A Physiologically Based Pharmacokinetic Model for 2,4-Toluenediamine Leached from Polyurethane Foam-Covered Breast Implants
Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low-dose exposure of patients to the carcinogen 2,4-toluenediamine (2,4-TDA) released from the degradation of the polyester urethane foam (PU) used in Meme silicone breast implants. The tissues are represented as five compa...
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| Veröffentlicht in: | Environmental health perspectives 1998-07, Vol.106 (7), p.393-400 |
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| creator | Luu, Hoan-My Do Hutter, Joseph C. Bushar, Harry F. |
| description | Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low-dose exposure of patients to the carcinogen 2,4-toluenediamine (2,4-TDA) released from the degradation of the polyester urethane foam (PU) used in Meme silicone breast implants. The tissues are represented as five compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g., fat), and richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino toluene) in rats given low doses of 2,4-TDA intravenously and subcutaneously. The rat model was extrapolated to simulate oral and implant routes in rats. After adjusting for human physiological parameters, the model was then used to predict the bioavailability of 2,4-TDA released from a typical 4.87-g polyester urethane foam implant found in a patient who weighed 58 kg with the Meme and had the breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was performed and the polyester urethane foam did present an unreasonable risk to health for the patient. |
| doi_str_mv | 10.1289/ehp.98106393 |
| format | Article |
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The tissues are represented as five compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g., fat), and richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino toluene) in rats given low doses of 2,4-TDA intravenously and subcutaneously. The rat model was extrapolated to simulate oral and implant routes in rats. After adjusting for human physiological parameters, the model was then used to predict the bioavailability of 2,4-TDA released from a typical 4.87-g polyester urethane foam implant found in a patient who weighed 58 kg with the Meme and had the breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was performed and the polyester urethane foam did present an unreasonable risk to health for the patient.</description><identifier>ISSN: 0091-6765</identifier><identifier>EISSN: 1552-9924</identifier><identifier>DOI: 10.1289/ehp.98106393</identifier><identifier>PMID: 9637796</identifier><language>eng</language><publisher>United States: National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare</publisher><subject>Algorithms ; Animals ; Blood plasma ; Body tissues ; Breast implants ; Breast Implants - adverse effects ; Carcinogens - chemistry ; Carcinogens - pharmacokinetics ; Dosage ; Drug design ; Excretion ; Female ; Foams ; Humans ; Injections, Intravenous ; Injections, Subcutaneous ; Metabolism ; Modeling ; Models, Biological ; Parametric models ; Phenylenediamines - chemistry ; Phenylenediamines - pharmacokinetics ; Polyurethanes - chemistry ; Rats ; Tissue Distribution</subject><ispartof>Environmental health perspectives, 1998-07, Vol.106 (7), p.393-400</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-f387315777b2d9f0ae620eae900295241c2da61bb31b53fd27d9cf3cfd647bde3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3434066$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3434066$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,860,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9637796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luu, Hoan-My Do</creatorcontrib><creatorcontrib>Hutter, Joseph C.</creatorcontrib><creatorcontrib>Bushar, Harry F.</creatorcontrib><title>A Physiologically Based Pharmacokinetic Model for 2,4-Toluenediamine Leached from Polyurethane Foam-Covered Breast Implants</title><title>Environmental health perspectives</title><addtitle>Environ Health Perspect</addtitle><description>Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low-dose exposure of patients to the carcinogen 2,4-toluenediamine (2,4-TDA) released from the degradation of the polyester urethane foam (PU) used in Meme silicone breast implants. The tissues are represented as five compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g., fat), and richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino toluene) in rats given low doses of 2,4-TDA intravenously and subcutaneously. The rat model was extrapolated to simulate oral and implant routes in rats. After adjusting for human physiological parameters, the model was then used to predict the bioavailability of 2,4-TDA released from a typical 4.87-g polyester urethane foam implant found in a patient who weighed 58 kg with the Meme and had the breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was performed and the polyester urethane foam did present an unreasonable risk to health for the patient.