Predicting the aquatic toxicity of commercial pesticide mixtures

Background: 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. Results: 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. Conclusions: 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. Background The environmental risk assessment of plant protection products (PPP) in the European Union (EU) relates to the individual active substances [1]. Depending on the outcome of the EU risk assessment, an active substance (a.s.) may be included in the positive list (the Annex I of the directive 91/414/EEC). Only PPP containing a.s. included in this Annex I can be authorized at the level of the member states. This principle is retained in the new EU regulation 1107/2009 [2], which repeals directive 91/414/EEC and shall apply from June 2011. The new regulation applies not only to PPP and their a.s., but also to other substances contained in commercial PPP, namely safeners, synergists, co-formulants, and adjuvants [2]. The four last component groups are hereafter designated additives. PPP generally represent a mixture of at least one a.s. combined with a number of different formulation additives [3]. The application of a specific PPP does therefore typically result in a potential exposure of non-target organisms to a mixture of chemicals. In addition to formulation additives, PPP can contain two or more active substances. These so-called combination products thereby constitute the specific case of mixtures of pesticidal a.s. that are deliberately released into the environment. Pesticidal a.s. frequently occur simultaneously in the aquatic environment [4-6]. Consequently, a need has repeatedly been stated to consider the joint effects of pesticide mixtures in the environmental risk assessment [7-9]. Because an experimental testing of all potentially relevant environmental mixtures of pesticides is not feasible simply due to the large number of a.s. and their respective combinations, so-called component-based (in silico) approaches can be considered as an alternative option for a predictive environmental risk assessment that takes joint effects of pesticide mixtures into account. Two basic concepts have been established for predicting additive joint effects based * Correspondence: [email protected] ECT Oekotoxikologie GmbH, Boettgerstr. 2-14, 65439 Flörsheim, Germany Full list of author information is available at the end of the article Coors and Frische Environmental Sciences Europe 2011, 23:22 http://www.enveurope.com/content/23/1/22 © 2011 Coors and Frische; licensee Springer. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. on the known toxicity of the individual mixture components: the concept of concentration addition (CA) for mixtures of substances with similar modes of actions and the concept of independent action (IA, also called response addition) for mixtures of substances with dissimilar modes of action [7,10,11]. In addition, combinations of these two concepts for mixtures of dissimilarly and similarly acting substances have been developed [10,8,12]. None of these concepts can predict non-additive (synergistic or antagonistic) interactions where the mixture components interfere with each other, e.g., through their toxico-kinetic or toxico-dynamic behavior. A recent state-of-the-art report on mixture toxicity summarizes the scientific background of mixture toxicity concepts as well as the implications of existing approaches for a predictive mixture toxicity assessment in the regulation of chemicals [13]. Deneer [14] and Belden et al. [15] provided an overview on published mixture toxicity studies that explicitly tested the power of one or both of the concepts (CA and IA) to predict the joint toxicity of mixtures of pesticides towards aquatic organisms. Their findings demonstrated that in the majority of experiments (80% and more), mixture toxicity predictions based on CA deviated from the observed mixture toxicity by less than factor 2. These studies [14,15] thus offer strong evidence that CA is a reasonably reliable concept to predict the mixture toxicity for a range of different a.s. combinations and various single-species endpoints in aquatic toxicology. The limits of these reviews are related to their databases, which consisted solely of experiments that were designed to explicitly test mixture toxicity. The findings obtained with these experiments have a limited generalization potential for prospective risk assessment purposes because the tested pesticide mixtures do not necessarily reflect environmentally relevant pesticide mixtures or mixtures that are present in commercial PPP, i.e., in combination products. Furthermore, the toxicity data for the individual substances and the mixtures in those studies were derived within the same experimental setting, i.e., presumably with identical test species tested in the same laboratory according to identical test protocols. In contrast, the toxicity data typically available for individual a. s. within the context of the regulatory hazard assessment show much higher heterogeneity with regard to test species, test protocols, and measured toxic effects. By investigating 119 combination products, the present study aims to extend the assessment of compliance between mixture toxicity prediction and observation to a broader range of combinations of pesticides, and specifically to those combinations that are present in commercially applied pesticide mixtures. By using toxicity data from regulatory data bases, the present study explicitly integrates the higher heterogeneity of the data that are typically available to risk assessors and thereby evaluates resulting uncertainty in potential regulatory decisions. As illustrated in Figure 1, the measured aquatic