March 2008 NIAID Research on ThimerosalOVERVIEWMercury is a naturally occurring chemical element found throughout the environment. Mercury is found in three forms: as a pure metal (as found in thermometers), as inorganic salts, and as an organic derivative. Humans and wildlife are exposed to all three forms. Most environmental mercury consists of the metallic and inorganic forms. Because mercury is everywhere, it is not possible to prevent all exposure to it. High levels of mercury, however, are toxic. Methyl mercury, the most common organic derivative of mercury, is mainly produced by microorganisms in water and soil. Methyl mercury is of particular concern because it can accumulate in certain edible freshwater and saltwater fish, especially in larger and older fish, to levels that are much greater than levels in the surrounding water. Methyl mercury also can accumulate in humans who eat these fish. Exposure to high levels of methyl mercury is toxic and can cause mental retardation, cerebral palsy, and seizures. The fetus is especially sensitive to methyl mercury exposure and may suffer brain damage or even death if exposed to high levels. Since the 1930s, thimerosal has been added to some vaccines and other products because it is effective in killing bacteria and in preventing bacterial contamination, particularly in multidose containers. When thimerosal is degraded or metabolized, one product is ethyl mercury, another organic derivative of mercury. Not much is known about the effects of thimerosal exposure on humans and how this compares to methyl mercury exposure. The only known side effects of receiving low doses of thimerosal in vaccines have been minor reactions such as redness and swelling at the injection site. In July 1999, U.S. Department of Health and Human Service agencies, The American Academy of Pediatrics, and vaccine manufacturers agreed that thimerosal should be reduced or eliminated in vaccines as a precautionary measure and to reduce exposure to mercury from all sources. Today, all routinely recommended licensed pediatric vaccines currently being manufactured for the U.S. market are either thimerosal-free or contain markedly reduced amounts of thimerosal. Thimerosal, however, remains in some vaccines given to adults and adolescents, as well as some pediatric vaccines not on the Recommended Childhood and Adolescent Immunization Schedule. Thimerosal is still a common preservative found in vaccines used outside the United States. The decision to move toward reduced or eliminated thimerosal in vaccines was based on the various Federal guidelines for methyl mercury exposure and the assumption that the health risks from methyl and ethyl mercury were the same. Methyl mercury exposure is primarily through fish consumption. People who regularly eat mercury-contaminated fish can accumulate methyl mercury in their body over time. Some of this methyl mercury may be passed from the mother to the fetus before birth and to infants through breast milk. The fetus is sensitive to damage from this exposure. Prior to the removal of thimerosal from childhood recommended vaccines, infants were exposed to ethyl mercury by intramuscular injection during vaccination, not by ingestion. Furthermore, infants received thimerosal from childhood vaccines that were administered days or months apart. In contrast, methyl mercury exposure, primarily from foods, tends to occur over a longer sustained period of time. More research is needed to determine if the guidelines for methyl mercury exposure are also appropriate guidelines for thimerosal. Additionally, guidelines for maximal levels for short-term exposure need to be established. The National Institute of Allergy and Infectious Diseases (NIAID) funds thimerosal research that focuses on better understanding what happens to thimerosal once it is introduced in the body and how this compares to current knowledge of methyl mercury pathways. NIAID-sponsored researchers from the University of Rochester in New York (one of NIAID's Vaccine Treatment and Evaluation Units) performed assessments of mercury levels in infants receiving routine immunizations. In addition, NIAID and the National Institute of Environmental Health Sciences (NIEHS) funded studies comparing the pharmacokinetics and tissue distribution of thimerosal and methyl mercury in non-human primates. ASSESSMENT OF MERCURY LEVELS IN INFANTS RECEIVING ROUTINE IMMUNIZATIONSNIAID-supported studies at the University of Rochester and the National Naval Medical Center in Bethesda, Maryland, assessed levels of mercury in the blood, hair, urine, and stool of 40 infants who received vaccines containing thimerosal and 21 infants who received vaccines without thimerosal, as controls. The infants studied were 6 months of age or younger. This study generated several important results.
The results were published in the November 30, 2002, issue of the The
Lancet. For more information see www.niaid.nih.gov/factsheets/thimerosalqa.htm. NIAID conducted a follow-up of the Rochester study in Argentina with 216 newborns and infants. The purpose of this study was to
Preliminary results confirmed findings of the first study done at the University of Rochester.
These results were published in the February 2008 issue of Pediatrics. Reference: Pichichero ME, Gentile A, Giglio N, Umido V, Clarkson T, Cernichiari E, Zareba G, Gotelli C, Gotelli M, Yan L, Treanor J. Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines. Pediatrics 121(2):e208-214 (2008). NIAID is also conducting an additional study in Argentina that focuses on premature (32 to 37 weeks gestational age) and low birth weight (2000 to <3000 grams) infants. Enrollment for this study is now complete. PHARMACOKINETICS AND TISSUE DISTRIBUTION OF THIMEROSAL, ETHYL MERCURY, AND METHYL MERCURY IN ANIMALSNIAID and NIEHS cosponsored studies in adolescent and infant monkeys to compare the pharmacokinetics and tissue distribution of thimerosal and methyl mercury. One group of animals in this study received a dose of thimerosal and a dose of thimerosal-free infant vaccines by injection weekly beginning at birth and continuing for 3 weeks. The vaccines were included in the study to mimic infant exposure as closely as possible. A second group of animals received methyl mercury orally on a weekly basis beginning at birth and continuing for 3 weeks. Blood levels of mercury were determined for each animal after each of the four exposures. After the fourth dose, animal tissues were analyzed to determine levels of mercury in target tissues, such as brain and kidney. Assays to determine mercury levels measure inorganic vs. organic mercury but do not distinguish whether the organic mercury is in the form of ethyl mercury from thimerosal or methyl mercury. Results from these studies indicate
This study indicates that methyl mercury is not a suitable reference for risk assessment from exposure to thimerosal. This study was not designed to measure any type of damage due to mercury exposure. The mechanisms by which organic mercury is converted to inorganic mercury in the brain are unknown. There is not a consensus as to whether inorganic mercury in brain causes damage or to what extent compared to organic mercury. These results were recently published in. Environmental Health Perspectives, Volume 113, Number 8, August 2005. Comparison of Mercury Exposures
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