Publikation:
LogD-based modelling and "Delta"logD as a proxy for pH-dependent action of ionizable chemicals reveal the relevance of both neutral and ionic species for fish embryotoxicity and possess great potential for practical application in the regulation of chemicals

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dc.contributor.authorKöhler, Heinz R.
dc.contributor.authorGräff, Thomas
dc.contributor.authorSchweizer, Mona
dc.contributor.authorMaletzki, Dirk
dc.contributor.authorKühnen, Ute
dc.contributor.authorvon der Ohe, Peter C.
dc.date.accessioned2024-06-16T12:54:19Z
dc.date.available2024-06-16T12:54:19Z
dc.date.issued2023
dc.description.abstractDepending on the ambient pH, ionizable substances are present in varying proportions in their neutral or charged form. The extent to which these two chemical species contribute to the pH-dependant toxicity of ionizable chemicals and whether intracellular ion trapping has a decisive influence in this context is controversially discussed. Against this background, we determined the acute toxicity of 24 ionizable substances at up to 4 different pH values on the embryonic development of the zebrafish, Danio rerio, and supplemented this dataset with additional data from the literature. The LC50 for some substances (diclofenac, propranolol, fluoxetine) differed by a factor of even >103 between pH5 and pH9. To simulate the toxicity of 12 acids and 12 bases, six models to calculate a pH-dependant logD value as a proxy for the uptake of potentially toxic molecules were created based on different premises for the trans-membrane passage and toxic action of neutral and ionic species, and their abilities to explain the real LC50 data set were assessed. Using this approach, we were able to show that both neutral and charged species are almost certainly taken up into cells according to their logD-based distribution, and that both species exert toxicity. Since two of the models that assume all intracellular molecules to be neutral overestimated the real toxicity, it must be concluded, that the toxic effect of a single charged intracellularly present molecule is, on the average, lower than that of a single neutral molecule. Furthermore, it was possible to attribute differences in toxicity at different pH values for these 24 ionizable substances to the respective deltas in logD at these pH levels with high accuracy, enabling particularly a full logD-based model on the basis of logPow as a membrane passage descriptor to be used for predicting potential toxicities in worst-case scenarios from existing experimental studies, as stipulated in the process of registration of chemicals and the definition of Environmental Quality Standards (EQS). © 2023 The Author(s).en
dc.format.extent1 Onlineresource (21 pages)
dc.format.mediumonline resource
dc.identifier.doihttps://doi.org/10.60810/openumwelt-922
dc.identifier.urihttps://openumwelt.de/handle/123456789/2085
dc.language.isoeng
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectZebrabärbling
dc.subjectÖkotoxizität
dc.titleLogD-based modelling and "Delta"logD as a proxy for pH-dependent action of ionizable chemicals reveal the relevance of both neutral and ionic species for fish embryotoxicity and possess great potential for practical application in the regulation of chemicals
dc.typeWissenschaftlicher Artikel
dc.type.dcmitext
dc.type.mediumcomputer
dspace.entity.typePublication
local.bibliographicCitation.journalTitleWater Research
local.bibliographicCitation.originalDOI10.1016/j.watres.2023.119864
local.bibliographicCitation.volume235 (2023)
local.collectionAufsätze
local.contributor.authorId00275662
local.contributor.authorId02188821
local.contributor.authorId(DE-588)175690766
local.contributor.authorId00376548
local.contributor.authorId(DE-588)1189178478
local.identifier.catalogId02497276
local.ingest.leader07314naa a2200000uu 4500
local.jointTitleLOGDBASED MODELLING AND DELTALOGD AS A PROXY FOR PHDEPENDENT ACTION OF IONIZABLE CHEMICALS REVEAL THE RELEVANCE OF BOTH NEUTRAL AND IONIC SPECIES FOR FISH EMBRYOTOXICITY AND POSSESS GREAT POTENTIAL FOR PRACTICAL APPLICATION IN THE REGULATION OF CHEMICALS
local.reviewtrue
local.sourcecatalog
local.source.urihttp://creativecommons.org/licenses/by-nc/4.0/deed.de
local.staffPublicationtrue
relation.isAuthorOfPublicationcb196f2d-de98-4109-bdbe-129178e81921
relation.isAuthorOfPublication3ff31848-6b87-4640-b8ee-ee6f717c8251
relation.isAuthorOfPublication8a15863c-b442-48fb-ae42-6f18436acb85
relation.isAuthorOfPublication.latestForDiscoverycb196f2d-de98-4109-bdbe-129178e81921
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