Fenvalerate isomers

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

However, during analysis of residual tissue radiocarbon 6 days after single oral administration of 2.5 mg/kg acid-labeled fenvalerate isomers, it was found that the Ba isomer showed a quite different pattern (Table IV), although the residual amounts themselves were in the order of less than Ip g equivalent/g wet tissue at the maximum. That is, in the analyzed tissues of both rats and mice, relatively higher residual radiocarbon from the Ba isomer was detected, as compared with the 3 other isomers, particularly in the adrenals, liver, mesenteric lymph node, and spleen. 

Finally, the enzymatic nature of CPIA-cholesterol ester formation will be briefly mentioned. None of the enzyme preparations of three known biosynthetic pathways for cholesterol esters, namely, acyl-CoA cholesterol Q-acyltransferase (ACAT), lecithin cholesterol 0-acyltransferase (LCAT), nor cholesterol esterase, was effective in producing CPIA-cholesterol ester from the Ba isomer or CPIA. In contrast, the 9,000 g supernatant or microsomal fractions from liver or kidney homogenate were found to be capable of producing CPIA-cholesterol ester without the addition of any cofactors. As substrate, only the Ba isomer was effective, and none of the 3 other fenvalerate isomers nor free CPIA was effective. The hepatic enzyme preparation also catalyzed hydrolysis of fenvalerate, and in this case all the 4 isomers were utilized as substrates. These facts imply that CPIA-cholesterol ester is formed from the Ba isomer through a transesterification reaction via intermediary acyl-enzyme complex. 

D. The 2R, aS isomer is the oidy fenvalerate isomer that caused granulatomous changes in liver, spleen, and mesenteric lymph node in rodents. 

E. The 2R, aR isomer has greatly reduced biological and toxicological properties when compared with other fenvalerate isomers. Isomers with an R configuration in the acid moiety degraded slightly faster than the insecticidally-active 25, aS, and 25, aR isomers. 

Esfenvalerate consists primarily of isomer D. Tan et al. (2007) reported on the complete separation of the four fenvalerate isomers by using a novel CSP prepared by connecting (R)-l-phenyl-2-(4-methylphenyl)ethylamine (PTE) amide derivative of (S)-isoleucine to aminopropyl silica gel, through a 2-amino-3,5-dinitro-l-carboxamido-benzene unit. The mobile phase was hexane 1, 2-dichloroethane 2-propanol (97.45 2.50 0.05). The order of elution was C, B, A, and D, respectively. In an earlier study, Papadopoulou-Mourkidou (1985) used a chiral column (BAKERBOND) and a mobile phase of 0.1% methanol, 0.3% 2-propanol, and 99.6% hexane (by volume) to separate all four isomers of fenvalerate. 

Omura T, Sato (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239 2370-2378 Paine ME, Khalighi M, Eisher JM, Shen DD, Kunze KOL, Cl M, Perkins JD, Thummel KE (1997) Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 283 1552-1562 Papadopoulou-Mourkidou E (1985) Direct analysis of fenvalerate isomers by liquid chromatography. Application to formulation and residue analysis of fenvalerate. Chromatographia 20 (6) 376-378... 

Pyrethroid Esters of Benzene Acetate. These insecticides have more extensive stmctural optimization in both acid and alcohol moieties. Fenvalerate [51630-58-17, a-cyano-(3-phenoxyphenyl)methyl (+)-(2R,5)"Ct"isoprop5i-4-chlorophenylacetate (24) d 1.17, vp 1.4 p.Pa at 25°C), a mixture of four isomers, is soluble in water to 0.3 mg/L The rat oral LD q is 450 mg/kg. Esfenvalerate [66230-04-4] is the (+)-2-(i, 5)-isomer (mp 59°C). The rat LD qS are 75, 458 (oral), and the rabbit dermal LD q is 2000 mg/kg. These pyrethroids are widely used general-purpose insecticides for field, vegetable, and fmit crops. 

The technical fenvalerate formulation is no longer being manufactured by the Dupont Company, although existing stocks may be used until exhausted. The new fenvalerate formulation is sold as Asana or Esfenvalerate, and contains only the 2S,aS isomer (A. Stavola, U.S. Environmental Protection Agency, personal communication, January 28, 1991). 

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. 

Fenvalerate is neither mutagenic nor teratogenic. Tumor-like growths in rodent tissues, however, were associated with the 2R,aS isomer — heretofore believed innocuous — more specifically, with its cholesterol conjugate. 

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... 

Fenvalerate intoxication effects may be reversible. Tadpoles of the northern leopard frog (Rana pipiens) that survived LC50 concentrations of the 5,5-isomer for 96 h appeared normal 7 days after being placed in clean water (Matema 1991). Fenvalerate-protective agents include diazepam and endosulfan. Diazepam provides up to 14-fold protection to frogs against toxic doses of fenvalerate (Cole and Casida 1983) endosulfan provides limited protection to estuarine fish and shrimp (Scott et al. 1987 Trim 1987). 

Bradbury, S.P., D.M. Symonik, J.R. Coats, and G.J. Atchison. 1987. Toxicity of fenvalerate and its constituent isomers to the fathead minnow, Pimephales promelas, and bluegill, Lepomis macrochirus. Bull. Environ. Contam. Toxicol. 38 727-735. 

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. 

Ohkawa, H., R. Kikuchi, and J.S. Miyamoto. 1980. Bioaccumulation and biodegradation of the (S)-acid isomer of fenvalerate (Sumicidin ) in an aquatic model ecosystem. Jour. Pestic. Sci. 5 11-22. 

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... 

Li Z, Zhang Z, Zhang L, Leng L (2009) Isomer- and enantioselective degradation and chiral stability of fenpropathrin and fenvalerate in soils. Chemosphere 76 509-516... 

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