The impact of long-term PM2.5 exposure on specific causes of death: exposure-response curves and effect modification among 53 million U.S. Medicare beneficiaries.

BACKGROUND: The shape of the exposure-response curve for long-term ambient fine particulate (PM2.5) exposure and cause-specific mortality is poorly understood, especially for rural populations and underrepresented minorities. METHODS: We used hybrid machine learning and Cox proportional hazard models to assess the association of long-term PM2.5 exposures on specific causes of death for 53 million U.S. Medicare beneficiaries (aged ≥65) from 2000 to 2008. Models included strata for age, sex, race, and ZIP code and controlled for neighborhood socio-economic status (SES) in our main analyses, with approximately 4 billion person-months of follow-up, and additionally for warm season average of 1-h daily maximum ozone exposures in a sensitivity analysis. The impact of non-traffic PM2.5 on mortality was examined using two stage models of PM2.5 and nitrogen dioxide (NO2). RESULTS: A 10 µg /m3 increase in 12-month average PM2.5 prior to death was associated with a 5% increase in all-cause mortality, as well as an 8.8, 5.6, and 2.5% increase in all cardiovascular disease (CVD)-, all respiratory-, and all cancer deaths, respectively, in age, gender, race, ZIP code, and SES-adjusted models. PM2.5 exposures, however, were not associated with lung cancer mortality. Results were not sensitive to control for ozone exposures. PM2.5-mortality associations for CVD- and respiratory-related causes were positive and significant for beneficiaries irrespective of their sex, race, age, SES and urbanicity, with no evidence of a lower threshold for response or of lower Risk Ratios (RRs) at low PM2.5 levels. Associations between PM2.5 and CVD and respiratory mortality were linear and were higher for younger, Black and urban beneficiaries, but were largely similar by SES. Risks associated with non-traffic PM2.5 were lower than that for all PM2.5 and were null for respiratory and lung cancer-related deaths. CONCLUSIONS: PM2.5 was associated with mortality from CVD, respiratory, and all cancer, but not lung cancer. PM2.5-associated risks of CVD and respiratory mortality were similar across PM2.5 levels, with no evidence of a threshold. Blacks, urban, and younger beneficiaries were most vulnerable to the long-term impacts of PM2.5 on mortality.

Cardiovascular Risk in COPD: Deciphering the Contribution of Tobacco Smoking.

BACKGROUND: The observation that COPD is an independent risk factor for cardiovascular disease (CVDs) comes from comparisons between smokers with COPD and smokers without COPD. The mechanisms that explain increased risk of CVD in patients with COPD are still unclear. OBJECTIVES: The goal of this study was to assess systemic arterial stiffness (a predictor of CVD mortality) and to evaluate its determinants in a group of patients with mild to moderate COPD secondary to organic dust exposure, tobacco smoking, or both. METHODS: Systemic arterial stiffness was assessed by using aortic pulse wave velocity (aPWV). Measurements were made in 142 patients with COPD and 155 healthy control subjects matched for age, sex, BMI, and tobacco smoking, exposed to tobacco smoking (n = 56/70 for COPD/control subjects, respectively), organic dusts (n = 44/48), or both (n = 42/37). RESULTS: aPWV was higher in COPD than in healthy controls in subjects exposed to tobacco smoking and to both organic dusts and tobacco smoking. By contrast, among never smokers exposed to organic dusts, patients with COPD and matched control subjects had similar aPWV. Multivariate analysis of the 142 patients with COPD (exposed to tobacco smoking and/or to organic dusts) showed that tobacco smoking was associated with high aPWV. Moreover, soluble suppression of tumorigenicity 2, a marker of major cardiovascular events, was correlated with aPWV in these patients. CONCLUSIONS: Analysis of an unselected group of patients with COPD with different causes suggests that: (1) COPD by itself is not sufficient to explain increased aPWV; and (2) tobacco smoking is a risk factor for elevated aPWV in COPD.

