Organophosphate Induced Delayed

Many of the studies on the neurological effects of oral exposure to organophosphate ester hydraulic fluids in animals have employed chickens as models instead of the more commonly used rodent models. For reasons that are not well understood, organophosphate-induced delayed neuropathy can be induced in chickens and cats, but not in mice or rats (Abou-Donia and Lapadula 1990). 

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. 

Lotti, M. (1986) Biological monitoring for organophosphate-induced delayed polyneuropathy, Toxicology Letters, 33 167-172. 

Lotti, M. (1987) Organophosphate-induced delayed polyneuropathy in humans perspectives for biomonitoring, Trends in Pharmacological Sciences, 8 176-177. 

Lotti M, Moretto A Organophosphate-induced delayed polyneuropathy. Toxicol Rev 2005 24 37. [PMID 16042503]... 

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... 

Lotti, M., Moretto, A. (2005). Organophosphate-induced delayed polyneuropathy. Toxicol. Rev. 24 37-49. 

Glynn, P. (2006). A mechanism for organophosphate-induced delayed neuropathy. Toxicol. Lett. 162 94-7. 

Lotti, M., Moretto, A., Zoppellari, R., Dainese, R., Rizzuto, N., Barusco, G. (1986). Inhibition of lymphocytic neuropathy target esterase predicts the development of organophosphate-induced delayed polyneuropathy. Arch. Toxicol. 59 176-9. 

Cholinesterase inhibition may persist for a period of days to weeks. Therefore, repeated exposure to azamethiphos over a period of time may result in the accumulation of enzyme inhibition and onset of acute toxicity. Azamethiphos does not appear to be capable of eliciting organophosphate-induced delayed neuropathy. Likewise, azamethiphos does not appear to be carcinogenic. 

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. 

AChEs and BuChEs are specialized carboxylic ester hydrolases that preferentially hydrolyze choline esters. They are classed among the B-esterases, enzymes that are inhibited by OPs. Another B-esterase is neuropathy target esterase (NTE), an enzyme associated with organophosphate-induced delayed neuropathy (OPIDN). Enzymes that actively hydrolyze OPs are known as A-esterases. They provide an important route of detoxification. Examples are par-aoxonase and DEPase (Table 1). The tertiary structure and amino acid sequences of several AChEs and BuChEs have been elucidated. 

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