In rats given a single dose of methylmercury, the 1:1 ratio of organic: inorganic mercury was reached after 50 days in liver and after 14 days in kidney, the main site of accumulation of inorganic mercury. Inorganic mercury represented less than 4% of the mercury in brain during the first 23 days after a single dose ... and only 3.4% after prolonged daily treatment ...
The main site of decomposition of methylmercury is the intestinal tract, where the portion secreted with bile or with cells shed from the intestinal wall is decomposed and the remainder is reabsorbed ... Most of the decomposition is carried out by intestinal bacterial flora; disruption of this bacterial activity by antibiotics prolonged the clearance half-time and decreased fecal excretion in both rats and mice ... Both demethylation and methylation occur. Cecal bacteria from rats methylated 2.3% of inorganic mercury at a dose of < 0.1 ug/g and less of doses > 0.1 ug/g ... Extrapolation of this rate of synthesis to human populations with intakes of 4.6 ug of inorganic mercury and 2.4 ug of organic mercury would add only 0.1 ug to the daily intake of methylmercury.
The reaction by which methylmercury is demethylated was investigated using several reactive oxygen modulators in a model using rat liver slices in vitro. The rate of conversion of methylmercury to inorganic mercury in vitro is similar to experiments in rats in vivo, indicating that the model is suitable for reproducing the bio-transformation of methylmercury. Results with various reagents suggest that the demethylation of methylmercury may be aided by superoxide anions produced by the electron transfer system in the inner mitochondrial membrane ...
The time required for methylmercury metabolism to inorganic mercury may account for the latent or silent period observed in epidemiological studies from methylmercury poisoning incidents in Japan and Iraq. During the latent period (both during and after the cessation of exposure) the patient feels no untoward effects. It is possible that a number of biochemical changes may take place in parallel during this period, and some may not be causatively related to the clinical outcome. /It was/ hypothesized that the carbon-mercury bond in methylmercury undergoes homolytic cleavage to release methyl free radicals. The free radicals are expected to initiate a chain of events involving peroxidation of lipid constituents of the neuronal cells. The onset of symptoms is delayed for the period of time that cellular systems are able to prevent or repair effects of lipid peroxidation. When the cellular defense mechanisms are overwhelmed, rapid and progressive degeneration of the tissue results. In the Iraqi poisoning incident, the latent period before toxic signs were noted varied from a matter of weeks to months. In contrast, the latency observed in the Japanese poisoning incident was as long as a year or more. The difference in duration may in part be due to the presence of selenium in the fish ingested by the Japanese population.
The general population is primarily exposed to methymercury through the diet. However, air and water, depending upon the level of contamination, can contribute significantly to the daily intake of total mercury. ... Fish and fish products are the dominant source of methylmercury in the diet ... Methylmercury in the human diet is almost completely absorbed into the bloodstream and distributed to all tissues within about 4 days. ... Methylmercury is converted to inorganic mercury in experimental animals and humans. ... The rate of excretion of mercury in both laboratory animals and humans is directly proportional to the simultaneous body burden and can be described by a single-compartment model with a biological half-time, in fish-eating humans, of 39-70 days ... In every animal species studied, the nervous system is a target of methylmercury, fetuses appearing to be at higher risk than adults. ... Methylmercury is fetotoxic in mice (single dose of 2.5-7.5 mg/kg); teratogenic in rats, and adversely affects the behavior of monkey offspring (mercury doses of 50-70 ug/kg per day before and during pregnancy). It also affects spermatogenesis in mice .... The clinical and epidemiological evidence indicates that prenatal life is more sensitive to the toxic effects of methylmercury than in adult life. The inhibition of protein synthesis is one of the earliest detectable biochemical effects in the adult brain ... Methylmercury can also react directly with important receptors in the nervous system, as shown by its effect on acetylcholine receptors in the peripheral nerves. In the case of prenatal exposure ... it affects normal neuronal development, leading to altered brain architecture, heterotopic cells and decreased brain size. Methylmercury may also be exerting an effect, perhaps through inhibition of the microtubular system, on cell division during critical stages in the formation of the central nervous system. ... No adverse effects /in adults/ have been detected with long-term daily methylmercury intakes of 3-7 ug/kg body weight (hair mercury concentrations of approximately 50-125 ug/g). Pregnant women may suffer effects at lower methylmercury exposure levels than non-pregnant adults, suggesting a greater risk for pregnant women. Severe derangement of the developing central nervous system can be caused by prenatal exposure to methylmercury. ... Evidence of pyschomotor retardation (delayed achievement of developmental milestones, a history of seizures, abnormal reflexes) was seen ... at maternal hair levels below those associated with severe effects. ... CONCLUSIONS: ... Certain groups with a high fish consumption may attain a blood methylmercury level ... associated with a low (5%) risk of neurological damage to adults. The fetus is at particular risk. ... There is a need for epidemiological studies on children exposed in utero to levels of methylmercury that result in peak maternal hair mercury levels below 20 ug/g, in order to screen for those effects only detectable by available psychological and behavioral tests.
