Computer models versus reality: How well do in silico models currently predict the sensitization potential of a substance

Teubner, Wera; Mehling, A.; Schuster, Paul; Guth, Katharina; Worth, Andrew; Burton, J. S.; Ravenzwaay, Bennard van; Landsiedel, Robert

doi:10.1016/j.yrtph.2013.09.007

Cited by 53 publications

(60 citation statements)

References 27 publications

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“…Some of these available (Q)SARs have been encoded into expert, knowledge-based systems that are available for the prediction of skin sensitization (e.g., Derek for Windows (DfW)), statistical systems (e.g., TOPKAT, MCASE) and hybrid systems (e.g., Tissue Metabolism Simulator (TIMES)). Comprehensive reviews and evaluation of expert systems, SARs and QSARs are available from ECETOC and in the form of publications from Patlewicz et al and Teubner et al (ECETOC, 2003;Patlewicz et al, 2008;Teubner et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

124

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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Section: Resultsmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

124

103

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“…Two such profilers are the protein-binding profilers based on OECD and OASIS algorithms (''Protein binding by OECD'', ''Protein binding by OASIS v1.2''). In order to also identify substances, which require abiotic or metabolic activation, the ''auto-oxidation profiler'' and the ''skin metabolism profiler'' were used Teubner et al, 2013.…”

Section: Oecd Qsar Toolboxmentioning

confidence: 99%

Assessing skin sensitization hazard in mice and men using non-animal test methods

Urbisch

Mehling²,

Guth

et al. 2015

Regulatory Toxicology and Pharmacology

Self Cite

325

253

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Sensitization, the prerequisite event in the development of allergic contact dermatitis, is a key parameter in both hazard and risk assessments. The pathways involved have recently been formally described in the OECD adverse outcome pathway (AOP) for skin sensitization. One single non-animal test method will not be sufficient to fully address this AOP and in many cases the use of a battery of tests will be necessary. A number of methods are now fully developed and validated. In order to facilitate acceptance of these methods by both the regulatory and scientific communities, results of the single test methods (DPRA, KeratinoSens, LuSens, h-CLAT, (m)MUSST) as well for a the simple '2 out of 3' ITS for 213 substances have been compiled and qualitatively compared to both animal and human data. The dataset was also used to define different mechanistic domains by probable protein-binding mechanisms. In general, the non-animal test methods exhibited good predictivities when compared to local lymph node assay (LLNA) data and even better predictivities when compared to human data. The '2 out of 3' prediction model achieved accuracies of 90% or 79% when compared to human or LLNA data, respectively and thereby even slightly exceeded that of the LLNA.

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“…In an independent evaluation of three different QSAR models developed for assessment of chemical sensitizers, estimated predictive accuracies ranged between 59-74% [41]. A more recent evaluation revealed that QSARs indeed are able to perform accurate predictions, with examples of models performing perfectly in limited chemical domains [42]. Thus, the authors conclude that while mechanistic models can be used to a certain degree under well-defined conditions, in silico models for sensitizers are currently not sufficient for accurate predictions in a broad chemical space.…”

Section: In Vitro Assaysmentioning

confidence: 99%

Prediction of Skin Sensitizers using Alternative Methods to Animal Experimentation

Johansson

Lindstedt

2014

Basic Clin Pharma Tox

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Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal-free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well-educated risk assessments based on weight of evidence.

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Computer models versus reality: How well do in silico models currently predict the sensitization potential of a substance

Cited by 53 publications

References 27 publications

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Assessing skin sensitization hazard in mice and men using non-animal test methods

Prediction of Skin Sensitizers using Alternative Methods to Animal Experimentation

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