Chronic effects of low level exposure to anticholinesterases - a mechanistic review

High dose exposure to anticholinesterases which results in symptomatic pois oning can have lasting consequences due to the trauma of intoxication, exci totoxicity, secondary hypoxic damage, and (for some agents) a delayed onset polyneuropathy (OPIDN). The potential effects of low level exposure are le ss well defined. The most reliable data comes from controlled clinical tria ls with specific agents. A single dose of sarin or repeated doses of metrif onate or mevinphos, have produced only transient adverse effects at doses c ausing substantial acetylcholinesterase inhibition. Other data comes from e pidemiological surveys. These have often used more sensitive indices than t he clinical studies, but are less reliable due to the difficulty of definin g exposure and matching control and exposed populations. Subtle, mainly cog nitive, differences between exposed and non-exposed populations are sometim es seen. Low level exposure can cause a reversible down-regulation of choli nergic systems, and a range of non-cholinesterase effects that are structur e-specific, and do not always parallel acute toxicity. Novel protein target s sensitive to low level exposure to some organophosphates are known to exi st in the brain, but their functional significance is not yet understood. ( C) 1998 Elsevier Science Ireland Ltd. All rights reserved.