Thimerosal

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Thimerosal (sometimes spelled as thimerosol and thiomersal[1] (http://www.ncirs.usyd.edu.au/facts/f-thiomersal.html)) (trade name: Merthiolate) is an organometallic compound used commonly since the 1930s as a preservative in some vaccines, cosmetics, tattoo inks, eye drops, and contact lens solutions. Such use has become increasingly controversial in recent years, due to concerns about potential neurotoxic properties of the mercury containing compound.

Its chemical formula is C₉H₉HgNaO₂S. In the body it is metabolized to ethylmercury (C₂H₅Hg⁺) and thiosalicylate. Thimerosal has proven to be highly effective against bacterial contamination in multidose containers of vaccinations [2] (http://jama.ama-assn.org/cgi/content/full/282/22/2114-a). Thimerosal causes susceptible bacteria to autolyze (breakdown its own cells with self-produced enzymes) via an unknown mechanism.

Material Safety Data Sheet [3] (http://chemdat.merck.de/pls/pi03/web2.search_page2?text=thimerosal&lang=4) MSDS

Synonyms: ethyl-2-mercaptobenzoato(2-)-O,S--mercurate sodium, mercury((o-carboxyphenyl)thio)ethyl sodium salt, mercurothiolate, merzonin sodium, SET, sodium ethylmercuric thiosalicylate, sodium merthiolate, thimerosalate, thiomersalate, merfamin, merthiolate, merthiolate sodium, merzonin, nosemack, merseptyl, 2-mercaptobenzoic acid mercury complex, elcide 75, thiomersal, ethylmercurithiosalicylic acid sodium salt, various other systematic and non-syematic names

Use: drug, antiinfective agent, preservative in cosmetics.

Molecular formula: C9H9HgO2SNa

CAS No: 54-64-8

EC No:

Physical data

Appearance: white or slightly yellow powder Melting point: ca. 232 C (decomposes) Boiling point: Vapour density: Vapour pressure: Specific gravity: Flash point: Explosion limits: Autoignition temperature: Water solubility: moderate

Stability

Stable. May degrade in sunlight. Incompatible with strong acids, strong bases, strong oxidizing agents, iodine, heavy metal salts.

Toxicology

Poison. Experimental neoplastigen and teratogen. Harmful by inhalation and ingestion. May cause reproductive damage. May be harmful through skin contact. Typical OEL 0.05 mg/m3.

Toxicity data

ORL-RAT LD50 75 mg kg-1

SCU-RAT LD50 98 mg kg-1

UNR-RAT LD50 40 mg kg-1

IVN-MUS LD50 30 mg kg-1

ORL-MUS LD50 91 mg kg-1

IPR-MUS LD50 54 mg kg-1

IAL-CHD LDLO 60 mg kg-1/4w-i

Personal protection

Safety glasses, adequate ventilation.

Contents

1 Thimerosal controversy 1.1 Background for the controversy 1.2 State of the controversy 1.2.1 Mainstream research findings 1.2.2 Differing effects of ethylmercury in Thimerosal containing vaccines 1.3 Stakeholder advocacy 1.3.1 Bolus exposure concerns 2 See also 3 Further reading 4 External links 4.1 Thimerosal related news 4.2 Vaccine safety 4.3 Vaccine critiques 5 References

Thimerosal controversy

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Background for the controversy

Resistance to vaccination programs first arose in 1853 and has remained active since, though with little success. The thimerosal controversy is a recent addition to this long-standing debate.

In 1997, Frank Pallone, a United States congressional representative from New Jersey, included an amendment to an Food and Drug Administration (FDA) reauthorization bill requiring the agency to "compile a list of drugs and foods that contain intentionally introduced mercury compounds and … [to] provide a quantitative and qualitative analysis of the mercury compounds in the list…."

On December 14, 1998 and April 29, 1999, the FDA posted notice to vaccine manufacturers to supply information about the use of mercury in vaccines. From the early 1970's until today, the number of vaccines regularly received by children in the US before the age of four has risen from two or three to up to twenty-two. Through its Center for Biologics Evaluation and Research (CBER), the FDA studied the results and found regularly vaccinated young children were injected with up to 187.5 μg of ethylmercury by the time they were six months old.

