Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal

Abstract

Thimerosal is a preservative that has been used in manufacturing vaccines since the 1930s. Reports have indicated that infants can receive ethylmercury (in the form of thimerosal) at or above the U.S. Environmental Protection Agency guidelines for methylmercury exposure, depending on the exact vaccinations, schedule, and size of the infant. In this study we compared the systemic disposition and brain distribution of total and inorganic mercury in infant monkeys after thimerosal exposure with those exposed to MeHg. Monkeys were exposed to MeHg (via oral gavage) or vaccines containing thimerosal (via intramuscular injection) at birth and 1, 2, and 3 weeks of age. Total blood Hg levels were determined 2, 4, and 7 days after each exposure. Total and inorganic brain Hg levels were assessed 2, 4, 7, or 28 days after the last exposure. The initial and terminal half-life of Hg in blood after thimerosal exposure was 2.1 and 8.6 days, respectively, which are significantly shorter than the elimination half-life of Hg after MeHg exposure at 21.5 days. Brain concentrations of total Hg were significantly lower by approximately 3-fold for the thimerosal-exposed monkeys when compared with the MeHg infants, whereas the average brain-to-blood concentration ratio was slightly higher for the thimerosal-exposed monkeys (3.5 ± 0.5 vs. 2.5 ± 0.3). A higher percentage of the total Hg in the brain was in the form of inorganic Hg for the thimerosal-exposed monkeys (34% vs. 7%). The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg. Knowledge of the toxicokinetics and developmental toxicity of thimerosal is needed to afford a meaningful assessment of the developmental effects of thimerosal-containing vaccines.

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

“…61 Despite its short half-life compared to inorganic mercury, it undergoes preferential accumulation in the CNS, affecting the microglia and producing strain-dependent neurotoxic effects in rodents. 62,63 This strain dependency, in conjunction with the present data, suggests that thimerosal could contribute to produce an unbalanced Ca 2 þ homeostasis in genetically vulnerable individuals. Indeed, a postnatal exposure to thimerosal is not reconcilable with the prenatal onset of neurodevelopmental anomalies leading to autism.…”

Blood-Cerebrospinal Fluid Barrier

“…Carneiro et al demonstrated a conversion of ethylmercury to inorganic mercury in murine brain tissue within 6 days after exposure to thiomersal. 12 The dealkylation of MeHgCl seems not to be as effective as after thiomersal application as reported by Burbacher et al 13 However, we could show clear differences between organic and inorganic compounds in the efflux behaviour across the cell culture model of the blood-CSF barrier indicating compounds differences.…”

“…27 An in vivo study comparing Hg blood levels two days after oral MeHg intake (20 mg kg À1 as MeHg hydroxide) and intramuscular thiomersal injection (20 mg kg À1 ) in infant monkeys demonstrated total blood Hg concentrations of 8-18 ng mL À1 (0.04-0.09 mM) and of 6-14 ng L À1 (0.03-0.07 mM), respectively. 13 The application in the blood facing compartment lead to similar transfer rates for all mercury compounds (Fig. 5A-C).…”

“…12 The observed presence of inorganic mercury in the brain tissue is likely to be due to a dealkylation of the organic Hg compounds as well as an oxidation of elemental mercury in the brain. 12,13 Besides the blood-brain barrier, the blood-cerebrospinal fluid (CSF) barrier represents a further interface for the access of mercury compounds into the brain. It is built up by epithelial cells of the choroid plexus, which separates the blood from the CSF.…”

Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders

“…Vahter et al [103] demonstrated that it was the ionic form of mercury (demethylated MeHg) that was most toxic and that it gradually accumulated in the brain over an 18 month period. Of special importance when comparing ethylmercury (EtHg) with MeHg brain toxicity, is that even though EtHg brain levels were 3-fold lower than MeHg, 34% of the EtHg was converted to the more toxic ionic form of mercury and only 7% of MeHg was converted in a similar time frame [104,105].…”