HAS THE USE OF THIMEROSOL
VACCINATIONS CAUSED AUTISM?
In recent years, it has been suggested that thimerosal
in some childhood vaccines could contribute to, or cause, a range
of neurodevelopmental disorders in children, most notably Autism,
syndrome and related Pervasive Developmental Disorders (PDDs),
or other cognitive disorders, including Attention
Deficit Hyperactivity Disorder (ADHD).
Critics of thimerosal containing vaccines (TCVs)
argue that the ethylmercury-based preservative may cause serious
side effects, especially when administered to young children who
have relatively undeveloped immune and neurological systems that
may be seriously affected.
It should be noted that thimerosal is not used
in all vaccinations, and its use has decreased since the debate
began. There are very few people who would claim children should
not be vaccinated as this will lead to Autism or Asperger's syndrome.
It is the use of thimerosal as a preservative in some vaccinations
that is a suggested cause of Pervasive Developmental Disorders.
Motivating factors for and against
There is concern on both sides of the debate in
regards to motivating factors. Those who denounce thimerosal suspect
that government agencies and pharmaceutical companies are denying
a connection for fear of financial liability and the creation of
mistrust in vaccinations. Those who deny a connection between thimerosal
and neurological disorders have charged thimerosal's critics as
being medically and scientifically unqualified, emotionally distraught,
or interested in pursuing litigation.
Thimerosal in decline despite lack of scientific
In July 1999, following a review of mercury-containing
food and drugs, the Centers for Disease Control (CDC) and the American
Academy of Pediatrics (AAP) asked vaccine makers to remove thiomersal
from vaccines as quickly as possible, and it has been phased out
of most U.S. and European vaccines. The precautionary principle
assumes that there is no harm in exercising caution even if it later
turns out to be unwarranted, but this 1999 action sparked confusion
and controversy that has diverted attention and resources away from
other efforts to find the causes of autism.
Thousands of lawsuits have been filed in the U.S.
to seek damages from alleged toxicity from vaccines, including those
purportedly from thiomersal preservatives. The scientific consensus—including
scientific and medical professional bodies and governmental agencies
such as the Food and Drug Administration, the Centers for Disease
Control and Prevention, and the World Health Organization—rejects
the hypothesis that exposure to thiomersal causes or contributes
to autism or other neurological disorders.
Background of controversy
After the FDA Modernization Act of 1997 mandated
a review and risk assessment of all mercury-containing food and
drugs in the US, vaccine manufacturers responded to FDA requests
to provide detailed information about the thimerosal content of
their preparations in December 1998 and April 1999. Upon conclusion
of this review, the FDA, in conjunction with the other members of
the US Public Health Service (USPHS), the National Institutes of
Health (NIH), CDC and Health Resources and Services Administration
(HRSA) in a joint statement with the American Academy of Pediatrics
"Our review revealed no evidence of harm
caused by doses of thimerosal found in vaccines, except for local
hypersensitivity reactions. At the time of our review, vaccines
containing thimerosal as a preservative could expose infants to
cumulative mercury at levels that exceed EPA recommendations during
the first 6 months of life. The clinical significance of this conclusion
is not currently known; EPA guidelines contain as much as a 10-fold
safety factor and such guidelines are meant to be starting points
for the evaluation of mercury exposure. However, reducing exposure
to thimerosal from vaccines is merited given the goal of reducing
human exposure to mercury from all sources, the feasibility of removing
thimerosal as a vaccine preservative, and the desirability of ensuring
public confidence in the safety of vaccines."
