270 results on '"Christian H Lindh"'
Search Results
252. Total plasma protein adducts of allergenic hexahydrophthalic and methylhexahydrophthalic anhydrides as biomarkers of long-term exposure
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Gunvor Johannesson, Christian H. Lindh, Seema Rosqvist, and Bo A. G. Jönsson
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Chromatography ,Epoxy Resins ,Metabolite ,Public Health, Environmental and Occupational Health ,Organic acid anhydride ,Urine ,chemistry.chemical_compound ,chemistry ,Chemical Industry ,Occupational Exposure ,Phthalic Anhydrides ,Blood plasma ,Linear Models ,Cluster Analysis ,Humans ,Toxicokinetics ,Solid phase extraction ,Hemoglobin ,Derivatization ,Biomarkers - Abstract
OBJECTIVES: The aim of this study was to evaluate the applicability of total plasma protein adducts (TPPA) of 2 sensitizing low-molecular-weight allergens, hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA), as biomarkers of long-term exposure. METHODS: Urine samples from occupationally exposed workers were analyzed for the levels of urinary metabolites of HHPA and MHHPA, and the levels were used as the index of exposure. In addition, blood samples were obtained from the same persons, and the levels of TPPA were determined. Reversed solid phase extraction, derivatization using pentafluorobenzyl bromide, and gas chromatography-mass spectrometry analysis in the negative ion chemical ionization mode were used to quantify the exposure. To assess the suitability of TPPA as a biomarker of exposure to the anhydrides, the TPPA levels were correlated to urinary metabolite levels and hemoglobin (Hb) adducts. The toxicokinetics of TPPA were also studied to determine the elimination half-time of the adducts. RESULTS: The levels of TPPA correlated exceptionally well with the metabolite levels in the urine sampled repeatedly, giving r=0.97 for HHPA and r=0.92 for MHHPA. The TPPA of HHPA correlated highly with the Hb adducts with r=0.86. There were also good correlations between single urinary determinations and the TPPA levels (r(s)=0.71 and 0.81, respectively, for HHPA and MHHPA). The in vivo decay of TPPA gave an elimination half-time of 22 days for HHPA and 24 days for MHHPA. CONCLUSIONS: TPPA levels of HHPA and MHHPA are excellent biomarkers of long-term exposure to anhydrides. (Less)
253. Exposure-response relationships for hexahydrophthalic and methylhexahydrophthalic anhydrides with total plasma protein adducts as biomakers
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Bo Jönsson, Jörn Nielsen, Hans Welinder, Lars Rylander, Seema Rosqvist, and Christian H. Lindh
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Adult ,Male ,medicine.medical_specialty ,Protein adducts ,Phthalic Acids ,Enzyme-Linked Immunosorbent Assay ,Exposure response relationships ,Air Pollutants, Occupational ,Immunoglobulin E ,Gastroenterology ,Internal medicine ,Occupational Exposure ,Blood plasma ,Medicine ,Humans ,Sweden ,Total plasma ,biology ,medicine.diagnostic_test ,business.industry ,Epoxy Resins ,Radioallergosorbent test ,Public Health, Environmental and Occupational Health ,Blood Proteins ,Middle Aged ,Phthalic Anhydrides ,biology.protein ,Biomarker (medicine) ,Female ,Antibody ,business ,Biomarkers - Abstract
OBJECTIVES: This study investigated the exposure-response relationships of hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA) and evaluated the applicability of the total plasma protein adducts (TPPA) of these anhydrides as biomarkers of exposure and risk. METHODS: In a cross-sectional study of 139 workers in a plant manufacturing electrical capacitors, the long-term exposure to HHPA and MHHPA was assessed through the quantification of TPPA using gas chromatography-mass spectrometry. Smoking and medical histories were obtained through questionnaires. Work-related symptoms of the eyes and airways were recorded. Specific immunoglobulin (Ig) E (radioallergosorbent test) and IgG (enzyme-linked immunosorbent assay) were determined in serum. RESULTS: The mean level of the TPPA of HHPA was 840 fmol/ml and that of the TPPA of MHHPA was 1700 fmol/ml. There was no correlation between the TPPA of HHPA and the TPPA of MHHPA. Of all the workers, 19% were found to be positive for specific IgE and 17-19% for IgG. Positive associations were observed between HHPA exposure and specific IgE and IgG and between MHHPA exposure and specific IgG. Regarding work-related symptoms, 27% of the workers had symptoms of the nose, 21% had symptoms of the eyes, 11% had symptoms of the lower airways, and 8% had nose bleeding. There were significant exposure-response relationships for symptoms of the eyes and nose for HHPA exposure. CONCLUSIONS: The results show that there is an exposure-response relationship for HHPA both with specific antibodies and with work-related symptoms and down to adduct levels of 40 fmol/ml plasma. In addition, the results elucidate the potential power of TPPA as a relevant index of exposure and risk. (Less)
