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Thiomersal

What is Thiomersal

Thiomersal (also known as thimerosal) is a mercury based preservative used in some vaccines and other pharmaceutical products such as antiseptics.

Should I be concerned that thiomersal is in some vaccines?

No, firstly because extensive research has shown that thiomersal in vaccines is safe and secondly because there is no thiomersal in the routine schedule childhood vaccines given in New Zealand to children.

What is Mercury?

Mercury is a naturally occurring element found in the earth’s crust, soil, water and the air. Mercury is released into the environment by volcanic eruptions, weathering of rocks and the burning of coal. Once released mercury can find its way through the food chain via fish and other animals. At high levels it can be toxic.

Mercury is found in three main forms:

metallic mercury which gives rise to mercury vapour,
inorganic mercury (a form in the environment and in animal tissues) and
organic mercury (the two main forms of which are methylmercury and ethylmercury).

These various forms of mercury are found in the air, earth, aquatic sediment, in fish (particularly in long lived fish such as sharks and oily fish such as tuna) and some forms of mercury are used in industry.

Not all mercury is created equally and some forms pose a greater health risk than others. For example mercury vapour is extremely dangerous whereas amalgam, used in dental fillings, has not been shown to pose a health risk.

Thiomersal and Mercury

Thiomersal (also known as thimerosal) is a mercury based preservative used since the 1930s in the manufacture of some vaccines and other pharmaceutical products such as antiseptics and contact lens solution. It is used to prevent bacterial and fungal growth. It has also been used during vaccine production both to inactivate certain organisms and toxins and to maintain a sterile production line.

Mercury in the body

The two organic forms of mercury, methylmercury and ethylmercury (in thiomersal), are closely related but they have important differences.

Methylmercury (found in fish) is more potent; accumulation in the body is more likely because the time taken for the body to eliminate it (known as the half life) is about 50 days.

Ethylmercury (in thiomersal) does not accumulate in the body to such an extent, because its half life is only about 7-10 days. Ethylmercury is rapidly converted in the body to inorganic mercury and excreted.

Mercury can have harmful effects on the central nervous system, skin and kidneys, cases of the toxic effects of mercury have been from methylmercury, not ethylmercury.

How much mercury is safe?

Mercury becomes harmful only after it reaches a certain level in the body. The toxicity depends on the amount of mercury consumed in relation to body weight and can accumulate over a period of time. Infants are therefore at greater risk than adults because they are smaller.

Safe levels of mercury have been estimated by different expert bodies and lie somewhere between 0.7- 3.3 µg/kg body weight/week (The World Health Organisation (WHO), Agency for Toxic Substances and Disease Registries (ATSDR), the Food and Drug Administration (FDA), and the Environmental Protection Agency (EPA). These levels have been deliberately calculated to be much lower than the level at which harm might occur. For example the Environmental Protection Agency (USA) level has been set ten times below the lowest level calculated as causing harm, so there is a large built-in safety margin.

Importantly these levels refer to methylmercury, whereas thiomersal contains ethylmercury, which is broken down and excreted more rapidly and does not accumulate in the body like methylmercury. Therefore the safety limits for ethylmercury will be much higher.

Thiomersal in vaccines given to NZ children

In 2000 New Zealand moved to phase out all thiomersal-containing vaccines in the NZ childhood schedule vaccines. Note that some influenza vaccines contain thiomersal.

Thiomersal has never been present in the MMR vaccine or any other live vaccine.

When thiomersal-containing vaccines were being used in the childhood schedule prior to 2000, the maximum number of doses of thiomersal-containing vaccines a 6 month old child might have received was as follows:

3 doses of diphtheria-tetanus-pertussis vaccine,
3 doses of hepatitis B vaccine, and
3 doses of Hib vaccine.

This would have resulted in a total intake of 175 µg of ethylmercury, which is equivalent to about 1.9 µg/kg body weight per week, for an average-sized baby. This level is well below the World Health Organization (WHO) limit for methylmercury. Studies measuring mercury levels in the blood of infants given thiomersal-containing vaccines have indicated that their blood concentrations of mercury did not rise above designated levels, except possibly transiently in a premature infant less than 1kg in weight (Lancet 2002; 360: 1737-41).

Thiomersal continues to be used in vaccines in many countries. The WHO’s Global Advisory Committee on Vaccine Safety (GAVSC) has concluded that "there is currently no evidence of mercury toxicity in infants, children or adults exposed to thiomersal-containing vaccines" and that "there is no reason to change current immunisation practices with thiomersal-containing vaccines on the grounds of safety".

What studies have been done to show this safety?

Many studies have been conducted including in Denmark, Sweden, the United States, and the United Kingdom. These have shown that there is no evidence of developmental or neurologic abnormalities resulting from the use of vaccines containing thiomersal. In 2004 a report by the Institutes of Medicine, an independent expert body in the United States, concluded that there is no association between autism and vaccines that contain thiomersal. Also in 2004 an extensive review of all the studies on thiomersal-containing vaccines and autism and neurodevelopmental disorders was published in the journal Paediatrics. Studies looking at autism, mental retardation, speech disorders, and attention deficit disorder, as well as other conditions were reviewed. Overall, the evidence indicated that autism and neurodevelopmental disorders are not associated with thiomersal in vaccines. The reviewers noted that the epidemiologic studies conducted that suggest a link (notably only by one pair of authors: Geier and Geier) have “significant design flaws that invalidate their conclusions”.

So why stop using vaccines that contain thiomersal?

Recommendations to remove thiomersal from vaccines were made for two main reasons.

