Neurotoxicity delayed peripheral

A delayed peripheral polyneuropathy, known as organophosphate-induced delayed neurotoxicity (OPIDN), from which recovery may be poor. 

Delayed peripheral neurotoxicity has been reported in animal studies. Soman produced severe delayed neuropathy in the atropinized hen assay at 1.5 mg/kg (Willems et al. 

B. Neurotoxicity, including convulsions and delayed peripheral neuropathy, may occur after exposure. 

A number of OPC are capable of rendering a delayed neurotoxic effect (DNE). This effect becomes apparent gradually, after a certain latent period (usually 14 to 21 days, sometimes 1 to 5 years after the acute poisoning survived) and is characterized clinically by the development of ataxia, muscular weakness, paresis and paralysis of the extremities. Morphologically, it is characterized by fiber demyelinization of spinal pathways and peripheral nerves. Till present time, near 40,000 cases have been described, when paresis and paralysis developed in human beings as a result of their exposure to OPC (TOCP, mipaphox, chloropyrophos, trichlorfon, etc.) [1],... 

In animal studies, repeated inhalation of chlorpyrifos at 287 Hg/m (near the theoretical maximum vapor concentration) for 13 weeks caused no treatment-related changes in urinalysis, hematology, clinical chemistry, terminal body and organ weights, or pathology. Induction of delayed polyneuropathy in animals occurs only at doses that exceed the LD50." Peripheral neurotoxic effects could occur in humans after massive exposures at almost lethal doses (from which the patient is saved by intensive medical intervention). The possibility that subtle neurobehavioral effects are associated with pesticide exposure cannot be ruled out. ... 

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... 

Randall, J.C., Yano, B.L., and Richardson, R. J., Potentiation of organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the central and peripheral nervous system of the adult hen distribution of axonal lesions, J. Toxicol. Environ. Health., 51(6), 571-590,1997. 

Husain, K., Peripheral biochemical marker for organophosphate induced delayed neurotoxicity, Biochem. In., 24, 1051, 1991. 

The delayed neurotoxic effect, also called OrganoPhosphate Induced Delayed Neurotoxicity (Neuropathy) (OPIDN), is characterized by sensoric and motoric disturbances of the peripheral nervous system (degeneration of... 

Organophosphorus esters that inhibit neurotoxic esterase, an enzyme present in the brain and peripheral nerves, are associated with delayed neurotoxicity (i.e., peripheral axonopathy). Although inhibition of neurotoxic esterase may not play a primary role in the development of the nerve lesions, it serves as a marker for potential damage. Chickens are often used as test animals for this effect. 

Estevez, J., Barril, J., Vilanova, E., 2012. Kinetics of inhibition of soluble peripheral nerve esterases by PMSF a non-stable compound that potentiates the organophosphorus-induced delayed neurotoxicity. Arch. Toxicol. 86 (5), 767-777. 

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