A replacement alternative to the rabbit eye irritation test has been sought for many years. First published in 1944 by FDA toxicologist J. H. Draize, the test, now known as the Draize Eye Test, has been used extensively to assess eye safety. It has also been a focal point for concern regarding its animal use. In 1992, Molecular Devices developed the Cytosensor Microphysiometer (CM) technology, an automated potentiometric online measurement of pH changes in cells, and evaluated it also for chemically induced irritation.
The method was included in some of the six major validation studies for eye irritation from 1991-1997. The results for CM were inconclusive as were those from other tests evaluated as stand-alone methods to fully replace the animal test. In 2002, the European Centre for the Validation of Alternative Methods (ECVAM) started applying concepts from evidence-based medicine, and opened validation to retrospective meta-analysis. This activity was done in collaboration with US counterpart ICCVAM/NICEATM, and the European Cosmetics Association, Colipa.
After a new, comprehensive evaluation of the prior available data, the ECVAM scientific advisory committee (ESAC) has recently accepted the CM as capable of identifying non-irritants for testing limited to water-soluble surfactants and water-soluble surfactant-containing mixtures. This 25-year development is remarkable and instructive in many respects. The authors see this as opening the door, at last, for an end to the use of animals as a standard requirement for eye irritation. Here, several of the people critically involved in this processes have summarized the important aspects of this history.

Fetal bovine serum (FBS) is a ubiquitously used essential supplement in cell culture media. However, there are serious scientific and ethical concerns about the use of FBS regarding its harvest and production. During the last three decades, FBS could be substituted by other supplements or by the use of defined chemical components in serum-free cell culture. A number of serum-free medium formulations have been described for mammalian and insect cell lines as well as for primary cultures. However, the switch to serum-free media still demands a time-consuming literature survey and a manufacturer search for appropriate medium formulations, respectively. Here we present the second collection of commercially available serum-free media in an updated, freely accessible interactive online database. Searches for serum-free media and continuous cell lines already adapted to serum-free culture can be performed according to various criteria. These include the degree of chemical definition, e.g. serum-free (SF), animal-derived component free (ADCF) or chemically defined (CD), and the type of medium, e.g. basal media, medium supplements, or full replacement media. In order to specify the cell lines that are adapted to serum-free media, search terms like species, organ, tissue, cell type and disease can be used. All commercially available serum-free media and adapted cell lines currently available from major distributors (e.g. ATCC, ECACC and DMSZ) are included in the database. Despite an extensive search for serum-free media and adapted cell lines, detailed information from certain companies and suppliers is still lacking and is specifically highlighted. It is intended to create a platform for the interactive exchange of information and experience by experts in the field in order to continuously improve and extend the serum-free online database. The database is accessible at http://www.goodcellculture.com/

The Center for Alternatives to Animal Testing – Europe (CAAT-EU) was founded based a collaboration between the Johns Hopkins Bloomberg School of Public Health and the University of Konstanz. CAAT-EU, housed at the University of Konstanz, will coordinate transatlantic activities to promote humane science in research and education, and participate, as partner or coordinator, in publicly and privately funded European projects. Thomas Hartung will serve as program liaison representing Johns Hopkins University and Marcel Leist as the University of Konstanz liaison.
CAAT-EU aims to:

• Set up transatlantic consortia for international research projects on alternative methods


• Establish a CAAT Europe faculty and advisory board composed of sponsor representatives and prominent academics from Europe


• Participate in the Transatlantic Think Tank for Toxicology (t4) devoted to conceptual work for the paradigm shift in toxicology


• Coordinate a series of information days in Europe on relevant developments in the US, similar to the 2009 series CAAT held in the US on EU issues (one on the 7th Amendment to the EU Cosmetics Directive and one on EU and US chemical regulation)


• Support ALTEX as the official journal of CAAT and CAAT-EU


• Develop strategic projects with sponsors to promote humane science and new toxicology, especially with CAAT faculty members


• Develop a joint education program between Johns Hopkins and the University of Konstanz, such as e-courses and the existing Humane Science Certificate program developed by CAAT, a student exchange program, and collaboration with the International Graduate School “Cell-based Characterization of De- and Regeneration” in Konstanz.

Developmental neurotoxicity (DNT) is a serious concern for environmental chemicals, as well as for food and drug constituents. Animal-based DNT models have relatively low sensitivity, and they are burdened by high work-load, cost and animal ethics. Murine embryonic stem cells (mESC) recapitulate several critical processes involved in the development of the nervous system if they are induced to differentiate into neural cells. They therefore represent an alternative toxicological model to predict human hazard. In this review, we discuss how mESC can be used for DNT assays. We have compiled a list of mRNA markers that define undifferentiated mESC (n = 42), neural stem cells (n = 73), astrocytes (n = 25) and the pattern of different neuronal and non-neuronal cell types generated (n = 57). We propose that transcriptional profiling can be used as a sensitive endpoint in toxicity assays to distinguish neural differentiation states during normal and disturbed development. Importantly, we believe that it can be scaled up to relatively high throughput whilst still providing rich information on disturbances affecting small cell subpopulations. Moreover, this approach can provide insight into underlying mechanisms and pathways of toxicity. We broadly discuss the methodological basis of marker lists and DNT assay design. The discussion is put in the context of a new generation of alternative assays (embryonic stem cell based DNT testing = ESDNT V2.0), that may later include human induced pluripotent stem cells, and that are not designed for 1:1 replacement of animal experiments, but are rather intended to improve human risk assessment by using independent scientific principles.