In 1997 the Office of Air Quality Planning & Standards and Office of Research and Development at The Environmental Protection Agency compiled the Mercury Study Report to Congress. This document, which covers the human health effects of mercury and mercury compounds, is one volume of U.S. EPA’s eight-volume Report.
Upon reading the Symptoms of Mercury Vapor-induced Neurotoxicity and the Toxicokinetics (the description of what rate a chemical will enter the body and what happens to it once it is in the body). It is apparent that mercury has great potential to mimmic symptoms of dementia and Alzheimer’s disease. While there exists strong correlation and a predominant route of exposure to 1/3 the U.S. population, no federal money has been spent looking at the connection between mercury and dementia or Alzheimer’s disease.
The purpose of this volume, Volume V, is to summarize the available health effects information for mercury and mercury compounds and to present U.S. EPA’s analysis for two critical pieces of the risk assessment paradigm described by the National Academy of Sciences in 1983. Specifically, this volume contains the hazard identification and dose-response assessments for three forms of mercury: elemental mercury, mercuric chloride (inorganic mercury),and methylmercury (organic mercury). In order to characterize risk for any populations, the evaluations presented in this volume must be combined with the assessment of exposure presented in Volume IV.
Environmental Protection Agency (EPA), Mercury Study Report to Congress
Office of Air Quality Planning & Standards and Office of Research and Development
Volume V: Health Effects of Mercury and Mercury Compounds
Chapter 3 presents summary information on the toxicity of elemental mercury, mercuric mercury and methylmercury to various organ systems.
The primary targets for toxicity of mercury and mercury compounds are the nervous system, the kidney, and the developing fetus. Other systems that may be affected include the respiratory, cardiovascular, gastrointestinal, hematologic, immune, and reproductive systems.
For each form of mercury and each of the endpoints addressed, information from epidemiological studies, human case studies, and animal toxicity studies is summarized in tabular form. Critical studies are discussed in the accompanying text.
Effects on the nervous system appear to be the most sensitive toxicological endpoint observed following exposure to elemental mercury.
Symptoms associated with elemental mercury-induced neurotoxicity include the following: tremors, initially affecting the hands and sometimes spreading to other parts of the body; emotional lability, often referred to as “erethism” and characterized by irritability, excessive shyness, confidence loss, and nervousness; insomnia; neuromuscular changes (e.g., weakness, muscle atrophy, muscle twitching); headaches; polyneuropathy (e.g., paresthesia, stockingglove sensory loss, hyperactive tendon reflexes, slowed sensory and motor nerve conduction velocities); and memory loss and performance deficits in test of cognitive function. At higher concentrations, adverse renal effects and pulmonary dysfunction may also be observed.
A few studies have provided suggestive evidence for potential reproductive toxicity associated with exposure to elemental mercury.
Data from two studies in rats demonstrate developmental effects of elemental mercury exposure. These were behavioral changes associated with both in utero and perinatal exposure.
Symptoms of Mercury Vapor-induced Neurotoxicity
The most prominent symptoms associated with mercury vapor-induced neurotoxicity include the following:
- tremors — initially affecting the hands and sometimes spreading to other parts of the body
- emotional lability — often referred to as “erethism” and characterized by irritability, excessive shyness, confidence loss and nervousness
- neuromuscular changes — weakness, muscle atrophy, muscle twitching
- polyneuropathy — paresthesias, stocking-glove sensory loss, hyperactive tendon reflexes, slowed sensory and motor nerve conduction velocities
- memory loss and performance deficits in tests of cognitive function
TOXICOKINETICS: (i.e., absorption, distribution, metabolism, and excretion) of mercury is highly dependent on the form of mercury to which a receptor has been exposed.
The absorption of elemental mercury vapor occurs rapidly through the lungs, but it is poorly absorbed from the gastrointestinal tract. Oral absorption of inorganic mercury involves absorption through the gastrointestinal tract; absorption information for the inhalation route is limited. Methylmercury is rapidly and extensively absorbed through the gastrointestinal tract.
