Low level exposures to organophosphorus esters may cause neurotoxicity
Introduction
Exposure to organophosphorus (OP) esters can cause several syndromes including acute cholinergic clinical episodes, the so-called Intermediate syndrome, organophosphate induced delayed neuropathy (OPIDN) and chronic neurological effects. Acute toxicity is produced by irreversible inactivation of the enzyme cholinesterases, the exact mechanism of the intermediate syndrome is not understood while the OPIDN is claimed to be ‘marked’ by the inhibition and subsequent ageing (dealkylation) of a protein enzyme in nerve cells called neuropathy target esterase (NTE). The ability to produce OPIDN is not even related to the degree of inhibition of AchE and there is no indication that the intermediate syndrome is related to the cholinergic effect of OP compounds. It took the medical and scientific body more than 50 years to recognise OPIDN despite its dramatic nature of clinical presentation.
Chronic neurological effects have been reported to occur either following one or more attacks of acute cholinergic episodes or following long-term, low-level (LTLL) exposure to OP compounds. In order to differentiate the chronic neurological effects from the rest of the OP syndromes, the term Chronic Organophosphate Induced Neuropsychiatric Disorder (COPIND) is used for ease of reference. The remit of this review is confined to providing affirmative evidence to the title statement that low-level exposure to OP esters may cause neurotoxicity. It is not the remit of this article to describe the profile of the chronic toxicity or to discuss the possible underlying mechanisms of such chronic toxicity. These have been described elsewhere (Jamal, 1997) but will be mentioned briefly, given the limited space.
Section snippets
Review of studies in the literature
Studies concerning the chronic effects of OP esters are discussed in this review under two different headings; studies of COPIND following one or more acute clinical cholinergic episodes and COPIND without preceding cholinergic attacks.
Conclusion
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Each and every study available in the literature concludes that chronic neurotoxicity can follow one or more acute clinical cholinergic episodes. The development of chronic neurotoxicity seems to be unrelated to the number or the severity of the acute cholinergic attacks.
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With regards to the relationship between long term low level exposure to OP (with no history of preceding acute cholinergic episodes) and development of chronic neurotoxicity, the following conclusions can be made: All studies
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