254. Consistency between serum concentrations of perfluorinated compounds measured in early and late gestation in a Swedish cohort
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Kristina Jakobsson, Agneta Holmäng, Christian H. Lindh, U. Andersson Hall, and Christel Nielsen
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Global and Planetary Change ,medicine.medical_specialty ,Epidemiology ,business.industry ,Late gestation ,Obstetrics ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Serum concentration ,Pollution ,Consistency (statistics) ,Cohort ,Medicine ,business
255. Biological monitoring of exposure to toluene diisocyanate
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Hans Welinder, Bo A. G. Jönsson, Christian H. Lindh, Margareta Littorin, Håkan Tinnerberg, and Carl Johan Sennbro
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Adult ,Male ,Sweden ,Chromatography ,Plasma samples ,Toluene diisocyanate ,Chemistry ,Public Health, Environmental and Occupational Health ,Urine ,Middle Aged ,Toxicology ,chemistry.chemical_compound ,Occupational Exposure ,Blood plasma ,Linear regression ,Linear Models ,Biomarker (medicine) ,Humans ,Female ,Monitoring methods ,Occupational exposure limit ,Toluene 2,4-Diisocyanate ,Biomarkers ,Chromatography, High Pressure Liquid - Abstract
OBJECTIVES :Toluene diisocyanate (TDI) is used in the manufacture of polyurethane and is a potent inducer of diseases of the airways. In this study, 2,4- and 2,6-toluenediamine in hydrolyzed urine and plasma were evaluated as biomarkers of exposure to 2,4- and 2,6-TDI, respectively. METHODS: For 81 exposed workers from nine different plants, the personal 8-hour time-weighted-average exposure to TDI was monitored by a filter method with 1-(2-methoxyphenyl)piperazine. In parallel, urinary samples (U1) were collected during the last 4 hours of the workshift. On a different occasion, blood samples and additional urinary samples (U2) were collected from the exposed workers, and also from a reference group consisting of 121 unexposed workers. The biomarker levels were determined in urine and plasma by the use of alkaline hydrolysis. RESULTS: There were strong associations between the personal air and biomarker levels, with correlation coefficients in the range of 0.75-0.88 for the U1 samples and in the range of 0.50-0.78 for the plasma samples. By weighted linear regression, the relations were calculated between the air and biomarker levels. The slopes of the obtained regression curves ranged from 1.8 to 2.7 m3/1 for air-urine and from 2.2 to 2.9 m3/1 for air-plasma, and the intercepts were all close to the origin of the coordinates. Through the extrapolation of these regression curves, biological exposure limits were calculated. CONCLUSIONS: The biological monitoring methods and strategies presented in this report are useful for assessing exposure to TDI in practice. (Less)
256. DNA methylation at GRIN2B partially mediates the association between prenatal bisphenol F exposure and cognitive functions in 7-year-old children in the SELMA study
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Carl-Gustaf Bornehag, Ali Alavian-Ghavanini, Joëlle Rüegg, Katherine Svensson, Christian H. Lindh, Elin Engdahl, and Ping-I Daniel Lin
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Male ,010504 meteorology & atmospheric sciences ,Bisphenol F ,EDCs ,Pharmacology and Toxicology ,010501 environmental sciences ,Health outcomes ,Bioinformatics ,GRIN2B ,01 natural sciences ,Cognition ,Phenols ,Pregnancy ,Hypersensitivity ,Humans ,Medicine ,GE1-350 ,Epigenetics ,Benzhydryl Compounds ,Child ,Association (psychology) ,0105 earth and related environmental sciences ,General Environmental Science ,Sweden ,DNA methylation ,biology ,business.industry ,BPF ,Farmakologi och toxikologi ,Asthma ,Environmental sciences ,Prenatal chemical exposure ,Prenatal Exposure Delayed Effects ,biology.protein ,Female ,business - Abstract
