Elsevier

NeuroToxicology

Volume 22, Issue 5, October 2001, Pages 667-675
NeuroToxicology

Contending with Contradictory Data in a Risk Assessment Context: The Case of Methylmercury

https://doi.org/10.1016/S0161-813X(01)00040-7Get rights and content

Abstract

Two large sample, prospective longitudinal studies — one in the Seychelles Islands in the Indian Ocean, the other in the Faroes Islands in the North Sea — were conducted during the 1990s to examine the effects of prenatal methylmercury exposure on intellectual function in childhood. The Faroes study found evidence linking this exposure to adverse outcome, but the Seychelles study did not. A peer review workshop held in Raleigh, NC, in 1998 concluded that the inconsistencies between the Faroes and Seychelles findings could be explained by differences in study design and sources of exposure. The US Environmental Protection Agency contracted with the National Academy of Sciences (NAS) to convene an expert panel to provide guidance for a new risk assessment for methylmercury. The NAS panel reviewed the Faroes and Seychelles studies in light of data from a smaller New Zealand study and other data not available to the Raleigh reviewers. These additional data provided evidence of adverse effects in studies whose design and source of exposure were similar to that in the Seychelles, leading the NAS panel to conclude that the weight of the evidence supported the Faroes findings. A power analysis, conducted by computing standardized regression coefficients for the three studies, indicated that many of the Faroes findings were so subtle that the power to detect them in the Seychelles study, despite its large sample size, was only about 50%. Because prospective epidemiological studies are often hampered by limited control over confounding and other factors, including unmeasured between cohort differences in genetic vulnerability and nutritional adequacy, inferences about toxicity often depend heavily on a qualitative assessment of the weight of the evidence from multiple studies.

Section snippets

INTRODUCTION

In 1998, the US Congress passed legislation requiring the US Environmental Protection Agency (EPA) to fund a National Academy of Sciences (NAS) expert panel to evaluate the toxicological effects of methylmercury. This legislation was passed in response to the EPA’s announcement of plans to conduct a new risk assessment for methylmercury based on findings from two recently published, large-scale, prospective longitudinal studies — one in the Seychelles Islands in the Indian Ocean (Davidson et

THE SEYCHELLES AND FAROE ISLANDS STUDIES

The Seychelles and Faroe Islands studies were conducted during the 1990s to investigate the neurodevelopmental risks associated with chronic, low-level exposure to methylmercury from fish. Both examined heavy fish consuming populations and performed extensive neuropsychological assessments during childhood. The Faroes are also exposed to methylmercury from a second source; namely, pilot whale meat, which bioaccumulates very significant levels of methylmercury. Methylmercury concentrations in

THE RALEIGH WORKSHOP

The contrasting findings from these two well-designed, state-of-the-art epidemiological studies presented a quandary to scientists and government regulators. How is it possible for one study to provide consistent evidence of adverse effect across a range of developmental outcomes while a second, well-designed large sample study does not find even a suggestion of adverse effect? To address this question, a peer review workshop was convened in Raleigh, NC, in November 1998, sponsored by the

THE NATIONAL ACADEMY OF SCIENCES (NAS) PANEL

In the fall of 1998, the EPA proposed new regulations to limit mercury emissions from coal-powered utility power plants in the midwest. Based on the contradictory findings from the Faroes and Seychelles studies, several midwestern Congressional representatives argued that the scientific basis for methylmercury toxicity at contemporary levels of environmental exposure is uncertain. Congressional representatives from the northeast, however, strongly supported reductions in the levels of

CONCLUSIONS

Prospective epidemiological studies in humans are often hampered by limited control over confounding and other factors, including unmeasured between cohort differences in genetic vulnerability, nutritional adequacy, and pattern of exposure. In the final analysis, inferences about toxicity, therefore, often depend heavily on qualitative assessments regarding the weight of the evidence across multiple studies, some of which are clearly sounder and more convincing than others. The New Zealand

Acknowledgements

I would like to thank the other members of the NAS panel (National Research Council, 2000) — Robert L. Goyer (chair), H. Vasen Aposhian, Lenore Arab, David C. Bellinger, Thomas M. Burbacher, Thomas A. Burke, Lynda M. Knobeloch, Louise M. Ryan, and Alan H. Stern — all of whom made significant contributions to the thinking and analyses reviewed in this paper.

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