A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals

Currently the only methods for non-genotoxic carcinogenic hazard assessment accepted by most regulatory authorities are lifetime carcinogenicity studies. However, these involve the use of large numbers of animals and the relevance of their predictive power and results has been scientifically challenged. With increased availability of innovative...

Translocation of differently sized and charged polystyrene nanoparticles in in vitro intestinal cell models of increasing complexity

Intestinal translocation is a key factor for determining bioavailability of nanoparticles (NPs) after oral uptake. Therefore, we evaluated three in vitro intestinal cell models of increasing complexity which might affect the translocation of NPs: a mono-culture (Caco-2 cells), a co-culture with mucus secreting HT29-MTX cells and a tri-culture...

Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: Expert opinions on the state of affairs and the way forward

Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being...

The OSIRIS Weight of Evidence approach: ITS for the endpoints repeated-dose toxicity (RepDose ITS)

In the FP6 European project OSIRIS, Integrated Testing Strategies (ITSs) for relevant toxicological endpoints were developed to avoid new animal testing and thus to reduce time and costs. The present paper describes the development of an ITS for repeated-dose toxicity called RepDose ITS which evaluates the conditions under which in vivo non...

OSIRIS, a quest for proof of principle for integrated testing strategies of chemicals for four human health endpoints

Chemical substances policies in Europe are aiming towards chemical safety and at the same time a reduction in animal testing. These goals are alleged to be reachable by mining as many relevant data as possible, evaluate these data with regard to validity, reliability and relevance, and use of these data in so-called Integrated Testing Strategies...

Toward in vitro biomarkers for developmental toxicity and their extrapolation to the in vivo situation

Introduction: Reliable in vitro and in silico assays as alternatives for in vivo developmental toxicity studies are urgently needed, for the replacement, reduction and refinement (3Rs) of animal use in toxicological research. Therefore, relevant biomarkers for in vivo developmental toxicity in in vitro assays are needed. Areas covered: The...

Toxicology in the 21st century - Working our way towards a visionary reality

In November 2009 the In Vitro Testing Industrial Platform (IVTIP) organized a meeting entitled '. Toxicology in the 21st century - working our way towards a visionary reality'. Participating delegates included scientists, key opinion leaders, developers and users of 3Rs-related tests and testing strategies. This paper summarizes the discussions...

T4 report. An expert consortium review of the EC-commissioned report "Alternative (non-animal) methods for cosmetics testing: Current status and future prospects - 2010"

The European cosmetics legislation foresees a review in 2011 and possible postponement of the 2013 marketing ban to enforce the testing ban for systemic and repeated-dose animal tests. For this purpose, a 119-page report commissioned by the European Commission was published recently. Here, a group of 17 independent experts from the US, Europe,...

Apolipoprotein E*3-Leiden transgenic mice mode for hypolipidaemic drugs

Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5) and gemfibrozil (CAS 25812-30-0) as well as a...