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ObjectivesWe conducted serological SARS-CoV-2 antibody testing from October to November 2020 to estimate the SARS-CoV-2 seroprevalence among firefighters/paramedics in Orange County (OC), California.MethodsOC firefighters employed at the time of the surveillance activity were invited to participate in a voluntary survey that collected demographic, occupational and previous COVID-19 testing data, and a SARS-CoV-2 immunoglobulin (Ig)G antibody blood test. We collected venous blood samples using mobile phlebotomy teams that travelled to individual fire stations, in coordination with an annual tuberculosis testing campaign for firefighters employed by OC Fire Authority (OCFA), and independently for firefighters employed by cities. We estimated seroprevalence and assessed several potential predictors of seropositivity.ResultsThe seroprevalence was 5.3% among 923 OCFA personnel tested, with 92.2% participating. Among firefighters self-reporting a previous positive COVID-19 antibody or PCR test result, twenty-one (37%) did not have positive IgG tests in the current serosurvey. There were no statistically significant differences in demographic characteristics between cases and non-cases. Work city was a significant predictor of case status (p=0.015). Seroprevalence (4.8%) was similar when aggregated across seven city fire departments (42%–65% participation). In total, 1486°C fire personnel were tested.ConclusionUsing a strong serosurvey design and large firefighter cohort, we observed a SARS-CoV-2 IgG seroprevalence of 5.3%. The seroprevalence among OC firefighters in October 2020 was lower than the general county population estimated seroprevalence (11.5%) in August. The difference may be due in part to safety measures taken by OC fire departments at the start of the pandemic, as well as differences in antibody test methods and/or duration of antibody response.

The carcinogenicity of perfluorooctanoic acid (PFOA) has been reviewed previously by several different regulatory agencies and researchers, with contradictory conclusions–especially regarding epidemiological findings on kidney cancer and testicular cancer. In addition, previous dose-response assessments have focused primarily on evidence from animal studies. This critical review summarizes peer reviewed epidemiological studies on PFOA and cancers of the kidneys and testes, using modified Hill’s criteria to assess the evidence for causation. We converted exposures to a common scale based on serum PFOA concentrations and applied meta-analysis to estimate the average increase in cancer risk reported by the studies with sufficient information to estimate serum PFOA. Using random effects meta-analysis, we found that the average relative increase in cancer risk per 10 ng/mL increase in serum PFOA for these studies is 16% (95% CI: 3%, 30%) for kidney cancer and 3% (95% CI: 2%, 4%) for testicular cancer. These associations are most likely causal, but results are limited by the small number of studies for testicular cancer, the overlapping study populations for several studies, and the lack of measured or modeled serum PFOA concentrations for several studies. Implications: Our review meta-analysis indicates an average increase in cancer risk per 10 ng/mL increase in serum PFOA for kidney and testicular cancers. These associations are most likely causal, but results are limited by the small number of studies for testicular cancer, the overlapping study populations for several studies, and the lack of measured or modeled serum PFOA concentrations for several studies. The weight of evidence could be even stronger with the addition of future studies conducted in large cohorts.

Background Water consumption is a necessity for human life, though it also presents an opportunity for exposure to harmful chemicals and toxins. In order to gain a better understanding of the potential levels of chronic exposure, accurate estimates of long-term water consumption are needed. Objective The objective of this study is to estimate long-term water consumption using a nationally representative sample of the US population. Methods In this study, we use a random effects model to obtain shrinkage estimates of average daily water consumption for National Health and Nutrition Examination Survey (NHANES) participants from 2005 to 2010, and compare to their empirical 2-day averages. Results Our results demonstrate that the shrinkage estimates yielded a reduction in estimated mean water consumption. The 95th percentile was reduced from 3292 to 2529 ml/day. In addition, standard deviation of water consumption for this group decreased from 1052 to 688 ml/day. Similar reductions in the mean and variance were observed stratifying by age and race. Significance Random effects models may provide a more accurate measure of daily water consumption and could be utilized for future exposure and risk assessments.

OBJECTIVE To determine if occupational exposure to dioxins is associated with an increased frequency of t(14;18) translocations. METHODS A cross-sectional analysis of serum dioxin levels and t(14;18) frequencies in peripheral blood mononuclear cells in 218 former chemical plant workers and 150 population controls. RESULTS The workers had significantly higher geometric mean serum levels of 2,3,7,8-TCDD (26.2 vs 2.5 ppt) and TEQ (73.8 vs 17.7 ppt) than controls. There were no significant differences in the prevalence or frequency of t(14;18) translocations in the workers compared to controls. Among former workers with current or past chloracne who were t(14;18) positive, the frequency of translocations significantly increased with quartiles of 2,3,7,8-TCDD and TEQ. CONCLUSION Chloracne appears to modulate the association between dioxin exposure and increased frequency of t(14;18) translocations.

Although congenital heart defects are the most common birth defects, occurring in nearly 1 in 100 births, many developing regions do not practice proper newborn cardiac screening, which uses pulse oximeter and stethoscope. We therefore designed and implemented an on-site training program of newborn cardiac screening for obstetric personnel in rural Yunnan province, China. The aims of this study were to evaluate whether the training improved trainees' knowledge on newborn cardiac screening and resulted in higher newborn cardiac screening rates. The training program, which started in July 2015 and lasted through 2016, trained 2,175 obstetric doctors and nurses from 104 rural hospitals. The trainees demonstrated significant knowledge improvement on the knowledge of cardiac screening. Additionally, before June 2016, the trained personnel performed proper cardiac screening on 44,614 (93.6%) newborn babies. Given the effectiveness and cost-efficiency of this program in Yunnan, we recommend similar programs be implemented in other developing areas.

