Mechanisms of pyrethroid neurotoxicity: Implications for cumulative risk assessment

https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.files/fileID/13730

Organophosphate toxicology: safety aspects of nonacetylcholinesterase secondary targets.

Mechanisms of selective action of pyrethroid insecticides.

A carboxylesterase with broad substrate specificity causes organophosphorus, carbamate and pyrethroid resistance in peach-potato aphids (Myzus persicae)

The more stable synthetic pyrethroids, the main subject of this review, are based on the earlier natural and synthetic pyrethroids, but differ so markedly from them in properties and activity as to constitute a new class of insecticides. The value of residual films of contact insecticides was fi rst demonstrated in 1935 (114) by the successful control of pests of stored products with natural pyrethrins in heavy white oil, but the active ingredients of the formulation were too unstable in light and too expensive to be used for controlling agricultural pests. However, with the advent of modern synthetic insecticides such as DDT in 1943, a range of stable and inexpensive insecticides with outstanding efficiency as residual deposits against agricultural and other pests became available. A succession of organochlo­ rine, organophosphate, and carbamate insecticides has been developed since then, but without any great increase in the general level of insecticidal activity. Subse­ quently, undue persistence, high mammalian toxicity, and development of resistance with some of these compounds have provoked increasing concern and have empha­ sized the inadequacy of present insecticides. The fi rst synthetic pyrethroids in which characteristically high activity against insects and low mammalian toxicity were combined with greatly increased stability were described in 1973 (49, 50). In addition to being more photostable under appropriate conditions than many of the common organophosphates and carba­ mates, several of the compounds were also more insecticidally active by at least one order of magnitude. With the structural requirements for photostable pyrethroids established, many new compounds were synthesized ( 1973-77) that retained the chemical and stereo­ chemical features of the parent molecule5-, and hence their biological activities. Appropriate examples were selected for practical trials and toxicological examina­ tion. Although the initial phases of field evaluation are barely complete, it is already apparent that the new compounds are outstandingly effective against many pests and, unless unforeseen toxicological hazards or other disadvantages are discovered,

The future of pyrethroids in insect control

Permethrin metabolism in rats.

Substrate-specificity and toxicological significance of pyrethroid-hydrolyzing esterases of mouse liver microsomes☆

Pesticide interactions: Effects of organophosphorus pesticides on the metabolism, toxicity, and persistence of selected pyrethroid insecticides

The metabolism of 20 pyrethroids has been examined to evaluate the contribution of detoxification in their selective action between insects and mammals. The studies utilized living houseflies, mice, or rats, or esterase and oxidase systems derived from these organisms. Pyrethroid-hydrolyzing esterases cleave the primary alcoholtrans- substituted-cyclopropanecarboxylates much faster than the correspondingcis-isomers but are ineffective in hydrolyzing secondary alcohol esters. Microsomal enzymes oxidize the (+)-trans-chrysanthemate moiety at thetrans-methyl group of the isobutenyl substituent and at one of the gem-dimethyl groups whereas the (+)-cis-isomer is attacked at either of the isobutenyl methyl groups. Products isomerized at C3 of the cyclopropane are also detected but only after ester cleavage and oxidation of an isobutenyl methyl group. Each alcohol moiety has its own unique sites for oxidation involving pentadienyl, allyl, benzylic methylene, and aromatic substituents. An enhancement of insecticidal activity is expected on replacement of the biodegradable groupings with substituents relatively resistant to metabolism but this may also increase the mammalian toxicity.

Loretta C. Gaughan

Papers

Permethrin metabolism in rats.

Substrate-specificity and toxicological significance of pyrethroid-hydrolyzing esterases of mouse liver microsomes☆

Pesticide interactions: Effects of organophosphorus pesticides on the metabolism, toxicity, and persistence of selected pyrethroid insecticides

Structure-biodegradability relationships in pyrethroid insecticides.

Radiosynthesis and metabolism in rats of the 1R isomers of the insecticide permethrin.