RESUMEN
The chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment.
Asunto(s)
Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Humanos , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente/métodos , Monitoreo del Ambiente/normas , Contaminantes Ambientales/análisis , Sustancias Peligrosas/análisis , Espectrometría de Masas/métodos , Medición de Riesgo/métodosRESUMEN
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 < 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 (ß = 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 (ß = -0.13, 95 % CI: -0.19, -0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (ß = -0.08, 95 % CI: -0.14, -0.02, 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 (ß = -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.
Asunto(s)
Índice de Masa Corporal , Exposición a Riesgos Ambientales , Contaminantes Ambientales , Ácidos Ftálicos , Humanos , Ácidos Ftálicos/orina , Adolescente , Niño , Europa (Continente) , Estudios Transversales , Masculino , Femenino , Contaminantes Ambientales/orina , Contaminantes Ambientales/metabolismo , Exposición a Riesgos Ambientales/análisis , Monitoreo BiológicoRESUMEN
Human biomonitoring (HBM) frameworks assess human exposure to hazardous chemicals. In this review, we discuss and summarize sample preparation procedures and analytical methodology for six groups of chemicals of emerging concern (CECs), namely diisocyanates, benzotriazoles, benzothiazoles, 4-methylbenzylidene camphor, isothiazolinones, fragrances, and non-phthalate plasticizers, which are increasingly detected in urine, however, are not yet widely included in HBM schemes, despite posing a risk to human health. The sample preparation procedures depend largely on the chemical group; however, solid-phase extraction (SPE) is most often used due to the minimized sample handling, lower sample volume, and generally achieving lower limits of quantification (LOQs) compared to other extraction techniques. In terms of sample analysis, LC-based methods generally achieve lower limits of quantification (LOQs) compared to GC-based methods for the selected six groups of chemicals owing to their broader chemical coverage. In conclusion, since these chemicals are expected to be more frequently included in future HBM studies, it becomes evident that there is a pressing need for rigorous quality assurance programs to ensure better comparability of data. These programs should include the reporting of measurement uncertainty and facilitate inter-laboratory comparisons among the reporting laboratories. In addition, high-resolution mass spectrometry should be more commonly employed to enhance the specificity and selectivity of the applied analytical methodology since it is underrepresented in HBM. Furthermore, due to the scarcity of data on the levels of these CECs in urine, large population HBM studies are necessary to gain a deeper understanding of the associated risks.
Asunto(s)
Perfumes , Plastificantes , Humanos , Benzotiazoles , OdorantesRESUMEN
Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants that may impact youth adiposity patterns. We investigated cross-sectional associations between PFAS and body mass index (BMI) in teenagers/adolescents across nine European countries within the Human Biomonitoring for Europe (HBM4EU) initiative. We used data from 1957 teenagers (12-18 yrs) that were part of the HBM4EU aligned studies, consisting of nine HBM studies (NEBII, Norway; Riksmaten Adolescents 2016-17, Sweden; PCB cohort (follow-up), Slovakia; SLO CRP, Slovenia; CROME, Greece; BEA, Spain; ESTEBAN, France; FLEHS IV, Belgium; GerES V-sub, Germany). Twelve PFAS were measured in blood, whilst weight and height were measured by field nurse/physician or self-reported in questionnaires. We assessed associations between PFAS and age- and sex-adjusted BMI z-scores using linear and logistic regression adjusted for potential confounders. Random-effects meta-analysis and mixed effects models were used to pool studies. We assessed mixture effects using molar sums of exposure biomarkers with toxicological/structural similarities and quantile g-computation. In all studies, the highest concentrations of PFAS were PFOS (medians ranging from 1.34 to 2.79 µg/L). There was a tendency for negative associations with BMI z-scores for all PFAS (except for PFHxS and PFHpS), which was borderline significant for the molar sum of [PFOA and PFNA] and significant for single PFOA [ß-coefficient (95% CI) per interquartile range fold change = -0.06 (-0.17, 0.00) and -0.08 (-0.15, -0.01), respectively]. Mixture assessment indicated similar negative associations of the total mixture of [PFOA, PFNA, PFHxS and PFOS] with BMI z-score, but not all compounds showed associations in the same direction: whilst [PFOA, PFNA and PFOS] were negatively associated, [PFHxS] associated positively with BMI z-score. Our results indicated a tendency for associations of relatively low PFAS concentrations with lower BMI in European teenagers. More prospective research is needed to investigate this potential relationship and its implications for health later in life.
