Environmental Exposures to Mercury PDF

ENVIRONMENTAL EXPOSURES TO MERCURY Mercury in the Environment  Mercury is a metal released into the ecosystem through both natural events, such as forest fires and volcanic eruptions, and through human activities, such as coal burning and metal smelting.  In its elemental fo...

ENVIRONMENTAL EXPOSURES TO MERCURY Mercury in the Environment  Mercury is a metal released into the ecosystem through both natural events, such as forest fires and volcanic eruptions, and through human activities, such as coal burning and metal smelting.  In its elemental form, mercury is stable in the air and can travel far from its emission source.  When deposited in the environment, mercury may be transformed by natural processes to its organic and toxic form, methylmercury.  Methylmercury can accumulate in living organisms such as plants, animals, and humans at levels that can pose serious health risks. Mercury in the Environment  Mercury exposure at elevated levels can have effects on human neurological, immune, and reproductive systems.  The primary route of exposure to mercury for humans is through the consumption of fish and certain wildlife species.  Over 90% of the fish advisories in Canada are due to mercury, and many fish and fish-eating birds and mammals are at risk from mercury exposure.  In the Arctic, levels of mercury remain high in some wildlife, and exposure to mercury through the consumption of traditional foods may pose health risks to northern Canadians. Metallic (elemental) mercury Hg 0 is a liquid metal at room temperature Mercury Rising (AMAP, 2011) Watch at: http://vimeo.com/54936 463 Sources of exposure to mercury and methylmercury in the environment Individual exposures Community exposures Source: http://webcam.srs.fs.fed.us/impacts/me rcury/  0 2+ Movement of mercury in the environment and metal speciation as Hg , Hg and methylmercury (MeHg) Mobilization from soil (or ice) and biomagnification of mercury within the aquatic environment chemical transformation mobilization atmospheric precipitation biomagnification in food chain uptake by small biota Fish Mercury Regulatory Values Canadian Food Inspection Agency has a 0.5 ppm limit on all retail-purchased fish except:  Shark  Swordfish  Fresh/frozen tuna Consumer advisory (2002) issued dietary advice for consumption of exempted fish:  General Adult Population: 1 meal per week  Women of Childbearing age: 1 meal per month  Young Children: 1 meal per month A non-enforceable guideline of 0.2 ppm is sometimes applied for risk assessments involving frequent fish consumers Advice on Sport Fishing in Ontario The guide includes: Sizes and amounts of fish you can safely eat How to choose fish with the lowest levels of contaminants Fish you should not eat (including special advice for children and pregnant women) How to prepare fish to reduce contaminants Different Guide contaminants Available for Free from: found in https://www.ontario.ca/page/eating-ontario-fish-2017-18 Ontario fish Mercury Tolerable Daily Intake Total Mercury for the General Population BCS 2007: 0.71 µg/kg/d Methylmercury for the General Population BCS 2007: 0.47 µg/kg/d WHO 2003: 0.23 µg/kg/d Methylmercury for Sensitive Sub-populations BCS 2007: 0.20 µg/kg/d Sport Fish Consumption Advisories  + + Organic