Global Vaccine Safety

Thiomersal in vaccines

Extract from report of GACVS meting of 6-7 June 2012, published in the WHO Weekly Epidemiological Record on 27 July 2012

In 1999, concerns were raised in the United States of America (USA) regarding exposure to mercury following immunization with thiomersal-containing vaccines. This was based on the calculation that the cumulative amount of mercury in primary infant immunization schedules in the USA potentially exceeded the recommended threshold set by its Environmental Protection Agency for methyl mercury. Hence, the policy decision in the USA to use only vaccines without thiomersal was based on a precautionary principle founded on the presumption of equal pharmacokinetics of ethyl mercury and methyl mercury, despite the fact that thiomersal contains only ethyl mercury.

Between 2002 and 2008, GAVCS reviewed several pharmacokinetic and epidemiological studies concerning thiomersal. Pharmacokinetic data in human infants, including premature and low birth-weight infants, established that the half-life of ethyl mercury is 3–7 days, and that ethyl mercury is efficiently excreted in the stools and does not accumulate over the long-term in blood, since levels returned to baseline within 30 days of vaccination.

At the June 2012 meeting, GACVS reviewed the most recently available information concerning the safety of thiomersal since it last reviewed this topic in 2008. A comprehensive review identified 28 publications that addressed mercury blood levels in the short and long term following vaccine administration, and epidemiological studies that examined the relation between thiomersal receipt and several health outcomes. Three ecological studies suggesting an association between thiomersal and neurodevelopmental disorders were found to be fraught with methodological flaws. In addition, the continuous increase in the number of cases of autism diagnosed in the USA despite removal of thiomersal from most vaccines strongly argues against a causal association (fulfilling the exposure and removal criteria). All other studies reviewed, which were conducted with more robust epidemiological designs and in different countries, failed to identify any association with neurodevelopmental disorders.

Recently published studies confirm that in all populations studied, including pre-term and low birth-weight babies, the half-life of ethyl mercury in blood is between 3 and 7 days. A quantitative risk assessment model for cumulative toxicity of thiomersal in humans by US Federal Drug Administration (FDA) was also reviewed. This methodology is based on a pharmacokinetic model of ethyl mercury and provides a framework for interpreting studies in animals and humans that evaluate linkages among dose, blood and brain levels, and toxicity. Using this framework the GACVS concluded that animal or human toxicity studies suggest that the levels of ethyl mercury attained in the blood and brain from cumulative doses of vaccines do not reach toxic levels, making biologically implausible any relation between thiomersal in vaccines and neurological toxicity.

Based on the current evidence, GACVS considers that no additional studies of the safety of thiomersal in vaccines are warranted and that available evidence strongly supports the safety of the use of thiomersal as a preservative for inactivated vaccines. GACVS believes that consideration of additional evidence suggestive of the contrary should be based on studies using the same high standards of epidemiological and causal inference needed for scientific research. Thiomersal allows millions of people worldwide to have access to life-saving vaccines and to date, no other safer and equally efficacious alternative has been identified for many vaccines.