Mercury is a natural element found in the environment. Throughout time, mercury has served many purposes in the areas of agriculture, industry, and medicine, including folk remedies. It also has been responsible for significant morbidity and mortality.
One of the most striking examples of morbidity was the disaster at Minamata Bay, Japan, where humans ingested fish and shellfish that were contaminated by methylmereury from the discharge of mercuric oxide from a nearby chemical plant.1 Thousands of people have been recognized as having diseases related to this exposure, with a considerable number of infants exhibiting significant neurodevelopmental disabilities at birth. A second devastating episode of acute mercury poisoning occurred in Iraq in the early 1970s when seed grain, pretreated with methylmercury as a fungicide, was inadvertently ingested in homemade bread.2 Hundreds of deaths and thousands of people with severe mercury intoxication were identified.
Even today, there are several reports each year of isolated mercury spills, usually related to elemental mercury found in old laboratory equipment such as thermometers and barometers from schools, labs, or hospitals. One incident closed a high school in the metropolitan Washington, DC, area for several months.3 Hundreds of area residents were screened for exposure to mercury, and 17 families were displaced from their homes during the evaluation and clean-up efforts.
This article reviews general information on sources of mercury and clinical syndromes, with an emphasis on recent government regulations and advisories that affect the pediatric population.
FORMS OF MERCURY
There are three general forms of mercury: elemental, inorganic, and organic. Elemental mercury, also known as quicksilver, can exist in liquid or vapor form. It is commonly found in thermometers, blood-pressure-measuring devices, batteries, and fluorescent light bulbs,4 as well as in ritualistic practices of certain ethnic populations.5 Several religious practices that incorporate use of mercury-containing substances include the following: Santería, a Cuban-based practice; Voodoo, a Haitian ritual; Palo Mayombe, a Caribbean worship; and Espiritismo, practiced in Puerto Rico.6
Attention has also been paid to mercury-containing dental amalgams that may contain nearly 50% mercury by weight. However, elemental mercury vapor in the environment largely comes from the burning of fossil fuels such as high sulfur coal. According to the Environmental Protection Agency (EPA) Mercury Study Report to Congress in 1997, manmade mercury pollution in the environment stems from coal-fire power plants (33%), industrial boilers (17.9%), municipal waste combustors (18.7%), medical waste incinerators (10.1%), and other sources (20.5%).7
Elemental mercury has a melting point of -38°C.8 Its volatility leads to significant toxicity from mercury vapor, which is lipid soluble, with approximately 80% easily passing through the lungs and entering the bloodstream.6 It is oxidized to the inorganic mercury form, which is then toxic to the kidneys and nervous system. Metallic mercury, once in the blood stream, may pass to a developing fetus and may be excreted in breast milk. Swallowed metallic mercury is virtually unabsorbed through the intestines.
There are several case reports of clinical presentations of elemental mercury poisoning mimicking the classic Mad Hatter character from Alice in Wonderland.9-10 Acute and chronic exposures, from accidental or occupational sources, may present with decreased appetite, restlessness, sweating, hypertension, tachycardia, an erythematous rash and erethism, a syndrome of red palms, emotional lability, and memory impairment. This constellation of symptoms initially may be hard to distinguish from other medical and psychiatric conditions and, therefore, a history of exposure to mercury is often critical to making the diagnosis.
Elemental mercury in dental amalgams has been reviewed."12 Despite elevation in urinary excretion of mercury correlating with the number of dental amalgams (estimated increased urinary concentrations of lpg per 10 dental amalgams), this amount of mercury is thought to be insignificant in comparison to other sources such as fish consumption.4 No associated clinical conditions have been linked with mercurycontaining dental amalgams. Removal of dental amalgams may result in transient elevations in urinary excretion and is therefore not recommended.13
Historically, inorganic mercury salts were commonly used as antibacterials, cathartics, folk remedies, and teething powders. Inorganic mercuric salts can be caustic to the skin and gastrointestinal tract. Less than 10% is generally absorbed; in certain instances, however, up to 40% may be absorbed through the stomach and the intestines.
