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Ground level ozone arises primarily from traffic, it is a powerful oxidant and its primary target organ is the lung. Most epidemiological studies reporting the health effects of ozone have estimated individual exposure from measurements obtained from outdoor monitors but surrogates of personal exposure may not adequately reflect personal exposures. Also, the main focus has been on infants and children. Our purpose was to assess associations between urban background ozone and indoor residential ozone levels as well as to investigate the effects of indoor residential ozone on lung function in 51 elderly non-smokers. Indoor ozone was measured passively in homes, while urban background outdoor ozone was monitored continuously at a fixed monitoring station located on the roof of the 20-m high university H.C. Ørsteds campus building in a park area. Lung function was measured at baseline as well as on three consecutive occasions, for each subject. The mean residential ozone levels were 1.33 ppb, and mean outdoor urban background levels were 27 ppb. Outdoor urban background ozone levels were not consistently associated with residential ozone. No significant changes in lung function were detected in association with residential ozone among healthy participants. In this study, we were unable to detect significant changes in lung function in association with increased levels of residential ozone amongst healthy elderly non-smokers.

Background: An association between air pollution and breast cancer risk has been suggested, but evidence is sparse and inconclusive. Methods: We included 22,877 female nurses from the Danish Nurse Cohort who were recruited in 1993 or 1999 and followed them for incidence of breast cancer (N = 1,145) until 2013 in the Danish Cancer Register. We estimated annual mean concentrations of particulate matter with diameter Results: We found no association between breast cancer and PM2.5 (HR, 0.99; 95% confidence interval, 0.94–1.10 per interquartile range of 3.3 μg/m3), PM10 (1.02; 0.94–1.10 per 2.9 μg/m3), or NO2 (0.99; 0.93–1.05 per 7.4 μg/m3). Conclusions: Air pollution is not associated with breast cancer risk. Impact: Exposure to air pollution in adulthood does not increase the risk of breast cancer, but more data on the effects of early exposure, before first birth, are needed. Cancer Epidemiol Biomarkers Prev; 26(3); 428–30. ©2016 AACR.

BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders.OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism.SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data.OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder.WIDER IMPLICATIONS: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.

Asthma is one of the most common chronic diseases worldwide affecting more than 300 million people. Symptoms are often non-specific and include coughing, wheezing, chest tightness, and shortness of breath. Asthma may be highly variable within the same individual over time. Although asthma results in death only in extreme cases, the disease is associated with significant morbidity, reduced quality of life, increased absenteeism, and large costs for society. Asthma can be diagnosed based on report of characteristic symptoms and/or the use of several different diagnostic tests. However, there is currently no gold standard for making a diagnosis, and some degree of misclassification and inter-observer variation can be expected. This may lead to local and regional differences in the treatment, monitoring, and follow-up of the patients. The Danish National Database for Asthma (DNDA) is slated to be established with the overall aim of collecting data on all patients treated for asthma in Denmark and systematically monitoring the treatment quality and disease management in both primary and secondary care facilities across the country. The DNDA links information from population-based disease registers in Denmark, including the National Patient Register, the National Prescription Registry, and the National Health Insurance Services register, and potentially includes all asthma patients in Denmark. The following quality indicators have been selected to monitor trends: first, conduction of annual asthma control visits, appropriate pharmacological treatment, measurement of lung function, and asthma challenge testing; second, tools used for diagnosis in new cases; and third, annual assessment of smoking status, height, and weight measurements, and the proportion of patients with acute hospital treatment. The DNDA will be launched in 2016 and will initially include patients treated in secondary care facilities in Denmark. In the nearby future, the database aims to include asthma diagnosis codes and clinical data registered by general practitioners and specialised practitioners as well. Keywords: asthma; clinical indicators; quality of care; database; prescription data; hospital data (Published: 8 November 2016) Citation: European Clinical Respiratory Journal 2016, 3 : 33903 - http://dx.doi.org/10.3402/ecrj.v3.33903

Background and objective More than 20 years ago it was hypothesised that pre- and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signalling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testis cancer. Several narrative reviews and weight of the evidence reports past years conclude that evidence has been accumulating to support the hypothesis. In particular one of these reviews has been criticised for preconceived views and selective reporting which has elicited a heated debate. The question is whether data now are available which allow systematic and transparent reviews of the epidemiological evidence and how such reviews should be conducted. We set out to identify available epidemiological evidence addressing male reproductive disorders following pre- and perinatal exposure and suggest methods for meta-analysis. Methods We performed a systematic search in PubMed and Embase to identify published data on the risk of hypospadias, cryptorchidism, low sperm counts and testis cancer following pre- and early infant exposure to xenobiotic environmental chemicals that in at least one intact organism have shown adverse effects due to endocrine disruption. We only included peer reviewed papers providing data on exposure to specific chemicals in utero or early infancy documented by measurements in biological specimens (maternal blood or urine, placenta tissue, cord blood, breast milk) and studies extrapolating fetal or early life exposure by measurements in adult life. Results We identified 24 independent studies that through 36 papers reported 116 associations between measured levels of endocrine disruptors and male reproductive disorders. Most studies addressed persistent organochlorines such as DDE (18 associations), PCBs (12 associations), DDT and HCB (each 12 associations) while studies on rapidly metabolised compounds as phthalate ethers and Bisphenol were few. The studies included altogether 2446 cases and 324 men provided semen samples. The completeness of reporting assessed by 11 items were considered very high (≥80%) in 14 of the studies but only 5 studies were considered at low risk of bias and confounding. Conclusion Although the epidemiological literature database is limited when using highly strict criteria for evaluation it seems sufficient for quantitative meta-analysis addressing on the hypothesis on environmental endocrine disrupting chemicals and male reproductive disorders. Systematic reviews addressing other other outcomes are warranted