mercury compounds: methylmercury (MeHg ), Ethylmercury (EtHg ), Dimethylmercury, and Thiomersal very lipophilic (supertoxic) Methylmercury (MeHg) (hydrophilic) Ethylmercury (EtHg) (hydrophilic) very hydrophilic ‘Molecular mimicry’: methylmercury (MeHg) mimics the methyl sulfur group in the amino acid methionine S S Hg + + CH3Hg + Cys --> CH3Hg-S-Cys MeHg + cysteine --> cysteinyl methylmercury (~ mimics methionine) Transport of methylmercury (CH 3Hg+) as a methionine mimic across the BBB via LAT1 luminal side (blood) abluminal side (brain) Transport of methylmercury (MeHg) and possibly ethylmercury (EtHg) across the BBB by LAT1 channel MTF1 = metal regulatory transcription factor 1 LAT1 = large aminoacid transporter 1 MT1a = metallothionine DMT1 = divalent metal transporter 1 Mercury Emissions are a Global Problem  Minamata Convention on Mercury The Minamata Convention on Mercury is a global treaty to protect human health and the environment from the adverse effects of mercury. January 19, 2013 – Agreement established in Geneva, Switzerland June 11, 2013 - First Signatory and Ratification: United States October 10, 2013 – Canada and 85 other countries sign Emission Controls:  Coal-fired power-plants, small-scale artisanal gold mines Banned new mercury mines (phase-out existing) Minamata Convention on Mercury Some mercury containing items (with alternative replacements) Production, Import, and Export to be banned by 2020:  Batteries (exception: Implantable medical device button cell)  Some compact fluorescent lamps  Switches, relays  Soaps and cosmetics  Thermometers, blood pressure devices Ratification of 50 signatories -> Enshrined in international law Minamata Convention on Mercury  The Minamata Convention on Mercury entered into force on August 16th, 2017.  The first Conference of the Parties (COP1) just took place from September 24th through 29th, 2017, in Geneva, Switzerland.  You can get more information on COP1 from their website at http://cop1.mercuryconvention.org/.  This was the opening video shown to the delegates at the Conference: https://youtu.be/ov_XC7uisHs.  2014 Ratifications:  2015 Ratifications: 2016/2017 2018 2019 New Countries: Antigua and Barbuda Costa Rica Peru Benin Denmark Sierra Leone Bolivia Ecuador Swaziland Botswana Gambia Switzerland Brazil India United Arab Canada Japan Emirates China Mali Zambia Mercury Emissions are a Global Problem 95% of anthropogenic mercury deposited in Canada comes from outside Canada China accounts for by far the most world-wide emissions of mercury  Mercury Emissions are a Global Problem http://www.downtoearth.org.in/news/amount-of-mercu ry-in-environment-grossly-underestimated-46278 What is Minamata Disease? What first brought the issue of mercury poisoning to the World’s attention? Why is it called the Minamata Convention on Mercury? WARNING DISTURBING IMAGES FOLLOW ON THE FOLLOWING MOVIE The following video shows:  Debilitating neurological effects in adults  Neurotoxic effects in cats  Congenital neurodevelopmental effects Minamata Bay https://www.youtube.com/watch?v=ihFkyPv1jtU Minamata Disease Areas around Minamata Bay Japan with outbreaks of prenatal mercury poisoning from the Chisso plastics plant 27 tons MeHg dumped into Minamata Bay Thousands affected Congenital harm through fetal exposure McCurry (2006) Japan Remembers Minamata. The Lancet.  