Abstract：
Recent years have seen an increase in the use of botanicals and natural substances (BNS) in consumer products such as cosmetics and household care products. Most work conducted to date to assess botanicals for human safety has focused their use as dietary supplements and thus on systemic toxicity. However, the induction of skin sensitization is a possible adverse effect of natural products in particular those that come into skin contact, especially for cosmetics that remain on the skin and are not rinsed off following use. Assessments of BNS ingredients are often challenging for a number of reasons: the BNS are complex mixtures that can be of mostly unknown composition; the composition can be highly variable even within the same plant species and dependent on how processed; the physical form of the BNS raw material can vary from a highly concentrated powdered extract to a liquid extract containing only a small percentage of the BNS; testing of the BNS raw materials in New Approach Methods (NAM) has uncertainty as these methods are often not developed or validated for complex mixtures. In this study, a reference set of 14 selected BNS which span the range of skin sensitization potential was complied. These data were used in a Weight of Evidence (WoE) approach to evaluate their skin sensitization potential with each of the data rich BNS being classified as either having strong evidence of inducing skin sensitization based on human topical use history, animal data, clinical data, composition data and NAM data, or having some but more limited (weak) evidence of inducing skin sensitization, or having strong evidence of no skin sensitization potential. When available data have sufficient potency related information, sensitization potency assessment is also provided based on WoE, classifying these BNS as either strong, moderate, or weak sensitizers, or non-sensitizers. An outline for a BNS skin sensitization risk assessment framework is proposed starting with exposure-based waiving and WoE assessment for higher exposures. In addition to demonstrating the application of the WoE approach, the reference set presented here provides a set of \'data rich\' botanicals which cover a range of sensitization potencies that could be used for evaluating existing test methods or aid in the development of new predictive models for skin sensitization.
摘要：
近年来，在化妆品和家用护理产品等消费品中，植物药和天然物质（BNS）的使用有所增加。迄今为止，为评估植物药的人类安全性而进行的大多数工作都集中在将其用作膳食补充剂，因此集中在全身毒性上。然而,皮肤致敏的诱导是天然产品的可能的不利影响，特别是那些进入皮肤接触，特别是对于保留在皮肤上并且在使用后不会被冲洗掉的化妆品。BNS成分的评估通常具有挑战性，原因有很多：BNS是复杂的混合物，其成分可能大多未知；即使在相同的植物物种中，成分也可能高度可变，并且取决于加工方式；BNS原料的物理形式可以从高度浓缩的粉末提取物到仅含少量BNS的液体提取物不等；在新方法方法（NAM）中对BNS原料的测试具有不确定性，因为这些方法通常未得到复杂的混合验证。在这项研究中,符合涵盖皮肤致敏潜力范围的14个选定BNS的参考集。这些数据用于证据权重（WoE）方法来评估他们的皮肤致敏潜力，每个数据丰富的BNS被分类为具有基于人类局部使用史诱导皮肤致敏的有力证据。动物数据,临床资料,合成数据和NAM数据，或者有一些但更有限的（弱）诱导皮肤致敏的证据，或有强有力的证据表明没有皮肤致敏的潜力。当可用数据具有足够的效力相关信息时，还提供了基于WoE的致敏效能评估，将这些BNS分类为强，中度,或者弱敏剂，或非致敏剂。提出了BNS皮肤致敏风险评估框架的大纲，首先是基于暴露的放弃和WoE评估以获得更高的暴露。除了展示WoE方法的应用外，这里提供的参考集提供了一组数据丰富的植物药，涵盖了一系列致敏效力，可用于评估现有的测试方法或帮助开发新的皮肤致敏预测模型。
