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.

Full report of GACVS meeting of 6-7 June 2012, published in the WHO Weekly Epidemiological Record on 27 July 2012

Extract from report of GACVS meeting of 18-19 June 2008, published in the WHO Weekly Epidemiological Record on 8 August 2008

The GACVS considered the presentation of a recently published pharmacokinetic study of mercury in premature and low-birth-weight infants who received a birth dose of hepatitis B vaccine containing thiomersal.⁶ The results suggest that exposure to thiomersal-containing vaccines does not result in accumulation of mercury in blood and that the blood half-life (2.9–4.1 days) of intramuscular ethyl mercury from thiomersal in vaccines in infants is substantially shorter than that of oral methyl mercury in adults. The study concluded that exposure guidelines based on oral methyl mercury may not be appropriate for use in assessing the risk of thiomersal in vaccines at dosages consistent with standard vaccination regimens.

The GACVS also considered the results of a study conducted in Italy that examined the neuropsychological performance 10 years after immunization in infancy with thiomersal-containing vaccines (Tozzi A., unpublished data, 2008). According to the results, higher thiomersal exposure through vaccines administered in the first year of life was significantly associated with lower scores on 2 neuropsychological outcomes (motor function, measured using the finger-tapping test, and language, measured using the Boston naming test). The differences in mean scores were very small, detected only in girls, of doubtful clinical relevance, and not consistent with results from other studies of ethyl mercury. The observed associations may reflect the effect of chance.

On the basis of the presented data, GACVS remains of the view that there is no evidence supporting any change in WHO’s recommendations for thiomersal-containing vaccines and the vaccination of low-birth-weight infants where indicated.

⁶Pichichero ME et al. Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines. Pediatrics 2008, 121:e208–e214 (http://pediatrics.aappublications.org/cgi/reprint/121/2/e208.pdf).

Full report of GACVS meeting of 18-19 June 2008, published in the WHO Weekly Epidemiological Record on 8 August 2008

Extract from report of GACVS meeting of 9-10 June 2005, published in the WHO Weekly Epidemiological Record on 15 July 2005

The Committee considered a recently published pharmacokinetic study of thiomersal (contains ethyl mercury) in macaque monkeys.⁴ The systemic disposition and distribution in the brain of total and inorganic mercury were compared in infant monkeys following administration of thiomersal-containing vaccines and those exposed to methyl mercury. Differences between the kinetics of ethyl mercury and methyl mercury were examined. The findings confirmed the view that methyl mercury is not suitable for risk assessment of thiomersal. Brain concentrations of total mercury were threefold lower with thiomersal, compared with methyl mercury, and the average ratio of brain–blood concentrations of mercury was slightly higher for thiomersal-exposed infant monkeys. However, differences in primate and human brain development and species differences in the pharmacokinetics of mercury and mercury-containing compounds limit extrapolation of the results in these experimental conditions to what might be expected in human infants.

GACVS was informed of 2 neurodevelopmental studies currently being conducted in the United States and Italy of children who had received thiomersal-containing vaccines during infancy according to the national immunization schedules. Data analysis is presently in progress and the Committee will consider the results when they are available.

Currently, GACVS remains of the view that there is no evidence supporting a causal association between neurobehavioural disorders and thiomersal-containing vaccines.

⁴Comparison of blood and brain mercury levels in infant monkeys exposed to methyl mercury or vaccines containing thiomersal. Environmental Health Perspectives, online 21 April 2005 (doi:10.1289/eph.7712; http://ehp.niehs.nih.gov/docs/2005/7712/abstract.html).

Full report of GACVS meeting of 9-10 June 2005, published in the WHO Weekly Epidemiological Record on 15 July 2005