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1.
  • Opstal-van Winden, Annemieke W. J., et al. (author)
  • Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
  • 2011
  • In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
  • Journal article (peer-reviewed)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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2.
  • Barregård, Lars, 1948, et al. (author)
  • Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
  • 2013
  • In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
  • Journal article (peer-reviewed)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.
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3.
  • Lyngso, J., et al. (author)
  • Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study
  • 2014
  • In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 29:2, s. 359-367
  • Journal article (peer-reviewed)abstract
    • Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: 24 days, long cycle: 32 days) and irregularities (7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95 confidence intervals (CIs). Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95 CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95 CI: 0.8; 3.5)]. The overall response rate was 45.3 with considerable variation between countries (91.3 in Greenland, 69.1 in Poland and 26.3 in Ukraine). Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), . The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study () supported by the European Commissions 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.
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4.
  • Thomsen, Anne Marie L., et al. (author)
  • Female exposure to phthalates and time to pregnancy : A first pregnancy planner study
  • 2017
  • In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 32:1, s. 232-238
  • Journal article (peer-reviewed)abstract
    • STUDY QUESTION Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)? SUMMARY ANSWER Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP) was associated with a longer TTP. WHAT IS KNOWN ALREADY Male exposure to phthalates is potentially associated with adverse effects on human fecundity in epidemiological studies, but little is known about the potential effects on female reproduction. STUDY DESIGN SIZE AND DURATION A cohort study with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort. PARTICIPANTS/MATERIALS, SETTING AND METHODS We analyzed MEP, MBP, MBzP and MEHP in female morning spot urine samples collected daily during the first 10 days of menstrual cycles after discontinuation of contraception. The exposure assessment was based on the mean of two measurements from each woman collected in a period of 6 menstrual cycles. We used Cox regression with discrete time to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol. MAIN RESULT AND ROLE OF CHANCE Urinary concentration of MEP was associated with a decreased fecundity (adjusted FR 0.79; 95% CI: 0.63; 0.99) corresponding to a 21% decreased probability of conception for each natural log (ln) unit increase in MEP. No significant association with TTP was found for MBP, MBzP and MEHP. LIMITATIONS REASONS FOR CAUTION Subfertile women were overrepresented in the study population due to exclusion of 77 high fertile women who became pregnant in the first cycle when urine collection began. WIDER IMPLICATIONS OF THE FINDINGS Our results suggest that female exposure to MEP may have an adverse effect on female fecundity, but these findings need to be replicated in a larger and newer cohort study with sufficient exposure contrast if the use of diethyl phthalate (DEP) and thereby MEP in the future potentially should be regulated in cosmetics and industrial consumer products.
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5.
  • Bornehag, Carl-Gustaf, 1957-, et al. (author)
  • Association of Prenatal Phthalate Exposure with Language Development in Early Childhood
  • 2018
  • In: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 172:12, s. 1169-1176
  • Journal article (peer-reviewed)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.
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6.
  • Faniband, Moosa H., et al. (author)
  • Human experimental exposure to glyphosate and biomonitoring of young Swedish adults
  • 2021
  • In: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1438-4639. ; 231
  • Journal article (peer-reviewed)abstract
    • Glyphosate (GLY), N-(phosphonomethyl) glycine, is the most widely used herbicide in the world. It is a broad-spectrum herbicide, also used in crop desiccation. Agricultural workers may be occupationally exposed and general populations may be exposed to GLY mainly through diet. We studied the kinetics of GLY by measuring the parent compound and its metabolite aminomethylphosphonic acid (AMPA) in urine samples of three volunteers after an experimental oral exposure. We further examined GLY exposure by measuring GLY and AMPA in spot urine samples of 197 young adults in the general population in Scania, southern Sweden. Urine samples were analyzed using LC-MS/MS. In the experimental exposure, three healthy volunteers received an oral dose equivalent to 50% of the ADI for GLY. Urinary samples were collected up to 100 h after the exposure. The excretion of GLY to urine seemed to follow first-order kinetics and a two-phase excretion. The excretion half-life of GLY (density adjusted) was 6–9 h in the rapid phase and 18–33 h in the slower phase. The total dose recovered as unchanged GLY in the urine samples of volunteers was 1–6%. The metabolite AMPA was found to be 0.01–0.04% of the total dose of GLY. In the population of young adults, the median concentration was below 0.1 μg/L and a maximum concentration being 3.39 μg/L (density adjusted). AMPA was generally detected in lower concentrations (maximum = 0.99 μg/L). A moderate correlation (Spearman's ρ = 0.56) was observed between GLY and AMPA concentrations. Overall, the results may suggest that GLY and AMPA partly originate from separate exposures and that unchanged GLY is a more suitable biomarker of exposure.
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7.
  • Fuhrimann, Samuel, et al. (author)
  • Exposure to pesticides and health effects on farm owners and workers from conventional and organic agricultural farms in Costa Rica : Protocol for a cross-sectional study
  • 2019
  • In: JMIR Research Protocols. - : JMIR Publications Inc.. - 1929-0748. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Background: Pesticide use is increasing in low- and middle-income countries (LMICs) including Costa Rica. This increase poses health risks to farm owners, farm workers, and communities living near agricultural farms. Objective: We aimed to examine the health effects associated with occupational pesticide exposure in farm owners and workers from conventional and organic smallholder farms in Costa Rica. Methods: We conducted a cross-sectional study involving 300 owners and workers from organic and conventional horticultural smallholder farms in Zarcero County, Costa Rica. During the baseline study visit, we administered a structured, tablet-based questionnaire to collect data on sociodemographic characteristics, pesticide exposure, and health conditions (eg, respiratory and allergic outcomes and acute pesticide intoxication symptoms) and administered a neurobehavioral test battery (eg, Finger Tapping Test and Purdue Pegboard); we measured blood pressure, anthropometry (height, weight, and waist circumference), and erythrocytic acetylcholinesterase activity and also collected urine samples. In addition, a functional neuroimaging assessment using near-infrared spectroscopy was conducted with a subset of 50 study participants. During the follow-up study visit (~2-4 weeks after the baseline), we administered participants a short questionnaire on recent pesticide exposure and farming practices and collected hair, toenail, and urine samples. Urine samples will be analyzed for various pesticide metabolites, whereas toenails and hair will be analyzed for manganese (Mn), a biomarker of exposure to Mn-containing fungicides. Self-reported pesticide exposure data will be used to develop exposure intensity scores using an exposure algorithm. Furthermore, exposure-outcome associations will be examined using linear and logistic mixed-effects regression models. Results: Fieldwork for our study was conducted between May 2016 and August 2016. In total, 113 farm owners and 187 workers from 9 organic and 83 conventional horticultural smallholder farms were enrolled. Data analyses are ongoing and expected to be published between 2019 and 2020. Conclusions: This study is one of the first to examine differences in health effects due to pesticide exposure between farm owners and workers from organic and conventional smallholder farms in an LMIC. We expect that this study will provide critical data on farming practices, exposure pathways, and how occupational exposure to pesticides may affect farm owners and workers’ health. Finally, we hope that this study will allow us to identify strategies to reduce pesticide exposure in farm owners and workers and will potentially lay the groundwork for a future longitudinal study of health outcomes in farm owners and workers exposed to pesticides.
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8.
  • Lenters, Virissa, et al. (author)
  • Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts : Multi-pollutant models based on elastic net regression
  • 2016
  • In: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:3, s. 365-372
  • Journal article (peer-reviewed)abstract
    • Background: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´‑DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.
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9.
