[NEUR2201]Thimerosal_Banner.jpg



























1. Introduction


shoot.jpgThis YouTube clip is an excerpt from “Scarborough Country”, a conservative political talk show broadcast live on MSNBC and hosted by former congressman, Joe Scarborough and was aired in 2005. Entitled “What Causes Child Autism?”, this interview with Robert Kennedy Jr., a senior attorney and outspoken opponent of childhood vaccination, is about his article “Deadly Immunity” published in Rolling Stone Magazine. It is an expose of the alleged cover-up by scientists of the hypothesised thimerosal-autism link. According to Kennedy the increase in vaccination schedule, from 10 vaccines prior to 1988 to 24 vaccines in 1989, caused a concurrent increase in the epidemiology of autism, suffered by 1 in 2500 American children in 1988 and 1 in 166 in 2005.

We believe this media item is of significant interest as it is a primary example of the widely held opinion that there is a causal link between the childhood exposure to mercury in the preservative Thimerosal contained in vaccines, and the large increase in the rate of diagnosed Autism spectrum disorders seen in the last 68 years (Tonge & Brereton, 2011). Despite many scientific investigations showing no evidence of this, the much publicized criticism of Thimerosal has lead to questioning of the safety of the vaccine schedule amongst the general public, and in previous years was concurrent with a decline in the rate of childhood Hepatitis B vaccines in America (Larson et al, 2011). With the world heath organization’s estimation of global vaccine preventable deaths at 1.4 million in 2002, we believe that it is of extreme importance that the public is presented with the scientific evidence regarding Thimerosal in vaccines and the development of Autism spectrum disorder in a clear, unbiased manner.


2. Neuroscientific Context



2.1 Background


Thimerosal (Figure 1) is a white or slightly yellow powdered organic mercury compound. It is 49.55% mercury by weight (Tan and Parkin, 2000), contains an ethyl mercury group, and when injected into the body is metabolised into ethyl mercury (EtHg) and thiosalicylic acid.

Thimerosal was "invented" by chemist Morris Kharasch who patented his work in 1927. It was later marketed by pharmaceutical company Eli Lilly and Company under the trade name Merthiolate and found great success in that very same sector. In addition to its antibacterial and antifungal properties, Thimerosal is also used in a variety of products including: nasal sprays, contact lens solutions and as a preservative in vaccines; the latter of which much controversy has arisen in the past decade.

Because of the increasing number of Thimerosal containing vaccines added to the infant immunisation schedule over the last two decades, an awareness of the potential for neurotoxicity by organic mercurial compounds has brought Thimerosal into the light. However systematic studies have found no evidence to indicate a correlation between vaccines and autism in children (Clements, 2004; Hviid, Stellfed, Wohlfhart, and Melbye, 2003; Stehr-Green, Tull, Stellfeld, and Mortenson, 2003). Nonetheless, the administration of Thimerosal as a preservative in vaccines for children has decreased over the years.

Figure 1: thimerosal chemical structure
Figure 1: thimerosal chemical structure

2.2 Neurotoxicity


Neurotoxicity is the alteration of the nervous system, usually due to the damage of nervous tissue, resulting from exposure to a neurotoxin. It is known that mercuric compounds are neurotoxic and that estimates of the toxic risks of Thimerosal are based on the assumption that EtHg is toxicologically similar to methyl mercury (MeHg). However, current research has shown that although EtHg is not as neurotoxic as its chemical relative MeHg, it nonetheless damages the nervous tissue.

