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Biomedical subjects

K Sexton

Publications and source records attributed to K Sexton.

At least 19 recordsLinked to original sources
PubMed2006

Conventional and toxicogenomic assessment of the acute pulmonary damage induced by the instillation of Cardiff PM10 into the rat lung.

There is strong epidemiological evidence of association between PM10 (particulate matter with an aerodynamic diameter less than or equal to 10 microm) and adverse health outcomes including death and increased hospital admissions for cardiopulmonary conditions. Ambient PM10 surrogates such as diesel exhaust particles (DEP), a common component of UK PM10 have been shown to induce lung inflammation in both humans and rodents. To date, few studies have reported on the toxicological response of UK PM10 in experimental animals. This study examines the pulmonary toxicological responses in male Sprague Dawley rats following the intratracheal instillation of Cardiff urban PM10. A mild but significant change in lung permeability was observed in the lung post-instillation of a high (10 mg) dose of the whole PM10 as adjudged by increases in lung to body weight ratio and total acellular lavage protein. Such effects were less marked following instillation of a water-soluble fraction (80% of the total mass) but histological examination showed that lung capillaries were swollen in size with this treatment. In conclusion, conventional toxicological, histological and toxicogenomic studies have indicated that Cardiff PM10 exhibits low bioreactivity in the form of mild permeability changes. Differential gene expression was observed when the lung was treated with whole PM10, containing durable particles, in comparison with the water-soluble fraction of PM10 that was devoid of particles. Such changes were linked to different histopathological events within the lung.

Air Pollutants↗
PubMed2001

Residential proximity to industrial sources of air pollution: interrelationships among race, poverty, and age.

This study builds on earlier work investigating statistical relationships between sociodemographic characteristics of populations and their residential proximity to industrial sources of air pollution. The analysis uses demographic data from the 1990 U.S. Census and industrial site data from the U.S. Environmental Protection Agency (EPA)'s 1990 Toxics Release Inventory (TRI). The focus is on examining interactions among race (African Americans and Whites), poverty (above and below household poverty threshold), and age (children from birth to 5 years of age and elderly people 65 years old or older). Results from three different study areas (Kanawha Valley in West Virginia, the Baton Rouge-New Orleans Corridor in Louisiana, and the greater Baltimore metropolitan area in Maryland) suggest there are important interactions among race, poverty, and age that are likely to have consequential ramifications for efforts aimed at investigating issues related to environmental justice. Our results indicate that a substantial proportion of all demographic groups studied live within a mile of the nearest facility, with values ranging from 22% of Whites above poverty in the Baton Rouge-New Orleans Corridor to 60% of African Americans below poverty in Baltimore. Likewise, a substantial proportion of all demographic groups also live within 2 miles of four or more industrial facilities, with values ranging from 16% for Whites above poverty in the Corridor to 70% for African Americans below poverty in Baltimore. In all three study areas, African Americans were more likely than Whites to (1) live in households with incomes below the household poverty line, (2) have children 5 years of age or younger, (3) live closer to the nearest industrial emissions source, and (4) live within 2 miles of multiple industrial emission sources. Findings indicate that, compared with White children, a substantially higher proportion of African-American children 5 years of age or younger lived in poor households that were located in relatively close proximity to one or more industrial sources of air pollution.

Adolescent↗
PubMed2001

Measurement of children's exposure to pesticides: analysis of urinary metabolite levels in a probability-based sample.

