BRMI

ARTICLES –

Thimerosal

in Vaccines

To view the amount of Thimerosol in today’s vaccines please scroll to the bottom of the page.

Thimerosal (or Thiomersal) is a trade name for an organic mercurial compound (sodium ethyl-mercury (Hg) thiosalicylate) that is 49.55% mercury (Hg) by weight, which rapidly decomposes in aqueous saline solutions into ethyl-Hg hydroxide and ethyl-Hg chloride. It has been widely used since the 1930s as a preservative in certain vaccines cosmetics, tattoo inks, eye drops and contact lens solutions as well as a disinfectant (e.g. Merthiolate). Because of its application as a vaccine preservative, almost every human and animal (domestic and farmed) that has received Thimerosal-containing vaccines have been exposed to ethyl-mercury. Concerns have been voiced about its use in vaccines because ethyl-mercury is highly toxic to human cells and has been shown to be nephrotoxic (kidney) and neurotoxic (Geier, D 2015; Clarkson, T 1997). There are over 165 studies that have focused on Thimerosal used as a preservative in many childhood vaccines, and found it to be harmful.  

Since there is insufficient data available regarding the toxic profile of ethylmercury, the FDA guidelines for methylmercury (MeHg) have been used to predict the potential toxicity of Thimerosal. This assumes that the toxicokinetic profile of the two organic mercury salts is similar. However, new studies prove that this is not the case. The main route of human exposure to MeHg is oral ingestion of seafood; for ethylmercury, human exposure is mainly by injection of thimerosal-containing vaccines. Compared with inorganic mercury salts, organic mercury (Thimerosal) is absorbed more effectively and thus has a greater toxic potential.

Specifically, Thimerosal is initially metabolized into ethyl-Hg compounds and thiosalicylate and rapidly binds onto thiol groups found on many proteins in human blood. It is then actively transported throughout the body and even across the blood-brain barrier into neuronal cells, where it significantly accumulates and may persist for months to years following exposure. There it damages neurons (brain cells), particularly in the dentate gyrus of the hippocampus and thalamus. Although Thimerosal-containing vaccines have been banned in several countries, it continues to be added to some vaccines in the US and many vaccines in the developing world.

Thiomersal – Not an Effective Antimicrobial

Mercury compounds have been used as disinfectants or antimicrobials since bacteriology began. For a long period of time mercurial compounds, such as mercury chloride, were thought to be useful in the killing of bacteria and other microorganisms. However, as early as 1943, it was reported that plasma preserved with 1:10,000 Thimerosal was still contaminated with viable microorganisms, and it was concluded that Thimerosal cannot be considered the ideal preservative. Morton et al. found that Thimerosal is not highly germicidal and does not possess high antimicrobial value in the presence of serum and other protein mediums. They further stated that the loss of antibacterial activity of mercurials in the presence of serum proves their incompatibility with serum. Furthermore, these investigators described that Thimerosal was 35-times more toxic to embryonic tissue cells than it was to bacteria, as well as more toxic to leukocytes (white blood cells) than bacteria (Morton, H 1948).

More recently, the effectiveness of Thimerosal as a preservative in Diphtheria–Tetanus–Pertussis (DTP) vaccine was evaluated by the US CDC.  The CDC researchers reported that the choice and level of the preservative for inclusion in the DTP vaccine were limited because of possible harmful effects on the vaccine’s antigenicity, plus the need to ensure the safety of the preservative. These investigators reported that Thimerosal used in the production of the DPT vaccine as an organic-Hg bacteriostatic agent was only weakly bactericidal. These investigators concluded that at currently used concentrations, Thimerosal is not an ideal preservative (Stetler, H 1985). Higher concentrations were not recommended because it might reduce vaccine potency or pose a danger to individuals receiving the vaccine. 

Other investigators have observed that Thimerosal failed to meet European Pharmacopoeia antimicrobial effectiveness acceptance criteria as a preservative due to lack of growth inhibition of Thimerosal on Staphylococcus aureus in both single and multi-challenge evaluations (Khandke, L 2011). These researchers have compared and described the toxicity levels of commonly used preservatives in vaccines and found that other non-mercurial, less toxic preservatives, such as 2-Phenoxyethanol, provided a superior antimicrobial effectiveness over Thimerosal for vaccine formulations. 

Despite the evidence that Thimerosal is a potent biologically toxin (Geier, D 2010), is not an effective antimicrobial, and that there are other less toxic and more effective preservatives available, Thimerosal continues to be used as a preservative in several vaccines to date throughout the world. This compound is a considerable source of mercury exposure for children (Kern, J 2011). 

Current use of Thimerosal in Vaccines

In the 1990s, an increasing number of different vaccines containing Thimerosal were introduced in vaccination schedules around the world, and thus, the average cumulative exposure to Thimerosal in infants has increased in recent years. In 1997, Frank Pallone, a U.S. congressman from New Jersey attached a simple, 133-word amendment to a Food and Drug Administration (FDA) reauthorization bill. This amendment gave the FDA 2 years 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 (21 USC 397 Section 413, 1997).” The bill — the FDA Modernization Act of 1997 — was signed into law on November 21, 1997. Neither the press nor the public took notice.

Eighteen months later, in May 1999, the FDA found that by 6 months of age, infants could receive as much as 75 μg of mercury from three doses of  diphtheria–tetanus–pertussis vaccine, 75 μg from three doses of the Haemophilus influenzae type b vaccine, and 37.5 μg from three doses of the hepatitis B vaccine — a total of 187.5 μg of mercury. Thus, cumulative doses of Hg exposure from Thimerosal-containing vaccines can be as high as 187.5 μg Hg in the first six months of life (Bingham, M 2005). Although this degree of exposure in the first six months of life has been reduced in the US in recent years, it remains unchanged in developing countries.

In June 2000, a joint statement on Thimerosal in vaccines was prepared by the American Academy of Family Physicians (AAFP), the American Academy of Pediatrics (AAP), the Advisory Committee on Immunization Practices (ACIP), and the Public Health Service (PHS) in response to:

1) the progress in achieving the national goal declared in July 1999 to remove Thimerosal from vaccines in the recommended childhood vaccination schedule, and

2) results of recent studies that examined potential associations between exposure to mercury in thimerosal-containing vaccines and health effects.

In this statement, AAFP, AAP, ACIP, and PHS recommend “continuation of the current policy of moving to vaccines that are free of Thimerosal as a preservative. Until adequate supplies are available, use of vaccines that contain Thimerosal as a preservative is acceptable.”

However, starting in April of 2002, the US Center for Disease Control began to recommend that influenza vaccines are given to infants and children, who were 6-to-23 months of age, when the only approved influenza vaccine for that age group was preserved with Thimerosal (Sanofi Pasteur’s Fluzone®). In addition, the US CDC recommended influenza vaccines be given to women who were pregnant in their second and third trimesters, when the only available influenza vaccines were also Thimerosal preserved. In addition, through 2010, the US CDC progressively widened the age range for annual influenza vaccine such that very young children were supposed to get two doses of influenza vaccine initially (at 6 and 7 months of age) and then receive an additional dose every year. All these vaccines administered contained Thimerosal.  By this time, the US CDC had also discontinued the “second-and-third-trimester” constraint on giving influenza vaccines to pregnant women.

