Intermediate Exposure Groups Research Articles

Population studies of disease related to community PFAS exposure in Sweden from fire-fighting foam contamination

Since the C8 Science Panel experiences, major community populations have been identified with PFAS exposure at comparable or, even higher levels. In Sweden in 2013 very high levels of PFOS and PFHxS, and to a lesser extent PFOA, were found in the drinking water from one of the two waterworks supplying the municipality of Ronneby. Community blood sampling confirmed the exposure with median serum levels of these PFAS for those living in the contaminated water district being 280, 257 and 15 ng/ml respectively. A wide number of health effects are being investigated with one priority to asses if the C8 “Probable Link” diseases are evident in this population. High cholesterol was found, but thyroid disease and ulcerative colitis were not associated with degree of PFAS exposure. Studies underway are addressing exposures during pregnancy, immune effects and cancers.To address thyroid disease, a cohort was formed, including all individuals who had lived at least one year in Ronneby during the period 1980-2013 (n~63,000) and linked to registers providing diagnoses and prescriptions for hyper- and hypothyroidism. In total, 16,150 individuals had ever been exposed, from home addresses linked to the contaminated water works. The hazard ratios did not indicate any excess risk of hyperthyroidism among those with contaminated water. For hypothyroidism, there was some evidence of increased risk for the intermediate exposure group (for women but not men), but no evidence of risk in the highest exposure subgroup, compared to the non-exposed. Apart from chance, there are differences in exposure and design which might explain the differences with the C8 study: this population has some raised PFOA, but much higher co-exposure to PFOS and PFHxS; this study includes all the community linked to routine records, but the C8 study identified disease from interviewing subjects who volunteered to participate.

Associations of Maternal Cell-Phone Use During Pregnancy With Pregnancy Duration and Fetal Growth in 4 Birth Cohorts.

Results from studies evaluating potential effects of prenatal exposure to radio-frequency electromagnetic fields from cell phones on birth outcomes have been inconsistent. Using data on 55,507 pregnant women and their children from Denmark (1996–2002), the Netherlands (2003–2004), Spain (2003–2008), and South Korea (2006–2011), we explored whether maternal cell-phone use was associated with pregnancy duration and fetal growth. On the basis of self-reported number of cell-phone calls per day, exposure was grouped as none, low (referent), intermediate, or high. We examined pregnancy duration (gestational age at birth, preterm/postterm birth), fetal growth (birth weight ratio, small/large size for gestational age), and birth weight variables (birth weight, low/high birth weight) and meta-analyzed cohort-specific estimates. The intermediate exposure group had a higher risk of giving birth at a lower gestational age (hazard ratio = 1.04, 95% confidence interval: 1.01, 1.07), and exposure-response relationships were found for shorter pregnancy duration (P < 0.001) and preterm birth (P = 0.003). We observed no association with fetal growth or birth weight. Maternal cell-phone use during pregnancy may be associated with shorter pregnancy duration and increased risk of preterm birth, but these results should be interpreted with caution, since they may reflect stress during pregnancy or other residual confounding rather than a direct effect of cell-phone exposure.

Residential magnetic fields exposure and childhood leukemia: a population-based case-control study in California.

Studies have reported an increased risk of childhood leukemia associated with exposure to magnetic fields. We conducted a large records-based case-control study of childhood leukemia risk and exposure to magnetic fields from power lines in California. The study included 5,788 childhood leukemia cases (born in and diagnosed in California 1986-2008) matched to population-based controls on age and sex. We calculated magnetic fields at birth addresses using geographic information systems, aerial imagery, historical information on load and phasing, and site visits. Based on unconditional logistic regression controlling for age, sex, race/ethnicity, and socioeconomic status using subjects geocoded to a basic standard of accuracy, we report a slight risk deficit in two intermediate exposure groups and a small excess risk in the highest exposure group (odds ratio of 1.50 (95% confidence interval [0.70, 3.23])). Subgroup and sensitivity analyses as well as matched analyses gave similar results. All estimates had wide confidence intervals. Our large, statewide, record-based case-control study of childhood leukemia in California does not in itself provide clear evidence of risk associated with greater exposure to magnetic fields from power lines, but could be viewed as consistent with previous findings of increased risk.

