Dose Range-Finding Report on the Immunotoxicity of Atrazine in Female B6C3F1> Mice (CAS No. 1912-24-9)
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) has been reported to be the most commonly employed herbicide in the United States. ATZ is routinely used in combating weeds in corn and sorghum crops and is also widely used in combination with other herbicides. As a result of its low biodegradability, it has a high potential for contaminating surface waters. Wide-spread contamination of ground water has been reported in the Midwest of the United States. Atrazine's potential environmental hazard for polluting drinking water has lead Italy to band this herbicide.
Atrazine was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the chemical manager. Thus, the purpose of these range-finding studies was to determine the doses of atrazine to be used in the protocol to determine the potential effects of atrazine on the immune system.
The range-finding studies were conducted in female B6C3F1 mice. The animals were administered atrazine daily for 14 days by oral gavage. Atrazine was prepared as a solution in sterile distilled water. In completing the range-finding protocol, three studies were conducted. In the first study, five dose levels of atrazine were used. The doses administered in the first study were 25, 50, 100, 250, and 500 mg/kg. In the second and third studies, doses of 25, 250, and 500 mg/kg were used.
The results of the atrazine range-finding studies demonstrate that, in the female B6C3F1 mouse, exposure to atrazine, administered by oral gavage for 14 days at doses of 500 mg/kg or less, was not overly toxic in that all of the animals survived the exposure period. However, exposure to doses of atrazine of 250 mg/kg or greater produced marked excitement in the animals. Decreases in body weight and body weight gain were observed at the 500 mg/kg dose level. Furthermore, significant decreases in spleen cell number, spleen weight and thymus weight were observed at doses of 250 and 500 mg/kg. Additionally, animals treated with the 500 mg/kg dose of atrazine had significant decreases in virtually all of the erythroid elements of the hematological parameters. Effects on these toxicological parameters suggested that a near maximum tolerated dose had been reached. No effect was observed in the plaque-forming cell assay on the IgM response to the T-dependent antigen sheep erythrocytes at any of the atrazine dose levels tested. However, an increase in the mixed leukocyte response was observed in animals treated with the 500 mg/kg dose of atrazine.
Based on the toxicological and immunological results of these range-finding studies, doses of 25, 250, and 500 mg/kg will be used in the atrazine protocol study.