Inorganic mercuric salts are known to affect the kidneys, predominantly causing nephropathy and glomerular damage. The childhood syndrome of acrodynia - symptoms of which include swollen, painful, red fingers and toes, a maculopapular rash, hypertension, peripheral neuropathy, and kidney dysfunction - was frequently reported in the 1940s in children exposed to teething powders and laxatives containing inorganic mercury salts.14 Inorganic mercury, once absorbed, does not enter the brain easily, but it can move through the blood stream to the developing fetus and may be excreted in breastmilk.
Organic mercury compounds, including methylmercury, ethylmercury, and phenylmercury, are highly lipid-soluble and therefore are readily absorbed through the gastrointestinal tract. They have been used as fungicides, pesticides, antiseptics, and preservative agents.
Methylmercury is ubiquitous in the environment because common bacteria readily methylate elemental mercury, converting it into the methylmercury form. Methylmercury can accumulate in the aquatic food chain, with the highest concentrations in larger predator fish and sea mammals that consume smaller fish. Fish consumption, as well as consumption of marine mammals and large game that also eat fish, are the main sources of methylmercury exposure in humans.
Methylmercury is 95% absorbed by the gastrointestinal tract after consumption and readily passes through the placenta and across the blood-brain barrier. It also passes through breast milk. Methylmercury can be neurotoxic to adults and children and teratogenic to the developing nervous system of the fetus. As previously mentioned, the Minamata Bay example illustrates how ingestion of highly contaminated fish led to clinical findings of cerebral palsy, microcephaly, seizures, and mental retardation in those children who were exposed prenatally.1 These children showed severe impairment even though their mothers were reported to have few, if any, clinical symptoms.
There are two ongoing longitudinal studies involving children in fish-eating populations, in the Republic of the Seychelles and the Faroe Islands.15-20 Children have been closely followed for 7 years with specific developmental and neurological screening tools. In correlating findings with maternal hair samples for mercury, investigators in the Faroe Islands were able to link impaired attention and memory with elevated maternal mercury levels in children at age 7." In contrast, in the Seychelles studies, no linkages were found between developmental or neurological abnormalities and maternal hair mercury levels in children at age 66 months.16-20
Researchers speculate that the differenees in the pattern of fish-eating habits may account for the different findings. In the Seychelles, mothers reported eating 12 fish-containing meals per week of different fish, but mothers in the Faroe Islands reported eating up to three meals per week of cod, with an occasional feast of pilot whale meat. Some speculate that the larger sea mammals, pilot whales, have larger amounts of methylmercury and may have more of an acute effect, depending on the developmental vulnerability of the person or fetus at the time of exposure.21,22 Further research is needed to determine the public health implications of fish consumption and methylmercury exposure.
Mercury Reference Levels
An outbreak of mass mercury poisoning occurred in Iraq in the early 1970s when mercury was used as a fungicide on seed grain strictly intended to be used for farming.2 The grain was inadvertently used by the local population during a period of months to make bread. Many of the affected victims were children, who experienced symptoms including emotional instability, speech disturbance, ataxia, deafness, and blindness.23 Studies of this population showed that the children did not seem to be more susceptible than adults at the same level of methylmercury exposure, and they appeared to have a greater capacity for recovery.24
Based on this experience, the EPA established a reference dose for mercury of 0.1 pg/kg per day. The National Academy of Sciences, using the Seychelles and Faroe Island studies, determined a reference dose for mercury to be the same.25 In contrast, the Agency for Toxic Substances and Disease Registry developed a proposed minimum risk level of 0.3 pg/kg per day, based on the Seychelles Island data.6 (Sidebar 1, see page 439.)