  • Mamsen, Linn Salto, et al. (author)
  • Concentration of perfluorinated compounds and cotinine in human foetal organs, placenta, and maternal plasma
  • 2017
  • In: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 596-597, s. 97-105
  • Journal article (peer-reviewed)abstract
    • Background Perfluoroalkyl substances (PFASs) are bio-accumulative pollutants, and prenatal exposure to PFASs is believed to impact human foetal development and may have long-term adverse health effects later in life. Additionally, maternal cigarette smoking may be associated with PFAS levels. Foetal exposure has previously been estimated from umbilical cord plasma, but the actual concentration in foetal organs has never been measured. Objectives The concentrations of 5 PFASs and cotinine – the primary metabolite of nicotine – were measured in human foetuses, placentas, and maternal plasma to evaluate to what extent these compounds were transferred from mother to foetus and to determine if the PFAS concentrations were associated with maternal cigarette smoking. Methods Thirty-nine Danish women who underwent legal termination of pregnancy before gestational week 12 were included; 24 maternal blood samples were obtained together with 34 placental samples and 108 foetal organs. PFASs and cotinine were assayed by liquid chromatography/triple quadrupole mass spectrometry. Results In foetal organs, the average concentrations of perfluorooctanesulphonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDa), and perfluorodecanoic acid (PFDA) were 0.6 ng/g, 0.2 ng/g, 0.1 ng/g, 0.1 ng/g, and 0.1 ng/g, respectively. A significant positive correlation was found between the exposure duration, defined as foetal age, and foetal to maternal ratio for all five PFASs and cotinine. Smokers presented 99 ng/g cotinine in plasma, 108 ng/g in placenta, and 61 ng/g in foetal organs. No correlation between the maternal cotinine concentrations and PFAS concentrations was found. Conclusions PFASs were transferred from mother to foetus, however, with different efficiencies. The concentrations of PFOS, PFOA, PFNA, PFUnDA, and PFDA in foetal organs were much lower than the maternal concentrations. Furthermore, a significant correlation between the exposure duration and all of the evaluated PFASs was found. The health-compromising concentrations of these substances during foetal development are unknown.
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10.
  • Rignell-Hydbom, Anna, et al. (author)
  • Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women
  • 2009
  • In: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 109:8, s. 991-996
  • Journal article (peer-reviewed)abstract
    • Environmental contaminants such as cadmium and persistent organochlorine pollutants have been proposed as risk factors of osteoporosis, and women may be at an increased risk. To assess associations between exposure to cadmium and two different POPs (2,2',4,4',5,5'-hexachlorobiphenyl CB-153, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene p,p'-DDE), on one hand, and bone effects, on the other, in a population-based study among postmenopausal (60-70 years) Swedish women with biobanked blood samples. The study included 908 women and was designed to have a large contrast of bone mineral densities, measured with a single photon absorptiometry technique in the non-dominant forearm. Biochemical markers related to bone metabolism were analyzed in serum. Exposure assessment was based on cadmium concentrations in erythrocytes and serum concentrations of CB-153 and p,p'-DDE. Cadmium was negatively associated with bone mineral density and parathyroid hormone, positively with the marker of bone resorption. However, this association disappeared after adjustment for smoking. The major DDT metabolite (p.p'-DDE) was positively associated with bone mineral density, an association which remained after adjustment for confounders, but the effect was weak. There was no evidence that the estrogenic congener (CB-153) was associated with any of the bone markers. In conclusion, no convincing associations were observed between cadmium and POPs, on one hand, and bone metabolism markers and BMD, on the other. (C) 2009 Elsevier Inc. All rights reserved.
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11.
  • Smit, L. A. M., et al. (author)
  • Prenatal exposure to environmental chemical contaminants and asthma and eczema in school-age children
  • 2015
  • In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 70:6, s. 653-660
  • Journal article (peer-reviewed)abstract
    • BackgroundEmerging evidence suggests that prenatal or early-life exposures to environmental contaminants may contribute to an increased risk of asthma and allergies in children. We aimed to the explore associations of prenatal exposures to a large set of environmental chemical contaminants with asthma and eczema in school-age children. MethodsWe studied 1024 mother-child pairs from Greenland and Ukraine from the INUENDO birth cohort. Data were collected by means of an interview-based questionnaire when the children were 5-9years of age. Questions from the ISAAC study were used to define asthma, eczema, and wheeze. We applied principal components analysis (PCA) to sixteen contaminants in maternal serum sampled during pregnancy, including perfluoroalkyl substances (PFASs), metabolites of diethylhexyl (DEHP) and diisononyl (DiNP) phthalates, PCB-153, and p,p-DDE. Scores of five principal components (PCs) explaining 70% of the variance were included in multiple logistic regression models. ResultsIn a meta-analysis that included both populations, the PC2 score, reflecting exposure to DiNP, was negatively associated with current eczema (OR 0.71, 95% CI 0.52-0.96). Other associations were not consistent between the two populations. In Ukrainian children, the PC3 score (DEHP) was positively associated with current wheeze (adjusted OR 1.56, 95% CI 1.03-2.37), whereas the PC5 score, dominated by perfluorooctanoic acid (PFOA), was inversely associated with current wheeze (OR 0.64, 0.41-0.99). In Greenlandic children, a negative association of PC4 (organochlorines) with ever eczema (OR 0.78, 0.61-0.99) was found. ConclusionsWe found limited evidence to support a link between prenatal exposure to environmental chemical contaminants and childhood asthma and eczema.
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12.
  • Alhamdow, Ayman, et al. (author)
  • Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
  • 2020
  • In: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 77:7, s. 488-495
  • Journal article (peer-reviewed)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.
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13.
  • Alhamdow, Ayman, et al. (author)
  • Low-level exposure to polycyclic aromatic hydrocarbons is associated with reduced lung function among Swedish young adults
  • 2021
  • In: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 197
  • Journal article (peer-reviewed)abstract
    • Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to adverse pulmonary effects. However, the impact of low-level environmental PAH exposure on lung function in early adulthood remains uncertain. Objectives: To evaluate the associations between urinary PAH metabolites and lung function parameters in young adults. Methods: Urinary metabolites of pyrene, phenanthrene, and fluorene were analysed in 1000 young adults from Sweden (age 22–25 years) using LC-MS/MS. Lung function and eosinophilic airway inflammation were measured by spirometry and exhaled nitric oxide fraction (FeNO), respectively. Linear regression analysis was used to evaluate associations between PAH metabolites and the outcomes. Results: Median urinary concentrations of 1-OH-pyrene, ∑OH-phenanthrene, and ∑OH-fluorene were 0.066, 0.36, 0.22 μg/L, respectively. We found inverse associations of ∑OH-phenanthrene and ∑OH-fluorene with FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC ratio (adjusted P < 0.05; all participants). An increase of 1% in ∑OH-fluorene was associated with a decrease of 73 mL in FEV1 and 59 mL in FVC. In addition, ∑OH-phenanthrene concentrations were, in a dose-response manner, inversely associated with FEV1 (B from −109 to −48 compared with the lowest quartile of ∑OH-phenanthrene; p trend 0.004) and FVC (B from −159 to −102 compared with lowest quartile; p-trend <0.001). Similar dose-response associations were also observed between ∑OH-fluorene and FEV1 and FVC, as well as between 1-OH-pyrene and FEV1/FVC (p-trend <0.05). There was no association between PAH exposure and FeNO, nor was there an interaction with smoking, sex, or asthma. Conclusion: Low-level PAH exposure was, in a dose-response manner, associated with reduced lung function in young adults. Our findings have public health implications due to i) the widespread occurrence of PAHs in the environment and ii) the clinical relevance of lung function in predicting all-cause and cardiovascular disease mortality.
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14.
  • Alhanti, Brooke, et al. (author)
  • Environmental exposures contribute to respiratory and allergic symptoms among women living in the banana growing regions of Costa Rica
  • 2022
  • In: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 79:7, s. 469-476
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: This research evaluates whether environmental exposures (pesticides and smoke) influence respiratory and allergic outcomes in women living in a tropical, agricultural environment. METHODS: We used data from 266 mothers from the Infants' Environmental Health cohort study in Costa Rica. We evaluated environmental exposures in women by measuring seven pesticide and two polycyclic aromatic hydrocarbons metabolites in urine samples. We defined 'high exposure' as having a metabolite value in the top 75th percentile. We collected survey data on respiratory and allergic outcomes in mothers as well as on pesticides and other environmental exposures. Using logistic regression models adjusted for obesity, we assessed the associations of pesticide exposure with multiple outcomes (wheeze, doctor-diagnosed asthma, high (≥2) asthma score based on symptoms, rhinitis, eczema and itchy rash). RESULTS: Current pesticide use in the home was positively associated with diagnosed asthma (OR=1.99 (95% CI=1.05 to 3.87)). High urinary levels of 5-hydroxythiabendazole (thiabendazole metabolite) and living in a neighbourhood with frequent smoke from waste burning were associated with a high asthma score (OR=1.84 (95%CI=1.05 to 3.25) and OR=2.31 (95%CI=1.11 to 5.16), respectively). Women who worked in agriculture had a significantly lower prevalence of rhinitis (0.19 (0.01 to 0.93)), but were more likely to report eczema (OR=2.54 (95%CI=1.33 to 4.89)) and an itchy rash (OR=3.17 (95%CI=1.24 to 7.73)). CONCLUSIONS: While limited by sample size, these findings suggest that environmental exposure to both pesticides and smoke may impact respiratory and skin-related allergic outcomes in women.
