[In vitro] Searching for Reliable Replacement Models in Topical Toxicology—Focus on Skin and Eye Toxicity

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  • Date 2017-03-10
[In vitro] Searching for Reliable Replacement Models in Topical Toxicology
—Focus on Skin and Eye Toxicity



안녕하세요. CND 관리자 입니다.

In vitro SOT 강연 시리즈 중에서 이번에는 피부와 안구 독성 모델에 대한 주제를 소개해 드립니다.


Dr. Kandarova 의 발표자료를 파일로 첨부하였습니다.



 

Helena Kandarova
MatTek Corp. & MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia

 

Dr. Kandarova presented an introduction to the use of models to predict human toxicity, especially several related to skin and eye toxicity. The audience responded to questions related to the content presented.
 

Lord Kelvin is reputed to have said, “If you can’t make a model of it, you do not understand it.” This maxim can be applied perfectly to the situation of searching for replacement models (i.e., models where animals are not required) in toxicology. The more we know about in vivo models used to study toxicity effects and the more we know about biological pathways and events that lead to their modulations and perturbations, the more precisely we can create reliable in vitro and in silico replacement systems to predict human toxicity. However, development of reliable and relevant replacement models is, in many cases, hindered by technical difficulties or lack of knowledge and, at later stages, by lack of scientific and regulatory willingness to accept the novel systems.

 

Major progress in development and broad acceptance of replacement models have been achieved in the area of topical toxicity. Since 2004, the Organization for Economic Cooperation and Development (OECD) Test Guidelines Program adopted three methods for skin irritation and four methods for skin corrosion testing that are based on the use of in vitro reconstructed human skin models. Reconstructed cornea models are being validated for general prediction of eye irritation, and they now are accepted by the US Environmental Protection Agency (EPA) for antimicrobial pesticides toxicity testing. This success was achieved because these in vitro systems are able to mimic with great fidelity many responses of native human tissues to toxic stimuli. However, one key problem in establishing reliable and relevant replacement models and methods is linked to the in vivo animal models used currently in regulatory toxicology. There are questions of their prediction accuracy for human responses despite acceptance of the animal models as the “gold standard” for human skin and eye toxicity. Animal models correctly predict only 40–70% of human responses depending on the toxicity endpoint. Therefore, in vitro assays calibrated against over-predictive or under-predictive in vivo animal assays may be challenged for their prediction accuracy. Ongoing scientific dialogue between the developers and users of these systems and involvement of the regulators at early stages of the validation processes makes the scientific, as well as regulatory, acceptance significantly easier.

 

A case study followed the presentation. Participants at each table took on the role of a member of an advocacy group, a government regulator, or a basic research scientist, reviewed data for a replacement test, and made a case for the validity of the new model.



출처: SOT (Society of Toxicolog) http://www.toxicology.org/education/pw/ivLectures.asp
 

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