Intake Fraction for the Indoor Environment: A Tool for Prioritizing Indoor Chemical Sources

Reliable exposure-based chemical characterization tools are needed to evaluate and prioritize in a rapid and efficient manner the more than tens of thousands of chemicals in current use. This study applies intake fraction (iF), the integrated incremental intake of a chemical per unit of emission, for a suite of indoor released compounds. A fugacity-based indoor mass-balance model was used to simulate the fate and transport of chemicals for three release scenarios: direct emissions to room air and surface applications to carpet and vinyl. Exposure through inhalation, dermal uptake, and nondietary ingestion was estimated. To compute iF, cumulative intake was summed from all exposure pathways for 20 years based on a scenario with two adults and a 1-year-old child who ages through the simulation. Overall iFs vary by application modes: air release (3.1 × 10^–3 to 6.3 × 10^–3), carpet application (3.8 × 10^–5 to 6.2 × 10^–3), and vinyl application (9.0 × 10^–5 to 1.8 × 10^–2). These iF values serve as initial estimates that offer important insights on variations among chemicals and the potential relative contribution of each pathway over a suite of compounds. The approach from this study is intended for exposure-based prioritization of chemicals released inside homes

Tracking Contributions to Human Body Burden of Environmental Chemicals by Correlating Environmental Measurements with Biomarkers

<div><p>The work addresses current knowledge gaps regarding causes for correlations between environmental and biomarker measurements and explores the underappreciated role of variability in disaggregating exposure attributes that contribute to biomarker levels. Our simulation-based study considers variability in environmental and food measurements, the relative contribution of various exposure sources (indoors and food), and the biological half-life of a compound, on the resulting correlations between biomarker and environmental measurements. For two hypothetical compounds whose half-lives are on the order of days for one and years for the other, we generate synthetic daily environmental concentrations and food exposures with different day-to-day and population variability as well as different amounts of home- and food-based exposure. Assuming that the total intake results only from home-based exposure and food ingestion, we estimate time-dependent biomarker concentrations using a one-compartment pharmacokinetic model. Box plots of modeled R² values indicate that although the R² correlation between wipe and biological (e.g., serum) measurements is within the same range for the two compounds, the relative contribution of the home exposure to the total exposure could differ by up to 20%, thus providing the relative indication of their contribution to body burden. The novel method introduced in this paper provides insights for evaluating scenarios or experiments where sample, exposure, and compound variability must be weighed in order to interpret associations between exposure data.</p></div

R² with different day-to-day variability of wipe concentrations for two compounds with 3 days of half-life (filled) and 2.3 years of half-life (empty).

<p>R² with different day-to-day variability of wipe concentrations for two compounds with 3 days of half-life (filled) and 2.3 years of half-life (empty).</p

R² between wipe and serum concentrations with different contribution of home exposure for two compounds with 3 days of half-life (filled) and 2.3 years of half-life (empty).

<p>R² between wipe and serum concentrations with different contribution of home exposure for two compounds with 3 days of half-life (filled) and 2.3 years of half-life (empty).</p

Mean R² at a specific variability for four types of variability (coefficient of variation (CV) or standard deviation (σ)) for two compounds with different half-lives (t_1/2).

<p>Mean R² at a specific variability for four types of variability (coefficient of variation (CV) or standard deviation (σ)) for two compounds with different half-lives (t_1/2).</p

Contribution of home exposure (%) to total exposure with different R² for two compounds with 3 days of half-life (filled) and 2.3 years of half-life (empty).

