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
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.