Thus, even though the US FDA eventually approved the reduced-Thimerosal and no-Thimerosal formulations of the tetanus-containing vaccines and some other vaccines, exposure to Thimerosal through vaccination continued. In 2013, more than half of all the influenza vaccines were still preserved with Thimerosal. 

To date, most routinely recommended pediatric vaccines manufactured for the U.S. market contain either no Thimerosal or trace amounts. Even though there are other more effective, non-toxic preservatives that could replace Thiomersal, it is still added particularly to multidose injectable vaccines, such as influenzas (flu). The cost-effectiveness of adding Thimerosal to multidose vaccines still overrides safety concerns. Thimerosal is still a preservative in some of the other US FDA-approved vaccines. Outside North America and Europe, many vaccines still contain Thiomersal. Clearly, Thimerosal should be banned and eliminated as a vaccine preservative throughout the world.

The culmination of the research that examines the effects of Thimerosal in humans indicates that it is a poison at minute levels with a plethora of deleterious consequences, and there is a clear cause for concern. To date, there are over 150 studies that show harm from Thimerosal including increased risk of neurodevelopmental disorders, such as autism, attention-deficit/hyperactivity disorder, and language and speech delay. The following selected articles describe Thimerosal as used in vaccines and its related biological toxic effects.

 

 

Adams, J. B., M. Baral, E. Geis, J. Mitchell, J. Ingram, A. Hensley, I. Zappia et al. “The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels.” Journal of Toxicology 2009 (2009).

Abstract

This study investigated the relationship of children’s autism symptoms with their toxic metal body burden and red blood cell (RBC) glutathione levels. In children ages 3–8 years, the severity of autism was assessed using four tools: ADOS, PDD-BI, ATEC, and SAS. Toxic metal body burden was assessed by measuring urinary excretion of toxic metals, both before and after oral dimercaptosuccinic acid (DMSA). Multiple positive correlations were found between the severity of autism and the urinary excretion of toxic metals. Variations in the severity of autism measurements could be explained, in part, by regression analyses of urinary excretion of toxic metals before and after DMSA and the level of RBC glutathione.

Carneiro, Maria Fernanda Hornos, Juliana Maria Oliveira Souza, Denise Grotto, Bruno Lemos Batista, Vanessa Cristina de Oliveira Souza, and Fernando Barbosa Jr. “A systematic study of the disposition and metabolism of mercury species in mice after exposure to low levels of thimerosal (ethylmercury).” Environmental Research 134 (2014): 218-227.

Abstract 

Thimerosal (TM) is an ethylmercury (etHg)-containing preservative used in some vaccines despite very limited knowledge on the kinetics and direct interaction/effects in mammals’ tissues after exposure. Thus, this study aimed to evaluate the kinetics of Hg species in mice in a time course analysis after intramuscular injection of TM, by estimating Hg half-lives in blood and tissues. Mice were exposed to one single intramuscular dose of 20 mg of Hg as TM. Blood, brain, heart, kidney and liver were collected at 0.5 hour (h), 1 h, 8 h, 16 h, 144 h, 720 h and 1980 h after TM exposure (n¼4). Hg species in animal tissues were identified and quantified by speciation analysis via liquid chromatography hyphenated with inductively coupled mass spectrometry (LC–ICP-MS). It was found that the transport of etHg from muscle to tissues and its conversion to inorganic Hg (inoHg) occur rapidly. Moreover, the conversion extent is modulated in part by the partitioning between EtHg in plasma and in whole blood, since etHg is rapidly converted in red cells but not in a plasma compartment. Furthermore, the dealkylation mechanism in red cells appears to be mediated by the Fenton reaction (hydroxyl radical formation). Interestingly, after 0.5 h of TM exposure, the highest levels of both etHg and inoHg were found in kidneys (accounting for more than 70% of the total Hg in the animal body), whereas the brain contributed least to the Hg body burden (accounts for o1.0% of total body Hg). Thirty days after TM exposure, most Hg had been excreted while the liver presented the majority of the remaining Hg. Estimated half-lives (in days) were 8.8 for blood, 10.7 for brain, 7.8 for heart, 7.7 for liver and 45.2 for kidney. Taken together, our findings demonstrated that TM (etHg) kinetics more closely approximates Hg2þ than methylmercury (meHg) while the kidney must be considered a potential target for etHg toxicity.

 

Dorea, Jose. “Low-dose mercury exposure in early life: relevance of thimerosal to fetuses, newborns and infants.” Current Medicinal Chemistry 20, no. 32 (2013): 4060-4069.

Abstract

This review explores the different aspects of constitutional factors in early life that modulate toxicokinetics and toxicodynamics of low-dose mercury resulting from acute ethylmercury (etHg) exposure in Thimerosal-containing vaccines (TCV). Major databases were searched for human and experimental studies that addressed issues related to early life exposure to TCV. It can be concluded that: a) mercury load in fetuses, neonates, and infants resulting from TCVs remains in blood of neonates and infants at sufficient concentration and for enough time to penetrate the brain and to exert a neurologic impact and a probable influence on neurodevelopment of susceptible infants; b) etHg metabolism related to neurodevelopmental delays has been demonstrated experimentally and observed in population studies; c) unlike chronic Hg exposure during pregnancy, neurodevelopmental effects caused by acute (repeated/cumulative) early life exposure to TCV-etHg remain unrecognized; and d) the uncertainty surrounding low-dose toxicity of etHg is challenging but recent evidence indicates that avoiding cumulative insults by alkyl-mercury forms (which include Thimerosal) is warranted. It is important to a) maintain trust in vaccines while reinforcing current public health policies to abate mercury exposure in infancy; b) generally support WHO policies that recommend vaccination to prevent and control existing and impending infectious diseases; and c) not confuse the ‘need’ to use a specific ‘product’ (TCV) by accepting as ‘innocuous’ (or without consequences) the presence of a proven ‘toxic alkyl-mercury’ (etHg) at levels that have not been proven to be toxicologically safe.

Dórea, José G. “Integrating experimental (in vitro and in vivo) neurotoxicity studies of low-dose thimerosal relevant to vaccines.” Neurochemical research 36, no. 6 (2011): 927-938.

