title: Evaluation and modeling of the impact of coexposures to VOC mixtures on urinary biomarkers.
abstract: BACKGROUND
  Urinary biomarkers are widely used among biomonitoring studies because of their ease of collection and nonintrusiveness. Chloroform and TEX (i.e., toluene, ethylbenzene, and m-xylene) are chemicals that are often found together because of common use. Although interactions occurring among TEX are well-known, no information exists on possible kinetic interactions between these chemicals and chloroform at the level of parent compound or urinary biomarkers.
  
  
  OBJECTIVE
  The objective of this study was therefore to study the possible interactions between these compounds in human volunteers with special emphasis on the potential impact on urinary biomarkers.
  
  
  METHODS
  Five male volunteers were exposed by inhalation for 6 h to single, binary, and quaternary mixtures that included chloroform. Exhaled air and blood samples were collected and analyzed for parent compound concentrations. Urinary biomarkers (o-cresol, mandelic, and m-methylhippuric acids) were quantified in urine samples. Published PBPK model for chloroform was used, and a Vmax of 3.4 mg/h/kg was optimized to provide a better fit with blood data. Adapted PBPK models from our previous study were used for parent compounds and urinary biomarkers for TEX.
  
  
  RESULTS
  Binary exposures with chloroform resulted in no significant interactions. Experimental data for quaternary mixture exposures were well predicted by PBPK models using published description of competitive inhibition among TEX components. However, no significant interactions were observed at levels used in this study.
  
  
  CONCLUSIONS
  PBPK models for urinary biomarkers proved to be a good tool in quantifying exposure to VOC.
authors.affiliation: a Department of Environmental and Occupational Health , ESPUM, IRSPUM, Université de Montréal , Montreal , QC , Canada .|b Chair of Toxicological Risk Assessment and Management, Université de Montréal , Montreal , QC , Canada , and.
authors.forename: Axelle
authors.initials: A
authors.lastname: Marchand
authors.affiliation: c Exposure and Biomonitoring Division, Environmental Health Sciences and Research Bureau, Health Canada , Ottawa , ON , Canada.
authors.forename: Rocio
authors.initials: R
authors.lastname: Aranda-Rodriguez
authors.affiliation: a Department of Environmental and Occupational Health , ESPUM, IRSPUM, Université de Montréal , Montreal , QC , Canada .
authors.forename: Robert
authors.initials: R
authors.lastname: Tardif
authors.affiliation: c Exposure and Biomonitoring Division, Environmental Health Sciences and Research Bureau, Health Canada , Ottawa , ON , Canada.
authors.forename: Andy
authors.initials: A
authors.lastname: Nong
authors.affiliation: a Department of Environmental and Occupational Health , ESPUM, IRSPUM, Université de Montréal , Montreal , QC , Canada .|b Chair of Toxicological Risk Assessment and Management, Université de Montréal , Montreal , QC , Canada , and.
authors.forename: Sami
authors.initials: S
authors.lastname: Haddad
mesh_terms: D000293:Adolescent; D000328:Adult; D001555:Benzene Derivatives / Q000493:pharmacokinetics / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002725:Chloroform / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine*; D003198:Computer Simulation; D003408:Cresols / Q000652:urine; D004784:Environmental Monitoring / Q000379:methods*; D006626:Hippurates / Q000652:urine; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008333:Mandelic Acids / Q000652:urine; D008954:Models, Biological; D011237:Predictive Value of Tests; D014050:Toluene / Q000493:pharmacokinetics / Q000652:urine; D016482:Urinalysis; D055549:Volatile Organic Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine*; D014992:Xylenes / Q000493:pharmacokinetics / Q000652:urine; D055815:Young Adult
chemical_list: D001555:Benzene Derivatives; D015415:Biomarkers; D003408:Cresols; D006626:Hippurates; D008333:Mandelic Acids; D055549:Volatile Organic Compounds; D014992:Xylenes; C031421:3-methylhippuric acid; D014050:Toluene; D002725:Chloroform; C004912:ethylbenzene; C037938:mandelic acid; C031285:3-xylene; C034047:2-cresol
keywords: PBPK modeling; VOC; mixtures; urinary biomarkers