Objectives Previous studies have shown that chemicals used in plastics manufacture are correlated with adverse health effects in humans, including reproductive abnormalities. Despite this growing evidence, little attention has been given to the potential health impact of highly exposed pregnant women employed in the plastics industry. The aim of this study was to assess the risk of cryptorchidism and hypospadias among boys born to mothers employed in the plastics industry using nationwide registers to extract maternal occupation and the child malformations of cryptorchidism and hypospadias. Methods The cohort included 864 747 boys born to a mother in employment during her pregnancy in Denmark from 1980–2007. These boys were followed for cryptorchidism and hypospadias from 1980–2009 comparing risks among sons of mothers working in the plastics industry (n = 5060) with sons of mothers working in other occupations (n = 717 921), including healthcare assistants and kitchen workers as references. Odds ratios (OR) with 95% confidence intervals (95% CI) were estimated using multiple logistic regression, adjusting for parental age, birth years, parity, and geographical region. Results Preliminary results show sons of women employed in the plastics industry were not at increased risk of cryptorchidism (107 cases; OR 1.15, 95% CI: 0.95–1.40) or hypospadias (28 cases; OR 0.82, 95% CI: 0.56–1.19) compared to boys of women in other occupations (18 338 cases) and (3099 cases), respectively. Conclusions This nationwide cohort study did not find an increased risk of cryptorchidism or hypospadias amongst sons of mothers working in the plastics industry.

Introduction: Experimental studies suggest that traffic-related ultrafine particles can cross blood-brain barrier leading to neurotoxicity and development of brain tumors in animals, but epidemiolo...

Background Air pollution has been considered a potent environmental risk factor for neuropathology through neuroinflammation and oxidative stress, which might also cause brain tumour formation. However, epidemiological evidence on the association between air pollution and brain tumours in humans is sparse, with no data on exposure to particles. In this study we aim to examine associations between long-term exposure to ambient air pollution and risk for development of brain tumours. Methods We used the Danish Nurse Cohort with 28,731 female nurses (age ≥ 44 years) recruited in 1993 or 1999 when self-reported information on lifestyle was collected. We obtained data on the incidence of brain tumours until 2013 from the Danish Cancer Register, and estimated annual mean concentrations of particulate matter with diameter 2.5 ), particulate matter with diameter 10 ), nitrogen oxides (NO x ) and nitrogen dioxide (NO 2 ) at the residence since 1990 using an atmospheric integrated chemistry-transport models system, and examined the association between the 3-year running mean of pollutants and brain tumour incidence using time-varying Cox regression, separately for total brain tumours, and for tumour subtypes by location (brain or meninges), and by malignancy (malignant or benign), and estimated hazard ratios and 95% confidence intervals per increase in interquartile range of exposure. Results Of 25,143 tumour-free nurses at recruitment, 121 developed brain cancer during 15.7 years of follow-up. We found a weak positive association between total brain tumours and PM 2.5 (1.06; 0.80–1.40 per 3.37 μg/m 3 ), NO 2 (1.09; 0.91–1.29) per 7.5 μg/m 3 , and NO x (1.02; 0.93–1.12 per 10.22 μg/m 3 ), and none with PM 10 (0.93; 0.70–1.23 per 3.31 μg/m 3 ). Associations with PM 2.5 and NO 2 were stronger for tumours located in meninges than in brain, and for benign than for malignant tumours. Finally, association of total brain tumours with PM 2.5 was modified by BMI, and was statistically significantly enhanced in obese women (2.03; 1.35–3.05). Conclusion We found weak evidence for association between risk of brain tumours and long-term exposure to air pollution in women older than 44 years. However, we present novel results that obese women may be susceptible, as well as a positive tendency towards elevated risk for meninges and benign tumours, which require further investigation.

Polychlorinated-biphenyls (PCBs) were introduced in the late 1920s and used until the 1970s when they were banned in most countries due to evidence of environmental build-up and possible adverse health effects. However they still persist in the environment, indoors and in humans. Indoor air in contaminated buildings may confer airborne exposure markedly above background regional PCB levels. To date, no epidemiological studies have assessed the health effects from exposure to semi-volatile PCBs in the indoor environment. Indoor air PCBs are generally less chlorinated than PCBs that are absorbed via the diet, or via past occupational exposure; therefore their health effects require separate risk assessment. Two separate cohorts of individuals who have either attended schools (n = 66,769; 26% exposed) or lived in apartment buildings (n = 37,185; 19% exposed), where indoor air PCB concentrations have been measured were created. An individual estimate of long-term airborne PCB exposure was assigned based on measurements. The cohorts will be linked to eight different national data sources on mortality, school records, residential history, socioeconomic status, and chronic disease and reproductive outcomes. The linking of indoor air exposures with health outcomes provides a dataset unprecedented worldwide. We describe a project, called HESPERUS (Health Effects of PCBs in Residences and Schools), which will be the first study of the long term health effects of the lower-chlorinated, semi-volatile PCBs in the indoor environment.