Ethylmercury, in the form of thimerosal, was used as a preservative agent in routine childhood immunizations prior to 1999. In July 1999, the American Academy of Pediatrics and the United States Public Health Service published a joint statement recommending the replacement of thimerosal in all vaccines.26 Less is known about the toxic effects of ethylmercury than of methylmercury, but the Food and Drug Administration (FDA) questioned whether infants receiving multiple thimerosal-containing vaccines may be exposed to higher than acceptable levels of mercury. As a result, all routine childhood vaccines in the United States are now thimerosal-free.27
Phenylmercury, previously used as a fungicide in latex paints, is known to be less toxic than both methylmercury and ethylmercury. It was removed from interior latex paints in 1991 because of the risk of inhaled mercury vapor.28
DIAGNOSIS AND TREATMENT
The most important means of diagnosing and treating mercury poisoning is identifying and removing the source of exposure. To do this, one must have an elevated index of suspicion based on clinical information, and appropriate questions must be asked to identify possible exposures.
An environmental history should contain questions regarding the home and school environments, possible exposures through parental occupations, hobbies, diet, and sources of potential industrial exposures. Organic mercury compounds can be measured in blood or hair samples, with generally accepted normative data available for comparison.
Exposure to inorganic mercury can be measured in urine using a 24-hour collection. Urine values ideally should be obtained by using a 24-hour urine sample and correcting for grams of creatinine in the sample. Levels greater than 10 to 20 pg/L suggest excessive exposure; with levels above 100 µg/L, neurologic signs may be present. Usual blood mercury levels in unexposed individuals are less than 20 pg/L.29 Of note, blood values may be normal shortly after exposure because of the short halflife of mercury in blood.
Prevention of mercury exposure is of paramount importance because treatment of mercury intoxication is quite controversial and treatment options are limited. If metallic mercury is spilled, such as from a broken thermometer, vacuuming the area is not recommended because this increases the risk of vaporization of the mercury, thus increasing the risk of absorption through the lungs. Rather, it is recommended to use paper to carefully lift the mercury beads and place them in a sealed plastic bag or an airtight container. The bag or container should be disposed of properly after contacting appropriate local or state health departments.
The FDA has not approved any chelation therapy for use in methylmercury or ethylmercury poisoning, although chelation has been used in some severe cases. D-penicillamine was one of the earliest chelators used to enhance urinary excretion of mercury, but recently more effective agents have been studied. Both meso-2-3dimercaptosuccimer and 2,3-dimercapto1-propanesulfonic acid enhance excretion of methylmercury, but they have limited stability and may actually be hannful because they may increase brain concentrations of mercury and other metals.29,30
A recent study in mice evaluated Nacetylcysteine (NAC) as a chelating agent for methylmercury, and results demonstrated NAC enhanced urinary excretion of methylmercury without increasing brain concentrations.30 NAC is otherwise known to be nontoxic, as it is frequently used in cases of acetaminophen toxicity. Therefore, NAC may be a promising agent for use as a chelator in patients with significant organic mercury poisoning.30
Chelating agents have been used in severe cases of elemental and inorganic mercury toxicity, although indications for use are not well established. Children with severe mercury poisoning should be treated with the assistance of physicians experienced in this area. These children need close neurological and developmental follow-ups.29
EPA AND FDA RECOMMENDATIONS
In December 2003, the FDA and EPA jointly released a new draft of a methylmercury consumer advisory.31 This is the first time these two federal organizations have combined their advice to produce a single advisory statement. The official advisory was finalized in March 2004.32 The statement is aimed at the high-risk population of pregnant women, women who may become pregnant, and nursing mothers. Whereas the FDA had previously advised that this population of women should avoid eating shark, swordfish, king mackerel, and tilefish, they had not addressed concerns regarding intake of tuna. This new advisory specifically addresses higher levels of mercury in tuna steaks and canned albacore tuna, recommending that women at risk eat no more than 4 to 6 oz of tuna once a week.
The advisory also continues to recommend that fishermen check local fish advisories for recommendations on locally caught fish, and to not eat any other fish in the same week as eating locally caught fish. Recommendations are extrapolated to children, with advice to follow the same rules but with smaller portion sizes allotted.32 (Sidebars 2 and 3, see pages 439 and 440.)
