Persisting behavioural and electroencephalographic effects of exposure to chlorphenvinphos, an organophosphorous pesticide, in laboratory animals.
Organophosphorous compounds (OPs) constitute a large proportion of insecticides used all over the world. Their insecticidal properties and acute toxicity in nontarget species derive from the inhibition of acetylcholinesterase (AChE) which disturbs the cholinergically mediated neurotransmission. OPs do not accumulate in living organisms and the acute signs and symptoms disappear as the AChE activity returns to normal level. Therefore, they are regarded as relatively safe. However, as some literature data suggest, after either acute or prolonged exposure to OPs subtle neurobehavioral impairments may persist long after normalization of AChE activity. The possibility that OPs exposure may induce such long-term effects is nowadays a problem of great concern for the regulatory agencies. Here we present a review of studies from our laboratory aimed at detecting neurobehavioural effects of exposure to chlorphenvinphos, an OP pesticide ((2-chloro-1-(2,4-dichlorophenyl) vinyl diethyl phosphate)--CVP)) in laboratory animals. In Poland, CVP is manufactured (250 tons/year) and used for crop protection. In a series of experiments we have demonstrated that: a) in rabbits, two i.p. exposures to CVP at the same sublethal dose at three-month interval resulted in a similar inhibition of blood AChE activity but the effect of the second exposure on body temperature and hippocampal EEG was smaller and less consistent than that of the first one. This would indicate that some permanent changes within the CNS may occur even after a single exposure to CVP; b) in rats, under conditions of repeated i.p. exposure to CVP (one injection/day for ten days) at a symptomatic (3.0 mg/kg) dose inhibiting blood and brain AChE activity by about 80%, the tolerance to CVP, assessed from the spontaneous locomotor behaviour, developed within four to five days. However, single exposure to CVP at a symptomatic (3.0 mg/kg) or subsymptomatic (1.0 mg/kg, less than 50% AChE inhibition) dose, or repeated exposure (one injection/day, for ten days) at subsymptomatic doses (1.0 mg/kg or 0.5 mg/kg) resulted in subtle changes in complex behaviours detectable after AChE activity in blood and in the brain had returned to the normal level. The changes--neophobia in the open field, an increased and more persistent emotional response to a stressful stimulus, and increased EEG arousal response to an external pain signalling stimulus--suggest an increased reactivity of the system or systems responsible for the induction of fear; c) direct intrahypothalamic injections of CVP, unlike those of oxotremorine, a direct stimulant of cholinergic muscarinic receptors, did not induce overt changes in the animal (rabbit) behaviour and EEG. This would indicate that the changes in the CNS functions after CVP exposure may be the consequence of increased cholinergic activity due to AChE inhibition rather than to a direct stimulation of cholinergic muscarinic receptors by CVP. The above findings provide experimental evidence that health effects of exposure to CVP, may persist after recovery of AChE activity in blood and in the brain.
Gralewicz
S
S
Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lódź, Poland.
Soćko
R
R
D000818:Animals; D000830:Animals, Laboratory; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002709:Chlorfenvinphos / Q000633:toxicity*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004569:Electroencephalography; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D011817:Rabbits; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects
D007306:Insecticides; D011976:Receptors, Muscarinic; D002709:Chlorfenvinphos