Previous studies have reported that
atrazine, a widely used
herbicide that selectively inhibits photosynthesis in broadleaf and grassy weeds, has adverse effects on reproductive function in the male, suggesting a direct effect of
atrazine on the hypothalamicpituitary-testicular axis. As yet, however, no studies have critically examined the doses of
atrazine that elicit such effects, and few have focused on the mechanism by which
atrazine acts. Herein we report a dose-response study of the effects of
atrazine ingestion on reproductive function in male Sprague-Dawley rats during a critical developmental period, the peripubertal period.
Atrazine was administered by gavage to rats from day 22 to day 47 of age, at doses of 1-200 mg/kg
body weight per day.
Atrazine administration of up to 50 mg/kg per day had no effect on any of the measured variables. Serum
testosterone concentration was reduced by
atrazine at doses of 100 and 200 mg/kg per day, as were seminal vesicle and ventral prostate weights. Intratesticular
testosterone concentration was reduced in parallel with serum
testosterone, suggesting that the reductions in serum
testosterone resulted from reduced
testosterone production by Leydig cells or from changes in
testosterone metabolism within the testis, or both. Serum
luteinizing hormone (LH) concentration was reduced despite the reduced serum
testosterone, suggesting an effect on the hypothalamus, the pituitary gland, or both. At the termination of the study, the average
body weight of rats receiving
atrazine at 100 mg/kg per day was found to be reduced by approximately 9%. This suggested the possibility that the effects of
atrazine on the reproductive tract may not be direct, but rather, the noted deficits of the male reproductive tract resulted from reduced food intake by the treated rats. We tested this by feeding control (vehicle-gavaged) rats amounts of food equivalent to that consumed by the
atrazine-fed rats, and then assessing reproductive tract endpoints. Even mild food restriction resulted in reductions in serum
testosterone concentration, in the weights of
androgen-dependent organs, and in serum LH concentration; the same deficits that were seen in
atrazine-gavaged rats. Indeed, the effects of
atrazine on the male reproductive tract seen in rats receiving
atrazine at greater than 50 mg/kg per day could not be distinguished from the effects of reduced food consumption. These results suggest that caution must be exercised before concluding that
atrazine (or any potentially toxic chemical) has direct, detrimental effects.