The Minnesota Children's Pesticide Exposure Study is a probability-based sample of 102 children 3-13 years old who were monitored for commonly used pesticides. During the summer of 1997, first-morning-void urine samples (1-3 per child) were obtained for 88% of study children and analyzed for metabolites of insecticides and herbicides: carbamates and related compounds (1-NAP), atrazine (AM), malathion (MDA), and chlorpyrifos and related compounds (TCPy). TCPy was present in 93% of the samples, whereas 1-NAP, MDA, and AM were detected in 45%, 37%, and 2% of samples, respectively. Measured intrachild means ranged from 1.4 microg/L for MDA to 9.2 microg/L for TCPy, and there was considerable intrachild variability. For children providing three urine samples, geometric mean TCPy levels were greater than the detection limit in 98% of the samples, and nearly half the children had geometric mean 1-NAP and MDA levels greater than the detection limit. Interchild variability was significantly greater than intrachild variability for 1-NAP (p = 0.0037) and TCPy (p < 0.0001). The four metabolites measured were not correlated within urine samples, and children's metabolite levels did not vary systematically by sex, age, race, household income, or putative household pesticide use. On a log scale, mean TCPy levels were significantly higher in urban than in nonurban children (7.2 vs. 4.7 microg/L; p = 0.036). Weighted population mean concentrations were 3.9 [standard error (SE) = 0.7; 95% confidence interval (CI), 2.5, 5.3] microg/L for 1-NAP, 1.7 (SE = 0.3; 95% CI, 1.1, 2.3) microg/L for MDA, and 9.6 (SE = 0.9; 95% CI, 7.8, 11) microg/L for TCPy. The weighted population results estimate the overall mean and variability of metabolite levels for more than 84,000 children in the census tracts sampled. Levels of 1-NAP were lower than reported adult reference range concentrations, whereas TCPy concentrations were substantially higher. Concentrations of MDA were detected more frequently and found at higher levels in children than in a recent nonprobability-based sample of adults. Overall, Minnesota children's TCPy and MDA levels were higher than in recent population-based studies of adults in the United States, but the relative magnitude of intraindividual variability was similar for adults and children.

Adolescent↗
PubMed2001

Metabolites of a tobacco-specific lung carcinogen in the urine of elementary school-aged children.

Limited data are available in the literature on carcinogen uptake by children exposed to environmental tobacco smoke (ETS). In this study, we quantified metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in the urine of elementary school-aged children participating in the School Health Initiative: Environment, Learning, Disease study, a school-based investigation of the environmental health of children. The metabolites of NNK are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). We also measured cotinine and its glucuronide (total cotinine). Urine samples were collected from 204 children. Seventy (34.3%) of these had total cotinine > or =5 ng/ml. NNAL or NNAL-Gluc was detected in 52 of 54 samples with total cotinine > or =5 ng/ml and in 10 of 20 samples with total cotinine < 5 ng/ml. Levels of NNAL plus NNAL-Gluc and total cotinine were significantly higher when exposure to ETS was reported than when no exposure was reported. However, even when no exposure to ETS was reported, levels of NNAL, NNAL-Gluc, and NNAL plus NNAL-Gluc were higher than in children with documented low exposure to ETS, as determined by cotinine levels < 5 ng/ml. Levels of NNAL, NNAL-Gluc, and cotinine were not significantly different in samples collected twice from the same children at 3-month intervals. Levels of NNAL plus NNAL-Gluc in this study were comparable with those observed in our previous field studies of adults exposed to ETS. There was a 93-fold range of NNAL plus NNAL-Gluc values in the exposed children. The results of this study demonstrate widespread and considerable uptake of the tobacco-specific lung carcinogen NNK in this group of elementary school-aged children, raising important questions about potential health risks. Our data indicate that objective biomarkers of carcinogen uptake are important in studies of childhood exposure to ETS and cancer later in life.

Biomarkers↗
PubMed2000

Comparison of short-term variations (15-minute averages) in outdoor and indoor PM2.5 concentrations.

Measurements of 15-min average PM2.5 concentrations were made with a real-time light-scattering instrument at both outdoor (central monitoring sites in three communities) and indoor (residential) locations over two seasons in the Minneapolis-St. Paul metropolitan area. These data are used to examine within-day variability of PM2.5 concentrations indoors and outdoors, as well as matched indoor-to-outdoor (I/O) ratios. Concurrent gravimetric measurements of 24-hr average PM2.5 concentrations were also obtained as a way to compare real-time measures with this more traditional metric. Results indicate that (1) within-day variability for both indoor and outdoor 15-min average PM2.5 concentrations was substantial and comparable in magnitude to day-to-day variability for 24-hr average concentrations; (2) some residences exhibited substantial variability in indoor aerosol characteristics from one day to the next; (3) peak values for indoor short-term (15-min) average PM2.5 concentrations routinely exceeded 24-hr average outdoor values by factors of 3-4; and (4) relatively strong correlations existed between indoor and outdoor PM2.5 concentrations for both 24-hr and 15-min averages.