The administration of Thimerosal immediately metabolises, releasing EtHg into the surrounding tissue and bloodstream. Once in the bloodstream, EtHg or inorganic mercury (formed by the deethylation of ethylmercury in the bloodstream) can readily travel along the bloodstream, pass the blood brain barrier and enter the brain (figure 2).



asdasd.jpg
Figure 2: Sources and metabolism pathway for different mercury species



2.2.1 Inorganic Mercury in the brain

Past research has found no evidence to substantiate that inorganic mercury retained in the CNS plays any neurotoxic role (Braeckman, Simoens, Rzeznik, and Raes, 1997). These findings are consistent with the rat experimental model conducted by Magos et al (1985) who found no direct involvement of inorganic mercury in triggering tissue damage even after repeated EtHg (Aschner and Ceccatelli, 2010). As such any neurotoxic effect exhibited after administration of Thimerosal will be considered as a result of the EtHg compound.

2.2.2 Ethyl Mercury in the brain

In vitro tests exploring the role of EtHg deposition on human cells have revealed that Thimerosal in concentrations relevant to vaccines are. In a comparison study of four different vaccine preservatives, Thimerosal-EtHg was found to be the most toxic (Geier, Jordan and Geier, 2010). However, Thimerosal-EtHg was less toxic that Mercury Chloride (Chanez, Flexor, and Bourre, 1989) but depending on the cell type, Thimerosal-EtHg could be just as potent as MeHg as a neurotoxin ( Rush, Hjelmhaug, and Lobner, 2009).
Administration of Thimerosal-EtHg to neuroblastoma (SK-SY-5Y) at concentration between 1nm to 10µM has been shown to cause neuronal cell death, mitochondrial damage (depolarisation of mitochondria, generation of reactive oxygen species and, releases of cytochrome c), reduced oxidative-reduction activity and increased levels of fragmented DNA. (Geier, King, and Geier, 2009; Parren, Barker, and Ehrich, 2005) Cortical neurons between 1-250um also undergoes neuronal cell death, fragmented DNA and changes in its cell permeability (Baskin, Ngo, and Didenko, 2003).
In vitro animal studies have also revealed other facts of the neuropathology of Thimerosal-EtHg. In the rat species, there was inhibition of sodium channels in the sensory neurons of the dorsal root ganglion (Song et al, 2000). In brain homogenate, synaptosomes and myelin, the Na+K+ATPase pump was inhibited (Chanez et al). The inhibition of the sodium and NA+K+ATPase pump would suggest a decrease/stop in the potential of neurons to fire Action Potentials (AP) and send/receive sensory/motor information between the CNS and the target limb. Sensory abnormality is thought to be a symptom of autism (Plaisted and Davis, 2009). Likewise in the hippocampal neurons, interactions between the GABA(A) and NMDA receptors are complex (Wyrembek et al). Because NMDA mimicks glutamate, the main excitatory neurotransmitter, and GABA(A), the main inhibitory neurotransmitter, complex interactions may lead to epileptic fits (Hughes, 2008).
Ultimately, the administration of Thimerosal and its mercurial compound, EtHg, has the potential to affect a wide range of structures in the CNS and their underlying functions.



2.3 Differences between Methyl and Ethyl Mercury Toxicity


Although Thimersol is metabolized into Ethyl mercury and thiosalicylate, the guidelines developed by the WHO, FDA and EPA on mercury toxicity are primarily based on epidemiological and laboratory studies of the neurotoxcitity of methyl mercury. As a result of this, and the fact that they are both short chain alkyl mercurials, it is often assumed that the properties and toxicity of methyl mercury on the human body are the same as that of ethyl mercury (Aschner & Ceccatelli, 2010) . However recent studies directly comparing the two have shown that the method of extrapolating Ethyl mercury’s potential toxicity from investigations on methyl mercury is flawed due to their structural differences, which affect their pharmokinetic behaviour (Garrecht & Austin, 2011).


new_image_neuro.jpg
Methyl Mercury (MeHg) Ethyl Mercury (EtHg)
Molecular weight: 215.6245 g/mol Molecular weight: 229.6155 g/mol

