| 1. |
- Desalegn, Anteneh, et al.
(author)
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Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study
- 2024
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In: ENVIRONMENT INTERNATIONAL. - 0160-4120 .- 1873-6750. ; 190
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Journal article (peer-reviewed)abstract
- Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. Objective: To evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. Method: We used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6-12 years, 2014-2021) and 2499 adolescents (10 studies, 12-18 years, 2014-2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. Results: In children, we found few associations in single pollutant models and no interactions by sex (p p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males ((3 = 0.08, 95% CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes ((3 =-0.13, 95 % CI:-0.19,-0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (& sum;DEHP) metabolites in females only ((3 =-0.08,95 % CI:-0.14,-0.02,p-interaction p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females ((3 =-0.11, 95 % CI:-0.25, 0.03, per joint exposure quantile). Conclusion: In this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.
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| 2. |
- Hay-Schmidt, Anders, et al.
(author)
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Prenatal exposure to paracetamol/acetaminophen and precursor aniline impairs masculinisation of male brain and behaviour
- 2017
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In: Reproduction. - : Bioscientifica. - 1470-1626 .- 1476-3990. ; 154:2, s. 145-152
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Journal article (peer-reviewed)abstract
- Paracetamol/acetaminophen (N-Acetyl-p-Aminophenol; APAP) is the preferred analgesic for pain relief and fever during pregnancy. It has therefore caused concern that several studies have reported that prenatal exposure to APAP results in developmental alterations in both the reproductive tract and the brain. Genitals and nervous system of male mammals are actively masculinised during foetal development and early postnatal life by the combined actions of prostaglandins and androgens, resulting in the male-typical reproductive behaviour seen in adulthood. Both androgens and prostaglandins are known to be inhibited by APAP. Through intrauterine exposure experiments in C57BL/6 mice, we found that exposure to APAP decreased neuronal number in the sexually dimorphic nucleus (SDN) of the preoptic area (POA) in the anterior hypothalamus of male adult offspring. Likewise, exposure to the environmental pollutant and precursor of APAP, aniline, resulted in a similar reduction. Decrease in neuronal number in the SDNPOA is associated with reductions in male sexual behaviour. Consistent with the changes, male mice exposed in uteri to APAP exhibited changes in urinary marking behaviour as adults and had a less aggressive territorial display towards intruders of the same gender. Additionally, exposed males had reduced intromissions and ejaculations during mating with females in oestrus. Together, these data suggest that prenatal exposure to APAP may impair male sexual behaviour in adulthood by disrupting the sexual neurobehavioral programming. These findings add to the growing body of evidence suggesting the need to limit the widespread exposure and use of APAP by pregnant women.
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| 3. |
- Jensen, Tina Kold, et al.
(author)
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Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010-2012)
- 2016
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In: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 124:7, s. 1107-1113
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Journal article (peer-reviewed)abstract
- BACKGROUND: Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)-the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported. OBJECTIVE: We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their male infants at 3 months of age (n = 273). METHODS: In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4-30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score. RESULTS: Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose-response patterns, and associations were not statistically significant (p > 0.05). CONCLUSION: We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population.
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| 4. |
- Callesen, Michael Thude, et al.
(author)
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Phthalate metabolites in urine and asthma, allergic rhinoconjunctivitis and atopic dermatitis in preschool children
- 2014
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In: International journal of hygiene and environmental health. - : Elsevier BV. - 1438-4639 .- 1618-131X. ; 217:6, s. 645-652
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Journal article (peer-reviewed)abstract
- Phthalate esters are among the most ubiquitous of indoor pollutants and have been associated with various adverse health effects. In the present study we assessed the cross-sectional association between eight different phthalate metabolites in urine and allergic disease in young children. As part of the Danish Indoor Environment and Children's Health study, urine samples were collected from 440 children aged 3-5 years, of whom 222 were healthy controls, 68 were clinically diagnosed with asthma, 76 with rhinoconjunctivitis and 81 with atopic dermatitis (disease subgroups are not mutually exclusive; some children had more than one disease). There were no statistically significant differences in the urine concentrations of phthalate metabolites between cases and healthy controls with the exception of MnBP and MECPP, which were higher in healthy controls compared with the asthma case group. In the crude analysis MnBP and MiBP were negatively associated with asthma. In the analysis adjusted for multiple factors, only a weak positive association between MEP in urine and atopic dermatitis was found; there were no positive associations between any phthalate metabolites in urine and either asthma or rhinoconjunctivitis. These findings appear to contradict earlier studies. Differences may be due to higher exposures to certain phthalates (e.g., BBzP) via non-dietary pathways in earlier studies, phthalates serving as surrogates for an agent associated with asthma (e.g., PVC flooring) in previous studies but not the present study or altered cleaning habits and the use of "allergy friendly" products by parents of children with allergic disease in the current study in contrast to studies conducted earlier.