CLASSIFICATION: C; possible human carcinogen. BASIS FOR CLASSIFICATION: Based on inadequate data in humans and limited evidence of carcinogenicity in animals. Male ICR and B6C3F1 mice exposed to methylmercuric chloride in the diet had an increased incidence of renal adenomas, adenocarcinomas and carcinomas. The tumors were observed at a single site and in a single species and single sex. The renal epithelial cell hyperplasia and tumors were observed only in the presence of profound nephrotoxicity and were suggested to be a consequence of reparative changes in the cells. Several nonpositive cancer bioasays were also reported. Although genotoxicity test data suggest that methylmercury is capable of producing chromosomal and nuclear damage, there are also nonpositive genotoxicity data. HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Limited. /Based on former classification system/
◈ What is methylmercury?
Methylmercury is an organic form of mercury. Methylmercury is found in water, soil, plants and animals. Methylmercury is different from elemental mercury, the type of mercury that is found in thermometers and some dental amalgams (tooth fillings) and inorganic mercury (which can be found in certain industries/occupational settings).
◈ Where does methylmercury come from?
Mercury in the air comes from natural sources, such as volcanic eruptions and forest fires, and man-made sources, such as coal-fired power plants. When mercury from the air enters water such as oceans, lakes, rivers and streams, the mercury is changed into methylmercury.
◈ How can I be exposed to methylmercury?
People can be exposed to methylmercury in many ways. The majority of methylmercury exposures are from eating fish, shellfish, and marine animals. These animals absorb methylmercury from the water through their gills and from the food they eat. Almost all fish contain some methylmercury. Methylmercury in small amounts is not likely to be harmful. However, high exposure can be toxic to humans.
◈ Do some fish have more methylmercury than others? Are there fish that I should avoid eating?
Eating fish is an important part of a healthy diet and is a good food choice for pregnancy. However, the U.S. Food and Drug Administration (FDA) and the U.S. Environmental Protection Agency (EPA) advise anyone who could become pregnant, those who are already pregnant, those who are nursing, and children under the age of 6 to avoid eating fish with high levels of methylmercury.Large fish, fish with long life-spans, and fish that eat other fish are more likely to have higher amounts of methylmercury.The following large fish have the highest levels of methylmercury and should be avoided during pregnancy and breastfeeding: shark, swordfish, king mackerel, marlin, orange roughy, bigeye tuna, and tilefish from the Gulf of Mexico. Also avoid eating whale meat and/or blubber (fat), as whales generally have high levels of methylmercury.
◈ If I am planning a pregnancy or I am already pregnant, what kind of fish can I eat, and how much?
Anyone who is pregnant or could become pregnant are advised to follow the FDA and EPA guidelines for fish consumption.The FDA and EPA have created a chart that categorize fish as “Best Choices,” “Good Choices,” and “Choices to Avoid” which can be found here: https://www.fda.gov/food/consumers/advice-about-eating-fish.A typical serving of fish is 4 ounces, weighed before cooking. For people who could become pregnant or who are currently pregnant, the FDA & EPA suggest eating up to 12 ounces (340 grams) of fish a week. This would equal 2 to 3 servings from their list of fish that fall under their “Best Choices” category, or 1 serving per week from the “Good Choices” category.There are different types (species) of tuna. So you will find different varieties of tuna listed for each category of choices. Canned light tuna (including skipjack) is listed under “Best Choices.” Albacore (white) tuna and yellowfin tuna can have higher mercury levels and are under “Good Choices.”
◈ Can I eat fish caught by family and friends from local waters?
