ArticleComputational toxicology (Amsterdam, Netherlands)2018
Utilizing Threshold of Toxicological Concern (TTC) with High Throughput Exposure Predictions (HTE) as a Risk-Based Prioritization Approach for thousands of chemicals.
Article in Computational toxicology (Amsterdam, Netherlands), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Safety assessment scheme for menstrual cups and application for the evaluation of a menstrual cup comprised of medical grade silicone.EBioMedicine · 2022Trial
- Integrative Assessment ofInternational journal of molecular sciences · 2025Article
- Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!Journal of toxicology and environmental health. Part B, Critical reviews · 2025Review
- Systematic Approaches for the Encoding of Chemical Groups: A Case Study.Chemical research in toxicology · 2024Article
- Online and Offline Prioritization of Chemicals of Interest in Suspect Screening and Non-targeted Screening with High-Resolution Mass Spectrometry.Analytical chemistry · 2024Review
- Workshop report: Challenges faced in developing inhalation thresholds of Toxicological Concern (TTC) - State of the science and next steps.Regulatory toxicology and pharmacology : RTP · 2023Article
- Cultured Meat Safety Research Priorities: Regulatory and Governmental Perspectives.Foods (Basel, Switzerland) · 2023Article
- Evaluating the utility of the Threshold of Toxicological Concern (TTC) and its exclusions in the biocompatibility assessment of extractable chemical substances from medical devices.Computational toxicology (Amsterdam, Netherlands) · 2022Article
- Developing an internal threshold of toxicological concern (iTTC).Journal of exposure science & environmental epidemiology · 2022Article
- Exposure forecasting - ExpoCast - for data-poor chemicals in commerce and the environment.Journal of exposure science & environmental epidemiology · 2022Review
- Considerations for Improving Metabolism Predictions forFrontiers in toxicology · 2022Review
- Estimating provisional margins of exposure for data-poor chemicals using high-throughput computational methods.Frontiers in pharmacology · 2022Article
- Implementing in vitro bioactivity data to modernize priority setting of chemical inventories.ALTEX · 2022Article
- Development and Evaluation of a Holistic and Mechanistic Modeling Framework for Chemical Emissions, Fate, Exposure, and Risk.Environmental health perspectives · 2021Article
- Evaluation of Existing QSAR Models and Structural Alerts and Development of New Ensemble Models for Genotoxicity Using a Newly Compiled Experimental Dataset.Computational toxicology (Amsterdam, Netherlands) · 2021Article
- Ecological Thresholds of Toxicological Concern: A Review.Frontiers in toxicology · 2021Review
- Internal Threshold of Toxicological Concern (iTTC): Where We Are Today and What Is Possible in the Near Future.Frontiers in toxicology · 2020Article
- Derivation of New Threshold of Toxicological Concern Values for Exposure via Inhalation for Environmentally-Relevant Chemicals.Frontiers in toxicology · 2020Article
- Evaluating potential refinements to existing Threshold of Toxicological Concern (TTC) values for environmentally-relevant compounds.Regulatory toxicology and pharmacology : RTP · 2019Article
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Authors and funding
5 authors.
Funding
Abstract
Regulatory agencies across the world are facing the challenge of performing risk-based prioritization of thousands of chemicals in commerce. Here, we present an approach using the Threshold of Toxicological Concern (TTC) combined with heuristic high-throughput exposure (HTE) modelling to rank order chemicals for further evaluation. Accordingly, for risk-based prioritization, chemicals with exposures > TTC would be ranked as higher priority for further evaluation whereas substances with exposures < TTC would be ranked as lower priority. An initial proof of concept, using a dataset of 7986 substances with previously modeled median and upper 95% credible interval (UCI) total daily median exposure rates showed fewer than 5% of substances had UCI exposures > the Cramer Class III TTC (1.5 μg/kg-day). We extended the analysis by profiling the same dataset through the TTC workflow published by Kroes et al (2004) which accounts for known exclusions to the TTC as well as structural alerts. UCI exposures were then compared to the appropriate class-specific TTC. None of the substances categorized as Cramer Class I or Cramer Class II exceeded their respective TTC values and no more than 2% of substances categorized as Cramer Class III or acetylcholinesterase inhibitors exceeded their respective TTC values. The modeled UCI exposures for the majority of the 1853 chemicals with genotoxicity structural alerts did exceed the TTC of 0.0025 μg/kg-day, but only 79 substances exceeded this TTC if median exposure values were used. For substances for which UCI exposures exceeded relevant TTC values, we highlight possible approaches for consideration to refine the HTE : TTC approach. Overall, coupling TTC with HTE offers promise as a pragmatic first step in ranking substances as part of a risk-based prioritization approach.
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