New findings about Thimerosal Neurotoxicity

Thimerosal (also known as thiomersal) is a mercury-containing organic compound (an organomercurial). Since the 1930s, it has been widely used as a preservative in a number of biological and drug products, including many vaccines, to help prevent potentially life-threatening contamination with harmful microbes. Over the past several years, because of an increasing awareness of the theoretical potential for neurotoxicity of even low levels of organomercurials and because of the increased number of thimerosal containing vaccines that had been added to the infant immunization schedule, concerns about the use of thimerosal in vaccines and other products have been raised.

 

In 2001 Thimerosal has been removed from or reduced to trace amounts in all vaccines routinely recommended for children 6 years of age and younger, except inactivated influenza vaccine. However, Rho D immunoglobulin shots containing Thimerosal are still recommended to pregnant women, and many vaccines given to children in developing countries and vaccines for adults still contain Thimerosal. Before 2001, the largest human exposure in the US was in children under 18 months of age undergoing routine child-hood immunization schedules. At that time, a child may have received a cumulative dose of over 200 µg/kg in the first 18 months of life. Although the neurotoxicity of methyl mercury has been relatively well studied, limited information is available on the relative neuro-developmental toxicity of ethylmercury, the mercury metabolite of Thimerosal.

 

The authors first examined the level of Thimerosal that would cause toxic damage to cells. They found that the higher the concentration of Thimerosal the greater the number of cells that were killed, although the nerve cell response occurred with only a 3-hour exposure, whereas the other cell line required a 48-hour exposure demonstrating that nerve cells are more sensitive to Thimerosal toxicity. “In both cell lines, a progressive increase in cyto-toxicity (decrease in viability) was observed when Thimerosal dose was progressively doubled from 2.5 µmol/L to 5, 10, and 20 µmol/L. Viability was reduced more than 50% in both cell lines with exposure to 10 µmol/L Thimerosal and less than 10% of cells survived a dose of 20 µmol/L.” The authors note, “Thimerosal induces oxidative stress and apoptosis by activating mitochondrial cell death pathways.

 

The authors then pretreated cells with N-Acetylcysteine (NAC) before adding a dose of 15 µmol/L Thimerosal. They found that NAC “provided significant protection against cell death”. The authors conclude that, “numerous clinical studies have demonstrated the efficacy of NAC in increasing intracellular glutathione levels and reducing oxidative stress in humans. Since cytotoxicity with both ethyl- and methyl- mercury have been shown to be mediated by glutathione depletion, dietary supplements that increase intracellular glutathione could be envisioned as an effective intervention to reduce previous or anticipated exposure to mercury. This approach would be especially valuable in the elderly and in pregnant women receiving Rho D immunoglobulin shots, and individuals who regularly consume mercury-containing fish.”  

 

The original study:

S.J. James, William Slikker III, Stepan Melnyk, Elizabeth New, Marta Pogribna, Stefanie Jernigan, Thimerosal Neurotoxicity is Associated with Glutathione Depletion: Protection with Glutathione Precursors, NeuroToxicology, 26/1 (2005) 1-8. DOI: 10.1016/j.neuro.2004.07.012

Related Studies
 

Chung-Wen Huang and Shiuh-Jen Jiang, Speciation of mercury by reversed-phase liquid chromatography with inductively coupled plasma mass spectrometric detection, J. Anal. At. Spectrom.,  8/5 (1993) 681 - 686. DOI: 10.1039/JA9930800681

 

Link database: Toxicity of Organo-mercury compounds
Link database: Research projects related to organo-mercury compounds
Link database: All about thimerosal (thiomersal)

 

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