Asunto(s)
Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Adolescente , Humanos , Fluorocarburos/análisis , Índice de Masa Corporal , Estudios Transversales , Estudios Prospectivos , Contaminantes Ambientales/análisisRESUMEN
Every day we are exposed to a cocktail of anthropogenic compounds many of which are biologically active and capable of inducing negative effects. The simplest way to monitor contaminants in a population is via human biomonitoring (HBM), however conventional targeted approaches require foreknowledge of chemicals of concern, often have compound specific extractions and provide information only for those compounds. This study developed an extraction process for human biomarkers of interest (BoE) in urine that is less compound specific. Combining this with an ultra-high resolution mass spectrometer capable of operating in full scan, and a suspect and non-targeted analysis (SS/NTA) approach, this method provides a more holistic characterization of human exposure. Sample preparation development was based on enzymatically hydrolysed urine spiked with 34 native standards and extracted by solid-phase extraction (SPE). HRMS data was processed by MzMine2 and 80% of standards were identified in the final data matrix using typical NTA data processing procedures.
Asunto(s)
Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Monitoreo Biológico , Biomarcadores , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente/métodos , Humanos , Espectrometría de Masas/métodosRESUMEN
Phthalates and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), bisphenols (BPs), parabens (PBs), and triclosan (TCS) are high-production-volume chemicals of pseudo-persistence that are concerning for the environment and human health. This study aims to assess the exposure to 10 phthalates, DINCH, and environmental phenols (3 BPs, 7 PBs, and TCS) of Slovenian men (n = 548) and lactating primiparous women (n = 536). We observed urinary concentrations comparable to studies from other countries and significant differences among the sub-populations. In our study, men had significantly higher levels of phthalates, DINCH, and BPs, whereas the concentrations of PBs in urine were significantly higher in women. The most significant determinant of exposure was the area of residence and the year of sampling (2008-2014) that mirrors trends in the market. Participants from urban or industrialized sampling locations had higher levels of almost all monitored analytes compared to rural locations. In an attempt to assess the risk of the population, hazard quotient (HQ) values were calculated for individual compounds and the chemical mixture. Individual analytes do not seem to pose a risk to the studied population at current exposure levels, whereas the HQ value of the chemical mixture is near the threshold of 1 which would indicate a higher risk. We conclude that greater emphasis on the risk resulting from cumulative exposure to chemical mixtures and additional studies are needed to estimate the exposure of susceptible populations, such as children.
Asunto(s)
Contaminantes Ambientales , Ácidos Ftálicos , Niño , Ácidos Dicarboxílicos , Exposición a Riesgos Ambientales/análisis , Ésteres , Femenino , Humanos , Lactancia , Masculino , Parabenos , FenolesRESUMEN
Human exposure to organic contaminants is widespread. Many of these contaminants show adverse health effects on human population. Human biomonitoring (HBM) follows the levels and the distribution of biomarkers of exposure (BoE), but it is usually done in a targeted manner. Suspect and non-targeted screening (SS/NTS) tend to find BoE in an agnostic way, without preselection of compounds, and include finding evidence of exposure to predicted, unpredicted known and unknown chemicals. This study describes the application of high-resolution mass spectrometry (HRMS)-based SS/NTS workflow for revealing organic contaminants in urine of a cohort of 200 children from Slovenia, aged 6-9 years. The children originated from two regions, urban and rural, and the latter were sampled in two time periods, summer and winter. We tentatively identified 74 BoE at the confidence levels of 2 and 3. These BoE belong to several classes of pharmaceuticals, personal care products, plasticizers and plastic related products, volatile organic compounds, nicotine, caffeine and pesticides. The risk of three pesticides, atrazine, amitraz and diazinon is of particular concern since their use was limited in the EU. Among BoE we tentatively identified compounds that have not yet been monitored in HBM schemes and demonstrate limited exposure data, such as bisphenol G, polyethylene glycols and their ethers. Furthermore, 7 compounds with unknown use and sources of exposure were tentatively identified, either indicating the entry of new chemicals into the market, or their metabolites and transformation products. Interestingly, several BoE showed location and time dependency. Globally, this study presents high-throughput approach to SS/NTS for HBM. The results shed a light on the exposure of Slovenian children and raise questions on potential adverse health effects of such mixtures on this vulnerable population.