In recent years, investigators in a variety of fields have reported that most published findings can not be replicated. This review evaluates the factors contributing to lack of reproducibility, implications for environmental epidemiology, and strategies for mitigation. Although publication bias and other types of selective reporting may contribute substantially to irreproducible results, underpowered analyses and low prevalence of true associations likely explain most failures to replicate novel scientific results. Epidemiologists can counter these risks by ensuring that analyses are well-powered or precise, focusing on scientifically justified hypotheses, strictly controlling type I error rates, emphasizing estimation over statistical significance, avoiding practices that introduce bias, or employing bias analysis and triangulation. Avoidance of p values has no effect on reproducibility if confidence intervals excluding the null are emphasized in a similar manner. Increased attention to exposure mixtures and susceptible subpopulations, and wider use of omics technologies, will likely decrease the proportion of investigated associations that are true associations, requiring greater caution in study design, analysis, and interpretation. Though well intentioned, these recent trends in environmental epidemiology will likely decrease reproducibility if no effective actions are taken to mitigate the risk of spurious findings.

Author(s): Parker, Daniel; Bruckner, Tim; Vieira, Veronica; Medina, Catalina; Minin, Vladimir; Felgner, Philip; Dratch, Alissa; Zahn, Matthew; Bartell, Scott; Boden-Albala, Bernadette | Abstract: COVID-19 is one of the largest public health emergencies in modern history. Here we present a detailed analysis from a large population center in Southern California (Orange County, population of 3.2 million) to understand heterogeneity in risks of infection, test positivity, and death. We used a combination of datasets, including a population-representative seroprevalence survey, to assess the true burden of disease as well as COVID-19 testing intensity, test positivity, and mortality. In the first month of the local epidemic, case incidence clustered in high income areas. This pattern quickly shifted, with cases next clustering in much higher rates in the north-central area which has a lower socio-economic status. Since April, a concentration of reported cases, test positivity, testing intensity, and seropositivity in a north-central area persisted. At the individual level, several factors (e.g., age, race/ethnicity, zip codes with low educational attainment) strongly affected risk of seropositivity and death.

Background The C8 Science Panel was composed of three epidemiologists charged with studying the possible health effects of PFOA in a highly exposed population in the mid-Ohio Valley. The Panel determined in 2012 there was a ‘probable link’ (i.e., more probable than not based on the weight of the available scientific evidence) between PFOA and high cholesterol, thyroid disease, kidney and testicular cancer, pregnancy-induced hypertension, and ulcerative colitis. Objective Here, former C8 Science Panel members and collaborators comment on the PFOA literature regarding thyroid disorders, cancer, immune and auto-immune disorders, liver disease, hypercholesterolemia, reproductive outcomes, neurotoxicity, and kidney disease. We also discuss developments regarding fate and transport, and pharmacokinetic models, and discuss causality assessment in cross-sectional associations among low-exposed populations. Discussion For cancer, the epidemiologic evidence remains supportive but not definitive for kidney and testicular cancers. There is consistent evidence of a positive association between PFOA and cholesterol, but no evidence of an association with heart disease. There is evidence for an association with ulcerative colitis, but not for other auto-immune diseases. There is good evidence that PFOA is associated with immune response, but uneven evidence for an association with infectious disease. The evidence for an association between PFOA and thyroid and kidney disease is suggestive but uneven. There is evidence of an association with liver enzymes, but not with liver disease. There is little evidence of an association with neurotoxicity. Suggested reductions in birthweight may be due to reverse causality and/or confounding. Fate and transport models and pharmacokinetic models remain central to estimating past exposure for new cohorts, but are difficult to develop without good historical data on emissions of PFOA into the environment. Conclusion Overall, the epidemiologic evidence remains limited. For a few outcomes there has been some replication of our earlier findings. More longitudinal research is needed in large populations with large exposure contrasts. Additional cross-sectional studies of low exposed populations may be less informative.

Supplemental Digital Content is available in the text., Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population, and were detected in public water systems serving approximately 16.5 million US residents during 2013–2015. Low birthweight was associated with PFAS exposures in previous studies. Methods: Birthweights for singleton births during 2013–2015 were obtained from CDC WONDER, multiply stratified by county, maternal age, race, education, smoking status, and parity. PFAS water concentrations were obtained from EPA UCMR3 database and aggregated by county. Multiple regression weighted by inverse variance was used to produce effect estimates equivalent to those that would be obtained from individual-level data on birthweight and confounders. Results: Adjusting for stratification demographic confounders (maternal age, race, education, smoking status, and parity), we found an average change in birthweight of 0.9 g (95% confidence interval [CI] = −0.5, 2.2), −1.3 g (−1.6, −0.9), −3.8 g (−4.9, −2.7), and −3.8 g (−4.3, −3.3) per ng/L increase in the population-weighted average perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid in public water supplies by county, respectively. We found an average change in birthweight of −1.0 g (95% CI = −1.2, −0.8) per ng/L increase in the sum of perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid concentrations in public water supplies. Conclusions: The direction and magnitude of association between PFAS and birthweight varied by PFAS chemical in this study. Conclusions are tempered by inherent limitations of the 2 public-use datasets, and by the sensitivity of our results to alternative methods such as mutual adjustment for co-exposures.

Our aim is to estimate associations between acute increases in particulate matter with diameter of 2.5 µm or less (PM2.5) concentrations and risk of infant bronchiolitis and otitis media among Massachusetts births born 2001 through 2008.Our case-crossover study included 20,017 infant bronchiolitis and 42,336 otitis media clinical encounter visits. PM2.5 was modeled using satellite, remote sensing, meteorological and land use data. We applied conditional logistic regression to estimate odds ratios (ORs) and confidence intervals (CIs) per 10-µg/m3 increase in PM2.5. We assessed effect modification to determine the most susceptible subgroups. Infant bronchiolitis risk was elevated for PM2.5 exposure 1 day (OR = 1.07, 95% CI = 1.03-1.11) and 4 days (OR = 1.04, 95% CI = 0.99-1.08) prior to clinical encounter, but not 7 days. Non-significant associations with otitis media varied depending on lag. Preterm infants were at substantially increased risk of bronchiolitis 1 day prior to clinical encounter (OR = 1.17, 95% CI = 1.08-1.28) and otitis media 4 and 7 days prior to clinical encounter (OR = 1.09, 95% CI = 1.02-1.16 and OR = 1.08, 95% CI = 1.02-1.15, respectively). In conclusion, preterm infants are most susceptible to infant bronchiolitis and otitis media associated with acute PM2.5 exposures.