Abstract 

There is a need to interpret neurotoxic studies to help deal with uncertainties surrounding pregnant mothers, newborns and young children who must receive repeated doses of Thimerosal-containing vaccines (TCVs). This review integrates information derived from emerging experimental studies (in vitro and in vivo) of low-dose Thimerosal (sodium ethyl mercury thiosalicylate). Major databases (PubMed and Web-of-science) were searched for in vitro and in vivo experimental studies that addressed the effects of low-dose Thimerosal (or ethylmercury) on neural tissues and animal behaviour. Information extracted from studies indicates that: (a) activity of low doses of Thimerosal against isolated human and animal brain cells was found in all studies and is consistent with Hg neurotoxicity; (b) the neurotoxic effect of ethylmercury has not been studied with co-occurring adjuvant-Al in TCVs; (c) animal studies have shown that exposure to Thimerosal-Hg can lead to accumulation of inorganic Hg in brain, and that (d) doses relevant to TCV exposure possess the potential to affect human neuro-development. Thimerosal at concentrations relevant for infants’ exposure (in vaccines) is toxic to cultured human-brain cells and to laboratory animals. The persisting use of TCV (in developing countries) is counterintuitive to global efforts to lower Hg exposure and to ban Hg in medical products; its continued use in TCV requires evaluation of a sufficiently nontoxic level of ethylmercury compatible with repeated exposure (co-occurring with adjuvant-Al) during early life.

 

 

Dórea, José G. “Making sense of epidemiological studies of young children exposed to thimerosal in vaccines.” Clinica Chimica Acta 411, no. 21-22 (2010): 1580-1586.

Abstract

Objective

To compare epidemiological studies dealing with neurological issues (compatible with Hg toxicity) linked to exposing newborns and infants to intramuscular doses of preservative-Hg resulting from vaccination with thimerosal-containing vaccines (TCV).

Methods

Major databases were searched for studies that addressed neurodevelopment outcomes other than autism. Eight studies were identified and compared.

Results

Information extracted from the studies done in the USA, the UK, and Italy is important in understanding the complex interplay of variables but insufficient to establish non-toxicity for infants and young children still receiving TCV: a) there is ambiguity in some studies reporting neurodevelopment outcomes that seem to depend on confounding variables; b) the risk of neurotoxicity due to low doses of thimerosal is plausible at least for susceptible infants; c) there is a need to address these issues in less developed countries still using TCV in pregnant mothers, newborns, and young children.

Conclusions

Since the use of TCV is still inevitable in many countries, this increases the need to protect vulnerable infants and promote actions that strengthen neurodevelopment. Developing countries should intensify campaigns that include breastfeeding among efforts to help prime the central nervous system to tolerate exposure to neurotoxic substances, especially thimerosal-Hg.

 

Fagan, D. G., J. S. Pritchard, Thomas W. Clarkson, and M. R. Greenwood. “Organ mercury levels in infants with omphaloceles treated with organic mercurial antiseptic.” Archives of Disease in Childhood 52, no. 12 (1977): 962-964.

Abstract

Samples of fresh and fixed tissues from infants with exomphalos treated by thiomersal application were analyzed for mercury content. The results showed that thiomersal can induce blood and organ levels of organic mercury which are well in excess of the minimum toxic level in adults and fetuses. The analysis of fresh and fixed tissues must be carefully controlled against normal tissues in order to interpret mercury levels accurately.

 

 

Gallagher, Carolyn M., and Melody S. Goodman. “Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997–2002.” Journal of Toxicology and Environmental Health, Part A 73, no. 24 (2010): 1665-1677.

Abstract

Universal hepatitis B vaccination was recommended for U.S. newborns in 1991; however, safety findings are mixed. The association between hepatitis B vaccination of male neonates and parental report of autism diagnosis was determined. This cross-sectional study used weighted probability samples obtained from National Health Interview Survey 1997–2002 data sets. Vaccination status was determined from the vaccination record. Logistic regression was used to estimate the odds for autism diagnosis associated with neonatal hepatitis B vaccination among boys age 3–17 years, born before 1999, adjusted for race, maternal education, and two-parent household. Boys vaccinated as neonates had threefold greater odds for autism diagnosis compared to boys never vaccinated or vaccinated after the first month of life. Non-Hispanic white boys were 64% less likely to have autism diagnosis relative to nonwhite boys. Findings suggest that U.S. male neonates vaccinated with the hepatitis B vaccine prior to 1999 (from vaccination record) had a threefold higher risk for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period. Nonwhite boys bore a greater risk.

 

Geier, Mark R., and David A. Geier. “Neurodevelopmental disorders after thimerosal-containing vaccines: a brief communication.” Experimental biology and medicine 228, no. 6 (2003): 660-664.

Abstract

We were initially highly skeptical that differences in the concentrations of thimerosal in vaccines would have any effect on the incidence rate of neurodevelopmental disorders after childhood immunization. This study presents the first epidemiologic evidence, based upon tens of millions of doses of vaccine administered in the United States, that associates increasing thimerosal from vaccines with neurodevelopmental disorders. Specifically, an analysis of the Vaccine Adverse Events Reporting System (VAERS) database showed statistical increases in the incidence rate of autism (relative risk [RR] = 6.0), mental retardation (RR = 6.1), and speech disorders (RR = 2.2) after thimerosal-containing diphtheria, tetanus, and acellular pertussis (DTaP) vaccines in comparison with thimerosal-free DTaP vaccines. The male/female ratio indicated that autism (17) and speech disorders (2.3) were reported more in males than females after thimerosal containing DTaP vaccines, whereas mental retardation (1.2) was more evenly reported among male and female vaccine recipients. Controls were employed to determine if biases were present in the data, but none were found. It was determined that overall adverse reactions were reported in similar-aged populations after thimerosal-containing DTaP (2.4 ± 3.2 years old) and thimerosal-free DTaP (2.1 ± 2.8 years old) vaccinations. Acute control adverse reactions such as deaths (RR = 1.0), vasculitis (RR = 1.2), seizures (RR = 1.6), ED visits (RR = 1.4), total adverse reactions (RR = 1.4), and gastroenteritis (RR = 1.1) were reported similarly after thimerosal containing and thimerosal-free DTaP vaccines. An association between neurodevelopmental disorders and thimerosal containing DTaP vaccines was found, but additional studies should be conducted to confirm and extend this study.

 

Geier, D. A., P. G. King, L. K. Sykes, and M. R. Geier. “A comprehensive review of mercury provoked autism.” Indian Journal of Medical Research 128, no. 4 (2008): 383.

