Metabolomics: A tool for early detection of toxicological effects and an opportunity for biology based grouping of chemicals—From QSAR to QBAR

Ravenzwaay, Bennard van; Herold, Michael; Kamp, Hennicke; Kapp, Michaela; Fabian, Eric; Looser, Ralf; Krennrich, G.; Mellert, W.; Prokoudine, A.; Strauss, Volker; Walk, T.; Wiemer, J.

doi:10.1016/j.mrgentox.2012.01.006

Cited by 96 publications

(60 citation statements)

References 23 publications

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“…The method resulted in 225 semi-quantitative analytes, 171 of which are chemically identified and 54 are structurally unknown. Analysis of the recorded metabolite profiles was performed making use of the MetaMap ® Tox database (van Ravenzwaay et al 2012a; cf. Information box MetaMap ® Tox methodology).…”

Section: Methodsmentioning

confidence: 99%

“…Metabolomic investigations have been established as useful tools to recognize early toxicological effects, already at stages preceding clinically observable findings. Metabolite level changes can be interpreted biochemically and by comparing alterations with those of about 500 reference compounds in the MetaMap ® Tox database, thereby revealing possible toxicological modes of action (MoAs, i.e., the specific biochemical interactions through which a substance produces its influence on key processes in living organisms; van Ravenzwaay et al 2007, 2010a, b, 2012a, b; ECETOC 2010; Kamp et al 2010). Since changes are detectable in body fluids, such as urine and plasma, metabolomics have the potential to reduce and refine animal testing.…”

Section: Introductionmentioning

confidence: 99%

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Effects of SiO2, ZrO2, and BaSO4 nanomaterials with or without surface functionalization upon 28-day oral exposure to rats

Buesen

Landsiedel

Sauer³

et al. 2014

Arch Toxicol

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The effects of seven nanomaterials (four amorphous silicon dioxides with or without surface functionalization, two surface-functionalized zirconium dioxides, and barium sulfate) upon 28-day oral exposure to male or female rats were investigated. The studies were performed as limit tests in accordance with OECD Test Guideline 407 applying 1,000 mg test substance/kg body weight/day. Additionally, the acute phase proteins haptoglobin and α2-macroglobulin as well as cardiac troponin I were determined, and metabolome analysis was performed in plasma samples. There were no test substance-related adverse effects for any of the seven nanomaterials. Moreover, metabolomics changes were below the threshold of effects. Since test substance organ burden was not analyzed, it was not possible to establish whether the lack of findings related to the absence of systemic exposure of the tested nanomaterials or if the substances are devoid of any potential for toxicity. The few published subacute oral or short-term inhalation studies investigating comparable nanomaterials (SiO2, ZrO2, and BaSO4) also do not report the occurrence of pronounced treatment-related findings. Overall, the results of the present survey provide a first indication that the tested nanomaterials neither cause local nor systemic effects upon subacute oral administration under the selected experimental conditions. Further investigations should aim at elucidating the extent of gastrointestinal absorption of surface-functionalized nanomaterials. Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-014-1337-0) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of SiO2, ZrO2, and BaSO4 nanomaterials with or without surface functionalization upon 28-day oral exposure to rats

Buesen

Landsiedel

Sauer³

et al. 2014

Arch Toxicol

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“…the metabolomics approach suggests toxicological modes of action at a relatively early timepoint (within 7 days) and can, thereby, facilitate safety decisions and lower costs through a reduced need for animal studies. the use of such omics tools to enhance the quality of read-across has been discussed by van Ravenzwaay et al (2012) (from QSAR to QBAR (quantitative biological activity relationships). An example of such biology based approaches can be seen by comparing the metabolome of di(2-ethyl-hexyl)phthalate and that of dibutylphthalate.…”

Section: The Concept Of Local Validitymentioning

confidence: 99%

Read-across approaches - misconceptions, promises and challenges ahead

Patlewicz

2014

ALTEX

109

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Summary Read-across is a data gap filling technique used within category and analogue approaches. It has been utilized as an alternative approach to address information requirements under various past and present regulatory programs such as the OECD High Production Volume Programme as well as the EU's Registration, Evaluation, Authorisation and restriction of CHemicals (REACH) regulation. Although read-across raises a number of expectations, many misconceptions still remain around what it truly represents; how to address its associated justification in a robust and scientifically credible manner; what challenges/issues exist in terms of its application and acceptance; and what future efforts are needed to resolve them. In terms of future enhancements, read-across is likely to embrace more biologicallyorientated approaches consistent with the Toxicity in the 21 st Century vision (Tox-21c). This Food forThought article, which is notably not a consensus report, aims to discuss a number of these aspects and, in doing so, to raise awareness of the ongoing efforts and activities to enhance read-across. It also intends to set the agenda for a CAAT read-across initiative in 2014CAAT read-across initiative in -2015 to facilitate the proper use of this technique.

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“…Transient perturbations to the transcriptome or proteome that occur in response to environmental exposures may be magnified at the level of the metabolome, making metabolomics a promising methodology for characterizing the molecular changes induced by xenobiotics and identifying new biomarkers of effect (29, 33–34). Among “omics” methodologies, metabolomics interrogates the levels of a relatively lower number of features and thus has strong statistical power compared to genome-wide and transcriptome-wide studies (35). Metabolomics is therefore a potentially sensitive method for identifying biochemical effects of external stressors.…”

Section: Exposomics and Metabolomicsmentioning

confidence: 99%

Future of environmental research in the age of epigenomics and exposomics

Holland¹

2017

Reviews on Environmental Health

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Abstract Environmental research and public health in the 21st century face serious challenges such as increased air pollution and global warming, widespread use of potentially harmful chemicals including pesticides, plasticizers, and other endocrine disruptors, and radical changes in nutrition and lifestyle typical of modern societies. In particular, exposure to environmental and occupational toxicants may contribute to the occurrence of adverse birth outcomes, neurodevelopmental deficits, and increased risk of cancer and other multifactorial diseases such as diabetes and asthma. Rapidly evolving methodologies of exposure assessment and the conceptual framework of the Exposome, first introduced in 2005, are new frontiers of environmental research. Metabolomics and adductomics provide remarkable opportunities for a better understanding of exposure and prediction of potential adverse health outcomes. Metabolomics, the study of metabolism at whole-body level, involves assessment of the total repertoire of small molecules present in a biological sample, shedding light on interactions between gene expression, protein expression, and the environment. Advances in genomics, transcriptomics, and epigenomics are generating multidimensional structures of biomarkers of effect and susceptibility, increasingly important for the understanding of molecular mechanisms and the emergence of personalized medicine. Epigenetic mechanisms, particularly DNA methylation and miRNA expression, attract increasing attention as potential links between the genetic and environmental determinants of health and disease. Unlike genetics, epigenetic mechanisms could be reversible and an understanding of their role may lead to better protection of susceptible populations and improved public health.

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Metabolomics: A tool for early detection of toxicological effects and an opportunity for biology based grouping of chemicals—From QSAR to QBAR

Cited by 96 publications

References 23 publications

Effects of SiO2, ZrO2, and BaSO4 nanomaterials with or without surface functionalization upon 28-day oral exposure to rats

Effects of SiO2, ZrO2, and BaSO4 nanomaterials with or without surface functionalization upon 28-day oral exposure to rats

Read-across approaches - misconceptions, promises and challenges ahead

Future of environmental research in the age of epigenomics and exposomics

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