Interlaboratory evaluation of methods to quantify skin-sensitizing hydroperoxides of limonene and linalool (II): Analysis in cosmetic bases

The fragrant terpenes limonene and linalool can form skin-sensitizing hydroperoxides (HPs) upon prolonged exposure to air. Sources of exposure of consumers to sensitizing doses of HPs have not been identified, and it is not clear whether fragranced products are a relevant source. Previously this question was addressed via analytical studies on fine fragrances; however, linalool and limonene are widely used in different consumer products, especially in other leave-on toiletries. Hence, analytical methods also need to be able to detect potential HPs in more complex consumer product matrices. Here we applied different simple extraction methods and a toolbox of analytical methods to creams and lotions. Blinded samples of a commercial skin cream and a body lotion were spiked with four different HPs at different doses. Five laboratories analysed the samples with a method based on HP reduction in the sample, followed by Extrelut((R)) NT extraction and GC-MS to quantify the formed alcohols. This method found an average recovery of spiked levels of 80-105%, with a relative standard deviation between laboratories of 11-25% in samples spiked with 100-200 g g(-1). Quantification was also possible in samples spiked with 20-50 g mL(-1), with a relative standard deviation between laboratories of 11-38%. Thus, this method can indirectly detect low levels of HPs in complex bases. In parallel, the same samples were analysed with three LC-based methods directly detecting the parent HPs: LC coupled with chemiluminescence, LC-Q-TOF-MS, and LC-orbitrap-MS. On average, the different analytes were detected with a recovery of 80-143%. No HPs were detected in the non-spiked products, despite the fact that they do contain linalool and limonene. Results of these studies indicate that consumer exposure can now be studied routinely in different product types as the required methods are ready for roll-out.