Abstract

Emerging evidence supports the theory that some autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibility, specifically a reduced ability to excrete mercury (Hg), and exposure to Hg at critical developmental periods. Elemental/inorganic Hg is released into the air/water where it becomes methylated and accumulates in animal tissues. The US population is primarily exposed to methyl-Hg by fish consumption. In addition, many pharmaceuticals have been, and some continue to be, a ubiquitous source of danger because they contain mercurials. Mercurials may be found in drugs for the eye, ear, nose, throat, and skin; in bleaching creams; as preservatives in cosmetics, tooth pastes, lens solutions, vaccines, allergy test and immunotherapy solutions; in antiseptics, disinfectants, and contraceptives; in fungicides and herbicides; in dental fillings and thermometers; and many other products. Hg has been found to cause immune, sensory, neurological, motor, and behavioural dysfunctions similar to traits defining/associated with ASDs, and that these similarities extend to neuroanatomy, neurotransmitters, and biochemistry. Furthermore, a review of molecular mechanisms indicates that Hg exposure can induce death, disorganization and/or damage to selected neurons in the brain similar to that seen in recent ASD brain pathology studies, and this alteration may likely produce the symptoms by which ASDs are diagnosed. Finally, a review of treatments suggests that ASD patients who undergo protocols to reduce Hg and/or its effects show significant clinical improvements in some cases. In conclusion, the overwhelming preponderance of the evidence favours acceptance that Hg exposure is capable of causing some ASDs

 

Geier, David A., Paul G. King, Brian S. Hooker, José G. Dórea, Janet K. Kern, Lisa K. Sykes, and Mark R. Geier. “Thimerosal: clinical, epidemiologic and biochemical studies.” Clinica Chimica Acta 444 (2015): 212-220

Conclusion

The culmination of the research that examines the effects of Thimerosal in humans indicates that it is a poison at minute levels with a plethora of deleterious consequences, even at the levels currently administered in vaccines.

Geier, David A., Sarah K. Jordan, and Mark R. Geier. “The relative toxicity of compounds used as preservatives in vaccines and biologics.” Medical Science Monitor 16, no. 5 (2010): SR21-SR27.

 

Abstract

We were initially highly skeptical that differences in the concentrations of thimerosal in vaccines would have any effect on the incidence rate of neurodevelopmental disorders after childhood immunization. This study presents the first epidemiologic evidence, based upon tens of millions of doses of vaccine administered in the United States, that associates increasing thimerosal from vaccines with neurodevelopmental disorders. Specifically, an analysis of the Vaccine Adverse Events Reporting System (VAERS) database showed statistical increases in the incidence rate of autism (relative risk [RR] = 6.0), mental retardation (RR = 6.1), and speech disorders (RR = 2.2) after thimerosal-containing diphtheria, tetanus, and acellular pertussis (DTaP) vaccines in comparison with thimerosal-free DTaP vaccines. The male/female ratio indicated that autism (17) and speech disorders (2.3) were reported more in males than females after thimerosal containing DTaP vaccines, whereas mental retardation (1.2) was more evenly reported among male and female vaccine recipients. Controls were employed to determine if biases were present in the data, but none were found. It was determined that overall adverse reactions were reported in similar-aged populations after thimerosal-containing DTaP (2.4 ± 3.2 years old) and thimerosal-free DTaP (2.1 ± 2.8 years old) vaccinations. Acute control adverse reactions such as deaths (RR = 1.0), vasculitis (RR = 1.2), seizures (RR = 1.6), ED visits (RR = 1.4), total adverse reactions (RR = 1.4), and gastroenteritis (RR = 1.1) were reported similarly after thimerosal containing and thimerosal-free DTaP vaccines. An association between neurodevelopmental disorders and thimerosal containing DTaP vaccines was found, but additional studies should be conducted to confirm and extend this study.

 

Geier, David A., Janet K. Kern, Paul G. King, Lisa K. Sykes, and Mark R. Geier. “A case-control study evaluating the relationship between Thimerosal-containing Haemophilus influenzae Type b vaccine administration and the risk for a pervasive developmental disorder diagnosis in the United States.” Biological trace element research 163, no. 1-2 (2015): 28-38.

Abstract

Thimerosal is an organic mercury (Hg)-containing compound (49.55 % Hg by weight) historically added to many multi-dose vials of vaccine as a preservative. A hypothesis testing case-control study evaluated automated medical records in the Vaccine Safety Datalink (VSD) for organic Hg exposure from Thimerosal in Haemophilus influenzae type b (Hib)-containing vaccines administered at specific times within the first 15 months of life among subjects diagnosed with pervasive developmental disorder (PDD) (n = 534) in comparison to controls. The generally accepted biologically non-plausible linkage between Thimerosal exposure and subsequent diagnosis of febrile seizure (n = 5886) was examined as a control outcome. Cases diagnosed with PDD received significantly more organic Hg within the first 6 months of life (odds ratio (OR) = 1.97, p < 0.001) and first 15 months of life (OR = 3.94, p < 0.0001) than controls, whereas cases diagnosed with febrile seizure were no more likely than controls to have received increased organic Hg. On a per microgram of organic Hg basis, cases diagnosed with a PDD in comparison to controls were at significantly greater odds (OR = 1.0197, p < 0.0001) of receiving increasing organic Hg exposure within the first 15 months of life, whereas cases diagnosed febrile seizure were no more likely than controls (OR = 0.999, p > 0.20) to have received increasing organic Hg exposure within the first 15 months of life. Routine childhood vaccination is an important public health tool to reduce the morbidity and mortality associated with infectious diseases, but the present study provides new epidemiological evidence of a significant relationship between increasing organic Hg exposure from Thimerosal-containing vaccines and the subsequent risk of PDD diagnosis in males and females.

 

Geier, David A., Paul G. King, Brian S. Hooker, José G. Dórea, Janet K. Kern, Lisa K. Sykes, and Mark R. Geier. “Thimerosal: clinical, epidemiologic and biochemical studies.” Clinica Chimica Acta 444 (2015): 212-220.

Abstract – Conclusion

The culmination of the research that examines the effects of Thimerosal in humans indicates that it is a poison at minute levels with a plethora of deleterious consequences, even at the levels currently administered in vaccines.

 

Geier, David A., and Mark R. Geier. “A meta-analysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 in the United States.” Neuroendocrinology Letters 27, no. 4 (2006): 401-413.

 

Abstract

BACKGROUND: Thimerosal is an ethylmercury-containing compound (49.6% mercury by weight) used as at the preservative level in vaccines (0.005% to 0.01%). METHODS: Statistical modeling in a meta-analysis epidemiological assessment of the Vaccine Adverse Event Reporting System (VAERS) for neurodevelopment disorders (NDs) reported following Diphtheria-Tetanus-whole-cell-Pertussis (DTP) vaccines in comparison to Diphtheria-Tetanus-whole-cell-Pertussis-Haemophilus Influenzae Type b (DTPH) vaccines (administered: 1994–1997) and following Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP), vaccines in comparison to Thimerosal-free DTaP vaccines (administered: 1997–2000), was undertaken. RESULTS: Significantly increased adjusted (sex, age, vaccine type, vaccine manufacturer) risks of autism, speech disorders, mental retardation, personality disorders, thinking abnormalities, ataxia, and NDs in general, with minimal systematic error or confounding, were associated with TCV exposure. CONCLUSION: It is clear from the results of the present epidemiological study and other recently published data associating mercury exposure with childhood NDs, additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially from Thimerosal-containing vaccines.

 

Geier, David A., Janet K. Kern, Paul G. King, Lisa K. Sykes, and Mark R. Geier. “The risk of neurodevelopmental disorders following a Thimerosal-preserved DTaP formulation in comparison to its Thimerosal-reduced formulation in the Vaccine Adverse Event Reporting System (VAERS).” J Biochem Pharmacol Res 2, no. 2 (2014): 64-73.

