The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment

Xenobiotics never appear as single, isolated substances in the environment but instead as multi-component mixtures. However, our understanding of the ecotoxicology of mixtures is far from sufficient. In this study, three active pharmaceutical ingredients (carbamazepine, diclofenac, and ibuprofen) an...

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Main Authors: Balázs Göbölös, Rózsa E. Sebők, Gyula Szabó, Gergő Tóth, Sándor Szoboszlay, Balázs Kriszt, Edit Kaszab, Judit Háhn
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/12/3/189
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author Balázs Göbölös
Rózsa E. Sebők
Gyula Szabó
Gergő Tóth
Sándor Szoboszlay
Balázs Kriszt
Edit Kaszab
Judit Háhn
author_facet Balázs Göbölös
Rózsa E. Sebők
Gyula Szabó
Gergő Tóth
Sándor Szoboszlay
Balázs Kriszt
Edit Kaszab
Judit Háhn
author_sort Balázs Göbölös
collection DOAJ
description Xenobiotics never appear as single, isolated substances in the environment but instead as multi-component mixtures. However, our understanding of the ecotoxicology of mixtures is far from sufficient. In this study, three active pharmaceutical ingredients (carbamazepine, diclofenac, and ibuprofen) and three pesticides (S-metolachlor, terbuthylazine, and tebuconazole) from the most frequently detected emerging micropollutants were examined for their acute cytotoxicity, both individually and in combination, by bioluminescence inhibition in <i>Aliivibrio fischeri</i> (NRRL B-11177). Synergy, additive effects, and antagonism on cytotoxicity were determined using the combination index (CI) method. Additionally, PERMANOVA was performed to reveal the roles of these chemicals in binary, ternary, quaternary, quinary, and senary mixtures influencing the joint effects. Statistical analysis revealed a synergistic effect of diclofenac and carbamazepine, both individually and in combination within the mixtures. Diclofenac also exhibited synergy with S-metolachlor and when mixed with ibuprofen and S-metolachlor. S-metolachlor, whether alone or paired with ibuprofen or diclofenac, increased the toxicity at lower effective concentrations in the mixtures. Non-toxic terbuthylazine showed great toxicity-enhancing ability, especially at low concentrations. Several combinations displayed synergistic effects at environmentally relevant concentrations. The application of PERMANOVA was proven to be unique and successful in determining the roles of compounds in synergistic, additive, and antagonistic effects in mixtures at different effective concentrations.
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spelling doaj.art-76a99ccb81cf40c8b93bcfb62298f97d2024-03-27T14:06:11ZengMDPI AGToxics2305-63042024-02-0112318910.3390/toxics12030189The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the EnvironmentBalázs Göbölös0Rózsa E. Sebők1Gyula Szabó2Gergő Tóth3Sándor Szoboszlay4Balázs Kriszt5Edit Kaszab6Judit Háhn7Department of Environmental Safety, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, 1 Páter Károly u., 2100 Gödöllő, HungaryDepartment of Environmental Safety, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, 1 Páter Károly u., 2100 Gödöllő, HungaryDepartment of Environmental Toxicology, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, 1 Páter Károly u., 2100 Gödöllő, HungaryDepartment of Environmental Safety, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, 1 Páter Károly u., 2100 Gödöllő, HungaryDepartment of Environmental Safety, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, 1 Páter Károly u., 2100 Gödöllő, HungaryDepartment of Environmental Safety, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, 1 Páter Károly u., 2100 Gödöllő, HungaryDepartment of Environmental Safety, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, 1 Páter Károly u., 2100 Gödöllő, HungaryDepartment of Environmental Safety, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, 1 Páter Károly u., 2100 Gödöllő, HungaryXenobiotics never appear as single, isolated substances in the environment but instead as multi-component mixtures. However, our understanding of the ecotoxicology of mixtures is far from sufficient. In this study, three active pharmaceutical ingredients (carbamazepine, diclofenac, and ibuprofen) and three pesticides (S-metolachlor, terbuthylazine, and tebuconazole) from the most frequently detected emerging micropollutants were examined for their acute cytotoxicity, both individually and in combination, by bioluminescence inhibition in <i>Aliivibrio fischeri</i> (NRRL B-11177). Synergy, additive effects, and antagonism on cytotoxicity were determined using the combination index (CI) method. Additionally, PERMANOVA was performed to reveal the roles of these chemicals in binary, ternary, quaternary, quinary, and senary mixtures influencing the joint effects. Statistical analysis revealed a synergistic effect of diclofenac and carbamazepine, both individually and in combination within the mixtures. Diclofenac also exhibited synergy with S-metolachlor and when mixed with ibuprofen and S-metolachlor. S-metolachlor, whether alone or paired with ibuprofen or diclofenac, increased the toxicity at lower effective concentrations in the mixtures. Non-toxic terbuthylazine showed great toxicity-enhancing ability, especially at low concentrations. Several combinations displayed synergistic effects at environmentally relevant concentrations. The application of PERMANOVA was proven to be unique and successful in determining the roles of compounds in synergistic, additive, and antagonistic effects in mixtures at different effective concentrations.https://www.mdpi.com/2305-6304/12/3/189<i>Aliivibrio fischeri</i>combination indexcarbamazepineNSAIDsterbuthylazineS-metolachlor
spellingShingle Balázs Göbölös
Rózsa E. Sebők
Gyula Szabó
Gergő Tóth
Sándor Szoboszlay
Balázs Kriszt
Edit Kaszab
Judit Háhn
The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment
Toxics
<i>Aliivibrio fischeri</i>
combination index
carbamazepine
NSAIDs
terbuthylazine
S-metolachlor
title The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment
title_full The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment
title_fullStr The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment
title_full_unstemmed The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment
title_short The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment
title_sort cocktail effects on the acute cytotoxicity of pesticides and pharmaceuticals frequently detected in the environment
topic <i>Aliivibrio fischeri</i>
combination index
carbamazepine
NSAIDs
terbuthylazine
S-metolachlor
url https://www.mdpi.com/2305-6304/12/3/189
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