Résumé

Objectif

Examiner les biomarqueurs de l'ingestion de méthylmercure (MeHg) chez les femmes et les enfants des populations consommant des poisson et fruits de mer au niveau mondial et caractériser le risque comparatif de la neurotoxicité sur le développement du fœtus.

Méthodes

Une recherche a été effectuée dans la documentation publiée rapportant les quantités totales de mercure (Hg) dans les cheveux et le sang des femmes et des enfants. Ces biomarqueurs ont été validés comme étant des mesures indirectes du MeHg, une neurotoxine que l'on trouve principalement dans les poissons et fruits de mer. Les biomarqueurs moyens et terminaux ont été extraits, stratifiés par contexte de consommation de poisons et fruits de mer et groupés par catégorie. Les médianes pour les distributions groupées des biomarqueurs moyens et terminaux ont été comparées avec le niveau de référence établi par un comité mixte d'experts de l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) et l'Organisation mondiale de la Santé (OMS).

Résultats

Les critères de sélection ont été satisfaits par 164 études concernant des femmes et des enfants dans 43 pays. Les biomarqueurs moyens groupés suggèrent une ingestion de MeHg plusieurs fois supérieure à la référence FAO/OMS chez les riverains consommateurs de poissons et vivant à proximité d’une zone d'orpaillage à petite échelle et bien au-delà de la référence chez les consommateurs de mammifères marins dans les régions arctiques. Dans les régions côtières de l'Asie du Sud-Est, du Pacifique occidental et de la Méditerranée, les biomarqueurs moyens se rapprochent de la référence. Bien que les deux premiers groupes aient un risque de neurotoxicité plus important que les derniers groupes, les régions côtières abritent le plus grand nombre de personnes à risque. Les biomarqueurs terminaux dans toutes les catégories indiquent que l'ingestion de MeHg est supérieure à la valeur de référence.

Conclusion

Il y a un besoin de politiques pour réduire l'exposition au Hg chez les femmes et les enfants, ainsi que pour surveiller les populations à haut risque, dont la majorité vit dans les pays à revenu faible et intermédiaire.

Resumen

Objetivo

Examinar los biomarcadores de la ingesta de metilmercurio (MeHg) en mujeres y niños procedentes de poblaciones que consumen pescados y mariscos a nivel global y describir el riesgo comparativo de neurotoxicidad del desarrollo fetal.

Métodos

Se realizó una búsqueda de la literatura publicada que informa sobre el mercurio total (Hg) en el cabello y la sangre de mujeres y niños. Estos biomarcadores son medidas indirectas validadas de MeHg, una neurotoxina que se encuentra sobre todo en el pescado y marisco. Se extrajeron biomarcadores de gama media y alta, los cuales se estratificaron por contexto de consumo de pescado y marisco y se agruparon por categorías. Se compararon las medianas de las distribuciones por grupos de gama media y alta con el nivel de referencia establecido por un comité mixto de expertos de la Organización para la Agricultura y la Alimentación (FAO) y la Organización Mundial de la Salud (OMS).

Resultados

164 estudios de mujeres y niños de 43 países cumplieron los criterios de selección. El grupo de biomarcadores de gama media indica una ingesta de MeHg varias veces superior a la referencia de la FAO/OMS en los ribereños que consumen pescado que viven cerca de una pequeña mina de oro, y muy superior a la referencia en los consumidores de mamíferos marinos en las regiones árticas. En las regiones costeras del sudeste de Asia, el Pacífico occidental y el Mediterráneo, los biomarcadores de gama media se acercan a la referencia. Aunque el riesgo de neurotoxicidad es mayor en los dos grupos anteriores que en el último, las regiones costeras albergan el mayor número de personas en riesgo. En todas las categorías, los biomarcadores de alta gama indican que la ingesta de MeHg es superior al valor de referencia.

Conclusión

Se necesitan políticas que reduzcan la exposición al Hg entre mujeres y niños, así como una vigilancia en las poblaciones de alto riesgo, la mayoría de las cuales viven en países de bajos y medianos ingresos.

ملخص

الغرض

فحص الواصمات البيولوجية لمدخول ميثيل الزئبق (MeHg) لدى المرأة والطفل من السكان الذين يتناولون المأكولات البحرية على مستوى العالمي، وتمييز المخاطر المقارنة للسمية العصبية التنموية للجنين.

الطريقة

يشير بحث تم إجراؤه في المؤلفات المنشورة إلى إجمالي الزئبق (Hg) في شعر ودم النساء والرضع. ويتم التحقق من هذه الواصمات البيولوجية من خلال التدابير غير المباشرة لميثيل الزئبق، وتوجد السمية العصبية بشكل أساسي في المأكولات البحرية. وتم استخلاص الواصمات البيولوجية المتوسطة والعليا، وتم تقسيمها إلى طبقات حسب سياق استهلاك المأكولات البحرية، وتم تجميعها حسب الفئات. وتم مقارنة متوسطات التوزيعات المتوسطة والعليا التي تم تجميعها مع المستوى المرجعي المحدد من قبل لجنة خبراء مشتركة تابعة لمنظمة الأغذية والزراعة ومنظمة الصحة العالمية.

النتائج

استوفت 164 دراسة للنساء والرضع من 43 دولة معايير الاختيار. وتشير الواصمات البيولوجية التي تم تجميعها إلى مدخول ميثيل زئبق يتجاوز مرات عديدة مرجع منظمتي الأغذية والزراعة والصحة العالمية لدى سكان الشواطئ الذين يتناولون الأسماك ويعيشون بالقرب من مناجم الذهب صغيرة الحجم، وبشكل زائد عن المرجع الخاص بمستهلكي الثدييات البحرية في مناطق القطب الشمالي. وفي المناطق الساحلية لجنوب شرق آسيا، وغرب المحيط الهادي والبحر المتوسط، يقترب متوسط الواصمات البيولوجية من المرجع. ورغم أن المجموعتين السابقتين معرضتان لمخاطر أعلى للإصابة بالسمية العصبية عن المجموعة الأخيرة، إلا أن المناطق الساحلية تعد موطناً لأكبر عدد معرض للخطر. وتشير الواصمات البيولوجية العليا عبر جميع الفئات إلى أن مدخول ميثيل الزئبق (MeHg) يتجاوز القيمة المرجعية.

الاستنتاج

هناك حاجة لسياسات تحد من التعرض للزئبق بين النساء والرضع، والترصد بالنسبة للسكان المعرضين لمخاطر عالية، والذين يعيش أكثرهم في البلدان المنخفضة الدخل والمتوسطة الدخل.

摘要

目的

调查在全球范围内妇女和婴儿从海产品消费中摄取的甲基汞（MeHg）的生物标志物，表征胎儿发育性神经中毒的相对风险。

方法

对报告妇女和婴儿毛发和血管中的总汞(Hg)含量的已发表文献进行检索。这些生物标志物是对MeHg经过验证的间接量度，MeHg是一种主要在水产品中发现的神经毒素。提取平均和高端生物标志物，并按海鲜消费环境进行分层，按类别汇集。将平均和高端汇集分布的中位值与联合国粮农组织（FAO）和世卫组织(WHO)联合专家委员会制定的参考水平进行比较。

结果

来自43个国家的164个有关妇女和婴儿的研究符合入选标准。汇集的平均生物标志物显示，居住在靠近小型金矿河边的鱼类消费人群中摄入MeHg超过FAO/WHO参考值数倍，在北极圈地区海洋哺乳动物的消费人群摄入量也大大超过参考水平。在东南亚、西太平洋和地中海沿海地区，平均生物标志物接近参考水平。尽管前两组的神经中毒风险比后者更高，沿海地区却是风险数量最多的地方。各个类别中，高端生物标记物表明MeHg摄入量超过了参考值。

结论

需要通过政策来减少妇女和婴儿的汞接触，同时对高风险人群进行监测，这些人群绝大多数在中低收入国家。

Резюме

Цель

Изучить биомаркеры поступления метилртути (MeHg) у женщин и детей из группы населения, потребляющего морепродукты, в мировом масштабе и охарактеризовать сравнительный риск отдаленного нейротоксического действия на плод.

Методы

Был проведен поиск опубликованной литературы, в которой сообщалось об общем содержании ртути (Hg) в волосах и крови женщин и детей. Эти биомаркеры являются подтвержденными репрезентативными индикаторами содержания MeHg – нейротоксина, обнаруживаемого главным образом в морепродуктах. После отбора биомаркеры среднего и высокого уровней были разделены по контексту потребления морепродуктов и сгруппированы по категориям. Медианные значения распределений биомаркеров для среднего и высокого уровней сравнивались с контрольным уровнем, установленным объединенным экспертным комитетом Продовольственной и сельскохозяйственной организации ООН (ФАО) и Всемирной организацией здравоохранения (ВОЗ).

