Meeting record – February 17 and 18, 2021

Chemicals Management Plan Science Committee

Attendees

Committee members

• Miriam Diamond (co-chair)
• Mike Rasenberg (co-chair)
• Jon Arnot
• Niladri Basu
• Richard Becker
• Weihsueh Chiu
• Elaine Cohen Hubal
• Michelle Embry
• Geoff Granville

Ad hoc members

• Bob Diderich [Head of Division, Environment, Health and Safety Division, Organisation for Economic Co-operation and Development (OECD)]
• Cristina de Avila (Head of Unit, Sustainable Chemicals, Directorate-General for Environment, European Commission)
• José Tarazona [Senior Scientific Officer, Scientific Committee and Emerging Risk Unit, European Food Safety Authority (EFSA)]
• Jeffery Morris (Chemical Policy Consultant, Jeff Morris Solutions LLC)

Government of Canada officials

• David Morin [Director General (DG), Safe Environments Directorate (SED), Healthy Environments and Consumer Safety Branch (HECSB), Health Canada (HC)] (Day 1)
• Nicole Davidson [Director, Existing Substances Risk Assessment Bureau (ESRAB), SED, HECSB, HC]
• Marc Demers [Acting Director, Ecological Assessment Division (EAD), Science and Risk Assessment Directorate (SRAD), Science and Technology Branch (STB), Environment and Climate Change Canada (ECCC)]
• Tara Barton-Maclaren (Senior Manager, ESRAB, SED, HECSB, HC)
• Angelika Zidek (Senior Manager, ESRAB, SED, HECSB, HC)
• Alison McLaughlin (Acting Senior Manager, ESRAB, SED, HECSB, HC)
• Heather Patterson (Manager, ESRAB, SED, HECSB, HC)
• Maya Berci [Director, New Substances Assessment and Control Bureau (NSACB), SED, HECSB, HC]
• Deborah Ratzlaff (NSACB, SED, HECSB, HC)
• Michele Regimbald-Krnel (Acting Director, Environmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, HECSB, HC)
• Brad Fisher (Manager, Risk Assessment Bureau, Consumer & Hazardous Product Safety Directorate, HECSB, HC)
• Mark Bonnell (Senior Science Advisor, EAD, SRAD, STB, ECCC)
• Don Gutzman (Manager, EAD, SRAD, STB, ECCC)
• Darren Porter (Acting Manager, EAD, SRAD, STB, ECCC)
• Jonathan Tigner (Manager, EAD, SRAD, STB, ECCC)

Secretariat

• Julie Chouinard (Manager, ESRAB, SED, HECSB, HC)
• Anthony Coles (Senior Policy Advisor, ESRAB, SED, HECSB, HC)
• Luc Nakashoji (Project Officer, ESRAB, SED, HECSB, HC)
• Marisol Eggleton (Manager, Assessment Priorities and Planning, EAD, SRAD, STB, ECCC)

Contractors

• Christine Norman (Retired - Former Director, ESRAB, SED, HECSB, HC)
• Robert Chénier (Retired - Former Director, EAD, SRAD, STB, ECCC)
• Marc Valois (Principal and Senior Consultant, The Intersol Group)
• Greg Leonard (Associate, The Intersol Group)

Overview

The Chemicals Management Plan (CMP) Science Committee (the committee) met virtually on February 17 and 18, 2021. The topic of the meeting was "The Evolution of Risk Assessment under the Canadian Environmental Protection Act, 1999". The meeting provided participants an opportunity to reflect on how Canada's Risk Assessment Program for existing substances has evolved under the CMP (2006-2020) and to explore potential future directions. Moving forward, there is considerable agreement that a future federal chemicals management program should maintain a strong risk assessment function.

Marc Valois, Principal and Senior Consultant of The Intersol Group, facilitated Day 1 and Day 2 proceedings. Outlined below is a brief summary of the meeting.

See Annex A for 'What We Heard' meeting notes.

Day 1

Agenda item #1 (Welcome/Review of agenda)

Nicole Davidson (Director, ESRAB, HECSB, HC) and Marc Demers (Acting Director, EAD, SRAD, STB, ECCC) opened the meeting, providing welcoming remarks and an overview of the forward meeting agenda.

Agenda item #2 (Introductions and declarations)

Round table introductions of Committee members and participants. The secretariat provided members the opportunity to make verbal statements to update their affiliations and interests statements.

Agenda item #3 (Facilitator's introduction)

Marc Valois (Principal and Senior Consultant of The Intersol Group) addressed logistical and technological issues concerning the virtual meeting format.

Agenda item #4 (Recap of Canada presentations)

Former and current Government of Canada officials (Christine Norman, Tara Barton-Maclaren and Marc Demers) provided a brief review of Canadian presentations from the February 8, 2021, pre-meeting webinar.

Agenda item #5 (Emerging trends, needs and challenges in chemical risk assessment from the OECD perspective)

Bob Diderich (Head of Division, Environment, Health and Safety Division, OECD) presented on the emerging chemical risk assessment context, issues and challenges faced by the OECD.

Agenda item #6 (The European Commission's chemicals strategy for sustainability)

Cristina de Avila (Head of Unit, Sustainable Chemicals, Directorate-General for Environment, European Commission) overviewed the European Commission's chemicals strategy for sustainability released in 2020, which features a policy vision of ensuring a toxic-free environment by 2030 by shifting to chemicals that are safe and sustainable.

Agenda item #7 (Emerging trends, needs and challenges in chemical risk assessment from the EFSA perspective)

José Tarazona (Senior Scientific Officer, Scientific Committee and Emerging Risk Unit, EFSA) introduced members to EFSA approaches for chemical risk assessment beyond 2020 calling for revolutionary transformations that exploit the promise of new approach methodologies (NAMs), and new health and environmental risk assessment paradigms to advance the effectiveness of risk assessments.

Agenda item #8 (Emerging trends, needs and challenges in chemical risk assessment)

Jeffery Morris (Chemical Policy Consultant, Jeff Morris Solutions LLC) provided a presentation on the role of social and economic factors in susceptibility as an important aspect of how to advance risk assessment.

Agenda item #9 (Key lessons learned from international perspectives)

Marc Valois (Principal and Senior Consultant of The Intersol Group) facilitated member engagement by asking the members to highlight key lessons learning from the international perspectives offered by ad hoc member presenters.

Agenda items #10 (Discussion of charge questions)

Members discussed charge question 1 in plenary with the facilitator taking notes on the electronic platform. Deliberations adjourned for the day.

Day 2

Agenda item #11 (Housekeeping items/Recap of day 1)

Marc Valois provided a recap of day 1.

Agenda items #12 and #13 (Discussion on charge questions)

Committee members engaged in productive breakout group discussions (followed by session summaries) on Charge Question 2 as they developed their responses.

Agenda items #14 (Wrap up and next steps)

Marc Valois closed member engagement on the charge questions and provided details on how the meeting report would be prepared and shared with members for review.

Agenda item #15 (Closing remarks)

Nicole Davidson (Director, ESRAB, HECSB, HC) closed the final meeting of the Committee by acknowledging and thanking the core members of the Committee for their time, commitment and expertise. She provided a special thank you to recent and present co-chairs; and shared her sincere appreciation for the leadership and dedication of the Committee in helping advance chemical management in Canada.

