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Exposure to perfluorooctane sulfonate (PFOS) is ubiquitous in populations and environments worldwide. Its long half-life in humans, indefinite persistence in the environment, and awareness of its widespread presence in drinking water make the human health assessment of PFOS a priority. While developmental, endocrine, and hepatic effects, and increased serum cholesterol are among the outcomes resulting from PFOS exposure, immunosuppression has also consistently emerged as an adverse effect. An in-depth review of the relevant scientific literature on the toxicology of PFOS has identified immunosuppression as a sensitive endpoint for PFOS toxicity. Here, we focus specifically on that endpoint and provide a detailed derivation of a Reference Dose (RfD) of 1.8 × 10 -6 mg/kg/day for chronic human exposure to PFOS. This RfD is based on decreased plaque-forming cell (PFC) response in mice, an endpoint that reflects suppression of the immune response to a foreign antigen. We additionally identify two endpoints in the epidemiology literature, decreased vaccine response and increased incidence of childhood infections, that are associated with PFOS exposure and that are consistent with and support the decreased PFC response endpoint from animal studies. We provide a weight of evidence analysis integrating the evidence from animal and epidemiology endpoints. Finally, we compare this RfD to the PFOS RfD derived by the United States Environmental Protection Agency (USEPA) Office of Water based on a developmental endpoint. Based on this comparison, and given our assessment, the USEPA RfD does not provide sufficient protection against the adverse health effects of PFOS. The RfD derived herein is intended to be public health protective and appropriately minimizes PFOS exposure based on available evidence., (Copyright © 2018 Elsevier Inc. All rights reserved.)

During much of the twentieth century, Jersey City, New Jersey was the leading center of chromate production in the United States. Chromate production produced huge volumes of chromium ore-processing residue containing many parts per million of hexavalent chromium. Starting in the 1990s, we undertook a series of studies to identify exposed populations, sources and pathways of exposure and the effectiveness of remediation activities in Jersey City. These studies revealed the effectiveness and success of the remediation activities. The sequence of studies presented here, builds on the lessons learned from each preceding study and illustrates how these studies advanced the field of exposure science in important ways, including the use of household dust as a measure of exposure to contaminants originating in the outdoor environment; development of effective and reproducible dust sampling; use of household dust to track temporal changes in exposure; understanding of the spatial relationship between sources of passive outdoor particulate emissions and residential exposure; use of focused biomonitoring to assess exposure under conditions of large inter-individual variability; and utility of linking environmental monitoring and biomonitoring. For chromium, the studies have demonstrated the use of Cr(+6)-specific analytical methods for measuring low concentrations of Cr(+6) in household dust and understanding of the occurrence of Cr(+6) in the background residential environment. We strongly recommend that environmental and public health agencies evaluate sites for their potential for off-site exposure and apply these tools in cases with significant potential as appropriate. This approach is especially important when contamination is widespread and/or a large population is potentially exposed. In such cases, these tools should be used to identify, characterize and then reduce the exposure to the off-site as well as on-site population. Importantly, these tools can be used in a demonstrable and quantifiable manner to provide both clarity and closure to concerned stakeholders.

Background: The most prominent non-occupational source of exposure to methylmercury is the consumption of fish. In this study we examine a fish consuming population to determine the extent of temporal exposure and investigate the extent to which single time estimates of methylmercury exposure based on blood-Hg concentration can provide reliable estimates of longer-term average exposure., Methods: Blood-mercury levels were obtained from a portion of the Arsenic Mercury Intake Biometric Study (AMIBS) cohort. Specifically, 56 Japanese women residing in the Puget Sound area of Washington State, US were sampled on three occasions across a one-year period., Results: An average of 135 days separated samples, with mean blood-mercury levels for the visits being 5.1, 6.6 and 5.0 μg/l and geometric means being 2.7, 4.5 and 3.1 μg/l. The blood-mercury levels in this group exceed national averages with geometric means for two of the visits being between the 90th and 95th percentiles of nationally observed levels and the lowest geometric mean being between the 75th and 90th percentile. Group means were not significantly different across sampling periods suggesting that exposure of combined subjects remained relatively constant. Comparing intra-individual results over time did not reveal a strong correlation among visits (r = 0.19, 0.50, 0.63 between 1st and 2nd, 2nd and 3rd, and 1st and 3rd sample results, respectively). In comparing blood-mercury levels across two sampling interval combinations (1st and 2nd, 2nd and 3rd, and 1st and 3rd visits, respectively), 58% (n = 34), 53% (n = 31) and 29% (n = 17) of the individuals had at least a 100% difference in blood-Hg levels., Conclusions: Point estimates of blood-mercury, when compared with three sample averages, may not reflect temporal variability and individual exposures estimated on the basis of single blood samples should be treated with caution as indicators of long-term exposure. Reliance on single blood samples can make predicting ongoing methylmercury exposure highly speculative due to the large intra-individual variability.