Asunto(s)
Atrazina , Plaguicidas , Compuestos Orgánicos Volátiles , Atrazina/análisis , Monitoreo Biológico , Biomarcadores , Cafeína/análisis , Niño , Diazinón , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente/métodos , Éteres , Humanos , Nicotina/análisis , Plaguicidas/análisis , Preparaciones Farmacéuticas , Plastificantes/análisis , Plásticos , PolietilenglicolesRESUMEN
Imatinib is a selective tyrosine kinase inhibitor used to treat chronic myeloid leukemia. It enters the environment by excretion from the body through urine and feces and is transferred with wastewater to a wastewater treatment plant. There, it can be degraded by activated sludge, forming a number of biotransformation products. Presence of imatinib and its potential transformation products in the environment can impose a high risk to aquatic organisms and human health, therefore it is important to obtain knowledge of its environmental fate. The data presented here is a result of a simulated biodegradation of imatinib at two levels of activated sludge using a batch biotransformation setup, with and without carbon source. The data was acquired with UHPLC-HRMS/MS and processed by MzMine2.36 [1]. The dataset presents a table of [M+H]+ features with retention times and corresponding MS/MS data. With development of new data mining tools this data can be used to identify new transformation products of imatinib and with it fully understand its environmental fate and the risk associated with its presence in the environment.
RESUMEN
The aim of this study is to utilize novel and powerful workflows with publicly available tools to efficiently process data and facilitate rapid acquisition of knowledge on environmental fate studies. Taking imatinib (IMA) as an example, we developed an efficient workflow to describe IMA biodegradation with activated sludge (AS) from wastewater treatment plants (WWTP). IMA is a cytostatic pharmaceutical; a selective tyrosine kinase inhibitor used to treat chronic myeloid leukemia. Its reported ecotoxic, endocrine and genotoxic effects imply high risk for aquatic wildlife and human health, however its fate in the environment is not yet well known. The study was conducted in a batch biotransformation setup, at two AS concentration levels and in presence and absence of carbon source. Degradation profiles and formation of IMA transformation products (TPs) were investigated using UHPLC-QqOrbitrap-MS/MS which showed that IMA is readily biodegradable. TPs were determined using multivariate statistical analysis. Eight TPs were determined and tentatively identified, six of them for first time. Hydrolysis of amide bond, oxidation, demethylation, deamination, acetylation and succinylation are proposed as major biodegradation pathways. TP235, the product of amide bond hydrolysis, was detected and quantified in actual wastewaters, at levels around 1 ng/L. This calls for more studies on the environmental fate of IMA in order to properly asses the environmental risk and hazard associated to IMA and its TPs.
Asunto(s)
Espectrometría de Masas en Tándem , Contaminantes Químicos del Agua , Biodegradación Ambiental , Biotransformación , Humanos , Mesilato de Imatinib , Programas Informáticos , Aguas Residuales , Contaminantes Químicos del Agua/análisis , Flujo de TrabajoRESUMEN
Chemicals such as bisphenols, parabens and triclosan are endocrine disrupting chemicals. They are used in a wide variety of consumer products, making human exposure to those chemicals widespread. In the present study, levels of three bisphenols (bisphenol A, F and S), 7 parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl-, butyl-, benzyl paraben) and triclosan were measured in first morning void from 246 Slovenian children and adolescents, aged 6-9 and 11-15 years and living in a rural region of Slovenia. Median levels of specific-gravity corrected levels for bisphenol A, bisphenol F, methyl paraben and ethyl paraben were 1.9, 0.085, 5.4 and 2.5 µg/L for children and 1.6, 0.11, 7.2 and 6.0 µg/L for adolescents, respectively. Median levels for all other endocrine disrupting chemicals were < LOQ. The levels are comparable with the levels reported in studies across the world. Exposure was age, sex, and location specific. Higher levels of bisphenol F and ethyl paraben were found in the samples of adolescents, while higher levels of methyl paraben were found in samples from girls. Furthermore, individuals living in one of the sampling locations, Goricko, were exposed to higher levels of bisphenol F and ethyl paraben than those in the remaining two sampling locations. Information about participants' dietary habits, use of food packaging and personal care products was obtained through questionnaires, and used to investigate associations between urinary levels of the biomarkers and potential exposure sources. High fat foods were associated with bisphenol A exposure, and cosmetics items such as lipstick and perfume with methyl paraben exposure. Significant correlation between methyl- and propyl paraben was observed in children's samples, suggesting similar exposure sources, while other compounds were not largely correlated, indicating independent sources. Furthermore, association between a single nucleotide polymorphism (SNP) in UGT2B15 gene and urinary levels of methyl and ethyl paraben was observed, showing the role of UGT2B15 isoform in methyl and ethyl paraben metabolism as well as indicating the SNP rs1902023 as a potential biomarker of susceptibility to adverse effects caused by the exposure. The present study reports exposure of children and adolescents in Slovenia to a wide range of different endocrine disrupting chemicals for the first time, connecting it to exposure patterns and exposure sources. The study is to the authors' knowledge the first that investigates direct connection between levels of urinary endocrine disrupting chemical biomarkers and genetic polymorphism in UGT2B15.