In comparison to the Ethyl mercury (EtHg), the cation Methyl mercury (MeHg) has a smaller molecular weight and therefore more readily binds to anionic tubular protein (–SH) groups of amino acids such as cysteine (Stratton, Gable & McCormick, 2001). In cells the complex formed from the binding of MeHg and cysteine, MeHg-S-Cys, mimics the structure of methionine, a neutral amino acid. It is through this mimicry that MeHg is able to pass through the blood brain barrier and into nerve cells where it impairs their function and exhibits toxic effects (Ni et al, 2011). Presently it is unclear whether ethyl mercury, in concentrations that result from exposure to vaccines, passes through the blood brain barrier and exhibits toxicity as readily as methyl mercury. It has been hypothesized that this may be due to the lack of an amino acid transport system like that available to methyl mercury (Humphrey, Cole, Pendergrass & Kiningham, 2005).

Additionally Methyl mercury and Ethyl mercury differ in that, Ethyl mercury, once it crosses the blood brain barrier is more rapidly converted into inorganic mercuric mercury, a compound that is not readily moved into the blood stream for elimination (Ni et al, 2011). A study conducted by Magos et al (1985) showed higher levels of accumulation of MeHg in the brain compared to EtHg, a factor which contributes to the greater toxicity of MeHg. Furthermore a study conducted by Burbacher et al (2005) also reported that the clearance half time for MeHg in the brain was 58 days on average, compared to 14 days for EtHg. Overall the scientific literature largely indicates that as EtHg decomposes and is removed from the body much faster than MeHg, the risk of Neurotoxicity and brain damage is much less for EtHg compared to MeHg (Schultz,2011).

2.4 High dose VS Low Dose exposure


The neurological effects of both methyl and ethyl mercury are both largely dependent on the concentration and the cumulative amount of mercury that a subject is exposed to over time (Schultz, 2010).

At high concentrations, over both short and long periods of time, Methyl mercury has been well established as a neurotoxin. Studies conducted after episodes of methyl mercury poisoning in Japan (from contaminated sea food) and Iraq (from grain treated with methyl-mercury fungicide) showed that high dose exposure to methyl mercury resulted in symptoms in adults such as paresthesia, ataxia, and impairments in speech, hearing and vision (Schultz,2010). Similarly studies have shown that exposure to high concentrations of ethyl mercury over both short and long periods of time have neurotoxic effects similar to that of methyl mercury including restlessness, impairments in speech, hearing and vision, hemiparesis, hallucination, comas and even death (Schultz, 2010).

While most studies investigating and comparing the effects of methyl and ethyl mercury on the blood brain barrier, total levels of mercury on the brain, clearance times and whole blood levels have used concentrations of mercury significantly higher than those contained in vaccines (Clarkson et al, 2003; Magos 1885) few studies have examined the effects of chronic low concentration exposure to methyl and ethyl mercury and the effects of accumulation. As previously mentioned, concerns regarding the neurotoxicity of mercury and its possible link autism and neurodegenerative disorders, are primarily based on the propensity of mercury to accumulate in the brain during this mode of chronic low concentration exposure employed in the vaccination schedule (Schultz, 2002).

At concentrations higher than the 25 micrograms of ethyl mercury contained in vaccines, it has been shown that methyl mercury accumulates in the brain and blood more and is cleared from the brain slower compared to ethyl mercury providing evidence that it is more neurotoxic (Magos, 1985; Magos 2003). Additionally when chronic low concentration exposure was investigated in an experiment designed to mimic the childhood vaccination schedule, Burbacher (2005) found that levels of organic mercury were lower in the brain in infant monkeys exposed to Thimerosal than those exposed to MeHg. It was also found that brain half clearance times were significantly lower in monkeys exposed to thimerosal compared to those exposed to MeHg.This effect was replicated in a study conducted by Zareba et al (2007) on mice, providing further evidence that at low doses ethyl mercury may be less neurotoxic than methyl mercury. In addition to this, a study conducted by Hornig, Chian and Lipkin (2004) on mice showed that autoimmune propensity influenced the effects of chronic low dose exposure to EtHg in the form of the vaccination schedule, which included growth delay reduced locomotion exaggerated response to novelty, and densely packed hyperchromic hippocampal neurons with altered glutamate receptors and transporters. These findings suggest that genetic influences may effect the development and severity of thimerosal related toxicity (Hornig, Chian & Lipkin, 2003).