Результаты

Критериям выбора соответствовали 164 исследования женщин и детей из 43 стран. Сгруппированные биомаркеры среднего уровня позволяют заключить, что поступление MeHg в несколько раз превышает контрольный уровень ФАО/ВОЗ у представителей населения прибрежных районов, потребляющих морепродукты и проживающих вблизи небольших месторождений золота, и значительно выше контрольного уровня – у потребителей морских млекопитающих в Арктике. В прибрежных районах Юго-Восточной Азии, Западной части Тихого океана и Средиземноморье биомаркеры среднего уровня близки к контрольному уровню. Несмотря на то, что две первые группы подвержены более высокому риску нейротоксичности, чем вторая, в указанных прибрежных районах проживает наибольшее число подверженных риску. Биомаркеры высокого уровня во всех категориях указывают на то, что поступление MeHg превышает контрольный уровень.

Вывод

Необходима разработка стратегий уменьшения воздействия Hg на женщин и детей и эпидемиологического надзора над населением, составляющим группу повышенного риска, большая часть которого проживает в странах с низким и средним уровнями доходов.

Introduction

The World Health Organization (WHO) considers mercury (Hg) among the top 10 chemicals of “major public health concern”.¹1 World Health Organization [Internet]. Mercury and health (Fact sheet No. 361). Geneva: WHO; 2013. Available from: http://www.who.int/mediacentre/factsheets/fs361/en/ [accessed 11 October 2013]
http://www.who.int/mediacentre/factsheet... Evidence of ubiquitous Hg contamination globally led to the recent Minamata Mercury Convention, a binding international treaty to control anthropogenic Hg emissions.²2 “Minamata” Convention agreed by nations: global mercury agreement to lift health threats from lives of millions world-wide. Geneva: United Nations Environment Programme; 2013. Available from: http://www.unep.org/hazardoussubstances/Portals/9/Mercury/Documents/INC5/press_release_mercury_Jan_19_2013.pdf [accessed 11 October 2013].
http://www.unep.org/hazardoussubstances/... A principal form of Hg to which general populations are exposed is methylmercury (MeHg). Transformation of Hg emissions to organic MeHg takes place in the aquatic environment, where MeHg bioaccumulates in food webs. In human beings MeHg exposure occurs predominantly through the consumption of seafood (including freshwater and marine varieties, shellfish and marine mammals).³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000.^–66 United Nations Environment Programme. DTIE Chemicals Branch. Guidance for identifying populations at risk from mercury exposure. Geneva: World Health Organization, Department of Food Safety, Zoonoses and Foodborne Diseases; 2008. Available from: http://www.who.int/foodsafety/publications/chem/mercuryexposure.pdf [accessed 11 October 2013].
http://www.who.int/foodsafety/publicatio... MeHg is a neurotoxin particularly harmful to the developing fetal brain.³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000.^–66 United Nations Environment Programme. DTIE Chemicals Branch. Guidance for identifying populations at risk from mercury exposure. Geneva: World Health Organization, Department of Food Safety, Zoonoses and Foodborne Diseases; 2008. Available from: http://www.who.int/foodsafety/publications/chem/mercuryexposure.pdf [accessed 11 October 2013].
http://www.who.int/foodsafety/publicatio... A large body of research has demonstrated an association of exposure in utero with developmental neurotoxicity (e.g. deficits in fine motor skills, language and memory) among populations that consume seafood regularly.³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000.^,77 Crump KS, Kjellström T, Shipp AM, Silvers A, Stewart A. Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. Risk Anal 1998;18:701–13. doi: http://dx.doi.org/10.1023/B:RIAN.0000005917.52151.e6 PMID:9972579
https://doi.org/10.1023/B:RIAN.000000591... ^–99 Myers GJ, Marsh DO, Davidson PW, Cox C, Shamlaye CF, Tanner M et al. Main neurodevelopmental study of Seychellois children following in utero exposure to methylmercury from a maternal fish diet: outcome at six months. Neurotoxicology 1995;16:653–64. PMID:8714870 Such studies have been used to develop health-based reference doses below which no appreciable risk of harm is thought to occur, including the provisional tolerable weekly intake (PTWI), established by the Joint Expert Committee on Food Additivies (JECFA) of the Food and Agriculture Organization (FAO) and WHO.⁶6 United Nations Environment Programme. DTIE Chemicals Branch. Guidance for identifying populations at risk from mercury exposure. Geneva: World Health Organization, Department of Food Safety, Zoonoses and Foodborne Diseases; 2008. Available from: http://www.who.int/foodsafety/publications/chem/mercuryexposure.pdf [accessed 11 October 2013].
http://www.who.int/foodsafety/publicatio... ^,1010 Joint FAO/WHO Expert Committee on Food Additives. In: Sixty-first meeting, Rome, 10–19 June 2003: summary and conclusions. Food and Agriculture Organization of the United Nations & World Health Organization; 2003. Available from: ftp://ftp.fao.org/es/esn/jecfa/jecfa61sc.pdf [accessed 11 October 2013].
ftp://ftp.fao.org/es/esn/jecfa/jecfa61sc... Recent research suggests harm at doses associated with relatively infrequent seafood consumption.¹¹11 Karagas MR, Choi AL, Oken E, Horvat M, Schoeny R, Kamai E et al. Evidence on the human health effects of low-level methylmercury exposure. Environ Health Perspect 2012;120:799–806. doi: http://dx.doi.org/10.1289/ehp.1104494 PMID:22275730
https://doi.org/10.1289/ehp.1104494...

Seafood species vary in MeHg content depending on contamination source, trophic level and other factors.¹²12 Mahaffey KR. Fish and shellfish as dietary sources of methylmercury and the omega-3 fatty acids, eicosahexaenoic acid and docosahexaenoic acid: risks and benefits. Environ Res 2004;95:414–28. doi: http://dx.doi.org/10.1016/j.envres.2004.02.006 PMID:15220075
https://doi.org/10.1016/j.envres.2004.02... ^–1414 Selin NE, Sunderland EM, Knightes CD, Mason RP. Sources of mercury exposure for US seafood consumers: implications for policy. Environ Health Perspect 2010;118:137–43. PMID:20056570 Seafood, on the other hand, is an important source of nutrients, including neuroprotective omega-3 polyunsaturated fatty acids.¹⁵15 Food and Nutrition Board, Institute of Medicine of the National Academies. Nesheim MC, Yaktine AL, editors. Seafood choices: balancing benefits and risks. Washington: National Academies Press; 2006. Research on the benefits and harms of seafood highlights the importance of choosing species low in MeHg and high in these polyunsaturated fatty acids and of ensuring that consumers have sufficient information to make such choices.¹⁵15 Food and Nutrition Board, Institute of Medicine of the National Academies. Nesheim MC, Yaktine AL, editors. Seafood choices: balancing benefits and risks. Washington: National Academies Press; 2006.^,1616 Mahaffey KR, Sunderland EM, Chan HM, Choi AL, Grandjean P, Mariën K et al. Balancing the benefits of n-3 polyunsaturated fatty acids and the risks of methylmercury exposure from fish consumption. Nutr Rev 2011;69:493–508. doi: http://dx.doi.org/10.1111/j.1753-4887.2011.00415.x PMID:21884130
https://doi.org/10.1111/j.1753-4887.2011... Well-designed seafood advisories can be helpful to this end,¹⁷17 Shimshack JP, Ward MB. Mercury advisories and household health trade-offs. J Health Econ 2010;29:674–85. doi: http://dx.doi.org/10.1016/j.jhealeco.2010.05.001 PMID:20609487
https://doi.org/10.1016/j.jhealeco.2010.... ^,1818 Lando AM, Zhang Y. Awareness and knowledge of methylmercury in fish in the United States. Environ Res 2011;111:442–50. doi: http://dx.doi.org/10.1016/j.envres.2011.01.004 PMID:21257163
https://doi.org/10.1016/j.envres.2011.01... but they exist in a small number of countries, most of which are high-income.¹⁹19 Sheehan MC. Risk of developmental neurotoxicity due to methylmercury in seafood: examining global exposures, susceptibility and policy. Johns Hopkins Bloomberg School of Public Health, Health Policy and Management Department; 2011. [Dissertation]. An estimated 400 million women of reproductive age in the world rely on seafood for at least 20% of their intake of animal protein; a large share of them live in low- and middle-income countries where access to information on MeHg content in seafood is not widely available.²⁰20 The state of world fisheries and aquaculture: world review of fisheries and aquaculture – part 1. Rome: Food and Agriculture Organization; 2010. Available from: http://www.fao.org/docrep/013/i1820e/i1820e01.pdf [accessed 12 October 2013].
http://www.fao.org/docrep/013/i1820e/i18... ^–2222 United Nations Environment Programme. Vital water graphics: an overview of the state of the world’s fresh and and marine waters. 2nd ed. New York: United Nations; 2008. Available from: http://www.unep.org/dewa/vitalwater/article176.html [accessed 12 October 2013].
http://www.unep.org/dewa/vitalwater/arti... Although the research conducted in the last two decades has highlighted the risk in subsistence fishing communities that practise artisanal and small-scale gold mining²³23 Passos CJ, Mergler D. Human mercury exposure and adverse health effects in the Amazon: a review. Cad Saude Publica 2008;24:S503–20. and among Arctic peoples whose diet consists of apex marine predators such as the pilot whale,²⁴24 Van Oostdam J, Donaldson SG, Feeley M, Arnold D, Ayotte P, Bondy G et al. Human health implications of environmental contaminants in Arctic Canada: A review. Sci Total Environ 2005;351-352:165–246. doi: http://dx.doi.org/10.1016/j.scitotenv.2005.03.034 PMID:16297438
https://doi.org/10.1016/j.scitotenv.2005... few researchers have compared MeHg exposures globally in women who consume seafood.

