Integrated fuzzy concentration addition–independent action (IFCA–IA) model outperforms two-stage prediction (TSP) for predicting mixture toxicity

Chemosphere ◽  
2009 ◽  
Vol 74 (5) ◽  
pp. 735-740 ◽  
Author(s):  
Zhuang Wang ◽  
Jingwen Chen ◽  
Liping Huang ◽  
Ying Wang ◽  
Xiyun Cai ◽  
...  
Keyword(s):  
Mixture Toxicity ◽  
Concentration Addition ◽  
Independent Action ◽  
Two Stage

Assessment and Prediction of Joint Toxicity of Aniline Derivatives

2013 ◽  
Vol 448-453 ◽  
pp. 217-220
Author(s):  
Hui Lin Ge ◽  
Shu Shen Liu ◽  
Hong Qiu Yuan ◽  
Gui Hao Yin ◽  
Yi Xie ◽  
...  
Keyword(s):  
Mixture Toxicity ◽  
Joint Effect ◽  
Concentration Addition ◽  
Joint Toxicity ◽  
Independent Action ◽  
Similarity Parameter ◽  
Toxicity Index ◽  
Aniline Derivatives ◽  
Toxic Units

The joint toxicity of aniline, 2-methylaniline, 3-methylaniline, 4-methylaniline, 2-nitroaniline, 3-nitroaniline, 4-nitroaniline, 2-chloroaniline, 3-chloroaniline, and 4-chloroaniline on photobacterium were predicted and evaluated by using concentration addition (CA) and independent action (IA) models, and joint effect indices including toxic units, additive index, mixture toxicity index, and similarity parameter. The tested mixture presented synergism.

scholarly journals Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

2014 ◽  
Author(s):  
Thomas Backhaus
Keyword(s):  
Empirical Data ◽  
Critical Review ◽  
Mixture Toxicity ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Ecological Interactions ◽  
Independent Action ◽  
Soil Organisms ◽  
Analytical Monitoring ◽  
Marine Flora

Analytical monitoring surveys routinely confirm that organisms in the environment are exposed to complex multi-component pharmaceutical mixtures. We are hence tasked with the challenge to take this into consideration when investigating the ecotoxicology of pharmaceuticals. This review first provides a brief overview of the fundamental approaches for mixture toxicity assessment, which is then followed by a critical review on the empirical evidence that is currently at hand on the ecotoxicology of pharmaceutical mixtures. It is concluded that, while the classical concepts of Concentration Addition and Independent Action (Response Addition) provide a robust scientific footing, several knowledge gaps remain. This includes in particular the need for more and better empirical data on the effects of pharmaceutical mixtures on soil organisms as well as marine flora and fauna, and exploring the quantitative consequences of toxicokinetic, toxicodynamic and ecological interactions. Increased focus should be put on investigating the ecotoxicology of pharmaceutical mixtures in environmentally realistic settings.

scholarly journals The Acute Single and Mixture Toxicity of Paraquat Dichloride and Deltamethrin to Guppy (Poecillia reticulata)

2021 ◽  
Author(s):  
Rully Adi Nugroho ◽  
Cornelis van Gestel
Keyword(s):  
Dose Level ◽  
Adult Male ◽  
Surface Waters ◽  
Poecilia Reticulata ◽  
Mixture Toxicity ◽  
Concentration Addition ◽  
Independent Action ◽  
Acute Effects ◽  
Reference Models ◽  
Guppy Fish

Abstract Although herbicide and insecticide contamination of surface waters normally occurs in the form of mixtures, the toxicity interactions displayed by such mixtures have only rarely been characterized. This study evaluated the acute effects of single pesticides (paraquat dichloride and deltamethrin, tested in their commercial formulations Gramoxone 276 SL and Decis 25EC) and their equitoxic mixtures on the survival of adult male guppy fish (Poecilia reticulata). Mixture toxicity was evaluated against the reference models of Concentration Addition (CA) and Independent Action (IA). In the single treatments, the 72h LC10 and LC50 values were 1.5 and 6.0 mg a.s. L-1 and 0.53 and 3.6 µg a.s. L-1 for paraquat dichloride and deltamethrin, respectively. The equitoxic mixtures showed significant paraquat dichloride-deltamethrin antagonism, both based on the CA and the IA model, without significant dose-level dependent deviations.

