HESI Global Insights September 2025

HESI Global is proud to announce the renewal of a Memorandum of Understanding (MOU) with the U.S. Food and Drug Administration (FDA) and the National Institute of Environmental Health Sciences (NIEHS), reaffirming their joint commitment to collaboration on the Botanical Safety Consortium (BSC). This new MOU, now valid for the next five years, reinforces the critical multi-sector framework that underpins the BSC’s mission to enhance the scientific basis for botanical ingredient safety.

This renewed partnership marks a significant milestone in HESI Global’s continued efforts to foster cross-sector collaboration for public health protection. Congratulations to all involved in making this achievement possible!

The Health and Environmental Sciences Institute (HESI Global) is pleased to announce that the United States Environmental Protection Agency (US EPA) Office of Pesticide Programs (OPP) and HESI Global have signed a co-sponsorship agreement for the 2025 Innovate EcoSafety Summit.

The 2025 Innovate EcoSafety Summit, is an inaugural international workshop (October 7–9, 2025, in Reykjavík) that will convene experts from academia, government, industry, and non-profits to advance ecological risk assessment and hazard evaluation through the application of New Approach Methodologies (NAMs), with a focus on reducing and replacing acute fish testing and advancing the science for evaluating chemical endocrine activity potential for fish and amphibians.

Disclaimer
The US EPA’s support of the Summit does not imply official endorsement of, or responsibility for, the opinions, ideas, data, products, or services presented in association with the Summit nor does it imply endorsement of general policies, activities, or products of HESI Global. The U.S. Environmental Protection Agency (EPA) logo is an identifying trademark of the EPA. The EPA logo is used here with permission for informational purposes only and to denote EPA as a co-sponsor.

We are proud to share that Dr. Carole Yauk, Chair of the HESI Board of Trustees and Professor at the University of Ottawa, has been named the recipient of the prestigious 2025 Alexander Hollaender Award by the Environmental Mutagenesis and Genomics Society (EMGS).

This award recognizes scientists who have made outstanding contributions to the application of environmental mutagenesis and genomics toward the protection of human health—principles that are deeply aligned with the HESI mission to advance science for a safer, more sustainable world.

Dr. Yauk is being honored for her pioneering work at the interface of genomics, regulatory science, and human health risk assessment. Through her leadership and research, she has advanced the use of molecular and genomic tools in environmental health decision-making, providing new insights into how environmental exposures affect gene expression and contribute to disease risk.

Her efforts have catalyzed transformative change in regulatory science, from the development of transcriptomic biomarkers to the integration of New Approach Methodologies (NAMs) in chemical safety assessment. These innovations have not only advanced the field scientifically but also helped reduce animal use and increase the precision of risk predictions—hallmarks of HESI’s scientific and ethical priorities.

In addition to her academic leadership, Dr. Yauk has been a long-time contributor to HESI programs and a champion of multi-sector collaboration. Her role as HESI Board Chair exemplifies her dedication to ensuring that cutting-edge science informs global policy and practice.

Dr. Yauk was formally recognized at the 2025 EMGS Annual Meeting. The Alexander Hollaender Award is one of EMGS’s highest honors, celebrating a legacy of scientific excellence and public health impact.

Please join us in congratulating Dr. Yauk on this well-deserved recognition!

Learn more about the award here: EMGS Alexander Hollaender Award
Learn more about HESI’s Board and mission: hesiglobal.org

HESI Global is proud to recognize Dr. Erin Maloney (Shell Global Solutions) for her leadership and tireless contributions as Co-Chair of the UVCB / Multi-Constituent Substances (MCS) Committee.

Dr. Maloney has advanced ecological risk assessment through her work on chemical prioritization methods and improvements to toxicity testing approaches, helping to strengthen more effective, science-based strategies for evaluating environmental impacts. Beyond her professional achievements, she brings enthusiasm and a collaborative spirit that strengthens every project she engages in.