EPA-PROPOSED INTERSTATE AIR QUALITY RULE
In December 2003, the EPA administrator signed the proposed Interstate Air Quality Rule to cut emissions of sulfur dioxide and nitrogen oxides.33 This proposal also includes regulations for mercury emissions from coal-burning power plants. The EPA Administrator, Mike Leavitt, described these new actions as "strengthen(ing) the Clean Air Act regulations and standards to bring Americans the most rapid and significant air quality improvement in a decade."33 The proposal outlines two approaches to reducing mercury emissions. One approach requires coal-fired power plants to install currently available pollution controls, thus reducing mercury emissions 29% by 2007. The other approach allows emissions trading, or the trading of credits between plants, with a mandatory declining mercury emissions cap to reduce mercury emissions by nearly 70% by 2018. The proposals will be open for discussion prior to implementation.33
Acute and chronic exposure to mercury can significantly affect the health of a population, specifically the children. Methylmercury may pose the highest threat, as it is ubiquitous in the environment and it is a potent neurotoxicant. Methylmercury easily passes through the placenta to the developing fetus. Elemental mercury, or quicksilver, also poses a threat to children because it may be found readily in schools, hospitals, and medicine cabinets, and its intriguing liquid nature may be enticing to children.
Pediatricians must be diligent in informing patients of possible exposure sources, and alerting them to new government advisories and recommendations. They should also be knowledgeable regarding classic clinical presentations of mercury toxicity. It is only in cases involving a knowledge of mercury that appropriate historical information is obtained and correct diagnoses are made. Preventing mercury exposure and consequent toxicity is of importance because therapies are controversial and long-term consequences may be significant.
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2. Bakir F, Damluji SF, Amin-Zaki L, et al. Methylmercury poisoning in Iraq. Science. 1973;181:230-241.
3. D.C. school to reopen after mercury spilL Available at: http://www.cnn.com/2003/EDUCATION/11/04/mercury.spill.school.ap/. Accessed June 3, 2004.
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5. Ozuah PO. Lesser MS, Woods JS, Choi H, Markowitz M. Mercury exposure in an urban pediatric population. Ambul Pediatr. 2003:3(1 ):24-26.
6. Agency for Toxic Substances and Disease Registry. Toxicological Profile for Mercury. Atlanta, GA: US Department of Health and Human Services, Public Health Service; 1999.
7. US Environmental Protection Agency. Mercury Study: Report to Congress. Washington, DC: EPA; 1997. Available at: http://www.epa.gov/oar/mercuryhtml. Accessed May 20, 2004.
8. Shih H, Gartner JC. Weight loss, hypertension, weakness, and limb pain in an 11-year-old boy. J Pediatr. 2001 ; 138(4):566-569.
9. Henningsson C, Hoffmann S, McGonigle L, Winter JS. Acute mercury poisoning (acrodynia) mimicking pheochromocytoma in an adolescent. J Pediatr. 1993; 122(2):252-253.
10. Carroll L. Alice's Adventures in Wonderland New York, NY: Golden Books; 1986.
11. Halbach S, Kremers L, Willruth H, et al. Systemic transfer of mercury from amalgam fillings before and after cessation of emission. Environ Res. 1998;77(2): 115-123.
12. Drexler H, Schaller K. The mercury concentration in breast milk resulting from amalgam fillings and dietary habits. Environ Res. 1998;77(2):124-129.
13. Committee to Coordinate Environmental Health and Related Programs, Subcommittee on Risk Management. Dental Amalgam: A Scientific Review and Recommended Public Health Service Strategy for Research, Education and Regulation. Washington, DC: US Department of Health and Human Services, United States Public Health Service; 1993. Available at: http://www.health.gov/environment/amal gaml/ct.htm. Accessed May 20, 2004.
14. American Academy of Pediatrics Committee on Environmental Health. Mercury. In: Etzel RA, ed. Pediatric Environmental Health. 2nd ed. EJJc Grove Village, EL: American Academy of Pediatrics; 2003:267-281.
