Comparison of conventional and advanced in vitro models in the toxicity testing of nanoparticles.

Humans are exposed to a wide variety of nanoparticles (NPs) present in the environment, in consumer, health and medical products, and in food. Conventional cytotoxicity testing compared to animal testing is less expensive, faster and avoids ethical problems at the expense of a lower predictive value. New cellular models and exposure conditions have been developed to overcome the limitations of conventional cell culture and obtain more predictive data. The use of three-dimensional culture, co-culture and inclusion of mechanical stimulation can provide physiologically more relevant culture conditions. These systems are particularly relevant for oral, respiratory and intravenous exposure to NPs and it may be assumed that physiologically relevant application of the NPs can improve the predictive value of in vitro testing. Various groups have used advanced culture and exposure systems, but few direct comparisons between data from conventional cultures and from advanced systems exist. In silico models may present another option to predict human health risk by NPs without using animal studies. In the absence of validation, the question whether these alternative models provide more predictive data than conventional testing remains elusive.