BACKGROUND: Accumulating evidence suggests that prenatal chemical exposure triggers epigenetic modifications that could influence health outcomes later in life. In this study, we investigated whether DNA methylation (DNAm) levels at the glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B) gene underlies the association between prenatal exposure to an endocrine disrupting chemical (EDC), bisphenol F (BPF), and lower cognitive functions in 7-year-old children. METHODS: Data from 799 children participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) pregnancy cohort was analyzed. Prenatal BPF exposure was assessed by measuring BPF levels in maternal urine. At age 7, DNAm of three CpG sites in a regulatory region of the GRIN2B gene was analyzed from buccal swabs using bisulfite-Pyrosequencing. Cognitive functions, including full-scale IQ and four subscales, were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Associations between prenatal BPF exposure and GRIN2B DNAm, as well as between GRIN2B DNAm and cognitive functions, were determined using regression models adjusted for potential confounders. Generalized structural equation models (gSEM) were used to evaluate if GRIN2B DNAm mediates the association between prenatal BPF exposure and cognitive functions at 7 years of age. RESULTS: Prenatal BPF exposure was positively associated with GRIN2B DNAm levels at the third CpG site (CpG3), while CpG3 methylation was inversely associated with cognitive test scores. Mediation analyses showed that CpG3 methylation exerted 6-9% of the association between BPF exposure and full-scale IQ, as well as verbal comprehension and perceptual reasoning in boys, while not significant in girls. CONCLUSIONS: This study is the first to identify locus-specific DNAm as a mediating factor underlying an epidemiological association between prenatal EDC exposure and cognitive functions in childhood. It also confirms previous findings, that GRIN2B DNAm is responsive to environmental exposures. Shared first authorship: Elin Engdahl och Katherine Svensson
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257. Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy
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Arash Derakhshan, Huan Shu, Maarten A.C. Broeren, Andreas Kortenkamp, Christian H. Lindh, Barbara Demeneix, Robin P. Peeters, Carl-Gustaf Bornehag, and Tim I.M. Korevaar
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Endocrine disrupting chemicals ,Pregnancy ,Human chorionic gonadotropin ,Placenta ,Environmental sciences ,GE1-350 - 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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- 2023
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258. Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Early Pregnancy and Small for Gestational Age in Southern Sweden
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Ellen Malm, Andreas Vilhelmsson, Hannah Högfeldt, Isabelle Deshayes, Karin Källén, Stefan R. Hansson, Christian H. Lindh, and Lars Rylander
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SGA ,PFAS ,endocrine disrupting chemical ,case control ,biobank ,fetal growth ,Chemical technology ,TP1-1185 - Abstract
Small for gestational age (SGA) is considered an adverse birth outcome. Per- and polyfluoralkyl substances (PFAS) have become increasingly investigated as contributing environmental factors, thus far with inconclusive results. The current study aimed to investigate the hypothesized association between increased maternal PFAS levels in early pregnancy and an increased risk for SGA birth. This population-based study used data from a sample of children born in Scania, Southern Sweden, between 1995 and 2009. Two groups were compared: cases born with SGA (n = 298) and non-SGA controls (n = 580). The cases consisted of two subgroups: one included women whose children’s growth in late pregnancy was in the lowest quartile, and another included women from the remaining growth quartiles. Corresponding maternal serum samples were collected from a biobank and analyzed for concentrations of four types of PFAS: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) using liquid chromatography–tandem mass spectrometry (LC/MS/MS). The results were combined with information from birth registers and analyzed using Mann–Whitney U-tests and logistic regression—unadjusted as well as adjusted for potential confounders. In conclusion, elevated maternal concentrations of PFAS were not associated with an increased risk of SGA birth. However, significant ORs were observed in a subgroup analysis restricted to women of Nordic origin (unadjusted OR 3.2 and adjusted OR 2.4) for PFHxS.
