Regulatory Toxicology And Pharmacology

ARTICLE IN PRESS
Regulatory Toxicology and Pharmacology xxx (2010) xxx–xxx

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Regulatory Toxicology and Pharmacology
journal homepage: www.elsevier.com/locate/yrtph

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: Genotoxicity. A COLIPA analysis
Stefan Pfuhler a, Annette Kirst b, MarilynAardema a,1, Norbert Banduhn c, Carsten Goebel d, Daisuke Araki e, Margit Costabel-Farkas f, Eric Dufour g, Rolf Fautz b, James Harvey h, Nicola J. Hewitt i, Jalila Hibatallah j, Paul Carmichael k, Martin Macfarlane k, Kerstin Reisinger c, Joanna Rowland l, Florian Schellauf m, Andreas Schepky n, Julia Scheel c,*
a

Procter & Gamble, Miami Valley Laboratories, 11810 East Miami River Road,Cincinnati, 45253 OH, USA KPSS – Kao Professional Salon Services GmbH, Pfungstaedter Strasse 92-100, 64297 Darmstadt, Germany c Henkel AG & Co. KGaA, Henkelstraße 67, 40589 Düsseldorf, Germany d Procter & Gamble, Darmstadt Innovation Center, Berliner Allee 65, 64274 Darmstadt, Germany e Kanebo Cosmetics, 89/91 Rue du Faubourg St Honoré, 75008 Paris, France f Johnson & Johnson GmbH, Johnson&Johnson-Platz 2,D-41470 Neuss, Germany g L’Oreal, River Plaza 25-29, quai Aulagnier 92600 Asnières-sur-Seine, France h GlaxoSmithKline R&D, Ware, Hertfordshire, UK i Scientific Writing Services, Wingertstrasse 25, 64390 Erzhausen, Germany j Chanel Parfums Beaute 135, Avenue Charles de Gaulle, 92525 Neuilly sur Seine, France k Unilever, Colworth Science Park, Sharnbrook, Bedford MK44 1LQ, UK l GlaxoSmithKlineConsumer HealthCare R&D, Weybridge, Surrey KT13 ODE, UK m COLIPA, Avenue Herrmann Debroux 15A, B-1160 Auderghem, Brussels, Belgium n Beiersdorf AG, BF 682, Unnastrasse 48, 20245 Hamburg, Germany
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a b s t r a c t
For the assessment of genotoxic effects of cosmetic ingredients, a number of well-established and regulatory accepted in vitro assays are in place. A caveat tothe use of these assays is their relatively low specificity and high rate of false or misleading positive results. Due to the 7th amendment to the EU Cosmetics Directive ban on in vivo genotoxicity testing for cosmetics that was enacted March 2009, it is no longer possible to conduct follow-up in vivo genotoxicity tests for cosmetic ingredients positive in in vitro genotoxicity tests to furtherassess the relevance of the in vitro findings. COLIPA, the European Cosmetics Association, has initiated a research programme to improve existing and develop new in vitro methods. A COLIPA workshop was held in Brussels in April 2008 to analyse the best possible use of available methods and approaches to enable a sound assessment of the genotoxic hazard of cosmetic ingredients. Common approaches ofcosmetic companies are described, with recommendations for evaluating in vitro genotoxins using non-animal approaches. A weight of evidence approach was employed to set up a decision-tree for the integration of alternative methods into tiered testing strategies. Ó 2010 Elsevier Inc. All rights reserved.

Article history: Received 19 January 2010 Available online xxxx Keywords: GenotoxicityCosmetic ingredients Alternative methods Hazard assessment Safety assessment

1. Introduction In vitro tests form an essential part of the assessment of genotoxicity and provide information on three major genetic endpoints,

namely (1) mutagenicity at a gene level, (2) chromosome breakage and/or rearrangements (clastogenicity), and (3) numerical chromosome aberrations (CA)2 (aneugenicity) (SCCP,2006a,b; Mueller et al., 2003; Dearfield et al., 2002; COM, 2000). In the past, in vivo

* Corresponding author. Fax: +49 211 798 12413. E-mail address: julia.scheel@henkel.com (J. Scheel). 1 Present address: Consulting LLC, 5315 Oakbrook Dr. Fairfield OH, 45014, USA. 2 Abbreviations used: ADME, absorption, distribution, metabolism and excretion; CA, chromosome aberration; CHO, Chinese hamster...