The FDA noted that while the vaccination schedule
at that time might have exceeded EPA standards for mercury exposure
during the first 6 months of life, it did not exceed those of the
FDA, Agency for Toxic Substances and Disease Registry (ATSDR), or
WHO. The FDA also noted some difficulty interpreting toxicity of
the ethylmercury in thiomersal because guidelines for mercury toxicity
were based primarily on studies of methylmercury. Despite the lack
of convincing evidence of toxicity of thiomersal, the USPHS and
AAP determined that thiomersal should be removed from vaccines as
a purely preventative measure and to increase public confidence
Due to continued public concern, the Centers for
Disease Control and the National Institutes of Health (NIH) asked
the National Academy of Science's (NAS) Institute of Medicine (IOM)
to establish an independent expert committee to review hypotheses
about existing and emerging immunization safety concerns. In 2001
the committee reported:
"The committee concludes that although the
hypothesis that exposure to thimerosal-containing vaccines could
be associated with neurodevelopmental disorders is not established
and rests on indirect and incomplete information, primarily from
analogies with methylmercury and levels of maximum mercury exposure
from vaccines given in children, the hypothesis is biologically
plausible. The committee also concludes that the evidence is inadequate
to accept or reject a causal relationship between thimerosal exposures
from childhood vaccines and the neurodevelopmental disorders of
autism, ADHD, and speech or language delay."
Social and political background
The FDA actions prompted autism advocates to consider
the possibility of thiomersal as a cause of autism. The indirect
evidence included analogy with neurotoxic effects of mercury compounds,
extrapolation from laboratory and animal studies, and comparisons
between trends in vaccination and autism cases.
This concept also gained support in the political
sphere, with Rep. Dan Burton and Rep. David Weldon openly supporting
this movement as well. A number of hearings were held in the Subcommittee
on Human Rights and Wellness, Committee on Government Reform, chaired
by Rep. Burton, on the topic of autism and vaccines. His staff concluded:
"Thimerosal used as a preservative in vaccines
in [sic] likely related to the autism
epidemic. This epidemic in all probability may have been prevented
or curtailed had the FDA not been asleep at the switch regarding
the lack of safety data regarding injected thimerosal and the sharp
rise of infant exposure to this known neurotoxin. Our public health
agencies’ failure to act is indicative of institutional malfeasance
for self-protection and misplaced protectionism of the pharmaceutical
Rationale for concern
Supporters of a link between thiomersal and autism
cite several lines of reasoning for their concerns, including:
Appeal for caution: precise thresholds for ethylmercury
toxicity have not been fully studied, and methylmercury is a poor
surrogate for studying the toxicity of thiomersal.
In vitro tests: cultured cells in laboratory show adverse effects
when exposed to ethylmercury.
An in vivo study reported in 2004 that autoimmune disease-sensitive
mice exposed to thiomersal had growth delay, reduced locomotion,
exaggerated response to new stimuli, and uncommon neuronal structure
in some brain areas. The exposure attempted to replicate the one-year
schedule for U.S. infants in 2001, adjusted for weight and age.
However, a similar 2007 study found no pervasive developmental neurotoxicity
in the same mouse strain. Also, while the intervals between
vaccination in human infants assure nearly complete clearance of
the organic species from the brain and blood, significant accumulation
would be expected for the accelerated schedule in the mouse pups.
Unscientific reports that autism is rarer in the Amish community
and other non-vaccinated groups. The reports are undercut by the
fact that Amish genes may differ from those in the general community,
that people in the Amish community have low exposures to many other
potential hazards (for example, pesticides and plastics) and that
increasingly, the Amish do receive at least some vaccinations.
Epidemiologic data: epidemiologic studies (all by Mark Geier) examined
population level correlation between thiomersal and autism.
Concern that mercury might have synergistic effects with other metals
Despite the 1999 recommendation by the USPSH and AAP, some vaccines
continue to contain non-trace amounts of thiomersal, mainly in vaccines
targeted against influenza and tetanus. Other products that
may contain thimerosal include products derived from blood plasma
such as Rho(D) Immune Globulin, pit viper antivenin and coral snake
antivenin, as well as black widow spider antivenin.
