Abstract
Short-chain per-fluoroalkyl substances (PFAS) have replaced long-chains in many applications, however the toxicity and its mode of action and interactions due to the large number of these compounds and their mixtures is still poorly understood. The paper aims to compare the effects on mouse liver organoids (target organ for bioaccumulation) of two long-chain PFAS (perfluorooctane sulfonate -PFOS-, perfluorooctanoic acid -PFOA) and two short-chain PFAS commonly utilized in the industry (heptafluorobutyric acid -HFBA-, Pentafluoropropionic anhydride-PFPA) to identify the mode of action of these classes of contaminants. Cytomorphological aberrations and ALT/GDH enzyme disruption were identified but no acute toxicity endpoint neither apoptosis was detected by the two tested short-chain PFAS. After cytomorphological analysis, it is evident that short-chain PFAS affected organoid morphology inducing a reduction of cytostructural complexity and aberrant cytological features. Conversely, EC50 values of 670 ± 30 µM and 895 ± 7 µM were measured for PFOS and PFOA, respectively, together with strong ALT/GDH enzyme disruption, caspase 3 and 7 apoptosis activation and deep loss of architectural complexity of organoids in the range of 500–1000 µM. Eventually, biochemical markers and histology analysis confirmed the sensitivity of organoid tests that could be used as a fast and reproducible platform to test many PFAS and mixtures saving time and at low cost in comparison with in vivo tests. Organoids testing could be introduced as an innovative platform to assess the toxicity to fast recognize potentially dangerous pollutants.
Highlights
Per-fluoroalkyl substances (PFAS) have been largely produced and commercialized in the second half of the 20th century [1] and have been found in many samples from urban areas to remote regions of the planet such as the Arctic trophic food webs [2,3]
perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were more toxic than short chain PFAS, as both HFBA and PFPA displayed no cell viability inhibition in the tested concentration range (100–1000 μM)
The acute toxicity tests performed on mouse liver organoids for both long- (PFOA and PFOS) and short-chain (HFBA and PFPA) PFAS displayed negative effects, with a marked disruption associated to long-chain compounds
Summary
Per-fluoroalkyl substances (PFAS) have been largely produced and commercialized in the second half of the 20th century [1] and have been found in many samples from urban areas to remote regions of the planet such as the Arctic trophic food webs [2,3]. This class of contaminants was recorded as ubiquitary in many environmental spheres: soil [4], groundwaters [5], surface and drinking waters [6–8], deep ocean [9], remote lakes, air [10] and eventually humans [11]. The studies mentioned illustrate and highlight the risks and concerns that characterize short-chain PFAS suggesting the need of risk assessment and usage regulation [26]
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