</description><subject>Algorithms</subject><subject>Animals</subject><subject>Blood plasma</subject><subject>Body tissues</subject><subject>Breast implants</subject><subject>Breast Implants - adverse effects</subject><subject>Carcinogens - chemistry</subject><subject>Carcinogens - pharmacokinetics</subject><subject>Dosage</subject><subject>Drug design</subject><subject>Excretion</subject><subject>Female</subject><subject>Foams</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Injections, Subcutaneous</subject><subject>Metabolism</subject><subject>Modeling</subject><subject>Models, Biological</subject><subject>Parametric models</subject><subject>Phenylenediamines - chemistry</subject><subject>Phenylenediamines - pharmacokinetics</subject><subject>Polyurethanes - chemistry</subject><subject>Rats</subject><subject>Tissue Distribution</subject><issn>0091-6765</issn><issn>1552-9924</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9rFDEYhoModa3evApzkJ46Nb8mmVyEdrG1sGIP9RwyyTed1MxkTWYKi_-8KbuWevL0QZ4nL9_Hi9B7gs8IbdUnGLZnqiVYMMVeoBVpGlorRflLtMJYkVpI0bxGb3K-xxiTVogjdKQEk1KJFfp9Xt0Mu-xjiHfemhB21YXJ4MqrSaOx8aefYPa2-hYdhKqPqaKnvL6NYYEJnDdj4dUGjB3Kpz7FsbqJYbckmAdTyGU0Y72OD5AKvkhg8lxdj9tgpjm_Ra96EzK8O8xj9OPyy-36a735fnW9Pt_Ulks81z1rJSONlLKjTvXYgKAYDCiMqWooJ5Y6I0jXMdI1rHdUOmV7ZnsnuOwcsGP0eZ-7XboRnIVpTibobfKjSTsdjdf_kskP-i4-aNIwRpgsASeHgBR_LZBnPfpsIZQrIC5ZE4kVU5z_X-S8bQUhRTzdizbFnBP0T9sQrB9b1aVV_bfVon94fsGTfKix8I97fp_nmJ5nUYalZpxxLAT7A_vsq6U</recordid><startdate>19980701</startdate><enddate>19980701</enddate><creator>Luu, Hoan-My Do</creator><creator>Hutter, Joseph C.</creator><creator>Bushar, Harry F.</creator><general>National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare</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>7ST</scope><scope>C1K</scope><scope>SOI</scope><scope>7U7</scope><scope>5PM</scope></search><sort><creationdate>19980701</creationdate><title>A Physiologically Based Pharmacokinetic Model for 2,4-Toluenediamine Leached from Polyurethane Foam-Covered Breast Implants</title><author>Luu, Hoan-My Do ; Hutter, Joseph C. ; Bushar, Harry F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-f387315777b2d9f0ae620eae900295241c2da61bb31b53fd27d9cf3cfd647bde3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Algorithms</topic><topic>Animals</topic><topic>Blood plasma</topic><topic>Body tissues</topic><topic>Breast implants</topic><topic>Breast Implants - adverse effects</topic><topic>Carcinogens - chemistry</topic><topic>Carcinogens - pharmacokinetics</topic><topic>Dosage</topic><topic>Drug design</topic><topic>Excretion</topic><topic>Female</topic><topic>Foams</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Injections, Subcutaneous</topic><topic>Metabolism</topic><topic>Modeling</topic><topic>Models, Biological</topic><topic>Parametric models</topic><topic>Phenylenediamines - chemistry</topic><topic>Phenylenediamines - pharmacokinetics</topic><topic>Polyurethanes - chemistry</topic><topic>Rats</topic><topic>Tissue Distribution</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luu, Hoan-My Do</creatorcontrib><creatorcontrib>Hutter, Joseph C.</creatorcontrib><creatorcontrib>Bushar, Harry F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>Toxicology Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Environmental health perspectives</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luu, Hoan-My Do</au><au>Hutter, Joseph C.</au><au>Bushar, Harry F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Physiologically Based Pharmacokinetic Model for 2,4-Toluenediamine Leached from Polyurethane Foam-Covered Breast Implants</atitle><jtitle>Environmental health perspectives</jtitle><addtitle>Environ Health Perspect</addtitle><date>1998-07-01</date><risdate>1998</risdate><volume>106</volume><issue>7</issue><spage>393</spage><epage>400</epage><pages>393-400</pages><issn>0091-6765</issn><eissn>1552-9924</eissn><abstract>Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low-dose exposure of patients to the carcinogen 2,4-toluenediamine (2,4-TDA) released from the degradation of the polyester urethane foam (PU) used in Meme silicone breast implants. The tissues are represented as five compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g., fat), and richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino toluene) in rats given low doses of 2,4-TDA intravenously and subcutaneously. The rat model was extrapolated to simulate oral and implant routes in rats. After adjusting for human physiological parameters, the model was then used to predict the bioavailability of 2,4-TDA released from a typical 4.87-g polyester urethane foam implant found in a patient who weighed 58 kg with the Meme and had the breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was performed and the polyester urethane foam did present an unreasonable risk to health for the patient.</abstract><cop>United States</cop><pub>National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare</pub><pmid>9637796</pmid><doi>10.1289/ehp.98106393</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | Jstor Complete Legacy; MEDLINE; TestCollectionTL3OpenAccess; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Algorithms Animals Blood plasma Body tissues Breast implants Breast Implants - adverse effects Carcinogens - chemistry Carcinogens - pharmacokinetics Dosage Drug design Excretion Female Foams Humans Injections, Intravenous Injections, Subcutaneous Metabolism Modeling Models, Biological Parametric models Phenylenediamines - chemistry Phenylenediamines - pharmacokinetics Polyurethanes - chemistry Rats Tissue Distribution |
| title | A Physiologically Based Pharmacokinetic Model for 2,4-Toluenediamine Leached from Polyurethane Foam-Covered Breast Implants |
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