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Mercury

Dose, Absorption, Distribution, Biotransformation, and Excretion of Mercury

This section provides a general overview of mercury toxicokinetics. Although the fate of the three main mercury species is intertwined in the body, each species is presented below separately for clarity. The estimates of dose, absorption, etc. are based on animal/human data; the fate of mercury in the body can vary between species as well as within species, and is especially dependent on age, sex, and pregnancy status. Although doses of the Hg species are presented separately, the toxicological response may be cumulative since the ultimate metabolite of elemental Hg and MeHg is ionic Hg.


Dose

Non-occupational exposure to mercury occurs mainly through air, food, drinking water, and dental amalgams. Table 1 displays the estimated daily intake of mercury species in micrograms per day. Retention values (in parentheses) are assumed to be 95% of intake for MeHg, 80% of elemental Hg vapor and 7% for ionic Hg compounds. Occupational exposures and incidental exposures (e.g. broken thermometers) may also occur but are not included. Mercury in vaccines is also excluded from the estimated dose chart, but is discussed below. See Toxicological Effects of Methylmercury , for specifics on the data sources and assumptions used in these dose estimates.

Table 1: Estimated Daily Intake and Retention (µg/day) of Mercury Species in the General Population

Exposure Elemental Hg Vapor Ionic Hg Compounds MeHg
Air 0.030
Food Sources
Fish* 0 0.600 (0.042) 1-6
Non-fish** 0 3.6 (0.25) 0
Drinking Water 0 0.050 (0.0035) 0
Dental Amalgams 3.9-21 (3.1-17) 0 0
Total 3.9-21 (3.1-17) 4.3 (0.3) 1-6

Exposure estimates are based U.S. population average consumption, which underestimates exposure to certain fish-eating subpopulations. The EPA estimates that 7% of women of childbearing age in the United States consume 0.1 µg/kg per day or more of mercury from fish harvested in high risk areas, and 1% of women consume 0.37 µg/kg per day or more. Mercury accumulated in these women is transferred to their children prenatally and in breast milk

** Mercury has been detected in meat and milk (probably due to soil intake of animals during grazing), and other foods such as brassicas and mushrooms. Plants may absorb mercury from the soil and air during normal growth.

Based on this table, the largest dose of elemental Hg is from dental amalgams, which are 9~50% mercury by weight. Levels of mercury vapor in the ambient environment are negligible. Amalgam fillings release the vapor into the oral cavity, and then mouth breathing carries the vapor to the lungs where it is absorbed. Excess chewing (e.g., bruxism or gum chewing) increases the release of vapor from the amalgams. The largest dose of MeHg is from fish.

Another form of mercury to which the general population is exposed (but which is not discussed in detail elsewhere in this website) is an ethyl mercury compound called thimerosal (CH3CH2-Hg+), which is used as a preservative in vaccines. . Thimerosal has been used in some vaccines since the 1930's. Although no serious harmful effects have been reported from thimerosal at doses used in vaccines, the Public Health Service agencies, the American Academy of Pediatrics, and vaccine manufacturers have been working to reduce or eliminate thimerosal in vaccines during the last few years as a precautionary measure. Currently, there is little evidence that exposure to thimerosal results in adverse effects; however, the long half-life of ethylmercury (~50 days on average) results in accumulation that could be harmful to the developing fetal brain, which is much more susceptible to organomercurial compounds than the adult brain.

The Food and Drug Administration (FDA) Modernization Act of 1997 called for the FDA to review and assess the risk from all food and drugs containing mercury. The FDA review concluded that the use of thimerosal as a preservative in vaccines might result in the intake of mercury during the first 6 months of life that exceeds the Environmental Protection Agency, but not the FDA, the Agency for Toxic Substances and Disease Registry, or the World Health Organization guidelines for methylmercury intake . Since there is insufficient toxicology data to fully evaluate ethylmercury, these federal safety standards are based mainly on methylmercury information.

Prior to the recent initiative to reduce or eliminate thimerosal from childhood vaccines, the maximum cumulative exposure to mercury via routine childhood vaccinations during the first six months of life was 187.5 micrograms. With the newly formulated vaccines, the maximum cumulative exposure during the first six months of life will now be less than three micrograms of mercury. Currently, thimerosal may still be used in the early stages of manufacturing of certain childhood vaccines, but only a trace remains after a purification process. Although the dose in childhood vaccines has been reduced, CDC is still planning a thorough investigation of thimerosal exposure through infant vaccines and risk of neurological disorders such as autism and other adverse effects. Note that the dose presented here for children 1-6 months of age is applicable to the United States. Levels of thimerosal in vaccines in other countries will vary.

Vaccines that are not typical infant vaccines still contain various levels of mercury in the US. For example, all influenza vaccines currently manufactured in the US contain 25 µg mercury/0.5 mL vaccine . For more information on mercury in vaccines, see endnote citations ii and iii.


Absorption

Table 2 summarizes the absorption of Hg species via the three main exposure routes. The information in this table and the tables which follow are taken predominantly from the following three sources:

1) Clarkson, Thomas W. The Three Modern Faces of Mercury. Environmental Health Perspectives. 2002. Volume 110, Supplement 1, pp.11-23.
2) Toxicological Effects of Methylmercury. National Academy of Sciences. National Academy Press. Washington, DC. 2000.
3) USEPA Mercury Study Report to Congress, Volume 5: http://www.epa.gov/ttn/oarpg/t3/reports/volume5.pdf, 1997.