Exposure to environmental toxicants and young children's cognitive and social development.

Background Understanding the role of environmental toxicant exposure on children's development is an important area of inquiry in order to better understand contextual factors that shape development and ultimately school readiness among young children. There is evidence suggesting negative links between exposure to environmental toxicants and negative physical health outcomes (i.e. asthma, allergies) in children. However, research on children's exposure to environmental toxicants and other developmental outcomes (cognitive, socioemotional) is limited. Objectives The goal of the current review was to assess the existing literature on the links between environmental toxicants (excluding heavy metals) and children's cognitive, socioemotional, and behavioral development among young children. Methods This literature review highlights research on environmental toxicants (i.e. pesticide exposure, bisphenol A, polycyclic aromatic hydrocarbons, tobacco smoke, polychlorinated biphenyls, flame retardants, phthalates and gas pollutions) and children's development across multiple domains. Results The results highlight the potential risk of exposure to multiple environmental toxicants for young children's cognitive and socioemotional development. Discussion Discussion will focus on the role of environmental toxicants in the cognitive and socioemotional development of young children, while highlighting gaps in the existing literature.

[Classification and risk assessment: complementary or mutually exclusive approaches?] / Classificazione delle sostanze e valutazione del rischio chimico: approcci complementari o incompatibili?

OBJECTIVES: Most classification schemes are based on hazard identification: this is particularly true for carcinogenic and reproductive effects. METHODS: These schemes are no longer adequate to take adequate decisions on risk management, and they appear outmoded. In addition, the induce communication and perception problems in the population, causing health scares and anxiety that are difficult to control and recover. RESULTS: Risk assessment requires an estimation of human exposure to be compared with the safe dose for humans (exposure or intake limits) estimated after hazard characterization based on dose-response relationship. CONCLUSIONS: The risk based approaches provide quantitative information on the potency of the substance that can be compared with duration, frequency and intensity of exposure and, therefore, properly inform graded risk management decisions, in relation to the expected characteristics of exposure.

Exposure to secondhand smoke among adults - Philippines, 2009.

INTRODUCTION: We assessed the differences in exposure to secondhand smoke (SHS) among adults at home, in indoor workplaces, and in various public places in the Philippines across various socio-demographic groups. METHODS: Data from the Global Adult Tobacco Survey conducted in 2009 in the Philippines were used. The data consist of survey answers from 9705 respondents from a nationally representative, multistage probability sample of adults aged 15 years or older. We considered that respondents were exposed to SHS if during the previous 30 days they reported that they lived in a home, worked in a building, or visited a public place where people smoked. The public places included in our analysis were indoor workplaces, public transportation vehicles, restaurants, government buildings or offices, and healthcare facilities. The differences in various socioeconomic and demographic groups' exposure to SHS in these places were also examined. RESULTS: Of respondents who reported working indoors, 36.8% were exposed to SHS. Men (43.3% [95% CI 39.7-46.9]) were more likely than women (28.8% [95% CI 25.4-32.4]) to be exposed to SHS (p < 0.001). Of those working in sites where smoking was not allowed, 13.9% were exposed to SHS, whereas 66.5% were exposed where smoking is allowed in some enclosed areas, and 90.7% were exposed where smoking is allowed everywhere. During the 30 days preceding the survey, more than 50% of those who took public transportation were exposed to SHS; exposure for those who visited public buildings was 33.6% in restaurants, 25.5% in government buildings or offices, and 7.6% in healthcare facilities. CONCLUSION: Despite a national law passed and several local government ordinances that have promulgated smoke-free workplaces, schools, government offices, and healthcare facilities, our findings show that a large proportion of adults were exposed to SHS at work and in public places, which offers opportunities to strengthen and improve enforcement of the smoke-free initiatives and ordinances in the Philippines.

Relationship between environmental exposure to pesticides and anthropometric outcomes of boys in the rural Western Cape, South Africa.

