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Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)
Citation:
Laws, S., R. Cooper, AND B. Riffle. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR). Presented at Society of Toxicology Meeting, March 10 - 14, 2013.
Impact/Purpose:
This abstract will be presented at the Society of Toxicology meeting March 10-14, 2013, San Antonio, TX.
Description:
While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone (P4) over 21 days after exposure to the chlorotriazine herbicide ATR. Adult Wistar male rats were dosed by oral gavage with 0, 5,25, 75, or 200 mg/kg/d given either as a single dose or multiple daily doses (7, 14, or 21 doses) at 0900 hrs (nadir of circadian CORT rhythm) and were decapitated 30 minutes after the last dose (n=lO/group). Necropsy body weight was significantly lower than controls (p <0.05) only in the 200 mg/kg group dosed for 21 days. Adrenal weights were unaffected by ATR at anytime point. Serum CORT was elevated in response to a single dose of ATR (LOEL 5mg/kg). Serum CORT was also increased following 7 (LOEL 75mg/kg), 14 (LOEL 25mg/kg), and 21 (LOEL 75mg/kg) daily doses. A similar profile was observed for serum P4 following a single dose (LOEL 25 mg/kg), 7 (LOEL 75 mg/kg), 14 (LOEL 75 mg/kg), or 21 (LOEL 200 mg/kg) doses of ATR. Urinary CORT (ratio of CORT/urinary creatinine), measured over a 6 hr period after dosing, was significantly increased in the ATR groups (e.g., LOEL for one dose = 75 mg/kg, LOEL for 21 doses = 75 mg/kg). These data demonstrate a HPA response after a single and multiple daily doses of ATR following the higher doses (e.g., 75 and 200 mg/kg), but the pattern of response was unclear at the lower doses examined (e.g. <25 mg/kg). This abstract does not reflect US. EPA policy.