How to facilitate the implementation of 3D models in China by applying good method practice for regulatory use.

The Organization for Economic Co-operation and Development (OECD) Guidance Document No. 34 and No. 286 on Good Method Practices (GIVIMPs) for the development and implementation of methods for regulatory use in human safety assessment have been endorsed.

Transferability and reproducibility of the EpiSkin™ Micronucleus Assay.

A novel in vitro 3D micronucleus assay was developed in China using the EpiSkin™ 3D human skin model. This EpiSkin™ Micronucleus Assay showed good predictivity and reproducibility during internal validation and is expected to contribute to in vitro genotoxicity testing as a follow-up for positive results from 2D micronucleus assay. Having developed the assay in one laboratory, further work focused on the transferability and inter-laboratory reproducibility in two additional Chinese authority laboratories (Guangdong Provincial Center for Disease Control and Prevention and Zhejiang Institute for Food and Drug Control).

A new 3D model for genotoxicity assessment: EpiSkin™ Micronucleus Assay.

The European Regulation on Cosmetics (no. 1223/2009) has prohibited the use of animals in safety testing since March 2009 for ingredients used in cosmetics. Irreversible events at the chromosome level (clastogenesis and aneugenesis) are commonly evaluated by scoring either micronuclei or chromosome aberrations using cell-based genotoxicity assays.

A ready-to-use integrated in vitro skin corrosion and irritation testing strategy using EpiSkin™ model in China.

The need of in vitro alternative methods has been increasing in toxicology research as well as in cosmetic industry in China recently. Following the establishment of China EpiSkin™ skin corrosion and irritation testing methods, both as stand-alone in vitro tests according to Organization for Economic Co-operation and Development (OECD) TG 431 and TG 439, the present study aims to evaluate the use of these two methods within the Integrated Approach on Testing and Assessment (IATA). The IATA, adopted by OECD as Guidance Document 203, provides guidance on the integration of existing and new data in a modular approach for classification and labelling of chemicals according to Globally Harmonized System of classification and labeling of chemicals (GHS) issued by the United Nations (UN).

A way forward of alternative methods in China: Implementation of skin corrosivity potential using in vitro reconstructed human epidermis.

The purpose of present study was to investigate the applicability of reconstructed human epidermis model to identify skin corrosive UN GHS Categories 1A, 1B/1C and non-corrosive chemicals in China. By using a commercialized reconstructed human epidermis model, China EpiSkin™ which had been proven to be applicable as a stand-alone test method to predict skin irritation in previous study, the predictive capacity of corrosion was assessed with 76 chemicals that included 30 reference chemicals recommended by OECD TG 431 in this study. The latter reference chemicals were tested in three runs, the within-laboratory reproducibility reached 100%, the accuracy was 90% for distinguishing corrosive and non-corrosive chemicals and 80% for sub-categorization (Cat.

In vitro skin irritation assessment becomes a reality in China using a reconstructed human epidermis test method.

The in vitro EpiSkin™ test method was validated in 2007 by the European Union Reference Laboratory for alternatives to animal testing (EURL ECVAM) as a full replacement method for the Draize acute skin irritation test and adopted in the OECD Test Guideline 439 in 2009. Based on the EpiSkin™ technology, the production of a reconstructed epidermis model has been established and standardized in China. The evaluation of the in vitro skin irritation test method using this EpiSkin™ model produced in China was performed on a set of 45 chemicals.

Deficiency of kinase suppressor of Ras1 prevents oncogenic ras signaling in mice.

In Drosophila and Caenorhabditis elegans, kinase suppressor of ras (KSR) positively modulates Ras/Raf-mitogen-activated protein kinase (MAPK) signaling. The precise signaling mechanism of mammalian KSR1 and its role in Ras-mediated transformation, however, remain uncertain. To gain insight into KSR1 function in vivo, we generated mice homozygous null for KSR1.