Evaluation and Prediction of Mixture Toxicity of PFOS and PFOA to Zebrafish (Danio rerio) Embryo

2012 ◽  
Vol 485 ◽  
pp. 297-300
Author(s):  
Guang Hui Ding ◽  
Jing Zhang ◽  
Man Wang ◽  
Yi Hong Chen ◽  
Guo Yi Luo ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Danio Rerio ◽  
Sulfonic Acid ◽  
Aquatic Organisms ◽  
Mixture Toxicity ◽  
Perfluorooctanoic Acid ◽  
Concentration Addition ◽  
Limited Information ◽  
Independent Action

Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have emerged as two concerning contaminants in recent years. However, there is limited information about their mixture toxicity to aquatic organisms. In the present study, the single and mixture toxicity of PFOA and PFOS to zebrafish (Danio rerio) embryo were tested, and the mixture toxicity was predicted by concentration addition (CA) and independent action (IA) models. It is found that PFOS and PFOA have synergistic effect at 96 hpf, while this kind of synergistic effect is not obvious at 72 hpf. CA and IA models both could predict the 72 h mixture toxicity, while underestimate the 96 h mixture toxicity.

scholarly journals The Acute Single and Mixture Toxicity of Paraquat Dichloride and Deltamethrin to Guppy (Poecilia reticulata)

2021 ◽  
Vol 29 (1) ◽  
pp. 47-53
Author(s):  
Rully Adi Nugroho ◽  
Cornelis Adrianus Maria van Gestel
Keyword(s):  
Dose Level ◽  
Adult Male ◽  
Surface Waters ◽  
Poecilia Reticulata ◽  
Mixture Toxicity ◽  
Concentration Addition ◽  
Independent Action ◽  
Acute Effects ◽  
Reference Models ◽  
Guppy Fish

Although herbicide and insecticide contamination of surface waters normally occurs in the form of mixtures, the toxicity interactions displayed by such mixtures have only rarely been characterized. This study evaluated the acute effects of single pesticides (paraquat dichloride and deltamethrin, tested in their commercial formulations Gramoxone 276 SL and Decis 25EC) and their equitoxic mixtures on the survival of adult male guppy fish (Poecilia reticulata). Mixture toxicity was evaluated against the reference models of Concentration Addition (CA) and Independent Action (IA). In the single treatments, the 72h LC10 and LC50 values were 1.5 and 6.0 mg a.s. L-1 and 0.53 and 3.6 µg a.s. L-1 for paraquat dichloride and deltamethrin, respectively. The equitoxic mixtures showed significant paraquat dichloride-deltamethrin antagonism, both based on the CA and the IA model, without significant dose-level dependent deviations.

scholarly journals Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

2014 ◽  
Vol 369 (1656) ◽  
pp. 20130585 ◽  
Author(s):  
Thomas Backhaus
Keyword(s):  
Empirical Data ◽  
Critical Review ◽  
Mixture Toxicity ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Ecological Interactions ◽  
Independent Action ◽  
Soil Organisms ◽  
Analytical Monitoring ◽  
Marine Flora

Analytical monitoring surveys routinely confirm that organisms in the environment are exposed to complex multi-component pharmaceutical mixtures. We are hence tasked with the challenge to take this into consideration when investigating the ecotoxicology of pharmaceuticals. This review first provides a brief overview of the fundamental approaches for mixture toxicity assessment, which is then followed by a critical review on the empirical evidence that is currently at hand on the ecotoxicology of pharmaceutical mixtures. It is concluded that, while the classical concepts of concentration addition and independent action (response addition) provide a robust scientific footing, several knowledge gaps remain. This includes, in particular, the need for more and better empirical data on the effects of pharmaceutical mixtures on soil organisms as well as marine flora and fauna, and exploring the quantitative consequences of toxicokinetic, toxicodynamic and ecological interactions. Increased focus should be put on investigating the ecotoxicology of pharmaceutical mixtures in environmentally realistic settings.

scholarly journals Medicines, shaken and stirred: a critical review on the ecotoxicology of pharmaceutical mixtures

2014 ◽  
Author(s):  
Thomas Backhaus
Keyword(s):  
Empirical Data ◽  
Critical Review ◽  
Mixture Toxicity ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Ecological Interactions ◽  
Independent Action ◽  
Soil Organisms ◽  
Analytical Monitoring ◽  
Marine Flora

Analytical monitoring surveys routinely confirm that organisms in the environment are exposed to complex multi-component pharmaceutical mixtures. We are hence tasked with the challenge to take this into consideration when investigating the ecotoxicology of pharmaceuticals. This review first provides a brief overview of the fundamental approaches for mixture toxicity assessment, which is then followed by a critical review on the empirical evidence that is currently at hand on the ecotoxicology of pharmaceutical mixtures. It is concluded that, while the classical concepts of Concentration Addition and Independent Action (Response Addition) provide a robust scientific footing, several knowledge gaps remain. This includes in particular the need for more and better empirical data on the effects of pharmaceutical mixtures on soil organisms as well as marine flora and fauna, and exploring the quantitative consequences of toxicokinetic, toxicodynamic and ecological interactions. Increased focus should be put on investigating the ecotoxicology of pharmaceutical mixtures in environmentally realistic settings.