Abstract

Mercury (Hg) exposure in human infants and fetuses has long been known to be significantly associated with neurodevelopmental disorders (NDs). Thimerosal (49.55% Hg by weight) is an ethyl-Hg containing compound added to many childhood vaccines as a preservative. A hypothesis testing case-control study was undertaken in the Vaccine Adverse Event Reporting System (VAERS) database (updated through September 2013) by examining 5,591 adverse event reports entered following Thimerosal-preserved Diphtheria-Tetanus-acellular-Pertussis (DTaP) (TripediaTM, Sanofi) administered from 1997-1999 (exposed) and following Thimerosal-reduced DTaP (TripediaTM, Sanofi) administered from 2004-2006 (unexposed). Cases were defined as individuals with adverse event reports with the outcomes of autism, speech disorder, mental retardation, or ND (at least of one these aforementioned specific outcomes being mentioned in the adverse event report). Controls were defined as individuals with adverse event reports without any mention of the specific case outcomes examined. Cases reported with the outcomes of autism (odds ratio = 7.67, p < 0.0001), speech disorders (odds ratio = 3.49, p < 0.02), mental retardation (odds ratio = 8.73, p < 0.0005), or ND (odds ratio = 4.82, p < 0.0001) were significantly more likely than controls to have received Thimerosalpreserved DTaP vaccine (exposed) in comparison to Thimerosal-reduced DTaP vaccine (unexposed). Though routine childhood vaccination is considered an important public health tool to reduce the morbidity and mortality associated with certain infectious diseases, this study supports a significant relationship between increased organic-Hg exposure from Thimerosal-preserved childhood vaccines and the child’s subsequent risk of a ND diagnosis.

 

Geier, David A., Brian S. Hooker, Janet K. Kern, Paul G. King, Lisa K. Sykes, and Mark R. Geier. “A two-phase study evaluating the relationship between Thimerosal-containing vaccine administration and the risk for an autism spectrum disorder diagnosis in the United States.” Translational Neurodegeneration 2, no. 1 (2013): 25.

Abstract

A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg) exposure from thimerosal-containing (49.55% Hg by weight) vaccines on the risk of neurodevelopmental disorders (NDs). Automated medical records were examined to identify cases and controls enrolled from their date-of-birth (1991–2000) in the Vaccine Safety Datalink (VSD) project. ND cases were diagnosed with pervasive developmental disorder (PDD), specific developmental delay, tic disorder or hyperkinetic syndrome of childhood. In addition, putative non-thimerosal-related outcomes of febrile seizure, failure to thrive and cerebral degenerations were examined. The cumulative total dose of Hg exposure from thimerosal-containing hepatitis B vaccine (T-HBV) administered within the first six months of life was calculated. On a per microgram of organic-Hg basis, PDD (odds ratio (OR) = 1.054), specific developmental delay (OR = 1.035), tic disorder (OR = 1.034) and hyperkinetic syndrome of childhood (OR = 1.05) cases were significantly more likely than controls to receive increased organic-Hg exposure. By contrast, none of the non-thimerosal related outcomes were significantly more likely than the controls to have received increased organic-Hg exposure. Routine childhood vaccination may be an important public health tool to reduce infectious disease-associated morbidity/mortality, but the present study significantly associates organic-Hg exposure from T-HBV with an increased risk of an ND diagnosis.

 

Geier, David A., Lisa K. Sykes, and Mark R. Geier. “A review of Thimerosal (Merthiolate) and its ethylmercury breakdown product: specific historical considerations regarding safety and effectiveness.” Journal of Toxicology and Environmental Health, Part B 10, no. 8 (2007): 575-596.

Abstract

Thimerosal (Merthiolate) is an ethylmercury-containing pharmaceutical compound that is 49.55% mercury and that was developed in 1927. Thimerosal has been marketed as an antimicrobial agent in a range of products, including topical antiseptic solutions and antiseptic ointments for treating cuts, nasal sprays, eye solutions, vaginal spermicides, diaper rash treatments, and perhaps most importantly as a preservative in vaccines and other injectable biological products, including Rho(D)-immune globulin preparations, despite evidence, dating to the early 1930s, indicating Thimerosal to be potentially hazardous to humans and ineffective as an antimicrobial agent. Despite this, Thimerosal was not scrutinized as part of U.S. pharmaceutical products until the 1980s, when the U.S. Food and Drug Administration finally recognized its demonstrated ineffectiveness and toxicity in topical pharmaceutical products, and began to eliminate it from these. Ironically, while Thimerosal was being eliminated from topicals, it was becoming more and more ubiquitous in the recommended immunization schedule for infants and pregnant women. Furthermore, Thimerosal continues to be administered, as part of mandated immunizations and other pharmaceutical products, in the United States and globally. The ubiquitous and largely unchecked place of Thimerosal in pharmaceuticals, therefore, represents a medical crisis.

 

Guzzi, Gianpaolo, Paolo D. Pigatto, Francesco Spadari, and Caterina AM La Porta. “Effect of thimerosal, methylmercury, and mercuric chloride in Jurkat T Cell Line.” Interdisciplinary toxicology 5, no. 3 (2012): 159-161.

Abstract

Mercury is a ubiquitous environmental toxicant that causes a wide range of adverse health effects in humans. Three forms of mercury exist: elemental, inorganic and organic. Each of them has its own profile of toxicity. The aim of the present study was to determine the effect of thimerosal, a topical antiseptic and preservative in vaccines routinely given to children, methyl mercury, and mercuric chloride on cellular viability measured by MTT in Jurkat T cells, a human T leukemia cell line. The treatment of Jurkat T cells with thimerosal caused a significant decrease in cellular viability at 1 μM (25%, p<0.05; IC50: 10 μM). Methyl mercury exhibited a significant decrease in cellular viability at 50 μM (33%, p<0.01; IC50: 65 μM). Mercuric chloride (HgCl2) did not show any significant change in cellular survival. Our findings showed that contrary to thimerosal and methyl mercury, mercuric chloride did not modify Jurkat T cell viability.

 

HEINONEN, OLLI P., SAMUEL SHAPIRO, RICHARD R. MONSON, STUART C. HARTZ, LYNN ROSENBERG, and DENNIS SLONE. “Immunization during pregnancy against poliomyelitis and influenza in relation to childhood malignancy.” International Journal of Epidemiology 2, no. 3 (1973): 229-236.

