Organophosphorus-induced delayed neuropathy

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.)... 

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. 

Ehrich, M., Jortner, B.S. (2001). Organophosphorus-induced delayed neuropathy. In Handbook of Pesticide Toxicology, 2nd edition (R. Krieger, ed.), pp. 987-1012. Academic Press, San Diego. 

Baker, T., Stanec, A., Methylprednisolone treatment of an organophosphorus-induced delayed neuropathy, Toxicol. Appl. Pharmacol., 79, 348-352,1985. 

No review of subacute, subchronic, or chronic toxicity of chemical warfare nerve agents would be complete without discussion of the significant paper by Munro et al. that reviewed both animal and human studies of the nerve agents tabun (GA), sarin (GB), and VX. These studies included subacute, subchronic, and chronic toxicity studies in animals. Special attention was paid to the phenomenon of Organophosphorus-Induced Delayed Neuropathy (OPIDN). Reproductive toxicity and carcinogenicity tests were reviewed as well as in vitro studies of mutagenicity. Munro et al. s findings can be summarized as follows ... 

Nerve conduction in organophosphorus-induced delayed neuropathy (OPIDN) was studied using adult white leghorn hen.s treated with ui-2-t -cresyl pho.sphate or di- -butyl-2,2-dichlorovinyi phosphate (Robertson et al, 1987). Refractoriness was decreased in the tibial nerve but it was incrca.sed in the sciatic nene, and the. strength-duration threshold was elevated for both nerves. However, it is not known how these changes are related to the mechanism of OPIDN,... 

N. Aldridge, Postscript to the symposium on organophosphorus compound-induced delayed neuropathy. Chem. Biol. Interact. 87(l-3) 463, 1993. 

Johnson, M.K., Glinn, P. (1990). Neuropathy target esterase (NTE) and organophosphorus-induced delayed polyneuropathy (OPIDP) recent advances. Toxicol. Lett. 82/83 459-63. 

Certain organophosphates may also induce delayed polyneuropathy, usually 2-3 weeks after a single exposure. The symptoms are tingling of hands and feet, sensory loss, progressive muscle weakness, and ataxia. Also, certain organophosphorus compounds are poor inhibitors of AChE but may, however, bind to another esterase, known as neuropathy target esterase (NTE) and induce 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. 

Selected Symptoms Of Organophosphorus Ester-Induced Delayed Neuropathy... 

It is known that human exposure to organophosphorus compounds can result in a variety of acute toxic effects. These arise primarily as a result of the inhibition of acetylcholinesterase. Signs of acute toxicity are due to effects on the central nervous system (anxiety, ataxia, hypotension), to muscarinic effects (wheezing, cough, rhinitis) and to nicotinic effects (muscle weakness, mydriasis and tachycardia). Other acute effects include chest tightness, abdominal cramps, confusion and convulsions. With some organophosphorus compounds, a specific syndrome may develop. This is delayed peripheral neuropathy or OP-induced delayed neuropathy (OPIDN). (For a more detailed discussion on the toxicity of organophosphorus compounds see Chapter 10.)... 

FIGURE 57.5. Subclasses of neuropathy target esterase (NTE) inhibitors. Type A inhibitors include phosphates, phosphonates, and phosphoramidates these are neuropathic and capable of aging. T pe B inhibitors include phosphinates, sulfonates, and carbamates these are nonneuropathic and not capable of aging. However, inhibition of NTE with a type B inhibitor will protect against organophosphorus compound-induced delayed neurotoxicity (OPIDN) from subsequently administered type A inhibitors. Reproduced with permission from Richardson (2005). 

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). 

Early high-toxicity pesticides such as TEPP and parathion have now fallen out of use. Organophosphorus pesticides (and in some cases other phosphate esters such as tricresyl phosphate) are now believed to produce several responses in humans. Acute symptoms can appear within hours of exposure, intermediate syndromes within days, and a delayed response which may take months or even years to develop. The latter is known as OP-induced neuropathy (OPIDN) and is difficult to treat and may be irreversible. 

---