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15.
  • Ali, Neserin, et al. (author)
  • Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
  • 2018
  • In: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.
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16.
  • Anand-Ivell, Ravinder, et al. (author)
  • Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias, and phthalate load : A large case-control study
  • 2018
  • In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:APR
  • Journal article (peer-reviewed)abstract
    • The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccessibility. We have used a large national biobank of amniotic fluid samples collected at routine amniocentesis to determine the impacts of exogenous endocrine disruptor load on specific fetal biomarkers at this critical time. While adrenal and testicular steroids are highly correlated, they are also mostly positively influenced by increasing phthalate load, represented by the metabolites 7cx-MMeHP and 5cx-MEPP, by perfluorooctane sulfonate (PFOS) exposure, and by smoking, suggesting an adrenal stress response. In contrast, the testis specific biomarkers insulin-like peptide 3 (INSL3) and androstenedione are negatively impacted by the phthalate endocrine disruptors. Using a case-control design, we show that cryptorchidism and hypospadias are both significantly associated with increased amniotic concentration of INSL3 during gestational weeks 13-16, and some, though not all steroid biomarkers. Cases are also linked to a specifically increased variance in the Leydig cell biomarker INSL3 compared to controls, an effect exacerbated by maternal smoking. No influence of phthalate metabolites or PFOS was evident on the distribution of cases and controls. Considering that several animal and human studies have shown a negative impact of phthalate load on fetal and cord blood INSL3, respectively, the present results suggest that such endocrine disruptors may rather be altering the relative dynamics of testicular development and consequent hormone production, leading to a desynchronization of tissue organization during fetal development. Being born small for gestational age appears not to impact on the testicular biomarker INSL3 in second trimester amniotic fluid.
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17.
  • Andersen, Christina, et al. (author)
  • Inhalation and dermal uptake of particle and gas phase phthalates - A human chamber exposure study
  • 2018
  • In: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514
  • Conference paper (peer-reviewed)abstract
    • We have exposed sixteen test subjects to particle and gas phase phthalates in the controlled chamber exposure study. Deuterium labelled phthalates were used to generate particle D4-DEHP (di(2-ethylhexyl) phthalate) and gas phase D4-DEP (diethyl phthalate) for exposures scenarios allowed studying the dermal only and combined inhalational and dermal uptake. Metabolites were measured in urine samples before and after three hours of exposure. The inhalation was the dominant route of uptake for both DEHP and DEP in this study design and exposure settings. Larger uptake of DEP compared to DEHP both via inhalation and dermal uptake was observed. Dermal uptake of DEHP was not observed in this study. Inhalational urinary excretion factors of the metabolites were found to be 0.73 for DEHP and 0.53 for DEP. This study also highlights the importance of taking into consideration the deposited dose of inhaled particles in studies of uptake of particles.
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18.
  • Andersen, Christina, et al. (author)
  • Inhalation and Dermal Uptake of Particle and Gas-phase Phthalates - A Human Exposure Study
  • 2018
  • In: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 52:21, s. 12792-12800
  • Journal article (peer-reviewed)abstract
    • Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labelled airborne phthalates: particle-phase D4-DEHP (di-(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone, and combined inhalation+dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014±0.00088 (µg kg-1 bw)/(µg m-3)/h. No dermal uptake of D4-DEHP was observed during the 3 hour exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation+dermal was 0.0067±0.0045 and 0.00073±0.00051 (µg kg-1 bw)/(µg m-3)/h for dermal uptake. Urinary excretion factors of metabolites after inhalation were estimated to 0.69 for D4-DEHP and 0.50 for D4-DEP. Under the described settings, the main uptake of both phthalates was through inhalation. The results demonstrate the differences in uptake of gas and particles, and highlights the importance of considering the deposited dose in particle uptake studies.
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19.
  • Andersson, Axel G, et al. (author)
  • High Exposure to Perfluoroalkyl Substances and Antibody Responses to SARS-CoV-2 mRNA Vaccine-an Observational Study in Adults from Ronneby, Sweden.
  • 2023
  • In: Environmental health perspectives. - 1552-9924. ; 131:8
  • Journal article (peer-reviewed)abstract
    • Per- and polyfluoroalkyl substances (PFAS) are widely used, environmentally ubiquitous, and stable chemicals that have been associated with lower vaccine-induced antibody responses in children; however, data on adults are limited. The drinking water from one of the two waterworks in Ronneby, Sweden, was heavily contaminated for decades with PFAS from firefighting foams, primarily perfluorohexane sulfonic acid and perfluorooctanesulfonic acid (PFOS). Vaccination against SARS-CoV-2 offered a unique opportunity to investigate antibody responses to primary vaccination in adults who had been exposed to PFAS.Our objective was to evaluate associations between PFAS, across a wide range of exposure levels, and antibody responses in adults 5 wk and 6 months after a two-dose vaccination regime against SARS-CoV-2.Adults age 20-60 y from Ronneby (n=309, median PFOS serum level 47ng/mL, fifth to 95th percentile 4-213ng/mL) and a group with background exposure (n=47, median PFOS serum level 4ng/mL) received two doses of the Spikevax (Moderna) mRNA vaccine. The levels of seven PFAS were measured in serum before vaccination. Serum immunoglobulin G antibodies against the SARS-CoV-2 spike antigen (S-Abs) were measured before vaccination and at 5 wk (n=350) and 6 months (n=329) after the second vaccine dose. Linear regression analyses were fitted against current, historical, and prenatal exposure to PFAS, adjusting for sex, age, and smoking, excluding individuals with previous SARS-CoV-2-infection.PFAS exposure, regardless of how it was estimated, was not negatively associated with antibody levels 5 wk [current PFOS: -0.5% S-Abs/PFOS interquartile range (IQR); 95% confidence interval (CI): -8, 7] or 6 months (current PFOS: 3% S-Abs/PFOS IQR; 95% CI: -6, 12) after COVID-19 vaccination.Following a strict study protocol, rigorous study design, and few dropouts, we found no indication that PFAS exposure negatively affected antibody responses to COVID-19 mRNA vaccination for up to 6 months after vaccination. https://doi.org/10.1289/EHP11847.
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20.
  • Axelsson, Jonatan, et al. (author)
  • Association between paternal smoking at the time of pregnancy and the semen quality in sons
  • 2018
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11, s. 0207221-0207221
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Maternal smoking during pregnancy has repeatedly been associated with decreased sperm counts in sons. Nevertheless, our team recently detected a lower total sperm count in the sons of smoking fathers as compared to sons of non-smoking fathers. Since paternal and maternal tobacco smoking often coincide, it is difficult to discriminate whether effects are mediated paternally or maternally when using questionnaire- or register-based studies. Therefore, getting an objective measure of the maternal nicotine exposure level during pregnancy might help disentangling the impact of paternally and maternally derived exposure. OBJECTIVES: Our aim was to study how paternal smoking at the time of the pregnancy was associated with semen quality in the sons after adjusting for the maternal levels of nicotine exposure during pregnancy. METHODS: We recruited 104 men (17-20 years old) from the general Swedish population. The participants answered a questionnaire about paternal smoking. Associations between smoking and semen volume, total sperm count, sperm concentration, morphology and motility were adjusted for levels of the nicotine metabolite cotinine in stored maternal serum samples obtained from rubella screening between the 6th and 35th week of pregnancy. We additionally adjusted for the estimated socioeconomic status. RESULTS: After adjusting for the maternal cotinine, the men of smoking fathers had 41% lower sperm concentration and 51% lower total sperm count than the men of non-smoking fathers (p = 0.02 and 0.003, respectively). This was robust to the additional adjustment. CONCLUSIONS: Our results suggest a negative association between paternal smoking and sperm counts in the sons, independent of the level maternal nicotine exposure during the pregnancy.
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21.
  • Axelsson, Jonatan, et al. (author)
  • Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study
  • 2020
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism. METHOD: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression. RESULTS: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles. CONCLUSION: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons.
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22.