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- 2023
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259. Exposure to perfluoroalkyl substances in early pregnancy and risk of sporadic first trimester miscarriage
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Sverre Wikström, Ghada Hussein, Annika Lingroth Karlsson, Christian H. Lindh, and Carl-Gustaf Bornehag
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Medicine ,Science - Abstract
Abstract Many first trimester sporadic miscarriages are unexplained and the role of environmental exposures is unknown. The present aim was to study if levels of Perfluoroalkyl substances (PFASs) in early pregnancy are associated with unexplained, sporadic first trimester miscarriage. The study was performed within the Swedish SELMA pregnancy cohort. Seventy-eight women with non-recurrent first trimester miscarriage were included and 1449 women were available as live birth controls. Eight PFASs were measured in first trimester serum. A doubling of perfluorooctanoic acid (PFOA) exposure, corresponding to an inter-quartile increase, was associated with an odds ratio (95%CI) for miscarriage of 1.48 (1.09–2.01) when adjusting for parity, age and smoking. Analyses per quartiles of PFOA exposure indicated a monotonic dose response association with miscarriage. A similar, but not significant, pattern was observed for perfluorononanoic acid (PFNA). For other PFAS, there were no associations with miscarriage. We have previously shown associations between early pregnancy PFAS exposures and preeclampsia, as well as lower birth weight. Now we report an association between PFOA and miscarriage within the same cohort, which may suggest shared but unknown mechanisms. The study can only represent a period of early placentation and clinical pregnancy loss during the second half of the first trimester.
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- 2021
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260. Persistent organic pollutants, pre-pregnancy use of combined oral contraceptives, age, and time-to-pregnancy in the SELMA cohort
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Richelle D. Björvang, Chris Gennings, Ping-I Lin, Ghada Hussein, Hannu Kiviranta, Panu Rantakokko, Päivi Ruokojärvi, Christian H. Lindh, Pauliina Damdimopoulou, and Carl-Gustaf Bornehag
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Persistent organic pollutants ,Combined oral contraceptives ,Time-to-pregnancy ,Fecundability ,Polychlorobiphenyls ,Organochlorinated pesticides ,Industrial medicine. Industrial hygiene ,RC963-969 ,Public aspects of medicine ,RA1-1270 - Abstract
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 (
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- 2020
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261. Associations between perfluoroalkyl substances and serum lipids in a Swedish adult population with contaminated drinking water
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Ying Li, Lars Barregard, Yiyi Xu, Kristin Scott, Daniela Pineda, Christian H. Lindh, Kristina Jakobsson, and Tony Fletcher
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Serum lipids ,Cholesterol ,Perfluoroalkyl substances (PFAS) ,Perfluorooctane sulfonic acid (PFOS) ,Perfluorooctanoic acid (PFOA) ,Perfluorohexane sulfonic acid (PFHxS) ,Industrial medicine. Industrial hygiene ,RC963-969 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Exposures to perfluoroalkyl substances (PFAS) have shown positive associations with serum lipids in previous studies. While many studies on lipids investigated associations with perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), there are only a few studies regarding other PFAS, such as perfluorohexane sulfonic acid (PFHxS). The purpose of the current study is to investigate if associations with serum lipids were present, not only for serum PFOS and PFOA, but also for PFHxS, and if the associations with PFAS remained also in a comparison based only on residency in areas with contrasting exposure to PFAS. Methods 1945 adults aged 20–60 were included from Ronneby, Sweden, a municipality where one out of two waterworks had been heavily contaminated from aqueous fire-fighting foams, and from a nearby control area. The exposure was categorized based on either been living in areas with contrasting PFAS exposure or based on the actual serum PFAS measurements. Regression analyses of serum lipids were fitted against serum PFAS levels, percentile groups, smooth splines and between exposed and reference