New Metals Toxicology Textbook mentions genetic susceptibilities to mercury
Below are excerpts from a new edition of the preeminent specialty toxicology textbook, Handbook on the Toxicology of Metals, 4th Edition, Nordberg, Fowler, Nordberg, and Friberg, editors (c. 2014 electronic, 2015 print).
Recent epidemiological studies have revealed that genetic polymorphisms can modify mercury metabolism and susceptibility to mercury exposure.
...a major contribution [to the daily intake of inorganic mercury] may result from the release of mercury vapor from dental amalgam fillings, if present...
Mercury uptake from amalgam increases tissue concentrations in the brain, plasma, and kidneys in proportion to the number of amalgam fillings.
The existence of cases with genetically determined high sensitivity to mercury ... is very likely, and represents a problem relevant to mercury vapor exposure from dental amalgam in the population.
[This is an extended excerpt from the section on sensitive groups.] The available data do not allow much precision in estimating the prevalence of people with susceptibility to low-dose mercury vapor exposure and with adverse side effects from dental amalgam. However, several large cohort studies comparing mortality and morbidity rates between amalgam bearers and amalgam-free people have revealed no differences (Bates et al., 2004; Bates, 2006; Björkman et al., 1996; Langworth et al., 1997). As cohort studies of this kind have limited statistical power and cannot detect prevalences of less than 10-20%, it can only be concluded that the prevalence does not exceed 10%. Prevalence in the order of 1% seems to tally best with clinical experience; the same order is seen for gluten intolerance in Western populations. It is unclear whether the fetus and children should be classified as a group susceptible to low-dose mercury vapor exposure or whether the observed effects are limited to specific genotypes present in the population. The interaction of mercury vapor exposure with brain development is likely to cause persistent sequelae and in that sense the group is more susceptible than the adult population; however, in terms of exposure dose there is at present no evidence of a difference in susceptibility. Several epidemiological studies have compared cohorts of children with dental amalgam fillings to children without amalgam fillings and no difference has been observed; however, all studies suffer from limited statistical power and they cannot exclude adverse effects with a prevalence of less than 10% (Bellinger et al., 2006; Lauterbach et al., 2008). There are, however, case-reference studies showing an association between mercury exposure from dental amalgam, urinary levels of coproporphyrin, and a prevalence of autism in children with a dose-response relation; these data suggest that the CPOX4 polymorphism confers susceptibility to low-dose mercury vapor exposure, resulting in an autism syndrome or modified behavior (Kern et al., 2010, Geier et al., 2009; Woods et al., 2012). Furthermore, the spectrum of gene activation in blood cells correlating with mercury concentration in blood differs between autistic and normally developed boys (Stamova et al., 2011). Baby teeth from 15 children with autism aged 6.1 ± 2.2 years had significantly (2.1-fold) higher mercury content compared to 11 typically developing control children, and no difference in zinc or lead content (Adams et al., 2007). However, in a similar study analyzing samples of enamel from deciduous teeth, no such difference was found (Abdullah et al., 2012), suggesting that the difference observed in the former study was caused by a difference in the mercury content of dentin and in exposure during infancy.
From a public health point of view, such evidence strongly indicates that genetic polymorphisms can give rise to increased susceptibility from exposure to mercury vapor. This aspect should be taken into consideration in risk evaluations of exposure to mercury vapor until evidence to the contrary is available.
[D]uring continuous exposure, the mercury concentrations in blood and urine are not correlated to concentrations of mercury in brain or kidney.
Fetal nerve tissue contains the cell type that shows the most sensitivity to the mercury ion Hg2+. Clear effects arise at the concentration level ... found in neonatal infants of amalgam-bearing mothers.
Regarding Thimerosal (ethylHg):
... the accumulation of inorganic Hg in the brain is likely to be larger [after exposure to ethylHg] than after exposure to MeHg as a consequence of faster biotransformation.
Some epidemiological studies on populations of infants have reported associations between vaccines containing thimerosal and autism, while others have not detected an association. The hypothesis linking thimerosal to autism is biologically plausible. On the one hand, MeHg and EthylHg have been shown to be neurodevelopmental toxicants, so it is possible that with repeated doses of EthylHg, neurodevelopmental interference could occur. On the other hand, because the incidence of autism is low (less than 1% in vaccinated infant populations), it is possible that only a rare sensitive genotype may be affected such that the statistical significance of an association would be difficult to establish. [Comment: the rate of full-blown autism may be less than 1%, but the rate of neruodevelopmental disorders in the US is one in six.]
As has already been said, it is biologically plausible that single doses of EtHg can interact with CNS development in genotypes susceptible to mercury exposure, considering that MeHg-susceptible genotypes have already been identified. From the available data, the risk does not seem to be negligible.
