Health effects and risk assessment

Detailed risk assessments for methylmercury have been recently published by national and international bodies (e.g., the (U.S.) National Research Council (NRC, 2000), the U.S. Environmental Protection Agency (U.S.EPA, 2001), and the Joint FAO/WHO Expert Committee on Food Additives (JECFA, 2003). These reports concluded that the developing brain is the main target for methylmercury toxicity, and they emphasized the prospective epidemiological studies as the main basis for deriving an exposure limit. The same conclusion was reached in UNEP's global assessment (UNEP, 2002). Evidence from poisoning outbreaks in Japan and Iraq have clearly demonstrated the severe and widespread damage that may occur to the brain when exposed to methylmercury during development. In Minamata, Japan, it was noted that the pregnant mother could appear in good health, while her child would be born with serious congenital methylmercury poisoning. However, the confirmation of methylmercury as the etiologic agent came late, and case-related exposure information was therefore difficult to obtain. After the Iraqi poisoning episode, which happened during a famine, exposure information was gleaned from segmental analysis of long hair strands from the mothers, while assuming a constant hair growth rate. Although these studies do not provide detailed dose-response relationships, they demonstrated the serious consequences of excess exposures to this neurotoxicant and documented that the developing brain is a highly sensitive target. This paper reviews the human evidence with particular emphasis on recent epidemiological data on neurobehavioral effects, and it discusses the uncertainties involved in assessing human health risks based on observational studies. Three major prospective cohort studies have been conducted in New Zealand, the Faroe Islands, and the Seychelles. Crosssectional studies of neurobehavioral function will also be considered, as will the recent evidence of methylmercury-associated cardiovascular disease.