BACKGROUND: Rural residents in the Western Cape (WC), South Africa (SA) are highly exposed to agricultural pesticides that could impact their reproductive development. However, epidemiological evidence of the effect of pesticides on pubertal growth is contradictory. OBJECTIVE: To investigate the effect of pesticide exposure measured using indices of environmental exposure to pesticides on the pubertal growth of boys in rural WC, SA. METHODS: A cross-sectional study of 269 boys (177 of whom gave a history of residing on farms) was conducted. A questionnaire was administered, height and weight were measured and body mass index was calculated. A proximity index (PI) and spraying index (SI) was developed, measuring the lifetime average home distance from pesticide spraying and average frequency of spraying pesticides on a farm, respectively. RESULTS: Median age of boys was 12.4 years (interquartile range 9.5 - 13.3). More than 60% boys had height and weight <50th percentile for age. After adjusting for confounders, PI was significantly associated with shorter stature and lower weight (-1.7 cm/10-fold decrease, p=0.02 and -1.24 kg/10-fold decrease, p=0.04; respectively) and SI was non-significantly associated (-1.4 cm/10-fold increase, p=0.05 and -1.1 cm/10-fold increase, p=0.06; respectively). Associations were stronger for boys aged <11 years and were weaker when excluding non- farm boys. There were no other associations between outcome and exposure. CONCLUSIONS: The use of quantitative exposure indices showed that lower heights and weights might be associated with pesticide exposure in farm boys v. non-farm boys, but not among farm boys. Lower anthropometric measurements among farm boys v. non-farm boys appear stronger at a younger age. The indices of environmental exposure to pesticides require further development.

Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort.

BACKGROUND: Risk factors for initial Pseudomonas aeruginosa (Pa) acquisition, particularly environmental exposures, are poorly understood. We aimed to identify such risk factors in order to inform prevention strategies and identify high-risk populations. METHODS: The study cohort included all participants in the U.S. EPIC Observational Study who had no prior Pa-positive respiratory cultures (N=889). Cox proportional hazard models were used to test the effects of factors on age at first Pa-positive respiratory culture. RESULTS: Cystic fibrosis (CF) genotype functional class had an important effect on age at initial Pa acquisition (hazard ratio (HR) comparing minimal to residual CFTR function 2.87 (95% CI 1.88, 4.39)). None of the modifiable risk factors evaluated, including cigarette smoke, hot tub use, breastfeeding, or daycare, was associated with age at Pa acquisition. Similarly, newborn screening was not associated with age at Pa acquisition (HR 0.85, 95% CI 0.66, 1.09). Key associations were validated in a CF Foundation National Patient Registry replication cohort. CONCLUSIONS: Given the ubiquitous presence of Pa in the environment, it may be that many imposed lifestyle changes will have less impact on age at initial Pa acquisition than genetic determinants.

Cancer and environment: definitions and misconceptions.

BACKGROUND: Scientific evidence supports an association between environmental exposures and cancer. However, a reliable estimate for the proportion of cancers attributable to environmental factors is currently unavailable. This may be related to the varying definitions of the term "environment." The current review aims to determine how the reporting of the definition of the environment and of the estimates of environmentally attributable risks have changed over the past 50 years. METHODS: A systematic literature search was performed to retrieve all relevant publications relating to the environment and cancer from January 1960 to December 2010 using PubMed, EMBASE, Scopus, and Web of Science. Definitions of the environment and environmentally attributable risks for cancer were extracted from each relevant publication. RESULTS: The search resulted in 261 relevant publications. We found vast discrepancies in the definition of the environment, ranging from broad (including lifestyle factors, occupational exposures, pollutants, and other non-genetic factors) to narrow (including air, water, and soil pollutants). Reported environmentally attributable risk estimates ranged from 1% to 100%. CONCLUSIONS: Our findings emphasize the discrepancies in reporting environmental causation of cancer and the limits of inference in interpreting environmentally attributable risk estimates. Rather than achieving consensus on a single definition for the environment, we suggest the focus be on achieving transparency for any environmentally attributable risks.

