Permethrin metabolism

Gaughan LC, Unai T, Casida JE (1977) Permethrin metabolism in rats. J Agric Food Chem 25 9-17... 

Papers from the symposium on the chemistry, biochemistry, and insecticidal action of natural and synthetic pyrethroids (Helsinki 1974, Third I.U.P.A.C. International Congress on Pesticide Chemistry) and the proceedings of a symposium on synthetic pyrethroids held at the 172nd A.C.S. Meeting (San Francisco, 1976) have been published. Other pyrethroid papers of interest include C n.m.r. spectra of synthetic pyrethroids (cf. Vol. 7, p. 20), gd.c. analysis of permethrin and bioresmethrin, further work (Vol. 7, p. 10) on permethrin metabolism in rats ... 

Permethrin, a pyrethrin pesticide, decreased the inhibition of brain cholinesterase activity by methyl parathion, but methyl parathion decreased the LD50 of permethrin when the two pesticides were simultaneously administered to rats (Ortiz et al. 1995). The potentiation of permethrin lethality may be due to the inhibition by methyl parathion of carboxylesterase, which metabolizes permethrin. 

Pednekar MD, Gandhi SR, Netrawali MS. 1987. Evaluation of mutagenic activities of endosulfan, phosalone, malathion, and permethrin, before and after metabolic activation, in the Ames Salmonella test. Bull Environ Contam Toxicol 38 925-933. 

The metabolism of permethrin will be taken more generally as an example of the metabolism of pyrethroids (Figure 12.2). The two types of primary metabolic attack are by microsomal monooxygenases and esterases. Monooxygenase attack involves... 

Metabolism of bifenthrin, S-bioallethrin, bioresmethrin, (S-cyfiuthrin. cypermethrin, m-permethrin, and fnmv-pennethrin were examined in rat and human hepatic... 

Pure human CESs (hCEl and hCE2), a rabbit CES (rCE), and two rat CESs (Hydrolases A and B) were used to study the hydrolytic metabolism of the following pyrethroids lR-trans-resmethrin (bioresmethrin), 1RS-1runs-permethrin, and 1RS-r/.v-pennethrin [28], hCEl and hCE2 hydrolyzed /ram-pemiethrin 8- and 28-fold more efficiently than m-permethrin (when kcat/Km values were compared), respectively. In contrast, hydrolysis of bioresmethrin was catalyzed efficiently by hCEl, but not by hCE2. The kinetic parameters for the pure rat and rabbit CESs were qualitatively similar to the human CESs when hydrolysis rates of the investigated pyrethroids were evaluated. Further, a comparison of pyrethroid hydrolysis by hepatic microsomes from rats, mice, and humans indicated that the rates for each compound were similar between species. 

The serum CES was purified to homogeneity to determine its contribution to pyrethroid metabolism in the rat [30]. Both trans-permethrin and bioresmethrin were effectively cleaved by this serum CES, but deltamethrin, esfenvalerate, a-cypermethrin, and m-permethrin were slowly hydrolyzed. Two model lipases produced no hydrolysis products from pyrethroids. These results demonstrated that extrahepatic esterolytic metabolism of specific pyrethroids might be significant. 

It was reported that the distribution and activities of esterases that catalyze pyrethroid metabolism using several human and rat tissues, including small intestine, liver, and serum, were examined [30]. The major esterase in human intestine was hCE2. //c/n.v-Permethrin was effectively hydrolyzed by pooled human intestinal microsomes (five individuals), while deltamethrin and bioresmethrin were not. This result correlated well with the substrate specificity of recombinant hCE2. In contrast, pooled rat intestinal microsomes (five animals) hydrolyzed trans-permethrin 4.5 times slower than the human intestinal microsomes. Furthermore, pooled samples of cytosol from human or rat liver were ca. half as hydrolytically active as the corresponding microsome fraction toward pyrethroids however, the cytosolic fractions had significant amounts (ca. 40%) of the total hydrolytic activity. Moreover, a sixfold interindividual variation in hCEl protein expression in human hepatic cytosols was observed. 

Nakamura Y, Sugihara K, Sone T, Isobe M, Ohta S, Kitamura S (2007) The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolysis products in rats. Toxicology 235 176-184... 

Takaku T, Mikata K, Matsui M, Nishioka K, Isobe N, Kaneko H (2011) In vitro metabolism of trans-permethrin and its major metabolites PBalc and PBacid, in humans. J Agric Food Chem 59 5001-5005... 

Many investigations of relevant enzymes in transformation of xenobiotics by aquatic species have shown that the similar enzymes observed in metabolism in soil, plant, and mammals play a role, such as esterases and oxidases [10, 159, 160]. Metabolism of pyrethroids has been most extensively studied in fish for cypermethrin (5) and permethrin (15). Aromatic hydroxylation at the 4 -position of the 3-phenoxybenzyl moiety followed by conjugation with glucuronic acid... 

Pyrethrins are naturally occurring pesticides derived from chrysanthemum plants. They are active against many insects and mites. Over-the-counter liquid and gel preparations of pyrethrins with piperonyl butoxide are available for the treatment of pediculosis (piperonyl butoxide inhibits the hydrolytic enzymes that metabolize the pyrethrins in the arthropod). A synthetic pyre-throid, permethrin (Elimite), is available by prescription. A lower concentration of permethrin (Nix) is available without prescription. Pyrethrins and permethrin are quite safe. 

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.)...

Pediculosis (lice) (head, body, genitals) Permethrin, phenothrin, carbnryl or malathion cmcicholinesterases, with safety depending on more rapid metabolism in man than in insects, and on low absorption). Usually two applications 1 days apart to kill lice from eggs that survive the first dose... 

The syntheses of phenothrin analogues of lower insecticidal activity and of other chrysanthemate esters have been reported. Further pyrethroid papers concern the relationship between insecticidal toxicity and cyclopropane substituents in pyret-hroids, the photochemistry of the most potent known pyrethroid,and the metabolism of permethrin in rats (c/. Vol. 6, p. 13). " ... 

Glickman, A.H., A.A.R. Hamid, D.E. Rickert and J.J. Lech. Elimination and metabolism of permethrin isomers in rainbow trout. Toxicol. Appl. Pharmacol. 57 88-98, 1981. 

Glickman, A.H., T. Shono, J.E. Casida and J.J. Lech. In vitro metabolism of permethrin isomers by carp and rainbow trout liver microsomes. J. Agric. Food Chem. 27 1038-1048, 1979. 

Pyrethroids. Pyrethroids, such as natural pyrethrins and synthetic analogs, allethrin, permethrin, and others, are well known for their neurotoxicity (48-59). However, as a major class of insecticide, they have a remarkable safety margin for mammals, principally because of the rapid metabolic degradation of pyrethroids in mammalian species (48-50). The acute toxicity of pyrethroids involves two distinct syndromes in rats and mice (49-51). The first one, T syndrome or tremor (Type I), is characterized by a rapid onset of tremor, initially in the limbs and gradually extending over the whole body. Death is associated with clonic seizures. The second... 

Also permethrin (34) is readily metabolised in the mammalian organisms and its metabolism pattern is similar to that of resmethrin (32) (Ruscoe, 1977 Gaughan et al. 1977). 

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