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| 2. |
- Bui, Thuy T., et al.
(author)
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Estimating uptake of phthalate ester metabolites into the human nail plate using pharmacokinetic modelling
- 2017
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 100, s. 148-155
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Journal article (peer-reviewed)abstract
- There is a lack of knowledge regarding uptake of phthalate esters (PEs) and other chemicals into the human nail plate and thus, clarity concerning the suitability of human nails as a valid alternative matrix for monitoring longterm exposure. In particular, the relative importance of internal uptake of phthalate metabolites (from e.g. blood) compared to external uptake pathways is unknown. This study provides first insights into the partitioning of phthalate-metabolites between blood and nail using pharmacokinetic (PK) modelling and biomonitoring data from a Norwegian cohort. A previously published PK model (Lorber PK model) was used in combination with measured urine data to predict serum concentrations of DEHP and DnBP/DiBP metabolites at steady state. Then, partitioning between blood and nail was assessed assuming equilibrium conditions and treating the nail plate as a tissue, assuming a fixed lipid and water content. Although calculated as a worst-case scenario at equilibrium, the predicted nail concentrations of metabolites were lower than the biomonitoring data by factors of 44 to 1300 depending on the metabolite. It is therefore concluded that internal uptake of phthalate metabolites from blood into nail is a negligible pathway and does not explain the observed nail concentrations. Ingtead, external uptake pathways are more likely to dominate, possibly through deposition of phthalates onto the skin/nail and subsequent metabolism. Modelling gaseous diffusive uptake of PEs from air to nail revealed that this pathway is unlikely to be important. Experimental quantification of internal and external uptake pathways of phthalates and their metabolites into the human nail plate is needed to verify these modelling results. However, based on this model, human nails are not a good indicator of internal human exposure for the phthalate esters studied.
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| 3. |
- Chen, Yiqin, et al.
(author)
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Persistent organic pollutants in infants and toddlers : Relationship between concentrations in matched plasma and faecal samples
- 2017
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 107, s. 82-88
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Journal article (peer-reviewed)abstract
- Early-childhood biomonitoring of persistent organic pollutants (POPs) is challenging due to the logistic and ethical limitations associated with blood sampling. We investigated using faeces as a non-invasive matrix to estimate internal exposure to POPs. The concentrations of selected POPs were measured in matched plasma and faecal samples collected from 20 infants/toddlers (aged 13 +/- 4.8 months), including a repeat sample time point for 13 infants (similar to 5 months apart). We observed higher rates of POP quantification in faeces (2 g dry weight) than in plasma (0.5 mL). Among the five chemicals that had quantification frequencies over 50% in both matrices, except for HCB, log concentration in faeces (C-f) and blood (C-b) were correlated (r > 0.74, P < 0.05) for p.p'-dichlorodiphenyldichloroethylene (p,p'-DDE), 2,3', 4,4', 5-pentachlorobiphenyl (PCB118), 2,2', 3,4,4', 5'-pentachlorobiphenyl (PCB138) and 2,2', 4,4', 5,5'-pentachlorobiphenyl (PCB153). We determined faeces: plasma concentration ratios (K-fb), which can be used to estimate C-b from measurements of C-f for infants/toddlers. For a given chemical, the variation in K-fb across individuals was considerable (CV from 0.46 to 0.70). Between 5% and 50% of this variation was attributed to short-term intra-individual variability between successive faecal samples. This variability could be reduced by pooling faeces samples over several days. Some of the remaining variability was attributed to longer-term intra-individual variability, which was consistent with previously reported observations of a decrease in K-fb over the first year of life. The strong correlations between C-f and C-b demonstrate the promise of using faeces for biomonitoring of these compounds. Future research on the sources of variability in K-fb could improve the precision and utility of this technique.
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| 4. |
- Choi, Hyunok, et al.
(author)
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Volatile organic compounds of possible microbial origin and their risks on childhood asthma and allergies within damp homes
- 2017
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 98, s. 143-151
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Journal article (peer-reviewed)abstract
- Background Risk of indoor exposure to volatile organic compounds of purported microbial origin on childhood symptoms of wheezing, rhinitis, and/or eczema, and doctor-diagnosed asthma, rhinitis, and eczema, respectively, remain unclear. Objective To test hypotheses that total sum of 28 microbial volatile organic compounds (Σ26 MVOCs): 1) poses independent risk on doctor-diagnosed asthma, rhinitis, and eczema, respectively, as well as multiple symptom presentation with a minimum of the two of the above conditions (i.e. case); 2) is associated with significant interaction with absolute humidity (AH) on additive scale. Methods In a case-control investigation, 198 cases and 202 controls were examined during November 2001 – March 2002 period through home indoor air sampling, air quality inspection, and health outcome ascertainment. Results Not only the Σ28 MVOCs but also the global MVOC index were significantly higher within the homes of the cases with a high AH, compared to the controls with a low AH (all Ps < 0.001). Only the cases, but not the controls, were associated with a dose-dependent increase in the exposure variables of interest (Σ28 MVOCs) per quartile increase in AH (P < 0.0001 for the cases; P = 0.780 for the controls). Only among the children who live in a high AH homes, a natural log (ln)-unit of Σ 28 MVOCs was associated with 2.5-times greater odds of the case status (95% CI, 1.0–6.2; P = 0.046), compared to 0.7-times the odds (95% CI, 0.4–1.0; P = 0.074) of the same outcome among the low AH homes. Specifically, joint exposure to a high MVOCs and high AH was associated with 2.6-times greater odds of the doctor-diagnosed asthma status (95% CI, 0.7–8.91; P = 0.137). Conclusion Joint occurrence of high Σ28 MVOCs and AH was associated with a significant increase in the case status and asthma risks in an additive scale.
