Risk Assessment Approaches英文资料.pdfVIP

Risk Assessment Approaches Presented to US EPA Office of Water October 16th , 2009 Larry Zobel, MD; Robert Rickard, Ph.D.; John Butenhoff, Ph.D.; Harvey Clewell, Ph.D. Risk Assessment Approaches for PFOS/PFOA Should Be Based On: • Internal dose as represented by serum PFOA PFOS concentrations • Multiple health endpoints that consider human relevance • Benchmark-dose methodology where possible • Appropriate Uncertainty Factors for assessment based on internal dose • Appropriate Relative Source Contribution based on available data Why Use Internal Dose? • Robust data set exist from human and experimental studies • Includes serum concentration data • Integrates all routes of exposure • Bridges PK differences • NOAEL/BMD have been established based on serum concentration Internal Dose in RiskAssessment (Butenhoff et al. 2004) Internal-Dose Risk Assessment 3M EHAD (2003) Examples of Internal-Dose Risk Assessments • EPA Draft PFOA Risk Assessment • German/EU “CSR” Biological DNEL • Minnesota HRLs • Butenhoff et al. (2004) • 3M PFOS “EHAD” (2003) • Tardiff et al. (2009) • Standard approach for pharmaceuticals Human Experience • Numerous human studies are available. • Results can be associated with known serum PFOS PFOA concentrations. • No causal associations have been observed. • Likely human “no-effect levels” based on studied endpoints in occupational cohorts are 5,000 ng/mL (ppb) for both PFOA and PFOS. Human Relevance • Rodent data must be interpreted based on human relevance of modes of action. • Non-human primate is best laboratory model. Benchmark Dose • Uses all study data • Normalizes species differences to a specific, defined level of r