Fenvalerate conjugate

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). 

Fenvalerate is not significantly absorbed or translocated in plants. Cotton, apples, and lettuce treated with fenvalerate contained surface residues of parent fenvalerate 8 weeks after treatment (Reed 1981). In addition to the parent compound, which accounted for 80% of all residues, identified metabolites included 3-phenoxybenzaldehyde, 3-phenoxybenzyl methylbutyric acid, and conjugates of these compounds. Half-time persistence of fenvalerate on plant surfaces is between 2 and 4 weeks, and degradation is primarily a result of weathering (Reed 1981). 

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. 

Miyamoto, J., H. Kaneko, and Y. Takamatsu. 1986. Stereoselective formation of a cholesterol ester conjugate from fenvalerate by mouse microsomal carboxyesterase(s). Jour. Biochem. Toxicol. 1 79-94. 

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

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... 

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... 

MIYAMOTO ET AL. Cholesterol Ester Conjugate from Fenvalerate... 

Similarly, in other mouse tissues and also in rat tissues, the presence of CPIA-cholesterol ester was demonstrated following administration of the Ba isomer or fenvalerate. Thus, CPIA-cholesterol ester proves now to be a novel type of conjugate which is more lipophilic than the parent compound and CPIA. 

Quistad et al. (1983), studied the elimination of " CF-labeled fluvalinate, and discovered that the hydroxy acid (CAS no. 82186-86-5), anUino acid (CAS no. 76338-73-3), glycine conjugate of the anilino acid, haloaniline (CAS no. 39885-50-2) and the sulfate of hydroxyhaloaniline (CAS no. 84960-10-1) were excreted in urine. Fluvalinate, hydroxyacid, anilino acid, and anilino acid conjugates were found in feces. According to Quistad et al. (1983), the ratio of fecal to urinary elimination is higher for fluvalinate than for fenvalerate (Kaneko et al. 1981b Ohkawa et al. 1979), deltamethrin (Cole et al. 1982 Ruzo et al. 1978), cypermethrin (Cole et al. 1982), and tralomethrin (Cole et al. 1982). 

Hydrolysis of the pyrethroids may occur prior to hydroxylation. For dichloro groups (i.e., cyfluthrin, cypermethrin and permethrin) on the isobutenyl group, hydrolysis of the trans-isomers is the major route, and is followed by hydroxylation of one of the gem-dimethyls, the aromatic rings, and hydrolysis of the hydroxylated esters. The cis-isomers are not as readily hydrolyzed as the tran -isomers and are metabolized mainly by hydroxylation. Metabolism of the dibromo derivative of cypermethrin, deltamethrin, is similar to other pyrethroids (i.e., cyfluthrin, cypermethrin, and permethrin) that possess the dichloro group. Type 11 pyrethroid compounds containing cyano groups (i.e., cyfluthrin, cypermethrin, deltamethrin, fenvalerate, fenpropathrin, and fluvalinate) yield cyanohydrins (benzeneacetonitrile, a-hydroxy-3-phenoxy-) upon hydrolysis, which decompose to an aldehyde, SCN ion, and 2-iminothia-zolidine-4-carboxylic acid (TTCA). Chrysanthemic acid or derivatives were not used in the synthesis of fenvalerate and fluvalinate. The acids (i.e., benzeneacetic acid, 4-chloro-a-(l-methylethyl) and DL-valine, Af-[2-chloro-4-(trifluoromethyl) phenyl]-) were liberated from their esters and further oxidized/conjugated prior to elimination. Fenpropathrin is the oifly pyrethroid that contains 2,2,3,3-tetramethyl cyclopropane-carboxylic acid. The gem-dimethyl is hydroxylated prior to or after hydrolysis of the ester and is oxidized further to a carboxylic acid prior to elimination. 

Hydrolysis products Alcohol Leaving groups, metabolites and conjugates Products for cypermethrin, deltamethrin, fenvalerate, fenpropathrin, fluvalinate and tralomethrin... 

Cyclopropanecarboxylic acid, 3-(2,2-dibromoethenyl)-2-(hydroxymethyl)-2-methyl-, cyano[3-(4-hydroxyphenoxy)phenyl]methyl ester CAS no. 70080-85-2 Hydrolysis Products Alcohol Leaving groups, metabolites and conjugates See cyhalothrin, cypermethrin, deltamethrin, fenvalerate, fenpropathrin, and fiuvalinate Cyanohydrin of PB aldehyde... 

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