QSAR-analysis and mixture toxicity as diagnostic tools: Influence of degraduation on the toxicity and mode of action of diuron in algae and daphnids

Neuwoehner, Judith, Zilberman, Tobias, Fenner, Kathrin and Escher, Beate I. (2010) QSAR-analysis and mixture toxicity as diagnostic tools: Influence of degraduation on the toxicity and mode of action of diuron in algae and daphnids. Aquatic Toxicology, 97 1: 58-67. doi:10.1016/j.aquatox.2010.08.009

Author Neuwoehner, Judith
Zilberman, Tobias
Fenner, Kathrin
Escher, Beate I.
Title QSAR-analysis and mixture toxicity as diagnostic tools: Influence of degraduation on the toxicity and mode of action of diuron in algae and daphnids
Journal name Aquatic Toxicology   Check publisher's open access policy
ISSN 0166-445X
Publication date 2010-04-01
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.aquatox.2010.08.009
Open Access Status Not Open Access
Volume 97
Issue 1
Start page 58
End page 67
Total pages 10
Editor M. J. Nikinmaa
D. Schlenk
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 030104 Immunological and Bioassay Methods
920405 Environmental Health
030404 Cheminformatics and Quantitative Structure-Activity Relationships
Abstract Even though the environmental occurrence of pesticide transformation products is well established, ecotoxicological data for transformation products are often lacking. Therefore, it remains an open question for regulators how to handle transformation products in the process of authorization and risk assessment. Transformation products may (1) possess a similar mode of toxic action as the parent compound, (2) exhibit unexpected effects towards non-target organisms or (3) contribute to overall mixture toxicity through baseline toxicity even if the specific activity of the parent compound is lost. In the present study, a systematic and integrated approach is presented to differentiate between these three options with the goal of identifying transformation products that significantly add to the risk posed by the parent compound. Quantitative structure–activity relationships (QSAR) and a toxic ratio (TR) analysis were used to evaluate the toxicity and mode of toxic action of the transformation products relative to the parent compound. In addition, mixture toxicity experiments were used as diagnostic tools to underpin the mode of action analysis and to elucidate whether the transformation products possess a similar risk potential as the parent compound. As an illustrative example, the phenylurea herbicide diuron was chosen since a sound basis of ecotoxicological data was available not only for diuron itself but also for most of its transformation products. Effects were investigated using the most sensitive species, algae, and the non-target organism Daphnia magna, for which a previous QSAR-analysis of literature data suggested a specific hazard. In the present study the primary transformation products 1-(3,4-dichlorophenyl)-3-methlyurea (DCPMU), 3-(3-chlorophenyl)-1,1-dimethylurea (MCPDMU), and 1-(3,4-dichlorophenyl)urea (DCPU) were identified as specific toxicants in algae, but as baseline toxicants in daphnids. The subsequent loss of the methylurea group during degradation, which formed 3,4-dichloroaniline, led to a clear detoxification in algae but to an increase in toxicity in daphnids. It could be shown that 3,4-dichloroaniline acted as baseline toxicant in algae, but showed a specific mode of toxic action in daphnids. Mixture toxicity experiments confirmed this mode of action analysis.
Keyword Transformation products
Baseline toxicity
Risk quotient
Toxic potential
Photosynthesis inhibition
Green algae
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 11 December 2009. Erratum publication details: Aquatic Toxicology, Volume 100, Issue 4, 15 November 2010, Page 377, Judith Neuwoehner, Tobias Zilberman, Kathrin Fenner, Beate I. Escher

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
National Research Centre for Environmental Toxicology Publications
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 27 times in Scopus Article | Citations
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Created: Sun, 07 Mar 2010, 12:30:02 EST by Professor Beate Escher on behalf of National Res Centre For Environmental Toxicology