When trying to assess whether this dosage was likely to cause damage, the CBER could not find guidelines for ethylmercury. Three federal agencies had published different safety guidelines on the common pollutant methylmercury. Without knowing whether ethylmercury was more or less toxic than methylmercury, they found the administered dosage exceeded the lowest guideline of those three published by the US agencies. All the guidelines had been set with a considerable margin of safety based on a study done on Iraqi children who had been exposed to methylmercury in utero. Vaccine exposures to ethylmercury are so-called bolus exposures; brief exposures to higher concentrations. Mercury exposure guidelines were often set based upon chronic exposures to lower doses over extended periods. The precise health impact of bolus versus chronic exposure is not known for ethylmercury.

From 1998 to 1999, the European Medicines Agency undertook a study of the effects of thimerosal, concluding "although there is no new evidence of harm caused by the level of exposure, it would be prudent to promote the general use of vaccines without thimerosal within the shortest possible time frame."

In June of 1999, Dr. Neal A. Halsey, the director of the Johns Hopkins University Institute for Vaccine Safety, and a vocal defender of vaccination policy, was apprised of the results of the CBER study and enlisted Dr. Walter Orenstein, the director of the Centers for Disease Control's (CDC) National Immunization Program to give advice. Along with leaders of the American Academy of Pediatrics (AAP), the group advised a cautious stance by informing physicians about the findings. Negotiations within the AAP resulted in a press release calling for a delay of Hepatitis B vaccines under certain circumstances.[4] (http://www.hepatitiscontrolreport.com/vol/www.aap.org/advocacy/releases/jointvacc.htm)

State of the controversy

Those who criticize the use of thimerosal in vaccines have sought to establish evidence of harm from the substance through several scientific inquries, all of which have been criticized by public health agencies, medical organizations, and pharmaceutical companies:

• Appeal to common sense: arguing that injecting an organic mercury compound straight into the tissue and bloodstream of small children has to be risky at best and most likely reckless [5] (http://www.generationrescue.org/pdf/bernard.pdf).

Appeal to common sense is not a valid argument and in this case the fallacy is exacerbated because most vaccines are delivered intramuscularly.

• In vitro tests to examine the effects of ethylmercury on living cells [6] (http://www.mothering.com/articles/growing_child/vaccines/toxic.html).

• In vivo test on lab animals to test for reactions [7] (http://www.nationalautismassociation.org/iom.php), [8] (http://www.generationrescue.org/pdf/miller.pdf).

• Mass data analysis of actual populations to discern patterns, ideally with a control group. This includes study of the incidence of autism in populations with varying use of thimerosal [9] (http://www.generationrescue.org/pdf/geier.pdf), [10] (http://www.washtimes.com/upi-breaking/20050526-025612-5956r.htm).

• Trend analysis following the gradual abolishment of thimerosal in vaccines, starting a few years ago.

Studies have shown that the autism diagnosis rate has increased in countries that have removed thimerosal from their vaccines [11] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12949291&dopt=Abstract)

• Proven cures. Parents and doctors report that autistic children who are treated for mercury poisoning recover.

Others have reported that they don't [12] (http://www.autism-watch.org/about/bio2.shtml) and there is a distinct lack of studies to support this claim.

Critics argue there there is compelling evidence ([13] (http://my.webmd.com/content/article/81/97024.htm) and [14] (http://www.jcca-online.org/client/cca/JCCA.nsf/objects/Volume+47-1-2/$file/Pages04-07.pdf), among others) thimerosal causes adverse effects, especially among certain vulnerable children, and may be a contributing factor for autism or other neurological disorders.

The majority of vaccine safety studies, widely embraced by medical authorities, have consistently discounted the potential harm from thimerosal containing vaccines (TCVs). Critics, in contrast, consistently question the integrity and validity of such studies, often pointing out alleged conflicts of interest among researchers and purported data manipulation. Critics have few conclusive studies to support their contentions. Studies by Mark Geier and his son David Geier are among the few available providing any substantive evidence for banning the use of thimerosal. However, one of their papers was alleged to be seriously defective by the AAP [15] (http://www.aap.org/profed/thimaut-may03.htm). The Geiers are accused of having their own conflicts of interest, as Mark Geier has been paid as an expert witness in litigation suits, [16] (http://www.immunizationinfo.org/assets/files/pdfs/geier_in_court_03-1009.pdf) and David Geier is the president of MedCon, a company which specialises in representing vaccine injury claimants in their attempts to obtain money from both the National Vaccine Injury Compensation Program and through civil litigation.

It is a well established fact that mercury is a powerful neurotoxin; how the mercury in thimerosal is absorbed or metabolized in the human body is less well known. Thimerosal itself provides no direct benefit to the person receiving a vaccine. It does however protect the vaccine recipient by reducing the likelihood of microbial contamination of multi-dose vials. The use of single dose vials largely eliminates the need to use preservatives such as thimerosal.

