Toxicity Testing for Assessment of Environmental Agents Interim Report (2006) / Chapter Skim
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3 Human Data
3 Human Data
Pages 71-91
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From page 71... ...
Given the importance of human data, this chapter reviews the various types of human data, provides examples of the use of human data in regulatory analyses, and considers the challenges to and possible advances in studies of the human population. Regarding availability of human data, clearly, no population data will be available on a chemical newly introduced to the marketplace, although there may be controlledexposure data, such as those from a clinical trial conducted on a pharmaceutical.
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From page 72... ...
Preclinical safety testing of investigational new drugs must satisfy the appropriate regulatory bodies that the first clinical trials in humans will pose minimal risk for subjects. The exhaustive nature of the preclinical assessment, which includes high-dose acute and multidose chronic studies in animals, means that only a few potential new drugs will be deemed sufficiently safe for administration to human volunteers.
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Some clinical information on acute exposures may be obtained from the Toxic Exposure Surveillance System, which contains data on over 36 million human poison-exposure cases compiled by the American Association of Poison Control Centers (Watson et al.
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. EPIDEMIOLOGIC STUDIES Epidemiologic studies typically investigate the relationship between exposure to a substance and potential health effects in a human population.
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Because of higher exposures in some workplaces relative to the general environment, the occupational setting has provided valuable information on the potential adverse effects of various chemicals. Although occupational exposure monitoring is done primarily for purposes of industrial hygiene and compliance with occupational exposure guidelines, the resulting data are
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USE OF HUMAN DATA FOR REGULATORY ANALYSES Human data have been used to estimate risk and to establish standards for environmental and occupational exposures. Table 3-2 provides TABLE 3-2 Examples of Risks or Standards Derived from Human Data For Drinking-Water Standards and Advisories Arsenic Cancer risks estimated from studies of bladder and other cancers in populations consuming arsenic-contaminated water (EPA 1984; NRC 1999; OEHHA 2004a)
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Hexavalent Cancer risks estimated from studies of lung cancer in workers in chromium the chromate production industry (Mancuso and Hueper 1951; Mancuso 1975, 1997) Ozone Criteria standard derived from controlled human chamber studies of lung-function decrements and respiratory symptoms after ozone exposure (EPA 2005a)
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From page 78... ...
When human data were available but not used as the principal data, a variety of reasons were provided, including the questionable relevance of the exposures, concurrent exposure to other chemicals, imprecise measurements of exposure and duration, inadequate consideration of confounding factors, inadequate statistical power, insufficient time after exposure to observe outcome, and the difficulty of using null results from epidemiologic studies. Epidemiologic studies have played a particularly important role in the assessment of population health risks associated with air pollutants.
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From page 79... ...
Three of the most common problems are that only uncertain or indirect estimates of human exposure are available; that epidemiologic studies may identify associations with chemical classes, such as organophosphate pesticides, or with consumer-product categories, such as insecticides, rather than specific chemicals; and that the indeterminate and often long latency period between exposure and disease creates logistical challenges for study design and adds to the uncertainty of results. Because of the complexity of epidemiologic datasets, there is a need to develop and refine statistical methods of analysis to address critical data issues, such as random and systematic exposure-measurement error, selection bias, the effects of residual confounding and unmeasured covariates, and errors in health-outcome ascertainment.
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Environmental monitoring has provided useful data for exposure assessments. For example, testing foods and drinking water for contaminants has allowed scientists to create reasonable exposure estimates from the test results and data on food and water consumption patterns.
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National Report on Human Exposure to Environmental Chemicals provides a continuing assessment of the U.S. population's exposure to environmental chemicals based on a statistical sample of the general population.
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For example, perchlorate, a drinking-water contaminant, is known to inhibit the uptake of iodide by the thyroid and thus possibly decrease the production of thyroid hormones. Inhibition of radioiodide uptake measured in a human clinical study has been used as a biomarker of effect in risk assessments performed by state environmental agencies and by the National Research Council (OEHHA 2004b; NRC 2005)
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Molecular and Genetic Epidemiology Molecular epidemiology and genetic epidemiology identify molecular biomarkers of exposure and effect and incorporate them into study designs to investigate gene-environment interactions and their associations with the etiology and distribution of disease. Studies incorporating biomarkers have demonstrated that genetic consequences of human exposure are measurable and definable in tissues from exposed people (Schroeder et al.
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Environmental-Health Tracking New efforts to collect data relevant to environmental health in human populations systematically may hold promise for improving the quality and quantity of data available for epidemiologic studies. The Institute of Medicine has stated that "every public health agency [should]
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There are at least four reasons to create an integrated environmental health surveillance system: tracking of environmental hazards, exposures, and disease can help to identify areas or groups in which exposure to an environmental hazard may be excessive and require reduction; trends can help to evaluate the success of environmental-protection and public-health measures; linkage of environmental-hazard information and disease information can help to generate hypotheses that require investigation; and a tracking network provides the foundation that researchers need to do scientific studies to identify the causes of disease. REFERENCES Axelson, O., E
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2001. Modeling lung cancer risk from diesel exhaust: Suitability of the railroad worker cohort for quantitative risk assessment.
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2001. Methylmercury Criteria Document: Fish Tissue Criterion for Methylmercury to Protect Human Health Document.
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2003. Association be tween gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver, Canada.
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Office of Environmental Health Hazard Assessment, California Environmental Pro tection Agency. June 2004 [online]
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2005. DNA adducts and lung cancer risk: A prospective study.
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1995. Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung.
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