Within the committee, she has been instrumental in progressing the committee’s pilot database of “Tier 0” information, as well as contributing to the development of an exposure-based, tiered risk assessment framework for prioritizing UVCBS. In her role as co-chair, Dr. Maloney is also contributing to discussions regarding next steps for the committee. Her guidance bridges scientific rigor with regulatory and industry needs, while her willingness to roll up her sleeves has ensured steady progress on complex projects.

We extend our deep gratitude to Dr. Maloney for her commitment, leadership, and lasting impact on the committee’s work.

HESI Global is pleased to announce that Dr. Michelle Embry, HESI Global Deputy Director, will be a featured speaker at the upcoming NC3Rs webinar titled “Artificial Intelligence in Safety Assessment: Perspectives for the Future”, taking place on Thursday, 25 September 2025 from 8:00–10:00 AM ET (14:00–16:00 CEST).

Co-hosted by the NC3Rs NAMs Network and the British Toxicology Society’s Mechanistic & Discovery Toxicology Specialty Section, this webinar will explore cutting-edge opportunities for applying AI and machine learning in toxicology. Attendees will hear from three leading experts on how these technologies are transforming safety assessment and reducing reliance on animal models.

Dr. Embry will present: “Overview of 2025 HESI Workshop: Building a Roadmap for AI-Enabled Human and Environmental Health Protection”, highlighting outcomes from the June 2025 HESI Global Workshop, which brought together global stakeholders to outline strategic next steps for integrating AI in safety science. Her talk will spotlight key takeaways, including ethical and technical considerations, and a collaboratively developed roadmap for responsibly leveraging AI in health and environmental protection.

This presentation aligns with HESI Global’s mission to provide science-based solutions to complex public and environmental health challenges. The 2025 HESI Global Workshop, and this upcoming webinar, are part of HESI’s broader commitment to catalyzing collaborative, multidisciplinary approaches to innovative science.

Registration is free and open to the public.
Secure your spot and learn more: NC3Rs Webinar Registration
Learn more about the HESI Global Workshop here: 2025 HESI Workshop Overview

Let’s continue shaping the future of AI in toxicology and health protection.

HESI Global is pleased to announce the publication of a new manuscript in Reproductive Toxicology, titled: “New Approach Methodologies for Assessing Developmental Toxicity of Pharmaceuticals: Case Examples and Future Directions.”

This cross-sector effort, led by the HESI Global Developmental and Reproductive Toxicology (DART) Committee, addresses a critical challenge in modern drug development: how to assess developmental toxicity (Dev Tox) more efficiently and ethically without compromising human safety. The paper explores the real-world application of New Approach Methodologies (NAMs) such as stem cell-based assays, zebrafish models, and computational tools.

The Issue
Developmental toxicity testing is a cornerstone of pharmaceutical safety, especially for protecting pregnant populations. Traditionally, this testing relies on animal studies in two species, which are costly, time-consuming, and resource-intensive.

The Problem
Despite scientific advances and the updated ICH S5(R3) guideline that supports use of NAMs, adoption remains limited. Challenges include uncertainty around assay predictivity, lack of shared case data, and hesitancy from regulatory stakeholders.

The Solution
The HESI Global team conducted an in-depth analysis of the current NAMs landscape, gathered input from pharmaceutical developers, and compiled case studies to illustrate how NAMs can complement or even replace traditional animal testing under the right conditions. The publication also provides forward-looking recommendations to facilitate broader regulatory acceptance.

The Benefit
This work directly supports HESI Global’s mission to develop collaborative, science-based solutions for global health challenges. By advancing the practical use of NAMs, this publication promotes a future of safer, more sustainable pharmaceutical development, while reducing reliance on animal models.

This is another strong example of how HESI Global convenes academia, industry, and government to solve complex toxicological challenges.

This publication is the first in a series from the committee on new approach methodologies for DART.

