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  • Barregård, Lars, 1948, et al. (författare)
  • Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
  • 2013
  • Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert, Inc.. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
  • Bornehag, Carl Gustaf, et al. (författare)
  • Association of Prenatal Phthalate Exposure with Language Development in Early Childhood
  • 2018
  • Ingår i: JAMA Pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 172:12, s. 1169-1176
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Prenatal exposure to phthalates has been associated with neurodevelopmental outcomes, but little is known about the association with language development. Objective: To examine the association of prenatal phthalate exposure with language development in children in 2 population-based pregnancy cohort studies. Design, Setting, and Participants: Data for this study were obtained from the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study conducted in prenatal clinics throughout Värmland county in Sweden and The Infant Development and the Environment Study (TIDES) conducted in 4 academic centers in the United States. Participants recruited into both studies were women in their first trimester of pregnancy who had literacy in Swedish (SELMA) or English or Spanish (TIDES). This study included mothers and their children from both the SELMA study (n = 963) and TIDES (n = 370) who had complete data on prenatal urinary phthalate metabolite levels, language delay, and modeled covariables. For SELMA, the data were collected from November 1, 2007, to June 30, 2013, and data analysis was conducted from November 1, 2016, to June 30, 2018. For TIDES, data collection began January 1, 2010, and ended March 29, 2016, and data analysis was performed from September 15, 2016, to June 30, 2018. Main Outcomes and Measures: Mothers completed a language development questionnaire that asked the number of words their children could understand or use at a median of 30 months of age (SELMA) and 37 months of age (TIDES). The responses were categorized as fewer than 25, 25 to 50, and more than 50 words, with 50 words or fewer classified as language delay. Results: In the SELMA study, 963 mothers, 455 (47.2%) girls, and 508 [52.8%] boys were included. In TIDES, 370 mothers, 185 (50.0%) girls, and 185 (50.0%) boys were included in this analysis. The prevalence of language delay was 10.0% in both SELMA (96 reported) and TIDES (37 reported), with higher rates of delay in boys than girls (SELMA: 69 [13.5%] vs 27 [6.0%]; TIDES: 12 [12.4%] vs 14 [7.6%]). In crude analyses, the metabolite levels of dibutyl phthalate and butyl benzyl phthalate were statistically significantly associated with language delay in both cohorts. In adjusted analyses, a doubling of prenatal exposure of dibutyl phthalate and butyl benzyl phthalate metabolites increased the odds ratio (OR) for language delay by approximately 25% to 40%, with statistically significant results in the SELMA study (dibutyl phthalate OR, 1.29 [95% CI, 1.03-1.63; P =.03]; butyl benzyl phthalate OR, 1.26 [95% CI, 1.07-1.49; P =.003]). A doubling of prenatal monoethyl phthalate exposure was associated with an approximately 15% increase in the OR for language delay in the SELMA study (OR, 1.14; 95% CI, 1.00-1.31; P =.05), but no such association was found in TIDES (OR, 0.98; 95% CI, 0.79-1.23). Conclusions and Relevance: In findings from this study, prenatal exposure to dibutyl phthalate and butyl benzyl phthalate was statistically significantly associated with language delay in children in both the SELMA study and TIDES. These findings, along with the prevalence of prenatal exposure to phthalates, the importance of language development, and the inconsistent results from a 2017 Danish study, suggest that the association of phthalates with language delay may warrant further examination.
  • Alhamdow, A., et al. (författare)
  • Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
  • 2020
  • Ingår i: Occupational and Environmental Medicine. - : BMJ Publishing Group Ltd. - 1351-0711 .- 1470-7926. ; 77:7, s. 488-495
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers. Methods We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation ofF2RL3andAHRRusing pyrosequencing. Results Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). n-ary sumation OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation ofF2RL3andAHRRin chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) forF2RL3_cg03636183, and -7.1 (-9.6 to -4.7) forAHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, n-ary sumation OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation ofAHRRCpG2. Conclusions Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation ofF2RL3andAHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.
  • Weiss, Jana M., et al. (författare)
  • Daily intake of phthalates, MEHP, and DINCH by ingestion and inhalation
  • 2018
  • Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 208, s. 40-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Phthalate esters, suspected endocrine disrupting chemicals, are used in a wide range of applications. Because phthalate esters are not covalently bound, they can easily leach into the indoor environment and associate to dust particles. Thus, exposure may occur through inhalation, ingestion, or contact with the skin. However, it is unclear to what degree indoor dust contributes to the daily intake of phthalate esters.This study investigates household dust as an exposure pathway for seven phthalate esters, the monoester MEHP, and the plasticizer DINCH. Household dust collected from children's sleeping rooms and from living rooms were analysed using gas and liquid chromatography tandem mass spectrometry. To compare two exposure pathways, different dust particle sizes were generated: a respirable fraction (<5 mu m) and an ingested particle fraction in the anticipated size range of skin adherence (<75 mu m). Modelling of dust inhalation and ingestion showed that the daily intake of dust-bound phthalate esters was likely to be 2 times (inhalation) to 12 times (ingestion) higher for 21-month-old children than for adults. These children's daily uptake of phthalate esters was 40-140 times higher through ingestion than inhalation. Furthermore, dust may be an exposure pathway for phthalate esters as well as for MEHP. Therefore, phthalate monoesters could be environmental contaminants of their own and need to be considered in health risk assessments. (C) 2018 Elsevier Ltd. All rights reserved.
