Oxidation permethrins

Fukushima M, Katagi T (2009) Iron-porphyrin catalyzed oxidation of permethrin and fenvalerate. J Pestic Sci 34 241-252... 

Hiatt, C.W., Haskins, W.T., Olivier, L. (1960) The action of sunlight on sodium pentachlorophenate. Am. J. Trop. Med. Hyg. 9,527-531. Hidaka, H., Nohara, K., Zhao, J., Serpone, N., Pelizzetti, E. (1992) Photo-oxidative degradation of the pesticide permethrin catalyzed by irradiated Ti02 semiconductor slurries in aqueous media. J. Photochem. Photobiol. A Chem. 64, 247-254. 

Figure 8.28 Metabolic pathways of trans-permethrin in animals, a-d indicate oxidative metabolic sites. The white arrow indicates esterase action. (From Matsu mu ra, F., Toxicology of Insecticides, 2nd ed., Plenum Press, New York, 1985. With permission.)...

Further studies following the same approach were carried out with Biaueiia genmnica, the German cockroach, L meda et al. (1988) compared the use of PBO, an oxidative inhibitor, with that of NIA 16288, both an oxidase and esterase inhibitor. The latter svnergized permethrin in this case, while the former had little effect. 

Abu-Quare A, Abou-Donia M (2000) Increased 8-hydroxy-2 -deoxyguanosine, a biomarker of oxidative DNA damage in rat urine following a single dermal dose of DEET (AA-diethyl-w-toluamide), and permethrin, alone and in combination. Toxicol Lett 117, 151-160. 

Abu-Qare. A. W., Suliman, H. B., and Abou-Donia, M. B. (2001). Induction of urinary excretion of 3-nitrotyrosine, a marker of oxidative stress, following administration of pyridostigmine Ixromide. DEET (Ai.AI-dtethyl-m-toluamide) and permethrin, alone and in combination in rats. Toxicol. Lett. 21HH, 127-134. 

Polyarylether ketone resin 60018-94-2 Permethrin 60047-17-8 Linalool oxide 60063-90-3... 

In a rat study involving the two isomers of bifenthrin, the major metabolites found in rat plasma (Smith et al. 2002 TuUman 1987) were the parent compound, the hydrolysis product, 2-MBP alcohol, [l l-biphenyl]-3-methanol, 2-methyl (CAS no. 76350-90-8), and the oxidized product of the alcohol, 2-MBP acid, [1,1 -biphenyl]-3-carboxylic acid (CAS no. 115363-11-6). The 2-MBP acid compound is analogous to 3-phenoxybenzoic acid (CAS no. 3739-38-6), the hydrolysis product of cypermethrin, deltamethrin, permethrin, and fenvalerate (Huckle et al. 1981a, b, 1984 lARC 1991 Woollen et al. 1992). In addition to these ester-cleaved products, 4 -OH, 2-MBP alcohol (CAS no. 115340-46-0) and 4 -OH, 2-MBP acid (CAS no. NA) were found. According to Kaneko (2010), these metaboUtes are metaboUcaUy converted to dimethoxy 2-MBP alcohol and dimethoxy 2-MBP acid. 

Choi and Soderlund (2006) identified human alcohol (ADH) and aldehyde dehydrogenases (ALDH) as the enzymes involved in the oxidation of PB alcohol (phenoxybenzyl alcohol) from trans-permethrin to PB acid (phenoxybenzoic acid) via phenoxybenzaldehyde. C -Permethrin was not metabolized to any extent in human liver fractions. Cytochrome P450 isoforms were not involved either in the hydrolysis of traws-permethrin or in the oxidation of the PB alcohol to the PB acid. 

The alcohol moiety of (IR-frans)- and (lR-c T)-phenothrin is rapidly metabolized and eliminated, with the major excreted metabolite being either free or conjugated 4-OH PB acid (CAS no. 35065-12-4) (Miyamoto et al. 1974 Miyamoto 1976). Intact esters of (IR, cis) phenothrin were excreted in feces, one being 4-OH phenothrin (CAS no. NA), another carboxy phenothrin (CAS no. 79897-38-4) and carboxy 4 -OH phenothrin (CAS no. 79861-56-6). Oxidation of one of the geminal dimethyl groups has also been reported (Miyamoto 1976). According to Elliott et al. (1976), phenothrin is metabolized like permethrin except for alterations on the isobutenyl group not seen for the dichlorovinyl side chain of permethrin. 

The metabolism of bifenthrin, S-bioallethrin, and crs-permethrin in rat and human hepatic microsomes was the result of oxidative processes, while the metabolism of bioresmethrin and cypermethrin in human hepatic microsomes was hydrolytic (not shown in Table 8). Cypermethrin and bioresmethrin were metabolized by oxidation and hydrolysis in rat hepatic microsomes. Tra/j -permethrin and (3-cyfluthrin were metabolized by both pathways in human and rat hepatic microsomes. 

Fig. 16 Dose-response curves are shown for the effects of permethrin (filled circle) and cyhalothrin (open circle) on rotenone sensitive NADH duroquinone oxidoreductase of SMP (subfraction of mitochondria protein). The oxidation of NADH was monitored spectrophotometrically. The data are the means SEM of assay triplicates. This figure is published with permission (Gassner et al. 1997)...

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. 

According to Mikata et al., the metabolism of bifenthrin, allethrin, resmethrin, P-cyfluthrin, cypermethrin, cw-permethrin, and /rans-permethrin was examined in rat and human hepatic microsomes (ScoUon et al. 2009). The intrinsic hepatic clearance of the pyrethroids was 5-15-fold greater to rat than to human nuCTosomes, except for /ranx-permethrin, which showed approximately 45 % greater clearance in human nuCTosomes. The metabolism of bifenthrin, allethrin and cix-permethrin in rat and in human hepatic nucrosomes was solely the result of oxidative processes. 

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