In vitro pharmacologic profiling aids systemic toxicity assessment of chemicals

Matthew J. Burbank, Predrag Kukić, Gladys Ouédraogo, J. Gerry Kenna, Nicola J. Hewitt, Duncan Armstrong, Annie E. Otto-Bruc, Johanna Ebmeyer, Mareike Boettcher, Ian Willox, Catherine Mahony · Toxicology and Applied Pharmacology · 2024

An adapted in vitro pharmacology profiling panel (APPP) was developed that included targets used in the pharmaceutical industry alongside additional targets whose cellular functions have been linked to systemic toxicities. This panel of 83 target assays was used to profile the activities of 129 cosmetic relevant chemicals with diverse chemical structures, physiochemical properties and cosmetic use types. Internal data consistency was proved robust, as evidenced by the reproducibility between single concentration and concentration-response data and showed good concordance with data reported in the ToxCast and drug excipient datasets. We discuss how the data can be analyzed and multiple potential contexts of use illustrated by case studies, alongside other new approach methodologies, to support cosmetic chemical risk assessments that do not require data from new animal studies. • An adapted in vitro pharmacology profiling panel (APPP) was developed. • Profiled activities of 129 cosmetic relevant chemicals. • Good reproducibility between single concentration and dose response data. • Data analysis and application demonstrated in case studies. • APPP aids systemic toxicity risk assessment.

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