SETAC Globe - Environmental Quality Through Science
5 October 2017
Volume 18 Issue 10

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Mixtures Risk Assessment: Outcomes From the Recent Focused Topic Meeting

Eric Van Genderen, Mary Ann Ottinger, Thomas Backhaus, Amy Beasley, Kevin Brix, Ed Furlong, Mark Johnson – Risk Assessment of Chemical Mixtures Focus Topic Meeting Steering Committee, SETAC North America

SETAC MixturesMixtures research has become the fundamental and practical nexus between novel analytical tools, in-depth ecotoxicological studies, screening procedures and pathway-based concepts.

The SETAC North America Focused Topic Meeting (FTM) on Risk Assessment of Chemical Mixtures was held from 6–8 September in Denver, Colorado. Nearly 100 scientists representing 10 countries and a spectrum of disciplines attended the three-day meeting. The FTM provided a review on the state of the science on the fate and effects of chemical mixtures, spanning all chemical classes, levels of biological organization and facets of the risk assessment paradigm.

By design, the FTM built upon previous SETAC workshops and activities related to mixtures by challenging speakers and participants to identify pragmatic and harmonized solutions for evaluating environment or health risks from mixtures. To accommodate such a broad range of interests, the meeting was divided into a series of five sessions representing the risk assessment framework – Problem Formulation, Exposure Assessment, Effects Assessment, Risk Assessment and Case Studies. Each session built upon the previous. The format was well-received and allowed for several facilitated discussion periods throughout the program.

These discussions proved to be an essential ingredient for identifying and exploiting linkages between different disciplines and interests. In particular, possibilities for bridging scientific evidence to policy and regulatory options were explored. In several cases, discussions led to the synthesis of ideas for aligning common objectives among stakeholders (e.g., data accessibility for regulators and database developers) and identifying where new techniques and data networks may inform the risk assessment process.

Below are some messages that came out of the interactions as well as session-specific highlights:

  • There is the need for developing, testing and implementing holistic (“One Health”) risk assessment protocols that consider complementary paradigms (effects- or exposure-based, organ- or system-specific, etc.)
  • Data access and resource sharing helps everybody! Effort is needed to promote transparency using centralized gateways and data hubs
  • Mixture data must be thoughtfully interpreted using statistics and examination of exposure and endpoint relevance
  • Deviation between predicted and observed mixture toxicity is consistently within a factor of 2–3 from additivity, a pattern that is largely independent of the type of mixture analyzed or ecotoxicological endpoints under observation
  • Concentration addition (CA) is appropriately conservative. However, the CA model is generally limited to screening (hazard) assessments due to its inability to make dose–response predictions

Problem Formulation

The Problem Formulation session provided overviews of mixture terminology and research approaches, regulatory frameworks, inter-disciplinary connections to emerging science (e.g., adverse outcome pathways and -omics), and societal considerations for an ever-increasing chemical dependence. The current challenges are threefold:

  1. Advancement of analytical techniques has led to increased data dependence and reliance on computational modeling
  2. Modeling complexity (and uncertainty) increases with increasing exposure scenarios
  3. Data accessibility is equally challenging for national or regional chemical management systems and database developers alike

Exposure Assessment

This session provided overviews of analytical techniques, monitoring programs and approaches for fingerprinting complex mixtures in laboratory and environmental media. New tools and technologies are helping expand knowledge of mixture complexity, but necessary cheminformatics are only in their infancy. Taking cues from other data-driven assessments (metabolomics) will efficiently assist development of interpretive paradigms. In addition, abiotic considerations related to land use, climate change and contaminant profiles must be further understood.

Effects Assessment

The Effects Assessment session provided an overview of the characterization and interpretation of biological effects of mixtures on health and the environment. At the sub-cellular level, researchers reported investigations into quantitative toxicogenomics and pathway-based approaches. Challenges at higher levels of organization were also discussed, including linkages between molecular pathways and phenotypic effects, and examination of exposure and endpoint relevance (species, endpoint, exposure duration, chemical combination and ratios, etc.). In general, it was evident that non-additive responses may result from both kinetic (e.g., compound facilitated transport, enzyme induction) and dynamic (e.g., competition for receptor site, enhanced cellular response) interactions.

Risk Assessment

The session provided an overview of frameworks and approaches for comprehensively assessing and managing the fate, transport and effects of chemical mixtures. The session balanced between practical applications of mixture models in risk assessments and investigating the usefulness of increasingly complex tools, such as pathway-based approaches. Generally, grouping strategies and tiered approaches were favored, for both organics and inorganics, in order to manage workflow and protection goals. In addition, the dichotomy between both prospective (product regulations) and retrospective (risk assessment) applications of mixtures research was discussed.

Case Studies

Case studes provided an overview of field applications using scientific methods and tools for characterizing environmental risks of complex chemical mixtures. In many cases, despite the complexity of the chemical signature, only a few substances are typically responsible for observed or predicted effects. Furthermore, there is the need for developing, testing and implementing more holistic (“One Health”) risk assessment protocols that consider complementary paradigms (effects- or exposure-based, organ- or system-specific, etc.).

Environmental Toxicology & Chemistry Focus Article

A Focus Article is currently being developed by the FTM steering committee.  Much has been done to improve our understanding of the effects of multiple-substance exposures on environmental and human health (e.g., exposome). The primary goal of this paper will be to bring recent information on mixtures to the forefront with a focus on risk assessment and new tools that can be further refined and investigated.

Authors’ contact information:,,,, and

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