Differential Sensitivity to Anticholinesterase Insecticides in the Juvenile Rat: Effects on Thermoregulation

Abstract

Organophosphate (OP) and carbamate (CB) insecticides inhibit cholinesterase (ChE) activity and induce acute hypothermia in adult rats. Studies showed that juveniles are generally more susceptible to neurotoxic insult than adults. However, little is known concerning the effects of OP and CB pesticides on thermoregulation in developing animals. Thus, alterations in core body temperature (Tc) in juvenile animals exposed to an OP and CB insecticide were investigated. Male rat pups were anesthetized on postnatal day (PND) 15 with metofane and a radio transmitter (Data Sciences) was implanted in the abdominal cavity to monitor Tc and motor activity (MA). Two days were allowed for recovery. The PND 17 pups were then dosed by oral gavage with the OP chlorpyrifos (CHP) (1, 5, 10, or 15 mg/kg) or the CB carbaryl (CAR) (10, 20, 80, 120, or 160 mg/kg) or the corn oil vehicle. Pups were returned to their dams and littermates immediately after dosing and monitored for the next several days. CHP doses of 10 and 15 mg/kg resulted in 1.0°C and 2.4°C reductions in Tc, respectively. Tc recovered to control levels by approximately 16 h after dosing. There was significant mortality in rats dosed with 15 mg/kg CHP (6 of 11). CAR doses of 10 to 80 mg/kg had little effect on Tc. The highest dose of CAR (160 mg/kg) resulted in a 1.3°C reduction in Tc that recovered in 9 h. In contrast, past studies found that adult male rats become hypothermic at CHP doses of >25 mg/kg, whereas a CAR dose of 50 mg/kg is effective at inducing hypothermia. Overall, it appears that during the development from preweanling to adult rat, there is a progressive attenuation in CHP- induced hypothermia. Conversely, CAR- induced hypothermia increases as a function of development.

We thank Drs. Lisa Leon and Rymond Mohaghegh for their review of the article. We also thank Peggy Becker for providing technical assistance.

This article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.