Freshwater fish caught from local waters may contain high levels of methylmercury or other local pollutants and might not be safe to eat. The EPA and state and local health departments monitor freshwater lakes and streams. Check with your local agency to see if the fish is safe to eat. If you eat fish caught by family or friends, check for fish advisories, which can be found here: https://fishadvisoryonline.epa.gov/Contacts.aspx. If there is no advisory, the recommendation is to eat only 1 serving and no other fish that week.
◈ Are there tests that can tell if I have high levels of methylmercury in my body?
Blood and hair can be tested to determine exposure to methylmercury. Blood tests are good for detecting methylmercury right after exposure occurs. Hair testing may be able to detect ongoing (chronic) mercury exposure. However, these tests can be hard to interpret. A urine test may not be as helpful in testing for methylmercury. You can discuss your exposure concerns with your healthcare providers to determine if testing would be appropriate for you and what type of testing is recommended. There is no standard recommendation to screen for methylmercury levels before or during pregnancy.
◈ I was exposed to methylmercury. Can this make it harder for me to get pregnant?
Some studies have suggested that mercury exposure might increase fertility problems. One study found blood levels of mercury were higher among females with infertility than a control group.
◈ Does exposure to methylmercury increase the chance for miscarriage?
Miscarriage is common and can occur in any pregnancy for many different reasons. It is not clear if exposure to methylmercury increases the chance for miscarriage as this has not been well studied. However, one study that measured blood levels of mercury did not find a higher chance for miscarriage.
◈ Can exposure to methylmercury increase the chance for birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Methylmercury at high levels can affect a developing baby. Methylmercury crosses the placenta and can be found in the baby’s blood at levels higher than those in the person who is pregnant. The baby’s brain is the most sensitive organ to the effects of methylmercury exposure. The brain continues to develop throughout the entire pregnancy, so high exposure at any time in the pregnancy can be concerning.The effects of methylmercury on human pregnancy have been documented by several events that occurred many years ago in Japan and Iraq. Children were born with birth defects following the contamination of the food supply by methylmercury. These were extreme situations where a number of adults also became sick and died from the contamination. The birth defects reported were small head size, brain damage, developmental delay, intellectual disability, blindness, muscle weakness, and seizures.
◈ Can exposure to methylmercury cause other pregnancy complications?
Some studies have suggested a chance for preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces (2500 grams) at birth). However, not all studies have reported this.
◈ Can exposure to methylmercury in pregnancy affect future behavior or learning for the child?
As mentioned, very high levels of methylmercury in the diet, as seen from contamination of food supplies in Japan and Iraq were able to affect brain development. These high levels of exposures are not typical. People in the U.S., who generally do not depend upon fish as their primary protein intake are unlikely to consume enough methylmercury from fish to cause harmful effects in a pregnancy. A study in another country, where people eat much more fish than is typically consumed in the U.S., reported that methylmercury from a balanced diet that includes fish is not likely to affect the development of the child from prenatal exposure. Another study found that children born to people who ate fish during pregnancy had higher IQ levels. This included persons who had somewhat increased levels of mercury; suggesting that other nutrients in fish might have had a protective effect.One study suggested that having exposure to higher levels of mercury in pregnancy might increase the chance of children maturing to puberty at a slightly younger age (called precocious puberty). This study has several limitations, so it is not proven that prenatal exposure to mercury was really the cause.
◈ To be safe, shouldn’t I just stop eating fish completely during pregnancy?
Fish can provide beneficial protein, long chain polyunsaturated fatty acids (such as omega-3 fatty acids), iodine, selenium, and vitamin D. These are all important for your health and the growth and development of a fetus. Some studies have found that people who eat fish during pregnancy have better pregnancy outcomes than those who do not eat fish. You can maximize the benefits of fish by choosing fish with low mercury levels.People who are pregnant should not eat raw fish, such as that found in sushi and sashimi. This is because raw fish may contain bacteria or parasites that could cause serious illness. While cooking fish reduces the risk of illness from bacteria and pathogens, it does not reduce the levels of methylmercury in the fish. Please see our fact sheet on eating meats and seafood at https://mothertobaby.org/fact-sheets/eating-raw-undercooked-or-cold-meats-and-seafood/ for more information.
◈ What if I ate more than the recommended amount of fish in a week during my pregnancy?
One week's consumption of fish probably would not greatly change the level of methylmercury in your body. Accidentally eating fish from the “Choices to Avoid” section one time, or eating more than the recommended amount of fish during 1 week is unlikely to increase the chance for birth defects or pregnancy complications. If you eat a lot of fish during 1 week, you can limit your fish consumption for the next week or two.