areas, adjusting for age, sex and BMI. Results Drinking water contamination caused high serum levels of PFOS (median 157 ng/ml) and PFHxS (median 136 ng/ml) and PFOA (median 8.6 ng/ml). These serum PFAS levels in the exposed groups were 5 to 100-fold higher than in the controls. In this population with mixed PFAS exposure, predominantly PFOS and PFHxS, PFAS exposure were positively associated with serum lipids. This was observed both when quantifying exposure as contrast between exposed and controls, and in terms of serum PFAS. Due to high correlations between each PFAS, we cannot separate them. Conclusions In conclusion, the present study provides further evidence of a causal association between PFAS and serum lipids, especially for PFHxS.
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- 2020
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262. Association of phthalate exposure with thyroid function during pregnancy
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Arash Derakhshan, Huan Shu, Maarten A.C. Broeren, Christian H. Lindh, Robin P. Peeters, Andreas Kortenkamp, Barbara Demeneix, Carl-Gustaf Bornehag, and Tim I.M. Korevaar
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Endocrine disrupting chemicals ,Pregnancy ,Thyroid ,Phthalates ,Environmental sciences ,GE1-350 - 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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- 2021
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263. Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women
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Richelle D. Björvang, Jasmin Hassan, Maria Stefopoulou, Kristina Gemzell-Danielsson, Matteo Pedrelli, Hannu Kiviranta, Panu Rantakokko, Päivi Ruokojärvi, Christian H. Lindh, Ganesh Acharya, and Pauliina Damdimopoulou
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Ovary ,Ovarian reserve ,Anti-Müllerian hormone ,Female fertility ,Persistent organic pollutants ,Environmental sciences ,GE1-350 - 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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- 2021
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264. Concentrations of perfluoroalkyl substances (PFASs) in human embryonic and fetal organs from first, second, and third trimester pregnancies
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Linn Salto Mamsen, Richelle D. Björvang, Daniel Mucs, Marie-Therese Vinnars, Nikos Papadogiannakis, Christian H. Lindh, Claus Yding Andersen, and Pauliina Damdimopoulou
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Environmental sciences ,GE1-350 - Abstract
Background: The persistent environmental contaminants perfluoroalkyl substances (PFASs) have gained attention due to their potential adverse health effects, in particular following early life exposure. Information on human fetal exposure to PFASs is currently limited to one report on first trimester samples. There is no data available on PFAS concentrations in fetal organs throughout all three trimesters of pregnancy. Methods: We measured the concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorohexane sulfonic acid (PFHxS) in human embryos and fetuses with corresponding placentas and maternal serum samples derived from elective pregnancy terminations and cases of intrauterine fetal death. A total of 78 embryos and fetuses aged 7–42 gestational weeks were included and a total of 225 fetal organs covering liver, lung, heart, central nervous system (CNS), and adipose tissue were analyzed, together with 71 placentas and 63 maternal serum samples. PFAS concentrations were assayed by liquid chromatography/triple quadrupole mass spectrometry. Results: All evaluated PFASs were detected and quantified in maternal sera, placentas and embryos/fetuses. In maternal serum samples, PFOS was detected in highest concentrations, followed by PFOA > PFNA > PFDA = PFUnA = PFHxS. Similarly, PFOS was detected in highest concentrations in embryo/fetal tissues, followed by PFOA > PFNA = PFDA = PFUnA. PFHxS was detected in very few fetuses. In general, PFAS concentrations in embryo/fetal tissue (ng/g) were lower than maternal serum (ng/ml) but similar to placenta concentrations. The total PFAS burden (i.e. the sum of all PFASs) was highest in lung tissue in first trimester samples and in liver in second and third trimester samples. The burden was lowest in CNS samples irrespective of fetal age. The placenta:maternal serum ratios of PFOS, PFOA and PFNA increased across gestation suggesting bioaccumulation in the placenta. Further, we observed that the ratios were higher in pregnancies with male fetuses compared to female fetuses. Conclusions: Human fetuses were intrinsically exposed to a mixture of PFASs throughout gestation. The compounds were detected in all analyzed tissues, suggesting that PFASs reach and may affect many types of organs. Collectively, our results demonstrate that PFASs pass the placenta and deposit to embryo and fetal tissues, calling for risk assessment of gestational exposures. Keywords: Prenatal exposure, Perfluoroalkyl substances, Maternal serum, Placenta, Fetal organs
