| 1. |
- Al Naggar, Yahya, et al.
(author)
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Chronic Exposure to Polystyrene Microplastic Fragments Has No Effect on Honey Bee Survival, but Reduces Feeding Rate and Body Weight
- 2023
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In: Toxics. - : MDPI. - 2305-6304. ; 11:2
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Journal article (peer-reviewed)abstract
- Microplastics (MPs), in the form of fragments and fibers, were recently found in honey samples collected in Ecuador as well as in honey bees collected from Denmark and China. However, little is known about how MPs impact bee health. To fill this knowledge gap, we investigated the potential toxicity of irregularly shaped polystyrene (PS)-MP fragments on honey bee health. In the first experiment of its kind with honey bees, we chronically exposed bees with a well-established gut microbiome to small (27 ± 17 µm) or large (93 ± 25 µm) PS-MP fragments at varying concentrations (1, 10, 100 µg mL−1) for 14 days. Bee mortality, food consumption, and body weight were all studied. We found that chronic exposure to PS-MP fragments has no effect on honey bee survival, but reduced the feeding rate and body weight, particularly at 10 µg PS-MP fragments per mL, which may have long-term consequences for honey bee health. The findings of this study could assist in the risk assessment of MPs on pollinator health.
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| 2. |
- Behbehani, M., et al.
(author)
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Ocean Acidification-Mediated Food Chain Transfer of Polonium between Primary Producers and Consumers
- 2023
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In: Toxics. - : MDPI AG. - 2305-6304. ; 11:1
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Journal article (peer-reviewed)abstract
- Phytoplankton and zooplankton are key marine components that play an important role in metal distribution through a food web transfer. An increased phytoplankton concentration as a result of ocean acidification and warming are well-established, along with the fact that phytoplankton biomagnify Po-210 by 3-4 orders of magnitude compared to the seawater concentration. This experimental study is carried out to better understand the transfer of polonium between primary producers and consumers. The experimental produced data highlight the complex interaction between the polonium concentration in zooplankton food, i.e. phytoplankton, its excretion via defecated fecal pellets, and its bioaccumulation at ambient seawater pH and a lower pH of 7.7, typical of ocean acidification scenarios in the open ocean. The mass of copepods recovered was 11% less: 7.7 pH compared to 8.2. The effects of copepod species (n = 3), microalgae species (n = 3), pH (n = 2), and time (n = 4) on the polonium activity in the fecal pellets (expressed as % of the total activity introduced through feeding) was tested using an ANOVA 4. With the exception of time (model: F-20,F- 215 = 176.84, p < 0.001; time: F-3 = 1.76, p = 0.16), all tested parameters had an impact on the polonium activity (copepod species: F-2 = 169.15, p < 0.0001; algae species: F-2 = 10.21, p < 0.0001; pH: F-1 = 9.85, p = 0.002) with complex interactions (copepod x algae: F-2 = 19.48, p < 0.0001; copepod x pH: F-2 = 10.54, p < 0.0001; algae x pH: F-2 = 4.87, p = 0.009). The experimental data underpin the hypothesis that metal bioavailability and bioaccumulation will be enhanced in secondary consumers such as crustacean zooplankton due to ocean acidification.
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| 3. |
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| 4. |
- Erdei, Anna Laura
(author)
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The Comparative Toxicity, Biochemical and Physiological Impacts of Chlorantraniliprole and Indoxacarb on Mamestra brassicae (Lepidoptera: Noctuidae)
- 2023
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In: Toxics. - : MDPI AG. - 2305-6304. ; 11
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Journal article (peer-reviewed)abstract
- Background: The cabbage moth, Mamestra brassicae, is a polyphagous pest that attacks several crops. Here, the sublethal and lethal effects of chlorantraniliprole and indoxacarb were investigated on the developmental stages, detoxification enzymes, reproductive activity, calling behavior, peripheral physiology, and pheromone titer of M. brasssicae. Methods: To assess pesticide effects, the second instar larvae were maintained for 24 h on a semi-artificial diet containing insecticides at their LC10, LC30, and LC50 concentrations. Results: M. brassicae was more susceptible to chlorantraniliprole (LC50 = 0.35 mg/L) than indoxacarb (LC50 = 1.71 mg/L). A significantly increased developmental time was observed with both insecticides at all tested concentrations but decreases in pupation rate, pupal weight, and emergence were limited to the LC50 concentration. Reductions in both the total number of eggs laid per female and the egg viability were observed with both insecticides at their LC30 and LC50 concentrations. Both female calling activity and the sex pheromone (Z11-hexadecenyl acetate and hexadecenyl acetate) titer were significantly reduced by chlorantraniliprole in LC50 concentration. Antennal responses of female antennae to benzaldehyde and 3-octanone were significantly weaker than controls after exposure to the indoxocarb LC50 concentration. Significant reductions in the enzymatic activity of glutathione S-transferases, mixed-function oxidases, and carboxylesterases were observed in response to both insecticides.
