Journal of Toxicology and Environmental Health, Part B, 2010
With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Stra... more With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.
Prenatal exposure to polychlorinated biphenyls (PCBs) and reproductive outcome was determined in ... more Prenatal exposure to polychlorinated biphenyls (PCBs) and reproductive outcome was determined in a population of 1112 women during 1987-1989. The women studied were from the Green Bay, Wisconsin area, thereby providing a population with potential PCB exposure from Lake Michigan sport fish consumption. All women with positive pregnancy tests from two Green Bay prenatal clinics were asked to complete a self-administered questionnaire on fish consumption, health and reproductive history, and other relevant issues and to provide blood samples for PCB analysis. A positive correlation was found between the amount of Lake Michigan fish mothers claimed to consume and their PCB serum levels. After the pregnancy period, reproductive outcome measures (fetal wastage; stillbirths; and birth weight, birth length, head circumference, ponderal index, and birth weight percentiles for live births) were abstracted from hospital labor reports. Typical negative associations between birth size measures and consumption of caffeine, smoking, and alcohol were found. Birth size was positively associated with gestational age, birth order, weight gain during pregnancy, male babies, and rural residence. Birth size was also associated with PCB exposure; however contrary to expectations, a positive association was found (P < 0.044) for most mothers (the exception being those mothers who gained more than 34 lb during their pregnancy). PCB exposures were lower than the other studies that found that birth size was negatively associated with PCB exposure.
We analyzed data from the Wisconsin Childhood Lead Poisoning Prevention Program to examine the di... more We analyzed data from the Wisconsin Childhood Lead Poisoning Prevention Program to examine the distribution of and trends in elevated blood lead levels among WIC-enrolled children from 1996 until 2000. Higher blood lead levels were seen among WIC-enrolled children, and although not statistically significant, the rate of blood lead level decline among WIC-enrolled children was greater than among non-WIC-enrolled children.
During July 2000_January 2002, the Wisconsin Division of Public Health conducted a study in 19 ru... more During July 2000_January 2002, the Wisconsin Division of Public Health conducted a study in 19 rural townships. A high percentage of private drinking-water wells in these townships contained traces of arsenic. Residents were asked to collect well-water samples and complete a questionnaire regarding residential history, consumption of drinking-water, and family health. In total, 2,233 household wells were tested, and 6,669
Inorganic arsenic is naturally oc- curring in groundwaters through- out the United States. This s... more Inorganic arsenic is naturally oc- curring in groundwaters through- out the United States. This study investigated arsenic exposure and self-report of 9 chronic diseases. We received private well-water samples and questionnaires from 1185 people who reported drink- ing their water for 20 or more years. Respondents with arsenic levels of 2 |ig/L or greater were statistically more likely to report
Page 1. Amercan Journal of Epidemiology Vol 135, No. 3 Copyright C 1992 by The Johns Hopkins Univ... more Page 1. Amercan Journal of Epidemiology Vol 135, No. 3 Copyright C 1992 by The Johns Hopkins University School erf Hyg«ne and Pubfc Health Printed in USA All rights reserved LETTERS TO THE EDITOR RE: "VASECTOMYAND THE RISK OF PROSTATE CANCER" ...
WMJ: official publication of the State Medical Society of Wisconsin
The 1999 US Government Accounting Agency (GAO) report to Congress documented that among children ... more The 1999 US Government Accounting Agency (GAO) report to Congress documented that among children in the United States, those served by federal health care programs had high rates of lead poisoning but low rates of blood lead testing. To further explore these findings, the Wisconsin Department of Health and Family Services initiated matching the state's blood lead test data file with the Medicaid eligibility file, and with the WIC Program enrollment file. This article examines data analyzed from the matched files for the year 1999. The results of the analysis of Wisconsin data shadowed the national findings contained in the GAO report. About half of the Wisconsin children enrolled in Medicaid and WIC have been screened, the majority of lead poisoned children in Wisconsin receive Medicaid (80%) and WIC (60%) services. Additional data collected by the department on the physical and environmental health of severely lead-poisoned children indicates that lead-coated surfaces and deterioration were identified as the primary source and cause of the poisoning. These findings support the Wisconsin recommendations for blood lead testing of 1 and 2 year olds living in older or renovated housing, and all children enrolled in Medicaid or WIC.
The prevalence of occupational pleural thickening in the United States in the mid-1970s was estim... more The prevalence of occupational pleural thickening in the United States in the mid-1970s was estimated; since asbestos often produces pleural thickening, this estimate in turn was used to estimate the prevalence of asbestos exposure. Chest x-rays obtained by the 1971-1975 National Health and Nutrition Examination Survey were reread by three readers using the International Labour Office criteria for diagnosis of pleural thickening consistent with dust exposure. All 289 x-rays showing any pleural abnormalities plus a 3-to-1 age-, sex-, and race-matched control series were reread. Using two of three readings as "positive," and extrapolating to the US population from this defined sample, the authors showed that 2.3% of males and 0.2% of females had occupational pleural thickening on x-ray, with a strong increase with age in white males. This provides a US population estimate of 1.3 million people with occupational pleural thickening and approximately 8 million people with asbes...
