Journal ArticleDOI
Screening for low aquatic bioaccumulation. 1. Lipinski's 'Rule of 5' and molecular size.
M. Nendza,M. Müller +1 more
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TLDR
Reliable indicators based on physico-chemical properties and molecular attributes of chemicals with low bioconcentration potential have been searched to de-prioritize non-accumulative chemicals to avoid unnecessary biotests that do not produce risk-relevant information.Abstract:
Aquatic bioconcentration factors are critical in PBT assessment of industrial chemicals under REACH. Reliable indicators based on physico-chemical properties and molecular attributes of chemicals with low bioconcentration potential have been searched to de-prioritize non-accumulative chemicals in order to avoid unnecessary biotests that do not produce risk-relevant information. Developed to screen drug candidates, Lipinski's ‘Rule of 5’ identifies chemicals with poor oral absorption based on criteria in partitioning, molecular weight and hydrogen bonding. This parameter ensemble has been supplemented with molecular diameter and tested for its adequacy to filter chemicals with low bioconcentration potential. Perhaps (not) surprisingly, the application of the ‘Rule of 5’ fails to protectively identify non-accumulative compounds because other processes dominate the uptake in aquatic environments as compared with oral absorption. No robust evidence was found for cut-offs in bioconcentration related to molecul...read more
Citations
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Journal ArticleDOI
Screening for PBT Chemicals among the “Existing” and “New” Chemicals of the EU
TL;DR: Analysis of the P, B, and T data for all chemicals considered here shows that the uncertainty in persistence data contributes most to the uncertaintyIn the number of potential PBT chemicals.
Book ChapterDOI
European Centre for Ecotoxicology and Toxicology of Chemicals
TL;DR: Gribble et al. as mentioned in this paper presented a revision of the previous edition article by Michael Gribble, volume 4, pp 504-506, © 2005, Elsevier Inc.
Journal ArticleDOI
PBT assessment under REACH: Screening for low aquatic bioaccumulation with QSAR classifications based on physicochemical properties to replace BCF in vivo testing on fish
TL;DR: The BCF waiving scheme was developed with a dataset of reliable BCFs for 998 compounds and externally validated with another 181 substances, and performs with 100% sensitivity, >50% efficacy, and complies with the OECD principles for valid QSARs.
Journal ArticleDOI
Novel pyrimidine-benzimidazole hybrids with antibacterial and antifungal properties and potential inhibition of SARS-CoV-2 main protease and spike glycoprotein
TL;DR: In this article, the properties of pyrimidine-linked benzimidazole derivatives with microwave assistance were confirmed by spectral analysis, and the ability of the synthesized compounds to inhibit the main protease and spike glycoprotein inhibitory of SARS-CoV-2 was investigated by assessing their mode of binding to the allosteric site of the enzyme using molecular docking.
Journal ArticleDOI
A tiered assessment strategy for more effective evaluation of bioaccumulation of chemicals in fish.
TL;DR: To aid future evaluations of bioaccumulation data, a proposed tiered assessment strategy is presented incorporating all available data on theBioaccumulative properties of a substance, and a revised scheme is recommended for improving the classification of the bio Accumulative potential of a substances.
References
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Journal ArticleDOI
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
Journal ArticleDOI
Relationship between bioconcentration in fish and steric factors of hydrophobic chemicals
Antoon Opperhulzen,Els W.v.d. Volde,Frank A. P. C. Gobas,Djlen A.K. Liem,Jan M.D. van der Steen,Otto Hutzinger +5 more
TL;DR: In this paper, a loss of membrane permeation is suggested for hydrophobic molecules with widths over 9.5 A. is proposed, which is based on diffusion and partition processes.
Journal ArticleDOI
Revisiting bioaccumulation criteria for POPs and PBT assessments.
Frank A. P. C. Gobas,Watze de Wolf,Lawrence P. Burkhard,Eric M J Verbruggen,Kathleen P. Plotzke +4 more
TL;DR: The proposed framework for bioaccumulation screening improves current practices by reducing miscategorization, making more effective use of available bio Accumulation data that currently cannot be considered, reducing the need for animal testing, and providing simpler and cheaper test protocols for animal studies in case animal studies are necessary.
Book
Absorption and drug development
TL;DR: Absorption and drug development, Absorption, drug development and drug discovery, کتابخانه دیجیتال جندی شاپور اهواز
Journal ArticleDOI
Partitioning of Substituted Phenols in Liposome−Water, Biomembrane−Water, and Octanol−Water Systems
TL;DR: A comparison with membrane vesicles from Rhodobacter sphaeroides shows that liposomes composed of zwitterionic phosphatidylcholine are appropriate model systems for mimicking the biomembrane−water partitioning behavior of all phenol species, i.e., neutral phenol, charged phenoxide, and ion pair.
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