Predicting the aquatic toxicity of commercial pesticide mixtures
TL;DR: The results suggest that the CA concept can be applied to predict the aquatic toxicity of commercial pesticide mixtures using the heterogeneous data typically available in a risk assessment context for a number of clearly identified combinations of test species and pesticide types with reasonably small uncertainty.
Abstract: Previous studies reported on a large (> 80%) compliance between the observed toxicity of pesticide mixtures and their toxicity as predicted by the concept of concentration addition (CA). The present study extents these findings to commercially sold and frequently applied pesticide mixtures by investigating whether the aquatic toxicity of 66 herbicidal and 53 fungicidal combination products, i.e., authorized plant protection products that contain two or more active substances, can reliably be predicted by CA. In more than 50% of cases, the predicted and observed mixture toxicity deviated by less than factor 2. An indication for a synergistic interaction was only detected with regard to algal growth inhibition for mixtures of fungicides that inhibit different enzymes of ergosterol biosynthesis. The greatest degree of compliance between prediction and observation was found for the acute toxicity of fungicidal products towards Daphnia and fish, while the greatest degree of underestimation of product toxicity occurred for the acute toxicity of herbicidal products towards Daphnia and fish. Using the lowest available toxicity measures within taxonomic groups as the most conservative approach resulted in a bias towards overestimation of product toxicity, but did not eliminate cases of considerable underestimation of product toxicity. The results suggest that the CA concept can be applied to predict the aquatic toxicity of commercial pesticide mixtures using the heterogeneous data typically available in a risk assessment context for a number of clearly identified combinations of test species and pesticide types with reasonably small uncertainty.
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TL;DR: A review of the current challenges facing the assessment of mixture effects and examines future areas of focus that seek to develop methodologies more suitable for environmental mixtures can be found in this article, where the authors show why accurate risk assessment of mixtures is vital by demonstrating the effect they can have on organisms in the environment.
Abstract: In the environment, organisms are exposed to a diverse array of chemicals in complex mixtures. The majority of approaches that aim to assess the risk of environmental chemical mixtures, including those used by regulatory bodies, use toxicity data generated from the individual component chemicals to predict the overall mixture toxicity. It is assumed that the behaviour of chemicals in a mixture can be predicted using the concepts of concentration or dose addition for chemicals with similar mechanisms of action or response addition for dissimilarly acting chemicals. Based on empirical evidence, most traditional risk assessment methods, such as toxic equivalency factors and the hazard index, make the assumption that the components of a mixture adhere to the concentration addition model. Thus, mixture toxicity can be predicted by the summation of the individual component toxicities. However in some mixtures, interactions can occur between chemicals or at target sites that alter the toxicity so that it is more or less than expected from the constituents. Many regulatory and experimental methods for predicting mixture toxicity rely on the use of a concentration addition model so that if interactions occur in mixtures, the risk posed may have been significantly underestimated. This is particularly concerning when considering environmental mixtures which are often highly complex and composed of indeterminate chemicals. Failure to accurately predict the effects chemicals will have if released into the environment, where they can form mixtures, can lead to unexpected detrimental effects on wildlife and ecosystems. The number of confounding factors that may alter the ecotoxicity of a mixture and the accuracy of predictive methods makes risk assessment of environmental mixtures a complex and intimidating task. With this in mind, this review aims show why accurate risk assessment of mixtures is vital by demonstrating the effect they can have on organisms in the environment. Furthermore, it also aims to look at the current challenges facing the assessment of mixture effects and examines future areas of focus that seek to develop methodologies more suitable for environmental mixtures.
142 citations
TL;DR: Nine metrics designed for estimating the total toxicity of mixtures regarding their relationship with an effect metric for stream macroinvertebrates were compared using monitoring data of biota and organic chemicals, mainly pesticides, from five studies comprising 102 streams in several regions of Europe and South-East Australia.
