Toxicology is the study of mechanisms by which chemicals damage or kill cells.
There are multiple mechanisms of toxicity, which may affect all cell types (basal) or may be organ-specific.
Extensive research using fresh and cryopreserved hepatocyte suspensions and cultures has been carried out to elucidate mechanisms of liver toxicity, such as mitotoxicity, cholestasis, fibrosis, inflammation, apoptosis, senescence and carcinogenicity (see HepaRG™ web site for toxicity endpoints).
Idiosyncratic hepatotoxicity has been linked to metabolism to chemically reactive metabolites and subsequent activation of the immune system (both of which exhibit polymorphisms), as well as alterations in gene patterns.
In the cosmetics and chemical industries, fresh and frozen skin from different anatomical sites is used routinely in safety assessment for predicting the potential local and systemic exposure to topically exposed chemicals. A number of Phase 1 and 2 metabolic activities of keratinocytes are measurable, making them suitable for investigating the toxicity of chemicals that are dermally metabolised before entering the systemic circulation.
Freshly isolated and cryopreserved keratinocytes and fibroblasts can be used in 2D conventional monolayer cultures and in 3D air: liquid interface organotypic cultures.