Pyrethroid insecticides, modeling

These chemorational techniques have generated great interest in, and high expectations for, the acceleration of development of innovative pesticides. However, many purportedly successful appHcations of QSAR procedures have reHed on the quaHtative insights traditionally associated with art-based pesticide development programs. Retrospective QSAR analyses have, however, been helpful in identifying the best compounds for specific uses (17). Chemorational techniques have also found some appHcations in the development of pesticides from natural product lead compounds, the best known examples being the synthetic pyrethroid insecticides (19) modeled on the plant natural product, pyrethmm. 

The compounds featured in Table 1.1 are considered briefly here. Pyrethrins are lipophilic esters that occur in Chrysanthemum spp. Extracts of flower heads of Chrysanthemum spp. contain six different pyrethrins and have been used for insect control (Chapter 12). Pyrethrins act upon sodium channels in a manner similar to p,p -DDT. The highly successful synthetic pyrethroid insecticides were modeled on natural pyrethrins. 

Parameters for Pyrethroid Insecticide QSAR and PBPK/PD Models for Human Risk Assessment... 

Table 1 Biological parameters required for pyrethroid insecticide physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models ...

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. 

At the present time, no predictive QSAR models were found that describe the neurotoxicity of the pyrethroids insecticides. 

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