Evaluation of the Cardiovascular Effects of Methylmercury Exposures: Current Evidence Supports Development of a Dose-Response Function for Regulatory Benefits Analysis

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. 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.