Modernizing persistence-bioaccumulation-toxicity (PBT) assessment with high throughput animal-free methods.

The assessment of persistence (P), bioaccumulation (B), and toxicity (T) of a chemical is a crucial first step at ensuring chemical safety and is a cornerstone of the European Union's chemicals regulation REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals). Existing methods for PBT assessment are overly complex and cumbersome, have produced incorrect conclusions, and rely heavily on animal-intensive testing. We explore how new-approach methodologies (NAMs) can overcome the limitations of current PBT assessment. We propose two innovative hazard indicators, termed cumulative toxicity equivalents (CTE) and persistent toxicity equivalents (PTE). Together they are intended to replace existing PBT indicators and can also accommodate the emerging concept of PMT (where M stands for mobility). The proposed "toxicity equivalents" can be measured with high throughput in vitro bioassays. CTE refers to the toxic effects measured directly in any given sample, including single chemicals, substitution products, or mixtures. PTE is the equivalent measure of cumulative toxicity equivalents measured after simulated environmental degradation of the sample. With an appropriate panel of animal-free or alternative in vitro bioassays, CTE and PTE comprise key environmental and human health hazard indicators. CTE and PTE do not require analytical identification of transformation products and mixture components but instead prompt two key questions: is the chemical or mixture toxic, and is this toxicity persistent or can it be attenuated by environmental degradation? Taken together, the proposed hazard indicators CTE and PTE have the potential to integrate P, B/M and T assessment into one high-throughput experimental workflow that sidesteps the need for analytical measurements and will support the Chemicals Strategy for Sustainability of the European Union.

Social Perception of Systemic Risks.

The article distinguishes between two types of risks: conventional and systemic risks. Conventional risks can be contained in space and time, follow linear cause-effect relationships and can be addressed with effective and pointed interventions into the cause-effect chain. Systemic risks, however, are characterized by high complexity, transboundary effects, stochastic relationships, nonlinear cause-effect patterns with tipping points, and are often associated with less public attention than they require. The article addresses the reasons why systemic risks seem to be attenuated in public perception. The article goes on to consider how the social amplification of risk framework is useful in the context of systemic risks and describes needed extensions of that framework. It identifies practical tools for assessing the significance of perceptions for systemic risk situations. Finally, it argues that a graphic representation and simulation of evolving systemic risks and potential countermeasures as well as a participatory deliberative approach of inclusive risk governance are suitable governance strategies for preventing, mitigating, or managing systemic risks.

Systemic Risks from Different Perspectives.

Systemic risks are characterized by high complexity, multiple uncertainties, major ambiguities, and transgressive effects on other systems outside of the system of origin. Due to these characteristics, systemic risks are overextending established risk management and create new, unsolved challenges for policymaking in risk assessment and risk governance. Their negative effects are often pervasive, impacting fields beyond the obvious primary areas of harm. This article addresses these challenges of systemic risks from different disciplinary and sectorial perspectives. It highlights the special contributions of these perspectives and approaches and provides a synthesis for an interdisciplinary understanding of systemic risks and effective governance. The main argument is that understanding systemic risks and providing good governance advice relies on an approach that integrates novel modeling tools from complexity sciences with empirical data from observations, experiments, or simulations and evidence-based insights about social and cultural response patterns revealed by quantitative (e.g., surveys) or qualitative (e.g., participatory appraisals) investigations. Systemic risks cannot be easily characterized by single numerical estimations but can be assessed by using multiple indicators and including several dynamic gradients that can be aggregated into diverse but coherent scenarios. Lastly, governance of systemic risks requires interdisciplinary and cross-sectoral cooperation, a close monitoring system, and the engagement of scientists, regulators, and stakeholders to be effective as well as socially acceptable.