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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.)

Although all chromite ore processing residue (COPR) sites near residential neighborhoods in Jersey City, New Jersey have undergone remediation, recent studies found widespread, but low levels of hexavalent chromium (Cr(+6)) in house dust both in Jersey City and in communities with no known sources of Cr(+6). This study was designed as a follow-up to determine whether there is an association between current Cr(+6) levels in house dust and urinary chromium concentrations in young children. Dust samples (N=369) were collected from 123 homes. The median Cr(+6) concentration was 3.3 μg/g (mean±SD 5.2±7.5) and the median Cr(+6) loading was 1.1 μg/m(2) (1.9±3.1). These levels were not elevated compared with previously reported levels in background communities (median concentration=3.5 μg/g; median loading=2.8 μg/m(2)). Urinary chromium concentrations were measured in spot urine samples collected from 150 children, ages 3 months to 6 years. The median uncorrected urinary chromium concentration was 0.19 μg/l (0.22±0.16). Current urinary chromium concentrations were significantly lower than those previously reported before and during remediation (t-test; P<0.001). Urinary chromium concentrations were not significantly higher in homes with high (75th or 90th percentile) Cr(+6) dust levels (concentration or loading) compared with other homes. Multiple linear regression was used to examine the relationship between Cr(+6) levels (concentration and loading) in house dust and urinary chromium concentrations (uncorrected and specific gravity corrected). Contrary to pre-remediation studies, we did not find a positive association between Cr(+6) levels in house dust and urinary chromium concentrations. The findings indicate that current Cr(+6) levels in house dust are not positively associated with children's chromium exposure as measured by urinary chromium, and the children's exposure to Cr(+6) in house dust is below the level that could be identified by urine sampling.

Although dieldrin׳s use in the U.S. was partially banned in the 1970s and its use was completely eliminated in 1987, dieldrin continues to be a common contaminant at hazardous waste sites. The USEPA׳s current cancer potency estimate for dieldrin was derived in 1987 and is based on the production of mouse liver tumors. Because of its environmental persistence and its relatively high USEPA cancer potency estimate, dieldrin functions as a cleanup "driver" in many hazardous site remediations. Since 1987, new risk assessment perspectives and new data on dieldrin׳s carcinogenic potential have arisen. This review presents a reassessment of dielrin׳s human cancer potential in light of these new data and new perspectives. Based on this reassessment, dieldrin may be carcinogenic through multiple modes of action. These modes of action may operate within the same tissue, or may be specific to individual tissues. Of the several possible carcinogenic modes of action for dieldrin, one or more may be more relevant to human cancer risk than others, but the relative importance of each is unknown. In addition, neither the details of the possible modes of action, nor the shape of the tumor dose-response curves associated with each are sufficiently well known to permit quantitative cancer dose-response modeling. Thus, the mouse liver tumor data used by the USEPA in its 1987 assessment remain the only quantitative data available for cancer dose-response modeling., (Copyright © 2014 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: Toenail-Hg levels are being used as a marker of methylmercury (MeHg) exposure in efforts to associate exposure with effects such as cardiovascular disease. There is a need to correlate this marker with more established biomarkers that presently underlie existing dose-response relationships in order to compare these relationships across studies., Methods: As part of the Arsenic Mercury Intake Biometric Study, toenail clippings were collected at three time points over a period of one year amongst females from within the population of Japanese living near Puget Sound in Washington State (US). Variability in temporal intra-individual toenail-Hg levels was examined and chronologically matched hair and toenail samples were compared to more accurately define the toxicokinetic variability of Hg levels observed between the two compartments., Results: Mean toenail-Hg values (n=43) for the 1st, 2nd and 3rd visits were 0.60, 0.60 and 0.56 ng/mg. Correlations were as follows: r=0.92 between 1st and 2nd clinic visits, r=0.75 between 1st and 3rd visits and r=0.87 between 2nd and 3rd visits. With few exceptions, toenail-Hg values from any visit were within 50-150% of the individual's mean toenail-Hg level. Nearly all participants had less than a two-fold change in toenail-Hg levels across the study period. A regression model of the relationship between toenail-Hg and hair-Hg (n = 41) levels representing the same time period of exposure, gave a slope (Hg ng/mg) of 2.79 for hair relative to toenail (r=0.954)., Conclusions: A chronologically matched hair-Hg to toenail-Hg ratio has been identified within a population that consumes fish regularly and in quantity. Intra-individual variation in toenail-Hg levels was less than two-fold and may represent dietary-based fluctuations in body burden for individuals consuming various fish species with different contaminant levels. The chronologically matched ratio will be useful for relating MeHg exposure and dose-response derived from toenail-Hg measurements to those derived from hair-Hg measurements in other studies, and may be useful in future investigations as an indicator of stable MeHg body burden within a population.

