EVISA Print | Glossary on | Contact EVISA | Sitemap | Home   
 Advanced search
The establishment of EVISA is funded by the EU through the Fifth Framework Programme (G7RT- CT- 2002- 05112).

Supporters of EVISA includes:

In vivo Quantification of the Transition of Brain Extracellular Mercury after Thimerosal Administration


Monomethylmercury (MMHg) is recognized as one of the most potent neurotoxins. While the chemistry of ethylmercury (EtHg) is not fundamentally different from that of methylmercury, its toxicity has often been discussed as totally different. The ethylmercury moiety is part of thimerosal (TMHg), which is used as a preservative in vaccines to prevent fungal and bacterial growth since the 1930s. After injection into the body, the EtHg moiety is released from TMHg to the surrounding tissues and therefore should follow the same toxicological pathways as other ETHg absorbed into the body from other sources. While numerous studies exist, showing the strong toxic effects produced by EtMg, the use of TMHg in vaccines has not been associated with any clear connections with serious human neurodevelopmental disorders.

While the use of TMHg in vaccines in Europe and the US has been considerably reduced after 1999, especially for children and pregnant women, the worldwide use of TMHg-containing vaccines is still important. While the brain in general is protected against the inflow of many exotic toxic substances by the blood-brain barrier (BBB), mercurial substances can overcome the barrier and cause serious toxic effects. Therefore, the investigation of mercury concentrations between blood and extracellular fluid (ECF) of the brain following the administration of TMHg is important for improving the knowledge of the neurotoxicity of TMHg.

The new study:
Researchers from Taiwan now developed a method for the in-vivo determination of the transition of brain extracellular mercury after thimerosal administration. In order to cope with the extremely low available sample volume, the low Hg concentration and the high salinity of the sample matrix, a microfluidic approach was developed based on microdialysis for sampling and photocatalyst-assisted vaporization for sample introduction to the ICP-MS. Under optimal operation conditions, the developed analytical system provided limits of detection (based on 3s) of 2.7 and 1.7 ng/L for MMHg and TMHg.   

Using this system, the transport of mercury to the brain of adult male Sprague-Dawley rats was studied after intraperitoneal administration of MMHg or TMHg in saline solution with a time resolution of about 13 min. The system was able to monitor the  rapid change of mercurial concentration appearing in ECF. The results of the animal experiments with the two organomercurials indicated extremely similar transition trends. Thus the researchers concluded, that the BBB penetration behaviour of TMHg is very similar to that of MMHg although the transport mechanism of TMHg remains unclear.    

The original publication:

Cheng-Hsing Lin, Cheng-Kuan Su, Yuh-Chang Sun, Development of Online Microdialysis–Microfluidic-Based Photocatalyst-Assisted Vaporization Device–Inductively Coupled Plasma-Mass Spectrometry Hyphenated Analytical System for in vivo Quantification of the Transition of Brain Extracellular Mercury after Thimerosal Administration, Microchem. J., 154 (2020) 104569. DOI: 10.1016/j.microc.2019.104569

Used techniques and instrumentation:

Agilent Technologies Inc.- Agilent 7500 a ICP-MS

Related studies

Janet K. Kern, David A. Geier, Kristin G. Homme, Mark R. Geier, Examining the evidence that ethylmercury crosses the blood-brain barrier, Environ. Toxicol.  Pharmacol., 74 (2020) 103312. DOI: 10.1016/j.etap.2019.103312

T.-T. Shih, J.-Y. Chen, Y.-T. Luo, C.-H. Lin, Y.-H. Liu, Y.-A. Su, P.-C. Chao, Y.-C. Sun, Development of a titanium dioxide-assisted preconcentration/on-site vapor-generation chip hyphenated with inductively coupled plasma-mass spectrometry for online determination of mercuric ions in urine samples, Anal. Chim. Acta., 1063 (2019) 82–90. DOI: 10.1016/j.aca.2019.02.035.