  • Axelsson, Jonatan, et al. (author)
  • Exposure to polycyclic aromatic hydrocarbons and nicotine, and associations with sperm DNA fragmentation
  • 2022
  • In: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 10:4, s. 740-748
  • Journal article (peer-reviewed)abstract
    • Background: Tobacco smoking has been reported to cause DNA fragmentation and has been suggested to cause mutations in spermatozoa. These effects have been ascribed to the action of polycyclic aromatic hydrocarbons (PAH) present in the smoke. Simultaneously, DNA fragmentation has been associated with mutagenesis. Objective: The aim of this study was to investigate whether levels of urinary biomarkers of PAH and nicotine exposure were associated with sperm DNA fragmentation. Methods: In the urine of 381 men recruited from two cohorts of young men (17–21 years old) from the general Swedish population, the PAH metabolites 1-hydroxypyrene and 2-hydroxyphenanthrene, as well as the nicotine metabolite cotinine, were measured. The sperm DNA fragmentation index (DFI) was analysed using the sperm chromatin structure assay. Associations between the DFI, and PAH metabolite levels as continuous variables as well as in quartiles, were studied by general linear models adjusted for abstinence time. A similar analysis was carried out for cotinine levels, according to which the men were categorised as “non-smoking” (n = 216) and “smoking” (n = 165). Results: No association was found between levels of any of the three biomarkers and DFI, either as a continuous variable (p = 0.87–0.99), or when comparing the lowest and the highest quartiles (p = 0.11–0.61). The same was true for comparison of men categorised as non-smoking or smoking (DFI 11.1% vs. 11.8%, p = 0.31). Discussion: We found no evidence of PAH or nicotine exposure to be associated with DFI, which does not exclude that these exposures may have other effects on sperm DNA. Conclusion: In these young men, levels of biomarkers of nicotine and PAH exposure were not associated with DFI.
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23.
  • Balatsouka, Dimitra, et al. (author)
  • The impact of nicotine on bone healing and osseointegration.
  • 2005
  • In: Clinical oral implants research. - : Wiley. - 0905-7161 .- 1600-0501. ; 16:3, s. 268-76
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To examine the short-term effect of nicotine on bone healing and osseointegration. MATERIAL AND METHODS: Sixteen female rabbits were divided into two groups. The test group was exposed to nicotine tartrate for 8 weeks and the control group was exposed to placebo. Nicotine or placebo was administered via a miniosmotic pump and plasma cotinine levels were measured weekly. The pump delivered 15 mg of nicotine/day for the animals in the test group. All rabbits had three tibial bone preparations. In the proximal and distal bone bed, implants were placed after 4 weeks (right tibia) and after 6 weeks (left tibia). Thus, 2- and 4-week healing groups were created. Removal torque test (RMT) was performed at the distal implants. Ground sections were made from the proximal and the central bone beds. The fraction of mineralized bone in contact to the implant (BIC) and the bone density within the implant threads (BD-i) were determined for the bone-implant specimens. For the central bone beds without implants the bone density (BD-c) in the bone defects was determined. RESULTS: No significant difference in RMT values was found between the test and the control group. Histomorphometric measurements of the BIC and the peri-implant BD-i showed no significant differences between the test and the control group after 2 or 4 weeks. Significant differences were, however, found between the 2- and 4-week samples. In the central bone beds, there was no significant difference in BD-c between the test and the control group. CONCLUSION: Nicotine exposure in a short period of time did not have a significant impact on bone healing or implant osseointegration in rabbits.
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24.
  • Barrón Cuenca, Jessika, et al. (author)
  • Pesticide exposure among Bolivian farmers : associations between worker protection and exposure biomarkers
  • 2019
  • In: Journal of Exposure Science and Environmental Epidemiology. - : Springer Science and Business Media LLC. - 1559-0631 .- 1559-064X.
  • Journal article (peer-reviewed)abstract
    • The use of pesticides has increased during the past decades, also increasing the risk of exposure to toxic pesticides that can cause detrimental health effects in the future. This is of special concern among farmers in low-to-middle-income countries that may lack proper training in the safe use of these chemicals. To assess the situation in Bolivia a cross-sectional study in three agricultural communities was performed (n = 297). Handling, use of personal protective equipment (PPE) and pesticide exposure were assessed by a questionnaire and measurements of urinary pesticide metabolites (UPMs). Results showed that methamidophos (65%) and paraquat (52%) were the most commonly used pesticides and that 75% of the farmers combined several pesticides while spraying. Notably, only 17% of the farmers used recommended PPEs while 84% reported to have experienced symptoms of acute pesticide poisoning after spraying. UPM measurements indicated high levels of exposure to chlorpyrifos, pyrethroids and 2,4D and that men generally were more highly exposed compared to women. Our study demonstrates that farmers who are better at following recommendations for pesticide handling and use of PPE had a significantly lower risk of having high UPM levels of most measured pesticides. Our results thus confirm the need of proper training of farmers in low-to-middle-income countries in proper protection and pesticide handling in order to reduce exposure levels and health problems.
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25.
  • Beck, Astrid L, et al. (author)
  • Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring : A prospective nested case-control study
  • 2024
  • In: International Journal of Cancer. - 0020-7136. ; 154:1, s. 71-80
  • Journal article (peer-reviewed)abstract
    • Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.
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26.
  • Benson, Thea Emily, et al. (author)
  • Urinary bisphenol a, f and s levels and semen quality in young adult danish men
  • 2021
  • In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:4
  • Journal article (peer-reviewed)abstract
    • Bisphenol A (BPA) is considered an endocrine disruptor and has been associated with deleterious effects on spermatogenesis and male fertility. Bisphenol F (BPF) and S (BPS) are struc-turally similar to BPA, but knowledge of their effects on male fertility remains limited. In this cross– sectional study, we investigated the associations between exposure to BPA, BPF, and BPS and semen quality in 556 men 18–20 years of age from the Fetal Programming of Semen Quality (FEPOS) cohort. A urine sample was collected from each participant for determination of BPA, BPF, and BPS concentrations while a semen sample was collected to determine ejaculate volume, sperm concen-tration, total sperm count, sperm motility, and sperm morphology. Associations between urinary bisphenol levels (continuous and quartile–divided) and semen characteristics were estimated using a negative binomial regression model adjusting for urine creatinine concentration, alcohol intake, smoking status, body mass index (BMI), fever, sexual abstinence time, maternal pre–pregnancy BMI, and first trimester smoking, and highest parental education during first trimester. We found no associations between urinary bisphenol of semen quality in a sample of young men from the general Danish population.
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27.
  • Berge, Trine L.L., et al. (author)
  • Bisphenol A in human saliva and urine before and after treatment with dental polymer-based restorative materials
  • 2019
  • In: European Journal of Oral Sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 127:5, s. 435-444
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to quantify bisphenol A (BPA) concentrations in saliva and urine before and after treatment with dental polymer-based restorative materials to assess if placement of this material is associated with increased BPA levels in saliva and urine. Twenty individuals in need of at least one dental restoration with polymer-based restorative material were included in this study. The participants were instructed to abstain from eating, drinking, and brushing their teeth for at least 10 h prior to sampling. Saliva and urine were collected before and 10 min (saliva only), 1 h, 24 h, and 1 wk after treatment. Samples were stored at −80°C before analyses. BPA in saliva and urine was determined with liquid chromatography/mass spectrometry. Linear mixed effects regression models were used for statistical analyses. There was a statistically significant increase of salivary BPA concentration directly after placement of the dental polymer-based restorations. Following placement, the concentration of BPA decreased exponentially with time. One week after treatment the BPA level in saliva was only marginally higher than before treatment. In urine, no statistically significant change of the BPA concentration was detected after treatment.
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28.
  • Bjermo, Helena, et al. (author)
  • Concentrations of phthalates and phenolic substances in urine from first-time mothers in Uppsala, Sweden: temporal trends 2009- 2018
  • 2019
  • Reports (other academic/artistic)abstract
    • Sedan 1996 samlas blod- och modersmjölksprover regelbundet in från förstföderskor i Uppsala i den så kallade POPUP-studien. Sedan 2009 tas också ett urinprov. I denna rapport har tidstrender för ftalater och fenolära ämnen studerats i urinprov insamlade mellan 2009 och 2018. Ftalater och fenolära ämnen metaboliseras relativt snabbt i kroppen och för flertalet är det därför en metabolit till själva huvudsubstansen som har analyserats.Totalt sett analyserades tolv metaboliter till sex ftalater, en metabolit till en ersättningskemikalie till ftalater, metaboliter till tre fosforbaserade flamskyddsmedel, två pesticidmetaboliter samt åtta fenolära ämnen, bland annat triclosan, bisfenol A, S och F. Analyserna utfördes av Lunds universitet. Syftet var att studera tidstrender för dessa olika ämnen under perioden 2009-2018.Resultaten visade en nedåtgående tidstrend för de ftalater som håller på att fasas ut samtidigt som metaboliten för en ersättare till ftalaterna ökade. Det omdiskuterade ämnet bisfenol A och triclosan visade nedåtgående trender medan en ersättningssubstans till bisfenol A, bisfenol F, snarare hade en omvänd u-formad kurva. Även en metabolit till insekticiden klorpyrifos minskade under perioden, möjligen som en konsekvens av att strängare gränsvärden införts i EU.Analyser av urin gör det möjligt att studera hur befolkningens exponering för snabbmetaboliserande substanser ser ut. Genom att analysera prover över tid kan man studera hur befolkningens exponering förändras efter att åtgärder för att begränsa vissa kemikalier satts in samt hur exponeringen för nya ersättningskemikalier utvecklas.
