Report to WHO: No New Concerns About Thimerosal

There is no new rigorous and scientifically valid evidence in the published literature that calls into question the 2008 decision by the World Health Organization to endorse the continued use of thimerosal as a safe preservative in multidose vaccines for children in the developing world.

In preparation for a treaty on environmental protection, the United Nations asked the World Health Organization for a consultation regarding the safety of mercury in vaccines in the overall context of mercury in the environment. My contribution was to summarize the literature on the safety of the mercury in vaccines from 2008 to the present, in order to learn whether there was anything new that might cause WHO to revise its 2008 decision that informed the previous UN treaty.

Mercury is everywhere in the environment, including the air and in the fish we eat. Mercury in the air is called "inorganic" mercury, mercury in fish is methylmercury, and mercury in vaccines is ethylmercury (thimerosal). Between 1989 and 1998, as more vaccines with earlier administration times were added to the recommended childhood immunization schedule, average cumulative exposure to ethylmercury from vaccines containing thimerosal subsequently rose. Calculations showed that some infants could receive, during their first year of life, doses of ethylmercury from childhood vaccines that exceeded limits set for methylmercury exposure established by some public health and environmental agencies. However, no evidence for harm from thimerosal was found.

The 1999 decision by the U.S. Food and Drug Administration and the American Academy of Pediatrics calling for the removal of thimerosal in vaccines sold in the United States was made in haste, based on the inaccurate presumption of identical pharmacokinetics of ethylmercury and methylmercury. In the United States and elsewhere in the developed world, multidose vials have been replaced with single-dose vials, which do not require a preservative. Doing this in poorer parts of the world would represent a very significant cost barrier to providing needed vaccines to the most vulnerable children.

I presented remotely at the United Nations Environmental Programme (UNEP)–convened Intergovernmental Negotiating Committee Meeting 4 (INC4), held April 3-4, 2012, at WHO headquarters in Geneva. The presentation will be made again on June 7 to WHO’s Global Advisory Committee on Vaccine Safety for their consideration and vote.

A total of five studies of blood and hair mercury in children have now been published, and all show that the foundational presumption of similar pharmacokinetics between methylmercury and ethylmercury was incorrect. The blood half-life of ethylmercury from thimerosal in vaccines in both full-term and premature infants is 10 times shorter than that of oral methylmercury in adults (Pediatrics 2008;121:e208-14; J. Pediatr. 2009;155:495-9). The worry that ethylmercury might accumulate between vaccination visits at 2, 4, and 6 months of age was unfounded and now disproven. The ethylmercury has a half-life of 4-5 days, not 45 days as with methylmercury in fish. Because of the differing pharmacokinetics, exposure guidelines based on oral methylmercury in adults were not accurate for children who received thimerosal-containing vaccines. Moreover, by 1 year of age the contribution of thimerosal ethylmercury to total mercury exposure in infants and children is multifold lower than the contribution from methylmercury in fish (Clin. Chim. Acta 2011;412:1563-6).

Of the 11 epidemiologic studies reviewed, the large, well-conducted ones show no association between thimerosal and increases in autism. The largest, from the California Department of Developmental Services, showed no recent decrease in autism in California despite the exclusion of more than trace levels of thimerosal from nearly all childhood vaccines. Following the removal of thimerosal from most vaccines used in the United States (except injectable multidose influenza vaccines), rates of diagnosed and reported autism have continued to escalate, strongly arguing against a causal association (Arch. Gen. Psychiatry 2008;65:19-24).

In another well-designed and executed study of managed care organization members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to the increased risk of autism spectrum disorders (Pediatrics 2010;126:656-64).

The handful of studies I did find that reported a link between thimerosal and autism were, to quote the term I use in my report, "specious." One lacked information about how subjects or controls were selected for inclusion in the study, with retrospective analysis in which a potentially false conclusion is reached based on an association (Neuro. Endocrinol. Lett. 2008;29: 272-80).

Another was a retrospective ecological study of a possible association between thimerosal exposure from vaccines and neurodevelopmental disorders. The control disorders selected (pneumonia, congenital anomalies, and failure to thrive) have not shown secular trends similar to those seen for neurodevelopmental disorders and an increase in use of vaccines containing thimerosal in the United States (J. Neurol. Sci. 2008;271:110-8).

Importantly, I found two studies regarding the use of the preservative 2-phenoxyethanol (2-PE) that call into question whether it is an acceptable alternative to thimerosal. One found that thimerosal is a superior preservative at 50 mcg/dose compared with 2-PE at 5 mg/dose in hepatitis B vaccines (Southeast Asian J. Trop. Med. Public Health 2010;41:876-82). The other found that while 2-PE was superior to thimerosal in inhibiting bacterial growth in the Prevnar 13 vaccine, it was less effective than thimerosal for controlling growth of Candida albicans or Aspergillus niger (Vaccine 2011;29:7144-53).

