Invited critical reviewCurrent issues in organophosphate toxicology
Section snippets
Organophosphorus: insecticides
Although a number of organic phosphorus (OP) compounds were synthesized in the 1800s, their development as insecticides only occurred in the late 1930s and early 1940s. The German chemist Gerhard Schrader is credited for the discovery of the general chemical structure of anticholinesterase OP compounds and for the synthesis of the first commercialized OP insecticide [Bladan, containing TEPP (tetraethyl pyrophosphate) as an active ingredient], and for one of the most known, parathion, in 1944 [1]
AChE and NTE as primary targets
The primary target for OPs is AChE, a B-esterase whose physiological role is that of hydrolyzing acetylcholine, a major neurotransmitter in the peripheral (autonomic and motor–somatic) and central nervous systems. OPs with a P = O moiety phosphorylate an hydroxyl group on serine in the active (esteratic) site of the enzyme, thus impeding its action on the physiological substrate (Fig. 2). The bond between the phosphorus atom and the esteratic site of the enzyme is much more stable than the bond
Continuing issues in OP toxicology
Despite having been around for over sixty years with an almost as long knowledge of their main mechanism of action and adverse health effects, OPs continue to be the subject of much research efforts. For example, a Medline search (August 2005) with the terms organophosphate/organophosphorus provided around 5000 hits since the year 2000, more than one fourth of all citations since the mid 1950s. The reasons for these research activities, in addition to the continuing high worldwide use of these
Conclusion
The use of OPs as insecticides in the agricultural and urban settings is still high and is expected to remain so, at least in the near future. While other classes of insecticides are gaining market share (e.g., pyrethroids) and new classes have been developed (e.g., neonicotinoids), the efficacy of OPs, their relatively low cost and their lack of bioaccumulation in the ecosystems, would support this prediction. Yet OPs display relatively limited selectivity (one exception may be malathion)
Acknowledgements
Research by the author is supported by grants from the National Institute of Environment Health (ES04696, ES07033, ES09601/EPA-R826886). Views expressed in this paper are solely of the author and not of the funding agencies.
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