title: Adjustment factors for toluene, styrene and methyl chloride by population modeling of toxicokinetic variability.
abstract: 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.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: anna-karin.mork@ki.se.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Mörk
authors.affiliation: Pharsight, a Certara™ Company, St. Louis, MO, USA.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Jonsson
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Johanson
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008737:Methyl Chloride / Q000633:toxicity*; D009010:Monte Carlo Method; D016273:Occupational Exposure / Q000032:analysis; D018570:Risk Assessment; D012997:Solvents / Q000633:toxicity; D020058:Styrene / Q000633:toxicity*; D014050:Toluene / Q000633:toxicity*; D066007:Toxicokinetics; D014691:Ventilation; D017132:Workplace
chemical_list: D012997:Solvents; D014050:Toluene; D020058:Styrene; D008737:Methyl Chloride
keywords: Assessment factor; Chloromethane; Monte Carlo simulation; Organic solvent; PBPK model; PBTK model; Risk assessment; Safety factor; Uncertainty factor