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Safety evaluation of dermal exposure to phthalates: Metabolism-dependent percutaneous absorption
Phthalates, known as reproductive toxicants and endocrine disruptors, are widely used as plasticizers in polyvinyl chloride products. The present study was conducted for risk identification of dermal exposure to phthalates. When dibutyl phthalate was applied to the skin of hairless rats and humans,...
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| Published in: | Toxicology and applied pharmacology 2017-08, Vol.328, p.10-17 |
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| container_title | Toxicology and applied pharmacology |
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| creator | Sugino, Masahiro Hatanaka, Tomomi Todo, Hiroaki Mashimo, Yuko Suzuki, Takamasa Kobayashi, Miho Hosoya, Osamu Jinno, Hideto Juni, Kazuhiko Sugibayashi, Kenji |
| description | Phthalates, known as reproductive toxicants and endocrine disruptors, are widely used as plasticizers in polyvinyl chloride products. The present study was conducted for risk identification of dermal exposure to phthalates. When dibutyl phthalate was applied to the skin of hairless rats and humans, only monobutyl phthalate appeared through the skin, and the permeability of the skin was higher than that after the application of the monoester directly. The inhibition of skin esterases made the skin impermeable to the metabolite following dermal exposure to dibutyl ester, whereas removal of the stratum corneum from the skin did not change the skin permeation behavior. Similar phenomena were observed for benzyl butyl phthalate. The skin permeability of monobenzyl phthalate was higher than that of monobutyl phthalate in humans, although the reverse was observed in rats. Species difference in skin permeation profile corresponded to the esterase activity of the skin homogenate. Di(2-ethylhexyl) phthalate, which was not metabolized by esterases in the skin, was not transported across the skin. These results suggest that highly lipophilic phthalates may be transported easily across the stratum corneum lipids. The water-rich viable layer may become permeable to these phthalates by their metabolism into monoesters, which are relatively hydrophilic. Skin metabolism is essential to the percutaneous absorption of phthalates. Because esterase activity has large inter-individual differences, further study will be needed for individual risk identification of dermal exposure to phthalates.
[Display omitted]
•Monophthalate, permeated through the skin after diphthalate application.•Characteristics of human skin cannot be determined from those of rat skin.•An accurate estimation of esterase activity in the skin requires a risk assessment. |
| doi_str_mv | 10.1016/j.taap.2017.05.009 |
| format | article |
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[Display omitted]
•Monophthalate, permeated through the skin after diphthalate application.•Characteristics of human skin cannot be determined from those of rat skin.•An accurate estimation of esterase activity in the skin requires a risk assessment.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2017.05.009</identifier><identifier>PMID: 28506834</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ABSORPTION ; Animals ; Dermal exposure ; Dibutyl Phthalate ; Diethylhexyl Phthalate - administration & dosage ; Diethylhexyl Phthalate - pharmacokinetics ; Diethylhexyl Phthalate - toxicity ; Environmental Exposure ; Environmental Pollutants - pharmacokinetics ; Environmental Pollutants - toxicity ; ESTERASES ; Esterases - antagonists & inhibitors ; Female ; HAZARDS ; Humans ; In Vitro Techniques ; Male ; Metabolism ; Middle Aged ; PHTHALATES ; Phthalic Acids - administration & dosage ; Phthalic Acids - pharmacokinetics ; Phthalic Acids - toxicity ; Plasticizers - administration & dosage ; Plasticizers - pharmacokinetics ; Plasticizers - toxicity ; RATS ; Rats, Hairless ; RISK ASSESSMENT ; Risk identification ; SAFETY ANALYSIS ; SKIN ; Skin - enzymology ; Skin Absorption ; Skin permeation ; Species Specificity</subject><ispartof>Toxicology and applied pharmacology, 2017-08, Vol.328, p.10-17</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-5c03d38d8fd5f05fb6a9d55488873161c1c0c952569a8ff9d40b64536db3e0643</citedby><cites>FETCH-LOGICAL-c538t-5c03d38d8fd5f05fb6a9d55488873161c1c0c952569a8ff9d40b64536db3e0643</cites><orcidid>0000-0002-4079-4023</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28506834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22722881$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Sugino, Masahiro</creatorcontrib><creatorcontrib>Hatanaka, Tomomi</creatorcontrib><creatorcontrib>Todo, Hiroaki</creatorcontrib><creatorcontrib>Mashimo, Yuko</creatorcontrib><creatorcontrib>Suzuki, Takamasa</creatorcontrib><creatorcontrib>Kobayashi, Miho</creatorcontrib><creatorcontrib>Hosoya, Osamu</creatorcontrib><creatorcontrib>Jinno, Hideto</creatorcontrib><creatorcontrib>Juni, Kazuhiko</creatorcontrib><creatorcontrib>Sugibayashi, Kenji</creatorcontrib><title>Safety evaluation of dermal exposure to phthalates: Metabolism-dependent percutaneous absorption</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Phthalates, known as reproductive toxicants and endocrine disruptors, are widely used as plasticizers in polyvinyl chloride products. The present study was conducted for risk identification of dermal exposure to phthalates. When dibutyl phthalate was applied to the skin of hairless rats and humans, only monobutyl phthalate appeared through the skin, and the permeability of the skin was higher than that after the application of the monoester directly. The inhibition of skin esterases made the skin impermeable to the metabolite following dermal exposure to dibutyl ester, whereas removal of the stratum corneum from the skin did not change the skin permeation behavior. Similar phenomena were observed for benzyl butyl phthalate. The skin permeability of monobenzyl phthalate was higher than that of monobutyl phthalate in humans, although the reverse was observed in rats. Species difference in skin permeation profile corresponded to the esterase activity of the skin homogenate. Di(2-ethylhexyl) phthalate, which was not metabolized by esterases in the skin, was not transported across the skin. These results suggest that highly lipophilic phthalates may be transported easily across the stratum corneum lipids. The water-rich viable layer may become permeable to these phthalates by their metabolism into monoesters, which are relatively hydrophilic. Skin metabolism is essential to the percutaneous absorption of phthalates. Because esterase activity has large inter-individual differences, further study will be needed for individual risk identification of dermal exposure to phthalates.