Human exposure to chemical contaminants can be characterized by examining biomarkers.²⁵25 Committee on Human Biomonitoring for Environmental Toxicants, National Research Council of the United States National Academies of Science. Human biomonitoring for environmental chemicals. Washington: National Academies Press; 2006. Total Hg in hair (THHg) and total Hg in blood (TBHg) are both validated biomarkers of MeHg intake correlated with seafood consumption in general human populations.⁴4 Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 2006;36:609–62. doi: http://dx.doi.org/10.1080/10408440600845619 PMID:16973445
https://doi.org/10.1080/1040844060084561... ^,2626 Berglund M, Lind B, Björnberg KA, Palm B, Einarsson O, Vahter M. Inter-individual variations of human mercury exposure biomarkers: a cross-sectional assessment. Environ Health 2005;4:20. doi: http://dx.doi.org/10.1186/1476-069X-4-20 PMID:16202128
https://doi.org/10.1186/1476-069X-4-20... Our goal was to review and synthesize the evidence from published studies reporting THHg and TBHg biomarkers to systematically compare global MeHg exposure among women and their infants from seafood-consuming populations. By identifying populations at higher risk, we aim to provide policy-makers with scientific evidence for the prioritization of risk reduction messages and targeted population surveillance.

Methods

Based on a pre-defined study protocol,²⁷27 Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–12. doi: http://dx.doi.org/10.1001/jama.283.15.2008 PMID:10789670
https://doi.org/10.1001/jama.283.15.2008... we performed a systematic electronic search of the peer-reviewed scientific literature (Box 1). Studies were selected in two stages: title and abstract screening, followed by full text review after application of exclusion criteria. We excluded studies not involving women or infants from general populations and not reporting a central THHg or TBHg biomarker estimate. When multiple articles reported on a single sample, we chose the most recent one with complete data. To ensure robust summary statistics, we excluded studies with less than 40 participants.

We extracted data on study design, population characteristics, measures of average (geometric mean or median) and high-end (90th or 95th percentile or maximum) biomarkers, exposure conditions and main covariates examined. Extracted biomarkers were organized into three subpopulation groups: non-pregnant women; pregnant women and mothers who had recently given birth; and infants (up to 12 months of age). Because biomarkers for more than one subpopulation with different levels of exposure were often reported in the same study, the subpopulation was our main level of analysis.

We stratified subpopulations into six mutually exclusive categories based on predictors of the body burden of MeHg. The most important of these predictors are seafood consumption frequency and seafood MeHg content. In most seafood species MeHg represents the largest fraction of total Hg (inorganic Hg representing a much smaller share). Thus, seafood MeHg concentration is commonly measured as total Hg in tissue.³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000.^,44 Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 2006;36:609–62. doi: http://dx.doi.org/10.1080/10408440600845619 PMID:16973445
https://doi.org/10.1080/1040844060084561... Seafood consumption estimates were reported in some studies; data on total Hg concentrations were rarely provided. Research suggests the following general hierarchy: marine mammals, other apex marine predators and some industrially-contaminated fish [containing several parts per million (ppm)]; large marine fish [containing up to 1 or more ppm]; most commercially purchased marine and freshwater fish [often containing less than 0.5 ppm] and  most shellfish [often containing less than 0.2 ppm].²³23 Passos CJ, Mergler D. Human mercury exposure and adverse health effects in the Amazon: a review. Cad Saude Publica 2008;24:S503–20.^,2424 Van Oostdam J, Donaldson SG, Feeley M, Arnold D, Ayotte P, Bondy G et al. Human health implications of environmental contaminants in Arctic Canada: A review. Sci Total Environ 2005;351-352:165–246. doi: http://dx.doi.org/10.1016/j.scitotenv.2005.03.034 PMID:16297438
https://doi.org/10.1016/j.scitotenv.2005... ^,2828 Pirrone N, Mahaffey K. Dynamics of mercury pollution on regional and global scales: atmospheric processes and human exposures around the world. New York: Springer; 2005.^–3131 Balshaw S, Edwards J, Daughtry B, Ross K. Mercury in seafood: mechanisms of accumulation and consequences for consumer health. Rev Environ Health 2007;22:91–113. PMID:17894202 Seafood intake is generally higher in coastal regions than inland³⁰30 Groth E 3rd. Ranking the contributions of commercial fish and shellfish varieties to mercury exposure in the United States: implications for risk communication. Environ Res 2010;110:226–36. doi: http://dx.doi.org/10.1016/j.envres.2009.12.006 PMID:20116785
https://doi.org/10.1016/j.envres.2009.12... ^,3232 Mahaffey KR, Clickner RP, Jeffries RA. Adult women’s blood mercury concentrations vary regionally in the United States: association with patterns of fish consumption (NHANES 1999–2004). Environ Health Perspect 2009;117:47–53. doi: http://dx.doi.org/10.1289/ehp.11674 PMID:19165386
https://doi.org/10.1289/ehp.11674... and seafood from globalized commercial sources predominates in many urban areas.¹⁴14 Selin NE, Sunderland EM, Knightes CD, Mason RP. Sources of mercury exposure for US seafood consumers: implications for policy. Environ Health Perspect 2010;118:137–43. PMID:20056570 We therefore generated six categories based on the following proxy predictors, reported in most studies: seafood source; seafood type; likely Hg contamination pathway; and residential context. Four categories included populations consuming seafood that was mainly self-caught and two included populations consuming seafood that was commercially purchased primarily (Table 1).

As recommended in guidelines for the systematic review of observational studies,²⁷27 Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–12. doi: http://dx.doi.org/10.1001/jama.283.15.2008 PMID:10789670
https://doi.org/10.1001/jama.283.15.2008... we evaluated study quality by examining the risk of bias in three areas: selection of participants (selection methods and reporting of exposure characteristics); exposure measurement (laboratory methods and quality control); and statistical methods and covariate analysis (evaluation of distribution shape, reporting of seafood intake and exposure to non-seafood sources of Hg).

We derived two summary distributions – central and upper bound – for each exposure category by pooling average and high-end biomarkers. For comparability, all TBHg biomarkers were converted to THHg-equivalent at a hair-to-blood ratio of 250:1.³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000.^,55 Environmental health criteria document 101: methylmercury. Geneva: International Program for Chemical Safety, World Health Organization; 1990. We summarized resulting statistical distributions using medians and percentiles. To interpret results, we compared distribution medians with the THHg-equivalent value of the PTWI dose (approximately 2.2 μg/g) established by the JECFA.¹⁰10 Joint FAO/WHO Expert Committee on Food Additives. In: Sixty-first meeting, Rome, 10–19 June 2003: summary and conclusions. Food and Agriculture Organization of the United Nations & World Health Organization; 2003. Available from: ftp://ftp.fao.org/es/esn/jecfa/jecfa61sc.pdf [accessed 11 October 2013].
ftp://ftp.fao.org/es/esn/jecfa/jecfa61sc... We also determined the share of subpopulations with average and high-end biomarkers over this reference. In sensitivity analysis we evaluated the impact on pooled biomarkers taking into account differences in participant selection, exposure measurement and statistical methods identified in the quality review. Given substantial heterogeneity in population exposure conditions, study designs and reporting, we did not undertake a meta-analysis. All data analysis was performed in Stata10 (StataCorp, College Station, United States of America).