Chronic particulate matter less than 2.5μm in diameter (PM2.5) exposure can leave infants more susceptible to illness. Our objective is to estimate associations of the chronic PM2.5 exposure with infant bronchiolitis and otitis media (OM) clinical encounters. We obtained all first time bronchiolitis (n=18,029) and OM (n=40,042) clinical encounters among children less than 12 and 36 months of age, respectively, diagnosed from 2001 to 2009 and two controls per case matched on birthdate and gestational age from the Pregnancy to Early Life Longitudinal data linkage system in Massachusetts. We applied conditional logistic regression to estimate odds ratios (OR) and confidence intervals (CI) per 2-μg/m3 increase in lifetime average satellite based PM2.5 exposure. Effect modification was assessed by age, gestational age, frequency of clinical encounter, and income. We examined associations between residential distance to roadways, traffic density, and infant bronchiolitis and OM risk. PM2.5 was not associated with infant bronchiolitis (OR=1.02, 95% CI=1.00, 1.04) and inversely associated with OM (OR=0.97, 95% CI=0.95, 0.99). There was no evidence of effect modification. Compared to infants living near low traffic density, infants residing in high traffic density had elevated risk of bronchiolitis (OR=1.23, 95% CI=1.14, 1.31) but not OM (OR=0.98, 95% CI=0.93, 1.02) clinical encounter. We did not find strong evidence to support an association between early-life long-term PM2.5 exposure and infant bronchiolitis or OM. Bronchiolitis risk was increased among infants living near high traffic density.

Temporal trends in plasma concentrations of per- and polyfluoroalkyl substances (PFAS) in free-ranging bottlenose dolphins (Tursiops truncatus) inhabiting two geographic areas: Indian River Lagoon, Florida over the years 2003–2015 and the waters surrounding Charleston, South Carolina over 2003–2013, were examined. Nine PFAS met the inclusion criteria for analysis based on percent of values below level of detection and sampling years. Proportionate percentiles parametric quantile regression assuming lognormal distributions was used to estimate the average ratio of PFAS concentrations per year for each chemical. Plasma concentrations decreased over time for perfluorodecanoate (PFDA), perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluoroundecanoate (PFUnDA) in both locations. Perfluorononanoate (PFNA) decreased with time in Indian River Lagoon dolphins. Perfluorododecanoate (PFDoDA) concentrations significantly increased over time among female Indian River Lagoon dolphins. Regulation and phaseout of specific PFAS groups may have led to the decreasing levels of those PFAS and increasing levels of other replacement PFAS.

Temporal trends in plasma concentrations of per- and polyfluoroalkyl substances (PFAS) in free-ranging bottlenose dolphins (Tursiops truncatus) inhabiting two geographic areas: Indian River Lagoon, Florida over the years 2003-2015 and the waters surrounding Charleston, South Carolina over 2003-2013, were examined. Nine PFAS met the inclusion criteria for analysis based on percent of values below level of detection and sampling years. Proportionate percentiles parametric quantile regression assuming lognormal distributions was used to estimate the average ratio of PFAS concentrations per year for each chemical. Plasma concentrations decreased over time for perfluorodecanoate (PFDA), perfluorohexane sulfonate (PFHxS), perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluoroundecanoate (PFUnDA) in both locations. Perfluorononanoate (PFNA) decreased with time in Indian River Lagoon dolphins. Perfluorododecanoate (PFDoDA) concentrations significantly increased over time among female Indian River Lagoon dolphins. Regulation and phaseout of specific PFAS groups may have led to the decreasing levels of those PFAS and increasing levels of other replacement PFAS.

HIV stigma is a harmful social phenomenon present in United States (US)-based health care settings. This study assessed the efficacy of a participatory PhotoVoice-informed stigma reduction training program focusing on people living with HIV (PLWH) and targeting health care workers. Seventy-three (N = 73) participants were assessed at baseline (T1), within approximately a week of the training (T2), and at a 3-month follow-up (T3) regarding their HIV/AIDS knowledge, attitudes towards PLWH, and observations of enacted HIV stigma. Findings indicated that the training increased knowledge and improved attitudes (β = 0.56, p 0.01; β = 0.58, p 0.01, respectively) at T2, but these effects diminished at T3 (β = - 0.03, p 0.05; β = - 0.29, p 0.05, respectively). The training did not, however, have an impact on observations of enacted stigma at T2 (β = 0.10, p 0.05) or at T3 (β = 0.02, p 0.05). Additional participatory stigma reduction programs that involve diverse groups of health care workers, offer salient study incentives, include time-saving training methods, and comprise a variety of stigma measures, may be particularly beneficial.

Background: Children born near New Bedford, Massachusetts, have been prenatally exposed to multiple environmental chemicals, in part due to an older housing stock, maternal diet, and proximity to the New Bedford Harbor (NBH) Superfund site. Chemical exposure measures are not available for all births, limiting epidemiologic investigations and potential interventions. Objective: We linked biomonitoring data from the New Bedford Cohort (NBC) and birth record data to predict prenatal exposures for all contemporaneous area births. Methods: We used prenatal exposure biomarker data from the NBC, a population-based cohort of 788 mother–infant pairs born during 1993–1998 to mothers living near the NBH, linked to their corresponding Massachusetts birth record data, to build predictive models for cord serum polychlorinated biphenyls (expressed as a sum, ΣPCBs), p,p′-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), cord blood lead (Pb), and maternal hair mercury (Hg). We applied the best fit models (highest pseudo R2), with multivariable smooths of continuous variables, to predict exposure biomarkers for all 10,270 births during 1993–1998 around the NBH. We used 10-fold cross validation to validate the exposure models and the bootstrap method to characterize sampling variability in the exposure predictions. Results: The 10-fold cross-validated R2 for the ΣPCBs, DDE, HCB, Pb, and Hg exposure models were 0.54, 0.40, 0.34, 0.46, and 0.40, respectively. For each exposure model, multivariable smooths of continuous variables improved the fit compared with linear models. Other variables with significant effects on exposure estimates were paternal education, maternal race/ethnicity, and maternal ancestry. The resulting exposure predictions for all births had variability consistent with the NBC measured exposures. Conclusions: Predictive models using multivariable smoothing explained reasonable amounts of variance in prenatal exposure biomarkers. Our analyses suggest that prenatal chemical exposures can be predicted for all contemporaneous births in the same geographic area by modeling available biomarker data for a subset of that population. https://doi.org/10.1289/EHP4849