Scientific consensus on controversy
The scientific consensus is reflected in another
committee report commissioned by the CDC by the Institute of Medicine
that follows up on the initial 2001 report. Since the 2001 report,
the IOM committee took into account new data that had been published
in the interim, including a number of large scale epidemiologic
studies focusing on the relationship between thiomersal and autism
in a number of countries including the US, Sweden, Denmark, and
The committee noted, in response to those who
cite in vitro or animal models as evidence for the link between
autism and thiomersal:
"However, the experiments showing effects
of thimerosal on biochemical pathways in cell culture systems and
showing abnormalities in the immune system or metal metabolism in
people with autism are provocative; the autism research community
should consider the appropriate composition of the autism research
portfolio with some of these new findings in mind. However, these
experiments do not provide evidence of a relationship between vaccines
or thimerosal and autism. In the absence of experimental or human
evidence that vaccination (either the MMR vaccine or the preservative
thimerosal) affects metabolic, developmental, immune, or other physiological
or molecular mechanisms that are causally related to the development
of autism, the committee concludes that the hypotheses generated
to date are theoretical only."
Based on an exhaustive review of the scientific
literature, the committee concludes:
"Thus, based on this body of evidence, the
committee concludes that the evidence favors rejection of a causal
relationship between thimerosal-containing vaccines and autism."
[bold in original]
This committee felt so strongly about this conclusion
that they state:
"The committee concludes that much more research
must be conducted on autism. However, research should be directed
towards those lines of inquiry most supported by the current state
of knowledge. The vaccine hypotheses are not currently supported
by the evidence."
Three large-scale controlled observational studies
have been reported on this issue; none have found an association
between thiomersal-containing vaccines (TCVs) and autism. A
study from Denmark noted no decrease in autism rates despite cessation
of TCVs and a UK study found that TCVs actually had a protective
effect with respect to autism. Because the Danish and UK studies
involved only diphtheria-tetanus-pertussis (DTP) or diphtheria-tetanus
(DT) vaccines, they are less relevant for the higher thiomersal
exposure levels that occurred in the U.S. For the U.S., a study
based on the Vaccine Safety Datalink found no association between
TCVs and autism. Some smaller studies have also found no association
between TCVs and autism and a study found no association
between thimerosal and the neurological signs of autism. Another
smaller study also found a protective effect: it reported a significantly
lower prevalence of Autism Spectrum Disorders among children exposed
to thimerosal (5.95 per 1,000 versus 8.27 per 1,000).
The research of Mark Geier, the main source of
epidemiologic data used by supporters of a link between thiomersal
and autism, has received considerable criticism, including charges
of not presenting methods and statistical analyses to others for
verification, improperly analyzing data taken from Vaccine Adverse
Event Reporting System, as well as either mislabelling or
confusing fundamental statistical terms in his papers.
Further evidence of the position of the scientific
consensus includes the rejection of a causal link between thimerosal
and autism by the main scientific and medical professional bodies
including the American Medical Association, the American Academy
of Pediatrics, the American College of Medical Toxicology,
the National Academy of Sciences, the Food and Drug Administration,
Centers for Disease Control and Prevention, the World Health
Organization, the Public Health Agency of Canada, and the
European Medicines Agency.
Effects of the controversy
In July 1999 the CDC and the AAP asked vaccine
makers to remove thiomersal from vaccines as quickly as possible,
and asked doctors to delay the birth dose of hepatitis B vaccine
in children not at risk for hepatitis. The CDC and the AAP followed
the precautionary principle, which assumes that there is no harm
in exercising caution even if it later turns out to be unwarranted,
but their action sparked confusion, controversy and some harm. About
10% of hospitals suspended the use of hepatitis B vaccine for all
newborns, and one child born to a Michigan mother infected with
hepatitis B virus died of it. The notion that thiomersal causes
autism caused some parents to have their children treated with chelation
therapy; about 10,000 autistic children in the U.S. receive mercury-chelating
agents every year, and in August 2005 a 5-year-old autistic boy
died from an arrhythmia caused by injection of the chelating agent
EDTA. The notion has also diverted attention and resources away
from efforts to determine the causes of autism.
1930s - first added to vaccines and other products
as a bactericide.