Results

Selected studies

Of 3042 articles identified in the published literature, we screened 1402 non-duplicates (1379 were identified by electronic search and 23 by hand search); we excluded 1120 and we reviewed the full texts of the remaining 282, from which we excluded 118 (Fig. 1). The remaining 164 articles, which reported total Hg biomarkers for 239 distinct subpopulations, were included in this review. Selected articles report biomarker concentrations for 63 943 women and infants from 43 countries (Table 2). Most (73%) studies were cross-sectional and over half (56%) reported THHg measures; the majority (79%) were published after 2001. Studies published in 1991–2001 were conducted primarily in populations consuming self-caught seafood; since 2001, the number of studies in consumers of seafood that is predominantly commercially purchased has increased notably in both absolute and relative terms (Fig. 2). The characteristics of the selected studies are provided in Table 3 and Table 4 (both available at: http://www.who.int/bulletin/volumes/92/04/13-116152).

Pooled biomarker concentrations

For 43 subpopulations of women and infants living near small-scale gold mining sites in Bolivia (Plurinational State of),³³33 Monrroy SX, Lopez RW, Roulet M, Benefice E. Lifestyle and mercury contamination of Amerindian populations along the Beni river (lowland Bolivia). J Environ Health 2008;71:44–50. PMID:19004394^,3434 Barbieri FL, Cournil A, Gardon J. Mercury exposure in a high fish eating Bolivian Amazonian population with intense small-scale gold-mining activities. Int J Environ Health Res 2009;19:267–77. doi: http://dx.doi.org/10.1080/09603120802559342 PMID:20183195
https://doi.org/10.1080/0960312080255934... Brazil,³⁵35 Boischio AAP, Barbosa A. Exposição ao mercúrio orgânico em populações Ribeirinhas do Alto Madeira, Rondônia, 1991: resultados preliminares. Cad Saude Publica 1993;9:155–60. Portugese doi: http://dx.doi.org/10.1590/S0102-311X1993000200006 PMID:15448836
https://doi.org/10.1590/S0102-311X199300... ^–5353 Vieira SM, de Almeida R, Holanda IBB, Mussy MH, Galvão RCF, Crispim PTB et al. Total and methyl-mercury in hair and milk of mothers living in the city of Porto Velho and in villages along the Rio Madeira, Amazon, Brazil. Int J Hyg Environ Health 2013;216:682–9. doi: http://dx.doi.org/10.1016/j.ijheh.2012.12.011 PMID:23340120
https://doi.org/10.1016/j.ijheh.2012.12.... ^,5959 Hacon S, Yokoo E, Valente J, Campos RC, da Silva VA, de Menezes ACC et al. Exposure to mercury in pregnant women from Alta Floresta-Amazon basin, Brazil. Environ Res 2000;84:204–10. doi: http://dx.doi.org/10.1006/enrs.2000.4115 PMID:11097793
https://doi.org/10.1006/enrs.2000.4115... ^,6060 Marques RC, Garrofe Dórea J, Rodrigues Bastos W, de Freitas Rebelo M, de Freitas Fonseca M, Malm O. Maternal mercury exposure and neuro-motor development in breastfed infants from Porto Velho (Amazon), Brazil. Int J Hyg Environ Health 2007;210:51–60. doi: http://dx.doi.org/10.1016/j.ijheh.2006.08.001 PMID:17011234
https://doi.org/10.1016/j.ijheh.2006.08.... Colombia,⁵⁴54 Olivero-Verbel J, Caballero-Gallardo K, Marrugo Negrete J. Relationship between localization of gold mining areas and hair mercury levels in people from Bolivar, north of Colombia. Biol Trace Elem Res 2011;144:118–32. doi: http://dx.doi.org/10.1007/s12011-011-9046-5 PMID:21476008
https://doi.org/10.1007/s12011-011-9046-... French Guiana,⁵⁵55 Cordier S, Grasmick C, Paquier-Passelaigue M, Mandereau L, Weber J-P, Jouan M. Mercury exposure in French Guiana: levels and determinants. Arch Environ Health 1998;53:299–303. doi: http://dx.doi.org/10.1080/00039899809605712
https://doi.org/10.1080/0003989980960571... ^–5757 Fujimura M, Matsuyama A, Harvard JP, Bourdineaud JP, Nakamura K. Mercury contamination in humans in Upper Maroni, French Guiana between 2004 and 2009. Bull Environ Contam Toxicol 2012;88:135–9. doi: http://dx.doi.org/10.1007/s00128-011-0497-3 PMID:22147084
https://doi.org/10.1007/s00128-011-0497-... Indonesia⁵⁸58 Bose-O’Reilly S, Drasch G, Beinhoff C, Rodrigues-Filho S, Roider G, Lettmeier B et al. Health assessment of artisanal gold miners in Indonesia. Sci Total Environ 2010;408:713–25. doi: http://dx.doi.org/10.1016/j.scitotenv.2009.10.070 PMID:19945736
https://doi.org/10.1016/j.scitotenv.2009... and Surinam⁶¹61 Mohan S, Tiller M, van der Voet G, Kanhai H. Mercury exposure of mothers and newborns in Surinam: a pilot study. Clin Toxicol (Phila) 2005;43:101–4. PMID:15822761 the pooled central distribution median THHg biomarker concentration was 5.4 µg/g (upper bound median: 23.1) (Table 5). Values were higher (8.2 µg/g; upper bound: 27.5) in the subgroup of rural riverine dwellers reliant on local freshwater fish and lower (1.4 µg/g; upper bound: 11.8) among urban dwellers consuming less fish. For 21 subpopulations from Arctic regions, including in Canada,⁶²62 Dewailly E, Ayotte P, Bruneau S, Lebel G, Levallois P, Weber JP. Exposure of the Inuit population of Nunavik (Arctic Quebec) to lead and mercury. Arch Environ Health 2001;56:350–7. doi: http://dx.doi.org/10.1080/00039890109604467 PMID:11572279
https://doi.org/10.1080/0003989010960446... ^–6666 Fontaine J, Dewailly E, Benedetti J-L, Pereg D, Ayotte P, Déry S. Re-evaluation of blood mercury, lead and cadmium concentrations in the Inuit population of Nunavik (Québec): a cross-sectional study. Environ Health 2008;7:25. doi: http://dx.doi.org/10.1186/1476-069X-7-25 PMID:18518986
https://doi.org/10.1186/1476-069X-7-25... Denmark (Greenland and the Faroe Islands),⁶⁷67 Grandjean P, Weihe P, Jørgensen PJ, Clarkson T, Cernichiari E, Viderø T. Impact of maternal seafood diet on fetal exposure to mercury, selenium, and lead. Arch Environ Health 1992;47:185–95. doi: http://dx.doi.org/10.1080/00039896.1992.9938348 PMID:1596101
https://doi.org/10.1080/00039896.1992.99... ^–6969 Nielsen ABS, Davidsen M, Bjerregaard P. The association between blood pressure and whole blood methylmercury in a cross-sectional study among Inuit in Greenland. Environ Health 2012;11:44. doi: http://dx.doi.org/10.1186/1476-069X-11-44 PMID:22747793
https://doi.org/10.1186/1476-069X-11-44... Norway,⁷⁰70 Odland JO, Nieboer E, Romanova N, Thomassen Y, Brox J, Lund E. Self-reported ethnic status of delivering women, newborn body mass index, blood or urine concentrations of toxic metals, and essential elements in sera of Norwegian and Russian Arctic populations. Int J Circumpolar Health 1999;58:4–13. PMID:10208065^,7171 Hansen S, Nieboer E, Sandanger TM, Wilsgaard T, Thomassen Y, Veyhe AS et al. Changes in maternal blood concentrations of selected essential and toxic elements during and after pregnancy. J Environ Monit 2011;13:2143–52. doi: http://dx.doi.org/10.1039/c1em10051c PMID:21738945
https://doi.org/10.1039/c1em10051c... the Russian Federation⁷²72 Klopov VP. Levels of heavy metals in women residing in the Russian Arctic. Int J Circumpolar Health 1998;57(Suppl 1):582–5. PMID:10093346 and the United States (state of Alaska),⁷³73 Arnold SM, Lynn TV, Verbrugge LA, Middaugh JP. Human biomonitoring to optimize fish consumption advice: reducing uncertainty when evaluating benefits and risks. Am J Public Health 2005;95:393–7. doi: http://dx.doi.org/10.2105/AJPH.2004.042879 PMID:15727965
https://doi.org/10.2105/AJPH.2004.042879... the pooled central distribution median result was 2.1 µg/g (upper bound: 9.8); values were higher (3.6 µg/g; upper bound: 24.3) for marine mammal and other self-caught seafood consumers and lower (0.4 µg/g; upper bound: 1.4) among those with a diet including less seafood and less reliant on these traditional foods.

