TY - JOUR
T1 - Population toxicokinetics of tetrachloroethylene
JF - Archives of Toxicology
Y1 - 1996/
SP - 347
EP - 355
A1 - Frédéric Y. Bois
A1 - Andrew Gelman
A1 - Jiming Jiang
A1 - Don Maszle
A1 - Lauren Zeise
A1 - George Alexeeff
KW - human metabolism
KW - pharmacokinetics
KW - population toxicokinetics
KW - tetrachloroethylene
AB - 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 tetrachloroethylene (PERC) in humans. We derive statistical distributions for the parameters of a physiological model of PERC, on the basis of data from Monster et al. (1979). The model adequately ﬁts both prior physiological information and experimental data. An estimate of the relationship between PERC exposure and fraction metabolized is obtained. Our median population estimate for the fraction of inhaled tetrachloroethylene that is metabolized, at exposure levels exceeding current occupational standards, is 1.5% [95% conﬁdence interval (0.52%, 4.1%)]. At levels approaching ambient inhalation exposure (0.001 ppm), the median estimate of the fraction metabolized is much higher, at 36% [95% conﬁdence interval (15%, 58%)]. This disproportionality should be taken into account when deriving safe exposure limits for tetrachloroethylene and deserves to be veriﬁed by further experiments.
VL - 70
U1 - 7.1

ER -