Toxicology computational

Mekenyan OG, Dimitrov SD, Pavlov TS, Veith GD. A systematic approach to simulating metabolism in computational toxicology. I. The TIMES heuristic modelling framework. Curr Pharm Des 2004 10 1273-93. 

Although there is considerable activity in developing computational toxicology for regulatory applications, the reality for the foreseeable future is that QSARs and related techniques are not yet sophisticated enough to replace whole animal testing. 

Keywords Alternatives to animal testing, Computational toxicology, In silico, In vitro, Predictive models, QSAR models, Regulation... 

Computational toxicology in drug development. Drug Discovery Today, 13, 303-310. 

Kavlock R, Dix D (2010) Computational toxicology as implemented by the U.S. EPA providing high throughput decision support tools for screening and assessing chemical exposure, hazard and risk. J Toxicol Environ Health B Crit Rev 13(2 ) 197-217... 

Judson R, Martin M, Egeghy P, Gangwal S, Reif D, Kothiya P, Wolf M, Cathey T, Transue T, Smith D, Vail J, Frame A, Mosher S, Cohen HE, Richard A (2012) Aggregating data for computational toxicology applications, the EPA ACToR system. Mol Toxicol 13(2) 1805-1831... 

Knudsen TB, Kavlock RJ (2008) Comparative bioinformatics and computational toxicology. In Abbott B, Hansen D (eds) Developmental toxicology, vol 3, Target organ toxicology series. Taylor and Francis, New York, pp 311-360... 

ACToR - Aggregated Computational Toxicology Resource. Toxicol. Appl. Pharmacol., 233 (1), 7-13. 

U S Environmental Protection Agency. ACToR Online (Aggregated Computational Toxicology Resource), (2008) http //actor. epa.gov/actor (last accessed 19 November 2008). 

Ekins, S. (ed.) (2007) Computational Toxicology Risk Assessment for Pharamaceutical and Environmental Chemicals, John Wiley Sons, Inc., Hoboken, NJ. 

U S Environmental Protection Agency National Center for Computational ToxicologyAggregated Computational Toxicology Resrouce Database (ACToR) http //actor.epa.gov/ (last accessed 29 April 2010). 

U.S. Environmental Protection Agency National Center for Computational Toxicology... 

J. Devillers, Application of QSARs in Aquatic Toxicology, in Computational Toxicology Risk Assessment for Pharmaceutical and Environmental Chemicals, ed. by S. Ekins (Wiley, Hoboken, 2007), pp. 651-675... 

JRC, European Chemicals Bureau, Computational Toxicology Group, http //ecb.jrc.it/qsar/. Accessed May 2008... 

In the context of computational toxicology, quantum chemical descriptors provide distinct probes to unravel mechanistic causes for the hazardous effects of chemical substances. At the same time, the level of theory employed may be crucial for the molecular property under analysis, which is particularly true for descriptors based on net atomic charges (that, in turn, are not physically observable, despite their intuitive meaning for charge-controlled intermolecular interactions). 

The ATSDR use of QSAR and models to predict toxicity is well described by El-Masri et al. (2002). In 1998, the ATSDR established a computational toxicology laboratory and initiated efforts to use Physiologically Based PharmacoKinetic (PBPK) models, BenchMark Dose (BMD) models, and QSARs. PBPK models are used by the ATSDR to ... 

BMD models are used to estimate human health guidance values for environmental substances. QSARs are used to provide data estimates for chemicals that lack adequate experimental documentation. The ATSDR uses two commercial computational toxicology models to make toxicity predictions based on QSARs. To increase confidence in the models predictions, ATSDR used the models similarity search features and established a minimum threshold similarity distance value of 0.25 to increase the probability that predicted toxicity values are close to nearest analog chemicals. 

El-Masri, H.A., Mumtaz, M.M., Choudhary, G., Cibulas, W., and De Rosa, C.T., Applications of computational toxicology methods at the Agency for Toxic Substances and Disease Registry, International J. Hyg. Environ. Health, 205, 63-69, 2002. 

Lyons M, Yang RSH, Mayeno AN, Reisfeld B. 2008. Computational toxicology of chloroform reverse dosimetry using Bayesian inference, Markov chain Monte Carlo simulation, and human biomonitoring data. Environ Health Perspect 116 1040-1046. 

Reisfeld B, Mayeno AN, Lyons MA, Yang RSH. 2007. Physiologically-based pharmacokinetic and pharmacodynamic modeling, in computational toxicology. In Ekins S, editor, Risk assessment for pharmaceutical and environmental chemicals. Hoboken (NJ) John Wiley Sons, p 33-69. 

The computational toxicology software programs and models were obtained by FDA/CDER/ICSAS through cooperative research and development agreements with MDL Information Systems and Lhasa Ltd (Benz, 2007)... 

Overall, these computational toxicology models and many others developed at the US Food and Drug Administration, Center for Drug Evaluation and Research, Informatics and Computational Safety Analysis Staff (ICSAS) can predict with considerable precision the toxicological... 

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