revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 209
2. HEALTH EFFECTS
18 months, and 74% 6 months after termination of exposure. The authors stated that the presence of
inorganic mercury in the brain was thought to be the result of demethylation of methylmercury in the brain.
In heavier monkeys, there was a limited distribution of mercury in the fat. A finding of higher brain
concentrations in the heavy monkeys than in those of normal weight was probably due to higher blood
mercury levels and a higher brain-to-blood distribution ratio. In vivo methylation of inorganic mercury, on
the other hand, was not shown to occur in occupationally exposed workers (Barregard et al. 1994a, 1994b),
contrary to the findings of previous in vitro studies.
Distribution of organic mercury is believed to involve complexes with proteins in the body. Methylmercury
associates with water-soluble molecules (e.g., proteins) or thiol-containing amino acids because of the high
affinity of the methylmercuric cation (CH3Hg + ) for the sulfhydryl groups (SH-) (Aschner and Aschner
1990). Complexes of methylmercury with cysteine or glutathione have been identified in blood, liver, and
bile (Aschner and Aschner 1990). The transport of methylmercury to the brain after subcutaneous injection
appears to be closely linked to thiol-containing amino acids (Aschner and Clarkson 1988). The methylmercury
cation can bind to the thiol group of the amino acid cysteine, forming a complex in which the
valence bonds link the mercury atom to adjacent iron and sulfur atoms at an 180E angle, creating a chemical
structure similar to that of the essential amino acid methionine (Clarkson 1995). In such a manner, methylmercury
can cross the blood-brain barrier "disguised" as an amino acid via a carrier-mediated system (i.e.,
transport is not solely the result of methylmercury’s lipid solubility). The uptake of methylmercury by the
brain is inhibited by the presence of other amino acids such as leucine, methionine, phenylalanine, and
other large neutral amino acids (Clarkson 1995).
The mechanism by which methylmercury crosses the blood-brain barrier has also been examined in the rat
using a rapid carotid infusion technique (Kerper et al. 1992). The results of this study also showed that
methylmercury may enter the brain as a cysteine complex. The uptake of Me 20 3Hg complexed with either
L- or D-cysteine was measured as a function of Me 20 3Hg-cysteine concentration in the injection solution.
There was a faster rate of uptake of Me 20 3Hg-L-cysteine as compared to the D-cysteine complex. The
nonlinearity of Me 20 3Hg-L-cysteine uptake with the increasing concentration suggests that transport of this
complex is saturable, while the D-cysteine complex is taken up by simple diffusion. The mechanism for the
distribution in the brain of inorganic mercury (resulting from the demethylation of organic mercury) is not
well understood.