Elevated internal exposure of children in simulated acute inhalation of volatile organic compounds: effects of concentration and duration
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When deriving health-based exposure limits in recent years, increasing attention has been drawn to susceptible subpopulations, in particular to children. We investigated the differences in kinetics between children and adults during inhalation of styrene as a typical category-3 volatile organic compound (VOC), i.e., a gas with a low reactivity and low water solubility allowing a high rate of alveolar absorption. Internal exposure was simulated using a physiologically based kinetic model over a broad range of airborne concentrations (1–1000 ppm) and for an exposure time of up to 8 h according to the scenario in the acute exposure guideline level (AEGL) program. Age-specific anatomical and physiological parameters and compound-specific data was derived from the literature. The calculated concentrations in arterial blood are higher in children than in adults, and are highest in the newborn. For an 8-h exposure to low concentrations, the calculated arterial concentration in the newborn is higher by a factor of 2.3 than in the adult. This is due mainly to the relatively high ventilation rate and the immature metabolism. With increasing airborne concentration, the ratio of arterial concentrations (newborn/adult) increases to a maximum of 3.8 at 130 ppm in ambient air, and declines with further increments of concentration to a value of 1.7. This is because the metabolism of the newborn becomes non-linear at lower concentrations than in adults. At high concentrations, metabolism is saturated in both age groups. For shorter exposures, the dose dependency of the concentration ratios (newborn/adult) is less pronounced. This is the first article to show that the intraspecies assessment factor may vary with concentration and duration of exposure.
KeywordsChildren Inhalation Kinetics Model Risk assessment Styrene
Acknowledgements. This work was supported by European Union (contract no. EVG1-CT-2002-00071) within Fifth Framework Program, and supported by Deutsche Forschungsgemeinschaft (DFG) as a project within DFG Research Center “Mathematics for key technologies”, Berlin, Germany.
- Abraham K, Mielke H, Huisinga W, Gundert-Remy U (2005) Internal exposure of children by acute inhalation of volatile organic compounds: the influence of chemical properties on the child/adult concentration ratio. Basic Clin Pharmacol Toxicol 96: in pressGoogle Scholar
- Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry MR, Rigas ML, Zartarian VG, Freeman NC (2000) Children’s exposure assessment: a review of factors influencing children’s exposure, and the data available to characterize and assess that exposure. Environ Health Perspect 108:475–486Google Scholar
- Fiserova-Bergerova V (1983) Modeling of inhalation exposure to vapors: uptake, distribution, and elimination, vols I and II. CRC Press, Boca Raton, FloridaGoogle Scholar
- Hattis D, Ginsberg G, Sonawane B, Smolenski S, Russ A, Kozlak M, Goble R (2003) Differences in pharmacokinetics between children and adults. II. Children’s variability in drug elimination half-lives and in some parameters needed for physiologically-based pharmacokinetic modeling. Risk Anal 23:117–142CrossRefPubMedGoogle Scholar
- ICRP Publication 89 (2003) Basic anatomical and physiological data for use in radiological protection: reference values. Elsevier, OxfordGoogle Scholar
- US-AEGL committee (2001) Standing operating procedures for developing acute exposure guideline levels for hazardous chemicals. National Academy Press, Washington DCGoogle Scholar
- US-EPA (1994) Methods for derivation of inhalation reference concentrations and application of inhalation dosimetry (doc. no. EPA/600/8-90/066F). Research Triangle Park, North CarolinaGoogle Scholar