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

High dose exposure to anticholinesterases which results in symptomatic poisoning can have lasting consequences due to the trauma of intoxication, excitotoxicity, secondary hypoxic damage, and (for some agents) a delayed onset polyneuropathy (OPIDN). The potential effects of low level exposure are less well defined. The most reliable data comes from controlled clinical trials with specific agents. A single dose of sarin or repeated doses of metrifonate or mevinphos, have produced only transient adverse effects at doses causing substantial acetylcholinesterase inhibition. Other data comes from epidemiological surveys. These have often used more sensitive indices than the clinical studies, but are less reliable due to the difficulty of defining exposure and matching control and exposed populations. Subtle, mainly cognitive, differences between exposed and non-exposed populations are sometimes seen. Low level exposure can cause a reversible down-regulation of cholinergic systems, and a range of non-cholinesterase effects that are structure-specific, and do not always parallel acute toxicity. Novel protein targets sensitive to low level exposure to some organophosphates are known to exist in the brain, but their functional significance is not yet understood.