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EFFECTS OF ACUTE PYRETHROID EXPOSURE ON THERMOREGULATION IN RATS.
Citation:
WOLANSKY, M., C. M. MACK, P. BECKER, K. M. CROFTON, AND C. J. GORDON. EFFECTS OF ACUTE PYRETHROID EXPOSURE ON THERMOREGULATION IN RATS. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
Description:
Pyrethroid insecticides produce acute neurotoxicity in mammals. According to the FQPA mandate, the USEPA is required to consider the risk of cumulative toxicity posed to humans through exposure to pyrethroid mixtures. Thermoregulatory response (TR) is being used to determine if the dose-additive action for motor function can be generalized to other endpoints in rats. Adult male Long Evans rats were monitored for 48 h for core temperature (Tc) and motor activity (MA) at 5 min intervals by surgically implanted radiotransmitters. Acute oral dose-response studies [n=6-13; 6 doses/compound] were carried out for a Type-I (Permethrin, PER, 5-220 mg/kg) and a Type-II (Deltamethrin, DLT, 0.5-12 mg/kg) pyrethroid. Both pyrethroids produced acute effects, including increased MA and compound-specific changes in TR that recovered within 12 hr after dosing. Area under the curve (AUC) from 1 to 7 hr post-dosing was determined for each pyrethroid dose and used for statistical analysis. PER elicited a hyperthermic response at 75-220 mg/kg. The TR dose-response to DLT was biphasic, with 1.5-3 mg/kg eliciting a significant elevation in Tc and higher doses eliciting a prolonged hypothermic response. In addition, animals dosed with 9-12 mg/kg DLT exhibited a slight elevation in Tc the day after exposure (0.16-0.22 ºC above controls). In a preliminary mixture study, the TR response to 220 mg/kg PER and 12 mg/kg DLT resulted in an approximate algebraic summation of the TR responses to the individual compounds: the AUCs for PER, DLT and the mixture were 12.4, -8.8, and 4.65 ºC.hr-1, respectively. Future work will include testing other pyrethroids and an environment relevant mixture of them using TR as a sensitive endpoint. This abstract does not necessarily reflect the policy of the US EPA