Appendix A: 'What was heard' meeting notes

• Introduction
• Context-setting materials and presentations
  • Government of Canada presentations
  • International presentations
  • Key lessons learned from international perspectives
• Charge Question 1: What is working well
• Charge Question 2: Areas of enhancement for a modernized risk assessment programs
  • Protection goals/Sustainability
  • One Health approach - the grand challenge
  • Problem formulation
  • Risk assessment modernization
  • International engagement
• Charge Question 3: Engagement mechanisms for accessing external scientific expertise
• Annex A: List of participants

Introduction

On February 17 and 18, 2021, Health Canada (HC) and Environment and Climate Change Canada (ECCC) hosted the final meeting of the Chemicals Management Plan (CMP) Science Committee (hereafter referred to as the Committee). The meeting, entitled 'The Evolution of Risk Assessment under the Canadian Environmental Protection Act, 1999,' was a virtual event with a pre-meeting webinar held on February 8, 2021.

The CMP was introduced in 2006 to strengthen the integration of chemicals management programs across the Government of Canada (GoC). CMP assessments take into consideration a range of uses and sources including those addressed by the Canadian Environmental Protection Act, 1999 (CEPA 1999), the Pest Control Products Act, the Canada Consumer Product Safety Act, and the Food and Drugs Act. In addition, the CMP includes extensive research, and the monitoring and surveillance of chemicals in humans and the environment.

The final Committee meeting was seen as an opportunity to reflect on how Canada's risk assessment program for existing substances has evolved under the CMP (2006-2020) and to explore potential future directions in order to inform a post-2020 vision for the future of the CMP.

To this end, meeting participants were asked to provide strategic science input by addressing 3 open-ended charge questions:

1. What elements of our current risk assessment program are working well?
2. What areas of enhancement should be considered for a modernized risk assessment program?
3. To access external scientific expertise in the future, what engagement mechanisms are most suitable and for what types of topics?

On the first day of the meeting, some Committee members discussed the distinction between scientific and policy issues with respect to the meeting topic. Some participants felt that certain topics were more policy-related and thus beyond the mandate of the Committee, while others viewed them as issues of broader interpretation of science appropriately discussed within the Committee.

During the discussion, the terms of reference for the Committee and the terms of reference for the Stakeholder Advisory Council were cited.

Senior GoC officials present at the meeting clarified that, for this meeting, they were seeking input and ideas on all aspects of the risk assessment program, from scientific considerations to program drivers (social, policy and science). GoC officials said this input would help guide the path forward in terms of scientific integrity, innovation, and how the expertise of the scientific community is engaged and leveraged. As such, views on all aspects of the program were welcomed at the meeting.

Designed as an idea-generating meeting, the format of the meeting did not allow for prioritizing or establishing consensus on the input gathered. Rather, this report provides a straightforward account of the diversity of thoughts and perspectives offered (that is, a 'what was heard' approach). While ideas have been grouped for clarity and to reduce repetition, their order does not indicate ranking or priority. The report includes and reflects the diversity in statements, which essentially means that there was not always a (full) agreement within the Committee on all statements reflected in this report.

Context-setting materials and presentations

To provide context for the discussion of the charge questions, a background paper was distributed to participants prior to the pre-meeting webinar. The paper focused on the evolution of the CEPA 1999 existing substances risk assessment program and on considerations for moving forward.

A series of presentations from GoC representatives and international experts during the webinar and the first day of the meeting also helped to set the stage. These presentations are briefly summarized below, followed by key points from the discussion period.

Government of Canada presentations

Evolution of existing substances risk assessment
Christine Norman, former Director, HC
Robert Chénier, former Director, ECCC

Christine Norman and Robert Chénier provided a summary of the background paper prepared for the Committee meeting and presented an overview of CMP to date. Key accomplishments include:

• Using a fit-for-purpose approach, the program has addressed nearly 4000 substances
• Assessments considered multiple sources of exposure (for example, environmental media, food, products), that is, a 'one assessment, many uses' approach
• Assessment outcomes have resulted in 180 risk management actions, as well as preventative actions for substances with high hazard characteristics

They specifically addressed the implementation of the identification of risk assessment priorities (IRAP) process; the evolution of a fit-for-purpose approach and a risk assessment toolbox; a progressive focus on new approach methodologies (NAMs^{Footnote 1}) for hazard characterization, priority-setting and assessment; improvements in characterization of fate and exposure; risk characterization; and the importance of domestic and international collaboration and partnerships.

Looking to the future of the CMP, they noted key considerations for moving forward including exploration of an ecological public health approach, enhanced priority-setting and information-gathering, moving forward with risk assessment modernization, and enhanced consideration of vulnerable populations-including occupation-based considerations in assessments, cumulative risk, and endocrine-disrupting chemicals.

Innovated science: Considerations for the future of chemical risk assessment in Canada
Tara Barton-Maclaren, Senior Manager, HC
Angelika Zidek, Senior Manager, HC

In their discussion of where chemical risk assessment is moving, Tara Barton-Maclaren and Angelika Zidek emphasized the need for new approaches. These include fit-for-purpose approaches, growth of NAMs, application of the adverse outcome pathway (AOP) framework, and strengthening of the data and computational infrastructure. Data sharing and computational approaches will become increasingly important, as will expansion of the exposure toolbox and consideration of occupational exposure.

In the discussion period, a program research-regulatory 'centre of excellence' (internal to government) was raised by the speakers as an effective model for developing new tools, sharing resources, and better integrating science into policy and decision-making.

Chemical evaluation in 2021 and beyond: An ecological perspective
Mark Bonnell, Senior Science Advisor, ECCC

Mark Bonnell provided an overview of topics including inherent toxicity, mechanisms across species, the concept of "one toxicology", what exposure means in an ecological context, and biomonitoring. He indicated that regulatory uptake of NAMs is starting, but has so far been limited in decision-making. On the data front, because Canada relies on international partners for much of its data needs, an integrated testing strategy would be very useful. Management of high volumes of data will be increasingly necessary, and that data will need to be effectively shared across the GoC. Hazard science and exposure science will need to be further developed, and regulations will have to be flexible enough to incorporate the accepted science.

International presentations

Emerging trends, needs and challenges in chemical risk assessment from the OECD perspective
Bob Diderich, Head of Division, Environment, Health and Safety Division, Organisation for Economic Co-operation and Development (OECD)

Bob Diderich explained how the OECD, through initiatives involving collaborative efforts across countries, is supporting transformation of chemical risk assessment. Areas of focus include biomarker testing and prediction [for example, progress with in vitro testing, OECD quantitative structure-activity relationship (QSAR) toolbox], absorption, distribution, metabolism and excretion (ADME) [for example, physiologically based kinetic (PBK) models] and exposure assessment (for example, harmonization of occupational exposure limits). To enhance regulatory uptake of NAMs, confidence must be established through case studies, documentation, mechanistic understanding, and integration into frameworks. Bringing NAMs into the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) can potentially change the game. Another trend in the European Union (EU) is the use of generic risk assessment [for example, for carcinogens, mutagens, reproductive hazards (CMRs) and specific use cases, certain fate properties] to streamline processes or allowing risk assessment to be skipped in certain cases.

The European Commission's chemicals strategy for sustainability
Cristina de Avila, Head of Unit, Sustainable Chemicals, Directorate-General for Environment, European Commission

Cristina de Avila explained that the goal of the European Green Deal is to help protect citizens and the environment and to encourage innovation so as to improve health and environmental protection and increase global competitiveness. Its chemicals policy is to ensure a toxic-free environment by 2030 through a shift to chemicals that are sustainable and safe. This target will be reached by boosting innovation, strengthening protective legislation, substituting substances of concern, and ensuring that all chemicals on the market are safe and sustainable. Carcinogens, endocrine disruptors, very persistent substances, immunotoxicants and neurotoxicants are specific targets. Consumers, including vulnerable populations, are of particular concern. Regulations will also be simplified and consolidated, and compliance, enforcement and market surveillance will be strengthened. On the international stage, the European Commission hopes to provide an example by promoting global strategic objectives, targets, standards and harmonization, prohibiting exports of banned chemicals, and providing sound management of chemicals with international cooperation.

