Estimated Soil Ingestion Rates for Use in Risk Assessment

Assessing the risks to human health posed by contaminants present in soil requires an estimate of likely soil ingestion rates. In the past, direct measurements of soil ingestion were not available and risk assessors were forced to estimate soil ingestion rates based on observations of mouthing behavior and measurements of soil on hands. Recently, empirical data on soil ingestion rates have become available from two sources (Binder et al., 1986 and van Wijnen et al., 1986). Although preliminary, these data can be used to derive better estimates of soil ingestion rates for use in risk assessments. Estimates of average soil ingestion rates derived in this paper range from 25 to 100 mg/day, depending on the age of the individual at risk. Maximum soil ingestion rates that are unlikely to underestimate exposure range from 100 to 500 mg. A value of 5,000 mg/day is considered a reasonable estimate of a maximum single-day exposure for a child with habitual pica.     

Daily Soil Ingestion Estimates for Children at a Superfund Site

Ingestion of contaminated soil by children may result in significant exposure to toxic substances at contaminated sites. Estimates of such exposure are based on extrapolation of short-term-exposure estimates to longer time periods. This article provides daily estimates of soil ingestion on 64 children between the ages of 1 and 4 residing at a Superfund site; these values are employed to estimate the distribution of 7-day average soil ingestion exposures (mean, 31 mg/day; median, 17 mg/day) at a contaminated site over different time periods. Best linear unbiased predictors of the 95th-percentile of soil ingestion over 7 days, 30 days, 90 days, and 365 days are 133 mg/day, 112 mg/day, 108 mg/day and 106 mg/day, respectively. Variance components estimates (excluding titanium and outliers, based on Tukey's far-out criteria) are given for soil ingestion between subjects (59 mg/day)2, between days on a subject (95 mg/day)2, and for uncertainty on a subject-day (132 mg/day)2. These results expand knowledge of potential exposure to contaminants among young children from soil ingestion at contaminated sites. They also provide basic distributions that serve as a starting point for use in Monte Carlo risk assessments.     

Bioaccessibility of Fukushima‐Accident‐Derived Cs in Soils and the Contribution of Soil Ingestion to Radiation Doses in Children

Ingestion of contaminated soil is one potential internal exposure pathway in areas contaminated by the Fukushima Daiichi Nuclear Power Plant accident. Doses from this pathway can be overestimated if the availability of radioactive nuclides in soils for the gastrointestinal tract is not considered. The concept of bioaccessibility has been adopted to evaluate this availability based on in vitro tests. This study evaluated the bioaccessibility of radioactive cesium from soils via the physiologically‐based extraction test (PBET) and the extractability of those via an extraction test with 1 mol/L of hydrochloric acid (HCl). The bioaccessibility obtained in the PBET was 5.3% ± 1%, and the extractability in the tests with HCl was 16% ± 3%. The bioaccessibility was strongly correlated with the extractability. This result indicates the possibility that the extractability in HCl can be used as a good predictor of the bioaccessibility with PBET. In addition, we assessed the doses to children from the ingestion of soil via hand‐to‐mouth activity based on our PBET results using a probabilistic approach considering the spatial distribution of radioactive cesium in Date City in Fukushima Prefecture and the interindividual differences in the surveyed amounts of soil ingestion in Japan. The results of this assessment indicate that even if children were to routinely ingest a large amount of soil with relatively high contamination, the radiation doses from this pathway are negligible compared with doses from external exposure owing to deposited radionuclides in Fukushima Prefecture.     

