Society of Toxicology Annual Meeting 2020: Physicians Committee Continues To Promote Modern Test Methods

As in previous years, Physicians Committee scientists are actively participating in sessions throughout the conference to advance their work in promoting effective, nonanimal toxicological test methods. 

We are again sponsoring events to engage and train toxicologists and regulatory scientists with scientific and policy initiatives to replace animal tests with more human-relevant methods, this year partnering with the Institute for In Vitro Sciences to present Frontiers in NAMs Training: Recent Advances in Computational and In Vitro Toxicology. We are also participating in two poster sessions to inform attendees of current topics in predictive toxicology and alternative test methods. 

Here is a select list of Physicians Committee-sponsored sessions or events. If you are attending SOT, we invite you to attend these sessions. Please contact Kristie Sullivan (ksullivan [at] pcrm.org (ksullivan[at]pcrm[dot]org)) for more information.

You can also download a curated list of other SOT scientific sessions and events of interest to scientists working with in vitro and computational methods.

Monday, March 16

Ancillary Meeting/Training: What AOPs can do for you: An introduction and hands-on experience

4:45-6:45 p.m., Hilton Anaheim, Capistrano AB

Join the Physicians Committee for Responsible Medicine and the Animal-Free Chemical Safety Alliance for a hands-on training on the Adverse Outcome Pathways (AOP) concept and program. Presenters will provide an updated overview of efforts to describe and apply AOPs for a variety of toxicological endpoints, and how AOP-related information is being used to support chemical safety assessment. Whether you are completely new to the concept or are looking to deepen your understanding, in order to develop AOPs or use them in your everyday toxicology career, there will be something for you at this session. Bring a computer for the hands-on portion. Contact ksullivan [at] pcrm.org (ksullivan[at]pcrm[dot]org) or kwillett [at] hsi.org (kwillett[at]hsi[dot]org) for more information.

Tuesday, March 17

Poster Session: Integrated Approaches to Testing and Assessment of Chemical Respiratory Sensitizers: A Weight-of-Evidence Assessment of Available Information to Derive a List of Reference Chemicals (Poster Board P101)

10:45 a.m. - 12:30 p.m., Convention Center Exhibit Hall

Authors (with Presenting Authors Underlined): K. Sullivan¹, N. Baker², S. Cochrane³, J. Ezendam⁴, G. Patlewicz⁵, R. Rajagopal³, E. Roggen⁶, R. Settivari⁷, and K. Sewald⁸. ¹Physicians Committee for Responsible Medicine, Washington, DC; ²Leidos, Research Triangle Park, NC; ³Unilever Safety and Environmental Assurance Centre, Sharnbrook, United Kingdom; ⁴Rijksinstituut voor Volksgezondheid en Milieu (RIVM), Bilthoven, Netherlands; ⁵US EPA, Research Triangle Park, NC; ⁶3RsMC ApS, Lyngby, Denmark; ⁷Corteva Agriscience, Newark, DE; and ⁸Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.

Abstract: An Adverse Outcome Pathway leading to chemical respiratory sensitization has been outlined and, despite progress made in developing hazard identification approaches to assess chemicals for this endpoint as well as high regulatory need, there remains a lack of internationally harmonized approaches to identify chemical respiratory allergens. In order to assess potential in vitro and in silico approaches, a reference list of ~120 putative chemical respiratory sensitizers was generated based on structural alerts; a weight of evidence-based approach was undertaken to validate the reference list based on human clinical, in vivo, non-human, and in vitro data. Well-defined criteria and a scoring matrix were used to curate the human data, taking into consideration the variability in tests performed by asthma clinics and laboratories alike, as well as uncertainties embedded in these analyses and reporting. To allow for a weight of evidence analysis, we are collecting all data but qualifying the data to reflect methodological quality. We are also making use of the Abstract Sifter literature review tool to identify additional potential respiratory sensitizers. Briefly, a set of PubMed MeSH terms describing adverse effects (AEs) for 92 known sensitizers was used to query a large database of chemicals and AEs, yielding over 7000 chemicals of potential interest. Work is ongoing to identify query terms which yield the most relevant papers. The resulting chemical list, which will be shared with regulatory agencies and the public, is an important step towards the assessment of potential test methods and the creation of internationally harmonized integrated approaches for the detection of chemical respiratory allergens. Does not necessarily represent US EPA policy.

