Predicting Potential Human Health Risk with the Tox21 10k Library
This study represents the first report applying IVIVE approaches and exposure comparisons using the entirety of the Tox21 federal collaboration chemical screening data, incorporating assay response efficacy and quality of concentration-response fits, and providing quantitative anchoring to first address the likelihood of human in vivo interactions with Tox21 compounds. This likelihood was assessed using a maximum blood concentration to in vitro response ratio approach (Cmax/AC50), analogous to decision-making methods for clinical drug-drug interactions. Fraction unbound in plasma (fup) and intrinsic hepatic clearance (CLint) parameters were estimated in silico and incorporated in a 3-compartment toxicokinetic (TK) model to first predict Cmax for in vivo corroboration using therapeutic scenarios.
This dataset is associated with the following publication:
Sipes, N., J. Wambaugh, R. Pearce, S. Auerbach, B. Wetmore, J. Hsieh, A. Shapiro, D. Sboboda, M. DeVito, and S. Ferguson. (ENVIRONMENTAL SCIENCE and TECHNOLOGY) An Intuitive Approach for Predicting Human Risk with the Tox21 10k Library. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, issue}: 10786-10796, (2017).
Complete Metadata
| accessLevel | public |
|---|---|
| bureauCode |
[
"020:00"
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|
| contactPoint |
{
"fn": "John Wambaugh",
"hasEmail": "mailto:wambaugh.john@epa.gov"
}
|
| description | This study represents the first report applying IVIVE approaches and exposure comparisons using the entirety of the Tox21 federal collaboration chemical screening data, incorporating assay response efficacy and quality of concentration-response fits, and providing quantitative anchoring to first address the likelihood of human in vivo interactions with Tox21 compounds. This likelihood was assessed using a maximum blood concentration to in vitro response ratio approach (Cmax/AC50), analogous to decision-making methods for clinical drug-drug interactions. Fraction unbound in plasma (fup) and intrinsic hepatic clearance (CLint) parameters were estimated in silico and incorporated in a 3-compartment toxicokinetic (TK) model to first predict Cmax for in vivo corroboration using therapeutic scenarios. This dataset is associated with the following publication: Sipes, N., J. Wambaugh, R. Pearce, S. Auerbach, B. Wetmore, J. Hsieh, A. Shapiro, D. Sboboda, M. DeVito, and S. Ferguson. (ENVIRONMENTAL SCIENCE and TECHNOLOGY) An Intuitive Approach for Predicting Human Risk with the Tox21 10k Library. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, issue}: 10786-10796, (2017). |
| distribution |
[
{
"title": "https://ntp.niehs.nih.gov/sandbox/ivive/",
"accessURL": "https://ntp.niehs.nih.gov/sandbox/ivive/"
},
{
"title": "Supporting Information_EST_FINAL_18JUL2017.pdf",
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"downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1395143/Supporting%20Information_EST_FINAL_18JUL2017.pdf"
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"title": "Table S1.xlsx",
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"downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1395143/Table%20S1.xlsx"
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|
| identifier | https://doi.org/10.23719/1395143 |
| keyword |
[
"ExpoCast",
"HTS",
"High throughput screening",
"IVIVE",
"Tox21",
"exposure",
"high throughput toxicokinetics",
"httk",
"in vitro to in vivo extrapolation (IVIVE)"
]
|
| license | https://pasteur.epa.gov/license/sciencehub-license.html |
| modified | 2017-07-19 |
| programCode |
[
"020:095"
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|
| publisher |
{
"name": "U.S. EPA Office of Research and Development (ORD)",
"subOrganizationOf": {
"name": "U.S. Environmental Protection Agency",
"subOrganizationOf": {
"name": "U.S. Government"
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|
| references |
[
"https://doi.org/10.1021/acs.est.7b00650",
"https://ntp.niehs.nih.gov/sandbox/ivive/"
]
|
| rights |
null
|
| title | Predicting Potential Human Health Risk with the Tox21 10k Library |