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- 2019
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265. Serum perfluoroalkyl substances in residents following long-term drinking water contamination from firefighting foam in Ronneby, Sweden
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Yiyi Xu, Christel Nielsen, Ying Li, Sofia Hammarstrand, Eva M. Andersson, Huiqi Li, Daniel S. Olsson, Karin Engström, Daniela Pineda, Christian H. Lindh, Tony Fletcher, and Kristina Jakobsson
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PFHxS ,PFOS ,PFOA ,Drinking water ,Environmental sciences ,GE1-350 - Abstract
Background: In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport. Objectives: To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined. Methods: Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants. Results: The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005–2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60. Discussion: The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure.
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- 2021
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266. Associations between serum concentrations of perfluoroalkyl substances and DNA methylation in women exposed through drinking water: A pilot study in Ronneby, Sweden
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Yiyi Xu, Simona Jurkovic-Mlakar, Christian H. Lindh, Kristin Scott, Tony Fletcher, Kristina Jakobsson, and Karin Engström
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Epigenetics ,Environmental pollutant ,Perfluoroalkyl substance ,PFAS ,Epigenetic aging ,EPIC chip ,Environmental sciences ,GE1-350 - Abstract
Background: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFAS is via epigenetic changes, such as DNA methylation. However, few studies have evaluated associations between PFAS exposure and DNA methylation among adults, and data is especially scarce for women. Furthermore, exposure to environmental pollutants has been associated with epigenetic age acceleration, but no studies have yet evaluated whether PFAS is associated with epigenetic age acceleration. Objectives: To investigate whether exposure to PFAS is associated with alteration of DNA methylation and epigenetic age acceleration among women. Methods: In this observational pilot study, 59 women (aged 20–47 years at enrollment in 2014) from Ronneby, Sweden, an area with historically high PFAS exposure due to local drinking water contamination, were divided into three PFAS exposure groups (low, medium, and high). Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip. Ingenuity Pathway Analysis was used for in silico functional assessment. Epigenetic age acceleration was derived from the DNA methylation data using Horvath’s epigenetic skin and blood clock. Results: 117 differentially methylated positions (q
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- 2020
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267. 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
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Neserin Ali, Stefan Ljunggren, Helen M. Karlsson, Aneta Wierzbicka, Joakim Pagels, Christina Isaxon, Anders Gudmundsson, Jenny Rissler, Jörn Nielsen, Christian H. Lindh, and Monica Kåredal
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Chamber study ,Welding fume particles ,Nasal lavage ,Effects ,Proteomics ,Mass spectrometry ,Medicine - Abstract
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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- 2018
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268. Per- and Polyfluoroalkyl Substances in Early Pregnancy and Risk for Preeclampsia: A Case-Control Study in Southern Sweden
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Lars Rylander, Christian H. Lindh, Stefan R. Hansson, Karin Broberg, and Karin Källén
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PFAS ,PFOA ,PFOS ,PFNA ,PFHxS ,preeclampsia ,Chemical technology ,TP1-1185 - Abstract
