| 1. |
- Alkaissi, Hammoudi, et al.
(författare)
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Genome-Wide Association Study to Identify Genes Related to Renal Mercury Concentrations in Mice
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : U.S. Department of Health and Human Services * National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 124:7, s. 920-926
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Following human mercury (Hg) exposure, the metal accumulates in considerable concentrations in kidney, liver, and brain. Although the toxicokinetics of Hg have been studied extensively, factors responsible for interindividual variation in humans are largely unknown. Differences in accumulation of renal Hg between inbred mouse strains suggest a genetic interstrain variation regulating retention or/and excretion of Hg. A. SW, DBA/2 and BALB/C mouse strains accumulate higher amounts of Hg than B10.S.OBJECTIVES: We aimed to find candidate genes associated with regulation of renal Hg concentrations.METHODS: A. SW, B10.S and their F1 and F2 offspring were exposed for 6 weeks to 2.0 mg Hg/L drinking water. Genotyping with microsatellites was conducted on 84 F2 mice for genome-wide scanning with ion pair reverse-phase high-performance liquid chromatography (IP RP HPLC). Quantitative trait loci (QTL) were established. Denaturing HPLC was used to detect single nucleotide polymorphisms for haplotyping and fine mapping in 184 and 32 F2 mice, respectively. Candidate genes (Pprc1, Btrc and Nfkb2) verified by fine mapping and QTL were further investigated by real-time polymerase chain reaction. Genes enhanced by Pprc1 (Nrf1 and Nrf2) were included for gene expression analysis.RESULTS: Renal Hg concentrations differed significantly between A. SW and B10. S mice and between males and females within each strain. QTL analysis showed a peak logarithm of odds ratio score 5.78 on chromosome 19 (p = 0.002). Haplotype and fine mapping associated the Hg accumulation with Pprc1, which encodes PGC-1-related coactivator (PRC), a coactivator for proteins involved in detoxification. Pprc1 and two genes coactivated by Pprc1 (Nrf1 and Nrf2) had significantly lower gene expression in the A. SW strain than in the B10. S strain.CONCLUSIONS: This study supports Pprc1 as a key regulator for renal Hg excretion.
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| 2. |
- Andersen, Zorana J., et al.
(författare)
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Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 European cohorts within the ESCAPE project
- 2017
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Ingår i: Journal of Environmental Health Perspectives. - Research triangle park : US department of health. - 0091-6765 .- 1552-9924. ; 125:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent.OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women.METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts – Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2.5μm, ≤10μm, and 2.5–10μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1.08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m(3)}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m(3)], PMcoarse[1.20 (95% CI: 0.96, 1.49 per 5 μg/m(3)], and NO(2) [1.02 (95% CI: 0.98, 1.07 per 10 μg/m(3)], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m(3), p=0.04].CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women.
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| 3. |
- Armstrong, Ben, et al.
(författare)
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The Role of Humidity in Associations of High Temperature with Mortality : A Multicountry, Multicity Study
- 2019
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Ingår i: Journal of Environmental Health Perspectives. - : The National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 127:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is strong experimental evidence that physiologic stress from high temperatures is greater if humidity is higher. However, heat indices developed to allow for this have not consistently predicted mortality better than dry-bulb temperature.Objectives: We aimed to clarify the potential contribution of humidity an addition to temperature in predicting daily mortality in summer by using a large multicountry dataset.Methods: In 445 cities in 24 countries, we fit a time-series regression model for summer mortality with a distributed lag nonlinear model (DLNM) for temperature (up to lag 3) and supplemented this with a range of terms for relative humidity (RH) and its interaction with temperature. City-specific associations were summarized using meta-analytic techniques.Results: Adding a linear term for RH to the temperature term improved fit slightly, with an increase of 23% in RH (the 99th percentile anomaly) associated with a 1.1% [95% confidence interval (CI): 0.8, 1.3] decrease in mortality. Allowing curvature in the RH term or adding terms for interaction of RH with temperature did not improve the model fit. The humidity-related decreased risk was made up of a positive coefficient at lag 0 outweighed by negative coefficients at lags of 1–3 d. Key results were broadly robust to small model changes and replacing RH with absolute measures of humidity. Replacing temperature with apparent temperature, a metric combining humidity and temperature, reduced goodness of fit slightly.Discussion:The absence of a positive association of humidity with mortality in summer in this large multinational study is counter to expectations from physiologic studies, though consistent with previous epidemiologic studies finding little evidence for improved prediction by heat indices. The result that there was a small negative average association of humidity with mortality should be interpreted cautiously; the lag structure has unclear interpretation and suggests the need for future work to clarify.
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| 4. |
- Barregård, Lars, 1948, et al.
