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Effects of Prenatal Exposure to a Low Dose Atrazine Metabolite Mixture on pubertal timing and prostrate Development of Male Long Evans Rats.
Stanko, J. P., R. R. Enoch, J. L. Rayner, C. C. Davis, D. C. Wolf, S. E. Fenton, AND D. E. Malarkey. Effects of Prenatal Exposure to a Low Dose Atrazine Metabolite Mixture on pubertal timing and prostrate Development of Male Long Evans Rats. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 30(4):540-549, (2010).
These studies address the potential of an acute gestational exposure to atrazine (ATR) and a defined mixture of four of its metabolites, to alter reproductive development of male rat offspring. The defined mixture was designed to mimic atrazine (or other triazine) metabolites as they might occur in ground/surface water, and was concentrated to provide three dosage levels for the experiments. Puberty was delayed and statistically significant effects of the mixture on prostate development were apparent at the two highest doses of the mixture following a five-day prenatal treatment of pregnant rat dams. The lowest effective dosage of 0.435 mg mixture/kg body weight is below the current acute developmental NOAEL for atrazine of 6.25 mg/kg/d and lowest observed adverse effect level (LOAEL) of 12.5 mg/kg/d (U.S. EPA SAB report, 2003) when compared on identical split dosing regimens.
The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73mg AMM/kg body weight (BW), vehicle, or 100mg ATR/kg BW positive control, on gestation days 15-19. Preputial separation was significantly delayed in 0.87 mg and 8.73mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION
DEVELOPMENTAL TOXICOLOGY BRANCH