Activities of Daily Living↗
PubMed1999

Adulteration of urine by "Urine Luck".

BACKGROUND: In vitro adulterants are used to invalidate assays for urine drugs of abuse. The present study examined the effect of pyridinium chlorochromate (PCC) found in the product "Urine Luck". METHODS: PCC was prepared and added to positive urine controls at concentrations of 0, 10, 50, and 100 g/L. The controls were assayed for methamphetamine, benzoylecgonine (BE), codeine and morphine, tetrahydrocannabinol (THC), and phencyclidine (PCP) with the Emit II (Syva) and Abuscreen Online (Roche) immunoassays, and by gas chromatography/mass spectrometry (GC/MS). Two tests were also developed to detect PCC in urine: a spot test to detect chromate ions using 10 g/L 1,5-diphenylcarbazide as the indicator, and a GC/MS assay for pyridine. We tested 150 samples submitted for routine urinalysis, compliance, and workplace drug testing for PCC, using these assays. RESULTS: Response rates decreased at 100 g/L PCC for all Emit II drug assays and for the Abuscreen morphine and THC assays. In contrast, the Abuscreen amphetamine assay produced apparently higher results, and no effect was seen on the results for BE or PCP. The PCC did not affect the GC/MS recovery of methamphetamine, BE, PCP, or their deuterated internal standards, but decreased GC/MS recovery of the opiates at both intermediate (50 g/L) and high (100 g/L) PCC concentrations and apparent concentrations of THC and THC-d3 at all PCC concentrations. Two of 50 samples submitted for workplace drug testing under chain-of-custody conditions were positive for PCC, whereas none of the remaining 100 specimens submitted for routine urinalysis or compliance drug testing were positive. CONCLUSIONS: PCC is an effective adulterant for urine drug testing of THC and opiates. Identification of PCC use can be accomplished with use of a spot test for the oxidant.

False Negative Reactions↗
PubMed1996

What can research contribute to regulatory decisions about the health risks of multiple chemical sensitivity?

Multiple Chemical Sensitivity (MCS), which may not be caused by chemicals at all, is a serious medical problem of unknown origin and uncertain etiology that raises many fundamental science and policy questions. Regulators, for example, are confronted with a dilemma: what, if anything, should be done to protect people from the scientifically uncertain health risks of exposures to extremely low levels of environmental chemicals. Regulatory agencies, such as the Environmental Protection Agency, do not have the luxury of waiting until conclusive scientific evidence is available before making a decision; however, our present lack of scientific understanding about MCS is so acute that it is not possible to ascertain whether the cause of MCS-related symptoms is chemical, biological, physical, psychosocial, or some combination thereof. Nevertheless, many MCS sufferers and advocates for the chemically induced hypothesis are clamoring for regulatory action to reduce putative health risks from very-low-level exposures to chemicals in the environment. Unless steps are taken to improve the quantity and quality of the existing scientific data base, we cannot, with any acceptable degree of certainty, evaluate the extent to which regulatory decisions about MCS are either protective of public health or cost-effective. This article examines how research can strengthen the scientific basis for risk-related decisions about MCS, and proposes a framework for establishing research directions and priorities. It is argued that high-priority research on MCS is distinguishable by four attributes: (1) results are valuable for risk-related decisions; (2) findings significantly advance scientific knowledge and understanding; and the hypothesis being tested is both (3) biologically plausible and (4) readily testable.

Decision Making↗
PubMed1995

Chemical mixtures from a public health perspective: the importance of research for informed decision making.