Over 900 died from severe methylmercury neurotoxicity  2200 officially recognized as being affected  In addition to physiological affects, social effects were rampant  10,000 others dropped a lawsuit against the Chisso Corporation after receiving out-of- court settlement in 1996  3000 others filed claims after poisoning criteria were relaxed  As of 2006, Government of Japan steadfastly held to 1977 MeHg poisoning definition which set a much higher bar  Victims of congenital MeHg poisoning remain as their parents and caregivers entering old age The Grassy Narrows and the White Dog Reserves  A Canadian example of mercury poisoning can be seen in the long- term impacts observed at the Grassy Narrows and White Dog First Nations Reserves located near Dryden, Ontario. The two communities were ravaged by mercury poisoning starting in the 1960's when a local paper mill began dumping toxicants, including methylmercury, into the English-Wabigoon River. Estimates suggest the Dryden Chemical Company mill deposited 10 tonnes of neurotoxicants into the system between 1962 and 1970, contaminating lakes and rivers for at least 250 km. Grassy Narrows MeHg Poisoning  MeHg reached very high levels in walleye and northern pike  Exposures substantially exceeded neurotoxicity thresholds  Approximately 60 individuals were diagnosed with Minamata disease by a Japanese MeHg expert  Dozens of these individuals were not recognized by the Mercury Disability Board  Health and economic disaster (community reliant of fishing and related industries)  Psychosocial and cultural effects  High percentage of deaths from drugs/alcohol  High rates of depression, anxiety, self-injury, and suicide Toxicology in the News TIMELINE: http://tvo.org/article/current-affairs/shared-values/how-the-waters-of-grassy-narrows-were-poison ed Class Discussion Any other thoughts or questions? Why not relocate the community? Who should pay for the clean-up? Molecular Sequestration: Another Example Selenium (Se)  A metalloid with extremely high affinity for mercury (inorganic and organic forms) in tissues.  Selenium has a million times greater affinity for mercury than does sulfur (S).  Selenoproteins bind and sequester mercury for prolonged periods (acts as sink).  It is thought to be a protective sequestration mechanism in target tissues (e.g., brain)  Controversy: Is selenium binding truly protective in the brain tissue? Case Study: MeHg Neurotoxicity and Selenium Toxic effects of high MeHg doses in humans and animals are well documented. There are clear adverse effects of exposures to high environmental concentrations of MeHg in both children and adults. However, the implications of low MeHg doses are controversial due to contrasting epidemiology results. To examine this, let’s look at the results of two separate epidemiological studies conducted on the effects of low level MeHg on two island nations with similar exposure level. Case Study: MeHg Neurotoxicity and Selenium Seychelles Islands An archipelago and country in the Indian Ocean, with a population of roughly 92,000 people. Seychelles has developed from a largely agricultural society to a diversified economy driven by the public sectors and tourism. Faroes Islands An archipelago