Novel Models for Accurate Estimation of Air–Blood Partitioning: Applications to Individual Compounds and Complex Mixtures of Neutral Organic Compounds

The air-blood partition coefficient (Kab) is extensively employed in human
health risk assessment
for chemical exposure. However, current Kab estimation approaches either require an extensive
number of parameters or lack precision. In this study, we present
two novel and parsimonious models to accurately estimate Kab values for individual neutral organic
compounds, as well as their complex mixtures. The first model, termed
the GC×GC model, was developed based on the retention times of
nonpolar chemical analytes on comprehensive two-dimensional gas chromatography
(GC×GC). This model is unique in its ability to estimate the Kab values for complex mixtures
of nonpolar organic chemicals. The GC×GC model successfully accounted
for the Kab variance
(R2 = 0.97) and demonstrated strong prediction
power (RMSE = 0.31 log unit) for an independent set of nonpolar chemical
analytes. Overall, the GC×GC model can be used to estimate Kab values for complex mixtures
of neutral organic compounds. The second model, termed the partition
model (PM), is based on two types of partition coefficients: octanol
to water (Kow) and air
to water (Kaw). The PM
was able to effectively account for the variability in Kab data (n = 344), yielding
an R2 value of 0.93 and root-mean-square
error (RMSE) of 0.34 log unit. The predictive power and explanatory
performance of the PM were found to be comparable to those of the
parameter-intensive Abraham solvation models (ASMs). Additionally,
the PM can be integrated into the software EPI Suite, which is widely
used in chemical risk assessment for initial screening. The PM provides
quick and reliable estimation of Kab compared to ASMs, while the GC×GC model is uniquely suited
for estimating Kab values
for complex mixtures of neutral organic compounds. In summary, our
study introduces two novel and parsimonious models for the accurate
estimation of Kab values
for both individual compounds and complex mixtures.