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The purpose of toxicology is to protect human health and the environment. To support this, the Organisation for Economic Co-operation and Development (OECD), operating via its Extended Advisory Group for Molecular Screening and Toxicogenomics (EAGMST), has been developing the Adverse Outcome Pathway (AOP) approach to consolidate evidence for chemical toxicity spanning multiple levels of biological organization. The knowledge transcribed into AOPs provides a structured framework to transparently organize data, examine the weight of evidence of the AOP, and identify causal relationships between exposure to stressors and adverse effects of regulatory relevance. The AOP framework has undergone substantial maturation in the field of hazard characterization of chemicals over the last decade, and has also recently gained attention from the radiation community as a means to advance the mechanistic understanding of human and ecological health effects from exposure to ionizing radiation at low dose and low dose-rates. To fully exploit the value of such approaches for facilitating risk assessment and management in the field of radiation protection, solicitation of experiences and active cooperation between chemical and radiation communities are needed. As a result, the Radiation and Chemical (Rad/Chem) AOP joint topical group was formed on June 1, 2021 as part of the initiative from the High Level Group on Low Dose Research (HLG-LDR). HLG-LDR is overseen by the OECD Nuclear Energy Agency (NEA) Committee on Radiation Protection and Public Health (CRPPH). The main aims of the joint AOP topical group are to advance the use of AOPs in radiation research and foster broader implementation of AOPs into hazard and risk assessment. With global representation, it serves as a forum to discuss, identify and develop joint initiatives that support research and take on regulatory challenges.

In Beaton et al., (2020), a cross-sectional study design was used to demonstrate that levels of self-compassion were lower in people with high traits of ADHD, compared to people with low traits of ADHD. This was partially explained by the levels of criticism that participants perceived. However, there are a number of restrictions with this study design. For example, the study relies on explicit measures that are vulnerable to a number of biases including recall bias, social-desirability, self-deceptive positivity and common method bias. Yet, trait self-compassion is viewed as an implicit - unconscious, habitual and automatic trait, which influences individuals to be more accepting and less judgemental towards intrinsic and extrinsic stressors. Therefore, we argue that a measure of self-compassion should be attainable through an implicit task, that is free from the interference of conscious cognition observed in explicit measures. Moreover, the study measured perceived criticism, and therefore it is inconclusive whether self-compassion is associated with levels of criticism perceived or objective levels of criticism. Consequently, the proposed study will use an experimental design to expand on the initial findings of Beaton et al., (2020) in two ways; firstly, it aims to determine if self-compassion is lower at a trait level in people with ADHD and secondly, it aims to manipulate levels of criticism to observe if there is a direct effect of criticism on implicit self-compassion.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as a result of natural cellular processes, intracellular signaling, or as adverse responses associated with diseases or exposure to oxidizing chemical and non-chemical stressors. The action of ROS and RNS, collectively referred to as reactive oxygen and nitrogen species (RONS), has recently become highly relevant in a number of adverse outcome pathways (AOPs) that capture, organize, evaluate and portray causal relationships pertinent to adversity or disease progression. RONS can potentially act as a key event (KE) in the cascade of responses leading to an adverse outcome (AO) within such AOPs, but are also known to modulate responses of events along the AOP continuum without being an AOP event itself. A substantial discussion has therefore been undertaken in a series of workshops named “Mystery or ROS” to elucidate the role of RONS in disease and adverse effects associated with exposure to stressors such as nanoparticles, chemical, and ionizing and non-ionizing radiation. This review introduces the background for RONS production, reflects on the direct and indirect effects of RONS, addresses the diversity of terminology used in different fields of research, and provides guidance for developing a harmonized approach for defining a common event terminology within the AOP developer community.