🔗 Access the publication:
Powles-Glover et al., 2025. New Approach Methodologies for Assessing Developmental Toxicity of Pharmaceuticals: Case Examples and Future Directions.  Reproductive Toxicology. https://doi.org/10.1016/j.reprotox.2025.109035

A new publication from the HESI Global Cardiac Safety Committee, titled “Validating and Using Cardiac NAMs for Toxicity Screening and Drug Development” (Pierson et al., International Journal of Toxicology, 2025), presents a comprehensive evaluation of novel, human-relevant models for assessing cardiac toxicity.

This work addresses longstanding challenges in drug development, where traditional animal models often fail to predict human cardiac outcomes. Through a multi-year FDA-funded grant, the committee assessed the performance of new approach methodologies (NAMs), including human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs), engineered heart tissues, and microfluidic vascular systems.

The publication outlines how these tools can detect key cardiac failure modes such as contractility changes, arrhythmias, and vascular injury earlier in the development process. It also provides insight into their potential integration into regulatory frameworks, with a focus on increasing predictive accuracy and reducing animal use.

This work supports HESI Global’s mission to collaboratively advance science for a safer, more sustainable world by promoting ethical, efficient, and scientifically robust alternatives for cardiac safety evaluation.

Read the full article here:
Pierson et al., 2025. Validating and Using Cardiac NAMs for Toxicity Screening and Drug Development. International Journal of Toxicology. https://doi.org/10.1177/10915818251375348

Thrombotic complications, such as myocardial infarction, stroke, and venous thrombosis, are leading contributors to late-stage drug attrition. Despite strong capabilities in detecting bleeding risks, current nonclinical safety assessments often fall short in identifying early prothrombotic imbalances—critical precursors to thrombosis that can go undetected until it’s too late.

A new publication from the HESI Global Cardiac Safety Committee, now available in Toxicologic Pathology, addresses this critical gap in nonclinical testing. The study, “Evaluation of Biomarkers to Detect Early Prothrombotic Imbalance in Rat Models of Hypercoagulability Induced by Thromboplastin Infusion and Hypofibrinolysis Induced by Tranexamic Acid,” explores innovative approaches to detecting prothrombotic states before overt symptoms appear.

Using rat models, the research team evaluated two distinct mechanisms: hypercoagulability triggered by thromboplastin infusion, and hypofibrinolysis induced by tranexamic acid. The study assessed a range of biomarkers to identify early signs of prothrombotic imbalance and compared their effectiveness to traditional coagulation screening tests.

Key Findings:
• D-dimer, thrombin-antithrombin complex (TAT), plasminogen activator inhibitor-1 (PAI-1), and Factor VIIa activity were the most sensitive markers of hypercoagulability.
• A kinetic turbidimetric assay was most effective for characterizing hypofibrinolysis.
• Traditional tests such as APTT, PT, and fibrinogen were relatively insensitive in this context, highlighting the need for more refined tools.

The findings support the use of tailored biomarker panels for a more nuanced and effective early assessment of prothrombotic states in preclinical drug development. This work exemplifies HESI’s mission to collaboratively develop science that leads to safer, more sustainable health solutions by proactively addressing critical challenges in drug safety evaluation.

Read the full article here: Brooks et al., 2025. Evaluation of Biomarkers to Detect Early Prothrombotic Imbalance in Rat Models of Hypercoagulability Induced by Thromboplastin Infusion and Hypofibrinolysis Induced by Tranexamic Acid. Toxicological Pathology. https://doi.org/10.1177/01926233251349767

A new commentary from HESI Global’s Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee, “Navigating complexity in modern toxicology: the role of omics in short-term in vivo studies,” offers a forward-looking perspective on how omics technologies are transforming chemical risk assessment.

Published in Toxicological Sciences, the article explores how integrating transcriptomics, metabolomics, and other omics endpoints into short-term (5–28 day) in vivo studies can offer earlier, more human-relevant insights into chemical toxicity. This approach supports faster decision-making, reduces reliance on long-term animal testing, and advances Next-Generation Risk Assessment (NGRA).

