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In vivo Quantification of the Transition of Brain Extracellular Mercury after Thimerosal Administration
(20.04.2020)
Researchers from Taiwan developed a method for the in-vivo determination of the transition of brain extracellular mercury after thimerosal administration.
Background:
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. Despite 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 7500a 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.
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T. Schwerdtle
,
Effects on and
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mercury species,
BMC Pharmacol. Toxicol., 17 (2016) 63.
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.
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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.
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.
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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
.
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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.
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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
.
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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
.
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, J. Appl. Toxicol., 27 (2007) 511–518.
DOI: 10.1002/jat.1272
.
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device for determination and speciation of mercury by AFS and HPLC-AFS
, J. Anal. At. Spectrom., 22 (2007) 330–334.
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.
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, Crit. Rev. Toxicol., 36 (2006) 609–662.
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.
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, Environ. Health Perspect., 113 (2005) 1015–1021.
DOI: 10.1289/ehp.7712
.
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, Toxicol. Lett., 154 (2004) 183–189.
DOI: 10.1016/j.toxlet.2004.07.014
.
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The three modern faces of mercury
, Environ. Health Perspect. 110 (2002) 11–23.
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.
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, Biochem. J., 367 (2002) 239–246.
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.
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, Pediatrics, 107 (2001) 1147–1154.
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.
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, N.K. Mottet, L.T. Friberg, S.B. Lind, J.S. Charleston, T.M. Burbacher,
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.
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Am. J. Physiol., 262 (1992) R761–R765.
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.
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DOI: 10.1007/bf00312571
.
Related information
US Food and Drug Administration, Thimerosal and vaccines
.
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
.
Committee for Medicinal Products for Human Use, CHMP position paper on thiomersal–Implementation of the warning statement relating to sensitisation.
Related EVISA Resources
Brief summary: Mercury Toxicity
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
July 2, 2018:
Thiomersal in influenza vaccine: more than just an adjuvant
December 18, 2017: Thimerosal and Autism: CDC Manipulation of Vaccine Data Reported in the Journal of American Physicians and Surgeons
November 12, 2017: Mercury and Autism: Is there a Link ?
February 15, 2017: Toxicity of organomercury compounds
May 5, 2014: Global policy on the use of mercury as a preservative in vaccine called discriminatory
September 12, 2013: Scientists reveal how organic mercury can interfer with vision
January 21, 2013: UNEP mercury treaty exempts vaccines for children
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
June 19, 2011: Committee for Socio-economic Analysis agrees on two draft opinions on restriction proposals for mercury compounds under REACH
last time modified: March 2, 2025
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