Aim The aim of this study was to determine reference values for oxygen saturation (SpO2 ) in neonates at mild and moderate altitudes. Methods Our study included 41 097 consecutively born, asymptomatic neonates from 35 hospitals, located in Yunnan, China, with altitudes ranging from 267 to 2202 m. Pre-and post-ductal SpO2 of each neonate was measured at 24 hours of age and before hospital discharge. All study participants, according to the altitude of birth, were categorised into three groups: low (0-500 m), mild (500-1500 m) and moderate altitude (1500-2500 m). Results Every 1000-m increase in altitude was associated with a 1.54 per cent decrease in mean SpO2 . The means of pre-ductal SpO2 at low, mild and moderate groups were 97.9%, 96.4% and 95.5%, respectively. We used the 2.5th percentile of SpO2 distribution as the cut-off for neonatal SpO2 screening and defined new cut-off values of ≤93% for mild altitudes, ≤92% for moderate altitudes and no adjustment for low altitudes. Conclusion We recommend revised cut-off values for neonatal SpO2 at mild and moderate altitudes and provide new values for paediatricians to refer to when screening neonates for severe congenital heart or lung diseases.

Generalized additive models (GAMs) with bivariate smoothers are frequently used to map geographic disease risks in epidemiology studies. A challenge in identifying health disparities has been the lack of intuitive and computationally feasible methods to assess whether the pattern of spatial effects varies over time. In this research, we accommodate time-stratified smoothers into the GAM framework to estimate time-specific spatial risk patterns while borrowing information from confounding effects across time. A backfitting algorithm for model estimation is proposed along with a permutation testing framework for assessing temporal heterogeneity of geospatial risk patterns across two or more time points. Simulation studies show that our proposed permuted mean squared difference (PMSD) test performs well with respect to type I error and power in various settings when compared with existing methods. The proposed model and PMSD test are used geospatial risk patterns of patent ductus arteriosus (PDA) in the state of Massachusetts over 2003-2009. We show that there is variation over time in spatial patterns of PDA risk, adjusting for other known risk factors, suggesting the presence of potential time-varying and space-related risk factors other than the adjusted ones.

Background Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population. Food, drinking water, consumer products, dust, and air have been assessed as PFAS exposure sources for humans. The effects of various types of carpeting on serum PFAS concentrations have been less studied, despite the known use of PFAS in stain-resistant carpet treatments. Objective This study aimed to examine the associations between serum PFAS concentrations and type of residential flooring among the general US population aged 12 years and older using the 2005–2006 National Health and Nutrition Examination Survey (NHANES). Methods We used multiple linear regressions adjusted for complex survey design and relevant covariates to analyze the relations between serum PFAS concentrations and type of floor covering (smooth surface, low pile carpet, medium to high pile carpet, and combination of carpet and smooth surface), as well as other potential exposure factors. We used multiple imputation to address missing values. Results We found significantly higher serum concentrations of perfluorohexane sulfonic acid (PFHxS) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) in US residents residing in homes with low pile carpeting compared with those residing in homes with smooth surface. We concluded that among US residents aged 12 years and older residing in homes with low pile carpeting in the home in 2005–2006, on average 24% and 19% of the PFHxS and MeFOSAA body burdens, respectively, could be attributed to carpeting. We found associations between other types of floor covering (medium to high pile carpet, combination of carpet and smooth surface) and some PFAS concentrations compared with the smooth surface, but these results were less consistent and generally not statistically significant. Additionally, a group Wald Chi-squared test showed a significant result for PFOS, indicating different contributions of various types of flooring to PFOS serum concentration. Significance Our results are representative of the general US population at the time of the survey, and potentially informative regarding ongoing PFAS exposure from a variety of sources including carpeting.

Many epidemiology studies have investigated associations of perfluorooctanoate (PFOA) exposures with a variety of adverse health outcomes for participants in the C8 Health Project. The exposure concentrations (i.e., air and groundwater) used in these studies were determined primarily based on participant’s residential locations. However, for residential addresses that could not be geocoded to the street level, the exposure concentrations were assigned based on population-weighted ZIP code centroid, which may result in exposure mischaracterization. The aim of this current study is to evaluate the potential impact of mischaracterized exposure concentrations due to geocoding uncertainty on the predicted serum PFOA concentrations and the epidemiological association between PFOA exposure and preeclampsia. For both workplace addresses and incompletely geocoded residential addresses, we used Monte Carlo (MC) simulation to assign alternate geographic locations within the reported ZIP code (instead of population-weighted ZIP code centroids) and the corresponding exposure concentrations. We found that mischaracterization of residential exposure due to population-weighted ZIP code centroid assignment had no significant impact on the serum PFOA concentration predictions and the epidemiological association of PFOA exposure with preeclampsia. In contrast, the uncertainty in workplace exposure moderately impacted the rank exposure among the participants. We observed a 41% increase in the average adjusted odds ratio of preeclampsia occurrence that may be due to differing proportions of cases (64.3%) and controls (54.5%) with workplace address geocodes during pregnancy. This finding suggests that differential exposure mischaracterization can be reduced by obtaining accurate exposure information such as street addresses and tap water consumption, for both workplaces and residences. The analysis we present is one approach for estimating the potential impacts of positional errors in a geocoding-based exposure assessment on exposure estimates and epidemiological study results.

