Fenvalerate mammals

Synthetic pyrethroids now account for at least 30% of the world insecticide market and are rapidly replacing other agricultural chemicals for control of insect pests. Fenvalerate is one of the more widely used synthetic pyrethroid insecticides. It is derived from a combination of a-cyano-3-phenoxybenzyl alcohol and a-isopropyl phenylacetate ester. Technical fenvalerate is a mixture of four optical isomers, each occurring in equal amounts but with different efficacies against insect pests. Fenvalerate does not usually persist in the environment for >10 weeks, and it does not accumulate readily in the biosphere. Time for 50% loss (Tb 1/2) in fenvalerate-exposed amphibians, birds, and mammals was 6 to 14 h for reptiles, terrestrial insects, aquatic snails, and fish it was >14 h to <2 days and for various species of crop plants, it was 2 to 28 days. Fenvalerate degradation in water is due primarily to photoactivity, and in soils to microbial activity. Half-time persistence in nonbiological materials is variable, but may range up to 6 days in freshwater, 34 days in seawater, 6 weeks in estuarine sediments, and 9 weeks in soils. 

In biological samples, fenvalerate neither persists for lengthy periods nor is readily accumulated (Smith and Stratton 1986 Cooper 1991). In general, fenvalerate is rapidly (i.e., Tb 1/2 of 6 to 14 h) excreted by amphibians, birds, and mammals has low persistence in various reptiles, terrestrial... 

Metabolism of fenvalerate proceeds by way of oxidation and hydrolysis to produce metabolites considered pharmacologically inactive or inferior to the parent compound. Insects and fish are extremely susceptible to fenvalerate when compared to mammals and birds. Interspecies differences are associated with rates of metabolism, excretion, absorption, esterase activity, and neurosensitivity. 

Fenvalerate is extremely toxic to representative nontarget aquatic organisms and to some beneficial terrestrial arthropods at concentrations substantially lower than those recommended to control pestiferous insects. Toxic effects are associated primarily with the 2.S, a.S -isomcr and are exacerbated at low temperatures. Birds, mammals, and terrestrial plants are normally tolerant. 

Adverse effects of fenvalerate on survival of terrestrial arthropods were observed at 0.002 to 0.015 pg whole-body topical application, O.llkg/ha aerial application, 5.4 mg/kg in the soil, 50 mg/kg in the diet, and 1.4 g/ant mound (Table 20.4). Synthetic pyrethroids are more effective in biological systems at low temperatures. The relative sensitivity of insects when compared with mammals is attributed in part to this negative temperature coefficient. Thus, warm-blooded animals are less affected than insects and other poikilotherms (Klaassen etal. 1986). Fenvalerate, for example, showed a negative correlation between temperature and toxicity to crickets (Acheta pennsylvanicus), being up to 1.9 times more toxic at 15°C than at 32°C (Harris etal. 1981). A similar case is made for honey bees (Apis mellifera) (Mayer et al. 1987) and for many species of aquatic invertebrates and fish (Mayer 1987). 

Table 20.7 Lethal and Sublethal Effects of Fenvalerate on Mammals...

Fenvalerate persists for <10 weeks in the environment and does not accumulate readily in the biosphere. Time for 50% loss (Tb 1/2) in fenvalerate-exposed amphibians, birds, and mammals is 6 to 14 h. For reptiles, terrestrial insects, aquatic snails, and fish, it is usually >14 h to <2 days and for crop plants, it is 2 to 28 days. In nonbiological compartments, Tb 1/2 is up to 6 days in freshwater, 34 days in seawater, 6 weeks in estuarine sediments, and 9 weeks in soils. 

Bennett, R.S., E.E. Klaas, J.R. Coats, and E.J. Kolbe. 1986. Fenvalerate concentrations in the vegetation, insects, and small mammals of an old-field ecosystem. Bull. Environ. Contam. Toxicol. 36 785-792. Bennett, R.S., Jr. E.E. Klaas, J.R. Coats, M.A. Mayse, and E.J. Kolbe. 1983. Fenvalerate residues in nontarget organisms from treated cotton fields. Bull. Environ. Contam. Toxicol. 31 61-65. 

Fenvalerate has low toxicity in mammals due to its rapid metabolic breakdown. It acts directly on nerve axons by prolonging sodium channel opening in cell membranes. Insects exposed to fenvalerate are quickly paralyzed exposure causes quick insect knockdown. In small animals, type II pyrethroids cause salivation, chewing, burrowing, choreoathetosis, and seizures. They also cause lower action potential amplitude, marked membrane depolarization, and eventual total neural activity blockade. Fenvalerate is likely to act both on peripheral and central nervous system. It is also a potent inhibitor of calcineurin (protein phosphatase 2B). 

Cl (119) CH3 C-0< J<5>J 0 Mammals. Proton NMR aided in the characterization of metabolite. One optical isomer of Fenvalerate was metabolized more rapidly than others. 

Fenvalerate[(RS)-a-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)iaovalerate] consists of four optical isomers due to the presence of two chiral carbons in the acid and alcohol moieties. Of the four isomers, one specific isomer ([2R,CXS]) was preferentially metabolized in mammals including rats and mice to a cholesterol ester which was formed by condensation of the acid moity with cholesterol. This conjugate does not seem to be produced via three known endogenous biosynthesis routes of cholesterol esters, but via transesterification mediated by microsomal... 

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