HESI Insights - September 2022

It is with great sadness and deep affection that we share news of the passing of former HESI Associate Director, Nancy Doerrer, on August 23, 2022. Nancy was a remarkable, joyful, skilled, sardonic, insightful, and treasured member of the staff and a dear friend and mentor to many of us. Her tenure at HESI extended from 2002 – 2015 when she left to spend more time with family while she tackled her diagnosis of advanced melanoma. Many of you have already reached out to share fond and funny memories of your interactions with her over the years…thank you for that.

It is our plan to find a means to keep her active in HESI’s memory and honor her spirit and commitment to science – more on that to come.
Those of us fortunate enough to have known her will forever appreciate that privilege. Thank you, Nancy. You are missed…

HESI’s Genetic Toxicology Technical Committee (GTTC) AOP working group’s article “AOP report: Development of an adverse outcome pathway for oxidative DNA damage leading to mutations and chromosomal aberrations” published March 2022, was recently selected as the Editor’s Choice Article by Environmental and Molecular Mutagenesis. This AOP is currently included in the OECD workplan and is awaiting approval and endorsement.

Congratulations to all the authors!

Click below to read the full article:
AOP report: Development of an adverse outcome pathway for oxidative DNA damage leading to mutations and chromosomal aberrations. Eunnara Cho, Ashley Allemang, Marc Audebert, Vinita Chauhan, Stephen Dertinger, Giel Hendriks, Mirjam Luijten, Francesco Marchetti, Sheroy Minocherhomji, Stefan Pfuhler, Daniel J. Roberts, Kristina Trenz, Carole L. Yauk. Environmental and Molecular Mutagenesis. 21 March 2022.

This article highlights the key aspects of a new tiered approach to assess the ecological risks of unknown or variable composition, complex reaction products, and biological materials (UVCBs).

Click below to read the full article:
The Path to UVCB Ecological Risk Assessment: Grappling with Substance Characterization. Salvito D, Fernandez M, Déglin SE, Samuel AJ, Lyon DY, Lawson N, MacLeod M. Environmental Toxicology and Chemistry. 12 August 2022.

Click to learn more about HESI’s UVCBs and Multi-Constituent Substances (MCS) Committee

This article summarizes the challenges associated with the modernization of agrochemical safety evaluation, proposes a potential roadmap, and seeks input and engagement from the broader community to advance this effort.

Click below to read the full article:
Transforming the Evaluation of Agrochemicals. Wolf DC, Bhuller Y, Cope R, Corvaro M, Currie R, Doe J, Doi A, Hilton G, Mehta J, Saltmiras D, Sewell F, Trainer M, Déglin SE. Pest Management Science. 26 August 2022. https://doi.org/10.1002/ps.7148

Click to learn more about HESI’s Transforming the Evaluation of Agrochemicals (TEA) Committee

This short review paper, written by members of the Botanical Safety Consortium, explores botanical induced renal injuries and introduces new approach methodologies (NAMs) that could be used to identify the nephrotoxic potential of botanicals.

Click below to read the full article:

Plant vs. Kidney: Evaluating Nephrotoxicity of Botanicals with the Latest Toxicological Tools. Pearson A, Gafner S, Rider CV, Embry M, Ferguson SS, Mitchell CA. 2022. Current Opinion in Toxicology. 31 August 2022. https://doi.org/10.1016/j.cotox.2022.100371

The African Continental Association for Food Protection hosted a webinar on risk assessment approaches for food safety: HESI and JIFSAN Initiatives. The webinar was co-presented by Dr. Clare Narrod (Director, Risk Analysis / Impact Evaluation Programs, JIFSAN) and Dr. Michelle Embry (Deputy Director, HESI), and provided an overview of ongoing programs within the Health and Environmental Sciences Institute (HESI) and the Joint Institute for Food Safety and Applied Nutrition (JIFSAN). The webinar started by providing context and the rationale behind the risk analysis process that is required by many countries for protecting the food supply, followed by a brief description of the courses covered in the JIFSAN Risk Analysis Training program. The HESI Risk Assessment in the 21st Century (RISK21) Framework was presented, with several relevant examples of its use highlighted, including a brief tutorial on the web-based visualization tool.

View the full recording here.

HESI made a strong showing at the 13^th ICEM Conference in Ottawa from August 27-September 1, 2022.  Conference highlights included a highly subscripted HESI-sponsored workshop on “Advancing the Next Generation of Genetic Toxicology and Cancer Risk Assessment” , multiple sessions featuring outputs from the HESI eSTAR and GTTC Committees, a HESI information session for students, trainees, and academic/government scientists, and a keynote lecture on ‘The Last Mile Problem in Environmental Health Protection Sciences” by HESI’s Executive Director, Dr. Syril Pettit.  The meeting was co-chaired by HESI Vice-Chair of the Board, Dr. Carole Yauk of University of Ottawa.  For many of us, this was the first large scale in-person event in several years and it was great to make new connections and reaffirm existing ones.

