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Chemical Specific Adjustment factors Workshop
Lipscomb, J. AND J. Zhao. Chemical Specific Adjustment factors Workshop. Presented at Toxicology and Risk Assessment Conference, West Chester, OH, April 07 - 10, 2014.
The World Health Organization, through the International Programme on Chemical Safety (IPCS), has established guidance on the use of mechanistic data to replace default uncertainty factors for interspecies extrapolation and intraspecies variability in deriving risk values such as Reference Doses (RfDs) and Tolerable Concentrations (TCs). This guidance informs the choice and application of data that can be used to replace defaults with chemical specific adjustment factors (CSAFs), resulting in values that better reflect the data for the chemical of interest. CSAFs fall on the continuum of the use of data in deriving risk values. At one end of the continuum is the use of the traditional defaults, while at the other end is the use of extensive chemical-specific data in physiologically-based pharmacokinetic (PBPK) modeling, or even biologically-based dose-response (BBDR) modeling. In between these two extremes is the use of categorical defaults (e.g., the dosimetric approach used in the U.S. EPA’s RfC and cancer risk assessment methods) and CSAFs. The CSAF framework is based on early work by Renwick and applied by IPCS. This approach first subdivides the uncertainty factors for interspecies differences (UFA) and human variability (UFH) into toxicokinetic (TK) and toxicodynamic (TD) components. The data relevant for each subcomponent is then evaluated to determine whether chemical-specific data can be used in place of the default. Any one or all of these four subfactors can be replaced by chemical-specific data. Use of the CSAF framework allows the improved use of available data in deriving risk values, and can assist in targeting new studies to address uncertainties and lead to more accurate risk values. CSAFs have been used by the U.S. EPA in deriving an RfD for boron and by Health Canada in deriving a TC for 2-butoxyethanol. This half-day workshop will provide a brief review of the use of uncertainty factors and historical perspective on the reliance on quantitative data to develop values for inter- and intraspecies extrapolation. The course will focus on the IPCS methodology for CSAF development, including the thinking process and steps used for evaluating data. Examples and classroom activities will be used as instructional aids. Participants are asked to bring a calculator.
This half day training workshop is presented to open-enrollment attendees typically representing industry, academia, government and consultant organizations. This workshop teaches the principles of analyzing toxicokinetic and toxicodynamic data to avoid the use of default values for some uncertainties, increasing the sceintific basis of risk assessment and decreasing uncertainty in resulting assessments. It communicates guidance developed by a World Health Organization working group, which included US EPA representation.
URLs/Downloads:CSAF TRAC 2014V1.PPTX
Record Details:Record Type: DOCUMENT (PRESENTATION/SLIDE)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL CENTER FOR ENVIRONMENTAL ASSESSMENT