Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

Kleinstreuer, Nicole; Smith, Alan M.; West, Paul R.; Conard, Kevin R.; Fontaine, Burr R.; Weir-Hauptman, A.; Palmer, Jessica; Knudsen, Thomas B.; Dix, David J.; Donley, Elizabeth L.R.; Cezar, Gabriela G.

doi:10.1016/j.taap.2011.08.025

Cited by 92 publications

(50 citation statements)

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“…Latest studies from ToxCast have demonstrated the feasibility of predictive modeling of fertility, blood vessel development, and prenatal developmental toxicity (Sipes et al, 2011a). Angiogenesis can be considered an example, as cell-agent based models (ABMs) for angiogenesis have been developed that recapitulate HTS data at a histological scale (Kleinstreuer et al, 2011). In this regard, (Q)SARs may become more informed as we train these read-across methods with information from HTS data and cellular ABMs.…”

Section: In Silico Approachesmentioning

confidence: 99%

“…In vitro work so far has combined mainly whole embryo culture and transcriptomics (Luijten et al, 2010) or the EST with metabolomics (Kleinstreuer et al, 2011;West et al, 2010), proteomics (Groebe et al, 2010;Klemm et al, 2008;Klemm and Schrattenholz, 2004;Seiler and Spielmann, 2011) or transcriptomics, as summarized recently (van Dartel and Piersma, 2011). These approaches use patterns or biomarkers derived from a training set of substances to identify substances with similar mode of action.…”

Section: Information-rich Single Testsmentioning

confidence: 99%

“…General Similar efforts should be extended for the (favorably human) EST (Kleinstreuer et al, 2011;West et al, 2010). The obvious potential of combing stem cell methods with Tox-21c approaches was stressed earlier (Chapin and Stedman, 2009).…”

Section: Pathways Of Toxicity (Pot) and Systems Toxicologymentioning

confidence: 99%

See 2 more Smart Citations

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

203

165

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Section: In Silico Approachesmentioning

confidence: 99%

Section: Information-rich Single Testsmentioning

confidence: 99%

See 1 more Smart Citation

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

203

165

View full text Add to dashboard Cite

“…Another solution to both of these issues is to develop and employ more complex, cellular and multi-scale, biologically based models that incorporate information and knowledge of the structure of the biological pathways being altered that include pharmacokinetic information and that explicitly include multiple levels of biological organization [9,26,27,[50][51][52][53]. This is the driver of our virtual tissue modelling research (http://www.epa.gov/ncct/v-Embryo/ http://www.epa.gov/ncct/ virtual_liver/).…”

Section: Discussionmentioning

confidence: 99%

In Vitro and Modelling Approaches to Risk Assessment from the U.S. Environmental Protection Agency ToxCast Programme

Judson

Houck

Martin

et al. 2014

Basic Clin Pharma Tox

128

101

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A significant challenge in toxicology is the 'too many chemicals' problem. Human beings and environmental species are exposed to tens of thousands of chemicals, only a small percentage of which have been tested thoroughly using standard in vivo test methods. This study reviews several approaches that are being developed to deal with this problem by the U.S. Environmental Protection Agency, under the umbrella of the ToxCast programme (http://epa.gov/ncct/toxcast/). The overall approach is broken into seven tasks: (i) identifying biological pathways that, when perturbed, can lead to toxicity; (ii) developing highthroughput in vitro assays to test chemical perturbations of these pathways; (iii) identifying the universe of chemicals with likely human or ecological exposure; (iv) testing as many of these chemicals as possible in the relevant in vitro assays; (v) developing hazard models that take the results of these tests and identify chemicals as being potential toxicants; (vi) generating toxicokinetics data on these chemicals to predict the doses at which these hazard pathways would be activated; and (vii) developing exposure models to identify chemicals for which these hazardous dose levels could be achieved. This overall strategy is described and briefly illustrated with recent examples from the ToxCast programme.

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“…the integrapected from this approach, especially applications in human stem cells. these are seen as highly promising, as they could provide insight into human toxicity pathways (Kleinstreuer et al, 2011).…”

Section: Metabolomicsmentioning

confidence: 99%

Systems toxicology

Härtung

2012

ALTEX

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Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

Cited by 92 publications

References 50 publications

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

In Vitro and Modelling Approaches to Risk Assessment from the U.S. Environmental Protection Agency ToxCast Programme

Systems toxicology

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