Integrated Testing Strategy for the Safety of Botanical Ingredients: A Case Study with German Chamomile Constituents

Publication: Appl In Vitro Tox
Software: ADMET Predictor®


Introduction: chamomile is a botanical ingredient commonly used in cosmetics, thus determination of skin sensitization effects of German chamomile constituents is critical for the safety of consumers. Nonetheless, a systematic investigation of skin sensitization potential of chamomile constituents is lacking. Non-animal methods for skin sensitization hazard evaluation have been progressively accepted as attractive alternatives to conventional animal models, especially when used in an integrated fashion.

Materials and Methods: In the present work, 30 constituents of German chamomile were investigated for skin sensitization using in silico, in chemico, and in vitro methods, including classification-quantitative structure–activity relationship (c-QSAR) models (ADMET predictor and CASE Ultra), an expert knowledge-based system (Derek Nexus), the Direct Peptide Reactivity Assay (DPRA), the high-throughput assay with dansylated cysteamine (HTS-DCYA), the KeratinoSens™ assay, and the human Cell Line Activation Test (h-CLAT).

Results and Discussion: Identical classification was found for 14 compounds upon comparison between computational and experimental methods. Seven compounds (umbelliferone, apigenin, kaempferol, isorhamnetin, nerol, α-terpinene, and carvone) were positive in both models, that is, in silico and experimental settings. Seven other compounds (caffeic acid, t-ferulic acid, cosemetin, hyperoside, α-terpineol, α-bisabolol, and chamazulene) were determined to be non-sensitizers instead.

Conclusions: Among the compounds positive in experimental settings, umbelliferone and farnesene should be regarded as a potential concern because of their positive classification and significant concentration in German chamomile.

By Cristina Avonto, Zemin Wang, Jongmin Ahn, Rajeshwar P. Verma, Nakissa Sadrieh, Olivia Dale, Shabana I. Khan, Amar G. Chittiboyina, and Ikhlas A. Khan