Skin Sensitization of Epoxyaldehydes: Importance of Conjugation

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• 作者：Tamara Delaine ; Lina Hagvall ; Johanna Rudb盲ck ; Kristina Luthman ; Ann-Therese Karlberg
• 刊名：Chemical Research in Toxicology
• 出版年：2013
• 出版时间：May 20, 2013
• 年：2013
• 卷：26
• 期：5
• 页码：674-684
• 全文大小：427K
• 年卷期：v.26,no.5(May 20, 2013)
• ISSN：1520-5010

文摘

Structure鈥揳ctivity relationship (SAR) models are important tools for predicting the skin sensitization potential of new compounds without animal testing. In compounds possessing a structural alert (aldehyde) and an activation alert (double bond), it is important to consider bioactivation/autoxidation (e.g., epoxidation). In the present study, we have explored a series of aldehydes with regard to contact allergy. The chemical reactivity of these 6 aldehydes toward a model hexapeptide was investigated, and their skin sensitization potencies were evaluated using the local lymph node assay (LLNA). Overall, we observed a similar trend for the in vitro reactivity and the in vivo sensitization potency for the structural analogues in this study. The highly reactive conjugated aldehydes (伪,尾-unsaturated aldehydes and 2,3-epoxyaldehydes) are sensitizing moieties, while nonconjugated aldehydes and nonterminal aliphatic epoxides show low reactivity and low sensitization potency. Our data show the importance of not only double bond conjugation to aldehyde but also epoxide鈥揳ldehyde conjugation. The observations indicate that the formation of nonconjugated epoxides by bioactivation or autoxidation is not sufficient to significantly increase the sensitization potency of weakly sensitizing parent compounds.