COMPARISONS OF THE ACUTE EFFECTS OF CHOLINESTERASE-INHIBITORS USING ANEUROBEHAVIORAL SCREENING BATTERY IN RATS

The clinical signs of intoxication produced by cholinesterase inhibito rs, many of which are used as pesticides, are considered important inf ormation for regulatory purposes. We conducted acute studies of cholin esterase inhibitors to compare their effects as determined by a functi onal observational battery (FOB) and motor activity. The acute effects of two carbamates (carbaryl, aldicarb) and five organophosphates (OP) (chlorpyrifos, diazinon, parathion, fenthion, and diisopropyl fluorop hosphate, or DFP) were evaluated on the day of dosing at the time of p eak effect, at 1 and 3 days, and 1 week after dosing (oral gavage, in corn oil). A high dose was selected that produced clear cholinergic si gns, and lower doses were chosen to produce a range of effects. Genera lly all cholinesterase inhibitors produced autonomic signs of choliner gic overstimulation (salivation, lacrimation, and miosis), hypothermia , mild tremors and mouth-smacking (chewing motions), lowered motor act ivity, decreased tail-pinch response, and altered neuromuscular functi on (gait changes and increased foot splay). The measures generally fou nd to be most sensitive on the day of dosing were body temperature, mo tor activity, gait, and the presence of mouth-smacking and fine tremor s. However, no single measure was the most sensitive across ail compou nds; for example, the lowest dose of fenthion decreased motor activity by 86% but did not alter the tail-pinch response, whereas the lowest dose of parathion did not lower activity but did decrease the tail-pin ch response. For some measures, differences in the slopes of the dose- response curves were evident. Many effects were still observed at 24 h , but recovery was apparent for all compounds. Interestingly, residual effects at 72 h were obtained with the carbamates (carbaryl, aldicarb ) as well as with the OP fenthion, but not with the other compounds. T hus, the overall clinical picture of toxicity was similar for these ch olinesterase inhibitors, but compound-specific differences emerged in terms of the individual measures, dose-response, and time course.