Thorne P S, Hawk C, Kaliszewski S D, Guiney P D
Department of Preventive Medicine and Environmental Health, College of Medicine, University of Iowa, Iowa City 52242.
Fundam Appl Toxicol. 1991 Nov;17(4):807-20. doi: 10.1016/0272-0590(91)90187-9.
The noninvasive mouse ear swelling assay (MESA) for contact allergy testing was evaluated using fragrance components and complex fragrance mixtures. The test materials represented weak sensitizers and nonsensitizers. Two versions of the MESA were investigated. Both were noninvasive and utilized only topical abdominal dosing and ear challenge with single applications in BALB/cBy mice. The vit A MESA differed from the regular MESA only in that mice were maintained on a diet with 17-fold higher levels of vitamin A (vit A) acetate beginning 3 weeks prior to induction. Sensitization reactions were determined by measuring the mean increase in ear swelling over baseline at 24, 48 and 72 hr postexposure. Irritation dose-response curves facilitated choosing a high nonirritating challenge dose. Sensitization dose-response curves were developed for cinnamaldehyde (CINN) and a complex fragrance mixture, F-16. From these curves, the SD50 was determined. This value represents the dose which sensitized half the animals and serves to rank the potency of compounds for allergic contact dermatitis and to compare values among different assays. The SD50 for CINN was 21.6% while the SD50vit A for F-16 was 26.6%. The other fragrance, isoeugenol (ISOE), and fragrance mixtures, F-07 and F-22, were also found to be weak sensitizers in the MESA and vit A MESA. The results in the MESA for CINN and ISOE were in the range observed with guinea pig test protocols but showed that the MESA was more sensitive than human test protocols. Two of the fragrance mixtures tested in the MESA gave comparable results in the Buehler guinea pig assay. However, the third (F-22) was negative in the Buehler assay and the MESA, but positive in the vit A MESA. The results of this work with weak sensitizers and the companion study (Thorne et al., 1991) with potent sensitizers at low doses illustrate that the noninvasive MESA is as sensitive as many standard guinea pig assays. In addition, it is easier and much less expensive to perform. The vit A MESA has the sensitivity and predictive power needed to test compounds and mixtures for contact sensitizing potency.
使用香料成分和复合香料混合物对用于接触性过敏测试的非侵入性小鼠耳部肿胀试验（MESA）进行了评估。测试材料包括弱致敏剂和非致敏剂。研究了两种版本的MESA。两者均为非侵入性，仅在BALB/cBy小鼠中采用单次局部腹部给药和耳部激发。维生素A MESA与常规MESA的不同之处仅在于，从诱导前3周开始，小鼠维持在醋酸维生素A（vit A）水平高17倍的饮食中。通过测量暴露后24、48和72小时耳部肿胀相对于基线的平均增加来确定致敏反应。刺激剂量反应曲线有助于选择高剂量的无刺激性激发剂量。绘制了肉桂醛（CINN）和复合香料混合物F-16的致敏剂量反应曲线。根据这些曲线确定了SD50。该值代表使一半动物致敏的剂量，用于对化合物引发过敏性接触性皮炎的效力进行排名，并比较不同试验中的值。CINN的SD50为21.6%，而F-16的vit A MESA的SD50为26.6%。还发现另一种香料异丁香酚（ISOE）以及香料混合物F-07和F-22在MESA和vit A MESA中也是弱致敏剂。CINN和ISOE在MESA中的结果在豚鼠试验方案所观察到的范围内，但表明MESA比人体试验方案更敏感。在MESA中测试的两种香料混合物在Buehler豚鼠试验中给出了可比的结果。然而，第三种（F-22）在Buehler试验和MESA中为阴性，但在vit A MESA中为阳性。这项关于弱致敏剂的研究结果以及（Thorne等人，1991年）关于低剂量强效致敏剂的配套研究表明，非侵入性MESA与许多标准豚鼠试验一样敏感。此外，它更容易操作且成本低得多。vit A MESA具有测试化合物和混合物接触致敏效力所需的灵敏度和预测能力。