Background: Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers. Objectives: We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease. Methods: Participants completed surveys during 2008–2011 reporting demographic, medical, and residential history information. Self-reported liver disease, including hepatitis, fatty liver, enlarged liver and cirrhosis, was validated with healthcare providers. Alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005–2006). Historically modeled PFOA exposure, estimated using environmental fate and transport models and participant residential histories, was analyzed in relation to liver biomarkers (n = 30,723, including 1,892 workers) and liver disease (n = 32,254, including 3,713 workers). Results: Modeled cumulative serum PFOA was positively associated with ALT levels (p for trend < 0.0001), indicating possible liver toxicity. An increase from the first to the fifth quintile of cumulative PFOA exposure was associated with a 6% increase in ALT levels (95% CI: 4, 8%) and a 16% increased odds of having above-normal ALT (95% CI: odds ratio: 1.02, 1.33%). There was no indication of association with either elevated direct bilirubin or GGT; however, PFOA was associated with decreased direct bilirubin. We observed no evidence of an effect of cumulative exposure (with or without a 10-year lag) on all liver disease (n = 647 cases), nor on enlarged liver, fatty liver, and cirrhosis only (n = 427 cases). Conclusion: Results are consistent with previous cross-sectional studies showing association between PFOA and ALT, a marker of hepatocellular damage. We did not observe evidence that PFOA increases the risk of clinically diagnosed liver disease. Citation: Darrow LA, Groth AC, Winquist A, Shin HM, Bartell SM, Steenland K. 2016. Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a Mid-Ohio Valley community. Environ Health Perspect 124:1227–1233; http://dx.doi.org/10.1289/ehp.1510391

Type 2 diabetes (T2D), historically affecting primarily older individuals, now affects younger people. Few studies have analyzed diabetes risk factors among younger individuals, including college students. We investigated risk in that overlooked population. A 2-part diabetes risk assessment survey was administered to University of California Irvine (UCI) students, faculty, and staff for 2 months. Part I, including 26 questions, assessed participants’ nutrition, physical activity, and stress management behaviors. Part II assessed risk according to American Diabetes Association (ADA) Risk Assessment’s 8 demographic and lifestyle questions producing a risk score. Scores and behavioral factors analyzed risk on individual and community levels. Recruitment included emails and flyers promoting the UCI Electronic Educational Environment survey link. According to the ADA Risk Assessment scores of the 915 respondents, only 4% are at high risk of developing T2D. Although these scores indicate a small population at risk, our survey revealed a high prevalence of individuals practicing multiple unhealthy lifestyle behaviors associated with diabetes. These multiple behaviors may lead to high percentages of college students developing T2D, despite current low ADA risk status. We conclude the ADA Risk Assessment is geared toward an older demographic and may reflect short-term risk rather than longer-term risks.

In toxicology studies hormesis refers to a dose–response relationship with a stimulatory response at low doses and an inhibitory response at high doses. In this manuscript, we particularly focus on a J-shaped dose–response relationship for binary cancer responses. We propose and examine two new flexible models for testing the hypothesis of hormesis in a Bayesian framework. The first model is parametric and enhances the flexibility of modeling a hormetic zone by using a non-linear predictor in a multistage model. The second model is non-parametric and allows multiple model specifications, weighting the contribution of each model via Bayesian model averaging (BMA). Simulation studies show that the non-parametric modeling approach with BMA provides robust sensitivity and specificity for detecting hormesis relative to the parametric approach, regardless of the shape of a hormetic zone.

Background Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. Aim We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. Methods We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p’-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. Results Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for > 80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. Conclusions Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.

Introduction: Children born near New Bedford, Massachusetts, USA have been prenatally exposed to environmental chemicals, in part due to an older housing stock, high fish consumption rates, and pro...

Introduction: Experimental studies of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) exposure in animals have reported developmental effects, liver and kidney toxicity, immun...

Background Associations between ambient particulate matter

SummaryPerfluorooctanoic acid (PFOA) is a persistent environmental contaminant that has been detected in >100 public water systems in the United States alone. A variety of epidemiological investigations of PFOA have been published, mostly using measured or modeled serum PFOA concentrations as the exposure metric. Comparison of drinking water PFOA concentrations to those study findings or to typical serum concentrations requires pharmacokinetic modeling. This brief communication describes an online Javascript calculator that easily plots the expected serum PFOA concentration over time and at steady state for adults after starting or stopping consumption of PFOA-contaminated water. Two examples of usage are provided, including increasing serum PFOA after ongoing consumption of contaminated water at the federal limit, and decreasing serum PFOA after carbon filtration began in a contaminated water system. https://doi.org/10.1289/EHP2820.

Chronic particulate matter less than 2.5μm in diameter (PM2.5) exposure can leave infants more susceptible to illness. Our objective is to estimate associations of the chronic PM2.5 exposure with infant bronchiolitis and otitis media (OM) clinical encounters. We obtained all first time bronchiolitis (n=18,029) and OM (n=40,042) clinical encounters among children less than 12 and 36 months of age, respectively, diagnosed from 2001–2009 and two controls per case matched on birthdate and gestational age from the Pregnancy to Early Life Longitudinal data linkage system in Massachusetts. We applied conditional logistic regression to estimate odds ratios (OR) and confidence intervals (CI) per 2-μg/m3 increase in lifetime average satellite based PM2.5 exposure. Effect modification was assessed by age, gestational age, frequency of clinical encounter, and income. We examined associations between residential distance to roadways, traffic density, and infant bronchiolitis and OM risk. PM2.5 was not associated with infant bronchiolitis (OR = 1.02, 95% CI = 1.00, 1.04) and inversely associated with OM (OR= 0.97, 95% CI = 0.95, 0.99). There was no evidence of effect modification. Compared to infants living near low traffic density, infants residing in high traffic density had elevated risk of bronchiolitis (OR = 1.23, 95% CI = 1.14, 1.31) but not OM (OR = 0.98, 95% CI = 0.93, 1.02) clinical encounter. We did not find strong evidence to support an association between early-life long-term PM2.5 exposure and infant bronchiolitis or OM. Bronchiolitis risk was increased among infants living near high traffic density.