2.5 Autism and Thimerosal


vaccines-contain-thimerosal.jpg

Autism is one of three neurodevelopmental disorders, classified as Autism Spectrum Disorders, and usually diagnosed in infancy with symptoms continuing on into adulthood (Schultz, 2010). Under DSM-IV the defining behavioural manifestations are impairment of social interaction, impairment of communication and stereotypic and repetitive behaviours (Wing, Gould, & Gillberg, 2011). The etiology of autism is complex, with genetics playing a significant role. However interactions with environmental factors in those with genetic predispositions may also be causal (IOM, 2004).

The first studies to link mercury neurotoxicity to autism were correlational. Wakefield (1998) studied children admitted for treatment in a gastroenterological unit and displayed developmental impairment, including language difficulties and loss of acquired skills, some of which were consistent with autism. Researchers found the onset of behavioural symptoms followed the injection of the measles, mumps and rubella (MMR) vaccination. Although it was later retracted for methodological and ethical issues, this study prompted public concern regarding the safety of vaccines.

The similarities between symptoms of mercury exposure and autism have also been used as an indication of a link between them, with obvious limitations, one being the symptoms listed are not restricted to either of the conditions. A simplified summary of some of the findings of Bernard, Enayati, Redwood, Roger, and Binstock (2001) is provided in Table 2.

Table 2. A summary of biological abnormalities of autism and mercury poisoning
Symptoms of Autism
Symptoms of Mercury Poisoning
Biochemical abnormalities such as low sulphate levels, low levels of gluthione, purine and pryrimidine metabolism errors, and mitochondrial dysfunctions in brain
Biochemical symptoms including blocking of sulphate transporters, inhibition of enzymes of glutathione, disruption of peroxidise and puritine metabolism, and disorderly mitochondrial activities in brain
Increased chances of developing allergies and autoimmune diseases such as rheumatoid arthritis
Abnormal immune functioning, including increased likelihood of allergies and autoimmune diseases and inhibition of lymphocytes, T-cells
Central nervous system is compromised; pathology in limbic system, neuronal disorganisation seen in, for example, depressed expression of NCAMs
Pathology in limbic system due to accumulation of mercury and disruption of neuronal organisation such as reduction of NCAMs
Neurochemical imbalance including decreased serotonin synthesis, lower dopamine levels, elevated noradrenaline, adrenaline, glutamate levels, and demyelination in brain
Affects neurochemical structures by, for example, preventing serotonin release and inhibiting transport, altering dopamine release, blocking adrenaline enzymes, and elevating glutamate levels
Neurophysiological abnormalities evident in EEGs and other autonomic disturbances such as elevated heart rate, poor circulation
Abnormal neurophysiological markers seen in abnormal EEGs and autonomic disturbances such as excessive sweating and poor circulation

Although experimental studies have failed to establish thimerosal’s role in causing autism, several studies have found autoimmune deficiencies may be the third variable that modulates the neurological effect of thimerosal (Burbacher et al., 2005; Hornig, Chian, & Lipkin, 2004; Mutter, Naumann, Schneider, Walach, & Haley, 2005). In one study, thimerosal was administered intramuscularly to either autoimmune disease sensitive or autoimmune disease-resistant strain mouse pups at 10 days, consistent with the stage of brain maturity in human infants when vaccinations are first given and mimics the vaccination schedule. Control mice were given saline injections. Clinical assessments (e.g. developmental and motor changes), behavioural studies (e.g. repetitive and exploratory activities) and histology and immunohistochemistry of the mice were assessed. The study found autoimmune disease-sensitive mice experienced growth retardation, hyperactivity and compact distribution of hyperchromic hippocampal neurons compared to autoimmune disease-resistant mice and control mice. However, there is evidence that the effects of ethyl mercury on mice are not comparable to human studies and human studies remain inconclusive (Chez, Chin, & Hung, 2004; Hornig et al., 2004).
Although research to date has not supported the casual role of Thimerosal in autism, public concern continues. Scientists are continuing to focus their research on identifying causes of autism, including the combined role of genetic deficiencies and environmental exposure in autism (Chez et al., 2004).

