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Y W Stevens

Publications and source records attributed to Y W Stevens.

28 records · Page 2Linked to original sources
PubMedDate not supplied

Cancer policy framework for: public health assessment of carcinogens in the environment.

Cancer remains at the forefront of public health concerns in the United States and throughout the world. Over the past 20 years a wide range of federal agencies and other organizations have been involved in developing policy statements, classification strategies, and assessment methods to address carcinogenesis and health risks. Each of these documents was developed in response to issues confronted by those organizations in pursuing their mission, often as a direct function of legislative mandates. In pursuing its mandated responsibilities, the Agency for Toxic Substances and Disease Registry (ATSDR) must address public health concerns associated with exposure to carcinogens in the context of all available relevant information. This information includes both technical data as well as science policy positions adopted by the range of organizations with programs germane to the assessment and/or regulation of carcinogens. Because of distinct differences in perspective, practice, and policy dictated by the mandated activities of these organizations and the rapidly evolving understanding of carcinogenesis, apparently divergent positions may be reflected in their conclusions. The differences outlined above, coupled with requests from the public, other agencies, and the private sector for a statement reflecting the Agency's position on science and science policy issues related to cancer, prompted the development of this policy. This document is intended to serve as a framework to guide the Agency in its programs and actions regarding carcinogens and to harmonize such efforts with those of other federal agencies and relevant organizations. This framework reflects an assessment of current practice within the Agency and defines the appropriate roles of conclusions derived by other groups, professional judgment, and emerging scientific principles in ATSDR's public health assessments of exposures to carcinogens. This Cancer Policy Framework is not intended to encompass the development of operational guidelines per se, although the Agency recognizes the utility of such efforts. A central theme of this Cancer Policy Framework is the use of risk analysis as an organizing construct based on sound biomedical and other scientific judgment to define plausible exposure ranges of concern rather than single numerical conclusions that may convey an artificial sense of precision. The development and use of innovative tools for exposure and dose response assessment (with particular emphasis on molecular epidemiology) are also endorsed.

Carcinogens, Environmental↗
PubMedDate not supplied

The Agency for Toxic Substances and Disease Registry's role in development and application of biomarkers in public health practice.

An overview of the Agency for Toxic Substances and Disease Registry's (ATSDR) biomarker program is presented in the context of the paradigm for biomarkers developed by the National Research Council (NRC, 1987, 1991). The status and projected utility of four biomarker studies conducted by NRC and sponsored by ATSDR, the Environmental Protection Agency (EPA), and the National Institute of Environmental Health Sciences (NIEHS) are discussed. These studies include a review of relevant research on biomarkers for specific toxicologic end points, including reproductive toxicology, pulmonary toxicology, neurotoxicology, and immunotoxicology. Also, the scope of related research on exposure characterization being conducted by the ATSDR-sponsored research program at Rutgers University is reviewed. The potential impact of biomarkers on public health assessments and on the range of ATSDR programs is described. Specifically, the role of biomarkers in dose reconstruction, in ATSDR's health studies program, and in the emerging field of molecular epidemiology is reviewed. In addition, future directions and research needs are addressed.

Animals↗
PubMedDate not supplied

In vitro differential metabolism of merbarone by xanthine oxidase and microsomal flavoenzymes. The role of reactive oxygen species.

Merbarone (MB), a nonsedating derivative of thiobarbituric acid, was recently found to induce profound hypouricemia. When incubated with xanthine oxidase (XO) and hypoxanthine in vitro, MB is both an inhibitor of XO and degraded by the XO-hypoxanthine interaction. Compared with allopurinol (Ki = 0.025 microM), MB is a very weak inhibitor of XO (Ki = 51 +/- 8 microM). MB interacts with XO in the presence of hypoxanthine to yield three chromatographically separate products. One of these products has been identified by HPLC retention time and spectral characteristics as 2-oxo-2-desthiomerbarone (2-oxo-MB). The other two products are thought to be S-oxide intermediates in the oxidative desulfuration of this drug. Formation of these products was blocked by catalase, suggesting that the conversion was dependent on reactive oxygen species (especially H2O2) generated by the hypoxanthine-XO system. This suggestion was confirmed by incubating MB with H2O2. In vitro studies with rat liver microsomes have documented the formation of 2-oxo-MB and 4'-OH-MB (4'-OH-MB), the latter being identified by the characteristic HPLC retention time of its acetylated derivative. The formation of 4'-OH-MB has many characteristics of a cytochrome P-450-dependent monooxygenase reaction (NADPH requirement and SKF 525-A inhibition); formation of 2-oxo-MB occurs by a different mechanism that is, as yet, uncharacterized. Incubation of kidney microsomes with MB generated 2-oxo-desthiomerbarone but no detectable 4'-OH-MB.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetic Anhydrides↗