Mercury can be found in — various chemical forms and compounds — metallic, inorganic and organic; their toxicological profiles have been better developed after massive exposures in Minamata, Japan, and Iraq, where immense exposures to methyl mercury resulted in severe neurologic consequences beginning in the 1950s and 1970s, respectively. Nowadays, we recognize that even very low methyl mercury exposure during prenatal life can be associated with delays on neurobehavioral development (1, 2).
Mercury Use and Emission
Mercury is recognized as a chemical of global concern due to its long-range transport in the atmosphere, its persistence in the environment, its ability to bio accumulate within food chains, and its significant negative effects on human health and the environment, even at relatively low exposures (2).
Natural emissions and re-emissions of mercury are estimated to be 4800 tons/year - outgassing of the Earth's mantle and crust; volcanic activity; geothermal processes; evaporation from soils and sediment, water bodies and vegetative surfaces; and release from forest fires and erosions. Anthropogenic emissions of mercury are estimated to account for approximately 2200 tons/year - fossil fuel combustion; deforestation, small and large-scale mining; metal, cement, and chlor-alkali production; waste incineration; and cremation (4, 5, 6).
From natural and anthropogenic sources, elemental mercury released into the atmosphere is chemically transformed into inorganic mercury that can reach terrestrial and aquatic ecosystems with precipitation. Through biological processes, inorganic mercury is transformed into organic mercury (mostly methyl mercury) which is bio-accumulates in food chains. Fish trophic level, migration patterns, and metabolic rates - among other factors - play a relevant role on the uneven methyl mercury distribution within food chains. Human exposures to methyl mercury occur mostly through fish consumption (1, 4).
Toxicology: Mercurial Forms and Compounds
1. Methyl mercury
Among adults and children, following ingestion, through bloodstream, methyl mercury target organs are the Central Nervous System - especially the cerebellum and the visual cortex, and the Peripheral Nervous System - targeting the spinal dorsal root ganglia. Disruptive mechanisms are related to the high affinity of methyl mercury cations to the sulfhydryl group and the ability of methyl mercury to mimic methionine, an essential amino acid. Due to this affinity of methyl mercury to sulfhydryl proteins, hair can be used as a biological indicator. Since methyl mercury cations are bound to the hair strands at the time of hair formation, it is possible to estimate methyl mercury exposure over time (1).
With a blood half-life of around 45 — 60 days after crossing the blood brain barrier, methyl mercury stays trapped within the CNS. On dose dependent bases, clinical symptoms and signs associated with methyl mercury exposure include paresthesia (loss of sensation in the extremities and around the mouth), ataxia (impairment of the gait), dysarthria (impairment of speech), hearing impediments tremor in the limbs and constriction of the visual fields. Research from the Iraq epidemic reveals that paresthesia was correlated with hair mercury levels in the range of 50 to 120 ppm, whereas ataxia, dysarthria, deafness and death were seen at hair mercury concentrations of 200, 350, 750 and 1,500 ppm, respectively (1).
During prenatal life, high maternal exposures can cause neurological disorders resembling cerebral palsy — microcephaly, hyper-reflexia, gross motor and mental impairments, blindness and deadness. In the developing brain, cell migration and cell division are affected by methyl mercury due to disruptions on cell substances synthesis, mitotic arrest, changes in synaptic formations and abnormal cellular-architecture, as well as other damages (1).
However, current evidence shows that delays on neuro and motor development during the first 6 — 8 years of life are associated with maternal exposure levels in the range of 5 — 30 ppm hair mercury concentrations. These conclusions are derived from cohort studies conducted where people rely on consumption of whales or marine fish. In the Faroe Islands, the non-observable effect levels (NOELs) were found in the range of 10 — 20 ppm; Seychelles Islands, with NOELS in the range of 20 — 30 ppm, and New Zealand (with NOELs of 7 — 8 or 20 — 25 depending on the inclusion of peak levels). These are relatively low exposures for NOELs related to the nervous system (2).
However, one must not neglect the benefits of fish consumption, especially omega 3 fatty acids, and selenium that counteracts methyl mercury toxicity (2). Fish advisories based on the evidence of each local context is required to ensure methyl mercury protection during prenatal and early postnatal life.