The Newark Bay Complex (NBC) is a significant historical repository of polychlorinated dibenzodioxins (PCDDs) and dioxin-like compounds. Detection of high levels of 2,3,7,8 tetrachloro-dibenzodioxins (TCDD) and its toxicological equivalents in blue crabs in the early 1990's led to a ban on the taking and distribution of crabs from the NBC. Despite this ban and ongoing communication outreach, surveys of crabbers in 1995, 2002 and 2005 by the New Jersey Department of Environmental Protection (NJDEP) showed that crabbing for recreational purposes and for significant dietary supplementation was continuing. At the time they were surveyed, the crabbers had been consuming these crabs for an average of 37% of their lives. Thus, exposure can be considered chronic. The surveys provided data on the duration, frequency and amount of NBC crab consumption. In 2004, the NJDEP sampled blue crabs in the NBC and analyzed the edible portions for 2,3,7,8 TCDD toxicity equivalent (TEQ) concentration. We have combined the survey-based exposure data and the 2,3,7,8 TCDD TEQ concentration data to produce an estimate of the lifetime cancer risk to NBC crabbers from dioxin-like compounds. We employed a point-estimate approach using discrete lower, central tendency and reasonable maximum exposure (RME) estimates of exposure factors and a probabilistic approach to exposure factors. Both approaches show central tendency lifetime cancer risk of greater than one-in-a-thousand (10(-3)) and an upper percentile/RME risk of approximately one-in-a-hundred (10(-2)). Little extrapolation is involved in applying the 2,3,7,8-TCDD TEQ concentration data in crabs to risk estimates in the population consuming those crabs. The ongoing and frequent nature of the crab collection minimizes the uncertainty often inherent in food recall surveys. These estimates point to the continued risk posed to NBC crab consumers and to the continuing importance of this resource which, with proper remediation, could provide ongoing benefit to the surrounding community., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The paper builds on existing literature, highlighting current understanding and identifying unresolved issues about MeHg exposure, health effects, and risk assessment, and concludes with a consensus statement. Methylmercury is a potent toxin, bioaccumulated and concentrated through the aquatic food chain, placing at risk people, throughout the globe and across the socioeconomic spectrum, who consume predatory fish or for whom fish is a dietary mainstay. Methylmercury developmental neurotoxicity has constituted the basis for risk assessments and public health policies. Despite gaps in our knowledge on new bioindicators of exposure, factors that influence MeHg uptake and toxicity, toxicokinetics, neurologic and cardiovascular effects in adult populations, and the nutritional benefits and risks from the large number of marine and freshwater fish and fish-eating species, the panel concluded that to preserve human health, all efforts need to be made to reduce and eliminate sources of exposure.

The recent article by Costa and Klein (2006) contains several inaccuracies about the federal drinking water standard for chromium. The federal drinking water standard for chromium is 100 ppb, not 50 ppb as stated by Costa and Klein, and it is based on non-carcinogenic effects, not a one in one million cancer risk level. The question of whether or not hexavalent chromium is carcinogenic via the oral route is the focus of much current interest and has major implications for regulation of chromium in drinking water and soil. The chronic drinking water study of hexavalent chromium currently being conducted by the National Toxicology Program will provide further information that will be useful in addressing this question.

Efforts to provide for public health protection from environmental contaminants in fish have resulted in various advisories or recommendations with regard to fish consumption from local, state, and federal agencies. These advisories are based on measured levels of contaminants in fish that are combined with values for body weight and portion size to produce an estimate of an "acceptable" consumption frequency (e.g., eat no more than once per month). Because values for body weight and portion size are generally generic default values, they do not necessarily relate to a specific population or to any individual in that population. Thus, the use of default values may result in underprotection or overprotection in any given case. Given the benefits of fish consumption and the risks from overexposure to various toxicants, vigilance is required by custodians of public health to ensure that populations are protected while being cautious not to over- or underprotect them. In this analysis, we examine the "acceptable" consumption limits derived for fish species/groups consumed by three specific populations and determine the extent of public health protection afforded by these limits. To accomplish this, the "acceptable" consumption frequencies are derived based, in part, on default assumptions and are compared to intakes calculated from empirically derived species-specific individual consumption and demographic data. Sensitivity analyses and population-specific probabilistic assessments of exposure are conducted to identify those values and/or assumptions which might significantly influence the resulting fish consumption advisories. Three populations were chosen for study based on their ability to represent populations of greatest concern: those most sensitive and/or those most exposed. We conclude from this investigation that consumption pattern data, contaminant data and body weight data together can be used to make fish consumption advisories more focused and, therefore, less likely to be under- or overprotective.