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 objective of this study was to estimate the contribution of a facility that processes steel production slag into raw material for cement production to local outdoor particle deposition in Camden, NJ. A dry deposition sampler that can house four 37-mm quartz fiber filters was developed and used for the collection of atmospheric particle deposits. Two rounds of particle collection (3-4 weeks each) were conducted in 8-11 locations 200-800 m downwind of the facility. Background samples were concurrently collected in a remote area located -2 km upwind from the facility. In addition, duplicate surface wipe samples were collected side-by-side from each of the 13 locations within the same sampling area during the first deposition sampling period. One composite source material sample was also collected from a pile stored in the facility. Both the bulk of the source material and the < 38 microm fraction subsample were analyzed to obtain the elemental source profile. The particle deposition flux in the study area was higher (24-83 mg/m2 x day) than at the background sites (13-17 mg/m2day). The concentration of Ca, a major element in the cement source production material, was found to exponentially decrease with increasing downwind distance from the facility (P < 0.05). The ratio of Ca/Al, an indicator of Ca enrichment due to anthropogenic sources in a given sample, showed a similar trend. These observations suggest a significant contribution of the facility to the local particle deposition. The contribution of the facility to outdoor deposited particle mass was further estimated by three independent models using the measurements obtained from this study. The estimated contributions to particle deposition in the study area were 1.8-7.4% from the regression analysis of the Ca concentration in particle deposition samples against the distance from the facility, 0-11% from the U.S. Environmental Protection Agency (EPA) Chemical Mass Balance (CMB) source-receptor model, and 7.6-13% from the EPA Industrial Source Complex Short Term (ISCST3) dispersion model using the particle-size-adjusted permit-based emissions estimates.

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.)

Background: Nearly all fish consumption advisories for methylmercury (MeHg) are based only on risk. There is a need to also address benefits, especially those from polyunsaturated fatty acids (PUFAs), in neurodevelopmental function and cardiovascular health. However, because MeHg and PUFA generally act on these same end points, disentangling risk and benefit is challenging., Objectives: We propose an approach for balancing risk and benefit that is based on the use of statistically dissociated measures of risk and benefit., Discussion: Because of mutual coexposure of MeHg and PUFAs in population-based studies and their opposite effect on many of the same end points, MeHg risk and PUFA benefit are tightly linked statistically, which results in mutual (negative) confounding. Thus, neither MeHg risk nor PUFA benefit can be accurately quantified without taking the other into account. A statistical approach that generates unconfounded risk and benefit coefficients for each end point can permit their subsequent recombination to describe the overall risk-benefit profile of each species of fish or fish diet. However, it appears that some end points may be adversely affected by MeHg without experiencing counterbalancing benefit from PUFAs. Such end points may drive consumption advisories and may preclude balancing of risk and benefit on the basis of other end points., Conclusions: Our thinking about fish consumption advisories now recognizes the need to balance risk and benefit. However, although statistical analysis of the appropriate data can eliminate mutual confounding, care is required to address the most sensitive end points that may be sensitive to risk and not benefit.

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- response function relating MeHg exposures with MIs for use in regulatory benefits analyses of future rules targeting Hg air emissions.

Background: Hexavalent chromium (Cr(6+)) has long been recognized as an inhalation carcinogen. Useful data on its carcinogenicity by ingestion have been slower to develop. The 2008 NTP chronic bioassay of sodium dichromate dihydrate in drinking water found clear evidence of carcinogenicity in rodents and allows a generalizable estimate of the human ingestion cancer potency of Cr(6+)., Objectives: To estimate the human ingestion cancer potency of Cr(6+) and evaluate its relevance for human exposure., Methods: Tumors of the small intestine in male mice were selected as the critical endpoint, for the derivation of cancer potency. Following the 2005 USEPA Cancer Risk Assessment Guidelines, the point of departure in the dose-response data was defined using benchmark-dose modeling. Linear extrapolation was carried out from the point of departure and interspecies dose conversion was based on allometric scaling of body weight., Results: Small intestine tumor incidence in male mice provided a robust and nearly identical fit with most available dose-response models using benchmark-dose modeling. A human equivalent cancer slope factor of 0.5 (mg/kg/day)(-1) was derived based on linear extrapolation from the point of departure. Statistical and kinetic analysis carried out on the NTP data as well as data reported in other studies support that the carcinogenicity of Cr(6+) did not result from an exceedance of the reduction capacity of the mouse gastrointestinal tract at the doses in the NTP study., Conclusions: Mouse gastric emptying time and human Cr(6+) dosing studies strongly suggest that even at doses considerably lower than those in the NTP study, Cr(6+) escapes reduction in both the mouse and human stomachs due to kinetic competition from Cr(6+) absorption and gastric emptying. The cancer potency derived from the NTP data is, therefore, deemed to be relevant and applicable to human exposure. Cr(6+) is, therefore, identified as "likely to be carcinogenic to humans" in accordance with the USEPA's cancer characterization rubric., (Copyright © 2010 Elsevier Inc. All rights reserved.)

