Novel technologies and an overall strategy to allow hazard assessment and risk prediction of chemicals, cosmetics, and drugs with animal-free methods

Several alternative methods to replace animal experiments have been accepted by legal bodies. An even larger number of tests are under development or already in use for non-regulatory applications or for the generation of information stored in proprietary knowledge bases. The next step for the use o...

Full description

Saved in:

Bibliographic Details
Published in:	ALTEX, alternatives to animal experimentation Vol. 29; no. 4; pp. 373 - 388
Main Authors:	Leist, Marcel, Lidbury, Brett A, Yang, Chihae, Hayden, Patrick J, Kelm, Jens M, Ringeissen, Stephanie, Detroyer, Ann, Meunier, Jean R, Rathman, James F, Jackson, Jr, George R, Stolper, Gina, Hasiwa, Nina
Format:	Journal Article
Language:	English
Published:	Germany 2012
Subjects:	Animal Testing Alternatives - methods Animals Cell Line Computer Simulation Cosmetics - toxicity Drug-Related Side Effects and Adverse Reactions Hazardous Substances - toxicity Humans Models, Biological Neurons - cytology Neurons - physiology Tissue Engineering Toxicity Tests - methods
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Several alternative methods to replace animal experiments have been accepted by legal bodies. An even larger number of tests are under development or already in use for non-regulatory applications or for the generation of information stored in proprietary knowledge bases. The next step for the use of the different in vitro methods is their combination into integrated testing strategies (ITS) to get closer to the overall goal of predictive "in vitro-based risk evaluation processes." We introduce here a conceptual framework as the basis for future ITS and their use for risk evaluation without animal experiments. The framework allows incorporation of both individual tests and already integrated approaches. Illustrative examples for elements to be incorporated are drawn from the session "Innovative technologies" at the 8th World Congress on Alternatives and Animal Use in the Life Sciences, held in Montreal, 2011. For instance, LUHMES cells (conditionally immortalized human neurons) were presented as an example for a 2D cell system. The novel 3D platform developed by InSphero was chosen as an example for the design and use of scaffold-free, organotypic microtissues. The identification of critical pathways of toxicity (PoT) may be facilitated by approaches exemplified by the MatTek 3D model for human epithelial tissues with engineered toxicological reporter functions. The important role of in silico methods and of modeling based on various pre-existing data is demonstrated by Altamira's comprehensive approach to predicting a molecule's potential for skin irritancy. A final example demonstrates how natural variation in human genetics may be overcome using data analytic (pattern recognition) techniques borrowed from computer science and statistics. The overall hazard and risk assessment strategy integrating these different examples has been compiled in a graphical work flow.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1868-596X 1868-596X
DOI:	10.14573/altex.2012.4.373