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| 5. |
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| 6. |
- Lizano Fallas, Veronica, et al.
(author)
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Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets
- 2023
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In: Toxics. - : MDPI. - 2305-6304. ; 11:2
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Journal article (peer-reviewed)abstract
- The impact of exposure to multiple chemicals raises concerns for human and environmental health. The adverse outcome pathway method offers a framework to support mechanism-based assessment in environmental health starting by describing which mechanisms are triggered upon interaction with different stressors. The identification of the molecular initiating event and the molecular interaction between a chemical and a protein target is still a challenge for the development of adverse outcome pathways. The cellular response to chemical exposure studied with omics could not directly identify the protein targets. However, recent mass spectrometry-based methods are offering a proteome-wide identification of protein targets interacting with s but unrevealing a molecular initiating event from a set of targets is still dependent on available knowledge. Here, we directly coupled the target identification findings from the proteome integral solubility alteration assay with an analytical hierarchy process for the prediction of a prioritized molecular initiating event. We demonstrate the applicability of this combination of methodologies with a test compound (TCDD), and it could be further studied and integrated into AOPs. From the eight protein targets identified by the proteome integral solubility alteration assay after analyzing 2824 human hepatic proteins, the analytical hierarchy process can select the most suitable protein for an AOP. Our combined method solves the missing links between high-throughput target identification and prediction of the molecular initiating event. We anticipate its utility to decipher new molecular initiating events and support more sustainable methodologies to gain time and resources in chemical assessment.
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| 7. |
- Malm, Ellen, et al.
(author)
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Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Early Pregnancy and Small for Gestational Age in Southern Sweden
- 2023
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In: Toxics. - 2305-6304. ; 11:9
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Journal article (peer-reviewed)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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| 8. |
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| 9. |
- Olstrup, Henrik, et al.
(author)
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The Long-Term Mortality Effects Associated with Exposure to Particles and NOx in the Malmö Diet and Cancer Cohort
- 2023
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In: Toxics. - : MDPI. - 2305-6304. ; 11:11
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Journal article (peer-reviewed)abstract
- In this study, the long-term mortality effects associated with exposure to PM10 (particles with an aerodynamic diameter smaller than or equal to 10 µm), PM2.5 (particles with an aerodynamic diameter smaller than or equal to 2.5 µm), BC (black carbon), and NOx (nitrogen oxides) were analyzed in a cohort in southern Sweden during the period from 1991 to 2016. Participants (those residing in Malmö, Sweden, born between 1923 and 1950) were randomly recruited from 1991 to 1996. At enrollment, 30,438 participants underwent a health screening, which consisted of questionnaires about lifestyle and diet, a clinical examination, and blood sampling. Mortality data were retrieved from the Swedish National Cause of Death Register. The modeled concentrations of PM10, PM2.5, BC, and NOx at the cohort participants’ home addresses were used to assess air pollution exposure. Cox proportional hazard models were used to estimate the associations between long-term exposure to PM10, PM2.5, BC, and NOx and the time until death among the participants during the period from 1991 to 2016. The hazard ratios (HRs) associated with an interquartile range (IQR) increase in each air pollutant were calculated based on the exposure lag windows of the same year (lag0), 1–5 years (lag1–5), and 6–10 years (lag6–10). Three models were used with varying adjustments for possible confounders including both single-pollutant estimates and two-pollutant estimates. With adjustments for all covariates, the HRs for PM10, PM2.5, BC, and NOx in the single-pollutant models at lag1–5 were 1.06 (95% CI: 1.02–1.11), 1.01 (95% CI: 0.95–1.08), 1.07 (95% CI: 1.04–1.11), and 1.11 (95% CI: 1.07–1.16) per IQR increase, respectively. The HRs, in most cases, decreased with the inclusion of a larger number of covariates in the models. The most robust associations were shown for NOx, with statistically significant positive HRs in all the models. An overall conclusion is that road traffic-related pollutants had a significant association with mortality in the cohort.