Abstract: Reliable characterization of exposure is indispensable for ecological risk assessment of chemicals. To deal with mixtures, several approaches have been developed, but their relevance for predicting ecological effects on communities in the field has not been elucidated. In the present study, we compared nine metrics designed for estimating the total toxicity of mixtures regarding their relationship with an effect metric for stream macroinvertebrates. This was done using monitoring data of biota and organic chemicals, mainly pesticides, from five studies comprising 102 streams in several regions of Europe and South-East Australia. Mixtures of less than 10 pesticides per water sample were most common for concurrent exposure. Exposure metrics based on the 5% fraction of a species sensitivity distribution performed best, closely followed by metrics based on the most sensitive species and Daphnia magna as benchmark. Considering only the compound with the highest toxicity and ignoring mixture toxicity was sufficient to estimate toxicity in predominantly agricultural regions with pesticide exposure. The multisubstance Potentially Affected Fraction (msPAF) that combines concentration and response addition was advantageous in the study where further organic toxicants occurred. We give recommendations on exposure metric selection depending on data availability and the involved compounds.
68 citations
TL;DR: The toxicity assessment was performed on binary mixtures (preservative + IWW) and carried out using the median-effect principle, which is a special case of the concept of Concentration Addition (CA).
64 citations
Cites methods or result from "Predicting the aquatic toxicity of ..."
...Several reviews have shown that CA provides a reliable and frequently used tool for predicting and assessing the ecotoxicity of multi-component mixtures (Belden et al., 2003; Kortenkamp et al., 2009; Coors and Frische, 2011)....
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...A two-fold deviation has been applied as a threshold to denote compliance between observed and predicted mixture toxicity in the present study in accordance with previous studies (Belden et al., 2007; Coors and Frische, 2011)....
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TL;DR: A review of recent research on pesticide mixture toxicity to aquatic biota and the methods employed to predict toxic effects can be found in this article, where the authors conclude that the concentration-addition model is a generally conservative and practical first-tier model for the ecological assessment of pesticide mixtures in aquatic systems.
Abstract: A major difficulty in addressing chemical mixtures through legislation or regulations revolves around our limited understanding of their potential impacts. This review provides an overview of recent research on pesticide mixture toxicity to aquatic biota and the methods employed to predict toxic effects. The most common approaches are to assume concentration-addition or independent action of chemicals in a mixture. There are a number of cases in the literature of interactions between pesticides. However, models accounting for possible interactions between mixture components are used infrequently. Although results are limited, studies investigating the effects of pesticide mixtures have not demonstrated significant synergism at environmentally relevant concentrations. Based on the results of our review, we conclude that the concentration-addition model is a generally conservative and practical first-tier model for the ecological assessment of pesticide mixtures in aquatic systems.
64 citations
Cites background or result from "Predicting the aquatic toxicity of ..."
...2010; Coors and Frische 2011). For example, in a review of pesticide mixture studies with regard to effects on aquatic crustaceans, insects, molluscs, algae, and fish, Deneer (2000) found that the concentration-addition (CA) model predicted effect concentrations within a factor of two in 90% of the 202 mixture studies examined....
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...2010; Coors and Frische 2011). For example, in a review of pesticide mixture studies with regard to effects on aquatic crustaceans, insects, molluscs, algae, and fish, Deneer (2000) found that the concentration-addition (CA) model predicted effect concentrations within a factor of two in 90% of the 202 mixture studies examined. Some deviations from the CA model were observed, particularly when an organophosphate (OP) or a carbamate was paired with another OP or a pyrethroid. Similar to the results of Deneer (2000), Belden et al . (2007) found that 88% of 207 experiments that evaluated the CA model had observed toxicity values that were within a factor of two of predicted values....
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...2010; Coors and Frische 2011)....
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...The authors concluded that the CA concept can be used to estimate the aquatic toxicity of commercial pesticide mixtures for some test species and pesticide types with reasonably small uncertainty (Coors and Frische 2011)....
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...In the majority of cases, pesticide mixtures cause toxic effects that are approximately additive (Eaton 1973; Hermens and Leeuwangh 1982; Hermens et al . 1984; Altenburger et al . 1996; Deneer 2000; Junghans et al. 2006; Belden et al . 2007; Syberg et al . 2009; Zhang et al . 2010; Coors and Frische 2011)....
