RESUMO
BACKGROUND: Hypospadias is a male genital tract defect for which an increase in prevalence has been documented over the last few decades. A role for environmental risk factors is suspected, including prenatal exposure to pesticides. OBJECTIVES: To study the risk of hypospadias in association with multiple pesticide measurements in meconium samples. METHODS: The Brittany Registry of Congenital Anomalies (France) conducted a case-control study between 2012 and 2018. Cases were hypospadias, ascertained by a pediatrician and a pediatric surgeon, excluding genetic conditions, following European Surveillance of Congenital Anomalies guidelines (N = 69). Controls (N = 135) were two male infants without congenital anomaly born after each case in the same maternity unit. Mothers in the maternity units completed a self-administered questionnaire, we collected medical data from hospital records, and medical staff collected meconium samples. We performed chemical analysis of 38 pesticides (parent compound and/or metabolite) by UHPLC/MS/MS following strict quality assurance/quality control criteria and blind to case-control status. We carried out logistic regression accounting for frequency-matching variables and major risk factors. RESULTS: Among the 38 pesticides measured, 16 (42%) were never detected in the meconium samples, 18 (47%) were in <5% of samples, and 4 (11%) in ≥5% of the samples. We observed an association between the detection of fenitrothion in meconium and the risk of hypospadias (OR = 2.6 [1.0-6.3] with n cases = 13, n controls = 21), but not the other pesticides. CONCLUSIONS: Our small study provides a robust assessment of fetal exposure. Fenitrothion's established antiandrogenic activities provide biologic plausibility for our observations. Further studies are needed to confirm this hypothesis.
Assuntos
Hipospadia , Praguicidas , Recém-Nascido , Lactente , Criança , Humanos , Masculino , Feminino , Gravidez , Hipospadia/induzido quimicamente , Hipospadia/epidemiologia , Mecônio/química , Praguicidas/toxicidade , Exposição Materna/efeitos adversos , Estudos de Casos e Controles , Espectrometria de Massas em Tandem , Fenitrotion/análise , França/epidemiologiaRESUMO
In an increasingly chemically polluted environment, rapidly characterizing the human chemical exposome (i.e., chemical mixtures accumulating in humans) at the population scale is critical to understand its impact on health. High-resolution mass spectrometry (HRMS) profiling of complex biological matrices can theoretically provide a comprehensive picture of chemical exposures. However, annotating the detected chemical features, particularly low-abundant ones, remains a significant obstacle to implementing such approaches at a large scale. We present Scannotation (https://github.com/scannotation/Scannotation_software), an automated and user-friendly suspect screening tool for the rapid pre-annotation of HRMS preprocessed data sets. This software tool combines several MS1 chemical predictors, i.e., m/z, experimental and predicted retention times, isotopic patterns, and neutral loss patterns, to score the proximity between features and suspects, thus efficiently prioritizing tentative annotations to verify. Scannotation and MS-DIAL4 were used to annotate blood serum samples of 75 Breton adolescents. Scannotation's combination of MS1-based chemical predictors allowed us to annotate 89 chemically diverse environmental compounds with high confidence (confirmed by MS2 when available). These compounds included 62% of emerging molecules, for which no toxicological or human biomonitoring data are reported in the literature. The complementarity observed with MS-DIAL4 results demonstrates the relevance of Scannotation for the efficient pre-annotation of large-scale exposomics data sets.
Assuntos
Expossoma , Humanos , Adolescente , Espectrometria de Massas/métodosRESUMO
The technological advances of cutting-edge high-resolution mass spectrometry (HRMS) have set the stage for a new paradigm for exposure assessment. However, some adjustments of the metabolomics workflow are needed before HRMS-based methods can detect the low-abundant exogenous chemicals in human matrixes. It is also essential to provide tools to speed up marker identifications. Here, we first show that metabolomics software packages developed for automated optimization of XCMS parameters can lead to a false negative rate of up to 80% for chemicals spiked at low levels in blood. We then demonstrate that manual selection criteria in open-source (XCMS, MZmine2) and vendor software (MarkerView, Progenesis QI) allow to decrease the rate of false negative up to 4% (MZmine2). We next report an MS1 automatized suspect screening workflow that allows for a rapid preannotation of HRMS data sets. The novelty of this suspect screening workflow is to combine several predictors based on m/z, retention time (Rt) prediction models, and isotope ratio to generate intermediate and global scorings. Several Rt prediction models were tested and hierarchized (PredRet, Retip, retention time indices, and a log P model), and a nonlinear scoring was developed to account for Rt variations observed within individual runs. We then tested the efficiency of this suspect screening tool to detect spiked and nonspiked chemicals in human blood. Compared to other existing annotation tools, its main advantages include the use of Rt predictors using different models, its speed, and the use of efficient scoring algorithms to prioritize preannotated markers and reduce false positives.
