Quantitative in vitro to in vivo extrapolation for human toxicology and drug development
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arXiv
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| Natura: | Preprint |
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2024
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| author | Cattelani, Luca del Giudice, Giusy Serra, Angela Fratello, Michele Saarimäki, Laura Aliisa Fortino, Vittorio Federico, Antonio Tsiros, Periklis Mannerström, Marika Toimela, Tarja Serchi, Tommaso Lynch, Iseult Doganis, Philip Sarimveis, Haralambos Greco, Dario |
| author_facet | Cattelani, Luca del Giudice, Giusy Serra, Angela Fratello, Michele Saarimäki, Laura Aliisa Fortino, Vittorio Federico, Antonio Tsiros, Periklis Mannerström, Marika Toimela, Tarja Serchi, Tommaso Lynch, Iseult Doganis, Philip Sarimveis, Haralambos Greco, Dario |
| contents | Traditional animal testing for toxicity is expensive, time consuming, ethically questioned, sometimes inaccurate because of the necessity to extrapolate from animal to human, and in most cases not formally validated according to modern standards. This is driving regulatory bodies and companies in backing alternative methods focusing on in silico and in vitro approaches. These are complex to implement and validate, and their wide adoption is not yet established despite legal directives providing an imperative. It is difficult to link a cell level response to effects on a whole organism, but the advances in high-throughput toxicogenomics towards elucidating the mechanism of action of substances are gradually reducing this gap and fostering the adoption of Next Generation Safety Assessment approaches. Quantitative in vitro to in vivo extrapolation (QIVIVE) methods hold the promise to reveal how to use in vitro -omics data to predict the potential for in vivo toxicity. They could improve lead compounds prioritisation, reduce time and costs, also in numbers of animal lives, and help with the complexity of extrapolating between species. We provide a description of QIVIVE state of the art, including how the problems of dosing and timing are being approached, how in silico simulation can take into account the variability of individuals, and how multiple techniques can be integrated to face complex tasks like the prediction of long term toxicity, including a close look into the open problems and challenges ahead. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2401_03277 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Quantitative in vitro to in vivo extrapolation for human toxicology and drug development Cattelani, Luca del Giudice, Giusy Serra, Angela Fratello, Michele Saarimäki, Laura Aliisa Fortino, Vittorio Federico, Antonio Tsiros, Periklis Mannerström, Marika Toimela, Tarja Serchi, Tommaso Lynch, Iseult Doganis, Philip Sarimveis, Haralambos Greco, Dario Quantitative Methods Traditional animal testing for toxicity is expensive, time consuming, ethically questioned, sometimes inaccurate because of the necessity to extrapolate from animal to human, and in most cases not formally validated according to modern standards. This is driving regulatory bodies and companies in backing alternative methods focusing on in silico and in vitro approaches. These are complex to implement and validate, and their wide adoption is not yet established despite legal directives providing an imperative. It is difficult to link a cell level response to effects on a whole organism, but the advances in high-throughput toxicogenomics towards elucidating the mechanism of action of substances are gradually reducing this gap and fostering the adoption of Next Generation Safety Assessment approaches. Quantitative in vitro to in vivo extrapolation (QIVIVE) methods hold the promise to reveal how to use in vitro -omics data to predict the potential for in vivo toxicity. They could improve lead compounds prioritisation, reduce time and costs, also in numbers of animal lives, and help with the complexity of extrapolating between species. We provide a description of QIVIVE state of the art, including how the problems of dosing and timing are being approached, how in silico simulation can take into account the variability of individuals, and how multiple techniques can be integrated to face complex tasks like the prediction of long term toxicity, including a close look into the open problems and challenges ahead. |
| title | Quantitative in vitro to in vivo extrapolation for human toxicology and drug development |
| topic | Quantitative Methods |
| url | https://arxiv.org/abs/2401.03277 |