In the discussion, issues such as essential use, defining safe and sustainable, and benign-by-design were raised. Cristina de Avila said that addressing these concerns was an ongoing process.

Emerging trends, needs and challenges in chemical risk assessment from the European Food Safety Authority (EFSA) perspective
Dr. José Tarazona, Senior Scientific Officer, Scientific Committee and Emerging Risk Unit, and former Head, Pesticides Unit, EFSA

José Tarazona said that a '(r)evolution' of the risk assessment paradigm was needed, incorporating NAMs data and integrating exposure assessment to produce more informative risk characterizations. By using the toxicology of the 21^st century, the One Health goal is to have healthy people, healthy animals, and a healthy environment. He explained that a shift from animal studies to an integrated paradigm using NAM-based integrated approaches to testing and assessment (IATAs) will provide a better understanding of chemical hazards and mechanistic processes.

For environmental risk assessment, the variability in environmental factors and use patterns will have to be taken into account. Specific protection goals can be defined on the basis of the concept of ecosystem services, using 5 factors: the ecological entity (organism to ecosystem), its attributes, the magnitude of acceptable impact, the temporal scale, and the spatial scale. The use of big data will support a move from risks to impacts directly relevant for environmental policy objectives. For pesticides and other agrochemicals, the separation between directly intended impacts, inevitable impacts and avoidable impacts is proposed. The EFSA New Approach Methodologies Project is working to move NAMs forward using collaborative case studies with researchers and risk assessors.

Emerging trends, needs and challenges in chemical risk assessment
Dr. Jeffery Morris, Chemical Policy Consultant, Jeff Morris Solutions LLC, and former Director, United States (U.S.) Environmental Protection Agency's (EPA) Office of Pollution Prevention and Toxics

Jeffery Morris discussed bringing social and economic factors into the process of identifying susceptibility to adverse effects from chemical exposure as a means to advance risk assessment. The current model for estimating human health impacts is incomplete, in the sense that human variability is typically captured only in biological terms, leading to a narrow concept of susceptibility and a limited view of what constitutes a subpopulation. Poverty, access to health care, lack of social services, crime, noise, congestion, environmental degradation, and reduced ability to conduct cultural practices are examples of relevant factors.

Engaging stakeholders in case studies can foster common understanding, facilitate transparency, allow for comparison, sensitivity and analysis, and shorten the period between investigation and application. The One Health approach discussed by the Committee in 2018 is an important direction, and including social and economic considerations supports that direction. Social justice considerations will be an important driver of policy action related to chemicals. Consideration of social and economic stressors in identifying susceptible and vulnerable subpopulations can play an important role in increasing the utility of chemical risk assessment to informing policy actions.

Key lessons learned from international perspectives

Following the presentations, Committee members and ad hoc members were asked to identify key lessons learned. They shared a number of observations, which have been grouped for clarity. This set of observations reflects the diversity in statements from the Committee members, which means that there was not always full agreement within the committee on all the observations presented. There is no implication that all participants agreed (either entirely or in part) with any individual comment.

Protection goals/sustainability

• Need to design a chemicals management plan that articulates a vision, with a renewed sense of integration that marries environmental protection with sustainability. Protection goals should be revisited.
• Determine the goal of the new program. Important to consider chemicals at the same level of importance as climate and the circular economy. All must be addressed to achieve sustainability.
• The thinking needs to be seven generations^{Footnote 2} ahead when addressing persistent chemicals.

One Health approach^{Footnote 3}

• Aspects of the One Health approach were touched upon across these presentations.
  • The One Health approach was described as a 'grand challenge' in recognition that the scientific understanding needed for developing and implementing One Health evaluation approaches is still at a nascent stage.
  • A vision with design thinking and sustainability principles is needed.
  • Case studies are important when new elements are added to a program, but are also needed for retrospective analysis. Engage stakeholders to facilitate transparency.
  • The move to One Health would result in a more integrated program that looks at chemical and non-chemical stressors.
  • It is critical to be clear on goals and take into account global issues such as climate change.

Problem formulation

• Defining the context and purpose of assessments is important for making them more targeted. Although this is working well within the program, additional work is needed to expand problem formulation and enhance inclusion of vulnerable populations.
• It is important for CMP to maintain the nimbleness to take a range of assessment types into account. Given that assessments are expected to become more complex, can the decision-making process be simplified?
• Emphasizing the resilience of the decision-making process is efficient in the long run. CMP has expeditiously assessed thousands of chemicals. Moving forward, it should be recognized that that it will rarely be possible to have comprehensive datasets on chemicals. It would be efficient to consider persistence, toxicity, mobility and exposure as individual attributes. Also, newer methods and models are needed that can integrate these attributes to support decision-making.
• The "persistent, bioaccumulative and toxic" (PBT) approach embedded in CEPA 1999 is often not aligned with actual exposures. Improved methods to identify priorities are needed (and must continue to be integrated into CMP as it evolves). The international community is considering ways to move to a more holistic approach, integrating hazard and risk data.
• When evaluating a body of evidence, science must be applied in a fit-for-purpose manner to achieve goals and outcomes.

Risk assessment modernization

• Risk assessment is at a transformative point in time with new approaches, big data and advanced modelling. There is a dynamic tension between reductionism and holism. There will be challenges in changing the culture of risk assessment practitioners as the science and practice of risk assessment moves forward.
• The decision to move beyond the current framework and the willingness of departments to go further than legal prescriptions are positives.
• Canada is doing a good job from an international perspective. The direction CMP is taking is well-aligned with science-based decision-making.
• Resilience and robustness are important. Decisions should lead to robust solutions that can be reversed or modified as new information becomes available.
• Effective and efficient science-based policy requires rigour. Processes must be transparent as to how science is integrated so that they can be refined as the science evolves.
• NAMs
  • The importance of NAMs is growing, not only in replacing animal testing (which is an important driver), but also in being more informative and predictive by better understanding mechanistic processes.
  • Case studies, documentation, mechanistic understanding, and integration into frameworks will be important for establishing confidence and proof-of-concept.
• Obtaining data on chemical use is a challenge. The importance of collaborative work/consortia and engaging the full spectrum of the supply chain (from international and local manufacturers through importers and to end users) was noted.
• The need for more integration, lessons learned from successes and failures, and consideration of social and economic factors to advance risk assessment were also noted.
• Depending on the intended purpose, the causal chain of events may need to be established for biomarkers of biological interaction/response in early key events to be used to infer adverse effects.
• As more integrative toxicity testing is developed, it is possible that not everything will be able to be explained mechanistically, particularly in earlier stages. Thus, less mechanistic approaches (for example, animal testing) must not be lost.
• An enhanced capacity to modify the tools and adapt the processes is important. This is not easy in the regulatory context.
• There are opportunities to use new tools that have not been best utilized in the past (multimedia modelling, multi-pathway analysis, etc.). These models can be moved forward in the evaluation process.
• Regulatory evaluations should be based on the best available science and weight of evidence. Hypotheses related to explicit or implicit inference models need to be rigorously evaluated and the performance of such inference models documented.
• There is an opportunity to use new tools in exposure science, including multimedia models. Efforts to develop scientific tools, such as biomonitoring equivalents, to enable interpretation of human biomonitoring data in a risk context should be a high priority and an integral part of programs such as the Canadian Health Measures Survey (CHMS) (Faure et al. 2020).
• Better consideration of chemicals in products throughout the product life cycle is needed.
• There is currently very limited opportunity for data generation, including exposure data, in the Canadian program. Policy development was suggested in order to strengthen this.