Background: Polychlorinated biphenyls (PCBs) are ubiquitously present in the environment and are suspected of carcinogenic, neurotoxic and immunotoxic effects. Significantly higher plasma concentrations of the congener PCB 28 occur in children compared to adults. Exposure in schools may contribute to this difference. Objective: To determine whether increased blood plasma concentrations of PCB 28 in Danish school children and mothers are associated with living in homes or attending schools constructed in the PCB period (1959–1977). Methods: PCB 28 was analyzed in plasma samples from 116 children aged 6–11 years and 143 mothers living in an urban and a rural area in Denmark and participating in the European pilot project DEMOCOPHES (Demonstration of a study to COordinate and Perform Human Biomonitoring on a European Scale). In Denmark, PCBs were used in construction in the period 1950–1977, and year of construction or renovation of the homes and schools was used as a proxy for indoor PCB exposure. Linear regression models were used to assess the association between potential PCB exposure from building materials and lipid adjusted concentrations of PCB 28 in plasma, with and without adjustment for potential confounders. Results: Among the 116 children and 143 mothers, we were able to specify home construction period in all but 4 children and 5 mothers leaving 111 children and 138 mothers for our analyses. The median lipid adjusted plasma PCB 28 concentration was 3 (range: 1–28) ng/g lipid in the children and 2 (range: 1–8) ng/g lipid in the mothers.Children living in homes built in the PCB period had significantly higher lipid adjusted plasma PCB 28 concentrations compared to children living in homes built before or after the PCB period. Following adjustment for covariates, PCB 28 concentrations in children were 40 (95% CI: 13; 68) percent higher than concentrations of children living in homes constructed at other times. Furthermore, children attending schools built or substantially refurbished in the PCB period also had significantly higher (46%, 95% CI: 22; 70) PCB 28 concentrations compared to children attending schools constructed before or after the PCB period, while their mothers had similar concentrations. Adjustment for the most prevalent congener, PCB 153, did not change this effect of home or school construction. When both home and school construction year were included in the models, the increase in lipid adjusted plasma PCB 28 for children living in or attending schools from the PCB period was no longer statistically significant. The individual effect of home and school construction periods could not be evaluated further with the available data. Conclusion: Our results suggest that PCB exposure in the indoor environment in schools and homes constructed during the PCB period may contribute significantly to children's plasma PCB 28 concentration. Efforts to minimize PCB exposure in indoor environments should be considered. Keywords: Polychlorinated biphenyl, Environmental exposure, PCB-exposed population, Residents, Homes, Year of construction

Background: Exposure to organochlorines has been examined as a potential risk factor for non-Hodgkin lymphoma (NHL), with inconsistent results that may be related to limited statistical power or to imprecise exposure measurements. Objective: Our purpose was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL. Methods: We conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997. Within the cohort we identified 256 persons diagnosed with NHL in the population-based nationwide Danish Cancer Registry and randomly selected 256 subcohort persons. We measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Associations between the 18 organochlorines and NHL were analyzed in Cox regression models, adjusting for body mass index. Results: Incidence rate ratios and confidence intervals (CIs) for interquartile range increases in concentrations of dichlorodiphenyltrichlorethane (DDT), cis-nonachlor, and oxychlordane were 1.35 (95% CI: 1.10, 1.66), 1.13 (95% CI: 0.94, 1.36), and 1.11 (95% CI: 0.89, 1.38), respectively, with monotonic dose–response trends for DDT and cis-nonachlor based on categorical models. The relative risk estimates were higher for men than for women. In contrast, no clear association was found between NHL and PCBs. Conclusion: We found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.

The first common genetic factor identified for pediatric asthma by genome-wide association is the chromosome 17q21 locus, harbouring the ORMDL3 gene. ORMDL3 is involved in facilitation of endoplasmic reticulum-mediated inflammatory responses, believed to underlie its asthma association. We investigated associations between the rs7216389 polymorphism in the 17q21 locus affecting ORMDL3 expression and the risk for recurrent wheeze and interactions with exposure to tobacco smoke and furred pets during pregnancy and infancy using a birth cohort of 101,042 infants. Rs7216389 was significantly associated with recurrent wheeze risk among 18-month-old infants. There was a 1.35-fold higher risk of recurrent wheeze among homozygous variant allele carriers compared with homozygous wild-type allele carriers. There was significant interaction between rs7216389 and domestic furred pets, with a positive association between pets and wheeze among homozygous wild-type carriers and a negative association among homozygous variant allele carriers. There was no interaction between rs7216389 and tobacco smoke exposure.

In a recent population-based case-control study using 2,400 cases of childhood cancer, we found a statistically significant association between residential radon and acute lymphoblastic leukemia risk.Traffic exhaust in the air enhances the risk association between radon and childhood leukemia.We included 985 cases of childhood leukemia and 1,969 control children. We used validated models to calculate residential radon and street NO(x) concentrations for each home. Conditional logistic regression analyses were used to analyze the effect of radon on childhood leukemia risk within different strata of air pollution and traffic density.The relative risk for childhood leukemia in association with a 10(3) Bq/m(3)-years increase in radon was 1.77 (1.11, 2.82) among those exposed to high levels of NO(x) and 1.23 (0.79, 1.91) for those exposed to low levels of NO(x) (p(interaction,) 0.17). Analyses for different morphological subtypes of leukemia and within different strata of traffic density showed a non-significant pattern of stronger associations between radon and childhood leukemia within strata of higher traffic density at the street address.Air pollution from traffic may enhance the effect of radon on the risk of childhood leukemia. The observed tendency may also be attributed to chance.

