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University of
Ottawa
Categorical Default Approaches to Uncertainty
Factor Development in Chemical Risk Assessment
Senate room (083) in Tabaret Hall, 550
Cumberland St
John C. Lipscomb PhD, DABT, F.A.T.S.
National Center for
Environmental Assessment,
Office of Research and Development,
U. S. Environmental Protection Agency, Cincinnati, OH
Thursday, October 30th, 2:00
PM
There have been a number of recent developments designed to incorporate increasingly data-informed approaches to consideration of uncertainty in human health risk assessment. Traditional default uncertainty factors of 10 fold each for interspecies (animal to human) differences and intraspecies (human) variability have been parsed into finer constituents, to address toxicokinetic (TK) and toxicodynamic (TD) components as a basis for chemical specific adjustments. An intermediate option between default and chemical specific adjustments, is categorical approaches, which draw on data from multiple chemicals as a basis to make and apply some generalizations. For example, Renwick and colleagues have recently evaluated interspecies differences in the TK of compounds categorized according to the key enzymes in their metabolic pathways.
This presentation will discuss two other methods to develop categorical
default values for interspecies extrapolation for inhaled and ingested
substances. For inhaled substances, categorical default factors
are based on measures of tissue exposure at the site of toxic insult – whether
in the respiratory tract or in systemic tissues. For ingested substances,
body weight scaling for interspecies based on allometric relationships
may be used. The application of these factors requires little
data other than knowledge of route of administration and site of action
and they represent one step in the increasingly data-informed continuum
between default and chemical-specific factors.
Dr. Lipscomb is a chemical manager developing risk assessment files
for the US EPA Integrated Risk Information System (IRIS). He
is leading the efforts of the US EPA’s Risk Assessment Forum
to produce guidance for Data Derived Extrapolation Factors, and is
active also in developing methodology to address chemical mixtures
and cumulative risk. He is an Associate Editor for Toxicological
Sciences, and with Edward Ohanian edited Toxicokinetics and
Risk Assessment (Informa, 2007). He has also worked with
the International Programme on Chemical Safety on initiatives for Chemical-Specific
Adjustment Factors and Best Practices for Physiologically Based Pharmacokinetic
Modeling for Risk Assessment.
Bette Meek
McLaughlin Centre for Population Health Risk assessment,
University of Ottawa
Introductory
presentation
John C. Lipscomp
US EPA
Presentation
on Categorical default approaches for uncertainty factors in chemical
risk assessment
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