 

Abstract

In a follow-up study of 50,897 pregnancies, poliomyelitis and influenza immunizations, and viral infections were evaluated as possible risk factors for the development of malignancies in the offspring born between 1959 and 1966. Ascertainment of malignancies was based on clinical follow-up during the first year of life and on mortality experience covering the first four years of life. In 18, 342 children whose mothers were vaccinated during pregnancy with killed polio vaccine there were 14 malignancies (7.6 per 10,000) and in 32, 555 non-exposed children there were 10 (3.1 per 10,000). In the vaccinated group, nine malignancies occurred in children whose mothers were immunized during the first four lunar months of pregnancy (13.2 per 10,000). Time clustering of administration of the vaccine was evident in mothers whose children developed malignancies. There were seven tumours derived from neural tissue in the exposed children (3.8 per 10,000) and one in the non-exposed children (0.3 per 10,000). Elimination of three microscopic tumours reduced the overall rates in the exposed and non-exposed groups to 6.5 and 2.8 per 10,000, respectively. There was no evidence of an excess of malignancies in children exposed in utero to attenuated live polio vaccine, to influenza vaccine, or to spontaneous viral infections.

 

Hooker, Brian, Janet Kern, David Geier, Boyd Haley, Lisa Sykes, Paul King, and Mark Geier. “Methodological issues and evidence of malfeasance in research purporting to show Thimerosal in vaccines is safe.” BioMed research international 2014 (2014).

Abstract

There are over 165 studies that have focused on Thimerosal, an organic-mercury (Hg) based compound, used as a preservative in many childhood vaccines, and found it to be harmful. Of these, 16 were conducted to specifically examine the effects of Thimerosal on human infants or children with reported outcomes of death; acrodynia; poisoning; allergic reaction; malformations; auto-immune reaction; Well’s syndrome; developmental delay; and neurodevelopmental disorders, including tics, speech delay, language delay, attention deficit disorder, and autism. In contrast, the United States Centers for Disease Control and Prevention states that Thimerosal is safe and there is “no relationship between Thimerosal containing vaccines and autism rates in children.” This is puzzling because, in a study conducted directly by CDC epidemiologists, a 7.6-fold increased risk of autism from exposure to Thimerosal during infancy was found. The CDC’s current stance that Thimerosal is safe and that there is no relationship between Thimerosal and autism is based on six specific published epidemiological studies coauthored and sponsored by the CDC. The purpose of this review is to examine these six publications and analyze possible reasons why their published outcomes are so different from the results of investigations by multiple independent research groups over the past 75+ years.

 

Kern, Janet K., Boyd E. Haley, David A. Geier, Lisa K. Sykes, Paul G. King, and Mark R. Geier. “Thimerosal exposure and the role of sulfation chemistry and thiol availability in autism.” International Journal of Environmental Research and Public Health 10, no. 8 (2013): 3771-3800.

Abstract

Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg by weight) that has been, and continues to be, used as a preservative in many childhood vaccines, particularly in developing countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been identified. Importantly, the emergence of ASD symptoms post-6 months of age temporally follows the administration of many childhood vaccines. The purpose of the present critical review is provide mechanistic insight regarding how limited thiol availability, abnormal sulfation chemistry, and decreased GSH reserve capacity in children with an ASD could make them more susceptible to the toxic effects of TM routinely administered as part of mandated childhood immunization schedules

 

Khandke, Lakshmi, Cindy Yang, Ksenia Krylova, Kathrin U. Jansen, and Abbas Rashidbaigi. “Preservative of choice for Prev (e) nar 13™ in a multi-dose formulation.” Vaccine 29, no. 41 (2011): 7144-7153.

Abstract

Development of a Prev(e)nar 13™ multi-dose vaccine, in support of vaccinating populations against pneumococcal disease, required the addition of a preservative to the vaccine formulation that met antimicrobial effectiveness tests based on the European Pharmacopoeia (EP) requirements, including deliberate multiple challenge studies and recommendation by the WHO Open Vial Policy. In this study, the antimicrobial effectiveness of several preservatives in Prev(e)nar 13™ formulations was evaluated. A Prev(e)nar 13™ formulation containing 2-Phenoxyethanol (2-PE) at a concentration of 5.0 mg/dose was stable and met EP recommended criteria for antimicrobial effectiveness tests when the formulation was kept over a 30-month period. In contrast, a recommended dose of Thimerosal, as a comparator, or other preservatives did not meet EP antimicrobial effectiveness acceptance criteria. The rate of growth inhibition of Thimerosal compared to 2-PE on Staphylococcus aureus, a resilient organism in these tests, was significantly slower in single and multi-challenge studies. These results indicate that 2-PE provides a superior antimicrobial effectiveness over Thimerosal for this vaccine formulation.

 

Koh, Karen J., Lachlan Warren, Lynette Moore, Craig James, and Geoffrey N. Thompson. “Wells’ syndrome following thiomersal‐containing vaccinations.” Australasian journal of dermatology 44, no. 3 (2003): 199-202.

Summary

A 3½‐year‐old boy presented on three occasions with painful, itchy, oedematous plaques on his limbs. On two occasions he had received hepatitis B vaccination 11–13 days previously, and on the third occasion received triple antigen (DTP) vaccination 10 days earlier. Skin biopsy revealed a prominent infiltrate of eosinophils involving the entire thickness of the dermis. In addition, there were prominent ‘flame figures’ consisting of eosinophilic necrotic collagen surrounded by granular basophilic debris. The clinical and histological pictures were consistent with Wells’ syndrome. The eruption settled on the second and third occasions with 0.1% mometasone furoate cream. Subsequent patch testing showed 2+ reaction to preservative thiomersal at 96 hours. This is the first description of Wells’ syndrome with typical clinical and histopathological features associated with thiomersal in two different vaccines.

 

Marques, Rejane C., José G. Dórea, Márlon F. Fonseca, Wanderley R. Bastos, and Olaf Malm. “Hair mercury in breast-fed infants exposed to thimerosal-preserved vaccines.” 

european Journal of Pediatrics 166, no. 9 (2007): 935-941.

Abstract 

Because of uncertainties associated with a possible rise in neuro-developmental deficits among vaccinated children, thimerosal-preserved vaccines have not been used since 2004 in the USA (with the exception of thimerosalcontaining influenza vaccines which are routinely recommended for administration to pregnant women and children), and the EU but are widely produced and used in other countries. We investigated the impact of thimerosal on the total Hg in hair of 82 breast-fed infants during the first 6 months of life. The infants received three doses of the hepatitis-B vaccine (at birth, 1 and 6 months) and three DTP (diphtheria, tetanus, and pertussis) doses at 2, 4 and 6 months, according to the immunization schedule recommended by the Ministry of Health of Brazil. The thimerosal in vaccines provided an ethylmercury (EtHg) exposure of 25 μgHg at birth, 30, 60 and 120 days, and 50 μgHg at 180 days. The exposure to vaccine-EtHg represents 80% of that expected from total breast milk-Hg in the first month but only 40% of the expected exposure integrated in the 6 months of breastfeeding. However, the Hg exposure corrected for body weight at the day of immunization was much higher from thimerosal- EtHg (5.7 to 11.3 μgHg/kg b.w.) than from breastfeeding (0.266 μgHg/kg b.w.). While mothers showed a relative decrease (−57%) in total hair-Hg during the 6 months lactation there was substantial increase in the infant’s hair-Hg (446%). We speculate that dose and parenteral mode of thimerosal-EtHg exposure modulated the relative increase in hair-Hg of breast-fed infants at 6 months of age.

