es9b03991_si_001.pdf (1.14 MB)
Physiologically Based Pharmacokinetic Modeling for Chlorinated Paraffins in Rats and Humans: Importance of Biliary Excretion
journal contribution
posted on 2019-12-03, 15:21 authored by Zhaomin Dong, Tong Li, Yi Wan, Yibin Sun, Jianying HuChlorinated paraffins (CPs) are chemicals with high production
volumes that can accumulate at high levels in general populations.
The pharmacokinetics of CPs as pollutants is unknown, and there is
no evidence that the medium chain chlorinated paraffins (MCCPs) and
long chain chlorinated paraffins (LCCPs) are safe replacements for
short chain chlorinated paraffins (SCCPs). In this study, SCCPs, MCCPs,
and LCCPs were first in vivo and in vitro exposed to rat and liver microsomes, respectively. Toxicokinetics of these compounds
were assessed and used to establish the corresponding physiologically
based pharmacokinetic (PBPK) models in rats. More than 90% of ingested
CPs were deposited in the liver and fat, and the compounds were extremely
resistant to metabolism and mostly eliminated via biliary excretion.
Then, humans’ external and internal exposures to CPs were investigated
for one year in Shenzhen, South China. The results were used to calibrate
the key parameters for the establishment of a PBPK model in humans.
In the PBPK models of rats and humans, the rate of biliary excretion
had the greatest influence on the accumulated levels and half-lives
of CPs. The body half-lives of human were estimated to be 5.1, 1.2,
and 0.6 years for SCCPs, MCCPs, and LCCPs, respectively, suggesting
the high accumulation of SCCPs in humans compared to other CPs.