Finding synergies for 3Rs – Toxicokinetics and read-across: Report from an EPAA partners' Forum

Laroche, Charles; Aggarwal, Manoj; Bender, Hans; Benndorf, Paul; Birk, Barbara; Crozier, Jonathan; Negro, Gianni Dal; Gaetano, Federica De; Desaintes, Christian; Gardner, Iain; Hubesch, Bruno; Irizar, Amaia; John, David; Kumar, Vikas; Lostia, Alfonso; Manou, Irene; Monshouwer, Mario; Müller, Boris; Paini, Alicia; Reid, Kirsty; Rowan, T.G.; Sachana, Magdalini; Schütte, Katrin; Stirling, Catrina; Taalman, R. D. F. M.; Aerts, Leon van; Weissenhorn, Renate; Sauer, Ursula G.

doi:10.1016/j.yrtph.2018.08.006

Cited by 32 publications

(11 citation statements)

References 68 publications

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“…The report identified cross-industry synergies in approaches, and highlighted the need to incorporate toxicokinetic information in read-across. 16 This evidences the increasing use of in silico tools across all sectors, highlighting the extensive economic and ethical contribution of this area of science.…”

Section: Applications Of In Silico Modelsmentioning

confidence: 97%

A Review of In Silico Tools as Alternatives to Animal Testing: Principles, Resources and Applications

et al. 2020

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Across the spectrum of industrial sectors, including pharmaceuticals, chemicals, personal care products, food additives and their associated regulatory agencies, there is a need to develop robust and reliable methods to reduce or replace animal testing. It is generally recognised that no single alternative method will be able to provide a one-to-one replacement for assays based on more complex toxicological endpoints. Hence, information from a combination of techniques is required. A greater understanding of the time and concentration-dependent mechanisms, underlying the interactions between chemicals and biological systems, and the sequence of events that can lead to apical effects, will help to move forward the science of reducing and replacing animal experiments. In silico modelling, in vitro assays, high-throughput screening, organ-on-a-chip technology, omics and mathematical biology, can provide complementary information to develop a complete picture of the potential response of an organism to a chemical stressor. Adverse outcome pathways (AOPs) and systems biology frameworks enable relevant information from diverse sources to be logically integrated. While individual researchers do not need to be experts across all disciplines, it is useful to have a fundamental understanding of what other areas of science have to offer, and how knowledge can be integrated with other disciplines. The purpose of this review is to provide those who are unfamiliar with predictive in silico tools, with a fundamental understanding of the underlying theory. Current applications, software, barriers to acceptance, new developments and the use of integrated approaches are all discussed, with additional resources being signposted for each of the topics.

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Section: Applications Of In Silico Modelsmentioning

confidence: 97%

A Review of In Silico Tools as Alternatives to Animal Testing: Principles, Resources and Applications

et al. 2020

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“…Within toxicology there are significant ethical and regulatory drivers for the replacement of higher organisms as the main focus for testing. In the development of 3 Rs (Replacement, Reduction, Refinement) approaches, functional 'omics techniques have already shown their potential value in screening for specific pathway effects (Laroche et al, 2018). Given knowledge of TK characteristics and an AOP, an assessment of phylogenetic conservation through comparative genomics could be used to evaluate the appropriateness of potential surrogates for use in assessing the effects of specifically acting chemicals targeting this pathway.…”

Section: Predictive Ecotoxicology For the 3 Rsmentioning

confidence: 99%

Species Sensitivity to Toxic Substances: Evolution, Ecology and Applications

Spurgeon

Lahive

Robinson

et al. 2020

Front. Environ. Sci.

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Because it is only possible to test chemicals for effects on a restricted range of species and exposure scenarios, ecotoxicologists are faced with a significant challenge of how to translate the measurements in model species into predictions of impacts for the wider range of species in ecosystems. Because of this challenge, within ecotoxicology there is no more fundamental aspect than to understand the nature of the traits that determine sensitivity. To account for the uncertainties of species extrapolations in risk assessment, “safety factors” or species sensitivity distributions are commonly used. While valuable as pragmatic tools, these approaches have no mechanistic grounding. Here we highlight how mechanistic information that is increasingly available for a range of traits can be used to understand and potentially predict species sensitivity to chemicals. We review current knowledge on how toxicokinetic, toxicodynamic, physiological, and ecological traits contribute to differences in sensitivity. We go on to discuss how this information is being used to make predictions of sensitivity using correlative and trait-based approaches, including comparisons of target receptor orthologs. Finally, we discuss how the emerging knowledge and associated tools can be used to enhance theoretical and applied ecotoxicological research through improvements in mechanistic modeling, predictive ecotoxicology, species sensitivity distribution development, mixture toxicity assessment, chemical design, biotechnology application and mechanistically informed monitoring.

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“…Advances in computational toxicology has led to different in silico tools like cheminformatics, toxicokinetics, toxicodynamics, systems biology and toxicogenomics for assessing neuronal risk in different species. Also, need for in silico approaches has been suggested by a panel of experts for alternative to experimental testing (Laroche et al 2018).…”

Section: Introductionmentioning

confidence: 99%

An integrative translational framework for chemical induced neurotoxicity – a systematic review

Deepika

Sharma

Schuhmacher

et al. 2020

Critical Reviews in Toxicology

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Many chemicals in day-to-day and industrial usage have ability to cross the blood brain barrier and develop neurotoxicity in human beings. There are numerous in vitro, in vivo, epidemiological and in silico studies developed to test the neurotoxicity of such chemicals. This systematic review summarized the endpoints and biochemical markers generated from in vitro models, organism-based models, human studies and in silico tools and how they are being used to translate the data for risk assessment of neurotoxic chemicals. With the advancement in experimental studies such as high throughput screening (e.g. proteomics, genomics), there is a huge potential of data generation related to genes and proteins facilitating deep understanding of molecular mechanisms of neurotoxicity. However, this demand a translational platform that can integrate the biological data from different studies mechanistically and thereby translated across intra and interspecies for neurotoxicity assessment. Further, this review proposed an integrative translational framework to assess the chemicals for neurotoxicity.

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Finding synergies for 3Rs – Toxicokinetics and read-across: Report from an EPAA partners' Forum

Cited by 32 publications

References 68 publications

A Review of In Silico Tools as Alternatives to Animal Testing: Principles, Resources and Applications

A Review of In Silico Tools as Alternatives to Animal Testing: Principles, Resources and Applications

Species Sensitivity to Toxic Substances: Evolution, Ecology and Applications

An integrative translational framework for chemical induced neurotoxicity – a systematic review

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