Philipp Strohmidel, Michael Sperling, Uwe Karst, Investigations on the binding of ethylmercury from thiomersal to proteins in influenza vaccines, J. Trace Elem. Med. Biol., 50 (2018) 100–104. DOI: 10.1016/j.jtemb.2018.06.011
José G. Dórea, Low-dose Thimerosal (ethyl-mercury) is still used in infants` vaccines: Should we be concerned with this form of exposure?, J. Trace Elem. Med. Biol., 49 (2018) 134–139. DOI: 10.1016/j.jtemb.2018.05.010

P. Hu, X. Wang, L. Yang, H. Yang, Y. Tang, H. Luo, X. Xiong, X. Jiang, K. Huang, Speciation of mercury by hydride generation ultraviolet atomization-atomic fluorescence spectrometry without chromatographic separation, Microchem J., 143 (2018) 228–233.DOI: 10.1016/j.microc.2018.08.013.

H. Lohren, J. Bornhorst, R. Fitkau, G. Pohl, H.-J. Galla, T. Schwerdtle, Effects on and transfer across the blood-brain barrier in vitro—Comparison of organic and inorganic mercury species, BMC Pharmacol. Toxicol., 17 (2016) 63. DOI: 10.1186/s40360-016-0106-5.

H. Li, Z. Xu, L. Yang, Q. Wang, Determination and speciation of Hg using HPLC-AFS by atomization of this metal on a UV/nano-ZrO2/HCOOH photocatalytic reduction unit, J. Anal. At. Spectrom., 30 (2015) 916–921. DOI: 10.1039/c4ja00455h.

W.A. Orenstein, J.A. Paulson, M.T. Brady, L.Z. Cooper, K. Seib, Global vaccination recommendations and thimerosal, Pediatrics, 131 (2013) 149–151.
DOI: 10.1542/peds.2012-1760.

K. Huang, K. Xu, X. Hou, Y. Jia, C. Zheng, L. Yang, UV-induced atomization of gaseous mercury hydrides for atomic fluorescence spectrometric detection of inorganic and organic mercury after high performance liquid chromatographic separation, J. Anal. At. Spectrom., 28 (2013) 510–515. DOI: 10.1039/C3JA30363B.

M. Xu, L. Yang, Q. Wang, Chemical interactions of mercury species and some transition and noble metals towards metallothionein (Zn7MT-2) evaluated using SEC/ICP-MS, RPHPLC/ESI-MS and MALDI-TOF-MS, Metallomics, 5 (2013) 855–860. DOI: 10.1039/c3mt00016h.

C.-K. Su, Y.-C. Sun, S.-F. Tzeng, C.-S. Yang, C.-Y. Wang, M.-H. Yang, In vivo monitoring of the transfer kinetics of trace elements in animal brains with hyphenated inductively coupled plasma mass spectrometry techniques, Mass Spectrom. Rev., 29 (2010) 392–424. DOI: 10.1002/mas.20240.

T.-T. Shih, W.-Y. Chen, Y.-C. Sun, Open-channel chip-based solid-phase extraction combined with inductively coupled plasma-mass spectrometry for online determination of trace elements in volume-limited saline samples, J. Chromatogr. A., 1218 (2011) 2342–2348. DOI: 10.1016/j.chroma.2011.02.037.

K.–j. Chen, I-h. Hsu, Y.-c. Sun, Determination of methylmercury and inorganic mercury by coupling short-column ion chromatographic separation, on-line photocatalyst-assisted vapor generation, and inductively coupled plasma mass spectrometry, J. Chromatogr. A., 1216 (2009) 8933–8938. DOI: 10.1016/j.chroma.2009.10.061.

M.E. Pichichero, A. Gentile, N. Giglio, M.M. Alonso, M.V.F. Mentaberri, G. Zareba, T. Clarkson, C. Gotelli, M. Gotelli, L. Yan, J. Treanor, Mercury levels in premature and low birth weight newborn infants after receipt of thimerosal-containing vaccines, J. Pediatr., 155 (2009) 495–499.e2. DOI: 10.1016/j.jpeds.2009.04.011.

G. Zareba, E. Cernichiari, R. Hojo, S.M. Nitt, B. Weiss, M.M. Mumtaz, D.E. Jones, T.W. Clarkson, Thimerosal distribution and metabolism in neonatal mice: comparison with methyl mercury, J. Appl. Toxicol., 27 (2007) 511–518. DOI: 10.1002/jat.1272.

