In vitro testing strategy for assessing the skin sensitizing potential of “difficult to test” cosmetic ingredients

Bergal, Mathilde; Puginier, Mickaël; Gerbeix, C.; Groux, Hervé; Roso, Alicia; Cottrez, Françoise; Milius, A.

doi:10.1016/j.tiv.2020.104781

Cited by 19 publications

(12 citation statements)

References 28 publications

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“…Despite the lack of UVCB-specific GHS guidance, testing strategies for hazard classification of UVCBs are under development. 105 Moreover, there is some evidence of partial GHS classification of certain UVCBs such as "Juniper, Juniperus virginiana" (CASRN 85085-41-2); 106 however, it is not clear how such classification was achieved, further supporting the need for specific transparent guidance for classifying UVCBs under GHS. In future guidance, some element to encode uncertainty could be introduced, e.g., as pictograms/classification/hazard statements to reflect uncertainty or incomplete understanding of the given UVCB composition and thus hazards.…”

Section: Hazard Assessment Of Uvcbsmentioning

confidence: 99%

“…Despite the lack of UVCB-specific GHS guidance, testing strategies for hazard classification of UVCBs are under development . Moreover, there is some evidence of partial GHS classification of certain UVCBs such as “Juniper, Juniperus virginiana ” (CASRN 85085-41-2); however, it is not clear how such classification was achieved, further supporting the need for specific transparent guidance for classifying UVCBs under GHS.…”

Section: Hazard Assessment Of Uvcbsmentioning

confidence: 99%

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The Next Frontier of Environmental Unknowns: Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological Materials (UVCBs)

Lai

Clark

Escher

et al. 2022

Environ. Sci. Technol.

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Substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) are over 70 000 "complex" chemical mixtures produced and used at significant levels worldwide. Due to their unknown or variable composition, applying chemical assessments originally developed for individual compounds to UVCBs is challenging, which impedes sound management of these substances. Across the analytical sciences, toxicology, cheminformatics, and regulatory practice, new approaches addressing specific aspects of UVCB assessment are being developed, albeit in a fragmented manner. This review attempts to convey the "big picture" of the state of the art in dealing with UVCBs by holistically examining UVCB characterization and chemical identity representation, as well as hazard, exposure, and risk assessment. Overall, information gaps on chemical identities underpin the fundamental challenges concerning UVCBs, and better reporting and substance characterization efforts are needed to support subsequent chemical assessments. To this end, an information level scheme for improved UVCB data collection and management within databases is proposed. The development of UVCB testing shows early progress, in line with three main methods: whole substance, known constituents, and fraction profiling. For toxicity assessment, one option is a whole-mixture testing approach. If the identities of (many) constituents are known, grouping, read across, and mixture toxicity modeling represent complementary approaches to overcome data gaps in toxicity assessment. This review highlights continued needs for concerted efforts from all stakeholders to ensure proper assessment and sound management of UVCBs.

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Section: Hazard Assessment Of Uvcbsmentioning

confidence: 99%

Section: Hazard Assessment Of Uvcbsmentioning

confidence: 99%

The Next Frontier of Environmental Unknowns: Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological Materials (UVCBs)

Lai

Clark

Escher

et al. 2022

Environ. Sci. Technol.

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“…In our experience, the most likely outcome of application of DAs consisting of testing strategies that rely primarily on in silico or in vitro results to poorly soluble or UVCB is "inconclusive" leading to the need for additional data or modified approaches. Similar issues have been noted for difficult to test cosmetic ingredients, in particular the difficulties in assessing KE1, leading to modified testing strategies specifically for poorly soluble or UVCB substances that avoids reliance on DPRA or QSAR assessment of KE1 (Bergal, et al 2020).…”

Section: Discussionmentioning

confidence: 83%

Challenges in integrating skin sensitization data for assessment of difficult to test substances