Pediatria ambiental: um tema emergente / Environmental pediatrics: an emerging issue

OBJETIVO: Revisar os artigos mais relevantes sobre a pediatria ambiental, seus efeitos potenciais para a saúde e, especialmente, seus avanços na prevenção. FONTES DOS DADOS: Foi realizada uma pesquisa utilizando as bases de dados MEDLINE/PubMed e SciELO. Foram revisados artigos de 1990 a 2010, além de capítulos de livros relacionados à pediatria ambiental. SÍNTESE DOS DADOS: Há uma variedade significativa de fatores que tornam as crianças altamente vulneráveis à exposição a riscos ambientais, associados principalmente ao consumo comparativamente maior de água, comida e ar por parte da criança, em relação ao seu peso corporal. De acordo com a Organização Mundial de Saúde, mais de 3 milhões de crianças menores de 5 anos morrem devido a doenças relacionadas ao meio ambiente. Aproximadamente 30-40 por cento das doenças pediátricas estão relacionadas a fatores ambientais. As crianças estão constantemente expostas a vários riscos ambientais para a saúde, dentre os quais se destacam: água contaminada, falta de condições adequadas de saneamento, poluição do ar, vetores de doenças, perigos químicos, injúrias e acidentes. CONCLUSÕES: Atualmente, os pediatras são desafiados a tratar das necessidades de saúde ligadas à pediatria ambiental. A história pediátrica deve ser mais abrangente, acrescentando-se questões pontuais que ajudem a identificar potenciais riscos ambientais. A conscientização e o entendimento sobre os efeitos nocivos das várias condições ambientais e o conhecimento sobre as medidas de prevenção relacionadas resultarão em intervenções oportunas e adequadas que melhorarão a saúde e o desenvolvimento das nossas crianças.

OBJECTIVE: To review the most relevant articles regarding environmental pediatrics, its potential effects on health, and especially its advances in prevention. SOURCES: A literature search was conducted using MEDLINE/PubMed and SciELO databases. Articles from 1990 to 2010 were reviewed, in addition to book chapters related to environmental pediatrics. SUMMARY OF THE FINDINGS: There is a significant variety of factors that make children highly vulnerable to environmental hazard exposure, which are mainly associated with children’s comparatively greater consumption of water, food, and air in relation to body weight. According to the World Health Organization, every year more than 3 million children under the age of 5 die because of environment-related conditions. Approximately 30 to 40 percent of pediatric diseases are related to environmental factors. Children are constantly exposed to various environmental health hazards, among which the following stand out: contaminated water, lack of adequate sanitation facilities, air pollution, disease vectors, chemical hazards, injuries, and accidents. CONCLUSIONS: Nowadays, pediatricians are challenged to address environmental pediatrics health care needs. The pediatric health history needs to be more comprehensive by adding pointed questions to help identify potential environmental risks. Awareness and understanding of the noxious effects of various environmental conditions and knowledge of the related prevention measures will result in timely and adequate interventions that will improve our children’s health and development.

A retrospective assessment of occupational exposure to elemental carbon in the U.S. trucking industry.

