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

MERCURY 309
2. HEALTH EFFECTS
mercury enter an oxidation-reduction cycle. Metallic mercury is oxidized to the divalent inorganic cation in
the red blood cells and lungs of humans and animals. Evidence from animal studies suggests the liver as an
additional site of oxidation. Absorbed divalent cation from exposure to mercuric mercury compounds can,
in turn, be reduced to the metallic or monovalent form and released as exhaled metallic mercury vapor. In
the presence of protein sulfhydryl groups, mercurous mercury (Hg + ) disproportionates to one divalent cation
(Hg +2 ) and one molecule at the zero oxidation state (Hg0 ). The conversion of methylmercury or phenylmercury
into divalent inorganic mercury can probably occur soon after absorption, also feeding into the
oxidation-reduction pathway.
A number of good physiologically based pharmacokinetic models are currently available for mercury,
including some that address developmental toxicity and maternal/fetal transfer. Two models were
constructed based upon data from the kinetics of methylmercury in rats. Farris et al. (1993) developed a
PBPK model that simulates the long-term disposition of methylmercury and its primary biotransformation
product, mercuric mercury, in the male Sprague-Dawley rat following a single oral nontoxic exposure. Gray
(1995) developed a PBPK model that simulates the kinetics of methylmercury in the pregnant rat and fetus.
The Gray model was developed to provide fetal and maternal organ methylmercury concentration-time
profiles for any maternal dosing regimen. Sundberg et al. (1998) fitted a three compartment model to the
elimination kinetics of methylmercury and inorganic mercury transfer to milk in lactating and nonlactating
mice. Luecke et al. (1997) developed a model based on human physiology but extended to simulate animal
data that depict internal disposition of two chemicals (singly or in combination) during pregnancy in the
mother and the embryo/fetus. Leroux et al. (1996) developed a biologically based-dose-response model to
describe the dynamics of organogenesis, based on the branching process models of cell kinetics. Gearhart et
al. (1995) developed a PBPK model to coherently describe methylmercury pharmacokinetics in a variety of
species (adult rat, monkey, and human), and to predict fetal levels of methylmercury from an in utero
exposure.
No information was identified on biomarkers of exposure for children. Mercury levels in hair, urine, and
blood are the standard measures of exposure. There are biomarkers for developmental effects that are unique
to specific ages and stages of development throughout the child’s developmental process. Developing the
best measures for evaluation of cognitive functions is an area of intense debate and on-going research.