A Meta-Analysis of Children's Hand-to-Mouth Frequency Data for Estimating Nondietary Ingestion Exposure

Because of their mouthing behaviors, children have a higher potential for exposure to available chemicals through the nondietary ingestion route; thus, frequency of hand-to-mouth activity is an important variable for exposure assessments. Such data are limited and difficult to collect. Few published studies report such information, and the studies that have been conducted used different data collection approaches (e.g., videography versus real-time observation), data analysis and reporting methods, ages of children, locations, and even definitions of "mouthing." For this article, hand-to-mouth frequency data were gathered from 9 available studies representing 429 subjects and more than 2,000 hours of behavior observation. A meta-analysis was conducted to study differences in hand-to-mouth frequency based on study, age group, gender, and location (indoor vs. outdoor), to fit variability and uncertainty distributions that can be used in probabilistic exposure assessments, and to identify any data gaps. Results of this analysis indicate that age and location are important for hand-to-mouth frequency, but study and gender are not. As age increases, both indoor and outdoor hand-to-mouth frequencies decrease. Hand-to-mouth behavior is significantly greater indoors than outdoors. For both indoor and outdoor hand-to-mouth frequencies, interpersonal, and intra-personal variability are approximately 60% and approximately 30%, respectively. The variance difference among different studies is much bigger than its mean, indicating that different studies with different methodologies have similar central values. Weibull distributions best fit the observed data for the different variables considered and are presented in this article by study, age group, and location. Average indoor hand-to-mouth behavior ranged from 6.7 to 28.0 contacts/hour, with the lowest value corresponding to the 6 to <11 year olds and the highest value corresponding to the 3 to <6 month olds. Average outdoor hand-to-mouth frequency ranged from 2.9 to 14.5 contacts/hour, with the lowest value corresponding to the 6 to <11 year olds and the highest value corresponding to the 6 to <12 month olds. The analysis highlights the need for additional hand-to-mouth data for the <3 months, 3 to <6 months, and 3 to <6 year age groups using standardized collection and analysis because of lack of data or high uncertainty in available data. This is the first publication to report Weibull distributions as the best fitting distribution for hand-to-mouth frequency; using the best fitting exposure factor distribution will help improve estimates of exposure. The analyses also represent a first comprehensive effort to fit hand-to-mouth frequency variability and uncertainty distributions by indoor/outdoor location and by age groups, using the new standard set of age groups recommended by the U.S. Environmental Protection Agency for assessing childhood exposures. Thus, the data presented in this article can be used to update the U.S. EPA's Child-Specific Exposure Factors Handbook and to improve estimates of nondietary ingestion in probabilistic exposure modeling.     

Children''s Exposure to Arsenic from CCA-Treated Wooden Decks and Playground Structures

CCA-treated wood is widely used in the fabrication of outdoor decks and playground equipment. Because arsenic can be removed from the surface of CCA-treated wood both by physical contact and by leaching, it is important to determine whether children who play on such structures may ingest arsenic in quantities sufficient to be of public health concern. Based on a review of existing studies, it is estimated that arsenic doses in amounts of tens of micrograms per day may be incurred by children having realistic levels of exposure to CCA-treated decks and playground structures. The most important exposure pathway appears to be oral ingestion of arsenic that is first dislodged from the wood by direct hand contact, then transferred to the mouth by children's hand-to-mouth activity. The next most important pathway appears to be dermal absorption of arsenic, while ingestion of soil that has become contaminated by leaching from CCA-treated structures appears to be of lesser importance, except possibly in the case of children with pica. Considerable uncertainty, however, is associated with quantitative estimates of children's arsenic exposure from CCA-treated wood. Priorities for refining estimates of arsenic dose include detailed studies of the hand-to-mouth transfer of arsenic, studies of the dermal and gastrointestinal absorption of dislodgeable arsenic, and studies in which doses of arsenic to children playing in contact with CCA-treated wood are directly determined by measurement of arsenic in their urine, hair, and nails.     

