HESI Insights - March 2022

THIS NEW WEBSITE WILL HELP CREATE AND GROW A COMMUNITY OF PRACTICE FOSTERING THE USE OF EPIDEMIOLOGY FOR QUANTITATIVE RISK ASSESSMENT. JOIN THE EPIFORA NETWORK BY CREATING A PROFILE IN THE EPIFORA DATABASE.

HESI’s Environmental Epidemiology Committee is launching a new website: Epifora (EPIdemiology FOr Risk Assessment; www.epifora.org) featuring the importance of epidemiology in quantitative risk assessment. The site is a one-stop-shop for educational materials such as webinars and publications relevant to this topic, as well as a new database of scientists of various seniority levels and expertise, with an interest in the field.

The Epifora Database will help bridge different activity sectors and disciplines, and facilitate collaboration and networking among all stakeholders willing to engage on the topic of epidemiology and risk assessment.

Whether you would like to learn more about the role of epidemiology in risk assessment, or whether you are looking for collaborators or mentors in a related field, we encourage you to visit our website and join the Epifora community of practice by creating a profile in our database.

For any questions or feedback, please contact Sandrine Deglin (sdeglin@hesigolbal.org)

Would you like to help crack the problem of UVCB/ Multi-Constituent Substances (MCS) risk assessment?

HESI’s UVCB/MCS Committee is currently developing an exposure-based, tiered ecological risk assessment approach for these substances. We are presently looking for stakeholders of all sectors to join us in fulfilling this challenging mission.

For details and contact information, see the committee webpage: https://hesiglobal.org/uvcb/

The Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee is exploring two new projects, one relating to cell painting for safety assessment and the other exploring the use of error corrected sequencing to predict tumorigenicity induced by non-genotoxic carcinogens. Both groups are looking for additional stakeholders.

Interested in finding out more? Please contact Saddef Haq (shaq@hesiglobal.org)

HESI’s Genetic Toxicology Technical Committee Historical Control Distribution (HCD) Working Group is querying laboratories about their experiences with compiling, maintaining and using historical control data and distributions for genetic toxicology assay acceptance and evaluation. The compiled data will be used to determine where consensus approaches exist and, where possible, make recommendations on compiling, maintaining and monitoring historical control data and distributions.

The survey is available on the HESI GTTC website here.

Completed surveys are requested by April 1, 2022.

For questions or more information, please contact Connie Chen.

If you are looking to learn more about the various aspects involved in immune safety evaluation as it pertains to drug development or human risk assessment, we encourage you to visit the recently launched website https://immunosafetyresource.org/

Exposure scientist Rick Neitzel, part of the leadership team for HESI’s Collaboration on Ototoxicity Risk Assessment (CORA) Committee, was quoted in a recent article on the environmental threat of urban noise pollution. Read the full article HERE.

CORA is a new HESI Scientific Committee whose mission is to better understand the impacts on the inner ear, resulting from co-exposures to noise and known and suspected ototoxic substances, in the pursuit of identifying safe exposure levels which minimize or eliminate the risk of ototoxicity to the consumer or worker.

As the newest Emerging Issues project, there is no fee to join CORA for the remainder of 2022. Click below to learn more about CORA!
https://hesiglobal.org/collaboration-on-ototoxicity-risk-assessment/

A physiologically based pharmacokinetic (PBPK) modeling approach can be a valuable tool used in the early stages of a chemical safety assessment program to optimize the design of longer-term animal toxicity studies or to interpret study results.

This proof of principle study, involving multiple test cases, demonstrates that a PBPK model can be developed as a research tool to integrate available absorption, distribution, metabolism, and excretion (ADME) data from shorter-term in vivo studies or in vitro assays to simulate longer term exposure, which can inform dose selection, dose spacing, or sample collection intervals in future whole animal studies. A PBPK model can also be used to interpret toxicity testing results, generate hypotheses on potential modes of action, or identify early mechanistic biomarkers. These capabilities can potentially reduce animal use in longer-term studies, as well as improve our understanding of the study outcomes by providing insight into the internal to external concentration (IEC) relationship.

Read full publication here:

Predicting nonlinear relationships between external and internal concentrations with physiologically based pharmacokinetic modeling.  Hoer D, Barton HA, Paini A, Bartels M, Ingle B, Domoradzki J, Fisher J, Embry M, Villanueva P, Miller D, Nguyen J, Zhang Q, Edwards SW, Tan YM. Toxicology and Applied Pharmacology. (April 1, 2022)

On October 21–22, 2020 the HESI (Health and Environmental Sciences Institute) Protein Allergens, Toxins, and Bioinformatics Committee, and the Society of Toxicology Food Safety Specialty Section co-hosted a virtual workshop titled “From Protein Toxins to Applied Toxicological Testing”.  Key outcomes of the workshop are highlighted in this publication.

