OPIDN—

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.)... 

Acute exposure to certain organophosphate esters produces a slowly developing neuropathy in humans, OPIDN, that is functionally characterized by initial weakness and subsequent ataxia and paralysis in the lower limbs (8-14 days or longer, following exposure) (Ecobichon 1991 Johnson 1975 Murphy 1986). 

In severe cases, paralysis may also affect the upper limbs. Recovery is usually slow and is not always complete. Tri-ort/20-cresyl phosphate (TOCP), an isomer found in tricresyl phosphate, was the first organophosphate ester linked to OPIDN, being responsible for an epidemic of paralysis in the southeastern United States that led to the name "ginger jake paralysis" (Smith 1930) (see Section 2.4). Current manufacturing processes for organophosphate ester hydraulic fluids are designed to minimize production of this isomer, although it is possible that fluids disposed of in the past may be contaminated. 

The mechanism of OPIDN is poorly understood, but, since all organophosphate esters that produce OPIDN are either direct cholinesterase inhibitors or are metabolically converted to cholinesterase inhibitors, inhibition of an esterase of some kind has generally been thought to be involved (Baron 1981). Certain... 

Two types of OPIDN have been described in animals (Abou-Donia and Lapadula 1990). Type I is produced by compounds with a pentavalent phosphorus (like TOCP), and Type II is produced by compounds with a trivalent phosphorus. Characteristics used to differentiate between the types of OPIDN include species selectivity, age sensitivity, length of latent period, and morphology of neuropathologic lesions. Thus, at doses that did not produce death due to acetylcholinesterase inhibition, TOCP (a Type I compound) produced lesions in the spinal cord of rats without producing ataxia. In contrast, triphenyl phosphite (a Type II compound) produced delayed (1 week) ataxia in the rat and a distribution of spinal cord lesions distinct from those produced by TOCP (Abou-Donia and Lapadula 1990). 

The available inhalation data for Durad MP280, Fyrquel 220, Cellulube 220, Skydrol 500B-4, and cyclotriphosphazene (reviewed in the next paragraph) are inadequate to derive intermediate-duration MRLs for these individual fluids, principally because the studies were conducted in species (rats or rabbits) that are generally considered to be insensitive to the delayed neurotoxicity of acute exposure to organophosphate esters. Cats, dogs, or nonhuman primates more accurately model the human expression of OPIDN than rats and rabbits, and studies in these species would provide a better basis for MRL derivation. 

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). 

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. 

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. 

No studies were located regarding organophosphate-induced delayed neurotoxicity (OPIDN) in humans or in animals after inhalation exposure to diazinon. 

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

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