Abstract:
:In vivo experiments are still widely used for the testing of lung toxicity but there is an ethical and legal obligation to replace, reduce and refine animal testing. Lung A549 cells could serve as an in vitro indicator for acute lung toxicity but little data about the correlation of the cytotoxicity in A549 cells and data leading to CLP classifications are available. We exposed A549 cells to 19 CLP-classified substances with doses of 25, 50, and 100 μg/cm2 either under submerged (SME) condition or with aerosols at the air-liquid interface (ALIF) and determined accuracy, precision, sensitivity and the F1 score with the CLP classifications H330, H332, or H335. When data from both exposure methods were combined, we found accuracies of 0.84 ± 0.05, precisions of 0.74 ± 0.1, sensitivities of 0.93 ± 0.08 and F1 scores of 0.82 ± 0.04. Separated from each other, ALIF exposure was more sensitive at any dose but, at higher doses, also less accurate and precise compared to SME. Considering the 19 substances tested, our data suggest that cytotoxicity in A549 cells could be a reliable in vitro indicator for in vivo toxicity. Thus, we discuss how A549 could be integrated into validation test guidelines.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Gohlsch K,Mückter H,Steinritz D,Aufderheide M,Hoffmann S,Gudermann T,Breit Adoi
10.1016/j.toxlet.2019.09.014subject
Has Abstractpub_date
2019-11-01 00:00:00pages
119-126eissn
0378-4274issn
1879-3169pii
S0378-4274(19)30285-1journal_volume
316pub_type
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