GSTM1 and GSTT1 Genes are Associated With DNA Damage of p53 Gene in Coke-oven Workers.

This study investigated whether variations in GSTT1 and GSTM1 gene are associated with the DNA damage level of p53 gene. We quantified urinary 1-hydroxypyrene using high-performance liquid chromatography, and examined the DNA damage level of p53 gene by real-time quantitative PCR in 756 coke-oven workers. Multiplex PCR was used to detect the presence or absence of genes. DNA damage levels of p53 gene in the high exposure group and intermediate exposure group were significantly higher than that of p53 gene in the low exposure group (P < 0.01). In coke-oven workers, the DNA damage levels of subjects with non-null genotype in GSTT1 or GSTM1 gene were significantly higher than that of those with the null genotype (P < 0.01). GSTT1 and GSTM1 may modulate DNA damage levels of p53 gene when exposed to polycyclic aromatic hydrocarbons.

Cognitive function and plasma BDNF levels among manganese-exposed smelters

ObjectivesTo explore the potential dose–response relationship between manganese (Mn) exposure and cognitive function and also plasma brain-derived neurotrophic factor (BDNF) levels in occupational Mn exposure workers.MethodsA total 819 workers were...

Domestic radon exposure and risk of childhood cancer: a prospective census-based cohort study from Switzerland

Background Exposure to domestic radon is hypothesized to cause childhood leukaemia but evidence from previous research has produced inconsistent results. Aims To investigate the association between domestic radon exposure and childhood leukaemia Methods A nationwide census-based cohort study including all children aged between 0 and 15 years and living in Switzerland on 5 December 5th 2000 was conducted. The follow-up period lasted until the date of diagnosis, death, emigration, the children becoming 16 years old or 31 December, 2008. Cox proportional hazard regression models were applied, adjusted for age, gender, birth order, socio-economic status of the parents, environmental gamma radiation and period effects. Exposure assessment for each individual home address was based on a radon prediction model, developed and validated with approximately 45,000 measurements carried out all over Switzerland. Results In total, 285 childhood leukaemia cancer cases were included in the study. Compared to the group of children exposed to a radon concentration below the median (&lt; 77.7 Bq/m³), the hazard ratio for the 10% highest exposed children (? 139.9 Bq/m³) was 0.99 (95% CI: 0.66, 1.49). The hazard ratios fort the intermediate exposure group (77.7-139.9 Bq/m³) was 0.87 (95%-CI: 0.67, 1.12). A separate analysis for acute lymphoblastic leukaemia (ALL), the most frequent subgroup of all leukaemias did not indicate significant associations either. Conclusions This census-based cohort study does not indicate an association between domestic radon concentration and childhood leukaemia. The observed lack of an association between domestic radon exposure and childhood leukaemia was found to be in line with estimated doses of domestic radon concentrations to red bone marrow.

In Vivo Tungsten Exposure Alters B-Cell Development and Increases DNA Damage in Murine Bone Marrow

