Hyeong-Moo Shin

Environmental Fate and Transport Modeling for Perfluorooctanoic Acid Emitted from the Washington Works Facility in West Virginia

Perfluorooctanoic acid (PFOA) has been detected in environmental samples in Ohio and West Virginia near the Washington Works Plant in Parkersburg, West Virginia. This paper describes retrospective fate and transport modeling of PFOA concentrations in local air, surface water, groundwater, and six municipal water systems based on estimates of historic emission rates from the facility, physicochemical properties of PFOA, and local geologic and meteorological data beginning in 1951. We linked several environmental fate and transport modeling systems to model PFOA air dispersion, transit through the vadose zone, surface water transport, and groundwater flow and transport. These include AERMOD, PRZM-3, BreZo, MODFLOW, and MT3DMS. Several thousand PFOA measurements in municipal well water have been collected in this region since 1998. Our linked modeling system performs better than expected, predicting water concentrations within a factor of 2.1 of the average observed water concentration for each of the six municipal water districts after adjusting the organic carbon partition coefficient to fit the observed data. After model calibration, the Spearmans rank correlation coefficient for predicted versus observed water concentrations is 0.87. These models may be useful for estimating past and future public well water PFOA concentrations in this region.

Perfluorooctanoic Acid Exposure and Cancer Outcomes in a Contaminated Community: A Geographic Analysis

Background: Perfluorooctanoic acid (PFOA) has been linked to cancer in occupational mortality studies and animal toxicologic research. Objective: We investigated the relationship between PFOA exposure and cancer among residents living near the DuPont Teflon-manufacturing plant in Parkersburg, West Virginia (WV). Methods: Our analyses included incident cases of 18 cancers diagnosed from 1996 through 2005 in five Ohio (OH) counties and eight WV counties. For analyses of each cancer outcome, controls comprised all other cancers in the study data set except kidney, pancreatic, testicular, and liver cancers, which have been associated with PFOA in animal or human studies. We applied logistic regression models to individual-level data to calculate adjusted odds ratios (AORs) and confidence intervals (CIs). For the combined analysis of OH and WV data, the exposure of interest was resident water district. Within OH, geocoded addresses were integrated with a PFOA exposure model to examine the relationship between cancer odds and categories of estimated PFOA serum. Results: Our final data set included 7,869 OH cases and 17,238 WV cases. There was a positive association between kidney cancer and the very high and high serum exposure categories [AOR = 2.0 (95% CI: 1.0, 3.9) n = 9 and 2.0 (95% CI: 1.3, 3.2) n = 22, respectively] and a null association with the other exposure categories compared with the unexposed. The largest AOR was for testicular cancer with the very high exposure category [2.8 (95% CI: 0.8, 9.2) n = 6], but there was an inverse association with the lower exposure groups, and all estimates were imprecise because of small case numbers. Conclusions: Our results suggest that higher PFOA serum levels may be associated with testicular, kidney, prostate, and ovarian cancers and non-Hodgkin lymphoma. Strengths of this study include near-complete case ascertainment for state residents and well-characterized contrasts in predicted PFOA serum levels from six contaminated water supplies.

Perfluorooctanoic Acid Exposure and Pregnancy Outcome in a Highly Exposed Community

Background: We assessed the association between perfluorooctanoic acid (PFOA) and pregnancy outcome in an area with elevated exposure to PFOA from drinking water contaminated by chemical plant releases. Methods: Serum PFOA was measured, and reproductive and residential histories were obtained during 2005–2006. We estimated serum PFOA levels at the time of pregnancy for 11,737 pregnancies occurring between 1990 and 2006, based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We assessed the association between PFOA and the odds of miscarriage, stillbirth, preeclampsia, preterm birth, term low birthweight, and birth defects, controlling for calendar time, age, parity, education, and smoking. PFOA exposure was evaluated as a continuous measure (with and without log transformation) and in quintiles, combining the lowest 2 quintiles (<6.8 ng/mL) as the referent. Results: Measures of association between PFOA and miscarriage, preterm birth, term low birthweight, and birth defects were close to the null. Odds of stillbirth were elevated in the fourth quintile only. For preeclampsia, the odds ratio was 1.13 (95% confidence interval = 1.00–1.28) for an interquartile shift in log-transformed PFOA, and the odds ratios were 1.1–1.2 across the upper 3 quintiles of exposure. Conclusions: In this large, population-based study in a region with markedly elevated PFOA exposure, we found no associations between estimated serum PFOA levels and adverse pregnancy outcomes other than possibly preeclampsia. Conclusions are tempered by inherent limitations in exposure reconstruction and self-reported pregnancy outcome information.