For 25 subpopulations whose self-caught fish from local waterways is affected by Hg-emitting industries in Brazil,⁷⁴74 Nilson SA Jr, Costa M, Akagi H. Total and methylmercury levels of a coastal human population and of fish from the Brazilian northeast. Environ Sci Pollut Res Int 2001;8:280–4. doi: http://dx.doi.org/10.1007/BF02987408 PMID:11601365
https://doi.org/10.1007/BF02987408... ^,7575 Kuno R, Roquetti MH, Becker K, Seiwert M, Gouveia N. Reference values for lead, cadmium and mercury in blood of adults from the metropolitan area of Sao Paulo (Brazil). Toxicol Letters 2010;196:1(S40). Chile,⁷⁶76 Bruhn CG, Rodŕiguez AA, Barrios C, Jaramillo VH, Becerra J, Gonzáles U et al. Determination of total mercury in scalp hair of pregnant and nursing women resident in fishing villages in the Eighth Region of Chile. J Trace Elem Electrolytes Health Dis 1994;8:79–86. PMID:7881281 China,⁷⁷77 Li Z, Wang Q, Luo Y. Exposure of the urban population to mercury in Changchun city, Northeast China. Environ Geochem Health 2006;28:61–6. doi: http://dx.doi.org/10.1007/s10653-005-9012-2 PMID:16528593
https://doi.org/10.1007/s10653-005-9012-... ^–8181 Pawlas N, Strömberg U, Carlberg B, Cerna M, Harari F, Harari R et al. Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco. Int J Occup Med Environ Health 2013;26:58–72. doi: http://dx.doi.org/10.2478/S13382-013-0071-9 PMID:23526195
https://doi.org/10.2478/S13382-013-0071-... Colombia,⁸²82 Olivero-Verbel J, Johnson-Restrepo B, Baldiris-Avila R, Güette-Fernández J, Magallanes-Carreazo E, Vanegas-Ramírez L et al. Human and crab exposure to mercury in the Caribbean coastal shoreline of Colombia: impact from an abandoned chlor-alkali plant. Environ Int 2008;34:476–82. doi: http://dx.doi.org/10.1016/j.envint.2007.10.009 PMID:18155151
https://doi.org/10.1016/j.envint.2007.10... Italy,⁸³83 Madeddu A, Sciacca S. Monitoraggio biologico sulla presenza di Hg, PCB e HCG in latte e capelli di donne residenti in un’area ad alta incidenza di nati malformati (Augusta). Ann Ig 2008;20(Suppl 1):59–64. Italian PMID:18773607^,8484 Deroma L, Parpinel M, Tognin V, Channoufi L, Tratnik J, Horvat M et al. Neuropsychological assessment at school-age and prenatal low-level exposure to mercury through fish consumption in an Italian birth cohort living near a contaminated site. Int J Hyg Environ Health 2013;216:486–93. doi: http://dx.doi.org/10.1016/j.ijheh.2013.02.004 PMID:23523155
https://doi.org/10.1016/j.ijheh.2013.02.... Kazakhstan,⁸⁵85 Hsiao H-W, Ullrich SM, Tanton TW. Burdens of mercury in residents of Temirtau, Kazakhstan I: hair mercury concentrations and factors of elevated hair mercury levels. Sci Total Environ 2011;409:2272–80. doi: http://dx.doi.org/10.1016/j.scitotenv.2009.12.040 PMID:20092877
https://doi.org/10.1016/j.scitotenv.2009... Mexico,⁸⁷87 Trasande L, Cortes JE, Landrigan PJ, Abercrombie MI, Bopp RF, Cifuentes E. Methylmercury exposure in a subsistence fishing community in Lake Chapala, Mexico: an ecological approach. Environ Health 2010;9:1. doi: http://dx.doi.org/10.1186/1476-069X-9-1 PMID:20064246
https://doi.org/10.1186/1476-069X-9-1... Morocco,⁸⁸88 Elhamri H, Idrissi L, Coquery M, Azemard S, El Abidi A, Benlemlih M et al. Hair mercury levels in relation to fish consumption in a community of the Moroccan Mediterranean coast. Food Addit Contam 2007;24:1236–46. doi: http://dx.doi.org/10.1080/02652030701329611 PMID:17852400
https://doi.org/10.1080/0265203070132961... Nicaragua,⁸⁹89 Lacayo M, Cruz A, Lacayo J, Fomsgaard I. Mercury contamination in Lake Xolotlan (Managua). Hydrobiol Bull 1991;25:173–6. doi: http://dx.doi.org/10.1007/BF02291251
https://doi.org/10.1007/BF02291251... Norway,¹¹⁵115 Brantsaeter AL, Haugen M, Thomassen Y, Ellingsen DG, Ydersbond TA, Hagve TA et al. Exploration of biomarkers for total fish intake in pregnant Norwegian women. Public Health Nutr 2010;13:54–62. doi: http://dx.doi.org/10.1017/S1368980009005904 PMID:19490733
https://doi.org/10.1017/S136898000900590... the Republic of Korea,⁸⁶86 Lim S, Chung H-U, Paek D. Low dose mercury and heart rate variability among community residents nearby to an industrial complex in Korea. Neurotoxicology 2010;31:10–6. doi: http://dx.doi.org/10.1016/j.neuro.2009.10.001 PMID:19833149
https://doi.org/10.1016/j.neuro.2009.10.... Romania,⁹⁰90 Bravo AG, Loizeau J-L, Bouchet S, Richard A, Rubin JF, Ungureanu V-G et al. Mercury human exposure through fish consumption in a reservoir contaminated by a chlor-alkali plant: Babeni reservoir (Romania). Environ Sci Pollut Res 2010;17:1422–32. doi: http://dx.doi.org/10.1007/s11356-010-0328-9
https://doi.org/10.1007/s11356-010-0328-... Slovakia,⁸¹81 Pawlas N, Strömberg U, Carlberg B, Cerna M, Harari F, Harari R et al. Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco. Int J Occup Med Environ Health 2013;26:58–72. doi: http://dx.doi.org/10.2478/S13382-013-0071-9 PMID:23526195
https://doi.org/10.2478/S13382-013-0071-... ^,9191 Palkovicova L, Ursinyova M, Masanova V, Yu Z, Hertz-Picciotto I. Maternal amalgam dental fillings as the source of mercury exposure in developing fetus and newborn. J Expo Sci Environ Epidemiol 2008;18:326–31. doi: http://dx.doi.org/10.1038/sj.jes.7500606 PMID:17851449
https://doi.org/10.1038/sj.jes.7500606... Sweden,⁹²92 Oskarsson A, Lagerkvist BJ, Ohlin B, Lundberg K. Mercury levels in the hair of pregnant women in a polluted area in Sweden. Sci Total Environ 1994;151:29–35. doi: http://dx.doi.org/10.1016/0048-9697(94)90483-9 PMID:8079150
https://doi.org/10.1016/0048-9697(94)904... Taiwan, China,⁹³93 Chang J-W, Pai M-C, Chen H-L, Guo H-R, Su H-J, Lee C-C. Cognitive function and blood methylmercury in adults living near a deserted chloralkali factory. Environ Res 2008;108:334–9. doi: http://dx.doi.org/10.1016/j.envres.2008.06.006 PMID:18675410
https://doi.org/10.1016/j.envres.2008.06... the United States⁹⁴94 Lincoln RA, Shine JP, Chesney EJ, Vorhees DJ, Grandjean P, Senn DB. Fish consumption and mercury exposure among Louisiana recreational anglers. Environ Health Perspect 2011;119:245–51. doi: http://dx.doi.org/10.1289/ehp.1002609 PMID:20980220
https://doi.org/10.1289/ehp.1002609... and Venezuela (Bolivarian Republic of),⁹⁵95 Rojas M, Nakamura K, Seijas D, Squiuante G, Pieters MA, Infante S. Mercury in hair as a biomarker of exposure in a coastal Venezuelan population. Invest Clin 2007;48:305–15. PMID:17853790 the pooled central THHg median biomarker was 0.8 µg/g (upper bound: 4.6). In 14 subpopulations consuming fish periodically from non-industry-contaminated waters in Botswana,⁹⁶96 Black FJ, Bokhutlo T, Somoxa A, Maethamako M, Modisaemang O, Kemosedile T et al. The tropical African mercury anomaly: lower than expected mercury concentrations in fish and human hair. Sci Total Environ 2011;409:1967–75. doi: http://dx.doi.org/10.1016/j.scitotenv.2010.11.027 PMID:21342703
https://doi.org/10.1016/j.scitotenv.2010... Canada,⁹⁷97 Girard M, Dumont C. Exposure of James Bay Cree to methylmercury during pregnancy for the years 1983–91. Water Air Soil Pollut 1995;80:13–9. doi: http://dx.doi.org/10.1007/BF01189648
https://doi.org/10.1007/BF01189648... ^–102102 Abdelouahab N, Mergler D, Takser L, Vanier C, St-Jean M, Baldwin M et al. Gender differences in the effects of organochlorines, mercury, and lead on thyroid hormone levels in lakeside communities of Quebec (Canada). Environ Res 2008;107:380–92. doi: http://dx.doi.org/10.1016/j.envres.2008.01.006 PMID:18313043
https://doi.org/10.1016/j.envres.2008.01... Norway,¹⁰³103 Jenssen MTS, Brantsæter AL, Haugen M, Meltzer HM, Larssen T, Kvalem HE et al. Dietary mercury exposure in a population with a wide range of fish consumption–self-capture of fish and regional differences are important determinants of mercury in blood. Sci Total Environ 2012;439:220–9. doi: http://dx.doi.org/10.1016/j.scitotenv.2012.09.024 PMID:23069934
https://doi.org/10.1016/j.scitotenv.2012... Sweden¹⁰⁴104 Johnsson C, Sällsten G, Schütz A, Sjörs A, Barregård L. Hair mercury levels versus freshwater fish consumption in household members of Swedish angling societies. Environ Res 2004;96:257–63. doi: http://dx.doi.org/10.1016/j.envres.2004.01.005 PMID:15364592
https://doi.org/10.1016/j.envres.2004.01... and the United States,¹⁰⁵105 Stewart P, Reihman J, Lonky E, Darvill T, Pagano J. Prenatal PCB exposure and neonatal behavioral assessment scale (NBAS) performance. Neurotoxicol Teratol 2000;22:21–9. doi: http://dx.doi.org/10.1016/S0892-0362(99)00056-2 PMID:10642111
https://doi.org/10.1016/S0892-0362(99)00... ^–107107 Schantz SL, Gardiner JC, Aguiar A, Tang X, Gasior DM, Sweeney AM et al. Contaminant profiles in Southeast Asian immigrants consuming fish from polluted waters in northeastern Wisconsin. Environ Res 2010;110:33–9. doi: http://dx.doi.org/10.1016/j.envres.2009.09.003 PMID:19811781
https://doi.org/10.1016/j.envres.2009.09... the value was 0.4 µg/g (upper bound: 2.8).

