Mammalian toxicity, pyrethroid insecticides

Pyrethroid insecticides are widely used because of their high activity as an insecticide and low mammalian toxicity. Pyrethroids are in group 3, sodium channel modulators. The pyrethroids have a highly nonpolar nature, low water solubility, and high affinity to soil and sediment particulate matter. Natural pyrethrin is extracted from the flowers of Chrysanthemum spp., and its use was already known in China in the first century A.D. Pyrethroids, synthetic analogues of pyrethrin, have been produced since 1940 [26]. 

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

The establishment of a common mechanism of mammalian toxicity for the pyrethroids is not a straight forward process, as it was for the organophosphorus and carbamate insecticides, due to the occurrence of multiple potential target sites and the varied action of pyrethroids at these sites as reviewed above. In view of... 

Abstract Metofluthrin (commercial name SumiOne, Eminence ) is a novel pyrethroid insecticide developed by Sumitomo Chemical Co., Ltd. Metofluthrin has extremely high insecticidal activity to various pest insects, especially to mosquitoes. In addition, Metofluthrin has relatively high volatility and low mammalian toxicity. Metofluthrin is therefore suitable for use not only in conventional mosquito control formulations such as coils and liquid vaporizers, but also in a variety of novel devices that do not require heating, such as fan vaporizers and paper and resin emanators. Here we describe the insecticidal activity of Metofluthrin mainly against mosquitoes in various formulations in both laboratory and field trials. 

A newer class of insecticides is the pyrethroids. These are synthetic derivatives of pyrethrins, which are natural extracts from chrysanthemums. Pyrethroids have been developed to be more stable (and thus more effective as insecticides) than the pyrethrins, which are particularly instable in light. Pyrethroids are frequently used as broad-spectrum insecticides. They have high insect toxicity, but lower mammalian toxicity than their organophosphate or carbamate counterparts. Pyrethroids are still limited in effectiveness due to their environmental lability, their high cost, and their potential for resistance development. 

Pyrethrins and synthetic pyrethroids are among the safest of the topically applied ectoparasiticides, because of their selective toxicity for insects (mam-malian-to-insect toxic dose ratio is greater than 1000, compared with 33 for organophosphates and 16 for carbamate insecticides). In contrast to the very wide margin of safety for mammalian species, pyrethroids are toxic to fish. The synergistic action of pyrethrins and piperonyl butoxide (in combination preparations) is due to the inhibition by piperonyl butoxide of the microsomal enzyme system of some arthropods. Preparations of synthetic pyrethroids (permethrin, cypermethrin) often contain a mixture of drug isomers in varying proportions. 

Prior to the advent of DDT and the organophosphates, the natural pyrethrins (32.33) found considerable use but were limited by their instability. The discovery of permethrin by Michael Elliot (3 4) proved a turning point for the new synthetic pyrethroids. Here were very active compounds that did not suffer from the stability problems of the natural compounds. And even now pyrethroid-like compounds continue to interest synthetic chemists due to their high insecticidal activity and relatively low mammalian toxicity. You would think that by now most of the very active compounds would have been found. but it seems that persistence and originality pay off. Workers at du Pont and FMC detail the structure-activity relationships for two groups of new pyrethroid-like compounds. Chemists at Dow reveal some of the intricacies in the synthesis of the cyclopropane carboxylate end of the molecule. 

Pyrethroids, due to their high insecticidal activity and low mammalian toxicity (1), have been the subject of much synthetic effort (1-2). Most of the commercially available synthetic pyrethroids are generally related in that they contain the same meta-phenoxvbenzvl alcohol, or some close derivative thereof in the molecule, two examples being permethrin and fenvalerate. 

For interior uses protected from the weather decay or mould protection may not needed and wood may be treated with an insecticide only. Historically, insecticides with unnecessarily high mammalian toxicities such as lindane, dieldrin, aldrin and chlorpyrifos were used. More recently these have been largely replaced with pyrethroids such as permethrin and cypermethrin, as well as chloronicotinyl and neonicotinoids, pyroles, and insect growth regulators. These insecticides may also be incorporated with a fungicide, such as IPBC or the triazoles, to provide a greater degree of protection. 

Pyrethroid insecticides (deltamethrin, NRDC 157, cismethrin), DDT analogs ( p,j> -DDT, (>,j> -DDT, methoxychlor, EDO), and a DDT-pyrethroid hybrid compound (GH401) enhanced veratridine-dependent sodium uptake by mouse brain synaptosomes The effectiveness of these compounds in the sodium uptake assay was in good agreement with their acute mammalian toxicities. , -DDT also enhanced veratridine-dependent sodium uptake by fish brain synaptosomes These findings demonstrate the utility of ion flux assays to study interactions of insecticides with sodium channels in the central nervous system and to explore species differences in insecticide target site sensitivity ... 

Certain kinds of cyclopropanecarboxylic acids are important in the production of pyrethroid, an insecticide with low mammalian toxicity [1]. For example, chrysanthemic acid is an acid component of allethrin (Fig. 1). Various kinds of alcohols have been developed to produce pyrethroids for special application [2]. Chrysanthemic acid has two chiral centers and there are four optical isomers. There is a close correlation between the chirality of a molecule and its biological activity [3]. In the case of chrysanthemic acid, the most effective isomer is shown to be the d-trans isomer, which is followed by the d-cis isomer whereas... 

Insecticides such as permethrin, benzyl benzoate, lindane, and pyrethrin have been used to treat lice. Pyrethrins are insecticides initially derived from certain species of chrysanthemum flowers. Synthetic pyrethroid insecticide is more stable with a similar activity and low mammalian toxicity and is called permethrin. Lindane (1,2,3,4,5,6 hexachlorocyclohexane) and benzyl benzoate have also been used as pediculocides. Lice infection is spread by direct contact or by wearing the clothing of an infected person. The control of secondary bacterial infection may require an antibiotic. 

The lead compound, which initiated interest in the neonicotinoids, is a nitro-methylene heterocycle, nithiazine (Figure 1) [1]. Nifhiazine, with its unique nitromethylene moiety, showed low mammalian toxicity, but its insecticidal potency and field stability were inferior to commercial organophosphates and pyrethroids. Thus, nithiazine was not of commercial use for pest control. However, the introduction of 6-choloronicotinyl and 2-nitroimino-imidazolidine moieties led to the development of the first commercial neonicotinoid imidacloprid (Figure 1)... 

Pyrethroids are synthetic analogues of the naturally occurring pyrethrins (isolated from Chrysanthemum sp.) and are popular insecticides for agricultural and domestic uses, with favorable properties like biodegradability and low mammalian toxicity. Prothrin 64 is a member of the furan-based class of p5n ethroids, which also includes the high-volume commercial insecticide resmethrin. Chang et al. recently... 

In general, synthetic pyrethroids are degraded by both abiotic and biotic pathways. Even though residues of synthetic pyrethroids have frequently been detected in soils, sediments, natural waters and agricultural products (Wang et al. 2011). The pyrethroid insecticides have low mammalian toxicity and persistence in... 

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