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MERCURY 196
2. HEALTH EFFECTS
dosing. The latter is of direct relevance to methylmercury risk assessments currently based on human
studies of short-term exposures, while the general public exposure is more typically continuous. Neither
model ran simulations nor validated against data for other species (including human). Nor did the models
address high-to-low dose extrapolations or different routes of exposure.
2.3.5.3 Discussion of Models
The Farris et al. Model for Methylmercury. The Farris et al. (1993) model is a physiologically
based model that simulates the long-term disposition of methylmercury and its primary biotransformation
product, mercuric mercury, in growing mammals following a single nontoxic oral dose of the parent
compound. The test animal used to develop and validate the model was the male Sprague-Dawley rat. A
tracer dose was used in the validation studies to preclude the possibility that the results would be biased by
toxic or saturation effects. The model incorporates a number of features, including a time-dependent
compartment for volume changes (i.e., the rats grew from 300 to 500 g in body weight over the 98-day time
course of the validation study), compartment volume-dependent clearances, and the recycling of mercury
from ingestion of hair by rats during grooming.
Risk assessment. The Farris et al. model has not been used in human risk assessment. The authors,
however, suggest that the model would be useful in developing a better understanding of species differences
and in predicting the affects of altered biochemical or physiological states on methylmercury pharmacokinetics.
For example, the authors suggest that the model can be adapted to simulate data for neonatal
animals or humans that are known to secrete glutathione poorly. It could also help elucidate the mercury
kinetics for animals that have altered bile flow or that have nonabsorbable sulfhydryl-containing resins.
Description of the model. The Farris et al. model consists of nine lumped compartments, each of
which represent a major site of mercury accumulation, elimination, or effect in mammals. The
compartment labeled “carcass” is a residual compartment and consists of all tissues and organs not
specifically represented by the other eight compartments in the model. A flow diagram of the model is
shown in Figure 2-5. The interdepartmental mass transport parameters used in the model are shown in
Table 2-6.
Methylmercury transport between all compartments except brain and hair is modeled as plasma flow limited
(i.e., plasma levels rapidly equilibrate with erythrocytes). Mercuric mercury transport parameters