March 2008

NIAID-Supported Studies on Mercury, Thimerosal, and Vaccine Safety

Overview

Thimerosal is a preservative that has been added to some vaccines and other products because it is effective in killing bacteria and in preventing bacterial contamination. When thimerosal is degraded or metabolized, one product is ethyl mercury.

In July 1999, U.S. Department of Health and Human Service (DHHS) agencies, including the National Institute of Allergy and Infectious Diseases (NIAID); 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. This decision 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. More research is needed to determine if the guidelines for methyl mercury are also appropriate guidelines for thimerosal.

NIAID thimerosal research 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.

How does methyl mercury exposure differ from thimerosal exposure?

There are important differences between methyl mercury exposure and thimerosal exposure.

• Thimerosal contains ethyl mercury, which is structurally different from methyl mercury.
• The timing and route of exposure are different for these two chemicals.

People usually become exposed to methyl mercury through eating fish containing high levels of the substance. Some of this methyl mercury may be passed from a mother to her fetus before birth and to infants through breast milk. Prior to the removal of thimerosal from childhood recommended vaccines, infants were exposed to thimerosal by intramuscular injection during vaccination, not by ingestion. Furthermore, infants received thimerosal from 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.

What is known about prenatal exposures to ethyl mercury?

There is minimal modern research to address whether or not ethyl mercury may be passed from a mother to her fetus before birth. As a precaution, DHHS and product manufacturers are working to reduce or eliminate thimerosal from products that may be given to pregnant women, such as Rho (D) Immune Globulin. Also, thimerosal-free versions of several adult vaccines are available for use.

Are the current mercury guidelines appropriate for assessing thimerosal exposure?

Methyl mercury guidelines assess a child's risk based on a continuing daily mercury exposure. As mentioned above, there are several important differences between methyl mercury exposure and thimerosal exposure. More research is needed to determine if the guidelines for methyl mercury exposure are also appropriate guidelines for thimerosal.

What research has NIAID supported to find out more about the effects of thimerosal exposure and how it compares with methyl mercury exposure?

NIAID has supported several studies to address these questions, including

• One completed study of mercury levels in infants who received vaccines containing thimerosal
• Two follow-up studies of mercury levels in infants who receive vaccines containing thimerosal
• One completed study of thimerosal and methyl mercury exposure in infant monkeys

What was the purpose of the published study about thimerosal and vaccinations?

NIAID-supported studies at the University of Rochester in New York and the National Naval Medical Center in Bethesda, Maryland, looked at levels of mercury in blood and other samples from 61 infants who had received routine immunizations with thimerosal-containing vaccines.

What types of samples were assessed?

Mercury levels were measured in blood, urine, and stool samples from infants at different times up to 28 days after vaccination. Researchers also looked at levels of mercury in samples of breast milk, mother's hair, and infant formula.

What were the primary results obtained from assessment of these samples?

• Blood levels of mercury were uniformly below safety guidelines for methyl mercury for all infants in this study.
• Mercury was cleared from the blood in infants exposed to thimerosal faster than would be predicted for methyl mercury.
• Infants excreted significant amounts of mercury in stool after thimerosal exposure, thus removing mercury from their bodies.

What can be concluded from the results of the Rochester study?

These results suggest that there are differences in the way thimerosal and methyl mercury are distributed, metabolized, and excreted. Thimerosal appears to be removed from the blood and body more rapidly than methyl mercury.

Where can I find more information on the Rochester study?

The results were published in the November 30, 2002, issue of the scientific journal, The Lancet.

Reference: Pichichero ME, Cernichiari E, Lopreiato J, and Treanor J. Mercury concentrations and metabolism in infants receiving vaccines containing thimerosal: a descriptive study. Lancet 360:1737-1741 (2002) www.thelancet.com

Why are these studies unique?

Because few study designs have been established to focus on infant metabolism of thimerosal versus methyl mercury, the Rochester study is making progress in a relatively new field.

Does NIAID plan to support any further research to assess mercury levels in infants who received vaccines containing thimerosal?

Yes. NIAID supported a follow-up study with a larger number of infants. The University of Rochester is collaborating with the Children's Hospital of Buenos Aires in Argentina to conduct this study. The Argentina clinicians measured mercury in blood and other samples from infants receiving routine vaccinations with thimerosal.

