A problem formulation framework for the application of in silico toxicology methods in chemical risk assessment.

The first step in the hazard or risk assessment of chemicals should be to formulate the problem through a systematic and iterative process aimed at identifying and defining factors critical to the assessment. However, no general agreement exists on what components an in silico toxicology problem formulation (PF) should include. The present work aims to develop a PF framework relevant to the application of in silico models for chemical toxicity prediction. We modified and applied a PF framework from the general risk assessment literature to peer reviewed papers describing PFs associated with in silico toxicology models. Important gaps between the general risk assessment literature and the analyzed PF literature associated with in silico toxicology methods were identified. While the former emphasizes the need for PFs to address higher-level conceptual questions, the latter does not. There is also little consistency in the latter regarding the PF components addressed, reinforcing the need for a PF framework that enable users of in silico toxicology models to answer the central conceptual questions aimed at defining components critical to the model application. Using the developed framework, we highlight potential areas of uncertainty manifestation in in silico toxicology PF in instances where particular components are missing or implicitly described. The framework represents the next step in standardizing in silico toxicology PF component. The framework can also be used to improve the understanding of how uncertainty is apparent in an in silico toxicology PF, thus facilitating ways to address uncertainty.

Ecological risk assessment of the Paraíba River estuary (Brazil): Plan for a tier 1 screening phase for the ecotoxicological line of evidence.

The knowledge produced in temperate regions is still used today to evaluate environmental problems in the tropics, without taking into consideration environmental differences, such as local conditions, the sensitivity and ecology of species, and exposure routes of contaminants, essential for understanding and determining the fate and toxicity of chemicals. Considering that Environmental Risk Assessment (ERA) studies for tropical systems are scarce and need to be adjusted, the present study aims at contributing to the awareness and development of tropical ecotoxicology. The estuary of the Paraíba River in Northeast Brazil was selected as a model study-case, as it is a large estuary, subjected to a heavy human pressure due to the numerous social, economic and industrial activities. The present study describes the framework for the problem formulation phase of the ERA process; it first includes a detailed integration of the scientific information available on the study area, to then derive the conceptual model, and finally present the analysis plan for the tier 1 screening phase. The latter is designed to be fundamentally supported by the ecotoxicological line of evidence, to ascertain, without delay, where and why there are environmental problems (i.e., adverse biological effects); ecotoxicological tools developed in temperate climates will be optimized to assess water quality in a tropical system. In addition to its intrinsic value for protecting the study area, the results of the present study are expected to provide an important baseline for conducting ERA in similar tropical aquatic systems across the globe.

Key challenges and developments in wildlife ecological risk assessment: Problem formulation.

Problem formulation (PF) is a critical initial step in planning risk assessments for chemical exposures to wildlife, used either explicitly or implicitly in various jurisdictions to include registration of new pesticides, evaluation of new and existing chemicals released to the environment, and characterization of impact when chemical releases have occurred. Despite improvements in our understanding of the environment, ecology, and biological sciences, few risk assessments have used this information to enhance their value and predictive capabilities. In addition to advances in organism-level mechanisms and methods, there have been substantive developments that focus on population- and systems-level processes. Although most of the advances have been recognized as being state-of-the-science for two decades or more, there is scant evidence that they have been incorporated into wildlife risk assessment or risk assessment in general. In this article, we identify opportunities to consider elevating the relevance of wildlife risk assessments by focusing on elements of the PF stage of risk assessment, especially in the construction of conceptual models and selection of assessment endpoints that target population- and system-level endpoints. Doing so will remain consistent with four established steps of existing guidance: (1) establish clear protection goals early in the process; (2) consider how data collection using new methods will affect decisions, given all possibilities, and develop a decision plan a priori; (3) engage all relevant stakeholders in creating a robust, holistic conceptual model that incorporates plausible stressors that could affect the targets defined in the protection goals; and (4) embrace the need for iteration throughout the PF steps (recognizing that multiple passes may be required before agreeing on a feasible plan for the rest of the risk assessment). Integr Environ Assess Manag 2022;00:1-16. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Risk management recommendations for environmental releases of gene drive modified insects.

