Adjustment factors for toluene, styrene and methyl chloride by population modeling of toxicokinetic variability
•We present data-driven AFs for human kinetic variability for 3 organic solvents.•The AFs are derived by population PBPK modeling.•We explore effects of age, gender and various workplace conditions.•For most groups and conditions our AFs are below 2.2.•For certain occupational exposure scenarios the...
Gespeichert in:
| Veröffentlicht in: | Regulatory toxicology and pharmacology 2014-06, Vol.69 (1), p.78-90 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 90 |
|---|---|
| container_issue | 1 |
| container_start_page | 78 |
| container_title | Regulatory toxicology and pharmacology |
| container_volume | 69 |
| creator | Mörk, Anna-Karin Jonsson, Fredrik Johanson, Gunnar |
| description | •We present data-driven AFs for human kinetic variability for 3 organic solvents.•The AFs are derived by population PBPK modeling.•We explore effects of age, gender and various workplace conditions.•For most groups and conditions our AFs are below 2.2.•For certain occupational exposure scenarios the AFs are up to 5.0.
The availability of experimental data suitable as a basis to quantify human variability in response to chemical exposure has increased in recent years. It has enabled scientifically based, data driven adjustment factors (AF) to be deployed in the risk assessment process. As part of this development, we derive AF for human toxicokinetic variability (HK) for three lipophilic organic solvents; toluene, styrene and methyl chloride using physiologically based pharmacokinetic (PBPK) models in a population framework. The Monte Carlo simulations cover the influence of age and gender on toxicokinetic variability in the general population, as well as workplace ventilation rates and fluctuations in exposure level and workload in adult male and female workers. The derived AFHK are below 2.2 (95th percentile) for all subpopulations, exposure scenarios and chemicals, except for markers of acute effects in workers, where the factors are up to 5.0. |
| doi_str_mv | 10.1016/j.yrtph.2014.02.015 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_523070</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0273230014000397</els_id><sourcerecordid>1676357203</sourcerecordid><originalsourceid>FETCH-LOGICAL-c430t-79226da1c0acc51528b68366dd0b8754468393b5d70e9748ffbc677b185a1be43</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi0EokvhFyAhHzmQMHYSO3vgUFV8SZW4wNnyx4T1NomD7bTk3-OyS4-cPB4974w0DyGvGdQMmHh_rLeYl0PNgbU18BpY94TsGOxFBXzfPSU74LKpeANwQV6kdAQA3vfyObngrWBN27c7Eq7ccU15wjnTQdscYqJDiDSHccUZ39GUt1gKqmdHJ8yHbaT2MIboHVKz0SUs66izDzOdgsPRzz9pGEr8t7fh1s-YvaV3Onpt_Ojz9pI8G_SY8NX5vSQ_Pn38fv2luvn2-ev11U1l2wZyJfecC6eZBW1txzreG9E3QjgHppdd25bfvjGdk4B72fbDYKyQ0rC-08xg21yS6jQ33eOyGrVEP-m4qaC9OrduS4WqK_eRUPi3J36J4deKKavJJ4vjqGcMa1JMSNF0kkNT0OaE2hhSijg8DmegHsyoo_prRj2YUcBVMVNSb84LVjOhe8z8U1GADycAy1nuPEaVrMfZovMRbVYu-P8u-ANgjqMA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1676357203</pqid></control><display><type>article</type><title>Adjustment factors for toluene, styrene and methyl chloride by population modeling of toxicokinetic variability</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Mörk, Anna-Karin ; Jonsson, Fredrik ; Johanson, Gunnar</creator><creatorcontrib>Mörk, Anna-Karin ; Jonsson, Fredrik ; Johanson, Gunnar</creatorcontrib><description>•We present data-driven AFs for human kinetic variability for 3 organic solvents.•The AFs are derived by population PBPK modeling.•We explore effects of age, gender and various workplace conditions.•For most groups and conditions our AFs are below 2.2.•For certain occupational exposure scenarios the AFs are up to 5.0.
