Methylmercury Seychelles studies

The diet in the two studies was also considerably different. The majority of the mercury exposure to the Faroe Island population came from whale meat (estimated at about 3 ppm in muscle tissue) with a relatively small portion coming from fish. Some of the mercury in whale meat is in the form of inorganic mercury. In the Seychelles study, all of the mercury came from fish as methylmercury with concentrations of around 0.3 ppm. Whale meat blubber is widely consumed in the Faroe Islands and also contains polychlorinated biphenyls (PCBs). Grandjean et al. (1995b) estimated a daily intake of 200 g of PCB. This value can be compared to the Tolerable Daily Intake of PCBs established by the FDA of 60-70 g/day for an adult. Further statistical analysis of the possible influence of PCBs on the observed study results needs to be conducted (see the discussion below on Peer Panel IReview of Kev Studies for additional comments). 

Based upon the discussions at the Raleigh workshop and the individual panel findings, as well as the aforementioned Atlanta expert panel review, ATSDR has determined that the Seychelles study represents the most appropriate and reliable database currently available for calculation of a chronic oral MRL from a population exposed only to methylmercury by a relevant route of exposure for the overall U.S. population. 

Again, ATSDR would like to strongly emphasize that both the Seychelles study and the Faroese study represent credible scientific contributions by widely respected research teams. Similarly, both studies extend our knowledge base well beyond that provided by the Iraqi study and make significant contributions to our understanding of the effects of low-level exposure to methylmercury by an exposure... 

To ensure a health guidance value based upon the best use of the Seychelles study data (widely considered the most relevant data available), ATSDR evaluated alternate MRL derivation methods for methylmercury. One such approach is to use the mean total mercury level of 6.8 ppm in maternal hair for the entire Seychellois study cohort. Using the same formula as in the previous MRL calculation,... 

Marsh DO, Clarkson TW, Myers GJ, et al. 1995a. The Seychelles study of fetal methylmercury exposure and child development introduction. Neurotoxicol 16(4) 583-596. 

To ensure a health guidance value based upon the best use of the Seychelles study data (widely considered the most relevant data available), ATSDR evaluated alternate MRL derivation methods for methylmercury. 

Marsh DO, Clarkson TW, Myers GJ, et al The Seychelles study of fetal methylmercury exposure and child development introduction. Neurotoxicology 16 583-596,1995a Marsh DO, Turner MD, Smith JC, et al Fetal methylmercury study in a Peruvian fisheating population. Neurotoxicology 16 717-726, 1995b Mastromatteo E Recent occupational health experiences in Ontario. J Occup Med 7 502-511, 1965... 

Several recent epidemiological studies have involved examination of populations that consume unusually high levels of fish. One of these, conducted in the islands of the Seychelles, has not so far revealed behavioral and learning impairments in children whose mothers exhibited mercury levels (measured in hair) higher than those typically seen in the United States and European countries. But another study, conducted in the Faroe Islands, turned up evidence of cognitive and behavioral impairments in children. Scientists have struggled to understand why two well-done studies have produced such different outcomes, and some possible reasons have been suggested. The EPA and public health officials have acted on the basis of the Faroe data, out of both caution and also because they seem to be supported by other, more limited data, and by experimental studies. The debate is not so much about whether methylmercury is a developmental toxicant, but rather over the dose required. 

On the basis of maternal hair concentration, the third study (conducted in the Seychelles) did not find any association between prenatal methylmercury exposure and adverse neuro-psychologic effects (Myers et al. 2003). Reasons for the discrepancies are not known but have been suggested to include differences in the child s age at testing, genetic susceptibilities of the populations, patterns of exposure (episodic vs continuous), and coexposure to polychlorinated biphenyls in the Faroes but not Seychelles populations (Rice et al. 2003). 

The second prospective study of in utero exposure to methylmercury was initiated in the Republic of Seychelles and enrolled about 800 mother-infant pairs (Myers et al., 1995). In contrast to the Faroe Islands study, the investigation in the Seychelles did not find evidence of methylmercury-related adverse effects on the neuro-behavioural development of children through nine years of age (Myers et al., 2003). In some instances, prenatal mercury exposure was actually associated with precocious behaviour, and important developmental milestones were reached more quickly in the most highly exposed subjects. 

Myers GJ, Davidson PW, Cox C, Shamlaye CF, Palumbo D, Cernichiari E, Sloane-Reeves J, Wilding GE, Kost J, Huang LS, Clarkson TW (2003) Prenatal methylmercury exposure from ocean fish consumption in the Seychelles child development study. Lancet, 361(9370) 1686-1692. 

