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Many studies evaluating methylmercury (MeHg) toxicity rely on whole blood total mercury (THg) measurements to estimate MeHg exposure. However, whole blood THg includes other forms of mercury (Hg), such as inorganic Hg, which have different exposure sources and toxicological effects than MeHg. Therefore, estimating the whole blood MeHg/THg ratio is critical to predicting MeHg exposure and, subsequently, efforts to establish an exposure–response relationship for use in risk assessment. A large, representative dataset (National Health and Nutrition Examination Survey (NHANES) 2011–2016) was used to determine the whole blood MeHg/THg ratio among (a) self-reported fish and shellfish consumers, ≥ 15 years of age (the “full adult” population (N = 5268 training dataset; N = 2336 test dataset)) and (b) female fish and shellfish consumers, 15–44 years of age (the “women of reproductive age” population (N = 1285 training dataset; N = 560 test dataset)). Unadjusted and adjusted linear and spline models with direct measurements for both THg and MeHg were evaluated. The mean whole blood MeHg/THg ratio was 0.75 (95% confidence interval (CI): 0.74, 0.75). This ratio was significantly higher among those with higher THg concentrations. All models exhibited excellent fit (adjusted R2 from 0.957 to 0.982). Performance was slightly improved in spline versus linear models. For the full adult population and women of reproductive age, the unadjusted spline model predicted whole blood MeHg concentrations of 5.65 µg/L and 5.55 µg/L, respectively, when the THg concentration was 5.80 µg/L. These results suggest that whole blood THg is a good predictor of whole blood MeHg among fish and shellfish consumers.

Systematic reviews are powerful tools for drawing causal inference for evidence-based decision-making. Published systematic reviews and meta-analyses of environmental and occupational epidemiology studies have increased dramatically in recent years; however, the quality and utility of published reviews are variable. Most methodologies were adapted from clinical epidemiology and have not been adequately modified to evaluate and integrate evidence from observational epidemiology studies assessing environmental and occupational hazards, especially in evaluating the quality of exposure assessments. Although many reviews conduct a systematic and transparent assessment for the potential for bias, they are often deficient in subsequently integrating across a body of evidence. A cohesive review considers the impact of the direction and magnitude of potential biases on the results, systematically evaluates important scientific issues such as study sensitivity and effect modifiers, identifies how different studies complement each other, and assesses other potential sources of heterogeneity. Given these challenges of conducting informative systematic reviews of observational studies, we provide a series of specific recommendations based on practical examples for cohesive evidence integration to reach an overall conclusion on a body of evidence to better support policy making in public health.

Fish/seafood consumption is a source of mercury; other dietary sources are not well described. This cross-sectional study used National Health and Nutrition Examination Survey (NHANES) 2011-2012 data. Participants self-reported consuming fish/seafood (N = 5427) or not (N = 1770) within the past 30 days. Whole blood total mercury (THg), methylmercury (MeHg), and urinary mercury (UHg) were determined. Diet was assessed using 24 h recall. Adjusted regression models predicted mercury biomarker concentrations with recent food consumption, while controlling for age, sex, education, and race/ethnicity. Geometric mean THg was 0.89 µg/L (95% confidence interval (CI): 0.78, 1.02) (seafood consumers) and 0.31 µg/L (95% CI: 0.28, 0.34) (non-seafood consumers); MeHg and UHg concentrations follow similar patterns. In adjusted regressions among seafood consumers, significant associations were observed between mercury biomarkers with multiple foods, including fish/seafood, wine, rice, vegetables/vegetable oil, liquor, and beans/nuts/soy. Among non-seafood consumers, higher THg was significantly associated with mixed rice dishes, vegetables/vegetable oil, liquor, and approached statistical significance with wine (p < 0.10); higher MeHg was significantly associated with wine and higher UHg was significantly associated with mixed rice dishes. Fish/seafood consumption is the strongest dietary predictor of mercury biomarker concentrations; however, consumption of wine, rice, vegetables/vegetable oil, or liquor may also contribute, especially among non-seafood consumers.

