scientific basis for the risk assessments conducted by EPA and other regulatory and health agencies. The committee also reviewed new findings that have emerged since the development of the current RfD and met with the investigators of major ongoing epidemiological studies to examine and compare the methods and results.

Mercury (Hg) is pervasive and persistent in the environment, released from a large variety of natural and anthropogenic sources. The serious health impacts of high-level exposures have long been recognized. Between 1950 and 1975, major poisoning episodes in Japan and Iraq resulted in outbreaks of serious neurotoxic effects, including death, and led to the identification of developmental neurotoxicity as the health effect of greatest concern following high-level episodic exposure. As a result of its well-recognized toxicity, widespread industrial use, and environmental persistence, Hg has been extensively studied. Compared with data bases on many other pollutants, there is a robust data base on Hg, which includes environmental fate and transport; examination of toxicokinetics and toxicodynamics; biological and environmental measures of exposure and dose; and in vitro, animal, and human studies for a broad range of toxicity end points.

Historically, epidemiological investigations have focused on high exposures and related health impacts. More recently, large prospective epidemiological studies have been conducted to examine chronic low-level MeHg exposure. These studies examined the association between subtle end points of neurotoxicity and prenatal exposure measured by maternal markers of prior exposure. These markers are presumed to reflect maternal MeHg exposure from fish consumption. The committee focused on these studies because they provide the most comprehensive evidence of low-dose MeHg toxicity and they examine the exposure pathway most relevant to U.S. population exposures, including the sensitive population of children who were exposed to MeHg in utero.

THE CURRENT EPA REFERENCE DOSE

EPA defines an RfD as an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime (EPA 1997a). The



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