Preeclampsia is one of the most common causes of perinatal and maternal morbidity/mortality. One suggested environmental risk factor is exposure to endocrine-disrupting pollutants such as per- and polyfluoroalkyl substances (PFAS). The present case-control study in southern Sweden aims to investigate the hypothesized association between serum concentrations of PFAS in early pregnancy and the risk of developing preeclampsia. The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Maternal serum samples were obtained from a biobank of samples collected in early pregnancy in connection with screening for infections. Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were analyzed using liquid chromatography-tandem-mass-spectrometry (LC/MS/MS). Among primiparous women, there were no differences in PFAS concentrations in early pregnancy between the cases and the controls whereas among multipara women, the cases had significantly higher concentrations of PFNA (median concentrations were 0.44 and 0.38 ng/mL, p = 0.04). When individual PFAS were categorized into quartiles and adjustment for potential confounders was performed, the women in the highest quartiles had no significant increased risks of developing preeclampsia as compared with women in the lowest category. In conclusion, the present study provides limited support for the hypothesized association between PFAS and preeclampsia in a population with relatively low exposure levels.
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- 2020
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269. Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children
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Kristin Larsson, Karin Ljung Björklund, Brita Palm, Maria Wennberg, Lennart Kaj, Christian H. Lindh, Bo A.G. Jönsson, and Marika Berglund
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Environmental sciences ,GE1-350 - Abstract
Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood.The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6–11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother–child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors.There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 μg/L; ΣDiNP 37.8 μg/L; MBzP 19.9 μg/L; MnBP 76.9 μg/L) than the mothers (ΣDEHP 38.4 μg/L; ΣDiNP 33.8 μg/L; MBzP 12.8 μg/L; MnBP 63.0 μg/L). Conversely, the mother's levels of parabens (MetP 37.8 μg/L; ProP 13.9 μg/L) and MEP (43.4 μg/L) were higher than the children's levels of parabens (MetP 6.8 μg/L; ProP 2.1 μg/L) and MEP (28.8 μg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p =
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- 2014
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270. Haemoglobin adducts and specific immunoglobulin G in humans as biomarkers of exposure to hexahydrophthalic anhydride.
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Bo A G Jonsson Christian H Lindh And Hans Welinder
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The aim of this study was to determine whether haemoglobin adducts Hb of hexahydrophthalic anhydride HHPA and HHPA specific immunoglobulin G IgG can be used as biomarkers of exposure to HHPA. The exposures of HHPA in 10 workers were determined from the mean urinary hexahydrophthalic acid HHP acid levels range 76-3300 nmol HHP acid mmol-1 creatinine during a period of 4 weeks. Blood was collected at the end of the period and Hb-HHPA adducts were analysed by gas chromatography mass spectrometry. The Hb-HHPA adduct levels ranged from 0.45 to 24.7 pmol g-1 Hb. There was a close correlation between the urinary HHP acid levels and the amount of Hb-HHPA adducts r = 0.87 . One day exposures to HHPA and methylhexahydrophthalic anhydride MHHPA in 142 workers were determined from analysis of urinary HHP acid range 0-3300 nmol HHP acid mmol-1 creatinine and methylhexahydrophthalic acid MHHP acid; range 0-1700 nmol MHHP acid mmol-1 creatinine. HHPA specific IgG were analysed in the 142 workers with an ELISA method. The optical density for HHPA specific IgG varied between 0 and 1.25. There was no statistically significant correlation between the sum of the urinary HHP acid and MHHP acid and the HHPA specific IgG r = 0.12; p = 0.14 . Thus, Hb-HHPA adducts seem to be applicable as biomarkers of exposure to HHPA while the possible role of HHPA specific IgG as an indicator of exposure has to be further evaluated.
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- 1997
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