Read the full article here:

“From Protein Toxins to Applied Toxicological Testing” virtual workshop identifies the need for a bioinformatic framework to assess novel food protein safety. Bauman PA, Doxey AC, Eberini I, Islamovic E, Jungo F, Kessenich C, Kough J, Krishanh M, Palazzolo L, Privalle L, Rodriguezi CE, Satchell KJF, Silvanovich A, Mouriès LP. Regulatory Toxicology and Pharmacology. June 2022.

The Botanical Safety Consortium (BSC) hosted a webinar on February 22nd, 2022 entitled “Chemical Safety of Phytomedicines – Perspectives for in vitro testing strategies?” presented by Dr. Dieter Schrenk, Senior Professor of Food Chemistry & Toxicology at the University of Kaiserslautern.

The webinar was attended by over 100 participants and the recording can be found HERE

Interested in learning more about the BSC? Please visit https://botanicalsafetyconsortium.org/

The eSTAR Committee hosted a webinar on February 17th, 2022 entitled “Tox-GAN: An AI Approach Alternative to Animal Studies – a Case Study with Toxicogenomics” presented by Dr. Weida Tong from the US FDA’s National Center for Toxicology Research.

The webinar was attended by over 80 participants and the recording can be found HERE

Interested in learning more about the Emerging Systems Toxicology for the Assessment of Risk (eSTAR) Committee? Please visit https://hesiglobal.org/emerging-systems-toxicology-for-assessment-of-risk-committee/

The Botanical Safety Consortium presented at the 7th German Pharm-Tox Summit. Connie Mitchell gave an overview of entitled “The Botanical Safety Consortium´s strategy to enhance the botanical safety toolkit” in a session on Food Toxicology on March 9th 2022. The session was attended by over 150 participants virtually.

Did you miss the Cell Therapy – TRAcking, Circulation & Safety (CT-TRACS) Committee Regulatory Perspectives Webinar?

Co-organized by EATRIS and Health and Environmental Sciences Institute (HESI). Talks by Tineke van den Hoorn, Kate Dabirsiaghi and Marta Rayo Lunar. The webinar had 140 registrants; 78 attended, from 14 countries.

This activity is part of the CT-TRACS Committee’s efforts to continue filling the knowledge gap about methods that can assess the fate of therapeutic cells and/or can help the timely identification of eventual unexpected effects while highlighting the regulatory component of these endeavors.

Watch the recording HERE.

Learn more about the CT-TRACS Committee here: https://hesiglobal.org/cell-therapy-tracking-circulation-safety-ct-tracs/

The HESI Cardiac Safety Committee convened their annual business meeting virtually this past month. The meeting featured keynote speaker, Dr. Wayne Cascio, US EPA, Working Group updates and discussion and breakout sessions focused on strategic planning.

Committee members were also recognized during an Award Session and HESI congratulates all 2022 Awardees:

• Khuram Chaudhary, GlaxoSmithKline
• Robert Hamlin, Ohio State University
• Emily Kaushik, Takeda
• Yevgeniya Koshman, AbbVie
• Jessica Palmer, Stemina Biomarker Discovery
• Florence Poitout, Charles River Laboratories
• Michael Pugsley, Cytokinetics
• Todd Wisialowski, Pfizer

Learn more about the Cardiac Safety Committee by visiting their webpage or contact Dr. E’Lissa Flores and Ms. Jennifer Pierson.
(eflores@hesiglobal.org; jpierson@hesiglobal.org)

Date: 18 March 2022
Time: 9:00 – 10:00 AM EST / 14:00 – 15:00 CET

The EnviroTox Database and Tools: Overview and application

The EnviroTox database contains 80,912 aquatic toxicity effects records representing 1,641 species and 4,267 unique chemical identifiers and was specifically developed to provide a curated dataset to explore the concept of the ecological threshold of toxicological concern (ecoTTC). These data are associated with physical chemistry data and curated taxonomic information, including a process that assigns acute and chronic effects, and that identifies PNECs based on the available data. Several mode of action schemes are also included to facilitate development of a best approach for grouping compounds. This database has been made freely available via a web-based query system that integrates the various tools. This interface allows users to explore and upload data, derive threshold values based on specific criteria, and explore the use and application of ecoTTCs.

This presentation will provide an overview of the EnviroTox database and tools, with a live demonstration on how this valuable resource can be used. Please visit www.envirotoxdatabase.org to give it a try!

