{"id":"https://openalex.org/W2145841223","doi":"https://doi.org/10.1093/toxsci/63.1.125","title":"A PBPK Modeling-Based Approach to Account for Interactions in the Health Risk Assessment of Chemical Mixtures","display_name":"A PBPK Modeling-Based Approach to Account for Interactions in the Health Risk Assessment of Chemical Mixtures","publication_year":2001,"publication_date":"2001-09-01","ids":{"openalex":"https://openalex.org/W2145841223","doi":"https://doi.org/10.1093/toxsci/63.1.125","mag":"2145841223","pmid":"https://pubmed.ncbi.nlm.nih.gov/11509752"},"language":"en","primary_location":{"id":"doi:10.1093/toxsci/63.1.125","doi":"https://doi.org/10.1093/toxsci/63.1.125","is_oa":false,"landing_page_url":"https://doi.org/10.1093/toxsci/63.1.125","pdf_url":null,"source":{"id":"https://openalex.org/S186282544","display_name":"Toxicological Sciences","issn_l":"1096-0929","issn":["1096-0929","1096-6080"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Toxicological Sciences","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5070588264","display_name":"Sami Haddad","orcid":"https://orcid.org/0000-0001-8906-9693","observed_orcids":["https://orcid.org/0000-0001-8906-9693"]},"institutions":[{"id":"https://openalex.org/I70931966","display_name":"Universit\u00e9 de Montr\u00e9al","ror":"https://ror.org/0161xgx34","country_code":"CA","type":"education","lineage":["https://openalex.org/I70931966"]}],"countries":["CA"],"is_corresponding":true,"raw_author_name":"S. Haddad","raw_affiliation_strings":["Groupe de recherche en toxicologie humaine (TOXHUM), Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Case Postale 6128, Succursale centre-ville, Montr\u00e9al, Qu\u00e9bec H3C 3J7, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Groupe de recherche en toxicologie humaine (TOXHUM), Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Case Postale 6128, Succursale centre-ville, Montr\u00e9al, Qu\u00e9bec H3C 3J7, Canada","institution_ids":["https://openalex.org/I70931966"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5070588264"],"corresponding_institution_ids":["https://openalex.org/I70931966"],"apc_list":{"value":4671,"currency":"USD","value_usd":4671},"apc_paid":null,"fwci":4.0191,"has_fulltext":false,"cited_by_count":130,"citation_normalized_percentile":{"value":0.93458046,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":93,"max":99},"biblio":{"volume":"63","issue":"1","first_page":"125","last_page":"131"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T13315","display_name":"Occupational Health and Safety in Workplaces","score":0.31049999594688416,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T13315","display_name":"Occupational Health and Safety in Workplaces","score":0.31049999594688416,"subfield":{"id":"https://openalex.org/subfields/2739","display_name":"Public Health, Environmental and Occupational Health"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10433","display_name":"Carcinogens and Genotoxicity Assessment","score":0.12720000743865967,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T13840","display_name":"Chemical Safety and Risk Management","score":0.1168999969959259,"subfield":{"id":"https://openalex.org/subfields/1504","display_name":"Chemical Health and Safety"},"field":{"id":"https://openalex.org/fields/15","display_name":"Chemical Engineering"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/chemical-mixtures","display_name":"chemical mixtures","score":0.9380000233650208},{"id":"https://openalex.org/keywords/health-risk-assessment","display_name":"health risk assessment","score":0.8330000042915344},{"id":"https://openalex.org/keywords/pharmacokinetic-interactions","display_name":"pharmacokinetic interactions","score":0.8849999904632568},{"id":"https://openalex.org/keywords/physiologically-based-pharmacokinetic-model","display_name":"physiologically based pharmacokinetic modeling","score":0.8379999995231628},{"id":"https://openalex.org/keywords/dichloromethane","display_name":"dichloromethane","score":0.8820000290870667},{"id":"https://openalex.org/keywords/benzene","display_name":"benzene","score":0.968999981880188},{"id":"https://openalex.org/keywords/toluene","display_name":"toluene","score":0.9959999918937683},{"id":"https://openalex.org/keywords/ethylbenzene","display_name":"ethylbenzene","score":0.9710000157356262},{"id":"https://openalex.org/keywords/m-xylene","display_name":"m-xylene","score":0.9829999804496765},{"id":"https://openalex.org/keywords/occupational-inhalation-exposure","display_name":"occupational