An assessment of thimerosal use in childhood vaccines.
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.


CONCLUSIONS
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.
Ball
L K
LK
Division of Vaccines and Related Products Applications, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Foodand Drug Administration, Rockville, Maryland 20852, USA. balll@cber.fda.gov
Ball
R
R
Pratt
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D000818:Animals; D002675:Child, Preschool; D017408:Guidelines as Topic; D006801:Humans; D006968:Hypersensitivity, Delayed; D007114:Immunization / Q000009:adverse effects; D007223:Infant; D008628:Mercury / Q000097:blood*; D008630:Mercury Poisoning / Q000453:epidemiology / Q000209:etiology; D008767:Methylmercury Compounds / Q000009:adverse effects / Q000633:toxicity; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects* / Q000633:toxicity; D018570:Risk Assessment; D013849:Thimerosal / Q000009:adverse effects* / Q000633:toxicity; D014481:United States; D014486:United States Food and Drug Administration; D014612:Vaccines / Q000009:adverse effects*
D008767:Methylmercury Compounds; D011310:Preservatives, Pharmaceutical; D014612:Vaccines; D013849:Thimerosal; D008628:Mercury