title: Diurnal variation in thermoregulatory response to chlorpyrifos and carbaryl in the rat.
abstract: Time of day of exposure is rarely considered in the study of insecticide toxicology. It would be expected that the circadian temperature rhythm (CTR) as well as the circadian rhythms of other physiological processes would affect the efficacy of anticholinesterase (antiChE) insecticides. The ability of antiChE insecticides to alter core temperature (T(c)) could be affected by time of exposure in relation to the CTR. To this end, we assessed time of exposure on the efficacy of the antiChE insecticides chlorpyrifos (CHP) and carbaryl (CAR) to alter T(c) in the rat. T(c) and motor activity (MA) were monitored by radiotelemetry. Rats were dosed orally with 0, 30, and 50 mg/kg CHP or 0, 25 and 75 mg/kg CAR at 09:00 and 15:00 h. Both insecticides caused an acute decrease followed by a delayed increase in T(c) by 24-48 h post-exposure. The temperature index (TI) (area under curve of DeltaT(c) with time) was significantly greater when CHP was given at 15:00 h as compared with 09:00 h. The maximum decrease in T(c) was similar for morning and afternoon CHP. The TI following CAR was similar for morning and afternoon exposure. CHP suppressed the 24 h MA equally when given in the morning and afternoon. CAR was more effective in reducing MA when given in the morning as compared with the afternoon. The T(c) increase measured 24 h after dosing was greater when CHP was given in the morning. Overall, time of day affected the thermoregulatory toxicity of CHP but not CAR. Another experiment showed that the hypothermic efficacy of oxotremorine, a muscarinic agonist, was greater when injected at 09:00 h as compared with 15:00 h. Hence, cholinergic stimulation is probably not the only mechanism to explain the effects of the chronotoxicogical effects of some antiChE insecticides.
authors.affiliation: Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, MD-74B, Research Triangle Park, NC, 27711, USA. gordon.christopher@epa.gov
authors.forename: C J
authors.initials: CJ
authors.lastname: Gordon
authors.forename: C M
authors.initials: CM
authors.lastname: Mack
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D012721:Carbaryl / Q000633:toxicity*; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002940:Circadian Rhythm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005508:Food Deprivation / Q000502:physiology; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013686:Telemetry
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D018721:Muscarinic Agonists; D010095:Oxotremorine; D004390:Chlorpyrifos; D012721:Carbaryl