<p>Contribution of home exposure (%) to total exposure with different R² for two compounds with 3 days of half-life (filled) and 2.3 years of half-life (empty).</p

Biomarker-Based Calibration of Retrospective Exposure Predictions of Perfluoro­octanoic Acid

Estimated historical exposures and serum concentrations of per­fluoro­octanoic acid (PFOA) have been extensively used in epidemio­logic studies that examined associations between PFOA exposures and adverse health outcomes among residents in highly exposed areas in the Mid-Ohio Valley. Using measured serum PFOA levels in 2005–2006, we applied two calibration methods to these retrospective exposure predictions: (1) multiplicative calibration and (2) Bayesian pharma­co­kinetic calibration with larger adjustments to more recent exposure estimates and smaller adjustments to exposure estimates for years farther in the past. We conducted simulation studies of various hypothetical exposure scenarios and compared hypothetical true historical intake rates with estimates based on mis-specified baseline exposure and pharma­co­kinetic models to find the method with the least bias. The Bayesian method outperformed the multiplicative method if a change to bottled water consumption was not reported or if the half-life of PFOA was mis-specified. On the other hand, the multiplicative method outperformed the Bayesian method if actual tap water consumption rates were systematically overestimated. If tap water consumption rates gradually decreased over time because of substitution with bottled water or other liquids, neither method clearly outperformed another. Calibration of retrospective exposure estimates using recently collected biomarkers may help reduce uncertainties in environmental epidemiologic studies

Indoor Residence Times of Semivolatile Organic Compounds: Model Estimation and Field Evaluation

Indoor residence times of semivolatile organic compounds (SVOCs) are a major and mostly unavailable input for residential exposure assessment. We calculated residence times for a suite of SVOCs using a fugacity model applied to residential environments. Residence times depend on both the mass distribution of the compound between the “mobile phase” (air and dust particles settled on the carpet) and the “non-mobile phase” (carpet fibers and pad) and the removal rates resulting from air exchange and cleaning. We estimated dust removal rates from cleaning processes using an indoor-particle mass-balance model. Chemical properties determine both the mass distribution and relative importance of the two removal pathways, resulting in different residence times among compounds. We conducted a field study after chlorpyrifos was phased out for indoor use in the United States in 2001 to determine the decreases in chlorpyrifos air concentrations over a one-year period. A measured average decrease of 18% in chlorpyrifos air concentrations indicates the residence time of chlorpyrifos is expected to be 6.9 years and compares well with model predictions. The estimates from this study provide the opportunity to make more reliable estimates of SVOCs exposure in the indoor residential environment

Risk-Based High-Throughput Chemical Screening and Prioritization using Exposure Models and in Vitro Bioactivity Assays

We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify relevant use scenarios (e.g., dermal application, indoor emissions). For each chemical and use scenario, exposure models are then used to calculate a chemical intake fraction, or a product intake fraction, accounting for chemical properties and the exposed population. We then combine these intake fractions with use scenario-specific estimates of chemical quantity to calculate daily intake rates (iR; mg/kg/day). These intake rates are compared to oral equivalent doses (OED; mg/kg/day), calculated from a suite of ToxCast in vitro bioactivity assays using in vitro-to-in vivo extrapolation and reverse dosimetry. Bioactivity quotients (BQs) are calculated as iR/OED to obtain estimates of potential impact associated with each relevant use scenario. Of the 180 chemicals considered, 38 had maximum iRs exceeding minimum OEDs (i.e., BQs > 1). For most of these compounds, exposures are associated with direct intake, food/oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models

Risk-Based High-Throughput Chemical Screening and Prioritization using Exposure Models and in Vitro Bioactivity Assays

We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify relevant use scenarios (e.g., dermal application, indoor emissions). For each chemical and use scenario, exposure models are then used to calculate a chemical intake fraction, or a product intake fraction, accounting for chemical properties and the exposed population. We then combine these intake fractions with use scenario-specific estimates of chemical quantity to calculate daily intake rates (iR; mg/kg/day). These intake rates are compared to oral equivalent doses (OED; mg/kg/day), calculated from a suite of ToxCast in vitro bioactivity assays using in vitro-to-in vivo extrapolation and reverse dosimetry. Bioactivity quotients (BQs) are calculated as iR/OED to obtain estimates of potential impact associated with each relevant use scenario. Of the 180 chemicals considered, 38 had maximum iRs exceeding minimum OEDs (i.e., BQs > 1). For most of these compounds, exposures are associated with direct intake, food/oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models