Aims/hypothesis: It has been suggested that air pollution may increase the risk of type 2 diabetes but data on particulate matter with diameter Aims/hypothesis: It has been suggested that air pollution may increase the risk of type 2 diabetes but data on particulate matter with diameter 2.5) are inconsistent. We examined the association between long-term exposure to PM 2.5 and diabetes incidence. Methods: We used the Danish Nurse Cohort with 28,731 female nurses who at recruitment in 1993 or 1999 reported information on diabetes prevalence and risk factors, and obtained data on incidence of diabetes from National Diabetes Register until 2013. We estimated annual mean concentrations of PM 2.5, particulate matter with diameter 10), nitrogen oxides (NO x) and nitrogen dioxide (NO 2) at their residence since 1990 using a dispersion model and examined the association between the 5-year running mean of pollutants and diabetes incidence using a time-varying Cox regression. Results: Of 24,174 nurses 1137 (4.7%) developed diabetes. We detected a significant positive association between PM 2.5 and diabetes incidence (hazard ratio; 95% confidence interval: 1.11; 1.02-1.22 per interquartile range of 3.1 μg/m 3), and weaker associations for PM 10 (1.06; 0.98-1.14 per 2.8 μg/m 3), NO 2 (1.05; 0.99-1.12 per 7.5 μg/m 3), and NO x (1.01; 0.98-1.05 per 10.2 μg/m 3) in fully adjusted models. Associations with PM 2.5 persisted in two-pollutant models. Associations with PM 2.5 were significantly enhanced in never smokers (1.24; 1.09-1.42), and augmented in obese (1.25; 1.06-1.47) and subjects with myocardial infarction (1.32; 0.86-2.02), but without significant interaction. Conclusions/interpretation: Fine particulate matter may the most relevant pollutant for diabetes development among women, and non-smokers, obese women, and heart disease patients may be most susceptible.

Background Although exposure to UV radiation is the major risk factor for skin cancer, theoretical models suggest that radon exposure can contribute to risk, and this is supported by ecological studies. We sought to confirm or refute an association between long-term exposure to residential radon and the risk for malignant melanoma (MM) and non-melanoma skin cancer (NMSC) using a prospective cohort design and long-term residential radon exposure.Methods During 1993-1997, we recruited 57,053 Danish persons and collected baseline information. We traced and geocoded all residential addresses of the cohort members and calculated radon concentrations at each address lived in from 1 January 1971 until censor date. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and confidence intervals (CI) for the risk associated with radon exposure for NMSC and MM, and effect modification was assessed.Results Over a mean follow-up of 13.6 years of 51,445 subjects, there were 3,243 cases of basal cell carcinoma (BCC), 317 cases of squamous cell carcinoma (SCC) and 329 cases of MM. The adjusted IRRs per 100 Bq/m(3) increase in residential radon levels for BCC, SCC and MM were 1.14 (95% CI: 1.03, 1.27), 0.90 (95% CI: 0.70, 1.37) and 1.08 (95% CI: 0.77, 1.50), respectively. The association between radon exposure and BCC was stronger among those with higher socio-economic status and those living in apartments at enrollment.Conclusion and Impact Long-term residential radon exposure may contribute to development of basal cell carcinoma of the skin. We cannot exclude confounding from sunlight and cannot conclude on causality, as the relationship was stronger amongst persons living in apartments and nonexistent amongst those living in single detached homes.

Background: Established causes of diabetes do not fully explain the present epidemic. High-level arsenic exposure has been implicated in diabetes risk, but the effect of low-level arsenic exposure in drinking water remains unclear. Objective: We sought to determine whether long-term exposure to low-level arsenic in drinking water in Denmark is associated with an increased risk of diabetes using a large prospective cohort. Methods: During 1993–1997, we recruited 57,053 persons. We followed each cohort member for diabetes occurrence from enrollment until 31 December 2006. We traced and geocoded residential addresses of the cohort members and used a geographic information system to link addresses with water-supply areas. We estimated individual exposure to arsenic using all addresses from 1 January 1971 until the censoring date. Cox proportional hazards models were used to model the association between arsenic exposure and diabetes incidence, separately for two definitions of diabetes: all cases and a more strict definition in which cases of diabetes based solely on blood glucose results were excluded. Results: Over a mean follow-up period of 9.7 years for 52,931 eligible participants, there were a total of 4,304 (8.1%) diabetes cases, and 3,035 (5.8%) cases of diabetes based on the more strict definition. The adjusted incidence rate ratios (IRRs) per 1-μg/L increment in arsenic levels in drinking water were as follows: IRR = 1.03 (95% CI: 1.01, 1.06) and IRR = 1.02 (95% CI: 0.99, 1.05) for all and strict diabetes cases, respectively. Conclusions: Long-term exposure to low-level arsenic in drinking water may contribute to the development of diabetes. Citation: Bräuner EV, Nordsborg RB, Andersen ZJ, Tjønneland A, Loft S, Raaschou-Nielsen O. 2014. Long-term exposure to low-level arsenic in drinking water and diabetes incidence: a prospective study of the Diet, Cancer and Health cohort. Environ Health Perspect 122:1059–1065; http://dx.doi.org/10.1289/ehp.1408198

Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.

