Testicular toxicity following oral administration of tri-o-cresyl phosphate (TOCP) in roosters.
Tri-o-cresyl phosphate (TOCP) is a neurotoxic organophosphorus compound that induces a characteristic central-peripheral distal axonopathy and Wallerian-type degeneration, 6-14 days after exposure. This organophosphorus compound-induced delayed neurotoxicity (OPIDN) has been extensively studied in the chicken, the standard test model. Reports of neurotoxic agents causing adverse effects on the male reproductive system initiated the present study which was designed to examine the effects of TOCP on the rooster. Previous work from this laboratory has demonstrated 100 mg TOCP/kg/day to be an OPIDN-inducing dose with minimal mortality in roosters. This dose level was administered to adult leghorn roosters (p.o., n = 10) for 18 consecutive days. By days 7-10 of the study, TOCP-treated birds exhibited limb paralysis characteristic of OPIDN. Analysis at termination revealed significant inhibition of neurotoxic esterase activity (NTE) in both brain and testis. There was also a slight decrease in brain acetylcholinesterase (AChe) activity. Sperm motility was shown to be greatly decreased. In addition, sections of formalin-fixed, methacrylate-embedded testes from TOCP-treated birds showed vacuolation of, and disorganization in the seminiferous epithelium. The marginal body weight decreases (17%) in treated animals were not considered to contribute to the testicular toxicity induced by TOCP. Parathion (O,O-diethyl-O-4-nitrophenyl phosphorothioate, 0.1 mg/kg/day, p.o., n = 3) was used as a positive control for AChE inhibition and a negative control for inducing OPIDN. Roosters treated continuously with parathion showed a decrease in brain AChE activity, but no changes in NTE, testicular histology, or limb function. These studies demonstrate the testicular toxicity of TOCP in roosters and suggest that this effect is not related to the chemical's anticholinergic action.
Somkuti, SG; Lapadula, DM; Chapin, RE; Lamb, JC; Abou-Donia, MB
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