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

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.