ABSTRACT
An organophosphorus insecticide EPN, O-ethyl-O, 4-nitrophenyl phenylphosphonothioate, is a stronger inhibitor of ChE activity than leptophos or cyanofenphos which are delayed neurotoxic organophosphorus insecticides, and it is usually difficult to demonstrate its delayed neurotoxicity with a single oral dose without atropinization. In this study, delayed neurotoxic effect of EPN was observed in non-atropinized hens by using the repeated pretreatment method.<BR>1) Three groups of hens were given preliminarily small dose of EPN such as 10mg/kg/day for 10 days, 5 mg/kg/day for 20 days and 10mg/kg/day for 20 days. Another group was not given any preliminary dose. After each pretreatment, these groups received a large amount of dose called ‘challenge dese’, 150mg/kg, 200mg/kg or 300mg/kg of EPN. During the pretreatmental period, only 2 out of 60 hens which received the pretreatment died.<BR>2) The mortality rate due to the acute toxicity after the challenge does in the group pretreated by 10 mg/kg/day for 20 days was significantly lower than in the non-pretreated group.<BR>3) It is clear that EPN shows delayed neurotoxicity in hens. Delayed neurotoxic effect was observed in all groups which were given repeatedly the pretreatment of EPN prior to each challenge dose. While the survived hens from the acute death in the non-pretreated group did not show any sign of delayed neurotoxicity. The specific relationship, however, was not observed between the anount and times of pretreatment and the incidence of delayed neurotoxicity.<BR>4) Delayed neurotoxic effects of EPN such as clinical symptomes, the cource of body-weight change and the findings of histopathological changes were just similar to those of leptophos and cyanofenphos.<BR>5) The results of this study suggest that the using of the repeated pretreatment method allows to give high concentrated organophosphorus compound without atropinization and to accurate assessment of delayed neurotoxicity of some organophosphates; these effects would otherwise not be detected using a single dose of LD<SUB>50</SUB>.