title: Cosmetics Europe compilation of historical serious eye damage/eye irritation in vivo data analysed by drivers of classification to support the selection of chemicals for development and evaluation of alternative methods/strategies: the Draize eye test Reference Database (DRD).
abstract: A thorough understanding of which of the effects assessed in the in vivo Draize eye test are responsible for driving UN GHS/EU CLP classification is critical for an adequate selection of chemicals to be used in the development and/or evaluation of alternative methods/strategies and for properly assessing their predictive capacity and limitations. For this reason, Cosmetics Europe has compiled a database of Draize data (Draize eye test Reference Database, DRD) from external lists that were created to support past validation activities. This database contains 681 independent in vivo studies on 634 individual chemicals representing a wide range of chemical classes. A description of all the ocular effects observed in vivo, i.e. degree of severity and persistence of corneal opacity (CO), iritis, and/or conjunctiva effects, was added for each individual study in the database, and the studies were categorised according to their UN GHS/EU CLP classification and the main effect driving the classification. An evaluation of the various in vivo drivers of classification compiled in the database was performed to establish which of these are most important from a regulatory point of view. These analyses established that the most important drivers for Cat 1 Classification are (1) CO mean ≥ 3 (days 1-3) (severity) and (2) CO persistence on day 21 in the absence of severity, and those for Cat 2 classification are (3) CO mean ≥ 1 and (4) conjunctival redness mean ≥ 2. Moreover, it is shown that all classifiable effects (including persistence and CO = 4) should be present in ≥60 % of the animals to drive a classification. As a consequence, our analyses suggest the need for a critical revision of the UN GHS/EU CLP decision criteria for the Cat 1 classification of chemicals. Finally, a number of key criteria are identified that should be taken into consideration when selecting reference chemicals for the development, evaluation and/or validation of alternative methods and/or strategies for serious eye damage/eye irritation testing. Most important, the DRD is an invaluable tool for any future activity involving the selection of reference chemicals.
authors.affiliation: Cosmetics Europe - The Personal Care Association, Brussels, Belgium.|European Commission Joint Research Centre, Institute for Health and Consumer Protection, EURL ECVAM/Systems Toxicology Unit, Ispra, VA, Italy.
authors.forename: João
authors.initials: J
authors.lastname: Barroso
authors.affiliation: Front End Innovation - Toxicology, Beiersdorf AG, Hamburg, Germany. Uwe.Pfannenbecker@Beiersdorf.com.
authors.forename: Uwe
authors.initials: U
authors.lastname: Pfannenbecker
authors.affiliation: Adriaens Consulting BVBA, Aalter, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Adriaens
authors.affiliation: Department of Predictive Biological Methods and Models, L'Oréal Research and Innovation, Aulnay Sous Bois, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Alépée
authors.affiliation: Product Safety Department, LVMH Recherche - LVMH Parfums et Cosmétiques, St. Jean de Braye Cedex, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Cluzel
authors.affiliation: Preclinical Development and Safety, Janssen Research and Development, Beerse, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: De Smedt
authors.affiliation: Toxicology Department, Chanel Parfums Beauté, Neuilly sur Seine, France.
authors.forename: Jalila
authors.initials: J
authors.lastname: Hibatallah
authors.affiliation: Cosmetics Europe - The Personal Care Association, Brussels, Belgium.
authors.forename: Martina
authors.initials: M
authors.lastname: Klaric
authors.affiliation: Biological and Clinical Research, Henkel AG and Co. KGaA, Düsseldorf, Germany.
authors.forename: Karsten R
authors.initials: KR
authors.lastname: Mewes
authors.affiliation: In Vitro Metabolism and Alternative Methods, Pierre Fabre, Castres, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Millet
authors.affiliation: In Vitro Metabolism and Alternative Methods, Pierre Fabre, Castres, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Templier
authors.affiliation: Central Product Safety, The Procter and Gamble Company, Egham, Surrey, UK.
authors.forename: Pauline
authors.initials: P
authors.lastname: McNamee
mesh_terms: D000818:Animals; D003358:Cosmetics / Q000009:adverse effects* / Q000145:classification* / Q000633:toxicity; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005060:Europe; D005123:Eye / Q000187:drug effects*; D006801:Humans; D007509:Irritants / Q000145:classification / Q000633:toxicity; D011817:Rabbits; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D003358:Cosmetics; D007509:Irritants
keywords: Chemicals selection; Draize eye test Reference Database; Drivers of classification; Eye irritation/serious damage to the eye; UN GHS/EU CLP; Validation of alternative methods