Under the FDA Modernization Act (FDAMA) of 1997, FDA carried out a comprehensive review of the use of thimerosal in childhood vaccines. Conducted in 1999, this review found no evidence of harm from the use of thimerosal as a vaccine preservative, other than local hypersensitivity reactions. As part of the FDAMA review, FDA evaluated the amount of mercury an infant might receive in the form of ethylmercury from vaccines under the U.S. recommended childhood immunization schedule and compared these levels with existing guidelines for exposure to methylmercury, as there are no existing guidelines for ethylmercury, the metabolite of thimerosal. At the time of this review in 1999, the maximum cumulative exposure to mercury from vaccines in the recommended childhood immunization schedule was within acceptable limits for the methylmercury exposure guidelines set by FDA, Agency for Toxic Substances and Disease Registry (ATSDR), and the World Health Organization (WHO). However, depending on the vaccine formulations used and the weight of the infant, some infants could have been exposed to cumulative levels of mercury during the first six months of life that exceeded EPA recommended guidelines for safe intake of methylmercury. As a precautionary measure, the Public Health Service (including FDA, National Institutes of Health [NIH], Centers for Disease Control and Prevention [CDC] and Health Resources and Services Administration [HRSA]) and the American Academy of Pediatrics issued a Joint Statement, urging vaccine manufacturers to reduce or eliminate thimerosal in vaccines as soon as possible. The U.S. Public Health Service agencies have collaborated with various investigators to initiate further studies to better understand any possible health effects from exposure to thimerosal in vaccines. Available data has been reviewed in several public forums including the Workshop on Thimerosal, held in Bethesda in August 1999 and sponsored by the National Vaccine Advisory Committee, two meetings of the Advisory Committee on Immunization Practices of the CDC, held in October 1999 and June 2000, and by the Institute of Medicine's Immunization Safety Review Committee in July 2001 and February 2004. Data reviewed did not demonstrate convincing evidence of toxicity from doses of thimerosal used in vaccines. In case reports of accidental high-dose exposures in humans to thimerosal or ethyl mercury toxicity was demonstrated only at exposures that were 100 or 1000 times that found in vaccines. In its report of October 1, 2001, the IOM's Immunization Safety Review Committee concluded that the evidence is inadequate to either accept or reject a causal relationship between thimerosal exposure from childhood vaccines and the neurodevelopmental disorders of autism, attention deficit hyperactivity disorder (ADHD), and speech or language delay. At that time the committee's conclusion was based on the fact that there were no published epidemiological studies examining the potential association between thimerosal-containing vaccines and neurodevelopmental disorders. The Committee did conclude that the hypothesis that exposure to thimerosal-containing vaccines could be associated with neurodevelopmental disorders was biologically plausible. However, additional studies were needed to establish or reject a causal relationship. The Committee stated that the effort to remove thimerosal from vaccines was "a prudent measure in support of the public health goal to reduce mercury exposure of infants and children as much as possible." In 2004, the IOM's Immunization Safety Review Committee again examined the hypothesis that vaccines, specifically the MMR vaccines and thimerosal containing vaccines, are causally associated with autism. In this report, the committee incorporated new epidemiological evidence from the U.S., Denmark, Sweden, and the United Kingdom, and studies of biologic mechanisms related to vaccines and autism that had become available since its report in 2001. The committee concluded that this body of evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism, and that hypotheses generated to date concerning a biological mechanism for such causality are theoretical only. Further, the committee stated that the benefits of vaccination are proven and the hypothesis of susceptible populations is presently speculative, and that widespread rejection of vaccines would lead to increases in incidences of serious infectious diseases like measles, whooping cough and Hib bacterial meningitis FDA is continuing its efforts toward reducing or removing thimerosal from all existing vaccines. Much progress has been made to date. FDA has been actively working with manufacturers, particularly those that manufacture childhood vaccines, to reach the goal of eliminating thimerosal from vaccines, and has been collaborating with other PHS agencies to further evaluate the potential health effects of thimerosal. Since 2001, all vaccines recommended for children 6 years of age and younger have contained either no thimerosal or only trace amounts, with the exception of inactivated influenza vaccines, which are marketed in both the preservative-free and thimerosal–preservative–containing formulations. Thimerosal-preservative free influenza vaccine licensed for use in children six to 59 months of age is available in limited supply. Nevertheless, FDA is in discussions with manufacturers of influenza vaccine regarding their capacity to increase the supply of vaccine without thimerosal as a preservative. Additionally, new pediatric vaccines that have received licensure do not contain thimerosal. | 