BackgroundExposure to particulate air pollution increases respiratory and cardiovascular morbidity and mortality, especially in elderly, possibly through inflammation and vascular dysfunction.MethodsWe examined potential beneficial effects of indoor air filtration in the homes of elderly, including people taking vasoactive drugs.Forty-eight nonsmoking subjects (51 to 81 years) in 27 homes were included in this randomized, double-blind, crossover intervention study with consecutive two-week periods with or without the inclusion of a high-efficiency particle air filter in re-circulating custom built units in their living room and bedroom. We measured blood pressure, microvascular and lung function and collected - blood samples for hematological, inflammation monocyte surface and lung cell damage markers before and at day 2, 7 and 14 during each exposure scenario.ResultsThe particle filters reduced the median concentration of PM2.5 from approximately 8 to 4 μg/m3 and the particle number concentration from 7669 to 5352 particles/cm3. No statistically significant effects of filtration as category were observed on microvascular and lung function or the biomarkers of systemic inflammation among all subjects, or in the subgroups taking (n = 11) or not taking vasoactive drugs (n = 37). However, the filtration efficacy was variable and microvascular function was within 2 days significantly associated with the actual PM2.5 decrease in the bedroom, especially among 25 subjects not taking any drugs.ConclusionSubstantial exposure contrasts in the bedroom and no confounding by drugs appear required for improved microvascular function by air filtration, whereas no other beneficial effect was found in this elderly population.

Background Particulate air pollution increases mortality and morbidity related to respiratory and cardiovascular diseases, especially for susceptible individuals such as the elderly, possibly throu...

BackgroundIncreased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist.ObjectiveTo investigate the long-term effect of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort.MethodsDuring 1993-1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced residential addresses from 1 January 1971 until 31 December 2009 and calculated radon concentrations at each address using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and 95% confidence intervals (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed.ResultsMedian estimated radon was 40.5 Bq/m(3). The adjusted IRR for primary brain tumour associated with each 100 Bq/m(3) increment in average residential radon levels was 1.96 (95% CI: 1.07; 3.58) and this was exposure-dependently higher over the four radon exposure quartiles. This association was not modified by air pollution.ConclusionsWe found significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies.

Obesity prevalence has more than doubled globally within the last 30 years. Obesity affects quality of life as well as impacts the risks and prognosis for a number of serious diseases. Established causes include a high calorie diet combined with a sedentary lifestyle and possibly the widespread cessation of smoking, but these do not fully explain the epidemic. Polychlorinated biphenyl congeners (PCBs) are endocrine-disrupting chemicals and evidence from animal experiments suggests an association with obesity development. Our knowledge of the effects of these compounds on weight gain in humans is limited. Our objective was to investigate the association between exposure to PCBs experienced by a general Danish population and development of obesity. We randomly selected 204 persons (113 obese and 91 overweight), aged ≥ 50 years, from a prospective Danish cohort of 57,053 persons and examined ten PCBs as potential determinants of abdominal obesity. Adipose tissue was collected upon enrolment and PCBs were quantified using gas chromatography-mass spectroscopy. Median levels of the included PCBs were lower in women, except for PCB118 and all PCBs were positively associated with increased abdominal circumference, although this association was not significant. These data indicate a positive link between PCBs and obesity. More work is needed to fully elucidate the complex role of compounds such as PCBs in the present obesity epidemic.

Radon-222 gas arises from the radioactive decay of radium-226 and has a 3.8 day half-life. This gas percolates up through soil into buildings, and if it is not evacuated there can be much higher exposure levels indoors than outdoors, which is where human exposure occurs. Radon exposure is classified as a human carcinogen and new Danish homes must be constructed to ensure indoor radon levels below 100 Bq/m(3) . Our purpose was to assess how well 200 newly constructed single-detached homes perform according to building regulations pertaining to radon and identify the association between indoor radon in these homes and municipality, home age, floor area, floor level, basement and outer wall and roof construction. Median (5-95 percentile) indoor radon levels were 36.8 (9.0 - 118) Bq/m(3) , but indoor radon exceeded 100 Bq/m(3) in fourteen of these new homes. The investigated variables explained nine percent of the variation in indoor radon levels and although associations were positive none of these were statistically significant. In the present study radon levels were generally low, but we found that fourteen (seven percent) of the 200 new homes had indoor radon levels over 100 Bq/m(3) . More work is needed to determine the determinants of indoor radon. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

High-level occupational radon exposure is an established risk factor for lung cancer. We assessed the long-term association between residential radon and lung cancer risk using a prospective Danish cohort using 57,053 persons recruited during 1993-1997. We followed each cohort member for cancer occurrence until 27 June 2006, identifying 589 lung cancer cases. We traced residential addresses from 1 January 1971 until 27 June 2006 and calculated radon at each of these addresses using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI) for lung cancer risk associated with residential radon exposure with and without adjustment for sex, smoking variables, education, socio-economic status, occupation, body mass index, air pollution and consumption of fruit and alcohol. Potential effect modification by sex, traffic-related air pollution and environmental tobacco smoke was assessed. Median estimated radon was 35.8 Bq/m(3). The adjusted IRR for lung cancer was 1.04 (95% CI: 0.69-1.56) in association with a 100 Bq/m(3) higher radon concentration and 1.67 (95% CI: 0.69-4.04) among non-smokers. We found no evidence of effect modification. We find a positive association between radon and lung cancer risk consistent with previous studies but the role of chance cannot be excluded as these associations were not statistically significant. Our results provide valuable information at the low-level radon dose range.