BACKGROUND: Despite considerable epidemiologic evidence about the health effects of chronic exposure to vehicle exhaust, efforts at defining the extent of risk have been limited by the lack of historical exposure measurements suitable for use in epidemiologic studies and for risk assessment. OBJECTIVES: We sought to reconstruct exposure to elemental carbon (EC), a marker of diesel and other vehicle exhaust exposure, in a large national cohort of U.S. trucking industry workers. METHODS: We identified the predictors of measured exposures based on a statistical model and used this information to extrapolate exposures across the cohort nationally. These estimates were adjusted for changes in work-related conditions over time based on a previous exposure assessment of this industry, and for changes in background levels based on a trend analysis of historical air pollution data, to derive monthly estimates of EC exposure for each job and trucking terminal combination between 1971 and 2000. RESULTS: Occupational exposure to EC declined substantially over time, and we found significant variability in estimated exposures both within and across job groups, trucking terminals, and regions of the United States. Average estimated EC exposures during a typical work shift ranged from < 1 µg/m³ in the lowest exposed category in the 1990s to > 40 µg/m³ for workers in the highest exposed jobs in the 1970s. CONCLUSIONS: Our results provide a framework for understanding changes over time in exposure to EC in the U.S. trucking industry. Our assessment should minimize exposure misclassification by capturing variation among terminals and across U.S. regions, and changes over time.

Chemically induced pheochromocytomas in rats: mechanisms and relevance for human risk assessment.

Pheochromocytomas are tumors originating from chromaffin cells of the adrenal medulla, which have been observed in numerous carcinogenicity studies. The authors have evaluated pheochromocytoma concurrence with other effects and the possible mechanisms, in order to assess the relevance of such data for the classification of carcinogenic effects and their relevance to humans. The evaluation revealed that pheochromocytomas occur with relatively higher frequency in male rats, especially when the following conditions are involved: hypoxia, uncoupling of oxidative phosphorylation, disturbance in calcium homeostasis, and disturbance of the hypothalamic endocrine axis. The underlying biochemical mechanisms suggest that other substances that interfere with these biochemical endpoints also produce pheochromocytomas. Such endpoints include enzymes involved in catecholamine synthesis, receptor tyrosine kinase (RET), hypoxia-inducible factor (HIF), succinate dehydrogenase, fumarate hydratase, and pyruvate dehydrogenase. To date, there is no indication that the substances inducing pheochromocytomas in animal experiments also induce corresponding tumors in humans. Because the mechanisms of action identified in rats are to be expected in humans, pheochromocytomas may be induced after exposure conditions similar to those used in the animal studies. Whether hereditary mutations represent a risk factor in humans is not clear. Pheochromocytomas that occur in animal experiments currently appear to have little relevance for conditions at the work place. When sufficiently documented and evaluated, such secondary pheochromocytomas are not relevant for classification and human risk assessment.

Using satellite derived land cover information for a multi-temporal study of self-reported recall of proximity to farmland.

Exposure misclassification is a major concern in epidemiologic studies. The potential for misclassification becomes even more problematic when participants are asked to recall historical information. Yet, historical information is important in cancer studies, where latency is long and causative exposures may have occurred years or even decades prior to diagnosis. Even though self-reported proximity to farmland is a commonly used exposure measure, the accuracy of recall is seldom, if ever validated. Geographic Information Systems (GISs) and land cover information derived from satellite imagery can allow researchers to assess the accuracy of this exposure measure, and to quantify the extent and importance of exposure misclassification. As part of a bladder cancer case-control study in Michigan, participants were asked whether they lived on a farm, or within a distance of 1/4, 1/4-1, 1-5, or >5 miles from farmland for each residence over their lifespan. Responses from 531 participants over two time periods--1978 and 2001--were investigated. Self reported proximity to farmland was compared to a "gold standard" derived from Michigan land cover files for the same time periods. Logistic regression and other statistical measures including sensitivity, specificity, and percentage matching were evaluated. In comparing self-reported and land cover-derived proximity to farmland, cases exhibited better agreement than controls in 2001 (adjusted OR=1.74; 95% CI=1.01, 2.99) and worse agreement in 1978, although not significantly (adjusted OR=0.74; 95% CI=0.47, 1.16). When comparing 2001 with 1978, both cases and controls showed better agreement in 2001, but only cases showed a significant difference (adjusted OR=2.36; 95% CI=1.33, 4.18). These differences in agreement may be influenced by differences in educational attainment between cases and controls, although adjustment for education did not diminish the association. Gender, age, number of years at residence, and geocoding accuracy did not influence agreement between the proximity approaches. This study suggests that proximity measures taken from satellite-derived land cover imagery may be useful for assessing proximity to farmland, and it raises some concerns about the use of self-reported proximity to farmland in exposure assessments.