High environmental tungsten levels were identified near the site of a childhood pre-B acute lymphoblastic leukemia cluster; however, a causal link between tungsten and leukemogenesis has not been established. The major site of tungsten deposition is bone, the site of B-cell development. In addition, our in vitro data suggest that developing B lymphocytes are susceptible to tungsten-induced DNA damage and growth inhibition. To extend these results, we assessed whether tungsten exposure altered B-cell development and induced DNA damage in vivo. Wild-type mice were exposed to tungsten in their drinking water for up to 16 weeks. Tungsten concentration in bone was analyzed by inductively coupled plasma mass spectrometry and correlated with B-cell development and DNA damage within the bone marrow. Tungsten exposure resulted in a rapid deposition within the bone following 1 week, and tungsten continued to accumulate thereafter albeit at a decreased rate. Flow cytometric analyses revealed a transient increase in mature IgD(+) B cells in the first 8 weeks of treatment, in animals of the highest and intermediate exposure groups. Following 16 weeks of exposure, all tungsten groups had a significantly greater percentage of cells in the late pro-/large pre-B developmental stages. DNA damage was increased in both whole marrow and isolated B cells, most notably at the lowest tungsten concentration tested. These findings confirm an immunological effect of tungsten exposure and suggest that tungsten could act as a tumor promoter, providing leukemic "hits" in multiple forms to developing B lymphocytes within the bone marrow.

SECONDHAND SMOKE: Parental Smoking May Set Up Children for Atherosclerosis

Vol. 118, No. 5 NewsOpen AccessSECONDHAND SMOKE: Parental Smoking May Set Up Children for Atherosclerosis Adrian Burton Adrian Burton Search for more papers by this author Published:1 May 2010https://doi.org/10.1289/ehp.118-a200aCited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Children frequently exposed to secondhand tobacco smoke may be at greater risk of developing atherosclerosis as adults, suggests new research published in the March 2010 issue of Circulation: Cardiovascular Quality and Outcomes. “Passive smoking has been associated with an increased risk of atherosclerosis in adults by altering arterial structure and lipid profiles, but there is growing evidence the trouble might begin in childhood,” explains first author Katariina Kallio, a research fellow at the Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland. “Our study shows changes do occur in the intima-media thickness of the arteries of healthy adolescents exposed to smoke, confirming this fear.”The study, which involved 494 healthy 13-year-olds, measured three preclinical indicators of atherosclerosis: the carotid and aortic intima-media thickness (i.e., the thickness of the walls of these arteries), flow-mediated dilation of the brachial artery (a measure of endothelial function), and plasma apolipoprotein B (ApoB) levels (a measure of circulating atherogenic lipoproteins).The researchers divided the children into low-, intermediate-, and high-exposure groups, which were determined on the basis of each child’s average serum cotinine level (0.1–0.4 ng/mL, 0.41–0.7 ng/mL, and 0.71–4.1 ng/mL, respectively) as measured at different times since age 8 years. High-resolution ultrasound scans showed the intima-media of the carotid artery was thicker in children in the high- and intermediate-exposure groups than in the low-exposure group. The same was true of the aortic intima-media. In addition, flow-mediated dilation in the brachial artery was significantly reduced in the high-exposure group.These preclinical signs of atherosclerosis were accompanied by significantly increased ApoB levels in the high-exposure group compared with the low-exposure group. Their ApoB/ApoA-1 ratios also were significantly higher, a predictor of atherosclerosis and endothelial dysfunction in adults. Associations persisted after accounting for other atherosclerosis risk factors including serum lipids, sex, pubertal status, diastolic blood pressure, and body mass index.“Intima-media thickness may be increased by a direct toxic effect of tobacco smoke, the enhanced binding of platelets to vessels causing the growth of vascular smooth muscle, or perhaps lipid peroxidation; we are not sure,” says Kallio. “Nor are we sure why ApoB is increased, although we believe liver enzyme function might be involved.”“Whether the changes seen are reversible on removing children from smoke exposure, and how long this would take, are also currently unknown,” comments John Cockcroft of the Wales Heart Research Institute, Cardiff University School of Medicine, who was not involved in the study.The publication of these findings coincides with a 24 March 2010 call by the Royal College of Physicians (RCP) to ban smoking in cars in the United Kingdom to reduce children’s exposure to secondhand smoke. Several U.S. states and parts of Australia and Canada already ban smoking specifically in cars carrying children. “What is clear,” says Cockcroft, “is that [this Finnish study] provides further evidence to support the RCP’s call for a ban on exposing children to smoke inhalation—a proposal that the authors themselves support.”FiguresReferencesRelatedDetailsCited by Yang B, Li M, Chen B, Xu Y and Li T (2012) Deterioration of endothelial function and carotid intima-media thickness in Tibetan male adolescents exposed to second-hand smoke, Journal of the Renin-Angiotensin-Aldosterone System, 10.1177/1470320312440901, 13:4, (413-419), Online publication date: 1-Dec-2012. Vol. 118, No. 5 May 2010Metrics About Article Metrics Publication History Originally published1 May 2010Published in print1 May 2010 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Using Lymphocyte and Plasma Hsp70 as Biomarkers for Assessing Coke Oven Exposure among Steel Workers