The availability of experimental data suitable as a basis to quantify human variability in response to chemical exposure has increased in recent years. It has enabled scientifically based, data driven adjustment factors (AF) to be deployed in the risk assessment process. As part of this development, we derive AF for human toxicokinetic variability (HK) for three lipophilic organic solvents; toluene, styrene and methyl chloride using physiologically based pharmacokinetic (PBPK) models in a population framework. The Monte Carlo simulations cover the influence of age and gender on toxicokinetic variability in the general population, as well as workplace ventilation rates and fluctuations in exposure level and workload in adult male and female workers. The derived AFHK are below 2.2 (95th percentile) for all subpopulations, exposure scenarios and chemicals, except for markers of acute effects in workers, where the factors are up to 5.0.</description><identifier>ISSN: 0273-2300</identifier><identifier>EISSN: 1096-0295</identifier><identifier>DOI: 10.1016/j.yrtph.2014.02.015</identifier><identifier>PMID: 24613484</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Assessment factor ; Child ; Child, Preschool ; Chloromethane ; Dose-Response Relationship, Drug ; Female ; Humans ; Infant ; Male ; Methyl Chloride - toxicity ; Monte Carlo Method ; Monte Carlo simulation ; Occupational Exposure - analysis ; Organic solvent ; PBPK model ; PBTK model ; Risk Assessment ; Safety factor ; Solvents - toxicity ; Styrene - toxicity ; Toluene - toxicity ; Toxicokinetics ; Uncertainty factor ; Ventilation ; Workplace</subject><ispartof>Regulatory toxicology and pharmacology, 2014-06, Vol.69 (1), p.78-90</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-79226da1c0acc51528b68366dd0b8754468393b5d70e9748ffbc677b185a1be43</citedby><cites>FETCH-LOGICAL-c430t-79226da1c0acc51528b68366dd0b8754468393b5d70e9748ffbc677b185a1be43</cites><orcidid>0000-0002-5259-4731</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0273230014000397$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24613484$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:128876198$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Mörk, Anna-Karin</creatorcontrib><creatorcontrib>Jonsson, Fredrik</creatorcontrib><creatorcontrib>Johanson, Gunnar</creatorcontrib><title>Adjustment factors for toluene, styrene and methyl chloride by population modeling of toxicokinetic variability</title><title>Regulatory toxicology and pharmacology</title><addtitle>Regul Toxicol Pharmacol</addtitle><description>•We present data-driven AFs for human kinetic variability for 3 organic solvents.•The AFs are derived by population PBPK modeling.•We explore effects of age, gender and various workplace conditions.•For most groups and conditions our AFs are below 2.2.•For certain occupational exposure scenarios the AFs are up to 5.0.
The availability of experimental data suitable as a basis to quantify human variability in response to chemical exposure has increased in recent years. It has enabled scientifically based, data driven adjustment factors (AF) to be deployed in the risk assessment process. As part of this development, we derive AF for human toxicokinetic variability (HK) for three lipophilic organic solvents; toluene, styrene and methyl chloride using physiologically based pharmacokinetic (PBPK) models in a population framework. The Monte Carlo simulations cover the influence of age and gender on toxicokinetic variability in the general population, as well as workplace ventilation rates and fluctuations in exposure level and workload in adult male and female workers. The derived AFHK are below 2.2 (95th percentile) for all subpopulations, exposure scenarios and chemicals, except for markers of acute effects in workers, where the factors are up to 5.0.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Assessment factor</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chloromethane</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Methyl Chloride - toxicity</subject><subject>Monte Carlo Method</subject><subject>Monte Carlo simulation</subject><subject>Occupational Exposure - analysis</subject><subject>Organic solvent</subject><subject>PBPK model</subject><subject>PBTK model</subject><subject>Risk Assessment</subject><subject>Safety factor</subject><subject>Solvents - toxicity</subject><subject>Styrene - toxicity</subject><subject>Toluene - toxicity</subject><subject>Toxicokinetics</subject><subject>Uncertainty factor</subject><subject>Ventilation</subject><subject>Workplace</subject><issn>0273-2300</issn><issn>1096-0295</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EokvhFyAhHzmQMHYSO3vgUFV8SZW4wNnyx4T1NomD7bTk3-OyS4-cPB4974w0DyGvGdQMmHh_rLeYl0PNgbU18BpY94TsGOxFBXzfPSU74LKpeANwQV6kdAQA3vfyObngrWBN27c7Eq7ccU15wjnTQdscYqJDiDSHccUZ39GUt1gKqmdHJ8yHbaT2MIboHVKz0SUs66izDzOdgsPRzz9pGEr8t7fh1s-YvaV3Onpt_Ojz9pI8G_SY8NX5vSQ_Pn38fv2luvn2-ev11U1l2wZyJfecC6eZBW1txzreG9E3QjgHppdd25bfvjGdk4B72fbDYKyQ0rC-08xg21yS6jQ33eOyGrVEP-m4qaC9OrduS4WqK_eRUPi3J36J4deKKavJJ4vjqGcMa1JMSNF0kkNT0OaE2hhSijg8DmegHsyoo_prRj2YUcBVMVNSb84LVjOhe8z8U1GADycAy1nuPEaVrMfZovMRbVYu-P8u-ANgjqMA</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Mörk, Anna-Karin</creator><creator>Jonsson, Fredrik</creator><creator>Johanson, Gunnar</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>7ST</scope><scope>7T2</scope><scope>7TV</scope><scope>7U1</scope><scope>7U2</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope><scope>ADTPV</scope><scope>AOWAS</scope><orcidid>https://orcid.org/0000-0002-5259-4731</orcidid></search><sort><creationdate>20140601</creationdate><title>Adjustment