CYTOTOXICITY OF ETHYLENE OXIDE PROPYLENE OXIDE COPOLYMERS IN CULTURED-MAMMALIAN-CELLS/

Cytotoxicity was measured in vitro for 8 ethylene oxide/propylene oxid e copolymers (EO/PO copolymers) using lactate dehydrogenase release fr om cultured mammalian cells as the endpoint. Three cell types were use d in these assays: Chinese hamster ovary cell line (AS52), rat lung ep ithelial cell line (LEC), and freshly isolated rat alveolar macrophage s (RAM). A range of cytotoxicity was seen with toxic effects observed from 20 to > 20,000 mu g/ml. The same relative order of toxicities wer e observed for all 3 cell lines although RAM cells appeared to be some what more sensitive. The in vitro cytotoxicity, as measured by LDH rel ease and microscopic observations of the cells, correlated poorly with the in vivo inhalation toxicity. The most lethal compounds following acute inhalation (UCON(R) 50-HB-5100 and UCON(R) 50-HB-2000) were amon g the least toxic in the in vitro cytotoxicity screen. Conversely the 2 compounds which were the most toxic in vitro (Pluronic(R) 17 R1 and Pluronic(R) L64) did not produce any unusual degree of toxicity in inh alation studies. The results of these experiments indicate that these in vitro mammalian cell assays will not be useful, at least for these classes of chemistry, in prediction of in vivo inhalation toxicity.