In vitro systems, on the other hand, are independent of nutritional and hormonal influence and can therefore elucidate the cellular basis of toxicity. They derive from a first-trimester foetus, and thus represent the gestational stage when the foetus is most susceptible to developmental anomalies. However, long-term culture of these cells from mammalian embryos has yet to be achieved. Moreover, differentiated alveolar epithelium arises at a much later stage of foetal development which is less susceptible to toxic processes. Nevertheless, L2 rat lung epithelial cells are also used in this system because of their metabolising capacity.
Tritiated proline is used as a label for the measurement of protein synthesis.
This was partly due to the fact that the culture medium contained leucine but not proline. Furthermore, proline is over-represented in collagenous proteins, and collagen synthesis was shown to be affected more specifically than other proteins in this cell strain. Leucine, on the other hand, is under-represented in protein manufactured by foetal lung fibroblasts. The predictive capability of the cytotoxicity tests will be compared with that of rodent tests in vivo. An initial set of 50 chemicals to be tested was chosen on the basis of available human toxicity data, and laboratories were encouraged to test this set of chemicals in their in vitro cytotoxicity assays.