Organophosphate Induced Delayed Neuropathy

Following exposure to certain OP pesticide compounds, a fiuther long-term complication has been described. This is OP-induced delayed neuropathy (OPIDN) which can appear between 1 and 3 weeks post-exposure. This peripheral neuropathy is characterised by incoordination, ataxia, spasticity and flaccid muscle paralysis. Unlike IMS, the condition begins in the lower Umbs and then spreads to the upper limbs. In severe cases, the result may be permanent quadriplegia. 

The condition has been shown histopathologically to be associated with changes at the distal section of a peripheral motor nerve with progressive demyeUnation. This is characterised by a reduction in nerve conduction velocity in clinical neurophysiological studies. 

OPIDN is thought to be mediated by OP acting not as an anticholinesterase but as a neurotoxic esterase. The condition is not seen in poisonings by aU OP pesticides and has not yet been reported in humans exposed to nerve gases. 

However, there are large differences between the databases of OP pesticide exposure and nerve agent exposure in humans. One report from the 1995 Tokyo sarin release concerned a patient who survived for 15 months following the attack and then showed signs of a distal sensory neuropathy. However, since he was on life support for much of this time, there is no clear link with sarin as a cause. 

In addition to OPIDN, in experimental animal studies, OP compounds have been shown to be associated with muscle necrosis in the region of the end plate of the NMJ. The clinical significance of this finding in humans remains unclear. 

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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). 

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... 

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

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. 

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. 

Exposure to insecticides also carries high risk for posttraumatic stress disorder. Insecticides exacerbate preexisting mental conditions, and atropine treatment of OP poisoning may induce psychotic symptoms. Incomplete assessment may overlook organophosphate-induced delayed neuropathy presenting as fatigue or weakness. 

Johnson, M. K., and Read, D. J. (1993). Prophylaxis against and promotion of organophosphate-induced delayed neuropathy by phenyl di-n-pcniyi phosphinate. Chem.-Biol Interaci. 87, 449-4.5.5. 

Organophosphate-induced delayed neuropathy is unrelated to the anticholinesterase (anti-ChE) effects of OP agents because many highly potent cholinergic OPs do not cause neuropathy, and other OP compounds such a.s tri-o-cresyl phosphate (which is not used as a pesticide) have only weak anti-ChE activity but are powerful inducers of neuropathy. The enzyme involved in organo-phosphatc-induced delayed neuropathy is neuropathy target esterase—lysophospholipase (Lush et al 1998 ... 

Assessment of Farmworker Risk from Organophosphate-Induced Delayed Neuropathy... 

Organophosphate Induced Delayed Neuropathy (OPIDN) and other long-term problems of organophosphorus ester (OP) agricultural chemicals pose special problems for risk assessment. Procedures have been developed over the years to evaluate the dangers from acute exposures to OPs, but the Insidious effects of repeated exposures to toxic chemicals are more difficult to anticipate and to detect. 

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