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

Rybacka, Aleksandra; Rudén, Christina; Andersson, Patrik L.

doi:10.1111/bcpt.12193

Cited by 12 publications

(6 citation statements)

References 24 publications

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“…The database of European high-and low-production volume chemicals (H&LPVCs) was retrieved as described previously (Rännar and Andersson, 2010;Rybacka et al, 2014) with an additional filtering process to further refine the quality of the database and delete a number of erroneous compounds (e.g. having incorrect atom connections in SMILES structures).…”

Section: 1mentioning

confidence: 99%

Identifying potential endocrine disruptors among industrial chemicals and their metabolites – development and evaluation of in silico tools

et al. 2015

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The aim of this study was to improve the identification of endocrine disrupting chemicals (EDCs) by developing and evaluating in silico tools that predict interactions at the estrogen (E) and androgen (A) receptors, and binding to transthyretin (T). In particular, the study focuses on evaluating the use of the EAT models in combination with a metabolism simulator to study the significance of bioactivation for endocrine disruption. Balanced accuracies of the EAT models ranged from 77-87%, 62-77%, and 65-89% for E-, A-, and T-binding respectively. The developed models were applied on a set of more than 6000 commonly used industrial chemicals of which 9% were predicted E- and/or A-binders and 1% were predicted T-binders. The numbers of E- and T-binders increased 2- and 3-fold, respectively, after metabolic transformation, while the number of A-binders marginally changed. In-depth validation confirmed that several of the predicted bioactivated E- or T-binders demonstrated in vivo estrogenic activity or influenced blood levels of thyroxine in vivo. The metabolite simulator was evaluated using in vivo data from the literature which showed a 50% accuracy for studied chemicals. The study stresses, in summary, the importance of including metabolic activation in prioritization activities of potentially emerging contaminants.

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Section: 1mentioning

confidence: 99%

Identifying potential endocrine disruptors among industrial chemicals and their metabolites – development and evaluation of in silico tools

et al. 2015

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“…The handling of VEGA, amongst others, was extensively described with three example compounds [53], but for bioconcentration factor prediction, not for the prediction of sensitization. Another study evaluated Toxtree, QTB and VEGA with pesticides, but was focused on different endpoints, namely the prediction of carcinogenicity, mutagenicity and reproductive toxicity [54]. There is an extensive review about (Q)SARs [55] that includes the endpoint skin sensitization, but does not focus on pesticides or the programs used here.…”

Section: Discussion On the Applicability Of (Q)sar Programsmentioning

confidence: 99%

Evaluation and improvement of QSAR predictions of skin sensitization for pesticides

Braeuning

Braeuning²,

Mielke

et al. 2018

SAR and QSAR in Environmental Research

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In vivo skin sensitization assays have to be provided by applicants to the competent authorities in the European Union for the approval of active substances (AS) in pesticides. This study aimed to test the practicability of in silico predictions for AS by freely available (Q)SAR tools to evaluate their use as a time-and costeffective alternative to animal testing in the context of the 3R concept. Predictions of skin sensitization for 48 selected sensitizing and non-sensitizing AS by the software programs CAESAR, Toxtree, OECD (Q)SAR Toolbox, CASE Ultra, Leadscope and SciQSAR were collected and compared. Different data evaluation methodologies (score definition, mean, weighted mean, threshold score definition) were applied to optimize the predictions. The calculation methods were internally cross-validated and further validated with an additional validation set of 80 AS. Although the presented calculation methodologies are not suitable as a stand-alone method, this study has shown weaknesses and strengths of some prominent (Q)SAR programs and diverse combinatorial options in the prediction of skin sensitization by pesticidal AS. The present study will help to foster discussions on in silico alternatives to animal testing in the pesticide area.

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“…The retrieved compounds were subjected for toxicity evaluation by discovery studio and TOXTREE (by IdeaConsult Ltd. (Sofia, Bulgaria) [13].…”

Section: Analysis Of Toxicitymentioning

confidence: 99%

Computational Design of Novel Oral Insulin Conjugates for the Development of Solid Oral Insulin Dosage Forms

REDDY

2020

Asian J Pharm Clin Res

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Objective: Insulin is used to manage diabetes mellitus by subcutaneous injections regulary, that has become a part of patients life and is distressing for patients. Hence, we anticipate to get rid of the usage of subcutaneous injections completely from the medicine world and would make the diabetic people to say as “farewell to painful injections.” Methods: Virtual screening method (for selection of carriers), Toxtree tool (for toxicity evaluation of carriers), and discovery studio tool (for pharmacophore designing, absorption, distribution, metabolism, excretion, and toxicity [ADMET] analysis, designing oral insulin conjugates (OICs), and interaction studies between insulin receptor and OICs) were used for proposed study. Results: We have screened 14 competent drug delivering molecules (DDMs) from seven chemical compound databases. The ADMET and pharmacophoric properties of DDMs were analyzed by drug-informatics’ tools. Consequently, the DDMs were mono, di, and poly conjugated by covalent bonding with various binding sites of monomeric and hexameric form of human insulin and insulin-lispro (Humalog®) individually; and novel OICs were generated. Its binding efficiency and biological activity with insulin-receptor were determined. Conclusion: Inulin and Vitamin-B1 are the novel, safe, and proficient carriers for oral delivery of insulin. Insulin lispro is the remarkable option for oral delivery than other insulin forms.

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

Cited by 12 publications

References 24 publications

Identifying potential endocrine disruptors among industrial chemicals and their metabolites – development and evaluation of in silico tools

Identifying potential endocrine disruptors among industrial chemicals and their metabolites – development and evaluation of in silico tools

Evaluation and improvement of QSAR predictions of skin sensitization for pesticides

Computational Design of Novel Oral Insulin Conjugates for the Development of Solid Oral Insulin Dosage Forms

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