Biotransformation and Enzymatic Reactions of Synthetic Pyrethroids in Mammals

Abstract

Synthetic pyrethroids, a major insecticide group, are used worldwide for controlling indoor and agricultural pests. Extensive mammalian metabolism studies have been carried out since the late 1960s, and major metabolic reactions have been found to be oxidation of the acid or alcohol moiety, ester cleavage, and conjugation reactions. In addition, various conjugation reactions occur in mammals, forming hydrophilic and lipophilic conjugates. Pyrethroids are generally rapidly metabolized in mammals and completely excreted from the body in a short period. Human and laboratory animals share similar metabolic reactions for pyrethroids. Oxidation reactions in humans are mediated by several CYP isoforms. On the other hand, ester bonds of pyrethroids are hydrolyzed mainly by carboxylesterase(s).

Bioconcentration and metabolism of <i>trans</i>-tetramethrin in fish

“…The phase-II metabolites of VI, VII, and VIII were formed via conjugation with glucuronic acid or amino acids such as taurine. Although no taurine conjugate was detected in mammalian metabolism of I, its existence has been reported for other pyrethroids 32) in mice and various aquatic organisms. 2,10,12,33) The BCF a of trans-I, 180-310, was approximately one order of magnitude below the internationally recognized criteria for bioaccumulative chemicals such as 2000 for PBT (persistent, bioaccumulative and toxic substance) and 5000 for POP (persistent organic pollutant).…”

“…2,11,12) The observed rapid degradation of trans-I, as compared to cis-I in the in vitro experiment, is considered to be the difference in susceptibility to esterases as reported in mammalian carboxylesterases with trans-and cispermethrin. 32) Incidentally, the BCF of the cis isomer was conservatively/conveniently estimated from the in vivo BCF of the trans isomer (180-310), in accordance with the assumption that k u is independent of the geometric isomerism and the cis/trans ratio of (k e +k m ) is identical to that of in vitro degradation rates (cis/trans=0.48). Then, the estimated BCF of the cis-I isomer was calculated to be 380-650, which was 2.1 times higher than the original BCF of trans-I but clearly below the international PBT and POP criteria of 2000-5000.…”

Biodegradation of Organophosphate and Pyrethroid Pesticides by Microorganims

“…The hCE1 preferentially hydrolyzed allethrin, resmethrin, deltamethrin, esfenvalerate and λ-cyhalothrin. However, hCE2 showed higher or similar hydrolysis activity toward baythroid, bifenthrin, cis-permethrin, trans-fluvalinate and tetramethrin than hCE1 (Yang et al 2009;Mikata et al 2012) (Fig. 3.26).…”

“…3.25 Mechanism for the carboxylesterase-mediated hydrolysis of permethrin (Wheelock et al 2005) while the metabolism of resmethrin and cypermethrin in human hepatic microsomes was solely the result of hydrolytic processes. Resmethrin and cypermethrin in rat hepatic microsomes and β-cyfluthrin and trans-permethrin in microsomes from both species were metabolized by both oxidative and hydrolytic pathways (Mikata et al 2012).…”

Mosquito Larvicides from Cyanobacteria

“…Pyrethroids are known to be non-toxic to mammals because they are quickly metabolized via oxidation and hydrolysis pathways (Mikata et al, 2011). However, many studies involving mammalian toxicity are accomplished with acute toxicity experiments.…”