TY - JOUR
T1 - Evaluating the performance of integrated approaches for hazard identification of skin sensitizing chemicals
AU - van der Veen, Jochem W.
AU - Rorije, Emiel
AU - Emter, Roger
AU - Natsch, Andreas
AU - van Loveren, Henk
AU - Ezendam, Janine
PY - 2014/8
Y1 - 2014/8
N2 - The currently available animal-free methods for the detection of skin sensitizing potential of chemicals seem promising. However, no single method is able to comprehensively represent the complexity of the processes involved in skin sensitization. To ensure a mechanistic basis and cover the complexity, multiple methods should be integrated into a testing strategy, in accordance with the adverse outcome pathway that describes all key events in skin sensitization. Although current majority voting testing strategies have proven effective, the performance of individual methods is not taken into account. To that end, we designed a tiered strategy based on complementary characteristics of the included methods, and compared it to a majority voting approach. This tiered testing strategy was able to correctly identify all 41 chemicals tested. In terms of total number of experiments required, the tiered testing strategy requires less experiments compared to the majority voting approach. On the other hand, this tiered strategy is more complex due the number of different alternative methods required, and predicted costs are similar for both strategies. Both the tiered and majority voting strategies provide a mechanistic basis for skin sensitization testing, but the strategy most suitable for regulatory decision-making remains to be determined.
AB - The currently available animal-free methods for the detection of skin sensitizing potential of chemicals seem promising. However, no single method is able to comprehensively represent the complexity of the processes involved in skin sensitization. To ensure a mechanistic basis and cover the complexity, multiple methods should be integrated into a testing strategy, in accordance with the adverse outcome pathway that describes all key events in skin sensitization. Although current majority voting testing strategies have proven effective, the performance of individual methods is not taken into account. To that end, we designed a tiered strategy based on complementary characteristics of the included methods, and compared it to a majority voting approach. This tiered testing strategy was able to correctly identify all 41 chemicals tested. In terms of total number of experiments required, the tiered testing strategy requires less experiments compared to the majority voting approach. On the other hand, this tiered strategy is more complex due the number of different alternative methods required, and predicted costs are similar for both strategies. Both the tiered and majority voting strategies provide a mechanistic basis for skin sensitization testing, but the strategy most suitable for regulatory decision-making remains to be determined.
KW - Skin sensitization
KW - Integrated testing strategy
KW - Keratinocytes
KW - Allergic contact dermatitis
KW - Animal-free testing
KW - LLNA
KW - QSAR
KW - DPRA
KW - Adverse outcome pathway
U2 - 10.1016/j.yrtph.2014.04.018
DO - 10.1016/j.yrtph.2014.04.018
M3 - Article
C2 - 24813372
SN - 0273-2300
VL - 69
SP - 371
EP - 379
JO - Regulatory Toxicology and Pharmacology
JF - Regulatory Toxicology and Pharmacology
IS - 3
ER -