Classic and temporal mixture synergism in terrestrial ecosystems: Prevalence, mechanisms and impacts

Invertebrate species living above and below ground are central to terrestrial food webs and key contributors to carbon cycling, soil fertility and pest control. Many of these important species are highly vulnerable to chemical pollution. The range of chemicals these species are regularly exposed to is becoming increasingly complex. For example, farmers now use 50% more types of pesticide on arable crops than they did 15 years ago and an ever-increasing diversity of chemicals enter ecosystems from our domestic and industrial wastes. A challenge for chemical producers, users and regulators is to find ways to maximise the benefits of chemical use, while minimising any negative effects. Scientific research to support better 'ecological risk assessment' of chemicals is central to meeting this challenge.

Many of the chemicals we use today come from new, less well studied, compound classes that can affect biological processes, in diverse ways, in different species. Our current lack of knowledge about these chemicals makes their ecological effects difficult to assess. Things become more complicated when we realise that pollutants almost always occur as mixtures. If we want to properly to address and avoid unwanted chemical impacts, we need to better understand and take account of chemical mixtures.

The most commonly used way to predict the likely effects of pollutant mixtures on invertebrates and ecosystems assumes that chemicals do not interact with each other and that, therefore, their toxicities can be added together. This relatively simple 'additive' approach has been shown to work most of the time. However, for a substantial proportion of mixtures (up to 20% depending on chemical classes included), the observed effects are worse than expected based on addition. Where such 'synergy' occurs, environmental protection policies for mixtures based on additivity will underestimate actual effects (see Fig. 1, Case for Support). Clearly this is a problem. To address it, we need to identify interactive chemical mixtures and predict the most likely causes of synergy. In turn, this requires us to understand how the mechanisms of toxicity of different chemicals in a mixture interplay with the different biochemical, physiological and ecological traits of exposed species to cause synergy. The main aim of this project is to gain and apply this knowledge.

Our own research has identified some chemical mixtures that are more likely to show synergy, with higher levels of toxicity to exposed invertebrates. For example, where: (a) a chemical affects the way that another is detoxified or activated; or (b) a chemical increases the biological uptake of another chemical; or (c) prior exposure to a chemical changes the biological toxicity of another chemical, depending on the timing of exposure. However, we are very far from understanding all cases. Thus, this project aims to transform our ability to identify, quantify and predict the potential for synergy in common terrestrial pollution scenarios (agrochemical use, waste inputs).

Working with partner agencies, we will identify potentially synergistic chemical pollutant mixtures, relevant to terrestrial ecosystems, and conduct experiments to test their effects on a range of invertebrate species. When we observe synergy in one species, other species will be tested to discover if this is a general effect. Biochemical and genetic methods will be used to identify mechanisms of toxicity and species traits associated with synergism, integrating this information to develop models and new predictive tools. To ensure the effects we see in the laboratory are relevant to the field, we will conduct studies in outdoor systems to test for the presence of synergism in natural communities. Ultimately, we will use our findings to produce a POSTnote 'White paper' detailing how future risk assessment policies can explicitly consider synergism to support environmental protection.

Multiple pesticide and waste inputs to terrestrial ecosystems create a wide range of mixture exposure scenarios. Being able to understand and predict the effects to these chemical cocktails is, therefore, critical for evidence based chemical management to support sustainable land management. There are a significant portion of mixtures for which synergistic (i.e. greater than additive) effects may occur. This potential for synergism creates one of the greatest challenges for mixtures risk assessment, because it is currently difficult to quantify and even harder to predict. Our mechanistically based predictions of synergism will be transformative for regulatory assessments, as they will address the deficits of the additive models commonly used to date that simply ignore such effects.

By engaging directly with regulators (project partners EA, CRD and DEFRA) our research will provide an evidence base to support legislation and regulation in the long term and so will be of considerable interest to the major agencies involved in chemical management in the UK (EA, CRD, DEFRA, SEPA, Natural England) and Europe (EFSA and ECHA). In tandem, engagement with the framing community (e.g. through project partners LEAF) will help to raise awareness of mixture effects and help ensure that any changes in practice are realistic, achievable and will support sustainable intensification through responsible agrochemical management.

We will be supplementing the expertise of our research team through the formation of an advisory group of international experts in the field: T. Jager (DEBtox Modelling), N. Cedergreen (Chemical Mixtures), D. Roelofs (Ecotoxicology) and K. Birkhofer (Ecosystem function); together with representatives from regulation (CRD - M. Reed/M. Clook) and the farming community (LEAF - L. Tippin). In addition key stakeholders have been incorporated as project partners, covering regulators (Dr M. Reed/DrM. Clook, CRD; Dr D. Ashton and Dr S. Hoy, EA; Dr S. Morris, Defra; Dr T. Gant, PHE) and land managers (L. Tippin, A. Midmer, LEAF). This partnership will allow us to input into product stewardship and regulation, as well as developing advice on usage profiles that limit the potential for unwanted synergistic effects.

Our impact outputs will be delivered through using the following routes as detailed in WP5 and our Impact Plan.

Workshops:
1. Prioritise mixture selection and overall design: Participation; Research team, Partner/advisory board.
2. Refine novel approaches for ecological risk assessment: Organized in partnership with SETAC; Participation; Regulators (e.g. CRD, EFSA, US-EPA) and the chemical industry (e.g. Syngenta, Bayer, BASF, ADAMA).

Written outputs:
High impact scientific publications (open access). POSTnote 'White paper': Road map for incorporating additive and synergistic effects into ecological risk assessment.

Training course:
1) Mixture toxicity analysis; 2) Physiological modelling for chemical mixtures; 3) Mechanistic traits in mixture toxicology; 4) Integration of ecotoxicological impact prediction into arable systems management.

Practitioner focused town meetings:
Interactive meetings to discuss the use and impacts of mixtures on farming practice and outcomes (pest control strategies, crops yields, ecosystem services and farmland biodiversity). Organised in partnership with LEAF. Participation; Members of SIRN network, ASSIST platform, NFU.

Web content and social media:
Page on CEH web site linked to other institutional pages; active project twitter feed; YouTube video material on synergism and mixture risk assessment practice.

Risk management guidance:
Outreach material developed in partnership with regulatory agencies and industry and user organisation partners on practice and challenges in mixtures risk assessment and management.