(författare)
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Blood Cadmium Levels and Incident Cardiovascular Events during Follow-up in a Population-Based Cohort of Swedish Adults: The Malmo Diet and Cancer Study
- 2016
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:5, s. 594-600
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cadmium exposure may increase the risk of cardiovascular disease. The only published longitudinal study on cadmium and incident cardiovascular disease was performed in American Indians with relatively high cadmium exposure. OBJECTIVES: Our aim was to examine the association between blood cadmium at baseline and incident cardiovascular events in a population-based study of Swedish men and women with cadmium levels similar to those of most European and U.S. populations. METHODS: A Swedish population-based cohort (n = 6,103, age 46-67 years) was recruited between 1991 and 1994. After we excluded those with missing data on smoking, 4,819 participants remained. Acute coronary events, other major cardiac events, stroke, and cardiovascular mortality were followed until 2010. Associations with blood cadmium (estimated from cadmium in erythrocytes) were analyzed using Cox proportional hazards regression including potential confounders and important cardiovascular risk factors. RESULTS: Hazard ratios for all cardiovascular end points were consistently increased for participants in the 4th blood cadmium quartile (median, 0.99 mu g/L). In models that also included sex, smoking, waist circumference, education, physical activity, alcohol intake, serum triglycerides, HbA1c, and C-reactive protein, the hazard ratios comparing the highest and lowest quartiles of exposure were 1.8 (95%CI: 1.2, 2.7) for acute coronary events, and 1.9 (1.3, 2.9) for stroke. Hazard ratios in never-smokers were consistent with these estimates. CONCLUSIONS: Blood cadmium in the highest quartile was associated with incident cardiovascular disease and mortality in our population-based samples of Swedish adults. The consistent results among never-smokers are important because smoking is a strong confounder. Our findings suggest that measures to reduce cadmium exposures are warranted, even in populations without unusual sources of exposure.
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| 5. |
- Beelen, Rob, et al.
(författare)
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Natural-Cause Mortality and Long-Term Exposure to Particle Components : An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 525-533
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Forskningsöversikt (refereegranskat)abstract
- Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter ( PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200ng/m(3)). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
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| 6. |
- Bennett, Deborah, et al.
(författare)
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Project TENDR : Targeting Environmental Neuro-Developmental Risks. The TENDR Consensus Statement
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Science. - 0091-6765 .- 1552-9924. ; 124:7, s. A118-A122
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Tidskriftsartikel (refereegranskat)abstract
- Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes-genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children's health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children's brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children's risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.
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| 7. |
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| 8. |
- Bornehag, Carl-Gustaf, 1957-, et al.
(författare)
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Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:1, s. 101-107
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and in a large number of consumer products. Because of reported health risks, diisononyl phthalate (DiNP) has been introduced as a replacement for di(2-ethylhexyl) phthalate (DEHP) in soft PVC. This raises concerns because animal data suggest that DiNP may have antiandrogenic properties similar to those of DEHP. The anogenital distance (AGD)-the distance from the anus to the genitals-has been used to assess reproductive toxicity. OBJECTIVE: The objective of this study was to examine the associations between prenatal phthalate exposure and AGD in Swedish infants. METHODS: AGD was measured in 196 boys at 21 months of age, and first-trimester urine was analyzed for 10 phthalate metabolites of DEP (diethyl phthalate), DBP (dibutyl phthalate), DEHP, BBzP (benzylbutyl phthalate), as well as DiNP and creatinine. Data on covariates were collected by questionnaires. RESULTS: The most significant associations were found between the shorter of two AGD measures (anoscrotal distance; AGDas) and DiNP metabolites and strongest for oh-MMeOP [mono(4-methyl-7-hydroxyloctyl) phthalate] and oxo-MMeOP [mono-(2-ethyl-5-oxohexyl) phthalate]. However, the AGDas reduction was small (4%) in relation to more than an interquartile range increase in DiNP exposure. CONCLUSIONS: These findings call into question the safety of substituting DiNP for DEHP in soft PVC, particularly because a shorter male AGD has been shown to relate to male genital birth defects in children and impaired reproductive function in adult males and the fact that human levels of DiNP are increasing globally.
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| 9. |
- Brantsaeter, Anne Lise, et al.
(författare)
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Organic Food Consumption during Pregnancy and Hypospadias and Cryptorchidism at Birth : The Norwegian Mother and Child Cohort Study (MoBa)
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:3, s. 357-364
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The etiologies of the male urogenital anomalies hypospadias and cryptorchidism remain unclear. It has been suggested that maternal diet and environmental contaminants may affect the risk of these anomalies via placental or hormonal disturbances. OBJECTIVES: We examined associations between organic food consumption during pregnancy and prevalence of hypospadias and cryptorchidism at birth. METHODS: Our study includes 35,107 women participating in the Norwegian Mother and Child Cohort Study (MoBa) who delivered a singleton male infant. Information about use of six groups of organically produced food (vegetables, fruit, bread/cereal, milk/dairy products, eggs, and meat) during pregnancy was collected by a food frequency questionnaire. Women who indicated that they sometimes, often, or mostly consumed organic foods in at least one of the six food groups were classified as organic food consumers in analyses. Hypospadias and cryptorchidism diagnoses were retrieved from the Medical Birth Registry of Norway. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression. RESULTS: Seventy-four male newborns were diagnosed with hypospadias (0.2%), and 151 with cryptorchidism (0.4%). Women who consumed any organic food during pregnancy were less likely to give birth to a boy with hypospadias (OR = 0.42; 95% CI: 0.25, 0.70, based on 21 exposed cases) than women who reported they never or seldom consumed organic food. Associations with specific organic foods were strongest for vegetable (OR = 0.36; 95% CI: 0.15, 0.85; 10 exposed cases) and milk/dairy (OR = 0.43; 95% CI: 0.17, 1.07; 7 exposed cases) consumption. No substantial association was observed for consumption of organic food and cryptorchidism. CONCLUSIONS: Consumption of organically produced foods during pregnancy was associated with a lower prevalence of hypospadias in our study population. These findings were based on small numbers of cases and require replication in other study populations.
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