Click to REGISTER

The following HESI Scientific Committees will be presenting at the upcoming Society of Toxicology meeting, which will be held virtually and in person in San Diego, CA March 27-31, 2022:

Platform Sessions

PBPK Models

Optimizing the Design of Repeated-Dose Animal Studies to Inform Human Health Risk Assessment by Integrating Exposure, In vitro, and In Silico Data; Platform session; Speaker Dr. Michelle Embry 3/31/2022 8:30 – 11:15

Immuno-safety

HESI Scientific Program Manager, E’Lissa Flores, was invited by the Education Committee of the Immunotoxicology Specialty Section (ITSS) of the Society of Toxicology (SOT) to speak at their 8th Networking/Mentoring event for student and postdoctoral trainees. This event allows trainees to meet experts from the ITSS working in academia, government, industry, nonprofits, and contract research organizations.

Posters

Botanical Society Consortium (BSC)

Application of In Silico and In Vitro Approaches for Evaluating Developmental and Reproductive Toxicity in Botanical Products, 3/28/2022 2:30:00 PM to 3/28/2022 4:15:00 PM

A Strategy for Developing a Framework of Genotoxicity Assays for Safety Assessment of Botanicals 3/30/2022 2:30:00 PM to 3/30/2022 4:15:00 PM

In Silico Prediction of Botanical Constituents’ Metabolites 3/30/2022 2:30:00 PM to 3/30/2022 4:15:00 PM

Physiologically based pharmacokinetic (PBPK) simulations and modeling of botanical constituents – TBD

Emerging Systems Toxicology for the Assessment of Risk (eSTAR)

A Collaborative Initiative to Establish Molecular Biomarkers for Assessing Risk of Chemical Carcinogenesis to Reduce Reliance on Conventional Rodent Carcinogenicity Studies, 3/30/2022 10:45:00 AM to 3/30/2022 12:30:00 PM

Registration and meeting details can be viewed on the SOT website here.

The Botanical Safety Consortium will have a session at the International Conference on the Science of Botanicals (ICSB 2022) entitled “Botanical Safety Assessment: Updates from the BSC”. The meeting is taking place March 28th-31st, 2022.

A description of the session and talks are below.

The Botanical Safety Consortium (BSC) was officially convened in November 2019 as a public-private partnership aimed at enhancing the botanical safety toolkit and bringing clarity to botanical dietary ingredient safety assessments. This partnership is the result of a Memorandum of Understanding (MOU) between the US Food and Drug Administration (FDA), the National Institute of Health’s National Institute of Environmental Health Sciences (NIEHS), and the Health and Environmental Sciences Institute (HESI). The BSC serves as a forum for global scientists from government, academia, consumer health groups, industry, and non-profit organizations to work collaboratively to generate a sound scientific basis for integrating existing data and the latest toxicology tools to evaluate the safety of botanical dietary supplements. The objectives of the BSC are to identify pragmatic, fit-for-purpose, in vitro & in silico assays to evaluate botanical safety; establish the appropriate levels of chemical characterization for complex botanical products; evaluate the application of these tools via comparison to the currently available safety information; and integrate these tools and approaches into a framework that can facilitate robust evaluation of botanical substances. Initial endpoints of focus are chemical analysis, genotoxicity, hepatotoxicity & ADME, developmental & reproductive toxicity, and systemic toxicity. This presentation will provide a brief overview of the BSC goals and strategies, and its ongoing work.

BSC ICSB 2022
15 minutes: Introduction to the Botanical Safety Consortium – Dr. Holly Johnson (APHA)
15 minutes: HPTLC Comparisons for Ashwagandha Root Extract – Dr. Anthony Fontana (Alkemist Labs)
20 minutes: Constituent Identification and Quantification talk – Dr. Richard van Breemen (OSU)
15 minutes: Method talk on Zebrafish embryos – Dr. Cammi Thornton (U Miss)
15 Minutes: ADME modeling and hepatoxicity – Dr. Amy Roe (P&G)
10 minutes: HESI Botanical Safety Consortium & Kamuzu University of Health Sciences Initiatives– Dr. Hellen Oketch (USP) and Dr. Stefan Gafner (ABC)

The HESI Cardiac Safety Committee is pleased to announce the second webinar in their Early Career Seminar Award Series. This competitive award is given to postdoctoral or early career scientists who have compelling research related to cardiovascular safety and risk assessment, and the webinar series offers an opportunity for awardees to share their research, learn from, and network with experts at HESI. The second webinar will feature the work of Dr. Arvin Soepriatna, Brown University, where he will present on ‘Human Atrial Cardiac Microtissues for Chamber-Specific Arrhythmic Risk Assessment,” and is scheduled for 8 April 2022 at 10:00 am ET.

Learn more on the events page.

HESI is among 30+ international organizations and companies supporting a series of annual Microphysiological systems (MPS) World Summits to present the latest scientific achievements, discuss the advances and challenges, and enable communication between young and newly interested scientists and pioneers of the MPS field.

HESI’s mission aligns with the proposed goal of the MPS World Summit of planning a series of global conferences on microphysiological systems towards bringing all stakeholders together from across sectors and career stages to promote the development and application of this technology, to facilitate its expanded scientific and regulatory use.