Once absorbed, elemental mercury is readily distributed throughout the body; it crosses both placental and blood-brain barriers. Elemental mercury is oxidized to inorganic divalent mercury by the hydrogen peroxidase-catalase pathway, which is present in most tissues. The oxidation of elemental mercury to the inorganic mercuric cation in the brain can result in retention in the brain. Inorganic mercury has poor lipophilicity and a reduced capacity for penetrating the blood-brain or placental barriers. Once elemental mercury crosses the placental or blood-brain barriers and is oxidized to the mercuric ion, return to the general circulation is impeded, and mercury can retained in brain tissue.
2.2.1 Elemental Mercury
Because of its lipophilicity, absorbed elemental mercury vapor readily distributes throughout the body, crossing the blood-brain barrier in humans (Hursh et al., 1976; Nordberg and Serenius, 1969) and the placenta in rats and mice (Clarkson et al., 1972). The distribution of absorbed elemental mercury is limited primarily by the oxidation of elemental mercury to the mercuric ion and reduced ability of the mercuric ion to cross membrane barriers. The oxidation is sufficiently slow, however, to allow distribution to all tissues and organs. Once it is oxidized to the mercuric ion, it is indistinguishable from Hg2+ from inorganic sources (i.e., the highest levels of mercury accumulate in the kidneys) (Hursh et al.1980; Rothstein and Hayes 1964). Based on an in vitro study by Hursh et al. (1988), oxidation of mercury in the blood is slow and, therefore, inhaled mercury reaches the brain primarily unoxidized (i.e., as dissolved vapor) and is available for rapid penetration into brain cells. Once in the brain, oxidation of elemental mercury to mercuric mercury in the brain enhances for the accumulation of mercury in these tissues (Hursh et al. 1988; Takahata et al. 1970).
For example, ten years after termination of exposure, miners exposed to elemental mercury vapor had high concentrations of mercury (120 ppm) in the brain (Takahata et al. 1970). A similar effect occurs when elemental mercury reaches the fetus and (after oxidation) accumulates in the tissues as inorganic mercury (Dencker et al.1983).
In the blood, elemental mercury initially distributes predominantly to the red blood cells; at 20 minutes, 98% of the mercury in the blood is found in the red blood cells. Several hours following parenteral, oral or inhalation exposure, however, a stable ratio of red blood cell mercury to plasma mercury of approximately 1:1 is established (Gerstner and Huff, 1977; Clarkson, 1972; Cherian et al., 1978). The rise in plasma mercury levels was suggested to be due to binding to protein sulfhydryl groups by mercuric mercury formed when the elemental mercury was oxidized.
2.4.1 Elemental Mercury
Excretion of mercury after exposure to elemental mercury vapor may occur via exhaled air, urine, feces, sweat and saliva. The pattern of excretion of elemental mercury changes as elemental mercury is oxidized to mercuric mercury. During and immediately after an acute exposure, when dissolved elemental mercury is still present in the blood, glomerular filtration of dissolved mercury vapor occurs, and small amounts of mercury vapor can be found in the urine (Stopford et al. 1978). Mercury vapor present in the blood may also be exhaled; human volunteers exhaled approximately 7% of the retained dose within the first few days after exposure (Hursh et al. 1976). The half-life for excretion via the lungs is approximately 18 hours. Approximately 80% of the mercury accumulated in the body is eventually excreted as mercuric mercury. As the body burden of mercury is oxidized from elemental mercury to mercuric mercury, the pattern of excretion becomes more similar to mercuric mercury excretion.
The majority of the excretion of mercuric mercury occurs in the feces and urine (Cherian et al.1978). During the first few days after exposure of humans to mercury vapor, approximately four times more mercury was excreted in the feces than in the urine (Cherian et al. 1978).
With time, as the relative mercury content of the kidneys increases, excretion by the urinary route also increases (Rothstein and Hayes 1964). Tissue levels of mercury decrease at different rates, but the half-life for excretion of whole-body mercury in humans (58 days) is estimated to be approximately equal to the half-life of elimination from the kidneys (64 days), where most of the body burden is located (Hursh et al. 1976).