Retrospective exposure estimation and predicted versus observed serum perfluorooctanoic acid concentrations for participants in the C8 Health Project.

Background: People living or working in eastern Ohio and western West Virginia have been exposed to perfluorooctanoic acid (PFOA) released by DuPont Washington Works facilities. Objectives: Our objective was to estimate historical PFOA exposures and serum concentrations experienced by 45,276 non-occupationally exposed participants in the C8 Health Project who consented to share their residential histories and a 2005–2006 serum PFOA measurement. Methods: We estimated annual PFOA exposure rates for each individual based on predicted calibrated water concentrations and predicted air concentrations using an environmental fate and transport model, individual residential histories, and maps of public water supply networks. We coupled individual exposure estimates with a one-compartment absorption, distribution, metabolism, and excretion (ADME) model to estimate time-dependent serum concentrations. Results: For all participants (n = 45,276), predicted and observed median serum concentrations in 2005–2006 are 14.2 and 24.3 ppb, respectively [Spearman’s rank correlation coefficient (rs) = 0.67]. For participants who provided daily public well water consumption rate and who had the same residence and workplace in one of six municipal water districts for 5 years before the serum sample (n = 1,074), predicted and observed median serum concentrations in 2005–2006 are 32.2 and 40.0 ppb, respectively (rs = 0.82). Conclusions: Serum PFOA concentrations predicted by linked exposure and ADME models correlated well with observed 2005–2006 human serum concentrations for C8 Health Project participants. These individualized retrospective exposure and serum estimates are being used in a variety of epidemiologic studies being conducted in this region.

Breastfeeding: a potential excretion route for mothers and implications for infant exposure to perfluoroalkyl acids.

Background: The presence of perfluoroalkyl acids (PFAAs) in breast milk has been documented, but their lactational transfer has been rarely studied. Determination of the elimination rates of these chemicals during breastfeeding is important and critical for assessing exposure in mothers and infants. Objectives: We aimed to investigate the association between breastfeeding and maternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). For a subset of the population, for whom we also have their infants’ measurements, we investigated associations of breastfeeding with infant serum PFAA concentrations. Methods: The present analysis included 633 women from the C8 Science Panel Study who had a child < 3.5 years of age and who provided blood samples and reported detailed information on breastfeeding at the time of survey. PFAA serum concentrations were available for all mothers and 8% (n = 49) of the infants. Maternal and infant serum concentrations were regressed on duration of breastfeeding. Results: Each month of breastfeeding was associated with lower maternal serum concentrations of PFOA (–3%; 95% CI: –5, –2%), PFOS (–3%; 95% CI: –3, –2%), PFNA (–2%; 95% CI: –2, –1%), and PFHxS (–1%; 95% CI: –2, 0%). The infant PFOA and PFOS serum concentrations were 6% (95% CI: 1, 10%) and 4% (95% CI: 1, 7%) higher per month of breastfeeding. Conclusions: Breast milk is the optimal food for infants, but is also a PFAA excretion route for lactating mothers and exposure route for nursing infants. Citation: Mondal D, Weldon RH, Armstrong BG, Gibson LJ, Lopez-Espinosa MJ, Shin HM, Fletcher T. 2014. Breastfeeding: a potential excretion route for mothers and implications for infant exposure to perfluoroalkyl acids. Environ Health Perspect 122:187–192; http://dx.doi.org/10.1289/ehp.1306613

Relationship of perfluorooctanoic acid exposure to pregnancy outcome based on birth records in the mid-Ohio Valley.