Greminger¹,

Goyak²,

Frasca³

et al. 2021

Preprint

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Classification of chemicals as skin sensitizers have traditionally relied on a small set of in vivo tests. Difficult to test substances, such as poorly soluble, mildly irritating, or those of Unknown or Variable Composition Complex reaction products or Biological Materials (UVCBs), producing weak or borderline results in Local Lymph Node Assay (LLNA), often benefit from additional data integration in a weight of evidence (WOE) approach. Advances in multiple testing and non-testing methodologies (in vivo, in vitro, and in silico) can now provide clarity and confidence in concluding on skin sensitization potential. Here we present several case studies using a WOE approach with difficult to test substances and highlight the utility of Toxicological Prioritization IndexTM (ToxPi™) as a comparative visualization and integration tool of toxicology studies. The three test chemicals chosen represent two poorly soluble substances, tetrakis (2-ethylbutyl) orthosilicate and decyl palmitate, and one UVCB substance, alkylated anisole. Data from in vivo and in vitro assays representing multiple key events within the skin sensitization adverse outcome pathway (e.g., direct peptide reactivity assay, human cell line activation test, GARD®Skin, LLNA) were either gathered from publicly available sources or specifically generated. Incorporating the data on our test chemicals as well as chemicals of a known sensitization class (sensitizer, irritating non-sensitizer, non-sensitizer) into ToxPi™ revealed biological activity profiles which were used to support class prediction for the three test chemicals. Using this method, the biological activity profiles for all three test chemicals were most consistent with a non-sensitizing class. This paper demonstrates that visualizing the WOE using mechanistic data maximizes the value of all data to the overall assessment of skin sensitization potential by reducing the uncertainty associated with any one individual assay.

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“…There might be time for the regulatory authorities to consider a change of the paradigm and accept negative in vitro results. Huge numbers of experimental animals are still employed to prove a negative result while numerous alternative methods, based on cells and tissues of human origin with better significance to clinical human practice, have recently demonstrated their accuracy and reliability (Myers et al, 2017;Bergal et al, 2020). The efficiency of KE1 and KE2 alternative methods might benefit from implementing the third method covering KE3 (e.g.…”

Section: Altex Preprint Publishedmentioning

confidence: 99%

Sensitization potential of medical devices detected by in vitro and in vivo methods

Svobodová

Rucki

Vlková

et al. 2021

ALTEX

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Medical devices have to be tested before marketing in accordance with ISO EN 10993-10 in order to avoid skin sensitization. This standard predominantly refers to the in vivo test; however, it doesn't exclude the use of in vitro methods, which have been sufficiently technically and scientifically validated for the purpose of medical devices testing. It is foreseen that due to the complexity of the sensitization endpoint, combination of several methods will be needed to address all key events occurring in the sensitization process. The objective of this pilot study was to evaluate sensitization potential of selected medical devices using a combination of in vitro (LuSens, OECD TG 442D), in chemico (DPRA, OECD TG 442C) and in vivo (LLNA DA, OECD TG 442A) methods and to suggest a possible testing strategy for the safety assessment of medical devices extracts. Overall, one of the 42 tested samples exhibited positive results in all employed test methods, while 33 samples were predicted as samples with non-sensitizing potential in all three performed methods. This study demonstrated good agreement between in vitro and in vivo results regarding the absence of skin sensitization potential; however, discrepancies in positive classification have been recorded. The mismatch between in vitro and in vivo results might be caused by specific response of the immune system of the living organism. The in vitro methods require optimization of procedure, in particular the choice of appropriate extraction vehicle and applied volumes.

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In vitro testing strategy for assessing the skin sensitizing potential of “difficult to test” cosmetic ingredients

Cited by 19 publications

References 28 publications

The Next Frontier of Environmental Unknowns: Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological Materials (UVCBs)

The Next Frontier of Environmental Unknowns: Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological Materials (UVCBs)

Challenges in integrating skin sensitization data for assessment of difficult to test substances

Sensitization potential of medical devices detected by in vitro and in vivo methods

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