Metabolic disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and skin administration in rats.
Identifieur interne : 005623 ( Main/Exploration ); précédent : 005622; suivant : 005624Metabolic disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and skin administration in rats.
Auteurs : Daryl J. Fediuk [Canada] ; Tao Wang ; Yufei Chen ; Fiona E. Parkinson ; Michael P. Namaka ; Keith J. Simons ; Frank J. Burczynski ; Xiaochen GuSource :
- International journal of toxicology [ 1092-874X ]
English descriptors
- KwdEn :
- Administration, Cutaneous, Administration, Intravenous, Animals, Benzophenones (administration & dosage), Benzophenones (blood), Benzophenones (pharmacokinetics), Benzophenones (urine), Cell Line, Tumor, Cell Proliferation (drug effects), DEET (administration & dosage), DEET (blood), DEET (pharmacokinetics), DEET (urine), Drug Synergism, Insect Repellents (administration & dosage), Insect Repellents (blood), Insect Repellents (pharmacokinetics), Insect Repellents (urine), Rats, Rats, Sprague-Dawley, Skin Absorption, Sunscreening Agents (administration & dosage), Sunscreening Agents (pharmacokinetics), Tissue Distribution.
- MESH :
- chemical , administration & dosage : Benzophenones, DEET, Insect Repellents, Sunscreening Agents.
- chemical , blood : Benzophenones, DEET, Insect Repellents.
- chemical , pharmacokinetics : Benzophenones, DEET, Insect Repellents, Sunscreening Agents.
- chemical , urine : Benzophenones, DEET, Insect Repellents.
- drug effects : Cell Proliferation.
- Administration, Cutaneous, Administration, Intravenous, Animals, Cell Line, Tumor, Drug Synergism, Rats, Rats, Sprague-Dawley, Skin Absorption, Tissue Distribution.
Abstract
Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model.
DOI: 10.1177/1091581812459893
PubMed: 23064701
Affiliations:
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Le document en format XML
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Parkinson</name></author><author><name sortKey="Namaka, Michael P" sort="Namaka, Michael P" uniqKey="Namaka M" first="Michael P" last="Namaka">Michael P. Namaka</name></author><author><name sortKey="Simons, Keith J" sort="Simons, Keith J" uniqKey="Simons K" first="Keith J" last="Simons">Keith J. Simons</name></author><author><name sortKey="Burczynski, Frank J" sort="Burczynski, Frank J" uniqKey="Burczynski F" first="Frank J" last="Burczynski">Frank J. 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Fediuk</name><affiliation wicri:level="4"><nlm:affiliation>Faculty of Pharmacy, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada. xgu@cc.umanitoba.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Faculty of Pharmacy, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Wang, Tao" sort="Wang, Tao" uniqKey="Wang T" first="Tao" last="Wang">Tao Wang</name></author><author><name sortKey="Chen, Yufei" sort="Chen, Yufei" uniqKey="Chen Y" first="Yufei" last="Chen">Yufei Chen</name></author><author><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name></author><author><name sortKey="Namaka, Michael P" sort="Namaka, Michael P" uniqKey="Namaka M" first="Michael P" last="Namaka">Michael P. Namaka</name></author><author><name sortKey="Simons, Keith J" sort="Simons, Keith J" uniqKey="Simons K" first="Keith J" last="Simons">Keith J. Simons</name></author><author><name sortKey="Burczynski, Frank J" sort="Burczynski, Frank J" uniqKey="Burczynski F" first="Frank J" last="Burczynski">Frank J. Burczynski</name></author><author><name sortKey="Gu, Xiaochen" sort="Gu, Xiaochen" uniqKey="Gu X" first="Xiaochen" last="Gu">Xiaochen Gu</name></author></analytic><series><title level="j">International journal of toxicology</title><idno type="eISSN">1092-874X</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Cutaneous</term><term>Administration, Intravenous</term><term>Animals</term><term>Benzophenones (administration & dosage)</term><term>Benzophenones (blood)</term><term>Benzophenones (pharmacokinetics)</term><term>Benzophenones (urine)</term><term>Cell Line, Tumor</term><term>Cell Proliferation (drug effects)</term><term>DEET (administration & dosage)</term><term>DEET (blood)</term><term>DEET (pharmacokinetics)</term><term>DEET (urine)</term><term>Drug Synergism</term><term>Insect Repellents (administration & dosage)</term><term>Insect Repellents (blood)</term><term>Insect Repellents (pharmacokinetics)</term><term>Insect Repellents (urine)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Skin Absorption</term><term>Sunscreening Agents (administration & dosage)</term><term>Sunscreening Agents (pharmacokinetics)</term><term>Tissue Distribution</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Benzophenones</term><term>DEET</term><term>Insect Repellents</term><term>Sunscreening Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Benzophenones</term><term>DEET</term><term>Insect Repellents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Benzophenones</term><term>DEET</term><term>Insect Repellents</term><term>Sunscreening Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="urine" xml:lang="en"><term>Benzophenones</term><term>DEET</term><term>Insect Repellents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Proliferation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Cutaneous</term><term>Administration, Intravenous</term><term>Animals</term><term>Cell Line, Tumor</term><term>Drug Synergism</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Skin Absorption</term><term>Tissue Distribution</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Manitoba</li></region><settlement><li>Winnipeg</li></settlement><orgName><li>Université du Manitoba</li></orgName></list><tree><noCountry><name sortKey="Burczynski, Frank J" sort="Burczynski, Frank J" uniqKey="Burczynski F" first="Frank J" last="Burczynski">Frank J. Burczynski</name><name sortKey="Chen, Yufei" sort="Chen, Yufei" uniqKey="Chen Y" first="Yufei" last="Chen">Yufei Chen</name><name sortKey="Gu, Xiaochen" sort="Gu, Xiaochen" uniqKey="Gu X" first="Xiaochen" last="Gu">Xiaochen Gu</name><name sortKey="Namaka, Michael P" sort="Namaka, Michael P" uniqKey="Namaka M" first="Michael P" last="Namaka">Michael P. Namaka</name><name sortKey="Parkinson, Fiona E" sort="Parkinson, Fiona E" uniqKey="Parkinson F" first="Fiona E" last="Parkinson">Fiona E. Parkinson</name><name sortKey="Simons, Keith J" sort="Simons, Keith J" uniqKey="Simons K" first="Keith J" last="Simons">Keith J. Simons</name><name sortKey="Wang, Tao" sort="Wang, Tao" uniqKey="Wang T" first="Tao" last="Wang">Tao Wang</name></noCountry><country name="Canada"><region name="Manitoba"><name sortKey="Fediuk, Daryl J" sort="Fediuk, Daryl J" uniqKey="Fediuk D" first="Daryl J" last="Fediuk">Daryl J. 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