In contrast to Cr(+3), Cr(+6) is carcinogenic and allergenic. Although Cr(+6) can occur naturally, it is thought that most soil Cr(+6) is anthropogenic, however, the extent of Cr(+6) in the background environment is unknown. Cr(+6)-containing chromite ore processing residue (COPR) from chromate manufacture was deposited in numerous locations in Jersey City (JC), New Jersey. In the 1990's, significantly elevated concentrations of total Cr (Cr(+6)+Cr(+3)) were found in house dust near COPR sites. We undertook a follow-up study to determine ongoing COPR exposure. We compared Cr(+6) in house dust in JC to selected background communities with no known sources of Cr(+6). Samples were collected from living areas, basements and window wells. Cr(+6) was detected in dust from all JC and background houses. In the JC homes, the mean (+ or - SD) Cr(+6) concentration for all samples was 3.9 + or - 7.0 microg/g (range: non-detect-90.4 microg/g), and the mean Cr(+6) loading was 5.8 + or - 15.7 microg/m(2) (range: non-detect-196.4 microg/m(2)). In background homes, the mean Cr(+6) concentrations of all samples was 4.6 + or - 7.8 microg/g, (range, 0.05-56.6 microg/g). The mean loading was 10.0 + or - 27.9 microg/m(2) (range, 0.22-169.3 microg/m(2)). There was no significant difference between Cr(+6) dust concentrations in Jersey City and background locations. Stratification by sample location within houses and sampling method gave similar results. Samples exceeding 20 microg/g were obtained only from single wood surfaces in different homes. Lower concentrations in window well samples suggests transport from outside is not the major source of indoor Cr(+6). Landscaping and groundcover may influence indoor Cr(+6). There appears to be a widespread low level background of Cr(+6) that is not elevated in Jersey City homes despite its historic COPR contamination. It is possible that house dust, in general, is a source of Cr(+6) exposure with potential implications for persistence of chromium allergic contact dermatitis., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Exposure to elemental mercury (Hg0) in residential buildings can occur from accidental spills, broken objects (thermometers, fluorescent fixtures, thermostats), and deliberate introduction, one mode of which involves cultural practices by individuals who believe dispersal of mercury in a residence will bring luck, enhance health or ward off harm., Objectives: To determine whether mercury vapor levels in common areas of residential buildings is higher in a community where cultural uses are likely (study areas S1, S2) than in a reference community (C1) where cultural use is unlikely, and whether levels can serve as a signal of significant cultural mercury use., Methods: We monitored Hg0 vapor with a portable spectrophotometer in the three communities. We randomly selected sites in S1 and C1 community, and also include sites in S2 specified by local health officials who suspected cultural mercury use. We evaluated 122 multifamily buildings and 116 outdoor locations., Findings: We found >25 ng/m3 Hg0 in 14% of buildings in study areas compared to only one reference building. In the latter we identified an accidental mercury spill from a bottle that had been brought into the building. Both the mean and maximum indoor mercury vapor levels were greater in the study communities than in the reference community. In all communities, we observed mean indoor Hg0 vapor concentration greater than outdoors, although in two-thirds of buildings, indoor levels did not exceed the area-specific outdoor upper-limit concentration., Conclusion: After controlling for factors that might influence Hg0 vapor levels, the most plausible explanation for greater Hg0 levels in the study area is a relationship to cultural use of mercury. None of the measured levels exceeded the ATSDR minimum risk level for residences of 200 ng/m3 Hg0 although levels in living quarters might be greater than those in the common areas.

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.

