Abstract and Introduction
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.
Methylmercury (MeHg) is a widespread and particularly toxic form of mercury (Hg). It results from the conversion of inorganic Hg to a methylated form by aquatic microorganisms and can bioaccumulate in the aquatic food web. Dietary intake of MeHg, primarily through ingestion of contaminated fish and seafood, is recognized as a significant public health concern, primarily because of its well-studied neurodevelopmental toxicity in fetuses and children. However, a growing body of evidence suggests that MeHg exposure may also lead to increased risks of adverse cardiovascular impacts in exposed populations.
In a comprehensive review of MeHg-related health effects in 2000, the National Research Council (NRC) concluded that neurodevelopmental impacts from prenatal MeHg exposures are the most sensitive and best-documented end points (NRC 2000). The report also found limited evidence of adverse cardiovascular effects at similar levels of exposure but did not reach firm conclusions on the cardiovascular impact of MeHg intake.
Since the publication of the NRC report, the U.S. Environmental Protection Agency (EPA) benefits assessments of rules controlling Hg emissions, such as the Clean Air Mercury Rule, have quantified neurodevelopmental benefits of reducing MeHg exposures to fetuses and children (U.S. EPA 2005). [For a diagram outlining the U.S. EPA's benefits assessment process, see Supplemental Material, Figure 1 (doi:10.1289/ehp.1003012).] However, Rice et al. (2010) developed a probabilistic analysis that characterized the plausible distribution of health and economic benefits associated with a reduction in MeHg exposure and reported that 80% of the benefits were associated with reductions in fatal heart attacks, and the remainder with IQ gains. Therefore, omitting these effects, if real, could result in a significant downward bias on the economic value of benefits ascribed to rules that control Hg emissions. Other assessments have reviewed the evidence for cardiovascular risk from MeHg exposure (Mozaffarian 2009; Stern 2005) and the balance of cardiovascular risks and benefits from MeHg exposure in conjunction with fish intake (Mozaffarian and Rimm 2006). However, previous assessments have not addressed the full range of potential cardiovascular health effects and have not focused on the development of dose– response relationships between MeHg and these individual cardiovascular effects.
Consistency and strength of association for Hg–cardiovascular risks: RRs and odds ratios (ORs). Abbreviations: CI, confidence interval; Max, maximum hair Hg. Adapted from Rice et al. (2010). "Swedish" results refer to NSHDS. The plot of the HPFS ("Health Professionals") represents the results of a separate multivariate analysis (n = 220) excluding subjects likely exposed occupationally to inorganic Hg (i.e., dentists). To convert toenail Hg levels reported in EURAMIC and HPFS to hair Hg levels, Rice et al. (2010) used the regression model developed by Ohno et al. (2007) from an analysis excluding women with artificial hair waving. To convert the Ery-Hg concentrations reported in NSHDS to hair Hg, Rice et al. (2010) first estimated the corresponding Hg levels expected in whole blood by multiplying the concentration of Hg in the erythrocytes by the specific gravity of erythrocytes (1,093 g/L) and the average male hematocrit (46%). They then used data from the World Health Organization that measured the distribution of MeHg between human erythrocytes and plasma (20:1) and a blood:hair partition estimate (Allen et al. 2007; Shipp et al. 2000).
In January 2010, the U.S. EPA convened a workshop in Washington, DC, to review the current science concerning cardiovascular impacts of MeHg exposures and to elicit recommendations about whether these effects should be included in benefits assessments of future Hg rules [for a list of questions posed by the U.S. EPA to workshop participants, see Supplemental Material (doi:10.1289/ehp.1003012)]. The invited panel consisted of nine individuals, all coauthors of this article, with expertise spanning epidemiology, clinical medicine, toxicology, risk and exposure assessment, biostatistics, and uncertainty analysis.
This article discusses the current literature and presents the recommendations of the assembled panel. In brief, we recommend the development of a dose–response function relating MeHg exposures with myocardial infarction (MI), for use in regulatory benefits analyses of future rules targeting Hg emissions.