Prospective identification of low molecular weight (LMW) respiratory sensitisers is difficult due to the current lack of adequate test methods. The direct peptide reactivity assay (DPRA) seems to be a promising method to determine the sensitisation potential of chemicals, since it determines the intrinsic characteristic of sensitisers to bind to proteins. It is already applied in the field of skin sensitisation and adaptation to respiratory sensitisation has started recently. This study further evaluates the ability of the DPRA to predict the respiratory sensitisation potential of chemicals. In addition, the added value of applying HPLC-MS and measurements after 20 minutes and 24 hours of incubation was evaluated. Eighteen respiratory sensitisers (10 haptens, 3 pre- and 5 pro-haptens) and fourteen non-sensitisers were tested with two model peptides. Based on peptide depletion, a prediction model was proposed for the identification of (respiratory) sensitisers. Application of mass spectrometry and measurements at two time-points increased prediction accuracy of the assay by resolving discordant results. The prediction model correctly identified all haptens and pre-haptens as sensitizers. The five pro-haptens were not identified as sensitisers, most likely due to lack of metabolic activity in the DPRA. All but one non-sensitiser was correctly predicted. The model therefore shows an accuracy of 78% for the tested dataset. Unfortunately, this assay cannot be used to distinguish respiratory from skin sensitisers. To make this distinction, the DPRA needs to be combined with other test methods that are able to identify respiratory sensitisers.
Authors: Dik S, Rorije E, Schwillens P, van Loveren H, Ezendam J. ;Full Source: Toxicological Science. 2016 Jul 29. pii: kfw130. [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Epub ahead of print] ;[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]