The ability to engineer gene drives (genetic elements that bias their own inheritance) has sparked enthusiasm and concerns. Engineered gene drives could potentially be used to address long-standing challenges in the control of insect disease vectors, agricultural pests and invasive species, or help to rescue endangered species. However, risk concerns and uncertainty associated with potential environmental release of gene drive modified insects (GDMIs) have led some stakeholders to call for a global moratorium on such releases or the application of other strict precautionary measures to mitigate perceived risk assessment and risk management challenges. Instead, we provide recommendations that may help to improve the relevance of risk assessment and risk management frameworks for environmental releases of GDMIs. These recommendations include: (1) developing additional and more practical risk assessment guidance to ensure appropriate levels of safety; (2) making policy goals and regulatory decision-making criteria operational for use in risk assessment so that what constitutes harm is clearly defined; (3) ensuring a more dynamic interplay between risk assessment and risk management to manage uncertainty through closely interlinked pre-release modelling and post-release monitoring; (4) considering potential risks against potential benefits, and comparing them with those of alternative actions to account for a wider (management) context; and (5) implementing a modular, phased approach to authorisations for incremental acceptance and management of risks and uncertainty. Along with providing stakeholder engagement opportunities in the risk analysis process, the recommendations proposed may enable risk managers to make choices that are more proportionate and adaptive to potential risks, uncertainty and benefits of GDMI applications, and socially robust.

Potential use of gene drive modified insects against disease vectors, agricultural pests and invasive species poses new challenges for risk assessment.

Potential future application of engineered gene drives (GDs), which bias their own inheritance and can spread genetic modifications in wild target populations, has sparked both enthusiasm and concern. Engineered GDs in insects could potentially be used to address long-standing challenges in control of disease vectors, agricultural pests and invasive species, or help to rescue endangered species, and thus provide important public benefits. However, there are concerns that the deliberate environmental release of GD modified insects may pose different or new harms to animal and human health and the wider environment, and raise novel challenges for risk assessment. Risk assessors, risk managers, developers, potential applicants and other stakeholders at many levels are currently discussing whether there is a need to develop new or additional risk assessment guidance for the environmental release of GD modified organisms, including insects. Developing new or additional guidance that is useful and practical is a challenge, especially at an international level, as risk assessors, risk managers and many other stakeholders have different, often contrasting, opinions and perspectives toward the environmental release of GD modified organisms, and on the adequacy of current risk assessment frameworks for such organisms. Here, we offer recommendations to overcome some of the challenges associated with the potential future development of new or additional risk assessment guidance for GD modified insects and provide considerations on areas where further risk assessment guidance may be required.

A Non-Convex Economic Dispatch Problem with Point-Valve Effect Using a Wind-Driven Optimisation Approach.

This study presents the efficiency of the wind-driven optimisation (WDO) approach in solving non-convex economic dispatch problems with point-valve effect. The best economic dispatch for a power system is one wherein the system can generate energy at a low cost. The calculation of the generating cost is subject to a number of constraints, such as the power demand for the entire system and the generation limit for each generator unit in the system. In addition, the system should also produce low power loss. The WDO optimisation technique is developed based on the concept of natural wind movement, which serves as a stabiliser to equalise the inequality of air pressure in the atmosphere. One major advantage of WDO over other techniques is its search accuracy. The proposed algorithm has been implemented in two systems, namely, the 10-generator and 40-generator systems. Both systems were tested in a Matlab environment. To highlight the capabilities of WDO, the results using this proposed technique are compared with the results obtained using flower pollination algorithm, moth flame optimisation, particle swarm optimisation and evolutionary programming techniques to determine the efficiency of the proposed approach in solving economic dispatch. The simulation results show the capability of WDO in determining the optimal power generation value with minimum generation cost and low rate of power loss.

Open Science in regulatory environmental risk assessment.

