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Applicability of QSAR analysis in dietary risk assessment

News details
Mar 11, 2011
Contact:
JRC, IHCP

In 2009-2010, the JRC carried out a project for the European Food Safety Authority (EFSA) on the applicability of QSAR analysis in the evaluation of the toxicological relevance of metabolites and degradates of pesticide active substances.

The project addressed the usefulness of different computational estimation methods, with an emphasis on Quantiative Structure-Activity Relationships (QSAR) models and expert systems. The project report describes their status in regard to human health hazard assessment and the assessment of absorption, distribution, metabolism and excretion (ADME) properties. The report also describes how QSARs and the predictions they generate should be assessed. It contains results from a survey carried out on the current use, by industry and governmental organisations, of computational methods in the assessment of chemicals in food. Finally the results of a research investigation exploring the usefulness of selected computational tools for the prediction of genotoxicity and carcinogenicity are presented. Emphasis was placed on these endpoints since they are of particular relevance when computational methods are use in the context of the Threshold of Toxicological Concern (TTC) approach. With a view to promoting computational methods in dietary risk assessment, recommendations for further work are given throughout the report. The final report is accessible from the EFSA website (JRC, 2010).

Subsequently, the JRC updated various aspects of this work, and carried out some additional research investigations, as documented in the following JRC scientific and technical reports:

  • the development of a conceptual framework for assessing the usefulness of QSAR models and expert systems, in terms of their practical applicability and the adequacy of their predictions (Worth et al., 2011);
  • a  review of computational models for acute and repeat-dose toxicity, including organ and system-specific toxicities (Lapenna et al., 2010);
  • a  review of computational models for genotoxicity and carcinogenicity (Serafimova et al., 2010);
  • a  review of computational models for developmental/reproductive toxicity, including endocrine-related effects (Lo Piparo et al., 2010);
  • a review of computational models for biokinetic properties, including oral bioavailability, human intestinal absorption, blood-brain barrier penetration, plasma protein binding, metabolism, and clearance (Mostrag-Szlichtyng & Worth, 2010a);
  • case studies on the applicability of QSARs for genotoxicity and carcinogenicity (Worth et al., 2010);
  • a case study on the in silico modelling of the microbial and human metabolism of the fungicide carbendazim (Mostrag-Szlichtyng & Worth, 2010b).

 

 

References

JRC (2010). Applicability of QSAR analysis to the evaluation of the toxicological relevance of metabolites and degradates of pesticide active substances for dietary risk assessment. Report from the European Commission’s Joint Research Centre (JRC) to the European Food Safety Authority (EFSA). Available on EFSA web site.

Lapenna S, Fuart-Gatnik M & Worth A (2010). Review of QSAR Models and Software Tools for predicting Acute and Chronic Systemic Toxicity. JRC Technical Report EUR 24639 EN. Publications Office of the European Union, Luxembourg. 

Lo Piparo E & Worth A (2010). Review of QSAR Models and Software Tools for predicting Developmental and Reproductive Toxicity. JRC Technical Report EUR 24522 EN. Publications Office of the European Union, Luxembourg.

Mostrag-Szlichtyng A & Worth A (2010a). Review of QSAR Models and Software Tools for predicting Biokinetic Properties. JRC Technical Report EUR 24377 EN. Publications Office of the European Union, Luxembourg. 

Mostrag-Szlichtyng A & Worth A (2010b). In silico modelling of microbial and human metabolism: a case study with the fungicide carbendazim. JRC Technical Report EUR 24523 EN. Publications Office of the European Union, Luxembourg.

Serafimova R, Fuart Gatnik M & Worth A (2010). Review of QSAR Models and Software Tools for predicting Genotoxicity and Carcinogenicity. JRC Technical Report EUR 24427 EN. Publications Office of the European Union, Luxembourg.

Worth A, Lapenna S, Lo Piparo E, Mostrag-Szlichtyng A & Serafimova R (2010). The Applicability of Software Tools for Genotoxicity and Carcinogenicity Prediction: Case Studies relevant to the Assessment of Pesticides. JRC Technical Report EUR 24640 EN. Publications Office of the European Union, Luxembourg.

Worth A, Lapenna S, Lo Piparo E, Mostrag-Szlichtyng A & Serafimova R (2011). A Framework for assessing in silico Toxicity Predictions: Case Studies with selected Pesticides. JRC Technical Report EUR 24705 EN. Publications Office of the European Union, Luxembourg.

Image credits
Human Sulfotransferase SULT1C2 in complex with pentachlorophenol - The image was generated by IHCP from PDB coordinates file 2GWH © RCSB Protein Data Bank (www.pdb.org).