[Display omitted]
•Monophthalate, permeated through the skin after diphthalate application.•Characteristics of human skin cannot be determined from those of rat skin.•An accurate estimation of esterase activity in the skin requires a risk assessment.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ABSORPTION</subject><subject>Animals</subject><subject>Dermal exposure</subject><subject>Dibutyl Phthalate</subject><subject>Diethylhexyl Phthalate - administration & dosage</subject><subject>Diethylhexyl Phthalate - pharmacokinetics</subject><subject>Diethylhexyl Phthalate - toxicity</subject><subject>Environmental Exposure</subject><subject>Environmental Pollutants - pharmacokinetics</subject><subject>Environmental Pollutants - toxicity</subject><subject>ESTERASES</subject><subject>Esterases - antagonists & inhibitors</subject><subject>Female</subject><subject>HAZARDS</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>PHTHALATES</subject><subject>Phthalic Acids - administration & dosage</subject><subject>Phthalic Acids - pharmacokinetics</subject><subject>Phthalic Acids - toxicity</subject><subject>Plasticizers - administration & dosage</subject><subject>Plasticizers - pharmacokinetics</subject><subject>Plasticizers - toxicity</subject><subject>RATS</subject><subject>Rats, Hairless</subject><subject>RISK ASSESSMENT</subject><subject>Risk identification</subject><subject>SAFETY ANALYSIS</subject><subject>SKIN</subject><subject>Skin - enzymology</subject><subject>Skin Absorption</subject><subject>Skin permeation</subject><subject>Species Specificity</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9kE1r3DAURUVo6UyS_oEsiqBrO0-WpZFLNyHkC1K6aALZqbL0xHjwWEaSQ-bf12aaLrt6m3Pv5R1CLhiUDJi83JXZmLGsgG1KECVAc0LWDBpZAOf8A1kD1KwAUC8rcprSDmairtknsqqUAKl4vSa_fxmP-UDx1fSTyV0YaPDUYdybnuLbGNIUkeZAx23emt5kTN_oD8ymDX2X9oXDEQeHQ6YjRjtlM2CYEjVtCnFc6s7JR2_6hJ__3jPyfHvzdH1fPP68e7i-eiys4CoXwgJ3XDnlnfAgfCtN44SolVIbziSzzIJtRCVkY5T3jauhlbXg0rUcQdb8jHw99oaUO51sl9FubRgGtFlX1aaqlGIzVR0pG0NKEb0eY7c38aAZ6EWq3ulFql6kahB6VjaHvhxD49Tu0f2LvFucge9HAOcHXzuMyz4OFl0Xl3kXuv_1_wHVhImq</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Sugino, Masahiro</creator><creator>Hatanaka, Tomomi</creator><creator>Todo, Hiroaki</creator><creator>Mashimo, Yuko</creator><creator>Suzuki, Takamasa</creator><creator>Kobayashi, Miho</creator><creator>Hosoya, Osamu</creator><creator>Jinno, Hideto</creator><creator>Juni, Kazuhiko</creator><creator>Sugibayashi, Kenji</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>OTOTI</scope><orcidid>https://orcid.org/0000-0002-4079-4023</orcidid></search><sort><creationdate>20170801</creationdate><title>Safety evaluation of dermal exposure to phthalates: Metabolism-dependent percutaneous absorption</title><author>Sugino, Masahiro ; Hatanaka, Tomomi ; Todo, Hiroaki ; Mashimo, Yuko ; Suzuki, Takamasa ; Kobayashi, Miho ; Hosoya, Osamu ; Jinno, Hideto ; Juni, Kazuhiko ; Sugibayashi, Kenji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-5c03d38d8fd5f05fb6a9d55488873161c1c0c952569a8ff9d40b64536db3e0643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ABSORPTION</topic><topic>Animals</topic><topic>Dermal exposure</topic><topic>Dibutyl Phthalate</topic><topic>Diethylhexyl Phthalate - administration & dosage</topic><topic>Diethylhexyl Phthalate - pharmacokinetics</topic><topic>Diethylhexyl Phthalate - toxicity</topic><topic>Environmental Exposure</topic><topic>Environmental Pollutants - pharmacokinetics</topic><topic>Environmental Pollutants - toxicity</topic><topic>ESTERASES</topic><topic>Esterases - antagonists & inhibitors</topic><topic>Female</topic><topic>HAZARDS</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>PHTHALATES</topic><topic>Phthalic Acids - administration & dosage</topic><topic>Phthalic Acids - pharmacokinetics</topic><topic>Phthalic Acids - toxicity</topic><topic>Plasticizers - administration & dosage</topic><topic>Plasticizers - pharmacokinetics</topic><topic>Plasticizers - toxicity</topic><topic>RATS</topic><topic>Rats, Hairless</topic><topic>RISK ASSESSMENT</topic><topic>Risk identification</topic><topic>SAFETY ANALYSIS</topic><topic>SKIN</topic><topic>Skin - enzymology</topic><topic>Skin Absorption</topic><topic>Skin