studied. In a number of experimental studies, exposure to high doses of atrazine resulted in increased weight loss not attributable to decreased food intake. Chronic studies of atrazine and simazine and their common metabolites show an elevated incidence of mammary tumors only in female Sprague Dawley (SD) rats. On the basis of the clear tumor increase in female SD rats, atrazine was proposed to be classified as a likely human carcinogen by US Environmental Protection Agency (EPA) in 1999. With Fischer rats, all strains of mice, and dogs, there was no evidence of increased incidence of atrazine-associated tumors of any type. Evidence related to the pivotal role of hormonal control of the estrus cycle in SD rats appears to indicate that the mechanism for mammary tumor induction is specific to this strain of rats and thus is not relevant to humans. In humans the menstrual cycle is controlled by estrogen released by the ovary rather than depending on the LH surge, as estrus is in SD rats. However, the relevance of the tumors to humans continues to be debated based on endocrine effects of triazines. No strong evidence exists for atrazine mutagenicity, while there is evidence of clastogenicity at elevated concentrations. Atrazine does not appear to interact strongly with estrogen receptors α or β but may interact with putative estrogen receptor GPR30 (G-protein-coupled receptor). A large number of epidemiologic studies conducted on manufacturing workers, pesticide applicators, and farming families do not indicate that triazines are carcinogenic in these populations. A rat-specific hormonal mechanism for mammary tumors has now been accepted by US EPA, International Agency for Research on Cancer, and the European Union. Chlorotriazines do influence endocrine responses, but their potential impact on humans appears to be primarily on reproduction and development and is not related to carcinogenesis.

Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France

“…Some toxic as Atrazine appears to interact strongly with a novel functional oestrogen transmembrane receptor, the G protein-coupled receptor 30 which is overexpressed in postpubertal germ cell tumours. 44,45 Other pathogenic processes could lead to spermatogenic defects. Environmental factors may either damage critical genes or alter gene expression by interfering with the epigenetic programming.…”

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“…However, later on, IARC removed atrazine from its list of suspected carcinogens (Jowa and Howd, 2011). Regardless of the various reports of atrazine effects on animals, the effects on humans are that due to a large oral dose of atrazine resulted in DNA lesions in the stomach, kidney, and liver of the rat (Pino et al, 1988).…”

Toxicity of Herbicides: Impact on Aquatic and Soil Biota and Human Health

“…However, a great number of epidemiological studies carried out with workers occupationally exposed to triazine herbicides indicate that these compounds do not have carcinogenic potential for these individuals. By analyses of different studies, it was observed that, although the chloro-s-triazine herbicides interfere in the endocrine responses of different species of mammals, their potential impact on humans seem to be mainly related to reproduction and development and not with human carcinogenesis [155].…”