Assessment and Validation of US EPA's OncoLogic® Expert System and Analysis of Its Modulating Factors for Structural Alerts

Benigni, Romualdo; Bossa, Cecilia; Alivernini, Silvia; Colafranceschi, Mauro

doi:10.1080/10590501.2012.681486

Cited by 15 publications

(8 citation statements)

References 13 publications

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“…Structural alerts (SA), like an expert system, can help identify key substructures to certain toxicity and avoid potential toxic compounds in very early stages. It has been widely applied not only in drug discovery, , but also in other fields such as cosmetic research and environmental protection …”

Section: Introductionmentioning

confidence: 99%

Evaluation of Different Methods for Identification of Structural Alerts Using Chemical Ames Mutagenicity Data Set as a Benchmark

Yang

et al. 2017

Chem. Res. Toxicol.

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Identification of structural alerts for toxicity is useful in drug discovery and other fields such as environmental protection. With structural alerts, researchers can quickly identify potential toxic compounds and learn how to modify them. Hence, it is important to determine structural alerts from a large number of compounds quickly and accurately. There are already many methods reported for identification of structural alerts. However, how to evaluate those methods is a problem. In this paper, we tried to evaluate four of the methods for monosubstructure identification with three indices including accuracy rate, coverage rate, and information gain to compare their advantages and disadvantages. The Kazius' Ames mutagenicity data set was used as the benchmark, and the four methods were MoSS (graph-based), SARpy (fragment-based), and two fingerprint-based methods including Bioalerts and the fingerprint (FP) method we previously used. The results showed that Bioalerts and FP could detect key substructures with high accuracy and coverage rates because they allowed unclosed rings and wildcard atom or bond types. However, they also resulted in redundancy so that their predictive performance was not as good as that of SARpy. SARpy was competitive in predictive performance in both training set and external validation set. These results might be helpful for users to select appropriate methods and further development of methods for identification of structural alerts.

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Section: Introductionmentioning

confidence: 99%

Evaluation of Different Methods for Identification of Structural Alerts Using Chemical Ames Mutagenicity Data Set as a Benchmark

Yang

et al. 2017

Chem. Res. Toxicol.

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“…OncoLogic has been freely available for use by the general public for over 10 years (http://www.epa.gov/oppt/sf/pubs/oncologic.htm). Two recent external validation studies (Mayer et al, 2008;Benigni et al, 2012a) showed >90% accuracy for the two batches of substances tested. However, application of the System is limited to fibers, metals, polymers and 50 classes of organic substances and not all substituents are covered.…”

Section: Chemical / Structural Class Approachmentioning

confidence: 88%

Report of the Workshop on a Framework for the Development and Use Of Integrated Approaches to Testing and Assessment

2017

OECD Series on Testing and Assessment

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“…No relevant structural alerts for genotoxicity were identified with the exception of the alert namely 'H-acceptor-path3-H-acceptor' detected by the profiler 'Structure Alerts for the in vivo micronucleus assay' The 'H-acceptor-path3-H-acceptor' refers to the possibility of non-covalent binding to DNA or proteins as a result of the presence of two bonded atoms connecting two hydrogen bond acceptors. However, the Panel noted that the positive predictivity of such alerts for in vivo genotoxicity was quite low, ranging from 'none' (34%) to 63% depending on the database, with a high incidence of false positives (Benigni et al, 2010(Benigni et al, , 2012.…”

Section: In Silicomentioning

confidence: 99%

Re‐evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a) as food additives

Younes¹,

Aggett²,

Aguilar³

et al. 2018

EFS2

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The present opinion deals with the re-evaluation of the safety of food-grade carrageenan (E 407) and processes Eucheuma seaweed (E 407a) used as food additives. Because of the structural similarities, the Panel concluded that processed Eucheuma seaweed can be included in the evaluation of food-grade carrageenan. Poligeenan (average molecular weight 10-20 kDa) has not been authorised as a food additive and is not used in any food applications. In its evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a), the Panel noted that the ADME database was sufficient to conclude that carrageenan was not absorbed intact; in a subchronic toxicity study performed with carrageenan almost complying with the EU specification for E 407 in rats, the no-observed-adverse-effect level (NOAEL) was 3,400-3,900 mg/kg body weight (bw) per day, the highest dose tested; no adverse effects have been detected in chronic toxicity studies with carrageenan in rats up to 7,500 mg/kg bw per day, the highest dose tested; there was no concern with respect to the carcinogenicity of carrageenan; carrageenan and processed Eucheuma seaweed did not raise a concern with respect to genotoxicity; the NOAEL of sodium and calcium carrageenan for prenatal developmental dietary toxicity studies were the highest dose tested; the safety of processed Eucheuma seaweed was sufficiently covered by the toxicological evaluation of carrageenan; data were adequate for a refined exposure assessment for 41 out of 79 food categories. However, the Panel noted uncertainties as regards the chemistry, the exposure assessment and biological and toxicological data. Overall, taking into account the lack of adequate data to address these uncertainties, the Panel concluded that the existing group acceptable daily intake (ADI) for carrageenan (E 407) and processed Eucheuma seaweed (E 407a) of 75 mg/kg bw per day should be considered temporary, while the database should be improved within 5 years after publication of this opinion.

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Assessment and Validation of US EPA's OncoLogic® Expert System and Analysis of Its Modulating Factors for Structural Alerts

Cited by 15 publications

References 13 publications

Evaluation of Different Methods for Identification of Structural Alerts Using Chemical Ames Mutagenicity Data Set as a Benchmark

Evaluation of Different Methods for Identification of Structural Alerts Using Chemical Ames Mutagenicity Data Set as a Benchmark

Report of the Workshop on a Framework for the Development and Use Of Integrated Approaches to Testing and Assessment

Re‐evaluation of carrageenan (E 407) and processed Eucheuma seaweed (E 407a) as food additives

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