| The International Society of Regulatory Toxicology and Pharmacology Presents | |
|
Co-Sponsors: Alkanolamines Panel - American Chemistry Council Cosmetic, Toiletries, and Fragrance Association Crop Life America Duane Morris LLP Exponent, Inc. Piperonyl Butoxide Task Force II Pyrethrins Joint Venture |
Mechanisms of Animal Liver Tumorigenesis and Their Application to Human Cancer Assessment
Preview of EPA's New Draft Cancer Assessment Guidelines January
23, 2003 Focus The USEPA anticipates release of its new Draft Cancer Assessment Guidelines as early as February 2003. An important feature of those guidelines will concern how mechanistic data should be used as part of the weight of evidence evaluation for potential human carcinogenicity. That issue has concerned many in the regulated community given that the interpretation and use of mechanistic data in cancer assessments will significantly influence regulatory determinations. The interpretation and use of mechanistic data may also influence product liability and toxic tort actions. EPA's 1999 Draft Cancer Assessment Guidelines specifically allowed the use of mechanistic data to support scientifically based approaches to cancer assessment. However, it remained unclear to many in the regulated community how and to what extent mechanistic information would be used to assess carcinogenicity. In this conference EPA will preview its new Draft Cancer Assessment Guidelines and conference participants will discuss, using specific examples related to rodent liver tumors, the role of mechanistic information in cancer assessments. Liver tumors have been observed in a number of oncogenicity studies conducted at the Maximum Tolerated Dose (MTD) in rodents using a wide variety of non-genotoxic compounds, including pesticides, pharmaceuticals, and industrial chemicals. Mechanistic studies on many of those compounds have identified non-genotoxic, threshold-dependent mechanisms of action, including cytotoxicity, mitogenicity, and induction of liver metabolism as likely mechanisms of oncogenicity. In many instances those mechanisms are unlikely to operate in humans at potential levels of exposure This conference will examine some of those mechanisms and discuss their importance to assessing human carcinogenicity. Speakers will generally address mechanisms of liver tumorigenesis, the application of mechanistic information to cancer assessments, and related legal, policy and regulatory issues. Jim Cogliano, author of EPA's new cancer guidelines will provide a preview of EPA's new Draft Cancer Assessment Guidelines. Two case studies will also be presented to facilitate discussion. The first will concern pyrethrins and phenobarbital, which have been shown to cause liver and thyroid tumors in high dose rat studies, likely through a threshold-dependent mechanism related to enzyme induction. The second concerns diethanolamine, which operates through a different threshold-based mechanism of action - choline deficiency. Agenda/Slide Presentations |
|
||||||||||||||||||||||||||||||
| achievement award | sponsors |