3. Analysis



3.1 Target Audience


This segment originally aired on 22nd June, 2005 on “Scarborough Country”, a program on cable news channel MSNBC. Given the nature of the channel and the political background of host Joe Scarborough, the program is targeted at adults. MSNBC remains popular with the aged 24-54 demographic (Gorman, 2010).

3.2 Purpose and Bias


“Scarborough Country” is an opinion program. Hence, Kennedy intended to persuade viewers of the dangers of vaccinations. His rhetoric and the selective choice of information are aimed to do just that. This is further emphasised by Joe Scarborough, whose personal experience with autism and his own suspicions regarding the cause of the condition, provides another passionate point of view.


The segment is highly biased. Kennedy provides extensive, albeit simplified, statistics that support his argument. For example, he compares the amount of mercury in vaccines for particular diseases to the guidelines set by trustworthy American institutes such as the Environment Protection Agency. These facts are presented in such a way that suggests a highly probable causal link between vaccines and autism. On the other hand, he refers to research that counters his arguments as “bad science” and compares it to “classic tobacco science”, without explicit reference to any of the research.

Simplifications and Quality of the Information


Kennedy's autism prevalence statistics are supported by the Centers for Disease Control and Prevention (2009). However, his interpretation and presentation of these figures are simplistic. Kennedy believes these increases to be representative of the increased incidence of autism in children, but they can also be accounted for by:

  1. Greater awareness and detection of autism
  2. Changes to the diagnostic criteria of autism
  3. Changes in reimbursement for medical services (Parker, Schwarz, Todd, & Pickering, 2004)

However, researchers also acknowledge that an actual increase in incidence of autism cannot be disregarded (Parker et al., 2004). Nevertheless, this does not point towards a relationship between Thimerosal and Autism, as Kennedy was suggesting.
Several epidemiological studies undertaken to examine the relationship concludes there is no causal relationship between Thimerosal and Autism (Hviid, Stellfeld, Wohlfahrt, & Melbye, 2004; Madsen et al., 2003; Taylor, 2006). A Danish study observed the incidence of Autism between 1971 and 1990, during which Thimerosal was used in vaccines, to the statistics recorded in the period between 1991 and 2000, where the practice was discontinued due to public health concerns (Madsen et al., 2003). The study found there was no evidence of a consistent increase in Autism prevalence during the period where Thimerosal was administered. Conversely, there was an increase in incidence after 1991, which was seen in children born after the removal of Thimerosal from vaccines. Parker et al. (2004) undertook a critical review of studies that examined the association between Thimerosal and Autism and found the three journal articles that found a relationship between Thimerosal and Autism were proposed by the same researcher and used overlapping data to produce such a link. The remaining seven studies did not find an association between Thimerosal and Autism. Similarly, a review by Schultz (2010) found the following:

Table_1.png

In addition, Kennedy’s argument that the cumulative mercury content of the recommended childhood vaccination schedule is “400 times” the US Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) guidelines for mercury exposure is a gross misrepresentation of the science and an oversimplification of the statistics. In 1999 an FDA review by the Center for Biologics Evaluation and Research calculated that the greatest amount of mercury that could be received via immunisation was 187.5 μg for a six month old, and 237.5 μg or 275 μg for a 2 year old (IOM, 2004). When compared to safety standards determined by FDA and EPA these cumulative totals were found to exceed the respective maximum daily intakes of 0.4 μg and 0.1 μg per kg of body weight per day (Baker, 2008). As a result, thimerosal was removed from vaccines and a six month old is now exposed to, at most, <3 μg, (IOM, 2004). However, a thorough analysis of the scientific and statistical evidence does not support Kennedy’s aforementioned assertion. Importantly the federal safety guidelines, for example those provided by EPA, are not pertinent to thimerosal-containing vaccines (Parker et al., 2004). The reasons for this are as follows:

