Search

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-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs

BackgroundMechanistic studies show that heavy metals interfere with the hematopoietic system by inhibiting key enzymes, which could lead to anemia. However, the link between children's exposure and red blood cell (RBC) parameters has been inconsistent. We aimed to summarize evidence on human studies exploring the association between exposure to lead, mercury, cadmium, arsenic, and chromium VI and RBC parameters in children.MethodsFollowing the PRISMA guidelines, we searched PubMed, Scopus, and Web of Science databases for studies published between January 2010 and April 2022. Eligible papers included human observational studies that directly assessed exposure (internal dose) to the heavy metals under study and RBC parameters in participants aged ≤ 18 years. We excluded studies using hospital-based samples. Study quality was assessed using the National Institutes of Health's Quality Assessment Tools for Cohort and Cross-Sectional Studies. We synthesized the evidence using vote counting based on the direction of the relationship.ResultsOut of 6,652 retrieved papers, we included a total of 38 (33 assessing lead, four mercury, two cadmium, and two arsenic; chromium VI was not assessed in any included paper). More than half of the studies were conducted in Asia. We found evidence of a positive relationship between lead concentration and hemoglobin (proportion of studies reporting negative relationships = 0.750; 95% Confidence Interval (CI) 0.583, 0.874) and mean corpuscular hemoglobin (0.875; 95% CI 0.546, 0.986), and a positive relationship with red cell distribution width (0.000; 95%CI 0.000, 0.379). When considering only good-quality studies (24% of the Pb studies), only the relationship with hemoglobin levels remained (0.875; 95% CI: 0.546, 0.986).ConclusionWe found evidence of a negative relationship between lead concentration and hemoglobin and mean corpuscular hemoglobin and of a positive relationship with red cell distribution width in children. We also identified a need to conduct more studies in European countries. Future studies should use standardized practices and make efforts to increase study quality, namely by conducting comprehensive longitudinal studies. Our findings support the need to take further actions to limit heavy metal exposure during childhood.

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000–2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011–2012, biobanked samples from the DEMOCOPHES project were used. For 2014–2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5–12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24–52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

The goal of this study was to evaluate the effects of two kinds of 24-week dietary interventions in haemodialysis patients, a traditional nutritional intervention without a meal before dialysis (HG1) and implementation of a nutritional intervention with a meal served just before dialysis (HG2), in terms of analysing the differences in the serum metabolic profiles and finding biomarkers of dietary efficacy. These studies were performed in two homogenous groups of patients (n = 35 in both groups). Among the metabolites with the highest statistical significance between HG1 and HG2 after the end of the study, 21 substances were putatively annotated, which had potential significance in both of the most relevant metabolic pathways and those related to diet. After the 24 weeks of the dietary intervention, the main differences between the metabolomic profiles in the HG2 vs. HG1 groups were related to the higher signal intensities from amino acid metabolites: indole-3-carboxaldehyde, 5-(hydroxymethyl-2-furoyl)glycine, homocitrulline, 4-(glutamylamino)butanoate, tryptophol, gamma-glutamylthreonine, and isovalerylglycine. These metabolites are intermediates in the metabolic pathways of the necessary amino acids (Trp, Tyr, Phe, Leu, Ile, Val, Liz, and amino acids of the urea cycle) and are also diet-related intermediates (4-guanidinobutanoic acid, indole-3-carboxyaldehyde, homocitrulline, and isovalerylglycine).

A study was conducted within the European Human Biomonitoring Initiative (HBM4EU) to characterize occupational exposure to Cr(VI). Herein we present the results of biomarkers of genotoxicity and oxidative stress, including micronucleus analysis in lymphocytes and reticulocytes, the comet assay in whole blood, and malondialdehyde and 8-oxo-2′-deoxyguanosine in urine. Workers from several Cr(VI)-related industrial activities and controls from industrial (within company) and non-industrial (outwith company) environments were included. The significantly increased genotoxicity (p = 0.03 for MN in lymphocytes and reticulocytes; p < 0.001 for comet assay data) and oxidative stress levels (p = 0.007 and p < 0.001 for MDA and 8-OHdG levels in pre-shift urine samples, respectively) that were detected in the exposed workers over the outwith company controls suggest that Cr(VI) exposure might still represent a health risk, particularly, for chrome painters and electrolytic bath platers, despite the low Cr exposure. The within-company controls displayed DNA and chromosomal damage levels that were comparable to those of the exposed group, highlighting the relevance of considering all industry workers as potentially exposed. The use of effect biomarkers proved their capacity to detect the early biological effects from low Cr(VI) exposure, and to contribute to identifying subgroups that are at higher risk. Overall, this study reinforces the need for further re-evaluation of the occupational exposure limit and better application of protection measures. However, it also raised some additional questions and unexplained inconsistencies that need follow-up studies to be clarified.