When considered from a public health perspective, the central question regarding chemical mixtures is deceptively simple: Are current approaches to risk assessment for chemical mixtures affording effective (adequate) and efficient (cost-effective) protection for members of our society? Answering this question realistically depends on an understanding of the hierarchical goals of public health (i.e. prevention, intervention, treatment) and an accurate evaluation of the extent to which these goals are being achieved. To allow decision makers to make informed judgments about the health risks of chemical mixtures, adequate scientific knowledge and understanding must be available to support risk assessment activities, which are an integral part of the regulatory decision making process. Designing and implementing relevant research depends on the existence of a feedback loop between researchers and regulators, where the information needs of regulators influence the nature and direction of research and the information and understanding generated by researchers improves the scientific basis for public health decisions. A clear, consistent, commonly accepted taxonomy for describing important mixture-related phenomena is a key factor in creating and maintaining the necessary feedback loop. Ultimately, both researchers and regulators share a common goal with regard to chemical mixtures; improving the state-of-the-science so that we can make informed decisions about protecting public health. A survey of research issues and needs that are crucial to attaining this goal is presented.

Decision Making↗
PubMed1995

Research to strengthen the scientific basis for health risk assessment: a survey of the context and rationale for mechanistically based methods and models.

Assessment of health risks is an integral part of regulatory decision-making that occurs at the interface between science (e.g. facts) and policy (e.g. values). Because existing scientific knowledge and understanding are often inadequate to answer the most critical risk-related questions, regulatory agencies have developed sets of formalized 'science policies' to extrapolate from existing data to real-life events and situations. These science policies, as, for example, the use of default assumptions or exposure scenarios, can introduce significant uncertainties into the final risk estimate. We survey the rationale for research to reduce extrapolation-related uncertainties, focusing specifically on the need to develop mechanistically based methods and models, including test methods to identify and characterize health effects, integrated human exposure models, physiologically based pharmacokinetic (PBPK) models and biologically based dose-response (BBDR) models.

Animals↗
PubMed1995

The importance of human exposure information: a need for exposure-related data bases to protect and promote public health.

As a subfield of public health, environmental health is concerned with evaluating and ameliorating the effects of people on the environment and the effects of the environment on people. Separating hazards from risks, and characterizing the magnitude, likelihood, and uncertainty of risks is at the heart of environmental health in the 1990s. To this end, a full range of data is needed, including data that characterize the distribution of hazards, the population potentially at risk, and the contact between people and pollution that creates the risk. Several government-sponsored data systems contain information on a range of exposure estimators. The challenge is to develop meaningful, properly validated models to identify public health needs and evaluate public health programs.

Data Collection↗
PubMed1995

Estimating exposure and dose to characterize health risks: the role of human tissue monitoring in exposure assessment.

Exposure assessment is an integral part of health risk characterization. Exposure assessments typically address three critical aspects of exposure: the number of people exposed to the environmental toxicant, at specific concentrations, for the time period of interest; the resulting dose; and the relative contribution of important sources and pathways to exposure/dose. Because historically both "point-of-contact" measurements and information about dose and related pharmacokinetic processes have been lacking, exposure assessments have had to rely on construction of "scenarios" to estimate exposure and dose. This could change, however, as advances in development of biologic markers of exposure and dose make it possible to measure and interpret toxicant concentrations in accessible human tissues. The increasing availability of "biomarkers," coupled with improvements in pharmacokinetic understanding, present opportunities to estimate ("reconstruct") exposure from measurements of dose and knowledge of intake and uptake parameters. Human tissue monitoring, however, is not a substitute for more traditional methods of measuring exposure, but rather a complementary approach. A combination of exposure measurements and dose measurements provides the most credible scientific basis for exposure assessment.

Biomarkers↗
PubMed1995

Science and policy in regulatory decision making: getting the facts right about hazardous air pollutants.

Hazardous air pollutants are regulated under Title III of the 1990 Clean Air Act Amendments. The Amendments replace the risk-based approach mandated in the 1977 Amendments with a prescriptive, technology-based approach requiring that maximum achievable control technology (MACT) be applied to all major industrial sources of 189 hazardous air pollutants. The change reflects political, rather than scientific consensus that the public health benefits justify the costs. The choice is put into perspective by looking at the interface between science and policy that occurs as part of regular decisionmaking. Particular emphasis is given to examining the interrelationships among facts (science), judgments (science policy), and policy (values) in the context of the risk assessment paradigm. Science and policy are discussed in relation to Title III, contrasting the political consensus for action with the scientific uncertainty about risks and benefits. It is argued that a balanced research program is needed to get the facts right about hazardous air pollutants, including research to meet statutory requirements, to reduce uncertainties in risk assessment, and to address strategic issues.

