In vitro measurement of skin sensitization hazard of mixtures and finished products: Results obtained with the SENS-IS assays

Cottrez, Françoise; Boitel, Elodie; Berrada-Gomez, M.-P.; Dalhuchyts, Hanna; Bidan, Catherine; Rattier, Sandy; Ferret, Pierre–Jacques; Groux, Hervé

doi:10.1016/j.tiv.2019.104644

Cited by 9 publications

(5 citation statements)

References 23 publications

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“…The main finding in this experimental setting was that the addition of the irritants did not lead to similar lowering of the sensitization threshold of cinnamal and EGDMA, suggesting that in the combination of allergen/irritant the type of the allergen has a decisive influence on the nature of the response. A comparative conclusion was also drawn after exposure to allergens in combination with irritants using the SENS‐IS assay 25 . In the present study, for the weaker allergen EGDMA, both cytotoxicity and EC 1.5 were considerably more altered by the addition of the irritants than for the moderate allergen cinnamal.…”

Section: Discussionmentioning

confidence: 47%

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Assessment of the different skin sensitization potentials of irritants and allergens as single substances and in combination using the KeratinoSens assay

et al. 2021

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Background People are exposed to mixtures containing allergens and irritants often causing contact dermatitis. Therefore, regulatory authorities require systematic information on the effects of mixtures on the sensitization threshold. In this study a moderate (cinnamal) and a weak (ethylene glycol dimethacrylate) allergen were combined with irritants covering different mechanisms of action (sodium dodecyl sulfate, salicylic acid, and α‐pinene). For a systematic approach, the single substances were initially tested using the KeratinoSens assay. Thereafter, each allergen was combined with noncytotoxic concentrations of the irritants. Method The KeratinoSens assay was applied for the single substances according to OECD (Organisation for Economic Co‐operation and Development) Test Guideline 442D. Based on these results, three noncytotoxic concentrations of the irritants were selected and applied simultaneously with 12 concentrations of the allergens to the KeratinoSens cells. Sensitization threshold and cytotoxicity were measured and compared with the individual testing. Results The combinations of allergens and irritants differed from the effects of the single substances and lowered the sensitization threshold. The quantitative approach allowed a clear description of the changes which varied by factors between 1.1 and 10.3. Conclusions Overall, the allergen was the prominent compound in the mixture and its nature appeared to determine the degree of the response.

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Section: Discussionmentioning

confidence: 47%

“…In a recent study, different allergens were combined with two irritants, SDS and lactic acid, and—as a marker for sensitization—the impact on expression of biomarkers in 3D reconstructed epidermis (SENS‐IS assay) was investigated 25 . Nonsensitizing doses of the allergens were combined with nonirritating doses of the irritants.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the different skin sensitization potentials of irritants and allergens as single substances and in combination using the KeratinoSens assay

et al. 2021

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“…This suggests that some commercial products may be irritating to humans when applied to the skin on a daily basis. Studies of alternative test methods to assess the safety of cosmetic products have been reported, including skin irritation evaluations by means of RhE models (Kose et al, 2018) and SENS-IS assays (Cottrez et al, 2020) and eye irritation evaluations by the STE test method (Abo et al, 2018). However, further studies are needed to compare the safety of different formulations and to define safety criteria.…”

Section: Discussionmentioning

confidence: 99%

A trial to predict skin irritancy of cosmetic products using cytotoxicity tests

Mezaki,

Manabe,

Nagumo

et al. 2023

Fundam. Toxicol. Sci.

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Alternatives to animal testing are being used to assess the safety of raw ingredients during the process of developing cosmetics. However, since cosmetic products are composed of a variety of raw ingredients, the safety of the product itself should also be tested. In this study, we attempted to evaluate the skin irritation potential of skin lotions by modifying existing alternative test methods. To evaluate the skin irritation potential of commercial skin lotions in the form of an objective indicator, we calculated their Irritation Score (IS) based on the results of searches using keywords related to skin irritation in review statements posted on Japanese cosmetics and beauty websites. We then modified the reconstructed human epidermis (RhE) test method to evaluate irritation by commercial skin lotions. The results showed that exposure to skin lotions with higher ISs tended to result in lower cell viability, and that exposure to many of the lotions with lower ISs resulted in higher cell viability. Next, we tried using an in vitro shortterm exposure (STE) test method to assess the skin irritation potential of skin lotions. By changing the test-substance exposure concentrations and exposure times in the STE test method, we were able to obtain results that correlated with those obtained by the modified RhE test method. In conclusion, both alternative methods were helpful for assessing the possibility of developing skin irritation of skin lotions. They may also be useful for screening formulations being developed and as means of evaluation before proceeding to human patch tests.

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“…We carried out similar studies with atranol and chloroatranol, key allergens of oak moss absolute, showing that the mixture in the natural extract was more potent at both sensitization and challenge than atranol and chloroatranol alone [15]. Finally, the ability of the SENS-IS assay, which uses an EpiSkin TM large model of 3D reconstructed human epidermis to detect such mixture effects, was evaluated very recently showing that it is efficient at detecting skin sensitizing hazards in complex mixtures and final products [16].…”

Section: Introductionmentioning

confidence: 98%

Chemical Compounds Responsible for Skin Allergy to Complex Mixtures: How to Identify Them?

Giménez‐Arnau

2019

Cosmetics

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In the cosmetics industry, various natural complex mixtures such as botanical extracts and essential oils are used. In addition, finished consumer products may contain a number of constituents of natural origin but many products are derived from organic synthesis too. Hence, finding skin sensitizers within this myriad of chemicals is an arduous task. Nowadays, methods validated by European dedicated instances to evaluate the allergenicity of chemicals are incapable of predicting the sensitization potential of complex mixtures, although research has progressed a lot in this direction recently. In this context, precisely identifying the culprit(s) responsible for skin sensitization in these mixtures is essential for risk assessment. This review is a short summary of approaches that identify allergens in chemical mixtures such as bioassay-guided chemical fractionation, structure-activity relationship studies, and recent methods allowing identification of reactive intermediates in natural extracts exposed to air oxidation. It is shown that substantial progress has been made, although the identification of sensitizers in complex mixtures continues to be puzzling.

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In vitro measurement of skin sensitization hazard of mixtures and finished products: Results obtained with the SENS-IS assays

Cited by 9 publications

References 23 publications

Assessment of the different skin sensitization potentials of irritants and allergens as single substances and in combination using the KeratinoSens assay

Assessment of the different skin sensitization potentials of irritants and allergens as single substances and in combination using the KeratinoSens assay

A trial to predict skin irritancy of cosmetic products using cytotoxicity tests

Chemical Compounds Responsible for Skin Allergy to Complex Mixtures: How to Identify Them?

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