Statement of Deborah C. Rice, Ph.D.,

Maine Department of Environmental Protection, Augusta, Maine

Health Effects of Methylmercury with Particular Reference to the U.S. Population

Hearing by the Senate Committee on Environment and Public Works, July 29, 2003

Deborah C. Rice, Ph.D., Maine Department of Environmental Protection, Augusta, Maine

deborah.c.rice@maine.gov, 207-287-7822

I would like to thank the Committee for this opportunity to present information on the adverse health consequences of exposure to methylmercury in the United States. Until three months ago, I was a senior toxicologist in the National Center for Environmental Assessment in the Office of Research and Development at the Environmental Protection Agency. I am a co-author of the document that reviewed the scientific evidence on the health effects of methylmercury for EPA, and which included the derivation of the acceptable daily intake level for methylmercury.

I would like to focus my presentation on four points that are key to understanding the health-related consequences of environmental mercury exposure. One: there is unequivocal evidence that methylmercury harms the developing human brain. Two: the Environmental Protection Agency used analyses of three large studies in its derivation of an acceptable daily intake level, including the study in the Seychelles Islands which found no adverse effects. Three: eight percent of women of child-bearing age in the United States have levels of methylmercury in their bodies above this acceptable level. And four: cardiovascular disease in men related to low levels of methylmercury has been documented, suggesting that a potentially large segment of the population may be at risk for adverse health effects.

The adverse health consequences to the nervous system of methylmercury exposure in humans were recognized in the 1950s with the tragic episode of poisoning in Minamata Bay in Japan, in which it also became clear that the fetus was more sensitive to the neurotoxic effects of methylmercury than was the adult. A similar pattern of damage was apparent in subsequent episodes of poisoning in Japan and Iraq. These observations focused the research community on the question of whether exposure to concentrations of methylmercury present in the environment might be producing neurotoxic effects that were not clinically apparent.

As a result, over half a dozen studies have been performed around the world to explore the effects of environmental methylmercury intake on the development of the child. Studies in the Philippines (Ramirez et al., 2003), the Canadian Arctic (McKeown-Eyssen et al., 1983), Ecuador (Counter et al., 1998), Brazil (Grandjean et al., 1999), French Guiana (Cordier et al., 1999) and Madeira (Murata et al., 1999) all found adverse effects related to the methylmercury levels in the children’s bodies. These included auditory and visual effects, memory deficits, deficits in visuospatial ability, and changes in motor function.

In addition to the above studies, there have been three major longitudinal studies on the effects of exposure to the mother on the neuropsychological function of the child: in the Faroe Islands in the North Atlantic (Grandjean et al., 1997), in the Seychelles Islands in the Indian Ocean (Myers et al., 1995), and in New Zealand (Kjellstrom et al., 1989). Two of these studies identified adverse effects associated with methylmercury exposure, whereas the Seychelles Islands study did not. Impairment included decreased IQ and deficits in memory, language processing, attention, and fine motor coordination. A National Research Council (NRC) National Academy of Sciences panel evaluated all three studies in their expert review, concluding that all three studies were well designed and executed (NRC, 2000). They modeled the relationship between the amount of methylmercury in the mother’s body and the performance of the child on a number of neuropsychological tests. From this analysis, they calculated a defined adverse effect level from several types of behavior in each of the three studies. These adverse effect levels represent a doubling of the number of children that would perform in the abnormally low range of function. The National Academy of Sciences panel also calculated an overall adverse effect level of methylmercury in the mother’s body for all three of the studies combined, including the negative Seychelles study. Thus the results of all three studies were included in a quantitative manner by the NRC.

The Environmental Protection Agency (EPA) used the analyses of the NRC in the derivation of the reference dose, or RfD, for methylmercury. The RfD is a daily intake level designed to be without deleterious effects over a lifetime. The EPA divided the defined deleterious effect levels calculated by the NRC by a factor of 10 in its RfD derivation. There are two points that need to be made in this regard. First, the factor of 10 does not represent a safety factor of 10, since the starting point was a level that doubled the number of low-performing children. Second, the EPA performed the relevant calculations for a number of measurements for each of the two studies that found deleterious effects a well as the integrative analysis that included all three studies modeled by the NRC, including the negative Seychelles study. The RfD is 0.10 ug/kg/day based on the Faroe Islands study alone or the integrative analysis of all three studies. The RfD would be lower than 0.10 ug/kg/day if only the New Zealand study had been considered. Only if the negative Seychelles Islands study were used exclusively for the derivation of the RfD, while ignoring the values calculated for the Faroe Islands and New Zealand studies, would the RfD be higher than the current value of 0.10 ug/kg/day. EPA believes that to do so would be scientifically unsound, and would provide insufficient protection to the U.S. population.

A substantial portion of U.S. women of reproductive age have methylmercury in their bodies that is above the level that corresponds to the EPA’s RfD. Data collected over the last two years as part of the National Health and Nutritional Examination Survey (NHANES 99+) designed to represent the U.S. population (CDC, Web) revealed that about eight percent of women of child-bearing age had blood levels of methylmercury above the level that the US EPA believes is “safe” (Schober et al., 2003). This translates into over 300,000 newborns per year potentially at risk for adverse effects on intelligence and memory, ability to pay attention, ability to use language, and other skills that are important for success in our highly technological society.

