A feasibility study developing an integrated testing strategy assessing skin irritation potential of chemicals.
The regulatory assessment of chemical safety is still driven by hazard testing in animals. The Registration, Evaluation, Authorisation and restriction of Chemicals (REACH) legislation and new technologies require a shift in the way in which safety assessments are conducted. Integrated testing strategies (ITSs) help in providing such a framework. Many of the ITS building blocks are already in use, but the concepts for their integration and application in a regulatory setting have yet to be fully implemented. This paper describes a feasibility study investigating how a combination of in silico, in vitro, and in vivo information could be applied in the assessment of skin irritation hazard. Therefore, a database of 100 existing and new chemicals was compiled. A number of strategies, both animal-free and inclusive of animal data were constructed and subsequently evaluated considering predictive capacities, severity of misclassifications and testing costs. Comparison of constructed ITS based on these assessment parameters identified best performing strategies for chemical classification. However, defining the in vivo test as the reference test limited the evaluation of the ITS inclusive of animal data. This study demonstrated that ITS can be constructed, evaluated and compared in a systematic fashion. To promote ITS, further guidance on construction and multi-parameter evaluation need to be developed.
Hoffmann
Sebastian
S
European Centre for the Validation of Alternative Methods (ECVAM), Institute of Health and Consumer Protection (IHCP), Joint Research Centre, European Commission, Via E.Fermi 2749, 21027 Ispra (VA), Italy. sebastian.hoffmann@jrc.it
Saliner
Ana Gallegos
AG
Patlewicz
Grace
G
Eskes
Chantra
C
Zuang
Valerie
V
Worth
Andrew P
AP
D000826:Animal Testing Alternatives / Q000379:methods; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004817:Epidermis / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005240:Feasibility Studies; D006801:Humans; D007509:Irritants / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D023421:Models, Animal; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D023422:Skin Irritancy Tests / Q000379:methods*; D015262:Xenobiotics / Q000737:chemistry / Q000145:classification / Q000633:toxicity*
D007509:Irritants; D015262:Xenobiotics