Alternative preservatives such as 2-PE have not been field tested, and therefore have not been proven to equal or surpass the proven preservative effectiveness of thimerosal. The potential risks of endorsing alternative preservatives such as 2-PE are unknown. Switching to single-dose vaccine vials adds about $1 per dose of each vaccine. That $1 is currently the cost of vaccinating a child with all of the current vaccines given in those countries, including pertussis, diphtheria/tetanus, hepatitis B, polio, measles, and Haemophilus influenzae B conjugate. It simply isn’t affordable or practical to do that. Not to mention unwise and unnecessary.

The United Nations is expected to vote on the environmental treaty this summer. The evidence suggests the 2008 endorsement of the use of thimerosal as a safe and effective preservative in vaccines for children worldwide should remain.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he received an honorarium to prepare this report from WHO and donated it to charity. All of his work on thimerosal in vaccines was supported by the National Institute of Allergy and Infectious Diseases. He said he has never received any payment from any vaccine or pharmaceutical company relating to thimerosal in vaccines or any product. He said he has received honoraria/consultant fees and his institution has received research grants from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell for new vaccine and product development, but none of these payments had any direct or indirect relationship to the evaluation of thimerosal in vaccines.

There is no new rigorous and scientifically valid evidence in the published literature that calls into question the 2008 decision by the World Health Organization to endorse the continued use of thimerosal as a safe preservative in multidose vaccines for children in the developing world.

In preparation for a treaty on environmental protection, the United Nations asked the World Health Organization for a consultation regarding the safety of mercury in vaccines in the overall context of mercury in the environment. My contribution was to summarize the literature on the safety of the mercury in vaccines from 2008 to the present, in order to learn whether there was anything new that might cause WHO to revise its 2008 decision that informed the previous UN treaty.

Mercury is everywhere in the environment, including the air and in the fish we eat. Mercury in the air is called "inorganic" mercury, mercury in fish is methylmercury, and mercury in vaccines is ethylmercury (thimerosal). Between 1989 and 1998, as more vaccines with earlier administration times were added to the recommended childhood immunization schedule, average cumulative exposure to ethylmercury from vaccines containing thimerosal subsequently rose. Calculations showed that some infants could receive, during their first year of life, doses of ethylmercury from childhood vaccines that exceeded limits set for methylmercury exposure established by some public health and environmental agencies. However, no evidence for harm from thimerosal was found.

The 1999 decision by the U.S. Food and Drug Administration and the American Academy of Pediatrics calling for the removal of thimerosal in vaccines sold in the United States was made in haste, based on the inaccurate presumption of identical pharmacokinetics of ethylmercury and methylmercury. In the United States and elsewhere in the developed world, multidose vials have been replaced with single-dose vials, which do not require a preservative. Doing this in poorer parts of the world would represent a very significant cost barrier to providing needed vaccines to the most vulnerable children.

I presented remotely at the United Nations Environmental Programme (UNEP)–convened Intergovernmental Negotiating Committee Meeting 4 (INC4), held April 3-4, 2012, at WHO headquarters in Geneva. The presentation will be made again on June 7 to WHO’s Global Advisory Committee on Vaccine Safety for their consideration and vote.

A total of five studies of blood and hair mercury in children have now been published, and all show that the foundational presumption of similar pharmacokinetics between methylmercury and ethylmercury was incorrect. The blood half-life of ethylmercury from thimerosal in vaccines in both full-term and premature infants is 10 times shorter than that of oral methylmercury in adults (Pediatrics 2008;121:e208-14; J. Pediatr. 2009;155:495-9). The worry that ethylmercury might accumulate between vaccination visits at 2, 4, and 6 months of age was unfounded and now disproven. The ethylmercury has a half-life of 4-5 days, not 45 days as with methylmercury in fish. Because of the differing pharmacokinetics, exposure guidelines based on oral methylmercury in adults were not accurate for children who received thimerosal-containing vaccines. Moreover, by 1 year of age the contribution of thimerosal ethylmercury to total mercury exposure in infants and children is multifold lower than the contribution from methylmercury in fish (Clin. Chim. Acta 2011;412:1563-6).

