title: Sex differences in urinary levels of several biological indicators of exposure: a human volunteer study.
abstract: The aim of the study was to quantify the variability on biological indicators of exposure between men and women for three well known solvents: methyl ethyl ketone, 1-methoxy-2-propanol and 1,1,1-trichloroethane. Another purpose was to explore the effect of selected CYP2E1 polymorphisms on the toxicokinetic profile. Controlled human exposures were carried out in a 12 m³ exposure chamber for each solvent separately, during 6h and at half of the threshold limit value. The human volunteers groups were composed of ten young men and fifteen young women, including ten women using hormonal contraceptive. An analysis of variance mainly showed an effect on the urinary levels of several biomarkers of exposure among women due to the use of hormonal contraceptive, with an increase of more than 50% in metabolites concentrations and a decrease of up to 50% in unchanged substances concentrations, suggesting an increase in their metabolism rate. The results also showed a difference due to the genotype CYP2E1*6, when exposed to methyl ethyl ketone, with a tendency to increase CYP2E1 activity when volunteers were carriers of the mutant allele. Our study suggests that not only physiological differences between men and women but also differences due to sex hormones levels can have an impact on urinary concentrations of several biomarkers of exposure. The observed variability due to sex among biological exposure indices can lead to misinterpretation of biomonitoring results. This aspect should have its place in the approaches for setting limits of occupational exposure.
authors.affiliation: Institute for Work and Health, University of Lausanne, 1011 Lausanne, Switzerland. catherine.tomicic@hospvd.ch
authors.forename: Catherine
authors.initials: C
authors.lastname: Tomicic
authors.forename: Michèle
authors.initials: M
authors.lastname: Berode
authors.forename: Anne
authors.initials: A
authors.lastname: Oppliger
authors.forename: Vincent
authors.initials: V
authors.lastname: Castella
authors.forename: Fabienne
authors.initials: F
authors.lastname: Leyvraz
authors.forename: Sophie-Maria
authors.initials: SM
authors.lastname: Praz-Christinaz
authors.forename: Brigitta
authors.initials: B
authors.lastname: Danuser
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D002074:Butanones / Q000493:pharmacokinetics* / Q000652:urine; D003278:Contraceptives, Oral, Hormonal / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000145:classification / Q000235:genetics; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009784:Occupational Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011409:Propylene Glycols / Q000493:pharmacokinetics* / Q000652:urine; D012737:Sex Factors; D012997:Solvents / Q000378:metabolism / Q000493:pharmacokinetics*; D011795:Surveys and Questionnaires; D014240:Trichloroethanes / Q000493:pharmacokinetics* / Q000652:urine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002074:Butanones; D003278:Contraceptives, Oral, Hormonal; D011409:Propylene Glycols; D012997:Solvents; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; C005216:propylene glycol methyl ether; C005222:methylethyl ketone; D019392:Cytochrome P-450 CYP2E1