inhalation exposure","score":0.8980000019073486},{"id":"https://openalex.org/keywords/tissue-dose","display_name":"tissue dose","score":0.640999972820282},{"id":"https://openalex.org/keywords/cancer-risk","display_name":"cancer risk","score":0.7760000228881836},{"id":"https://openalex.org/keywords/threshold-limit-values","display_name":"threshold limit values","score":0.6959999799728394}],"concepts":[{"id":"https://openalex.org/C185867374","wikidata":"https://www.wikidata.org/wiki/Q2562769","display_name":"Physiologically based pharmacokinetic modelling","level":3,"score":0.8943184614181519},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6065168976783752},{"id":"https://openalex.org/C2779777708","wikidata":"https://www.wikidata.org/wiki/Q6033622","display_name":"Inhalation exposure","level":3,"score":0.5337492227554321},{"id":"https://openalex.org/C2779533485","wikidata":"https://www.wikidata.org/wiki/Q409184","display_name":"Ethylbenzene","level":3,"score":0.5295693874359131},{"id":"https://openalex.org/C12174686","wikidata":"https://www.wikidata.org/wiki/Q1058438","display_name":"Risk assessment","level":2,"score":0.48075056076049805},{"id":"https://openalex.org/C33070731","wikidata":"https://www.wikidata.org/wiki/Q7218","display_name":"Toxicology","level":1,"score":0.4063914120197296},{"id":"https://openalex.org/C107872376","wikidata":"https://www.wikidata.org/wiki/Q321355","display_name":"Environmental chemistry","level":1,"score":0.3900918662548065},{"id":"https://openalex.org/C2778142098","wikidata":"https://www.wikidata.org/wiki/Q15779","display_name":"Toluene","level":2,"score":0.35935163497924805},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.3204340934753418},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.21864137053489685},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.2044600546360016},{"id":"https://openalex.org/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.14769643545150757},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.08820199966430664},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.08598843216896057},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.0},{"id":"https://openalex.org/C38652104","wikidata":"https://www.wikidata.org/wiki/Q3510521","display_name":"Computer security","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000395","descriptor_name":"Air Pollutants, Occupational","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001554","descriptor_name":"Benzene","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D001555","descriptor_name":"Benzene Derivatives","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D004347","descriptor_name":"Drug Interactions","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008752","descriptor_name":"Methylene Chloride","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009930","descriptor_name":"Organic Chemicals","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D014050","descriptor_name":"Toluene","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D014835","descriptor_name":"Volatilization","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014992","descriptor_name":"Xylenes","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D018570","descriptor_name":"Risk Assessment","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019540","descriptor_name":"Area Under Curve","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019570","descriptor_name":"Inhalation Exposure","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020711","descriptor_name":"Threshold Limit Values","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1093/toxsci/63.1.125","doi":"https://doi.org/10.1093/toxsci/63.1.125","is_oa":false,"landing_page_url":"https://doi.org/10.1093/toxsci/63.1.125","pdf_url":null,"source":{"id":"https://openalex.org/S186282544","display_name":"Toxicological Sciences","issn_l":"1096-0929","issn":["1096-0929","1096-6080"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-2","ki-jl-2","medline","norway-2","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Toxicological Sciences","raw_type":"journal-article"},{"id":"pmid:11509752","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/11509752","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Toxicological sciences : an official journal of the Society of Toxicology","raw_type":"Journal