Of the 11 epidemiologic studies reviewed, the large, well-conducted ones show no association between thimerosal and increases in autism. The largest, from the California Department of Developmental Services, showed no recent decrease in autism in California despite the exclusion of more than trace levels of thimerosal from nearly all childhood vaccines. Following the removal of thimerosal from most vaccines used in the United States (except injectable multidose influenza vaccines), rates of diagnosed and reported autism have continued to escalate, strongly arguing against a causal association (Arch. Gen. Psychiatry 2008;65:19-24).

In another well-designed and executed study of managed care organization members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to the increased risk of autism spectrum disorders (Pediatrics 2010;126:656-64).

The handful of studies I did find that reported a link between thimerosal and autism were, to quote the term I use in my report, "specious." One lacked information about how subjects or controls were selected for inclusion in the study, with retrospective analysis in which a potentially false conclusion is reached based on an association (Neuro. Endocrinol. Lett. 2008;29: 272-80).

Another was a retrospective ecological study of a possible association between thimerosal exposure from vaccines and neurodevelopmental disorders. The control disorders selected (pneumonia, congenital anomalies, and failure to thrive) have not shown secular trends similar to those seen for neurodevelopmental disorders and an increase in use of vaccines containing thimerosal in the United States (J. Neurol. Sci. 2008;271:110-8).

Importantly, I found two studies regarding the use of the preservative 2-phenoxyethanol (2-PE) that call into question whether it is an acceptable alternative to thimerosal. One found that thimerosal is a superior preservative at 50 mcg/dose compared with 2-PE at 5 mg/dose in hepatitis B vaccines (Southeast Asian J. Trop. Med. Public Health 2010;41:876-82). The other found that while 2-PE was superior to thimerosal in inhibiting bacterial growth in the Prevnar 13 vaccine, it was less effective than thimerosal for controlling growth of Candida albicans or Aspergillus niger (Vaccine 2011;29:7144-53).

Alternative preservatives such as 2-PE have not been field tested, and therefore have not been proven to equal or surpass the proven preservative effectiveness of thimerosal. The potential risks of endorsing alternative preservatives such as 2-PE are unknown. Switching to single-dose vaccine vials adds about $1 per dose of each vaccine. That $1 is currently the cost of vaccinating a child with all of the current vaccines given in those countries, including pertussis, diphtheria/tetanus, hepatitis B, polio, measles, and Haemophilus influenzae B conjugate. It simply isn’t affordable or practical to do that. Not to mention unwise and unnecessary.

The United Nations is expected to vote on the environmental treaty this summer. The evidence suggests the 2008 endorsement of the use of thimerosal as a safe and effective preservative in vaccines for children worldwide should remain.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he received an honorarium to prepare this report from WHO and donated it to charity. All of his work on thimerosal in vaccines was supported by the National Institute of Allergy and Infectious Diseases. He said he has never received any payment from any vaccine or pharmaceutical company relating to thimerosal in vaccines or any product. He said he has received honoraria/consultant fees and his institution has received research grants from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell for new vaccine and product development, but none of these payments had any direct or indirect relationship to the evaluation of thimerosal in vaccines.

There is no new rigorous and scientifically valid evidence in the published literature that calls into question the 2008 decision by the World Health Organization to endorse the continued use of thimerosal as a safe preservative in multidose vaccines for children in the developing world.

In preparation for a treaty on environmental protection, the United Nations asked the World Health Organization for a consultation regarding the safety of mercury in vaccines in the overall context of mercury in the environment. My contribution was to summarize the literature on the safety of the mercury in vaccines from 2008 to the present, in order to learn whether there was anything new that might cause WHO to revise its 2008 decision that informed the previous UN treaty.

Mercury is everywhere in the environment, including the air and in the fish we eat. Mercury in the air is called "inorganic" mercury, mercury in fish is methylmercury, and mercury in vaccines is ethylmercury (thimerosal). Between 1989 and 1998, as more vaccines with earlier administration times were added to the recommended childhood immunization schedule, average cumulative exposure to ethylmercury from vaccines containing thimerosal subsequently rose. Calculations showed that some infants could receive, during their first year of life, doses of ethylmercury from childhood vaccines that exceeded limits set for methylmercury exposure established by some public health and environmental agencies. However, no evidence for harm from thimerosal was found.

The 1999 decision by the U.S. Food and Drug Administration and the American Academy of Pediatrics calling for the removal of thimerosal in vaccines sold in the United States was made in haste, based on the inaccurate presumption of identical pharmacokinetics of ethylmercury and methylmercury. In the United States and elsewhere in the developed world, multidose vials have been replaced with single-dose vials, which do not require a preservative. Doing this in poorer parts of the world would represent a very significant cost barrier to providing needed vaccines to the most vulnerable children.

