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

MERCURY 302
2. HEALTH EFFECTS
Whether differences in xenobiotic metabolism make the child more or less susceptible also depends on
whether the relevant enzymes are involved in activation of the parent compound to its toxic form or in
detoxification. There may also be differences in excretion, particularly in the newborn who has a low
glomerular filtration rate and has not developed efficient tubular secretion and resorption capacities (Altman
and Dittmer 1974; NRC 1993; West et al. 1948). Children and adults may differ in their capacity to repair
damage from chemical insults. Children also have a longer lifetime in which to express damage from
chemicals; this potential is particularly relevant to cancer.
Certain characteristics of the developing human may increase exposure or susceptibility while others may
decrease susceptibility to the same chemical. For example, the fact that infants breathe more air per
kilogram of body weight than adults may be somewhat counterbalanced by their alveoli being less
developed, so there is a disproportionately smaller surface area for absorption (NRC 1993).
Adverse health effects from different forms of mercury differ primarily because of differences in kinetics
rather than mode of action. As discussed in the introduction to this section, children have different, and
sometimes dramatically different, morphology or physiology that alters the way toxic compounds are
absorbed and distributed throughout their bodies. For mercury compounds, preventing entry into the
systemic circulation is the best means to prevent adverse effects. Once mercury enters the circulation, the
tissues that end up as target sites are those that accumulate the most mercuric ion or the ones that are most
often exposed to mercuric ion. That is why the kidney is a prime target site, for in fulfilling its major role
of filtering and purifying the blood, the kidney is continually exposed to ionic mercury. The central
nervous system is a major target site because mercuric ion also concentrates in the brain compartment.
Ironically, it may be the blood-brain barrier that contributes to, rather than prevents, mercuric ion
“trapping” in the brain. A current hypothesis is that once lipophilic forms of mercury cross the bloodbrain
barrier, they are oxidized to more hydrophilic species and become trapped inside the brain
compartment. This “one way” only kinetic pathway results in continually increasing brain mercuric
ion levels, as long as nonpolar forms are in the blood stream. Even small amounts of nonpolar mercury
(