Next-generation biomonitoring of the early-life chemical exposome in neonatal and infant development

Jamnik, Thomas; Flasch, Mira; Braun, Dominik; Fareed, Yasmin; Wasinger, Daniel; Seki, David; Berry, David; Berger, Angelika; Wisgrill, Lukas; Warth, Benedikt

doi:10.1038/s41467-022-30204-y

Cited by 34 publications

(43 citation statements)

References 56 publications

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“…In the long-term longitudinal breast milk study, where one mother collected her breast milk across a total of 87 days, 30 of the most contaminated samples according to Jamnik et al . were selected to compare the hydrolysis efficiencies of the two tested enzyme mixtures H. pomatia and BGS recombinant with an undigested control [24]. The majority of the signals were observed in three classes of xenobiotics, namely plasticizers, phytoestrogens, and personal care products.…”

Section: Resultsmentioning

confidence: 99%

“…Reference standards of the 86 assessed xenobiotics were used for the quantitative assessment and are listed in the supplementary information. For detailed information such as MS/MS parameters, transitions, retention times, reference standard concentrations, as well as purchasing information please refer to Jamnik et al (2022) [24]. The reference standards were combined and dissolved in 10% ACN at final concentrations of 0.3-100 ng/mL for subsequent use as standard calibrants.…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

“…This indicates that a low number of xenobiotics are actually transferred to the infant, in comparison to the 59 xenobiotics found in urine (Table S12). In the long-term longitudinal breast milk study, where one mother collected her breast milk across a total of 87 days, 30 of the most contaminated samples according to Jamnik et al were selected to compare the hydrolysis efficiencies of the two tested enzyme mixtures H. pomatia and BGS recombinant with an undigested control [24]. The majority of the signals were (c) personal care products.…”

Section: Application To Breast Milkmentioning

confidence: 99%

“…The solution was prepared by adding 1 mL of 13 C18 ZEN to 19 mL ACN:MeOH (1:1). All prepared reference standards and solutions were stored at -20°C until required [24].…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

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A broad, exposome-type evaluation of xenobiotic phase II biotransformation in human biofluids by LC-MS/MS

Fareed¹,

Braun²,

Flasch³

et al. 2022

Preprint

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Xenobiotics are chemicals foreign to a specific organism that humans are exposed to on a daily basis through their food, drugs and the environment. These molecules are frequently metabolized to increase polarity and subsequent excretion. During sample preparation, deconjugation of phase II metabolites is a critical step to capture the total exposure to chemicals in liquid chromatography mass spectrometry assays (LC-MS). Knowledge on deconjugation efficiencies of different enzymes and the extend of conjugation in human biofluids has primarily been investigated for single compounds or individual chemical classes. In this study, the performance of three beta-glucuronidase and arylsulfatase mixtures from H. pomatia, from recombinant sources (BGS), and from Escherichia coli combined with recombinant arylsulfatase (ASPC) was compared and the efficiency of phase II deconjugation was monitored in breast milk, urine and plasma. An innovative LC-MS/MS biomonitoring method encompassing more than 80 highly diverse xenobiotics (e.g., plasticizers, industrial chemicals, mycotoxins, phytoestrogens, pesticides) was utilized for the comprehensive investigation of phase II conjugation in experiments investigating levels in breast milk and urine obtained from breastfeeding women. Overall, it was confirmed that H. pomatia is the most efficient enzyme in hydrolyzing different classes of xenobiotics for future exposome-scale biomonitoring studies. The recombinant BGS formulation, however, provided better results for breast milk samples, primarily due to lower background contamination, a major issue when employing the typically applied crude H. pomatia extracts. A deeper understanding of the global xenobiotic conjugation patterns will be essential for capturing environmental and food-related exposures within the exposome framework more comprehensively.

