Applicability of in vitro tests for skin irritation and corrosion to regulatory classification schemes: Substantiating test strategies with data from routine studies

Kolle, Susanne N.; Sullivan, Kristie; Mehling, Annette; Ravenzwaay, Bennard van; Landsiedel, Robert

doi:10.1016/j.yrtph.2012.08.015

Cited by 11 publications

(10 citation statements)

References 15 publications

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“…Whereas simple local reactions, such as irritation or corrosion can be relatively easily reproduced in vitro using only one model (Kolle et al ., ), the challenge is much harder when we focus on complex mechanisms such as immune reactions and allergy. Nevertheless, the development of in vitro skin sensitization models is an immediate and major challenge for the cosmetic industry (Goebel et al ., ).…”

Section: Discussionmentioning

confidence: 97%

“…However, more recently Antonopoulos et al (2008) showed that IL18 should play a more central role in the cutaneous immune response and as this cytokine is constitutively expressed by human keratinocytes (Naik et al, 1999) we decided to use it as a sensitization marker in our model. Whereas simple local reactions, such as irritation or corrosion can be relatively easily reproduced in vitro using only one model (Kolle et al, 2013), the challenge is much harder when we focus on complex mechanisms such as immune reactions and allergy. Nevertheless, the development of in vitro skin sensitization models is an immediate and major challenge for the cosmetic industry (Goebel et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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Development of a multiparametric in vitro model of skin sensitization

Guyard‐Nicodème

Gerault

Platteel³

et al. 2014

J of Applied Toxicology

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Most animal experiments on cosmetics safety are prohibited and since March 2013, this obligation includes sensitization tests. However, until now there has been no validated alternative in vitro method. In this work, 400 compounds used in the cosmetic industry were selected to cover the greatest diversity of structures, biological activities and sensitizing potential. These molecules were submitted to a series of tests aimed at reproducing essential steps in sensitization and to distinguish between sensitization and irritations, i.e., transcutaneous permeation (factor A), haptenation (factor B), sensitization cytokines production (factor C) and acute toxicity (factor D). The transcutaneous diffusion was measured on human skin explants using Franz cells. Haptenation was tested in solution on human serum albumin. Sensitization cytokine production was investigated by measurement of interleukin-18 release by keratinocytes. Acute toxicity was determined using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(75) cell viability test. As only sufficiently stable, soluble and detectable compounds are usable, 33, 72, 68 and 68 molecules were finally tested on factors A, B, C and D, respectively, and 32 were completely screened by the four factors. The individual correlation of the four factors with the reference in vivo tests was limited but the combination of these factors led to a correlation between in vivo and in vitro assays of 81.2% and the safety of the test (risk of false negative) reached 96.8%. The techniques employed are simple and inexpensive and this model of four tests appears as a promising technique to evaluate in vitro the skin sensitization potential of unknown molecules.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Development of a multiparametric in vitro model of skin sensitization

Guyard‐Nicodème

Gerault

Platteel³

et al. 2014

J of Applied Toxicology

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“…Most toxicological studies are a legal obligation. The REACH regulation (27) (35,36). It seems obvious, that more than one proprietary method should be adopted in the respective TG in order to avoid monopolies but resources may be too scarce to adopt as many as one hundred methods.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…However, applying differing regional classification systems (EU CLP, the United States Environmental Protection Agency (US EPA), The Brazilian Health Regulatory Agency (Anvisa)) to the in vivo data as a reference in the validation of in vitro tests can affect the performance of in vitro methods(36). This illustrates the difficulties imposed on test method developers faced with the need to maintain the validation status of in vitro methods, in line with diverse classification requirements(36). Curren explored how alternative methods could be used for testing eye irritation hazards of antimicrobial household cleaning products(41).…”

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confidence: 99%

Workshop on acceleration of the validation and regulatory acceptance of alternative methods and implementation of testing strategies

Piersma

Burgdorf

Louekari

et al. 2018

Toxicology in Vitro

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This report describes the proceedings of the BfR-RIVM workshop on validation of alternative methods which was held 23 and 24 March 2017 in Berlin, Germany. Stakeholders from governmental agencies, regulatory authorities, universities, industry and the OECD were invited to discuss current problems concerning the regulatory acceptance and implementation of alternative test methods and testing strategies, with the aim to develop feasible solutions. Classical validation of alternative methods usually involves one to one comparison with the gold standard animal study. This approach suffers from the reductionist nature of an alternative test as compared to the animal study as well as from the animal study being considered as the gold standard. Modern approaches combine individual alternatives into testing strategies, for which integrated and defined approaches are emerging at OECD. Furthermore, progress in mechanistic toxicology, e.g. through the adverse outcome pathway approach, and in computational systems toxicology allows integration of alternative test battery results into toxicity predictions that are more fine-tuned to the human situation. The road towards transition to a mechanistically-based human-focused hazard and risk assessment of chemicals requires an open mind towards stepping away from the animal study as the gold standard and defining human biologically based regulatory requirements for human hazard and risk assessment.

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“…However, similar to other test systems, there are limitations. Examples include known interferences with some chemical groups as well as a lack of experience with such systems and their potential shortcomings for the testing of complex mixtures or formulations including agrochemicals (Kolle et al 2012).…”

Section: Status Quomentioning

confidence: 99%

Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions

et al. 2015

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The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European "regulatory status quo", while elucidating new perspectives for regulatory toxicity testing.

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Applicability of in vitro tests for skin irritation and corrosion to regulatory classification schemes: Substantiating test strategies with data from routine studies

Cited by 11 publications

References 15 publications

Development of a multiparametric in vitro model of skin sensitization

Development of a multiparametric in vitro model of skin sensitization

Workshop on acceleration of the validation and regulatory acceptance of alternative methods and implementation of testing strategies

Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions

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