Assuntos
Algoritmos , Metabolômica , Software , Espectrometria de MassasRESUMO
An original multiresidue method based on thermal extraction (TE) and gas chromatography/tandem mass spectrometry (GC/MS/MS) was developed to simultaneously quantify, from a very small amount of sample (a few milligrams), a wide range of concerning SVOCs, including polycyclic musks, organochlorines (OCs), organophosphates (OPs), oxadiazolones, polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), phthalates and pyrethroids, in indoor settled dust. Method limits of quantification (LOQs) ranged from 5 ng g-1 for PCBs, oxadiazon, 4,4'-DDE and 4,4'-DDT to 2000 ng g-1 for DEHP for a 2 mg sample of sieved dust. The proposed method was successfully validated in terms of accuracy and precision via replicate analysis of four different standard reference materials (SRMs 1649b (Urban Dust), 2585 (Organic Contaminants in House Dust), 2786 and 2787 (Fine Atmospheric Particulate Matter)) supplied by the National Institute of Standards and Technology (NIST) and was applied to five real indoor settled dust samples collected in French schools. In addition, its performance was compared to that of a previously published method based on pressurized liquid extraction (PLE) and GC/MS/MS. The different results obtained demonstrate the advantages of the proposed method over conventional methods and illustrate its two main features: i) its ease of use and very rapid implementation in only three steps (sieving, weighing and analysis), which make it particularly appropriate for environmental monitoring programs and large-scale studies, and ii) its ability to precisely and accurately quantify a wide range of SVOCs from trace (a few ng g-1) to highly concentrated (several mg g-1) compounds from only 2 mg of sieved dust.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Monitoramento Ambiental/métodos , Compostos Orgânicos Voláteis/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Organofosfatos/análise , Ácidos Ftálicos/análise , Bifenilos Policlorados/análise , Hidrocarbonetos Policíclicos Aromáticos/análiseRESUMO
People are exposed to multiple pollutants, especially indoors, in particular through ingestion of indoor settled dust. In the perspective of a cumulative risk assessment, a multi-residue analytical method based on pressurized liquid extraction (PLE) and gas chromatography/tandem mass spectrometry (GC/MS/MS) was developed for the simultaneous analysis in indoor dust of several classes of semi-volatile organic compounds (SVOCs) of health concern, from trace to highly concentrated compounds, including musk fragrances, organochlorines (OCs), organophosphates (OPs), polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), phthalates and pyrethroids. The method was validated in terms of limits of quantification (LOQ), and accuracy and precision via spiking experiments on an inert material (Celite(®) 545) and replicate analysis of the standard reference material SRM 2585 supplied by the National Institute of Standards and Technology (NIST). Method LOQs for 200 mg samples of sieved dust were 26 ng g(-1) for PCBs and some OCs, 65 ng g(-1) for musks, OPs, PAHs, PBDEs, pyrethroids, other OCs and some phthalates, 132 ng g(-1) for butylbenzylphthalate (BBP), 197 ng g(-1) for tributylphosphate and 1579 ng g(-1) for other phthalates. Quadratic calibration curves were established for each compound by analyzing at least five calibration solutions and exhibited determination coefficients higher than 0.999. The method was successfully applied to the SRM 2585 and seven real indoor dust samples. The results obtained on SRM 2585 demonstrate both excellent reproducibility and agreement with the indicative, reference or certified values and provide, for the first time, indicative concentrations for chlorpyrifos, diazinon, diisononylphthalate (DiNP) and tetramethrin. The results obtained on real dust samples illustrate the ability of the proposed method to quantify a wide range of SVOCs in a single analysis, making it appropriate for environmental monitoring programs or large-scale studies with a large number of samples.