Pyrethroid insecticides, chirality, isomers

Pyrethroid insecticides can exist as enantiomers because they have two chiral centers, i.e., asymmetric carbons at C-l and C-3. An enantiomer exhibits optical activity and R/S configuration. Thus, a pyrethroid can show as either dextrorotatory (+) or levorotatory (-) isomer. A pyrethoid also can exist as either R or S form. However, only C-l is important to the biological activity of these compounds, and, for activity, it must be in the R position. As shown next, to be the 1R form, the -COOR group must be below the page. The IS form, which has -COOR group above the page, is nontoxic. Therefore, the active isomer of deltamethrin is expressed as (+)-ris-(lR) deltamethrin. The active isomer of permethrin is (lR)-ds-permethrin. 

In this review, we have concentrated on the development of (1) in vivo metabolic data (i.e., and K, etc.), (2) QSAR, and (3) mechanistic models and their application for building PBPK/PD models. The development of the pyrethroid insecticides for agricultural and home use is complicated by their chemistry, in that they each possess one to four chiral centers, increasing the number of isomeric forms by a factor of 2 (where = the number of chiral centers). Isomer mixtures and individual isomers are commonly both subjected to testing for insecticidal activity. The fewer the number of active forms, the easier it is to test them for insecticidal activity, toxicity, and to buUd PBPK/PD models for them. The pyrethroids on which we focus in this review are presented in Table 2, along with their trivial and CAS names and their structures. Table Al (Appendix A) defines the acronyms and abbreviations used in the text, while Table A2 (Appendix A) defines the chemical and mathematical expressions that are presented in this review. 

The sections on the metabolism and neurotoxicity of the pyrethroids in this review provide a starting point that feeds into the physiological and biochemical parameters that are needed to develop PBPK/PD models for assessing risks to the pyrethroids. The development of such pyrethroid model parameters requires knowledge of their discovery, chemistry, chirality, their isomers, and their chromatographic separation. To this end. Sect. 2 above (viz.. Nature of Pyrethroid Insecticides) was developed with a listing of 15 of the most important pyrethroids... 

Oi N, Horiba M, Kitahara H (1981) Gas chromatographic separation of optical isomers of chrysanthemic acid on an optically active stationary phase. Agric Biol Chem 45(6) 1509-1510 Oi N, Kitahara H, Kira R (1990) Enantiomer separation of pyrethroid insecticides by high-performance liquid chromatography with chiral stationary phases. J Chromatogr A 515 441 50... 

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... 

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