1. The EPA recommendation has a factor of safety ten times higher than the accepted threshold for neurotoxic effects, and is set for pregnant women, rather than children nor adults, as foetuses are more susceptible to mercurial poisoning (Parker et al., 2004).

2. It is based on data of MeHg environmental contamination and subsequent oral ingestion, in particular the case of methylmercuric fungicide and wheat flour in Iraq in the 1970s, rather than information on the effects of low-level intravenous doses of EtHg (Baker, 2008). There is substantial evidence to suggest that MeHg and EtHg differ in terms of pharmokinetics and metabolism despite similar chemical structures (Aschner & Ceccatelli, 2010; Baker, 2008; Berman, et al., 2007; Parker, et al., 2004). Therefore, an analogy between MeHg and EtHg as used in the safety guidelines is invalid and would greatly overestimate the risk of neurotoxicity.

3. The EPA standards assume daily mercury exposure cumulating over time. This is inconsistent with the immunisation schedule as children receive vaccines at the most frequent monthly. Furthermore, as the half-life in the brain for injected EtHg is significantly less than ingested MeHg (Aschner & Ceccatelli, 2010; Nelson & Bauman, 2003), and children clear EtHg faster than adults due to the allometric relationship between metabolism and fractional power (Magos, 2003) the risk of neurological damage is reduced when compared to daily MeHg doses.



4. Appendix



We began our research by looking for a media items within our areas of interest including drug addiction, attraction, false memories, ADHD and Autism. One of our group members had come across “Vaccine Wars”, a documentary detailed much of the debate surrounding this issue. A quick search revealed that there were a significant number of media items from a range of perspectives regarding this issue because of the controversial nature of this topic.

We chose this particular video primarily because we felt it reflected the nature of this assessment task as well as the broader role of the media in communicating and influencing public knowledge of science. Specifically, an interesting aspect about this debate was captured in the role of Robert F. Kennedy Jr. who possesses limited scientific knowledge of the neuroscientific context of the issue, yet commands attention from the public when citing skewed statistics and biased journal articles.

Largely due to the hysteria surrounding this issue, numerous scientific, peer-reviewed studies have been published that both dispute and support many of the claims put forward by Robert F. Kennedy Jr. The research papers used in the analysis of the media item were selected based on the robustness of their findings and conclusions and relevance to topic. This was achieved through analysis of the methodology and results of these studies and comparing findings to other similar studies.


To Richard,



We found using the wiki discussion page a little difficult and so decided to use facebook instead. We've provided you with a link so that you can see some of our correspondence. If that doesn’t work, you should be able to log onto facebook and search for NEUR2201 Assignment. Sorry for the inconvenience.



Kind regards,



Autism and Thimerosal Group (Glen Jonatan z3289453, Kani Shang z3330775, Jessica Sandaman z3330679, and Josie Miligan-Saville z3332000)



http://www.facebook.com/groups/140645076022446/




5. References


Aschner, M., & Ceccatelli, S. (2010). Are neuropathological conditions relevant to ethylmercury exposure?. Neurotoxicity Research, 18, 59-68.

Baker, J. P. (2008). Mercury, vaccines, and autism: One controversy, three histories. American Journal of Public Health, 98, 244-253.

Baskin, D.S., Ngo, H., Didenko, V.V. (2003). Thimerosal induces DNA breaks, caspase-3 activation, membrane damage, and cell death in cultured human neurons and fibroblasts. Toxicological Sciences, 74, 361-368.

