Predicting points of departure and potency categories for fragrance ingredients by integrating OECD in vitro models.

Autor: Lee I; Research Institute for Fragrance Materials, Inc., 1200 MacArthur Blvd, Suite 306, Mahwah, NJ, USA. Electronic address: ilee@rifm.org., Na M; Research Institute for Fragrance Materials, Inc., 1200 MacArthur Blvd, Suite 306, Mahwah, NJ, USA; Estee Lauder Companies, Melville, NY, 11747, USA., Lavelle M; Research Institute for Fragrance Materials, Inc., 1200 MacArthur Blvd, Suite 306, Mahwah, NJ, USA., Schember I; Research Institute for Fragrance Materials, Inc., 1200 MacArthur Blvd, Suite 306, Mahwah, NJ, USA., Ryan C; ToxTech Solutions, LLC, Milan, IN, USA., Gerberick GF; GF3 Consultancy, LLC, West Chester, OH, USA., Natsch A; Givaudan Suisse SA, Kemptpark 50, 8310, Kemptthal, Switzerland., Api AM; Research Institute for Fragrance Materials, Inc., 1200 MacArthur Blvd, Suite 306, Mahwah, NJ, USA.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2024 Nov; Vol. 193, pp. 114998. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1016/j.fct.2024.114998
Abstrakt: Continuous potency assessment is crucial for conducting quantitative risk assessment (QRA) of sensitizers. Quantitative regression models, based on in vitro methods, have been developed to calculate points of departure for use in skin sensitization QRA. These models calculate a point of departure as a predicted value for Local Lymph Node Assay (LLNA) EC3 or potency value (PV), integrating data from the kinetic Direct Peptide Reactivity Assay (kDPRA), KeratinoSens (KS) assay, and human Cell Line Activation Test (h-CLAT). The goal of this study was to determine how in vitro predicted EC3s and PVs compare to published reference data. In vitro data were combined in point of departure regression models to predict EC3s and PVs. These points of departure were then grouped into sensitization potency categories, such as extreme, strong, moderate, weak, very weak, or non-sensitizer, as previously described. Trends in potency distribution and high concordance between predicted EC3 and PV categories and published potency categories were observed. Furthermore, the median absolute fold-misprediction ranged between 1.8 and 2.5 for models predicting EC3 and between 1.7 and 3.4 for those predicting PVs. These regression models are a promising animal alternative for determining sensitization quantitative potency for fragrance ingredients, thereby facilitating QRA.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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