In the 2000 report of the National Research Council's Committee on the Toxicological Effects of Methylmercury (MeHg), various adverse health effects potentially associated with MeHg exposure including cardiovascular effects were considered. At that time, the committee concluded that neurodevelopmental toxicity was the most sensitive endpoint but recognized emerging evidence of potential cardiovascular effects at low levels of exposure. The committee recommended that these potential effects be addressed through the uncertainty factors applied to the development of the neurodevelopmental reference dose (RfD). This approach was adopted by the US EPA in its derivation of the methylmercury RfD. Since that time, additional studies have become available. The available studies addressing the broad categories of heart disease (including myocardial infarction (MI) and ischemic heart disease), hypertension, and heart rate variability are critically reviewed here. Overall, the evidence linking realistic rates of MeHg exposure from fish consumption to cardiovascular disease suggests an association with heart disease, particularly MI. The apparent antagonistic interaction of MeHg and n-3 fatty acids contained in fish suggests a causal mechanism. As different individuals and populations characteristically consume different species of fish, the risk of cardiovascular effects may not be a simple function of MeHg exposure but its assessment may well need to take n-3 fatty acid intake into account also. The case for significant adverse effects of MeHg on blood pressure at current levels of exposure is weaker. This effect, observed in childhood, does not appear to persist into adolescence, and animal studies are difficult to interpret given the high doses employed. The decrease in heart rate variability related to fetal exposure to MeHg in the same cohort appears to persist into early adolescence and may reflect developmental neurophysiological alterations that are consistent with the developmental neuropsychological effects also observed in that cohort. However, the cardiovascular significance of this effect with regard to its direct effect on health or its ability to predict other, more direct, health effects is unclear. At present, the studies of the Finnish cohort relating MeHg exposure to acute MI and coronary heart disease appear to provide the strongest basis for a formal quantitative risk assessment of the cardiovascular effects of MeHg.

Background: The U.S. Environmental Protection Agency (U.S. EPA) has estimated the neurological benefits of reductions in prenatal methylmercury (MeHg) exposure in past assessments of rules controlling mercury (Hg) emissions. A growing body of evidence suggests that MeHg exposure can also lead to increased risks of adverse cardiovascular impacts in exposed populations. Data extraction: The U.S. EPA assembled the authors of this article to participate in a workshop, where we reviewed the current science concerning cardiovascular health effects of MeHg exposure via fish and seafood consumption and provided recommendations concerning whether cardiovascular health effects should be included in future Hg regulatory impact analyses. Data synthesis: We found the body of evidence exploring the link between MeHg and acute myocardial infarction (MI) to be sufficiently strong to support its inclusion in future benefits analyses, based both on direct epidemiological evidence of an MeHg-MI link and on MeHg's association with intermediary impacts that contribute to MI risk. Although additional research in this area would be beneficial to further clarify key characteristics of this relationship and the biological mechanisms that underlie it, we consider the current epidemiological literature sufficiently robust to support the development of a dose-response function. Conclusions: We recommend the development of a dose-function relating MeHg exposures with MIs for use in regulatory benefits analyses of future rules targeting Hg air emissions. [ABSTRACT FROM AUTHOR]

Several previous studies of exposure to chromium waste in New Jerseyhave shown that Cr levels are elevated in household dust in homes adjacent to waste sites and that Cr levels in the urine of residents near sites are also elevated compared to control populations. It has not been possible until now, however, to examine these external and internal measures of exposure together in a large population to determine whether the external exposure is predictive of the internal exposure. We investigated the relationship between various adjusted and unadjusted measures of spot urine Cr concentration and household dust Cr from residents and residences adjacent to known Cr waste sites. Statistically significant bivariate relationships were found between log-transformed urine Cr concentration and Cr dust concentration (micrograms of Cr per gram of dust) but not Cr dust loading (nanogram Cr per square centimeter). Log-transformed urine concentration was used as the dependent variable in multiple regression analysis of the total population (n = 329), the population 10 years old (n = 262), with Cr dust concentration as a mandatory independent variable. Other potential direct influences on urine Cr were investigated as potential confounders of this relationship. In the final models for the entire population and those 10 years old, Cr dust concentration remained significant. This suggests that exposure of young children to Cr in household dust accounts for much of the relationship in the entire population. [ABSTRACT FROM AUTHOR]