Histopathology remains the cornerstone of nonclinical toxicology, providing direct evidence of cellular and tissue-level alterations that occur in response to chemical or biological exposure. In chronic toxicity (OECD 452) and carcinogenicity (OECD 453) studies, microscopic evaluation of tissues is crucial for identifying both early degenerative lesions and late-stage proliferative or neoplastic changes. The interpretation of…
Safety pharmacology studies assess the potential of a drug candidate to produce unintended effects on vital physiological systems, including cardiovascular, respiratory, and central nervous system (CNS) function. While toxicology studies evaluate systemic toxicity and target organ damage, safety pharmacology specifically focuses on acute, functional disruptions that may not involve cellular injury or histopathological changes. These…
The liver and kidneys are primary sites of xenobiotic metabolism and clearance, making them common targets in preclinical toxicity studies. Understanding the mechanistic basis of hepatic and renal injury in chronic and subchronic animal models is critical for interpreting toxicological data and assessing human relevance. Hepatotoxicity may result from reactive metabolite formation, mitochondrial dysfunction, bile…
Comparative toxicokinetics (TK) play a fundamental role in evaluating systemic exposure across species used in regulatory toxicology. These data are essential for bridging animal study results to human risk assessment, particularly in the context of Investigational New Drug (IND) applications. TK profiles are assessed in both rodent and non-rodent species during single- and repeated-dose toxicity…
Determining an appropriate starting dose for first-in-human (FIH) clinical trials is one of the most critical decisions in early-phase drug development. Regulatory guidance from the FDA and EMA encourages the use of scientifically grounded dose selection strategies that incorporate both preclinical toxicity findings and mechanistic pharmacology data. Traditionally, the No Observed Adverse Effect Level (NOAEL)…
Toxicology plays a pivotal role in the preclinical assessment of drugs, guiding the Investigational New Drug (IND) application process. This review summarizes recent advances in toxicological studies relevant to IND applications, including in vitro, in vivo, and computational approaches. Emerging technologies such as organ-on-chip systems, high-throughput screening, and predictive toxicology models are evaluated for their…
Adverse Outcome Pathways (AOPs) are conceptual frameworks that provide a mechanistic understanding of how exposure to a chemical or stressor can lead to adverse outcomes in biological systems. AOPs help connect the molecular initiating event (MIE), which is the initial interaction between a chemical and a biological target, to an adverse outcome at a higher…
Regulatory guidelines in toxicology provide frameworks and recommendations for conducting toxicological studies, assessing the safety of chemicals, and managing potential risks to human health and the environment. These guidelines are developed by regulatory agencies at the national and international levels and serve as important references for industry, researchers, and policymakers. Here are some key regulatory…
Toxicity testing is an essential component of the regulatory evaluation and safety assessment of medical devices. Medical devices are subject to rigorous testing to ensure that they are safe and do not pose significant risks to patients or users. The toxicity testing of medical devices involves assessing the potential adverse effects that the device or…
Nanomaterials, which are materials with dimensions on the nanometer scale (1-100 nanometers), have unique properties and applications across various industries. However, their potential toxicity and impact on human health and the environment have raised concerns. Assessing the toxicity of nanomaterials is crucial for ensuring their safe use and minimizing potential risks. Here are some key…