The controversies over thimerosal have been slow to draw attention from the media. In June, 2005, a parent led group, Generation Rescue, placed a full page add in the New York Times in an effort to overcome a perceived lack of public debate over the use of thimerosal. In May of 2005, Rolling Stone and Salon.com published an article by Robert F. Kennedy, Jr. linking the CDC, FDA and Bill Frist to major drug companies, including GlaxoSmithKline, Merck, Wyeth, and Aventis Pasteur, which had continued using thimerosal in vaccines despite alleged possession of studies showing the evidence of harm critics contend it causes [17] (http://www.salon.com/news/feature/2005/06/16/thimerosal/). Kennedy's article described the 2004 NAS report as deeply flawed, and that it was launched explicitly to avoid release of a previously embargoed 2000 study by CDC epidemeologist Thomas Verstraeten that concluded that thimerserol appeared to be responsible for a dramatic increase in autism in children. These interpretations have been described as intellectually dishonest by defenders of extant vaccine policies [18] (http://skeptico.blogs.com/skeptico/2005/06/robert_f_kenned.html).

Kennedy, an attorney and son of a former US attorney general, also wrote, "More than 500,000 kids currently suffer from autism, and pediatricians diagnose more than 40,000 new cases every year. The disease was unknown until 1943, when it was identified and diagnosed among eleven children born in the months after thimerosal was first added to baby vaccines in 1931."

However cases of autism have been identifed from historical records as far back as the 18^th century

Rollingstone has since admited that some parts of the article were in error

Many claims in the article have come under attack from pro-thimerosal bloggers who have accused that article of quote mining, confusing correlation and causation, double standards in looking at "conflicts of interest (in reference to the Gries) and the "hidden hordes" fallacy [19] (http://oracknows.blogspot.com/2005/06/saloncom-flushes-its-credibility-down.html).

Senator Frist, according to a Huffington Post report [20] (http://www.huffingtonpost.com/thenewswire/archive/2005/06/abc-bosses-tell-abc-news-.html), tacked on the "Eli Lilly Protection Act" as a rider to the 2002 homeland security bill to shield drug companies from liability stemming from anticipated suits that may eventually total in the billions of dollars. The rider was repealed when Congress reconvened in 2003, after a public outcry, but the provisions of the rider are slated for reintroduction.

Mainstream research findings

In a 2004 report, the United States National Academy of Science's (NAS) Institute of Medicine (IOM) concluded "this body of evidence favors rejection of a causal relationship between thimerosal-containing vaccines (TCVs) and autism, and that hypotheses generated to date concerning a biological mechanism for such causality are theoretical only" [21] (http://www.fda.gov/cber/vaccine/thimerosal.htm). Before the IOM released its final version of the report[22] (http://www.iom.edu/report.asp?id=20155), one influential researcher, whose work found "no consistent significant association" [23] (http://pediatrics.aappublications.org/cgi/content/full/112/5/1039) between the preservative and neurodevelopmental outcomes, nevertheless wrote in a medical journal, "The bottom line is and has always been the same: an association between thimerosal and neurological outcomes could neither be confirmed nor refuted, and therefore, more study is required" [24] (http://pediatrics.aappublications.org/cgi/content/full/113/4/932). The research is still intensely debated [25] (http://pediatrics.aappublications.org/cgi/eletters/112/5/1039).

The US National Institute of Allergy and Infectious Diseases (NIAID) states, "Not much is known about the effects of thimerosal exposure on humans and how this compares to methylmercury exposure. The only known side-effects of receiving low doses of thimerosal in vaccines have been minor reactions such as redness and swelling at the injection site" [26] (http://www.niaid.nih.gov/factsheets/thimerosal.htm).

Differing effects of ethylmercury in Thimerosal containing vaccines

The latest controversy surrounds a newly-released, NIH-funded primate study [27] (http://ehp.niehs.nih.gov/docs/2005/7712/abstract.html), [28] (http://ehp.niehs.nih.gov/press/042105.html), conducted by Dr. Thomas Burbacher [29] (http://depts.washington.edu/chdd/MRDDRC/researchaffiliates/burbacher.html), an associate professor of environmental health and the director of the primate research center at the University of Washington. In his study, the effects of injected ethylmercury were compared with those of orally administered methylmercury in order to ascertain whether methylmercury provided a suitable reference for assessing the effects of ethylmercury found in thimerosal. The study revealed significant differences between methyl- and ethylmercury metabolism.

