Fate of chemicals in skin after dermal application: does the in vitro skin reservoir affect the estimate of systemic absorption?
Recent international guidelines for the conduct of in vitro skin absorption studies put forward different approaches for addressing the status of chemicals remaining in the stratum corneum and epidermis/dermis at the end of a study. The present study investigated the fate of three chemicals [dihydro...
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| Veröffentlicht in: | Toxicology and applied pharmacology 2004-03, Vol.195 (3), p.309-320 |
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| creator | Yourick, Jeffrey J Koenig, Michael L Yourick, Debra L Bronaugh, Robert L |
| description | Recent international guidelines for the conduct of in vitro skin absorption studies put forward different approaches for addressing the status of chemicals remaining in the stratum corneum and epidermis/dermis at the end of a study. The present study investigated the fate of three chemicals [dihydroxyacetone (DHA), 7-(2
H-naphtho[1,2-d]triazol-2-yl)-3-phenylcoumarin (7NTPC), and disperse blue 1 (DB1)] in an in vitro absorption study. In these studies, human and fuzzy rat skin penetration and absorption were determined over 24 or 72 h in flow-through diffusion cells. Skin penetration of these chemicals resulted in relatively low receptor fluid levels but high skin levels. For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 h. Little of the DHA that penetrates into skin is actually available to become systemically absorbed. 7NTPC remaining in the skin after 24 h was approximately 14.7% of the applied dose absorbed. Confocal laser cytometry studies with 7NTPC showed that it is present across skin in mainly the epidermis and dermis with intense fluorescence around hair. For DB1, penetration studies found approximately 10% (ethanol vehicle) and 3% (formulation vehicle) of the applied dose localized in mainly the stratum corneum after 24 h. An extended absorption study (72 h) revealed that little additional DB1 was absorbed into the receptor fluid. Skin levels should not be considered as absorbed material for DHA or DB1, while 7NTPC requires further investigation. These studies illustrate the importance of determining the fate of chemicals remaining in skin, which could significantly affect the estimates of systemically available material to be used in exposure estimates. We recommend that a more conclusive means to determine the fate of skin levels is to perform an extended study as conducted for DB1. |
| doi_str_mv | 10.1016/j.taap.2003.07.015 |
| format | Article |
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H-naphtho[1,2-d]triazol-2-yl)-3-phenylcoumarin (7NTPC), and disperse blue 1 (DB1)] in an in vitro absorption study. In these studies, human and fuzzy rat skin penetration and absorption were determined over 24 or 72 h in flow-through diffusion cells. Skin penetration of these chemicals resulted in relatively low receptor fluid levels but high skin levels. For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 h. Little of the DHA that penetrates into skin is actually available to become systemically absorbed. 7NTPC remaining in the skin after 24 h was approximately 14.7% of the applied dose absorbed. Confocal laser cytometry studies with 7NTPC showed that it is present across skin in mainly the epidermis and dermis with intense fluorescence around hair. For DB1, penetration studies found approximately 10% (ethanol vehicle) and 3% (formulation vehicle) of the applied dose localized in mainly the stratum corneum after 24 h. An extended absorption study (72 h) revealed that little additional DB1 was absorbed into the receptor fluid. Skin levels should not be considered as absorbed material for DHA or DB1, while 7NTPC requires further investigation. These studies illustrate the importance of determining the fate of chemicals remaining in skin, which could significantly affect the estimates of systemically available material to be used in exposure estimates. We recommend that a more conclusive means to determine the fate of skin levels is to perform an extended study as conducted for DB1.