Mid-1980s - used as a preservative in virtually all whole-cell DPT
vaccines, which were routinely administered four times each to children
before eighteen months of age, starting at two months.
Late 1980s - Hib vaccines are recommended for administration to
children at eighteen months. They contain thiomersal.
Early 1990s - In the USA three doses of Hepatititis B vaccine (at
that time containing Thiomersal) are recommended for infants under
six months of age, beginning on the day of birth; four doses of
Hib are recommended within an eighteen month period, beginning at
Late 1990s - three of the vaccines included in Vaccination schedules
for children between six and eighteen months of age contain thiomersal.
1999 - The American Academy of Pediatrics requests removal of thiomersal
from all pediatric vaccines.
2001 - The Institute of Medicine, citing insufficient evidence,
is unable to prove or disprove any link between thiomersal and autism.
However, they conclude that a causal connection between thiomersal
and autism is "biologically plausible".
2002 - The USA Centers for Disease Control (CDC) and the USA Food
and Drug Administration (FDA) state that: although thiomersal was
to be discontinued in some paediatric vaccines, they would not be
recalling any unused stocks, as there is no proof that low doses
of thiomersal is dangerous, and that the change was purely cautionary.
2004 - The Institute of Medicine, based on new information from
epidemiological studies undertaken since its 2001 report, rejects
the hypothetical causative link between thiomersal and autism.
2006 - Some vaccines provided by the World Health Organization for
children in developing countries contain the same amounts of thiomersal
as vaccines used previously for American children. Current vaccination
schedules give these in a shorter time period.
2006 - In the latest review by the WHO committee, the conclusion
previously reached was reaffirmed that there is no evidence of toxicity
in infants, children or adults exposed to thiomersal in vaccines.
2007 - Theresa and Michael Cedillo, the parents of 12-year-old Michelle
Cedillo asked a federal court Monday June 11, to find that their
child's autism was caused by common childhood vaccines.
2007 - Mike Enzi, the ranking member on the United States Senate
Committee on Health, Education, Labor, and Pensions, issued a report
assessing allegations about thimerosal and autism. The report substantiated
allegations that there were shortcomings in the Institute of Medicine's
conflict screening procedures, that thimerosal is used in third-world
childhood vaccines, and that late-1990s EPA mercury guidelines were
inappropriate for vaccines and caused many individuals to conclude
that ethyl mercury can be linked to autism. Several other allegations
were not substantiated.
1 Burton D (2003). "Mercury in medicine report"
(PDF). Congressional Record 149: E1011–30.
2 Offit PA (2007). "Thimerosal and vaccines—a cautionary tale".
N Engl J Med 357 (13): 1278–9.
3 Doja A, Roberts W (2006). "Immunizations and autism: a review
of the literature". Can J Neurol Sci 33 (4): 341–6. PMID 17168158.
4 Thimerosal in vaccines. Center for Biologics Evaluation and Research,
U.S. Food and Drug Administration (2007-09-06). Retrieved on 2007-10-01.
5 Autism cases in vaccine court:
Sugarman SD (2007). "Cases in vaccine court—legal battles over
vaccines and autism". N Engl J Med 357 (13): 1275–7. PMID 17898095.
U.S. Court of Federal Claims (2007-09-28). Vaccine Program/Office
of Special Masters Omnibus Autism Proceeding. Retrieved on 2007-11-24.
6 Centers for Disease Control (2007-01-08). Mercury and Vaccines
(Thimerosal). Retrieved on 2007-07-22.
7 World Health Organization (2006-07-01). Thiomersal and vaccines:
questions and answers. Retrieved on 2007-07-22.
8 American Academy of Pediatrics (1999-09-01). Joint Statement of
the American Academy of Pediatrics and the US Public Health Service
(USPHS). Retrieved on 2007-07-22.