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Section: Resultsmentioning

confidence: 99%

Section: Chemicals and Reagentsmentioning

confidence: 99%

Section: Application To Breast Milkmentioning

confidence: 99%

“…The solution was prepared by adding 1 mL of 13 C18 ZEN to 19 mL ACN:MeOH (1:1). All prepared reference standards and solutions were stored at -20°C until required [24].…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

See 2 more Smart Citations

A broad, exposome-type evaluation of xenobiotic phase II biotransformation in human biofluids by LC-MS/MS

Fareed¹,

Braun²,

Flasch³

et al. 2022

Preprint

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“…Measurements were performed using the method based on Jamnik et al (2022). A 1290 Infinity II LC system (Agilent) was coupled to a QTrap 6500 + mass spectrometer equipped with an electrospray ionization (ESI) source (Sciex).…”

Section: Low-resolution Lc-ms/ms Analysismentioning

confidence: 99%

Comparing the sensitivity of low- and high-resolution mass spectrometry for xenobiotic trace analysis: A exposome-type case study

Flasch

Koellensperger

Warth

2022

Preprint

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The chemical exposome consists of all environmental exposures experienced throughout a lifetime. Liquid chromatography high-resolution mass spectrometry (HRMS) is common in untargeted exposome-wide analyses of xenobiotics in biological samples; however, human biomonitoring approaches usually utilize targeted low-resolution triple quadrupole (QQQ) mass spectrometry tailored to a small number of chemicals. HRMS can identify novel contaminants over a broad mass range but the detection of molecules from low-level exposure amidst a background of highly-abundant endogenous molecules has proven to be difficult. In this study, high- and low-resolution mass spectrometry with identical chromatography was utilized to determine the limits of quantitation (LOQ) of >100 xenobiotics and estrogenic hormones in pure solvent and human urine. For HRMS analyses, the median LOQ was 0.9 and 1.2 ng/mL in solvent and urine, respectively and for low-resolution QQQ measurements, the median LOQ was 0.1 and 0.2 ng/mL in solvent and urine, respectively. To evaluate the calculated LOQs in complex biological samples, spot urine samples from 24 Nigerian females were measured. The higher LOQ values for HRMS resulted in less quantified low-abundance analytes and decreased the number of compounds detected below the LOQ. Even at chronic low-dose exposure, such compounds might be relevant for human health because of a high individual toxicity or potential mixture effects. Nevertheless, HRMS enabled the additional screening for exposure to unexpected/unknown analytes, including emerging compounds and biotransformation products. Therefore, a synergy between high- and low-resolution mass spectrometry may currently be the best option to elucidate and quantify xenobiotics in exposome-wide association studies (ExWAS).

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Prenatal exposure to pesticide mixture in Argentina: A pilot study in puerperal women from Santa Fe province

Colussi,

Martinez,

Bellenger

et al. 2024

Birth Defects Research

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IntroductionThe epidemiological investigation of congenital anomalies (CA) represents a challenge due to the multiplicity of associated risk factors, notably environmental ones. The monitoring of genotoxic effects in different populations is a useful tool in human biomonitoring and has great biological importance in estimating the exposure risks to complex mixtures of chemical substances.ObjectiveThis study aimed to determine the presence of environmental xenobiotics and evaluate their genotoxic effect, in mothers of newborns with and without CA, and the possible association/correlation between those biomarkers and CA.Materials and methodsA descriptive case and control cross‐sectional study was developed on 290 postpartum women from Santa Fe, Argentina.ResultsSignificant differences were observed between both groups, for places of residence and gynecological variables. Metabolites of organochlorine (OC), organophosphate (OP), and pyrethroid (PYR) pesticides were detected. The most frequently detected compounds were atrazine (ATZ) (57.14%), carbendazim (CBZ) (46.42%), and methylparaben (46.42%), among others. A positive correlation was found between the number of pesticides in blood and genotoxic variables. On the other hand, mothers of children with genitourinary anomalies were the ones with the highest concentrations of ATZ and OP.Discussion and conclusionThese results showed a deep background in the health reality of Santa Fe, which could greatly impact the health of future adults, who have been born preterm. On the other hand, the mixture of pesticides detected confirms the environmental living conditions of women and the transplacental exposure to these compounds in each pregnancy. The potential effects on long‐term descendent health are unknown and unpredictable.

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Next-generation biomonitoring of the early-life chemical exposome in neonatal and infant development

Cited by 34 publications

References 56 publications

A broad, exposome-type evaluation of xenobiotic phase II biotransformation in human biofluids by LC-MS/MS

A broad, exposome-type evaluation of xenobiotic phase II biotransformation in human biofluids by LC-MS/MS

Comparing the sensitivity of low- and high-resolution mass spectrometry for xenobiotic trace analysis: A exposome-type case study

Prenatal exposure to pesticide mixture in Argentina: A pilot study in puerperal women from Santa Fe province

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