Toxicity Characteristics of the 2-Chlorotriazines Atrazine and Simazine

Atrazine and simazine are chlorotriazine herbicides used broadly in agriculture to control annual grasses and broadleaf weeds. An extensive database on the toxicity of these triazines has been developed to support the safety of their use in agriculture. Atrazine and simazine have very low acute toxicity, with oral LD 50 S of >3000 mg/kg in rats. The results of a total of 38 mutagenicity studies on atrazine and 35 studies on simazine were included in a weight-of-the-evidence evaluation of the mutagenicity data leading to the conclusion that neither triazine possesses genotoxic activity. Oncogenicity studies in three strains of mice for both atrazine and simazine are negative. Neither triazine is oncogenic to male Sprague-Dawley (SD) rats nor is atrazine oncogenic to male and female Fischer 344 rats. However, in female SD rats both chlorotriazines induce the early occurrence and/or increased incidence of mammary gland tumors. Results of additional studies suggest that endocrinologic changes related to triazine administration are likely responsible for the mammary gland effects in female SD rats, and that a threshold dose exists for these findings.