U.S. Environment Protection Agency benchmark doses for dichotomous cancer responses are often estimated using a multistage model based on a monotonic dose-response assumption. To account for model uncertainty in the estimation process, several model averaging methods have been proposed for risk assessment. In this article, we extend the usual parameter space in the multistage model for monotonicity to allow for the possibility of a hormetic dose-response relationship. Bayesian model averaging is used to estimate the benchmark dose and to provide posterior probabilities for monotonicity versus hormesis. Simulation studies show that the newly proposed method provides robust point and interval estimation of a benchmark dose in the presence or absence of hormesis. We also apply the method to two data sets on carcinogenic response of rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Background: Decreased heart rate variability (HRV) has been associated with future cardiac morbidity and mortality and is often used as a marker of altered cardiac autonomic balance in studies of health effects of airborne particulate matter. Fewer studies have evaluated associations between air pollutants and cardiac arrhythmia. Objectives: We examined relationships between cardiac arrhythmias, HRV, and exposures to airborne particulate matter. Methods: We measured HRV and arrhythmia with ambulatory electrocardiograms in a cohort panel study for up to 235 hr per participant among 50 nonsmokers with coronary artery disease who were ≥ 71 years of age and living in four retirement communities in the Los Angeles, California, Air Basin. Exposures included hourly outdoor gases, hourly traffic-related and secondary organic aerosol markers, and daily size-fractionated particle mass. We used repeated measures analyses, adjusting for actigraph-derived physical activity and heart rate, temperature, day of week, season, and community location. Results: Ventricular tachycardia was significantly increased in association with increases in markers of traffic-related particles, secondary organic carbon, and ozone. Few consistent associations were observed for supraventricular tachycardia. Particulates were significantly associated with decreased ambulatory HRV only in the 20 participants using ACE (angiotensin I–converting enzyme) inhibitors. Conclusions: Although these data support the hypothesis that particulate exposures may increase the risk of ventricular tachycardia for elderly people with coronary artery disease, HRV was not associated with exposure in most of our participants. These results are consistent with previous findings in this cohort for systemic inflammation, blood pressure, and ST segment depression. Citation: Bartell SM, Longhurst J, Tjoa T, Sioutas C, Delfino RJ. 2013. Particulate air pollution, ambulatory heart rate variability, and cardiac arrhythmia in retirement community residents with coronary artery disease. Environ Health Perspect 121:1135–1141; http://dx.doi.org/10.1289/ehp.1205914

Bayesian methods can be used to incorporate external information into epidemiologic exposure-response analyses of silica and lung cancer.We used data from a pooled mortality analysis of silica and lung cancer (n = 65,980), using untransformed and log-transformed cumulative exposure. Animal data came from chronic silica inhalation studies using rats. We conducted Bayesian analyses with informative priors based on the animal data and different cross-species extrapolation factors. We also conducted analyses with exposure measurement error corrections in the absence of a gold standard, assuming Berkson-type error that increased with increasing exposure.The pooled animal data exposure-response coefficient was markedly higher (log exposure) or lower (untransformed exposure) than the coefficient for the pooled human data. With 10-fold uncertainty, the animal prior had little effect on results for pooled analyses and only modest effects in some individual studies. One-fold uncertainty produced markedly different results for both pooled and individual studies. Measurement error correction had little effect in pooled analyses using log exposure. Using untransformed exposure, measurement error correction caused a 5% decrease in the exposure-response coefficient for the pooled analysis and marked changes in some individual studies.The animal prior had more impact for smaller human studies and for one-fold versus three- or 10-fold uncertainty. Adjustment for Berkson error using Bayesian methods had little effect on the exposure-response coefficient when exposure was log transformed or when the sample size was large. See video abstract at, http://links.lww.com/EDE/B160.

Introduction Bayesian methods can be used to combine human and animal data for exposure-response analyses. We apply a framework recommended in a recent National Academies report on the US EPA risk assessment process, extending the method to adjust for exposure measurement error. Methods We used epidemiological data from a pooled mortality analysis of silica and lung cancer (n = 65,980), and animal data from pooled analysis of chronic silica inhalation studies of rats. Bayesian analyses were conducted with either diffuse or informative priors based on the animal data, several different cross-species extrapolation factors, and human exposure measurement error corrections in the absence of a gold standard, assuming Berkson-type error that increased with increasing exposure (which can induce bias in Cox models). Analyses were conducted using untransformed and log transformed cumulative exposure. Results With 3-fold or 10-fold uncertainty in the cross-species extrapolation factor, the animal prior had little effect on results for pooled epidemiological analyses and only modest effects for some individual epidemiological studies. In contrast, assuming 1-fold uncertainty produced markedly different results for both pooled and individual epidemiological studies. Measurement error correction had little effect in pooled analyses using log exposure. Using untransformed exposure, measurement error correction caused a 5% decrease in the exposure-response coefficient for the pooled analysis and more marked changes for some individual studies. Measurement error correction had little effect on the exposure-response coefficient when exposure was log transformed or when the sample size was large. Conclusions The Bayesian framework is a principled method for combining human and animal data, with posterior effect estimates reflecting a weighted average of the animal and human results. It may be particularly useful when human data are sparse.

Introduction: Toxicological studies show that chronic exposure to particulate matter less than 2.5µm in diameter (PM2.5) can alter immune function, which may make individuals, especially infants, m...

© 2016 Elsevier Inc. We recently utilized a suite of environmental fate and transport models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations, and also assessed the association of those concentrations with preeclampsia for participants in the C8 Health Project (a cross-sectional study of over 69,000 people who were environmentally exposed to PFOA near a major U.S. fluoropolymer production facility located in West Virginia). However, the exposure estimates from this integrated model relied on default values for key independent exposure parameters including water ingestion rates, the serum PFOA half-life, and the volume of distribution for PFOA. The aim of the present study is to assess the impact of inter-individual variability and epistemic uncertainty in these parameters on the exposure estimates and subsequently, the epidemiological association between PFOA exposure and preeclampsia. We used Monte Carlo simulation to propagate inter-individual variability/epistemic uncertainty in the exposure assessment and reanalyzed the epidemiological association. Inter-individual variability in these parameters mildly impacted the serum PFOA concentration predictions (the lowest mean rank correlation between the estimated serum concentrations in our study and the original predicted serum concentrations was 0.95) and there was a negligible impact on the epidemiological association with preeclampsia (no change in the mean adjusted odds ratio (AOR) and the contribution of exposure uncertainty to the total uncertainty including sampling variability was 7%). However, when epistemic uncertainty was added along with the inter-individual variability, serum PFOA concentration predictions and their association with preeclampsia were moderately impacted (the mean AOR of preeclampsia occurrence was reduced from 1.12 to 1.09, and the contribution of exposure uncertainty to the total uncertainty was increased up to 33%). In conclusion, our study shows that the change of the rank exposure among the study participants due to variability and epistemic uncertainty in the independent exposure parameters was large enough to cause a 25% bias towards the null. This suggests that the true AOR of the association between PFOA and preeclampsia in this population might be higher than the originally reported AOR and has more uncertainty than indicated by the originally reported confidence interval.

