Conditional Toxicity Value (CTV) Predictor: An In Silico Approach for Generating Quantitative Risk Estimates for Chemicals.

Environmental Health Perspectives
Jessica A WignallWeihsueh A Chiu

Abstract

Human health assessments synthesize human, animal, and mechanistic data to produce toxicity values that are key inputs to risk-based decision making. Traditional assessments are data-, time-, and resource-intensive, and they cannot be developed for most environmental chemicals owing to a lack of appropriate data. As recommended by the National Research Council, we propose a solution for predicting toxicity values for data-poor chemicals through development of quantitative structure-activity relationship (QSAR) models. We used a comprehensive database of chemicals with existing regulatory toxicity values from U.S. federal and state agencies to develop quantitative QSAR models. We compared QSAR-based model predictions to those based on high-throughput screening (HTS) assays. QSAR models for noncancer threshold-based values and cancer slope factors had cross-validation-based Q2 of 0.25-0.45, mean model errors of 0.70-1.11 log10 units, and applicability domains covering >80% of environmental chemicals. Toxicity values predicted from QSAR models developed in this study were more accurate and precise than those based on HTS assays or mean-based predictions. A publicly accessible web interface to make predictions for any chemical of i...Continue Reading

References

May 1, 1990·Mutation Research·C C TravisM W Yambert
Feb 23, 2002·Journal of Molecular Graphics & Modelling·Alexander Golbraikh, Alexander Tropsha
May 30, 2009·Environmental Health Perspectives·Richard JudsonEdwin Smith
Jun 25, 2010·Journal of Chemical Information and Modeling·Denis FourchesAlexander Tropsha
Mar 10, 2011·Chemical Research in Toxicology·Richard S JudsonDavid J Dix
Mar 6, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ivan RusynAlexander Tropsha
Apr 19, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Russell S ThomasMelvin E Andersen
Apr 23, 2013·Environmental Health Perspectives·Raymond R TiceJohn R Bucher
Jun 14, 2013·Environmental Science & Technology·John F WambaughElaine A Cohen Hubal
Feb 27, 2014·Environmental Health Perspectives·Jessica A WignallIvan Rusyn
Apr 15, 2014·Environmental Health Perspectives·Daniel KrewskiIla Cote
Nov 5, 2014·ALTEX·Grace PatlewiczThomas Hartung
Dec 3, 2014·Expert Opinion on Drug Metabolism & Toxicology·Vinícius Gonçalves MaltarolloKathia Maria Honorio
Dec 3, 2014·Regulatory Toxicology and Pharmacology : RTP·Sneha BhatiaAnne Marie Api
Feb 7, 2015·Regulatory Toxicology and Pharmacology : RTP·Robert JollyVijay Gombar
Apr 11, 2015·Regulatory Toxicology and Pharmacology : RTP·G PatlewiczB Hubesch
May 27, 2015·Environmental Health Perspectives·Weihsueh A Chiu, Wout Slob
Jun 19, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·John F WambaughR Woodrow Setzer
Aug 8, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Barbara A WetmoreMelvin E Andersen
Aug 15, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Richard S JudsonRussell S Thomas
Feb 20, 2016·SAR and QSAR in Environmental Research·S D DimitrovO G Mekenyan
Feb 26, 2016·Environmental Health Perspectives·Kamel MansouriRichard S Judson
Jul 12, 2010·Molecular Informatics·Alexander Tropsha
Dec 17, 2010·Molecular Informatics·Fiorella RuggiuDragos Horvath
Aug 11, 2016·Chemical Research in Toxicology·Caroline L PintoPatience Browne
Sep 23, 2016·Risk Analysis : an Official Publication of the Society for Risk Analysis·Elizabeth HolmanGeorge Gray
Sep 25, 2016·Risk Analysis : an Official Publication of the Society for Risk Analysis·Elizabeth HolmanGeorge Gray
Sep 28, 2016·Advances in Experimental Medicine and Biology·Grace PatlewiczNicholas Ball

❮ Previous
Next ❯

Citations

Mar 4, 2020·Reviews on Environmental Health·Michelle L HeacockWilliam A Suk
Sep 24, 2020·Risk Analysis : an Official Publication of the Society for Risk Analysis·Weihsueh A Chiu, Greg M Paoli
Oct 20, 2020·Risk Analysis : an Official Publication of the Society for Risk Analysis·Olivier JollietPeter Fantke
Oct 31, 2020·Environmental Health Perspectives·Xuehua LiKiwao Kadokami
Oct 30, 2020·Environment International·Nicolò AurisanoPeter Fantke
Oct 28, 2020·International Journal of Molecular Sciences·Jacob Spiegel, Hanoch Senderowitz
Dec 17, 2020·Risk Analysis : an Official Publication of the Society for Risk Analysis·Adam M Finkel, George M Gray
Feb 16, 2021·Indoor Air·Mohamed BayatiChung-Ho Lin
Feb 5, 2021·Journal of Environmental Management·Elizabeth R RogersChung-Ho Lin
Nov 20, 2020·International Journal of Hygiene and Environmental Health·Mohamed BayatiChung-Ho Lin
Sep 25, 2019·Regulatory Toxicology and Pharmacology : RTP·G HelmanI Shah
Jan 26, 2021·Environmental Toxicology and Chemistry·Hans PluggeJakub Kostal
Apr 29, 2021·Environmental Science & Technology·Gabrielle P BlackThomas M Young
Jul 1, 2021·Journal of Exposure Science & Environmental Epidemiology·Nicolò AurisanoOlivier Jolliet
Dec 24, 2021·Environmental Science & Technology·Cynthia Faye IsleyMark Patrick Taylor

❮ Previous
Next ❯

Software Mentioned

R
TOPKAT
CTV Predictor
rcdk ”
ToxTree
RepDose
CTV
Chemistry Development Kit ( CDK
OECD QSAR toolbox
JSME Molecular Editor

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.