Charge Question 1: What is working well

In a plenary discussion on Day 1, participants addressed Charge Question 1: What elements of our current risk assessment program are working well? Observations have been grouped for clarity. As is the case for the other charge questions, the order of presentation herein does not indicate a ranking or priority. This set of observations reflects the diversity in statements from the Committee, which means that there was not always full agreement within the Committee on all the observations presented. There is no implication that all participants agreed (either entirely or in part) with any individual observation.

Protection goals/Sustainability

• HC and ECCC work well together. There is collaboration between HC and ECCC towards a holistic approach. Bringing ecological and human health together leads to a stronger program. The program works well across sectors to achieve policy goals.

Problem formulation

• The pragmatic flexible approach that has been used, has allowed for evolution and uptake of innovations happening globally.
• A 'one assessment, many uses' approach has been enhanced through CMP.
• The program has done well in priority-setting approaches and data gathering.
• Many noted the utility and forward vision of the program in introducing IRAP, while noting the need to better articulate how decisions on priority-setting are made.
• Assessment strategies have evolved well, including toxicity assessment and fate and exposure assessment.

Risk assessment modernization

• What Canada has been doing with NAMs is exemplary.
  • The work towards advancing the use of bioactivity exposure ratio (BER) approaches in a risk-based decision context is good.
  • Ecological Risk Classification of organic substances (ERC) and Ecological Risk Classification of Inorganic Substances (ERC-I) was precedent-setting.
• Canada's involvement in various working parties and OECD guidance documents was praised. Canada's representation at OECD and other international forums should be continued (even enhanced). Such involvement helps influence new directions taken in the context of regulatory risk assessment around the world. Thus, resources directed towards Canada's participation in OECD are wisely invested. The Committee has been a good venue for addressing scientific issues.
• The close relationship between academics and policy makers was noted.
• The enhanced biomonitoring program is very important. It is integrated and seamless and adds a lot of value.

International engagement

• Only a few countries have robust chemicals management programs, and Canada is among them. These few countries set the global stage. Canada has been quite active in global forums (for example, OECD, World Health Organization). There is thus an opportunity here for continued Canadian leadership, exporting of ideas, setting the stage and expectations, building global capacity, etc.
• Starting to use International Uniform Chemical Information Database (IUCLID) opens opportunities (data sharing, collaboration) for the future; however, the quality and suitability of data in repositories like IUCLID and other sources requires careful consideration.

Charge Question 2: Areas of enhancement for a modernized risk assessment program

On Day 2 of the meeting, participants split into breakout groups to address Charge Question 2: What areas of enhancement should be considered for a modernized risk assessment program? The results of these discussions and related commentary provided during plenary reports are provided below. The topics have been grouped for clarity. As is the case for the other charge questions, the order of presentation herein does not indicate a ranking or priority. This set of observations reflects the diversity in statements from the Committee, which means that there was not always full agreement within the Committee on all the observations presented. There is no implication that all participants agreed (either entirely or in part) with any individual observation.

Protection goals and sustainability

• Update protection goals under CMP to cast environmental and human health protection in the larger context of sustainability and progress towards a circular economy. This idea blends with the One Health concept.
• Updated protection goals may also need to take into account the expanded concepts of vulnerability, susceptibility, and environmental justice (see vulnerable populations section under One Health approach).
• For environmental risk assessments, establish specific protection goals directly connected to policy targets (sustainability, conservation of biodiversity, etc.) that could be applicable to chemicals but also to other stressors (EFSA approach on ecosystem services is one option but there are others). This would facilitate the integration of the risk characterization results for different chemicals and chemical groups and the link with environmental impact assessments.
• Chemical assessment/management must fit into the larger context of environmental and human health protection.
• Consider how emerging/emerged pressures (for example, climate change, global pandemics) will impact chemical management needs.
• Protection goals could also encompass disaster response.
• Need to include projections into the future when planning CMP. Where is the program headed and what issues will be present in 10 to 20 years or more (50+)?
• Consider the intersection of chemicals management with waste management, pesticide management, etc.
• In some cases, (for example, persistence-sufficient hazard classification) a hazard-based approach, as opposed to a risk-based approach, should be considered to ensure long-term protection of the environment.
• Include climate neutrality. In efforts to achieve climate neutrality, the international community is already facing many dilemmas in terms of chemicals use. Decisions taken in response to these dilemmas may be long-lived and, if the choices are wrong, it will build a problematic legacy for future generations.
• Another goal for protection is the need to align with the recognition of increased total chemical production, which is predicted to double by 2030. A chemical-by-chemical approach may not account for the total increase in chemical production, which is a stressor.
• Overall, a modernized risk assessment program should be regulatory relevant. Science is the building block of regulatory policies, and subsequently, of regulatory action. This has 2 main aspects: timely availability of the science and depth of science needed to make decisions.
• It is crucial that a risk assessment program is directly tied to risk management needs in order to ensure regulatory relevance.
• Consider chemicals over their life cycle from resource extraction and manufacturing to use and end-of-life. End-of-life considerations interface with challenges of waste (including hazardous waste) management.
• The science policy roadmap under One Health could be expanded. This represents a more readily operational step towards One Health, for example green chemistry and building in modern approaches such as benign-by-design.
  • Need to understand the strengths and limitations of green chemistry. Functionality can override benign-by-design. Expand consideration within an alternatives assessment framework, that is, is this needed (which gets into "essential use" concept)?
  • Many ideas on informed substitution were discussed at the Committee meeting on informed substitution.
  • To operationalize informed substitution, need to consider the option of doing something a different way (for example, seek alternatives other than "drop in" replacements); innovation always goes in one direction - need to consider other options (more traditional options); consideration of product development path (where did we come from, how did we get here, do we really need the technology at all/how essential is this substance/product?); incorporate all issues in cost-benefit analysis.
  • Essentially, green chemistry and building in modern approaches need to be determined in light of use of application.
  • Engagement with universities and research bodies is also important in order to bring the change towards green chemistry (benign-by-design).

One Health approach - the 'grand challenge'

Science policy roadmap for implementing the One Health approach

• Link ecological and human health (One Health).
• Consider what the key policy objectives are in instituting One Health. Set the policy goal and identify the science questions to address those goals.
• Consider what science questions need to be addressed if chemical risk assessment is to inform decisions and actions to meet those goals.
• Bring these factors into the risk characterization and assessment space. Create a mapping of proposed opportunities to integrate factors.
• Use case examples, for example, starting with a disease, such as breast cancer.^{Footnote 4}
• Need to better understand the determinants of health and to use them to structure the needs for science within CMP.
• Connect the social determinants of health with the protection goals. There is good experience with Parkinson's disease. The only way to get to risk assessment is from a mechanistic approach.
• Need to look both retrospectively and prospectively.
• The CEPA 1999 assessment program does not have a mandate to lead in comprehensive One Health approaches. However, it could contribute to broader departmental efforts relating to One Health.

Vulnerable populations

• While consideration of vulnerable populations will likely be on a substance-by-substance basis, are there basic scenarios that could be added to life stages that are traditionally considered (infants, children, etc.)?
• Practically, this means folding in considerations such as occupational health exposures, low socioeconomic status (SES) - populations, racialized populations, and ecosystem populations impacted by habitat loss.
• There are challenges with surveillance programs in low SES homes to inform human health assessments; there is a lack of data to identify and quantify vulnerable populations.
• Consideration should be given to addressing racial, cultural and other diversities across Canada with respect to differences in uses of products, differential exposures and differential sensitivities (e.g., skin lightening products (not covered by cosmetic regulations), hair straightening products, specialty products imported by some immigrant communities.).

