A toxicokinetic model for predicting the tissue distribution and elimination of organic and inorganic mercury following exposure to methyl mercury inanimals and humans. II. Application and validation of the model in humans

The objective of this study was to develop a biologically based dynamical m odel describing the disposition kinetics of methyl mercury and its inorgani c mercury metabolites in humans following different methyl mercury exposure scenarios. The model conceptual and functional representation was similar to that used for rats but relevant data on humans served to determine the c ritical parameters of the kinetic behavior. It was found that the metabolic rate of methyl mercury was on average 3 to 3.5 times slower in humans than in rats. Also, excretion rates of organic mercury from the whole body into feces and hair were 100 and 40 times smaller in humans, respectively, and urinary excretion of organic mercury in humans was found to be negligible. The human transfer rate of inorganic mercury from blood to hair was found t o be 5 times lower than that of rats. On the other hand, retention of inorg anic mercury in the kidney appeared more important in humans than in rats: the transfer rate of inorganic mercury from blood to kidney was 19 times hi gher than in rats and that from kidney to blood 19 times smaller. The excre tion rate of inorganic mercury from the kidney to urine in humans was found to be twice that of rats. With these model parameters, simulations accurat ely predicted human kinetic data available in the published literature for different exposure scenarios. The model relates quantitatively mercury spec ies in biological matrices (blood, hair, and urine) to the absorbed dose an d tissue burden at any point in time. Thus, accessible measurements on thes e matrices allow inferences of past, present, and future burdens. This coul d prove to be a useful tool in assessing the health risks associated with v arious circumstances of methyl mercury exposure. (C) 2001 Academic Press.