1 research outputs found
Chemical Space Covered by Applicability Domains of Quantitative Structure–Property Relationships and Semiempirical Relationships in Chemical Assessments
A significant number of chemicals registered in national
and regional
chemical inventories require assessments of their potential “hazard”
concerns posed to humans and ecological receptors. This warrants knowledge
of their partitioning and reactivity properties, which are often predicted
by quantitative structure–property relationships (QSPRs) and
other semiempirical relationships. It is imperative to evaluate the
applicability domain (AD) of these tools to ensure their suitability
for assessment purpose. Here, we investigate the extent to which the
ADs of commonly used QSPRs and semiempirical relationships cover seven
partitioning and reactivity properties of a chemical “space”
comprising 81,000+ organic chemicals registered in regulatory and
academic chemical inventories. Our findings show that around or more
than half of the chemicals studied are covered by at least one of
the commonly used QSPRs. The investigated QSPRs demonstrate adequate
AD coverage for organochlorides and organobromines but limited AD
coverage for chemicals containing fluorine and phosphorus. These QSPRs
exhibit limited AD coverage for atmospheric reactivity, biodegradation,
and octanol–air partitioning, particularly for ionizable organic
chemicals compared to nonionizable ones, challenging assessments of
environmental persistence, bioaccumulation capability, and long-range
transport potential. We also find that a predictive tool’s
AD coverage of chemicals depends on how the AD is defined, for example,
by the distance of a predicted chemical from the centroid of the training
chemicals or by the presence or absence of structural features