The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing
Open accessAbstract
We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compared against regulatory exposure estimates, providing an activity-to-exposure ratio (AER) useful for a risk-based ranking strategy. As ToxCast efforts expand (ie, Phase II) beyond food-use pesticides toward a wider chemical domain that lacks exposure and toxicity information, prediction tools become increasingly important. In this study, in vitro hepatic clearance and plasma protein binding were measured to estimate OEDs for a subset of Phase II chemicals. OEDs were compared against high-throughput (HT) exposure predictions generated using probabilistic modeling and Bayesian approaches generated by the U.S. Environmental Protection Agency (EPA) ExpoCast program. This approach incorporated chemical-specific use and national production volume data with biomonitoring data to inform the exposure predictions. This HT exposure modeling approach provided predictions for all Phase II chemicals assessed in this study whereas estimates from regulatory sources were available for only 7% of chemicals. Of the 163 chemicals assessed in this study, 3 or 13 chemicals possessed AERs < 1 or < 100, respectively. Diverse bioactivities across a range of assays and concentrations were also noted across the wider chemical space surveyed. The availability of HT exposure estimation and bioactivity screening tools provides an opportunity to incorporate a risk-based strategy for use in testing prioritization.
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Cites
The Simcyp ® Population-based ADME Simulator
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“…million cells)) experimentally measured in hepatocytes to represent whole organ clearance with units of l/h: Clint ¼ Cluin vitro HPGL Vl l 106ll 60 min 1 h Where HPGL¼hepatocytes per gram liver (110 million cells/g liver; (Barter et al., 2007)) and Vl¼ liver volume (1596 g; Johnson et al., 2005).”
BackgroundMethodThe Tox21 robotic platform for the assessment of environmental chemicals – from vision to reality
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Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms
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Self-citationExenatide effects on statin pharmacokinetics and lipid response
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Cited by
Thomas, R. S., Bahadori, T., Buckley, T. J., Cowden, J., Deisenroth, C., Dionisio, K. L., Frithsen, J. B., Grulke, C. M., Gwinn, M. R., Harrill, J. A., et al. (2019) · Toxicological Sciences · doi:10.1093/toxsci/kfz058 · Cited by 373
Self-citationNyffeler, J., Willis, C., Lougee, R., Richard, A., Paul-Friedman, K., & Harrill, J. A. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.114876 · Cited by 136
Harrill, J., Shah, I., Setzer, R. W., Haggard, D., Auerbach, S., Judson, R., & Thomas, R. S. (2019) · Current Opinion in Toxicology · doi:10.1016/j.cotox.2019.05.004 · Cited by 101
Self-citationHarrill, J. A., Freudenrich, T., Wallace, K., Ball, K., Shafer, T. J., & Mundy, W. R. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.04.001 · Cited by 86
Chiu, W. A., Lynch, M. T., Lay, C. R., Antezana, A., Malek, P., Sokolinski, S., & Rogers, R. D. (2022) · Environmental Health Perspectives · doi:10.1289/ehp10103 · Cited by 57
Metadata
- Authors
- Wetmore, B. A., Wambaugh, J. F., Allen, B., Ferguson, S. S., Sochaski, M. A., Setzer, R. W., Houck, K. A., Strope, C. L., Cantwell, K., Judson, R. S., LeCluyse, E., Clewell, H. J., Thomas, R. S., & Andersen, M. E.
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-08-06
- Volume
- 148
- Issue
- 1
- Pages
- 121-136
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- OpenAlex
- W1879339955
- Cited by
- 234
- References
- 5
- FWCI
- 12.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Wetmore, B. A., Wambaugh, J. F., Allen, B., Ferguson, S. S., Sochaski, M. A., Setzer, R. W., Houck, K. A., Strope, C. L., Cantwell, K., Judson, R. S., LeCluyse, E., Clewell, H. J., Thomas, R. S., & Andersen, M. E. (2015). Incorporating High-Throughput Exposure Predictions With Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing. Toxicological Sciences. https://doi.org/10.1093/toxsci/kfv171
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