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29.
  • Bjorvang, Richelle D., et al. (author)
  • Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies
  • 2022
  • In: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 208
  • Journal article (peer-reviewed)abstract
    • Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21-43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linne Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Miillerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.
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30.
  • Bjorvang, Richelle D., et al. (author)
  • Persistent organic pollutants, pre-pregnancy use of combined oral contraceptives, age, and time-to-pregnancy in the SELMA cohort
  • 2020
  • In: Environmental Health. - : BMC. - 1476-069X. ; 19:1
  • Journal article (peer-reviewed)abstract
    • Background We are exposed to several chemicals such as persistent organic pollutants (POPs) in our everyday lives. Prior evidence has suggested that POPs may have adverse effects on reproductive function by disrupting hormone synthesis and metabolism. While there is age-related decline of fertility, the use of hormonal combined oral contraceptives (COCs) and its association to return of fertility remains controversial. The goal of this study is to investigate the association between exposure to POPs, both individually and as a mixture, and fecundability measured as time-to-pregnancy (TTP) according to pre-pregnancy use of COCs and age. Methods Using the SELMA (Swedish Environmental Longitudinal Mother and Child, Allergy and Asthma) study, we have identified 818 pregnant women aged 18-43 years (mean 29 years) with data on how long they tried to get pregnant and what was their most recently used contraceptive method. These data were collected at enrollment to the study (median week 10 of pregnancy). Concentrations of 22 POPs and cotinine were analyzed in the blood samples collected at the same time as the questions on TTP and pre-pregnancy use of contraceptive. Analyses were done on the association between POPs exposure and TTP measured as continuous (months) and binary (infertile for those with TTP > 12 months). To study the chemicals individually, Cox regression and logistic regression were used to estimate fecundability ratios (FRs) and odds ratios (ORs), respectively. Weighted quantile sum (WQS) regression was used to investigate the chemicals as a mixture where chemicals of concern were identified above the 7.6% threshold of equal weights. To perform the subgroup analysis, we stratified the sample according to use of COCs as the most recent pre-pregnancy contraception method and age (< 29 years, and >= 29 years). The models were adjusted for parity, regularity of menses, maternal body mass index (BMI) and smoking status, and stratified as described above. Results Prior to stratification, none of the POPs were associated with fecundability while increased exposure to HCB, PCB 74 and 118 had higher odds of infertility. Upon stratification, POP exposure was significantly associated with longer TTP in women aged >= 29 years who did not use COC. Specifically, PCBs 156, 180, 183, and 187 were associated with reduced fecundability while PCBs 99, 153, 156, 180, 183, and 187 had higher odds of infertility. As a mixture, we identified the chemicals of concern for a longer TTP include PCBs 118, 156, 183, and 187. Moreover, chemicals of concern identified with increased odds of infertility were PCB 74, 156, 183, 187, and transnonachlor. Conclusion Serum concentrations of selected POPs, both as individual chemicals and as a mixture, were significantly associated with lower fecundability and increased odds of infertility in women aged 29 years and above not using COC as their most recent pre-pregnancy contraceptive. Our findings suggest that pre-pregnancy use of oral contraceptive and age may modify the link between POPs and fecundability. The differences of specific chemicals in the individual analysis and as a mixture support the need to study combination effects of chemicals when evaluating reproductive outcomes.
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31.
  • Björvang, Richelle D., et al. (author)
  • Mixtures of persistent organic pollutants are found in vital organs of late gestation human fetuses
  • 2021
  • In: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 283
  • Journal article (peer-reviewed)abstract
    • Persistent organic pollutants (POPs) are industrial chemicals with long half-lives. Early life exposure to POPs has been associated with adverse effects. Fetal exposure is typically estimated based on concentrations in maternal serum or placenta and little is known on the actual fetal exposure. We measured the concentrations of nine organochlorine pesticides (OCPs), ten polychlorinated biphenyl (PCB) congeners, and polybrominated diphenyl ether (PBDE) congeners by gas chromatography – tandem mass spectrometry in maternal serum, placenta, and fetal tissues (adipose tissue, liver, heart, lung and brain) in 20 pregnancies that ended in stillbirth (gestational weeks 36–41). The data were combined with our earlier data on perfluoroalkyl substances (PFASs) in the same cohort (Mamsen et al. 2019). HCB, p,p’-DDE, PCB 138 and PCB 153 were quantified in all samples of maternal serum, placenta and fetal tissues. All 22 POPs were detected in all fetal adipose tissue samples, even in cases where they could not be detected in maternal serum or placenta. Tissue:serum ratios were significantly higher in later gestations, male fetuses, and pregnancies with normal placental function. OCPs showed the highest tissue:serum ratios and PFAS the lowest. The highest chemical burden was found in adipose tissue and lowest in the brain. Overall, all studied human fetuses were intrinsically exposed to mixtures of POPs. Tissue:serum ratios were significantly modified by gestational age, fetal sex and placental function. Importantly, more chemicals were detected in fetal tissues compared to maternal serum and placenta, implying that these proxy samples may provide a misleading picture of actual fetal exposures.
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32.
  • Björvang, Richelle D., et al. (author)
  • Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women
  • 2021
  • In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 155
  • Journal article (peer-reviewed)abstract
    • Industrial chemicals such as persistent organic pollutants (POPs) have been associated with reduced fertility in women, including longer time-to-pregnancy (TTP), higher odds for infertility, and earlier reproductive senescence. Fertility is highly dependent on the ovarian reserve, which is composed of a prenatally determined stock of non-growing follicles. The quantity and quality of the follicles decline with age, thereby eventually leading to menopause. In the clinical setting, assessing ovarian reserve directly through the histological analysis of follicular density in ovaries is not practical. Therefore, surrogate markers of ovarian reserve, such as serum anti-Müllerian hormone (AMH) are typically used. Here, we studied associations between chemical exposure and ovarian reserve in a cohort of pregnant women undergoing elective caesarean section (n = 145) in Stockholm, Sweden. Full data (histological, clinical, serum) were available for 50 women. We estimated the size of the reserve both directly by determining the density of follicles in ovarian cortical tissue samples, and indirectly by measuring AMH in associated serum samples. Concentrations of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenylethers (PBDEs) and 9 perfluoroalkyl substances (PFAS) were determined in serum, and clinical data were retrieved from electronic medical records. Healthy follicle densities (median 0, range 0–193 follicles/mm3) and AMH levels (median 2.33 ng/mL, range 0.1–14.8 ng/mL) varied substantially. AMH correlated with the density of growing follicles. Twenty-three chemicals detected in more than half of the samples were included in the analyses. None of the chemicals, alone or as a mixture, correlated with AMH, growing or atretic follicles. However, HCB, transnonachlor, PCBs 74 and 99 were associated with decreased non-growing follicle densities. HCB and transnonachlor were also negatively associated with healthy follicle density. Further, mixture of lipophilic POPs (PBDE 99, p,p’-DDE, and PCB 187) was associated with lower non-growing follicle densities. In addition, exposure to HCB, p,p’-DDE, and mixture of OCPs were significantly associated with higher odds of infertility. The results suggest that exposure to chemicals may reduce the size of ovarian reserve in humans, and strongly encourage to study mechanisms behind POP-associated infertility in women in more detail.
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33.
  • Bornehag, Carl-Gustaf, 1957-, et al. (author)
  • Prenatal Phthalate Exposures and Anogenital Distance in Swedish Boys
  • 2015
  • In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:1, s. 101-107
  • Journal article (peer-reviewed)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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34.
  • Caporale, N., et al. (author)
  • From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
  • 2022
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
  • Journal article (peer-reviewed)abstract
    • Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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35.