A Probabilistic Arsenic Exposure Assessment for Children Who Contact CCA-Treated Playsets and Decks, Part 1: Model Methodology, Variability Results, and Model Evaluation

Concerns have been raised regarding the safety of young children who may contact arsenic residues while playing on and around chromated copper arsenate (CCA)-treated wood playsets and decks. Although CCA registrants voluntarily canceled the production of treated wood for residential use in 2003, the potential for exposure from existing structures and surrounding soil still poses concerns. The EPA's Office of Research and Development developed and applied the probabilistic Stochastic Human Exposure and Dose Simulation model for wood preservatives (SHEDS-Wood) to estimate children's absorbed dose of arsenic from CCA. Skin contact with, and nondietary ingestion of, arsenic in soil and wood residues were considered for the population of children in the United States who frequently contact CCA-treated wood playsets and decks. Model analyses were conducted to assess the range in population estimates and the impact of potential mitigation strategies such as the use of sealants and hand washing after play events. The results show predicted central values for lifetime annual average daily dose values for arsenic ranging from 10(-6) to 10(-5) mg/kg/day, with predicted 95th percentiles on the order of 10(-5) mg/kg/day. There were several orders of magnitude between lower and upper percentiles. Residue ingestion via hand-to-mouth contact was determined to be the most significant exposure route for most scenarios. Results of several alternative scenarios were similar to baseline results, except for the scenario with greatly reduced residue concentrations through hypothetical wood sealant applications; in this scenario, exposures were lower, and the soil ingestion route dominated. SHEDS-Wood estimates are typically consistent with, or within the range of, other CCA exposure models.     

Effect of Particle Size on Risk Assessment of Direct Soil Ingestion and Metals Adhered to Children's Hands at Playgrounds

The quantity of heavy metals in soil is measured after 2‐mm sieving in Japan for risk assessment of direct soil ingestion. A study was conducted on the relationship between the size of soil particles and quantity of heavy metals in soil, and the particle‐size distribution of soil adhered to children's hands, and the risks of direct intake of soil considering the particle sizes ingested were evaluated. The results showed that smaller particles had a tendency to contain more heavy metals than bigger ones, that the particle size of approximately 90% of the soil particles from playgrounds adhered to children's hands was less than 100 μm, and that 2‐mm sieving in preparation for measuring heavy metal content caused underestimation of the risk of direct soil intake. The amount of heavy metals on children's hands after playing outside was investigated. Various metals and soil were adhered to their hands, and the amount of soil adhered could be estimated from the concentration of metals. To develop accurate risk assessment, the particle‐size distribution of ingested soil and more detailed scenarios of soil intake are necessary.     

Field Measurement of Dermal Soil Loading Attributable to Various Activities: Implications for Exposure Assessment

Estimates of soil adherence to skin are required for assessment of dermal exposures to contaminants in soils. Previously available estimates depend heavily on indirect measurements and/or artificial activities and reflect sampling of hands only. Results are presented here from direct measurement of soil loading on skin surfaces of volunteers before and after normal occupational and recreational activities that might reasonably be expected to lead to soil contact. Skin surfaces assayed included hands, forearms, lower legs, faces and/or feet. Observed hand loadings vary over five orders of magnitude (roughly from 10^–3 to 10² mg/cm²) and are dependent upon type of activity. Hand loadings within the current default range of 0.2 to 1.0 mg/cm² were produced by activities providing opportunity for relatively vigorous soil contact (rugby, farming). Loadings less than 0.2 mg/cm² were found on hands following activities presenting less opportunity for direct soil contact (soccer, professional grounds maintenance) and on other body parts under many conditions. The default range does not, however, represent a worst case. Children playing in mud on the shore of a lake generated geometric mean loadings well in excess of 1 mg/cm² on hands, arms, legs, and feet. Post-activity average loadings on hands were typically higher than average loadings on other body parts resulting from the same activity. Hand data from limited activities cannot, however, be used to conservatively predict loadings that might occur on other body surfaces without regard to activity since non-hand loadings attributable to higher contact activities exceeded hand loadings resulting from lower contact activities. Differences between pre- and post-activity loadings also demonstrate that dermal contact with soil is episodic. Typical background (pre-activity) geometric mean loadings appear to be on the order of 10^-2 mg/cm² or less. Because exposures are activity dependent, quantification of dermal exposure to soil will remain inadequate until data describing relevant human behavior (type of activity, frequency, duration including interval before bathing, clothing worn, etc.) are generated.     