Please see the 2022 Summit event page for more details (https://mpsworldsummit.com/session/hybrid-conference/).

The Summit will be a hybrid event, held May 30^th-June 3^rd, 2022. For questions about the initiative, feel free to reach out to HESI’s contact point: Lucilia Mouriès (lmouries@hesiglobal.org).

Cell Therapy – TRAcking, Circulation, & Safety (CT-TRACS) Committee has been invited to present at the upcoming meetings.

March 14, 2022 – online meeting

The n-TRACK “Stem Cell NanoImaging – Advances and Applications Conference” (https://www.n-track.eu/stem-cell-nanoimaging-advances-and-applications-conference/)

May 25, 2022 – London, UK

The Advanced Therapies 2022 Congress (https://www.terrapinn.com/congress/advanced-therapies/) on CT-TRACS’ pilot project “new approaches for identification of potential off-target mutations associated with CRISPR genome editing in cell therapies”.

Save the Date! The following are internal meetings:

March 14-15, 2022 – HESI COMPARE Annual Meeting

April 26-27, 2022 – HESI ITC Spring Business Meeting

May 4-5, 2022 – HESI DART Spring Business Meeting

May 16-17, 2022 – GTTC Annual Meeting

May 19-20, 2022 – HESI CT-TRACS Spring Business Meeting

CALL FOR APPLICATIONS: The HESI Immuno-safety Technical Committee (ITC) is excited to announce a new Immuno-Safety Mentorship Program for graduate students working in immunology, toxicology, pathology, or a related field. This program will allow meaningful interactions between trainees and mentors to provide insight on various career pathways and discuss how to streamline the mentees’ long-term goals. The first cohort will be from May – July 2022 with 4-5 one-on-one mentor meetings.

More information, including the application to apply, can be found on the ITC website HERE.

Deadline to apply is 4 April 2022.

The Genetic Toxicology Technical Committee (GTTC) is proud to announce the launch of a new professional development award, geared towards graduate students or postdoctoral fellows in the fields of genetic toxicology and genomics. Awardees will receive up to $1000 USD  to be applied towards scientific conferences, workshops or courses that will build core competencies and transferrable skills and/or share your research. Awardees will also be welcomed to attend GTTC’s Annual Meeting in May 2022 to learn about emerging projects and science at HESI and to network with experts in the gene toxicology field.

Deadline for submission is April 1, 2022.

For more information or to apply, please see the website.

HESI THRIVE Letters of Intent deadline has been extended to April 11th, 2022. Submissions are open to international applicants.

THRIVE provides seed grants for clinical and translational research and technology-based solutions that enhance our ability to predict when and how adverse effects may occur in patients who have received cancer treatment. THRIVE also supports the development of approaches to avoid or lessen these effects.

THRIVE is interested in research that will advance our:
• Fundamental understanding of cancer drug or therapy-related toxicity
• Ability to identify and translate critical biomarkers of toxicity
• Models (in vitro, in vivo, in silico) of pediatric or adult drug exposure that predict early or impending toxicities
• Understanding the role of protective co-therapies or modified exposure protocols on the onset of therapy-induced damage; and
• Identification of novel protective therapies or dosing strategies.

KEY DATES
• April 11th, 2022: Letters of Intent are due
• May 23rd, 2022: Invitations to submit full proposal
• June 20th, 2022: Full proposals due
• July 29th, 2022: Awards selection and notification
• August 5th, 2022: Award period initiates

Read about our 2021 THRIVE Winners

More information can be found at https://hesithrive.org/

It is hard to believe that we are already two years into the COVID-19 pandemic. Fortunately, there are signs of a far greater tool chest to combat much of the virus’ most serious and frequently deadly health effects around the globe. We are starting to see restrictions loosen in many parts of the world which means in-person meetings are once again a possibility for the scientific community. Against this background, the HESI Annual Meeting in Washington DC will be a hybrid meeting this coming June 8-9, 2022, and I hope that many HESI members will be able to join in person. Hopefully, the effects of the virus will continue to decline and we can all go back to our post COVID lives with many opportunities for the in-person contact that most of us appreciate so dearly.

In retrospect, we learned some important lessons during the last two years in scientific areas that are also part of HESI’s portfolio. I think it is important for all of us to recognize the tremendous accomplishments pharmaceutical and public health sciences have made developing an array of testing systems, a variety of vaccines and several antiviral drugs that are now capable of protecting us against the most serious health effects of COVID-19. This is an enormous undertaking in a short timeframe. COVID-19 has resurfaced a number of persistent global scientific challenges around food security and the link between human and veterinary health practices that could be ripe for future HESI programming.

Kind Regards,

Martin van den Berg, PhD, ERT
HESI Chair