A classification framework and practical guidance for establishing a mode of action for chemical carcinogens
Abstract
The recently released U.S. Environmental Protection Agency (U.S. EPA) Supplemental Guidance for Assessing Risk from Early Life Exposure to Carcinogens (SGAC) provides guidance to account for potential increased early life susceptibility to carcinogens that are acting via a mutagenic mode of action. While determination of the mode of carcinogenic action is central to the SGAC procedures and other regulatory risk assessments, little guidance is given as to the approaches, criteria, and nature of the evidence required to define a mutagenic mode of action. The purpose of this paper is to provide a framework along with practical guidance for the process of assigning a mode of action. Strengths, weaknesses, reliability, and choice of a test battery are discussed for select bacterial, cell culture, whole animal and human cell assays. Common confounding factors of induced pathology, cytolethality, and regenerative cell proliferation in rodent cancer bioassays are discussed along with approaches to account for these effects in assigning a mode of action and in risk assessments. Specific examples are given to illustrate the complexity in generating a data set sufficient to move from the default regulatory position of assuming a genotoxic...Continue Reading
References
Chloroform inhalation exposure conditions necessary to initiate liver toxicity in female B6C3F1 mice
Citations
Toxicity and genotoxicity of water and sediment from streams on dotted duckweed (Landoltia punctata)
An evaluation of the mode of action framework for mutagenic carcinogens case study: Cyclophosphamide
Related Concepts
Related Feeds
Cancer Metabolism
In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.
Adenoma, Liver Cell
Liver Cell Adenoma or hepatic adenoma is a rare benign tumor. It is associated with birth control use or pregnancy. Discover the latest research on Liver Cell Adenoma here.