The OSIRIS Weight of Evidence approach: ITS mutagenicity and ITS carcinogenicity

Buist, Harrie; Aldenberg, Tom; Escher, Sylvia; Entink, Rinke Klein; Kühne, Ralph; Marquart, Hans; Pauné, Eduard; Rorije, Emiel; Schüürmann, Gerrit; Kroese, Dinant

doi:10.1016/j.yrtph.2013.01.002

Cited by 17 publications

(16 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3) showed that even with the use of a recently developed ITS tool for mutagenicity [8], the mutagenic compounds were predicted as non-mutagenic and therefore not prioritised for further testing. The rat liver S9 metabolism simulator implemented in the QSAR Toolbox was used for producing potential metabolites of the 13 commonly predicted false negatives.…”

Section: Resultsmentioning

confidence: 99%

“…Particularly, problematic compounds (frequently identified as false negatives) were also studied using a recently developed ITS tool for mutagenicity [8]. The assessment was based on in silico data studies from ChemProp (http://www.ufz.de/index.php?en=6738) that includes two models for bacterial gene mutation.…”

Section: Methodsmentioning

confidence: 99%

“…The weight-of-evidence approach is used in integrated testing strategies (ITSs) that aim to evaluate the data with respect to their validity, reliability and relevance for REACH registration procedure [7]. Recently, ITS were developed including the use of (Q)SAR data to assess carcinogenicity and mutagenicity [8] which are also discussed in this MiniReview.…”

mentioning

confidence: 99%

See 2 more Smart Citations

On the Use of In Silico Tools for Prioritising Toxicity Testing of the Low‐Volume Industrial Chemicals in REACH

Rybacka

Rudén

Andersson

2014

Basic Clin Pharma Tox

View full text Add to dashboard Cite

This study was conducted to evaluate the utility of a selection of commercially and freely available non-testing tools and to analyse how REACH registrants can apply these as prioritisation tool for low-volume chemicals. The analysis was performed on a set of organic industrial chemicals and pesticides with extensive peer-reviewed risk assessment data. Analysed in silico model systems included Derek Nexus, Toxtree, QSAR Toolbox, LAZAR, TEST and VEGA, and results from these were compared with expert-judged risk classification according to the classifying, labelling and packaging (CLP) regulation. The most reliable results were obtained for carcinogenicity; however, less reliable predictions were derived for mutagenicity and reproductive toxicity. A group of compounds frequently predicted as false negatives was identified. These were relatively small molecules with low structural complexity, for example benzene derivatives with hydroxyl-, amino-or aniline-substituents. A rat liver S9 metabolite simulator was applied to illustrate the importance of considering metabolism in the risk assessment procedure. We also discuss outcome of combining predictions from multiple model systems and advise how to apply in silico tools. These models are proposed to be used to prioritise low-volume chemicals for testing within the REACH legislation, and we conclude that further guidance is needed so that industry can select and apply models in a reliable, systematic and transparent way.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

On the Use of In Silico Tools for Prioritising Toxicity Testing of the Low‐Volume Industrial Chemicals in REACH

Rybacka

Rudén

Andersson

2014

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…In silico tools are essentially computer models, able to make predictions for a non-evaluated compound based on knowledge extracted from a collection of structurally related substances with experimental toxicity data. Progressively acknowledged by regulatory bodies, in silico tools are gaining importance in toxicology not only as a first tier screening tool, but also for complementing in vivo and in vitro test results (for example, Buist et al 2013;Nendza et al 2013;Schilter et al 2014;Scholz et al 2013). Their widespread use, however, remains limited due to (1) the non-flexibility of the current regulatory framework, strictly describing the required experimental tests, (2) the oversupply of computer models while often uncertainty exists as to which model (combination) is most suitable to assess a given (type of) substance for a particular endpoint, and (3) the rather poor predictive capacity for toxicological endpoints other than Ames mutagenicity (Barber and Myatt 2016).…”

mentioning

confidence: 99%

Safeguarding human health using in silico tools?

et al. 2017

View full text Add to dashboard Cite

“…of the combined information content, taking into account methods to assess the overall level of uncertainty or level of confidence, and considering opportunities for consensus modelling. Respective computerized ITS schemes for the human endpoints skin sensitization, mutagenicity and carcinogenicity(Buist et al, 2013), repeated-dose toxicity(Tluczkiewicz et al, 2013), and for the environmental endpoints aquatic toxicity and bioconcentration are available through the free-of-charge OSIRIS webtool (OSIRIS, 2011).…”

mentioning

confidence: 99%

Perspectives for integrating human and environmental risk assessment and synergies with socio-economic analysis

Péry

Schüürmann

Ciffroy³

et al. 2013

Science of The Total Environment

View full text Add to dashboard Cite

For more than a decade, the integration of human and environmental risk assessment (RA) has become an attractive vision. At the same time, existing European regulations of chemical substances such as REACH (EC Regulation No. 1907/2006), the Plant Protection Products Regulation (EC regulation 1107/2009) and Biocide Regulation (EC Regulation 528/2012) continue to ask for sector-specific RAs, each of which have their individual information requirements regarding exposure and hazard data, and also use different methodologies for the ultimate risk quantification. In response to this difference between the vision for integration and the current scientific and regulatory practice, the present paper outlines five medium-term opportunities for integrating human and environmental RA, followed by detailed discussions of the associated major components and their state of the art. Current hazard assessment approaches are analyzed in terms of data availability and quality, and covering non-test tools, the integrated testing strategy (ITS) approach, the adverse outcome pathway (AOP) concept, methods for assessing uncertainty, and the issue of explicitly treating mixture toxicity. With respect to exposure, opportunities for integrating exposure assessment are discussed, taking into account the uncertainty, standardization and validation of exposure modeling as well as the availability of exposure data. A further focus is on ways to complement RA by a socio-economic assessment (SEA) in order to better inform about risk management options. In this way, the present analysis, developed as part of the EU FP7 project HEROIC, may contribute to paving the way for integrating, where useful and possible, human and environmental RA in a manner suitable for its coupling with SEA.

show abstract

The OSIRIS Weight of Evidence approach: ITS mutagenicity and ITS carcinogenicity

Cited by 17 publications

References 27 publications

On the Use of In Silico Tools for Prioritising Toxicity Testing of the Low‐Volume Industrial Chemicals in REACH

On the Use of In Silico Tools for Prioritising Toxicity Testing of the Low‐Volume Industrial Chemicals in REACH

Safeguarding human health using in silico tools?

Perspectives for integrating human and environmental risk assessment and synergies with socio-economic analysis

Contact Info

Product

Resources

About