Contribution of New Technologies to Characterisation and Prediction of Adverse Effects


Rouquié D, Heneweer M, Botham J, Ketelslegers H, Markell L, Pfister T, Steiling W, Strauss V, Hennes C. 2014.
Contribution of New Technologies to Characterization and Prediction of Adverse Effects.

Critical Reviews in Toxicology. Accepted for publication in 2014. Posted online January 2015. Doi:10.3109/10408444.2014.986054

A taskforce was set up to investigate how newly developed methods in toxicity testing contribute to hazard and risk assessment of chemicals. The taskforce aimed at identifying the opportunities and current limitations of these new methods in comparison with traditional studies in laboratory animals. Identification of the potential hazards of chemicals has traditionally relied on studies in laboratory animals where changes in clinical pathology and histopathology compared to untreated controls defined an adverse effect. More recently, a paradigm shift in toxicity testing has been proposed, mainly driven by concerns over animal welfare but also thanks to the development of new methods. Currently, technologies based on computer modelling, isolated cell systems and genetics, are available to provide detailed insight in toxicological Mode of Action (MOA) of adverse effects observed in laboratory animals.
The vision described as Toxicity Testing in the 21st century (Tox21c) aims at predicting toxic effects in animals, based on these above-mentioned new technologies. At present, a practical application of the Tox21c vision is still far away. While moving towards toxicity prediction based on these new technologies, a stepwise reduction of animal testing is foreseen by combining animal tests with new technologies. Furthermore, newly developed methods will also be increasingly applied, in conjunction with established methods in order to gain trust in these new methods. This confidence is based on a critical scientific prerequisite: the establishment of a causal link between data obtained with new technologies and adverse effects manifested in animal studies. It is proposed to apply the principles described in the WHO/IPCS framework of MOA to obtain this link. Finally, an international database of known MOAs obtained in laboratory animals using data-rich chemicals will facilitate regulatory acceptance and could further help in the validation of the adverse outcome pathway concepts.