ISRTP Workshop
EPA's New
(Proposed) Guidance For Assessing Cancer Risks from Early Life
Exposures:
Genotoxic Mode of Action and Implications for Human Health-Based
Standards
February
10, 2005
Wyndham Hotel
Baltimore, MD
Scope and Purpose
ISRTP will host a workshop to explore scientific issues related to the implementation of EPA's proposed new science policy for assessing cancer risks from early life exposures and to explore how implementation of the Agency's proposed policy might affect regulation of suspected carcinogens. Specifically, the ISRTP workshop will: 1) explore how mutagenicity might be established as the carcinogenic mode of action for chemicals to which the proposed guidance will be applied, and 2) examine how implementation of this proposed policy might affect risk-based human health exposure limits, action levels, and remediation standards for water, air, and soil, as well as the pesticide registration process.
Background
In February of 2003, EPA released Draft Final Guidelines for Carcinogen Risk Assessment. Prior to their release, ISRTP explored those new guidelines in a conference held on January 23, 2003. During that conference, EPA unveiled important changes in science policy that subsequently appeared in the Agency's new document (presentations online at http://www.isrtp.org).
In addition to releasing its Draft Final Guidelines in February of 2003, EPA also released an external review draft of its Supplemental Guidance for Assessing Cancer Susceptibility from Early-Life Exposure to Carcinogens, a compendium to the Cancer Assessment Guidelines. The Supplemental Guidance proposed adjusting estimates of lifetime cancer risk for certain suspected carcinogens to account for potential increased early life susceptibility. It is anticipated that EPA may release the Final Cancer Guidelines and Supplemental Guidance in the next months.
Although the draft Supplemental Guidance would appear to apply only to chemicals that have demonstrated a mutagenic mode of action for carcinogenesis, there has been some concern and confusion concerning the scope of the Guidance. EPA's cancer assessment Guidelines lay out a framework for determining a mode of action and allow that the mode of action may change with factors such as dose or route of exposure. The terms "mutagenic," "genotoxic," and "DNA-reactive", however, have been defined in different ways within the scientific and regulatory communities and through time. Therefore, it is necessary to establish how to determine whether a chemical has a mutagenic mode of action as envisioned by the Guidelines and Supplemental Guidance. This workshop will explore that issue as an initial effort that will be followed by a more comprehensive conference later in 2005 to address mode of action determinations for a broader array of toxic effects.
Although it is uncertain at this time how EPA will apply its mode of action criteria to determining which chemicals are carcinogenic by a mutagenic mode of action, some state agencies and public interest groups have started to apply the draft Supplemental Guidance. Although the science underlying the proposed guidance has been extensively discussed during EPA's public comment period for the Draft Final Guidelines and Supplemental Guidance, there has been little public discussion to date concerning how the new guidance will impact risk-based public health and remediation standards or decisions. Because implementation of the new approach for early-life exposure may significantly affect many sectors of the regulatory and regulated community, this workshop will also explore implementation issues using case studies.