strict diagnostic requirements and case defini- tions assumed that the disease was a charac- teristic all-or-none phenomenon, thereby excluding less distinctive cases and obscuring the dose–effect relationship. The first likely cases of developmental methylmercury poisoning were described in 1952 (Engleson and Herner 1952) and sub- sequently reported from Minamata (Harada 2004; Social Scientific Study Group on Minamata Disease 1999); replication in labo- ratory animals was published in 1972 (Spyker et al. 1972), and the first prospective popula- tion study of prenatal methylmercury toxicity due to contaminated seafood in humans was published in 1986 (Kjellström et al. 1986). However, scientific consensus on prena- tal vulnerability was hampered by focusing on uncertainties in the evidence, and inter- national agreement on the need for protection against prenatal exposures was reached only in 2003. Environmental methylation of mercury in sediment was discovered accidentally because systematic studies of the environmental fate of mercury were not conducted and because initial studies focused only on the total mer- cury concentration. Recognition of food chain contamination and environmental bio- accumulation of methylmercury was therefore delayed. A key experiment showing that cats developed the characteristic disease when fed effluent water from a polluting factory was suppressed by the sponsoring company, and the detailed results became available only after a delay of 40 years (Eto et al. 2001). Industry representatives advanced alternative explana- tions and used the early diversity of scientific opinions for its legal argument that toxicity was not the responsibility of industry, nor could it have been anticipated, thereby causing a sub- stantial delay of remediation, compensation, and prevention. After the publication of new data on adverse effects of low-level exposures to methylmercury, regulatory agencies requested scientific scrutiny. Expert committees empha- sized uncertainties and weaknesses in the available data. Less attention was paid to the question of what could have been known, given the research methods and possibilities, and whether developmental neurotoxicity at low methylmercury doses could be ruled out. The reports also generally ignored that meas- urement imprecision most likely resulted in an underestimation of the true effects. Instead, more research was recommended. The insistence on solid evidence promoted by polluters and regulatory agencies there- fore agreed with a desire among research- ers to expand scientific activities in this area. However, the wish to obtain more complete proof had the untoward effect of delaying corrective action. Although Jun Ui’s critique (D’Itri and D’Itri 1978), given in the introduction of this review, referred to Japanese regulatory agencies themselves being afflicted by signs of methylmercury poisoning, here we suggest that environmental health research, too, has suffered tunnel vision, forgetfulness, lack of 2.02 1.98 ) 1.94 c e s m ( P E BA 1.90 1.86 1.82 0.01 U.S. EPA (2001) JECFA (2003) JECFA (1978) 0.10 1.00 10.00 Hair mercury (µg/g) Figure 1. Association between brainstem auditory evoked potential (BAEP) latency (interpeak III–IV at 20 Hz) and dietary exposure to methylmercury (reflected by hair mercury concentration) in 14-year-old Faroese children. Data are from examinations of a Faroese cohort of 878 subjects at 14 years of age. Each vertical line represents one subject, dotted lines indicate the 95% confidence limits, and arrows represent three methylmercury exposure limits. Modified from Murata et al. (2004). Environmental Health Perspectives • volume 118 | number 8 | August 2010 Environmental health lessons from methylmercury coordination, and some of the other symp- toms noted in poisoning cases. Like methyl- mercury poisoning itself, such abnormalities deserve preventative action. Ref Rencs Ahlmark A. 1948. Poisoning by methyl mercury compounds. Br J Ind Med 5(3):117–119. Akagi H, Grandjean P, Takizawa Y, Weihe P. 1998. Methyl- mercury dose estimation from umbilical cord concen- trations in patients with Minamata disease. Environ Res 77(2):98–103. Amin-Zaki L, Majeed MA, Clarkson TW, Greenwood MR. 1978. Methylmercury poisoning in Iraqi children: clinical observa- tions over two years. BMJ 1(6113):613–616. Bakir F, Damluji SF, Amin-Zaki L, Murtadha M, Khalidi A, al-Rawi NY, et al. 1973. Methylmercury poisoning in Iraq. Science 181(96):230–241. Borg K. 1969. Kvicksilverproblematikken inom vår terrestriske fauna, dess upptäckt och vidareutveckling. Nord Hyg Tidskr 50:9–13. Budtz-Jorgensen E, Grandjean P, Weihe P. 2007. Separation of risks and benefits of seafood intake. Environ Health Perspect 115:323–327. Budtz-Jorgensen E, Keiding N, Grandjean P. 2004. Effects of exposure imprecision on estimation of the benchmark dose. Risk Anal 24(6):1689–1696. Budtz-Jorgensen E, Keiding N, Grandjean P, Weihe P, White RF. 2003. Consequences of exposure measurement error for confounder identification in environmental epidemiology. Stat Med 22(19):3089–3100. Clarkson TW, Magos L. 2006. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 36(8):609–662. Clarkson TW, Strain JJ. 2003. Nutritional factors may modify the toxic action of methyl mercury in fish-eating popula- tions. J Nutr 133(5 suppl 1):1539S–1543S. Crump KS, Kjellstrom T, Shipp AM, Silvers A, Stewart A. 1998. Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. Risk Anal 18(6):701–713. Davis LE, Kornfeld M, Mooney HS, Fiedler KJ, Haaland KY, Orrison WW, et al. 1994. Methylmercury poisoning: long- term clinical, radiological, toxicological, and pathological studies of an affected family. Ann Neurol 35(6):680–688. Dietz R, Outridge PM, Hobson KA. 2009. Anthropogenic contri- butions to mercury levels in present-day Arctic animals—a review. Sci Total Environ 407(24):6120–6131. D’Itri PA, D’Itri FM. 1978. Mercury contamination: a human tragedy. Environ Manag 2(1):3–16. Edwards GN. 1865. Two cases of poisoning by mercuric methide. Saint Bartholomew’s Hosp Rep 1:141–150. Endo T, Haraguchi K, Hotta Y, Hisamichi Y, Lavery S, Dalebout ML, et al. 2005. Total mercury, methyl mercury, and selenium levels in the red meat of small cetaceans sold for human consumption in Japan. Environ Sci Technol 39:5703–5708. Engleson G, Herner T. 1952. Alkyl mercury poisoning. Acta Paediatr 41(3):289–294. Eto K, Yasutake A, Korogi Y, Akima M, Shimozeki T, Tokunaga H, et al. 2002. Methylmercury poisoning in common marmosets—MRI findings and peripheral nerve lesions. Toxicol Pathol 30(6):723–734. Eto K, Yasutake A, Nakano A, Akagi H, Tokunaga H, Kojima T. 2001. Reappraisal of the historic 1959 cat experiment in Minamata by the Chisso factory. Tohoku J Exp Med 194(4):197–203. European Commission. 2001. Commission Regulation (EC) No 466/2001 of 8 March 2001 Setting Maximum Levels for Certain Contaminants in Foodstuffs. Available: http://eur-lex. europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2001:077:0001: 0013:EN:PDF [accessed 8 July 2010]. European Food Safety Authority. 2004. Opinion of the Scientific Panel on Contaminants in the Food Chain Related to Mercury and Methylmercury in Food. EFSA-Q-2003-030. Brussels:European Food Safety Authority. Available: http:// www.efsa.europa.eu/en/scdocs/doc/34.pdf [accessed 8 July 2010]. European Union. 2007. Directive 2007/51/EC of the European Parliament and of the Council of 25 September 2007 Amending Council Directive 76/769/EEC Relating to Restrictions on the Marketing of Certain Measuring 1143