Synergistic effects of chemical mixtures: How frequent is rare?

Martin, Olwenn

doi:10.1016/j.cotox.2023.100424

Cited by 7 publications

(6 citation statements)

References 18 publications

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“…Previous reviews highlighted that synergy is a fairly rare phenomenon in mixtures [35,36]; however, in our study, synergistic effects occurred in more than 70% of the cocktails in at least one effective concentration, and non-toxic terbuthylazine had a toxicity-enhancing effect in all mixtures but two. Moreover, while most of the mixtures that we tested showed increased synergy in proportion to the increased concentration, ibuprofen and tebuconazole paired with carbamazepine or S-metolachlor showed synergy at low, environmentally relevant concentrations.…”

Section: Discussioncontrasting

confidence: 71%

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

Göbölös,

Sebők,

Szabó

et al. 2024

Toxics

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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 Aliivibrio fischeri (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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Section: Discussioncontrasting

confidence: 71%

“…Martin reported in his 2023 review that there were 761 different publications on mixture toxicology between 2007 and 2017. At the same time, nearly two-thirds of these experiments investigated the effects of binary mixtures [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

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

Göbölös,

Sebők,

Szabó

et al. 2024

Toxics

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“…It may be possible to do this for specific buildings, but the analysis would be uncertain. Therefore, we assume that all harm is additive and acknowledge that there is a possibility that harm may be under or overestimated in some circumstances and that there is currently no limit value where the additive total harm principle becomes invalid, but it might be identified in the future …”

Section: Discussionmentioning

confidence: 99%

“…Indoor air comprises contaminant mixtures, and although synergies for some contaminant combinations exist, − evidence of chronic synergies remains limited. , When synergies are identified, they are found to be rare at the concentrations typically found in buildings. − Knowledge of air contaminant synergies in LCA is also scarce . Most approaches for multiple contaminant exposures follow the Concentration Addition principle, and components are combined additively. − Therefore, we also apply the additive approach to our model, aligning it with existing risk assessment methods. ,, Furthermore, when evaluating the total harm (in DALYs) from exposure to a mixture of indoor air contaminants, it is common to use an additive approach to combine the health impacts from each contaminant. ,− …”

Section: Methodsmentioning

confidence: 99%

“…Therefore, we assume that all harm is additive and acknowledge that there is a possibility that harm may be under or overestimated in some circumstances and that there is currently no limit value where the additive total harm principle becomes invalid, but it might be identified in the future. 48 Both the epidemiological and toxicological data that underpin the HIs and the concentrations are linked to chronic effects and exposures, and so, it is not possible to consider acute health effects with them. For some of the contaminants, such as the reactive oxidizing species, including ozone and nitrogen dioxide, acute impacts from elevated short-term exposures may be more important than the chronic harm we calculate.…”

Section: Contaminant Ranking and Prioritizationmentioning

confidence: 99%

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Harm from Residential Indoor Air Contaminants

Morantes,

Jones,

Molina

et al. 2023

Environ. Sci. Technol.

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This study presents a health-centered approach to quantify and compare the chronic harm caused by indoor air contaminants using disability-adjusted life-year (DALY). The aim is to understand the chronic harm caused by airborne contaminants in dwellings and identify the most harmful. Epidemiological and toxicological evidence of population morbidity and mortality is used to determine harm intensities, a metric of chronic harm per unit of contaminant concentration. Uncertainty is evaluated in the concentrations of 45 indoor air contaminants commonly found in dwellings. Chronic harm is estimated from the harm intensities and the concentrations. The most harmful contaminants in dwellings are PM 2.5 , PM 10−2.5 , NO 2 , formaldehyde, radon, and O 3 , accounting for over 99% of total median harm of 2200 DALYs/10 5 person/year. The chronic harm caused by all airborne contaminants in dwellings accounts for 7% of the total global burden from all diseases.

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