The commentary also addresses key challenges, such as variability in data analysis pipelines and the need for regulatory alignment, and highlights the eSTAR Committee’s collaborative work to develop standardized, reproducible methods for deriving transcriptomic points of departure (tPODs).

This work exemplifies HESI’s mission to generate science-based solutions that protect human and environmental health through cross-sector collaboration.

Read the full article here:
Mitchell et al., 2025. Navigating complexity in modern toxicology: the role of omics in short-term in vivo studies. Toxicological Sciences. https://doi.org/10.1093/toxsci/kfaf120

On August 26, the HESI Committee on Transforming the Evaluation of Agrochemicals (TEA), with support from the Global Risk Assessment Training Center (GRATC) and in collaboration with SETAC Latin America, hosted a symposium focused on the safety evaluation of agrochemicals in South America.

The event brought together over 20 regulatory scientists from 9 Latin American countries, along with representatives from academia and industry, fostering dialogue on regional needs and priorities in this critical area.

The symposium provided a valuable platform for regulators and scientists from other sectors to share perspectives, exchange knowledge, and help us better understand the needs to advance the evaluation of plant protection products in this part of the world, but also explore opportunities for collaboration.

A special thank you to Dr. Eliana Munarriz (University of Buenos Aires and HESI Global Board Member) for her invaluable efforts in connecting HESI Global to the Latin American regulatory community!

HESI Global had a strong presence at SETAC Latin America, held in Lima, Peru from August 26 – 29, 2025, with Drs. Sandrine Deglin, Michelle Embry, and Julie Krzykwa representing the organization.

Dr. Michelle Embry delivered an invited plenary lecture titled “Towards One Health: Toxicokinetics at the Intersection of Human and Ecological Health,” and co-chaired sessions on Human Health Risk Assessment, and New Approach Methodologies (NAMs).

Dr. Sandrine Deglin gave an oral presentation titled “Transforming the Evaluation of Agrochemicals” as part of the session “Fertilizers, Pesticides and Plant Protection Products: Environmental Chemistry, Fate and Transport, Toxicity, and Risk Assessment.”

In addition, the work of HESI’s UVCB committee was featured in a poster presentation: “Tripartite Perspectives on Challenges and Opportunities for the Environmental Testing and Assessment of Substances of Unknown or Variable Composition, Complex Reaction Products, or Biological materials (UVCBs).”

The event underscored HESI’s commitment to advancing science-based solutions to address complex health and environmental challenges across Latin America and beyond.

HESI had a strong presence at the 13th World Congress on Alternatives and Animal Use in the Life Sciences (WC13), held in Rio de Janeiro, Brazil, from August 31 to September 4, 2025.

Dr. Sandrine Deglin (HESI Global) and Dr. Shadia Catalano (Corteva Agriscience) co-chaired a session titled “Exposure-Based Human Risk Assessment to Minimize Unnecessary Animal Testing for Agrochemicals.” This session spotlighted key elements of the new safety evaluation paradigm developed by HESI’s Committee on Transforming the Evaluation of Agrochemicals (TEA).

Dr. Deglin presented the Committee’s conceptual model, and additional speakers demonstrated potential applications of this framework to reduce reliance on animal testing while maintaining robust safety standards.

A special thank you to Ms. Elaine Freeman (Exponent, Inc.), Dr. Philip Marx-Stoelting (BfR), and Dr. Gina Hilton (PETA Science Consortium International) for their thoughtful presentations and contributions to a highly successful session.

This engagement reflects HESI’s ongoing commitment to advancing science-based, human-relevant, and ethical approaches to safety assessment for a more sustainable future.

The inaugural ecoNAMs webinar, titled “State of the science for bioaccumulation: an integrated, weight of evidence approach,” took place on 10 September 2025, drawing more than 450 attendees and nearly 900 registrants worldwide.

