Mercury Levels Following Thimerosal Exposure in Infant Nonhuman Primates

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Mercury Levels Following Thimerosal Exposure in
Infant Nonhuman Primates

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The Controversy Thimerosal in Vaccines
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EPA Standard for Methylmercury based on Human
Studies of Exposure through Fish Consumption
During Pregnancy and Changes in Test Scores for
Exposed Offspring. Report supported EPAs action
to lower RfD to 0.1ug/kg/day
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The Controversy Thimerosal in Vaccines
Mercury exposure from vaccines during first 6
months of life exceeds EPA standard for
methylmercury.
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The Controversy Thimerosal in Vaccines
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The Controversy Thimerosal in Vaccines
1999 Statement from American Academy of
Pediatrics and US Public Health
Service Conclusion Thimerosal containing
vaccines should be removed as soon as possible to
reduce exposure to mercury.
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• Question in 2000
• What do we know about what happens to the
  mercury in Thimerosal (or ethylmercury) when it
  is injected in infants (human or animal).

• Answer Very Little

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Study Design Adult Rats Oral Exposure 5 Daily
Doses 8 mg Hg/kg/day Blood and Brain Organic and
Inorganic Hg Levels (collected 3 and 10 days
after last exposure)
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Results from 1985 Study Comparing Methylmercury
and Ethylmercury in Adult Rats.
Results -Blood Concentrations Organic Hg in Blood
Higher for Ethylmercury Group Inorganic Hg in
Blood Higher for Ethymercury Group
The Comparative Toxicology of Ethyl- and
Methylmercury. Arch Toxicol 57260-267, 1985
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Results from 1985 Study Comparing Methylmercury
and Ethylmercury in Adult Rats.
Results -Brain Concentrations Organic Hg in Brain
Lower for Ethylmercury Group Inorganic Hg in
Brain Higher for Ethylmercury Group
The Comparative Toxicology of Ethyl- and
Methylmercury. Arch Toxicol 57260-267, 1985
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Results from 1985 Study Comparing Methylmercury
and Ethylmercury in Adult Rats.
Ratio of Total Hg in Brain to Blood Lower in
Ethylmercury Group 0.027 (ethyl) vs 0.095
(methyl) Conclusion MeHg ratio will
over-estimate brain Hg concentration for
Ethylmercury
The Comparative Toxicology of Ethyl- and
Methylmercury. Arch Toxicol 57260-267, 1985
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Comparisons of Methylmercury, Ethylmercury and
Thimerosal, 2003
Journal of Applied Toxicology, 23263-269 2003
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(No Transcript)
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Estimates of Mercury Doses from Vaccines
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Thimerosal Monkey Study Design and Schedule
1Dose of MeHg in µg/kg 2Dose of ethylmercury in
µg/kg 3Days after most recent dose 4Days after
last (4th) dose
From Burbacher, et al. Comparison of Blood and
Brain Mercury Levels in Infant Monkeys Exposed to
Methylmercury or Vaccines Containing Thimerosal.
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Weight Gain of Infant Monkeys During Study
From Burbacher, et al. Comparison of Blood and
Brain Mercury Levels in Infant Monkeys Exposed to
Methylmercury or Vaccines Containing Thimerosal.
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Comparison of Model Predicted and Observed Mean
Blood Total Hg Concentration During and After
Four Weekly Oral Doses (20 ?g/kg) of Methylmercury
Methylmercury Total Mercury in Blood Half-Life
21.5 days
From Burbacher, et al. Comparison of Blood and
Brain Mercury Levels in Infant Monkeys Exposed to
Methylmercury or Vaccines Containing Thimerosal.
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Comparison of Mean Blood Total Hg Concentration
During and After Four Weekly I.M. Injections of
Vaccine Containing Thimerosal at 20 ?g/Kg Hg
Thimerosal Total Mercury in Blood Half-Life 6.9
days
From Burbacher, et al. Comparison of Blood and
Brain Mercury Levels in Infant Monkeys Exposed to
Methylmercury or Vaccines Containing Thimerosal.
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Projected Levels of Hg in Blood of Infants after
administration of Vaccines
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Mean (SE) Total Mercury Concentrations in Brain
of Oral Methylmercury and I.M. Thimerosal Groups
Sacrifice or Washout Period (Brain) MeHg
Half-Life 59.5(24.1) days Thimerosal
Half-Life 24.2(7.4) days
From Burbacher, et al. Comparison of Blood and
Brain Mercury Levels in Infant Monkeys Exposed to
Methylmercury or Vaccines Containing Thimerosal.
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Mean (SE) Inorganic Mercury Concentrations in
Brain of Oral Methylmercury and I.M. Thimerosal
Groups
Sacrifice or Washout Period (Brain) Half-Life
could not be estimated (previous estimates over 1
year)
From Burbacher, et al. Comparison of Blood and
Brain Mercury Levels in Infant Monkeys Exposed to
Methylmercury or Vaccines Containing Thimerosal.
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Brain to Blood Ratios for Total Mercury for Oral
Methylmercury and I.M. Thimerosal Groups
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Review of Study Results and Recommendations

• Methylmercury is not a good reference for
  Thimerosal Risk
• Absorption rate and initial distribution in blood
  are similar
• Blood clearance rates are different (thimerosal
  cleared more quickly)
• Brain levels of total mercury are different
  (levels are lower for thimerosal)
• Brain clearance of total mercury are different
  (thimerosal cleared more quickly)
• Ratio of total mercury in brain to blood is
  different (thimerosal is higher)
• Brain levels of inorganic mercury are different,
  with no clearance (levels are higher for
  thimerosal)
• Future studies of Thimerosal should focus on the
  neurotoxic effects of organic and inorganic
  mercury following exposure.
• Inorganic mercury has been associated with
  activation of microglia in the brain of adult non
  human primates (neuro inflammation)
• Inorganic mercury has a very long half-life in
  the brain (years)
• A recent report suggests that neuro inflammation
  is present in brains of autistic children
• Information on the developmental neurotoxicity of
  thimerosal is critical if we are to respond to
  public concerns regarding the safety of childhood
  immunizations.

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Our Priorities for Future Studies

• Current Tissue
• Studies of Brains of Thimerosal and Control
  Animals
• Studies of Brains of Methylmercury Animals
• Mercury Analysis of Remaining Tissue
• New Animals
• Dose-Response Design for Thimerosal
• Analysis of Thimerosal, Ethyl, Methyl and
  Inorganic Mercury in Blood and Tissue
• Longer Duration Sacrifice or Washout Times
• Measurement of Developmental Milestones
  (cognitive, social, sensory, etc.)

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Acknowledgments

• Co Investigators
• Danny Shen (University of Washington)
• Kim Grant (University of Washington)
• Noelle Liberato (University of Washington)
• Tom Clarkson (University of Rochester)
• Elsa Cernichiari (University of Rochester)
• Staff of the Infant Primate Research Laboratory
  at the University of Washington

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Previous Studies on Demethylation of Mercury in
the Brain of Nonhuman Primates
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Previous Studies on Demethylation of Mercury in
the Brain of Nonhuman Primates
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Previous Studies on Demethylation of Mercury in
the Brain of Nonhuman Primates
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Previous Studies on Demethylation of Mercury in
the Brain of Nonhuman Primates
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Previous Studies on Demethylation of Mercury in
the Brain of Nonhuman Primates
Inorganic Mercury Deposits Located in Microglia
and Astrocytes
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Annals of Neurology, Vol 5767-81, 2005