I would like to further comment here on the use of a factor of 10 by EPA to derive the allowable daily intake level (RfD) for methylmercury from the defined effect levels calculated by the National Research Council. The RfD corresponds to roughly 1 part per million (ppm) of methylmercury in maternal hair, from the defined effect level of about 11 ppm calculated by the NRC. But we know that there is no evidence of a threshold below which there are no adverse effects down to about 2–3 ppm in hair, the lowest levels in the Faroe Islands study. In fact, there is evidence from both the Faroe Islands (Budtz-Jrrgensen et al., 2000) and New Zealand (Louise Ryan, Harvard University, personal communication) studies that the change in adverse effect in the child as a function of maternal methylmercury level may be greater at lower maternal methylmercury levels than at higher ones. Therefore, the so-called safety factor almost certainly is less than 10, and may be closer to non-existent. Babies born to women above the RfD may be at actual risk, and not exposed to a level 10 times below a risk level.

There is an additional concern regarding the potential for adverse health consequences as a result of environmental exposure to methylmercury. Several years ago, a study in Finnish men who ate fish found an association between increased methylmercury levels in hair and atherosclerosis, heart attacks, and death (Salonen et al., 1995, 2000). Two new studies in the U.S. and Europe found similar associations between increased methylmercury levels in the bodies of men and cardiovascular disease (Guallar et al., 2002; Yoshizawa et al., 2002). Effects have been identified at hair mercury levels below 3 ppm. It is not known whether there is a level of methylmercury exposure that will not cause adverse effects. It is important to understand that the cardiovascular effects associated with methylmercury may put an additional, very large proportion of the population at risk for adverse health consequences as a result of exposure to methylmercury from environmental sources.

In summary, there are four points that I would like the Committee to keep in mind. First, at least eight studies have found an association between methylmercury levels and impaired neuropsychological performance in the child. The Seychelles Islands study is anomalous in not finding associations between methylmercury exposure and adverse effects. Second, both the National Research Council and the Environmental Protection Agency included the Seychelles Islands study in their analyses. The only way the acceptable level of methylmercury could be higher would be to ignore the two major positive studies that were modeled by the NRC, as well as six smaller studies, and rely solely on the single study showing no negative effects of methylmercury. Third, there is a substantial percentage of women of reproductive age in the United States with levels of methylmercury in their bodies above what EPA considers a safe level. As a result of this, over 300,000 newborns each year are exposed to methylmercury above levels US EPA believes to be “safe”. Fourth, increased exposure to methylmercury may result in atherosclerosis, heart attack, and even death from heart attack in men, suggesting that an additional large segment of the population may be at risk as a result of environmental methylmercury exposure.

Thank you for your time and attention.

References

Budtz-Jrrgensen, E., P. Grandjean, N. Keiding, et al. 2000. Benchmark dose calculations of methylmercury-associated neurobehavioral deficits. Toxicology Letters 112-113, 193-199.

Center for Disease Control and Prevention. Second National Report on Human Exposure to Environmental Chemicals. http://www.cdc.gov/exposurereport/pdf/SecondNER.pdf.

Cordier, S., and Garel, M. 1999. Neurotoxic risks in children related to exposure to methylmercury in French Guiana. INSERM U170 and U149—Study financed by the Health Monitoring Institute, National Institute of Health and Medical Research.

Counter, S.A., Buchanan, L.H., Laurell, G., and Ortega, F. 1998. Blood mercury and auditory neuro-sensory responses in children and adults in the Nambija gold mining area of Ecuador. Neurotoxicology 19, 185–196.

Grandjean, P., Weihe, P., White, R.F., Debes, F., Araki, S., Yokoyama, K., Murata, K., Srrensen, N., Dahl, R., and Jrrgensen, P.J. 1997. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicology and Teratology 19, 417-428.

Grandjean, P., White, R.F., Nielsen, A., Cleary, D., de Oliviera Santos, E.C. 1999. Methylmercury neurotoxicity in Amazonian children downstream from gold mining. Environmental Health Perspectives 107, 587-591.

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Kjellstrom, T., Kennedy, P., Wallis, S., and Mantell, C. 1989. Physical and mental development of children with prenatal exposure to mercury from fish. Stage 2: Interviews and psychological tests at age 6. National Swedish Environmental Protection Board, Report 3642 (Solna, Sweden).

McKeown-Eyssen, C.E., Ruedy, J., and Neims, A. 1983. Methylmercury exposure in Northern Quebec II. Neurological findings in children. American Journal of Epidemiology 118, 470–479.

Myers, G.J., Marsh, D.O., Cox, C., Davidson, P.W., Shamlaye, C.F., Tanner, M.A., Choi, A., Cernichiari, E., Choisy, O., and Clarkson, T.W. 1995. A pilot neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from a maternal fish diet. Neurotoxicology 16, 629–638.

Murata, K., Weihe, P., Renzoni, A., Debes, F., Vasconcelos, R., Zino, F., Araki, S., Jrrgensen, P.J., White, R.F., Grandjean, P. 1999. Delayed evoked potentials in children exposed to methylmercury from seafood. Neurotoxicology and Teratology 21, 343-348.

NRC (National Research Council). 2000. Toxicological effects of methylmercury. Committee on the Toxicological Effects of Methylmercury, Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Council. Washington, DC: National Academy Press.

Ramirez, G.B., Pagulayan, O., Akagi, H., Rivera, A.F., et al. 2003. Tagum Study II, Follow-up study at two years of age after prenatal exposure to mercury. Pediatrics 111, e289–e295.

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