Organochlorine pesticides are ubiquitously present in the environment and suspected of carcinogenic, neurological and immunological effects. Our objective was to identify determinants of adipose tissue levels of organochlorine pesticides experienced by a general Danish population. Adipose tissue was collected upon enrolment of 245 randomly selected persons from a prospective cohort of 57,053 persons enrolled between 1993 and 1997. We examined geography, gender, age, lactation, body mass index (BMI) and intake of nine dietary groups and tap water drinks, as potential determinants of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene, hexachlorocyclohexane, dieldrin, hexachlorobenzene, cis-nonachlor, trans-nonachlor and oxychlordane. Living in Copenhagen city and age at enrolment showed positive associations with all compounds. BMI was positively associated with all compounds except cis-nonachlor. Fatty-fish consumption showed positive associations with cis-nonachlor, trans-nonachlor, DDT and dieldrin and fruit and vegetables were inversely associated with dieldrin. Determinant estimates of trans-nonachlor were similar to estimates of total chlordanes while cis-nonachlor and oxychlordane seemed to differ. This is one of the first studies of organochlorine pesticides predictors in adipose tissue and contributes to the ongoing debate about exposure sources of these compounds. Single determinants varied among the individual compounds, even within related chlordane residues, suggesting that organochlorine pesticides should not be treated as a homogenous group.

Organochlorine pesticides are present in the environment and suspected of causing serious health effects. Diet has been the main exposure source, but indoor source release is gaining focus. Within a monitoring study of polychlorinated biphenyls of Danish buildings built during the 1960s and 1970s, we coincidently determined extreme levels of dichlorodiphenyltrichloroethane (DDT) levels in two of ten random samples. This raises concern and further large scale investigations are warranted to confirm this.

Polychlorinated biphenyls (PCBs) are ubiquitously present in the environment and suspected of carcinogenic, neurological, and immunological effects. Our purpose was to identify predictors of adipose tissue levels of mono-, di-, and tri-ortho-substituted PCBs experienced by a general population and to establish whether predictors vary according to substitution group. In this study of 245 randomly selected persons from a prospective Danish cohort of 57,053 persons, we examined geographical area, age, lactation, BMI, and intake of eight major dietary groups as potential determinants of adipose concentrations of mono-, di-, and tri-ortho-substituted PCBs by linear regression analyses. Lactation, BMI, and intake of fruit, vegetables, and dairy products showed negative associations with PCB concentrations in adipose tissue in all models, and living in Copenhagen city, age, and consumption of fish (particularly fatty fish) were positively associated. The associations between several of the predictors and mono-ortho-substituted PCBs tended to differ from the associations found for di- and tri-ortho-substituted PCBs. In conclusion, geography, age, lactation, BMI, and consumption of fatty fish consistently predicted the concentration of PCBs in adipose tissue. Our results indicate that predictors of PCBs varied according to substitution group, suggesting that ortho-substituted groups should be analyzed separately.

Particulate air pollution is associated with increased risk of pulmonary diseases and detrimental outcomes related to the cardiovascular system, including altered vessel functions. This study's objective was too evaluate the effects of ambient particle exposure on the blood-gas permeability, lung function and Clara cell 16 (CC16) protein release in healthy young subjects. Twenty-nine nonsmokers participated in a randomized, two-factor crossover study with or without biking exercise for 180 min and with 24-h exposure to particle-rich (6169-15,362 particles/cm(3); 7.0-11.6 microg/m(3) PM(2.5); 7.5-15.8 microg/m(3) PM(10-2.5)) or filtered (91-542 particles/cm(3)) air collected above a busy street. The clearance rate of aerosolized (99m)Tc-labeled diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) was measured as an index for the alveolar epithelial membrane integrity and permeability of the lung blood-gas barrier after rush-hour exposure. Lung function was assessed using body plethysmography, flow-volume curves, and measurements of the diffusion capacity of carbon monoxide. CC16 was measured in plasma and urine as another marker of alveolar integrity. Particulate matter exposure had no significant effect on the epithelial membrane integrity using the methods available in this study. Exercise increased the clearance rate of (99m)Tc-DTPA indicated by a 6.8% (95% CI: 0.4-12.8%) shorter half-life and this was more pronounced in men than women. Neither particulate matter exposure nor exercise had an effect on the concentration of CC16 in plasma and urine or on the static and dynamic volumes or ventilation distribution of the lungs. The study thus demonstrates increased permeability of the alveolar blood-gas barrier following moderate exercise, whereas exposure to ambient levels of urban air particles has no detectable effects on the alveolar blood-gas barrier or lung function.

