Innovative organotypic in vitro models for safety assessment: aligning with regulatory requirements and understanding models of the heart, skin, and liver as paradigms

The development of improved, innovative models for the detection of toxicity of drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new products safely to market in a cost-effective and timely manner. In addition, improvement in models to detect toxicity may reduce the incidence of unexpected post-marketing toxicity and reduce or eliminate the need for animal testing. The safety of novel products of the pharmaceutical, chemical, or cosmetics industry must be assured; therefore, toxicological properties need to be assessed. Accepted methods for gathering the information required by law for approval of substances are often animal methods. To reduce, refine, and replace animal testing, innovative organotypic in vitro models have emerged. Such models appear at different levels of complexity ranging from simpler, self-organized three-dimensional (3D) cell cultures up to more advanced scaffold-based co-cultures consisting of multiple cell types. This review provides an overview of recent developments in the field of toxicity testing with in vitro models for three major organ types: heart, skin, and liver. This review also examines regulatory aspects of such models in Europe and the UK, and summarizes best practices to facilitate the acceptance and appropriate use of advanced in vitro models

Subcycle interference upon tunnel ionization by counter-rotating two-color fields

We report on three-dimensional (3D) electron momentum distributions from single ionization of helium by a laser pulse consisting of two counter-rotating circularly polarized fields (390 and 780 nm). A pronounced 3D low-energy structure and subcycle interferences are observed experimentally and reproduced numerically using a trajectory-based semiclassical simulation. The orientation of the low-energy structure in the polarization plane is verified by numerical simulations solving the time-dependent Schrödinger equation.This Rapid Communication was supported by the DFG Priority Programme “Quantum Dynamics in Tailored Intense Fields” of the German Research Foundation (Project No. DO 604/29-1). A.H. and K.H. acknowledge support from the German Merit Foundation. A.K. acknowledges support from the Wilhelm and Else Heraeus Foundation