Y. Yin, J. Liang, L. Yang, Q. Wang, Vapour generation at a UV/TiO2 photocatalysis reaction device for determination and speciation of mercury by AFS and HPLC-AFS, J. Anal. At. Spectrom., 22 (2007) 330–334. DOI: 10.1039/b614555h.

T.W. Clarkson, L. Magos, The toxicology of mercury and its chemical compounds, Crit. Rev. Toxicol., 36 (2006) 609–662. DOI: 10.1080/10408440600845619.

T.M. Burbacher, D.D. Shen, N. Liberato, K.S. Grant, E. Cernichiari, T. Clarkson, Comparison of blood and brain mercury levels in infant monkeys exposed to methylmercury or vaccines containing thimerosal, Environ. Health Perspect., 113 (2005) 1015–1021. DOI: 10.1289/ehp.7712.

G.J. Harry, M.W. Harris, L.T. Burka, Mercury concentrations in brain and kidney following ethylmercury, methylmercury and thimerosal administration to neonatal mice, Toxicol. Lett., 154 (2004) 183–189. DOI: 10.1016/j.toxlet.2004.07.014.

T.W. Clarkson, The three modern faces of mercury, Environ. Health Perspect. 110 (2002) 11–23. DOI: 10.1289/ehp.02110s111.

T.A. Simmons-Willis, A.S. Koh, T.W. Clarkson, N. Ballatori, Transport of a neurotoxicant by molecular mimicry: the methylmercury–L-cysteine complex is a substrate for human Ltype large neutral amino acid transporter (LAT) 1 and LAT2, Biochem. J., 367 (2002) 239–246. DOI: 10.1042/BJ20020841.

L.K. Ball, R. Ball, R.D. Pratt, An assessment of thimerosal use in childhood vaccines, Pediatrics, 107 (2001) 1147–1154. DOI: 10.1542/peds.107.5.1147.

M.E. Vahter, N.K. Mottet, L.T. Friberg, S.B. Lind, J.S. Charleston, T.M. Burbacher, Demethylation of methyl mercury in different brain sites of Macaca fascicularis monkeys during long-term subclinical methyl mercury exposure, Toxicol. Appl. Pharmacol., 134 (1995) 273–284. DOI: 10.1006/taap.1995.1193.

M. Vahter, N.K. Mottet, L. Friberg, B. Lind, D.D. Shen, T. Burbacher, Speciation of mercury in the primate blood and brain following long-term exposure to methyl mercury, Toxicol. Appl. Pharmacol., 124 (1994) 221–229. DOI: 10.1006/taap.1994.1026

L.E. Kerper, N. Ballatori, T.W. Clarkson, Methylmercury transport across the blood-brain barrier by an amino acid carrier, Am. J. Physiol., 262 (1992) R761–R765.DOI: 10.1152/ajpregu.1992.262.5.R761.

U. Ulfvarson, Distribution and excretion of some mercury compounds after long term exposure, Int. Arch. Gewerbepath. Gewerbehyg., 19 (1962) 412–422.DOI: 10.1007/bf00312571.

Related information

World Health Organization, Thiomersal.
European Medicines Agency, EMEA public statement on thiomersal in vaccines for human use–Recent evidence supports safety of thiomersal-containing vaccines.

 Related EVISA Resources

Brief summary: ICP-MS - A versatile detection system for speciation analysis
Link database: Toxicity of Organo-mercury compounds
Link database: Research projects related to organo-mercury compounds

Related EVISA News

January 14, 2013: United Nations Global Mercury Treaty: Fifth and final session
December 18, 2012: Pediatricians Argue to Keep Thimerosal in Some Vaccines
December 9, 2012: Mercury in fish more dangerous than previously believed; Scientists urge for effective treaty ahead of UN talks
October 12, 2012: Prenatal mercury intake linked to ADHD
July 15, 2012: World Health Organization Fails In Its Effort To Defend Mercury In Vaccines Before United Nations
October 28, 2011: WHO worries mercury treaty could affect costs and availability of vaccines
August 8, 2011: UNEP Global Mercury Treaty May Include Ban on Mercury in Medicine

last time modified: April 20, 2020


Imprint     Disclaimer

© 2003 - 2010 by European Virtual Institute for Speciation Analysis ( EVISA )