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.