The Chem Ducky - The Toxicity of Mercury

Different types of Mercury

By Sebby Leung

There are various forms of mercury. Its organic forms— ethylmercury, methylmercury, and dimethylmercury— are toxic to humans because they can easily pass through cellular barriers. Their properties as nonpolar molecules allow them to travel across the hydrophobic, inner layer of the cellular membrane. Thus, the organic forms of mercury can be absorbed into the skin and don’t necessarily need to be ingested to cause harm (although it can take time for mercury to affect someone through skin absorption).

However, the most common exposure to organic mercury is through contaminated food, especially fish that contain traces of methylmercury. Because methylmercury takes long to excrete, it can accumulate easily in one’s body, causing toxicity to persist. For reference, the half-life of MeHg is roughly 70 days through one’s excrement, meaning that it can take up to a year to remove around 97% of the mercury in one’s system. The danger from MeHg comes from the fact that it accumulates within vital areas, such as neurological systems, bone marrow, kidneys, the brain, and even the placenta or fetus in pregnant women. This means that MeHg exposure can completely disrupt lives through fetal brain damage, developmental delays, and spontaneous miscarriage.

Ethylmercury, a similar form of mercury to MeHg, also has similar impacts on cells, except it lasts 33% longer than MeHg. Dimethylmercury, on the other hand, is much more dangerous in comparison. From just minimal absorption through the skin, dimethylmercury can result in death and is extremely toxic to humans.

But what about mercury’s inorganic forms? Similarly, there are three general forms of inorganic mercury; metallic mercury (MgO), mercurous mercury (Hg22+), and mercuric mercury (Hg2+). Mercury's chemical and physical states influence its toxicity—mercurous compounds have lower toxicity due to reduced water solubility, while mercuric compounds have higher toxicity due to increased solubility and corrosiveness. In terms of their effects on humans, HgO causes symptoms like vomiting, abdominal pain, and emotional changes. While it is a liquid at room temperature, it can form a vapor due to high vapor pressure. As a result, a majority of this mercury (80%) is inhaled, 7-10% is ingested, and 1% is absorbed through the skin. This form of mercury is found in gold and silver extraction industries as well as dental fillings (an alloy of mercury and other metals).

The toxicity of this form of mercury comes from its ability to bind to amino acids with sulfur, like cysteine, and accumulates in the brain, kidneys, thyroid, and liver easily. If MgO reaches the bloodstream, it would oxidize rapidly; but, because the CNS (central nervous system) often absorbs the MgO before oxidation, this may not occur often. MgO leaves a noticeable trace on the body that ranges from days to months, but is retained for years if present in the nervous system. People who inhale MgO contract acute poisoning, resulting in shortness of breath, cough, fever, muscular pain, and headaches.

Mercurous and mercuric compounds exist as Hg22+ or Hg2+, but more commonly as Hg2Cl2 or Hg2SO4. This kind of mercury tends to convert to HgO and Hg2+ under normal conditions and is not absorbed very well in the gastrointestinal system unless oxidized. It rarely remains in the body long-term, but has been linked to rare conditions like pink disease, the side effects of which are pink discoloration, severe skin irritation, and an abnormally high heart rate. Memory issues, skin and eye irritation, reproductive and immune system dysfunction, mood changes, and weight loss are other symptoms commonly found with mercuric compounds. However, it’s effectively excreted compared to its organic counterparts, with 80% being eliminated in around 42 days. Symptoms usually arise hours post-ingestion and persist for days. Chronic exposure usually results from occupational inhalation or prolonged ingestion of mercury-containing compounds (e.g., diuretics or cathartics).

A quick comparison of different forms of Hg is shown below:

Mercury, in its organic form methylmercury (MeHg), is a deadly substance in contaminated animals, like fish. Through bioaccumulation, the process of a substance building up within the food chain, MeHg cyclically spreads from menial prey to humans. As mentioned before, high doses of MeHg cause severe hearing loss, speech and vision impairments, neuronal death, and in pregnant women, impairs fetal brain development. Maternal mercury levels as low as 10-20 µg/g have been shown to cause problems in children due to its ability to overcome the brain’s protective blood-brain barrier.

