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Integrated Use of Alternative Methods for Evaluating the skin sensitization Potencies of Five Frequently Used Preservatives in Cosmetics

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China Detergent & Cosmetics 2023年第2期8卷 38-47页

作者： Wang Rui Wang Huan Han Yu-qing Zhao Jinfeng Yan Shiyu Pan Yao Department of Cosmetics College of Chemistry and Materials EngineeringBeijing Technology and Business UniversityChina Beijing Key Laboratory of Plant Research and Development China Institute of Cosmetic Regulatory Science Beijing Technology and Business UniversityChina

In vitro skin sensitization testing methods based on the adverse outcome pathway(AOP)were used to evaluate the skin sensitization potencies of 5 commonly used *** to the“2 out of 3”principle of the integrated approaches to testing and assessment(IATA)the direct peptide reactivity assay(DPRA)and the human cell line activation test(h-CLAT)were used to detect the preservatives commonly used in cosmetics,including *** paraben,propyl paraben,imidazolidinyl urea and DMDM *** DPRA and the h-CLA were carried out according to the OEC442C and 442E guidelines,*** results show *** and methyl paraben are both negative in DPRA and h-CLAT while imidazolidinyl urea and DMDM hydantoin are both positive in these two *** paraben has negative result in DPRA but positive result in ***,imidazolidiny urea and DMDM hydantoin are sensitizers,while phenoxyethanol and methylparaben are *** animal and human data into consideration,it is predicted that propyl paraben should be a *** combination of DPRA and h-CLAT can make up for the limitations of using a single method,and it is suitable for the preliminary screening of cosmetic raw materials according to skin sensitization.

关键词： skin sensitization preservative alternative method DPRA h-CLAT AOP

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Application of in Vitro Alternative Tests Based on AOP in skin sensitization Evaluation of Cosmetics

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China Detergent & Cosmetics 2023年第2期8卷 31-37页

作者： Ying Mengchao Xiao Ping Hong Xinyu Sun Jingqiu Huo Qian Li Chen Chen Tian Tao Gonghua Shanghai Municipal Center For Disease Control&Prevention China NMPA Key Laboratory for Monitoring and Evaluation of Cosmetics State Environmental Protection Key Laboratory of the Assessment of Effects of Emerging Pollutants on Environmental and Human HealthChina

To evaluate and discuss two novels in vitro alternative tests which based on the 2nd and 4th event of the AOP in skin sensitization and their application in skin sensitization evaluation of cosmetics in *** DSens(DSens method)and Jurkat(TCPA method)were used as the test models and 9 of reference chemicals and 12 kinds of cosmetic products were used to confirm and assess the application capability in skin *** results showed that the DSens method was more sensitive to the reference chemicals compare to the TCPA *** the results of cosmetic products showed a high consistency between these two assays and h-CLAT or in vivo *** the new screening method for skin sensitization evaluation of cosmetics,the in vitro alternative tests based on AOP have certain *** reasonable combination strategy can bring a bright future for the development and application of animal alternative test in China.

关键词： skin sensitization in vitro alternative methods T cell activation cosmetic safety assessment

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Evaluation of Dermal Irritation and skin sensitization by Curaderm

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International Journal of Clinical Medicine 2020年第9期11卷 548-558页

作者： T. Chase K. E. Cham B. E. Cham Australasian Medical Research Port Vila Republic of Vanuatu

Purpose: To establish whether Curaderm, a topical pharmacotherapy for skin cancer, irritates or sensitizes normal skin. Methods: The dermal irritation and skin sensitization toxicity of Curaderm were investigated in rabbits and guinea pigs in compliance with the Organization for Economic Cooperation and Development guideline. To assess dermal irritation, rabbits were dermally exposed to Curaderm for varying periods of time. To assess hypersensitivity, the guinea-pig maximisation test was applied. Results: Curaderm was only negligibly irritating using the criteria of erythema and oedema. Curaderm did not produce any sensitization toxicity of the skin. Conclusion: These studies confirm the non-toxic observations on normal skin experienced in the clinical setting when treating skin cancer and reinforce the specificity of Curaderm towards cancer cells.

关键词： Curaderm BEC Solamargine skin Cancer Dermal Irritation skin sensitization Psoriasis

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Advancing the predictivity of skin sensitization by applying a novel HMOX1 reporter system

Advancing the predictivity of skin sensitization by applying...

