We observed that blood mercury levels after intramuscular administration of thimerosal-containing vaccines to premature and low birth weight newborns were at their highest level shortly after vaccination and returned to pre-vaccination levels within about 10 days. Using a model that accounted for baseline mercury levels, ethyl mercury dosage, and timing of vaccination, we estimated that the blood half-life of mercury after administration of thimerosal was 4.97 to 6.3 days. Our estimate of mercury blood half-life after intramuscular ethyl mercury is consistent with recent comparison of the pharmacokinetics of mercury after intramuscular ethyl mercury in term newborns 5
and infant rhesus macaques. 10
The importance of blood levels of ethyl mercury for assessing toxicity is unknown, but blood levels have been shown to be a predictor of toxicity for methyl mercury exposure. 11,12
The low levels of mercury detected in this study suggest low risk for toxicity from this exposure.
There was an increase in stool mercury levels shortly after vaccination, which slowly fell afterward. This pattern is consistent with enterohepatic excretion similar to that described for methyl mercury; however these observations were made on spot (as opposed to 24-hour) collections, therefore, it is not possible to draw conclusions regarding the proportion of administered mercury that was eliminated in the stool and kinetics of the elimination process.
Because brain biopsies obviously could not be done, the use of the kidney (also a sensitive tissue to mercury toxicity) as a surrogate organ to assess toxicity seems reasonable. There was no evidence of significant urinary excretion of mercury in this study, similar to previous observations with methyl mercury and there was no damage to the kidney as evidenced by no significant changes in levels of urine GGT. The kidney, like the brain, is a sensitive issue to mercury toxicity.
Methyl mercury (CH3
) and ethyl mercury (CH3
) have similar chemical structures, and these two short chain-chain alkyl mercurials generally have been assumed to possess similar toxicologic properties; however, much less information has been available for ethyl mercury, especially for humans. Animal data indicate that ethyl mercury, like methyl mercury, is readily transported to all tissues but has a shorter half-life10
. Little is known about possible enterohepatic cycling and fecal excretion of ethyl mercury.
In 2000, Stajich et al reported measurements of total mercury levels before and after vaccinations with a hepatitis B vaccine that contained 12.5 μg of ethyl mercury in 15 preterm infants. 13
The premature infants by study design were ≤ 1000 grams (mean 748 grams); they received hepatitis B vaccine at birth. Mean pre-vaccination blood mercury level was 0.54 ± 0.79 ng/mL and the mean post-vaccination level was 7.36 ± 4.99 ng/mL, measured 48-72 hours after vaccination. These levels of mercury are clearly higher than those that we measured. However, an allometric adjustment based on differences between our study group’s mean weight of 2.4 kg and the Stajich et al mean weight of 0.7 kg allows the conclusion that the results are consistent and that expected blood mercury levels can be predicted based on birth weight and ethyl mercury dose (Table II).
This study has several limitations. Because methyl mercury was present in the blood of most study children prior to vaccination, our measurements of mercury post vaccination represent a mixture of ethyl mercury from the vaccines and methyl mercury from transplacental passage from mother to infant. Our measurements may therefore overestimate the actual amount of blood mercury contributed by ethyl mercury from vaccines. We were unable to determine the fate of the mercury after it leaves the blood, because our sampling was limited to blood, urine, and stool, therefore the data do not allow any conclusions about the proportion of the administered ethyl mercury that is ultimately excreted in the stools or the time course of that excretion, only that excretion occurs by the gastrointestinal route and that the kidneys do not seem to play an important role.
Our study provides data that may be useful in assessing the risks related to ethyl mercury exposure of prematurely born and low birth weight infants who receive thimerosal at dosages consistent with standard vaccination regimens. Concerns have been raised that administration of vaccines that contain thimerosal could cause an increased risk for autism. Epidemiologic studies have generally concluded that there is no evidence for such an association. 14-16
This study completes the assessment of the full range of thimerosal blood elimination kinetics from preterm infants who receive a birth dose of HBV vaccine, through infants to 6 months old 4,5
. The results suggest that the risk assessment regarding exposure to thimerosal used as a preservative should be reevaluated in light of the demonstrated shorter blood half-life of ethyl mercury after vaccination.