factors for toluene, styrene and methyl chloride by population modeling of toxicokinetic variability</title><author>Mörk, Anna-Karin ; Jonsson, Fredrik ; Johanson, Gunnar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-79226da1c0acc51528b68366dd0b8754468393b5d70e9748ffbc677b185a1be43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Assessment factor</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chloromethane</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Methyl Chloride - toxicity</topic><topic>Monte Carlo Method</topic><topic>Monte Carlo simulation</topic><topic>Occupational Exposure - analysis</topic><topic>Organic solvent</topic><topic>PBPK model</topic><topic>PBTK model</topic><topic>Risk Assessment</topic><topic>Safety factor</topic><topic>Solvents - toxicity</topic><topic>Styrene - toxicity</topic><topic>Toluene - toxicity</topic><topic>Toxicokinetics</topic><topic>Uncertainty factor</topic><topic>Ventilation</topic><topic>Workplace</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mörk, Anna-Karin</creatorcontrib><creatorcontrib>Jonsson, Fredrik</creatorcontrib><creatorcontrib>Johanson, Gunnar</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>Health and Safety Science Abstracts (Full archive)</collection><collection>Pollution Abstracts</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Regulatory toxicology and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mörk, Anna-Karin</au><au>Jonsson, Fredrik</au><au>Johanson, Gunnar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adjustment factors for toluene, styrene and methyl chloride by population modeling of toxicokinetic variability</atitle><jtitle>Regulatory toxicology and pharmacology</jtitle><addtitle>Regul Toxicol Pharmacol</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>69</volume><issue>1</issue><spage>78</spage><epage>90</epage><pages>78-90</pages><issn>0273-2300</issn><eissn>1096-0295</eissn><abstract>•We present data-driven AFs for human kinetic variability for 3 organic solvents.•The AFs are derived by population PBPK modeling.•We explore effects of age, gender and various workplace conditions.•For most groups and conditions our AFs are below 2.2.•For certain occupational exposure scenarios the AFs are up to 5.0.
The availability of experimental data suitable as a basis to quantify human variability in response to chemical exposure has increased in recent years. It has enabled scientifically based, data driven adjustment factors (AF) to be deployed in the risk assessment process. As part of this development, we derive AF for human toxicokinetic variability (HK) for three lipophilic organic solvents; toluene, styrene and methyl chloride using physiologically based pharmacokinetic (PBPK) models in a population framework. The Monte Carlo simulations cover the influence of age and gender on toxicokinetic variability in the general population, as well as workplace ventilation rates and fluctuations in exposure level and workload in adult male and female workers. The derived AFHK are below 2.2 (95th percentile) for all subpopulations, exposure scenarios and chemicals, except for markers of acute effects in workers, where the factors are up to 5.0.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>24613484</pmid><doi>10.1016/j.yrtph.2014.02.015</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-5259-4731</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0273-2300 |
| ispartof | Regulatory toxicology and pharmacology, 2014-06, Vol.69 (1), p.78-90 |
| issn | 0273-2300 1096-0295 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_523070 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Adolescent Adult Assessment factor Child Child, Preschool Chloromethane Dose-Response Relationship, Drug Female Humans Infant Male Methyl Chloride - toxicity Monte Carlo Method Monte Carlo simulation Occupational Exposure - analysis Organic solvent PBPK model PBTK model Risk Assessment Safety factor Solvents - toxicity Styrene - toxicity Toluene - toxicity Toxicokinetics Uncertainty factor Ventilation Workplace |
| title | Adjustment factors for toluene, styrene and methyl chloride by population modeling of toxicokinetic variability |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T17%3A19%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Adjustment%20factors%20for%20toluene,%20styrene%20and%20methyl%20chloride%20by%20population%20modeling%20of%20toxicokinetic%20variability&rft.jtitle=Regulatory%20toxicology%20and%20pharmacology&rft.au=M%C3%B6rk,%20Anna-Karin&rft.date=2014-06-01&rft.volume=69&rft.issue=1&rft.spage=78&rft.epage=90&rft.pages=78-90&rft.issn=0273-2300&rft.eissn=1096-0295&rft_id=info:doi/10.1016/j.yrtph.2014.02.015&rft_dat=%3Cproquest_swepu%3E1676357203%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1676357203&rft_id=info:pmid/24613484&rft_els_id=S0273230014000397&rfr_iscdi=true |