Evaluation of the cytotoxicity of the first ten MEIC chemicals in 3T3 mouse fibroblasts with and without microsomal activation, using the neutral red assay

By Rasmussen, E.S.

The cytotoxicity of the first ten MEIC chemicals was evaluated by determination of neutral red uptake in BALB/C 3T3 mouse fibroblasts both with and without the addition of a microsomal activation system. The IC20 values of all the chemicals tested without microsomes were significantly correlated to in vivo data on acute systemic toxicity. The use of microsomes weakened the overall correlation with the in vivo data. Useful information regarding the activation of acetylsalicylic acid, iron sulphate, methanol and ethanol was obtained using microsomes, while misleading information was obtained regarding the metabolism of paracetamol, diazepam, digoxin and ethylene glycol. In the case of alcohol metabolism, the Aroclor 1254 induction of rat liver enzymes seems to parallel the induction of cytochrome P450 IIE1, which is known to metabolise a number of alcohols to free radicals which might exert a variety of cytotoxic effects. For this reason, the use of Aroclor 1254 induction in cytotoxicity and genotoxicity testing is questioned.