Adjustment factors for toluene, styrene and methyl chloride by population modeling of toxicokinetic variability

作者：Mork Anna Karin^*; Jonsson Fredrik; Johanson Gunnar

来源：Regulatory Toxicology and Pharmacology, 2014, 69(1): 78-90.

DOI：10.1016/j.yrtph.2014.02.015

• Monte Carlo simulation
• PBPK model
• PBTK model
• Chloromethane
• Organic solvent
• Risk assessment
• Assessment factor
• Uncertainty factor
• Safety factor

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 AF(HK) 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.

• 出版日期2014-6