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MERCURY 207
2. HEALTH EFFECTS
suggests that generally good agreement between the model simulated results and the published values
indicate that the model accurately reflects the underlying biological processes and that scaling factors for
species-to-species extrapolations should be considered.
High-low dose extrapolations. No data were presented to evaluate the utility of the model for high-
to-low dose extrapolations. A continuous exposure was simulated, but it was not validated against
published data.
Interroute extrapolation. Only the intravenous route of exposure was evaluated. No data were
presented to evaluate the validity of the model in extrapolating to an oral, inhalation, or dermal route of
exposure. No compartment was included in the model for the lungs. Although a skin compartment was
included in the model, absorption from a dermal application of methylmercury was not addressed.
2.4 MECHANISMS OF ACTION
2.4.1 Pharmacokinetic Mechanisms
The absorption of metallic mercury through the lungs is by rapid diffusion. It is suggested that oral
absorption of inorganic mercury compounds depends on their dissociation in the intestinal tract. In several
cases, the underlying mechanism for the toxic effects of mercury has been attributed to the high affinity of
mercury for protein-containing sulfhydryl or thiol groups.
The mechanism of absorption for metallic mercury vapors is rapid diffusion across alveolar membranes
(Berlin et al. 1969; Clarkson 1989). Mercury distribution in the brains of mercury-sensitive SJL/N mice
exposed for 10 weeks (5 days per week) to relatively high concentrations (0.5–1.0 mg/m 3 ) of mercury vapor
was found to be affected by the magnitude of exposure (Warfvinge 1995). In animals exposed to 0.5 mg/m 3
for 19 hours a day or 1 mg/m 3 for 3 hours a day, mercury was found in almost the entire brain, whereas in
those exposed to 0.3 mg/m 3 for 6 hours a day, mercury was primarily found in the neocortical layer V, the
white matter, the thalamus, and the brain stem. In mice exposed to 1 mg/m 3 for just 1.5 hours a day, the
white matter and brain stem were the targets for mercury accumulation. These findings in mice were
generally in agreement with brain distribution patterns observed in mercury-sensitive rats (Schionning et al.
1991; Warfvinge et al. 1992), except that the white matter was not found to be a target for mercury
accumulation.