Skin sensitization in chemical risk assessment: Report of a WHO/IPCS international workshop focusing on dose–response assessment

Loveren, Henk Van; Cockshott, Amanda; Gebel, Thomas; Gundert‐Remy, Ursula; Jong, Wim H. de; Matheson, Joanna; McGarry, Helen F.; Musset, Laurence; Selgrade, MaryJane K.; Vickers, Carolyn

doi:10.1016/j.yrtph.2007.11.008

Cited by 77 publications

(30 citation statements)

References 30 publications

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“…The biological mechanism of skin sensitization is well known, the concepts for replacing animal testing for this hazard have been developed in a series of projects (Rovida et al, 2013;Van Loveren et al, 2008;Maxwell et al, 2011), and there are many in vitro methods that are either validated or at an advanced state of validation, as well as a validated in vivo method (Local lymph node assay, LLNA) that may serve as reference (NIH, 1999).…”

Section: The Example Of Skin Sensitizationmentioning

confidence: 99%

Integrated testing strategies (ITS) for safety assessment

Rovida

2015

ALTEX

147

128

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SummaryIntegrated testing strategies (ITS), as opposed to a single definitive test or fixed batteries of tests, are expected to efficiently combine different information sources in a quantifiable fashion to satisfy an information need, in this case for regulatory safety assessments. With increasing awareness of the limitations of each individual tool and the development of highly targeted tests and predictions, the need for combining pieces of evidence increases. The discussions that took place during this workshop, which brought together a group of experts coming from different related areas, illustrate the current state of the art of ITS, as well as promising developments and identifiable challenges. The case of skin sensitization was taken as an example to understand how possible ITS can be constructed, optimized and validated. This will require embracing and developing new concepts such as adverse outcome pathways (AOP), advanced statistical learning algorithms and machine learning, mechanistic validation and "Good ITS Practices".Keywords: in vitro methods, testing strategy, Tox21c, skin sensitization, computational toxicology this is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited. *A report of t 4 -the transatlantic think tank for toxicology, a collaboration of the toxicologically oriented chairs in Baltimore, Konstanz and Utrecht sponsored by the Doerenkamp-Zbinden Foundation; participants do not represent their institutions and do not necessarily endorse all recommendations made.

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Section: The Example Of Skin Sensitizationmentioning

confidence: 99%

Integrated testing strategies (ITS) for safety assessment

Rovida

2015

ALTEX

147

128

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“…Quantitative risk assessment of sensitizers utilizes HRIPT in combination with LLNA 50 though recent literature mentions the ethical concerns associated with HRIPT. 159 Human tests for assessment of chemicals as sensitizers is ethical based on written informed consent of patients and is conducive as a comparison of the skin sensitization challenge to improve robustness of historical or novel control approaches. 12 Detail protocols and factors implicated in HRIPT have been cited in the literature.…”

Section: Human Repeated Insulin Patch Test (Hript)mentioning

confidence: 99%

Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis

et al. 2011

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Skin sensitization remains a major environmental and occupational health hazard. Animal models have been used as the gold standard method of choice for estimating chemical sensitization potential. However, a growing international drive and consensus for minimizing animal usage have prompted the development of in vitro methods to assess chemical sensitivity. In this paper, we examine existing approaches including in silico models, cell and tissue based assays for distinguishing between sensitizers and irritants. The in silico approaches that have been discussed include Quantitative Structure Activity Relationships (QSAR) and QSAR based expert models that correlate chemical molecular structure with biological activity and mechanism based read-across models that incorporate compound electrophilicity. The cell and tissue based assays rely on an assortment of mono and co-culture cell systems in conjunction with 3D skin models. Given the complexity of allergen induced immune responses, and the limited ability of existing systems to capture the entire gamut of cellular and molecular events associated with these responses, we also introduce a microfabricated platform that can capture all the key steps involved in allergic contact sensitivity. Finally, we describe the development of an integrated testing strategy comprised of two or three tier systems for evaluating sensitization potential of chemicals.

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“…[6] This corroborates the opinion of an IPC/WHO workshop that concluded that the LLNA has never been validated for mixtures. [7] Lalko and Api [8] investigated the use of the LLNA of seven well-characterized essential oils. Whilst some correlation was seen between the expected sensitization potency of the oil based on consideration of the individual components, this was not the case for three of the oils tested.…”

Section: Considerations For Toxicological Studiesmentioning

confidence: 99%

Special Issue 40th ISEO: toxicological challenges for essential oils in REACH

Ellis

2010

Flavour & Fragrance J

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Regulation on the registration, evaluation, authorization and restriction of chemicals (REACH) requires that substances produced or imported at ≥ 1 tonne/year in the European Community (EC) are submitted for registration following a phased-in timetable according to tonnage until 2018. Toxicological and ecotoxicological information is required for submission, along with a risk assessment that considers consumer, occupational and environmental exposures. These requirements apply to natural aromatic extracts (mainly essential oils, but also concretes, resinoids, absolutes, etc.), termed 'natural complex substances' (NCSs), in REACH, and present a unique set of challenges, not only due to the cost and administrative burden for essential oils producers and importers, but also in the approach used for the toxicological evaluation of these oils. Identifi cation of representative specifi cations for the conduct of studies and natural variability of product composition is an important and complex area to resolve, even before studies can begin. Adaptation of toxicological test methods to essential oils and the interpretation of results and use in risk assessment present perhaps the greatest challenge. Alternative test and evaluation strategies for essential oils, based on a components approach, off er the potential for strategic testing in achieving REACH compliance. Diff erent approaches may apply, dependent on whether the NCS, which belongs to the category of substances called UVCB in REACH, is a 'simple' well-defi ned substance, e.g. sweet orange peel oil, or one that is complex in nature and is not usually fully characterized, e.g. vetiver oil. Industry has already started work through REACH consortia and industry association activities, yet further refi nement in the assessment approach and experience in dossier submission and acceptance with the European Chemicals Agency (ECHA) remains a real challenge for essential oils producers and importers.

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Skin sensitization in chemical risk assessment: Report of a WHO/IPCS international workshop focusing on dose–response assessment

Cited by 77 publications

References 30 publications

Integrated testing strategies (ITS) for safety assessment

Integrated testing strategies (ITS) for safety assessment

Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis

Special Issue 40th ISEO: toxicological challenges for essential oils in REACH

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