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Organophosphate: definition.


http://www.pesticides.gov.uk/anticholinesterase/op_definition.htm

Definition of Organophosphate (OPs) and Their Toxicology

  1. The term organophosphate (OP) is generally understood to mean an organic derivative of phosphoric or similar acids. There are many different OPs and they differ to some extent in their properties. Many OPs inhibit an enzyme known as acetylcholinesterase (the effect of which is described in paragraph 2). This is a class effect of OPs, but not all OPs (e.g. glyphosate) demonstrate this effect. Some OPs react with other proteins such as neuropathy target esterase, and this reaction is associated with the effects detailed in paragraph 5.

  2. Inhibitors of acetylcholinesterase affect certain nerve junctions in animals, as well as parasympathetic effector sites (the heart, lungs, stomach, intestines, urinary bladder, prostate, eyes and salivary glands). The transmission of impulses across nerve junctions involves the release of a transmitter chemical, which, in the case of many nerves, is acetylcholine. To stop the nerve continuing to transmit the message, the transmitter, acetylcholine, must be broken down immediately after it has had its effect. This breakdown is brought about by an enzyme, acetylcholinesterase. By inhibiting the enzyme acetylcholinesterase, OPs prevent the nerve junction from functioning properly. In the case of most OPs and all medicinal and pesticidal anticholinesterase OP products this effect is either reversible, the rate of re-activation of the enzyme being dependent on the chemical structure of the OP, or recoverable by synthesis of new enzyme.

  3. OPs can be carefully selected, on the basis of their chemical structure, so that they are very effective agents against their target pest or insect and the risk to humans can be controlled by following the recommended precautions. The efficacy of OP products as pesticides and as human and veterinary medicines relates to the inhibition of acetylcholinesterase in the target pest species.

  4. In humans, anticholinesterase OPs have broadly similar actions to those seen in other species. Acetylcholinesterase inhibition causes acute effects in humans and other mammals. The symptoms in humans, which generally occur when acetylcholinesterase activity has been reduced by about 50%, may include: headache, exhaustion and mental confusion together with blurred vision, sweating, salivation, chest tightness, muscle twitching and abdominal cramps. The severity of the effects depends on the degree of acetylcholinesterase inhibition. The more severe effects can include muscle paralysis leading to severe difficulty in breathing, so requiring respiratory support. Convulsions and unconsciousness can occur. Recovery depends on elimination of the OP product from the body and return of acetylcholinesterase activity. However, as noted in paragraph 1, not all OPs are anticholinesterases, and compounds such as glyphosate exhibit quite different toxic effects. Furthermore some non-OPs are anticholinesterases and these compounds have similar toxicity to anticholinesterase OPs, an example of this being the carbamate insecticides.

  5. Some OPs may also work by another mechanism, that is, causing an OP-induced delayed effect on the peripheral nerves. This is known as OP induced delayed polyneuropathy (OPIDP). OPIDP is a delayed effect caused by die-back in the long nerves, thus affecting the limb extremities. OPIDP is associated with, but not necessarily caused by, inhibition of another enzyme known as neuropathy target esterase (NTE). The capacity of OPs to inhibit NTE and cause OPIDP does not correlate with their capacity to inhibit acetylcholinesterase. Any OP product which is shown by laboratory tests to be likely to produce OPIDP in humans, will not be authorised in the UK. A number of studies of OP products currently or previously used in UK sheep dip, have shown them to have no potential to produce delayed polyneuropathy in animal tests.

  6. Another known toxicological effect of OPs in humans has been termed the intermediate syndrome. This can follow severe acute poisoning, sometimes as a result of a suicide attempt, and causes temporary paralysis of the proximal muscles (muscles nearest to the central line of the body e.g. respiratory, neck and upper part of limb muscles; the distal muscles of the limb are not affected so grip strength may be preserved). Since this includes the respiratory muscles, respiratory support is necessary to keep the patient alive. The precise reasons for the development of intermediate syndrome are not clear but explanations which have been advanced include myopathy (muscular damage), depolarisation blockade (blocking impulses at the neuromuscular junction and paralysing the muscles) and Guillain-Barre syndrome-like effects (muscle weakness, numbness and pins and needles in limbs).

  7. There are postulated long-term effects of OPs following long-term low-level exposure. Some studies on low-level exposure have shown subtle effects (e.g. slower reaction times) in specialised tests for neurological function, whereas others have shown no change in different neuropsychological and neurophysiological tests. The alleged theories and mechanisms are sometimes not related to acetylcholinesterase activity.

 Taken from the Official Group on OPs Report to Ministers

NOTE: In relation to the effects of organophosphates, you may wish to be aware that a Working Group of the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) was set up under the Chairmanship of Professor Woods to review the evidence of possible ill health effects of organophosphates.  Details of the work of this group and their report, which was published on 26 November 1999, is Leave Our Siteavailable on their website hosted by the Department of Health.


Crown Copyright 2000 
13 February 2001