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Is there synergistic interaction between fungicides inhibiting different enzymes in the ergosterol biosynthesis pathway in toxicity tests with the green alga Raphidocelis subcapitata?
(2018) Coors, Anja; Vollmar, Pia; Kehrer, Anja; Sacher, Frank
Products used for plant protection or as biocides often contain more than one active substance together with numerous formulation additives. The environmental risk assessment for such commercial mixtures applies as default the concept of concentration addition. There is remaining regulatory concern, however, that underestimation of risks can occur if components in the mixture interact synergistically, i.e., elicit effects greater than those predicted by concentration addition. While cases of true synergism appear to be rare, the combination of substances targeting different steps in the same biosynthesis pathway was pointed out as one potential case of synergistic interaction although mechanistic explanations are lacking. The present study aimed to verify this hypothesis using the green alga Raphidocelis subcapitata as the regulatory standard test organism for which such synergism had been indicated earlier. Algal growth inhibition tests were conducted with mixtures of ergosterol biosynthesis inhibitors (tebuconazole, fenpropidin, and fenpropimorph). The fungicides were first tested individually to derive reliable data for a mixture toxicity prediction. The here determined toxicity estimates for two of the fungicides were considerably lower than the endpoints in the regulatory dossiers, which had been used for earlier mixture toxicity predictions. Experimentally observed toxicity estimates for the mixtures deviated <2.6-fold from the predicted values. Hence, the hypothesis of synergistic interaction between fungicides targeting different enzymes in the ergosterol biosynthesis was clearly not confirmed for the green alga R. subcapitata. Overall, the present study demonstrates the importance of reliable and correct input data for mixture toxicity predictions in order to avoid erroneous conclusions on non-additive (synergistic) interactions. © Springer Science+Business Media, LLC, part of Springer Nature 2018
Photolysis of mixtures of UV filters octocrylene and ethylhexyl methoxycinnamate leads to formation of mixed transformation products and different kinetics
(2019) Schneider, Franziska; Jentzsch, Franziska; Reich, M.; Kümmerer, K.
The treatment with ultraviolet (UV) light is a well-known technique for water disinfection. Photodegradation by UV light is in discussion as measure for advanced water treatment that could provide a potential removal option for micropollutants. Micropollutants such as ingredients from personal care products are also present in grey water. Grey water gets increasingly attention as a source for water reuse. For that purpose it has to be treated. UV-treatment is an option. However, the knowledge on the fate of micropollutants within such a treatment is little. Therefore, we investigated the fate of the UV filters ethylhexyl methoxycinnamate (EHMC), and octocrylene (OCR) as for both UV filters the presence in grey water was reported. OCR as a single compound was investigated with regard to its degradation kinetics and possible photo-transformation products (photo-TPs). These results were compared with those of EHMC previously reported in literature. The mixture of the two UV filters was also investigated to reveal if mixture effects occur regarding the elimination of the UV filters and the formation of TPs. A medium pressure mercury vapor lamp (200-400 nm) was employed for photolysis. This study shows that OCR itself was eliminated below the limit of detection after 256 min and that photo-TPs were formed. The photolysis of the mixture demonstrated alterations of the degradation rates and patterns. Additional TPs were formed by the reaction of the UV filters or TPs with each other. The study shows that more attention should be paid to mixture-effects and mixture-TPs that may cause further follow-up effects. © 2019 Elsevier B.V. All rights reserved.
Approaches to mixture risk assessment of PFASs in the European population based on human hazard and biomonitoring data
(2023) Bil, Wienecke; Govarts, Eva; Zeilmaker, M. J.; Kolossa-Gehring, Marike; Vogel, Nina
Per- and polyfluoroalkyl substances (PFASs) are a highly persistent, mobile, and bioaccumulative class of chemicals, of which emissions into the environment result in long-lasting contamination with high probability for causing adverse effects to human health and the environment. Within the European Biomonitoring Initiative HBM4EU, samples and data were collected in a harmonized way from human biomonitoring (HBM) studies in Europe to derive current exposure data across a geographic spread. We performed mixture risk assessments based on recent internal exposure data of PFASs in European teenagers generated in the HBM4EU Aligned Studies (dataset with N = 1957, sampling years 2014-2021). Mixture risk assessments were performed based on three hazard-based approaches: the Hazard Index (HI) approach, the sum value approach as used by the European Food Safety Authority (EFSA) and the Relative Potency Factor (RPF) approach. The HI approach resulted in the highest risk estimates, followed by the RPF approach and the sum value approach. The assessments indicate that PFAS exposure may result in a health risk in a considerable fraction of individuals in the HBM4EU teenager study sample, thereby confirming the conclusion drawn in the recent EFSA scientific opinion. This study underlines that HBM data are of added value in assessing the health risks of aggregate and cumulative exposure to PFASs, assuch data are able to reflect exposure from different sources and via different routes. © 2022 The Authors

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