For 102 coastal or island-dwelling subpopulations consuming seafood that is predominantly commercially purchased, the combined central median THHg concentration was 0.8 µg/g (upper bound: 6.8). On the Atlantic coast, the pooled result for 35 subpopulations in Brazil,¹⁰⁸108 Carneiro MFH, Moresco MB, Chagas GR, de Oliveira Souza VC, Rhoden CR, Barbosa F Jr. Assessment of trace elements in scalp hair of a young urban population in Brazil. Biol Trace Elem Res 2011;143:815–24. doi: http://dx.doi.org/10.1007/s12011-010-8947-z PMID:21225477
https://doi.org/10.1007/s12011-010-8947-... Canada,⁹⁹99 Belles-Isles M, Ayotte P, Dewailly E, Weber J-P, Roy R. Cord blood lymphocyte functions in newborns from a remote maritime population exposed to organochlorines and methylmercury. J Toxicol Environ Health A 2002;65:165–82. doi: http://dx.doi.org/10.1080/152873902753396794 PMID:11820504
https://doi.org/10.1080/1528739027533967... ^,109109 Legrand M, Arp P, Ritchie C, Chan HM. Mercury exposure in two coastal communities of the Bay of Fundy, Canada. Environ Res 2005;98:14–21. doi: http://dx.doi.org/10.1016/j.envres.2004.07.006 PMID:15721879
https://doi.org/10.1016/j.envres.2004.07... France,¹¹⁰110 Albert I, Villeret G, Paris A, Verger P. Integrating variability in half-lives and dietary intakes to predict mercury concentration in hair. Regul Toxicol Pharmacol 2010;58:482–9. doi: http://dx.doi.org/10.1016/j.yrtph.2010.08.020 PMID:20804806
https://doi.org/10.1016/j.yrtph.2010.08.... ^,111111 Drouillet-Pinard P, Huel G, Slama R, Forhan A, Sahuquillo J, Goua V et al. Prenatal mercury contamination: relationship with maternal seafood consumption during pregnancy and fetal growth in the ‘EDEN mother-child’ cohort. Br J Nutr 2010;104:1096–100. PMID:20487582 Norway,¹¹⁵115 Brantsaeter AL, Haugen M, Thomassen Y, Ellingsen DG, Ydersbond TA, Hagve TA et al. Exploration of biomarkers for total fish intake in pregnant Norwegian women. Public Health Nutr 2010;13:54–62. doi: http://dx.doi.org/10.1017/S1368980009005904 PMID:19490733
https://doi.org/10.1017/S136898000900590... Portugal,¹¹⁷117 Renzoni A, Zino F, Franchi E. Mercury levels along the food chain and risk for exposed populations. Environ Res 1998;77:68–72. doi: http://dx.doi.org/10.1006/enrs.1998.3832 PMID:9600797
https://doi.org/10.1006/enrs.1998.3832... Spain,¹¹⁸118 Ramon R, Murcia M, Aguinagalde X, Amurrio A, Llop S, Ibarluzea J et al. Prenatal mercury exposure in a multicenter cohort study in Spain. Environ Int 2011;37:597–604. doi: http://dx.doi.org/10.1016/j.envint.2010.12.004 PMID:21239061
https://doi.org/10.1016/j.envint.2010.12... Sweden,⁸¹81 Pawlas N, Strömberg U, Carlberg B, Cerna M, Harari F, Harari R et al. Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco. Int J Occup Med Environ Health 2013;26:58–72. doi: http://dx.doi.org/10.2478/S13382-013-0071-9 PMID:23526195
https://doi.org/10.2478/S13382-013-0071-... ^,9292 Oskarsson A, Lagerkvist BJ, Ohlin B, Lundberg K. Mercury levels in the hair of pregnant women in a polluted area in Sweden. Sci Total Environ 1994;151:29–35. doi: http://dx.doi.org/10.1016/0048-9697(94)90483-9 PMID:8079150
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https://doi.org/10.1093/aje/kwr375... the pooled central TTHg median was 0.4 µg/g (upper bound: 2.9).

Comparison with provisional tolerable weekly intake

The median of the pooled central THHg biomarker distribution for women and infants in rural riverine communities near tropical gold mining sites reached nearly four times the FAO/WHO PTWI reference level of 2.2 ug/g (Fig. 3), while the upper-bound median reached more than 10 times this reference. Some individual high-end biomarkers exceeded 50 µg/g, the lower end of the range found in the neurological syndrome known as Minamata disease,⁴4 Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 2006;36:609–62. doi: http://dx.doi.org/10.1080/10408440600845619 PMID:16973445
https://doi.org/10.1080/1040844060084561... associated with accidental industrial Hg poisoning in Japan in the 1950s and 1960s (Fig. 4). The median of the central THHg biomarker distribution in Arctic traditional food consumers exceeded the reference by 63%, while the upper bound median was over 10 times the value. For women and infants in the industry and fishing categories, central estimate medians were below the international reference, although the industry central median was twice that of the fishing category; most high-end biomarkers were above it. For those in the Pacific coastal subcategory, the 75th percentile approached the reference value; the upper bound median was nearly three times this value and nearly all high-end biomarkers exceeded it. Central biomarkers were below the PTWI in the Atlantic. However in many subpopulations in the Mediterranean they exceeded this reference, while the upper bound median was nearly four times the reference and most high-end biomarkers exceeded it. For the inland category, the central estimate median was well below the reference, but nearly 80% of the high-end biomarkers exceeded it.

Study quality

A majority (78%) of selected studies were based on convenience samples taken from seafood-consuming populations. Some details of the seafood context were provided in most (71%) studies, but in the others this information was sparse. Laboratory protocols for THHg and TBHg detection were nearly universally reported (91%). Most (82%) protocols were based on cold vapour atomic absorption spectrometry (CV-AAS) or inductively-coupled plasma mass spectrometry (ICP-MS) and a majority (74%) reported laboratory quality control procedures. In 86% of studies, distributions were transformed to lognormal scale and summarized using geometric means or medians. More than half (55%) of the studies reported maximums as high-end estimates, while the remainder reported 90th or 95th percentiles. Only 51% of studies reported some seafood intake data and 25% evaluated non-seafood sources of Hg.

Discussion

We found that biomarkers of MeHg intake were of greatest health concern among three categories of seafood-consuming women and their infants: (i) rural riverside dwellers living near tropical small-scale gold mining with diets dependent on locally-caught freshwater fish; (ii) those in Arctic regions for whom apex food-chain marine mammals are a dietary staple; and (iii) coastal inhabitants, particularly in the Pacific and Mediterranean, who probably consume seafood that is primarily commercially sourced. In the first group, average Hg biomarkers suggest MeHg intake exceeds by several fold the level considered by WHO and FAO to pose no substantial risk of developmental neurotoxicity. In the second group, average biomarkers suggest MeHg intake well over the reference value. In the third group, biomarkers suggest an important share of the population approach or exceed the reference level. High-end biomarkers in all three groups indicate body burdens of MeHg in the range associated in epidemiological studies with observable neurological damage. While average biomarkers in other groups suggest that MeHg intake is below the recommended level, most upper bound biomarkers in these categories exceed the reference, which shows that even in groups with lower average exposure certain populations are at risk.