Problem formulation

• Grouping of substances
  • Grouping has become an important issue for policy makers. Many new tools have become available and now might be a good time to evaluate them.
  • Identify and evaluate new tools and approaches useful in the future grouping of substances. A suite of new tools exists that should be reviewed/considered to modernize grouping for assessment beyond just chemical structure (based on biological activity, ADME, toxico/pharmaco-kinetic tools, toxicogenomics profiling, exposure, etc.).
  • The same could be said for "read across." There is a lot of talk of classes of chemicals and assumptions that they behave similarly within a class, but there may be nuances within classes/groups and it's important to identify differences.
  • Promote a "class and sub-class approach" to deal with similar chemicals rather than taking a chemical-by-chemical approach. A prime example is per- and polyfluoroalkyl substances (PFAS).
  • Continue to develop some of the grouping approaches (for example, those used in ERC2) to help facilitate the development of these groupings [based on structure, chemistry, physical-chemical properties, mode of action (MOA), exposure including use, fate, etc., sensitive species/populations, etc.].
  • Promoting class and grouping approaches can help avoid regrettable substitution and increase effectiveness of assessment approaches.
  • HC and ECCC have had successes and failures with respect to grouping of substances. Groupings must be chosen carefully to do it well. HC and ECCC continue to move forward in this area.
  • NAMs can provide better characterization of complex mixtures to help identify classes.
  • Introduce new tools in the context of risk management. New methods can let you be more robust in how you group chemicals.
• Problem formulation is of value in further defining protection goals and incorporating the decision context and acceptable level of uncertainty within a weight-of-evidence approach.

Risk assessment modernization

Data acquisition and management in the "Big Data Era"

Data generation

• Use current provisions (CEPA 1999 section 46, section 68 and section 71) more aggressively for data generation. Consider regular updates of the Domestic Substances List in addition to focused surveys. Require data from importers, manufacturers, formulators and suppliers when there are good grounds to do so.
• Use IRAP or problem formulations to trigger data generation to fill data gaps; be less willing to accept gaps and ask for them to be filled.
• Incentivize industry to generate new data (NAMs, big data), submit it, and somehow make it available publicly, while also protecting their interests/intellectual property (IP), etc. Block chain technologies are advancing quickly.
• Industry generates data for research and development (R&D); consideration should be given as to how to make it available to the GoC while protecting the interests of the generator.
• Fund HC and ECCC to generate data in-house in key strategic areas.
• Create synergies with other international efforts to connect systems, data platforms and results.

Create the necessary database/information-sharing infrastructure

• This has been identified in every Committee meeting to date. Outline the needs and develop the strategy for the various needs.
• The entire program needs a deeper, more systematic investment in data science/data analytics and data management.
• Develop strategies to ensure data quality, data curation and oversight.
• Datasets are getting larger, and biology and chemistry are getting more complex. Consider how data will be managed, and by whom.
• Modern risk assessment will need to deal with the size and scope of the data and will need the expertise to interpret it and integrate it into assessment activities.
• Create a chemicals management program that attracts recent graduates with skills such as bioinformatics to the public service.

Integrated data management to support scientific research programs and risk assessment

• Online databases and frameworks for assembling, organizing, evaluating and using various data sources:
  • Enter data in type-specific templates for exposure and toxicity data. For example, for exposure data, ensure consideration of diverse media (air, blood, dust, etc.) and related details (gas phase, bulk, lipid, etc.), units of values, limit of detection (LOD)/limit of quantitation (LOQ) (and detection frequency and replacement value techniques for values less than LOD/LOQ), number of samples, as well as links to primary sources (reports, publications).
  • Enter new and recent data first; bring in older data over a 5 to 10 year period.
  • Mandatory reporting (data entry into system) for all GoC-funded projects (when no confidential business information or IP issues exist).
• Make data management a priority. It will have enormous benefits for the scientists, evaluators, managers and the public.
• Data management is even more important for NAMs.

Informatics

• Determine how to best use IT to improve data collection and linkage, sharing, curation, integration and dissemination.
• Build the expertise and the IT infrastructure needed to underpin the program in the big data era.
• Better data dissemination practice, i.e., dissemination of test results that are used in the risk assessments via IUCLID and eChemPortal.
  • Integrate disparate data streams for decisions using visualization, statistical modelling, machine learning. Examples of data streams include socioeconomic factors (Marvel et al. 2021) and One Health/public health considerations.

NAM Strategy

• Focus on NAMs (including informatics) as a strategic goal.
• Acknowledge the range of use of NAMs in 3 key areas:
  1. for replacing in vivo data or developing better models than in vivo models
  2. for screening and prioritization when there are no data or very limited data
  3. for a mechanistic understanding that may include consideration of the general population and vulnerable populations and/or ecosystems
• Recognise that reduced animal testing underpins move towards NAM.
• "Stay the course" for risk-based NAMs, including adding ADME inputs for human and ecological models as a standard.
• Develop and encourage the development of exposure-based NAMs, especially for consumer and open field applications, for example, an extension of "P"-based properties.
• Identify appropriate "cumulative exposure/mixture-based" NAMs (Hsieh et al. 2021).^{Footnote 5}
• Establish principles for evaluating, documenting and communicating scientific confidence in NAMs. Examples here include BERs, exposure NAMs, PBT approach, "residence time" methods, and toxicogenomic profiling that can be actualized in a fit-for-purpose manner that links the methods to different decision contexts.
• Determine how to best use IT to improve data collection and linkage, sharing, curation and integration. Build the expertise and the IT infrastructure needed to underpin the program in the big data era.
• Maintain the current international focus to gain global support and knowledge sharing.
• Consider the value of NAMs for exploring unique human diseases where existing animal models do not exist or are limited (for example, neurotoxicity, cardiotoxicity).
• Update the ERC-Organic and Inorganic Approach, and actively maintain/update the ERC Approach, on an ongoing basis.
• Do not focus exclusively on in vitro. Currently, some QSARs (Wignall et al. 2018) may be as accurate or more accurate and more precise than NAM-PODs (points of departure) based on in vitro bioactivity (for example, ToxCast Administered Equivalent Doses). Both have uncertainties.
• Leverage the considerable work that the life cycle impact assessment (LCIA) community is doing (for example, USEtox) in terms of addressing large numbers of chemicals in a consistent and integrated way (including ongoing development of new QSAR model for PODs).
• Make sure that NAMs for hazard assessment address both point of departure and hazard classification for programs where classification is needed.
• Promote NAMs to expedite chemical screening and increase knowledge of mechanisms.
  • Increase the ability of NAMs to account for genetic and phenotypic variability in order to better capture "real world" exposure situations (multiple stressors) for both ecological and human health situations.
  • In addition to screening applications, consider how NAMs could be used for quantitative risk assessment. Many NAMs initially developed for screening might also have application in the quantitative risk assessment space.
  • Improve dosimetry to improve translation between administered dose and "real" doses.
  • Consider how to purposefully develop and ultimately (commercially)-deliver NAMs. It has been ad hoc, reactionary, and targeted thus far. How can NAMs development be more purposeful in terms of design and long-term sustainability? Who are the NAM developers and how are they being incentivized (for example, think U.S. EPA EcoTox Challenge)? How is the private sector brought into developing new assays?
  • Take advantage of the opportunity available to Canada to show leadership (provide toolkit) and capitalize on existing strengths.
  • Continue to retain flexibility in approaches that will allow NAMs to be considered/used where appropriate and feasible.
  • Do not only rely on traditional data (empirical animal models, for example) to determine utility of NAMs.
  • Consider NAMs as part of a weight-of-evidence approach that is tied to the protection goal(s).
• Additional discussion and commentary:
  • Further evaluation of NAMs including examination of dosimetry as well as scrutiny for potential bias.
  • Some NAMs are not best geared towards systemic toxicity. There are challenges with translating in vivo tests into appropriate NAMs.
  • Is Canada going to be an importer or exporter of NAMs? How can the country build capacity for both creation and implementation of NAMs?
    • Animal testing can be considered old science, but to move NAMs forward, we need to focus on the context of regulatory toxicology to integrate new knowledge.
    • UVCBs (substances of unknown or variable composition, complex reaction products, or biological materials) should be a new strategic focus, though this goes beyond NAMs.
    • It is important not to get too boxed in by focusing on traditional toxicology as the end goal. We need to merge the two worlds of NAMs and TAMs (traditional assessment methods).