Article"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.554.1989","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.554.1989","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"http://toxsci.oxfordjournals.org/content/63/1/125.full.pdf","raw_type":"text"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9537000060081482,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":12,"referenced_works":["https://openalex.org/W1970679490","https://openalex.org/W1983282636","https://openalex.org/W1985476973","https://openalex.org/W1989080288","https://openalex.org/W1993006119","https://openalex.org/W1998211865","https://openalex.org/W2001652959","https://openalex.org/W2029333481","https://openalex.org/W2069099568","https://openalex.org/W2092136686","https://openalex.org/W2319227608","https://openalex.org/W2488712353"],"related_works":["https://openalex.org/W7096558674","https://openalex.org/W7045553489","https://openalex.org/W7099341125","https://openalex.org/W1984024051","https://openalex.org/W2025031102","https://openalex.org/W2071630971","https://openalex.org/W7098907235","https://openalex.org/W2114036701","https://openalex.org/W7099486015","https://openalex.org/W2004897529"],"abstract_inverted_index":{"The":[0,50,230,242],"objectives":[1],"of":[2,43,52,62,83,94,118,135,184,200,213,225,256,259],"the":[3,32,53,60,63,72,122,141,159,167,182,197,201,215,223,246,251,254,257],"present":[4,247],"study":[5,248],"were:":[6],"(1)":[7],"to":[8,26,30,40,59,127],"develop":[9],"a":[10,92,152,264],"risk":[11,34,55,217,269],"assessment":[12,56],"methodology":[13,29,57],"for":[14,19,75,143,158,176,218,250],"chemical":[15,77,85,145],"mixtures":[16,42],"that":[17,156],"accounts":[18],"pharmacokinetic":[20,261],"interactions":[21,164,262],"among":[22],"components,":[23],"and":[24,48,161,192,228],"(2)":[25],"apply":[27],"this":[28],"assess":[31],"health":[33],"associated":[35],"with":[36],"occupational":[37],"inhalation":[38],"exposure":[39,148,189,194],"airborne":[41],"dichloromethane,":[44],"benzene,":[45],"toluene,":[46],"ethylbenzene,":[47],"m-xylene.":[49],"basis":[51],"proposed":[54],"relates":[58],"characterization":[61],"change":[64],"in":[65,78,96,245,267],"tissue":[66,116,124],"dose":[67,117,227],"metrics":[68],"(e.g.,":[69,130],"area":[70],"under":[71],"concentration-time":[73],"curve":[74],"parent":[76,84],"tissues":[79],"[AUCtissue],":[80],"maximal":[81],"concentration":[82],"or":[86],"metabolite":[87],"[Cmax],":[88],"quantity":[89],"metabolized":[90],"over":[91],"period":[93],"time)":[95],"humans,":[97],"during":[98,146,187,232],"mixed":[99,147,188],"exposures":[100,234],"using":[101,113,151,237],"PBPK":[102,154,240],"models.":[103],"For":[104,196],"systemic":[105],"toxicants,":[106],"an":[107,203,238],"interaction-based":[108,170,204,239],"hazard":[109,171],"index":[110,172],"was":[111,149,173,208,235],"calculated":[112,175,221],"data":[114],"on":[115],"mixture":[119,153,233,268],"constituents.":[120],"Initially,":[121],"AUCtarget":[123],"(AUCtt)":[125],"corresponding":[126],"guideline":[128],"values":[129],"threshold":[131],"limit":[132],"value":[133],"[TLV])":[134],"individual":[136],"chemicals":[137],"were":[138],"obtained.":[139],"Then,":[140],"AUCtt":[142,185,231],"each":[144,177,219],"obtained":[150,186,236],"model":[155],"accounted":[157],"binary":[160],"higher":[162],"order":[163],"occurring":[165],"within":[166],"mixture.":[168],"An":[169],"then":[174],"toxic":[178],"effect":[179],"by":[180],"summing":[181],"ratio":[183],"(predefined":[190],"mixture)":[191],"single":[193],"(TLV).":[195],"carcinogenic":[198],"constituents":[199],"mixture,":[202],"response":[205],"additivity":[206],"approach":[207],"applied.":[209],"This":[210],"method":[211],"consisted":[212],"adding":[214],"cancer":[216],"constituent,":[220],"as":[222],"product":[224],"q*tissue":[226],"AUCtt.":[229],"model.":[241],"approaches":[243],"developed":[244],"permit,":[249],"first":[252],"time,":[253],"consideration":[255],"impact":[258],"multichemical":[260],"at":[263],"quantitative":[265],"level":[266],"assessments.":[270]},"counts_by_year":[{"year":2026,"cited_by_count":3},{"year":2025,"cited_by_count":3},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":4},{"year":2022,"cited_by_count":9},{"year":2021,"cited_by_count":4},{"year":2020,"cited_by_count":6},{"year":2019,"cited_by_count":5},{"year":2018,"cited_by_count":5},{"year":2017,"cited_by_count":6},{"year":2016,"cited_by_count":4},{"year":2015,"cited_by_count":5},{"year":2014,"cited_by_count":3},{"year":2013,"cited_by_count":5},{"year":2012,"cited_by_count":9}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}
