The Need for Guidance on Immunotoxicity Risk Assessment by EPADocs


									The Need for Guidance on Immunotoxicity Risk Assessment

Authors: Andrew Rooney1, Dori Germolec2, Robert Luebke3, Michael Luster4, Resha Putzrath5,
Yung Yang6, and Susan Makris1
  U.S. EPA/Office of Research and Development (ORD)/National Center for Environmental
Assessment (NCEA)
  National Institute for Environmental Health Sciences (NIEHS)
  U.S. EPA/ORD/National Health and Environmental Effects Research Laboratory (NHEERL)
  National Institute of Occupational Safety and Health (NIOSH)
  U.S. EPA/ORD/Risk Assessment Forum (RAF)
  U.S. EPA/ Office of Prevention, Pesticides, and Toxic Substances (OPPTS)/Office of Pesticide
Programs (OPP)

Keywords: immunotoxicity, immunosuppression, risk assessment, susceptible populations

Several EPA program offices and other Federal agencies or programs routinely evaluate
immunotoxicity data or require immunotoxicity testing under regulatory statute, yet there exists
only minimal guidance regarding the use of these data in human health risk assessment.
Although the need for development of Agency-wide immunotoxicology risk assessment
guidance had been explored in the 1990s, this issue is again receiving increased attention, in part
because guidance in this area is key for Integrated Risk Information System (IRIS) health
assessments and other Agency risk assessment documents. In 2004, a Scoping Group meeting
was conducted to evaluate interest and expertise within the Agency and determine whether there
was sufficient consensus to develop guidance. Key Program Offices participated in this meeting,
which resulted in a recommendation of the project to the Risk Assessment Forum (RAF). Some
of the challenging topics that were identified by the Scoping Group as critical for inclusion in the
guidance were (1) determining how the subcategories of the broader topic of immunotoxicology
(e.g., immunosuppression, hypersensitivity, autoimmunity, asthma) would be addressed in a
guidance document, (2) the application of acute or short-term exposures (which are the basis of
typical immunotoxicity testing protocols) to chronic risk assessment paradigms, (3) defining
adverse versus non-adverse immunological responses, and (4) addressing susceptible
populations. The Scoping Group developed a strategy for moving forward, and a Technical
Panel was assembled, consisting of members of the Scoping Group plus a limited number of
additional experts in immunotoxicology, developmental toxicology, and risk assessment. Since
the topic involves complex and controversial issues of cross-Agency concern, a multi-office,
inter-Agency RAF Core Working Group was established from the Technical Group members;
NIOSH, and NIEHS are participants. This Core Working Group is drafting a guidance document
focused on immunosuppression that incorporates consideration of susceptible populations.
Immunosuppression was selected as a first topic as it is both timely and tractable. As this
document matures, it will be forwarded for review and comment to the full Technical Panel and
to additional inter-Agency experts in the areas of immunotoxicology and risk assessment before
beginning standard RAF, intra-Agency, inter-Agency, and public review.
Point of Contact:
Andrew Rooney
Health Scientist
Building B
Research Triangle Park, NC 27709

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