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The AOP framework has undergone substantial maturation in the field of hazard characterization of chemicals over the last decade, and has also recently gained attention from the radiological protection and research communities as a means to advance the mechanistic understanding of human and ecological health effects from exposure to ionizing radiation at low dose and low dose-rates. To fully exploit the value of such approaches for facilitating risk assessment and management in the field of radiation protection, solicitation of experiences and active cooperation between chemical and radiation communities are needed. As a result, the Radiation and Chemical (Rad/Chem) AOP joint topical group was formed on June 1, 2021 as part of the initiative from the High Level Group on Low Dose Research (HLG-LDR). HLG-LDR is overseen by the OECD Nuclear Energy Agency (NEA) Committee on Radiological Protection and Public Health (CRPPH). The main aims of the joint AOP topical group are to advance the use of AOPs in radiation research and foster broader implementation of AOPs into hazard and risk assessment. With global representation, it serves as a forum to discuss, identify and develop joint initiatives that support research and take on regulatory challenges. The Rad/Chem AOP joint topical group aims to actively liaise with the OECD EAGMST AOP developmental program to collectively advance areas of common interest and, specifically, provide recommendations for harmonization of the AOP framework to accommodate non-chemical stressors, such as radiation. The current presentation will provide an overview of the mission and work of the Topical Group., The 1st Adverse Outcome Pathways Community of Practice Symposium 2022

The objective of this thesis was to characterize the microbiology of subsurface fracture water at a location within the Canadian Shield considered as a prospective host site for a geologic repository. Repository performance and long-term safety predictions for geologic confinement of radioactive waste rely on understanding the natural microbial processes that occur within a host formation; however, the inaccessibility of the crystalline terrestrial subsurface means that this habitat is difficult to explore and as such is largely unknown. The area characterized is located within the boundary of the Chalk River Laboratories site, situated within the Central Gneissic Belt of the Grenville province (formed 1.5 and 1.0 ba years before present); the site is also situated within the Ottawa-Bonnechere graben (formed 0.5 ba before present). Fracture water was accessed from one 34 m deep open drill hole and six cased and sealed drill holes; the Westbay Multilevel Groundwater Monitoring system preserved the natural fracture flow enabling discrete fracture water sampling at multiple depths via each of the sealed drill holes. This thesis combined multiple datasets in an exploratory analysis for drivers of subsurface microbial assembly within an ecological framework of selection, dispersal, drift and diversification across two spatial extents: 25 km3 and 1 km3. The outcomes of the multivariate analyses, null models and generalized linear models identified prospective source waters and distributional relationships of total and viable cell counts with fracture water sulfate and manganese. Random processes (dispersal, drift and diversification) explain close to 50% of the variance of the phylogenetic beta diversity among the component taxa. Selection associated with differential abundance of the 16S rRNA gene V4 region and spatial and environmental factors identified sulfate and organic carbon plus manganese and a spatial coefficient. Selection by differential abundance was not a major driver of community assembly; accounting for ~4% each of the total abundances linked to sulfate and manganese. At a spatial scale less than 1 km3, it may be possible to identify either greater significance for sulfate and manganese or to identify additional environmental factors linked to selection. Demonstrated metabolism included nitrate reduction (common across all sampling locations and at each sampling campaign) and sulfate reduction (observed at one sampling campaign). The distributions of total and viable cell counts correspond with the distributions of sulfate and manganese, respectively. The fracture water was a source of sulfate and manganese, but not a source of nitrate. A limited analysis of rock porewater identified sulfate and nitrogen compounds (ammonia, nitrite and nitrate) in parts per million concentrations, suggesting that the rock is a source of these compounds, and this finding warrants an assessment of rock weathering as a driver of selection at these sampling locations. Phylogenetic relationships across sampling locations showed that the component taxa were more closely related than expected by chance; this pattern suggests that, at the spatial scale of the analysis, competitive exclusion was not a driver of subsurface community assembly. Co-existence of close relatives may be biologically relevant—and thus be a sign of diversification—or this pattern may reflect the 16S rRNA gene copy number combined with intra-genomic heterogeneity greater than the 97% sequence similarity threshold for binning sequencing reads into organizational taxonomical units (OTUs). The distribution of genes for energy metabolism was uniform across all sampling locations. A metatranscriptome assessment would help differentiate between the genes present from the genes expressed. Testing for a wider range of demonstrated metabolic capabilities would support RNA-level gene expression analyses. Overall, applying the ecological framework of four main drivers of community assembly show that, at the spatial scale of the sampling, up to 50% of the variance among community dynamics reflect randomness. Approximately ~1% of the total abundance was linked to measured metabolism; at smaller spatial scales, ~8% of the total 16S rRNA gene abundance was linked to differential abundances across—potentially connected--sampling locations. By sampling at smaller spatial scales, therefore, it may be possible to discern additional metabolic and selective processes. These data will inform models for the performance and long-term safety of geological repositories.

