| 1. |
- Akesson, A, et al.
(författare)
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Cadmium-induced effects on bone in a population-based study of women
- 2006
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 114:6, s. 830-834
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Tidskriftsartikel (refereegranskat)abstract
- High cadmium exposure is known to cause bone damage, but the association between low-level cadmium exposure and osteoporosis remains to be clarified. Using a population-based women's health survey in southern Sweden [Women's Health in the Lund Area (WHILA)] with no known historical cadmium contamination, we investigated cadmium-related effects on bone in 820 women (53-64 years of age). We measured cadmium in blood and urine and lead in blood, an array of markers of bone metabolism, and forearm bone mineral density (BMD). Associations were evaluated in multiple linear regression analysis including information on the possible confounders or effect modifiers: weight, menopausal status, use of hormone replacement therapy, age at menarche, alcohol consumption, smoking history, and physical activity. Median urinary cadmium was 0.52 mu g/L adjusted to density (0.67 mu g/g creatinine). After multivariate adjustment, BMD, parathyroid hormone, and urinary deoxypyridinoline (U-DPD) were adversely associated with concentrations of urinary cadmium (p < 0.05) in all subjects. These associations persisted in the group of never-smokers, which had the lowest cadmium exposure (mainly dietary). For U-DPD, there was a significant interaction between cadmium and menopause (p = 0.022). Our results suggest negative effects of low-level cadmium exposure on bone, possibly exerted via increased bone resorption, which seemed to be intensified after menopause. Based on the prevalence of osteoporosis and the low level of exposure, the observed effects, although slight, should be considered as early signals of potentially more adverse health effects.
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| 2. |
- Akesson, AA, et al.
(författare)
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Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure
- 2005
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 113:11, s. 1627-1631
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Tidskriftsartikel (refereegranskat)abstract
- Cadmium is a well-known nephrotoxic agent in food and tobacco, but the exposure level that is critical for kidney effects in the general population is not defined. Within a population-based women's health survey in southern Sweden (Women's Health in the Lund Area, WHILA), we investigated cadmium exposure in relation to tubular and glomerular function, from 1999 through early 2000 in 820 women (71% participation rate) 53-64 years of age. Multiple linear regression showed cadmium in blood (median, 0.38 mu g/L) and urine (0.52 mu g/L; density adjusted = 0.67 mu g/g creatinine) to be significantly associated with effects on renal tubules (as indicated by increased levels of human complex-forming protein and N-acetyl-beta-D-glucosaminidase in urine), after adjusting for age, body mass index, blood lead, diabetes, hypertension, and regular use of nephrotoxic drugs. The associations remained significant even at the low exposure in women who had never smoked. We also found associations with markers of glomerular effects: glomerular filtration rate and creatinine clearance. Significant effects were seen already at a mean urinary cadmium level of 0.6 mu g/L (0.8 mu g/g creatinine). Cadmium potentiated diabetes-induced effects on kidney. In conclusion, tubular renal effects occurred at lower cadmium levels than previously demonstrated, and more important, glomerular effects were also observed. Although the effects were small, they may represent early signs of adverse effects, affecting large segments of the population. Subjects with diabetes seem to be at increased risk.
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| 3. |
- Akre, Olof, et al.
(författare)
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Maternal and gestational risk factors for hypospadias
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:8, s. 1071-1076
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. OBJECTIVES: Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors. METHODS: We conducted a case-control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls. RESULTS: A diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) 4.6, 95% confidence interval (CI), 1.6-13.3]. Boys born to obese [body mass index (BMI) > ;= 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6, 95% CI, 1.2-5.7) compared with boys born to mothers with a normal weight (BMI = 20-24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy's risk of hypospadias 2.0-fold (95% CI, 1.1-3.7) and 1.8-fold (95% CI, 1.2-2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6, 95% CI, 1.1-53). CONCLUSIONS: A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.
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| 4. |
- Alm, Henrik, et al.
