Citations that appear below are to publications listed in Dr. Bogen's CV
Quantitative Risk Assessment Methods
While at LLNL, Dr. Bogen served as a Member of the National Academy of Sciences/National Research Council (NRC) committees that issued Science and Judgment in Risk Assessment (1994, reprinted in 1996 as a student edition) and Review of the Army’s Technical Guides on Assessing and Managing Chemical Hazards to Deployed Personnel (2004). The Science and Judgment in Risk Assessment report, known as “the Blue Book”—the second NRC report to focus on regulatory (particularly U.S. EPA environmental carcinogen) risk assessment methodology—was prepared by NRC at Congressional request in the Clean Air Act Amendments of 1990 as a follow-up to NRC’s first report on this topic, Risk Assessment in the Federal Government: Managing the Process (1986), known as the “Red Book.” The Science and Judgment report recommended systematic distinction between and appropriate analysis of uncertainty and inter-individual variability in environmental health risk analysis, citing and adopting nomenclature and mathematical (e.g., nested Monte Carlo) approaches Dr. Bogen developed for this purpose in my UCB SPH doctoral dissertation and related publications (see Bogen 1986 dissertation; Bogen 1990 book; Bogen & Spear 1987 Risk Anal; Bogen & McKone 1988 Risk Anal; McKone & Bogen 1991 Environ Sci Technol, 1992 Regul Toxicol Pharmacol; Bogen 1995 Risk Anal). At LLNL and Exponent, Dr. Bogen continued to develop methods for uncertainty and inter-individual variability analysis applications to exposure and health risk assessment and management (see Bogen 1995 Risk Anal; Robison et al. 1997 Health Phys; Bogen et al. 1997 Health Phys; Daniels et al. 2000 Water Air Soil Pollut; Bogen 2005 Risk Anal; Bogen & Gouveia 2008 J Hazard Mater A; Bogen et al. 2009 Toxicol Sci).
Cooked-Meat Carcinogen Exposure Assessment & Epidemiology
As a project co-investigator in a 5-year NCI/NCI-P01-funded study centered at LLNL, Dr. Bogen focused on heterocyclic amine (HA) cooked-meat mutagen carcinogenic potency and human dietary exposure characterization (the principal HA, PhIP, was first identified at LLNL) (see Bogen 1994 Mutat Res; Bogen 1994 Food Chem Toxicol; Bogen 1995 Molec Environ Mutagen; Layton et al. 1995 Carcinogenesis). As co-investigator in a 5-year follow-up study funded by a NCI/NCI-P01 grant centered at LLNL, Dr. Bogen led an epidemiological study in collaboration with Professor Elizabeth Holly at the UCSF School of Medicine that investigated associations between prostate cancer screening outcome and dietary HA exposures in African-American men screened at a clinic in Oakland, CA, for which he co-designed and supervised in-person administration of a dietary HA-intake questionnaire to study participants and directed all multi-institution IRB-approval aspects of the study (see Keating et al. 2000 Cancer Causes Control; Bogen & Keating 2001 J Environ Sci Health). As principal investigator of a follow-up 3-year expanded epidemiology study funded by the U.S. Department of Defense Prostate Cancer Research Program, Dr. Bogen continued leading the same multi-institution collaborative team and succeeded in detecting a significant HA-exposure-related elevation in screening indices of prostate cancer in our clinic-based study population (see Bogen et al. 2007 Prostate Cancer Prostatic Dis). He also collaborated on follow-up HA-risk-related studies (see Keating et al. 2007 J Am Dietetic Assoc; Louis et al. 2007 J Toxicol Environ Health, 2008 Neuroepidemiol).