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| 5. |
- Grandjean, Philippe, et al.
(author)
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The faroes statement : human health effects of developmental exposure to chemicals in our environment.
- 2008
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In: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 102:2, s. 73-5
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Journal article (peer-reviewed)abstract
- The periods of embryonic, foetal and infant developmentare remarkably susceptible to environmental hazards. Toxicexposures to chemical pollutants during these windows ofincreased susceptibility can cause disease and disability ininfants, children and across the entire span of human life.Among the effects of toxic exposures recognized in the pasthave been spontaneous abortion, congenital malformations,lowered birthweight and other adverse effects. These outcomesmay be readily apparent. However, even subtle changes causedby chemical exposures during early development may leadto important functional deficits and increased risks ofdisease later in life. The timing of exposure during early lifehas therefore become a crucial factor to be considered intoxicological assessments.During 20–24 May 2007, researchers in the fields of environmentalhealth, environmental chemistry, developmentalbiology, toxicology, epidemiology, nutrition and paediatricsgathered at the International Conference on Fetal Programmingand Developmental Toxicity, in Tórshavn, FaroeIslands. The conference goal was to highlight new insightsinto the effects of prenatal and early postnatal exposure tochemical agents, and their sustained effects on the individualthroughout the lifespan. The conference brought togetherresearchers to focus on human data and the translationof laboratory results to elucidate the environmental risks tohuman health.
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| 6. |
- Have Beck, Iben, et al.
(author)
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Association Between Prenatal and Early Postnatal Exposure to Perfluoroalkyl Substances and IQ Score in 7-Year-Old Children From the Odense Child Cohort
- 2023
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In: American Journal of Epidemiology. - 0002-9262. ; 192:9, s. 1522-1535
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Journal article (peer-reviewed)abstract
- Perfluoroalkyl substances (PFAS) are persistent chemicals capable of crossing the placenta and passing into breast milk. Evidence suggests that PFAS exposure may affect brain development. We investigated whether prenatal or early postnatal PFAS exposure was associated with intelligence quotient (IQ) scores in schoolchildren from the Odense Child Cohort (Denmark, 2010–2020). We assessed concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) in maternal serum collected during the first trimester of pregnancy and in child serum at age 18 months. At 7 years of age, children completed an abbreviated version of the Wechsler Intelligence Scale for Children, Fifth Edition, from which Full Scale Intelligence Quotient (FSIQ) and Verbal Comprehension Index scores were estimated. In multiple linear regression analyses conducted among 967 mother-child pairs, a doubling in maternal PFOS and PFNA concentrations was associated with a lower FSIQ score, while no significant associations were observed for PFOA, PFHxS, or PFDA. PFAS concentrations at age 18 months and duration of breastfeeding were strongly correlated, and even in structural equation models it was not possible to differentiate between the opposite effects of PFAS exposure and duration of breastfeeding on FSIQ. PFAS exposure is ubiquitous; therefore, an association with even a small reduction in IQ is of public health concern.
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| 7. |
- Meltzer, Helle Margrete, et al.
(author)
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Enhancing Human Biomonitoring Studies through Linkage to Administrative Registers–Status in Europe
- 2022
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:9
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Journal article (peer-reviewed)abstract
- Record linkage of human biomonitoring (HBM) survey data with administrative register data can be used to enhance available datasets and complement the possible shortcomings of both data sources. Through record linkage, valuable information on medical history (diagnosed diseases, medication use, etc.) and follow-up information on health and vital status for established cohorts can be obtained. In this study, we investigated the availability of health registers in different EU Member States and EEA countries and assessed whether they could be linked to HBM studies. We found that the availability of administrative health registers varied substantially between European countries as well as the availability of unique personal identifiers that would facilitate record linkage. General protocols for record linkage were similar in all countries with ethical and data protections approval, informed consent, approval by administrative register owner, and linkage conducted by the register owner. Record linkage enabled cross-sectional survey data to be used as cohort study data with available follow-up and health endpoints. This can be used for extensive exposure-health effect association analysis. Our study showed that this is possible for many, but not all European countries.
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| 8. |
- Scheike, Thomas, et al.
(author)
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Time Trends in Human Fecundability in Sweden.
