Neurotoxicity OPIDN

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. 

M.B. Abou-Donia, The cytoskeleton as a target for organophosphorus ester-induced delayed neurotoxicity (OPIDN). Chem. Biol. Interact. 87(l-3) 383, 1993. 

FIGURE 57.5. Subclasses of neuropathy target esterase (NTE) inhibitors. Type A inhibitors include phosphates, phosphonates, and phosphoramidates these are neuropathic and capable of aging. T pe B inhibitors include phosphinates, sulfonates, and carbamates these are nonneuropathic and not capable of aging. However, inhibition of NTE with a type B inhibitor will protect against organophosphorus compound-induced delayed neurotoxicity (OPIDN) from subsequently administered type A inhibitors. Reproduced with permission from Richardson (2005). 

Histological examination of hens exposed to TOCP revealed a wallerian dying-back degeneration of the larger diameter axons and myelin sheaths. If the neuropathic target esterase is inhibited by 70%, the typical organophophorus ester-induced delayed neurotoxicity (OPIDN) will follow after an approximate 7-14 day delay. 

Randall, J.C., Yano, B.L., and Richardson, R. J., Potentiation of organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the central and peripheral nervous system of the adult hen distribution of axonal lesions, J. Toxicol. Environ. Health., 51(6), 571-590,1997. 

Abou-Donia, M, B. (1993). The cytoskelcton as a target for organ-opho.sphorous cster-induccd delayed neurotoxicity (OPIDN). Ctmn. Bioi. Interact. 87,. 383-393. 

Organophosphorus ester-induced delayed neurotoxicity (OPIDN) has been recognized as a clinical syndrome in humans and animals for over 50 years. After an exposure to certain organophosphates occurs, incoordination, ataxia, spasticity, and flaccid paralysis develop over the following 1 to 3 weeks the paralysis begins distally in the lower limbs and eventually spreads to the upper limbs. Part or all of the lesion may be reversible, but in its... 

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