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.

Human exposure to polycyclic aromatic hydrocarbons (PAHs) can be assessed by biomonitoring of their urinary mono-hydroxylated metabolites (OH-PAHs). Limited information exists on the human pharmacokinetics of OH-PAHs. This study aimed to investigate the excretion half-life of 1-hydroxypyrene (1-PYR), the most used biomarker for PAH exposure, and 9 other OH-PAHs following a dietary exposure in 9 non-smoking volunteers with no occupational exposure to PAHs. Each person avoided food with known high PAH-content during the study period, except for a high PAH-containing lunch (barbecued chicken) on the first day. Individual urine samples (n = 217) were collected from 15 hours before to 60 hours following the dietary exposure. Levels of all OH-PAHs in all subjects increased rapidly by 9–141 fold after the exposure, followed by a decrease consistent with first order kinetics, and returned to background levels 24–48 hours after the exposure. The average time to reach maximal concentration ranged from 3.1 h (1-naphthol) to 5.5 h (1-PYR). Creatinine-adjusted urine concentrations for each metabolite were analyzed using a non-linear mixed effects model including a term to estimate background exposure. The background-adjusted half-life estimate was 3.9 h for 1-PYR and ranged 2.5–6.1 h for the other 9 OH-PAHs, which in general, were shorter than those previously reported. The maximum concentrations after the barbecued chicken consumption were comparable to the levels found in reported occupational settings with known high PAH exposures. It is essential to consider the relatively short half-life, the timing of samples relative to exposures, and the effect of diet when conducting PAH exposure biomonitoring studies.

As part of an extensive modeling effort on the air–soil-groundwater transport pathway of perfluorooctanoic acid (PFOA), this study was designed to compare the performance of different air dispersion modeling systems (AERMOD vs. ISCST3), and different approaches to handling incomplete meteorological data using a data set with substantial soil measurements and a well characterized point source for air emissions. Two of the most commonly used EPA air dispersion models, AERMOD and ISCST3, were linked with the EPA vadose zone model PRZM-3. Predicted deposition rates from the air dispersion model were used as input values for the vadose zone model to estimate soil concentrations of PFOA at different depths. We applied 34 years of meteorological data including hourly surface measurements from Parkersburg Airport and 5 years of onsite wind direction and speed to the air dispersion models. We compared offsite measured soil concentrations to predictions made for the corresponding sampling depths, focusing on soil rather than air measurements because the offsite soil samples were less likely to be influenced by short-term variability in emission rates and meteorological conditions. PFOA concentrations in surface soil (0–30 cm depth) were under-predicted and those in subsurface soil (>30 cm depth) were over-predicted compared to observed concentrations by both linked air and vadose zone model. Overall, the simulated values from the linked modeling system were positively correlated with those observed in surface soil (Spearman’s rho, R sp = 0.59–0.70) and subsurface soil ( R sp = 0.46–0.48). This approach provides a useful modeling scheme for similar exposure and risk analyses where the air–soil-groundwater transport is a primary contamination pathway.