The webinar featured presentations from Dr. Pippa Curtis-Jackson, Senior Specialist at the Chemical Assessment Unit or the United Kingdom Environment Agency, and Dr. Michelle Embry, Deputy Director of the Health and Environmental Sciences Institute (HESI Global). A recording of the event is available here.

This presentation marked the first in a new ecoNAMs webinar series on the use of new approach methodologies (NAMs) in ecotoxicology. The series is co-organized by the European Medicines Agency, the Health and Environmental Sciences Institute, the National Institute for Environmental Studies (NIES, Japan), PETA Science Consortium International e.V., the US Environmental Protection Agency, and the US Food and Drug Administration.

This initiative reflects HESI Global’s mission to foster global collaboration and deliver science-based solutions to complex health and environmental challenges.

More information on this webinar series is available at: https://www.thepsci.eu/eco-nams-webinars/

The 2025 Environmental Mutagenesis and Genomics Society (EMGS) Annual Meeting took place in Rochester, New York from 6–10 September. HESI Global was well represented – from Board member Dr. Carole Yauk receiving the Alexander Hollaendar award to active contributions across the program by scientists from the Genetic Toxicology Technical Committee (GTTC), the Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee, and the Botanical Safety Consortium (BSC).
HESI participants chaired sessions, delivered invited talks, contributed to symposia, and shared new science through poster presentations, underscoring the Institute’s role in advancing collaborative, evidence-based approaches to toxicology and risk assessment. A full listing of HESI-related programming is available online here.

Highlights from HESI Global committees included:

• A poster presentation from the Botanical Safety Consortium Genotoxicity Working Group, sharing updates on their recent progress;
• A session co-chaired by Connie Chen, HESI Senior Advisor, tackled the question of whether the error corrected sequencing revolution for genotoxicity had arrived. (The general consensus was that it was dependent on the context of use!)
• A session co-chaired by Raechel Puglisi, HESI Scientific Program Manager, Wen Sun (Pfizer), and Anthony Lynch (GSK) titled ‘Improving Hazard Identification of Nitrosamines: Enhancing the Ames Assay and Mammalian Cell Approaches’ highlighted work from the HESI Nitrosamines Research Program.
• A talk by Connie Mitchell, HESI Senior Scientific Program Manager, on miRNA biomarkers developed through the eSTAR program.
• A presentation by James Alper Alcarez (University of Ottawa and GTTC professional development trainee awardee) on eSTAR’s Error-Corrected Sequencing Project.
• GTTC professional development travel awardees, Ms. Josie Jabbour (University of Ottawa) and Ms. Gloria Melzi (University of Milan), presented on their ongoing research.

From foundational awards to cutting-edge science, HESI’s presence at EMGS 2025 reflected our commitment to shaping the future of safety science through cross-sector collaboration and innovation. Committee members were able to enjoy a robust social program to catch-up with and meet new friends and make long-lasting memories along the way.

On September 11, HESI Global Senior Scientific Program Manager Connie Mitchell and Botanical Safety Consortium (BSC) Steering Committee Member Dr. Amy Roe (Procter & Gamble) delivered a webinar titled “The Botanical Safety Consortium: Five Years Driving Collaborative Progress in Botanical Safety” as part of the US FDA’s Office of Food Chemical Safety, Dietary Supplements, and Innovation (OFCSDSI) Seminar Series.

The session drew participation from over 180 FDA staff members, underscoring strong regulatory interest in botanical safety. The presentation highlighted BSC’s mission to enhance the safety assessment of botanical ingredients through a collaborative, science-driven approach. Dr. Roe and Ms. Mitchell outlined key milestones from the Consortium’s five-year journey, including the development of fit-for-purpose New Approach Methodologies (NAMs), strategic partnerships, and publication of peer-reviewed studies advancing botanical safety science.

