A comparative survey of chemistry-driven in silico methods to identify hazardous substances under REACH

Nendza, Monika; Gabbert, Silke; Kühne, Ralph; Lombardo, Anna; Roncaglioni, Alessandra; Benfenati, Emilio; Benigni, Romualdo; Bossa, Cecilia; Strempel, Sebastian; Scheringer, Martin; Fernández, Alberto; Ralló, Robert; Giralt, Francesc; Dimitrov, S.; Mekenyan, Ovanes G.; Bringezu, Frank; Schüürmann, Gerrit

doi:10.1016/j.yrtph.2013.05.007

Cited by 45 publications

(10 citation statements)

References 109 publications

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“…For compounds that lacked non‐occupational health‐based exposure benchmarks (REL, RfC, or RfD) and had detection frequencies >60%, we reviewed information from online databases which aggregate information on chemical hazards from a broader set of authoritative lists, GoodGuide's ScoreCard and the Healthy Building Network's Pharos Project . We also applied QSAR models (Virtual models for property Evaluation of chemicals within a Global Architecture [VEGA]) to predict potential toxicity for mutagenicity, carcinogenicity, developmental toxicity, and skin sensitization for all compounds with good reliability scores (See SI Hazard Assessment for further details). VEGA utilizes multiple models for some health endpoints and may yield contradictory predictions.…”

Section: Methodsmentioning

confidence: 99%

VOC exposures in California early childhood education environments

et al. 2016

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Little information exists about exposures to volatile organic compounds (VOCs) in early childhood education (ECE) environments. We measured 38 VOCs in single-day air samples collected in 2010-2011 from 34 ECE facilities serving California children and evaluated potential health risks. We also examined unknown peaks in the GC/MS chromatographs for indoor samples and identified 119 of these compounds using mass spectral libraries. VOCs found in cleaning and personal care products had the highest indoor concentrations (d-limonene and decamethylcyclopentasiloxane [D5] medians: 33.1 and 51.4 μg/m³, respectively). If reflective of long-term averages, child exposures to benzene, chloroform, ethylbenzene, and naphthalene exceeded age-adjusted "safe harbor levels" based on California's Proposition 65 guidelines (10 lifetime cancer risk) in 71%, 38%, 56%, and 97% of facilities, respectively. For VOCs without health benchmarks, we used information from toxicological databases and quantitative structure-activity relationship models to assess potential health concerns and identified 12 VOCs that warrant additional evaluation, including a number of terpenes and fragrance compounds. While VOC levels in ECE facilities resemble those in school and home environments, mitigation strategies are warranted to reduce exposures. More research is needed to identify sources and health risks of many VOCs and to support outreach to improve air quality in ECE facilities.

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Section: Methodsmentioning

confidence: 99%

VOC exposures in California early childhood education environments

et al. 2016

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“…Beyond aquatic endpoints, which are out of the scope of the present paper, the OSIRIS project produced interesting results in the area of repeated-dose toxicity (Tluczkiewicz et al, 2013) and reviewes opportunities for predicting physico-chemical properties in the regulatory context (Nendza et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Integrated testing strategies (ITS) for safety assessment

Rovida

2015

ALTEX

145

128

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SummaryIntegrated testing strategies (ITS), as opposed to a single definitive test or fixed batteries of tests, are expected to efficiently combine different information sources in a quantifiable fashion to satisfy an information need, in this case for regulatory safety assessments. With increasing awareness of the limitations of each individual tool and the development of highly targeted tests and predictions, the need for combining pieces of evidence increases. The discussions that took place during this workshop, which brought together a group of experts coming from different related areas, illustrate the current state of the art of ITS, as well as promising developments and identifiable challenges. The case of skin sensitization was taken as an example to understand how possible ITS can be constructed, optimized and validated. This will require embracing and developing new concepts such as adverse outcome pathways (AOP), advanced statistical learning algorithms and machine learning, mechanistic validation and "Good ITS Practices".Keywords: in vitro methods, testing strategy, Tox21c, skin sensitization, computational toxicology this is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited. *A report of t 4 -the transatlantic think tank for toxicology, a collaboration of the toxicologically oriented chairs in Baltimore, Konstanz and Utrecht sponsored by the Doerenkamp-Zbinden Foundation; participants do not represent their institutions and do not necessarily endorse all recommendations made.

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“…The European Union has adopted a legislation named REACh [6,7] (Registration, Evaluation, Authorization, and Restriction of Chemicals) on chemical products, which is applied in the European Union since 2007. This legislation improves the regulatory framework of the European Union on chemicals and encourages the use of alternative research methods based on in vivo and in vitro tools [8,9]. Because of the large number of in vitro tests in general used, a variety of harmonized approaches are set up by REACh [10] and the OECD (Organization for the Economic Cooperation and Development) Test Guidelines [11] (TG).…”

Section: Introductionmentioning

confidence: 99%

Ames Test Prediction on High Energy Molecules by On‐The‐Fly QSAR (OTF‐QSAR)

Alliod

Chemelle

Jacob

et al. 2016

Propellants Explo Pyrotec

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In collaboration with Herakles, a research program was set up to have, in the future, optimized tools for predicting the toxicity of High Energy Molecules (HEM). Because of the number of mutagenicity tests commonly use in the society, a variety of internationally agreed testing protocols on chemicals was set up, described by REACh (Registration, Evaluation, Authorization and Restriction of Chemicals) and OECD (Organization for the Economic Cooperation and Development). The first test described for the mutagenicity is the Ames test. Several methods can be used to predict toxicity such as (Quantitative) Structure Activity Relationship [(Q)SAR] and “On‐The‐Fly” QSAR (OTF‐QSAR). The aim of this paper is to evaluate the reliability of the SAR and the OTF‐QSAR predictions in accordance with various similarities used. The goal is to obtain a good prediction tool for the Ames test. The prediction tool is compared with softwares often used in the scientific community. It was found that the OTF‐QSAR predictions were more accurate and increased the efficiency of predictions. The precision of the system increases as the degree of similarity increased. A new zone was discovered and the best similarity found and refined. At the end of the study, we validate the similarity information and the OTF‐QSAR on HEM molecules.

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A comparative survey of chemistry-driven in silico methods to identify hazardous substances under REACH

Cited by 45 publications

References 109 publications

VOC exposures in California early childhood education environments

VOC exposures in California early childhood education environments

Integrated testing strategies (ITS) for safety assessment

Ames Test Prediction on High Energy Molecules by On‐The‐Fly QSAR (OTF‐QSAR)

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