Hormesis and precaution: the twain shall meet.

Regulatory focus on quantifying risk of disease or death from exposure to hazardous substances via monotonic dose-response models has downplayed or even rejected potential benefits to human health from exposures to low (sub-threshold) doses, and thus represented by either U-shaped or J-shaped models. On the other hand, most environmental health policy hypothesizes, without firm evidence, that cancer risk is proportional to exposure at low doses of current ambient exposures. An acceptable exposure is determined by either setting a somewhat arbitrary ;acceptable' level of risk, such as one in a million excess individual lifetime cancer risk or, in the case of several types of animal toxicological test results, applying multiplicative safety factors to a specific concentration, generally derived from a benchmark dose or NOAEL. This seemingly precautionary approach is questionable in light of much experimental evidence indicating protective effects of exposure at low doses - U-shaped or J-shaped models. We demonstrate that incorporating the possibility of hormesis into regulatory decision-making is precautionary, while use of default results in policy conflicts with precaution.

Disease proportions attributable to environment.

Population disease proportions attributable to various causal agents are popular as they present a simplified view of the contribution of each agent to the disease load. However they are only summary figures that may be easily misinterpreted or over-interpreted even when the causal link between an exposure and an effect is well established. This commentary discusses several issues surrounding the estimation of attributable proportions, particularly with reference to environmental causes of cancers, and critically examines two recently published papers. These issues encompass potential biases as well as the very definition of environment and of environmental agent. The latter aspect is not just a semantic question but carries implications for the focus of preventive actions, whether centred on the material and social environment or on single individuals.

Inferring past pesticide exposures: a matrix of individual active ingredients in home and garden pesticides used in past decades.

BACKGROUND: In retrospective studies of the health effects of home and garden pesticides, self-reported information typically forms the basis for exposure assessment. Study participants generally find it easier to remember the types of pests treated than the specific pesticides used. However, if the goal of the study is to assess disease risk from specific chemicals, the investigator must be able to link the pest type treated with specific chemicals or products. OBJECTIVES: Our goal was to develop a "pesticide-exposure matrix" that would list active ingredients on the market for treating different types of pests in past years, and provide an estimate of the probability that each active ingredient was used. METHODS: We used several different methods for deriving the active ingredient lists and estimating the probabilities. These methods are described in this article, along with a sample calculation and data sources for each. RESULTS: The pesticide-exposure matrix lists active ingredients and their probabilities of use for 96 distinct scenarios defined by year (1976, 1980, 1990, 2000), applicator type (consumer, professional), and pest type (12 categories). Calculations and data sources for all 96 scenarios are provided online. CONCLUSIONS: Although we are confident that the active ingredient lists are reasonably accurate for most scenarios, we acknowledge possible sources of error in the probability estimates. Despite these limitations, the pesticide-exposure matrix should provide valuable information to researchers interested in the chronic health effects of residential pesticide exposure.

[The role of environmental factors in Parkinson's disease may depend on disease onset age]. / Wplyw czynników srodowiskowych moze zalezec od wieku zachorowania na chorobe Parkinsona.

