For toxicokinetics, the timeframe was 5-7 years to develop the models still lacking to predict lung absorption and renal/biliary excretion; and even longer to integrate the methods to fully replace animal toxicokinetic models. For the systemic toxicological endpoints of repeat dose toxicity, carcinogenicity and reproductive toxicity, the time necessary for full replacement could not even be estimated (Adler et al., 128 2011).