  • Conejo-Bolaños, L. Diego, et al. (author)
  • Prenatal current-use pesticide exposure and children's neurodevelopment at one year of age in the Infants' Environmental Health (ISA) birth cohort, Costa Rica
  • 2024
  • In: Environmental Research. - 0013-9351. ; 249
  • Journal article (peer-reviewed)abstract
    • Background: Pesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. Objective: We evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants’ Environmental Health (ISA) birth cohort. Methods: To determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1–3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). Results: We found higher prenatal urinary 2,4-D concentrations were associated with lower language (βper ten-fold increase = −2.0, 95 % confidence interval (CI) = −3.5, −0.5) and motor (βper ten-fold increase = −2.2, 95 %CI = −4.2, −0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (βper ten-fold increase = −1.9, 95 %CI = −4.7, 0.8), and lower motor composite scores among boys (βper ten-fold increase = −3.8, 95 % CI = −7.7, 0.1) but not girls (βper ten-fold increase = 2.3, 95 %CI = −1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. Discussion: Prenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.
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36.
  • Corrales Vargas, Andrea, et al. (author)
  • Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica
  • 2022
  • In: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 810
  • Journal article (peer-reviewed)abstract
    • Background: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. Objectives: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). Methods: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. Results: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: β = −0.79 (95%CI = −1.51, −0.08) and β = −0.29 (95%CI = −0.62, −0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (β = 0.04 (95%CI = 0.00, 0.07 per 1 μg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. Discussion: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.
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37.
  • De Loma, Jessica, et al. (author)
  • Arsenic exposure and biomarkers for oxidative stress and telomere length in indigenous populations in Bolivia
  • 2022
  • In: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 231
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Women living in the Bolivian Andes are environmentally exposed to arsenic, yet there is scarce information about arsenic-related effects in this region. Several biomarkers for telomere length and oxidative stress (mitochondrial DNA copy number, mtDNAcn; 8-Oxo-2'-deoxyguanosine, 8-oxo-dG; and 4-hydroxy nonenal mercapturic acid, 4-HNE-MA) have been previously linked to arsenic, and some of which are prospective biomarkers for cancer risk.OBJECTIVE AND HYPOTHESIS: To evaluate associations between arsenic exposure and telomere length, mtDNAcn, 8-oxo-dG, and 4-HNE-MA in Bolivians. Arsenic exposure was hypothesized to be positively associated with all four toxicity biomarkers, particularly in individuals with a less efficient arsenic metabolism.METHODS: The study encompassed 193 indigenous women. Arsenic exposure was assessed in urine as the sum of inorganic arsenic metabolite concentrations (U-As) measured by HPLC-HG-ICP-MS, and in whole blood as total arsenic (B-As) measured by ICP-MS. Efficiency of arsenic metabolism was evaluated by a polymorphism (rs3740393) in the main arsenic methylating gene AS3MT measured by TaqMan allelic discrimination, and by the relative fractions of urinary inorganic arsenic metabolites. Telomere length and mtDNAcn were determined in peripheral blood leukocytes by quantitative PCR, and urinary 8-oxo-dG and 4-HNE-MA by LC-MS/MS.RESULTS: U-As and B-As were associated with longer telomeres and higher mtDNAcn, particularly in women with a less efficient arsenic metabolism. Urinary 8-oxo-dG and 4-HNE-MA were positively associated with U-As, but only 4-HNE-MA was associated with B-As. Arsenic metabolism efficiency did not have a clear effect on the concentrations of either of these biomarkers.CONCLUSION: Bolivian women showed indications of arsenic toxicity, measured by four different biomarkers. Telomere length, mtDNAcn, and 4-HNE-MA were positively associated with both U-As and B-As. The association of arsenic exposure with telomere length and mtDNAcn was only present in Bolivian women with a less efficient metabolism. These findings call for additional efforts to evaluate and reduce arsenic exposure in Bolivia.
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38.
  • Derakhshan, Arash, et al. (author)
  • Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy
  • 2023
  • In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
  • Journal article (peer-reviewed)abstract
    • Background: Human chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated. Objectives: To investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations. Methods: We utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture. Results: In 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: −0.06 [−0.11 to −0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: −0.13 [−0.19 to −0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with −0.27 lower hCG (95% CI: −0.34 to −0.19). Discussion: Higher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs. 
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39.
  • Derakhshan, Arash, et al. (author)
  • Association of per- and polyfluoroalkyl substances with thyroid homeostasis during pregnancy in the SELMA study
  • 2022
  • In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 167
  • Journal article (peer-reviewed)abstract
    • ObjectivesTo investigate the association of exposure to per- and polyfluoroalkyl substances (PFAS) during early pregnancy with markers of the maternal thyroid system.MethodsSerum concentrations of seven PFAS as well as thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Outcomes were concentrations of TSH and thyroid hormones, FT4/FT3 or TT4/TT3 ratios, TSH/FT4 ratio as a marker of the negative feedback loop, TT4/FT4 or TT3/FT3 ratios as markers of the binding of thyroid hormones to binding proteins.ResultsThe study population comprised 2,008 women with median (95% range) gestational age of 10 (6–14) weeks. There was no association between PFAS and TSH. Higher PFNA, PFDA, PFHpA and PFOA levels were associated with a higher FT4 (largest effect estimate for PFDA: β [95% CI]: 0.27 [0.10 to 0.45], P = 0.002). Higher PFUnDA levels, but no other PFAS, were associated with a lower FT3 (β [95% CI]: −0.05 [-0.09 to −0.01], P = 0.005). Higher PFUnDA levels were associated with lower TT4 (β [95% CI]: −1.58 [-3.07 to −0.09]) and there was an inverted U-shaped association of PFOS with TT4 (P = 0.03). Higher PFDA, PFUnDA, PFHpA levels were associated with a lower TT3. Overall, higher PFAS concentrations were associated with a higher FT4/FT3 ratio and a higher TT4/TT3 ratio. There was no association of PFAS with the TSH/FT4 ratio. Higher concentrations of several PFAS were associated with lower TT4/FT4 and TT3/FT3 ratios.ConclusionsThese findings translate results from experimental studies suggesting that exposure to PFAS may interfere with the thyroid system during pregnancy. Further experimental studies should take into account human evidence to better understand the potential underlying mechanisms of thyroid disruption by PFAS exposure.
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40.
  • Derakhshan, A., et al. (author)
  • Association of phthalate exposure with thyroid function during pregnancy
  • 2021
  • In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 157
  • Journal article (peer-reviewed)abstract
    • Background: The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear. Aim: To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy. Methods: Urinary concentrations of phthalate metabolites and serum concentrations of thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4) and free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (2007-ongoing), a population-based prospective cohort. Results: In the 1,996 included women, higher di-ethyl-hexyl phthalate (DEHP) metabolites were associated with a lower FT4 (β [SE] for the molar sum: −0.13 [0.06], P = 0.03) and a higher TSH/FT4 ratio (0.003 [0.001], P = 0.03). Higher concentrations of di-iso-nonyl phthalate (DINP) metabolites were associated with a lower TT4 (β [SE] for the molar sum: 0.93 [0.44], P = 0.03) as well as with lower TT4/FT4 and TT4/TT3 ratios. Higher metabolites of both dibutyl and butyl-benzyl phthalate (DBP and BBzP) were associated with lower T4/T3 ratio (free and total) and higher FT4/TT4 and FT3/TT3 ratios. A higher diisononyl cyclohexane dicarboxylate (DINCH) metabolite concentration was associated with a higher TT3. Conclusions: These results translate results from experimental studies suggesting that exposure to phthalates may interfere with the thyroid system during pregnancy. This is also true for compounds that have been introduced to replace known disruptive phthalates. Further experimental studies should take into account the human evidence to better investigate the potential underlying mechanisms of thyroid disruption by phthalates.
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41.
  • Derakhshan, A., et al. (author)
  • Association of urinary bisphenols and triclosan with thyroid function during early pregnancy
  • 2019
  • In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 133
  • Journal article (peer-reviewed)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.
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42.
