A physiologically based pharmacokinetic (PBPK) model for methyl mercury (MeHg) in monkey and human
- K.S. Crump Group, Georgia, Ruston, LA (United States); and others
A PBPK model for MeHg was developed which coherently describes MeHg pharmacokinetics in the adult rat, monkey and man, and predicts fetal levels of MeHg from in utero exposure. The model includes a description of enterohepatic recirculation of MeHg, conversion to inorganic mercury in tissues and intestinal flora, slowly reversible incorporation of mercury in tissues, and excretion of both organic and inorganic mercury into urine, feces, and hair. The adult submodel includes compartments representing the red blood tells (RBC), plasma, brain, liver, kidney, gut intestinal lumen, gut tissue, hair, richly and slowly perfused tissues, and placenta. The fetal submodel includes compartments representing RBC`s, plasma, brain, and remaining body mass. Two features of the model structure which are critical to prediction of the kinetics of MeHg in different species is the use of separate RBC and plasma compartments, allowing the use of species specific RBC/plasma ratios, and biliary excretion with enterohepatic recirculation. Published tissue and blood MeHg concentrations were used to derive the partition coefficients and RBC/plasma ratios to adjust for species differences in MeHg distribution. Validation involved comparing the model simulations with data from repeated dosing studies in animals and humans, and from accidental human exposures. The model will be used to investigate maternal MeHg intake as it relates to measured blood and hair MeHg concentrations, and to fetal exposure.
- OSTI ID:
- 210490
- Report Number(s):
- CONF-9509139--
- Country of Publication:
- United States
- Language:
- English
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