I presented remotely at the United Nations Environmental Programme (UNEP)–convened Intergovernmental Negotiating Committee Meeting 4 (INC4), held April 3-4, 2012, at WHO headquarters in Geneva. The presentation will be made again on June 7 to WHO’s Global Advisory Committee on Vaccine Safety for their consideration and vote.

A total of five studies of blood and hair mercury in children have now been published, and all show that the foundational presumption of similar pharmacokinetics between methylmercury and ethylmercury was incorrect. The blood half-life of ethylmercury from thimerosal in vaccines in both full-term and premature infants is 10 times shorter than that of oral methylmercury in adults (Pediatrics 2008;121:e208-14; J. Pediatr. 2009;155:495-9). The worry that ethylmercury might accumulate between vaccination visits at 2, 4, and 6 months of age was unfounded and now disproven. The ethylmercury has a half-life of 4-5 days, not 45 days as with methylmercury in fish. Because of the differing pharmacokinetics, exposure guidelines based on oral methylmercury in adults were not accurate for children who received thimerosal-containing vaccines. Moreover, by 1 year of age the contribution of thimerosal ethylmercury to total mercury exposure in infants and children is multifold lower than the contribution from methylmercury in fish (Clin. Chim. Acta 2011;412:1563-6).

Of the 11 epidemiologic studies reviewed, the large, well-conducted ones show no association between thimerosal and increases in autism. The largest, from the California Department of Developmental Services, showed no recent decrease in autism in California despite the exclusion of more than trace levels of thimerosal from nearly all childhood vaccines. Following the removal of thimerosal from most vaccines used in the United States (except injectable multidose influenza vaccines), rates of diagnosed and reported autism have continued to escalate, strongly arguing against a causal association (Arch. Gen. Psychiatry 2008;65:19-24).

In another well-designed and executed study of managed care organization members, prenatal and early-life exposure to ethylmercury from thimerosal-containing vaccines and immunoglobulin preparations was not related to the increased risk of autism spectrum disorders (Pediatrics 2010;126:656-64).

The handful of studies I did find that reported a link between thimerosal and autism were, to quote the term I use in my report, "specious." One lacked information about how subjects or controls were selected for inclusion in the study, with retrospective analysis in which a potentially false conclusion is reached based on an association (Neuro. Endocrinol. Lett. 2008;29: 272-80).

Another was a retrospective ecological study of a possible association between thimerosal exposure from vaccines and neurodevelopmental disorders. The control disorders selected (pneumonia, congenital anomalies, and failure to thrive) have not shown secular trends similar to those seen for neurodevelopmental disorders and an increase in use of vaccines containing thimerosal in the United States (J. Neurol. Sci. 2008;271:110-8).

Importantly, I found two studies regarding the use of the preservative 2-phenoxyethanol (2-PE) that call into question whether it is an acceptable alternative to thimerosal. One found that thimerosal is a superior preservative at 50 mcg/dose compared with 2-PE at 5 mg/dose in hepatitis B vaccines (Southeast Asian J. Trop. Med. Public Health 2010;41:876-82). The other found that while 2-PE was superior to thimerosal in inhibiting bacterial growth in the Prevnar 13 vaccine, it was less effective than thimerosal for controlling growth of Candida albicans or Aspergillus niger (Vaccine 2011;29:7144-53).

Alternative preservatives such as 2-PE have not been field tested, and therefore have not been proven to equal or surpass the proven preservative effectiveness of thimerosal. The potential risks of endorsing alternative preservatives such as 2-PE are unknown. Switching to single-dose vaccine vials adds about $1 per dose of each vaccine. That $1 is currently the cost of vaccinating a child with all of the current vaccines given in those countries, including pertussis, diphtheria/tetanus, hepatitis B, polio, measles, and Haemophilus influenzae B conjugate. It simply isn’t affordable or practical to do that. Not to mention unwise and unnecessary.

The United Nations is expected to vote on the environmental treaty this summer. The evidence suggests the 2008 endorsement of the use of thimerosal as a safe and effective preservative in vaccines for children worldwide should remain.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he received an honorarium to prepare this report from WHO and donated it to charity. All of his work on thimerosal in vaccines was supported by the National Institute of Allergy and Infectious Diseases. He said he has never received any payment from any vaccine or pharmaceutical company relating to thimerosal in vaccines or any product. He said he has received honoraria/consultant fees and his institution has received research grants from GlaxoSmithKline, Sanofi Pasteur, Pfizer, Novartis, and Crucell for new vaccine and product development, but none of these payments had any direct or indirect relationship to the evaluation of thimerosal in vaccines.