Comparison of six bioassays for assessing in vitro acute toxicity and structure-activity relationships for vinyl chloride monomer, its main metabolites and derivates

The in vitro cytotoxicity and structure-activity-relationship (SAR) of vinyl chloride monomer, its main metabolites (chloroethanol, chloroacetaldehyde, acetaldehyde, chloroacetic acid) and some structurally-related substances (di-chloroethane, ethanol, glycolic acid, thioglycolic acid, ethylene glycol and di-ethylene glycol) were tested and compared with six bioassays performed on L-929 murine fibroblasts and ciliated protozoa Tetrahymena pyriformis GL. Major differences of cytotoxicity exist between the tested substances. Moreover, DTP, RNA, MTT and NRI assays appeared to be the four most sensitive assays. The best concordance of results was observed between MTT and NRI (r = 0.998), between MTT and CB (r = 0.979) and between RNI and CB (r = 0.969), but also between DTP and MTT (r = 0.929), between DTP and RNI (r = 0.933) and between DTP and CB (r = 0.941). Significant correlation between the in vitro biological responses of both models and in vivo data of tested substances was noted. Cytotoxicity increased concurrently with the lipophilicity coefficient; this relationship was statistically significant for both the in vivo and in vitro data obtained with the MTT, NRI and CB assays.