Several factors led to examination of mercury-containing preservatives in childhood vaccines. Over the past decade there has been increased attention focused on the health effects of human exposure to mercury, particularly methyl mercury. In 1994, the EPA revised its Reference Dose (RfD) for methylmercury exposure, lowering its guideline for safe exposure from 0.3 to 0.1 microgram per kilogram body weight per day. Prospective studies (in the Seychelles, Faroe Islands and others) of the effects of low dose exposure to methylmercury in the diet were published , and some of these studies raised concern that neurodevelopmental outcomes in children may be subtly affected when their mothers were exposed to methylmercury from dietary sources at levels that were previously thought to be safe. Also in the 1990's, the CDC's Advisory Committee on Immunization Practices (ACIP) and other recommending bodies added new vaccines (e.g., hepatitis B, Hib), some of which contained thimerosal as a preservative, to the routine childhood immunization schedule. Additionally, beginning in 1996, the replacement of whole cell DTP-Hib combination vaccines with separately administered DTaP and Hib vaccines increased the amount of thimerosal that some infants might have received (depending on vaccine formulation(s) received). In light of efforts by various federal agencies to decrease human exposure to mercury from various sources, and the potential increase in infant exposure to thimerosal from vaccines, FDA undertook review of this issue. Thus, while enactment of FDAMA 1997 provided an official mechanism for review of this issue, the use of thimerosal as a preservative in vaccines had already begun to be considered by FDA. During the past ten years, FDA has provided informal and formal advice to manufacturers recommending that new vaccines under development be formulated without thimerosal as a preservative. FDA had previously reviewed thimerosal use in biological products, including vaccines, in 1976. This review evaluated exposure to thimerosal from biological products using the 1974 American Academy of Pediatrics "Red Book" immunization schedule and concluded that, with the exception of long term immune globulin replacement therapy, "no dangerous quantity of mercury is likely to be received from biologic products in a lifetime." Of note, immune globulin products licensed in the U.S. no longer use thimerosal as a preservative. | 
