In assessing the distribution and metabolism of toxic compounds in the body, measurements are not always feasible for ethical or technical reasons. Computer modeling offers a reasonable alternative, but the variability and complexity of biological systems pose unique challenges in model building and adjustment. Recent tools from population pharmacokinetics, Bayesian statistical inference, and physiological modeling can be brought together to solve these problems. As an example, we modeled the distribution and metabolism of benzene in humans. We derive statistical distributions for the parameters of a physiological model of benzene, on the basis of existing data. The model adequately fits both prior physiological information and experimental data. An estimate of the relationship between benzene exposure (up to 10 ppm) and fraction metabolized in the bone marrow is obtained and is shown to be linear for the subjects studied. Our median population estimate for the fraction of benzene metabolized, independent of exposure levels, is 52% (90% confidence interval, 47-67%). At levels approaching occupational inhalation exposure (continuous 1 ppm exposure), the estimated quantity metabolized in the bone marrow ranges from 2 to 40 mg/day.
BT - Environmental Health Perspectives C1 -7.1
DA - 12/1996 IS - Suppl 6 LA - eng N2 -In assessing the distribution and metabolism of toxic compounds in the body, measurements are not always feasible for ethical or technical reasons. Computer modeling offers a reasonable alternative, but the variability and complexity of biological systems pose unique challenges in model building and adjustment. Recent tools from population pharmacokinetics, Bayesian statistical inference, and physiological modeling can be brought together to solve these problems. As an example, we modeled the distribution and metabolism of benzene in humans. We derive statistical distributions for the parameters of a physiological model of benzene, on the basis of existing data. The model adequately fits both prior physiological information and experimental data. An estimate of the relationship between benzene exposure (up to 10 ppm) and fraction metabolized in the bone marrow is obtained and is shown to be linear for the subjects studied. Our median population estimate for the fraction of benzene metabolized, independent of exposure levels, is 52% (90% confidence interval, 47-67%). At levels approaching occupational inhalation exposure (continuous 1 ppm exposure), the estimated quantity metabolized in the bone marrow ranges from 2 to 40 mg/day.
PY - 1996 SP - 1405 EP - 1411 T2 - Environmental Health Perspectives TI - Population toxicokinetics of benzene. Environmental Health Perspectives UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469729/ VL - 104 ER -