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2018中国遗传学会第十次全国会员代表大会暨学术讨论会

作者：钟国瑞 Haojian Li Jing Bai Shihui Pang Changsheng He Xinyi Du Haijie Wang Qixiao Zhang Shuilin Xie Hongli Du Renke Dai 黄黎珍 School of Biology and Biological Engineering South China University of Technology Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering South China University of Technology

Reporter cell lines are a particularly useful tool to screen for the skin sensitization potential of chemicals. Current cell models based on Keap1-Nrf2 mimic induction by conducting antioxidant response element-luciferase plasmids. However, plasmid-based reporters may ignore comprehensive aspects of induction, thus affecting the accuracy of hazard identification. Herein, we developed a novel HaCaT-based reporter system, EndoSens, whereby luciferase was specifically inserted into the cassette for heme oxygenase（decycling） 1（HMOX1, the most consistent marker induced by skin sensitizers） by CRISPR/Cas9. Testing data from 20 coded substances showed an accuracy of 90%, sensitivity of 91.7%, and specificity of 87.5%, which exceeded the OECD requirement. Among the 35 chemicals examined, predictivity was better than reported for the validated KeratinoSens?. These results indicate that the EndoSens assay could advance the predictivity of skin sensitization, thus making it a promising tool for in vitro skin sensitization testing.

关键词： skin sensitization Keratinocyte activation Reporter cell line CRISPR/Cas9

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Development and application of a novel method to assess exposure levels of sensitizing and irritating substances leaching from menstrual hygiene products

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Emerging Contaminants 2021年第1期7卷 116-123页

作者： Q.Marcelis A.Gatzios E.Deconinck V.Rogiers T.Vanhaecke B.Desmedt Department of In Vitro Toxicology and Dermato-Cosmetology Vrije Universiteit BrusselLaarbeeklaan 1031090JetteBelgium Medicines and Health Products SciensanoJuliette Wytsmanstraat 141050BrusselsBelgium

Menstrual hygiene products(MHPs)like tampons,sanitary towels and panty liners are widely used by women and come in close contact with the intimate parts of the human body,which consist of mucosae that lack the important barrier function of normal ***,substances leaching from MHP can easily penetrate and become systemically *** study aims to develop a new in chemico methodology that allows to identify and measure realistic consumer exposure levels of several skin sensitizers and irritants leaching from MHPs under simulated use *** assess the leaching of chemicals from MHPs,a menstrual fluid simulant(MFS)simulating pH,osmolarity and protein binding was first ***,an analytical methodology was developed for nine well-known skin sensitizers and skin *** short,the MFS samples underwent salting-out assisted liquid-liquid extraction before ultra-high performance liquid chromatography coupled with a triple-quadrupole mass spectrometry *** was performed according to the total error approach with acceptability limits of±15%regarding the total analytical error(including systematic and random bias).Fifteen commercially available MHPs were *** products were found to leach at least one of the following five sensitizing and irritating compounds:a-isomethyl ionone,benzyl salicylate,hexyl cinnamaldehyde,linalool and *** was the most abundant compound leaching from the MHPs,with leaching concentration levels measured to 28.22 mg/*** addition,the leaching level of benzyl salicylate was found to be 11.03 mg/*** latter fragrance concentration is above 10 mg/g and would trigger mandatory labelling if the Cosmetic Regulation would apply for ***,none of the identified and quantified skin sensitizers were mentioned on the *** conclusion,this novel methodology makes it possible to estimate realistic human exposure levels to skin sensitizers and irritants through the use of M

关键词： Consumer product safety Menstrual hygiene products Fragrance skin sensitization skin irritation

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基于子结构的递归分割树方法预测化合物皮肤致敏性(英文)

基于子结构的递归分割树方法预测化合物皮肤致敏性(英文)

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第十一届全国计算（机）化学学术会议

作者：芦静郑明月王雍沈倩诚罗小民蒋华良陈凯先中国科学院上海药物研究所新药研究国家重点实验室药物发现与设计中心

＜正＞skin sensitization is an important toxic endpoint to be taken into account in the risk assessment of *** this paper,SAR（structure-activity relationships） analysis was performed on the skin sensitization potential of 320 compounds with local lymph node assay（LLNA） *** fragments were extracted by GASTON（GrAph/Sequence/Tree extractiON） based on ’quickstart principle’ from the training set.8 fragments of which the accuracy Q is significantly higher than 0.73（p＜0.1） were retained to make up an indicator descriptor *** fragment descriptor and 8 other physicochemical descriptors closely related to the endpoint,were calculated to construct the recursive partitioning tree（RP tree） for *** balanced accuracy of the training set and test set in the leave-one-out model were 0.846 and 0.800,*** results highlight that fragment-based RP tree is a preferable method for identifying skin ***,the selected fragments provide useful structural information for exploring sensitization mechanisms, and RP tree creates a graphic tree to identify the most important properties of skin sensitization. They can provide some instruction for designing of drugs with lower sensitizability.

关键词： skin sensitization LLNA SAR Fragment Recursive partitioning tree Substructure mining algorithm

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