Abstract:
:Chemical sensitization is a serious condition caused by small reactive molecules and is characterized by a delayed type hypersensitivity known as allergic contact dermatitis (ACD). Contact with these molecules via dermal exposure represent a significant concern for chemical manufacturers. Recent legislation in the EU has created the need to develop non-animal alternative methods for many routine safety studies including sensitization. Although most of the alternative research has focused on pure chemicals that possess reasonable solubility properties, it is important for any successful in vitro method to have the ability to test compounds with low aqueous solubility. This is especially true for the medical device industry where device extracts must be prepared in both polar and non-polar vehicles in order to evaluate chemical sensitization. The aim of this research was to demonstrate the functionality and applicability of the human reconstituted skin models (MatTek Epiderm(®) and SkinEthic RHE) as a test system for the evaluation of chemical sensitization and its potential use for medical device testing. In addition, the development of the human 3D skin model should allow the in vitro sensitization assay to be used for finished product testing in the personal care, cosmetics, and pharmaceutical industries. This approach combines solubility, chemical reactivity, cytotoxicity, and activation of the Nrf2/ARE expression pathway to identify and categorize chemical sensitizers. Known chemical sensitizers representing extreme/strong-, moderate-, weak-, and non-sensitizing potency categories were first evaluated in the skin models at six exposure concentrations ranging from 0.1 to 2500 µM for 24 h. The expression of eight Nrf2/ARE, one AhR/XRE and two Nrf1/MRE controlled gene were measured by qRT-PCR. The fold-induction at each exposure concentration was combined with reactivity and cytotoxicity data to determine the sensitization potential. The results demonstrated that both the MatTek and SkinEthic models performed in a manner consistent with data previously reported with the human keratinocyte (HaCaT) cell line. The system was tested further by evaluating chemicals known to be associated with the manufacture of medical devices. In all cases, the human skin models performed as well or better than the HaCaT cell model previously evaluated. In addition, this study identifies a clear unifying trigger that controls both the Nrf2/ARE pathway and essential biochemical events required for the development of ACD. Finally, this study has demonstrated that by utilizing human reconstructed skin models, it is possible to evaluate non-polar extracts from medical devices and low solubility finished products.
journal_name
Cutan Ocul Toxicoljournal_title
Cutaneous and ocular toxicologyauthors
McKim JM Jr,Keller DJ 3rd,Gorski JRdoi
10.3109/15569527.2012.667031subject
Has Abstractpub_date
2012-12-01 00:00:00pages
292-305issue
4eissn
1556-9527issn
1556-9535journal_volume
31pub_type
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journal_title:Cutaneous and ocular toxicology
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doi:10.3109/15569527.2012.708956
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journal_title:Cutaneous and ocular toxicology
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journal_title:Cutaneous and ocular toxicology
pub_type: 杂志文章
doi:10.1080/15569520500278690
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journal_title:Cutaneous and ocular toxicology
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doi:10.3109/15569527.2011.573832
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journal_title:Cutaneous and ocular toxicology
pub_type: 杂志文章
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journal_title:Cutaneous and ocular toxicology
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更新日期:2010-06-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
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doi:10.3109/15569527.2014.910802
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journal_title:Cutaneous and ocular toxicology
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doi:10.1080/15569527.2017.1373121
更新日期:2018-06-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
pub_type: 评论,信件
doi:10.3109/15569527.2011.584928
更新日期:2011-12-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
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更新日期:2019-03-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
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doi:10.3109/15569527.2013.808654
更新日期:2014-06-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
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doi:10.3109/15569527.2013.796480
更新日期:2014-06-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
pub_type: 杂志文章
doi:10.1080/15569520802143600
更新日期:2008-01-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
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journal_title:Cutaneous and ocular toxicology
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doi:10.3109/15569527.2015.1058273
更新日期:2016-01-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
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doi:10.1080/15569527.2016.1209770
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journal_title:Cutaneous and ocular toxicology
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更新日期:2014-09-01 00:00:00
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更新日期:2020-12-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
pub_type: 杂志文章
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更新日期:2017-09-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
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journal_title:Cutaneous and ocular toxicology
pub_type: 临床试验,杂志文章
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更新日期:2016-12-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
pub_type: 杂志文章
doi:10.3109/15569527.2015.1072544
更新日期:2016-01-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
pub_type: 杂志文章
doi:10.1080/15569527.2019.1594874
更新日期:2019-09-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
pub_type: 杂志文章
doi:10.3109/15569520903496746
更新日期:2010-03-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
pub_type: 杂志文章
doi:10.3109/15569527.2013.806524
更新日期:2014-06-01 00:00:00
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journal_title:Cutaneous and ocular toxicology
pub_type: 临床试验,杂志文章
doi:10.1080/15569527.2017.1311337
更新日期:2017-12-01 00:00:00