ORGANOPHOSPHORUS-INDUCED DELAYED NEUROTOXICITY - A COMPARATIVE-STUDY OF THE EFFECTS OF TRI-ORTHO-TOLYL PHOSPHATE AND TRIPHENYL PHOSPHITE ONTHE CENTRAL-NERVOUS-SYSTEM OF THE JAPANESE-QUAIL

The neurotoxic effects of single oral doses of tri-ortho-tolyl phospha te (TOTP) (500 mg/kg body weight) or single subcutaneous injections of triphenyl phosphite (TPP) (62.5-500mg/kg body weight) were in vestiga ted in the Japanese quail (Coturnix coturnix japonica). Oral doses of TOTP resulted in no detectable clinical signs while injections of TPP resulted in mild ataxia to severe paralysis depending upon the dosage level. At 24hr postdosing, whole-brain activity of neuropathy target e sterase (NTE) was inhibited by 90% in birds exposed to TOTP and by 11- 87% in birds injected with TPP. Oral doses of TOTP resulted in only sp arse Fink-Heimer silver-impregnated degeneration in the white matter o f the cerebellum with no degeneration noted in any other region of the brain. Injections of TPP resulted in widespread degeneration in large numbers of brainstem nuclei and tracts and in all cerebellar foliae a nd deep nuclei. These results indicate that the Japanese quail respond s differentially to exposure to TOTP and TPP. Oral doses of TOTP do no t result in clinical signs or in significant amounts of degeneration i n the brain even though NTE activity is inhibited by 90%. In contrast, injections of TPP at higher dosage levels yield severe clinical signs , widespread axonal and terminal degeneration in the CNS, and signific ant inhibition of NTE activity. This sharp dichotomy in relative sensi tivity to TOTP and TPP in the Japanese quail suggests that each compou nd may have its own unique effect on CNS structure and function. In ad dition, the relationship between levels of NTE inhibition and the onse t of clinical signs or neuropathology remains unclear. (C) 1995 Intox Press, Inc.