between the Norwegian Sea and the North Atlantic approximately halfway between Norway and Iceland. Its economy is almost entirely dependent on fishing and fish farming. Case Study: MeHg Neurotoxicity and Selenium Seychelles islanders Faroes islanders fish diet – med-high MeHg Pilot whale diet – med-high MeHg high LC-PUFA and high Se low LC-PUFA and low Se Seychelles children Faroes children normal impaired brain development brain development Case Study: MeHg Neurotoxicity and Selenium Case Study: MeHg Neurotoxicity and Selenium Selenium protects against MeHg toxicity in humans and animals. MeHg exposure impacts selenoenzyme activities. Selenium sequestration may be the major toxic mechanism of methylmercury poisoning. (from Ralston 2010) Competing Paradigms of Hg-Se Interactions Hypothesis 1: Se is a Hg Antagonist (Conventional Paradigm) Selenium sequesters mercury to prevent harm Hypothesis 2: Hg is a Se Antagonist (Proposed Paradigm) Mercury sequesters selenium and prevents Se from participating in selenoenzyme synthesis Selenium binding is the harm Summary: MeHg Neurotoxicity and Selenium Rich dietary selenium (e.g., selenocysteine) protects against MeHg Se supplementation treatment of MeHg toxicity Restore normal weight gain Limits progression of neurotoxicity MeHg inhibits selenoenzymes through selenium sequestration Because Hg’s binding affinities for Se are up to a million times higher than for sulfur, its second-best binding partner, MeHg irreversibly sequesters selenium, directly impairing selenoenzyme activities and their synthesis. Selenoenzymes are required to prevent and reverse oxidative damage throughout the body, particularly in the brain and neuroendocrine tissues. So How do We Quantify this Relationship? Since the selenium present in food (like fish) protects against MeHg exposures at the same time, actual risks of MeHg exposure must assess both elements. The Selenium Health Benefit Value (SeHBV) of various seafoods has been established to reflect not only the mercury contamination present, but also the selenium content in seafoods. This approach uses molar ratios and absolute amounts of mercury and selenium present to calculate an index that may describe MeHg risk.  Selenium Health Benefit Value 𝑆𝑒𝐻𝐵𝑉 = 𝑆𝑒 𝜇 𝑚𝑜𝑙 × 𝑆𝑒( 𝜇 𝑚𝑜𝑙 𝑘𝑔 ) − 𝐻𝑔 𝜇 𝑚𝑜𝑙 × ( 𝐻𝑔 𝜇 𝑚𝑜𝑙 𝑘𝑔 ) ( 𝑘𝑔 ) ( 𝑘𝑔 ) 𝑘𝑔 𝜇 𝑚𝑜𝑙 𝑘𝑔 𝜇 𝑚𝑜𝑙 𝐻𝑔 𝑆𝑒 SeHBV ≥ 0 : ↑[Se]; ↑Se:Hg → Net Benefit SeHBV < 0 : ↑[Hg]; ↑Hg:Se → Net Risk Selenium Health Benefit Value 𝑆𝑒 ( 𝑘𝑔 ) ( 𝑘𝑔 ) 𝜇 𝑚𝑜𝑙 𝜇 𝑚𝑜𝑙 𝐻𝑔 𝑆𝑒 𝜇 𝑚𝑜𝑙 𝐻𝑔 𝜇 𝑚𝑜𝑙 𝑆𝑒𝐻𝐵𝑉 = × − × ( 𝑘𝑔 ) ( 𝑘𝑔 ) 𝑘𝑔 𝜇 𝑚𝑜𝑙 𝑘𝑔 𝜇 𝑚𝑜𝑙 𝐻𝑔 𝑆𝑒 Health Canada: https://food-nutrition.canada.ca/c nf-fce/index-eng.jsp USDA: http://ndb.nal.usda.gov/ndb/searc h/list Selenium Health Benefit Value Northern Pike (Esox lucius) Look up [Se] from Health Canada CNF: 50 µg/100 g = 500 µg/kg Molecular Weights: Convert to µmol/kg: Hg: 200.59 g/mol Se: 78.96 g/mol = 500 µg/kg ÷78.96 g/mol [Se] = 6.33 µmol/kg Selenium Health Benefit Value Northern Pike (Esox lucius) Look up [Hg] from Health Canada BCS (2007): 0.25 mg/kg = 250 µg/kg Molecular Convert to µmol/kg: Weights: Hg: 200.59 g/mol = 250 µg/kg ÷200.59 g/mol Se: 78.96 g/mol [Hg] = 1.25 µmol/kg HHRA of Mercury in Fish and Health Benefits of Fish Consumption (HC BCS, 2007): http://www.hc-sc.gc.ca/fn-an/alt_formats/hpfb-dgps