BACKGROUND AND PURPOSE: Various factors are suspected to participate in PD onset and include environment-related factors and workplace exposure to pesticides, metals and hydrocarbons. Nevertheless, results of epidemiological research are inconsistent. Some authors emphasize hydrocarbons exposure to younger patients. Our aim was to compare PD risk factors to onset age. MATERIAL AND METHODS: Of 174 patients with idiopathic PD, without dementia, two subgroups were isolated: 65 patients with early onset PD (EOPD) below 50 (n=65, age 52.8+/-7.6 years, onset 42.8+/-5.3 years) and 109 patients with late onset (LOPD) above 50 (n=109, age 67.8+/-7.0, onset 60.8+/-6.7 years). Various environmental factors reported in literature were analyzed. RESULTS: The univariate analysis showed that factors significantly predisposing to EOPD are vocational education (OR 3.24, 95%CI 1.50-7.00, p<0.003), smoking (OR 1.94, 95%CI 1.02-3.69, p<0.05), well water consumption at 20-40 (OR 2.77, 95%CI 1.31-5.86, p<0.008), and after 40 (OR 4.84, 95%CI 1.95-11.99, p<0.0007), side-effects following exposure to paints (OR 2.26, 95%CI 1.10-4.66, p<0.03) and exposure to solvents (OR 1.98, 95%CI 0.96-4.07, p<0.07) on borderline significance. Drinking well water both between 20-40 and after 40 involved a substantial increase in EOPD (OR 6.57, 95%CI 2.43-17.75, p<0.0002). Education only at a primary level proved to be protective against EOPD (OR 0.20, 95%CI 0.07-0.55, p<0.002). The multivariate logistic regression model demonstrated that independent EOPD risk factors are smoking (OR 2.20, 95%CI 1.07-4.53, p<0.04) and well water consumption both between 20-40 and after 40 (OR 8.29, 95%CI 2.73-25.23, p<0.0002), whilst the independent protective factor is education only at a primary level (OR 0.17, 95%CI 0.05-0.53, p<0.003). CONCLUSIONS: Our research demonstrated that a number of independent environmental factors significantly affect the risk of PD onset at younger ages. Presumably, some of the observed differences in the results of research of various authors into PD risk factors may be caused by ignoring onset age within the researched patients.

Tobacco industry opposition to designating environmental tobacco smoke through E-codes.

This manuscript examines the public policy importance of 1993, United States Department of Health and Human Services actions to require doctors and hospitals to report a new external cause of injury code or E-code for environmental tobacco smoke related to causes of death such as lung cancer and severe heart disease. Methods included a qualitative archival analysis of all previously internal tobacco industry documents, pertinent newspaper and magazine articles, Americans for Nonsmokers' Rights database, and pertinent websites regarding environmental tobacco smoke and E-codes from 1993 to 1998. The E-code has continued to the present because of scientific and administrative recognition that environmental tobacco smoke is conclusively linked to illness and death. The industry argued that the E-code was unnecessary because of costs to business and no conclusive scientific evidence linking environmental tobacco smoke with pulmonary and cardiovascular deaths. This regulatory action based on current scientific evidence and medical decision-making contradicts the industry's claim that no deaths are conclusively associated with environmental tobacco smoke.

Genotoxicity of environmental agents assessed by the alkaline comet assay.