Table 2: Absorption of Mercury Species Via the Three Major Exposure Routes

Elemental Hg
Ionic Hg
MeHg
Inhalation 75-85% of an inhaled dose of the vapor is absorbed by the body (human studies). 97% of absorption occurs through the lungs. Data are limited. Absorption via inhalation is estimated at 40% (dog study). Vapors of MeHg can be absorbed; the amount is unknown
Oral < 0.01% of an ingested dose is absorbed from the GI tract (rat study). Absorption from the GI tract following oral dose is estimated at 7-15% (human study). A mouse study indicates that absorption is approximately 20% Approximately 95% of MeHg in fish is absorbed from the GI tract (human studies). The exact site of absorption is unknown.
Dermal Dermal absorption rate = 0.024 ng Hg/cm2 skin for every 1 mg/m3 in the air (human study). < 3% of total amount of elemental Hg absorbed by the body is from dermal exposure Approximately 2-3% of a dermally applied dose of mercuric chloride was absorbed during a 5-hour period (guinea pig study). Approximately 2-3% of a dermally applied dose of mercuric chloride was absorbed during a 5-hour period (guinea pig study

Distribution

Table 3 describes the transport of mercury species throughout the body.

Table 3: Distribution of Mercury Species in the Human Body

Elemental Hg
Ionic Hg
MeHg
Absorption results in rapid diffusion across the lungs and entrance into the bloodstream, where it is distributed throughout the body (because it is lipophilic), including the blood-brain barrier and the placenta. The ingested dose is rapidly distributed from the the GI tract to the blood and organs. Mercuric Hg has a high affinity for sulfhydryl groups in the RBCs and plasma. The highest concentration is in the kidneys. Mercuric mercury induces metallothionein production in the kidneys, which may contribute to the kidney’s accumulation of mercuric mercury. It does not cross readily cross the blood-brain barrier or the placenta because of its ionic charge. The percentage of absorbed MeHg from the GI tract that is distributed to the blood ranges from 1% to 10% About 5% is absorbed into the bloodstream and is distributed to all tissues within a few days. The concentration in RBCs is roughly 20X the concentration in plasma. Maximum levels (~10%) occur in the brain, in 5-6 days. It is also readily transferred to the fetus and the fetal brain. The high mobility of methyl mercury in the body is not due to lipid solubility. It is present in the body as water-soluble complexes mainly attached to the sulfur atom of thiol ligands. MeHg transport across the blood-brain barrier occurs via a MeHg-L-cysteine complex, which is transported by the L-system (leucine preferring) amino acid carrier.


Biotransformation (metabolism)

Table 4 delineates the metabolic pathways of mercury species within the body.

Table 4. Biotransformation of Hg Species in the Human Body

Elemental Hg
Ionic Hg
MeHg
Elemental Hg is oxidized in the red blood cells by catalase and hydrogen peroxide to divalent ionic (mercuric) Hg. Mercuric Hg is unstable in vivo and has been shown to convert to elemental Hg (rat study). It can also be methylated by intestinal flora, but cannot be methylated in body tissues. MeHg is stable in the body compared to other species. It is slowly demethylated to mercuric Hg in tissue macrophages, intestinal flora, and the fetal liver. Although these sites of demethylation are known, the enzymes in mammalian tissues responsible for the biotransformation have not yet been identified. It is metabolized to ionic mercury at a rate of around 1% of the body burden per day. The mercuric Hg resides for long periods of time in the CNS, probably in an inert form.


Excretion

Table 5 presents the elimination routes of mercury from the body.

Table 5: Elimination of Mercury Species from the Human Body

Elemental Hg
Ionic Hg
MeHg
Approximately 7-14% of inhaled mercury vapor is exhaled within a week after exposure. The rest of the elemental Hg is either excreted via sweat and saliva, or is excreted as mercuric Hg. Approximately 80% is excreted as mercuric Hg via feces and urine. Half-life elimination is approximately 58 days. This is slightly more than 1% of the body burden/day. Approximately 85% of an oral dose is excreted via feces within a couple days. Most of the absorbed ionic Hg is excreted in urine. Smaller amounts are excreted in saliva, bile, sweat, exhalation, and breast milk. Half-life excretion ranges from 49-96 days. The major routes of excretion are bile and feces. MeHg undergoes enterohepatic cycling where it is secreted into bile, and then partly reabsorbed and returned to the liver. Most MeHg is eliminated by demethylation and then excretion of the ionic form in the feces (~90% in feces as mercuric Hg). This process does not occur in nursing infants due to incomplete development; their process of elimination is not understood. Breast milk is also a route of excretion.

The range of half-life elimination has been estimated at 45-90 days (although much faster for lactating females). Individuals who are exposed regularly to MeHg reach a steady-state body burden in about 5 half-lives (~1year).


The range of half-life elimination has been estimated at 45-90 days (although much faster for lactating females). Individuals who are exposed regularly to MeHg reach a steady-state body burden in about 5 half-lives (~1year).


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