A possible way to alleviate the public skepticism toward regulatory science is to increase transparency by making all data and value judgments used in regulatory decision making accessible for public interpretation, ideally early on in the process, and following the concepts of Open Science. This paper discusses the opportunities and challenges in strengthening Open Science initiatives in regulatory environmental risk assessment (ERA). In this discussion paper, we argue that the benefits associated with Open Science in regulatory ERA far outweigh its perceived risks. All stakeholders involved in regulatory ERA (e.g., governmental regulatory authorities, private sector, academia, and nongovernmental organizations), as well as professional organizations like the Society of Environmental Toxicology and Chemistry, can play a key role in supporting the Open Science initiative, by promoting the use of recommended reporting criteria for reliability and relevance of data and tools used in ERA, and by developing a communication strategy for both professionals and nonprofessionals to transparently explain the socioeconomic value judgments and scientific principles underlying regulatory ERA. Integr Environ Assess Manag 2021;17:1229-1242. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Gene Drive-Modified Organisms: Developing Practical Risk Assessment Guidance.

Risk assessors, risk managers, developers, potential applicants, and other stakeholders at many levels discuss the need for new or further risk assessment guidance for deliberate environmental releases of gene drive-modified organisms. However, preparing useful and practical guidance entails challenges, to which we offer recommendations based on our experience drafting guidance.

Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives.

Advances in molecular and synthetic biology are enabling the engineering of gene drives in insects for disease vector/pest control. Engineered gene drives (that bias their own inheritance) can be designed either to suppress interbreeding target populations or modify them with a new genotype. Depending on the engineered gene drive system, theoretically, a genetic modification of interest could spread through target populations and persist indefinitely, or be restricted in its spread or persistence. While research on engineered gene drives and their applications in insects is advancing at a fast pace, it will take several years for technological developments to move to practical applications for deliberate release into the environment. Some gene drive modified insects (GDMIs) have been tested experimentally in the laboratory, but none has been assessed in small-scale confined field trials or in open release trials as yet. There is concern that the deliberate release of GDMIs in the environment may have possible irreversible and unintended consequences. As a proactive measure, the European Food Safety Authority (EFSA) has been requested by the European Commission to review whether its previously published guidelines for the risk assessment of genetically modified animals (EFSA, 2012 and 2013), including insects (GMIs), are adequate and sufficient for GDMIs, primarily disease vectors, agricultural pests and invasive species, for deliberate release into the environment. Under this mandate, EFSA was not requested to develop risk assessment guidelines for GDMIs. In this Scientific Opinion, the Panel on Genetically Modified Organisms (GMO) concludes that EFSA's guidelines are adequate, but insufficient for the molecular characterisation (MC), environmental risk assessment (ERA) and post-market environmental monitoring (PMEM) of GDMIs. While the MC,ERA and PMEM of GDMIs can build on the existing risk assessment framework for GMIs that do not contain engineered gene drives, there are specific areas where further guidance is needed for GDMIs.

Advancing ecological risk assessment on genetically engineered breeding stacks with combined insect-resistance traits.

To inform the ecological risk assessment (ERA) of a transgenic crop with multiple insecticidal traits combined by conventional breeding (breeding stack), a comparative field study is customarily conducted to compare transgenic protein concentrations in a breeding stack to those in corresponding component single events used in the breeding process. This study tests the hypothesis that transgenic protein expression will not significantly increase due to stacking, such that existing margins of exposure erode to unacceptable levels. Corroboration of this hypothesis allows for the use of existing non-target organism (NTO) effects tests results, where doses were based on the estimated environmental concentrations determined for a component single event. Results from over 20 studies comparing expression profiles of insecticidal proteins produced by commercial events in various combinations of conventionally-bred stacks were examined to evaluate applying previously determined no-observed-effect concentrations (NOECs) to stack ERAs. This paper presents a large number of tests corroborating the hypothesis of no significant increase in insecticidal protein expression due to combination by conventional breeding, and much of the variation in protein expression is likely attributed to genetic and environmental factors. All transgenic protein concentrations were well within conservative margins between exposure and corresponding NOEC. This work supports the conclusion that protein expression data generated for single events and the conservative manner for setting NTO effects test concentrations allows for the transportability of existing NOECs to the ERA of conventionally-bred stacks, and that future tests of the stated hypothesis are no longer critically informative for ERA on breeding stacks.