Abstract

Several insecticides known to cause delayed neurotoxicity were examined for antitransport activity. The rat optic nerve served as the means to measure fast axoplasmic transport of proteins when the following chemicals were injected: O-methyl O-4-bromo-2,5-dichlorophenyl phenylphosphonothioate (leptophos); O-methyl O-2,5-dichlorophenyl phenylphosphonothioate; O-ethyl O-4-nitrophenyl phenylphosphonothioate; O-ethyl O-4-cyanophenyl phenylphosphonothioate (cyanofenphos); and O-methyl O-2,4-dichlorophenyl phenylphosphonothioate (S-Seven). Tri-o-cresyl phosphate and O,O-diethyl O-4-nitrophenyl phosphorothioate (parathion) were used as positive and negative controls, respectively. L-[³H]Proline (50 µCi) and 5 µl of the compound of interest (0.3 µmol) were injected into the vitreous humor of one eye (in dimethyl formamide/saline solution v/v) and a similar solution lacking the drug was introduced into the contralateral eye as a control. Marked inhibition of fast axoplasmic transport was observed by all phenylphosphonothioate esters and tri-o-cresyl phosphate. No antitransport activity was observed with parathion. The 40-50% lower transport activity in animals treated with delayed neurotoxins, as compared with activity in the negative control (parathion-treated) animals, offers preliminary support to the hypothesis that impairment of fast axoplasmic transport may be involved in the mechanism of action of neurotoxic organophosphorus esters.