TRIPHENYL PHOSPHITE NEUROPATHY DIFFERS FROM ORGANOPHOSPHORUS‐INDUCED DELAYED NEUROPATHY IN RATS

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Abstract
The topographies of neuropathic damage produced by triphenyl phosphite (TPP) and tri-ortho-cresyl phosphate (TOCP) are contrasted in the present study. Long-Evans, male rats were exposed (sc) to single (0.1ml kg-1; 1.0 ml kg-1) or multiple (2×1.0 ml kg-1; 3×1.0 ml kg-1) doses of TPP, and sampled 1–3 weeks after exposure. Additional animals were dosed acutely with TOCP (1160 mg kg-1, p.o.) alone or in combination with multiple doses of TPP (2×1 ml kg-1). Functional changes, seen in multiple-dosed TPP-rats included tail-kinking, circling, and ataxia. Neuropathological damage seen in all but the 0.1 ml kg-1 treated animals consisted of degeneration of the ventrolateral and ventral columns of the spinal cord at all levels, and moderate peripheral nerve fibre damage. Medullary brainstem involvement consisted of axonal swellings and fragmented axons in the medial longitudinal fasciculus, the reticular formation, and the inferior cerebellar peduncles. Tissues examined from TOCP-treated rats displayed severe degeneration of the fasciculus gracilis at the cervical level, mild involvement of the dorsolateral columns at the lumbar levels and a sparing of all other cord and brainstem regions. Rats treated with neuropathic doses of both TPP and TOCP showed a composite pattern of degeneration that included damaged sites characteristic of the individual neurotoxicants. These data indicate that the neuropathic profile of TPP differs markedly from the delayed neuropathy (OPIDN) associated with exposure to model organophosphorus compounds such as TOCP.