Increasingly, health departments are being pressed by the public to respond to disease risk with ... more Increasingly, health departments are being pressed by the public to respond to disease risk with cluster investigations in communities and neighborhoods. This is a direct result of growing concern about the role that the environment may play in disease risk. While extensive analyses directly inputing exposures or numbers at risk are often necessary to thoroughly investigate clusters, it is quite useful to perform an exploratory analysis with existing morbidity and mortality data as a first level of response. To meet this need for timely evaluation, the authors describe a user-friendly Statistical Analysis System (SAS) program called SMRFIT to automate community disease cluster evaluations. The program creates frequency tables for number at risk and number of disease outcomes for the community, balance of parent county, and balance of state. SMRFIT then constructs standardized mortality ratios, with the community compared with balance of county and balance of state referents. Poisson...
Pleural thickening on x-ray is a specific marker for exposure to asbestos, which in turn carries ... more Pleural thickening on x-ray is a specific marker for exposure to asbestos, which in turn carries an excess risk for lung disease and cancer. In World War II, a large cohort of asbestos workers was employed in shipyards in the United States. About 30 years have elapsed between their exposure and the 1974 Health and Nutrition Examination Survey (HANES I), done on a probability sample of US residents. A defined subgroup of subjects between ages 18 and 75 years (n = 6758) had chest x-rays. All films read by HANES as showing pleural changes (n = 289), and a 3 to 1, age-, sex-, race-matched control series were re-read by three readers using the International Labor Organization criteria for diagnosis of pleural pneumoconiosis. Using 2/3 readings as positive, 2.3% of males and 0.2% of females had pleural changes on x-ray, with a strong increase with age in white males. This provides a US population estimate of 1.3 million people with pleural changes in the mid-1970s. If about 12% of asbesto...
Journal of Occupational and Environmental Medicine, 2007
From the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (Drs McElroy and Tre... more From the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (Drs McElroy and Trentham-Dietz, Mr Hampton, and Dr Newcomb), Madison, WI; Department of Medicine, Vanderbilt University and the Vanderbilt-Ingram Cancer Center (Dr Egan), Nashville, TN; ...
Journal of Toxicology and Environmental Health, Part B, 2010
With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Stra... more With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.
Prenatal exposure to polychlorinated biphenyls (PCBs) and reproductive outcome was determined in ... more Prenatal exposure to polychlorinated biphenyls (PCBs) and reproductive outcome was determined in a population of 1112 women during 1987-1989. The women studied were from the Green Bay, Wisconsin area, thereby providing a population with potential PCB exposure from Lake Michigan sport fish consumption. All women with positive pregnancy tests from two Green Bay prenatal clinics were asked to complete a self-administered questionnaire on fish consumption, health and reproductive history, and other relevant issues and to provide blood samples for PCB analysis. A positive correlation was found between the amount of Lake Michigan fish mothers claimed to consume and their PCB serum levels. After the pregnancy period, reproductive outcome measures (fetal wastage; stillbirths; and birth weight, birth length, head circumference, ponderal index, and birth weight percentiles for live births) were abstracted from hospital labor reports. Typical negative associations between birth size measures and consumption of caffeine, smoking, and alcohol were found. Birth size was positively associated with gestational age, birth order, weight gain during pregnancy, male babies, and rural residence. Birth size was also associated with PCB exposure; however contrary to expectations, a positive association was found (P < 0.044) for most mothers (the exception being those mothers who gained more than 34 lb during their pregnancy). PCB exposures were lower than the other studies that found that birth size was negatively associated with PCB exposure.
We analyzed data from the Wisconsin Childhood Lead Poisoning Prevention Program to examine the di... more We analyzed data from the Wisconsin Childhood Lead Poisoning Prevention Program to examine the distribution of and trends in elevated blood lead levels among WIC-enrolled children from 1996 until 2000. Higher blood lead levels were seen among WIC-enrolled children, and although not statistically significant, the rate of blood lead level decline among WIC-enrolled children was greater than among non-WIC-enrolled children.