  • Gyllenhammar, Irina, et al. (author)
  • Concentrations of phthalate metabolites and phenolic substances in urine from first-time mothers in Uppsala, Sweden: temporal trends 2009-2014
  • 2016
  • Reports (other academic/artistic)abstract
    • POPUP studien startade 1996, där blod- och modersmjölksprover regelbundet samlas in från förstföderskor i Uppsala. Sedan 2009 tas också ett urinprov från kvinnorna. I denna studie har ftalater och fenolära ämnen studerats i urinprov insamlade 2009-2014. Dessa ämnen metaboliseras relativt snabbt i kroppen och för flertalet är det en metabolit till själva huvudsubstansen som har analyserats i urinen.Totalt sett analyserades 13 ftalatmetaboliter till 6 ftalater, en metabolit till en ersättningskemikalie till ftalater, en metabolit till ett fosforbaserat flamskyddsmedel, två pesticidmetaboliter samt 15 fenolära ämnen, t ex triklosan, bisfenol A, S och F, av Lunds universitet. Syftet var att studera tidstrender för de olika ämnena under perioden 2009-2014.Resultaten visade att flera av de äldre ftalaterna som håller på att fasas ut har en nedåtgående trend. Samtidigt kunde en ökande trend ses för en metabolit till ett ämne som nu används som ersättare till ftalater. Bisfenol A (BPA) som är ett mycket omdiskuterat ämne visade en nedåtgående tidstrend medan bisfenol F som pekats ut som en av ersättarna till BPA istället hade en ökande trend. Även triclosan visade en minskande trend som troligtvis beror på att ämnet har minskat i användning.Analyser av urin gör det möjligt att studera hur befolkningens exponering för snabbmetaboliserande substanser ser ut. Hur exponeringen förändras med tiden efter att olika åtgärder har satts in för att begränsa problematiska kemikalier samt hur befolkningens exponering för nya ersättningskemikalier har utvecklats.
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43.
  • Gyllenhammar, Irina, et al. (author)
  • Concentrations of phthalate metabolites and phenolic substances in urine from first-time mothers in Uppsala, Sweden, sampled 2019-2021 and temporal trends for the period 2009-2021
  • 2023
  • Reports (other academic/artistic)abstract
    • Sedan 1996 samlas blod- och modersmjölksprover regelbundet in från förstföderskor i Uppsala i den så kallade POPUP-studien. Sedan 2009 tas också ett urinprov. I denna rapport redovisas halter av ftalater och fenolära ämnen i urin från förstföderskor provtagna 2019-2021 samt tidstrender för perioden 2009-2021. Ftalater och fenolära ämnen metaboliseras relativt snabbt i kroppen och för flertalet är det därför en metabolit till själva huvudsubstansen som har analyserats.Totalt sett analyserades tio metaboliter till sex ftalater, två metaboliter till en ersättningskemikalie till ftalater, tre bisfenoler, metaboliter till fyra fosforbaserade flamskyddsmedel (PFR), två pesticidmetaboliter, fyra metaboliter till Polycykliska aromatiska kolväten (PAH) samt de fenolära ämnena triklosan och bensofenon-3 (BP-3) i urin. Analyserna utfördes av Lunds universitet. Resultaten visade att en metabolit till ftalaten dietylftalat (DEP) förekom i högst halter i urin, följt av sex andra metaboliter till olika ftalater och BP-3. För samtliga ämnen låg halterna i urin från mammor provtagna 2019-2021 under de föreslagna vägledande nivåer (HBM-GV) som bedöms att inte innebär en risk för människor. Tidstrenderna för perioden 2009-2021 visade nedåtgående trender för de flesta av substanserna, t ex för ftalater, bisfenol A, en metabolit till insekticiden klorpyrifos och triklosan. För bisfenol S, som är en ersättare till bisfenol A, och för en metabolit till pyretroider (insekticider) sågs istället ökande trender. Analyser av urin gör det möjligt att studera befolkningens exponering för snabbmetaboliserade substanser. Genom att analysera prover över tid kan man studera hur befolkningens exponering förändras efter att åtgärder för att begränsa vissa kemikalier satts in samt hur exponeringen för nya ersättningskemikalier utvecklas.
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44.
  • Gyllenhammar, Irina, et al. (author)
  • Diverging temporal trends of human exposure to bisphenols and plastizisers, such as phthalates, caused by substitution of legacy EDCs?
  • 2017
  • In: Environmental Research. - : Elsevier BV. - 0013-9351. ; 153, s. 48-54
  • Journal article (peer-reviewed)abstract
    • Phthalates and phenolic substances were investigated in urine samples from first-time mothers in Uppsala, Sweden, collected between 2009 and 2014. These substances have a comparably fast metabolism and urinary metabolites are predominantly analysed. The main aim was to investigate if measures to decrease production and use of certain phthalates and bisphenol A (BPA) have resulted in decreased human exposure, and to determine if exposures to replacement chemicals have increased. Temporal trends were evaluated for metabolites (n=13) of seven phthalates, a phthalate replacer, four different bisphenols, triclosan, one organophosphate-based flame retardant, and for two pesticides. The results showed downward trends of several phthalates which are in the process of being regulated and phased out. Concomitantly, an increasing trend was seen for a metabolite of the phthalate replacer Di-iso-nonylcyclohexane 1,2-dicarboxylate (DiNCH). Bisphenol A (BPA) showed a downward trend, whereas bisphenol F, identified as one of the substitutes for BPA, showed an increasing trend. The decreasing trend of triclosan is likely due to declining use within the EU. Temporal trend studies of urine samples make it possible to investigate human exposure to rapidly metabolised substances and study how measures taken to regulate and replace problematic chemicals affect human exposure.
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45.
  • Holmberg, Sara, et al. (author)
  • High levels of vitamin D associated with less ischemic heart disease - a nested case-control study among rural men in Sweden
  • 2017
  • In: AAEM. - : Institute of Rural Health. - 1232-1966 .- 1898-2263. ; 24:2, s. 288-293
  • Journal article (peer-reviewed)abstract
    • Introduction and objective. Low levels of serum vitamin D have been associated with increased occurrence of ischemic heart disease (IHD), but findings are inconsistent, e.g. seasonal variation is not always considered in the analyses. The aim of this study was to investigate whether vitamin D is associated with IHD among rural middle-aged men in Sweden when seasonal variation is taken into account. Materials and method. A nested case-control study was performed within a population-based cohort of Swedish farmers and rural residents followed for 20 years. Outcomes were from national health registers. For 276 cases (IHD at any time during follow-up), and for 276 aged-matched controls free of cardiovascular diseases or diabetes, serum levels of vitamin D (25-hydroxyvitamin D-3) were analyzed with liquid chromatography/tandem mass spectrometry (LC/MS/MS), in stored blood samples drawn at the baseline survey in 1990-91. The odds ratio (OR) with 95% confidence intervals (CI) of IHD for vitamin D-quartiles (based on measured as well as adjusted for month of sampling) was evaluated in logistic regression models; potential confounders were taken into account. Results. The measured mean vitamin D levels were 27.6 ng/ml(standard deviation (sd) 8.2 ng/ml) and 28.8 ng/ml (sd 9.0) among cases and controls, respectively. Compared to the quartile with the lowest month-adjusted vitamin D levels, the risk of IHD was significantly lower in the highest quartile (OR=0.46, 95% CI 0.25-0.84, p=0.012) in the fully-adjusted model. Conclusion. Rural Swedish men in the highest quartile of serum vitamin D had halved relative risk of IHD, compared to those in the lowest quartile.
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46.
  • Jönsson, Bo AG, et al. (author)
  • Tidstrender för och halter av perfluorerade alkylsyror (PFAAs) i serum samt ftalatmetaboliter och alkylfenoler i urin hos unga svenska män och kvinnor– Resultat från den fjärde uppföljningsundersökningen år 2013
  • 2014
  • Reports (other academic/artistic)abstract
    • Bakgrund:Studier av tidstrender är viktiga för riskvärdering, för att följa resultat av interventioner och för åtgärder för att minska exponeringen. Studiens huvudsyfte har varit att undersöka halter och tidstrender för perfluorerade kemikalier i serum samt ftalatmetaboliter och alkylfenoler i urin hos unga män och kvinnor. För detta har vi tidigare valt att använda oss av mönstringsundersökningen, som de flesta svenska män hittills har genomgått vid omkring 18 års ålder. När mönstringen nu slopats har vi istället samlade in prover från gymnasieelever i den sista årskursen. Vi utökade även studien så både kvinnor och män nu studeras.Metoder:Unga personer från fem olika år har hittills studerats. År 2000 samlades serumprover från 274 mönstrande och urinprover från 234, år 2004 samlades serum- och urinprover från 200 mönstrande, år 2006 serumprover från 200 mönstrande och åren 2009-2010 (benämns som 2010 i den fortsatta rapporten) serumprover från 100 mönstrande och urinprover från 314 samt slutligen år 2013 serum och urinprover från 107 kvinnliga och 97 manliga gymnasieelever i tredje årskursen. I den nu aktuella uppföljningen analyserades 15 perfluorerade alkylsyror (PFAAs) i serum, 10 ftalatmetaboliter från fem olika ftalater, fyra alkylfenoler av vilka tre var bisfenoler samt triklosan i urin. Dessutom analyserades metaboliterna till pesticiderna klorpyrifos (triklorpyridinol ,TCP) och gruppen pyretroider (3-fenoxibensoesyra, 3-PBA) samt 1-hydroxypyren en biomarkör för PAH exponering i urin. Bisfenol A analyserades även i 258 urinprover från 2010. Samtliga analyser utfördes med vätskekromatografi kopplat till en tandem masspektrometer. Trender analyserades med Jonckheere-Terpstra testet och skillnader mellan grupper med Mann-Whitneys U test.Resultat:Halterna av de flesta PFAAs i serum verkade minska mellan 2010 och 2013. De kreatininjusterade halterna för MEP, MBP, MBzP och MEHP för åren 2000, 2004, 2010 och 2013 visade alla en sjunkande trend. Dessutom visade inte halterna av diisononylftalatmetaboliterna en ökande trend vilket hade förväntats från andra studier. Halterna av BPA verkade minska relativt kraftigt mellan 2010 och 2013 vilket så vitt vi vet är den första tidstenden för denna substans. 