  • Ali, Neserin, et al. (författare)
  • Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.
  • 2016
  • Ingår i: Nanotoxicology. - : Informa Healthcare. - 1743-5404 .- 1743-5390. ; 10:2, s. 226-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
  • Bornehag, Carl-Gustaf, 1957-, et al. (författare)
  • Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys
  • 2015
  • Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 123:1, s. 101-107
  • 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.
  • Derakhshan, A., et al. (författare)
  • Association of urinary bisphenols and triclosan with thyroid function during early pregnancy
  • 2019
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 133
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Bisphenols and triclosan are considered as potential thyroid disruptors. While mild alterations in maternal thyroid function can result in adverse pregnancy and child developmental outcomes, there is still uncertainty whether bisphenols or triclosan can interfere with thyroid function during pregnancy. Objectives: We aimed to investigate the association of urinary bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF) and triclosan with early pregnancy thyroid function. Methods: This study was embedded in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA), a population-based prospective pregnancy cohort. In total, 1996 participants were included in the current study. Maternal urinary concentrations of three bisphenols and triclosan, collected at median (95% range) 10 (6–14) weeks of pregnancy as well as serum concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were measured. Results: Higher BPA levels were associated with lower TT4 concentrations (non-monotonic, P = 0.03), a lower FT4/FT3 ratio (β [SE] -0.02 [0.01], P = 0.03) and a lower TT4/TT3 ratio (β [SE] -0.73 [0.27], P = 0.008). Higher BPF levels were associated with a higher FT3 (β [SE] 0.01 [0.007], P = 0.04). There were no associations between other bisphenols or triclosan and absolute TSH, (F)T4 or (F)T3 concentrations. The association of BPA with thyroid function differed with gestational age. The negative association of BPA with FT4/FT3 and TT4/TT3 ratios was only apparent in early but not late gestation (P for interaction: 0.003, 0.008, respectively). Conclusion: These human data during pregnancy substantiate experimental findings suggesting that BPA could potentially affect thyroid function and deiodinase activities in early gestation.
  • Larsson, Kristin, et al. (författare)
  • Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children.
  • 2014
  • Ingår i: Environment International. - : Elsevier. - 1873-6750 .- 0160-4120. ; 73, s. 323-333
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood. The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6-11years old) and investigate potential predictors of the exposure. Urine samples from 98 mother-child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors. There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5μg/L; ΣDiNP 37.8μg/L; MBzP 19.9μg/L; MnBP 76.9μg/L) than the mothers (ΣDEHP 38.4μg/L; ΣDiNP 33.8μg/L; MBzP 12.8μg/L; MnBP 63.0μg/L). Conversely, the mother's levels of parabens (MetP 37.8μg/L; ProP 13.9μg/L) and MEP (43.4μg/L) were higher than the children's levels of parabens (MetP 6.8μg/L; ProP 2.1μg/L) and MEP (28.8μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p=<0.001; MnBP p=0.001-0.002), which is probably due to higher presence of PVC in floorings and wall coverings in this area, whereas the levels of parabens were higher among the children in the urban area (MetP p=0.003; ProP p=0.004) than in the rural area. The levels of high molecular weight phthalates were associated with consumption of certain foods (i.e. chocolate and ice cream) whereas the levels of parabens were associated with use of cosmetics and personal care products.
  • Li, Ying, et al. (författare)
  • Half-lives of PFOS, PFHxS and PFOA after end of exposure to contaminated drinking water
  • 2018
  • Ingår i: Occupational and Environmental Medicine. - : BMJ Publishing Group. - 1470-7926 .- 1351-0711. ; 75:1, s. 46-51
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Municipal drinking water contaminated with perfluorinated alkyl acids had been distributed to one-third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from 16 December 2013.OBJECTIVE: To determine the rates of decline in serum perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), and their corresponding half-lives.METHODS: Up to seven blood samples were collected between June 2014 and September 2016 from 106 participants (age 4-84 years, 53% female).RESULTS: Median initial serum concentrations were PFHxS, 277 ng/mL (range 12-1660); PFOS, 345 ng/mL (range 24-1500); and PFOA, 18 ng/mL (range 2.4-92). The covariate-adjusted average rates of decrease in serum were PFHxS, 13% per year (95% CI 12% to 15%); PFOS, 20% per year (95% CI 19% to 22%); and PFOA, 26% per year (95% CI 24% to 28%). The observed data are consistent with a first-order elimination model. The mean estimated half-life was 5.3 years (95% CI 4.6 to 6.0) for PFHxS, 3.4 years (95% CI 3.1 to 3.7) for PFOS and 2.7 years (95% CI 2.5 to 2.9) for PFOA. The interindividual variation of half-life was around threefold when comparing the 5th and 95th percentiles. There was a marked sex difference with more rapid elimination in women for PFHxS and PFOS, but only marginally for PFOA.CONCLUSIONS: The estimated half-life for PFHxS was considerably longer than for PFOS and PFOA. For PFHxS and PFOS, the average half-life is shorter than the previously published estimates. For PFOA the half-life is in line with the range of published estimates.
  • Opstal-van Winden, Annemieke W. J., et al. (författare)
  • Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
  • 2011
  • Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort. Methods: In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS). Results: Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3a(desArg)), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3a(desArg) and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer. Conclusions: We show that serum protein profiles are already altered up to three years before breast cancer detection.
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