Generation of DNA damage is considered to be an important initial event in carcinogenesis. A considerable battery of assays exists for the detection of different genotoxic effects of compounds in experimental systems, or for investigations of exposure to genotoxic agents in environmental or occupational settings. Some of the tests may have limited use because of complicated technical setup or because they only are applicable to a few cell types. The single cell gel electrophoresis (comet) assay is technically simple, relatively fast, cheap, and DNA damage can be investigated in virtually all mammalian cell types without requirement for cell culture. The aim of this thesis was to evaluate the comet assay as a genotoxicity test in genetic toxicology of environmental agents, encompassing both experimental animal models and biomonitoring. The comet assay detects strand breaks (SB). The cells are embedded in agarose and lysed, generating nucleus-like structures in the gel (referred to as nucleoids). Following alkaline electrophoresis, the DNA strands migrate toward the anode, and the extent of migration depends on the number of SB in the nucleoid. The migration is visualized and scored in a fluorescence microscope after staining. Broad classes of oxidative DNA damage can be detected as additional SB if nucleoids are incubated with bacterial DNA glycosylase/endonuclease enzymes. Oxidized pyrimidines and purines can be detected by incubation with endonuclease III and formamidopyrimidine DNA glycosylase, respectively. The animal experimental studies indicated that the comet assay was able to detect genotoxic effects of diesel exhaust particles in lung tissue, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced DNA damage in colon epithelial cells and liver tissue, and benzene-induced damage in bone marrow and liver cells. The strength of the comet assay was further outlined by application of repair enzymes, indicating no oxidative DNA base damage following IQ treatment. High levels of oxidative DNA lesions were detected after exposure to benzene or X-ray irradiation. The comet assay did not detect DNA damage in colon or liver following ingestion of diets containing of high contents of animal fat or sucrose, although other indices of DNA damage were found. Determined from the results of a large Japanese study, the discrimination between carcinogens and non-carcinogens appears to be similar between the comet assay and alkaline elution, which also detects SB. This suggests that the comet assay is a reliable genotoxicity test in animal experimental systems. In the biomonitoring studies, we investigated the effect of common exposures and lifestyle factors (rather than effects of known carcinogens) on the level of oxidative DNA damage in mononuclear blood cells of humans. In the first study, based on repeated measurements, it was shown that interindividual variation and seasonal variation were major determinants for the basal level of SB, whereas no effect of age, exercise, or antioxidant intake could be detected. The effect of exercise was further investigated under both normoxic and hypoxic circumstances, showing a strong effect of hypoxia, and only effect of exercise in terms of SB in hypoxia. In a placebo-controlled parallel dietary fruit and vegetable (or the corresponding amount of antioxidants) intervention study, no effects of the level of oxidative DNA damage or sensitivity to hydrogen peroxide were observed. Although this may seem in contrast to other antioxidant intervention studies, a critical literature survey of antioxidant intervention studies on oxidative DNA damage suggested that well-controlled studies tended to show no effect of antioxidant supplementation. In summary, the aggregated data from the publications included in this thesis, and other publications encompassing the comet assay, indicate that the comet assay is a reliable method for detection of DNA damage in tissues of experimental animals. Although not all types of genotoxic exposures should be expected to result in DNA damage in mononuclear blood cells, the comet assay seems to be a valuable tool for detection of genotoxic exposure in humans. The comet assay indicates that DNA damage is abundant in mammalian cells and affected by lifestyle and many environmental exposures, including diet, exercise, hypoxia, and sunlight.

Factores de riesgo psicosocial, asociados a ansiedad y depresión en los trabajadores administrativos de una institución de educación superior en Pereira, 2003 / Psychosocial Risk Factors Associated with Anxiety and Depression in Administrative Workers in a Higher Education Institute in Pereira 2003

El objetivo de esta investigación fue establecer la asociación entre los factores de riesgo psicosocial inherentes al trabajo con depresión y ansiedad, en el área administrativa de una institución de educación superior en Pereira, segundo semestre de 2003, y recomendar estrategias de intervención de los riesgos psicosociales para mejorar la Salud Mental de los trabajadores a través del Área de Salud Ocupacional de la Institución. Se tomó el total de la población equivalente a 74 personas, con edades entre 17 y 61 años; nivel de escolaridad medio-alto, y una antigüedad laboral de 1 a 6 o más años. Se empleó una metodología de tipo descriptivo. Los instrumentos empleados fueron: la encuesta para la identificación de factores de riesgo psicosociales elaborada por Guillermo Bocanument Zuluaga y Norby Piedad Berján para el ISS, y la escala auto aplicada de Zung para depresión y ansiedad. Los resultados fueron analizados en el programa estadístico Epi Info versión 6.0, y en el análisis se encontró una relación entre el riesgo psicosocial carga mental y la ansiedad. El 10.7 por cien de la población se encontró con algún nivel de depresión o de riesgo de padecerla, y en el 20.3 por cien se halló algún nivel de ansiedad.