permeation</topic><topic>Species Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sugino, Masahiro</creatorcontrib><creatorcontrib>Hatanaka, Tomomi</creatorcontrib><creatorcontrib>Todo, Hiroaki</creatorcontrib><creatorcontrib>Mashimo, Yuko</creatorcontrib><creatorcontrib>Suzuki, Takamasa</creatorcontrib><creatorcontrib>Kobayashi, Miho</creatorcontrib><creatorcontrib>Hosoya, Osamu</creatorcontrib><creatorcontrib>Jinno, Hideto</creatorcontrib><creatorcontrib>Juni, Kazuhiko</creatorcontrib><creatorcontrib>Sugibayashi, Kenji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sugino, Masahiro</au><au>Hatanaka, Tomomi</au><au>Todo, Hiroaki</au><au>Mashimo, Yuko</au><au>Suzuki, Takamasa</au><au>Kobayashi, Miho</au><au>Hosoya, Osamu</au><au>Jinno, Hideto</au><au>Juni, Kazuhiko</au><au>Sugibayashi, Kenji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety evaluation of dermal exposure to phthalates: Metabolism-dependent percutaneous absorption</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>328</volume><spage>10</spage><epage>17</epage><pages>10-17</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><abstract>Phthalates, known as reproductive toxicants and endocrine disruptors, are widely used as plasticizers in polyvinyl chloride products. The present study was conducted for risk identification of dermal exposure to phthalates. When dibutyl phthalate was applied to the skin of hairless rats and humans, only monobutyl phthalate appeared through the skin, and the permeability of the skin was higher than that after the application of the monoester directly. The inhibition of skin esterases made the skin impermeable to the metabolite following dermal exposure to dibutyl ester, whereas removal of the stratum corneum from the skin did not change the skin permeation behavior. Similar phenomena were observed for benzyl butyl phthalate. The skin permeability of monobenzyl phthalate was higher than that of monobutyl phthalate in humans, although the reverse was observed in rats. Species difference in skin permeation profile corresponded to the esterase activity of the skin homogenate. Di(2-ethylhexyl) phthalate, which was not metabolized by esterases in the skin, was not transported across the skin. These results suggest that highly lipophilic phthalates may be transported easily across the stratum corneum lipids. The water-rich viable layer may become permeable to these phthalates by their metabolism into monoesters, which are relatively hydrophilic. Skin metabolism is essential to the percutaneous absorption of phthalates. Because esterase activity has large inter-individual differences, further study will be needed for individual risk identification of dermal exposure to phthalates.
[Display omitted]
•Monophthalate, permeated through the skin after diphthalate application.•Characteristics of human skin cannot be determined from those of rat skin.•An accurate estimation of esterase activity in the skin requires a risk assessment.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28506834</pmid><doi>10.1016/j.taap.2017.05.009</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-4079-4023</orcidid><oa>free_for_read</oa></addata></record> |
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| source | ScienceDirect Journals |
| subjects | 60 APPLIED LIFE SCIENCES ABSORPTION Animals Dermal exposure Dibutyl Phthalate Diethylhexyl Phthalate - administration & dosage Diethylhexyl Phthalate - pharmacokinetics Diethylhexyl Phthalate - toxicity Environmental Exposure Environmental Pollutants - pharmacokinetics Environmental Pollutants - toxicity ESTERASES Esterases - antagonists & inhibitors Female HAZARDS Humans In Vitro Techniques Male Metabolism Middle Aged PHTHALATES Phthalic Acids - administration & dosage Phthalic Acids - pharmacokinetics Phthalic Acids - toxicity Plasticizers - administration & dosage Plasticizers - pharmacokinetics Plasticizers - toxicity RATS Rats, Hairless RISK ASSESSMENT Risk identification SAFETY ANALYSIS SKIN Skin - enzymology Skin Absorption Skin permeation Species Specificity |
| title | Safety evaluation of dermal exposure to phthalates: Metabolism-dependent percutaneous absorption |
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