Before this study, few researchers had systematically compared the global exposures and risks linked to MeHg intake from seafood. Brune et al. reviewed Hg biomarker studies – published from 1976 to 1990 – of general populations exposed through various sources and found the highest values among seafood consumers in Greenland and Japan.¹⁹⁷197 Brune D, Nordberg GF, Vesterberg O, Gerhardsson L, Wester PO. A review of normal concentrations of mercury in human blood. Sci Total Environ 1991;100:235–82. doi: http://dx.doi.org/10.1016/0048-9697(91)90380-W PMID:2063184
https://doi.org/10.1016/0048-9697(91)903... Sioen et al. estimated contaminant and nutrient intake in general populations based on global seafood availability data and found the estimated MeHg intake to be highest in Japan and the Pacific islands, followed by the Nordic and Mediterranean regions.¹⁹⁸198 Sioen I, De Henauw S, Van Camp J, Volatier J-L, Leblanc J-C. Comparison of the nutritional-toxicological conflict related to seafood consumption in different regions worldwide. Regul Toxicol Pharmacol 2009;55:219–28. doi: http://dx.doi.org/10.1016/j.yrtph.2009.07.003 PMID:19589366
https://doi.org/10.1016/j.yrtph.2009.07.... A recent European regional study examining biomarkers showed the highest MeHg exposure to be in Mediterranean countries.¹⁹⁹199 Bellanger M, Pichery C, Aerts D, Berglund M, Castaño A, Cejchanová M et al.; DEMO/COPHES. Economic benefits of methylmercury exposure control in Europe: monetary value of neurotoxicity prevention. Environ Health 2013;12:3. doi: http://dx.doi.org/10.1186/1476-069X-12-3 PMID:23289875
https://doi.org/10.1186/1476-069X-12-3... Our findings are broadly consistent with these studies and with the literature describing MeHg exposure and risk in specific subsistence fishing communities. This review adds to the evidence by synthesizing the findings from the two most recent decades of published international Hg biomarker data specifically for women and infants and by examining, in a single study, MeHg exposure in populations consuming self-caught and commercially purchased seafood.

Several limitations affect the interpretation of our results. Our goal was to compare MeHg exposure across various international groups of women and infants from seafood-consuming populations. However, incomplete reporting prevented us from evaluating the share of non-consumers of seafood in each study. Furthermore, most studies used convenience samples that may not have been representative of the populations from which they were taken. In sensitivity analysis we pooled biomarkers excluding the several large representative population surveys (which have a higher share of non-consumers of seafood than other studies). However, this did not alter our findings. Physiological differences in MeHg metabolism and elimination by life stage are well known²⁰⁰200 Stern AH, Smith AE. An assessment of the cord blood:maternal blood methylmercury ratio: implications for risk assessment. Environ Health Perspect 2003;111:1465–70. doi: http://dx.doi.org/10.1289/ehp.6187 PMID:12948885
https://doi.org/10.1289/ehp.6187... and the FAO/WHO reference dose was established based on maternal biomarkers. Thus, in sensitivity analysis we also combined biomarkers excluding infants. This resulted in slightly lower medians for the Arctic and gold mining categories and higher ones for the coastal and inland categories.

TBHg is a better indicator of recent MeHg exposure than THHg, which is a better measure of longer-term MeHg exposure.³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000.^,44 Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 2006;36:609–62. doi: http://dx.doi.org/10.1080/10408440600845619 PMID:16973445
https://doi.org/10.1080/1040844060084561... ^,66 United Nations Environment Programme. DTIE Chemicals Branch. Guidance for identifying populations at risk from mercury exposure. Geneva: World Health Organization, Department of Food Safety, Zoonoses and Foodborne Diseases; 2008. Available from: http://www.who.int/foodsafety/publications/chem/mercuryexposure.pdf [accessed 11 October 2013].
http://www.who.int/foodsafety/publicatio... Although this difference may be important among sporadic seafood consumers, the majority of our subpopulations were regular seafood consumers. Conversion of TBHg biomarkers to THHg equivalents is likely to have resulted in some measurement error. However, the range of hair-to-blood ratios reported in our studies was similar to the range on which the standard conversion ratio is based, which minimizes this bias.⁵5 Environmental health criteria document 101: methylmercury. Geneva: International Program for Chemical Safety, World Health Organization; 1990. When we pooled only THHg biomarkers, medians were slightly higher across most categories (although some categories had few observations). Despite the use of laboratory methods that relied on commonly employed protocols, detection techniques are subject to variation³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000.^,1111 Karagas MR, Choi AL, Oken E, Horvat M, Schoeny R, Kamai E et al. Evidence on the human health effects of low-level methylmercury exposure. Environ Health Perspect 2012;120:799–806. doi: http://dx.doi.org/10.1289/ehp.1104494 PMID:22275730
https://doi.org/10.1289/ehp.1104494... and quality control practices were not uniformly reported. Sensitivity analysis examining only studies using CV-AAS or similar procedures resulted in slightly higher biomarkers for the Arctic category.

Population Hg biomarker distributions are often skewed to the right, so that central tendency is best captured by geometric means or medians.³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000. Thus, in reporting our main results we chose to exclude the small number of studies reporting only arithmetic means. Including arithmetic means yielded higher results for the inland category. To give greater weight to estimates from larger samples, we pooled biomarkers using sample-size weighting. Doing so yielded higher summary biomarkers in the Arctic and coastal categories. Variations in the share of MeHg in total Hg have been reported, both among frequent and infrequent seafood consumers,²³23 Passos CJ, Mergler D. Human mercury exposure and adverse health effects in the Amazon: a review. Cad Saude Publica 2008;24:S503–20.^,201201 Dye BA, Schober SE, Dillon CF, Jones RL, Fryar C, McDowell M et al. Urinary mercury concentrations associated with dental restorations in adult women aged 16–49 years: United States, 1999–2000. Occup Environ Med 2005;62:368–75. doi: http://dx.doi.org/10.1136/oem.2004.016832 PMID:15901883
https://doi.org/10.1136/oem.2004.016832... depending in part on exposure to Hg sources other than seafood (such as elemental Hg in dental amalgams or inorganic Hg compounds in skin-lightening creams).³3 Committee on Toxicological Effects of Methylmercury, National Research Council of the United States, National Academies of Science. Toxicological effects of methylmercury. Washington: National Academies Press; 2000.^,2929 Mahaffey KR, Clickner RP, Bodurow CC. Blood organic mercury and dietary mercury intake: National Health and Nutrition Examination Survey, 1999 and 2000. Environ Health Perspect 2004;112:562–70. PMID:15064162 Most of the one quarter of selected studies examining non-seafood sources of Hg assessed the presence of dental amalgams, mainly in infrequent consumers of seafood; while this inorganic Hg source is best measured with urinary biomarkers, in cases where this exposure is important TBHg biomarkers may overestimate MeHg.²⁶26 Berglund M, Lind B, Björnberg KA, Palm B, Einarsson O, Vahter M. Inter-individual variations of human mercury exposure biomarkers: a cross-sectional assessment. Environ Health 2005;4:20. doi: http://dx.doi.org/10.1186/1476-069X-4-20 PMID:16202128
https://doi.org/10.1186/1476-069X-4-20... We eliminated high outlier biomarkers due to suspected non-seafood sources wherever these were noted by authors (most were in subpopulations where skin-lightening creams were used). Nevertheless, other sources of Hg exposure influencing high-end measures cannot be excluded. These limitations in the underlying data suggest that our findings should be interpreted cautiously. However, most sensitivity analyses resulted in higher biomarker summary statistics than the main findings we report; we chose conservative assumptions for our main results.

