Ld. Kier et al., CYTOTOXICITY OF ETHYLENE OXIDE PROPYLENE OXIDE COPOLYMERS IN CULTURED-MAMMALIAN-CELLS/, Drug and chemical toxicology, 18(1), 1995, pp. 29-41
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.