Organophosphate-Induced Delayed Neuropathy

Abstract

Although the cholinesterase-inhibiting effects of organophosphate (OP) compounds were not utilized until the time of World War II, the ability of some of these chemicals to cause an irreversible, progressive delayed neuropathy was recognized as early as the 1890s, when a 15% solution of tri-ortho-cresyl phosphate (TOCP, or tri-ortho-tolyl phosphate, TOTP) was used to treat tuberculosis. A number of incidents of organophosphate-induced delayed neuropathy (OPIDN) have been reported since then, with TOTP identified as the neurotoxic contaminant of cresyl phosphates associated with these poisonings. Large numbers of humans were affected in some of these incidents, including over 50,000 Americans who ingested a TOTP-contaminated alcoholic extract of ginger during the era of prohibition (1930s), 10,000 Moroccans who ingested TOTP-contaminated cooking oil in the 1950s, and 600 Indians who consumed TOTPcontaminated rapeseed oil in 1988. Early studies determined that not every OP compound was capable of causing OPIDN and that all animal species were not uniformly susceptible. Clinical evidence of progressive, irreversible OPIDN has been observed in humans, water buffalo, sheep, cats, ferrets, chickens, and a number of other species; laboratory rodents (e.g., rats, mice), however, do not demonstrate progressive locomotor effects after exposure (1–7).