title: The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?
abstract: Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems.
authors.affiliation: GLP Center, Center, Catholic University of Daegu, Keongsan, Gyeongsangbuk-do, Korea.
authors.forename: Yeong-Chul
authors.initials: YC
authors.lastname: Park
authors.affiliation: Dept. of Preventive Korean Medicine, School of Korean Medicine, Sangji University, Wonju, Korea.
authors.forename: Sundong
authors.initials: S
authors.lastname: Lee
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
keywords: Biotransformation; Cytochrome P450; Reactivation; Reactive intermediates; Reversibility vs. irreversibility; Toxicokinetics vs. toxicodynamics