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TL;DR: It was found that the toxicity of climbazole is mostly similar to that of other DMI fungicides, whereas it proved to be particularly toxic to primary producers, and it was demonstrated here that for an ionizable compound such as climbingazole, the soil pH can have a considerable influence on phytotoxicity.
Abstract: Emerging pollutants such as personal care products can reach the environment via effluents from wastewater treatment plants (WWTPs) and digested sludge. Only recently, the antidandruff agent and antimycotic climbazole was detected for the first time in a WWTP effluent with concentrations up to 0.5 µg/L. Climbazole acts as a C14-demethylase inhibitor (DMI) fungicide and thus has a high efficacy against fungi, but knowledge of its potential environmental impact is lacking. Therefore, the aim of the present study was to characterize climbazole's ecotoxicity by conducting standard biotests with organisms representing different trophic levels from the aquatic as well as the terrestrial ecosystems. It was found that the toxicity of climbazole is mostly similar to that of other DMI fungicides, whereas it proved to be particularly toxic to primary producers. The lowest median effective concentrations (EC50s) were determined for Lemna minor, at 0.013 mg/L (biomass yield), and Avena sativa, at 18.5 mg/kg soil dry weight (shoot biomass). Reduction of frond size in water lentils and shoot length in higher plants suggested an additional plant growth–retarding mode of action of climbazole. In addition, it was demonstrated here that for an ionizable compound such as climbazole, the soil pH can have a considerable influence on phytotoxicity. Environ Toxicol Chem 2013;32:2816–2825. © 2013 SETAC
55 citations
Cites background from "Predicting the aquatic toxicity of ..."
...Particularly for mixtures containing DMI fungicides, additive or even more than additive effects have been reported [42,43]....
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References
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TL;DR: A quantitative analysis of the toxicity of drugs or poisons applied jointly requires that they be administered at several dosages in mixtures containing fixed proportions of the ingredients, and the presence of synergism is indicated.
Abstract: Summary
A quantitative analysis of the toxicity of drugs or poisons applied jointly requires that they be administered at several dosages in mixtures containing fixed proportions of the ingredients. From a study of the dosage-mortality curves for several such mixtures, preferably in comparison with equivalent curves for the isolated active ingredients, most cases of combined action can be classified into one of three types:
(1) The first type is that in which the constituents act independently and diversely, so that the toxicity of any combination can be predicted from that of the isolated components and from the association of susceptibilities to the two components. The coefficient of association can be measured experimentally and should be constant at all proportions of the ingredients. When high, the toxicity of the mixture is reduced. The form of the dosage-mortality curve has been examined for several hypothetical mixtures. Whenever the curves for the two constituents were assumed to differ in slope, there was a relatively abrupt bend in the curve for the mixture, the rectilinear segments above and below the break approaching in slope the values for the original constituents. This observation indicates that in homogeneous populations the slope of a dosage-mortality curve is of toxicological significance. Since the same numerical relations would be expected if a single poison were to have two independent lethal effects within the animal, there is theoretical basis for fitting the linear segments of a dosage-mortality curve separately when a break occurs after transformation to probits and logarithms. This argument has been extended to time-mortality experiments to explain the smoothly concave curves characteristic of natural mortality.
(2) The second type of joint action is that in which the constituents act independently but similarly, so that one ingredient can be substituted at a constant ratio for any proportion of a second without altering the toxicity of the mixture. With homogeneous populations, dosage-mortality curves for the separate ingredients and for all mixtures should be parallel. Although by hypothesis the susceptibility to one ingredient is completely correlated with that to the other, mixtures in this category are more toxic than in the preceding class where association may vary from 0 to 1. The numerical relations have been illustrated by an experiment on the toxicity to the house-fly of solutions containing pyrethrin and rotenone. A mixture with a little less than four equitoxic units of pyrethrin to one of rotenone agreed closely with the definition but one in which the ingredients were about equally balanced showed a significantly greater toxicity than expected on the hypothesis of independent action, indicating the presence of synergism.