The concerns aroused by methylmercury in fish, arising from the susceptibility of the developing brain to this neurotoxicant, led to the design and execution of two large prospective studies. One was located in the Seychelle islands, which lie in the Indian Ocean. The other was located in the Faroe Islands, which lie in the North Sea. Both communities consume large quantities of seafood. In the Seychelles, it is almost exclusively in the form of fish. In the Faroes, virtually all the methylmercury comes from the consumption of pilot whales, which are also contaminated with polychlorinated biphenyls (PCBs). Both studies assayed maternal exposures to methylmercury. In the Seychelles, maternal hair was used as the index it reflects the history of blood levels. The Faroes study relied primarily on cord blood. 

The chronic oral MRL for methylmercury is based upon the Seychelles Child Development Study (SCDS), in which over 700 mother-infant pairs have, to date, been followed and tested from parturition through 66 months of age (Davidson et al. 1998). The SCDS was conducted as a double-blind study and... 

On November 18-20, 1998, a workshop on Scientific Issues Relevant to the Assessment of Health Effects from Exposure to Methylmercury was conducted in Raleigh, North Carolina. The workshop was jointly sponsored by the U.S. Department of Health and Human Services (DHHS), the National Institute of Environmental Health Sciences (NIEHS), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the U.S. Environmental Protection Agency (EPA), the National Oceanic and Atmospheric Administration (NOAA), the Office of Science and Technology Policy (OSTP), the Office of Management and Budget (OMB), and ATSDR. The purpose of this workshop was to discuss and evaluate the major epidemiologic studies that associated methylmercury exposure and the results of an array of developmental measures in children. These studies monitored and evaluated exposed populations in Iraq, the Seychelles Islands, the Faroe Islands, and the Amazon River Basin. A number of animal studies were also considered in support of a human health risk assessment. 

There are differences in the outcomes of these epidemiology studies on low level chronic exposures to methylmercury in foods. Davidson et al. (1998) report no adverse developmental effects associated with prenatal and postnatal exposure to methylmercury in fish in a Seychelles Island cohort of children at age 66 months (n=708). The exposure levels are reflected in maternal hair levels of 6.8 ppm for the prenatal exposure (SD=4.5, n=711) and children s hair levels of 6.5 ppm (SD=3.3, n=708) for both the prenatal and subsequent postnatal exposure. The age-appropriate main outcome measures included (1) the... 

Davidson PW, Myers GJ, Cox C, et al. 1998. Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment Outcomes at 66 months of age in the Seychelles child development study. JAMA 280(8) 701-707. 

Experimental design. This MRL is based on the results of the Seychelles Child Development Study (SCDS), a series of evaluations on a population in the Seychelles Islands. The chronic oral MRL for methylmercury is based upon the Seychelles Child Development Study (SCDS), in which over 700 mother-infant pairs have, to date, been followed and tested from parturition through 66 months of age (Davidson et al. 1998). The SCDS was conducted as a double-blind study and used maternal hair mercury as the index of fetal exposure. Enrollees were recruited by the head nurse/hospital midwife by asking the mothers if they wished to participate in the study when they arrived at the hospital for delivery. The first 779 who did not decline participation became the mothers in the study cohort. Of the initial 779 mothers enrolled in the study at parturition, 740 remained at the predetermined child testing age of 6.5 months,... 

Davidson, P.W., G.J. Myers, C. Cox, C. Axtell, C. Shamlaye, J. Sloane-Reeves, E. Cemichiari, L. Needham, A. Choi, Y. Wang, M. Berlin, and T.W. Clarkson. 1998. Effects of prenatal and postnatal methylmercury exposure from fish consumption on neurodevelopment Outcomes at 66 months of age in the Seychelles Child Development Study. JAMA 280 (8) 701-707. 

Shamlaye, and T.W. Clarkson. 1998. Semiparametric modeling of age at achieving developmental milestones after prenatal exposure to methylmercury in the Seychelles child development study. Environ. Health Perspect. 106(9) 559-564. 

Axell T, Nilner K, Nilsson B Clinical evaluation of patients referred with symptoms related to oral galvanism. Swed Dent J 7 169-178,1983 Axtell CD, Cox C, Myers GJ, et al Association between methylmercury exposure from fish consumption and child development at five and a half years of age in the Seychelles Child Development Study an evaluation of nonlinear relationships. Environ Res 84 71-80, 2000... 

Myers GJ, Davidson PW, Cox C, et al Neurodevelopmental outcomes of Seychellois children sixty-six months after in utero exposure to methylmercury from a maternal fish diet pilot study. Neurotoxicology 16 639-652, 1995a Myers GJ, Davidson PW, Cox C, et al Summary of the Seychelles child development study on the relationship of fetal methylmercury exposure to neurodevelopment. Neurotoxicology 16 711-716,1995b... 

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