EPA Science Inventory

4-AMINOBIPHENYL & DNA REACTIVITY: CASE STUDY WITHIN THE CONTEXT OF THE 2006 IPCS HUMAN RELEVANCE FRAMEWORK FOR ANALYSIS OF A CANCER MODE OF ACTION FOR HUMANS

Citation:

COHEN, S. M., A. R. BOOBIS, M. MEEK, R J. PRESTON, AND D. B. MCGREGOR. 4-AMINOBIPHENYL & DNA REACTIVITY: CASE STUDY WITHIN THE CONTEXT OF THE 2006 IPCS HUMAN RELEVANCE FRAMEWORK FOR ANALYSIS OF A CANCER MODE OF ACTION FOR HUMANS. CRITICAL REVIEWS IN TOXICOLOGY. CRC Press LLC, Boca Raton, FL, 36:803-819, (2006).

Description:

The IPCS Human Relevance Framework was evaluated for a DNA-reactive (genotoxic) carcinogen, 4-aminobiphenyl, based on a wealth of data in animals and humans. The mode of action involves metabolic activation by N-hydroxylation, followed by N-esterification leading to the formation of a reactive electrophile, which binds covalently to DNA, principally to deoxyguanosine, leading to an increased rate of DNA mutations and ultimately to the development of cancer. In humans and dogs, the urinary bladder urothelium is the target organ, whereas in mice it is the bladder and liver; in orther species, other tissues can be involved. Differences in organ specificity are thought to be due to differences in metabolic activation versus inactivation. Bsed on qualitative and quantitative considerations, the mode of action is possible in humans. Other biological processes, such as toxicity and regenerative proliferation, can significantly influence the dose response of 4-aminobiphenyl-induced tumors. Based on the IPCS Human Relevance Framework, 4-aminobiphenyl would be predicted to be a carcinogen in humans, and this is corroborated by extensive epidemiologic evidence. The IPCA Human Relevance Framework is useful in evaluating DNA-reactive carcinogens.

Purpose/Objective:

To determine whether 4-aminobiphenyl would be predicted to be a carcinogen in humans based on the IPCS Human Relevance Framework

URLs/Downloads:

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 12/20/2006
Completion Date: 12/31/2006
Record Last Revised: 06/21/2007
Record Created: 12/21/2006
Record Released: 12/21/2006
OMB Category: Other
Record ID: 161956

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

ASSOCIATE DIRECTOR FOR HEALTH

IMMEDIATE OFFICE