a/pdf/nutrition/merc_fish_poisson-eng.pdf Selenium Health Benefit Value Northern Pike (Esox lucius) If [Se] = 6.33 µmol/kg; [Hg] = 1.25 µmol/kg: Calculate Se:Hg Ratio [Se]:[Hg] = 6.33 ÷1.25 = 5.08 Calculate Hg:Se Ratio [Hg]:[Se] = 1.25 ÷ 6.33 = 0.20 Selenium Health Benefit Value Northern Pike (Esox lucius) GOOD! Specie [Se] Se:Hg [Hg] Hg:Se Se s HBV E. 6.33 5.08 1.25 0.20 31.9 lucius 𝑆𝑒𝐻𝐵𝑉 = 𝑆𝑒 𝜇 𝑚𝑜𝑙 × ( 𝑆𝑒 𝑘𝑔 ) − 𝐻𝑔 𝜇 𝑚𝑜𝑙 × ( 𝜇 𝑚𝑜𝑙 𝐻𝑔 ) 𝜇 𝑚𝑜𝑙 𝑘𝑔 ( 𝑘𝑔 ) ( 𝑘𝑔 ) 𝑘𝑔 𝜇 𝑚𝑜𝑙 𝑘𝑔 𝜇 𝑚𝑜𝑙 𝐻𝑔 𝑆𝑒 What happens to Se HBV if the Hg content of the pike goes up to 2.8 mg/kg? Selenium Health Benefit Value Northern Pike (Esox lucius) QUICK REVIEW: Selenium Health Benefit Value 𝑆𝑒𝐻𝐵𝑉 = 𝑆𝑒 𝜇 𝑚𝑜𝑙 × ( 𝑆𝑒 𝑘𝑔 ) − 𝐻𝑔 𝜇 𝑚𝑜𝑙 × ( 𝜇 𝑚𝑜𝑙 𝐻𝑔 ) 𝜇 𝑚𝑜𝑙 𝑘𝑔 ( 𝑘𝑔 ) ( 𝑘𝑔 ) 𝑘𝑔 𝜇 𝑚𝑜𝑙 𝑘𝑔 𝜇 𝑚𝑜𝑙 𝐻𝑔 𝑆𝑒 Look up [Se] from Health Canada CNF: e.g., 50 µg/100 g = 500 µg/kg Convert to µmol/kg: MAKE SURE YOU DO = 500 µg/kg ÷ 78.96 g/mol THE MOLAR [Se] = 6.33 µmol/kg CORRECTION! Look up [Hg] from Health Canada BCS (2007): 0.25 mg/kg = 250 µg/kg Molecular Convert to µmol/kg: Weights: Hg: 200.59 g/mol = 250 µg/kg ÷ 200.59 g/mol Se: 78.96 g/mol [Hg] = 1.25 µmol/kg Updated Se:Hg Criterion MAKE SURE YOU DO THE MOLAR CORRECTION! Molecular Weights: All units still in µmol/kg Hg: 200.59 g/mol Se: 78.96 g/mol Selenium Health Benefit Value Homework Choose 1 Fish from Appendix I of HC BCS (2007) Look up the average [Hg] concentration for this fish Look up the [Se] concentration from the CNF Calculate the SeHBV to determine if this fish has enough Se to “offset” the risk from Hg Calculate the HBVSe using Ralston’s updated equation. Don’t forget to do the molar adjustment to the concentration!  Reality Check: Balancing Mercury Risks and Nutrient Benefits  Other nutritional benefits are ignored (e.g., LC n-3 PUFA)  Little evidence of inadequate selenium intakes in North America. The same cannot be said for LC n-3 PUFA.  Other contaminant risks are ignored (e.g., PCBs)  The risks of selenosis and the complexity of selenium speciation are ignored.  To my knowledge, no regulatory agency relies on these Seafood Safety Criteria for decision making.  Advising people to limit some fish (and eat more of others) can reinforce inequities.  Decreasing global emissions (i.e., the Minamata Convention) is the only long-term solution. PRESENTATION TITLE PAGE 55 Hg and Pb and the risk of fetal toxicity during early human development Mercury Lead Environmental Occurrence Food/ Inorganic Hg (Amalgam) Inorganic – Many Sources Water Organic Hg (MeHg in Organic - Unlikely fish) Air Transport Only Transport and Exposure (dusts) Soil Reservoir But Not Reservoir and Exposure Exposure (Soil/Dust) Nutrient Interactions Nutrient Selenocysteine Ca2+, Fe2+, Zn2+? Effects No effect of GI absorption Ca2+, Fe2+ decrease AFgit Reduces toxicity at target Storage Major: Muscle; Minor: Major: Bone; Minor: Baby teeth Site Hair Biomarke Hair, Blood, Finger/toe- Blood, Teeth, Bone r nails*  Hg and Pb and the risk of fetal toxicity during early human development Mercury Lead Fetal Exposure Placenta Fetus Blood Hg > Fetus Blood Pb = Maternal Blood Maternal Blood Hg Pb Retention Apparently low (fast Apparently High (Bone storage) turnover) Maternal Current Exposure > Body Body burden > Current Exposure Status Burden Milk-Fed Babies Breast Breastmilk Hg < Maternal Breastmilk Pb