Methylmercury and brain development: imprecision and underestimation of developmental neurotoxicity in humans.
Methylmercury is now recognized as an important developmental neurotoxicant, though this insight developed slowly over many decades. Developmental neurotoxicity was first reported in a Swedish case report in 1952, and from a serious outbreak in Minamata, Japan, a few years later. Whereas the infant suffered congenital poisoning, the mother was barely harmed, thus reflecting a unique vulnerability of the developing nervous system. Nonetheless, exposure limits for this environmental chemical were based solely on adult toxicity until 50 years after the first report on developmental neurotoxicity. Even current evidence is affected by uncertainty, most importantly by imprecision of the exposure assessment in epidemiological studies. Detailed calculations suggest that the relative imprecision may be as much as 50%, or greater, thereby substantially biasing the results toward the null. In addition, as methylmercury exposure usually originates from fish and seafood that also contains essential nutrients, so-called negative confounding may occur. Thus, the beneficial effects of the nutrients may appear to dampen the toxicity, unless proper adjustment is included in the analysis to reveal the true extent of adverse effects. These problems delayed the recognition of low-level methylmercury neurotoxicity. However, such problems are not unique, and many other industrial compounds are thought to cause developmental neurotoxicity, mostly with less epidemiological support than methylmercury. The experience obtained with methylmercury should therefore be taken into account when evaluating the evidence for other substances suspected of being neurotoxic.
Harvard School of Public Health, Boston, MA, USA. pgrand@hsph.harvard.edu
Philippe
P
Grandjean
Katherine T
KT
Herz
D001921:Brain / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*
D008767:Methylmercury Compounds
Ambul Pediatr. 2003 Jan-Feb;3(1):18-23
12540249
Neurotoxicol Teratol. 2001 Jul-Aug;23(4):305-17
11485834
Arch Environ Health. 1990 Nov-Dec;45(6):355-8
2270954
Neurotoxicology. 1995 Winter;16(4):597-612
8714866
Arch Gewerbepathol Gewerbehyg. 1956;15(2):186-202
13395401
Environ Res. 1989 Aug;49(2):318-32
2473897
Environ Res. 2010 Apr;110(3):226-36
20116785
Ann Epidemiol. 2006 Jun;16(6):439-47
16275013
Neurotoxicology. 2009 Jan;30(1):37-46
18992767
Br J Ind Med. 1948 Jul;5(3):117-9
18873550
Stat Med. 2003 Oct 15;22(19):3089-100
12973789
Environ Health Perspect. 1995 Sep;103 Suppl 6:135-42
8549462
Neurotoxicology. 1995 Winter;16(4):689-704
8714873
Crit Rev Toxicol. 1995;25(1):1-24
7734058
Am J Epidemiol. 1983 Oct;118(4):470-9
6637974
Head Neck Surg. 1980 Mar-Apr;2(4):312-20
7364587
Lancet. 2003 Aug 23;362(9384):664-5; author reply 665
12944071
Environ Res. 1993 Oct;63(1):157-69
8404770
Neurotoxicol Teratol. 1997 Nov-Dec;19(6):417-28
9392777
Environ Res. 2010 Oct;110(7):699-704
20673887
Lancet. 2006 Dec 16;368(9553):2167-78
17174709
Am J Epidemiol. 2008 May 15;167(10):1171-81
18353804
Crit Rev Toxicol. 2008;38(10):877-93
19012089
Environ Health Perspect. 2007 Mar;115(3):323-7
17431478
Neurotoxicol Teratol. 2009 Sep-Oct;31(5):267-74
19595760
Pure Appl Chem. 2010 Jan 25;82(2):383-391
20419070
Science. 1973 Jul 20;181(4096):230-41
4719063
Environ Health Perspect. 2008 Aug;116(8):1085-91
18709170
Neurotoxicology. 2008 Sep;29(5):776-82
18590765
World Health Organ Tech Rep Ser. 1978;(631):1-39
107662
Arch Neurol. 1987 Oct;44(10):1017-22
2443112
Lancet. 2003 May 17;361(9370):1667-8
12767728
Clin Toxicol. 1981 Nov;18(11):1311-8
7341057
Br Med J. 1978 Mar 11;1(6113):613-6
630256
Risk Anal. 2004 Dec;24(6):1689-96
15660622
Acta Paediatr. 1952 May;41(3):289-94
12976117
Curr Opin Pediatr. 2008 Apr;20(2):178-83
18332715