Objectives 1-Methylnaphthalene (1-MN) is composed of 2 benzene rings and belongs to polycyclic aromatic hydrocarbons. The metabolism of 1-MN in laboratory animals and bacteria leads to the formation of 1-naphthoic acid (1-NA). Material and Methods In this study the distribution of 1-NA in lung, liver, spleen, kidney and urinary excretion of 1-NA in rats after single and repeated inhalation exposure to 1-MN vapors were investigated. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cytochrome were measured of the rats. Genotoxic effects were evaluated with the in vitro micronucleus test on V79 hamster fibroblasts. Results The concentrations of 1-NA in the tissues of rats after single and repeated exposure to 1-MN were dependent on the exposure dose. High levels of 1-NA were found in kidneys of animals after the single and repeated exposure to 1-MN. With an increase of 1-MN dose, an increase in the activity of cytochrome P450 (CYP1A1 and CYP1A2) was observed in the liver of rats. Compared to control animals, significantly higher ALT activity was noted in serum of rats exposed to 1-MN. The micronuclei frequency in V79 cells exposed to 1-MN (in the range of analyzable concentrations; i.e., 5–25 μg/ml) did not differ significantly from the vehicle control, whereas urine extracts from rats exposed to 1-MN induced a significant increase in the frequency of micronuclei compared to urine extracts from the group of control animals. Conclusions Metabolism of 1-MN in rats after the inhalation exposure leading to 1-NA was mainly observed during the first day after the end of exposure. It is likely that 1-MN metabolites present in rat urine can induce the increased micronuclei frequency as was shown in V79 cells. Int J Occup Med Environ Health. 2022;35(6):731–46

Lipidomics belongs to the family of the so-called omics domains, which, based on modern chemical technologies, strive to explain the biological principles of the organism’s functioning. Main biological functions of lipids include energy storage, the formation of cell membranes, and participation in the transmission of biological signals, and their dysregulation is responsible for the development of pathological states. Thanks to lipid profiling, potential biomarkers for disease diagnosis and prognosis can be identified. This paper discusses selected examples of the use of lipidomic tests in the diagnosis of the kidney, metabolic and neoplastic diseases based on research papers published over the last few years (since 2016). Only works based on the study of human biological material by mass spectrometry methods were taken into account. The examples of lipidomics application presented in this publication are only a few of the possibilities of this technique. As potential possibilities have already been discovered, the next step for the research community is to work on standardization of the approach to lipidomic research and to develop bioinformatics methods that allow efficient processing and analysis of large amounts of data generated in this technique. Int J Occup Med Environ Health. 2022;35(2):111–26

Arsenic (As) exposure causes numerous adverse health effects, which can be reduced by the nutrients involved in the metabolism of iAs (inorganic As). This study was carried out on two groups of copper-smelting workers: WN, workers with a urinary total arsenic (tAs) concentration within the norm (n = 75), and WH, workers with a urinary tAs concentration above the norm (n = 41). This study aimed to analyze the association between the intake level of the nutrients involved in iAs metabolism and the signal intensity of the metabolites that were affected by iAs exposure. An untargeted metabolomics analysis was carried out on urine samples using liquid chromatography–mass spectrometry, and the intake of the nutrients was analyzed based on 3-day dietary records. Compared with the WN group, five pathways (the metabolism of amino acids, carbohydrates, glycans, vitamins, and nucleotides) with twenty-five putatively annotated metabolites were found to be increased in the WH group. In the WN group, the intake of nutrients (methionine; vitamins B2, B6, and B12; folate; and zinc) was negatively associated with six metabolites (cytosine, D-glucuronic acid, N-acetyl-D-glucosamine, pyroglutamic acid, uridine, and urocanic acid), whereas in the WH group, it was associated with five metabolites (D-glucuronic acid, L-glutamic acid, N-acetyl-D-glucosamine, N-acetylneuraminic acid, and uridine). Furthermore, in the WH group, positive associations between methionine, folate, and zinc intake and the signal intensity of succinic acid and 3-mercaptolactic acid were observed. These results highlight the need to educate the participants about the intake level of the nutrients involved in iAs metabolism and may contribute to further considerations with respect to the formulation of dietary recommendations for people exposed to iAs.

Exposure to hexavalent chromium Cr(VI) may occur in several occupational activities, placing workers in many industries at risk for potential related health outcomes. Untargeted metabolomics was applied to investigate changes in metabolic pathways in response to Cr(VI) exposure. We obtained our data from a study population of 220 male workers with exposure to Cr(VI) and 102 male controls from Belgium, Finland, Poland, Portugal and the Netherlands within the HBM4EU Chromates Study. Urinary metabolite profiles were determined using liquid chromatography mass spectrometry, and differences between post-shift exposed workers and controls were analyzed using principal component analysis. Based on the first two principal components, we observed clustering by industrial chromate application, such as welding, chrome plating, and surface treatment, distinct from controls and not explained by smoking status or alcohol use. The changes in the abundancy of excreted metabolites observed in workers reflect fatty acid and monoamine neurotransmitter metabolism, oxidative modifications of amino acid residues, the excessive formation of abnormal amino acid metabolites and changes in steroid and thyrotropin-releasing hormones. The observed responses could also have resulted from work-related factors other than Cr(VI). Further targeted metabolomics studies are needed to better understand the observed modifications and further explore the suitability of urinary metabolites as early indicators of adverse effects associated with exposure to Cr(VI).