Research Retrospective Exposure Estimation and Predicted versus Observed Serum Perfluorooctanoic Acid Concentrations for Participants in the C8 Health Project Hyeong-Moo Shin, 1 Veronica M. Vieira, 2 P. Barry Ryan, 3 Kyle Steenland, 3 and Scott M. Bartell 4 1 School of Social Ecology, University of California, Irvine, California, USA; 2 Department of Environmental Health, Boston University, Boston, Massachusetts, USA; 3 Department of Environmental Health, Emory University, Atlanta, Georgia, USA; 4 Program in Public Health, Department of Statistics, and Department of Epidemiology, University of California, Irvine, California, USA B ackground : People living or working in eastern Ohio and western West Virginia have been exposed to perfluorooctanoic acid (PFOA) released by DuPont Washington Works facilities. O bjectives : 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 con- sented to share their residential histories and a 2005–2006 serum PFOA measurement. M ethods : We estimated annual PFOA exposure rates for each individual based on predicted cali- brated water concentrations and predicted air concentrations using an environmental fate and trans- port 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. R esults : 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 (r s ) = 0.67]. For participants who provided daily public well water consumption rate and who had the same resi- dence 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 (r s = 0.82). C onclusions : Serum PFOA concentrations predicted by linked exposure and ADME models cor- related well with observed 2005–2006 human serum concentrations for C8 Health Project partici- pants. These individualized retrospective exposure and serum estimates are being used in a variety of epidemiologic studies being conducted in this region. K ey words : exposure, perfluorooctanoic acid, pharmacokinetics, serum. Environ Health Perspect 119:1760–1765 (2011). http://dx.doi.org/10.1289/ehp.1103729 [Online 3 August 2011] Perfluorooctanoic acid (PFOA, or C8) is one of the two most studied and prevalent world- wide perfluorinated compounds, along with perfluorooctane sulfonate (PFOS). PFOA has been used in the manufacture of Teflon® and other fluoropolymers. The primary sources of PFOA to the environment are direct emissions from the manufacturing facilities to air and water, indirect emissions from landfill leaching to groundwater, and farther long-range trans- port via ocean current and atmospheric disper- sion (McMurdo et al. 2008; Shin et al. 2011). Effluent from wastewater treatment plants may also contribute to PFOA contamination in the general environment (Loganathan et al. 2007; Sinclair and Kannan 2006). In spite of the voluntary phase-out on the use of PFOA by major manufacturing companies, the detec- tion of PFOA in wastewater influent indicates it has been released from consumer products made of this chemical (Loganathan et al. 2007). When products that contain PFOA are used indoors, it accumulates indoors, espe- cially in house dust (Strynar and Lindstrom 2008). Other potential sources of PFOA for human intake are assumed to be food and beverages, which are either primarily contami- nated or secondarily contaminated by food packaging materials (Begley et al. 2005). In the United States, PFOA was detected in the serum of most people with a median of 4 ppb in 2003–2004, 2005–2006, and 2007–2008 [National Health and Nutrition Examination Survey (NHANES) 2011]. Although there have been some animal studies of the toxic effects of PFOA (Abdellatif et al. 1991; Andersen et al. 2008; Kennedy et al. 2004; Lau et al. 2006, 2007; Luebker et al. 2005; Nilsson et al. 1991), the health effects in human subjects are still largely unknown (Steenland et al. 2010). Three longi- tudinal studies reported half-life estimates for PFOA in human serum: a) a median of 3.5 years from a study of 28 retired workers with 5 years of follow-up (Olsen et al. 2007); b) a median of 2.3 years from a study of 200 peo- ple who were exposed to contaminated public water, after 1 year of follow-up (Bartell et al. 2010); and c) a geometric mean of 3.3 years from 138 participants (45 children, 46 moth- ers, and 47 men) in a German study who were also exposed via drinking water, after 2 years of follow-up (Brede et al. 2010). Drinking water in the Mid-Ohio Valley has been presumably contaminated with PFOA released from the DuPont Washington Works facilities near Parkersburg, West Virginia, since 1951. PFOA emissions steadily increased as production of PFOA- related products increased over time, peak- ing in 1999 and then sharply decreasing after control strategies were implemented (DuPont volume 2008). PFOA emitted from the stacks was transported according to prevailing wind directions and settled to the ground surface by wet or dry deposition. Deposited PFOA infil- trated through the unsaturated zone, a region between the land surface and groundwater aquifer, with precipitation, and it eventually reached the saturated groundwater aquifer. PFOA released into the Ohio River contami- nated the groundwater aquifer that interacts with the river (Shin et al. 2011). We recently developed a more sophisti- cated multicompartment environmental fate and transport model to estimate retrospec- tive year-by-year PFOA concentrations in air, groundwater, and six public water supplies involved in the C8 Health Project, a cross- sectional study conducted from 2005 to 2006 (Shin et al. 2011). In this study, we linked retrospective air and water concentration predictions from the Shin et al. (2011) model to individual residen- tial histories for 45,276 participants from the C8 Health Project, predicting year-by-year PFOA exposures based on their individual residential histories and likely water sources. We then linked these individual annual expo- sure estimates to an absorption, distribution, metabolism, and excretion (ADME) model to predict annual PFOA serum concentra- tions for each individual, and compared those predicted serum concentrations to observed 2005–2006 serum measurements. Address correspondence to H.-M. Shin, University of California, Davis, One Shields Avenue, MS1-C, Davis, CA 95616 USA. Telephone: (949) 648-1614. Fax: (949) 824-9863. E-mail: hmshin@ucdavis.edu Supplemental Material is available online (http:// dx.doi.org/10.1289/ehp.1103729). We thank T. Fletcher and D. Mondal, who gener- ously provided data for the maternal–infant transfer component of the pharmacokinetic model. This research was funded by the C8 Class Action Settlement Agreement (Circuit Court of Wood County, WV) between DuPont and plaintiffs, which resulted from releases into drinking water of the chemical perfluorooctanoic acid (PFOA, or C8). Funds are administered by an agency that reports to the court. Our work and conclusions are indepen- dent of either party to the lawsuit. Funding was also provided by the Research and Education in Green Materials Program at University of California, Irvine (award UC-44157). The findings and conclusions in this paper are those of the authors. The authors declare they have no actual or potential competing financial interests. Received 25 March 2011; accepted 3 August 2011. 119 | number 12 | December 2011 • Environmental Health Perspectives

Although a single measurement of urinary cotinine is often used for biological monitoring, the validity of this measurement for estimating long-term exposure has not been well evaluated. The purpose of this study was to determine the efficacy of using a single measurement per person to estimate long-term smoking exposure in an elderly population. Analysis was conducted using a cohort of elderly subjects for whom multiple urinary cotinine measurements had been collected over eight weeks. The mixed-effects model of urinary cotinine indicated that interpersonal variability was greater than temporal variability. The efficacy of using single measurements to track the mean long-term exposure of a population is supported by the relatively consistent population averages. The classification of high and low exposure groups using a single measurement or using eight measurements produced similar group distributions. When using cut-off levels of 20 and 100 μg cotinine/g creatinine, 9.3% and 5.6% of individual exposures were misclassified, respectively, when using a single measurement. Urinary cotinine can be a useful biomarker for characterizing exposure to tobacco smoke. Although the incidence of misclassification decreased with an increase in the number of measurements, a single measurement of the urinary cotinine level may accurately represent long-term exposure to tobacco smoke.

Regression of log serum concentrations or log urine concentrations on time elapsed after primary exposure ceases is a common method for estimating the elimination rates and corresponding half-lives for environmental contaminants. However, this method produces bias in the presence of ongoing background exposures. A general formula for the amount of bias introduced by background exposures under any single compartment pharmacokinetic model is derived here, and simpler expressions and graphical results are presented for the special case of regularly spaced biomarker measurements. The formulas are also applied to evaluate the potential bias from background exposures in recently published half-life estimates for perfluorooctanoate. These published half-lives are likely to be overestimated because of bias from background exposures, by about 1-26%. Background exposures can contribute substantial bias to half-life estimates based on longer follow-up times, even when the background contribution constitutes a small fraction of total exposure at baseline.

This analysis examines differences between measured ambient indoor, and personal sulfate concentrations across cities, seasons, and individuals to elucidate how these differences may impact PM2.5 exposure measurement error. Data were analyzed from four panel studies conducted in Atlanta, Baltimore, Boston, and Steubenville (OH). Among the study locations, 1912 person-days of personal sulfate data were collected over 396 days involving 245 individual sampling sessions. Long-term differences in ambient and personal levels averaged over time are examined. Differences between averaged ambient and personal sulfate among and within cities were observed, driven by between subject and city differences in sulfate infiltration, F(inf), from outdoors to indoors. Neglecting this source of variability in associations may introduce bias in studies examining long-term exposures and chronic health. Indoor sulfate was highly correlated with and similar in magnitude to personal sulfate, suggesting indoor PM monitoring may be another means of characterizing true exposure variability.