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Biomedical subjects

Alan H Stern

Publications and source records attributed to Alan H Stern.

12 recordsLinked to original sources

Comments on article "Toxicity and carcinogenicity of chromium compounds in humans" by Costa and Klein.

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.

Administration, Oral↗

Comparison of indoor mercury vapor in common areas of residential buildings with outdoor levels in a community where mercury is used for cultural purposes.

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.

Air Pollutants↗

A review of the studies of the cardiovascular health effects of methylmercury with consideration of their suitability for risk assessment.

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.

Adolescent↗

An examination of the trade-offs in public health resulting from the use of default exposure assumptions in fish consumption advisories.

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.

Animals↗

Mercury in commercial fish: optimizing individual choices to reduce risk.

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.

Animals↗

A revised probabilistic estimate of the maternal methyl mercury intake dose corresponding to a measured cord blood mercury concentration.

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.

Environmental Monitoring↗

Fish availability in supermarkets and fish markets in New Jersey.

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.

Animals↗

Do recent data from the Seychelles Islands alter the conclusions of the NRC Report on the toxicological effects of methylmercury?

In 2000, the National Research Council (NRC), an arm of the National Academy of Sciences, released a report entitled, "Toxicological Effects of Methylmercury." The overall conclusion of that report was that, at levels of exposure in some fish- and marine mammal-consuming communities (including those in the Faroe Islands and New Zealand), subtle but significant adverse effects on neuropsychological development were occurring as a result of in utero exposure. Since the release of that report, there has been continuing discussion of the public health relevance of current levels of exposure to Methylmercury. Much of this discussion has been linked to the release of the most recent longitudinal update of the Seychelles Island study. It has recently been posited that these findings supercede those of the NRC committee, and that based on the Seychelles findings, there is little or no risk of adverse neurodevelopmental effects at current levels of exposure. In this commentary, members of the NRC committee address the conclusions from the NRC report in light of the recent Seychelles data. We conclude that no evidence has emerged since the publication of the NRC report that alters the findings of that report.

Animals↗

An assessment of the cord blood:maternal blood methylmercury ratio: implications for risk assessment.

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.

Adult↗

Concepts in developing health-based indicators for ozone.

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.

Air Pollutants↗