9 Ball LK, Ball R, Pratt RD (2001). "An assessment of thimerosal
use in childhood vaccines". Pediatrics 107 (5): 1147–54. PMID
10 Immunization Safety Review Committee, Board on Health Promotion
and Disease Prevention, Institute of Medicine (2001). Immunization
Safety Review: Thimerosal-Containing Vaccines and Neurodevelopmental
Disorders. Washington, DC: National Academy Press. ISBN 0-309-09008-3.
11 DeStefano F (2007). "Vaccines and autism: evidence does
not support a causal association". Clin Pharmacol Ther 82 (6):
756–9. doi:10.1038/sj.clpt.6100407. PMID 17928818.
12 Burbacher TM, Shen DD, Liberato N, Grant KS, Cernichiari E, Clarkson
T (2005). "Comparison of blood and brain mercury levels in
infant monkeys exposed to methylmercury or vaccines containing thimerosal".
Environ Health Perspect 113 (8): 1015–21. PMID 16079072.
13 In vitro tests:
James SJ, Slikker W III, Melnyk S, New E, Pogribna M, Jernigan S
(2005). "Thimerosal neurotoxicity is associated with glutathione
depletion: protection with glutathione precursors". Neurotoxicology
26 (1): 1–8. doi:10.1016/j.neuro.2004.07.012. PMID 15527868.
Baskin DS, Ngo H, Didenko VV (2003). "Thimerosal induces DNA
breaks, caspase-3 activation, membrane damage, and cell death in
cultured human neurons and fibroblasts". Toxicol Sci 74 (2):
361–8. PMID 12773768.
Ueha-Ishibashi T, Oyama Y, Nakao H et al. (2004). "Effect of
thimerosal, a preservative in vaccines, on intracellular Ca2+ concentration
of rat cerebellar neurons". Toxicology 195 (1): 77–84. doi:10.1016/j.tox.2003.09.002.
14 Hornig M, Chian D, Lipkin WI (2004). "Neurotoxic effects
of postnatal thimerosal are mouse strain dependent". Mol Psychiatry
9 (9): 833–45. doi:10.1038/sj.mp.4001529. PMID 15184908.
15 Berman RF, Pessah IN, Mouton PR, Mav D, Harry J (2007). "Low
level neonatal thimerosal exposure: further evaluation of altered
neurotoxic potential in SJL mice". Toxicol Sci. doi:10.1093/toxsci/kfm265.
16 Clarkson TW, Magos L (2006). "The toxicology of mercury
and its chemical compounds". Crit Rev Toxicol 36 (8): 609–62.
doi:10.1080/10408440600845619. PMID 16973445.
17 Olmsted D. "The age of autism: the last word", UPI,
2007-07-18. Retrieved on 2007-07-23.
18 Geier studies:
Geier DA, Geier MR (2006). "A meta-analysis epidemiological
assessment of neurodevelopmental disorders following vaccines administered
from 1994 through 2000 in the United States". Neuro Endocrinol
Lett 27 (4): 401–13. PMID 16807526.
Geier DA, Geier MR (2006). "An assessment of downward trends
in neurodevelopmental disorders in the United States following removal
of Thimerosal from childhood vaccines". Med Sci Monit 12 (6):
CR231–9. PMID 16733480.
Geier DA, Geier MR (2006). "An evaluation of the effects of
thimerosal on neurodevelopmental disorders reported following DTP
and Hib vaccines in comparison to DTPH vaccine in the United States".
J Toxicol Environ Health A 69 (15): 1481–95. PMID 16766480.
Geier DA, Geier MR (2006). "Early downward trends in neurodevelopmental
disorders following removal of thimerosal-containing vaccines".
J Am Phys Surg 11 (1): 8–13.
Geier DA, Geier MR (2007). "A prospective study of mercury
toxicity biomarkers in autism spectrum disorders". J Toxicol
Environ Health A 70 (20): 1723–30. doi:10.1080/15287390701457712.
19 Mutter J, Naumann J, Schneider R, Walach H, Haley B (2005). "Mercury
and autism: accelerating evidence?" (PDF). Neuro Endocrinol
Lett 26 (5): 439–46. PMID 16264412. Retrieved on 2007-08-15.