BackgroundHsp70, an early-response protein induced when organisms are confronted with simple or complicated environmental stresses, can act as either a cellular protector or a danger signal.ObjectivesThe goal of this study was to evaluate levels of lymphocyte and/or plasma Hsp70 as biomarkers for assessing exposure response to complex coke oven emissions (COEs).MethodsWe recruited 101 coke oven workers and determined levels of polycyclic aromatic hydrocarbon (PAH) exposure, urinary 1-hydroxypyrene (1-OHP), genotoxic damage by comet assay and micronuclei test, and other markers of damage, including plasma malondialdehyde (MDA) and lactate dehydrogenase (LDH). These were compared to levels of lymphocyte (intra-cellular) and plasma (extracellular) Hsp70 using Western blots and enzyme-linked immunosorbent assays (ELISA), respectively.ResultsWe observed a COEs-related dose-dependent increase in levels of DNA damage, micronuclei rate, MDA concentration, and LDH activity. Lymphocyte Hsp70 levels increased in the intermediate-exposure group (1.39 ± 0.88) but decreased in the high-exposure group (1.10 ± 0.55), compared with the low-exposure group. In contrast, plasma Hsp70 levels progressively increased as the dose of exposure increased. Negative correlations were seen between lymphocyte Hsp70 levels and olive tail moment and LDH activity in the intermediate- and high-exposure groups. However, we observed positive correlations between plasma Hsp70 levels and LDH activity in the low and intermediate groups.ConclusionsIn workers exposed to COEs, high lymphocyte Hsp70 levels may provide protection and high plasma Hsp70 levels may serve as a danger marker. Larger validation studies are needed to establish the utility of Hsp70 as a response marker.

Beryllium particulate exposure and disease relations in a beryllium machining plant.

We examined the relationship between exposure to beryllium and the presence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers in a beryllium precision machining facility. Twenty workers with BeS or CBD (cases) were compared with 206 worker-controls in a case-control study. Exposure for each job title was measured using cascade impactors placed in the workers' breathing zone to measure total beryllium exposure and exposure to particles < 6 microns and < 1 micron in aerodynamic diameter. Cumulative exposure was calculated as sigma (job title exposure estimate x years in job title). Individual lifetime-weighted (LTW) exposure was calculated as sigma [(job title exposure x years in job title) divided by total years employment)]. Workers in the case group were more likely to have worked as machinists (odds ratio, 4.4; 95% confidence interval, 1.1 to 17.5) than those in the control group. The median cumulative exposure was consistently greater in the cases compared with the controls for all exposure estimates and particle size fractions, although this was not statistically significant. The median cumulative exposure was 2.9 micrograms/m3-years in the cases versus 1.2 micrograms/m3-years in the controls for total exposure, and 1.7 micrograms/m3-years in the cases versus 0.5 microgram/m3-years in the controls for exposure to particles < 6 microns in diameter. With cumulative exposure categorized into low-, intermediate-, and high-exposure groups, the odds ratios were 2.4 (95% confidence interval, 0.7 to 8.2) for the intermediate-exposure group and 1.2 (95% confidence interval, 0.4 to 4.2) for the high-exposure group compared with the low-exposure group. The median LTW exposure was 0.25 microgram/m3 in both groups. The median LTW exposure to particles < 6 microns was 0.20 microgram/m3 in the cases compared with 0.14 microgram/m3 in the controls. The differences in cumulative and LTW exposure were not statistically significant. None of the 22 workers with LTW exposure < 0.02 microgram/m3 had BeS or CBD. Twelve workers (60%) in the case group had LTW exposures > 0.20. In conclusion, increased cumulative and LTW exposure to total and respirable beryllium was observed in workers with CBD or BeS compared with the controls. These results support efforts to control beryllium exposure in the workplace.

