Test Design, Mixture Characterization, and Data Evaluation

Jonker, M.; Gerhardt, A.; Backhaus, Till; Gestel, C.A.M. van

doi:10.1201/b10292-5

Cited by 15 publications

(27 citation statements)

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“…Traditionally, isobole designs have been used to evaluate the binary mixture toxicity [13,14,18,19]. Traditionally, isobole designs have been used to evaluate the binary mixture toxicity [13,14,18,19].…”

Section: Discussionmentioning

confidence: 99%

“…Several concepts for the prediction of mixture toxicity have been introduced in the literature; however, 2 principal concepts, concentration addition and independent action, have been used in most mixture toxicity studies [13,14]. Several concepts for the prediction of mixture toxicity have been introduced in the literature; however, 2 principal concepts, concentration addition and independent action, have been used in most mixture toxicity studies [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…Several concepts for the prediction of mixture toxicity have been introduced in the literature; however, 2 principal concepts, concentration addition and independent action, have been used in most mixture toxicity studies [13,14]. In the independent action model, the mixture effect can be calculated from the effects caused by the individual components as a statistically independent event [9,13,14]. In the concentration addition model, a toxic unit (concentration/x% effective concentration) of the mixture can be expressed as the sum of the toxic units of each chemical [8,13,14].…”

Section: Introductionmentioning

confidence: 99%

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Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Watanabe

Tamura

Abe

et al. 2015

Environmental Toxicology and Chemistry

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Principles of concentration addition and independent action have been used as effective tools to predict mixture toxicity based on individual component toxicity. The authors investigated the toxicity of a pharmaceutical mixture composed of the top 10 detected active pharmaceutical ingredients (APIs) in the Tama River (Tokyo, Japan) in a relevant concentration ratio. Both individual and mixture toxicities of the 10 APIs were evaluated by 3 short-term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, the daphnid Ceriodaphnia dubia, and the zebrafish Danio rerio. With the exception of clarithromycin toxicity to alga, the no-observed-effect concentration of individual APIs for each test species was dramatically higher than the highest concentration of APIs found in the environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25 times, 100 times, and 15,000 times higher concentrations, respectively, than the environmental concentrations of individual APIs. Predictions by concentration addition and independent action were nearly identical for alga, as clarithromycin was the predominant toxicant in the mixture. Both predictions described the observed mixture toxicity to alga fairly well, whereas they slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by concentration addition and independent action. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either concentration addition or independent action.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Several concepts for the prediction of mixture toxicity have been introduced in the literature; however, 2 principal concepts, concentration addition and independent action, have been used in most mixture toxicity studies [13,14]. In the independent action model, the mixture effect can be calculated from the effects caused by the individual components as a statistically independent event [9,13,14]. In the concentration addition model, a toxic unit (concentration/x% effective concentration) of the mixture can be expressed as the sum of the toxic units of each chemical [8,13,14].…”

Section: Introductionmentioning

confidence: 99%

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Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Watanabe

Tamura

Abe

et al. 2015

Environmental Toxicology and Chemistry

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“…Moreover, to test the joint effect of Cu‐hydroxide (the fungicide with the strongest effect on fungal biomass; see ) and S, a mixture experiment was conducted using an ‘A in the presence of B’‐design (Jonker et al . ). All Cu‐hydroxide concentrations tested in the single‐substance experiments (Table ) were applied in combination with a fixed concentration of 0·2 mg S L −1 , which approximates the maximum PEC.…”

Section: Methodsmentioning

confidence: 97%

Inorganic fungicides as routinely applied in organic and conventional agriculture can increase palatability but reduce microbial decomposition of leaf litter

Zubrod

Feckler

Englert

et al. 2015

Journal of Applied Ecology

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Summary1. The application of fungicides is considered an indispensable measure to secure crop production. These substances, however, may unintentionally enter surface waters via run-off, potentially affecting the microbial community. To assess such risks adequately, authorities recently called for suitable test designs involving relevant aquatic micro-organisms. 2. We assessed the structural and functional responses of leaf-associated microbial communities, which play a key role in the breakdown of allochthonous leaf material in streams, towards the inorganic fungicides copper (Cu) and elemental sulphur (S). These substances are of particular interest as they are authorized for both conventional and organic farming in many countries of the world. We used the food choice of the amphipod shredder Gammarus fossarum (indicative for micro-organism-mediated leaf palatability) as well as microbial leaf decomposition as functional endpoints. Moreover, the leaf-associated microbial communities were characterized by means of bacterial density, fungal biomass and community composition facilitating mechanistic understanding of the observed functional effects. 3. While Gammarus preferred Cu-exposed leaves over unexposed ones, microbial leaf decomposition was reduced by both Cu and S (up to 30%). Furthermore, Cu exposure decreased bacterial densities (up to 60%), stimulated the growth of leaf-associated fungi (up to 100%) and altered fungal community composition, while S did not affect any of the assessed structural endpoints. 4. Synthesis and applications. We observed both structural and functional changes in leafassociated microbial communities at inorganic fungicide concentrations realistic for surface water bodies influenced by conventional and organic farming. Our data hence justify a careful re-evaluation of the environmental safety of the agricultural use of these compounds. Moreover, inclusion of an experimental design similar to the one used in this study in lower tier environmental risk assessments of antimicrobial compounds may aid to safeguard the integrity of aquatic microbial communities and the functions they provide.

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“…With the TU approach, the total toxic unit (TTU) of 2 metals in each exposure treatment can be calculated using Equation 3 [16,19,37,38,48]. This procedure was also used in the MixTox model approach.…”

Section: Effect Analysismentioning

confidence: 99%

Acute toxicity of binary-metal mixtures of copper, zinc, and nickel to Pimephales promelas: Evidence of more-than-additive effect

Lynch

Hoang

O’Brien

2015

Environmental Toxicology and Chemistry

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Metal mixture toxicity has been studied for decades. However, the results are not consistent, and thus ecological risk assessment and regulation of mixtures has been difficult. The objective of the present study was to use a systematic experimental design to characterize the toxicity of binary-metal mixture of Cu, Zn, and Ni to Pimephales promelas, typically to determine whether the effect of these binary-metal mixtures on P. promelas is more-than-additive. Standard 96-h toxicity tests were conducted with larval P. promelas based on US Environmental and Protection Agency methods to determine metal mixture effects. All experiments were conducted in synthetic moderately hard water with no addition of dissolved organic matter. Three different effect analysis approaches, the MixTox model, the Finney model, and the toxic unit method, were used for comparison. The results indicate that the toxicity of Cu+Zn, Cu+Ni, and Zn+Ni mixtures to P. promelas was more-than-additive. Among the 3 mixtures, the effect of the Cu+Ni mixture was the most profound. The results of the present study are useful for applications to models such as the metal mixture biotic ligand model. More research should be conducted to determine the mechanisms of acute and chronic toxicity of metal mixtures.

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Test Design, Mixture Characterization, and Data Evaluation

Cited by 15 publications

References 0 publications

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

Inorganic fungicides as routinely applied in organic and conventional agriculture can increase palatability but reduce microbial decomposition of leaf litter

Acute toxicity of binary-metal mixtures of copper, zinc, and nickel to Pimephales promelas: Evidence of more-than-additive effect

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