Analysis of public oral toxicity data from REACH registrations 2008-2014

Lade...
Vorschaubild
Dateien
Luechtefeld_0-365909.pdf
Luechtefeld_0-365909.pdfGröße: 2.2 MBDownloads: 305
Datum
2016
Autor:innen
Luechtefeld, Thomas
Maertens, Alexandra
Russo, Daniel P.
Zhu, Hao
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
European Union (EU): 681002
Projekt
EUToxRisk21
Open Access-Veröffentlichung
Open Access Gold
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Alternatives to Animal Experimentation : ALTEX. 2016, 33(2), pp. 111-122. ISSN 0946-7785. eISSN 1868-8551. Available under: doi: 10.14573/altex.1510054
Zusammenfassung

The European Chemicals Agency, ECHA, made available a total of 13,832 oral toxicity studies for 8,568 substances up to December 2014. 75% of studies were from the retired OECD Test Guideline 401 (11% TG 420, 11% TG 423 and 1.5% TG 425). Concordance across guidelines, evaluated by comparing LD50 values ≥ 2000 or < 2000 mg/kg body weight from chemicals tested multiple times between different guidelines, was at least 75% and for their own repetition more than 90%. In 2009, Bulgheroni et al. created a simple model for predicting acute oral toxicity using no observed adverse effect levels (NOAEL) from 28-day repeated dose toxicity studies in rats. This was reproduced here for 1,625 substances. In 2014, Taylor et al. suggested no added value of the 90-day repeated dose oral toxicity test given the availability of a low 28-day study with some constraints. We confirm that the 28-day NOAEL is predictive (albeit imperfectly) of 90-day NOAELs, however, the suggested constraints did not affect predictivity. 1,059 substances with acute oral toxicity data (268 positives, 791 negatives, all Klimisch score 1) were used for modeling: The Chemical Development Kit was used to generate 27 molecular descriptors and a similarity-informed multilayer perceptron showing 71% sensitivity and 72% specificity. Additionally, the k-nearest neighbors (KNN) algorithm indicated that similarity-based approaches alone may be poor predictors of acute oral toxicity, but can be used to inform the multilayer perceptron model, where this was the feature with highest information value.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Datensätze
Zitieren
ISO 690LUECHTEFELD, Thomas, Alexandra MAERTENS, Daniel P. RUSSO, Costanza ROVIDA, Hao ZHU, Thomas HARTUNG, 2016. Analysis of public oral toxicity data from REACH registrations 2008-2014. In: Alternatives to Animal Experimentation : ALTEX. 2016, 33(2), pp. 111-122. ISSN 0946-7785. eISSN 1868-8551. Available under: doi: 10.14573/altex.1510054
BibTex
@article{Luechtefeld2016Analy-35665,
  year={2016},
  doi={10.14573/altex.1510054},
  title={Analysis of public oral toxicity data from REACH registrations 2008-2014},
  number={2},
  volume={33},
  issn={0946-7785},
  journal={Alternatives to Animal Experimentation : ALTEX},
  pages={111--122},
  author={Luechtefeld, Thomas and Maertens, Alexandra and Russo, Daniel P. and Rovida, Costanza and Zhu, Hao and Hartung, Thomas}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/35665">
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:creator>Zhu, Hao</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-10-18T08:13:50Z</dc:date>
    <dc:contributor>Rovida, Costanza</dc:contributor>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Russo, Daniel P.</dc:creator>
    <dc:contributor>Russo, Daniel P.</dc:contributor>
    <dc:contributor>Hartung, Thomas</dc:contributor>
    <dc:creator>Luechtefeld, Thomas</dc:creator>
    <dc:contributor>Zhu, Hao</dc:contributor>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/35665"/>
    <dc:language>eng</dc:language>
    <dcterms:issued>2016</dcterms:issued>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Hartung, Thomas</dc:creator>
    <dc:contributor>Luechtefeld, Thomas</dc:contributor>
    <dcterms:title>Analysis of public oral toxicity data from REACH registrations 2008-2014</dcterms:title>
    <dc:contributor>Maertens, Alexandra</dc:contributor>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/35665/3/Luechtefeld_0-365909.pdf"/>
    <dc:creator>Maertens, Alexandra</dc:creator>
    <dc:creator>Rovida, Costanza</dc:creator>
    <dcterms:abstract xml:lang="eng">The European Chemicals Agency, ECHA, made available a total of 13,832 oral toxicity studies for 8,568 substances up to December 2014. 75% of studies were from the retired OECD Test Guideline 401 (11% TG 420, 11% TG 423 and 1.5% TG 425). Concordance across guidelines, evaluated by comparing LD50 values ≥ 2000 or &lt; 2000 mg/kg body weight from chemicals tested multiple times between different guidelines, was at least 75% and for their own repetition more than 90%. In 2009, Bulgheroni et al. created a simple model for predicting acute oral toxicity using no observed adverse effect levels (NOAEL) from 28-day repeated dose toxicity studies in rats. This was reproduced here for 1,625 substances. In 2014, Taylor et al. suggested no added value of the 90-day repeated dose oral toxicity test given the availability of a low 28-day study with some constraints. We confirm that the 28-day NOAEL is predictive (albeit imperfectly) of 90-day NOAELs, however, the suggested constraints did not affect predictivity. 1,059 substances with acute oral toxicity data (268 positives, 791 negatives, all Klimisch score 1) were used for modeling: The Chemical Development Kit was used to generate 27 molecular descriptors and a similarity-informed multilayer perceptron showing 71% sensitivity and 72% specificity. Additionally, the k-nearest neighbors (KNN) algorithm indicated that similarity-based approaches alone may be poor predictors of acute oral toxicity, but can be used to inform the multilayer perceptron model, where this was the feature with highest information value.</dcterms:abstract>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2016-10-18T08:13:50Z</dcterms:available>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/35665/3/Luechtefeld_0-365909.pdf"/>
    <dc:rights>Attribution 4.0 International</dc:rights>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen