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 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.

Zinc and nickel binary mixtures act additively on the tropical mysid Mysidopsis juniae

2016 ◽  
Vol 67 (3) ◽  
pp. 301 ◽  
Author(s):  
Lívia Pitombeira de Figuerêdo ◽  
Jeamylle Nilin ◽  
Allyson Queiroz da Silva ◽  
Évila Pinheiro Damasceno ◽  
Susana Loureiro ◽  
...  
Keyword(s):  
Binary Mixtures ◽  
Conceptual Models ◽  
Anthropogenic Activities ◽  
Mixture Toxicity ◽  
Marine Species ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Mortality Data ◽  
Chemical Toxicity ◽  
Single Chemical

Heavy metals may appear in the environment as a result of different anthropogenic activities, such as agriculture practices, industry and mining. They can reach aquatic environments as complex mixtures, and single chemical toxicity as a baseline for risk assessment can underestimate the impairment of ecosystems. The aim of the present study was to evaluate combined toxicity of binary mixtures of zinc and nickel to the tropical mysid Mysidopsis juniae. Acute toxicity was assessed and mixture toxicity was modelled using the conceptual models for concentration addition and independent action to predict whether both metals act additively or whether they interact with each other inside the organism. For that, the observed mortality data were compared with the modelled data. For the single toxicity assessment, results showed that nickel induced higher toxicity than did zinc, with lethal concentrations to 50% of the organisms of 180±30μgL–1 and 260±40μg zinc L–1 respectively. In binary mixtures, both metals acted additively and no interactions were predicted by using the conceptual models. The present study has highlighted the need to fill the gaps in toxicity studies using marine species and approaches that can help improve the assessment of accurate risk in the environment.

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 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.

scholarly journals Screening level mixture risk assessment of pharmaceuticals in STP effluents

2013 ◽  
Author(s):  
Thomas Backhaus ◽  
Maja Karlsson
Keyword(s):  
Mixture Toxicity ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Individual Risk ◽  
Single Substance ◽  
Rough Approximation ◽  
Realistic Assessment ◽  
Few Data ◽  
Mixture Risk Assessment

We modeled the ecotoxicological risks of the pharmaceutical mixtures emitted into the environment from STP effluents. The classic mixture toxicity concept of Concentration Addition was used to calculate the total expect risk of the analytically determined mixtures, compare the expected impact of seven effluent streams and pinpoint the most sensitive group of species. Single substance-based assessments underestimate the actual risks from pharmaceutical mixtures often by more than a factor of 1 000 in several of the surveyed effluent streams, clearly indicating the need to take the joint presence of pharmaceuticals into consideration in order to provide an environmentally realistic assessment for a given water body. The mixture risk quotients regularly exceed 1, indicating a potential risk for the environment, depending on the specific environmental conditions, in particular the dilution in the recipient stream. The top 10 mixture components explain more than 95% of the mixture risk in all cases. A mixture toxicity assessment cannot go beyond the underlying single substance data. The lack of data on the chronic toxicity of most pharmaceuticals as well as the very few data available for in vivo fish toxicity has to be regarded as a major knowledge gap in this context. On the other hand, ignoring Independent Action or even using the sum of individual risk quotients as a rough approximation of Concentration Addition does not have a major impact on the final risk estimate.

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 Status Quo in Data Availability and Predictive Models of Nano-Mixture Toxicity

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 124
Author(s):  
Tung X. Trinh ◽  
Jongwoon Kim
Keyword(s):  
Predictive Models ◽  
Computational Models ◽  
Experimental Studies ◽  
Mixture Toxicity ◽  
Quantitative Structure Activity Relationship ◽  
Toxicity Assessment ◽  
Current Data ◽  
Data Availability ◽  
Concentration Addition ◽  
Living Organisms

Co-exposure of nanomaterials and chemicals can cause mixture toxicity effects to living organisms. Predictive models might help to reduce the intensive laboratory experiments required for determining the toxicity of the mixtures. Previously, concentration addition (CA), independent action (IA), and quantitative structure–activity relationship (QSAR)-based models were successfully applied to mixtures of organic chemicals. However, there were few studies concerning predictive models for toxicity of nano-mixtures before June 2020. Previous reviews provided comprehensive knowledge of computational models and mechanisms for chemical mixture toxicity. There is a gap in the reviewing of datasets and predictive models, which might cause obstacles in the toxicity assessment of nano-mixtures by using in silico approach. In this review, we collected 183 studies of nano-mixture toxicity and curated data to investigate the current data and model availability and gap and to derive research challenges to facilitate further experimental studies for data gap filling and the development of predictive models.

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 The predictability of mixture toxicity of demethylase inhibiting fungicides to Daphnia magna depends on life-cycle parameters

2014 ◽  
Author(s):  
Enken Hassold ◽  
Thomas Backhaus
Keyword(s):  
Daphnia Magna ◽  
Mixture Toxicity ◽  
Toxicity Assessment ◽  
Concentration Addition ◽  
Specific Effects ◽  
Predictive Quality ◽  
Dmi Fungicides ◽  
Reproduction Test ◽  
Fecundity Reduction

A variety of different fungicides is found simultaneously in surface waters, among which demethylase inhibitors (DMIs) are a major group. The joint toxicity of four DMIs from different chemical classes (Fenarimol, Prochloraz, Triadimefon and Pyrifenox) was investigated in the reproduction test with Daphnia magna, following an extended protocol according to ISO 10706. We assessed the toxicity of the DMI mixtures across different endpoints and effect levels and evaluated the predictability of their joint action using Concentration Addition (CA) and Independent Action (IA). The mixture reduced fecundity, delayed molting and caused characteristic malformations in offspring in a concentration-dependend manner which is possibly due to an anti-ecdysteroid action, as previously described for individual DMIs. However, also mixture-specific effects were observed: exposed daphnids reached sexual maturity already after the third juvenile molt, and thus significantly earlier than unexposed daphnids, which needed four juvenile molts to reach maturity. This effect is not caused by any of the DMIs alone. Additionally, the percentage of aborted broods was synergistically higher than expected by either CA or IA. IA underestimates the mixture toxicity for all parameters. The predictive quality of CA differed between life history responses, but was always within a factor of two to the observed toxicity. The parameter “fecundity reduction, counting only normally developed offspring” was the most sensitive endpoint, while the parameter “fecundity reduction, counting all living offspring” was slightly less sensitive. The mixture caused a 90% reduction in fecundity at individual concentrations that only provoke 7% effect or less, which calls for a mixture-specific toxicity assessment of DMI fungicides.

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