The evidence presented in this section indicates that single doses of around 10 μg EtHg can interfere with brain development. From a health point of view, the precautionary principle should be applied until the safety of EtHg in vaccines is proven, and the use of EtHg in vaccines should be avoided for the vaccination of pregnant women.
Recent epidemiological studies have revealed that genetic polymorphisms can modify mercury metabolism and susceptibility to mercury exposure.
...a major contribution [to the daily intake of inorganic mercury] may result from the release of mercury vapor from dental amalgam fillings, if present...
Mercury uptake from amalgam increases tissue concentrations in the brain, plasma, and kidneys in proportion to the number of amalgam fillings.
The existence of cases with genetically determined high sensitivity to mercury ... is very likely, and represents a problem relevant to mercury vapor exposure from dental amalgam in the population.
[This is an extended excerpt from the section on sensitive groups.] The available data do not allow much precision in estimating the prevalence of people with susceptibility to low-dose mercury vapor exposure and with adverse side effects from dental amalgam. However, several large cohort studies comparing mortality and morbidity rates between amalgam bearers and amalgam-free people have revealed no differences (Bates et al., 2004; Bates, 2006; Björkman et al., 1996; Langworth et al., 1997). As cohort studies of this kind have limited statistical power and cannot detect prevalences of less than 10-20%, it can only be concluded that the prevalence does not exceed 10%. Prevalence in the order of 1% seems to tally best with clinical experience; the same order is seen for gluten intolerance in Western populations. It is unclear whether the fetus and children should be classified as a group susceptible to low-dose mercury vapor exposure or whether the observed effects are limited to specific genotypes present in the population. The interaction of mercury vapor exposure with brain development is likely to cause persistent sequelae and in that sense the group is more susceptible than the adult population; however, in terms of exposure dose there is at present no evidence of a difference in susceptibility. Several epidemiological studies have compared cohorts of children with dental amalgam fillings to children without amalgam fillings and no difference has been observed; however, all studies suffer from limited statistical power and they cannot exclude adverse effects with a prevalence of less than 10% (Bellinger et al., 2006; Lauterbach et al., 2008). There are, however, case-reference studies showing an association between mercury exposure from dental amalgam, urinary levels of coproporphyrin, and a prevalence of autism in children with a dose-response relation; these data suggest that the CPOX4 polymorphism confers susceptibility to low-dose mercury vapor exposure, resulting in an autism syndrome or modified behavior (Kern et al., 2010, Geier et al., 2009; Woods et al., 2012). Furthermore, the spectrum of gene activation in blood cells correlating with mercury concentration in blood differs between autistic and normally developed boys (Stamova et al., 2011). Baby teeth from 15 children with autism aged 6.1 ± 2.2 years had significantly (2.1-fold) higher mercury content compared to 11 typically developing control children, and no difference in zinc or lead content (Adams et al., 2007). However, in a similar study analyzing samples of enamel from deciduous teeth, no such difference was found (Abdullah et al., 2012), suggesting that the difference observed in the former study was caused by a difference in the mercury content of dentin and in exposure during infancy.
From a public health point of view, such evidence strongly indicates that genetic polymorphisms can give rise to increased susceptibility from exposure to mercury vapor. This aspect should be taken into consideration in risk evaluations of exposure to mercury vapor until evidence to the contrary is available.
[D]uring continuous exposure, the mercury concentrations in blood and urine are not correlated to concentrations of mercury in brain or kidney.
Fetal nerve tissue contains the cell type that shows the most sensitivity to the mercury ion Hg2+. Clear effects arise at the concentration level ... found in neonatal infants of amalgam-bearing mothers.
Regarding Thimerosal (ethylHg):
... the accumulation of inorganic Hg in the brain is likely to be larger [after exposure to ethylHg] than after exposure to MeHg as a consequence of faster biotransformation.
Some epidemiological studies on populations of infants have reported associations between vaccines containing thimerosal and autism, while others have not detected an association. The hypothesis linking thimerosal to autism is biologically plausible. On the one hand, MeHg and EthylHg have been shown to be neurodevelopmental toxicants, so it is possible that with repeated doses of EthylHg, neurodevelopmental interference could occur. On the other hand, because the incidence of autism is low (less than 1% in vaccinated infant populations), it is possible that only a rare sensitive genotype may be affected such that the statistical significance of an association would be difficult to establish. [Comment: the rate of full-blown autism may be less than 1%, but the rate of neruodevelopmental disorders in the US is one in six.]
As has already been said, it is biologically plausible that single doses of EtHg can interact with CNS development in genotypes susceptible to mercury exposure, considering that MeHg-susceptible genotypes have already been identified. From the available data, the risk does not seem to be negligible.
The evidence presented in this section indicates that single doses of around 10 μg EtHg can interfere with brain development. From a health point of view, the precautionary principle should be applied until the safety of EtHg in vaccines is proven, and the use of EtHg in vaccines should be avoided for the vaccination of pregnant women.