New Experimental Methods to Measure Dermal Uptake Kinetics, Ultra-Low Occupational 238Pu Exposures, and Low-Dose Radiogenic Cell Killing
Dr. Bogen's experimental work at LLNL examined in vivo dermal uptake of organics into hairless guinea pigs, and he explored unexpected observations from that study by pioneering the application of accelerator mass spectrometry (AMS) to real-time dermal penetration kinetics research using human surgical tissue, leading to a surprising hypothesis that uptake-rates measured using in vivo methods generally and substantially exceed estimates based on conventional in vitro diffusion-cell methods (see Bogen et al. 1992 Fund Appl Toxicol; Bogen 1994 J Expos Anal Environ Epidemiol; Bogen et al. 1998 J Expos Anal Environ Epidemiol). Follow-up analysis at Exponent considerably strengthened this conclusion (Bogen 2013 Risk Anal). At LLNL, Dr. Bogen pioneered two additional experimental methods: (1) AMS-based ultrasensitive reconstruction of historical plutonium-238 dose to plutonium workers over a 20-year period at LLNL using archived alpha-spectrometry plates that previously had yielded only apparent background-level counts (see LLNL report: Bogen et al. 2004); and (2) application of gel-microdrop flow cytometry to assess hypersensitivity-related non-monotonic reduction in cell survival after gamma radiation exposure in collaboration with scientists at the Cross Cancer Institute in Alberta, Canada (see Bogen et al. 2001 Toxicol; Enns et al. 2004 Molec Cancer Res).
PBPK-Based Environmental and Occupational Exposure Assessment
At LLNL, Dr. Bogen developed novel, efficient approaches to physiologically based pharmacokinetic (PBPK) model applications (see Bogen 1988 Regul Toxicol Pharmacol; Bogen & Hall 1989 Regul Toxicol Pharmacol; Daniels et al. 2000 Water Air Soil Pollut; Bogen 2006 Risk Anal), and applied those approaches to chemical-specific health risk assessment reports LLNL prepared on behalf of federal and state agencies such the California Department of Health Services and California Environmental Protection Agency (see LLNL Reports: Reed et al. 1987; Bogen et al. 1987, 1988, 1992a-b; Layton et al. 1987; Daniels et al. 1998; Bogen 2001). At LLNL and Exponent, Dr. Bogen continued to develop and apply PBPK-based approaches to environmental carcinogen and occupational (dermal pesticide) exposure assessment, to facilitate biologically based health risk assessment (see Bogen & Gold 1997 Regul Toxicol Pharmacol; Bogen & Singhal 2016 J Environ Sci Health B; Bogen & Heilman 2015 Crit Rev Toxicol).
Mechanistic Models of Tumorigenesis, Cancer Risk, and Low-Dose Dose Response
Chemical and radiogenic tumorigenesis and cancer risk assessment and associated risk policy issues have been of continuing research interest to Dr. Bogen (Bogen 1980 J Law Technol; Bogen 1983 J Health Politics Policy Law; Lichtenberg et al. 1989 J Environ Econ Management; Bogen 1989 J Natl Cancer Inst; Bogen 1990 Fund Appl Toxicol;. Bogen 1994 Mutat Res; Layton et al. 1995 Carcinogenesis; Bogen 1995 Molec Environ Mutagen; Bogen et al. 1997 Health Phys; Bogen & Gold 1997 Regul Toxicol Pharmacol; Bogen 1998 Hum Exper Toxicol; Bogen 2001 Hum Ecol Risk Assess; Bogen & Witschi 2002 Carcinogenesis; Enns et al. 2004 Molec Cancer Res; Bogen 2008 Risk Anal [SOT RASS Top-10 Publication Award]; Bogen 2014 Dose-Response; Bogen 2014a-b Risk Anal; Bogen & Heilman 2015 Crit Rev Toxicol; Bogen 2016 Risk Anal [SRA Best Paper of the Year Award]; Bogen et al. 2017 Toxicol Reports [EPRI-funded research on low-dose dose-response for arsenic-induced cytotoxicity, on which Dr. Bogen collaborated with Professor Samuel Cohen, M.D., at the University of Nebraska Medical Center]; Bogen 2017 Risk Anal; Bogen 2017 Dose-Response [see Figure 1 below]; Kerger 2017a-b Human Ecol Risk Assess). As part of this research focus, Dr. Bogen proposed a new, epigenetic dysregulation-driven model of tumorigenesis and considered its dose-response implications (Bogen 2013 Med Hypoth; Bogen 2017 Adv Molec Toxicol).