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| 5. |
- Gomis, Melissa I., et al.
(author)
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Historical human exposure to perfluoroalkyl acids in the United States and Australia reconstructed from biomonitoring data using population-based pharmacokinetic modelling
- 2017
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 108, s. 92-102
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Journal article (peer-reviewed)abstract
- Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) are found in the blood of humans and wildlife worldwide. Since the beginning of the 21st century, a downward trend in the human body burden, especially for PFOS and PFOA, has been observed while there is no clear temporal trend in wildlife. The inconsistency between the concentration decline in human serum and in wildlife could be indicative of a historical exposure pathway for humans linked to consumer products that has been reduced or eliminated. In this study, we reconstruct the past human exposure trends in two different regions, USA and Australia, by inferring the historical intake from cross-sectional biomonitoring data of PFOS, PFOA and PFHxS using a population-based pharmacokinetic model. For PFOS in the USA, the reconstructed daily intake peaked at 4.5 ng/kg-bw/day between 1988 and 1999 while in Australia it peaked at 4.0 ng/kg-bw/day between 1984 and 1996. For PFOA in the USA and Australia, the peak reconstructed daily intake was 1.1 ng/kg-bw/day in 1995 and 3.6 ng/kg-bw/day in 1992, respectively, and started to decline in 2000 and 1995, respectively. The model could not be satisfactorily fitted to the biomonitoring data for PFHxS within reasonable boundaries for its intrinsic elimination half-life, and thus reconstructing intakes of PFHxS was not possible. Our results indicate that humans experienced similar exposure levels and trends to PFOS and PFOA in the USA and Australia. Our findings support the hypothesis that near-field consumer product exposure pathways were likely dominant prior to the phase-out in industrialized countries. The intrinsic elimination half-life, which represents elimination processes that are common for all humans, and elimination processes unique to women (i.e., menstruation, cord-blood transfer and breastfeeding) were also investigated. The intrinsic elimination half-lives for PFOS and PFOA derived from model fitting for men were 3.8 and 2.4 years, respectively, for the USA, and 4.9 and 2 years respectively for Australia. Our results show that menstruation is a depuration pathway for PFOA for women, similarly but to a lesser extent compared to previous reports for PFOS. However menstruation, cord-blood transfer and breastfeeding together do not fully explain the apparently more rapid elimination of PFOA and PFOS by women compared to men; the intrinsic elimination half-lives in women were up to 13% lower for PFOS and up to 12% lower for PFOA compared to the corresponding half-lives in men.
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| 6. |
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| 7. |
- Larsson, Kristin, et al.
(author)
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Phthalates, non-phthalate plasticizers and bisphenols in Swedish preschool dust in relation to children's exposure
- 2017
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 102, s. 114-124
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Journal article (peer-reviewed)abstract
- Children are exposed to a wide range of chemicals in their everyday environments, including the preschool. In this study, we evaluated the levels of phthalates, non-phthalate plasticizers and bisphenols in dust from 100 Swedish preschools and identified important exposure factors in the indoor environment. In addition, children's total exposure to these chemicals was determined by urine analysis to investigate their relation with dust exposure, and to explore the time trends by comparing with children who provided urine fifteen years earlier. The most abundant plasticizers in preschool dust were the phthalates di-isononyl phthalate (DiNP) and di-(2-ethylhexyl) phthalate (DEHP) with geometric mean levels of 450 and 266. μg/g dust, respectively, and the non-phthalate plasticizers bis(2-ethylhexyl) terephthalate (DEHT) and diisononylcyclohexane-1,2-dicarboxylate (DiNCH) found at 105 and 73. μg/g dust, respectively. The levels of several substitute plasticizers were higher in newer preschools, whereas the levels of the strictly regulated phthalate di-n-butyl phthalate (DnBP) were higher in older preschools. The presence of foam mattresses and PVC flooring in the sampling room were associated with higher levels of DiNP in dust. Children's exposure from preschool dust ingestion was below established health based reference values and the estimated exposure to different phthalates and BPA via preschool dust ingestion accounted for 2-27% of the total exposure. We found significantly lower urinary levels of BPA and metabolites of strictly regulated phthalates, but higher levels of DiNP metabolites, in urine from the children in this study compared to the children who provided urine samples fifteen years earlier.