Mercury’s toxicity in the nervous system comes from its ability to create reactive oxygen species (ROS). ROS is a normal byproduct of cellular processes, but MeHg forms an excess, resulting in oxidative damage to cellular structures and a lot of health problems. ROSes are especially harmful because of oxygen’s high electronegativity, which often damages whole systems' processes and functions. For example, when the ROS attacks a lipid cell membrane, the membrane tends to lose electrons to oxygen (oxidized) and becomes unstable. MeHg further damages molecules that are important for transmitting electrical signals, such as the nervous system, causing more cell death. To solve this problem, selenium supplementation has been suggested as it forms stable complexes, protecting the body from the harmful effects of mercury.

Mercury’s inorganic and organic forms have additionally been associated with genetic damage, disrupting DNA's structure and repair mechanisms. Again, this can be done through oxidative damage through ROS destabilizing structures within the body. Mercury induces species like superoxide anions and hydroxyl radicals, potentially causing DNA strand breaks and base modifications that can potentially produce dysfunctional proteins. Mercury exposure also increases the rates of mutation in DNA and changes in the number and structure of chromosomes. In fact, when human fetal liver cells were exposed to HgCl2(inorganic mercury), there was up to a 200% increase in nuclear damage over 7 days at 0.5 µM. Organic mercury was proven to be even more toxic than inorganic, with a clear correlation of MeHg exposure and chromosomal damage.

Mercury exposure similarly impairs the process of cell division. In cell division, microtubules bond to the chromosomes and separate the sister chromatids and thus segregate DNA— but mercury disrupts those microtubules.

Mercury exposure additionally impairs the immune cells’ ability to neutralize ROS damage. Mercury alters the ability of T cells, B cells, and macrophages which all participate in breaking down pathogens, reducing the proliferation of these vital immune cells. Mercury can also mimic antigens that trigger the immune response in healthy tissues— the exact same immune response found in an autoimmune disease. Thus, mercury exposure is linked to autoimmune diseases such as multiple sclerosis, arthritis, psoriasis, and scleroderma. Mercury also deregulates pathways relating to the immune response, altering immune signaling and gene expression. Mercury fosters bacterial growth which may bind to the mercury and thus detoxify the body, but if antibiotics are used to kill bacteria, the mercury may be released back into the body to have the immune-related conditions.

Mercury exposure negatively impacts both fertility and fetal development. In women, mercury causes menstrual irregularities, and in pregnancies, mercury crosses the placenta, resulting in spine, brain, skull, and size defects in children. These developmental delays are not only seen within the womb but outside as well. In women with higher concentrations of mercury, their breast milk often contains it which is fed to the child, increasing risks of conditions like autism. In men, mercury is an endocrine disruptor, lowering testosterone and impacting testicular health.

Mercury could be a potential cancer-causing substance due to its ability to cause oxidation through ROS, gene expression changes, and a weakened immune system. Thiols, an organic group containing sulfur and hydrogen, are often found within antioxidants that protect against damage from ROS. Since mercury tends to bond with the sulfur, it binds tightly to this group and destroys the antioxidant’s function of protecting cells from oxidative damage. Additionally, changes in the gene expression caused by mercury can halt the repair mechanisms and further contribute to the body’s ability to not be able to detect and act upon newly mutated cells.

