Managing Partner, D&B ChemTox LLC, Waterford, CT, USA.
Published: September 2021
AI Article Synopsis
Article Abstract
Permitted daily exposure (PDE) values are used by some toxicologists to support the safety qualification of various types of impurities found in a drug substance (DS) or drug product (DP). Permitted daily exposure values are important tools for the toxicologist, but one must be aware of their limitations to ensure that they are used appropriately and effectively in the risk assessment process. First, a toxicologist must always perform a comprehensive analysis of all available animal and human safety data for an impurity, including identifying any data gaps that may exist. Second, if adequate data are available and there are no genotoxicity concerns, an appropriate well-designed repeat-dose toxicity study in animals should be chosen to calculate the PDE. It is important to note that PDE values qualify general systemic toxicity and not necessarily local toleration end points such as irritation and sensitization that are more concentration than dose dependent. In addition, a PDE value calculated from a general toxicity study in animals may not necessarily qualify for reproductive toxicology end points. Lastly, PDE values should never be thought of as analytical limits for or acceptable levels of an impurity in a DS or DP, as this ignores quality considerations. Using safety information from several chemicals as proxy impurities, this article serves as an educational primer to facilitate a better understanding of the development and use of PDE values in the risk assessment process.
Author's Affiliation: Health Services Research, Department of Health Administration and Policy, College of Public Health, George Mason University, Fairfax, Virginia.
Background And Objectives: Basal cell carcinoma (BCC) is the most common form of skin cancer, originating from basal cells in the skin's outer layer. It frequently arises from prolonged exposure to ultraviolet (UV) radiation from the sun or tanning beds. Although BCC rarely metastasizes, it can cause significant local tissue damage if left untreated.
Organophosphate flame retardants have been widely used in plastic products since the early 2000s. Unfortunately, these compounds leach out of the plastics over time and are carcinogenic, developmental toxins, and endocrine disruptors. Due to the high usage levels and stable nature of the compounds, widespread contamination of the environment has now been observed.
Introduction: Erectile dysfunction is often a consequence of stressful situations, lack of adequate sleep and rest, and sedentary lifestyles. The profession of locomotive engineer implies the presence of these negative factors, which in addition provoke high blood pressure and the development of hypertension.
Materials And Methods: A total of 85 patients of the urological and therapeutic departments of the "Clinical Hospital "Russian Railways Medicine" in the city of Barnaul", working as locomotive drivers or assistant drivers, were examined.
Objective: This study aimed to investigate the effect of psoralidin, a natural phenolic coumarin compound, on MK-801-induced neurotoxicity that may cause Alzheimer's disease and to determine the phosphodiesterase (PDE)-related molecular mechanism of action.
Materials And Methods: In this study, neurotoxicity was performed using the MK-801 in the HT-22 cell line. The effects of compounds on the proliferation of HT-22 cells were determined by Real-Time Cell Analysis (RTCA).
We analyze travelling wave (TW) solutions for nonlinear systems consisting of an ODE coupled to a degenerate PDE with a diffusion coefficient that vanishes as the solution tends to zero and blows up as it approaches its maximum value. Stable TW solutions for such systems have previously been observed numerically as well as in biological experiments on the growth of cellulolytic biofilms. In this work, we provide an analytical justification for these observations and prove existence and stability results for TW solutions of such models.