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2003.07.015</identifier><identifier>PMID: 15020193</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Absorption ; Administration, Cutaneous ; Animals ; Anthraquinones - administration & dosage ; Anthraquinones - metabolism ; Anthraquinones - pharmacokinetics ; Chemicals ; Coumarins - administration & dosage ; Coumarins - metabolism ; Coumarins - pharmacokinetics ; Dihydroxyacetone - administration & dosage ; Dihydroxyacetone - metabolism ; Dihydroxyacetone - pharmacokinetics ; Female ; Humans ; In Vitro Techniques ; Rats ; Skin ; Skin - metabolism ; Skin Absorption ; Tissue Distribution ; Triazoles - administration & dosage ; Triazoles - metabolism ; Triazoles - pharmacokinetics</subject><ispartof>Toxicology and applied pharmacology, 2004-03, Vol.195 (3), p.309-320</ispartof><rights>2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-6cda3a481361527a9cec36c197ebe414fb89637ce78564babf8845bf18445d243</citedby><cites>FETCH-LOGICAL-c449t-6cda3a481361527a9cec36c197ebe414fb89637ce78564babf8845bf18445d243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2003.07.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15020193$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yourick, Jeffrey J</creatorcontrib><creatorcontrib>Koenig, Michael L</creatorcontrib><creatorcontrib>Yourick, Debra L</creatorcontrib><creatorcontrib>Bronaugh, Robert L</creatorcontrib><title>Fate of chemicals in skin after dermal application: does the in vitro skin reservoir affect the estimate of systemic absorption?</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Recent international guidelines for the conduct of in vitro skin absorption studies put forward different approaches for addressing the status of chemicals remaining in the stratum corneum and epidermis/dermis at the end of a study. The present study investigated the fate of three chemicals [dihydroxyacetone (DHA), 7-(2
H-naphtho[1,2-d]triazol-2-yl)-3-phenylcoumarin (7NTPC), and disperse blue 1 (DB1)] in an in vitro absorption study. In these studies, human and fuzzy rat skin penetration and absorption were determined over 24 or 72 h in flow-through diffusion cells. Skin penetration of these chemicals resulted in relatively low receptor fluid levels but high skin levels. For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 h. Little of the DHA that penetrates into skin is actually available to become systemically absorbed. 7NTPC remaining in the skin after 24 h was approximately 14.7% of the applied dose absorbed. Confocal laser cytometry studies with 7NTPC showed that it is present across skin in mainly the epidermis and dermis with intense fluorescence around hair. For DB1, penetration studies found approximately 10% (ethanol vehicle) and 3% (formulation vehicle) of the applied dose localized in mainly the stratum corneum after 24 h. An extended absorption study (72 h) revealed that little additional DB1 was absorbed into the receptor fluid. Skin levels should not be considered as absorbed material for DHA or DB1, while 7NTPC requires further investigation. These studies illustrate the importance of determining the fate of chemicals remaining in skin, which could significantly affect the estimates of systemically available material to be used in exposure estimates. We recommend that a more conclusive means to determine the fate of skin levels is to perform an extended study as conducted for DB1.</description><subject>Absorption</subject><subject>Administration, Cutaneous</subject><subject>Animals</subject><subject>Anthraquinones - administration & dosage</subject><subject>Anthraquinones - metabolism</subject><subject>Anthraquinones - pharmacokinetics</subject><subject>Chemicals</subject><subject>Coumarins - administration & dosage</subject><subject>Coumarins - metabolism</subject><subject>Coumarins - pharmacokinetics</subject><subject>Dihydroxyacetone - administration & dosage</subject><subject>Dihydroxyacetone - metabolism</subject><subject>Dihydroxyacetone - pharmacokinetics</subject><subject>Female</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Rats</subject><subject>Skin</subject><subject>Skin - metabolism</subject><subject>Skin Absorption</subject><subject>Tissue Distribution</subject><subject>Triazoles - administration & dosage</subject><subject>Triazoles - metabolism</subject><subject>Triazoles - pharmacokinetics</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS1ERbeFP8AB-cQt6UzsxAlCQqiiLVKlXkDiZjnORPWSrIPtXak3fjpOdyVucLEP_t5743mMvUUoEbC52pbJmKWsAEQJqgSsX7ANQtcUIIR4yTYAEguA9sc5u4hxCwCdlPiKnWMNFWAnNuz3jUnE_cjtI83Omilyt-PxZz7MmCjwgcJsJm6WZcrPyfndBz54ijw90ooeXAr-KAgUKRy8C1k6kk3PCMXk5lNGfIppTeGmjz4sq9mn1-xszKn05nRfsu83X75d3xX3D7dfrz_fF1bKLhWNHYwwskXRYF0p01myorHYKepJohz7tmuEsqTaupG96ce2lXU_YitlPVRSXLL3R98l-F_7PJWeXbQ0TWZHfh-1QlUphfV_QVRdKxqBGayOoA0-xkCjXkL-anjSCHotSG_1WpBeC9KgNDy7vzu57_uZhr-SUyMZ-HgEKC_j4CjoaB3tLA0u5J3qwbt_-f8BTKijNw</recordid><startdate>20040315</startdate><enddate>20040315</enddate><creator>Yourick, Jeffrey J</creator><creator>Koenig, Michael L</creator><creator>Yourick, Debra L</creator><creator>Bronaugh, Robert L</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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20040315</creationdate><title>Fate of chemicals in skin after dermal application: does the in vitro skin reservoir affect the estimate of systemic absorption?