 

Morton, Harry E., Leon L. North, and Frank B. Engley. “The bacteriostatic and bactericidal actions of some mercurial compounds on hemolytic streptococci: in vivo and in vitro studies.” Journal of the American Medical Association 136, no. 1 (1948): 37-41.

 

Abstract

Two outbreaks of group A streptococcal abscesses following receipt of diphtheria-tetanus toxoid-pertussis (DTP) vaccine from different manufacturers were reported to the Centers for Disease Control (CDC) in 1982. The clustering of the immunization times of cases, the isolation of the same serotype of Streptococcus from all cases in each outbreak, and the absence of reported abscesses associated with receipt of the same lots of vaccine in other regions of the country, suggest that each outbreak was probably caused by contamination of a single 15-dose vial of vaccine. The preservative thimerosal was present within acceptable limits in unopened vials from the same lot of DTP vaccine in each outbreak. Challenge studies indicate that a strain of Streptococcus from one of the patients can survive up to 15 days in DTP vaccine at 4°C. Contamination of vials during manufacturing would have required survival of streptococci for a minimum of 8 months. Preservatives in multidose vaccine vials do not prevent short-term bacterial contamination. Options to prevent further clusters of streptococcal abscesses are discussed. The only feasible and cost-effective preventive measure now available is careful attention to sterile technique when administering vaccine from multidose vials.

 

Mrozek-Budzyn, Dorota, Renata Majewska, Agnieszka Kieltyka, and Malgorzata Augustyniak. “Neonatal exposure to Thimerosal from vaccines and child development in the first 3 years of life.” Neurotoxicology and Teratology 34, no. 6 (2012): 592-597.

Abstract 

Neonatal exposure to Thimerosal from vaccines and child development were examined. Neonatal exposure to Thimerosal affects psychomotor development. No association was found between Thimerosal exposure and mental tests scores.

 

Patrizi, Annalisa, Laura Rizzoli, Colombina Vincenzi, Pompilio Trevisi, and Antonella Tosti. “Sensitization to thimerosal in atopic children.” Contact Dermatitis 40, no. 2 (1999): 94-97.

 

Abstract

Thimerosal is an organic mercurial compound widely used as a preservative in vaccines, eyedrops, and contact lens cleaning and storage solutions. 5 infants, 2 female and 3 male, ranging in age from 7 to 28 months and affected by atopic dermatitis (AD) diagnosed according to the Hanifin and Rajka criteria, experienced an exacerbation of their clinical condition 2–10 days after mandatory vaccinations with vaccines containing thimerosal. Cutaneous lesions of nummular eczema appeared on the trunk, limbs and face. All patients were patch tested with serial dilutions of thimerosal in petrolatum. A positive patch test reaction to thimerosal 0.1% pet. was observed in all 5 children. 3 of them also showed a positive reaction at 0.01% and 0.05% pet. Despite their thimerosal‐hypersensitivity, all children completed the entire series of mandatory vaccinations, care being taken to use different needles for injection and aspiration of the vaccine. The 2‐year follow‐up did not reveal other episodes of exacerbation of the AD after vaccination. The present study confirms the high frequency of sensitization to thimerosal in atopic children and suggests that vaccination can cause clinical symptoms in sensitized children. Nevertheless, sensitization to thimerosal does not prevent children from continuing with mandatory vaccinations.

 

Pichichero, Michael E., Angela Gentile, Norberto Giglio, Veronica Umido, Thomas Clarkson, Elsa Cernichiari, Grazyna Zareba et al. “Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines.” Pediatrics 121, no. 2 (2008): e208-e214.

Abstract

The blood half-life of intramuscular ethyl mercury from thimerosal in vaccines in infants is substantially shorter than that of oral methyl mercury in adults. Increased mercury levels were detected in stools after vaccination, suggesting that the gastrointestinal tract is involved in ethyl mercury elimination. Because of the differing pharmacokinetics of ethyl and methyl mercury, exposure guidelines based on oral methyl mercury in adults may not be accurate for risk assessments in children who receive thimerosal-containing vaccines.

 

Rose, Shannon, Rebecca Wynne, Richard E. Frye, Stepan Melnyk, and S. Jill James.“Increased susceptibility to ethylmercury-induced mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines.” Journal of toxicology 2015 (2015).

 

Abstract

The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction.

 

Sharpe, Martyn A., Taylor L. Gist, and David S. Baskin. “B-lymphocytes from a population of children with autism spectrum disorder and their unaffected siblings exhibit hypersensitivity to thimerosal.” Journal of Toxicology 2013 (2013).

Abstract

The role of thimerosal containing vaccines in the development of autism spectrum disorder (ASD) has been an area of intense debate, as has the presence of mercury dental amalgams and fish ingestion by pregnant mothers. We studied the effects of thimerosal on cell proliferation and mitochondrial function from B-lymphocytes taken from individuals with autism, their nonautistic twins, and their nontwin siblings. Eleven families were examined and compared to matched controls. B-cells were grown with increasing levels of thimerosal, and various assays (LDH, XTT, DCFH, etc.) were performed to examine the effects on cellular proliferation and mitochondrial function. A subpopulation of eight individuals (4 ASD, 2 twins, and 2 siblings) from four of the families showed thimerosal hypersensitivity, whereas none of the control individuals displayed this response. The thimerosal concentration required to inhibit cell proliferation in these individuals was only 40% of controls. Cells hypersensitive to thimerosal also had higher levels of oxidative stress markers, protein carbonyls, and oxidant generation. This suggests certain individuals with a mild mitochondrial defect may be highly susceptible to mitochondrial specific toxins like the vaccine preservative thimerosal.

 

Stetler, Harrison C., Paul L. Garbe, Diane M. Dwyer, Richard R. Facklam, Walter A. Orenstein, Gary R. West, K. Joyce Dudley, and Alan B. Bloch. “Outbreaks of group A streptococcal abscesses following diphtheria-tetanus toxoid-pertussis vaccination.” Pediatrics 75, no. 2 (1985): 299-303.

Abstract

Two outbreaks of group A streptococcal abscesses following receipt of diphtheria-tetanus toxoid-pertussis (DTP) vaccine from different manufacturers were reported to the Centers for Disease Control (CDC) in 1982. The clustering of the immunization times of cases, the isolation of the same serotype of Streptococcus from all cases in each outbreak, and the absence of reported abscesses associated with receipt of the same lots of vaccine in other regions of the country, suggest that each outbreak was probably caused by contamination of a single 15-dose vial of vaccine. The preservative thimerosal was present within acceptable limits in unopened vials from the same lot of DTP vaccine in each outbreak. Challenge studies indicate that a strain of Streptococcus from one of the patients can survive up to 15 days in DTP vaccine at 4°C. Contamination of vials during manufacturing would have required survival of streptococci for a minimum of 8 months. Preservatives in multidose vaccine vials do not prevent short-term bacterial contamination. Options to prevent further clusters of streptococcal abscesses are discussed. The only feasible and cost-effective preventive measure now available is careful attention to sterile technique when administering vaccine from multidose vials.