The injected ethylmercury cleared from the bloodstream much more rapidly than ingested methylmercury. However, the study also found that a larger fraction of the ethylmercury that remained in the primates' brains was converted to potentially more harmful inorganic compounds. Burbacher did not draw conclusions regarding the relative toxicity of ethylmercury versus methylmercury, but did warn that methylmercury is likely not a suitable reference for evaluating ethylmercury toxicity. In an interview, Burbacher commented

"The bottom line is that trying to assess the effects of a compound with very little or no data is not a good thing to do. ... Unfortunately, we started doing studies on this compound way too late. Basic information like this should've been available decades ago."[30] (http://www.insidebayarea.com/dailyreview/localnews/ci_2679632)

Stakeholder advocacy

Autism advocacy groups (including Safe Minds, [31] (http://www.safeminds.org/pressroom/press_releases/2005-04-21-Burbacher-Vaccine-Mercury-Trapped-Brain.pdf)) and United States Congressman Dave Weldon,[32] (http://weldon.house.gov/News/DocumentSingle.aspx?DocumentID=7902) point out thimerosal was previously injected into children without sufficient understanding of its effects.

Public concerns about possible thimerosal toxicity have led to the production of many thimerosal-free vaccines as a precautionary measure to ensure vaccination is not rejected out of fear. In terms similar to the NIAID, the United States Centers for Disease Control and Prevention (CDC) states: "The level of mercury exposure from vaccines is low. There is no evidence to suggest that thimerosal in vaccines causes any health problems in children and adults other than minor reactions like swelling at the injection site."[33] (http://www.cdc.gov/nip/vacsafe/concerns/thimerosal/thimerosal-vacs-facts.htm) It further states: "All routinely recommended licensed vaccines that are currently being manufactured for children in the U.S. (except some influenza (flu) vaccine and Td (tetanus-diphtheria) vaccines) contain no thimerosal or only trace amounts."

Bolus exposure concerns

In the US, intermittent bolus exposure to ethylmercury from thimerosal containing vaccines often began at birth. Bolus exposures may have peaked in the US toward the end of the 20th century, or as recently as 2003, according to research published by Mark Geier. In the early 1970's, US children were receiving only two or three vaccines before age four, but today that number has risen to approximately 22 vaccines, a seven fold increase. [34] (http://bmj.bmjjournals.com/cgi/eletters/330/7500/1154#106916)

TCV use outside the USA of thimerosal in vaccines continues in a lessening number of countries, the use of thimerosal as a vaccine preservative having been banned in a growing number of countries, including Japan and Denmark.

See also

• Autism
• Autism epidemic
• Bernard Rimland
• Controversies in autism
• David Kirby
• Generation Rescue
• Iatrogenesis
• Metallothionein
• Safe Minds
• Vaccine controversy

Further reading

• David Kirby, Evidence of Harm - Mercury in Vaccines and the Autism Epidemic: A Medical Controversy. 2005. see the Kirby link for links to reviews.

External links

Thimerosal related news

• News-Leader.com (http://springfield.news-leader.com/news/today/20050512-Senatevotestoli.html) - Missouri: 'Senate votes to limit mercury in childhood vaccine', James Goodwin, Springfield News-Leader (May 12, 2005)
• Science Daily (http://www.sciencedaily.com/releases/2004/05/040519064239.htm) - 'Vaccines Are Not Associated With Autism, Report Says' (May 19, 2004)
• "Deadly immunity" (http://www.salon.com/news/feature/2005/06/16/thimerosal/index_np.html) recent article on Salon, in the anti-thimerosal camp. (June 16, 2005) One place it is being critized is in this Slashdot discussion. (http://science.slashdot.org/science/05/06/21/0433248.shtml?tid=191&tid=14)