Related to this research focus, Dr. Bogen served during 2016–2017 as Chair-Elect and Chair of the Society for Risk Analysis Dose-Response Specialty Group.
Figure 1. Re-analysis of combined beta-lactamase (bla) reporter assay data on ARE activation by 9 hepatotoxic chemicals in HepG2 cells in vitro examined at 12 concentrations (~5 replicates/concentration).* Points = arithmetic mean % activity (PA), error bars = ±1 SDM (inner bars) and ±1 SD (outer bars). Dashed horizontal lines correspond to PA = 0% and 25%. Nonlinear J-shaped fit (solid curve, R^2 = 0.987) includes an initial linear slope that is significantly negative (p < 10^–4 by 2-tail t-test). Source: Bogen (2017, Dose-Response).
*Study data kindly made available by Drs. M Xia and R Huang of the National Institutes of Health National Center for Advancing Translational Sciences, who are co-authors of: Shukla et al. Profiling environmental chemicals for activity in the antioxidant response element signaling pathway using a high throughput screening approach. Environ Health Perspect 2012; 120(8):1150–6.
Occupational, Environmental, Ecological, and Consumer Chemical Exposure & Risk Assessment
Dr. Bogen collaborated on published assessments of occupational, environmental, consumer-product, and ecological exposures to chemicals including benzene, formaldehyde, and pesticides (Sheehan et al. 2010, 2017 Risk Anal; Bogen & Reiss 2012 Risk Anal; Bogen & Sheehan 2014 Risk Anal). For the California Department of Justice he developed a screening-level assessment of hazards to children posed by multi-route exposure to six phthalates from consumer products regulated under California A.B. 1108 and Proposition 65 (Bogen and Goswami 2013 report to CalDOJ). As part of this research focus, Dr. Bogen also developed the first published approach for quantitative assessment of sensitizer-specific risks of allergic contact dermatitis (ACD) elicitation in sensitized individuals, in relation to applied dermal load of a metallic or organic sensitizer, based on a new analysis of previously published clinical patch test data (Bogen & Garry 2017 Risk Anal). This new approach (see Figure 2) has broad potential applications to characterizing ACD-elicitation risks for occupational, medical-device, and consumer-product exposures (e.g., via sustained dermal contact incurred using wearable technologies—a burgeoning industry that already has experienced incidents of unexpected product-associated ACD elicitation).
Figure 2. Dose response for combined ACD-elicitation risk data on Ni and five organic sensitizers (open points) using sensitizer-specific values of dermal load all scaled by corresponding ACD-eliciting potency relative to Ni (n = # points fit, N = # patients) compared to a common lognormal ACDER model fit (solid line) obtained by analysis of covariance for linear regression. Solid point indicates the EN 1811 reference dermal load for Ni of 0.5 μg/cm2. Patch test data on ACD elicited by Cr(VI) and Cr(III) (not shown) are also consistent with this model. Source: Bogen & Garry (2017).
Co-inventor on five DNA-technology patents
Dr. Bogen is a co-inventor on five patents awarded to the Regents of the University of California, based on his research at LLNL:
Patent 6,270,972: Kit for detecting nucleic acid sequences using competitive hybridization probes, August 7, 2001 (with J.N. Lucas and T. Straume).
Patent 6,027,879: Detection and isolation of nucleic acid sequences using a bifunctional hybridization probe, February 22, 2000 (with J.N. Lucas and T. Straume).
Patent 5,783,387: Method for identifying and quantifying nucleic acid sequence aberrations, July 21, 1998 (with J.N. Lucas and T. Straume).
Patent 5,731,153: Identification of random nucleic acid sequence aberrations using dual capture probes which hybridize to different chromosome regions, March 24, 1998 (with J.N. Lucas and T. Straume).
Patent 5,616,465: Detection and isolation of nucleic acid sequences using competitive hybridization probes, April 1, 1997 (with J.N. Lucas and T. Straume).