(författare)
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Proteomic evaluation of neonatal exposure to 2,2,4,4,5-pentabromodiphenyl ether
- 2006
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 114:2, s. 254-259
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to the brominated flame retardant 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE-99) during the brain growth spurt disrupts normal brain development in mice and results in disturbed spontaneous behavior in adulthood. The neurodevelopmental toxicity of PBDE-99 has been reported to affect the cholinergic and catecholaminergic systems. In this study we use a proteomics approach to study the early effect of PBDE-99 in two distinct regions of the neonatal mouse brain, the striatum and the hippocampus. A single oral dose of PBDE-99 (12 mg/kg body weight) or vehicle was administered to male NMRI mice on neonatal day 10, and the striatum and the hippocampus were isolated. Using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), we found 40 and 56 protein spots with significantly (p < 0.01) altered levels in the striatum and the hippocampus, respectively. We used matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS) to determine the protein identity of 11 spots from the striatum and 10 from the hippocampus. We found that the levels of proteins involved in neurodegeneration and neuroplasticity (e.g., Gap-43/neuromodulin, stathmin) were typically altered in the striatum, and proteins involved in metabolism and energy production [e.g., alpha-enolase; gamma-enolase; ATP synthase, H+ transporting, mitochondrial F1 complex, beta subunit (Atp5b); and alpha-synuclein] were typically altered in the hippocampus. Interestingly, many of the identified proteins have been linked to protein kinase C signaling. In conclusion, we identify responses to early exposure to PBDE-99 that could contribute to persistent neurotoxic effects. This study also shows the usefulness of proteomics to identify potential biomarkers of developmental neurotoxicity of organohalogen compounds.
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| 5. |
- Amzal, Billy, et al.
(författare)
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Population Toxicokinetic Modeling of Cadmium for Health Risk Assessment
- 2009
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Ingår i: Journal of Environmental Health Perspectives. - : US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE. - 0091-6765 .- 1552-9924. ; 117:8, s. 1293-1301
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cadmium is a widespread environmental pollutant that has been shown to exert toxic effects on kidney and bones in humans after long-term exposure. Urinary cadmium concentration is considered a good biomarker of accumulated cadmium in kidney, and diet is the main source of cadmium among nonsmokers. OBJECTIVE: Modeling the link between urinary cadmium and dietary cadmium intake is a key step in the risk assessment of long-term cadmium exposure. There is, however, little knowledge on how this link may vary, especially for susceptible population strata. METHODS: We used a large population-based study (the Swedish Mammography Cohort), with repeated dietary intake data covering a period of 20 years, to compare estimated dietary cadmium intake with urinary cadmium concentrations on an individual basis. A modified version of the Nordberg-Kjellstrom model and a one-compartment model were evaluated in terms of their predictions of urinary cadmium. We integrated the models and quantified the between-person variability of cadmium half-life in the population. Finally, sensitivity analyses and Monte Carlo simulations were performed to illustrate how the latter model could serve as a robust tool supporting the risk assessment of cadmium in humans. RESULTS: The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability. We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability. CONCLUSIONS: Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.
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| 6. |
- Athanasiadou, Maria, et al.
(författare)
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Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE metabolites in young humans from Managua, Nicaragua.
- 2008
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Ingår i: Environ Health Perspect. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:3, s. 400-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our aim was to investigate exposure to polybrominated diphenyl ethers (PBDEs) in a young urban population in a developing country, with focus on potentially highly exposed children working informally as scrap scavengers at a large municipal waste disposal site. We also set out to investigate whether hydroxylated metabolites, which not hitherto have been found retained in humans, could be detected. METHODS: We assessed PBDEs in pooled serum samples obtained in 2002 from children 11-15 years of age, working and sometimes also living at the municipal waste disposal site in Managua, and in nonworking urban children. The influence of fish consumption was evaluated in the children and in groups of women 15-44 years of age who differed markedly in their fish consumption. Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical analyses were performed by gas chromatography/mass spectrometry, using authentic reference substances. RESULTS: The children living and working at the waste disposal site showed very high levels of medium brominated diphenyl ethers. The levels observed in the referent children were comparable to contemporary observations in the United States. The exposure pattern was consistent with dust being the dominating source. The children with the highest PBDE levels also had the highest levels of hydroxylated metabolites. CONCLUSIONS: Unexpectedly, very high levels of PBDEs were found in children from an urban area in a developing country. Also, for the first time, hydroxylated PBDE metabolites were found to bioaccumulate in human serum.
