Radiosynthesis and metabolism in rats of the 1R isomers of the insecticide permethrin

Elliott, M.; Janes, Norman F.; Pulman, David A.; Gaughan, Loretta C.; Unai, Tadaaki; Casida, John E.

doi:10.1021/jf60204a007

Cited by 52 publications

(30 citation statements)

References 14 publications

(26 reference statements)

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“…Additionally, hCE-1 and hCE-2 hydrolyzed trans-permethrin (C3) 12-fold and 5-fold faster, respectively, than the corresponding cis-isomers. The results were consistent with previous animal studies [22,23] showing that trans-permethrin ester is hydrolyzed more rapidly than its cis-isomer. Furthermore, no significant cis-permethrin metabolism is observed in either human liver cytosolic or microsomal fractions [24].…”

supporting

confidence: 93%

Characterization of pyrethroid hydrolysis by the human liver carboxylesterases hCE-1 and hCE-2

Nishi

Huang

Kamita

et al. 2006

Archives of Biochemistry and Biophysics

104

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Carboxylesterases hydrolyze a large array of endogenous and exogenous ester-containing compounds, including pyrethroid insecticides. Herein, we report the specific activities and kinetic parameters of human carboxylesterase (hCE)-1 and hCE-2 using authentic pyrethroids and pyrethroid-like, fluorescent surrogates. Both hCE-1 and hCE-2 hydrolyzed type I and II pyrethroids with strong stereoselectivity. For example, the trans-isomers of permethrin and cypermethrin were hydrolyzed much faster than corresponding cis-counterparts by both enzymes. Kinetic values of hCE-1 and hCE-2 were determined using cypermethrin and 11 stereoisomers of the pyrethroid-like, fluorescent surrogates. K m values for the authentic pyrethroids and fluorescent surrogates were in general lower than those for other ester-containing substrates of hCEs. The pyrethroid-like, fluorescent surrogates were hydrolyzed at rates similar to the authentic pyrethroids by both enzymes, suggesting the potential of these compounds as tools for high throughput screening of esterases that hydrolyze pyrethroids. KeywordsCarboxylesterase; Pyrethroid; Fluorescent substrate Synthetic pyrethroid insecticides represented about 17% of the global pesticide market in 2002 [1]. In the coming years, the use of pyrethroids is predicted to further increase with the phase out of the use of organophosphorus insecticides. Additionally, due to the emergence and reemergence of mosquito-vectored diseases such as West Nile fever, Japanese encephalitis, and dengue fever, pyrethroids are being used with increased frequency against adult mosquitoes * Corresponding author. Fax: +1 530 752 1537.E-mail address: bdhammock@ucdavis.edu (B.D. Hammock). NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript [2]. Because of the increased agricultural and residential usage of pyrethroids, human exposure to these compounds is also expected to increase.Pyrethroids are ester-containing compounds consisting of various acid and alcohol moieties. Type I pyrethroids are esters of primary alcohols, whereas type II pyrethroids are esters of secondary alcohols that contain a cyano group at the α-carbon of the alcohol moiety. Chiral centers can exist in both the acid and alcohol moieties, leading to the existence of several stereoisomers for each pyrethroid. Ester hydrolysis by carboxylesterases and oxidation by cytochrome P450s are the main detoxification routes of pyrethroids in animals [3]. Differences in the activities of carboxylesterases and P450s between mammals and insects contribute to the low mammalian toxicity of pyrethroids (i.e., pyrethroids are metabolized faster in mammals than in insects) [3]. In general, whole animals or liver microsomes have been used to study pyrethroid metabolism in mammals, and little has been done to identify the specific carboxylesterase isozymes that hydrolyze pyrethroids [4]. Butte and Kemper [5]have shown ester-hydrolytic activities in human serum using pyrethroid-like colorimetric substrates that are not hydrolyzed by acylesterase, ...

