Low-Level Sarin Neurotoxicity and its Modulation by Pyridostigmine
Abstract
The possibility that a combination of exposures to organophosphate esters (OPs) and the carbamate pyridostigmine bromide (PB) would lead to nerve damage in Gulf War veterans was studied by treating hens and mice with known neuropathic OPs diisopropyl fluorophosphate (DFP), triorthocresyl phosphate (TOCP), sarin and with PB. Subthreshold and threshold levels inducing nerve damage were established in hens repeatedly treated with TOCP and DFP. Multiple doses of sarin did not result in organophosphate induced delayed neuropathy (OPIDN). PB breached the blood/brain barrier at high lethal doses, but apparently not at low dose levels. TOCP did not induce OPIDN in mice at levels 85 times higher than levels that induced OPIDN in hens. Evidence was not obtained that PB enhanced TOCP induced neural damage in the hen. However, evidence was obtained that PB and DFP together caused neuropathological changes not seen after equivalent treatments with DFP alone. The study revealed additive effects of the OPs and PB on cholinesterase activity in brain that were not evident on the morphological or overt symptom levels. In summary, the data do not support the hypothesis that low level exposures to neuropathic OPs and to PB result in OPIDN.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2003
- Accession Number
- ADA419302
Entities
People
- Barry W. Wilson
Organizations
- University of California