Ancillary Meeting: Alternatives for Acute Toxicity Testing: Updates and Planned Activities

5-6 p.m., Hilton Anaheim, California Ballroom A

Stakeholders will present updates on ongoing efforts toward the development, evaluation, and implementation of new approach methodologies for acute toxicity testing. Scientists from government, industry, and NGOs will provide brief presentations in the areas of acute oral and inhalation toxicity, skin and eye irritation, and skin sensitization followed by an opportunity for open discussion.

Wednesday, March 18

Ancillary Meeting: Frontiers in NAMs Training: Recent Advances in Computational and In Vitro Toxicology

5-6:30 p.m., Hilton Anaheim, Laguna A

Knowledge of available New Approach Methodologies (NAMs) to assess toxicology, including in silico and in vitro approaches, is becoming a requirement for practicing industry and government toxicologists alike. This session will provide an update on the development of NAMs for product safety, including new regulatory activities, new science for inhalation toxicity assessment, and the EPA Chemistry Dashboard, the largest database of chemical information and tools available. Bring your laptops to follow along with a demonstration of the Dashboard! Contact ksullivan [at] pcrm.org (ksullivan[at]pcrm[dot]org) for more information.

Speakers

• Kristie Sullivan, Physicians Committee: Introduction and Update on NAM Implementation
• Holger Behrsing, IIVS: Respiratory Toxicology: Modelling Inhalation Exposures and Advancing Airway Test Systems
• Grace Patlewicz, EPA: EPA’s Chemistry Dashboard Introduction and Demonstration

Thursday, March 19

Poster Session: A Novel In Vitro Skin Irritation Test Designed for Antimicrobial Cleaning Products Using the Phenion FT Human Skin Model (Poster Board P161)

8:30-11:30 a.m., Convention Center Exhibit Hall

Authors (with Presenting Authors Underlined): K. E. Page¹, K. Sullivan², W. Westerink³, and C. S. Roper⁴. ¹The Clorox Company, Pleasanton, CA; ²Physicians Committee for Responsible Medicine, Washington, DC; ³Charles River, Den Bosch, Netherlands; and ⁴Charles River, Edinburgh, United Kingdom.

Abstract: Human and animal skin both have excellent barrier functions protecting against external hazards, a characteristic that is utilized in the in vivo skin irritation test; OECD test guideline (TG) 405. Conversely, the currently accepted 3D tissue models (e.g., EpiDerm^TM) used in OECD TG 439 have poor barrier functionality. Consequently, the standard OECD TG 439 over-predicts the irritation potential of antimicrobial cleaning products; complex chemical mixtures designed to kill microbial cells. Therefore, a New Approach Methodology (NAM) was developed using the Phenion^®FT model, which was designed for dermal absorption testing with an improved barrier function compared to existing 3D models. Ten antimicrobial cleaning products were tested using the OECD TG 439 with Phenion^® FT. The test articles each contained one of the following active ingredients: sodium hypochlorite, hydrogen peroxide, quaternary amines, glycolic acid and citric acid. All formulations selected were previously tested in OECD TGs 405 and 439 with in vivo EPA Categories II, III, and IV and OECD Category 2, 3, and No Category. Phenion^® FT and EpiDerm^TM (OECD TG 439) were compared to OECD TG 405 data. Phenion^® FT correctly predicted 8/10 formulations, whereas EpiDerm^TM correctly predicted 4/10 formulations. The Phenion^® FT model did not correctly identify Category 3 formulations which OECD TG 439 is not designed to predict. Both 3D tissue models gave a borderline Category 2 prediction for one of the Category 3 formulations. As OECD 405 is known to have variability, these in vitro models may have correctly categorized this mixture. The variability in the animal test must be taken into account when evaluating NAMs. In conclusion, for antimicrobial formulations, this modified OECD TG 439 method provides superior predictive GHS classifications (Category 2 and No Category). Additional work will be performed to improve prediction of the optional GHS Category 3 and the US EPA Categories.