(3) Synergism forms the third type of joint action, characterized by a toxicity greater than that predicted from studies on the isolated constituents. It is the reverse of antagonism, which has not been considered directly. Two methods are proposed for the analysis of synergism. The more direct is to relate equitoxic dosages of mixture to its percentage composition in terms of the more active ingredient. When both are in logarithms the relation is linear over a useful range of compositions. This procedure preserves the original structure of the experiment, can be extended readily to three or more ingredients and leads to a convenient practical result. Theoretically it is less satisfactory than a second method in which for equitoxic dosages of each mixture the content of one ingredient (A) is related to the content of the other (B.) The equation which satisfies this relation most completely is (1 +k1A) Bi=k2, where the three constants are computed from the experimental data. When the exponent i is equal to 1, only two constants need be determined and their product, k1k2, is proposed as a measure of the intensity of synergism.
The synergism between a nitro-phenol and petroleum oil has been computed by both methods. For mixtures containing from 0·5 to 5% of the nitrophenol, the deposit of mixture (Dc) killing 98 % of the eggs of a plant bug could be expressed adequately in terms of the percentage of the phenol (Q) as log Dc= 0·687-0·307 log Q, for 98% of overwintering San Jose scale as log Dc= 0·472 -0·363 log Q. All observations, including those for a 0·1 % mixture and for oil alone which were omitted in the first method, could be fitted satisfactorily in terms of the separate ingredients. For plant bug eggs at LD50, (1+25·6A) B= 4·29 and for San Jose scale (1 + 66·7 A) B= 2·73: in both cases i= 1 and the intensity of synergism 110 and 182 respectively.
The full procedure has also been applied to the constituents of seven samples of Derris root. One sample gave an unaccountably low toxicity and was omitted. The log LD 50 of ether extract for the remaining six was related to the percentage composition of two components in the extract, rotenone (A) and dehydro mixture (B.) Since the toxicity of extract could be expressed almost entirely in terms of these particular two constituents, they were then related to each other by the second method. None of the samples contained a very small proportion of one ingredient, so that several equations were equally applicable, one of them being (1+0–714A) B= 56·1, from which the intensity of synergism was 40.
The problem of measuring synergism in fumigants has been discussed briefly.
1,970 citations
"Predicting the aquatic toxicity of ..." refers background in this paper
...IA is the appropriate conceptual assumption for predicting the joint toxicity of mixtures composed of substances with dissimilar modes of toxic action [8,20], while the CA prediction will often overestimate the toxicity for such mixtures [4,9,21,22]....
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Journal Article•
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TL;DR: In this paper, the authors examined the effect of pool walking on renal function in pregnant women and found that the renin-angiotensin-aldosterone levels were suppressed during pool walking, resulting in higher total urine volume and creatinine clearance.
Abstract: Background This study aimed to examine the effect of pool walking on renal function in pregnant women. Methods Fifteen pregnant women (mean gestational age, 37.8 weeks) walked in a pool (depth 1.3 m) for 1 h. A few days later, they walked on a street for 1 h. Within each activity, the starting and ending levels of plasma renin activity (PRA) and serum aldosterone (SA) were compared using paired t-test. Total urine volume, creatinine clearance, and change in PRA levels between each activity were compared by t-test. Regression coefficients for total urine volume and creatinine clearance during pool walking were estimated by linear regression and additionally controlled for the change in PRA levels. Land walking served as the reference group. Results Within each activity, the renin-angiotensin-aldosterone levels were suppressed during pool walking: the mean starting and ending values of PRA and SA were 6.8 vs. 5.5 ng/mL/h (p=0.002) and 654 vs. 473 pg/mL (p=0.02), respectively. Compared to land walking, the decrease in PRA level was more evident in pool walking (−1.27 vs. 0.81 ng/mL/h, p=0.004), resulting in higher total urine volume and creatinine clearance in pool walking (both p Conclusions Pool walking may temporarily improve renal function in pregnant women, partly through the suppressed renin-angiotensin-aldosterone system. Clinical Trial Registration URL: https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000010618 Unique Identifier: UMIN000009051
1,354 citations
"Predicting the aquatic toxicity of ..." refers background in this paper
...Because extensive information regarding both pharmacodynamics and pharmacokinetics is needed to actually judge the similarity of the mode of action of two or more chemicals [23], the preference of IA above CA based on the known or assumed mode of action has been questioned [23-26]....