Towards an integrative paradigm

• Improve AOP and MOA pathway-based approaches
  • Develop quantitative models of dose and time responses; key events and key event relationships; dose (at the site of action); and intensity of perturbation over time.
  • The spectrum of levels of biological complexity should be considered within the context of fit-for-purpose approach. AOPs, key characteristics (KC), and alternative experimental models (for example, tissue chips) should all be part of the toolbox.
  • Leverage and improve use of AOPs/mechanistic approaches by integrating exposure/toxicokinetics at each stage. Ensure integration of the aggregate exposure pathway (AEP) framework with the AOP.
• Testing and assessment
  • Build the process around a tiered, risk-based framework that integrates exposure at each decision node. The tiers should begin with the least complex, most efficient methods and progress to the most complex, more resource-intensive methods.
  • Support what is already ongoing and will further expand; however, some animal testing may need to continue to increase understanding and validation, until a full change in paradigm can be achieved.
• Merge measurements and models
  • Models and measurements are both needed. It is best to formally develop programs to make the most of both types of data.
  • Need an improved understanding of the merits and limitations of both measurements and models.
  • Merging these data streams helps address uncertainty, prioritize data generation needs, etc.
  • More integration addresses uncertainty and challenges in chemical-by-chemical assessments as well as cumulative risk assessment (combined exposure to multiple chemicals).
  • Include the following:
    • Emissions data [for example, National Pollutant Release Inventory (NPRI)] and emissions models [for example, -Chemicals in Products - Comprehensive Anthropospheric Fate Estimation (CiP-CAFE) (Li & Wania, 2016; Li 2020), emission scenario documents (ESDs), life cycle tools)]
    • Wastewater treatment plant (WWTP) measurements (influent, effluent) and WWTP models (for example, sewage treatment plant (STP))
    • Monitoring data and indoor and outdoor fate and transport models - helps address uncertainty in estimating persistence (system recovery times, etc.)
    • Biomonitoring data with exposure and bioaccumulation models - helps address uncertainty in toxicokinetic and bioaccumulation methods
    • Full spectrum of measurements across the production-to-exposure (external and internal) continuum and similar full-spectrum and modular models
  • Bring suspect screening analysis (SSA)/non-targeted analysis (NTA) (and metabolite/degradate) data into these frameworks to help put NAM exposure information into context; improves interpretation and ensures appropriate use of data
• Expand/continue to promote new developments in the exposure space.
  • Refining models, developing new approaches, expanding monitoring programs with a strategic focus to develop the infrastructure to capture, house, and share these data and tools.
  • Exposure needs to better account for variability and key uncertainties. Important to capture vulnerable populations.
  • Exposure estimates need to reduce uncertainty, linking emissions to exposure in order to inform effect.
  • Exposure assessments lay the groundwork for risk mitigation should a chemical be designated as toxic; thus, there is a need to ensure that drivers of exposure are sufficiently captured.
• Consideration should be given to including the key characteristics approach, or aspects of the approach, in the toolbox.
  • In terms of mechanistic data, in addition to AOPs and MOAs, the "key characteristics" approach should be part of the toolbox. This is a hybrid "mechanistic"- "empirical" approach. It can be very useful for organizing data for integration and analysis [for example, cancer (Guyton et al. 2018; Krewski et al. 2019; Smith et al. 2016), endocrine disrupting chemicals (EDCs)(La Merrill et al. 2020) and reproduction (Luderer et al. 2019; Arzuaga et al. 2019)].
    • Members shared perspectives on the strengths and limitations of the key characteristics approach (Becker et al. 2017)
• Integrate hazard data streams.
  • Apply existing and emerging toxicokinetic-/ADME methods (models) for in vivo and in vitro test systems to align exposures (doses) across hazard/bioactivity tests to improve comparisons of responses between NAMs and TAMs (traditional assessment methods) for ecological and human toxicology.
  • Cannot effectively compare responses, or ground truth NAMs, without first getting the exposure/dose in the same units; this helps address uncertainty in toxicology.
  • This integration will make the most of available data and ensure that new and emerging data are placed in the correct context with historical (TAMs) data sources.
  • Animal studies will still be needed to better understand systemic toxicity.
• On transparency, conduct a systematic review of the evidence with mapping, synthesis, and integration.
  • Ensure transparency through the different tiers of assessment.
  • This is critical to rigorous consideration of the science base and to transparent documentation of the decisions made in evaluating and using the science in decisions (U.S. EPA 2020).