Long-term carcinogenicity of pan masala in Swiss mice.

Carcinogenicity of pan masala, a dry powdered chewing mixture of areca nut, catechu, lime, spices and flavoring agents was evaluated by means of the long-term animal bio-assay 6- to 7-week old male and female S/RVCri mice were divided randomly into intermediate and lifetime exposure groups and fed normal diet without pan masala-(zero dose) or diet containing 2.5% and 5% pan masala. Animals in the intermediate-exposure group (n = 10/gender/dose group) were killed after 6, 12 or 18 months of treatment, while those in the lifetime-exposure group (n = 54/gender/dose group) were killed when moribund or at the termination of the experiment at 24 months. Several tissues were processed for histopathological examination. The body weight and survival rate of mice fed pan masala were lower than that of the controls. Histopathological observations of tissues from control animals did not reveal any neoplastic alterations. However, lifetime feeding of pan masala induced adenoma of the liver, stomach, prostate and sebaceous glands, also forestomach papilloma, liver hamartoma, hepatoma and hemangioma, carcinoma of the forestomach, adenocarcinoma of the lung and liver, and testicular lymphoma. Neoplastic lesions appeared mainly in the liver (n = 13), stomach (n = 3) and lung (n = 8). Lung adenocarcinoma, the most frequent malignant tumor type, was observed in 2/120 mice in the intermediate-exposure group and in 8/216 animals in the lifetime-exposure group. Statistical analysis of tumor-induction data revealed a significant dose-related increase in lung adenocarcinomas but not in liver and stomach neoplasms indicating that lung is the major target tissue for the carcinogenic action of pan masala.

Monitoring of occupational exposure to polycyclic aromatic hydrocarbons in a carbon-electrode manufacturing plant

An investigation is presented of occupational exposure to polycyclic aromatic hydrocarbons (PAH) in a carbon-electrode manufacturing plant, as assessed by three monitoring methods, viz. environmental monitoring of the external dose by analysis of personal air samples, biological monitoring of the internal dose by analysis of urinary 1-hydroxypyrene (1-OHpyrene), and biological effect monitoring by dosimetry of PAH-DNA adducts in blood lymphocytes. On the basis of job conditions, workers at the plant were divided into three groups with presumed low, intermediate and high exposure to air-borne PAH, respectively. All air samples showed levels of total PAH below the current MAC-value in the Netherlands, which is 200 μg/m3, whereas the benzo[a]pyrene level was occasionally higher than the recommended concentration of 2 μg/m3. The values of 1-OHpyrene in urine from the intermediate and high exposure groups were significantly higher than those of the low exposure group, namely 3.6- and 8.2-fold, respectively. Clear external and internal exposure was thus demonstrated for workers of the high and intermediate exposure groups, but this did not result in a measurable effect at the DNA level in blood lymphocytes. Tobacco smoking, on the other hand, caused a significant increase of the levels of PAH-DNA adducts but did not affect 1-OHpyrene values. These data suggest that smoking is a more important risk factor for adverse health effects, i.e. cancer, than occupational exposure to PAH in this plant.

