Research Institute for Fragrance Materials, Inc, Woodcliff Lake, New Jersey, USA.
Toxys B.V, Oegstgeest, The Netherlands.
Environ Mol Mutagen. 2023 Apr;64(4):234-243. doi: 10.1002/em.22532. Epub 2023 Mar 28.
To determine the utility of the ToxTracker assay in animal alternative testing strategies, the genotoxic potential of four fragrance materials (2-octen-4-one, lauric aldehyde, veratraldehyde, and p-methoxy cinnamaldehyde) were tested in the ToxTracker assay. These materials have been previously evaluated in an in vitro as well as in vivo micronucleus assay, conducted as per OECD guidelines. In addition to these studies, reconstructed human skin micronucleus studies were conducted on all four materials. All four materials were positive in an in vitro micronucleus assay but were negative in both in vivo and 3D skin micronucleus assays. The ToxTracker assay, in combination with in silico methods to predict metabolism was used to identify mechanisms for the misleading positive outcomes observed in the in vitro micronucleus assays. The results show that the ToxTracker assay, in conjunction with in silico predictions, can provide the information needed to aid in the identification of an appropriate animal alternative follow-up assay, for substances with positive results in the standard in vitro test battery. Thus, the ToxTracker assay is a valuable tool to identify the genotoxic potential of fragrance materials and can aid with replacing animal-based follow-up testing with appropriate animal alternative assay(s).
为了确定 ToxTracker 测定法在动物替代测试策略中的效用，我们在 ToxTracker 测定法中测试了四种香料材料（2-辛烯-4-酮、月桂醛、藜芦醛和对甲氧基肉桂醛）的遗传毒性潜力。这些材料之前已经根据 OECD 指南在体外和体内微核测定法中进行了评估。除了这些研究外，我们还对所有四种材料进行了重建人体皮肤微核研究。所有四种材料在体外微核测定法中均呈阳性，但在体内和 3D 皮肤微核测定法中均为阴性。ToxTracker 测定法与预测代谢的计算方法相结合，用于确定在体外微核测定法中观察到的误导性阳性结果的机制。结果表明，ToxTracker 测定法与计算方法相结合，可以提供所需的信息，以帮助识别标准体外测试组合中阳性结果物质的适当动物替代后续测定法。因此，ToxTracker 测定法是一种识别香料材料遗传毒性潜力的有价值工具，并有助于用适当的动物替代测定法替代基于动物的后续测试。