21 Institute for Vaccine Safety (2007-07-12). Thimerosal Content
in Some US Licensed Vaccines. Retrieved on 2007-07-23.
22 Food and Drug Administration (2004-09-09). Mercury in Plasma-Derived
Products. Retrieved on 2007-07-23.
23 Immunization Safety Review Committee, Board on Health Promotion
and Disease Prevention, Institute of Medicine (2004). Immunization
Safety Review: Vaccines and Autism. Washington, DC: The National
Academies Press. ISBN 0-309-53275-2.
24 Hviid A, Stellfeld M, Wohlfahrt J, Melbye M (2003). "Association
between thimerosal-containing vaccine and autism". JAMA 290
(13): 1763–6. PMID 14519711.
25 Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B (2004).
"Thimerosal exposure in infants and developmental disorders:
a retrospective cohort study in the United kingdom does not support
a causal association". Pediatrics 114 (3): 584–91. doi:10.1542/peds.2003-1177-L.
26 Verstraeten T, Davis RL, DeStefano F et al. (2003). "Safety
of thimerosal-containing vaccines: a two-phased study of computerized
health maintenance organization databases". Pediatrics 112
(5): 1039–48. PMID 14595043.
27 Heron J, Golding J, ALSPAC Study Team (2004). "Thimerosal
exposure in infants and developmental disorders: a prospective cohort
study in the United kingdom does not support a causal association".
Pediatrics 114 (3): 577–83. doi:10.1542/peds.2003-1176-L. PMID 15342824.
28 Madsen KM, Lauritsen MB, Pedersen CB et al. (2004). "Thimerosal
and the occurrence of autism: negative ecological evidence from
Danish population-based data". Pediatrics 112 (3): 604–6. PMID
29 Thompson WW, Price C, Goodson B et al. (2007). "Early thimerosal
exposure and neuropsychological outcomes at 7 to 10 years".
N Engl J Med 357 (13): 1281–92. PMID 17898097. Lay summary – NNii
30 Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D (2006).
"Pervasive developmental disorders in Montreal, Quebec, Canada:
prevalence and links with immunizations". Pediatrics 118 (1):
e139–50. doi:10.1542/peds.2005-2993. PMID 16818529.
31 Parker SK, Schwartz B, Todd J, Pickering LK (2004). "Thimerosal-containing
vaccines and autism spectrum disorder: a critical review of published
original data". Pediatrics 114 (3): 793–804. doi:10.1542/peds.2004-0434.
PMID 15342856. Erratum (2005) Pediatrics 115 (1), 200. doi:10.1542/peds.2004-2402.
32 American Medical Association (2004-05-18). AMA Welcomes New IOM
Report Rejecting Link Between Vaccines and Autism. Retrieved on
33 American Academy of Pediatrics (2004-05-18). What Parents Should
Know About Thimerosal. Retrieved on 2007-07-23.
34 Kurt TL (2006). "ACMT position statement: the Iom report
on thimerosal and autism" (PDF). J Med Toxicol 2 (4): 170–1.
35 National Advisory Committee on Immunization (2007). "Thimerosal:
updated statement. An Advisory Committee Statement". Can Commun
Dis Rep 33 (ACS-6): 1–13. PMID 17663033.
36 European Medicines Agency (2004-03-24). EMEA Public Statement
on Thiomersal in Vaccines for Human Use. Retrieved on 2007-07-22.
37 Mercury and vaccines (thimerosal). Centers for Disease Control
and Prevention (2007-06-05). Retrieved on 2007-10-01.
38 Statement on thiomersal (World Health Organization, July 2006)
39 Enzi MB (2007). Thimerosal and Autism Spectrum Disorders: alleged
misconduct by government agencies and private entities (PDF). Retrieved
Click here for the full
range of Asperger's and Autism fact sheets at www.autism-help.org
This autism fact sheet is licensed under the GNU
Free Documentation. It is derivative of an Autism and Asperger's
syndrome-related articles at http://en.wikipedia.org