Neurotoxicity organophosphate-induced

One of the main human health concerns about organophosphate esters is the potential for neurotoxicity reactions, in particular a condition known as organophosphate-induced delayed neurotoxicity (OPIDN). Tri-ort/20-cresyl phosphate (TOCP) has been identified as one of the more potent OPIDN neurotoxins in humans, and was formerly a constituent in some organophosphate ester hydraulic fluid products (Marino 1992 Marino and Placek 1994). Production processes now routinely remove virtually all the TOCP. For instance, tricresyl phosphate (TCP) products now typically are manufactured to contain over 98% meta and para isomers and virtually no TOCP (Marino and Placek 1994). Products containing these compounds associated with OPIDN have now entirely disappeared from commercial use, and the vast majority of the industrial organophosphate esters are based on triaryl phosphates with no halogenated components (Marino 1992). At waste disposal sites, however, site contaminants from older product formulations containing the ortho form may be encountered. 

No studies were located regarding organophosphate-induced delayed neurotoxicity (OPIDN) in humans or in animals after inhalation exposure to diazinon. 

Diazinon MG-8 (purity 87%) has been tested for organophosphate-induced delayed neurotoxicity in chickens (Jenkins 1988). Ten hens (Red Heavy breed) were used as a control group and received... 

The subcommittee considered other possible toxicity end points, notably neurotoxicity, associated with GD exposure. Organophosphate compounds like GD may act directly on nerve cell receptors or, by inhibiting neural AChE, interfere with neuromuscular transmission and produce delayed-onset subjunctional muscle damage. In addition, some organophosphate compounds cause a neurotoxic effect (organophosphate-induced delayed neuropathy, or OPIDN) that is not associated with ChE inhibition. Emerging research in this area might indicate alternative... 

Ho, I.K. and B. Hoskins. 1983. Basal Ganglia Dopamine-Gamma Aminobutyric Acid-Acetylcholine Interaction in Organophosphate-Induced Neurotoxicity. Second Annual Report. AD B091748. U.S. Army Medical Research and Development Command, Fort Detrick, Frederick, MD. 

Tiffany-Castiglioni, E., Venkatraj, V., Wild, J.R. (2006). In vitro models for testing organophosphate-induced neurotoxicity and remediation. In Toxicology of Organophosphate and Carbamate Compounds (R.C. Gupta, ed.), pp. 315-37. Elsevier/ Academic Press, San Diego, CA. 

Cholinesterase inhibition can sometimes persist for weeks thus, repeated exposures to small amounts of this material may result in accumulation of acetylcholinesterase inhibition with possible sudden-onset acute toxicity. Chlorpyrifos may be capable of causing organophosphate-induced delayed neurotoxicity in humans a massive overdose resulted in signs characteristic of delayed neurotoxicity. Animal studies generally indicate, however, that doses several times higher than the LD50 would be required to initiate delayed neurotoxicity. 

Sokolovskaya, L.G., Sigolaeva, L.V., Eremenko, A.V., Makhaeva, G.F., Strakhova, N. N., Malygin, V.V., Richardson, R. J., and Kurochkin, I. N., Electrochemical analysis of neuropathy target esterase activity by 1-methoxyphenazine methosulfate modified tyrosinase carbon paste electrode progress in biomonitoring of organophosphate-induced delayed neurotoxicity, Biotechnol. Letter (In press). 

After acute effects subside, OPs produce a condition called the intermediate syndrome mediated through the enzyme neurotoxic esterase (Annau 1992). Symptoms consist of muscle weakness developing days after initial symptoms. Organophosphate-induced delayed neurotoxicity, a second delayed OP effect, develops weeks after exposure (Davis and Richardson 1980 Ecobichon 1996 Willems et al. 1984). Another condition described as wasting away results from toxic by-products generated during synthesis of OP insecticides, especially malathion (Chambers 1992). 

Husain, K., Peripheral biochemical marker for organophosphate induced delayed neurotoxicity, Biochem. In., 24, 1051, 1991. 

This enzyme may be measured in studies of organophosphate-induced neurotoxicities. More recently, its cardioprotective role in association with high-density lipoprotein has received some attention. Paraoxanase has also been used as marker of hepatotoxicity (Gil et al. 1994 Hernandez et al. 1997 Ferre et al. 2002). 

Pope, C., diLorenzo, K., and Ehrich, M. (1995). Po.s.siblc involvement of a neurotrophic factor during the early. stages of organophosphate-induced delayed neurotoxicity. Toxicol, l-ett. 75, n 1-117. 

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