Daily Inhalation Rate and Time‐Activity/Location Pattern in Japanese Preschool Children

Lack of data on daily inhalation rate and activity of children has been an issue in health risk assessment of air pollutants. This study aimed to obtain the daily inhalation rate and intensity and frequency of physical activity in relation to the environment in Japanese preschool children. Children aged four–six years (n= 138) in the suburbs of Tokyo participated in this study, which involved three days' continuous monitoring of physical activity using a tri‐axial accelerometer and parent's completion of a time/location diary during daily life. The estimated three‐day mean daily inhalation rate (body temperature, pressure, saturated with water vapor) was 9.9 ± 1.6 m³/day (0.52 ± 0.09 m³/kg/day). The current daily inhalation rate value of 0.580 m³/kg/day proposed for use in health risk assessment in Japan is confirmed to be valid to calculate central value of inhaled dose of air pollutants in five‐ to six‐year‐old children. However, the 95th percentile daily inhalation rate of 0.83 m³/kg/day based on measurement for five‐year‐old children is recommended to be used to provide an upper bound estimate of exposure that ensure the protection of all five‐ to six‐year‐old children from the health risk of air pollutants. Children spent the majority of their time in sedentary and light level of physical activity (LPA) when indoors, while 85% of their time when outdoors was spent in LPA and moderate‐to‐vigorous physical activity. The results suggest the need to consider variability of minute respiratory ventilation rate according to the environment for more refined short‐term health risk assessment.     

A Probabilistic Arsenic Exposure Assessment for Children Who Contact Chromated Copper Arsenate (CCA)-Treated Playsets and Decks, Part 2: Sensitivity and Uncertainty Analyses

A probabilistic model (SHEDS-Wood) was developed to examine children's exposure and dose to chromated copper arsenate (CCA)-treated wood, as described in Part 1 of this two-part article. This Part 2 article discusses sensitivity and uncertainty analyses conducted to assess the key model inputs and areas of needed research for children's exposure to CCA-treated playsets and decks. The following types of analyses were conducted: (1) sensitivity analyses using a percentile scaling approach and multiple stepwise regression; and (2) uncertainty analyses using the bootstrap and two-stage Monte Carlo techniques. The five most important variables, based on both sensitivity and uncertainty analyses, were: wood surface residue-to-skin transfer efficiency; wood surface residue levels; fraction of hand surface area mouthed per mouthing event; average fraction of nonresidential outdoor time a child plays on/around CCA-treated public playsets; and frequency of hand washing. In general, there was a factor of 8 for the 5th and 95th percentiles and a factor of 4 for the 50th percentile in the uncertainty of predicted population dose estimates due to parameter uncertainty. Data were available for most of the key model inputs identified with sensitivity and uncertainty analyses; however, there were few or no data for some key inputs. To evaluate and improve the accuracy of model results, future measurement studies should obtain longitudinal time-activity diary information on children, spatial and temporal measurements of residue and soil concentrations on or near CCA-treated playsets and decks, and key exposure factors. Future studies should also address other sources of uncertainty in addition to parameter uncertainty, such as scenario and model uncertainty.     

