Biomedical subjects

D W North

Publications and source records attributed to D W North.

5 recordsLinked to original sources

PubMed1999

Monograph: reassessment of human cancer risk of aldrin/dieldrin.

In 1987, the US Environmental Protection Agency (EPA) classified aldrin and dieldrin as category B2 carcinogens, i.e. probable human carcinogens, based largely on the increase in liver tumors in mice fed either organochlorine insecticide. At that date, the relevant epidemiology was deemed inadequate to influence the cancer risk assessment. More time has now elapsed since early exposures of manufacturing workers to aldrin/dieldrin; therefore, updated epidemiological data possess more power to detect exposure-related differences in cancer risk and mortality. Also, recent experimental studies provide a plausible mode of action to explain the mouse specificity of dieldrin-induced hepatocarcinogenesis and call into question the relevance of this activity to human cancer risk. This monograph places this new information within the historic and current perspectives of human cancer risk assessment, including EPA's 1996 Proposed Guidelines for Carcinogen Risk Assessment. Updated epidemiological studies of manufacturing workers in which lifetime exposures to aldrin/dieldrin have been quantified do not indicate increased mortality or cancer risk. In fact, at the middle range of exposures, there is evidence of a decrease in both mortality from all causes and cancer. Recent experimental studies indicate that dieldrin-induced hepatocarcinogenesis in mice occurs through a nongenotoxic mode of action, in which the slow oxidative metabolism of dieldrin is accompanied by an increased production of reactive oxygen species, depletion of hepatic antioxidant defenses (particularly alpha-tocopherol), and peroxidation of liver lipids. Dieldrin-induced oxidative stress or its sequelae apparently result in modulation of gene expression that favors expansion of initiated mouse, but not rat, liver cells; thus, dieldrin acts as a nongenotoxic promoter/accelerator of background liver tumorigenesis in the mouse. Within the framework of EPA's Proposed Guidelines for Carcinogen Risk Assessment, it is proposed that the most appropriate cancer risk descriptor for aldrin/dieldrin, relating to the mouse liver tumor response, is 'not likely a human carcinogen', a descriptor consistent with the example of phenobarbital cited by EPA.

Aldrin↗

PubMed1999

A perspective on nuclear waste.

The management of spent nuclear fuel and high-level nuclear waste has the deserved reputation as one of the most intractable policy issues facing the United States and other nations using nuclear reactors for electric power generation. This paper presents the author's perspective on this complex issue, based on a decade of service with the Nuclear Waste Technical Review Board and Board on Radioactive Waste Management of the National Research Council.

Geological Phenomena↗

PubMed1997

Inorganic arsenic: a need and an opportunity to improve risk assessment.

This paper presents views on the current status of (inorganic) arsenic risk assessment in the United States and recommends research needed to set standards for drinking water. The opinions are those of the Arsenic Task Force of the Society for Environmental Geochemistry and Health, which has met periodically since 1991 to study issues related to arsenic risk assessment and has held workshops and international conferences on arsenic. The topic of this paper is made timely by current scientific interest in exposure to and adverse health effects of arsenic in the United States and passage of the Safe Drinking Water Act Amendment of 1996, which has provisions for a research program on arsenic and a schedule mandating the EPA to revise the maximum contaminant level of arsenic in drinking water by the year 2001. Our central premise and recommendations are straightforward: the risk of adverse health effects associated with arsenic in drinking water is unknown for low arsenic concentrations found in the United States, such as at the current interim maximum contaminant level of 50 microg/l and below. Arsenic-related research should be directed at answering that question. New epidemiological studies are needed to provide data for reliable dose-response assessments of arsenic and for skin cancer, bladder cancer, or other endpoints to be used by the EPA for regulation. Further toxicological research, along with the observational data from epidemiology, is needed to determine if the dose-response relationship at low levels is more consistent with the current assumption of low-dose linearity or the existence of a practical threshold. Other recommendations include adding foodborne arsenic to the calculation of total arsenic intake, calculation of total arsenic intake, and encouraging cooperative research within the United States and between the United States and affected countries.

Arsenic↗

PubMed1997

Risk characterization: A bridge to informed decision making.

Regulatory decisions should be made in the most expert and informed way since they are precipitated by real and perceived threats to human health, under the glare of public scrutiny. In 1994, the National Research Council (NRC) reported that the U.S. Environmental Protection Agency's (USEPA's) overall approach to assessing risks is fundamentally sound, but the Agency must more clearly establish the scientific and policy basis for risk estimates and better communicate the associated uncertainties. On March 21, 1995, USEPA issued a risk characterization policy and guidance. In this policy, an effective risk characterization must fully and clearly characterize risks and disclose the scientific analysis, uncertainties, assumptions, and science policy that underlie decisions throughout the risk assessment process. A number of regulatory reform bills which required risk characterization as part of all Federal risk assessments were introduced by the 104th Congress. The purpose of this workshop was to familiarize Society of Toxicology members with: (1) key elements to be considered in risk characterization and (2) new advances in risk characterization addressed by Federal and State agencies, industry, academia, NRC, and Presidential/Congressional Commission on Risk Assessment and Risk Management. Furthermore, the main objective was to engage the audience in discussing the proper role of science in risk assessment-risk management interface to make informed decisions in the face of scientific uncertainty.

Decision Making↗

PubMed1995

Limitations, definitions, principles and methods of risk analysis.

Decisions on veterinary biologicals involve large uncertainties, complexities which cut across many scientific and technical disciplines, and large potential adverse impacts on public health and on important sectors of the economy. How should risk assessment help to guide the decision process on veterinary biologicals? How can risk assessment practices be harmonized internationally, given the different regulatory traditions and institutions of different countries? A broad view of risk assessment is needed, that risk assessment is a framework for summarizing applicable scientific judgement in support of regulatory decision-making. Support for this view of risk assessment is found in the major reports which have defined risk assessment as currently practised by many regulatory agencies in the United States of America (USA). However, some interested and affected parties perceive risk assessment in the USA as overly quantitative and narrowly focused on regulatory standards for carcinogens. An example of risk assessment for microbial contamination indicates how quantitative methods can be used when data are sparse and decisions must be made in the face of great uncertainty. Such quantitative methods can be used to improve communication about risk, to promote consensus in support of controversial decisions, and to identify valuable opportunities for research to reduce the important sources of uncertainty.

Animals↗