Neuropathologic and electrophysiologic effects of organophosphorus delayed neurotoxicants on the central nervous system of the rat.

摘要

Certain organophosphorus chemicals (OPs) cause organophosphorus-induced delayed neurotoxicity (OPIDN). In order to enhance the rat model of Type I and Type II OPIDN, the Fink-Heimer silver impregnation technique was used to determine the extent of degeneration in the central nervous system (CNS) of adult male Long-Evans rats after exposure to a single dose of diisopropyl phosphorofluoridate (DFP) (4 mg/kg body weight, sc), a Type I OP, or to three doses of triphenyl phosphite (TPP{dollar}sb{lcub}rm i{rcub}{dollar}) (1184 mg/kg body weight, sc), a Type II OP, at three day intervals. DFP rats did not display clinical signs, and at twenty-eight days after dosing, CNS degeneration was confined to the rostral gracile fasciculus and nucleus. The results provide evidence the rat may not be suited for study of Type I OPs relative to species which exhibit clinical signs and more extensive CNS degeneration such as the chicken or ferret. TPP{dollar}sb{lcub}rm i{rcub}{dollar} rats exhibited hindlimb ataxia, circling, and backward movement. CNS degeneration, examined after onset of clinical signs, consisted of widespread degeneration in the hindbrain, midbrain, and forebrain. The results indicate the rat is suitable for study of the effects of Type II OPs.; A second study evaluated the effects of TPP{dollar}sb{lcub}rm i{rcub}{dollar} on function of CNS sensory systems. Adult male Long-Evans rats were dosed dermally on two successive days with corn oil (5 rats) or with TPP at 450 (10 rats) or 600 (2 rats) mg/kg body weight and were evaluated by observation of movement, an evoked potential (EP) battery, and a neuropathological assessment. Most low dose rats became slightly ataxic. Auditory brainstem, flash, and somatosensory evoked potential results indicated slight effects. High dose rats developed hindlimb ataxia, circling, and backward movement. EPs indicated moderate brainstem effects and severe cerebral cortical effects. Vacuoles which contained degenerating axons occurred in deeper layers of the cerebral cortex. The results indicate that Type II OPs interfere with the function of CNS sensory systems.