NIAID is also conducting an additional study in Argentina that focuses on enrollment of premature (32 to 37 weeks gestational age) and low birth weight (2,000 to less than 3,000 grams) infants. Enrollment for this study is complete. Although some thimerosal-containing vaccines still are given to children in Argentina, most vaccines now given to children in the United States are either thimerosal-free or contain markedly reduced amounts of thimerosal.

What does NIAID hope to learn from the follow-up studies of thimerosal and vaccines in infants?

The goals of these studies are to assess the levels of mercury in the blood and other samples from infants receiving thimerosal-containing vaccines as part of their routine immunization schedule and to obtain more samples closer to the time of vaccination.

Preliminary results from the first portion of the study including 216 infants in Argentina confirmed findings of the first study done at University of Rochester.

• Blood mercury levels do not show accumulation between vaccinations in children; the levels drop to pre-vaccination levels within 30 days.
• Mercury excretion in stools follows vaccination with thimerosal-containing vaccines.

Where can I find more information on the study in Argentina?

The results were published in the February 2008 issue of the scientific journal, Pediatrics.

What is the purpose of the studies of thimerosal and methyl mercury exposure in infant monkeys?

NIAID supported studies in infant and adolescent monkeys to compare the distribution, metabolism, and clearance of mercury after exposure to thimerosal and methyl mercury. Infant monkeys were exposed to either thimerosal or methyl mercury on a weekly basis. Blood levels of mercury were determined for each animal after each exposure. The development and behavior of the monkeys was also monitored. After the fourth dose, animal tissues were analyzed to determine levels of mercury in target tissues, such as brain and kidney. These studies will provide information to help determine whether or not the guidelines for methyl mercury are also appropriate for thimerosal.

Are the results available for the completed studies of thimerosal and methyl mercury exposure in infant monkeys?

Currently the investigators of this study are completing their analyses of the data obtained from this study. Preliminary results indicate

• Mercury, in the form of methyl mercury (oral ingestion) and thimerosal (intramuscular injection with vaccines) were both readily absorbed and distributed into blood and brain.
• Total (organic plus inorganic) mercury was cleared from both blood and brain faster after thimerosal exposure than after methyl mercury exposure.
• Levels of total mercury measured in blood and in brain were lower after thimerosal exposure than after methyl mercury exposure.
• The proportion of brain mercury that was inorganic was higher in thimerosal-exposed animals compared with methyl mercury.
• The absolute amount of inorganic mercury was higher in thimerosal-exposed animals compared with methyl mercury.
• During weekly doses of methyl mercury, total mercury in blood continued to accumulate, while during weekly doses of thimerosal, there was little accumulation of total mercury in blood.

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 published in Environmental Health Perspectives. For more information, see http://ehp.niehs.nih.gov/docs/2005/7712/abstract.html.

More information

National Institute of Allergy and Infectious Diseases
Division of Microbiology and Infectious Diseases
www.niaid.nih.gov/dmid/vaccines

U.S. Department of Health and Human Services
National Vaccine Program Office
200 Independence Avenue, S.W.
Washington, DC 20201
1-877-696-6775 or 202-619-0257
www.hhs.gov/nvpo

Centers for Disease Control and Prevention
National Immunization Program
Mailstop E-05
1600 Clifton Road NE
Atlanta, GA 30333
1-800-CDC-INFO (1-800-232-4636)
www.cdc.gov/nip

Food and Drug Administration
Center for Biologics Evaluation and Research
CBER Ombudsman (HFM-4)
1401 Rockville Pike, Suite 200N
Rockville, MD 20852-1448
1-800-835-4709 or 301-827-1800
www.fda.gov/cber/vaccine/thimerosal.htm

Health Resources and Services Administration
National Vaccine Injury Compensation Program
5600 Fishers Lane
Rockville, MD 20857
1-800-338-2382
www.hrsa.gov/vaccinecompensation

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

The National Institutes of Health (NIH)-The Nation's Medical Research Agency-includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

Department of Health and Human Services

National Institutes of Health (NIH) Bethesda, Maryland 20892

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