Abstract

Administration of the organophosphate pesticide chlorpyrifos (CHP) to the male rat at a dose of 25–80 mg/kg (p.o.) results in hypothermia followed by a delayed fever lasting for several days. These are high doses of CHP that cause marked cholinergic stimulation. It is important to understand if chronic exposure to CHP would evoke changes in thermoregulation that are comparable to the acute administration. Male rats of the Long-Evans strain were subjected to dietary treatment of 0, 1, or 5 mg/(kg day) CHP for 6 months. A limited amount of food was given per day to maintain body weight at 350 g. The constant body weight allowed for the regulation of a consistent dosage of CHP per kg body weight throughout the feeding period. Core temperature ( T a) and motor activity (MA) were monitored by radio telemetric transmitters implanted in the abdominal cavity. After 5 months of treatment, T c and MA were monitored in undisturbed animals for 96 h. CHP at 5 mg/(kg day) led to a slight elevation in T c without affecting MA. The rats were then administered a challenge dose of CHP (30 mg/kg, p.o.) while T c and MA were monitored. Rats fed the 1 and 5 mg/kg CHP diets showed a significantly greater hypothermic response and reduction in MA following CHP challenge compared to controls. The restricted feeding schedule resulted in marked changes in the pattern of the circadian rhythm. Therefore, in another study, rats were treated ad libitum for 17 days with a CHP diet that resulted in a dosage of 7 mg CHP/(mg day). There was a significant increase in T c during the daytime but not during the night throughout most of the treatment period. Overall, chronic CHP was associated with a slight but significant elevation in T c and greater hypothermic response to a CHP challenge. This latter finding was unexpected and suggests that chronic exposure to CHP sensitizes the rat's thermoregulatory response to acute CHP exposure.

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