Excretion via the urine may be increased if mercury-induced damage of the renal tubular epithelium has happened and exfoliation of damaged mercury-containing cells occurs (Magos 1973).
The following conclusions progress from those with greater certainty to those with lesser certainty.
The three forms of mercury discussed in this Report can present a human health hazard.
Neurotoxicity is the most sensitive indicator of adverse effects in humans exposed to elemental mercury and methylmercury.
Immune-mediated kidney toxicity is the most sensitive indicator of toxic effects of exposure to inorganic mercury. This judgement is largely based on results in experimental animals.
Methylmercury is a developmental toxicant in humans.
Elemental mercury is a developmental toxicant in experimental animals. If the mechanisms of action producing developmental toxicity in animals occur in humans, elemental mercury is very likely to produce developmental effects in exposed human populations.
U.S. EPA has made no estimate of dose response for developmental effects of elemental mercury.
Methylmercury and inorganic mercury produce tumors in experimental animals at toxic doses. If the mechanisms of action which induced tumors in the animal models could occur in humans, it is possible that tumors could be induced in exposed humans by these forms of mercury. It is likely, however, that cancer would be induced only after mercury exposures in excess of those producing other types of toxic response.
VOLUME 4: An Assessment of Exposure to Mercury in the United States
5. POPULATION EXPOSURES – NON-DIETARY SOURCES
5.1 Dental Amalgams
Dental amalgams have been the most commonly used restorative material in dentistry. A typical amalgam consists of approximately 50% mercury by weight. The mercury in the amalgam is continuously released over time as elemental mercury vapor (Begerow et al., 1994). Research indicates that this pathway contributes to the total mercury body burden, with mercury levels in some body fluids correlating with the amount and surface area of fillings for non- ccupationally exposed individuals (Langworth et al., 1991; Olstad et al., 1987; Snapp et al., 1989). For the average individual an intake of 2-20 μg/day of elemental mercury vapor is estimated from this pathway (Begerow et al., 1994).
Additionally, during and immediately following removal or installation of dental amalgams supplementary exposures of 1-5 μg/day for several days can be expected (Geurtsen 1990). Approximately 80% of the elemental mercury vapor released by dental amalgams is expected to be re-absorbed by the lungs (Begerow et al., 1994). In contrast, dietary inorganic mercury absorption via the gastrointestinal tract is known the be about 7%.
The contribution to the body burden of inorganic mercury is thus, greater from dental amalgams than from the diet or any other source.
The inorganic mercury is excreted in urine, and methylmercury is mainly excreted in feces.
WE THINK THE SCIENCE HAS COME TO A DIFFERENT CONCLUSION THAN THIS STATEMENT FROM THE EPA. PLEASE READ THE FOLLOWING ARTICLE.
Since urinary mercury levels will only result from inorganic mercury intake, which occurs almost exclusively from dietary and dental pathways for members of the general public, it is a reasonable biomonitor of inorganic mercury exposure.
Urinary mercury concentrations from individuals with dental amalgams generally range from 1-5 μg/day, while for persons without these fillings it is generally less than 1 μg/day (Zander et al., 1990). It can be inferred that the difference represents mercury that originated in dental amalgams. Begerow et al., (1994) studied the effects of dental amalgams on inhalation intake of elemental mercury and the resulting body burden of mercury from this pathway. The mercury levels in urine of 17 people aged 28-55 years were monitored before and at varying times after removal of all dental amalgam fillings (number of fillings was between 4-24 per person). Before amalgam removal, urinary mercury concentrations averaged 1.44 μg/g creatinine. In the immediate post-removal phase (up to 6 days), concentrations increased by an average of 30%, peaking at 3 days post-removal. After this phase mercury concentrations in urine decreased continuously and by twelve months had dropped to an average of 0.36 μg/g creatinine. This represents a four-fold decrease from pre-removal steady-state urinary mercury levels.