Background: Human exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA following dermal exposure. Objective: To examine the absorption, distribution, metabolism and excretion of BPA in humans following dermal administration. Methods: We dermally administered deuterated BPA (d6-BPA) to 10 subjects (6 men and 4 women) at a dose of 100 µg/kg over a 12-hour period and conducted blood and urine analysis from the beginning of dosing through a three- or six-day period. We present time-course serum and urine concentrations of total and unconjugated (“free”) d6-BPA and used this information to calculate terminal half-life and area under the curve. Results and Conclusions: Detectable serum levels of total d6-BPA were observed at 1.4 h after the start of dosing, and a maximum serum concentration (Cmax) of 3.26 nM was observed. Free d6-BPA was detectable in serum 2.8 h after start of dermal administration, with Cmax of 0.272 nM. Beginning at approximately seven hours and continuing to 12 h (which corresponds to cessation of exposure), the concentration of free and total serum d6-BPA plateaued. The terminal half-lives of total d6-BPA and free d6-BPA in the body were 21.4 ± 9.81 h and 17.6 ± 7.69 h, respectively. Elimination from the body was rate-limited by kinetics in the dermal compartment. Free d6-BPA was a greater percentage of the area under the curve of total serum BPA (8.81%) compared to the 0.56% observed in our previously published oral study. Recovery of total d6-BPA in urine was

Objective We performed a systematic review of the epidemiology literature to identify the neurodevelopmental effects associated with phthalate exposure. Data sources and study eligibility criteria Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of neurodevelopmental effects in humans, and outcomes were selected for full systematic review based on data availability. Study evaluation and synthesis methods Studies of neurodevelopmental effects were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. For studies of cognition and motor effects in children ≤4 years old, a random effects meta-analysis was performed. Results The primary outcomes reviewed here are (number of studies in parentheses): cognition (14), motor effects (9), behavior, including attention deficit hyperactivity disorder (20), infant behavior (3), and social behavior, including autism spectrum disorder (7). For each phthalate/outcome combination, there was slight or indeterminate evidence of an association, with the exception of motor effects for BBP, which had moderate evidence. Conclusions and implications of key findings Overall, there is not a clear pattern of association between prenatal phthalate exposures and neurodevelopment. There are several possible reasons for the observed null associations related to exposure misclassification, periods of heightened susceptibility, sex-specific effects, and the effects of phthalate mixtures. Until these limitations are adequately addressed in the epidemiology literature, these findings should not be interpreted as evidence that there are no neurodevelopmental effects of phthalate exposure. The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA.

Systematic review (SR) is a rigorous methodology applied to synthesize and evaluate a body of scientific evidence to answer a research or policy question. Effective use of systematic-review methodology enables use of research evidence by decision makers. In addition, as reliance on systematic reviews increases, the required standards for quality of evidence enhances the policy relevance of research. Authoritative guidance has been developed for use of SR to evaluate evidence in the fields of medicine, social science, environmental epidemiology, toxicology, as well as ecology and evolutionary biology. In these fields, SR is typically used to evaluate a cause-effect relationship, such as the effect of an intervention, procedure, therapy, or exposure on an outcome. However, SR is emerging to be a useful methodology to transparently review and integrate evidence for a wider range of scientifically informed decisions and actions across disciplines. As SR is being used more broadly, there is growing consensus for developing resources, guidelines, ontologies, and technology to make SR more efficient and transparent, especially for handling large amounts of diverse data being generated across multiple scientific disciplines. In this article, we advocate for advancing SR methodology as a best practice in the field of exposure science to synthesize exposure evidence and enhance the value of exposure studies. We discuss available standards and tools that can be applied and extended by exposure scientists and highlight early examples of SRs being developed to address exposure research questions. Finally, we invite the exposure science community to engage in further development of standards and guidance to grow application of SR in this field and expand the opportunities for exposure science to inform environment and public health decision making.