During July 2000_January 2002, the Wisconsin Division of Public Health conducted a study in 19 ru... more During July 2000_January 2002, the Wisconsin Division of Public Health conducted a study in 19 rural townships. A high percentage of private drinking-water wells in these townships contained traces of arsenic. Residents were asked to collect well-water samples and complete a questionnaire regarding residential history, consumption of drinking-water, and family health. In total, 2,233 household wells were tested, and 6,669
Inorganic arsenic is naturally oc- curring in groundwaters through- out the United States. This s... more Inorganic arsenic is naturally oc- curring in groundwaters through- out the United States. This study investigated arsenic exposure and self-report of 9 chronic diseases. We received private well-water samples and questionnaires from 1185 people who reported drink- ing their water for 20 or more years. Respondents with arsenic levels of 2 |ig/L or greater were statistically more likely to report
Page 1. Amercan Journal of Epidemiology Vol 135, No. 3 Copyright C 1992 by The Johns Hopkins Univ... more Page 1. Amercan Journal of Epidemiology Vol 135, No. 3 Copyright C 1992 by The Johns Hopkins University School erf Hyg«ne and Pubfc Health Printed in USA All rights reserved LETTERS TO THE EDITOR RE: "VASECTOMYAND THE RISK OF PROSTATE CANCER" ...
WMJ: official publication of the State Medical Society of Wisconsin
The 1999 US Government Accounting Agency (GAO) report to Congress documented that among children ... more The 1999 US Government Accounting Agency (GAO) report to Congress documented that among children in the United States, those served by federal health care programs had high rates of lead poisoning but low rates of blood lead testing. To further explore these findings, the Wisconsin Department of Health and Family Services initiated matching the state's blood lead test data file with the Medicaid eligibility file, and with the WIC Program enrollment file. This article examines data analyzed from the matched files for the year 1999. The results of the analysis of Wisconsin data shadowed the national findings contained in the GAO report. About half of the Wisconsin children enrolled in Medicaid and WIC have been screened, the majority of lead poisoned children in Wisconsin receive Medicaid (80%) and WIC (60%) services. Additional data collected by the department on the physical and environmental health of severely lead-poisoned children indicates that lead-coated surfaces and deterioration were identified as the primary source and cause of the poisoning. These findings support the Wisconsin recommendations for blood lead testing of 1 and 2 year olds living in older or renovated housing, and all children enrolled in Medicaid or WIC.
The prevalence of occupational pleural thickening in the United States in the mid-1970s was estim... more The prevalence of occupational pleural thickening in the United States in the mid-1970s was estimated; since asbestos often produces pleural thickening, this estimate in turn was used to estimate the prevalence of asbestos exposure. Chest x-rays obtained by the 1971-1975 National Health and Nutrition Examination Survey were reread by three readers using the International Labour Office criteria for diagnosis of pleural thickening consistent with dust exposure. All 289 x-rays showing any pleural abnormalities plus a 3-to-1 age-, sex-, and race-matched control series were reread. Using two of three readings as "positive," and extrapolating to the US population from this defined sample, the authors showed that 2.3% of males and 0.2% of females had occupational pleural thickening on x-ray, with a strong increase with age in white males. This provides a US population estimate of 1.3 million people with occupational pleural thickening and approximately 8 million people with asbes...
Increasingly, health departments are being pressed by the public to respond to disease risk with ... more Increasingly, health departments are being pressed by the public to respond to disease risk with cluster investigations in communities and neighborhoods. This is a direct result of growing concern about the role that the environment may play in disease risk. While extensive analyses directly inputing exposures or numbers at risk are often necessary to thoroughly investigate clusters, it is quite useful to perform an exploratory analysis with existing morbidity and mortality data as a first level of response. To meet this need for timely evaluation, the authors describe a user-friendly Statistical Analysis System (SAS) program called SMRFIT to automate community disease cluster evaluations. The program creates frequency tables for number at risk and number of disease outcomes for the community, balance of parent county, and balance of state. SMRFIT then constructs standardized mortality ratios, with the community compared with balance of county and balance of state referents. Poisson...
Pleural thickening on x-ray is a specific marker for exposure to asbestos, which in turn carries ... more Pleural thickening on x-ray is a specific marker for exposure to asbestos, which in turn carries an excess risk for lung disease and cancer. In World War II, a large cohort of asbestos workers was employed in shipyards in the United States. About 30 years have elapsed between their exposure and the 1974 Health and Nutrition Examination Survey (HANES I), done on a probability sample of US residents. A defined subgroup of subjects between ages 18 and 75 years (n = 6758) had chest x-rays. All films read by HANES as showing pleural changes (n = 289), and a 3 to 1, age-, sex-, race-matched control series were re-read by three readers using the International Labor Organization criteria for diagnosis of pleural pneumoconiosis. Using 2/3 readings as positive, 2.3% of males and 0.2% of females had pleural changes on x-ray, with a strong increase with age in white males. This provides a US population estimate of 1.3 million people with pleural changes in the mid-1970s. If about 12% of asbesto...
Journal of Occupational and Environmental Medicine, 2007
From the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (Drs McElroy and Tre... more From the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (Drs McElroy and Trentham-Dietz, Mr Hampton, and Dr Newcomb), Madison, WI; Department of Medicine, Vanderbilt University and the Vanderbilt-Ingram Cancer Center (Dr Egan), Nashville, TN; ...
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