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Low-Dose, Gestational Exposure to Atrazine Does Not Alter Postnatal Reproductive Development of Male Offspring
Citation:
Impact/Purpose:
The purpose of this work was to determine the effect of low-dose gestational exposure to atrazine on sensitive endpoints of reproductive development. The techniques developed from these studies can be used to study gestation effects of other environmental chemicals important to the Agency.
Description:
There is growing evidence that xenobiotic exposure during the perinatal period may result in a variety of adverse outcomes when the developing organism attains adulthood. Maternal stress and subsequent exposure of the fetus to excess glucocorticoids may underlie these effects. Previous studies have demonstrated that high gestational doses of the chlorotriazine herbicide, atrazine (ATR), alter reproductive development of the male rat. ATR also acutely increases circulating glucocorticoids in adult rats. Therefore, the current studies investigated the development of male Sprague Dawley rat offspring following 1) lower doses of ATR during gestation and 2) an ATR dosing regimen designed to increase daily maternal glucocorticoid exposure. Timed-pregnant dams were administered I, 5,20, or 100 mg/kg/d ATR from gestation day 14-21 in a single oral gavage dose once per day (s.i.d) or the same dosage of ATR split into two doses per day (b.i.d.) to elevate glucocorticoid levels during the nadir and peak of the diurnal rhythm. Lower doses of ATR (1-20 mg/kg/d) administered s.i.d, or b.i.d, did not alter offspring body weight, neonatal testosterone production, timing of puberty, anogenital distance, adult testosterone or luteinizing hormone levels, or adult androgen-sensitive tissue weights. A similar level of maternal toxicity was observed at 100 mg/kg/d in both studies; however, this dosage administered b.i.d. resulted in significantly higher mortality of offspring after birth. Although birth weight was significantly reduced in high-dose litters of both studies (and remained lower through PND 59 in s.i.d, offspring), the reproductive development of these offspring was not altered. We conclude that gestational exposure to ATR at lower dosages ( ≤20 mg/kg/d) has no significant effect on pup survival or the male developmental endpoints assessed in these studies. Significant offspring mortality may have precluded observations of altered development in highdose litters. This abstract does not necessarily reflect EPA policy