Seção: ArtigosTítulo: Unveiling variability and uncertainty for better science and decisions on cancer risks from environmental chemicals / Kenneth T. BogenAutor: Bogen, Kenneth T.Notas: Sumario: The National Research Council 2009 Silver Book panel report included a recommendation that the U.S. Environmental Protection Agency (EPA) should increase all of its chemical carcinogen (CC) potency estimates by ~7-fold to adjust for a purported median-vs.-mean bias that I recently argued does not exist (Bogen KT. Does EPA underestimate cancer risks by ignoring susceptibility differences?, Risk Analysis, 2014; 34(10):17801784). In this issue of the journal, my argument is critiqued for having flaws concerning: (1) intent, bias, and conservatism of EPA estimates of CC potency; (2) bias in potency estimates derived from epidemiology; and (3) human-animal CC-potency correlation. However, my argument remains valid, for the following reasons. (1) EPA's default approach to estimating CC risks has correctly focused on bounding average (not median) individual risk under a genotoxic mode-of-action (MOA) assumption, although pragmatically the approach leaves both inter-individual variability in CCsusceptibility, and widely varying CC-specific magnitudes of fundamental MOA uncertainty, unquantified. (2) CC risk estimates based on large epidemiology studies are not systematically biased downward due to limited sampling from broad, lognormal susceptibility distributions. (3) A good, quantitative correlation is exhibited between upper-bounds on CC-specific potency estimated from human vs. animal studies (n = 24, r = 0.88, p = 2 × 10-8). It is concluded that protective upper-bound estimates of individual CC risk that account for heterogeneity in susceptibility, as well as risk comparisons informed by best predictions of average-individual and population risk that address CC-specific MOA uncertainty, should each be used as separate, complimentary tools to improve regulatory decisions concerning low-level, environmental CC exposures.Registros relacionados: En: Risk analysis : an international journal. - McLean, Virginia : Society for Risk Analysis, 1987-2015 = ISSN 0272-4332. - 06/10/2014 Volumen 34 Número 10 - octubre 2014 Outras classificações: 7Direitos: In Copyright (InC)Referencias externas:
