The Panel on Health Risks and Toxicological Effects of Methylmercury: Donna Mergler, Henry A. Anderson, Laurie Hing Man Chan, Kathryn R. Mahaffey, Michael Murray, Mineshi Sakamoto and Alan H. Stern Methylmercury Exposure and Health Effects in Humans: A Worldwide Concern The paper builds on existing literature, highlighting current understanding and identifying unresolved issues about MeHg exposure, health effects, and risk assess- ment, 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 socio- economic spectrum, who consume predatory fish or for whom fish is a dietary mainstay. Methylmercury devel- opmental 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 popula- tions, 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. INTRODUCTION The Panel on Health Risks and Toxicological Effects of Methylmercury received the mandate to describe and synthesize current scientific knowledge on methylmercury (MeHg) expo- sure and its effects in humans and to identify research gaps. The present paper is not intended to be a comprehensive review and presentation of all the literature on MeHg exposure and effects in humans but builds on earlier literature, other reviews, and more recent literature in highlighting the current understanding in the field and what we consider to be remaining unresolved issues. Humans are exposed to different forms of mercury (Hg), and potential health risks from forms other than MeHg can occur, including mercury vapor from dental amalgams, as well as from occupational exposures (e.g., dental offices, chloralkali plants, fluorescent lamp factories, mercury mining) and from artesanal and small-scale gold and silver mining operations (1– 5), the present document does not cover these exposures, because the pathways of exposure and effects differ from those for MeHg. Here, we examine issues of MeHg exposure, studies on its health effects and major risk assessments, and conclude with our consensus statement. MeHg Exposure Sources of exposure. Methylmercury contamination poses a particular challenge to public health because this toxicant is mainly contained in fish, a highly nutritious food, with known benefits for human health. Moreover, fish are culturally vital for many communities and constitute an important global com- modity. Although we often refer to ‘‘fish’’ in a generic way, all fish do not have similar amounts of mercury. As a result of bioaccumulation of MeHg through multiple levels of the aquatic food web, higher tropic-level pelagic fish can be contaminated with MeHg at concentrations in excess of 1 part per million (ppm). The concentrations of total Hg vary widely across fish and shellfish species, with the mean values differing by as much as 100-fold (6). Methylmercury is bound to proteins, as well as to free amino acids, that are components of muscle tissues, and are not removed by any cooking or cleaning processes that do not destroy muscle tissues. Although in general, MeHg accumulates in fish through the food chain, consumption of farmed fish can also lead to MeHg exposures, in part, because of the presence of MeHg in feed (7). Some studies have shown no significant difference in MeHg levels in farmed vs. wild salmon, although concentrations in both cases are relatively low (8, 9). Although fish and shellfish are the predominant sources of MeHg in the diets of humans and wildlife, a few reports of other sources exist. Rice cultivated in areas contaminated with mercury can contain relatively high levels of MeHg (10). Methylmercury has also been reported in organ meats of terrestrial animals (11), as well as in chicken and pork, probably as a result of the use of fish meal as livestock feed (12). Some communities also have higher MeHg exposure because of the consumption of fish-eating marine mammals (13, 14). Profiles of exposure. Although most reports on MeHg exposure focused on specific populations generally assumed to have high levels of fish consumption, estimates of general populations exposure exist for the United States (15, 16), Germany (17), and Japan (18) [summarized in Pirrone and Mahaffey (19)]. For populations that are not selected on the basis of high fish consumption, mean hair Hg levels generally range from .0.1 lgg 1 to ,1.0 lgg 1 (20–25). The mean blood Hg for such populations is generally in the range of ,1.0 lgL 1 to ,5.0 lgL 1 , although, worldwide there are fewer data on MeHg exposure based on blood than on hair. In the United States nationally, about 5–10% of the population of women of childbearing age have hair levels exceeding 1.0 lgg 1 (16) and blood levels exceeding 5 lgL 1 (26). In Japan, where more fish is consumed, 73.7% of women of this age have hair levels above 1.0 lgg 1 and 1.7% above 5 lgg 1 (18). In Germany, the 1998 geometric mean blood level was 0.58 lgL 1 (17). High levels of Hg exposure were identified in numerous fish- eating populations throughout the world [for reviews see: Pirrone and Mahaffey (19)]. Many of these live near oceans, major lakes and rivers, or hydroelectric dams, and are often dependent on local catch, with fish an integral part of their cultural traditions. In the sea islands of the Faroes and Seychelles, median mothers’ hair Hg concentrations were 4.5 lgg 1 [with 27% above 10 lgg 1 (27)] and 5.8 lgg 1 (28), respectively. In the river basins of the Amazon, where a large number of studies was carried out on populations for whom freshwater fish is a dietary mainstay, median hair Hg levels typically range between 5 lgg 1 and 15 lgg 1 (29–34). Despite the importance of local catch, fish is also a global commodity and market fish, such as shark, tuna, and swordfish, or canned white tuna (35), consumed by persons living far away from the source can likewise have high levels of MeHg. In the United States, individuals with high blood Hg concentrations were reported among affluent urbanites who ate large quantities Ambio Vol. 36, No. 1, February 2007 3 Ó Royal Swedish Academy of Sciences 2007 http://www.ambio.kva.se