Elemental mercury has been imbued with magical properties for millennia, and various cultures use elemental mercury in a variety of superstitious and cultural practices, raising health concerns for users and residents in buildings where it is used. As a first step in assessing this phenomenon, we compared mercury vapor concentration in common areas of residential buildings versus outdoor air, in two New Jersey cities where mercury is available and is used in cultural practices. We measured mercury using a portable atomic absorption spectrometer capable of quantitative measurement from 2 ng/m3 mercury vapor. We evaluated the interior hallways in 34 multifamily buildings and the vestibule in an additional 33 buildings. Outdoor mercury vapor averaged 5 ng/m3; indoor mercury was significantly higher (mean 25 ng/m3; p<0.001); 21% of buildings had mean mercury vapor concentration in hallways that exceeded the 95th percentile of outdoor mercury vapor concentration (17 ng/m3), whereas 35% of buildings had a maximum mercury vapor concentration that exceeded the 95th percentile of outdoor mercury concentration. The highest indoor average mercury vapor concentration was 299 ng/m3, and the maximum point concentration was 2,022 ng/m3. In some instances, we were able to locate the source, but we could not specifically attribute the elevated levels of mercury vapor to cultural use or other specific mercury releases. However, these findings provide sufficient evidence of indoor mercury source(s) to warrant further investigation.

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.

Most attention to the risks from fish consumption has focused on recreational anglers and on fish caught by individuals, but the majority of fish that people eat are purchased from commercial sources. We examined mercury levels in three types of fish (tuna, flounder, bluefish) commonly available in New Jersey stores, sampling different regions of the state, in communities with high and low per capita incomes, and in both supermarkets and specialty fish markets. We were interested in species-specific levels of mercury in New Jersey fish and whether these levels were similar to data generated nationally by the Food and Drug Administration (FDA; mainly from 1990 to 1992) on the same types of fish. Such information is critical for providing public health advice. We were also interested in whether mercury levels in three common species of fish differed by region of the state, economic neighborhood, or type of store. We found significant species differences, with tuna having the highest levels and flounder the lowest levels. There were no significant differences in mercury levels as a function of type of store or economic neighborhood. There was only one regional difference: flounder from fish markets along the Jersey shore had higher mercury levels than flounder bought in other markets. We also examined mercury levels in six other commonly available fish and two shellfish from central New Jersey markets. There were significant differences in availability and in mercury levels among fish and shellfish. Both shrimp and scallops had total mercury levels < 0.02 ppm (wet weight). Large shrimp had significantly lower levels of mercury than small shrimp. For tuna, sea bass, croaker, whiting, scallops, and shrimp, the levels of mercury were higher in New Jersey samples than those reported by the FDA. Consumers selecting fish for ease of availability (present in > 50% of markets) would select flounder, snapper, bluefish, and tuna (tuna had the highest mercury value), and those selecting only for price would select whiting, porgy, croaker, and bluefish (all with average mercury levels < 0.3 ppm wet weight). Flounder was the fish with the best relationship among availability, cost, and low mercury levels. We suggest that state agencies responsible for protecting the health of their citizens should obtain information on fish availability in markets and fish preferences of diverse groups of citizens and use this information to select fish for analysis of contaminant levels, providing data on the most commonly eaten fish that will help people make informed decisions about risks from fish consumption.

In 2001, the U.S. Environmental Protection Agency (EPA) adopted a revised reference dose (RfD) for methyl mercury (MeHg) of 0.1 microg/kg/day. The RfD is based on neurologic developmental effects measured in children associated with exposure in utero to MeHg from the maternal diet. The RfD derivation proceeded from a point of departure based on measured concentration of mercury in fetal cord blood (micrograms per liter). The RfD, however, is a maternal dose (micrograms per kilogram per day). Reconstruction of the maternal dose corresponding to this cord blood concentration, including the variability around this estimate, is a critical step in the RfD derivation. The dose reconstruction employed by the U.S. EPA using the one-compartment pharmacokinetic model contains two areas of significant uncertainty: It does not directly account for the influence of the ratio of cord blood: maternal blood Hg concentration, and it does not resolve uncertainty regarding the most appropriate central tendency estimates for pregnancy and third-trimester-specific model parameters. A probabilistic reassessment of this dose reconstruction was undertaken to address these areas of uncertainty and generally to reconsider the specification of model input parameters. On the basis of a thorough review of the literature and recalculation of the one-compartment model including sensitivity analyses, I estimated that the 95th and 99th percentiles (i.e., the lower 5th and 1st percentiles) of the maternal intake dose corresponding to a fetal cord blood Hg concentration of 58 microg/L are 0.3 and 0.2 microg/kg/day, respectively. For the 99th percentile, this is half the value previously estimated by the U.S. EPA.

