Challenges to evidence synthesis and identification of data gaps in human biomonitoring

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The increasing number of human biomonitoring (HBM) studies undertaken in recent decades has brought to light the need to harmonise procedures along all phases of the study, including sampling, data collection and analytical methods to allow data comparability. The first steps towards harmonisation are the identification and collation of HBM methodological information of existing studies and data gaps. Systematic literature reviews and meta-analyses have been traditionally put at the top of the hierarchy of evidence, being increasingly applied to map available evidence on health risks linked to exposure to chemicals. However, these methods mainly capture peer-reviewed articles, failing to comprehensively identify other important, unpublished sources of information that are pivotal to gather a complete map of the produced evidence in the area of HBM. Within the framework of the European Human Biomonitoring Initiative (HBM4EU) initiative-a project that joins 30 countries, 29 from Europe plus Israel, the European Environment Agency and the European Commission-a comprehensive work of data triangulation has been made to identify existing HBM studies and data gaps across countries within the consortium. The use of documentary analysis together with an up-to-date platform to fulfil this need and its implications for research and practice are discussed.HBM4EU has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032.info:eu-repo/semantics/publishedVersio

Concurrent Assessment of Phthalates/HEXAMOLL® DINCH Exposure and Wechsler Intelligence Scale for Children Performance in Three European Cohorts of the HBM4EU Aligned Studies

Information about the effects of phthalates and non-phthalate substitute cyclohexane-1,2-dicarboxylic acid diisononyl ester (HEXAMOLL® DINCH) on children's neurodevelopment is limited. The aim of the present research is to evaluate the association between phthalate/HEXAMOLL® DINCH exposure and child neurodevelopment in three European cohorts involved in HBM4EU Aligned Studies. Participating subjects were school-aged children belonging to the Northern Adriatic cohort II (NAC-II), Italy, Odense Child Cohort (OCC), Denmark, and PCB cohort, Slovakia. In each cohort, children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score (FSIQ) of the Wechsler Intelligence Scale of Children test using three different editions. The children's urine samples, collected for one point in time concurrently with the neurodevelopmental evaluation, were analyzed for several phthalates/HEXAMOLL® DINCH biomarkers. The relation between phthalates/HEXAMOLL® DINCH and FSIQ was explored by applying separate multiple linear regressions in each cohort. The means and standard deviations of FSIQ were 109 ± 11 (NAC-II), 98 ± 12 (OCC), and 81 ± 15 (PCB cohort). In NAC-II, direct associations between FSIQ and DEHP's biomarkers were found: 5OH-MEHP+5oxo-MEHP (β = 2.56; 95% CI 0.58-4.55; N = 270), 5OH-MEHP+5cx-MEPP (β = 2.48; 95% CI 0.47-4.49; N = 270) and 5OH-MEHP (β = 2.58; 95% CI 0.65-4.51; N = 270). On the contrary, in the OCC the relation between DEHP's biomarkers and FSIQ tended to be inverse but imprecise (p-value ≥ 0.10). No associations were found in the PCB cohort. FSIQ was not associated with HEXAMOLL® DINCH in any cohort. In conclusion, these results do not provide evidence of an association between concurrent phthalate/DINCHHEXAMOLLR DINCH exposure and IQ in children.This work received external funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 733032 [“European Human Biomonitoring Initiative” (HBM4EU)] and received co-funding from the author’s organizations. NAC-II: This research was funded by: the European Union through its Sixth Framework Program for RTD (contract “PHIME” No. FOOD-CT-2006-016253); the Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, Italy (RC 12/12 funded by Ministry of Health—Italy); CROME LIFE Project “Cross-Mediterranean Environment and Health Network” (LIFE12 ENV/GR/001040). OCC: The cohort was funded by the Odense University Hospital, Denmark; the Region of Southern Denmark, The Municipality of Odense, Denmark; The University of Southern Denmark; the Mental Health Service of the Region of Southern Denmark; Odense Patient data Exploratory Network (OPEN), Den mark; The Danish Center for Hormone Disrupting Chemicals (MST-611-00012); The Danish Research Council (4004-00352B_FSS); Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404); Sygeforsikring Danmark (journalnr. 2021-0173); The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation. PCB: PCB cohort was funded by the Slovak Research and Development Agency, project no. APVV-0571-12 and the Ministry of Health of the Slovak Republic, project no. 2014/47-SZU-11. The APC was funded by the European Union’s Horizon 2020 research and innovation program under grant agreement No. 733032.S

Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review

The production of plastic products, which requires phthalate plasticizers, has resulted in the problems for human health, especially that of reproductive health. Phthalate exposure can induce reproductive disorders at various regulatory levels. The aim of this review was to compile the evidence concerning the association between phthalates and reproductive diseases, phthalates-induced reproductive disorders, and their possible endocrine and intracellular mechanisms. Phthalates may induce alterations in puberty, the development of testicular dysgenesis syndrome, cancer, and fertility disorders in both males and females. At the hormonal level, phthalates can modify the release of hypothalamic, pituitary, and peripheral hormones. At the intracellular level, phthalates can interfere with nuclear receptors, membrane receptors, intracellular signaling pathways, and modulate gene expression associated with reproduction. To understand and to treat the adverse effects of phthalates on human health, it is essential to expand the current knowledge concerning their mechanism of action in the organism

Urinary Phthalate Biomarkers during Pregnancy, and Maternal Endocrine Parameters in Association with Anthropometric Parameters of Newborns

Adverse birth outcomes present risk factors resulting in neonatal morbidity and mortality. Sufficient maternal hormonal concentrations are crucial for normal foetal development. Previous studies have shown a relationship between phthalate exposure and maternal hormonal levels during pregnancy. This study aims to investigate if neonatal anthropometric parameters are associated with maternal endocrine parameters during the ≤15th week of gestation and the third trimester of pregnancy concerning phthalate exposure in pregnant women from Nitra, Slovakia. We used high-performance liquid chromatography, tandem mass spectrometry (HPLC-MS/MS), and electro-chemiluminescence immunoassay to quantify urinary concentrations of phthalates and serum concentrations of hormones and sex hormone-binding globulin (SHBG), respectively. We observed a mostly positive correlation between neonatal anthropometric parameters (gestational age, birth length, birth weight, head circumference) and maternal concentration of phthalate metabolites (p ≤ 0.05). The hierarchical multivariate regression results showed a statistically significant association between Apgar score at 5 min after delivery, gestational age, birth weight, head circumference, and maternal endocrine parameters during pregnancy (p ≤ 0.05), adjusted to phthalate metabolites. To the best of our knowledge, our study is the first to indicate that prenatal exposure to phthalates may also affect birth outcomes through interaction with the maternal endocrine system

Risk of Abdominal Obesity Associated with Phthalate Exposure of Nurses

Background: Occupational health hazards associated with phthalate exposure among nurses are still not well understood. Methods: We used high-performance liquid chromatography and tandem mass spectrometry to analyze phthalates. Anthropometric measurements and questionnaires were conducted. Results: We observed associations between mono-benzyl phthalate (MBzP) and body mass index (BMI), hip circumference (HC), waist circumference (WC), waist to height ratio (WHtR), and fat mass index (FMI), visceral fat content, BMI risk and hip index risk (HIrisk), adjusted to consumer behavior and consumer practices (r = 0.36–0.61; p ≤ 0.046). In the same model, we detected an association between mono-n-butyl phthalate (MnBP) and waist to hip ratio (WHR; r = 0.36; p = 0.046), mono-carboxy-isononyl phthalate (cx-MiNP) and BMI (r = 0.37; p = 0.043), HC (r = 0.4; p = 0.026) and WHtR (r = 0.38; p = 0.037), between mono-oxo-isononyl phthalate oxo (MiNP) and HC (r = 0.36; p = 0.045), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (oxo-MEHP) and HIrisk (r = 0.38–0.41; p ≤ 0.036), between oxo-MEHP and Anthropometric Risk Index (ARI risk; r = 0.4; p = 0.028). We detected a relationship between BMI and MBzP (β = 0.655; p p = 0.003), between hip circumference and MBzP (β = 0.486; p p = 0.001), and sum of secondary metabolites of diisononyl phthalate (∑DiNP; β = 0.307; p = 0.016). We observed a relationship between fat content and MBzP (β = 0.302; p = 0.033), OH-MnBP (β = −0.736; p = 0.006) and MiBP (β = 0.547; p = 0.046), visceral fat content and MBzP (β = 0.307; p = 0.030), HI-risk and MBzP (β = 0.444; p = 0.001), ARI-risk and sum of di-n-butyl phthalate metabolites (∑DnBP; β = 0.337; p = 0.018). We observed an association between the use of protective equipment with cx-MiNP. Conclusions: Occupational exposure to phthalates may induce abdominal obesity and result in obesity-related metabolic disorders