Chemical-specific screening criteria for interpretation of biomonitoring data for volatile organic compounds (VOCs) - application of steady-state PBPK model solutions

Aylward, Lesa L., Kirman, Chris R., Blount, Ben C. and Hays, Sean M. (2010) Chemical-specific screening criteria for interpretation of biomonitoring data for volatile organic compounds (VOCs) - application of steady-state PBPK model solutions. Regulatory Toxicology and Pharmacology, 58 1: 33-44. doi:10.1016/j.yrtph.2010.05.011


Author Aylward, Lesa L.
Kirman, Chris R.
Blount, Ben C.
Hays, Sean M.
Title Chemical-specific screening criteria for interpretation of biomonitoring data for volatile organic compounds (VOCs) - application of steady-state PBPK model solutions
Journal name Regulatory Toxicology and Pharmacology   Check publisher's open access policy
ISSN 0273-2300
1096-0295
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1016/j.yrtph.2010.05.011
Open Access Status Not yet assessed
Volume 58
Issue 1
Start page 33
End page 44
Total pages 12
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Abstract The National Health and Nutrition Examination Survey (NHANES) generates population-representative biomonitoring data for many chemicals including volatile organic compounds (VOCs) in blood. However, no health or risk-based screening values are available to evaluate these data from a health safety perspective or to use in prioritizing among chemicals for possible risk management actions. We gathered existing risk assessment-based chronic exposure reference values such as reference doses (RfDs), reference concentrations (RfCs), tolerable daily intakes (TDIs), cancer slope factors, etc. and key pharmacokinetic model parameters for 47 VOCs. Using steady-state solutions to a generic physiologically-based pharmacokinetic (PBPK) model structure, we estimated chemical-specific steady-state venous blood concentrations across chemicals associated with unit oral and inhalation exposure rates and with chronic exposure at the identified exposure reference values. The geometric means of the slopes relating modeled steady-state blood concentrations to steady-state exposure to a unit oral dose or unit inhalation concentration among 38 compounds with available pharmacokinetic parameters were 12.0μg/L per mg/kg-d (geometric standard deviation [GSD] of 3.2) and 3.2μg/L per mg/m3 (GSD=1.7), respectively. Chemical-specific blood concentration screening values based on non-cancer reference values for both oral and inhalation exposure range from 0.0005 to 100μg/L; blood concentrations associated with cancer risk-specific doses at the 1E-05 risk level ranged from 5E-06 to 6E-02μg/L. The distribution of modeled steady-state blood concentrations associated with unit exposure levels across VOCs may provide a basis for estimating blood concentration screening values for VOCs that lack chemical-specific pharmacokinetic data. The screening blood concentrations presented here provide a tool for risk assessment-based evaluation of population biomonitoring data for VOCs and are most appropriately applied to central tendency estimates for such datasets.
Keyword Biomonitoring
Pharmacokinetic models
Risk assessment
Volatile organic compounds
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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