The 8th IWGT meeting, held in Ottawa, Canada from 23-26 August, was a satellite meeting to the ICEM held every four years. The outcome of these working group meetings is data-driven consensus recommendations, which regularly serve as the basis for regulatory guidance language. The HESI GTTC and eSTAR committee’s work was featured in each of the five working groups. The discussions and consensus recommendations will be submitted for publication in peer-reviewed literature.

The Botanical Safety Consortium’s pre-Congress Event on “Development of a Toolkit to Evaluate Botanical Safety” was a great success! The dynamic and engaging talks were followed by a short panel discussion and audience questions related to the future of botanical safety and how collaborative, multi-partite partnerships can serve as catalysts to advance this important field. Speakers hailed from six countries and covered topics including the regulation of botanicals, chemical analyses of botanicals for safety assessment, and new approach methodologies for botanical toxicity screening. In addition, the session featured two speakers from the West-African Green Medicine Initiative, which is aimed at providing sustainable integration of traditional medicine into the universal health care system by establishing strong scientific evidence and supporting the development of medicinal products with controlled pharmaceutical quality.

The full program is available HERE.

Please join us for an upcoming webinar, organized by the HESI Next Generation Ecological Risk Assessment Committee: Dr. Marlo Jeffries (TCU) will present ongoing research related to the Fish Embryo Toxicity Test in a talk titled Investigating the Predictive Power of Sublethal Endpoints for Fish Embryo Toxicity Tests.

The fish embryo acute toxicity (FET) test is known to be less sensitive than the fish acute test for some chemicals, including neurotoxicants. Thus, there is an interest in identifying additional endpoints that can improve FET test performance. The goal of this project was to advance alternative toxicity testing methods by determining whether select developmental abnormalities—snout-vent length, eye size, and pericardial area—are linked to adverse alterations in ecologically-relevant behaviors and delayed mortality. Fathead minnow (Pimephales promelas) FET tests were conducted with 3,4-dicholoroaniline, cadmium, and perfluorooctanesulfonic acid (PFOS) and developmental abnormalities were quantified. Surviving eleutheroembryos were reared in clean water to 14 days post fertilization (dpf), during which time behaviors and mortality were evaluated. None of the abnormalities evaluated were predictive of behavioral alterations; however, embryos with ≥14% reductions in length or ≥3.54-fold increases in pericardial area had an 80% chance of mortality by 14 dpf. When these abnormalities were used as markers of mortality, the LC50s for cadmium and PFOS were less than those calculated using only standardized FET test endpoints and similar to those obtained via larval fish tests, indicating that the snout-vent length and pericardial area warrant consideration as standard FET test endpoints.

Click to Register

The HESI Developmental and Reproductive Toxicology Committee (DART) is launching a trainee program to heighten the awareness of career opportunities within DART and to provide guidance to aspiring toxicologist who like to make an impact on the field.

On September 16th from 10:30 am -1:30pm EST the committee will be a hosting it’s first-ever FREE Fall DART Career Symposium. This event is open to all graduate students and post- doctoral trainees who may be interesting learning more about careers in DART. Attendees will hear from scientific leaders from various sectors who will share their journey while providing invaluable career insight. This is an event you don’t want to miss!

Register for the event here. https://hesiglobal.org/event/hesi-dart-fall-career-sumposium/
Learn more about our upcoming DART Trainee opportunities by signing up for our mailing list when visiting the HESI website (Keep watch for the purple pop-out). For a sneak peak of future activities Watch Video HERE.

HESI will be attending the International Congress of Toxicology in Maastricht, Netherlands from 18-21 September 2022. Details below.

19 September 2022, 10am – NeuTox Committee Presentation

Session 03: (Target organ): Minimally-invasive Biomarkers of Central Nervous System Toxicity

• Ruth Roberts (Chair and Director of Drug Discovery, University of Birmingham, UK): Overview of Fluidic Biomarkers of CNS toxicity – The HESI Consortium Approach

21 September 2022, 11:00 – 13:00 – HESI PBPK Committee Session

Session 28: Putting the Puzzle Together: Multiple Lines of Evidence to Inform Design and Interpretation of Long-Term, Repeated-Dose Animal Studies to Inform Human Health Risk Assessment [Michelle Embry and Jos Bessems, chairs]

• Nynke Kramer (Wageningen University, NL): In Vitro and In Silico Tools for Estimating Chemical-Specific Kinetic Processes
• Cecilia Tan (United States Environmental Protection Agency, USA): Applying Physiologically Based Pharmacokinetic (PBPK) Modeling to Design and Optimize Animal Toxicity Studies
• Alicia Paini (European Commission, Joint Research Centre, IT): Using Adverse Outcome Pathways (AOPs) to Support Tiered-Testing Strategies for Toxicity Assessment
• Jeanne Domoradzki / Marco Covaro (Corteva Agriscience, USA): Putting the puzzle together: Integrated Weight of Evidence (WoE) Approach to Optimize Animal Toxicity Studies

Poster – HESI Botanical Safety Consortium

• New Approach Methodologies to Evaluate Botanical Safety – poster by Michelle Embry, HESI Botanical Safety Consortium

BSC Annual Meeting: Due to continued uncertainties with COVID-19, feedback from our stakeholders and the goals of the meeting, we have decided to make this year’s Botanical Safety Consortium’s Annual Meeting FULLY Virtual. The full agenda is now available here!

