RT Journal Article
SR Electronic
T1 Characterizing Extractables and Leachables Chemical Space to Support In Silico Toxicological Hazard Assessments
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 237
OP 311
DO 10.5731/pdajpst.2022.012819
VO 78
IS 3
A1 Johnson, Candice
A1 Bassan, Arianna
A1 Kiehl, Doug
A1 Paskiet, Diane
A1 Pavan, Manuela
A1 Parris, Patricia
A1 Whelan, Geraldine
A1 Burild, Anders
A1 Myatt, Glenn J.
YR 2024
UL http://journal.pda.org/content/78/3/237.abstract
AB This article describes the development of a representative dataset of extractables and leachables (E&L) from the combined Extractables and Leachables Safety Information Exchange (ELSIE) Consortium and the Product Quality Research Institute (PQRI) published datasets, representing a total of 783 chemicals. A chemical structure-based clustering of the combined dataset identified 142 distinct chemical classes with two or more chemicals across the combined dataset. The majority of these classes (105 chemical classes out of 142) contained chemicals from both datasets, whereas 8 classes contained only chemicals from the ELSIE dataset and 29 classes contain only chemicals from the PQRI dataset. This evaluation also identified classes containing chemicals that were flagged as potentially mutagenic as well as potent (strong or extreme) dermal sensitizers by in silico tools. The prevalence of alerting structures in the E&L datasets was approximately 9% (69 examples) for mutagens and 3% (25 examples) for potent sensitizers. This analysis showed that most (80%; 20 of 25) E&L predicted to be strong or extreme dermal sensitizers were also flagged as potential mutagens. Only two chemical classes, each containing three chemicals (alkyl bromides and isothiocyanates), were uniquely identified in the PQRI dataset and contained chemicals predicted to be potential mutagens and/or potent dermal sensitizers.