There is considerable interest in fish consumption, contaminant loads in edible fish, and the risk from consuming fish. Both the benefits and the risks from eating fish are publicized. Most of this attention has focused on recreational anglers and self-caught fish, although the vast majority of fish that people eat are purchased from commercial sources: fish markets and supermarkets. We examined the availability of fish in supermarkets and specialty fish markets in New Jersey, including three regions of the state in communities with high and low per capita incomes (upscale vs. downscale neighborhoods). We were particularly interested in examining whether consumers could determine what type of fish they were buying and whether it was farm-raised or wild. Flounder and salmon were the most commonly available fish, followed by bluefish and tilapia. There were few significant differences in the availability of fish as a function of region. Fish were equally available in fish markets and supermarkets, although snappers were more available in fish markets. The most common fish (found in over 60% of stores) were equally available in upscale and downscale neighborhood stores. However, there were some significant differences in less common fish; butterfish, croaker, monkfish, porgy, and whiting were more available in downscale markets, and halibut, sole, and swordfish were more available in upscale markets. Information available to consumers on labels varied markedly: (1) most labels were generic but some indicated species (e.g., Spanish vs. Boston mackerel, Chilean vs. Black sea bass, mako vs. black-tip shark, rainbow vs. steelhead trout); (2) in many cases, labels indicated whether catfish or salmon were farmed or wild, but usually that information was lacking; (3) sometimes, the labels indicated the location where fish were caught (salmon); and (4) sometimes, there was information on both species and type (e.g., farm/wild for salmon). In most cases, labels gave only a fish name and price. Consumers would be able to make more informed choices if the provenance of fish was clearly stated. State agencies might improve information available to consumers by providing distributors and markets with guidelines about the types of information necessary for consumers to make informed decisions about the fish they eat. When asked, counter staff often could not answer where fish originated from. Finally, there should be partnerships between government agencies responsible for public health, risk assessors, and consumers to ascertain the types of information consumers want and to provide the best available information to consumers.

In the current U.S. Environmental Protection Agency reference dose (RfD) for methylmercury, the one-compartment pharmacokinetic model is used to convert fetal cord blood mercury (Hg) concentration to a maternal intake dose. This requires a ratio relating cord blood Hg concentration to maternal blood Hg concentration. No formal analysis of either the central tendency or variability of this ratio has been done. This variability contributes to the overall variability in the dose estimate. A ratio of 1.0 is implicitly used in the model, but an uncertainty factor adjustment is applied to the central tendency estimate of dose to address variability in that estimate. Thus, incorporation of the cord:maternal ratio and its variability into the estimate of intake dose could result in a significant change in the value of the RfD. We analyzed studies providing data on the cord:maternal blood Hg ratio and conducted a Monte Carlo-based meta-analysis of 10 studies meeting all inclusion criteria to generate a comprehensive estimate of the central tendency and variability of the ratio. This analysis results in a recommended central tendency estimate of 1.7, a coefficient of variation of 0.56, and a 95th percentile of 3.4. By analogy to the impact of the similar hair:blood Hg ratio on the overall variability in the dose estimate, incorporation of the cord:maternal ratio may support a 3-fold uncertainty factor adjustment to the central tendency estimate of dose to account for pharmacokinetic variability. Whether the information generated in this analysis is sufficient to warrant a revision to the RfD will depend on the outcome of a comprehensive reanalysis of the entire one-compartment model. We are currently engaged in such an analysis.

Objectives: The traditional manner to evaluate whether regulatory controls meet their public health goals of reducing adverse health effects associated with exposure to environmental pollutants is to compare measured concentrations of the target pollutant in the environment with a standard. A complementary approach is also to measure health-based indicators, e.g., changes in the prevalence of adverse health outcomes attributed to the pollutant. This manuscript presents the concepts of using asthma emergency room (ER) visits and hospital admission as potential health-based indicators for ozone., Methods: The frequency of ER visits and hospital admissions for asthma in New Jersey in 1995 was compared with daily ozone concentrations, to establish the consistency of the relationship and the presence of potential confounders, and to establish whether routinely documented adverse outcomes in asthmatics could serve as health-based indicators., Results: A mathematical model relating ER visits and hospital admissions of asthmatics to ozone concentration was developed for 1995, which was to be used as a baseline year within a health-based indicator program. A coherent relationship was found between same-day ambient air ozone concentrations and ER visits and 2-day time-lagged ambient ozone and hospital admissions during 1995; pollen was identified as a confounder and the association between ER visits and ozone concentration was similar to that determined for 1986 to 1990., Conclusions: Sufficient databases exist for ER visits by asthmatics in Northern and Central New Jersey, and throughout the state for hospital admissions, for these health outcomes to be used as health-based indicators, complementing air-monitoring data in assessing whether improvements in public health are occurring because of reduction in emissions of precursors of ozone.