Меню
КартаВръзкиТемиБългарияНощта (K-TRIO)Мария Склодовска-КюриЗа ученициЗа учителиМетодологияИзненадай ме
H2020Докторантска мрежа2017–2021

in3 · An integrated interdisciplinary approach to animal-free chemical and nanomaterial safety assessment

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период
2017-01-01 → 2021-06-30
Финансиране от ЕС
3 860 843 €
Участници
19
Схема
MSCA-ITN-ETN

Линиите свързват координатора с партньорите.

Накратко на български

Нови методи за оценка на безопасността на химикали и наночастици се тестват чрез използването на индуцирани стволови клетки вместо опити върху гризачи. Това помага за намаляване на използването на животни и осигурява по-точни данни за човешката физиология.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

An integrated interdisciplinary approach to animal-free chemical and nanomaterial safety assessment

Chemicals and manufactured nanoparticles that we are exposed to need to be tested for their potential to cause harm. Safety evaluation of such products has been traditionally reliant on rodent based assays. While animal models are similar to human physiology in several ways, they can differ significantly in the handling of certain chemicals. Additionally, there are ethical concerns pertaining to the use of animals for safety evaluation and thus the EU is actively supporting animal alternatives via the Reduction Refinement and Replacement (3Rs) of animal use in toxicological testing strategies. Over the past decade there has been a major focus on human cells as tools for chemical safety assessment. Many cell lines however, exhibit cancerous phenotypes and thus have, by definition, an abnormal cell physiology. While primary human cells recapitulate normal cell physiology to a greater extent, it is difficult to obtain a continuous source of high-quality material or practically impossible for tissues such as the brain. In 2006, Takahashi and Yamanaka discovered a method to reprogrammed somatic cells into stem cells, termed induced Pluripotent Stem Cells (iPSC). iPSC permanently self-renew and cand be potentially differentiated into any cell type. Thus, it is now possible to generate normal non-cancerous pluripotent cells from any individual and differentiate them into target cells of interest. Modern approaches to toxicology are mechanism focused and have benefited greatly from the use of transcriptomics and related methodologies that allow unbiased experimentation high-content data covering a multitude of potential pathways. However, high-content data streams pose a problem for their application to risk assessment as specialist knowledge is often required. A potential solution is the creation of contextual frameworks of the progression of a toxic event, from its molecular initiating event (MIE), to secondary, tertiary and further downstream cascading key events (KEs), leading eventually to a pathology or adverse outcome. This concept of Adverse Outcome Pathways (AOP) is gaining momentum as a pragmatic method to enable the application of deeply mechanistic data to chemical risk assessment steered by the OECD and the EU regulatory agencies. The in3 project aimed to build on previous knowledge and activities by focusing to mechanistic studies using iPSC, linking exposure to hazard, creating biokinetic models and integrating in vitro data with in silico tools.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

All chemicals whether they are drugs, cosmetics, agrochemicals or others need to be tested for their safety to man and the environment. The use of whole animal studies for the prediction of adverse effects in man, is problematic due to species dependent effects, high costs and a large burden to animals in terms of numbers and suffering. While there have been major improvements in human in vitro and in silico techniques, there is still a lack of an integrated risk assessment platform. The in3 proposal aims to significantly further the development of animal-free chemical and nanomaterial (NM) safety evaluation by creating a scientific and training program aimed at integrating human in vitro testing with computational approaches. The project will focus on human induced pluripotent stem cells (hiPSC) derived tissues, including liver, kidney, brain, lung and vasculature and to utilise mechanistic toxicology, quantitative adverse outcome pathways, biokinetics, cheminformatics and modelling approaches to derive testable prediction models. hiPSC present the major advantages provide non-cancerous derived tissues with identical genetic backgrounds. All Early Stage Researchers (ESRs) will work towards the same goal, utilising the same chemicals, donor cells, assays and software packages. All data will be centrally housed in standardised formats, appropriately annotated and linked with protocols and material information. While ESRs will hone their skills in their own field of expertise, they will also collaborate to create an in depth safety evaluation testing platform for the chosen test compounds. By interaction, problem solving, training and secondments over the three years, they will acquire a unique set of interdisciplinary skills for chemical and NM safety assessment. The project aims to accelerate the realisation of animal-free safety assessment and to graduate 15 PhD students with the ideal skill sets to carry out the strategy designed in in3 in the near future.

Оригинален текст от CORDIS (на английски).

Участници

Връзки

Данни: CORDIS, © Европейски съюз