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Main Title Murine Susceptibility to Organophosphorus-Induced Delayed Neuropathy (OPIDN).
Author Veronesi, B. ; Padilla, S. ; Blackmon, K. ; Pope, C. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. Neurotoxicology Div. ;North Carolina Univ. at Chapel Hill.
Publisher c1991
Year Published 1991
Report Number EPA/600/J-91/017;
Stock Number PB91-183491
Additional Subjects Toxicology ; Disease susceptibility ; Tritolyl phosphates ; Mice ; Histology ; Spinal cord ; Axons ; Esterases ; Enzyme inhibitors ; Reprints ; Organophosphorus-induced delayed neuropathy(OPIDN)
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NTIS  PB91-183491 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 16p
Abstract
The study reports that CD-1 strain mice are neuropathologically and biochemically responsive to acute doses of tri-ortho-cresyl phosphate (TOCP). Young (25-30 g) male and female animals were exposed (po) to a single dose of TOCP (580-3480 mg/kg) and sampled for neurotoxic esterase (NTE) activity at 24 and 44 hr postexposure and for neuropathic damage 14 days later. Biochemically, high intragroup variability existed at the lower doses, and at higher levels of TOCP exposure (i.e., > or = 1160 mg/kg), mean brain NTE inhibition never exceeded 68%. Hen and mouse brain NTE activity, assayed in vitro for sensitivity to inhibition by tolyl saligenin phosphate (TSP), the active neurotoxic metabolite of TOCP, showed similar IC50 values. Histologically, highly variable spinal cord damage was recorded throughout treatment groups and mean damage scores followed a dose-response pattern with no apparent correlation to threshold (i.e., > or = 65%) inhibition of brain NTE activity. Topographically, axonal degeneration in the mouse spinal cord predominated in the lateral and ventral columns of the upper cervical cord. Unlike the rat, which displays degeneration in the upper cervical cord's dorsal columns (i.e., gracilis fasciculus) in response to TOCP intoxication, treated mice showed minimal damage to this tract. To examine this discrepancy further, ultrastructural morphometric analysis of axon diameters in the cervical cord was performed in control mice and rats. These results indicated that in both species, the largest diameter (> or = 4 microm) axons are housed in the ventral columns of the cervical spinal cord, suggesting that axon length and diameter may not be the only criteria underlying fiber tract vulnerability in OPIDN. (Copyright (c) 1991 Academic Press, Inc.)