Strengthening fate and exposure characterization

• Enhanced exposure data generation and sharing (sources, emissions, occurrences, uses, etc.) is needed.
• Harness geospatial data integration and visualization: Is geographical mapping for broadly defined exposure assessment-not just chemicals, but also industrial facilities, socio-economic factors, the built environment, disasters, etc.- within the scope of a potential future CMP?
  • Could include landscape perspective for humans exposed through environment and ecological risk assessment.
• The integration of exposure tools and models is a priority. One of the problems for implementing the "one substance, one assessment" approach in the EU is that the exposure approaches, models and tools currently used in the different sectoral areas have been developed independently over decades and are not necessarily compatible; it is therefore difficult to do integrated exposure assessments.
• There are opportunities to better capture sources and conditions of use across supply chains. It was recognized that supply chain challenges were broader than simply informing exposure characterization.
• There are policy implications if HC and ECCC are more aggressive in requiring data generation, notably increasing requirements on stakeholders, including industry, to supply such data.
• Need for strategic investment from government in exposure data generation, including environmental monitoring and biomonitoring as well as exposure model parameter data, that is, chemical degradation half-lives in various environmental media.
• In terms of biomonitoring and environmental monitoring, is there a "banking" program so that samples can be saved for later analysis (for example, emerging contaminants, new analytical methods)?
• Develop new tools and approaches for the use of exposure information that can be efficiently collected.
• Increase investment in non-targeted analytical methods.
• Connect prospective and retrospective risk assessment methodologies and tools. This will allow the integration of modelling predictions and monitoring data.
• Industry needs to be more proactive in describing the processes in which their chemicals are involved so that emission scenarios and release estimates are more robust.
• There is a need to increase knowledge on the presence of chemicals in products/articles to further reduce the uncertainty in exposure assessment.
• Models require data. At this point, there can be no advancement or proper use of these models without additional data collection.
• The computational methods, tools, and capacity are now available to develop national-scale assessments that incorporate/consider local, geographically-based metrics. CMP assessments should consider appropriate scale of exposure, relevant to the receptors under consideration.
• Threshold of toxicological concern (TTC) and internal TTC (iTTC) for prioritization and risk-based decision-making:
  • Fully explore the scientific opportunities and challenges in Canada [with Accelerating the Pace of Chemical Risk Assessment (APCRA) and with the OECD] on utility of the TTC and iTTC to prioritize and make risk-based decisions.
  • When compared to PODs from NAMs (for example, ToxCast), the corresponding TTC value was more protective "90% of the time." This suggests when TTCs can be used with confidence to support health protective decision-making as an efficient first or early tier (Friedman et al. 2020).
• Complex mixtures.
  • Consider how a modernized risk assessment program will deal with mixtures. Once the chemical world has been assessed (on a single chemical basis), consider how then to tackle the real-world issue of mixtures. This should be built into modern risk assessment.
  • Develop strategies to address mixtures (quantitative where possible, but also qualitatively) and also consider other stressors (modulating factors, etc.).
  • Complex mixtures encompass UVCBs but also disaster-related contamination, etc.
    • Assessments of UVCBs have been undertaken in the past, and there have sometimes been challenges, for example, the Petroleum Sector Stream Approach (PSSA) experience initiated under the first phase of the CMP. These require input from external experts to ensure the substance or class of substances being considered is amenable to assessment.
• Increase efforts to evaluate polymers, UVCBs and mixtures.
  • Several methods (for example, chemical fate and transport modelling) are not sufficiently developed. Impurities and degradation products need to be considered with polymers.
  • It is important to recognize trends in chemical production which, in some cases, have moved from monomers to polymers.
  • Consideration also needs to be given to naturally complex substances (NCS).
• Consideration should be given to addressing very persistent (vP) substances.
  • Consider vP as a sufficient criterion for evaluating "CEPA toxic" chemicals.
  • vP, following from the EU approach, considers the accumulation of the particular chemical in question into the future and the limited ability to mitigate that chemical burden.
  • Consider that the risk associated with pollution of very persistent (and very mobile) substances in itself merits attention, for example, microplastics.
  • Consider the realm of CMP (chemicals management) versus issues related to solid waste management. How can CMP better link with other regulatory areas within GoC to tackle something like plastics? Gets at the life cycle assessment issues mentioned as well.
  • Persistence on its own is not enough to classify a chemical as "CEPA toxic."
  • Function must be taken into account. Need to look at the life cycle of the molecule. For example, chemicals that do not break down under high pressure and temperature can be desirable.
  • Our capacity to assess toxicity in real environments is not great. Risk assessment may not be the best way to assess toxicity.
• Physical and biological science fields tend to dominate risk assessment, with traditional disciplines being toxicology, exposure science, epidemiology, etc. Modern risk assessment should increase the size of the "tent" to find ways to draw in social sciences. These disciplines tend to follow in risk management, but their researchers/ideas/methods/skills need to be brought into core and traditional risk assessment. Need to ensure NAMs are economically feasible and socially responsible. Incorporate more social factors into decisions.

International engagement

• As only a handful of countries worldwide have chemicals management plan programs and are at the forefront of modernizing risk assessment, there is an opportunity (but also an obligation) to educate and build scientific capacity. Inside Canada, steps should be taken to deepen engagements with universities to co-develop new graduate programs and research partnerships. This will not only help advance the R&D underpinning NAMs and new approaches, but also help create a pipeline of skilled individuals for GoC recruitment. As most other countries do not have such programs, Canada can help build capacity elsewhere through various schemes, such as workshops and exchanges.
• Establish research-regulatory forums ('virtual centres of excellence').^{Footnote 6}
  • These forums would facilitate transfer of knowledge, ideas and be useful for addressing challenges.
  • These forums would facilitate opportunities to incorporate best available science in decision-making.
  • Would also help prioritize research needs with regulatory challenges.
  • Theme-based networks/working groups could be set up to address issues as they arise (as has been done in the past) and provide expertise/targeted research to regulatory program on an ad hoc
• International supply chain
  • Initiate a formal project to understand the impact of international supply chain issues and problems in context of exposure assessment, with particular focus on data gathering, product monitoring, GHS-related impacts/opportunities, and how to improve reporting and enforcement. Involve external stakeholders [other government departments (OGDs), industry, provinces/territories, and U.S. via an invigorated Regulatory Cooperation Council (RCC), OECD].
  • Should anticipate changes in how the global supply chain will change post-COVID. There may be some de-globalization.
  • Need external stakeholder engagement.
• Investment in (international) data and tools sharing (through OECD).
  • Other countries have been investing in data management (EU, U.S., Australia, New Zealand, etc.) to a greater extent than Canada.
  • IUCLID is not perfect, but provides some standardization.

Charge Question 3: Engagement mechanisms for accessing external scientific expertise

In the final session of the meeting, participants addressed Charge Question 3: To access external scientific expertise in the future, what engagement mechanisms are most suitable and for what types of topics? As is the case for the other charge questions, the order of presentation herein does not indicate a ranking or priority. This set of observations reflects the diversity in statements from the Committee, which means that there was not always full agreement within the committee on all the observations presented.

• HC and ECCC should review expectations from "external science input" with respect to content, format, timing and process for meetings, and should update the current model.
  1. HC and ECCC should consider their needs around:
     • complexity of content-based discussions, for example, data sources/big data/IT.
     • current and future cutting-edge NAMs, including those for cumulative risk and assessment of "real world mixtures" (for example, NAMs that can integrate multicomponent exposure into "test system perturbations"). Other areas include a review of zebrafish, etc., as indicator species, looking for sentinel species/markers for long-term monitoring, and investigating the "geomatics" interface (that is, air quality/water quality/soil quality data) with population health data, as well as investigating the potential to consider susceptibility/vulnerable population factors.
     • tie-in between prioritization/data gaps/assessment/risk management needs (that is, problem formulation plus).
     • potential sources of content (academia, regional contexts, international efforts/coordination).
  2. For future program-related activities, create a smaller group of core experts and enhance ad hoc inputs to ensure best current advice on a meeting-specific basis.
  3. Move away from the current standard of formal in-person meetings to allow enhanced flexibility.
  4. HC and ECCC should determine to what extent they wish to consider "vision" and "stakeholder-related" factors when obtaining science advice (vs. stakeholder advice); best performed internally before seeking expert external science advice.
     • Departments may want to consider re-creating a 21st century equivalent of the 1990s-era Toxic Substances Research Initiative (TSRI), a focused research initiative with identified targets, goals and budgets, using an expert multi-stakeholder input process. TSRI successfully delivered results on a number of fronts, including enabling cleanup of hot spots such as the Sydney tar ponds, environmental monitoring in remote areas such as the Arctic, and specific health and ecological studies on potential "toxics", model development, and training. Many of today's problems are different, but the TSRI model helped train the current generation. Government could give the initiative a mandate to support a set of One Health-oriented investigations in the field.
     • Suggest that for certain challenges- such as those related to where to prioritize science questions for advancing the One Health Approach-virtual formal, structure expert elicitation exercises may be useful to identify what strategies can be employed to reduce uncertainty around establishing causal relationships between stressors and disease.
• Look to science committees implemented by other chemicals management and related programs.
• More input is needed from the social sciences, policy analysts, health geographers, etc.
  • For implementing effective policy, defining protection goals based on social determinants, science and risk communication, and community engagement.
  • Which disciplines are needed depends on the particular question at hand.
• Computational behaviour modelling could be an example of another sub-discipline or a specific area that needs input.
  • Bioethicists will have a greater role in addressing the challenges in understanding the impacts of adverse outcomes and what and how to ethically communicate.
  • It is not a small task to identify the right people to answer the right questions and access that expertise.
• Exchange program with international colleagues (such as U.S. EPA, ECHA, EFSA).
• The U.S. EPA STAR program (focused RFA) and/or government-academic (researcher) partnerships driven by a particular need but is an example of how Canada could engage more academics.
  • Some of the U.S. EPA STAR programs are actually "cooperative agreements" in which external researchers and agency scientists have a more collaborative/interactive relationship, as opposed to outright grants for which the relationship is more arms-length.
• GoC should consider hosting temporary fellowships/appointments/post-doctoral positions to access expertise and enable understanding of regulatory/policy among scientific community.
• Regulatory-research centres of excellence: see Implementation through collaboration under Charge Question 2.
• Promote challenge competitions (for example, U.S. EPA EcoTox Challenge) for innovators.
• Host virtual expert workshops on ad hoc Conduct focused workshops/meetings on key science areas to bring in various scientific experts globally.
• Ensure that science contributions are unbiased and foster critical analysis that includes systems-based analytical approaches as well as reductionist, detailed approaches necessary to understand mechanisms. A range of approaches is necessary to make robust decisions.
• Continue participation in APCRA. Identify additional APCRA-like case studies that could be built upon within and outside of APCRA.
• Flexible approach with engagement.
  • Experts should be involved according to the questions being asked. This allows for incorporating new scientific approaches and viewpoints.
  • Experts external to government with familiarity with the CMP process are also needed. This allows for continuity and also understanding the regulatory context and needs.
• Increase cooperation and engagement of researchers in the risk assessment process; in particular, facilitate the incorporation of new knowledge, innovative tools and models into regulatory assessments.
• OECD
  • Continue engaging the international expert community through the OECD. Many mechanisms of engagement include involvement in case studies, standardization of methods, AOP development, etc.
    • OECD extended: There are a number of groups in the OECD [for example, Extended Advisory Group for Molecular Screening and Toxicogenomics (EAGMST)] that have considerable integrated/linked science capacity available.
• Visiting scientist opportunities within the departments.
• Continue to explore case studies - what has worked, but more so, what has not worked. Science progresses according to what has not worked, which gives us insights into the science and the regulatory context.
• Re-energize the RCC.
• Create opportunities for broader scientific participation in the design, conduct and interpretation of APCRA case examples. Involve experts beyond those in government.
• Create opportunities for public-private partnerships or cooperative agreements between government, academia and industry. Consider small business opportunities.
• Continue to engage with Canadian scientists and students to foster and maintain capacity in developing new approaches and solutions for policy-relevant questions.
• Provide and create increased opportunities for training and education on methods/models/approaches. Step up education on new methods and how they can be employed.