Vaccine safety

• FDA.gov (http://www.fda.gov/cber/vaccine/thimerosal.htm) - "Thimerosal in Vaccines", US Food and Drug Administration
• FDA.gov (http://www.fda.gov/cber/blood/mercplasma.htm) - "Mercury in Plasma-Derived Products", US Food and Drug Adminstration
• CDC.gov (http://www.cdc.gov/nip/vacsafe/concerns/thimerosal/default.htm) - "Mercury and Vaccines", US Centers for Disease Control
• Merck.de (http://chemdat.merck.de/pls/pi03/web2.search_page2?text=817043&lang=4) - 'Thimerosal USP' (manufacturer's product info)
• NoMercury.org (http://nomercury.org/science/documents/LATimes-Merck_Memo_2-8-05.pdf) - Memo from Merck regarding thimerosal's use in vaccines
• QuackWatch.org (http://www.quackwatch.org/03HealthPromotion/immu/thimerosal.html) - Misconceptions about Immunization: 'Misconception #11, Thimerosal Causes Autism: Chelation Therapy Can Cure It'
• SpikedOnline.com (http://www.spiked-online.com/Articles/00000006DDBF.htm) - 'Immune to the facts: Is the UK media to blame for the anti-MMR scare?', Dr. Michael Fitzpatrick (March 23, 2003)
• VaccineSafety.edu (http://www.vaccinesafety.edu/Testimony-O99.htm) - 'In Vitro studies of pure thimerosal and vaccines with and without thimerosal added as a preservative: Comparison to Hg(II) toxicity', Testimony before the House Committe on Government Reform, Boyd E. Haley, (April 9, 2001)
• OpinionJournal.com (http://www.opinionjournal.com/editorial/feature.html?id=110004700) - 'Autism and vaccines: Activists wage a nasty campaign to silence scientists', editorial, Wall Street Journal (February 16, 2004)

Vaccine critiques

• IOM.edu (http://www.iom.edu/Object.File/Master/19/029/0.pdf) - Statement of Rep. Dave Weldon, M.D., Member of Congress, before the US Institute of Medicine, strongly suggesting a link between thimerosol and autism (February 9, 2004)
• MumsNet.com (http://www.mumsnet.com/bigissues/vaccinations.html) - 'Are the CDC, the FDA, and other health agencies covering up evidence that a mercury preservative in children's vaccines caused a rise in autism?', Andrea Rock (March/April 2004)
• NoMercury.org (http://www.nomercury.org/) - 'Helping to make our Nation mercury-free...state by state'
• Weldon.House.gov (pdf) (http://weldon.house.gov/UploadedFiles/RepWeldonMDonIOM.pdf) - Speech to Congress by Rep. Dave Weldon, M.D., on autism epidemic, claiming IOM report flawed (June 18, 2004)

References

• AAPPublications.org (http://pediatrics.aappublications.org/cgi/content/full/112/6/1394) - 'Do Vaccines Contain Harmful Preservatives, Adjuvants, Additives, or Residuals?', Paul A. Offit, MD, Rita K. Jew, PharmD, Pediatrics, Vol 112, No 6, pp. 1394-1397, December, 2003
• AAPPublications.org (http://pediatrics.aappublications.org/cgi/content/full/107/5/1147) - 'An Assessment of Thimerosal Use in Childhood Vaccines', Leslie K. Ball, MD, Robert Ball, MD, MPH, and R. Douglas Pratt, MD, MPH, Pediatrics Vol 107, No 5, May 2001, pp. 1147-1154
• AAPPublications.org (http://pediatrics.aappublications.org/cgi/content/abstract/112/3/604) - 'Thimerosal and the Occurrence of Autism: Negative Ecological Evidence From Danish Population-Based Data', Kreesten M. Madsen, MD, Marlene B. Lauritsen, MD, Carsten B. Pedersen, Msc, Poul Thorsen, MD, PhD, Anne-Marie Plesner, MD, PhD, Peter H. Andersen, MD and Preben B. Mortensen, MD, DMSc, Pediatrics Vol 112, No 3, September 2003, pp. 604-606
• AAPPublications.org (http://pediatrics.aappublications.org/cgi/content/full/112/5/1039) - 'Safety of Thimerosal-Containing Vaccines: A Two-Phased Study of Computerized Health Maintenance Organization Databases', Thomas Verstraeten, Robert L Davis et al, Pediatrics Vol 112, No 5, November 2003, pp 1039-1048
• AAPPublications.org (http://pediatrics.aappublications.org/cgi/content/full/113/4/932) - 'Thimerosal, the Centers for Disease Control and Prevention, and GlaxoSmithKline', Thomas Verstraeten, Pediatrics, Vol 113 No 4, April 2004, pp. 932.
• JFPOnline.com (http://www.jfponline.com/content/2000/08/jfp_0800_07310.asp) - 'Reconnoitering the Antivaccination Web Sites: News From the Front', Laeth Nasir, MBBS, Journal of Family Practice (October, 2003)
• JPandS.org (http://www.jpands.org/vol8no1/geier.pdf) - 'Thimerosal in Childhood Vaccines, Neurodevelopment Disorders and Heart Disease in the United States' Mark and David Geier, Journal of American Physicians and Surgeons, Vol 8, No 1, Spring, 2003nl:Thimerosal