2. Ethyl mercury
Ethyl mercury is also organic mercury; it is used in thiomersal as a vaccine preservative. The similarities and differences between ethyl and methyl mercury have been under attention (7). Ethyl mercury has a blood half-life (3 to 7 days), much shorter than methyl mercury (45 — 60 days), and therefore it is mostly excreted from the body and does not accumulate in the central nervous system. Epidemiological studies investigating associations of neurobehavioral disorders and use of thiomersal vaccines from the UK and Denmark did not challenge the safety of vaccines in infants. Additionally, there appeared to be methodological problems and uncertainties in the US significant associations between neurodevelopment disorders and thiomersal vaccines were found (8). During a meeting in June of 2012, based on an extensive review, the Global Advisory Committee on Vaccine Safety concluded that the amount of ethyl mercury in the blood and brain from cumulative doses of vaccines does not reach toxic levels; thus, it is biologically implausible that any correlation between thiomersal in vaccines and neurological toxicity is existent (9).
3. Metallic mercury
Metallic mercury is converted into inorganic mercury in the central nervous systems. Clinical effects of metallic mercury exposure are oral disturbances (metallic taste), tremor (in fingers, eyelids, lips or tongue) and erethism — psychogenic manifestations with irritability and outburst of temper. The mad hatter persona of Lewis Carol's Alice in Wonderland is considered to be a tentative depiction of occupational exposure to metallic mercury during fur hat production.
Current exposures to metallic mercury occur in the context of gold mining, when miners burn the gold mercury amalgam. Dental personnel are exposed to mercury on the amalgam manipulation. In the health sector, mercury thermometers are easily broken, especially in the pediatrics or emergency departments of hospitals, and leaked mercury can be easily volatilized and inhaled by people nearby. Blood and urine mercury levels can be used to evaluate these exposures (10).
4. Inorganic mercury
Inorganic mercury has been found as an ingredient in skin lightening products due to its property of preventing melanin formation. Kidney damage is one major consequence of inorganic mercury. Nephrotic syndrome with high levels of protein in the urine was found among people using mercury-containing skin lightening creams. Skin rashes, discoloration and scarring may also occur (10, 11).
The United Nations Environment Programme's Global Mercury Assessment 2013: Sources, Emissions, Releases, and Environmental Transport.
1. World Health Organization — International Program on Chemical Safety (1990) — Environmental health criteria 101 — methylmercury.
2. Nesheim, MC and Yaktine, AL (2007). Seafood choices — balancing benefits and risks. Institute of Medicine of the National Academies. The National Academies Press, Washington, DC, USA.
3. WHO — Public Health and Environment - Preventing disease through healthy environments — Exposure to mercury a major public health concern.
4. Pirrone, N and Mason, R. (2008). Mercury Fate and Transport in the Global Atmosphere: Measurements, Models and Policy Implications. Interim Report of the UNEP Global Mercury Partnership on Mercury Air Transport and Fate Research partnership area.
5. UNEP Chemicals Branch (2008). The Global Atmospheric Mercury Assessment: Sources, Emissions and Transport.
6. Selin, NE, Jacob, DJ, Park, RJ, Yantosca, RM, Strode, S, Jaeglé, L and Jaffe, D (2007). Chemical cycling and deposition of atmospheric mercury: Global constraints from observations." Journal of Geophysical Research-Atmopsheres, 112, D02308, doi:10.1029/2006JD007450.
7. Clarkson, TW (2002) — The three modern faces of mercury. Environmental Health Perspectives 110(1):11-23.
8. WHO information on thiomersal presented to INC3: UNEP(DTIE)/Hg/INC.3/6. Available in Spanish.
9. WHO — Global Advisory Committee on Vaccine Safety.
10. WHO-IPCS, UNEP and International Labour Organization (2003). Elemental mercury and inorganic mercury compounds: human health effects — Concise International Chemical Assessment Document 50. Geneva.
11. WHO Public Health and Environment (2012). Preventing disease through healthy environments — Mercury in skin lightening products.