Bio: Dr. Hollnagel is a lead scientist and regulatory toxicologist at Dow Europe in Switzerland with experience in product safety and regulatory assessments of cosmetic ingredients, home care products, food contact materials, medical devices, excipients, food additives and industrial chemicals. Dr. Hollnagel chairs the Cefic Polymer Issues Team, the Issue Team of the Cefic Long-range Research Initiative and is a member of the ECETOC Scientific Committee. Dr. Hollnagel chairs the ILSI Europe Task Force on the Threshold of Toxicological Concern and is current and past member of several ILSI Expert Groups and ECETOC task forces. Her current main research interests are TTC, polymer and coexposure risk assessment. Dr. Hollnagel graduated as Food Chemist and earned her PhD degree in molecular toxicology from the University of Potsdam, Germany. She holds certifications by the Swiss and European Federation of Toxicologists and is a Diplomate of the American Board of Toxicologists.

Abstract: The threshold of toxicological concern (TTC) approach is particularly valuable for chemicals, such as natural constituents or contaminants, for which toxicity data, or even reference materials, are unavailable. Extension of the TTC approach for use in screening complex mixtures has been proposed, for example for cosmetics, botanical extracts, and industrial chemicals (Smith et al. 2005; Little et al. 2017). However, application of the TTC approach to complex mixtures ideally requires identification of the structures of all constituents present, with only few unknowns accepted and then assessed against the Cramer Class III threshold. Furthermore, where toxicity data are unavailable, mode of action data are lacking as well, so that decisions about which chemicals to include within a mixture assessment group, i.e., based on dose additivity, are challenging. Due to the highly conservative nature of TTC, assuming dose additivity for all mixture components lacking mode of action information will often prevent the conclusion that an exposure to such mixture is safe when applying TTC thresholds. The learnings of a working group of the International Life Sciences Institute Europe about the suitability of existing computational tools such as for structure-based and metabolism-based grouping of constituents will be presented for a case study mixture.

References:

1. Smith RL et al. A procedure for the safety evaluation of natural flavor complexes used as ingredients in food: essential oils. Food Chem Toxicol. 2005 Mar;43(3):345-63.

2. Little JG, et al. In silico approach to safety of botanical dietary supplement ingredients utilizing constituent-level characterization. Food Chem Toxicol. 2017 Sep;107(Pt A):418-429.