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| About Richard Beger (FDA) |
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Richard D. Beger, (Ph.D.) is currently Branch Chief, Center for Metabolomics, in the Division of Systems Toxicology at the FDA’s National Center for Toxicological Research in Jefferson, Arkansas. He received his Ph.D. theoretical biophysics from Purdue University in 1991. He performed a two year postdoctoral fellowship at Johns Hopkins Medical School, Department of Biophysics and Biophysical Chemistry in Baltimore, MD and a 5 year postdoctoral position at Wesleyan University, Department of Chemistry in Middletown, CT. He has been at the National Center for Toxicological Research (NCTR), US FDA, in Jefferson, AR for the last eight years. He is an adjunct Associate Professor in Department of Biochemistry and Molecular Biology at the University of Arkansas for Medical Sciences. He is an active member of the Society of Toxicology since 2004 and on the technical advisory board for the Metabolomics Society. He is involved with the Metabolomics Society quest for developing Metabolomics reporting standards.
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Comparison of TEFs and REPs Predicted by Quantitative Spectrometric Data-Activity Relationships and REPs Determined by a Luciferase Gene Expression Assay for 1,3,7,8-TCDD and 1,2,3,4,7-PeCDD
Richard Beger, Jon Wilkes, Bruce Hass, Dan Buzatu, Ralph Kodell (1)
Lisa Pence, Jeffrey Archer, Lisa Jennings, Mary Kim Halbert (2)
(1) NCTR, FDA and (2) ARL, Jefferson, AR 72079, USA
Previous work demonstrated that carbon nuclear magnetic resonance (13C-NMR) data could be correlated to toxic equivalency factors (TEFs) of the 29 polychlorinated dioxin-like compounds (polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), or polychlorinated biphenyls (PCBs)) for which non-zero TEFs have been defined. Such correlations are called quantitative spectrometric data-activity relationship (QSDAR) models. An improved QSDAR model predicted TEFs as 0.037 and 0.004, respectively, for 1,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,4,7-pentachlorodibenzo-p-dioxin (PeCDD), both of which are among the 390 congeners for which zero value TEFs are assumed. A QSDAR model of relative potency (REP) values estimated values as 0.115 and 0.020, respectively. Both models indicated that these two congeners are likely to exhibit significant dioxin-like toxicity. If very many such congeners should have non-zero values, TEF-based risk assessments of some dioxin, furan, or PCB contaminated sites or foods may be underestimating toxicity. We used a luciferase gene expression in vitro assay based on mouse liver cells to determine experimental REPs of 0.027 and 0.013, for 1,3,7,8-TCDD and 1,2,3,4,7-PeCDD, respectively. The corresponding QSDAR-estimated and gene-expression assayed values were in close agreement. We proposed QSDAR estimates as first approximations that give reasonably accurate estimates. This study showed that QSDAR prediction followed by a relatively inexpensive in vitro assay could be used to nominate a few candidates among hundreds for expensive in vivo evaluation. Success here suggested that in silico and in vitro nomination protocols may enable practical risk assessment for toxic endpoints when members of a large chemical family display different degrees of toxicity operating through a common mechanism.
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