Introduction
What is thimerosal?
Chemical structure and properties
Historical and current uses
Pharmacokinetics and metabolism
Toxicological Profile
Safety assessments and guidelines
Public controversy and communication
Conclusions
References
Further reading
Decades of scientific investigation reveal that thimerosal, a widely used vaccine preservative, is safe and does not cause neurotoxicity, yet public controversy persists, underscoring the need for transparent science communication in global immunization efforts.
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Introduction
This article addresses ongoing concerns surrounding the use of thimerosal in vaccines by examining its chemical properties, biological activity, and safety record, thereby providing an evidence-based understanding of its role in modern medicine and recommendations for the future.
What is thimerosal?
Thimerosal, often referred to by its brand name Merthiolate, is an organomercury compound used for its antiseptic and antifungal properties.1 Thimerosal can be found in various medical applications, some of which include immunoglobulin (Ig) preparations, skin test antigens, and antivenins.
Despite being used in vaccines since the 1930s, thimerosal has been heavily scrutinized by the public, especially since the early 2000s. Several agencies and news articles have raised concerns about the frequent use of thimerosal as a vaccine preservative, stating mercury exposure and cautioning against its use, especially for children and pregnant or lactating mothers.2
Chemical structure and properties
Thimerosal is the trade name for sodium ethylmercurithiosalicylate, an ethylmercury-based organometallic compound containing a thiosalicylate group. First discovered and patented by Morris Kharasch in 1928, thimerosal was developed in an effort to expand its antimicrobial and antifungal properties to prevent contamination in biological and pharmaceutical products.1
Thimerosal breaks down into ethylmercury and thiosalicylate, both of which have been validated as relatively safe for pharmacological use. Nevertheless, ethylmercury remains the primary source of ongoing debates about thimerosal.1-3
Although chemically similar to methylmercury, a known environmental toxin that causes mercury poisoning, ethylmercury differs significantly in its biological metabolism, tissue retention, and excretion rate.3 These chemical distinctions are fundamental to understanding the safety profile of this preservative.
Historical and current uses
Thimerosal has been used as a preservative in a wide range of biological products since its invention. The antimicrobial properties of thimerosal have also been utilized in the manufacturing of household products, such as ophthalmic solutions, nasal sprays, and vaccines.1,2
Historically, thimerosal was included in the hepatitis B, diphtheria-tetanus-pertussis (DTP), and Haemophilus influenzae type B (Hib) pediatric vaccines. However, public concerns regarding potential mercury exposure led health agencies in the United States and Europe to recommend removing or reducing thimerosal from childhood vaccines as a precautionary measure in the early 2000s.4
Today, thimerosal is still used in some influenza vaccines, particularly those in multi-dose formulations. However, most routine pediatric vaccines in countries like the U.S. and Canada are now thimerosal-free or contain only trace amounts of this preservative.5
Verify: Some flu vaccines contain a small amount of ethyl-mercury. Here's why
Pharmacokinetics and metabolism
Thimerosal is typically administered through an intramuscular injection, after which it is rapidly metabolized into methylmercury, which is then absorbed into the bloodstream and distributed throughout the body. Unlike methylmercury, which accumulates in tissues and has an extended biological half-life of 40-50 days, ethylmercury is cleared between four and 10 days after exposure.6
Ethylmercury is primarily eliminated from the body through fecal excretion, with only a small proportion retained in the brain or other tissues. Several studies comparing ethylmercury to methylmercury have demonstrated that ethylmercury exposure is associated with lower blood and brain mercury concentrations over time, which significantly reduces the potential for toxicity.7
These lower time-associated ethylmercury accumulations were independently validated across both non-human primate and human infants. Among infants, a maximum mean post-vaccination blood ethylmercury concentration of five nanograms per milliliter (ng/mL) has been reported, which is significantly lower than the U.S. Environmental Protection Agency (EPA) reference dose of 5.8 ng/mL for methylmercury, further confirming the safety of thimerosal.6-8
Toxicological Profile
Methylmercury is a highly toxic form of mercury that is often found in industrial pollution and contaminated fish.5
Comparisons between the toxicological profiles of methylmercury and ethylmercury reveal that methylmercury can cause severe physiological effects, particularly neurodevelopmental issues, including toxicity-induced mortality. Importantly, ethylmercury has rarely been linked to adverse neurological outcomes or death, with no evidence supporting the neurotoxic effects of ethylmercury at the levels used in approved vaccines.
To date, multiple thimerosal-containing vaccines have been administered to large cohorts of infants based on the standard immunization schedule in the 1990s. Among these vaccinated individuals, estimated mercury exposure remained below safety thresholds recommended by the U.S. Food and Drug Administration (FDA) and World Health Organization (WHO).8,9
Unintended, high-dose thimerosal exposure, such as through accidental ingestion or inappropriate injection of thimerosal-containing compounds, has the potential to cause immediate toxicity. These scenarios are rare and have not been observed in clinical settings.8
Safety assessments and guidelines
Several major global health organizations, including the U.S. Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO, and the Food and Drug Administration (FDA have conducted independent reviews on the safety of thimerosal. These investigations have consistently reported no evidence of harm caused by thimerosal in vaccines, even among large cohorts of over one thousand children.5,6,8
A series of epidemiological studies reviewed by the U.S. Institute of Medicine (IOM), which is currently known as the National Academy of Medicine (NAM), similarly concluded that there is no credible evidence linking thimerosal to autism spectrum disorders or other developmental delays10.