Decades of research to understand the impacts of various types of environmental occupational and medical stressors on human health have produced a vast amount of data across many scientific disciplines. Organizing these data in a meaningful way to support risk assessment has been a significant challenge. To address this and other challenges in modernizing chemical health risk assessment, the Organisation for Economic Cooperation and Development (OECD) formalized the adverse outcome pathway (AOP) framework, an approach to consolidate knowledge into measurable key events (KEs) at various levels of biological organisation causally linked to disease based on the weight of scientific evidence (http://oe.cd/aops). Currently, AOPs have been considered predominantly in chemical safety but are relevant to radiation. In this context, the Nuclear Energy Agency’s (NEA’s) High-Level Group on Low Dose Research (HLG-LDR) is working to improve research co-ordination, including radiological research with chemical research, identify synergies between the fields and to avoid duplication of efforts and resource investments. To this end, a virtual workshop was held on 7 and 8 October 2020 with experts from the OECD AOP Programme together with the radiation and chemical research/regulation communities. The workshop was a coordinated effort of Health Canada, the Electric Power Research Institute (EPRI), and the Nuclear Energy Agency (NEA). The AOP approach was discussed including key issues to fully embrace its value and catalyze implementation in areas of radiation risk assessment. A joint chemical and radiological expert group was proposed as a means to encourage cooperation between risk assessors and an initial vision was discussed on a path forward. A global survey was suggested as a way to identify priority health outcomes of regulatory interest for AOP development. Multidisciplinary teams are needed to address the challenge of producing the appropriate data for risk assessments. Data management and machine learning tools were highlighted as a way to progress from weight of evidence to computational causal inference.

Decades of research to understand the impacts of various types of environmental occupational and medical stressors on human health have produced a vast amount of data across many scientific disciplines. Organizing these data in a meaningful way to support risk assessment has been a significant challenge. To address this and other challenges in modernizing chemical health risk assessment, the Organisation for Economic Cooperation and Development (OECD) formalized the adverse outcome pathway (AOP) framework, an approach to consolidate knowledge into measurable key events (KEs) at various levels of biological organisation causally linked to disease based on the weight of scientific evidence (http://oe.cd/aops). Currently, AOPs have been considered predominantly in chemical safety but are relevant to radiation. In this context, the Nuclear Energy Agency’s (NEA’s) High-Level Group on Low Dose Research (HLG-LDR) is working to improve research co-ordination, including radiological research with chemical research, identify synergies between the fields and to avoid duplication of efforts and resource investments. To this end, a virtual workshop was held on 7 and 8 October 2020 with experts from the OECD AOP Programme together with the radiation and chemical research/regulation communities. The workshop was a coordinated effort of Health Canada, the Electric Power Research Institute (EPRI), and the Nuclear Energy Agency (NEA). The AOP approach was discussed including key issues to fully embrace its value and catalyze implementation in areas of radiation risk assessment. A joint chemical and radiological expert group was proposed as a means to encourage cooperation between risk assessors and an initial vision was discussed on a path forward. A global survey was suggested as a way to identify priority health outcomes of regulatory interest for AOP development. Multidisciplinary teams are needed to address the challenge of producing the appropriate data for risk assessments. Data management and machine learning tools were highlighted as a way to progress from weight of evidence to computational causal inference.