  •  
47.
  • Jørgensen, Kristian T., et al. (author)
  • Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine
  • 2014
  • In: Environmental Health: A Global Access Science Source. - 1476-069X. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Background: Perfluoroalkyl substances (PFAS) are suggested to affect human fecundity through longer time to pregnancy (TTP). We studied the relationship between four abundant PFAS and TTP in pregnant women from Greenland, Poland and Ukraine representing varying PFAS exposures and pregnancy planning behaviors. Methods: We measured serum levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in 938 women from Greenland (448 women), Poland (203 women) and Ukraine (287 women). PFAS exposure was assessed on a continuous logarithm transformed scale and in country-specific tertiles. We used Cox discrete-time models and logistic regression to estimate fecundability ratios (FRs) and infertility (TTP >13 months) odds ratios (ORs), respectively, and 95% confidence intervals (CI) according to PFAS levels. Adjusted analyses of the association between PFAS and TTP were done for each study population and in a pooled sample. Results: Higher PFNA levels were associated with longer TTP in the pooled sample (log-scale FR∈=∈0.80; 95% CI 0.69-0.94) and specifically in women from Greenland (log-scale FR∈=∈0.72; 95% CI 0.58-0.89). ORs for infertility were also increased in the pooled sample (log-scale OR∈=∈1.53; 95% CI 1.08-2.15) and in women from Greenland (log-scale OR∈=∈1.97; 95% CI 1.22-3.19). However, in a sensitivity analysis of primiparous women these associations could not be replicated. Associations with PFNA were weaker for women from Poland and Ukraine. PFOS, PFOA and PFHxS were not consistently associated with TTP. Conclusions: Findings do not provide consistent evidence that environmental exposure to PFAS is impairing female fecundity by delaying time taken to conceive.
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48.
  • Kimblad, Agnes, et al. (author)
  • Decreased sperm counts in Swedish users of oral tobacco
  • 2022
  • In: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 10:6, s. 1181-1188
  • Journal article (peer-reviewed)abstract
    • Background: Smoke-free tobacco via moist oral snuff (snus) is used daily in more than 20% of Swedish men. Negative effects of cigarette smoking on sperm parameters are well documented, unlike for snuff, despite relevance also for other smoke-free nicotine products. Objectives: We wanted to investigate whether reproductive parameters differed between users and non-users of snuff, and whether the amount of snuff and nicotine exposure mattered. Materials and methods: Men (n = 613) from the general population, recruited 2000–2010, were physically examined, answered questions on smoking and snuff use, and delivered urine, blood and semen samples. Sperm concentration, total sperm count, semen volume, percent morphologically normal and progressively motile sperm, and DNA fragmentation index (by the Sperm Chromatin Structure Assay) and reproductive hormones were analysed. Nicotine exposure was measured through urinary levels of cotinine. We used general linear models, with adjustments including cigarette smoking, and for semen parameters also abstinence time. Results: After adjustments, total sperm count was 24% lower (P = 0.03) and testosterone 14% higher (P < 0.001) in 109 users of snuff than in non-users, whereas cotinine was positively associated with testosterone and oestradiol (P < 0.001). Numbers of boxes of snuff used per week were associated with testosterone and FSH (P < 0.001). Discussion: Applied to the general population, the consumption of smoke-free tobacco by the use of snuff was associated with a lower sperm count and a higher testosterone, for which the extent seemed to play a role. Conclusions: Independent of smoking, consumption of snuff was associated with lower total sperm count and different hormone levels. Applying these results to a reported association between sperm count and the chance of pregnancy, men who used snuff would have about a 10% lower chance of fathering a child.
  •  
49.
  • Krais, Annette M., et al. (author)
  • Biomarkers after Controlled Inhalation Exposure to Exhaust from Hydrogenated Vegetable Oil (HVO)
  • 2021
  • In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:12
  • Journal article (peer-reviewed)abstract
    • Hydrogenated vegetable oil (HVO) is a renewable diesel fuel used to replace petroleum diesel. The organic compounds in HVO are poorly characterized; therefore, toxicological properties could be different from petroleum diesel exhaust. The aim of this study was to evaluate the exposure and effective biomarkers in 18 individuals after short-term (3 h) exposure to HVO exhaust and petroleum diesel exhaust fumes. Liquid chromatography tandem mass spectrometry was used to analyze urinary biomarkers. A proximity extension assay was used for the measurement of inflammatory proteins in plasma samples. Short-term (3 h) exposure to HVO exhaust (PM1 ~1 µg/m3 and ~90 µg/m3 for vehicles with and without exhaust aftertreatment systems, respectively) did not increase any exposure biomarker, whereas petroleum diesel exhaust (PM1 ~300 µg/m3 ) increased urinary 4-MHA, a biomarker for p-xylene. HVO exhaust from the vehicle without exhaust aftertreatment system increased urinary 4-HNE-MA, a biomarker for lipid peroxidation, from 64 ng/mL urine (before exposure) to 141 ng/mL (24 h after exposure, p < 0.001). There was no differential expression of plasma inflammatory proteins between the HVO exhaust and control exposure group. In conclusion, short-term exposure to low concentrations of HVO exhaust did not increase urinary exposure biomarkers, but caused a slight increase in lipid peroxidation associated with the particle fraction.
  •  
50.
  • Krais, Annette M, et al. (author)
  • Detection of the fungicide transformation product 4-hydroxychlorothalonil in serum of pregnant women from Sweden and Costa Rica
  • 2024
  • In: Journal of Exposure Science & Environmental Epidemiology. - 1559-064X. ; 34:2, s. 270-277
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: 4-hydroxychlorothalonil (HCT, R182281), a transformation product of the fungicide chlorothalonil, was recently identified in human serum and breast milk. There are indications that HCT may be more toxic and environmentally persistent than chlorothalonil.OBJECTIVE: Our aim was to investigate serum concentrations of HCT in pregnant women in Sweden and Costa Rica.METHODS: We developed a quantitative analytical method for HCT using liquid chromatography tandem mass spectrometry. We measured HCT in 1808 serum samples from pregnant women from the general population in Sweden (1997-2015) and in 632 samples from 393 pregnant women from an agricultural population in Costa Rica (2010-2011). In Swedish samples, we assessed time trends and investigated seasonality. In the Costa Rican samples, we evaluated variability between and within women and explanatory variables of HCT concentrations.RESULTS: HCT was detected in all serum samples, and the limit of detection was 0.1 µg/L. The median HCT concentration in the Swedish samples was 4.1 µg/L (interquartile range [IQR] of 2.9 - 5.8 µg/L), and 3.9 times higher in the Costa Rican samples (median: 16.1 µg/L; IQR: 10.6 - 25.0 µg/L). We found clear seasonal variation with higher concentrations in the first half of each year among Swedish women. In the Costa Rican study, women working in agriculture and living near banana plantations had higher HCT concentrations, whilst higher parity and having a partner working in agriculture were associated with decreased HCT, and no clear seasonal pattern was observed.IMPACT STATEMENT: For the first time, this study quantifies human exposure to the fungicide chlorothalonil and/or its transformation product 4-hydroxychlorothalonil (HCT, R182281) and finds higher serum concentrations in women from a tropical agricultural setting as compared with women from the general population in Sweden.
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