These extensive studies have led the WHO to endorse the use of thimerosal in multi-dose vials, particularly for low- and middle-income countries where single-dose vials are not economically feasible. The inclusion of thimerosal in these vaccines allows for cost-effective vaccine delivery while maintaining stringent safety standards by preventing microbial contamination.8
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Public controversy and communication
Thimerosal remains a controversial topic in public health and vaccine safety discourse due to its purported association with autism. This claim was popularized in the late 1990s and early 2000s; however, multiple large-scale investigations have refuted these associations.11
Unfortunately, the legacy of this controversy has had a significant impact on vaccine confidence. Misinformation, often amplified by online platforms and celebrity endorsements, has also contributed to persistent public skepticism about the potential harm of vaccine ingredients.2
The devastating effects of vaccine hesitancy emphasize the importance of transparent and science-based communication strategies from healthcare professionals and public health institutions. Restoring trust requires ongoing engagement, consistent messaging, and clear explanations of the risks and benefits of vaccine preservatives like thimerosal.2
Conclusions
Thimerosal is a chemically distinct and well-characterized compound that has been widely used to preserve the safety and efficacy of vaccines, especially in multi-dose formats. Decades of scientifically validated evidence have confirmed that ethylmercury, the metabolic byproduct of thimerosal, does not accumulate in the body, has a short biological half-life, and does not cause neurotoxicity at exposure levels typical of vaccine administration.
Public concerns about thimerosal, particularly concerning autism, have been addressed and refuted through robust epidemiological studies and international regulatory reviews. Despite these efforts, the spread of misinformation necessitates active public health communication and education.
As the world seeks to expand vaccine access equitably, particularly in global immunization campaigns, preservatives such as thimerosal remain critical tools for the safe distribution of affordable vaccines.
References
- Magos, L. (2003). Neurotoxic character of thimerosal and the allometry of safety margins. Toxicology Letters, 140–141, 365–372. DOI: 10.1002/jat.918 https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/jat.918
- Leask J, Willaby HW, Kaufman J. The big picture in addressing vaccine hesitancy. Hum Vaccin Immunother. 2014;10(9):2600-2. doi: 10.4161/hv.29725. Epub 2014 Nov 19. PMID: 25483479; PMCID: PMC4975059, https://pmc.ncbi.nlm.nih.gov/articles/PMC4975059
- Clarkson, T. W., & Magos, L. (2006). The toxicology of mercury and its chemical compounds. Critical Reviews in Toxicology, 36(8), 609–662. DOI: 10.1080/10408440600845619, https://www.tandfonline.com/doi/full/10.1080/10408440600845619
- Ball, L. K., Ball, R., & Pratt, R. D. (2001). An assessment of thimerosal use in childhood vaccines. Pediatrics, 107(5), 1147–1154. DOI: 10.1542/peds.107.5.1147, https://publications.aap.org/pediatrics/article-abstract/107/5/1147/66202/An-Assessment-of-Thimerosal-Use-in-Childhood?redirectedFrom=fulltext
- Centers for Disease Control and Prevention. (2023). Thimerosal and Vaccines. https://www.cdc.gov/vaccine-safety/about/thimerosal.html
- Pichichero, M. E., Cernichiari, E., Lopreiato, J., & Treanor, J. (2002). Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: a descriptive study. The Lancet, 360(9347), 1737–1741. DOI: 10.1016/S0140-6736(02)11682-5, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)11682-5/fulltext
- Burbacher, T. M., Shen, D. D., Liberato, N., et al. (2005). Comparison of blood and brain mercury levels in infant monkeys exposed to methylmercury or vaccines containing thimerosal. Environmental Health Perspectives, 113(8), 1015–1021. DOI: 10.1289/ehp.7712, https://ehp.niehs.nih.gov/doi/10.1289/ehp.7712
- World Health Organization. (2011). Vaccines and immunization: Thiomersal, https://www.who.int/news-room/questions-and-answers/item/vaccines-and-immunization-thiomersal
- Young, H. A., Geier, D. A., & Geier, M. R. (2008). Thimerosal exposure in infants and neurodevelopmental disorders: An assessment of computerized medical records in the Vaccine Safety Datalink. Journal of the Neurological Sciences, 271(1-2), 110-118. DOI: 10.1016/j.jns.2008.04.002, https://www.sciencedirect.com/science/article/abs/pii/S0022510X08001573
- Institute of Medicine (IOM). (2004). Immunization safety review: Vaccines and autism. National Academies Press. DOI: 10.17226/10997, https://nap.nationalacademies.org/catalog/10997/immunization-safety-review-vaccines-and-autism
- Taylor, L. E., Swerdfeger, A. L., & Eslick, G. D. (2014). Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies. Vaccine, 32(29), 3623–3629. DOI: 10.1016/j.vaccine.2014.04.085, https://www.sciencedirect.com/science/article/abs/pii/S0264410X14006367?via%3Dihub
Further Reading