Case Study on the DASS Evaluation of Fatty Acid Methyl Ester Group Using Alternative Skin Sensitization Test Methods

<p> The evaluation of skin sensitisation without using animals is conducted in accordance with 2o3 DA and ITS DA defined in OECD GL No.497 (Defined Approaches on Skin Sensitisation; DASS), based on the results of three alternative tests corresponding to each Key Event. We focused on a group of fatty acid methyl esters that are difficult to dissolve in water and have different test results in mice and guinea pigs. We conducted a verification about DASS and made a discussion considering existing animal data and physicochemical properties.</p><p> The test substances used were a group of fatty acid methyl esters (C6; Methyl hexanoate, C10; Methyl Caprate, C12; Methyl laurate, C18:0; Methyl stearate). The alternative methods used were KE1: ADRA, KE2: EpiSensA (scheduled to be included in OECD TG No.442E), and KE3: h-CLAT. Derek Nexus and OECD QSAR toolbox were used as in silico tools.</p><p> In the case of short-to-medium chain (C6~12) fatty acid methyl esters, the alternative method test results were negative for ADRA, positive for EpiSensA, and inconclusive for h-CLAT. Based on this, the DASS assessment could not be applied because of being inconclusive for both 2o3 and ITS. Therefore, by utilizing the DA proposed as RTS (RhE based Testing Strategy) using EpiSensA (3D skin model), it matched the guinea pig animal results and became UN GHS NC (equivalent to negative). Short-to-medium chain (C6~12) fatty acid methyl esters, although positive in LLNA, were considered not to be sensitizers based on the DASS or RTS, using physical-chemical characteristics and other test results.</p>