Transcriptomic points of departure from the aquatic insect Chironomus dilutus for 22 per- and polyfluoroalkyl substances (PFAS) and their use in chemical hazard screening.

High throughput (HTP) assays using aquatic species are being developed in response to the large number of chemicals in or entering commerce with little aquatic toxicological data. Transcriptomic points of departure (tPODs) coupled to HTP assays have shown promise in efficiently assessing possible toxicity of chemicals. With thousands of identified per- and polyfluoroalkyl substances (PFAS) such strategies are required to assess their potential hazard to aquatic species. This study investigated the utility of a HTP transcriptomic assay with an aquatic insect (Chironomus dilutus) to assess the toxicity of 22 PFAS. Larval C. dilutus were exposed for 24-hr in 96-well microplates to a concentration series of each PFAS. Following exposure, tPODs were calculated from the transcriptomic data. The tPODs ranged from 3 µg/L for 6:2 fluorotelomer sulfonic acid to 1602 µg/L for perfluoropentanoic acid. These values were compared to tPODs previously derived for fathead minnow (Pimephales promelas), Daphnia magna, a microalga (Raphidocelis subcapitata) and from mammalian cell culture HTP assays. In addition, C. dilutus tPODs were compared to published surface water concentrations which were typically orders of magnitude lower than the tPOD. The C. dilutus HTP assay showed promise as a New Approach Methodology (NAM) to assess the toxicity of chemicals, such as PFAS, as part of a tiered hazard evaluation strategy.