Author Archives: 21centrurytox

ToxStrategies Information Specialist Ms. Seneca Fitch is among a group of scientists from the regulatory community, academia, the pharmaceutical industry, and consulting who have published an article in Scientific Reports (an open-access publication of the journal Nature). The paper investigates why some new drugs, having survived the rigorous process of animal and human testing necessary to bring them to market, end up causing unexpected, and sometimes severe, adverse drug reactions in the wider patient population (killing more than 10,000 patients annually in the United States). The authors point out that a battery of new tests and techniques have emerged in the last few decades (referred to as new approach methods [NAMs]) to study the mechanisms of toxicity of chemicals and identify endpoints of concern. Pursuing three separate evidence streams for specific drugs associated with drug-induced liver injury, they propose a “paired-compound approach” to comparing various tests, to reach a systematic, transparent, and evidence-based approach to drug development. 

ToxStrategies’ scientists have proposed potential expansions of the use cases for the threshold of toxicological concern (TTC) in human health risk assessment applications. Analyses indicate that conservative TTC values for chemicals are, on average, approximately six-fold lower than IRIS derived reference dose (RfD) values for noncancer effects. The findings have three potential applications: (1) serve as provisional toxicity values estimated from TTC Cramer Classifications in data-poor or emergency situations, (2) serve as a comparator for toxicity criteria derived by multiple agencies or stakeholders, and (3) identify RfD values that might warrant reanalysis when they are substantially lower than their corresponding TTC value. Importantly, the findings reaffirm the health protective nature of TTC values, with the majority of TTC values being lower than their corresponding RfD values.

The open-access article was published in Regulatory Toxicology and Pharmacology.

Dr. Susan Borghoff, Director of ToxStrategies’ Center of Excellence for 21^st Century Toxicology, was invited to participate in the inaugural Conference on Reducing Animal Testing for Chemical Safety, convened on December 17, 2019, by EPA’s Office of Pesticide Programs. Approximately 60 scientists from government, academia, and industry were present at the full-day meeting, and were joined by more than 600 individuals in the morning session via teleconference. The gathered experts in environmental and chemical safety research discussed advancements in New Approach Methods (NAMs), to assess the current state of chemical safety research and discuss scientifically valid alternatives to animal testing. According to EPA, “This event, which will take place annually, is a major step in implementing [the Agency’s vision] to aggressively pursue reductions in animal testing.”

Dr. Borghoff brought her expertise in study design and managing research and regulatory-driven toxicology to the breakout group that discussed “Variability and Relevance of Current Animal Tests and Expectations of NAMs.” In her 30-year career, Dr. Borghoff has managed diverse research programs for both industry and government clients. Recent efforts have been focused on the development and implementation of a framework to evaluate both in vitro and in vivo mechanistic data into hazard characterization.

The Center of Excellence in 21st Century Toxicology (21CT; a division of ToxStrategies) was well represented at the 44th annual summer meeting of The Toxicology Forum (TFF), held July 9–11 in Baltimore. Dr. Susan Borghoff, 21CT Director, served on the Organizing Committee and also participated in the session titled, “Integration of Toxicokinetics and the Kinetically-Derived Maximum Dose into Toxicity Testing and Risk Assessment.” Dr. Borghoff’s presentation was, “Kinetically Derived Maximum Dose: A Key Initiating Event Impacting Need for Mode-of-Action Investigations of High-Dose-Specific Toxicity.”

ToxStrategies is pleased to announce the establishment of The Center of Excellence for 21^st Century Toxicology (21CT). The Center will focus on supporting the transition in toxicological science to in vitro and computational toxicology through the design and implementation of 21^st century methods in risk assessment. 21CT is designed to be a science hub, providing expertise in cell-based science, computational toxicology, targeted in vivo studies, pharmacokinetics, in vitro–to–in vivo extrapolation (IVIVE), rapid exposure assessment, systematic literature reviews for evidence-based toxicology, and Adverse Outcome Pathway–based safety assessments. 21CT’s mission is to help guide our clients through the rapidly changing regulatory landscape that is affecting many business sectors, including the chemical, agrichemical, consumer products, pharmaceutical, and cosmetics industries, and to lead the way in the conduct of in vitro–based safety assessments.

The Center will be led by Dr. Susan Borghoff. Dr. Borghoff has expertise in identifying modes of action for endocrine-active chemicals, respiratory toxicants, and carcinogens, and applying pharmacokinetic modeling in risk assessment. Dr. Borghoff focuses her broad toxicology experience on incorporating data generated using new 21^st century tools and technologies to replace traditional approaches, supporting both discovery and regulatory needs.