Improving Risk Assessment Calculations for Traditional Foods Through Collaborative Research with First Nations Communities

As industrial development is increasing near northern Canadian communities, human health risk assessments (HHRA) are conducted to assess the predicted magnitude of impacts of chemical emissions on human health. One exposure pathway assessed for First Nations communities is the consumption of traditional plants, such as muskeg tea (Labrador tea) (Ledum/Rhododendron groenlandicum) and mint (Mentha arvensis). These plants are used to make tea and are not typically consumed in their raw form. Traditional practices were used to harvest muskeg tea leaves and mint leaves by two First Nations communities in northern Alberta, Canada. Under the direction of community elders, community youth collected and dried plants to make tea. Soil, plant, and tea decoction samples were analyzed for inorganic elements using inductively coupled plasma‐mass spectrometry. Concentrations of inorganic elements in the tea decoctions were orders of magnitude lower than in the vegetation (e.g., manganese 0.107 mg/L in tea, 753 mg/kg in leaves). For barium, the practice of assessing ingestion of raw vegetation would have resulted in a hazard quotient (HQ) greater than the benchmark of 0.2. Using measured tea concentrations it was determined that exposure would result in risk estimates orders of magnitude below the HQ benchmark of 0.2 (HQ = 0.0049 and 0.017 for muskeg and mint tea, respectively). An HHRA calculating exposure to tea vegetation through direct ingestion of the leaves may overestimate risk. The results emphasize that food preparation methods must be considered when conducting an HHRA. This study illustrates how collaboration between Western scientists and First Nations communities can add greater clarity to risk assessments.     

Urinary Excretion of Chromium Following Ingestion of Chromite-Ore Processing Residues in Humans: Implications for Biomonitoring

Biomonitoring programs for urinary chromium (Cr) typically attempt to evaluate occupational exposure via the inhalation route. This study investigated whether Cr can be detected in the urine of people following the ingestion of soils that contain relatively high concentrations of chromium in chromite ore processing residue (COPR). To evaluate the reasonableness of using urinary monitoring to assess environmental exposure, six volunteers ingested 400 mg of soil/day (low-dose group), two others ingested 2.0 g of soil/day (high-dose group) for 3 consecutive days, and one person ingested a placebo on each of 3 days. The soil and COPR mixture contained concentrations of total chromium (Cr) and hexavalent chromium [Cr(VI)] of 103 ± 20 and 9.3 ± 3.8 mg/kg, respectively. Therefore, the low-dose group ingested 41 μg Cr/day [including 3.7 μg Cr(VI)] and the high-dose group ingested 206 μg Cr/day [including 18.6 μg Cr(VI)] on each of 3 consecutive days. All urine samples were collected and analyzed individually for total Cr on the day prior to dosing, during the 3 days of dosing, and up to the first void 48 h after the last dose. No significant increases in urinary Cr excretion were found when background excretion data were compared with data following each of the 3 days of dosing or in daily mean urine concentrations of the high- vs the low-dose groups. It appears that Cr present in a soil and COPR mixture at Cr doses up to 200 μg/day is not sufficiently bioavailable for biomonitoring of urine to be informative. These results are consistent with previously published findings suggesting that incidental exposure to dusts and soils containing comparable levels of Cr will not result in increased concentrations of Cr in urine.     

The Cancer Risk Associated with Residential Exposure to Soil Containing Radioactive Coal Combustion Residuals

Coal combustion residuals (CCRs) are composed of various constituents, including radioactive materials. The objective of this study was to utilize methodology on radionuclide risk assessment from the Environmental Protection Agency (EPA) to estimate the potential cancer risks associated with residential exposure to CCR‐containing soil. We evaluated potential radionuclide exposure via soil ingestion, inhalation of soil particulates, and external exposure to ionizing radiation using published CCR radioactivity values for ²³²Th, ²²⁸Ra, ²³⁸U, and ²²⁶Ra from the Appalachia, Illinois, and Powder River coal basins. Mean and upper‐bound cancer risks were estimated individually for each radionuclide, exposure pathway, and coal basin. For each radionuclide at each coal basin, external exposure to ionizing radiation contributed the greatest to the overall risk estimate, followed by incidental ingestion of soil and inhalation of soil particulates. The mean cancer risks by route of exposure were 2.01 × 10⁻⁶ (ingestion), 6.80 × 10⁻⁹ (inhalation), and 3.66 × 10⁻⁵ (external), while the upper bound cancer risks were 3.70 × 10⁻⁶ (ingestion), 1.18 × 10⁻⁸ (inhalation), and 6.15 × 10⁻⁵ (external), using summed radionuclide‐specific data from all locations. The upper bound cancer risk from all routes of exposure was 6.52 × 10⁻⁵. These estimated cancer risks were within the EPA's acceptable cancer risk range of 1 × 10⁻⁶ to 1 × 10⁻⁴. If the CCR radioactivity values used in this analysis are generally representative of CCR waste streams, then our findings suggest that CCRs would not be expected to pose a significant radiological risk to residents living in areas where contact with CCR‐containing soils might occur.     