Mixture Effects of 3 Mechanistically Different Steroidogenic Disruptors (Prochloraz, Genistein, and Ketoconazole) in the H295R Cell Assay

2015 ◽  
Vol 34 (6) ◽  
pp. 534-542 ◽  
Author(s):  
Frederik Knud Nielsen ◽  
Cecilie Hurup Hansen ◽  
Jennifer Anna Fey ◽  
Martin Hansen ◽  
Bent Halling-Sørensen ◽  
...  
Keyword(s):  
Cell Line ◽  
Endocrine Disruptors ◽  
Mixture Toxicity ◽  
Concentration Addition ◽  
Mixture Effects ◽  
Modes Of Action ◽  
Cell Assay ◽  
17Β Estradiol ◽  
H295r Cells ◽  
The Individual

Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β-estradiol) were analyzed using gas chromatography and tandem mass spectrometry (GC-MS/MS) to investigate the effects throughout the steroidogenic pathway. Current modeling approaches often rely on models assuming compounds acting independently and that the individual effects in some way can be summarized to predict a mixture effect. In H295R cells with an intact steroidogenic pathway, such assumptions may not be feasible. The purpose of this study was therefore to evaluate whether effects of a mixture with differing modes of action followed or deviated from additivity (concentration addition) and whether the H295R cell line was suitable for evaluating mixture toxicity of endocrine disruptors with different modes of action. The compounds were chosen because they interfere with steroidogenesis in different ways. They all individually decrease the concentrations of the main sex steroids downstream but exert different effects upstream in the steroidogenic pathway. Throughout the study, we observed lowest observed effect concentrations of mixtures at levels 2 to 10 times higher than the predicted EC50, strongly indicating antagonistic effects. The results demonstrate that chemical analysis combined with the H295R cell assay is a useful tool also for studying how mixtures of endocrine disruptors with differing modes of action interfere with the steroidogenic pathway and that existing models like concentration addition are insufficient in such cases. Furthermore, for end points where compounds exert opposite effects, no relevant models are available.

scholarly journals Concentration Addition, Independent Action and Generalized Concentration Addition Models for Mixture Effect Prediction of Sex Hormone Synthesis In Vitro

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70490 ◽  
Author(s):  
Niels Hadrup ◽  
Camilla Taxvig ◽  
Mikael Pedersen ◽  
Christine Nellemann ◽  
Ulla Hass ◽  
...  
Keyword(s):  
Sex Hormone ◽  
Concentration Addition ◽  
Independent Action ◽  
Mixture Effect ◽  
Hormone Synthesis

scholarly journals Novel Segmented Concentration Addition Method to Predict Mixture Hormesis of Chlortetracycline Hydrochloride and Oxytetracycline Hydrochloride to Aliivibrio fischeri

2020 ◽  
Vol 21 (2) ◽  
pp. 481 ◽  
Author(s):  
Huilin Ge ◽  
Min Zhou ◽  
Daizhu Lv ◽  
Mingyue Wang ◽  
Defang Xie ◽  
...  
Keyword(s):  
Mixture Toxicity ◽  
Practical Significance ◽  
Concentration Addition ◽  
High Concentration ◽  
Cross Point ◽  
Antagonistic Action ◽  
Interval Method ◽  
Molar Ratios ◽  
Ca Model ◽  
Aliivibrio Fischeri

Hormesis is a concentration-response phenomenon characterized by low-concentration stimulation and high-concentration inhibition, which typically has a nonmonotonic J-shaped concentration-response curve (J-CRC). The concentration addition (CA) model is the gold standard for studying mixture toxicity. However, the CA model had the predictive blind zone (PBZ) for mixture J-CRC. To solve the PBZ problem, we proposed a segmented concentration addition (SCA) method to predict mixture J-CRC, which was achieved through fitting the left and right segments of component J-CRC and performing CA prediction subsequently. We selected two model compounds including chlortetracycline hydrochloride (CTCC) and oxytetracycline hydrochloride (OTCC), both of which presented J-CRC to Aliivibrio fischeri (AVF). The seven binary mixtures (M1–M7) of CTCC and OTCC were designed according to their molar ratios of 12:1, 10:3, 8:5, 1:1, 5:8, 3:10, and 1:12 referring to the direct equipartition ray design. These seven mixtures all presented J-CRC to AVF. Based on the SCA method, we obtained mixture maximum stimulatory effect concentration (ECm) and maximum stimulatory effect (Em) predicted by SCA, both of which were not available for the CA model. The toxicity interactions of these mixtures were systematically evaluated by using a comprehensive approach, including the co-toxicity coefficient integrated with confidence interval method (CTCICI), CRC, and isobole analysis. The results showed that the interaction types were additive and antagonistic action, without synergistic action. In addition, we proposed the cross point (CP) hypothesis for toxic interactive mixtures presenting J-CRC, that there was generally a CP between mixture observed J-CRC and CA predicted J-CRC; the relative positions of observed and predicted CRCs on either side of the CP would exchange, but the toxic interaction type of mixtures remained unchanged. The CP hypothesis needs to be verified by more mixtures, especially those with synergism. In conclusion, the SCA method is expected to have important theoretical and practical significance for mixture hormesis.

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