Air Pollutants↗
PubMed1992

The role of scientific research in risk assessment and risk management decisions.

Risk-based decisions are an integral part of societal efforts to protect the public from the harmful health effects of environmental pollution. Scientific information about the magnitude and extent of risks experienced by people and about the causes of those risks is a critical factor in setting priorities and choosing cost-effective mitigation strategies. To be effective in strengthening risk assessment and risk management decisions, research must focus on developing four types of predictive tools: (1) methods to screen and characterize toxicity; (2) biologically based dose-response models; (3) physiologically based pharmacokinetic models; and (4) integrated human exposure models. This approach is the key to reducing the uncertainties currently associated with many environmental health problems.

Decision Support Techniques↗
PubMed1992

EPA priorities for biologic markers research in environmental health.

Recent advances in molecular and cellular biology allow for measurement of biologic events or substances that may provide markers of exposure, effect, or susceptibility in humans. The application of these new and emerging techniques to environmental health offers the possibility of significantly reducing the uncertainties that traditionally hamper risk assessments. The U.S. Environmental Protection Agency (EPA) health research program emphasizes the validation of appropriate biologic markers and their application to high-priority Agency issues. The rationale for EPA's biomarker research program is presented, and future research directions are discussed. Exposure biomarkers will receive most of the research emphasis in the near term, particularly body burden indicators of exposure to high-priority chemicals, such as benzene, ozone, selected heavy metals, and organophosphate pesticides. Research on effects biomarkers will attempt to validate the relationship between the observed biological effects and adverse health consequences in humans, especially for cancer, pulmonary toxicity, immunotoxicity, and reproductive/developmental toxicity.

Animals↗
PubMed1991

Irritant effects of formaldehyde exposure in mobile homes.

This paper reports the irritant effects associated with formaldehyde exposures in mobile homes. Week-long, integrated formaldehyde concentrations were measured using passive monitors in summer and winter while the mobile home residents continued their normal activities. Information on acute health problems, chronic respiratory/allergic illnesses, smoking behavior, demographic variables, and time spent at home was obtained on over 1000 individuals during the sampling period. Measured formaldehyde concentrations varied from under the limit of detection (0.01 ppm) to 0.46 ppm. Formaldehyde exposure was estimated for each individual by multiplying the concentration measured in his or her home by the time he or she spent at home. Irritant effects were found to be associated with formaldehyde exposure after controlling for age, sex, smoking status, and chronic illnesses using a logistic procedure. Some of the interaction terms found to be significant indicated that there were synergistic effects between formaldehyde exposure and chronic health problems.

Adolescent↗
PubMed1991

Human exposure assessment and public health.

The scientific basis for public and private actions to ameliorate environmental health risks is the suspected or verified link between environmental exposures and human health effects. Exposure information is a key parameter, along with data on dose-response relationships, in determining which environmental health risks are unacceptable. Moreover, human exposures are the standard by which we judge the success of measures to prevent or reduce those risks that are deemed unacceptable. The concept of "total human exposure" has gained credence as a useful and viable framework by which to assess environmental exposures. It places exposures in the context of the continuum beginning with pollutant emissions to the environment and ending with human health consequences. The advent of biologic exposure markers, as well as effects and susceptibility markers, promises the opportunity to more accurately characterize total human exposures for environmental contaminants; thereby enhancing the quality of health risk assessments. The U.S. Environmental Protection Agency plays a significant role in the validation, application, and interpretation of biologic markers, with a lesser but important role in their development. Because the Agency is involved in virtually all phases of the biologic markers issue, EPA scientists have identified important research questions and developed plans to address those questions over the next several years. The EPA is positioned to promote the science necessary to bring biologic markers to bear on environmental issues and to interpret the results for risk assessment, risk management, and risk communication.

Biomarkers↗