Delayed neuropathic agents

CHAPTER 57 Biomarkers and Biosensors of Delayed Neuropathic Agents... 

Agriculture has been fortunate to be relatively free of mass outbreaks of OPIDN. The major chemical offender has been the plasticizer and lubricant trl-ortho-cresyl phosphate (TOCP). Contamination of various products with TOCP has paralyzed thousands of people since the turn of the century ( ). OPs in use In agriculture that have been shown to be neuropathic Include the cotton defoliant DEF and the pesticides EPN, haloxon and leptophos (not registered In the US). Neuropathic OPs used experimentally Include DFP and mlpafox one nerve gas (sarin) has been shown to cause OPIDN and there Is evidence another (soman) Is also a delayed neuropathic agent ( ). Recently, Wilson et al. ( ) found that isofenphos (IFF) caused OPIDN In hens. 

NEUROPATHY TARGET ESTERASE AS A BIOMARKER AND BIOSENSOR OE DELAYED NEUROPATHIC AGENTS... 

Gordon, J.J., R.H. Inns, M.K. Johnson, L. Leadbeater, M.P. Maidment, D.G. Upshall, G.H. Cooper, and R.L. Rickard. The Delayed Neuropathic Effects of Nerve Agents and Some Other Organophosphorus Compounds." Archives of Toxicology 52 (1983) 71-82. 

Gordon, J.J., Inns, R.H., Johnson, M.K., Leadbeater, L., Maidment, M.P., Upshall, D.G., Cooper, G.H. et al. (1983). The delayed neuropathic effects of nerve agents and some other organophosphorous compounds. Arch. Toxicol. 52 71-82. 

FIGURE 57.3. Examples of delayed neuropathic (DN) agents containing pentavalent phosphorus ethyl n-octylphosphono-fluoridate (EOPF) and 2-(2-methylphenoxy)-4iT-l,3,2-benzodiox-aphosphorin-2-oxide [2-(2-methylphenoxy)-BDPO], the active metabolite of the archetypal DN agent, tri-o-cresyl phosphate (TOCP) (Wu and Casida, 1995). 

The apparent half-life of aging depends upon the enzyme, inhibitor, pH, and temperature. However, NTE inhibited with most neuropathic agents exhibits aging half-lives on the order of several minutes, so that the week delay between exposure and appearance of signs of OPIDN is not due to the time required for aging of phosphylated NTE (Jianmongkol et al, 1999 Johnson, 1982 Kropp and Richardson, 2007 Richardson, 1992). 

In keeping with the concept of the RIP discussed under Relative Inhibitory Potency , above, inhibition of lymphocyte and/or platelet NTE and possibly erythrocyte LysoPC hydrolase should be used in conjunction with inhibition of erythrocyte AChE and plasma butyryl-cholinesterase (BChE) to assess the likelihood that an exposure to OP compounds would produce cholinergic and/ or delayed neuropathic effects. Erythrocyte AChE inhibition has long been used as a biomarker of exposure to conventional nerve agents or OP insecticides (Lotti, 1995 Wilson and Henderson, 1992). BChE can be sensitive to both conventional and DN agents, and its inhibition could thus serve as a general biomarker for OP agents (Kropp and Richardson, 2007 Van der Schans et al, 2008). 

Gordon JJ, InnsRH, Johnson MK el al. (1983). The delayed neuropathic effects of nerve agents and some other organophosphate compounds. Arch Toxicol, 51, 71-82. 

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