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| 10. |
- Pennoyer, Emily H., et al.
(author)
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Unknown Organofluorine Mixtures in U.S. Adult Serum : Contribution from Pharmaceuticals?
- 2023
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In: Toxics. - : MDPI. - 2305-6304. ; 11:5
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Journal article (peer-reviewed)abstract
- Organofluorines occur in human serum as complex mixtures of known and unidentified compounds. Human biomonitoring traditionally uses targeted analysis to measure the presence of known and quantifiable per- and polyfluoroalkyl substances (PFAS) in serum, yet characterization of exposure to and quantification of PFAS are limited by the availability of methods and analytical standards. Studies comparing extractable organofluorine (EOF) in serum to measured PFAS using organofluorine mass balance show that measurable PFAS only explain a fraction of EOF in human serum and that other sources of organofluorine may exist. The gap in fluorine mass balance has important implications for human biomonitoring because the total body burden of PFAS cannot be characterized and the chemical species that make up unidentified EOF are unknown. Many highly prescribed pharmaceuticals contain organofluorine (e.g., Lipitor, Prozac) and are prescribed with dosing regimens designed to maintain a therapeutic range of concentrations in serum. Therefore, we hypothesize organofluorine pharmaceuticals contribute to EOF in serum. We use combustion ion chromatography to measure EOF in commercial serum from U.S. blood donors. Using fluorine mass balance, we assess differences in unexplained organofluorine (UOF) associated with pharmaceutical use and compare them with concentrations of organofluorine predicted based on the pharmacokinetic properties of each drug. Pharmacokinetic estimates of organofluorine attributable to pharmaceuticals ranged from 0.1 to 55.6 ng F/mL. Analysis of 44 target PFAS and EOF in samples of commercial serum (n = 20) shows the fraction of EOF not explained by Σ44 PFAS ranged from 15% to 86%. Self-reported use of organofluorine pharmaceuticals is associated with a 0.36 ng F/mL (95% CL: -1.26 to 1.97) increase in UOF, on average, compared to those who report not taking organofluorine pharmaceuticals. Our study is the first to assess sources of UOF in U.S. serum and examine whether organofluorine pharmaceuticals contribute to EOF. Discrepancies between pharmacokinetic estimates and EOF may be partly explained by differences in analytical measurements. Future analyses using EOF should consider multiple extraction methods to include cations and zwitterions. Whether organofluorine pharmaceuticals are classified as PFAS depends on the definition of PFAS.
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| 11. |
- Rahman, Mizanur, et al.
(author)
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Comparable response following exposure to biodiesel and diesel exhaust particles in advanced multicellular human lung models
- 2023
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In: Toxics. - : MDPI. - 2305-6304. ; 11:6
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Journal article (peer-reviewed)abstract
- Biodiesel is considered to be a sustainable alternative for fossil fuels such as petroleum-based diesel. However, we still lack knowledge about the impact of biodiesel emissions on humans, as airways and lungs are the primary target organs of inhaled toxicants. This study investigated the effect of exhaust particles from well-characterized rapeseed methyl ester (RME) biodiesel exhaust particles (BDEP) and petro-diesel exhaust particles (DEP) on primary bronchial epithelial cells (PBEC) and macrophages (MQ). The advanced multicellular physiologically relevant bronchial mucosa models were developed using human primary bronchial epithelial cells (PBEC) cultured at air–liquid interface (ALI) in the presence or absence of THP-1 cell-derived macrophages (MQ). The experimental set-up used for BDEP and DEP exposures (18 µg/cm2 and 36 µg/cm2) as well as the corresponding control exposures were PBEC-ALI, MQ-ALI, and PBEC co-cultured with MQ (PBEC-ALI/MQ). Following exposure to both BDEP and DEP, reactive oxygen species as well as the stress protein heat shock protein 60 were upregulated in PBEC-ALI and MQ-ALI. Expression of both pro-inflammatory (M1: CD86) and repair (M2: CD206) macrophage polarization markers was increased in MQ-ALI after both BDEP and DEP exposures. Phagocytosis activity of MQ and the phagocytosis receptors CD35 and CD64 were downregulated, whereas CD36 was upregulated in MQ-ALI. Increased transcript and secreted protein levels of CXCL8, as well as IL-6 and TNF-α, were detected following both BDEP and DEP exposure at both doses in PBEC-ALI. Furthermore, the cyclooxygenase-2 (COX-2) pathway, COX-2-mediated histone phosphorylation and DNA damage were all increased in PBEC-ALI following exposure to both doses of BDEP and DEP. Valdecoxib, a COX-2 inhibitor, reduced the level of prostaglandin E2, histone phosphorylation, and DNA damage in PBEC-ALI following exposure to both concentrations of BDEP and DEP. Using physiologically relevant multicellular human lung mucosa models with human primary bronchial epithelial cells and macrophages, we found BDEP and DEP to induce comparable levels of oxidative stress, inflammatory response, and impairment of phagocytosis. The use of a renewable carbon-neutral biodiesel fuel does not appear to be more favorable than conventional petroleum-based alternative, as regards of its potential for adverse health effects.
