New Poster: Next Generation Risk Assessment Approach for Inhalation: Polymer Case Studies

Next Generation Risk Assessment (NGRA) is an exposure-led, hypothesis-driven approach that integrates new approach methodologies (NAMs) to assure human safety without animal data. We are currently evaluating a NGRA approach for inhalation exposures using hypothetical case studies of a film-forming polymer in personal care products (e.g. antiperspirants) and a silane in cleaning products.

Impairment of mucociliary clearance, lung fibrosis and lung surfactant inhibition were identified as the relevant endpoints for the most common consumer exposure scenarios (e.g. daily use of an antiperspirant). To investigate these endpoints, two cell models were selected for in vitro testing: the MucilAir™-HF cell model (Epithelix) a system which shows ciliated as well as mucous producing cells typical for the bronchial region and the EpiAlveolar™ cell model (MatTek) a coculture system out of AT1 and AT2 (surfactant producing) cells, fibroblasts and THP1 cell representing the most common cells of the alveolar tract. In addition to the two case study chemicals another 16 benchmark substances were selected either due to their well-known effects in the specific areas of the lung, history of safe use and/or due to chemical or physical similarities to the case study chemicals.

Linking the in vitro point of departures to the relevant in vivo consumer exposure level is essential to evaluate the usefulness of the in vitro test systems. Therefore, consumer habits and practises were used to derive an airborne concentration (mg/m3) for each chemical and exposure scenario, which was then transformed into deposited mass in the bronchial and alveolar region (µg/cm2) using MPPDv2.8. Cells were exposed daily for up to 12 days in vitro and different endpoints measured every other day. Preliminary results indicate that the alveolar model was more sensitive to some of the pro- inflammatory benchmark substances tested. Polyhexamethylene guanidine phosphate for example induces a mild inflammatory response in the MucilAir™-HF system over the 12 days’ treatment while inducing significant cytotoxicity in the EpiAlveolar™ cell model after only 4 days of exposure. Results on mucocilliary clearance are inconclusive since Benzalkonium chloride for example showed no significant effects.

View the poster here.


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