Particulate matter from wood smoke may cause health effects through generation of oxidative stress with resulting damage to DNA. We investigated oxidatively damaged DNA and related repair capacity in peripheral blood mononuclear cells (PBMC) and measured the urinary excretion of repair products after controlled short-term exposure of human volunteers to wood smoke. Thirteen healthy adults were exposed first to clean air and then to wood smoke in a chamber during 4h sessions, 1 week apart. Blood samples were taken 3h after exposure and on the following morning, and urine was collected after exposure, from bedtime until the next morning. We measured the levels of DNA strand breaks (SB), oxidized purines as formamidopyrimidine-DNA-glycosylase (FPG) sites and activity of oxoguanine glycosylase 1 (hOGG1) in PBMC by the comet assay, whereas mRNA levels of hOGG1, nucleoside diphosphate linked moiety X-type motif 1 (hNUDT1) and heme oxygenase 1 (hHO1) were determined by real-time RT-PCR. The excretion of 8-oxo-7,8-dihydro-oxoguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in urine was measured by high performance liquid chromatography purification followed by gas chromatography with mass spectrometry. The morning following exposure to wood smoke the PBMC levels of SB were significantly decreased and the mRNA levels of hOGG1 significantly increased. FPG sites, hOGG1 activity, expression of hNUDT1 and hHO1, urinary excretion of 8-oxodG and 8-oxoGua did not change significantly. Our findings support that exposure to wood smoke causes systemic effects, although we could not demonstrate genotoxic effects, possibly explained by enhanced repair and timing of sampling. Pernille Hogh Danielsen, Elvira Vaclavik Brauner, Ryszard Olinski, Rafal Rozalski, Peter Moller and Steffen Loft are partners in ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943).

The comet assay is popular for assessments of genotoxicity, but the comparison of results between studies is challenging because of differences in experimental procedures and reports of DNA damage in different units. We investigated the variation of DNA damage in mononuclear blood cells (MNBCs) measured by the comet assay with focus on the variation related to alkaline unwinding and electrophoresis time, number of cells scored, as well as the putative benefits of transforming the primary end points to common units by the use of reference standards and calibration curves. Eight experienced investigators scored pre-made slides of nuclei differently, but each investigator scored constantly over time. Scoring of 200 nuclei per treatment was associated with the lowest residual variation. Alkaline unwinding for 20 or 40 min and electrophoresis for 20 or 30 min yielded different dose-response relationships of cells exposed to gamma-radiation and it was possible to reduce the variation in oxidized purines in MNBCs from humans by adjusting the level of lesions with protocol-specific calibration curves. However, there was a difference in the level of DNA damage measured by different investigators and this variation could not be reduced by use of investigator-specific calibration curves. The mean numbers of lesions per 10(6) bp in MNBCs from seven humans were 0.23 [95% confidence interval (CI): 0.14-0.33] and 0.31 (95% CI: 0.20-0.55) for strand breaks (SBs) and oxidized guanines, respectively. In conclusion, our results indicate that inter-investigator difference in scoring is a strong determinant of DNA damage levels measured by the comet assay. Environmental Cancer Risk, Nutrition and Individual Susceptibility, a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘Food Quality and Safety’ (Contract No 513943).

There is growing concern that air pollution exposure increases the risk of lung cancer. The mechanism of action is related to particle-induced oxidative stress and oxidation of DNA. Humans exposed to urban air with vehicle emissions have elevated levels of oxidized guanine bases in blood cells and urine. Animal experimental studies show that pulmonary and gastrointestinal exposure is associated with elevated levels of oxidized guanines in the lung and other organs. Collectively, there is evidence indicating that exposure to traffic-related air pollution particles is associated with oxidative damage to DNA and this might be associated with increased risk of cancer. The work was partly supported by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (Contract No. 513943) and the Danish Research Councils.

Rationale. Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction and indoor air may be most important. Objective. We investigated effects of controlled exposure to indoor air particles on microvascular function as the primary endpoint and biomarkers of inflammation and oxidative stress as secondary endpoints in a healthy elderly population. Methods. Twenty-one non-smoking couples participated in a randomized, double-blind, cross-over study with two consecutive 48-h exposures to either particle filtered or non-filtered air (2533-4058 and 7718-12988 particles per cm3, respectively) in their homes. Measurements and results. Microvascular function was assessed non-invasively by measuring digital peripheral artery tone following arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation factors, P-selectin, plasma amyloid A, C-reactive protein, fibrinogen, interleukin-6, tumor necrosis factor alpha, protein oxidation measured as 2-aminoadipic semialdehyde in plasma, urinary 8-iso-prostaglandin F2 and blood pressure. Indoor air filtration significantly improved microvascular function by 8.1% (95% confidence interval: 0.4-16.3%) and the particulate matter (diameter was more important than the total number concentration (10-700 nm) for these effects. Microvascular function was significantly associated with personal exposure to iron, potassium, copper, zinc, arsenic and lead in the fine fraction. After Bonferroni correction none of the secondary biomarkers, changed significantly. Conclusion. Reduction of particle exposure by filtration of recirculated indoor air for only 48-hours improved microvascular function in healthy elderly citizens suggesting that this may be a feasible way of reducing the risk of cardiovascular disease.

