OPIDN delayed neuropathy

A few OP compounds cause delayed neuropathy in vertebrates because they inhibit another esterase located in the nervous system, which has been termed neuropathy target esterase (NTE). This enzyme is described in Chapter 10, Section 10.2.4. OPs that cause delayed neuropathy include diisopropyl phosphofluoridate (DFP), mipafox, leptophos, methamidophos, and triorthocresol phosphate. The delay in the appearance of neurotoxic symptoms following exposure is associated with the aging process. In most cases, nerve degeneration is not seen with initial inhibition of the esterase but appears some 2-3 weeks after commencement of exposure, as the inhibited enzyme undergoes aging (see Section 16.4.1). The condition is described as OP-induced delayed neuropathy (OPIDN). 

Acute oral exposure to several organophosphate ester hydraulic fluids produced deaths in rabbits, chickens, and cows. The deaths were associated with severe cholinergic symptoms or symptoms of organophosphorus induced delayed neuropathy (OPIDN). (See Section 22.2 A for further details on the neurological effects.)... 

Organophosphate Ester Hydraulic Fluid. The most widely examined target of organophosphate ester hydraulic fluids is the nervous system. Two types of neurological effects have been observed following exposure to certain organophosphate ester hydraulic fluids cholinergic symptoms associated with acetylcholinesterase inhibition and delayed neuropathy (OPIDN). 

About 1-A days after apparent recovery from the acute poisoning, an intermediate syndrome of muscle paralysis can occur, requiring prolonged ventilation before strength returns. A minority of organophosphorus compounds can cause a delayed, chronic, peripheral neuropathy (organophosphorus-induced delayed neuropathy - OPIDN), first manifest some weeks after acute poisoning. 

OPIDN OSHA organophosphorous-induced delayed neuropathy Occupational Safety and Health Administration... 

Application of in vitro test methods have become advantageous in specific cases, such as structurally defined compounds and delayed neuropathy, since target cell data and biochemical processes associated in delayed neuropathy are known. Microscopic studies reveal that cases of OPIDN have degeneration of axons followed by demyelination of the nervous system.25,26 Epidemiologic studies have indicated mild impairment of the brainstem, spinal cord, and peripheral nerve functions in Gulf War veterans.27 Such studies are consistent with the spectrum of OPIDN syndrome. The main nerve agents have been shown to inhibit NTE in vitro as well as in vivo. Sarin has been shown to produce delayed neurotoxicity when administered at higher doses in protected hens.25-27... 

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... 

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. 

The term delayed neurotoxicity may be used to describe any type of toxicity to the nervous system involving a delay between the precipitating chemical exposure and the appearance of neurological signs or symptoms. However, this designation usually refers to organophosphorus (OP) compound-induced delayed neurotoxicity (or delayed neuropathy) (OPIDN), also known as OP compound-induced delayed polyneuropathy (OPIDP). 

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