Dr. A. J. van't Veen AJ.

Department of Dermatology and Venereology, Erasmus University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.

Drugs 2001;61(5):565-72

http://www.ncbi.nlm.nih.gov/entrez/PubMed&list_uids=11368282&dopt=Abstract

The inorganic mercurial thiomersal (merthiolate) has been used as an effective preservative in numerous medical and non-medical products since the early 1930s. Both the potential toxicity of thiomersal and sensitisation to thiomersal in relation to the application of thiomersal-containing vaccines and immunoglobulins, especially in children, have been debated in the literature. The very low thiomersal concentrations in pharmacological and biological products are relatively non-toxic, but probably not in utero and during the first 6 months of life. The developing brain of the fetus is most susceptible to thiomersal and, therefore, women of childbearing age, in particular, should not receive thiomersal-containing products. Definitive data of doses at which developmental effects occur are not available. Moreover, revelation of subtle effects of toxicity needs long term observation of children. The ethylmercury radical of the thiomersal molecule appears to be the prominent sensitiser. The prevalence of thiomersal hypersensitivity in mostly selected populations varies up to 18%, but higher figures have been reported. The overall exposure to thiomersal differs considerably between countries. In many cases a positive routine patch test to thiomersal should be considered an accidental finding without or, probably more accurately, with low clinical relevance. In practice, some preventive measures can be taken with respect to thiomersal hypersensitivity. However, with regard to the debate on primary sensitisation during childhood and renewed attention for a reduction of children's exposure to mercury from all sources, the use of thiomersal should preferably be eliminated or at least be reduced. In 1999 the manufacturers of vaccines and immunoglobulins in the US and Europe were approached with this in mind. The potential toxicity in children seems to be of much more concern to them than the hidden sensitising properties of thiomersal. In The Netherlands, unlike many other countries, the exposure to thiomersal from pharmaceutical sources has already been reduced. Replacement of thiomersal in all products should have a high priority in all countries.

An assessment of thimerosal use in childhood vaccines.

Ball LK, Ball R, Pratt RD.

Division of Vaccines and Related Products Applications, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852, USA. balll@cber.fda.gov

Pediatrics 2001 May;107(5):1147-54

http://www.ncbi.nlm.nih.gov/entrez/PubMed&list_uids=11331700&dopt=Abstract

BACKGROUND: On July 7, 1999, the American Academy of Pediatrics and the US Public Health Service issued a joint statement calling for removal of thimerosal, a mercury-containing preservative, from vaccines. This action was prompted in part by a risk assessment from the Food and Drug Administration that is presented here. METHODS: The risk assessment consisted of hazard identification, dose-response assessment, exposure assessment, and risk characterization. The literature was reviewed to identify known toxicity of thimerosal, ethylmercury (a metabolite of thimerosal) and methylmercury (a similar organic mercury compound) and to determine the doses at which toxicity occurs. Maximal potential exposure to mercury from vaccines was calculated for children at 6 months old and 2 years, under the US childhood immunization schedule, and compared with the limits for mercury exposure developed by the Environmental Protection Agency (EPA), the Agency for Toxic Substance and Disease Registry, the Food and Drug Administration, and the World Health Organization. RESULTS: Delayed-type hypersensitivity reactions from thimerosal exposure are well-recognized. Identified acute toxicity from inadvertent high-dose exposure to thimerosal includes neurotoxicity and nephrotoxicity. Limited data on toxicity from low-dose exposures to ethylmercury are available, but toxicity may be similar to that of methylmercury. Chronic, low-dose methylmercury exposure may cause subtle neurologic abnormalities. Depending on the immunization schedule, vaccine formulation, and infant weight, cumulative exposure of infants to mercury from thimerosal during the first 6 months of life may exceed EPA guidelines. CONCLUSION: Our review revealed no evidence of harm caused by doses of thimerosal in vaccines, except for local hypersensitivity reactions. However, some infants may be exposed to cumulative levels of mercury during the first 6 months of life that exceed EPA recommendations. Exposure of infants to mercury in vaccines can be reduced or eliminated by using products formulated without thimerosal as a preservative.

Pediatric Vaccines Ask The Expert

Thimerosal and Vaccines

From Medscape Pediatrics

Question

Why is mercury in vaccines of sudden concern in the United States?

Response

from Robert W. Steele, MD, 01/15/2002

http://www.medscape.com/viewarticle/420699

Thimerosal is a derivative of ethyl mercury and a preservative that has been used in medical products since the 1930s. It is used to help ensure that these products do not become contaminated by microorganisms. In a review of pediatric vaccines in 1999, the US Food and Drug Administration (FDA) found that mercury exposure from vaccines containing thimerosal was within the safety margins established by the FDA, the Agency for Toxic Substances and Disease Registry, and the World Health Organization for methyl mercury, a closely related organomercurial. However, it was determined that the maximum amount of ethyl mercury from thimerosal in vaccines could have exceeded the Environmental Protection Agency (EPA) guidelines that were established for methyl mercury, depending on the vaccine formulations received. The EPA guidelines were meant to be protective of the developing fetus. Therefore, it was felt that adopting the EPA guidelines would provide an even greater margin of safety for infants and small children.

There are no data or evidence of any harm caused by the level of exposure that some children may have encountered by following the existing immunization schedule. Nonetheless, because the theoretical possibility exists, the US Public Health Service, the American Academy of Pediatrics, and the American Academy of Family Physicians set a goal of removing thimerosal from vaccines in the United States as soon as possible.

In August 1999, the FDA approved a thimerosal-free hepatitis B vaccine manufactured by Merck and Co., and in March 2000, approved a thimerosal-reduced (less than 0.5 mcg of mercury per dose) hepatitis B vaccine manufactured by Glaxo SmithKline. In March 2001, the FDA approved a newly formulated version of Aventis Pasteur's Tripedia, a diphtheria, tetanus, and acellular pertussis (DTaP) vaccine containing only a trace of thimerosal (less than 0.5 mcg of mercury per dose.) Additionally, Wyeth-Lederle Vaccines and Pediatrics market a single-dose, thimerosal-free formulation of its Haemophilus influenzae type b (Hib) vaccine in the United States. This effectively concludes the process of eliminating thimerosal from the routine immunizations given to children in the United States.