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THE EFFECTS OF AN ORGANOPHOSPHATE (OP)-CARBAMATE (CB) PESTICIDE MIXTURE ON CORE TEMPERATURE AND MOTOR ACTIVITY IN THE RAT.
Citation:
Mack, C M., C. Gennings, D. Herr, AND C J. Gordon. THE EFFECTS OF AN ORGANOPHOSPHATE (OP)-CARBAMATE (CB) PESTICIDE MIXTURE ON CORE TEMPERATURE AND MOTOR ACTIVITY IN THE RAT. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
Pesticide risk assessment has traditionally been based on the toxicological response to single agents. Dose-additivity has been the default in risk assessment evaluations of pesticides with a common mechanism of action, but there could be supra-additive or infra-additive interactions of pesticide mixtures. We have found that rats exposed to anticholinesterase OP or CB pesticides display a transient hypothermia followed by a delayed fever. Thus, the hypothesis of additivity of an OP/CAR mixture may be assessed using thermoregulatory endpoints. A fixed-ratio ray design was developed from single chemical dose-responses to assess the effects of a mixture of the OP chlorpyrifos (CHP) and the CB carbaryl (CAR). Adult, male Long-Evans rats were surgically implanted with radio transmitters (Data Sciences) to monitor core temperature (Tc) and motor activity (MA). After recording a 24 hr baseline of Tc and MA, rats were dosed orally with corn oil, 30 mg/kg CHP, 75mg/kg CAR, or one of the following 2:1 mixtures of CHP:CAR; 4.7:2.3, 9.3:4.7, 14.0:7.0, 18.7:9.3, or 23.3:11.7 mg/kg. Exposure to pure CHP and CAR yielded an acute, marked reduction in Tc followed by a delayed fever for at least one day post dose. The hypothermic response to the binary mixtures was diminished compared to the pure chemicals. A mixture of 23.3:11.7 mg/kg led to a hypothermic response half that of 30 mg/kg CHP (assuming dose-additivity, the hypothermic response of these two treatments should be equal). However, the CHP:CAR mixtures >14.0:7.0 mg/kg led to a delayed fever similar to that elicited by pure CHP. MA post dosing was reduced in the 30 mg/kg CHP group, whereas the mixtures did not affect MA. Overall, there is an infra-additive response to a mixture of CHP:CAR when assessed by the hypothermic response. This response is mediated through stimulation of cholinergic thermoregulatory pathways. The delayed fever, mediated by non-cholinergic systems, is unaffected by the CHP:CAR mixture. This abstract does not necessarily reflect US EPA policy.