Berman, R. F., Pessah, I. N., Mouton, P. R., Mav, D., & Harry, J. (2008). Low-level neonatal thimerosal exposure: Further evaluation of altered neurotoxic potential in SJL mice. Toxicological Sciences, 101, 294-309.

Bernard, S., Enayti, A., Redwood, L., Roger, H., & Binstock, T. (2001). Autism: A Novel Form of Mercury Poisoning. Medical Hypotheses, 56(4), 462-471.

Braeckman, B., Simoens, C., Rzeznik, U., and Raes, H.(1997). Effect of sublethal doses of cadmium, inorganic mercury and methylmercury on the cell morphology of an insect cell line (Aedes albopictus, C6/36). Cell Biology International, 21, 823-832.

Burbacher, T.M., Grant, K.S., Mayfield, D.B, Gilbert S.G., Rice, D.C.( 2005). Prenatal methylmercury exposure affects spatial vision in adult monkeys. Toxicology Applied Pharmacology, 208: 21-28.

Chanez, C., Flexor, M.A., Bourre, J.M. (1989)Effect of organic and inorganic mercuric salts on NA+K+ATPase in different cerebral fractions in control and intrauterine growth-retarded rats: alterations induced by serotonin. Neurotoxicology, 10, 699-706.

Chez, M.G., Chin, K.C., & Hung, P.C. (2004). Immunizations, Immunology, and Autism. Autism and Autistic Spectrum Disorders, 11(3), 214-217.

Clements, J.C. (2004). The evidence for the safety of thimerosal in newborn and infant vaccines. Vaccine, 22, 1854-1861.

Hornig, M., Chian, D., & Lipkin W.I. (2004). Neurotoxic Effects of Postnatal Thimerosal Are Mouse Strain Dependent. Molecular Psychiatry, 9, 833-845.

Hughes, J.R. (2008). A review of recent reports on autism: 1000 studies published in 2007. Epilepsy and Behaviour, 13, 425-437.

Humphrey, M.L., Cole, M.P., Pendergrass, J.C., & Kiningham, K.K.(2005). Mitochondrial Mediated Thimerosal Induced Apoptosis in a Human Neuroblastoma Cell Line (SK-N-SH). Neurotoxicology, 26:3, 407-416.

Hviid, A., Stellfeld, M., Wohlfahrt, J., & Melbye, M. (2003). Association Between Thimerosal-Containing Vaccine and Autism. JAMA, 290, 1763-1766.

Institute of Medicine of the National Academies. (2004). Immunization safety review: Vaccines and autism. Washington: The National Academies Press.

Garrecht, M., Austin, D.W. (2011). The Plausibility of a Role for Mercury in the Etiology of Autism: A Cellular Perspective. Toxicology and Environmental chemistry. 96:3, 1251-1273.

Geier, D.A., King, P.G., Geier, M.R. (2009) Mitochondrial dysfunction, impaired oxidative-reduction activity, degeneration, and death in neuronal and fetal cells induced by low-level exposure to thimerosal and other compounds. Toxicological & Environmental Chemistry, 91, 735-749.

Geier, D.A., Jordan, S.K., Geier, M.R. (2009. The relative toxicity of compounds used as preservatives in vaccines and biologics. Medical Science Monitor, 16, SR21-SR27.

Gorman, B. (2010, September 28). MSNBC Beats CNN In Total Day In 3Q Among A25-54, First Time Since 2Q 2001. TV By Numbers. Retrieved from http://tvbythenumbers.zap2it.com/2010/09/28/msnbc-beats-cnn-in-total-day-in-3q-among-a25-54-first-time-since-2q-2001/65585/

Madsen, K.M., Lauristen, M.B., Pedersen, C.B., Thorsen P., Plesner, A., Andersen, P.H., Mortensen, & P.B. (2003). Thimerosal and the Occurrence of Autism: Negative Ecological Evidence from Danish Population-Based Data. Paediatrics, 112, 604-606.

