Extended Virtual Screening Strategies To Link Antiandrogenic Activities and Detected Organic Contaminants in Soils

A tiered screening strategy based
on extensive virtual fractionation and elucidation was developed to
simplify identification of toxicants in complex environments. In tier1-virtual
fractionation, multivariate analysis (MVA) was set up as an alternative
of physical fractionation. In tier2-virtual structure elucidation,
in-house quantitative structure–retention relationship (QSRR)
models and toxicity simulation methods were developed to simplify
nontarget identification. The efficiency of the tiered virtual strategy
was tentatively verified by soil samples from a chemical park contaminated
by antiandrogenic substances. Eight out of 18 sites were detected
as antiandrogenic, while none of them exhibited androgenic agonist
potencies. Sixty-seven peaks were selected for further identification
by MVA, among which over 90% were verified in androgenic fractions
in traditional effect-directed analysis (EDA). With 579 tentative
structures generated by in silico fragmentation, 74% were elucidated
by QSRR and 65% were elucidated by in silico toxicity prediction.
All prior peaks were identified at different confidence levels with
over 40% of the identified peaks above confidence level 2b, which
has been increased over 40% with less than half of the time spent
compared to traditional EDA. Such a combination of tiered virtual
screening methods provides more efficient and rapid identifications
of key toxicants at contaminated sites.