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| 8. |
- Lind, Lars, et al.
(author)
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Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample
- 2017
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In: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 98, s. 212-218
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Journal article (peer-reviewed)abstract
- Objectives: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p, p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.Results: Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allelewas 192 ng/g lipid (p= 1.5x10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19: 41520351; p= 2.2 x 10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p= 6.2 x 10(-9)) located 7 kb downstreamthe CYP2B6 gene (cg27089200, position chr19: 41531976). This CpG-sitewas also related to the lead SNP (p = 3.8 x 10(-35)), but mediated only 4% of the effect of the lead SNP on p, p'-DDE levels.Conclusion: Circulating levels of p, p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p, p'-DDE levels.
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| 9. |
- Lind, Lars, et al.
(author)
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Mixture effects of 30 environmental contaminants on incident metabolic syndrome : A prospective study
- 2017
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 107, s. 8-15
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Journal article (peer-reviewed)abstract
- Background: Several cross-sectional studies have linked different environmental contaminants to the metabolic syndrome (MetS). However, mixture effects have not been investigated and no prospective studies exist regarding environmental contaminants and the MetS.Objectives: To study mixture effects of contaminants on the risk of incident MetS in a prospective fashion.Methods: Our sample consisted of 452 subjects from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years) free from the MetS at baseline, being followed for 10 years. At baseline, 30 different environmental contaminants were measured; 6 polychlorinated biphenyls (PCBs), 3 organochlorine (OC) pesticides, one dioxin, one polybrominated diphenyl ether (all in plasma), 8 perfluoroalkyl substances (in plasma) and 11 metals (in whole blood). The MetS was defined by the ATPIII/NCEP criteria. Gradient boosted Classification and Regression Trees (CARTs) was used to evaluate potential synergistic and additive mixture effects on incident MetS.Results: During 10-year follow-up, 92 incident cases of the MetS occurred. PCB126, PCB170, hexachlorobenzene (HCB) and PCB118 levels were all associated with incident MetS in an additive fashion (OR 1.73 for a change from 10th to 90th percentile (95% CI 1.24-3.04) for PCB126, OR 0.63 (0.42-0.78) for PCB170, OR 1.44 (1.09-2.20) for HCB and OR 1.46 (1.13-2.43) for PCB118). No synergistic effects were found.Conclusion: A mixture of environmental contaminants, with PCB126, PCB170, HCB and PCB118 being the most important, showed associations with future development of the MetS in an additive fashion in this prospective study. Thus, mixture effects of environmental contaminants could contribute to the development of cardiometabolic derangements.
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| 10. |
- Ljunggren, Stefan, et al.
(author)
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Alterations in high-density lipoprotein proteome and function associated with persistent organic pollutants
- 2017
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In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 98, s. 204-211
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Journal article (peer-reviewed)abstract
- There is a growing body of evidence that persistent organic pollutants (POPs) may increase the risk for cardiovascular disease (CVD), but the mechanisms remain unclear. High- density lipoprotein (HDL) acts protective against CVD by different processes, andwe have earlier found that HDL from subjects with CVD contains higher levels of POPs than healthy controls. In the present study, we have expanded analyses on the same individuals living in a contaminated community and investigated the relationship between the HDL POP levels and protein composition/ function. HDL from17 subjectswas isolated by ultracentrifugation. HDL protein composition, using nanoliquid chromatography tandemmass spectrometry, and antioxidant activity were analyzed. The associations of 16 POPs, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, with HDL proteins/functionswere investigated by partial least square and multiple linear regression analysis. Proteomic analyses identified 118 HDL proteins, of which ten were significantly (p b 0.05) and positively associated with the combined level of POPs or with highly chlorinated PCB congeners. Among these, cholesteryl ester transfer protein and phospholipid transfer protein, as well as the inflammatory marker serum amyloid A, were found. The serum paraoxonase/arylesterase 1 activity was inversely associated with POPs. Pathway analysis demonstrated that up- regulated proteinswere associatedwith biological processes involving lipoproteinmetabolism, while down- regulated proteinswere associatedwith processes such as negative regulation of proteinases, acute phase response, platelet degranulation, and complement activation. These results indicate an association between POP levels, especially highly chlorinated PCBs, and HDL protein alterations that may result in a less functional particle. Further studies are needed to determine causality and the importance of other environmental factors. Nevertheless, this study provides a first insight into a possible link between exposure to POPs and risk of CVD.
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