Estimated IQ losses in infants born to seafood consuming mothers serve as an alternative means of characterizing the public health impact of MeHg exposure. As an illustration, we applied a dose–response relationship (0.18 infant IQ point lost for every ppm increase in maternal THHg)²⁰²202 Axelrad DA, Bellinger DC, Ryan LM, Woodruff TJ. Dose-response relationship of prenatal mercury exposure and IQ: an integrative analysis of epidemiologic data. Environ Health Perspect 2007;115:609–15. doi: http://dx.doi.org/10.1289/ehp.9303 PMID:17450232
https://doi.org/10.1289/ehp.9303... that has been used to estimate the economic costs associated with Hg contamination²⁰³203 Griffiths C, McGartland A, Miller M. A comparison of the monetized impact of IQ decrements from mercury emissions. Environ Health Perspect 2007;115:841–7. doi: http://dx.doi.org/10.1289/ehp.9797 PMID:17589589
https://doi.org/10.1289/ehp.9797... ^,204204 Trasande L, Landrigan PJ, Schechter C. Public health and economic consequences of methyl mercury toxicity to the developing brain. Environ Health Perspect 2005;113:590–6. doi: http://dx.doi.org/10.1289/ehp.7743 PMID:15866768
https://doi.org/10.1289/ehp.7743... to our pooled upper bound biomarkers. The resulting interquartile range of estimated IQ loss spanned from 1 to 13 points for the gold mining, Arctic and coastal subpopulation categories. IQ losses at the higher end of this range may be sufficient to contribute to mild mental retardation, defined as an IQ between 50 and 69 points. Among subsistence fishing populations in the Amazon, an assessment of global burden of disease showed an incidence of mild mental retardation of up to 17.4 cases per 1000 infants²⁰⁵205 Poulin J, Gibb H. Mercury: assessing the environmental burden of disease at national and local levels (Environmental burden of disease series no. 16). Geneva: World Health Organization; 2008. and separate research identified MeHg-associated deficits in memory and learning in adults.²⁰⁶206 Yokoo EM, Valente JG, Grattan L, Schmidt SL, Platt I, Silbergeld EK. Low level methylmercury exposure affects neuropsychological function in adults. Environ Health 2003;2:8. doi: http://dx.doi.org/10.1186/1476-069X-2-8 PMID:12844364
https://doi.org/10.1186/1476-069X-2-8... IQ losses in the lower end of the range may contribute to borderline intellectual functioning, characterized by memory and executive function deficits.²⁰⁷207 Alloway TP. Working memory and executive function profiles of individuals with borderline intellectual functioning. J Intellect Disabil Res 2010;54:448–56. doi: http://dx.doi.org/10.1111/j.1365-2788.2010.01281.x PMID:20537050
https://doi.org/10.1111/j.1365-2788.2010... Although such minor losses in IQ may go unnoticed in an individual, they can cause an important shift in intellectual capacity at the population level, as documented in the case of lead.²⁰⁸208 Fewtrell L, Kaufmann R, Pruss-Ustun A. Lead: assessing the environmental burden of disease at national and local levels (Environmental burden of disease series no. 2). Geneva: World Health Organization; 2003. IQ loss represents only one facet of the neurological harm resulting from MeHg; our analysis did not include recent research suggesting neurological effects at lower dose¹¹11 Karagas MR, Choi AL, Oken E, Horvat M, Schoeny R, Kamai E et al. Evidence on the human health effects of low-level methylmercury exposure. Environ Health Perspect 2012;120:799–806. doi: http://dx.doi.org/10.1289/ehp.1104494 PMID:22275730
https://doi.org/10.1289/ehp.1104494... or other documented effects, such as adverse cardiovascular outcomes.²⁰⁹209 Roman HA, Walsh TL, Coull BA, Dewailly É, Guallar E, Hattis D et al. Evaluation of the cardiovascular effects of methylmercury exposures: current evidence supports development of a dose-response function for regulatory benefits analysis. Environ Health Perspect 2011;119:607–14. doi: http://dx.doi.org/10.1289/ehp.1003012 PMID:21220222
https://doi.org/10.1289/ehp.1003012...

Systematic reviews provide an opportunity to identify gaps in a body of research. Small-scale gold mining is practiced in 70 countries,²¹⁰210 Mercury use in artisanal and small scale gold mining (module 3). Geneva: United Nations Environment Programme; 2008. Available from: http://www.chem.unep.ch/mercury/awareness_raising_package/E_01-16_BD.pdf [accessed 13 October 2013].
http://www.chem.unep.ch/mercury/awarenes... but we found Hg biomarker studies meeting our criteria in only six. We identified studies in 23 coastal countries, although per capita seafood consumption data suggest that many other such countries warrant study.²⁰20 The state of world fisheries and aquaculture: world review of fisheries and aquaculture – part 1. Rome: Food and Agriculture Organization; 2010. Available from: http://www.fao.org/docrep/013/i1820e/i1820e01.pdf [accessed 12 October 2013].
http://www.fao.org/docrep/013/i1820e/i18... Although reviews of subsistence fishing populations in the Amazon and Arctic are available, few have been conducted for coast-dwelling frequent seafood consumers (e.g. in south-eastern Asia or the Mediterranean) or for fishing populations near abandoned chloralkali plants and other aquatic sources of Hg contamination. We found population-based Hg biomonitoring surveys in only a handful of countries; most are high-income and have relatively low per capita seafood consumption.

It was beyond the scope of this review to assess time trends in Hg biomarkers. Without major policy changes, projections indicate that global anthropogenic Hg emissions are likely to increase.²¹¹211 Streets DG, Zhang Q, Wu Y. Projections of global mercury emissions in 2050. Environ Sci Technol 2009;43:2983–8. doi: http://dx.doi.org/10.1021/es802474j PMID:19475981
https://doi.org/10.1021/es802474j... Moreover, modelling suggests that any reduction in Hg emissions is likely to take time to translate into reduced MeHg in seafood.²¹²212 Sunderland EM, Selin NE. Future trends in environmental mercury concentrations: implications for prevention strategies. Environ Health 2013;12:2. doi: http://dx.doi.org/10.1186/1476-069X-12-2 PMID:23289850
https://doi.org/10.1186/1476-069X-12-2... Declines in Hg biomarkers in humans have been observed in association with changes in seafood consumption habits in various populations. This finding reinforces the importance of carefully designed public health messages intended to reduce MeHg exposure.¹⁹⁹199 Bellanger M, Pichery C, Aerts D, Berglund M, Castaño A, Cejchanová M et al.; DEMO/COPHES. Economic benefits of methylmercury exposure control in Europe: monetary value of neurotoxicity prevention. Environ Health 2013;12:3. doi: http://dx.doi.org/10.1186/1476-069X-12-3 PMID:23289875
https://doi.org/10.1186/1476-069X-12-3... ^,212212 Sunderland EM, Selin NE. Future trends in environmental mercury concentrations: implications for prevention strategies. Environ Health 2013;12:2. doi: http://dx.doi.org/10.1186/1476-069X-12-2 PMID:23289850
https://doi.org/10.1186/1476-069X-12-2... In subsistence fishing populations, the cultural importance of seafood harvesting and the scarcity of alternative animal protein sources suggest the existence of complex tradeoffs in guiding seafood consumption and the need for well-targeted messages. In predominantly urban seafood-consuming coastal populations, commercial seafood advisories may be an appropriate choice for reaching at-risk populations.¹⁹19 Sheehan MC. Risk of developmental neurotoxicity due to methylmercury in seafood: examining global exposures, susceptibility and policy. Johns Hopkins Bloomberg School of Public Health, Health Policy and Management Department; 2011. [Dissertation]. Because of seafood’s important nutritional benefits, all such messages should aim to encourage a shift away from large apex predator species and towards those with lower MeHg and higher polyunsaturated fatty acid content, rather than to reduce seafood intake.

Conclusion

In this review of biomarkers of MeHg intake in women and infants from 164 studies across 43 countries, we found a very high risk in tropical riverine populations near gold mining sites and in traditional Arctic populations. In both groups, biomarkers suggest average MeHg intake exceeds the FAO/WHO recommendation, although their share of the global total of seafood-consuming women and infants is likely to be fairly small. We also found an elevated risk among seafood consumers in the coastal regions of south-eastern Asia, the western Pacific and the Mediterranean; a large share of the world’s seafood-consuming women and their infants is likely to be found in this group because of its large population. In other populations for whom data were available, average indicators of risk were lower and generally within international intake recommendations. However, women and infants with high exposure to MeHg were evident across all exposure categories. Although sources of bias were present, these results should help to set broad priorities for preventive policy and research.

The findings of this review underscore the importance of WHO’s call for enhanced population monitoring and risk communication to women of reproductive age regarding healthful seafood choices.¹1 World Health Organization [Internet]. Mercury and health (Fact sheet No. 361). Geneva: WHO; 2013. Available from: http://www.who.int/mediacentre/factsheets/fs361/en/ [accessed 11 October 2013]
http://www.who.int/mediacentre/factsheet... One of the provisions of the Minamata Convention aims to protect vulnerable populations from Hg exposure through public education and other measures.²¹³213 Draft Minamata Convention on Mercury. Geneva: United Nations Environment Programme; 2013. Available from: http://www.unep.org/hazardoussubstances/Portals/9/Mercury/Documents/INC5/INC5_7asterisk_final%20report_26%2008_e.pdf [accessed 9 December 2013].
http://www.unep.org/hazardoussubstances/... The Convention is a potentially important strategic tool to reach the populations at highest risk through development of seafood advisory risk messages for commercial seafood consumers, targeted community-based interventions for subsistence fishing groups and regular population surveillance.

References

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