Monitoring of Occupational Exposure to Polycyclic Aromatic Hydrocarbons in a Carbon-electrode Manufacturing Plant

An investigation is presented of occupational exposure to polycyclic aromatic hydrocarbons (PAH) in a carbon-electrode manufacturing plant, as assessed by three monitoring methods, viz. environmental monitoring of the external dose by analysis of personal air samples, biological monitoring of the internal dose by analysis of urinary 1-hydroxypyrene (1-OHpyrene), and biological effect monitoring by dosimetry of PAH-DNA adducts in blood lymphocytes. On the basis of job conditions, workers at the plant were divided into three groups with presumed low, intermediate and high exposure to air-borne PAH, respectively. All air samples showed levels of total PAH below the current MAC-value in the Netherlands, which is 200µg/m3, whereas the benzo[a]pyrene level was occasionally higher than the recommended concentration of 2 µg/m3 The values of 1-OHpyrene in urine from the intermediate and high exposure groups were significantly higher than those of the low exposure group, namely 3.6- and 8.2-fold, respectively. Clear external and internal exposure was thus demonstrated for workers of the high and intermediate exposure groups, but this did not result in a measurable effect at the DNA level in blood lymphocytes. Tobacco smoking, on the other hand, caused a significant increase of the levels of PAH-DNA adducts but did not affect 1 -OHpyrene values. These data suggest that smoking is a more important risk factor for adverse health effects, i.e. cancer, than occupational exposure to PAH in this plant. © 1998 British Occupational Hygiene Society. Published by Elsevier Science Ltd.

Organization of proteins in mammalian mitochondrial ribosomes. Accessibility to lactoperoxidase-catalyzed radioiodination.

To assess the relative exposure of individual ribosomal proteins (r-proteins) in the large and small subunits of the bovine mitochondrial ribosome, we used a double label iodination technique. Regions of r-proteins exposed in purified ribosomal subunits were labeled with 131I using the lactoperoxidase-catalyzed iodination system, and additional reactive groups available upon denaturing the r-proteins in urea were labeled with 125I using the chloramine-T mediated reaction. The ratio of 131I to 125I incorporated into individual proteins under these conditions is representative of the degree of exposure for each of the proteins in the subunits. In this manner, the r-proteins have been grouped into 3 classes depending on their degree of exposure: high exposure, intermediate exposure, and essentially buried. While both subunits have a few proteins in the "highly exposed" group, and a large number of proteins in the "intermediate exposure" group, only the large ribosomal subunit has an appreciable number of proteins which appear essentially buried. The more buried proteins may serve mainly structural roles, perhaps acting as "assembly proteins," since many from this group bind to ribosomal RNA. The more superficially disposed proteins may comprise binding sites for macromolecules that interact with ribosomes during protein synthesis, as well as stabilizing the association of the large and small subribosomal particles.

An environmental health survey of drinking water contamination by leachate from a pesticide waste dump in Hardeman County, Tennessee.

Ground water that was used as a source of potable water by residents of a small community became contaminated by leachate from a 300,000 barrel pesticide waste dump. An environmental health survey of the residents and an apparent control group was conducted to determine if any adverse health effects resulting from exposure to the toxic compounds, many of which were hepatotoxins, could be detected. The survey utilized a health questionnaire, a clinical examination, and a biochemical screening. The latter included analysis of serum for liver and kidney function parameters, determination of hepatitis A and B serology, and bile acid determinations on fasting and postprandial serum and urine specimens. Air and water from representative homes and urine from study participants were analyzed for selected organic compounds. The biochemical screening was conducted on two occasions 2 months apart. The initial hepatic profile testing revealed elevated concentrations of the serum enzymes, alkaline phosphatase and serum glutamic oxaloacetic transaminase, in residents who had used the contaminated water. During follow-up testing of these same persons 2 months later, these values were significantly reduced, as were postprandial serum concentrations of the bile acid of cholyglycine. Six individuals in the exposed group had slight hepatomegaly compared to one individual in the intermediate exposure group and none in the controls. Concentrations of carbon tetrachloride were as high as 18,700 microgram/L in the well water samples. The biochemical and clinical observations are suggestive of a transitory liver injury probably related to exposure to the contaminated drinking water.