Papers by Joseph Rodricks
Critical Reviews in Toxicology, 2010
�������������������������������������������������������������������������������������������������... more ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 422 1� Introduction ����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 424 2� Hazard assessment ������������������������������������������������������������������������������������������������������������������������������������������������������������������������ 425 2�1� Human safety and tolerability studies of triclosan �������������������������������������������������������������������������������������������������������������� 425 2�1�1� Studies by the oral route ������������������������������������������������������������������������������������������������������������������������������������������������� 425 2�1�2� Studies by the dermal route ������������������������������������������������������������������������������������������������������������������������������������������� 425
The Open Epidemiology Journal, 2011
Critical Reviews in Food Science and Nutrition, 2009
The methodology used to establish tolerable upper intake levels (UL) for nutrients borrows heavil... more The methodology used to establish tolerable upper intake levels (UL) for nutrients borrows heavily from risk assessment methods used by toxicologists. Empirical data are used to identify intake levels associated with adverse effects, and Uncertainty Factors (UF) are applied to establish ULs, which in turn inform public health decisions and standards. Use of UFs reflects lack of knowledge regarding the biological events that underlie response to the intake of a given nutrient, and also regarding the sources of variability in that response. In this paper, the Key Events Dose-Response Framework (KEDRF) is used to systematically consider the major biological steps that lead from the intake of the preformed vitamin A to excess systemic levels, and subsequently to increased risk of adverse effects. Each step is examined with regard to factors that influence whether there is progression toward the adverse effect of concern. The role of homeostatic mechanisms is discussed, along with the types of research needed to improve understanding of dose-response for vitamin A. This initial analysis illustrates the potential of the KEDRF as a useful analytical tool for integrating current knowledge regarding dose-response, generating questions that will focus future research efforts, and clarifying how improved knowledge and data could be used to reduce reliance on UFs.
Regulatory Toxicology and Pharmacology, 2004
Perfluorooctanoate (PFOA), an environmentally and metabolically stable perfluorinated carboxylic ... more Perfluorooctanoate (PFOA), an environmentally and metabolically stable perfluorinated carboxylic acid, has been detected in the serum of children, adults and the elderly from the United States with the upper bound of the 95th percentile estimate in the range of 0.011-0.014 lg/mL (ppm). In this risk characterization, margins of exposure (MOE), which can provide a realistic perspective on potential for human risk, were determined by comparison of general population serum PFOA concentrations with serum concentrations from toxicological studies that are associated with the lower 95% confidence limit of a modeled 10 percent response or incidence level (LBMIC 10) using USEPA BMDS software. The LBMIC 10 was estimated using surrogate data from other studies or pharmacokinetic relationships if serum PFOA data were not available. Modeled dose-responses (with resulting LBMIC 10 values) included post-natal effects in rats (29 lg/mL), liver-weight increase (23 lg/mL), and bodyweight change (60 lg/mL) in rats and monkeys, and incidence of Leydig cell adenoma (125 lg/mL) in rats. MOE values based on the upper bound 95th percentile population serum PFOA concentration were large, ranging from 1600 (liver-weight increase) to 8900 (Leydig cell adenoma). These MOE values represent substantial protection of children, adults, and the elderly.
American Journal of Epidemiology, 2001
Dose-Response
Federal regulatory agencies had, by the 1970s, been charged with enforcing a host of new laws req... more Federal regulatory agencies had, by the 1970s, been charged with enforcing a host of new laws requiring that they establish controls on human exposures to chemicals necessary to protect health. The agencies relied upon a methodology introduced in the 1950s to identify safe levels of exposure to chemicals known to display toxicity. During the 2 decades prior to the 1970s, federal authorities had come to treat carcinogens as distinct from other toxic agents, and to regard them as unsafe at any level of exposure, and no systematic methods had been developed to deal with the rapidly increasing numbers of carcinogens. Beginning in the mid-1970s, some scientists and policy makers in regulatory agencies, including the present author, began to propose adopting emerging quantitative methods to evaluate the risks of carcinogens and introduced new notions of safety based on explicit consideration of risk. Quantitative risk assessment rose to prominence in the decade reviewed in this article (1974-1984) and began to replace the unsystematic approaches that provided no view of how well health would be protected under various regulatory controls. This article offers the author's recollections of that important decade.
Risk analysis, 1994
The National Institute of Occupational Safety and Health (NIOSH) recently completed a vital statu... more The National Institute of Occupational Safety and Health (NIOSH) recently completed a vital status update adding 6 years of observation on the rubber workers known as the Pliofilm cohort. Using traditional standardized mortality ratio (SMR) analysis, we investigate the impact of the additional information gathered in the NIOSH update. We also compare the effect of using three sets of job-, plant-, and year-specific exposure estimates on the evaluation of benzene's leukemogenicity. The lack of any additional cases of multiple myeloma does not support trends toward elevated risks for this endpoint (as had been observed earlier), and there is no indication of increased incidences of solid tumors (as predicted by animal studies). Qualitatively, which exposure estimates are used does not alter the conclusions. The data added in the update did not greatly modify the estimated relative risk of leukemia associated with benzene exposure, but did confirm previous findings that occupational exposure to high concentrations had leukemogenic potential. The fact that leukemia has not been observed in any individual who started employment in Pliofilm production after 1950 suggests that the observed leukemia cases could be a response to very high levels of benzene exposure that occurred during the early years of this manufacturing process.
The American Statistician, 1982
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Papers by Joseph Rodricks