Data from: Evaluating in vitro-in vivo extrapolation of toxicokinetics

Prioritizing the risk posed by thousands of chemicals potentially present
in the environment requires exposure, toxicity, and toxicokinetic (TK)
data, which are often unavailable. Relatively high throughput, in vitro TK
(HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have
been developed to predict TK, but most of the in vivo TK data available to
benchmark these methods are from pharmaceuticals. Here we report on new,
in vivo rat TK experiments for 26 non-pharmaceutical chemicals with
environmental-relevance. Both intravenous and oral dosing were used to
calculate bioavailability. These chemicals, and an additional 19 chemicals
(including some pharmaceuticals) from previously published in vivo rat
studies, were systematically analyzed to estimate in vivo TK parameters
(e.g., volume of distribution (Vd), elimination rate). For each of the
chemicals, rat-specific HTTK data were available and key TK predictions
were examined: oral bioavailability, clearance, Vd, and uncertainty. For
the non-pharmaceutical chemicals, predictions for bioavailability were not
effective. While no pharmaceutical was absorbed at less than 10%, the
fraction bioavailable for non-pharmaceutical chemicals was as low as 0.3%.
Total clearance was generally more under-estimated for non-pharmaceuticals
and Vd methods calibrated to pharmaceuticals may not be appropriate for
other chemicals. However, the steady-state, peak, and time-integrated
plasma concentrations of non-pharmaceuticals were predicted with
reasonable accuracy. The plasma concentration predictions improved when
experimental measurements of bioavailability were incorporated. In
summary, HTTK and IVIVE methods are adequately robust to be applied to
high throughput in vitro toxicity screening data of
environmentally-relevant chemicals for prioritizing based on human health
risks.