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TL;DR: This review seeks to show the crucial role of target sites, interactions with the target site(s), and mechanisms for an adequate and efficient ecotoxicological risk assessment and recommends the use of internal effect concentrations and target site concentrations as a mixture toxicity parameter.
Abstract: In contrast to the general research attitude in the basic sciences, environmental sciences are often goal-driven and should provide the scientific basis for risk assessment procedures, cleanup, and precautionary measures and finally provide a decision support for policy and management. Hence, the prominent role of mechanistic studies in ecotoxicology is not only to understand the impact of pollutants on living organisms but also to deduce general principles for the categorization and assessment of effects. The goal of this review is, therefore, not to provide an exhaustive coverage of modes of toxic action and their underlying biochemical mechanisms but rather to discuss critically the application of this knowledge in ecotoxicological risk assessment. Knowing the mechanism or, at least, the mode of toxic action is indispensable for developing descriptive and predictive models in ecotoxicology. This review seeks to show the crucial role of target sites, interactions with the target site(s), and mechanisms ...
463 citations
"Predicting the aquatic toxicity of ..." refers methods in this paper
...While this classification scheme, being at least partly based on known molecular targets, could with some reason be called a mechanism-ofaction classification [37], we used the more general term mode-of-action also when more detailed mechanistic information is available about the underlying biochemical processes....
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TL;DR: Results indicate that the CA model may be used as a slightly conservative, but broadly applicable model with a relatively small likelihood of underestimating effects due to interactions.
Abstract: Results of published pesticide mixture toxicity experiments conducted with aquatic organisms were compiled and evaluated to assess the accuracy of predictive mixture models. Three types of models were evaluated: Concentration addition (CA), independent action (IA), and simple interaction (SI). The CA model was the most often tested (207 experiments), followed by SI (59) and IA (37). The reviewed experiments are listed in the Supplemental material to provide a resource for future investigators. The predictive accuracy of each model was quantified for each experiment by the model deviation ratio (MDR), which was calculated by dividing the predicted toxicity by the observed toxicity. Eighty-eight percent of all experiments that evaluated the CA model had observed effective concentrations within a factor of 2 of predicted values (MDR values from 0.5–2.0). The median MDR was 1, about 5% of MDRs were less than 0.5, and about 5% were greater than 2, indicating unbiased estimates overall. The predictive accuracy of CA and IA models was influenced, however, by the different modes of action (MOA) of the pesticides. For experiments with pesticides with the same MOA, CA more accurately predicted effective concentrations for more experiments compared to IA, which tended to underpredict toxicity. The IA model was somewhat more accurate than the CA model for most mixtures with different MOAs, but in most cases there were relatively small differences between the models. Additionally, 80% of SI experiments had an MDR value below 2.0 despite a bias towards experiments that are likely to have an interaction. Thus, results indicate that the CA model may be used as a slightly conservative, but broadly applicable model with a relatively small likelihood of underestimating effects due to interactions.
372 citations
"Predicting the aquatic toxicity of ..." refers background or methods or result in this paper
...The strong underrepresentation of fungicides in previous meta-studies [14,15] may therefore at least partly explain their finding of a higher compliance between CA prediction and mixture toxicity observation....
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...The frequency distribution of the model deviation ratio (MDR), which had been introduced by [15], was used as illustration of the uncertainty of the CA prediction....
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...[15] summarized 207 experiments with mixtures of pesticides explicitly testing CA in aquatic organisms....
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...These are exactly the kind of mixtures hardly represented in the literature [14,15]....
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...Yet, two previous studies [14,15] that reviewed available literature on mixture toxicity experiments reported a much higher percentage of cases with such a degree of compliance....
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TL;DR: A U.S. Geological Survey assessment shows widespread occurrence of pesticides, with concentrations in many streams at levels that may have effects on aquatic life and fish-eating wildlife.
Abstract: A U.S. Geological Survey assessment shows widespread occurrence of pesticides, with concentrations in many streams at levels that may have effects on aquatic life and fish-eating wildlife.
362 citations
"Predicting the aquatic toxicity of ..." refers background in this paper
...frequently occur simultaneously in the aquatic environment [4-6]....
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