Api Anne Marie
Research Institute for Fragrance Materials Inc., Hackensack, NJ, USA.
Dermatology. 2002;205(1):84-7. doi: 10.1159/000063153.
The Research Institute for Fragrance Materials Inc. (RIFM) has approached sensitization studies with fragrance materials as primary prevention of sensitization in the healthy, normal population. Secondary prevention, or avoidance of elicitation, most often suggested by dermatologists for patients presenting with dermatitis, has not been part of its program effort. Historically, RIFM evaluated the sensitization potential of fragrance materials using the human maximization test method; no animal models were used. In general, petrolatum was used as the vehicle. This is a harsh procedure whose main use may provide a measure of the uppermost limits of sensitization. Treating skin with sodium lauryl sulfate may be problematic and finding a laboratory to conduct the study may also be difficult. In addition, using a human predictive test method for both hazard and safety assessments is not ideal. The current practice involves a hazard assessment using an animal model, followed by a safety assessment in a human repeated-insult patch test (HRIPT). The animal test method is used to identify the sensitization potential and a no-effect level. Following a review of the no-effect level and the maximum skin level, a safety assessment in humans can be conducted. RIFM also modified the original vehicle used in sensitization testing, since petrolatum presents two major difficulties: solubility and inconsistent effects on skin penetration. Since the greatest exposure to fragrance materials is considered to be from a cologne-type product, ethanol was chosen as a more realistic vehicle. Further modification resulted in combinations of ethanol and diethyl phthalate, due to diethyl phthalate's use in many perfume formulations as a solvent and fluidizer. Human testing should not be conducted as a hazard assessment. If conducted as a safety study, induction of sensitization should be a rare occurrence. Thus, follow-up studies are not meaningful since the number of sensitized volunteers would be low. However, following a series of the RIPTs with various concentrations of hydroxycitronellal, RIFM identified a group of 41 individuals who became sensitized. An extensive 3-phase use study, with 3 diagnostic patch tests and 4 whole-body dermatological examinations showed that most subjects were able to use a bar soap, a moisurizing lotion and cologne-type products with up to 1% hydroxycitronellal. In subjects where sensitization was induced by predictive testing, no serious recurring adverse dermatological conditions developed.
香料成分研究协会（RIFM）已将香料成分的致敏性研究作为对健康正常人群致敏性的一级预防措施。二级预防，即避免激发，这是皮肤科医生针对患有皮炎的患者最常建议采取的措施，但并非该协会项目工作的一部分。从历史上看，RIFM使用人体最大化试验方法评估香料成分的致敏潜力；未使用动物模型。一般来说，凡士林被用作赋形剂。这是一个苛刻的程序，其主要用途可能是提供致敏上限的一种衡量方法。用十二烷基硫酸钠处理皮肤可能存在问题，而且找到进行该研究的实验室也可能很困难。此外，使用人体预测试验方法进行危害和安全性评估并不理想。目前的做法是先用动物模型进行危害评估，然后在人体重复刺激斑贴试验（HRIPT）中进行安全性评估。动物试验方法用于确定致敏潜力和无作用水平。在审查无作用水平和最大皮肤暴露水平之后，可以进行人体安全性评估。RIFM还对致敏性测试中使用的原始赋形剂进行了改进，因为凡士林存在两个主要问题：溶解性以及对皮肤渗透的影响不一致。由于认为对香料成分的最大暴露来自古龙水类产品，因此选择乙醇作为更现实的赋形剂。进一步改进后形成了乙醇和邻苯二甲酸二乙酯的组合，因为邻苯二甲酸二乙酯在许多香水配方中用作溶剂和增塑剂。人体测试不应作为危害评估进行。如果作为安全性研究进行，致敏的诱导应该很少发生。因此，后续研究没有意义，因为致敏志愿者的数量会很少。然而，在对不同浓度的羟基香茅醛进行一系列HRIPT之后，RIFM确定了一组41名致敏个体。一项广泛的三阶段使用研究，包括3次诊断性斑贴试验和4次全身皮肤病检查，结果表明大多数受试者能够使用含有高达1%羟基香茅醛的香皂、保湿乳液和古龙水类产品。在通过预测性测试诱导致敏的受试者中，没有出现严重的复发性不良皮肤病状况。