The meeting is free and open to all.

Click to Register

Registration is now open! HESI’s Developmental and Reproductive Toxicology (DART) committee will be hosting a hybrid workshop in Washington, DC, titled “Interpretation of developmental and reproductive toxicity in regulatory contexts and frameworks”. Space will be limited for in-person attendance, but a virtual option will be available for those who are unable to travel.

Register on the event page here.

For more information contact Connie Chen (cchen@hesiglobal.org)

The Health and Environmental Sciences Institute (HESI) & Safety Pharmacology Society (SPS) present a new, on-demand training opportunity: A closer look at the new ICH E14/S7b Q&A’s and Training Materials. The target audience includes all sponsors (small and large; other stakeholders in pharma), safety pharmacologists and toxicologists participating in the delivery of the nonclinical data, clinicians, and regulators. See the course content below.

Overview of the ICH E14/7B Q&A Training Materials
Introduction – David Strauss, FDA, United States
Integrated Risk Assessment – Zhihua Li, FDA, United States
In Vitro – Derek Leishman, Lilly
In Vivo – Hugo Vargas, Amgen
Conclusions – David Strauss, FDA, United States

Case Studies and Scenarios for 5.1
Moderator: Christine Garnett, FDA, United States
Speakers – Corina Dota, EFPIA & Wendy Wu, FDA, United States
Topics covered: E14 Pathways and New Options, Clinical Scenarios, Integrated Nonclinical Data
(in vitro & in vivo)

Case Studies and Scenarios for 6.1
Moderator: Christine Garnett, FDA, United States
Speakers – Hugo Vargas, Amgen & Flora Musuamba Tshinanu, FAGG-AFMPS, Europe
Topics covered: E14 Pathways and New Options, Clinical Scenarios, Integrated Nonclinical Data
(in vitro & in vivo)
Summary of integrated risk data

Training Goals
1. Recognize when nonclinical data may be used in the regulatory QT assessment, including understanding the difference between 5.1 and 6.1.
2. Recognize quality hERG and in vivo studies:
a. Are the studies of reasonable quality with the appropriate quality measures?
b. Is the study consistent with the performing lab’s experience with reference agents?
3. Gain familiarity with clinical exposure definitions and how margins are defined to understand the hERG and in vivo margin.
4. Recognize a double-negative nonclinical package.
5. Understand what information is needed to justify the integrated QTc risk assessment.
6. Understand that there can be mitigation around some of the nonclinical study features.
7. Understand timing of various assays and how to progress to clinic.
8. Understand the flexibility of these guidelines and what alternatives may be implemented.

This training is being provided complimentary for SPS and HESI members, and offered to nonmembers for $49.00 USD until 31 December 2022.

Click to link to training course

Contact Jennifer Pierson at jpierson@hesiglobal.org for details.

Cardiac Safety Committee:

• Early Career Scientific Seminar Series Award
  • Accepting Applications: Sept 19th – Nov 1st
  • Who can Apply? Postdocs and early career scientists

Genetic Toxicology Technical Committee:

• Early Career Scientific Seminar Series Award
  • Accepting Applications: Oct 10th – Dec 2nd
  • Who can Apply? Postdocs and early career scientists
• Professional Development Award
  • Accepting Applications: Sept 26th – Nov 7th

I’ve always been impressed by HESI’s ability to bring together the number of researchers it does, from across sectors and disciplines to work together on addressing some truly significant health and environmental sciences challenges. The collaborative environment HESI creates, and the scientific and creative intellect HESI staff provide are critical factors in why scientists make HESI their partner of choice when faced with these such challenges.

This month’s Insights highlights just a handful of HESI’s diverse scientific portfolio and the breadth of output’s that are achievable taking HESI’s collaborative, solutions-driven approach. If you want to be part of this and are facing a scientific challenge that would benefit from HESI’s approach, please reach out to HESI staff, or board members to discuss how we can help you and consider submitting a project proposal using the mechanism above.

Finally, like Ruth last month, I’d also like to thank both Jon Cook and Martin van den Berg as outgoing President and Chair respectively. Their leadership, guidance, and commitment to HESI over such a difficult period has been inspiring and it has been a pleasure to work alongside them over the past few years.

Kind Regards,

Anthony Holmes, PhD, President of HESI Assembly