Elevated internal exposure of children in simulated acute inhalation of volatile organic compounds: effects of concentration and duration.
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.
Abraham
Klaus
K
Federal Institute for Risk Assessment, Thielallee 88-92, 14195 Berlin, Germany. k.abraham@bfr.bund.de
Mielke
Hans
H
Huisinga
Wilhelm
W
Gundert-Remy
Ursula
U
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008954:Models, Biological; D009930:Organic Chemicals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020058:Styrene / Q000008:administration & dosage / Q000493:pharmacokinetics; D013997:Time Factors; D014835:Volatilization
D009930:Organic Chemicals; D020058:Styrene