Options for incorporating children’s inhaled dose into human health risk assessment

Abstract

Increasing attention has been placed on inhalation dosimetry in children because of children's greater air intake rate and unique windows of vulnerability for various toxicants and health outcomes. However, risk assessments have not incorporated this information because dosimetric adjustments have focused upon extrapolation across species rather than across age groups within the human population. The objectives of this study were to synthesize information regarding child/adult intake and dosimetry differences for particles and gases for potential application to risk assessment. Data and models gathered at a 2006 workshop and more recent studies were reviewed to better understand lung development and inhaled dose in children. The results show that child/adult differences exist both on a chemical intake basis and on a deposited or systemic dose basis. These differences can persist for several years and are not captured by standard intraspecies uncertainty factors or by USEPA's reference concentration (RfC) methodology. Options for incorporating children's inhalation exposures into human risk assessments include (1) 3-fold default air intake adjustment for the first 3 years of life with a reduced factor for older children; (2) superseding this default via simplified dosimetry models akin to USEPA's RfC methodology modified for children; (3) utilizing more sophisticated models with better anatomical and air flow descriptions; (4) running these models with input distributions to reflect interchild variability; (5) developing more advanced approaches involving imaging techniques and computational fluid dynamic (CFD) models. These options will enable children's inhaled dose to have a quantitative role in risk assessment that has been lacking and will establish a basis for ongoing research.

EPHECT III: Health risk assessment of exposure to household consumer products

“…In addition, an AF of 5 for intra-species variability was applied, as proposed by Nielsen et al (2007) for the variation in thresholds of sensory irritation within the human population. Taking into account that no experimental data on sensory irritation support an additional AF for sensitive population groups (Dourson et al, 2010;Ginsberg et al, 2010), the resulting short-term CEL was 45 mg/m 3 (8 ppm).…”

“…Following continuous exposure of 54 volunteers to acrolein vapour for 40 min, during which acrolein concentration gradually increased from 0 to 0.6 ppm during the first 35 min and then remained constant, subjective eye irritation was considered the first adverse effect, reported at 0.09 ppm (0.21 mg/m 3 ). Considering that no experimental data support the use of an AF for the protection of susceptible population groups from sensory irritation (Dourson et al, 2010;Ginsberg et al, 2010), an intra-species AF of 5 was applied to the NOAEL value of 0.09 ppm (0.21 mg/m 3 ), as suggested for the variation in thresholds of sensory irritation within the human population (Nielsen et al, 2007) and obtained from the standard deviation of nasal pungency thresholds by assuming a log-normal distribution of the thresholds in the general population (Hau et al, 2000). Further, an AF of 2 for the LOAEL-to-NOAEL extrapolation was applied, as suggested by Nielsen et al (2007) for sensory irritation and supported by Alexeeff et al (2002), leading to the derivation of a short-term CEL for acrolein exposure of 9 ppb (21 μg/m 3 ).…”

“…An intra-species AF of 5 was applied, as suggested for the variation in thresholds of sensory irritation within the human population, in order to protect the general population (Nielsen et al, 2007) and obtained from the standard deviation of nasal pungency thresholds by assuming a log-normal distribution (Hau et al, 2000). As no experimental data on sensory irritation support an additional AF for sensitive sub-groups (Dourson et al, 2010;Ginsberg et al, 2010), the resulting CEL for acute exposure to D-limonene was 90 mg/m 3 (16 ppm). Regarding long-term effects of D-limonene exposure, HRA was based on extrapolation from short-term data due to the absence of adequate long-term toxicological data.…”

Enhancement of ICRP's Lung Deposition Model for Pathogenic Bioaerosols

“…The surface areas of the extrathoracic, tracheobronchial, and alveolar regions for 176 cm adults are 160, 2363, and 777417 cm 2 , respectively, while for 60-cm infants they are 40, 1570, 37704 cm 2 , respectively (Ginsberg et al 2005(Ginsberg et al , 2010. Again, as in Figure 3c, the upper bounds of NRDA i are plotted for three different bioaerosols in Figure 3d.…”

“…Given the significantly lower breathing flow rates in infants, the normalized dose ET, TB, Al, and TD are lower for all bioaerosols. However, infants and children have significantly smaller lung and lung area compared to adults (ICRP 1994;Ginsberg et al 2005Ginsberg et al , 2008Ginsberg et al , 2010. Thus to compare the lung loading among infants and adults, the numerator and denominator of Equation (22) are divided with the respective lung surface areas (A i ) to get the normalized relative dose per unit area (NRDA) at section i:…”