References

Arzuaga X, Smith MT, Gibbons CF, Skakkebæk NE, Yost EE, Beverly BEJ, Hotchkiss AK, Hauser R, Pagani RL, Schrader SM, et al. 2019. Proposed Key Characteristics of Male Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Evidence in Human Health Hazard Assessments. Environ Health Perspect, 127(6) https://pubmed.ncbi.nlm.nih.gov/31199676/

Becker RA, Dreier DA, Manibusan MK, Tony Cox LA, Simon TW, Bus JS. 2017. How well can carcinogenicity be predicted by high throughput "characteristics of carcinogens" mechanistic data? Regul Toxicol Pharmacol, 90:185-196. https://pubmed.ncbi.nlm.nih.gov/28866267/

Faure S, Noisel N, Werry K, Karthikeyan S, Aylward LL, St-Amand A. 2020. Evaluation of human biomonitoring data in a health risk-based context: An updated analysis of population level data from the Canadian Health Measures Survey. International Journal of Hygiene and Environmental Health, 223(1), 267-280. https://www.sciencedirect.com/science/article/pii/S1438463919304626

Friedman KP, Gagne M, Loo L, Karamertzanis P, Netzeva T, Sobanski T, Franzosa JA, Richard AM, Lougee RR, Gissi A, et al. 2020. Utility of In Vitro Bioactivity as a Lower Bound Estimate of In Vivo Adverse Effect Levels and in Risk-Based Prioritization. Toxicological Sciences, 173(1):202-225. https://academic.oup.com/toxsci/article-abstract/173/1/202/5571376

Guyton KZ, Rieswijk L, Wang A, Chiu WA, Smith MT. 2018. Key Characteristics Approach to Carcinogenic Hazard Identification. Chem Res Toxicol. 31(12): 1290-1292. https://pubmed.ncbi.nlm.nih.gov/30521319/

Hsieh N, Chen Z, Rusyn I, Chiu WA. 2021. Risk Characterization and Probabilistic Concentration-Response Modeling of Complex Environmental Mixtures Using New Approach Methodologies (NAMs) Data from Organotypic in Vitro Human Stem Cell Assays. Environmental Health Perspectives, 129(1). https://ehp.niehs.nih.gov/doi/full/10.1289/EHP7600

Krewski D, Bird M, Al-Zoughool M, Birkett N, Billard M, Milton B, Rice JM, Grosse Y, Cogliano VJ, Hill MA, et al. 2019. Key characteristics of 86 agents known to cause cancer in humans. Journal of Toxicology and Environmental Health, Part B, 22:7-8, 244-263, DOI: 10.1080/10937404.2019.1643536

La Merrill MA, Vandenberg LN, Smith MT, Goodson W, Browne P, Patisaul HB, Guyton KZ, Kortenkamp A, Cogliano VJ, Woodruff TJ, et al. 2020. Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification. Nat Rev Endocrinol 16(1):45-57. https://pubmed.ncbi.nlm.nih.gov/31719706/

Li L. 2020. Developing models for tracking the fate of chemicals in products in the total environment. In: Modeling the Fate of Chemicals in Products. Singapore: Springer Nature. https://www.springerprofessional.de/en/developing-models-for-tracking-the-fate-of-chemicals-in-products/17320218

Li L, Wania F. 2016. Tracking chemicals in products around the world: introduction of a dynamic substance flow analysis model and application to PCBs. Environ Int 94:674-686.

Luderer U, Eskenazi B, Hauer R, Korach KS, McHale CM, Moran F, Rieswijk L, Solomon G, Udagawa O, Zhang L, et al. 2019. Proposed Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment. Environ Health Perspect, 127(7) https://pubmed.ncbi.nlm.nih.gov/31322437/

Marvel SW, House JS, Wheeler M, Song K, Zhou Y, Wright FA, Chiu WA, Rusyn I, Motsinger-Reif A, Reif DM. 2021. The COVID-19 Pandemic Vulnerability Index (PVI) Dashboard: Monitoring County-Level Vulnerability Using Visualization, Statistical Modeling, and Machine Learning. Environmental Health Perspectives, 129(1). https://ehp.niehs.nih.gov/doi/10.1289/EHP8690

Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kaylock RJ, Lambert PF, et al. 2016. Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis. Environ Health Perspect, 124(6). https://pubmed.ncbi.nlm.nih.gov/26600562/

[U.S. EPA] United States Environmental Protection Agency. 2020. ORD Staff Handbook for Developing IRIS Assessments (Public Comment Draft, Nov 2020). U.S. EPA Office of Research and Development, Washington, DC, EPA/600/R-20/137, 2020. https://cfpub.epa.gov/ncea/iris_drafts/recordisplay.cfm?deid=350086

Wignall JA, Muratov E, Sedykh A, Guyton KZ, Tropsha A, Rusyn I, Chiu WA. 2018. Conditional Toxicity Value (CTV) Predictor: An In Silico Approach for Generating Quantitative Risk Estimates for Chemicals. Environmental Health Perspectives, 126(5). https://ehp.niehs.nih.gov/doi/full/10.1289/EHP2998

Annex A: List of participants