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ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE HPA-AXIS ACTIVATION AND CAUSE CONDITIONED TASTE AVERSION.
Citation:
HOTCHKISS, M. G., R. L. COOPER, AND S. C. LAWS. ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE HPA-AXIS ACTIVATION AND CAUSE CONDITIONED TASTE AVERSION. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
This abstract is inteded to present data concernig the effects of atrazine, a chlorotriazine herbicide on measure of gastointestinal distress and potential Involvement of such effects on HPA-axis activation observed after administration of atrazine
Description:
Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a NOEL equal to 5mg/kg. The mechanism for these effects is unknown. To test whether administration of ATR causes hypothalamic-pituitaryadrenal (HPA)axisactivationthroughtheproduction ofageneralizedstressresponseresulting from gastrointestinal distress, we conducted both conditioned taste aversion (CTA) and pica behavior experiments. CTA is a classical conditioning paradigm that uses single trial learning of an association between consumption of a novel food (i.e. sucrose) and the development of an altered internal state, not necessarily gastrointestinal distress per se. Alternatively, pica behavior (consumption of a non-nutritive substance, i.e. kaolin) is displayed by animals given nauseainducing chemicals that do not possess an emetic (vomiting) reflex. Adult male Wistar rats were given a single oral dose of ATR (0, 5, 25, 50, 100, or 200mg/kg), the primary ATR metabolite desethyl-desisorpropyl atrazine (DACT; 135mg/kg), or lithium chloride (LiCI; 127mg/kg). Results from the CTA experiment demonstrate a clear dose-response for ATR, with a NOEL of 5mg/kg. Animals dosed with DACT or LiCI developed aversions comparable to the highest dose of ATR. The pica experiment showed that lower doses (5-50mg/kg) of ATR had no effect, as measured 6 and 24 hours post-dosing, nor did DACT. However, the highest dose of ATR (200mg/kg) and LiCI did induce pica behavior at both time points. These data demonstrate that increases in ACTH and CORT secretion following administration of ATR occur at doses that are without effect on the display ofpica behavior, indicating that the HPA-axis activation caused by ATR is not the result of gastrointestinal distress. This abstract does not necessarily reflect EPA policy.