Magos, L, Brown, A.W, Sparrow S., Bailey, E., Snowden, R.T., Skipp, W.R. (1985). The Comparative Toxicology of Ethyl and Methyl Mercury. Arch Toxicology 57:260-267.

Magos, L. (2003). Neurotoxic character of thimerosal and the allometric extrapolation of adult clearance half-time to infants. Journal of Applied Toxicology, 23, 263-269.

Mutter, J., Naumann, J., Schneider, R., Walach, H., & Haley, B. (2005). Mercury and Autism: Accelerating Evidence?. Neuroendocrinology Letters, 26(5), 439-446.

Ni, M., Li, X., Dos Santos, A.P.M., Farina, M., Da Rocha, J.B.T., Avila, D.S, Soldin, O.P, Rongzhu, L., Aschner, M. (2011). Mercury. Reproductive and Developmental Toxicology, 415-459.

Nelson, K. B., & Bauman, M. L. (2003). Thimerosal and autism?. Pediatrics, 111, 674-679.

Parker, S. K., Schwartz, B., Todd, J., & Pickering, L. K. (2004). Thimerosal-containing vaccines and autistic spectrum disorder: A critical review of published original data. Pediatrics, 114, 793-804.

Parren, D.K., Barker, A., Ehrich, M. (2005) Effects of thimerosal on NGF signal transduction and cell death in neuroblastoma cells. Toxicological Sciences, 86, 132-140.


Rush, T., Hjelmhaug, J., Lobner, N. (2009). Effects of chelators on mercury, iron, and lead neurotoxicity in cortical culture. Neurotoxicology, 30, 47-51.

Schultz, S. T. (2010). Does thimerosal or other mercury exposure increase the risk for autism?. ACTA Neurobiologiae Experimentals, 70(2), 187-195.

Song, J., Jang, Y.Y., Shin, Y.K., Lee, M.Y., Lee, C. (2000). Inhibitory action of thimerosal, a sulfhydryl oxidant, on sodium channels in rat sensory neurons. Brain Research, 864, 105-113.

Stehr-Green, P., Tull, P., Stellfeld, M., Mortenson, P.-B. (2003) Autism and thimerosal-containing vaccines: lack of consistent evidence for an association. American Journal of Preventive Medicine, 25, 101-106.

Stratton, K.R., Gable, A., McCormick, M.C. (2001). Immunization Safety Review: Thimerosal Containing Vaccines and Neurodevelopmental Disorders. Washington: National Academy Press.

Tan, M., Parkin, J.E. (2000) Route of decomposition of thiomersal (thimerosal). International Journal of Pharmaceutics, 208, 23-34.

Taylor, B. (2006). Vaccines and the Changing Epidemiology of Autism. Child: Care, Health and Development, 32(5), 511-519.

Wakefield, A., Murch, S., Anthony, A., Linnell, J., Casson, D., Malik,…,Walker-Smith, J. (1998). Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet, 351, 637-641.

Wing, L., Gould, J., & Gillberg, C. (2011). Autism spectrum disorders in the DSM-V: Better or worse than the DSM-IV?. Research in Developmental Disabilities, 32, 768-773.

Wyrembek, P., Szczuraszek, K., Majewsja, M.D., Mozrzymas, J.W. (2010). Intermingled modulatory and neurotoxic effects of thimerosal and mercuric ions on electrophysiological responses to GABA and NMDA in hippocampal neurons. Journal of Physiology and Pharmacology, 61, 753-768.

Zareba, G., Cernichiari, E., Hojo, R., McNitt, S., Weiss, B., Mumtaz, M. M., Jones, D.E., Clarkson, T.W. (2007) Thimerosal Distribution and Metabolism in Neonatal Mice: Comparison with Methyl Mercury. Journal of Applied Toxicology, 27: 511-518.