Integrating Experimental (In Vitro and In Vivo) Neurotoxicity Studies of Low-dose Thimerosal Relevant to Vaccines

Abstract

There is a need to interpret neurotoxic studies to help deal with uncertainties surrounding pregnant mothers, newborns and young children who must receive repeated doses of Thimerosal-containing vaccines (TCVs). This review integrates information derived from emerging experimental studies (in vitro and in vivo) of low-dose Thimerosal (sodium ethyl mercury thiosalicylate). Major databases (PubMed and Web-of-science) were searched for in vitro and in vivo experimental studies that addressed the effects of low-dose Thimerosal (or ethylmercury) on neural tissues and animal behaviour. Information extracted from studies indicates that: (a) activity of low doses of Thimerosal against isolated human and animal brain cells was found in all studies and is consistent with Hg neurotoxicity; (b) the neurotoxic effect of ethylmercury has not been studied with co-occurring adjuvant-Al in TCVs; (c) animal studies have shown that exposure to Thimerosal-Hg can lead to accumulation of inorganic Hg in brain, and that (d) doses relevant to TCV exposure possess the potential to affect human neuro-development. Thimerosal at concentrations relevant for infants' exposure (in vaccines) is toxic to cultured human-brain cells and to laboratory animals. The persisting use of TCV (in developing countries) is counterintuitive to global efforts to lower Hg exposure and to ban Hg in medical products; its continued use in TCV requires evaluation of a sufficiently nontoxic level of ethylmercury compatible with repeated exposure (co-occurring with adjuvant-Al) during early life.

Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts

“…A number of studies examined the potential of Al adjuvant-containing vaccines to elicit inflammation, attention deficit hyperactivity disorders, delays in speech or language development (Tomljenovic and Shaw 2011a, 2011b, 2012), neurodevelopmental delay (Dorea 2011, 2012a, 2012b) and impaired cognition (Couette et al 2009). These concerns were highlighted by Dorea and Marques (2010) who reported that infants receiving immunizations were given 225–1750 μg Al per injection.…”

Comparative study on methyl- and ethylmercury-induced toxicity in C6 glioma cells and the potential role of LAT-1 in mediating mercurial-thiol complexes uptake

“…In the early 1930s, ethylmercury thiosalicylate, known as thimerosal, was introduced as a preservative in many medicinal preparations and vaccines (Pless and Risher, 2000). Experimental studies indicate that animal exposure to thimerosal-Hg (which spontaneously generates EtHg and thiosalicylate in aqueous medium) can lead to accumulation of inorganic Hg in brain (for a review, see Dórea, 2011). Although it is known that thimerosal causes significant neurotoxicity in experimental ( in vitro and in vivo ) models, in vivo data indicate its shorter half-life compared with MeHg (Burbacher et al, 2005), which explains its lower neurotoxic potency.…”

Blood-Cerebrospinal Fluid Barrier

“…3 Exposure to MeHg occurs predominantly via the consumption of contaminated fish. 4 A further organic mercury compound of significant toxicological concern is thiomersal, which is used as a preservative in pharmaceutical products including vaccines 5 and releases ethylmercury (EtHg) in aqueous solution. 6 In vivo studies in the rat brain 7 and in vitro studies in bovine capillary endothelial cells 8 demonstrated that the MeHg-cysteine conjugate (MeHg-S-Cys) enters the capillary endothelium of the blood-brain barrier via neutral amino acid transporters.…”