Derivation of a Target Level of Lead in Soil at Residential Sites Corresponding to a De Minimis Contribution to Blood Lead Concentration1

Inability to define either a clear toxicologic threshold or a stochastic all-or-nothing (cancer-type) response model for the noncarcinogenic effects of lead (Pb) in young children has posed difficulties for derivation of risk-based target levels of Pb in residential soil. Approaches based on empirical relationships between Pb levels in blood (PbB) and Pb in soil suffer from inability to specify the numerous variables which mediate between these two quantities. Approaches based on achieving a toxicologically de minimis target PbB level (e.g., 10 μg/dl) are subject to large uncertainty in estimating the distribution of existing PbB levels in a specific exposed population and in estimating the relative contribution from nonsoil sources of Pb. The multisource contribution to the distribution of PbB makes this approach unsuited for determination of a target Pb level in a single medium. An alternative approach is presented based on achieving a de minimis contribution to PbB (ΔPbB) from soil. Contributions to Pb exposure from outdoor soil and indoor soil-derived dust (ISDD) are modeled and appropriate values are suggested for input parameters. This analysis predicts that chronic exposure of young children to 200 μg Pb/g (ppm) in residential soil will result in a ΔPbB of 2 μg Pb/dl blood. This concentration of Pb in soil may provide an appropriate target level for residential soil when other significant sources of Pb exposure are present. In other cases, this approach can be used to predict a soil concentration of Pb corresponding to an appropriate non-de minimisΔPbB.     

Statistical Distributions of Daily Breathing Rates for Narrow Age Groups of Infants and Children

Children may be more susceptible to toxicity from some environmental chemicals than adults. This susceptibility may occur during narrow age periods (windows), which can last from days to years depending on the toxicant. Breathing rates specific to narrow age periods are useful to assess inhalation dose during suspected windows of susceptibility. Because existing breathing rates used in risk assessment are typically for broad age ranges or are based on data not representative of the population, we derived daily breathing rates for narrow age ranges of children designed to be more representative of the current U.S. children's population. These rates were derived using the metabolic conversion method of Layton (1993) and energy intake data adjusted to represent the U.S. population from a relatively recent dietary survey (CSFII 1994–1996, 1998). We calculated conversion factors more specific to children than those previously used. Both nonnormalized (L/day) and normalized (L/kg-day) breathing rates were derived and found comparable to rates derived using energy estimates that are accurate for the individuals sampled but not representative of the population. Estimates of breathing rate variability within a population can be used with stochastic techniques to characterize the range of risk in the population from inhalation exposures. For each age and age-gender group, we present the mean, standard error of the mean, percentiles (50th, 90th, and 95th), geometric mean, standard deviation, 95th percentile, and best-fit parametric models of the breathing rate distributions. The standard errors characterize uncertainty in the parameter estimate, while the percentiles describe the combined interindividual and intra-individual variability of the sampled population. These breathing rates can be used for risk assessment of subchronic and chronic inhalation exposures of narrow age groups of children.     

