Organophosphate compounds neurotoxic

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... 

The subcommittee considered other possible critical end points, notably neurotoxicity, associated with VX exposure. Organophosphate compounds like VX might act directly on nerve cell receptors or, by inhibiting neural AChE, interfere with neuromuscular transmission and produce... 

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. 

Jamal, G.A., Long-term neurotoxic effects of organophosphate compounds. Adverse Drug React. Toxicol. Rev., 14, 85, 1995. 

Delayed neurotoxicity results from degeneration of the axons followed by demyelination (14,15,23). Clinical manifestation includes sensory disturbances, ataxia, weakness, muscle twitching and, in severe cases, complete flaccid paralysis ( 15). A fair number of organophosphate compounds are capable of inducing delayed neurotoxicity. Of the 250 organophosphates (not all pesticides) tested for delayed neurotoxicity in chickens, 47% (117 chemicals) showed positive responses (23). Notable examples of pesticides which possess this neurotoxicity are leptophos, EPN, merphos, dichlorvos, and... 

Ballantyne, B.C. and Marrs, T.C. (Eds.) (1992). Clinical and Experimental Toxicology of Organophosphates and Carbamates—A wide-ranging collection of chapters giving a broad coverage of the toxicology of these important neurotoxic compounds. 

Organophosphate Ester Hydraulic Fluids. A number of studies have been conducted on organophosphate ester hydraulic fluids because of the well known neurotoxic effects caused by organophosphorus insecticides, organophosphorus nerve gases, and tri-ort/w-cresyl phosphate (TOCP). The following manifestations of acute exposure to organophosphorus compounds have been described ... 

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

Organophosphate Ester Hydraulic Fluids. Neurotoxicity is a concern from acute dermal, inhalation, or oral exposure to organophosphate ester hydraulic fluids because of the well-established susceptibility of humans to the cholinergic and delayed neuropathic properties of certain organophosphate ester compounds... 

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. 

Studies on the scaleless chicken are underway examining its suitability as a model for assessing toxicity of organophosphates. The first compound selected for field trials was the defoliant DEF (S,S,S-tributylphosphorotrithioate) used during the harvesting of cotton in California and Arizona in the fall (October-November) when air movements are frequently restricted by inversions. DEF has been the subject of sufficient complaints to place it on the pre-RPAR list, although there are no reports of acute or delayed neurotoxicity in humans when it and related chemicals are used according to recommendations. It both inhibits cholinesterases and causes delayed neurotoxicity in hens (3,6). 

Abou-Donia, M.B. (1992). Tri-phenyl phosphite a type II organophosphoras compound-induced delayed neurotoxic agent. In Organophosphates Chemistry, Fate, and Effects (J.E. Chambers, P.E. Levi, eds), pp. 327-51. Academic Press, San Diego. 

Makhaeva and Malygin discuss the problem of organophosphate-induced delayed neurotoxicity (OPIDN) in connection with possibility of using neuropathic OP compounds for chemical terrorism. 

No common structural denominator is apparent between the organophosphates to which this biological effect may be attributed, although the inclusion of a 2-chloroethyl group has been considered to lead to neurotoxicity whereas diethylphosphate compounds are devoid of this effect [107]. 

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