15. Grandjean P, White R, Weihe P, J0rgensen PJ. Neurotoxic risk caused by stable and variable exposure to methylmercury from seafood. Ambul Pediatr. 2003;3(1): 18-23.
16. Crump KS, Van Landingham C, Shamlaye C, et al. Benchmark concentrations for methylmercury obtained from the Seychelles Child Development Study. Environ Health Perspect. 2000;108(3):257-263.
17. Axtell CD, Myers GJ, Davidson PW, et al. Semiparametric modeling of age at achieving developmental milestones after prenatal exposure to methylmercury in the Seychelles Child Development Study. Environ Health Perspect 1998;106(9):559-564.
18. Davidson PW, Myers GJ, Cox C, et al. Effects of prenatal and postnatal mediylmercury exposure from fish consumption on neurodevelopmenL JAMA. 1998;28O(8):701-707.
19. Myers GJ, Davidson PW, Cox C, et al. Prenatal methylmercury exposure from ocean fish consumption in the Seychelles Child Development Study. Lancet. 2003:361 (9370): 1686-1692.
20. Clarkson TW, Strain JJ. Nutritional factors may modify the toxic action of methylmercury in fish-eating populations. J Nutr. 2003; 133(5 Suppl 1):1539s-1543s.
21. Lyketsos CG. Should pregnant women avoid eating fish? Lessons from the Seychelles. Lancet. 2003;361:1667-1668.
22. Keiding N, Budtz-j0rgensen E, Grandjean P. Prenatal methylmercury exposure in the Seychelles. Lancet. 2003;362(9370):664-7.
23. Kazantzis G, ??-Mufti AW, Copplestone JF, Majid MA, Mahmoud RM. Epidemiology of organomercury poisoning in Iraq. UJ. Clinical features and their changes with time. Bull World Health Organ. 1976;53 Suppl: 49-57.
24. Amin-Zaki L, Majeed MA, Clarkson TW, Greenwood MR. Methylmercury poisoning in Iraqi children: clinical observations over two years. Br Med J. 1978;1(6113):613-616.
25. National Academy of Sciences, Committee on the Toxicological Effects of Methylmercury, Commission on Life Sciences, National Research Council. Toxicological Effects of Methylmercury. Washington, DC: National Academy Press; 2000.
26. Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and the Public Health Service. MMWR Morb Mortal WkIy Rep. 1999;48(26):563-565.
27. Ball LK, Ball R Pratt RD. An assessment of thimerosal use in childhood vaccines. Pediatrics. 2001;107(5):1147-1154.
28. Agocs MM Etzel RA, Parrish RG1 et al. Mercury exposure from interior latex paint N Engl J Med. 1990:323(16): 1096-1 101.
29. Goldman LR, Shannon MW; American Academy of Pediatrics: Committee on Environmental Health. Technical report: mercury in the environment: implications for pediatricians. Pediatrics. 2001;108(1):197-205.
30. Ballatoi N, Leiberman MW, Wang W. N-acetylcysteine as an antidote in methylmercury poisoning. Environ Health Perspect. 1998;106(5):267-271.
31. Overview of the Draft FDA/EPA Methylmercury (MeHg) Consumer AdvisoryfUS Food and Drug Administration web site]. 2003. Available at http://www.fda.gov/oc/opacom/mehgadvisory 1011.html. Accessed May 18, 2004.
32. US Department of Health and Human Services, and US Environmental Protection Agency. FDA and EPA Announce the Revised Consumer Advisory on Methylmercury in Fish. Available at: htto://www.fda.gov/bbs/topics/news/2004/new0 1038html. Accessed June 3, 2004.
33. Clean Air Proposals Promise Sharp Power Plant Pollution Reductions [US Environmental Protection Agency web site]. December 15, 2003. Available at http://yoeeimte.epa.gov/opa/adrnpress.nsf/b 1 ab9f485b098972852562e7004dc68 6/b886%2d46c43fa385256dfd(X)7870df?OpenDocument Accessed May 18, 2004.
Mercury Reference Levels