Aldrin and Dieldrin: A Reevaluation of the Cancer and Noncancer Dose‐Response Assessments

The dose‐response analyses of cancer and noncancer health effects of aldrin and dieldrin were evaluated using current methodology, including benchmark dose analysis and the current U.S. Environmental Protection Agency (U.S. EPA) guidance on body weight scaling and uncertainty factors. A literature review was performed to determine the most appropriate adverse effect endpoints. Using current methodology and information, the estimated reference dose values were 0.0001 and 0.00008 mg/kg‐day for aldrin and dieldrin, respectively. The estimated cancer slope factors for aldrin and dieldrin were 3.4 and 7.0 (mg/kg‐day)^?1, respectively (i.e., about 5‐ and 2.3‐fold lower risk than the 1987 U.S. EPA assessments). Because aldrin and dieldrin are no longer used as pesticides in the United States, they are presumed to be a low priority for additional review by the U.S. EPA. However, because they are persistent and still detected in environmental samples, quantitative risk assessments based on the best available methods are required. Recent epidemiologic studies do not demonstrate a causal association between aldrin and dieldrin and human cancer risk. The proposed reevaluations suggest that these two compounds pose a lower human health risk than currently reported by the U.S. EPA.     

Physiological Daily Inhalation Rates for Health Risk Assessment in Overweight/Obese Children,Adults, and Elderly

Physiological daily inhalation rates reported in our previous study for normal‐weight subjects 2.6–96 years old were compared to inhalation data determined in free‐living overweight/obese individuals (n = 661) aged 5–96 years. Inhalation rates were also calculated in normal‐weight (n = 408), overweight (n = 225), and obese classes 1, 2, and 3 adults (n = 134) aged 20–96 years. These inhalation values were based on published indirect calorimetry measurements (n = 1,069) and disappearance rates of oral doses of water isotopes (i.e., ²H₂O and H₂¹⁸O) monitored by gas isotope ratio mass spectrometry usually in urine samples for an aggregate period of over 16,000 days. Ventilatory equivalents for overweight/obese subjects at rest and during their aggregate daytime activities (28.99 ± 6.03 L to 34.82 ± 8.22 L of air inhaled/L of oxygen consumed; mean ±  SD) were determined and used for calculations of inhalation rates. The interindividual variability factor calculated as the ratio of the highest 99th percentile to the lowest 1st percentile of daily inhalation rates is higher for absolute data expressed in m³/day (26.7) compared to those of data in m³/kg‐day (12.2) and m³/m²‐day (5.9). Higher absolute rates generally found in overweight/obese individuals compared to their normal‐weight counterparts suggest higher intakes of air pollutants (in μg/day) for the former compared to the latter during identical exposure concentrations and conditions. Highest absolute mean (24.57 m³/day) and 99th percentile (55.55 m³/day) values were found in obese class 2 adults. They inhale on average 8.21 m³ more air per day than normal‐weight adults.     

Derivation of Noncancer Reference Values for Acrylonitrile

Dose‐response assessments were conducted for the noncancer effects of acrylonitrile (AN) for the purposes of deriving subchronic and chronic oral reference dose (RfD) and inhalation reference concentration (RfC) values. Based upon an evaluation of available toxicity data, the irritation and neurological effects of AN were determined to be appropriate bases for deriving reference values. A PBPK model, which describes the toxicokinetics of AN and its metabolite 2‐cyanoethylene oxide (CEO) in both rats and humans, was used to assess the dose‐response data in terms of an internal dose measure for the oral RfD values, but could not be used in deriving the inhalation RfC values. Benchmark dose (BMD) methods were used to derive all reference values. Where sufficient information was available, data‐derived uncertainty factors were applied to the points of departure determined by BMD methods. From this assessment, subchronic and chronic oral RfD values of 0.5 and 0.05 mg/kg/day, respectively, were derived. Similarly, subchronic and chronic inhalation RfC values of 0.1 and 0.06 mg/m³, respectively, were derived. Confidence in the reference values derived for AN was considered to be medium to high, based upon a consideration of the confidence in the key studies, the toxicity database, dosimetry, and dose‐response modeling.