The Consortium’s work directly supports HESI’s mission of developing science-based solutions to complex health and environmental challenges. By applying modern toxicological approaches to botanicals, complex mixtures with unique testing challenges, the BSC is helping to modernize risk assessment practices and improve public health protections. Its contributions are also aligned with HESI’s broader goals of innovation, cross-sector collaboration, and translational science.

Looking ahead, the BSC will continue to expand its scientific toolkit, strengthen stakeholder engagement, and publish data that improves decision-making around botanical safety. For more information on the BSC, visit https://botanicalsafetyconsortium.org

On September 11th & 12th, HESI Global’s Antibody Drug Conjugate (ADC) Safety Committee, in partnership with the Dana-Farber Cancer Institute, hosted an invitational workshop at Harvard Medical School on “The Pathogenesis of ADC-Associated Clinical Toxicities: Ocular and ILD (Interstitial Lung Disease).”

Attended by over 200 participants, this 2-day event brought together a diverse group of academic researchers, industry scientists, clinicians, and regulatory stakeholders to explore two of the most challenging toxicities associated with ADC therapies—ocular toxicity and interstitial lung disease—where the underlying pathophysiology remains unclear.

The workshop program featured clinical perspectives, mechanistic insights, nonclinical case studies, cross-disciplinary expert panels, and audience discussions, all designed to stimulate dialogue and collaborative thinking. By bridging preclinical and clinical perspectives, participants worked to identify knowledge gaps, clarify biological pathways, and explore strategies to address key gaps. The insights generated during this workshop will help inform the development of ADCs with reduced toxicity without compromising therapeutic benefit, and ultimately improve patient outcomes.

HESI Global is excited to announce two open positions for Senior Scientific Program Manager roles, each with a unique focus area:

1. Environmental Health & Risk Assessment
2. Biologics & Advanced Therapeutics

Why HESI Global?

Join a mission-driven nonprofit where science drives public good. At HESI Global, your work will advance safety science, protect public and environmental health, and promote sustainable decision-making. You’ll collaborate with world-renowned experts from academia, government, and industry, working at the forefront of scientific progress that matters.

Full job descriptions and application details can be found here: https://hesiglobal.org/careers/

If you’re ready to bring your expertise to a collaborative, high-impact scientific community, we encourage you to apply today!

At HESI Global, collaboration is our foundation. This month’s newsletter offers a compelling snapshot of how HESI Global’s partnerships and scientific initiatives are driving meaningful progress in health and environmental sciences.

From renewed agreements with the FDA and NIEHS to our co-sponsorship of the 2025 Innovate EcoSafety Summit with the US EPA, HESI Global continues to be a trusted convener of cross-sector expertise. These milestones reflect our commitment to advancing public health through transparent, inclusive, and science-based collaboration.

Our global impact is evident in recent events across Latin America and Europe, where HESI Global teams engaged with regulators, academics, and industry leaders to shape the future of agrochemical safety, toxicology, and risk assessment. Whether through plenary lectures in Peru, interactive workshops in Brazil, or webinars with international agencies, HESI Global is creating platforms for shared learning and innovation.

The scientific output featured this month—from developmental and cardiac toxicity to biomarker discovery and omics integration—are more than research. They are collaborative blueprints for developing globally impactful science.

Looking ahead, our calendar is filled with opportunities to connect, learn, and lead. From the upcoming EcoSafety Summit in Iceland to workshops in the Netherlands, Belgium, and the U.S., HESI Global is continuing to expand its partnerships and deepen its impact.

None of HESI Global’s achievements would be possible without the dedication and expertise of our incredible staff, committee members, and collaborators around the world. I’d like to extend my heartfelt thanks and congratulations to all those recognized in this issue for their leadership, scientific contributions, and commitment to advancing our shared mission. It is through your time, talent, and tireless engagement that HESI Global continues to be a catalyst for collaborative, impactful, science-based solutions.

Kind regards,
Gary Minsavage, PhD, DABT, MBA
HESI Global Board of Trustee Member and President of Assembly