Proposal for environmental mixture risk assessment in the context of the biocidal product authorization in the EU

Abstract

Background: The EU Council and Parliament recently agreed on a new regulation that will implement a new EU-wide, harmonized system for the authorization for biocidal products. Such products are in most cases multi-component mixtures of one or more active substances plus a range of co-formulants that serve different purposes, e.g. as stabilizers or preservatives. They are only allowed on the European market if their intended use does not lead to unacceptable risks for the environment. Consequently, the assessment of possible combination effects is a critically important step during the regulatory environmental risk assessment of biocidal products. However, no specific guidance is at hand on how combination effects should be accounted for during the regulatory environmental risk assessment of biocidal products. Results and Conclusions: A tiered approach was developed that accommodates different data situations, optimizes resource usage, limits biotesting as far as possible and ensures adequate protection of the environment. It mainly builds on using Concentration Addition as a component-based approach for mixture toxicity prediction, complemented by whole product tests where appropriate. Concentration Addition is either approximated by summing up PEC/PNEC ratios or as sums of toxic units. The competing concept of Independent Action was assessed as not being suitable for incorporation into a tiered approach without explicit confirmatory studies, as it might otherwise lead to an underestimation of the actual environmental risk.

Predicting acute and chronic effects of wood preservative products in daphnia magna and pseudokirchneriella subcapitata based on the concept of concentration addition

“…While the prediction–observation comparisons based on EC10 values carried higher reliability because of available and reasonably tight confidence intervals, MDRs derived from NOEC values resulted in similar conclusions despite the inherent problem of assuming (incorrectly) identical effect levels for the used NOEC values. The 2 examples of mixtures assessed in a chronic test provided some evidence that the usage of NOEC instead of ECx values as suggested for pragmatic reasons does not introduce much greater error.…”

Introduction

“…However, at such low doses, the interpretation of data is tricky and controversial, as illustrated by the conclusions derived by different groups of experts (Kortenkamp et al, 2009; SCCS, SCHER, SCENIHR, 2011) from a study with fish (Hermens et al, 1985), two studies with algae (Walter et al, 2002;Faust et al, 2003), and one study using an in vitro cellular test (Payne et al, 2001). Synergistic interactions have been documented for pesticides considering both biocidal products (Bjergager et al, 2011;Backhaus et al, 2013) and mixtures commonly detected in aquatic habitats (Laetz et al, 2009). They include toxicokinetic, metabolic, and toxicodynamic interactions.…”

Assessing the risks posed by mixtures of chemicals in freshwater environments: case study of Lake Geneva, Switzerland

“…Furthermore, even for heterogeneous mixtures with similarly and dissimilarly acting substances, the predictions with CA and IA give an adequate range of the mixture toxicity, within which observed effects are found . CA is often proposed as ‘worst case’ for assessing the mixture effects of co‐occurring substances, because it usually gives predictions of mixture toxicity higher than IA. Therefore, despite the simplicity of the mixture models described, and the difficulty of fulfilling the assumptions the make, for example, by being certain that the mode of action between the substances is strictly similar or strictly dissimilar, these models are now largely adopted to predict mixture effects of multiple compounds.…”

“…Furthermore, CA provides good to excellent predictions of the observed mixture toxicity for many studies, within a small range of deviation (observed toxicity rarely exceeding predictions by a factor of 2), even regardless of the mode of action of substances in the mixture, i.e., when CA is applied with substances having dissimilar modes of action. This range can be used as a security factor for the mixture effect predictions that may account for potential synergistic interactions . Therefore, CA is often recommended as the default precautionary model as mentioned above.…”

“…Therefore, this methodology is considered as a ‘worst case’ assessment and may be used as a first level environmental risk assessment for chemical mixtures . A similar approach was also recently proposed to assess the environmental risk for biocidal products composed of different chemicals during the EU authorization process or to assess the mixture risk of chemicals including their transformation products …”