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| 7. |
- Barraza-Villarreal, Albino, et al.
(författare)
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Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren.
- 2008
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Ingår i: Environmental health perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:6, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. OBJECTIVE: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS: We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (Fe(NO)), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. RESULTS: An increase of 17.5 microg/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [95% confidence interval (CI), 1.01-1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98-1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00-1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter <2.5 microm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 sec (FEV(1)) (p=0.048) and forced vital capacity (FVC) (p=0.012) in asthmatic children and with FVC (p=0.021) in nonasthmatic children. Fe(NO) and FEV(1) were inversely associated (p=0.005) in asthmatic children. CONCLUSIONS: Exposure to PM(2.5) resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.
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| 8. |
- Barregård, Lars, 1948, et al.
(författare)
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Renal effects of dental amalgam in children: the New England children's amalgam trial.
- 2008
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Ingår i: Environmental health perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:3, s. 394-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mercury is nephrotoxic and dental amalgam is a source of mercury exposure. METHODS: Children 6-10 years of age (n = 534) with two or more posterior teeth with caries but no prior amalgam restorations, were randomized to one of two treatments--amalgam or resin composite (white fillings)--used for caries treatment during 5 years of follow-up. The primary outcome was change in IQ, but important secondary outcomes were effects on markers of glomerular and tubular kidney function: urinary excretion of albumin, alpha-1-microglobulin (A1M), gamma-glutamyl transpeptidase (gamma-GT), and N-acetyl-beta-d-glucosaminidase (NAG). These markers were measured on several occasions during the trial, together with urinary mercury and covariates. We evaluated the results using repeated-measures analyses. RESULTS: There were no significant differences between treatment groups in average levels of renal biomarkers, nor significant effects of number of dental amalgams on these markers. There was, however, a significantly increased prevalence of microalbuminuria (MA) among children in the amalgam group in years 3-5 (adjusted odds ratio 1.8; 95% confidence interval, 1.1-2.9). Most of these cases are likely to be temporary MA, but 10 children in the amalgam group had MA in both years 3 and 5, versus 2 children in the composite group (p = 0.04). There were no differences in the occurrence of high levels of renal tubular markers (A1M, gamma-GT, or NAG). CONCLUSIONS: The increase in MA may be a random finding, but should be tested further. The results did not support recent findings in an observational study of an effect of low-level mercury on tubular biomarkers in children.
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| 9. |
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| 10. |
- Bonde, Jens Peter, et al.
(författare)
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Fertility and markers of male reproductive function in Inuit and European populations spanning large contrasts in blood levels of persistent organochlorines
- 2008
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 116:3, s. 269-277
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: We synthesized the main findings from an international epidemiologic study on the impact of biopersistent organic pollutants (POPs) on human reproductive function. DATA SOURCES AND EXTRACTION: We used a database with interview and biological data from 2,269 women and their spouses, and 18 published core papers. DATA SYNTHESIS: The study did not provide direct evidence of hormone-like activity of the polychlorinated biphenyl (PCB) congener CB-153 and the main dichlorodiphenyltrichloroethane (DDT) metabolite, 1 1 1 -dichloro-2,2-bis (p-chlorophenyl) ethylene (p,p'-DDE), as serum concentrations of these compounds were not consistently related to either endogenous or exogenous hormone activity in serum. Nevertheless several links bewteen POP exposure and biomarkers of male reproductive function were identified. First, an association between high CB-153 serum levels and low sperm counts was detected within a subgroup of men with short androgen receptor CAG repeat length. Second, a relationship between increased CB-153 serum concentrations and decreased sperm motility was seen in all four studied regions, and indications of reduced neutral alpha-glucosidase activity in seminal plasma point to a post-testicular effect. Third, damage of sperm chromatin integrity was considerably less frequent in Greenlandic Inuits compared with that in European groups, and only in the latter was impairment of sperm chromatin integrity related to POPs. Despite these effects, fertility in terms of time taken to conceive was not related to POPs except in Inuits. A likely explanation of the latter was not identified. CONCLUSIONS: POPs may interfere with male reproductive function without major impact on fertility. The data do not provide direct evidence for endocrine disruption, hence other mechanisms should also be considered.
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