Example Of A Custom Assay Followed By IVIVE To Prioritize Compounds

Scott Stephanoff Case Studies

Case Study On The Use Of Quantitative In Vitro To In Vivo Extrapolation (QIVIVE) To Prioritize Estrogen-Active Compounds In An In Vitro Human Uterotrophic Assay Customer Problem Estrogenic compounds operate as endocrine disruptors which affect the endocrine system. In fact, there are concerns about these chemicals producing adverse developmental, reproductive and neurological effects in humans. The American Chemistry Council (ACC) …

Translating In Vitro Inhalation Study To Human Equivalence

Scott Stephanoff Case Studies

NAM-Based Prediction Of Point-Of-Contact Toxicity In The Lung: A Case Example With 1,3-Dichloropropene Purpose Chemicals can be inhaled in different physical states (gases, and vapors) that can cause a wide range of adverse health effects, ranging from irritation at the portal of entry (respiratory tract) to systemic diseases in the body. Inhaled chemicals interface along the airway epithelium and interact …

Use Of PBPK Models For Prioritizing Compounds

Scott Stephanoff Case Studies

Development of an Internal Threshold of Toxicological Concern (iTTC) Purpose With current regulatory mandates for reduction and elimination of animal experimentation, compounds developed for cosmetic ingredients and marketed in the European Union (EU) cannot be tested in animals. In response, research into a multitude of non-animal testing methods (in silico and in vitro) and safety evaluation techniques were pursued and …

Understanding The Mode Of Action Of Lead Candidates

Scott Stephanoff Case Studies

Using In Silico And In Vitro Tools To Discover Drivers Of Sensitivity To Novel Cancer Therapeutics Client Problem Our client developed a family of compounds that were effective at stopping the growth of tumors in animal models. Although the founding compound had a known target, second generation chemistries had improved therapeutic indices but no longer hit the expected target. Therefore, …

Extrapolate In Vitro Lung Data To Humans

Scott Stephanoff Case Studies

NAM-Based Prediction Of Point-Of-Contact Toxicity In The Lung: A Case Example With 1,3-Dichloropropene Purpose Chemicals can be inhaled in different physical states (gases, and vapors) that can cause a wide range of adverse health effects, ranging from irritation at the portal of entry (respiratory tract) to systemic diseases in the body. Inhaled chemicals interface along the airway epithelium and interact …

Understanding The Mode Of Action Of A Food Contaminant Acetamide

Scott Stephanoff Case Studies

The Use Of Transcriptomics To Support Risk Assessment For The Food Contaminant Acetamide* Purpose As a byproduct of food processing, acetamide is a simple amide which occurs in milk, egg, beef, and roasted coffee bean products. An ammonia fiber expansion (AFEXTM) process produces highly digestible and inexpensive commercial animal feed from crop residue (e.g., corn stalks). This benefits ruminant livestock …

Assessing Liver And Endocrine Toxicity Of Fluorocarbon Compounds

Scott Stephanoff Case Studies

Purpose Fluorinated chemistries have been heavily scrutinized due their long half-lives and reported bioactivity. Several compounds have been shown to be modulators of ligand-activated nuclear receptors. This includes agonists for peroxisome proliferator-activated receptor alpha (PPARα), a key regulator of lipid metabolism regulating genes and associated with liver hypertrophy and tumorigenicity in rodents. Additionally, fluorinated compounds have been found to activate …

Applying Read Across for REACH Registration

Scott Stephanoff Case Studies

A ScitoVation Case Study A potential use case for these technologies is to augment a read-across argument for REACH registration. For illustration, consider a hypothetical class of chemicals that differ by substitution of an alkyl group (Figure- IMAGE1). Many compounds in the class have been well studied, and there is a general understanding that toxicity in a known target organ …

Implementing Mode-of-Action Investigative Toxicology into Risk Assessments Through New Alternative Approaches

Scott Stephanoff Blog

Posted by Leslie Recio, PhD DABT Like all the biological sciences, the genomic revolution has significantly impacted the science and practice of toxicology. Although regulatory toxicology relies on animal studies for use in risk assessments, there is an ongoing shift to non-animal test methods and use of genomic tools in the safety assessment of new drug candidates and environmental chemicals …