Background: Prenatal exposure to ambient PM2.5, (i.e., fine particulate matter, aerodynamic diameter ≤ 2.5 μm) has been associated with preterm birth and low birth weight. The association between prenatal PM2.5 exposure and intrauterine inflammation (IUI), an important risk factor for preterm birth and neurodevelopmental outcomes, has not been evaluated. Objectives: We aimed to investigate the association between maternal exposure to PM2.5 and IUI in the Boston Birth Cohort, a predominantly urban low-income minority population. Methods: This analysis included 5,059 mother–infant pairs in the Boston Birth Cohort. IUI was assessed based on intrapartum fever and placenta pathology. PM2.5 exposure was assigned using data from the U.S. EPA’s Air Quality System. Odds ratios (OR) and 95% confidence intervals (CI) quantified the association of maternal PM2.5 exposure during preconception and various periods of pregnancy with IUI. Results: Comparing the highest with the lowest PM2.5 exposure quartiles, the multi-adjusted association with IUI was significant for all exposure periods considered, including 3 months before conception (OR = 1.52; 95% CI: 1.22, 1.89), first trimester (OR = 1.93; 95% CI: 1.55, 2.40), second trimester (OR = 1.67; 95% CI: 1.35, 2.08), third trimester (OR = 1.53; 95% CI: 1.24, 1.90), and whole pregnancy (OR = 1.92; 95% CI: 1.55, 2.37). Conclusions: Despite relatively low exposures, our results suggest a monotonic positive relationship between PM2.5 exposure during preconception and pregnancy and IUI. IUI may be a sensitive biomarker for assessing early biological effect of PM2.5 exposure on the developing fetus. Citation: Nachman RM, Mao G, Zhang X, Hong X, Chen Z, Soria CS, He H, Wang G, Caruso D, Pearson C, Biswal S, Zuckerman B, Wills-Karp M, Wang X. 2016. Intrauterine inflammation and maternal exposure to ambient PM2.5 during preconception and specific periods of pregnancy: the Boston Birth Cohort. Environ Health Perspect 124:1608–1615; http://dx.doi.org/10.1289/EHP243

During a systematic review of epidemiological evidence on health risk from exposure to environmental chemicals, it may be necessary to develop criteria for evaluating the quality of exposure measur...

To determine the balance of metabolism of free bisphenol A (BPA) to the inactive conjugate, BPA glucuronide (BPAG), in neonates.Free BPA and BPAG concentrations were measured in 78 urine samples collected between December 2012 and August 2013 from a cohort of 44 healthy full term (≥ 37 weeks' gestation) neonates at 2 intervals (3-6 days and 7-27 days of age). A questionnaire was administered at the time of sample collection. Neonates recruited into the study were born in an urban, tertiary care hospital.Only BPAG was detected in the urine samples; concentrations ranged from0.1 μg/L to 11.21 μg/L (median: 0.27 μg/L). Free BPA concentrations were below the limit of quantification of 0.1 μg/L. Age, but not sex or type of diet, was significantly associated with urinary BPAG concentration (P = .002).Our results illustrate widespread BPA exposure in healthy full-term neonates and efficient conjugation of BPA to its readily excretable and biologically inactive form (BPAG) as early as 3 days of age. Factors other than type of diet may be important contributors to BPA exposure in neonates.

Background: Although previous studies suggest that exposure to traffic-related pollution during childhood increases the risk of childhood overweight or obesity (COWO), the role of early life exposu...

When a comprehensive report on BPA was published in 2008, few data were available to assess the extent to which known poor glucuronidation capacity impacts BPA internal dose in infants and young children. In this paper, evidence that has emerged since the 2008 report is summarized, including: 1) human biomarker studies in children aged 0-5 years; 2) animal studies of neonatal toxicokinetics; and 3) physically based pharmacokinetic (PBPK) models. To address limitations in these studies, we recommend more human biomonitoring studies in children aged 0-5 years in which unmetabolized (free) BPA and BPA metabolites are separately quantified and detailed quality-control data are reported, investigation of metabolic differences between humans and animal species used for the study of BPA metabolism, and enzyme ontogeny studies, which along with biomonitoring studies would reduce uncertainty in PBPK models of early-life BPA metabolism.

Infants are exposed to the endocrine disruptor bisphenol A (BPA) through breast milk and baby formula. Detoxication by conjugation of BPA may be limited in infants. We demonstrate BPA exposure in 11 neonates and 1 young infant, but find no evidence of a low capacity for BPA conjugation.