Background: Perfluorooctanoic acid (PFOA) is a potential cause of adverse pregnancy outcomes, but previous studies have been limited by low exposures and small study size. Objectives: Using birth certificate information, we examined the relation between estimated PFOA exposure and birth outcomes in an area of West Virginia and Ohio whose drinking water was contaminated by a chemical plant. Methods: Births in the study area from 1990 through 2004 were examined to generate case groups of stillbirth (n = 106), pregnancy-induced hypertension (n = 224), preterm birth (n = 3,613), term low birth weight (n = 918), term small-for-gestational-age (SGA) (n = 353), and a continuous measure of birth weight among a sample of term births (n = 4,534). A 10% sample of term births ≥ 2,500 g were selected as a source of controls (n = 3,616). Historical estimates of serum PFOA were derived from a previously developed fate and transport model. In a second study, we examined 4,547 area births linked to a survey with residential history data. Results: In the analysis based only on birth records, we found no consistent evidence of an association between estimated PFOA exposure and stillbirth, pregnancy-induced hypertension, preterm birth, or indices of fetal growth. In the analysis of birth records linked to the survey, PFOA was unrelated to pregnancy-induced hypertension or preterm birth but showed some suggestion of an association with early preterm birth. Measures of growth restriction showed weak and inconsistent associations with PFOA. Conclusions: Based on the analysis using the health survey, these results provide little support for an effect of PFOA exposure on most pregnancy outcomes, except for early preterm birth and possibly fetal growth restriction.

Exposure to Perfluoroalkyl Acids and Markers of Kidney Function among Children and Adolescents Living near a Chemical Plant

Background: Serum levels of perfluorooctanoic acid (PFOA) have been associated with decreased renal function in cross-sectional analyses, but the direction of the association is unclear. Objectives: We examined the association of measured and model-predicted serum PFOA concentrations with estimated glomerular filtration rate (eGFR), a marker of kidney function, in a highly exposed population (median serum PFOA, 28.3 ng/mL). Methods: We measured serum creatinine, PFOA, perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) and calculated eGFR in 9,660 children 1 to < 18 years of age at study enrollment. We predicted concurrent and historical serum PFOA concentrations using a validated environmental, exposure, and pharmacokinetic model based on individual residential histories, and used linear regression to estimate the association between eGFR and measured and predicted serum PFOA concentrations. We hypothesized that predicted serum PFOA levels would be less susceptible to reverse causation than measured levels. Results: An interquartile range increase in measured serum PFOA concentrations [IQR ln(PFOA) = 1.63] was associated with a decrease in eGFR of 0.75 mL/min/1.73 m2 (95% CI: –1.41, –0.10; p = 0.02). Measured serum levels of PFOS, PFNA, and PFHxS were also cross-sectionally associated with decreased eGFR. In contrast, predicted serum PFOA concentrations at the time of enrollment were not associated with eGFR (–0.10; 95% CI: –0.80, 0.60; p = 0.78). Additionally, predicted serum PFOA levels at birth and during the first ten years of life were not related to eGFR. Conclusions: Our findings suggest that the cross-sectional association between eGFR and serum PFOA observed in this and prior studies may be a consequence of, rather than a cause of, decreased kidney function.

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.

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.

Indoor inhalation intake fractions of fine particulate matter: review of influencing factors

Exposure to fine particulate matter (PM2.5 ) is a major contributor to the global human disease burden. The indoor environment is of particular importance when considering the health effects associated with PM2.5 exposures because people spend the majority of their time indoors and PM2.5 exposures per unit mass emitted indoors are two to three orders of magnitude larger than exposures to outdoor emissions. Variability in indoor PM2.5 intake fraction (iFin,total ), which is defined as the integrated cumulative intake of PM2.5 per unit of emission, is driven by a combination of building-specific, human-specific, and pollutant-specific factors. Due to a limited availability of data characterizing these factors, however, indoor emissions and intake of PM2.5 are not commonly considered when evaluating the environmental performance of product life cycles. With the aim of addressing this barrier, a literature review was conducted and data characterizing factors influencing iFin,total were compiled. In addition to providing data for the calculation of iFin,total in various indoor environments and for a range of geographic regions, this paper discusses remaining limitations to the incorporation of PM2.5 -derived health impacts into life cycle assessments and makes recommendations regarding future research.