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| 12. |
- Sapounidou, Maria, et al.
(author)
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From Cohort to Cohort : A Similar Mixture Approach (SMACH) to Evaluate Exposures to a Mixture Leading to Thyroid-Mediated Neurodevelopmental Effects Using NHANES Data
- 2023
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In: Toxics. - : MDPI. - 2305-6304. ; 11:4
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Journal article (peer-reviewed)abstract
- Prenatal exposure to a mixture (MIX N) of eight endocrine-disrupting chemicals has been associated with language delay in children in a Swedish pregnancy cohort. A novel approach was proposed linking this epidemiological association with experimental evidence, where the effect of MIX N on thyroid hormone signaling was assessed using the Xenopus eleuthero-embryonic thyroid assay (XETA OECD TG248). From this experimental data, a point of departure (PoD) was derived based on OECD guidance. Our aim in the current study was to use updated toxicokinetic models to compare exposures of women of reproductive age in the US population to MIX N using a Similar Mixture Approach (SMACH). Based on our findings, 66% of women of reproductive age in the US (roughly 38 million women) had exposures sufficiently similar to MIX N. For this subset, a Similar Mixture Risk Index (SMRIHI) was calculated comparing their exposures to the PoD. Women with SMRIHI > 1 represent 1.1 million women of reproductive age. Older women, Mexican American and other/multi race women were less likely to have high SMRIHI values compared to Non-Hispanic White women. These findings indicate that a reference mixture of chemicals identified in a Swedish cohort—and tested in an experimental model for establishment of (PoDs)—is also of health relevance in a US population.
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| 13. |
- Sherif, Moustafa, et al.
(author)
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Genotoxicity of Occupational Pesticide Exposures among Agricultural Workers in Arab Countries : A Systematic Review and Meta-Analysis
- 2023
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In: Toxics. - : MDPI. - 2305-6304. ; 11:8
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Research review (peer-reviewed)abstract
- Exposure to pesticides in Arab countries is a significant public health concern due to extensive agricultural activity and pesticide use. This systematic review aimed to evaluate the genotoxic effects of agricultural pesticide exposure in the region, identify research gaps, and assess methodological limitations. Following the PRISMA guidelines, a comprehensive search yielded five relevant studies conducted in Egypt, Syria, and Jordan. Various genotoxicity assays were employed, revealing a higher level of DNA damage in exposed compared to non-exposed individuals. Farmers exposed to pesticides exhibited a significantly higher occurrence of chromosomal translocation (t(14;18)), micronuclei, and chromosomal aberrations. However, only two studies assessed cytotoxicity indirectly. The studies predominantly focused on male participants, with variations in sample size and pesticide types. The lack of detailed exposure data necessitates cautious interpretation. This review underscores the need for further research on the genotoxicity of occupational pesticide exposure in the Middle East. Future studies should adopt robust study designs, collect biological and environmental samples, conduct repeated sampling, analyze seasonal variations, and encompass diverse study sites associated with specific crop groups.
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| 14. |
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| 15. |
- Vogel, N, et al.
(author)
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Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
- 2023
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In: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
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Journal article (peer-reviewed)abstract
- Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.
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| 16. |
- Vogel, N, et al.
(author)
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Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
- 2023
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In: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
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Journal article (peer-reviewed)abstract
- Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.
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