Fenvalerate metabolism

The proposed fenvalerate metabolic pathways in dogs (Kaneko et al. 1984) suggest that species differences and pathways are important and require more research. 

Fenvalerate and other a-cyano pyrethroids, however, are consistently more resistant to oxidative attack than their noncyano analogs. Liver is the predominant site of fenvalerate metabolism via hydrolysis by one or more hepatic microsomal esterases inhibition of these enzymes results in enhanced toxicity. Hydrolysis has also been demonstrated in plasma, kidney, stomach, and brain tissues. Except for brain, however, these tissues were relatively unimportant in the detoxification process. 

Parent chemical or metabolite number for cross-reference to Table E7 (Appendix E, Fenvalerate) Metabolism source, Kaneko and Miyamoto (2001) and Kaneko (2010). See footnotes in Table D1 (Appendix D)... 

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. 

Metabolism of the 2,S -isomers proceeds sequentially hydroxylation at the phenoxy group, hydrolysis of the cyano group, and cleavage of the ester linkage (Coats et al. 1989). Fenvalerate and the IS-isomers yield two ester metabolites in feces from hydroxylation at the 4 - and 2 -phenoxy positions. Other significant metabolites were 3-phenoxybenzoic acid and its hydroxy derivatives from the alcohol moiety, 3-(4-chlorophenyl) isovaleric acid and its hydroxy derivatives from the acid moiety, and thiocyanate and carbon dioxide from the cyano moiety (Ohkawa et al. 1979). A slow elimination rate characterizes fenvalerate and other a-cyano pyrethroids when compared with... 

Terrestrial plants are relatively unaffected by fenvalerate at recommended application rates, as judged by negligible uptake of fenvalerate from treated soils, formation of numerous fenvalerate conjugates that are pharmacologically inactive, and metabolism of the liberated cyano group into amino acids and eventually carbohydrate and protein (Miyamoto 1988). 

Akhtar, M.H. 1983. Metabolism of fenvalerate by a chicken liver enzyme preparation. Jour. Agricul. Food Chem. 31 1080-1083. 

Akhtar, M.H., H.L. Trenholm, and R.M.G. Hamilton. 1989. Metabolism of fenvalerate in laying hens. Jour. 

El-Sewedy, S.M., M.H. Mostata, E.A. El-Bassiouni, A. Abdel-Rafee, and A.H. El-Sebae. 1982. Effect of fenvalerate on kynurenine metabolizing enzymes and acid ribonuclease of mouse liver. Jour. Environ. Sci. Health B17 571-579. 

Flodstrom, S., L. Wamgard, S. Ljungquist, and U.G. Ahlborg. 1988. Inhibition of metabolic cooperation in vitro and enhancement of enzyme altered foci incidence in rat liver by the pyrethroid insecticide fenvalerate. Arch. Toxicol. 61 218-223. 

Golenda, C.F. and A.J. Forgash. 1989. The distribution and metabolism of fenvalerate in pyrethroid-resistant and susceptible house flies. Pestic. Biochem. Physiol. 33 37-48. 

Kaneko, H., M. Matsuo, and J. Miyamoto. 1986. Differential metabolism of fenvalerate and granuloma formation. I. Identification of a cholesterol ester derived from a specific chiral isomer of fenvalerate. Toxicol. Appl. Pharmacol. 83 148-156. 

Kaneko, H., H. Ohkawa, and J. Miyamoto. 1981. Comparative metabolism of fenvalerate and the [25,aS]-isomer in rats and mice. Jour. Pestic. Sci. 6 371-326. 

McKenney, C.L., Jr. and D.B. Hamaker. 1984. Effects of fenvalerate on larval development of Palaemonetes pugio (Holthuis) and on larval metabolism during osmotic stress. Aquat. Toxicol. 5 343-355. 

McKenney, C.L., Jr. D.E. Weber, D.M. Celestial, and M.A. MacGregor. 1998. Altered growth and metabolism of an estuarine shrimp (Palaemonetes pugio) during and after metamorphosis onto fenvalerate-laden sediment. Arch. Environ. Contam. Toxicol. 35 464-471. 

Mikami, N., J. Yoshimura, T. Katagi, H. Yamada, and J. Miyamoto. 1985. Metabolism of the photo-decarboxy-lated derivative of fenvalerate in rats. Jour. Pestic. Sci. 10 273-284. 

Mumtaz, M.M. and R.E. Menzer. 1986. Comparative metabolism and fate of fenvalerate in Japanese quail (Cotumix coturnix japonica) and rats (Rattus norvegicus). Jour. Agricul. Food Chem. 34 929-936. 

Reddy, P.M. and M. Bashamohideen. 1988. Toxic impact of fenvalerate on the protein metabolism in the branchial tissue of a fish, Cyprinus carpio. Current Sci. 57 211-212. 

Symonik, D.M., J.R. Coats, S.P. Bradbury, G.J. Atchison, and J.M. Clark. 1989. Effect of fenvalerate on metabolic ion dynamics in the fathead minnow (Pimephales promelas) and bluegill (Lepomis macrochi-rus). Bull. Environ. Contam. Toxicol. 42 821-828. 

In addition, three types of lipophilic conjugates have been found in pyrethroid metabolism studies (Fig. 4). They are cholesterol ester (fenvalerate) [15], glyceride (3-PBacid, a common metabolite of several pyrethroids) [16], and bile acid conjugates (fluvalinate) [17]. It is noteworthy that one isomer out of the four chiral isomers of fenvalerate yields a cholesterol ester conjugate from its acid moiety [15]. This chiral-specific formation of the cholesterol ester has been demonstrated to be mediated by transesterification reactions of carboxylesterase(s) in microsomes, not by any of the three known biosynthetic pathways of endogenous cholesterol esters... 

Ohkawa H, Kaneko H, Tsuji H, Miyamoto J (1979) Metabolism of fenvalerate (sumicidin) in rats. J Pestic Sci 4 143-155... 

Okuno Y, Seki T, Ito S, Kaneko H, Watanabe T, Yamada H, Miyamoto J (1986) Differential metabolism of fenvalerate and granuloma formation II. Toxicological significance of a lipophilic conjugate from fenvalerate. Toxicol Appl Pharmacol 83 157-169... 

Lee PW, Powell WR, Steams SM, McConnell OJ (1987) Comparative aerobic soil metabolism of fenvalerate isomers. J Agric Food Chem 35 384-387... 

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