</title><author>Yourick, Jeffrey J ; Koenig, Michael L ; Yourick, Debra L ; Bronaugh, Robert L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-6cda3a481361527a9cec36c197ebe414fb89637ce78564babf8845bf18445d243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Absorption</topic><topic>Administration, Cutaneous</topic><topic>Animals</topic><topic>Anthraquinones - administration & dosage</topic><topic>Anthraquinones - metabolism</topic><topic>Anthraquinones - pharmacokinetics</topic><topic>Chemicals</topic><topic>Coumarins - administration & dosage</topic><topic>Coumarins - metabolism</topic><topic>Coumarins - pharmacokinetics</topic><topic>Dihydroxyacetone - administration & dosage</topic><topic>Dihydroxyacetone - metabolism</topic><topic>Dihydroxyacetone - pharmacokinetics</topic><topic>Female</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Rats</topic><topic>Skin</topic><topic>Skin - metabolism</topic><topic>Skin Absorption</topic><topic>Tissue Distribution</topic><topic>Triazoles - administration & dosage</topic><topic>Triazoles - metabolism</topic><topic>Triazoles - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yourick, Jeffrey J</creatorcontrib><creatorcontrib>Koenig, Michael L</creatorcontrib><creatorcontrib>Yourick, Debra L</creatorcontrib><creatorcontrib>Bronaugh, Robert L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yourick, Jeffrey J</au><au>Koenig, Michael L</au><au>Yourick, Debra L</au><au>Bronaugh, Robert L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fate of chemicals in skin after dermal application: does the in vitro skin reservoir affect the estimate of systemic absorption?</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2004-03-15</date><risdate>2004</risdate><volume>195</volume><issue>3</issue><spage>309</spage><epage>320</epage><pages>309-320</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><abstract>Recent international guidelines for the conduct of in vitro skin absorption studies put forward different approaches for addressing the status of chemicals remaining in the stratum corneum and epidermis/dermis at the end of a study. 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H-naphtho[1,2-d]triazol-2-yl)-3-phenylcoumarin (7NTPC), and disperse blue 1 (DB1)] in an in vitro absorption study. In these studies, human and fuzzy rat skin penetration and absorption were determined over 24 or 72 h in flow-through diffusion cells. Skin penetration of these chemicals resulted in relatively low receptor fluid levels but high skin levels. For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 h. Little of the DHA that penetrates into skin is actually available to become systemically absorbed. 7NTPC remaining in the skin after 24 h was approximately 14.7% of the applied dose absorbed. Confocal laser cytometry studies with 7NTPC showed that it is present across skin in mainly the epidermis and dermis with intense fluorescence around hair. For DB1, penetration studies found approximately 10% (ethanol vehicle) and 3% (formulation vehicle) of the applied dose localized in mainly the stratum corneum after 24 h. An extended absorption study (72 h) revealed that little additional DB1 was absorbed into the receptor fluid. Skin levels should not be considered as absorbed material for DHA or DB1, while 7NTPC requires further investigation. These studies illustrate the importance of determining the fate of chemicals remaining in skin, which could significantly affect the estimates of systemically available material to be used in exposure estimates. We recommend that a more conclusive means to determine the fate of skin levels is to perform an extended study as conducted for DB1.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15020193</pmid><doi>10.1016/j.taap.2003.07.015</doi><tpages>12</tpages></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Absorption Administration, Cutaneous Animals Anthraquinones - administration & dosage Anthraquinones - metabolism Anthraquinones - pharmacokinetics Chemicals Coumarins - administration & dosage Coumarins - metabolism Coumarins - pharmacokinetics Dihydroxyacetone - administration & dosage Dihydroxyacetone - metabolism Dihydroxyacetone - pharmacokinetics Female Humans In Vitro Techniques Rats Skin Skin - metabolism Skin Absorption Tissue Distribution Triazoles - administration & dosage Triazoles - metabolism Triazoles - pharmacokinetics |
| title | Fate of chemicals in skin after dermal application: does the in vitro skin reservoir affect the estimate of systemic absorption? |
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