Abstract

The chemical structure of organophosphate compounds (OPs) is a well-known factor which modifies the acute toxicity of these compounds. We compared ventilation at rest and cholinesterase activities in male Sprague-Dawley rats poisoned with dimethyl paraoxon (DMPO) and diethyl paraoxon (DEPO) at a subcutaneous dose corresponding to 50% of the median lethal dose (MLD). Ventilation at rest was recorded by whole body plethysmography. Total cholinesterase activities were determined by radiometric assay. Both organophosphates decreased significantly the respiratory rate, resulting from an increase in expiratory time. Dimethyl-induced respiratory toxicity spontaneously reversed within 120 min post-injection. Diethyl-induced respiratory toxicity was long-lasting, more than 180 min post-injection. Both organophosphates decreased cholinesterase activities from 10 to 180 min post-injection with the same degree of inhibition of total cholinesterase within an onset at the same times after injection. There were no significant differences in residual cholinesterase activities between dimethyl and diethyl paraoxon groups at any time. The structure of the alkoxy-group is a determinant factor of the late phase of poisoning, conditioning duration of toxicity without significant effects on the magnitude of alteration of respiratory parameters. For same duration and magnitude of cholinesterase inhibition, there was a strong discrepancy in the time-course of effects between the two compounds.

Highlights

  • Organophosphate (OP) compounds are used primarily as pesticides in agricultural settings but have been developed into chemical weapons including nerve agents

  • The median lethal dose (MLD) of diethyl paraoxon (DEPO) was previously measured at 0.43 mg/kg [11]

  • At T0, there were no significant differences in core temperature between control and dimethyl paraoxon (DMPO) and DEPO groups

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Summary

Introduction

Organophosphate (OP) compounds are used primarily as pesticides in agricultural settings but have been developed into chemical weapons including nerve agents. Organophosphates account for the majority of pesticide-related unintentional or intentional poisonings in lower- and middle-income countries [1]. There is a wide estimation of the number of deaths related to OP poisonings. Over a short period of recent time, values were 100,000 [2], 260,000 [3], and 300,000 deaths per year [4]. Toxics 2019, 7, x FOR PEER REVIEW. Respiratory failure is still considered the primary cause of death in acute organophosphate of agricultural organophosphorus pesticides. The mechanism poisonings [5].

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