Frans-Permethrin

The results suggested that a significant portion of the microsomal activity was catalyzed by hCE-2. An antibody was not available for detecting or measuring hCE-2. Turnover numbers ( cat/ m> mM min ) indicate that trani-permethrin is as efficiently hydrolyzed by hCE-1 as it is for hCE-2. Bioresmethrin is not hydrolyzed by hCE-2 suggesting that metabolism is primarily mediated by hCE-1. The rates of hydrolytic metabolism by rabbit carboxylesterase followed the order bioresmethrin > frans-permethrin > cA-permethrin > deltamethrin > alpha-cypermethrin. Ross et al. (2006) did not extrapolate hydrolytic in vitro V ,ax values (nmol min mg ofmicrosomalprotein)intoin vivo values (p,mol h kg of body weight (bwt)) for use in PBPK models. 

Crow et al. (2007) examined the catalytic activity of carboxylesterase (rCE proteins hCE-1 and hCE-2) on Type 1 pyrethroids (i.e., IRS frans-permethrin (98% pure, 93% trans and 5% cis), IRS cA-permethrin (99% pure), IR trans-resmethrin (bioresmethrin, 99% pure, 97% trans and 2% cis)). Type 11 pyrethroids (i.e., alpha-cypermethrin (99% pure, mixture of isomers), lambda-cyhalothrin (99% pure, mixture of isomers), and deltamethrin (99% pure)). 

Human intestinal microsomes effectively hydrolyzed frans-permethrin however, bioresmethrin, and deltamethrin were not metabolized in the intestine to any appreciable extent. Human hepatic microsomes and cytosol contained both hCE-1 and hCE-2 when examined by native PAGE (polyacrylamide gel electrophoresis) human intestine contained only hCE-2. Table 8 gives the kinetic parameters obtained by Crow et al. (2(X)7) with tranr-permethrin and liver and intestinal carboxylesterases. 

Using the parent compound depletion method, pyrethroid metabolic rate constants (i.e., Umax and K, hast, etc.) for hydroxylation by cytochrome P450 enzymes or hydrolysis by carboxylesterases were developed by Scollon et al. (2009). The sources of the enzymes were rat and human microsomes. The pyrethroids they studied included bifenthrin, S-bioallethrin, bioresmethrin, p-cyfluthrin, cypermethrin, cis-permethrin, and frans-permethrin. The depletion method considers multiple hydroxylations as a single biotransformation at sites on either the acid or alcohol moieties, or on a combination of both. The metabolic pathways (Tables D1-D15 and E1-E15 of Appendices D and E, respectively) require Umax, Am, and values for the individual hydroxylated and hydrolyzed products. It is interesting that only bioresmethrin and cypermethrin per se were found to actually be hydrolyzed. 

Dichlorovinyl acid, see Permethrin cis-Dichlorovinyl acids, see Permethrin frans-Dichlorovinyl acids, see Permethrin els- (Dichlorovinyl) dimethyl cyclopropanecarboxy lie acid, see Permethrin... 

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. 

Just as previous studies showed, isomer selectivity was a common phenomenon in biodegradation of pyrethroids in soil, as observed for the permethrinase enzyme, which has a strong preference for the fran -isomer of permethrin. However, EstP, PytH and PytZ appear to have no isomer specificity (Maloney et al. 1993 Guo et al. 2009 Wu et al. 2006 Zhai et al. 2012 Russel et al. 2011). 

---