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supporting

confidence: 93%

Characterization of pyrethroid hydrolysis by the human liver carboxylesterases hCE-1 and hCE-2

Nishi

Huang

Kamita

et al. 2006

Archives of Biochemistry and Biophysics

104

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“…4 Permethrin is essentially odorless and retains its high insecticidal activity, particularly against mosquitoes and ticks, even after several washings of the impregnated fabric. 5 Despite its lipophilic nature and chlorine content, 6 permethrin presents little envirormental persistence and is readily biodegraded in soil. 7 b.…”

Section: Discussionmentioning

confidence: 99%

Dermal Penetration and Distribution of 14C-Labeled Permethrin Isomers

Snodgrass¹,

Nelson²

1982

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“…The less desirable properties of chlorinated hydrocarbon insecticides are associated with their lipophilicity and inert chemical structures so that they are stored in the fatty tissues of organisms rather than being metabolized and eliminated. Although pyrethroids are similar to the chlorinated hydrocarbons in some of their physical properties, much evidence from research in the past decade (59)(60)(61)(62)(63)(64)(65)(66)(67)(68) suggests that the structural features of pyrethroids render them susceptible to mammalian detoxification systems, so that by one or more of several possible pathways they are rapidly converted to more polar compounds and are excreted in the urine or feces.…”

Section: Physical Properties Of Pyrethroids and Other Insecticidesmentioning

confidence: 99%

“…(6), (7)]. This hydroxylation reaction will be IN suppressed on aromatic rings deactivated byhalogen substituents as in the chlorinated hydrocarbon insecticides and elsewhere, but phenoxy groups seem (1) especially susceptible (65,68). This may contribute to the extremely low mammalian toxicity ofphenothrin (11,65) and, in the important instance of permethrin, partly explain the lower oral toxicity which Barnes and Verscholyle (9,18) found for (2) both trans and cis isomers compared with the corresponding isomers of the 5-benzyl-3-furylmethyl esters.…”

Section: Physical Properties Of Pyrethroids and Other Insecticidesmentioning

confidence: 99%

“…This may contribute to the extremely low mammalian toxicity ofphenothrin (11,65) and, in the important instance of permethrin, partly explain the lower oral toxicity which Barnes and Verscholyle (9,18) found for (2) both trans and cis isomers compared with the corresponding isomers of the 5-benzyl-3-furylmethyl esters. An interesting recent observation (68) is that when oxidation of the trans-methyl group in the (3) isobutenyl side chain of chrysanthemates, the first Environmental Health Perspectives metabolic reaction established for pyrethroids (59,62) is not possible, as in dichlorovinylcyclopropane esters, one of the adjacent gemdimethyl groups on the cyclopropane ring is attacked eq. (1) No reports have yet been published of the mammalian toxicity or the nature of the metabolic products from the a-isopropyl aryl acetates, although from general considerations of chemical reactivity, ester cleavage should be relatively hindered in this series of compounds.…”

Section: Physical Properties Of Pyrethroids and Other Insecticidesmentioning

confidence: 99%

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Properties and applications of pyrethroids.

Elliott¹

1976

Environ Health Perspect

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Improved understanding of the factors determining the insecticidal activity, the mammalian toxicity, and the stability in air and light of natural and synthetic pyrethroids has led to a series of new compounds with a very favorable combination of properties. Their characteristicsinclude outstanding potency to insects, low toxicity to mammals associated with rapid metabolic breakdown and, in appropriate cases, adequate stability on plant surfaces even in bright sunlight. Initial tests indicate that even the more stable compounds are degraded rapidly in soil, so if the trials at present in progress reveal no toxicological or environmental hazards, within a few years synthetic pyrethroids should be available to control a wide range of domestic, veterinary, horticultural, agricultural, and forest pests at low rates of application.

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Radiosynthesis and metabolism in rats of the 1R isomers of the insecticide permethrin

Cited by 52 publications

References 14 publications

Characterization of pyrethroid hydrolysis by the human liver carboxylesterases hCE-1 and hCE-2

Characterization of pyrethroid hydrolysis by the human liver carboxylesterases hCE-1 and hCE-2

Dermal Penetration and Distribution of 14C-Labeled Permethrin Isomers

Properties and applications of pyrethroids.

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