 

Stratton, Kathleen, Alicia Gable, Marie C. McCormick, and Institute of Medicine (US) Immunization Safety Review Committee. “Thimerosal-containing vaccines and neurodevelopmental disorders.” In Immunization Safety Review: Thimerosal-Containing Vaccines and Neurodevelopmental Disorders. National Academies Press (US), 2001.

Conclusion

The committee sees significant reasons for continued public health attention to concerns about thimerosal exposure and neurodevelopmental disorders. The committee considered the burden of the potential adverse neurodevelopmental outcomes and of vaccine-preventable disorders, and it considered the extent of continued use of thimerosal-containing products. Therefore, the committee considers the presence of thimerosal in pediatric vaccines to be a significant issue, and it supports precautionary public health efforts to reduce mercury exposure. It is important to resolve whether or not children might have experienced neurodevelopmental disorders because of an unrecognized incremental mercury burden from thimerosal given the responsibility for assuring the safest vaccines possible.

 

Trümpler, Stefan, Wiebke Lohmann, Björn Meermann, Wolfgang Buscher, Michael Sperling, and Uwe Karst. “Interaction of thimerosal with proteins—ethylmercury adduct formation of human serum albumin and β-lactoglobulin A.” 

Metallomics 1, no. 1 (2009): 87-91.

 

Abstract

The interaction of thimerosal, an ethylmercury-containing bactericide and fungicide used as preservative in vaccines and other drugs, with free thiols in proteins has been investigated using gradient reversed phase liquid chromatography (LC) with inductively coupled plasma mass spectrometry (ICP-MS) and electrospray mass spectrometry (ESI-MS) detection. As model proteins, β-lactoglobulin A (18.4 kDa) from bovine milk and human serum albumin (66.5 kDa) have been used. Physiological conditions upon an intravenous injection of thimerosal-containing drugs were mimicked. The formation of ethylmercury–protein adducts was proved and the identification of the binding site of ethylmercury, a free thiol residue in the peptide T13 was achieved after tryptic digestion of β-lactoglobulin A.

 

Trümpler, Stefan, Björn Meermann, Sascha Nowak, Wolfgang Buscher, Uwe Karst, and Michael Sperling. “In vitro study of thimerosal reactions in human whole blood and plasma surrogate samples.” Journal of Trace Elements in Medicine and Biology 28, no. 2 (2014): 125-130.

Abstract

Because of its bactericidal and fungicidal properties, thimerosal is used as a preservative in drugs and vaccines and is thus deliberately injected into the human body. In aqueous environment, it decomposes into thiosalicylic acid and the ethylmercury cation. This organomercury fragment is a potent neurotoxin and is suspected to have similar toxicity and bioavailability like the methylmercury cation. In this work, human whole blood and physiological simulation solutions were incubated with thimerosal to investigate its behaviour and binding partners in the blood stream. Inductively coupled plasma with optical emission spectrometry (ICP-OES) was used for total mercury determination in different blood fractions, while liquid chromatography (LC) coupled to electrospray ionisation time-of-flight (ESI-TOF) and inductively coupled plasma-mass spectrometry (ICP-MS) provided information on the individual mercury species in plasma surrogate samples. Analogous behaviour of methylmercury and ethylmercury species in human blood was shown and an ethylmercury-glutathione adduct was identified.

 

Young, Heather A., David A. Geier, and Mark R. Geier. “Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink.” Journal of the neurological sciences 271, no. 1-2 (2008): 110-118.

Abstract

The study evaluated possible associations between neurodevelopmental disorders (NDs) and exposure to mercury (Hg) from Thimerosalcontaining vaccines (TCVs) by examining the automated Vaccine Safety Datalink (VSD). A total of 278,624 subjects were identified in birth cohorts from 1990–1996 that had received their first oral polio vaccination by 3 months of age in the VSD. The birth cohort prevalence rate of medically diagnosed International Classification of Disease, 9th revision (ICD-9) specific NDs and control outcomes were calculated. Exposures to Hg from TCVs were calculated by birth cohort for specific exposure windows from birth-7 months and birth-13 months of age. Poison regression analysis was used to model the association between the prevalence of outcomes and Hg doses from TCVs. Consistent significantly increased rate ratios were observed for autism, autism spectrum disorders, tics, attention deficit disorder, and emotional disturbances with Hg exposure from TCVs. By contrast, none of the control outcomes had significantly increased rate ratios with Hg exposure from TCVs. Routine childhood vaccination should be continued to help reduce the morbidity and mortality associated with infectious diseases, but efforts should be undertaken to remove Hg from vaccines. Additional studies should be conducted to further evaluate the relationship between Hg exposure and NDs. 

 

Zimmermann, Luciana T., Danúbia B. Santos, Aline A. Naime, Rodrigo B. Leal, José G. Dórea, Fernando Barbosa Jr, Michael Aschner, João Batista T. Rocha, and Marcelo Farina. “Comparative study on methyl-and ethylmercury-induced toxicity in C6 glioma cells and the potential role of LAT-1 in mediating mercurial-thiol complexes uptake.” 

Neurotoxicology 38 (2013): 1-8.

Abstract

Various forms of mercury possess different rates of absorption, metabolism and excretion, and consequently, toxicity. Methylmercury (MeHg) is a highly neurotoxic organic mercurial. Human exposure is mostly due to ingestion of contaminated fish. Ethylmercury (EtHg), another organic mercury compound, has received significant toxicological attention due to its presence in thimerosal-containing vaccines. This study was designed to compare the toxicities induced by MeHg and EtHg, as well as by their complexes with cysteine (MeHg-S-Cys and EtHg-S-Cys) in the C6 rat glioma cell line. MeHg and EtHg caused significant (p < 0.0001) decreases in cellular viability when cells were treated during 30 min with each mercurial following by a washing period of 24 h (EC50 values of 4.83 and 5.05 μM, respectively). Significant cytotoxicity (p < 0.0001) was also observed when cells were treated under the same conditions with MeHg-S-Cys and EtHg-S-Cys, but the respective EC50 values were significantly increased (11.2 and 9.37 μM). l-Methionine, a substrate for the l-type neutral amino acid carrier transport (LAT) system, significantly protected against the toxicities induced by both complexes (MeHg-S-Cys and EtHg-S-Cys). However, no protective effects of l-methionine were observed against MeHg and EtHg toxicities. Corroborating these findings, l-methionine significantly decreased mercurial uptake when cells were exposed to MeHg-S-Cys (p = 0.028) and EtHg-S-Cys (p = 0.023), but not to MeHg and EtHg. These results indicate that the uptake of MeHg-S-Cys and EtHg-S-Cys into C6 cells is mediated, at least in part, through the LAT system, but MeHg and EtHg enter C6 cells by mechanisms other than LAT system.