Chemicals produced by various industrial sectors such as drugs, cosmetics, agrochemicals
and industrial chemicals are obliged to undergo a rigorous safety assessment before their entry into the
market. Today the standard information requirements providing the necessary details on the toxicity of
the individual compounds are mainly derived from tests performed in laboratory animals. The principal
drawbacks of such in vivo tests are their length, cost, the remaining uncertainty for humans and the
associated ethical concerns. Therefore there is a strong desire of toxicologists to compile the increasing
scientific knowledge as well as emerging technologies and methodologies in a framework that drives
safety assessments towards a mechanistic understanding of chemically induced toxicity.
An integer part of such modern toxicology are human based in vitro tests that are designed to allow a
high throughput of substances and to specifically elucidate relevant toxicological mechanisms. The
most promising source of human cells are stem cells since these cells can be propagated in vitro
indefinitely, provide all toxicologically relevant target cells and they do not exhibit unwanted
characteristics of cell lines with a carcinogenic origin.
However, the establishment of in vitro toxicity tests based on human pluripotent stem cells is
challenging since differentiation protocols are often unstable, the cell cultures are not pure and the
differentiation is not leading to fully matured cells that are toxicologically relevant. A first step in test
development to tackle these challenges is the establishment of high quality standards which will support
the reproducibility of test results within a laboratory set up but also between laboratories.
In the last years, many progress have been made to develop test systems particularly in areas of toxicity
where human cellular models are not available but strong interspecies variations exists such as
developmental toxicity, cardiotoxicity and hepatotoxicity. However, no pluripotent stem cell- based
toxicity test has been formally validated yet.
Keywords: Human pluripotent stem cells, toxicity testing, in vitro tests, safety assessment.
