The use of omics-based approaches in regulatory toxicology: an alternative approach to assess the no observed transcriptional effect level

Quercioli, Daniele; Roli, Andrea; Morandi, Elena; Perdichizzi, Stefania; Polacchini, Laura; Rotondo, Francesca; Vaccari, Monica; Villani, Marco; Serra, Roberto; Colacci, Annamaria

doi:10.1016/j.microc.2017.01.029

Cited by 8 publications

(6 citation statements)

References 22 publications

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“…A conservative approach is taken by groups that focus on the "No-Transcriptional-Effect-Level" (NOTEL), threshold at which no effect on the transcriptome is observed (Pisani et al 2015;Quercioli et al 2018;Zarbl et al 2010). As to be expected, the derived NOTELs were considerably lower than the "No-Observed-Adverse-Effect-Levels" (NOAELs).…”

Section: Risk Assessmentmentioning

confidence: 99%

Mode of action-based risk assessment of genotoxic carcinogens

et al. 2020

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The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B1, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs.

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Section: Risk Assessmentmentioning

confidence: 99%

Mode of action-based risk assessment of genotoxic carcinogens

et al. 2020

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“…Transformics is able to describe the entire process, anchoring the molecular machinery to the oncotransformation biological endpoint and as such can be regarded as a useful tool in the integrated testing strategy for carcinogenesis chemical hazard assessment. Gene modulation data can be used to calculate thresholds for events at the molecular level ( 54 ). In this context, transformics has the potential to improve the knowledge of dose–response relationships including providing the biological understanding to underpin statistical methods of analyzing dose–response data, such the benchmark dose approach, promoted by national and international Governmental organizations ( 55–57 ).…”

Section: Discussionmentioning

confidence: 99%

The transformics assay: first steps for the development of an integrated approach to investigate the malignant cell transformation in vitro

et al. 2018

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“…Molecular tools have been proposed as a sensitive approach capable of detecting organism-level effects very early on, with potential predictive power in determining a future deterioration of a populations fitness 6 – 9 . The advent of functional genomics technologies provides powerful tools that can be used to identify more complex molecular signatures that are predictive of toxicity 10 – 17 .…”

Section: Introductionmentioning

confidence: 99%

Modeling the metabolic profile of Mytilus edulis reveals molecular signatures linked to gonadal development, sex and environmental site

Kronberg

Byrne

Jansen

et al. 2021

Sci Rep

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The monitoring of anthropogenic chemicals in the aquatic environment including their potential effects on aquatic organisms, is important for protecting life under water, a key sustainable development goal. In parallel with monitoring the concentrations of chemicals of concern, sentinel species are often used to investigate the biological effects of contaminants. Among these, bivalve molluscs such as mussels are filter-feeding and sessile, hence an excellent model system for measuring localized pollution. This study investigates the relationship between the metabolic state of the blue mussel (Mytilus edulis) and its physiology in different environments. We developed a computational model based on a reference site (relatively unpolluted) and integrated seasonal dynamics of metabolite relative concentrations with key physiological indicators and environmental parameters. The analysis of the model revealed that changes in metabolite levels during an annual cycle are influenced by water temperature and are linked to gonadal development. This work supports the importance of data-driven biology and its potential in environmental monitoring.

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The use of omics-based approaches in regulatory toxicology: an alternative approach to assess the no observed transcriptional effect level

Cited by 8 publications

References 22 publications

Mode of action-based risk assessment of genotoxic carcinogens

Mode of action-based risk assessment of genotoxic carcinogens

The transformics assay: first steps for the development of an integrated approach to investigate the malignant cell transformation in vitro

Modeling the metabolic profile of Mytilus edulis reveals molecular signatures linked to gonadal development, sex and environmental site

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