Firstly, it was to reduce exposure in very small premature babies with low body weight in whom there was a theoretical risk that the intake of mercury from repeated doses of thiomersal-containing vaccines could have been high.

Secondly, the intent has been to reduce total exposure to mercury in babies and young children in a world where other environmental sources (particularly in food such as fish) may be more difficult to eliminate.

Along with these recommendations, guidelines have been developed on limiting the consumption of certain types of fish, particularly in the diet of pregnant women and young children.

Thiomersal containing vaccines have been replaced with single dose vaccine vials or alternative preservatives have been used.

Mercury, vaccines and autism

Mercury poisoning does not lead to autism.

In 1971 Iraq imported grain that had been inadvertently fumigated with methymercury. People consumed bread baked from this contaminated grain resulting in one of the worst single source mercury poisonings in history. There were 6500 people hospitalized and 450 died. Pregnant woman delivered babies with epilepsy and mental retardation however they did not deliver babies with an increased risk of autism.

There have been several large studies comparing the risk of autism in children who received vaccines containing thiomersal to those who did not. The studies were well designed and reproducible, consistently finding that the incidence of autism was the same in both groups.

Studies of the head size, speech patterns, vision, coordination and sensitization of children poisoned by mercury show that the symptoms of mercury poisoning are clearly different from the symptoms of autism.

Women in the USA were occasionally exposed to mercury when they were given a product called RhoGam when their blood type was not compatible with their baby’s blood type. This was to prevent the blood mismatch harming the baby. The product RhoGam contained thiomersal as a preservative. Babies exposed to RhoGam did not have a higher risk for autism than babies who never received RhoGam

Causes of Autism

Autism clearly has a genetic basis. When one identical twin has autism, the chance that the other twin has autism is about 90% however for fraternal twins the chance is less than 10%

There are also environmental causes of autism. Mothers who took thalidomide early in pregnancy had babies at increased risk for autism. Also, mothers who suffered rubella early in pregnancy have babies at increased risk of autism, however babies infected with the virus after birth do not develop autism. There are clearly windows early in development for viruses or drugs to cause autism however later in pregnancy or after birth the window appears closed.

Although thalidomide and rubella virus can cause autism in pregnancy, evidence suggests mercury does not.

Table 1. Vaccines available in New Zealand and their level of thiomersal

Vaccine Trade name Manufacturer Thiomersal
Hepatitis B H-B-VaxII* preservative-free CSL/MSD Nil
DTPa Infanrix and Tripacel GSK, CSL Nil
DTPa-hepatitis B Infanrix-Hep B GlaxoSmithKline Nil
DTPa-IPV Infanrix-IPV GlaxoSmithKline Nil
DTPa-hepatitis B-IPV Infanrix-Penta GlaxoSmithKline Nil
DTPa-hepatitis B-IPV-Hib B PRPT Infanrix-Hexa GlaxoSmithKline Nil
dTap Boostrix (adult) GSK Nil
Hepatitis B - Hib B PRP-OMP Comvax MSD Nil
Haemophilus influenza B OMP Liquid PedVaxHIB MSD Nil
Haemophilus influenzae B PRPT ActHib) Pasteur Mérieux Nil
Haemophilus influenzae B HbOC HibTITER Lederle Nil
Measles, mumps, rubella MMR II, Priorix MSD, GSK Nil
Meningococcal group B vaccine MeNZB Chiron Nil
Meningococcal group C conjugate vaccines Meningitec, Menjugate, NeisVac-C Wyeth, CSL, Baxter Nil
Oral polio vaccine OPV CSL Nil
Inactivated polio vaccine (IPV) IPOL Aventis Pasteur Nil
Polysaccharide pueumococcal vaccine Pneumovax 23 MSD Nil
7-valent pneumococcal conjugate vaccine Prevenar Lederle Nil
Varicella vaccine Varilrix GSK Nil
Varicella vaccine Varivax CSL/MSD Nil
Influenza vaccine Vaxigrip, Fluvax Aventis Pasteur, CSL Nil
Combined diphtheria and tetanus vaccine CDT CSL 50 micrograms
Adult diphtheria and tetanus vaccine ADT CSL 50 micrograms
Diphtheria vaccine CSL 50 micrograms
Hepatitis B Engerix B Adult GlaxoSmithKline <2 micrograms
*Influenza vaccines Fluarix, Influvac, Fluvax GlaxoSmithKline, Solvay, CSL 50 micrograms
Japanese encephalitis vaccine JE Vax CSL 35 micrograms
Q fever vaccine Q vax CSL 50 micrograms
Tetanus Tet-tox CSL 25 micrograms
Hepatitis A Havrix 1440 GSK Nil
Hepatitis A Havrix Jr GSK Nil
Hepatitis A Vaqta (adult) MSD Nil
Hepatitis A Vaqta (paed) MSD Nil
Hepatitis A Avaxim Aventis Nil
Hepatitis A and B Twinrix GSK Nil
Hepatitis A and B Twinrix Jr GSK Nil
Cholera Dukoral (oral) Sanofi Pasteur Nil
Meningococcal Menomune ACYW-135 Sanofi Pasteur Nil
Meningococcal Mencevax ACYW-135 GSK Nil
Pneumococcal Pneumovax 23 MSD Nil

* This product should be considered equivalent to thiomersal-free products. This vaccine may contain trace amounts (<0.3 mcg) of mercury left after post-production thiomersal removal; these amounts have no biological effect. JAMA 1999;282(18) and JAMA 2000;283(16).