- 2008
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In: Epidemiology. - 1531-5487. ; 19:2, s. 191-196
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Journal article (peer-reviewed)abstract
- BACKGROUND:: Trends in biologic fertility are elusive. Possible negative trends in male reproductive health are still debated, and their effect on human fertility might be negligible. Time-to-pregnancy (TTP) is a functional measure of couple fecundability. METHODS:: We analyzed data on TTP among 832,000 primiparous women 20 years of age and older in the nationwide Swedish Medical Birth Registry from 1983 through 2002. This age restriction led to an exclusion of 10% of primiparous pregnancies. Subfertility (TTP >/=1 year) was analyzed as a function of maternal age, calendar time at initiation of attempt, and birth cohort-taking into account the truncation problems that are inherent in birth-based retrospective sampling. RESULTS:: Subfertility generally decreased over successive birth cohorts. When studied as a period effect, a transient increase in subfertility was seen in the early 1990s. Subfertility increased with age, except that for women in their late 1930s, an apparent decrease was observed, particularly among the early cohorts. CONCLUSION:: We found decreasing subfertility over time. We speculate that these patterns might be related to a Sweden-specific decrease over time in sexually transmitted diseases, to changes in sexual behavior induced by socioeconomic conditions, or to broader biologic or educational trends.
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| 9. |
- Shu, Huan, 1980-
(author)
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Phthalates : On the issue of sources, human uptake, time trends and health effects
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Human health depends on a well-functioning endocrine system to regulate hormone release for normal bodily functions. Endocrine disrupting chemicals (EDCs) constitutes a group of chemicals, included in many commonly used products, (e.g., PVC flooring), with properties proven or suspected to interact with the natural hormone system in humans and animals. EDCs are manmade compounds (there are also natural compounds with such properties) that can bind to cell receptors and mimic or block the functions of natural hormones potentially resulting in adverse human health effects.One type of widely concerning EDC is phthalates. Since phthalates create weak chemical bonds when they are added into different products, they readily leach into the surrounding environment. Phthalate metabolites can therefore be frequently measured in human biological samples. Major public health concerns regarding EDCs over the past three decades have focused on phthalates. According to the World Health Organization, EDCs are suspected to be associated with altered reproductive function in males and females, increased incidence of breast cancer, abnormal growth patterns and neurodevelopmental delays in children, as well as changes in immune function.The thesis shows that PVC flooring in the home is a source for human uptake of phthalates, that replacement of phthalates in soft PVC products have an impact on human uptake of these chemicals, and that exposure for phthalates in early life increase the risk for airway disorders in children.As we have shown, ongoing regulations on phthalates is of importance for human uptake. Ultimately, individuals can make small changes in their consumer product choices that can lead to changes in uptake of chemicals with endocrine disrupting properties. Philosophically, we all have a responsibility to protect future generations from dangerous chemicals.
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| 10. |
- Sigvaldsen, Annika, et al.
(author)
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Early-life exposure to perfluoroalkyl substances and serum antibody concentrations towards common childhood vaccines in 18-month-old children in the Odense Child Cohort
- 2024
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In: Environmental Research. - 0013-9351. ; 242
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Journal article (peer-reviewed)abstract
- Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with reduced antibody response to childhood vaccinations. Previous studies have mostly focused on antibodies against diphtheria or tetanus, while fewer studies have assessed antibodies toward attenuated viruses, such as measles, mumps or rubella (MMR). Therefore, we set out to determine associations between prenatal and early postnatal PFAS exposure and vaccine-specific Immunoglobulin G (IgG) in the background-exposed Odense Child Cohort. Blood samples were drawn in pregnancy at gestation weeks 8–16 and from the offspring at age 18 months. In the maternal serum samples we quantified perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). In the offspring serum samples we quantified the same five PFAS compounds and IgG towards diphtheria, tetanus and MMR. A total of 880 and 841 children were included in the analyses of diphtheria and tetanus or MMR, respectively. Multiple linear regression models were used for estimation of difference in virus-specific IgG per doubling of PFAS concentrations. Maternal PFAS concentrations were non-significantly inversely associated with most vaccine-specific antibody concentrations. Likewise, child PFAS concentrations were associated with non-significant reductions of antibodies towards tetanus and MMR. A significant reduction in the percent difference in mumps antibody concentration per doubling of child PFNA (−9.2% (95% confidence interval: −17.4;-0.2)), PFHxS (−8.3% (−15.0;-1.0) and PFOS (−7.9% (−14.8;-0.4) was found. These findings are of public health concern, as inadequate response towards childhood vaccines may represent a more general immune dysfunction.
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