Mercury exposure is strongly associated with heart diseases such as atherosclerosis, coronary heart disease, stroke, myocardial infarction, hypertension, and cardiac arrhythmias. These are a result of an inflammatory response that mercury induces, deteriorating the vascular system which includes the blood vessels that carry blood to our body and back to the heart. It also affects ion channels that maintain the electrical signal of the order of cardiac muscle contraction pumping blood inside the heart. Specifically, it interferes with calcium concentrations, and since cardiac cells require calcium to contract, it would cause dysfunctions in heart muscle contractions. Mercury also reduces the availability of nitric oxide(NO) that is responsible for dilating blood vessels and disrupts mitochondrial function, impairing the energy production in heart cells. Higher mercury levels found in urine and hair are associated with lower levels of hemoglobin in the body (the molecule that brings oxygen in the blood to the cells) and lower blood cell count as well.

Mercury vapor is easily absorbed through the lungs when inhaled, attacking the respiratory system. 80% of inhaled mercury vapor enters the bloodstream, where it can penetrate the blood-brain barrier and placenta. It damages the alveoli, or the air sacs where oxygen and carbon dioxide are exchanged between lungs and bloodstream. This leads to diseases such as chemical pneumonitis, bronchitis, and pulmonary fibrosis. Mercury can trigger an immune response that creates excess collagen in lung tissue (fibrosis) which impairs respiratory function by blocking gas exchange. Vapor mercury can additionally turn into a divalent mercury Hg²⁺ that interacts with thiolate molecules like cysteine (an amino acid) which is even more toxic.

Inorganic mercury mainly accumulates in the kidney and is reabsorbed into the body as by bonding to two cysteine amino acids, forming Cys-S-Hg-SCys. Mercury exposure also epigenetically alters the kidney tissues through histone acetylation, which increases DNA expression in some areas, and DNA methylation, which decreases expression in some genes. It also changes the expression of aquaporins—more of these induce more water reabsorption into the body. In Indonesia, urinary mercury levels >7 μg/L were linked to renal dysfunction. Thus, kidney dysfunction occurs from a mercury-induced disruption in aquaporin channel amounts.

Trophic cascades are when one position in the food chain causes a chain reaction of impacts throughout the entire ecosystem. Mercury acts as a direct cause to these cascades through its toxic effects, through bioaccumulation, as mentioned before. Mercury’s trophic cascade has a ripple effect, as species either gain too many predators and can’t survive or lose their direct predators and experience an exponential population growth. This results in an overall loss of biodiversity and destabilizes ecosystems— both of which are major ecological threats.

Mercury is also extremely toxic to the soil and plants, disrupting food chains at its very roots. When mercury leeches into soil, it kills microbes which are important in nutrient cycling. Mercury concentrations as low as 4.4 mg Hg/kg of soil can impact microbes within the soil. In plants, mercury ions are reactive with sulfur-containing proteins, which disrupt basic life processes such as producing chlorophyll (necessary for photosynthesis), water retention, and the uptake of minerals.

Mercury is extremely toxic to both invertebrates and vertebrates. In invertebrates, mercury impacts basic living functions such as movement, feeding, growth, and development. The impacts are tenfold if early life stages such as eggs, embryos, or larvae are exposed to mercury, reducing both the gene pool and biodiversity. In vertebrates, the two most toxic forms of mercury are methylmercury (MeHg) and mercuric chloride (HgCl₂) which, as discussed before, disrupt hormones for reproduction, cause liver and kidney damage, impair thinking and motor functions, and so much more. Mercury’s widespread destruction on pretty much all life displays its ability to destabilize entire ecosystems if not closely monitored.

Citation:

Wu, Y., Osman, A. I., Hosny, M., Elgarahy, A. M., Eltaweil, A. S., Rooney, D. W., Chen, Z., Rahim, N. S., Sekar, M., Gopinath, S. C. B., Rani, N. N. I. M., Batumalaie, K., & Yap, P. (2024). The toxicity of mercury and its chemical compounds: molecular mechanisms and environmental and human health implications: A Comprehensive review. ACS Omega, 9(5), 5100–5126. https://doi.org/10.1021/acsomega.3c07047

Page updated

Google Sites

Report abuse