◈ What if I am breastfeeding my baby?
Follow the same FDA & EPA guidelines described above for eating fish when breastfeeding. When the dietary guidelines are followed, the level of methylmercury is considered compatible with breastfeeding. Very few studies have been done to evaluate breastfed infants exposed to high levels of methylmercury in breast milk; and the results are not clear. If tests during pregnancy or after delivery show high levels of methylmercury in your system, then you should discuss the safety of breastfeeding with your healthcare provider. Be sure to talk to your healthcare provider about all your breastfeeding questions.
◈ If a male is exposed to methylmercury could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Some studies have suggested that high levels of mercury may cause infertility while other studies have not. There is no information suggesting that a father’s exposure to methylmercury can cause birth defects or learning difficulties in his children. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.
... This study investigated the effects of prenatal exposure to MeHg and Hg vapor on Hg concentrations in the brain of neonatal rats. Female Long-Evans hooded rats were exposed to MeHg (0, 3, 6, or 9 ppm as drinking solution), Hg vapor (0, 300, or 1,000 ug/cu m for 2 hr/day), or the combination of both, from 30 days before breeding through gestational day 18. On postnatal day 4, whole brains were taken from one male and one female from each of four litters in each treatment group to assess organic and inorganic Hg in the brain by cold vapor atomic absorption spectrometry. Statistical analysis using linear mixed effects models showed that MeHg dose was the primary determinant of both organic and inorganic brain Hg levels. For both outcomes, ... significant interactions between MeHg and Hg vapor exposure /were found/...
Complexing with L-cysteine or glutathione has particular toxicological significance. In rats, injection of L-cysteine with methylmercury changed the short-term distribution of the latter by decreasing the plasma concentration and increasing the concentrations in brain, liver, and kidney. D-Cysteine had similar effects but did not increase the concentration of mercury in brain ... GSH had less effect on the brain uptake of methylmercury than L-cysteine ... Increased uptake by brain was also achieved by administration of a cysteine-supplemented diet ... The stimulatory effect of L-cysteine may be due to the structural similarity between the methylmercury-cysteine complex and L-methionine, which permits use of the same L-amino acid transport system ... L-Cysteine can also increase the biliary excretion of methylmercury, after a delay for conversion to GSH ...
/It was/ estimated that lowest level of methyl mercury in the brain capable of inducing onset of symptoms of intoxication to be 6 ug/g. Twelve victims of the Minimata disaster were reported to have brain concentrations ranging from 2.6 to 24 ug Hg/g ... "Normal" brain Hg levels (neutron activation analysis) in the Eastern US, based on autopsy samples from 7 individuals (age range: 33 to 79 years) ranged from 0.02 to 2.0 ug/g wet weight ... The range for a full term stillborn was 0.04 to 0.05 ng/g. Analysis of similar brain areas ... from a larger sampling (30 to 100 individuals ranging in age from neonates to 91 years) from the same study area revealed a range 0.02 to 2.59 ug Hg/g ... A similar range has been reported more recently ...
Mercury is excreted into the hair of methylmercury-exposed humans and animals. Incorporation of mercury into hair is irreversible, and hair analysis is thus a useful tool for monitoring exposure to methylmercury. Segmental analysis of hair may be used to provide a historical record of exposure patterns.
Methylmercury is excreted in breast milk ... The ratio of mercury in breast milk to mercury in whole blood was approximately 1:20 in women exposed to methylmercury via contaminated grain in Iraq between 1971 and 1972 ... Evidence from the Iraqi poisoning incident also showed that lactation decreased blood mercury clearance halftimes from 75 days in males and nonlactating females to 42 days in lactating females; the faster clearance due to lactation was confirmed in mice ... In mice, of the total mercury in the breast milk, approximately 60% was estimated to be methylmercury. /It was/ found that 16% of mercury in human breast milk is methylmercury. Studies in animals indicate that the mercury content of breast milk is proportional to the mercury content of plasma.
In rat and monkey neonates, excretion of methylmercury is severely limited ... In rats dosed prior to 17 days of age, essentially no mercury was excreted ... By the time of weaning, the rate of excretion had increased to adult levels. The failure of neonates to excrete methylmercury may be associated with the inability of suckling infants to secrete bile ... and the decreased ability of intestinal microflora to demethylate methylmercury during suckling