BACKGROUND: Particulate matter, especially ultrafine particles (UFPs), may cause health effects through generation of oxidative stress, with resulting damage to DNA and other macromolecules. OBJECTIVE: We investigated oxidative damage to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of number concentration (NC) to four size modes with average diameters of 12, 23, 57, and 212 nm. DESIGN: Twenty-nine healthy adults participated in a randomized, two-factor cross-over study with or without biking exercise for 180 min and with exposure to particles (NC 6169-15362/cm(3)) or filtered air (NC 91-542/cm(3)) for 24 hr. METHODS: The levels of DNA strand breaks (SBs), oxidized purines as formamidopyrimidine DNA glycolase (FPG) sites, and activity of 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1) in PBMCs were measured by the Comet assay. mRNA levels of OGG1, nucleoside diphosphate linked moiety X-type motif 1 (NUDT1), and heme oxygenase-1 (HO1) were determined by real-time reverse transcriptase-polymerase chain reaction. RESULTS: Exposure to UFPs for 6 and 24 hr significantly increased the levels of SBs and FPG sites, with a further insignificant increase after physical exercise. The OGG1 activity and expression of OGG1, NUDT1, and HO1 were unaltered. There was a significant dose-response relationship between NC and DNA damage, with the 57-nm mode as the major contributor to effects. Concomitant exposure to ozone, nitrogen oxides, and carbon monoxide had no influence. CONCLUSION: Our results indicate that UFPs, especially the 57-nm soot fraction from vehicle emissions, causes systemic oxidative stress with damage to DNA and no apparent compensatory up-regulation of DNA repair within 24 hr. This work was supported by the Danish National Research Councils and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: “Food Quality and Safety” (contract no 513943).

We investigated whether there is an interaction between distance from residence at birth to nearest power line and domestic radon and traffic-related air pollution, respectively, in relation to childhood leukemia risk. Further, we investigated whether adjusting for potential confounders alters the association between distance to nearest power line and childhood leukemia. We included 1024 cases aged

Aim / Background: Obesity prevalence has more than doubled globally within the last 30 years. Obesity affects life quality and impacts the risks and prognosis for a number of serious diseases. Established causes include a high caloric diet combined with a sedentary lifestyle and possibly the widespread cessation of smoking. These do not fully explain the epidemic and evidence from animal experiments suggests PCBs predict obesity development. Knowledge on effects of these compounds as determinants of human abdominal obesity is limited. Methods: In the current study we investigated whether low dose exposure to PCBs in adipose tissue experienced by a general Danish population predicted increased abdominal circumference. We used 214 persons, aged ≥ 50 years that had previously been used as healthy controls in a study investigating PCBs and risk of non-Hodgkins lymphoma. Adipose tissue was collected upon enrolment and PCBs were quantified using gas chromatography-mass spectroscopy. Results: Median levels of the included PCBs were lower in women, except for PCB118. All PCBs were positively associated with increased abdominal circumference, although this association was non-significant. Conclusion: These data indicate a positive link between PCBs and increased abdominal circumference. More work is needed to elucidate the role of compounds such as PCBs in development of the present obesity epidemic.

Background Particulate air pollution is associated with increased risk of cardiovascular events although the involved mechanisms are poorly understood. The objective of the present study was to investigate the effects of controlled exposure to ambient air fine and ultrafine particles on microvascular function and biomarkers related to inflammation, haemostasis and lipid and protein oxidation. Methods Twenty-nine subjects participated in a randomized, two-factor crossover study with or without biking exercise for 180 minutes and with 24 hour exposure to particle rich (number concentrations, NC: 11600 ± 5600 per cm3, mass concentrations: 13.8 ± 7.4 μg/m3 and 10.5 ± 4.8 μg/m3 for PM10-2.5 and PM2.5, respectively) or particle filtered (NC: 555 ± 1053 per cm3) air collected above a busy street. Microvascular function was assessed non-invasively by measuring digital peripheral artery tone following arm ischemia. Biomarkers included haemoglobin, red blood cells, platelet count, coagulation factors, C-reactive protein, fibrinogen, interleukin-6, tumour necrosis factor α, lag time to copper-induced oxidation of plasma lipids and protein oxidation measured as 2-aminoadipic semialdehyde in plasma. Results No statistically significant differences were observed on microvascular function or the biomarkers after exposure to particle rich or particle filtered air. Conclusion This study indicates that exposure to air pollution particles at outdoor concentrations is not associated with detectable systemic inflammation, lipid or protein oxidation, altered haemostasis or microvascular function in young healthy participants.

Traffic is one of the major sources of harmful airborne particles worldwide. To relate exposure to adverse health effects it is important to determine the deposition probability of the inhaled particles in the human respiratory tract. The size-dependent deposition of 12-580 nm particles was measured with a novel setup in 9 healthy subjects breathing by mouth on the windward side of a busy street in Copenhagen, Denmark. The aerosol was characterized both at the curbside and, to obtain the background concentration, at rooftop level. Particle hygroscopicity, a key parameter affecting respiratory tract deposition, was also measured at the same time of exposure. The total deposition fraction of the curbside particles in the range 12-580 nm was 0.60 by number, 0.29 by surface area, and 0.23 by mass. The deposition fractions of the "traffic exhaust" contribution, calculated as the hydrophobic fraction of the curbside particles, was 0.68, 0.35, and 0.28 by number, surface area, and mass, respectively. The deposited amount of traffic exhaust particles was 16 times higher by number and 3 times higher by surface area compared to the deposition of residential biofuel combustion particles investigated previously (equal inhaled mass concentrations). This was because the traffic exhaust particles had both a higher deposition probability and a higher number and surface area concentration per unit mass. To validate the results, the respiratory tract deposition was estimated by using the well-established ICRP model. Predictions were in agreement with experimental results when the effects of particle hygroscopicity were considered in the model.