SUSCEPTIBILITY OF VARIOUS AREAS OF THE NERVOUS-SYSTEM OF HENS TO TOCP-INDUCED DELAYED NEUROPATHY

Sensitivity of in-life parameters, biochemical endpoints, and suscepti bility of Various areas of the chicken nervous system to delayed neuro pathy induced by tri-orthocresyl phosphate (TOCP) was assessed. Groups of hens were exposed to a single oral dose of TOCP of 0, 50, 200 or 5 00 mg/kg and the animals observed for 21 days. Perfusion fixed paraffi n embedded tissue sections were stained with Bodian's silver and Luxol blue and semi-thin epoxy sections with toluidine blue. Sciatic and ti bial nerves, lumbosacral, midthoracic, and upper cervical spinal cord, medulla oblongata and cerebellum were examined using a semiquantitati ve scoring system. In pair-dosed hens inhibition of brain and spinal c ord neurotoxic esterase (NTE) and cholinesterase and of plasma and ery throcyte cholinesterases was determined 24 hr and 48 hr after administ ration. At all dose levels NTE in brain and spinal cord and plasma cho linesterase was inhibited markedly. Quantitative inhibition of NTE was seen also in absence of neuropathy. Ataxia and body weight loss occur red in high-dose animals only, while dose-related neuropathy was seen in the distal tibial nerve, medulla oblongata and cerebellum. Ataxia w as correlated best with neuropathy in peripheral nerves while degenera tion of nerve fibers in the cerebellum, seen best in mid-longitudinal sections, was the most sensitive histological indicator of TOCP-induce d delayed neuropathy. The particular susceptibility of spinocerebellar neurons was recognized long ago, but often has been neglected in dela yed neurotoxicity studies and respective guidelines. Optimal sensitivi ty of toxicity tests is a prerequisite for risk assessment, can be cos t efficient, and nowadays should be a main interest of animal welfare in order to reduce animals' suffering. Based on these data, determinat ion of NTE inhibition together with histopathological examination of l ongitudinal sections of distal tibial nerves, mid-longitudinal section s of rostral cerebellum and cross sections of upper cervical spinal co rd represents an optimally sensitive and cost efficient test requireme nt. (C) 1996 Inter Press, Inc.