Nontarget mass spectrometry and in silico molecular characterization of air pollution from the Indian subcontinent

Papazian, S; D'Agostino, LA; Sadiktsis, I; Froment, J; Bonnefille, B; Sdougkou, K; Xie, HY; Athanassiadis, I; Budhavant, K; Dasari, S; Andersson, A; Gustafsson, O; Martin, JW
2022 | Commun. Earth Environ. | 3 (1)
ambient , brown carbon , chemistry , dark-matter , diversity , evolution , organic aerosol , particulate matter , transport , variability
A combination of high-resolution mass spectrometry and computational molecular characterization techniques can structurally annotate up to 17% of organic compounds in fine particulate matter in highly polluted air sampled in the Maldives. Fine particulate-matter is an important component of air pollution that impacts health and climate, and which delivers anthropogenic contaminants to remote global regions. The complex composition of organic molecules in atmospheric particulates is poorly constrained, but has important implications for understanding pollutant sources, climate-aerosol interactions, and health risks of air pollution exposure. Here, comprehensive nontarget high-resolution mass spectrometry was combined with in silico structural prediction to achieve greater molecular-level insight for fine particulate samples (n = 40) collected at a remote receptor site in the Maldives during January to April 2018. Spectral database matching identified 0.5% of 60,030 molecular features observed, while a conservative computational workflow enabled structural annotation of 17% of organic structures among the remaining molecular dark matter. Compared to clean air from the southern Indian Ocean, molecular structures from highly-polluted regions were dominated by organic nitrogen compounds, many with computed physicochemical properties of high toxicological and climate relevance. We conclude that combining nontarget analysis with computational mass spectrometry can advance molecular-level understanding of the sources and impacts of polluted air.

Revisiting old lessons from classic literature on persistent global pollutants This article belongs to Ambio’s 50th Anniversary Collection. Theme: Environmental contaminants

2021 | Ambio | 50 (3) (534-538)
chemical regulation , environmental contaminants , mercury , persistent , polychlorinated
Looking back 50 years at classic literature was a reminder of inspiring discoveries and clever theories that were formative to the field of environmental chemistry, but also of the irreparable costs that persistent global pollutants have had on ecosystems and human society. In my view, these three papers have greatly impacted contemporary science and influenced development of policies that have limited the spread of hazardous contaminants. At the same time, a sobering reality is that reversing decades of past pollution has proven impossible in our lifetime, and global trends are dire for both legacy and emerging contaminants. Lessons in these papers are clear to most environmental scientists, but I argue have not resulted in adequate investment in infrastructure or manpower to enable systematic unbiased searching for pollutants as proposed by Soren Jensen in 1972. Acknowledging that the costs of new global contaminants will be too high, we must incentivize safer chemicals and their sustainable use, increase international exchange of lists of chemicals in commerce, and coordinate international efforts in nontarget screening to identify new contaminants before they circulate the world.

Interaction of prenatal bisphenols, maternal nutrients, and toxic metal exposures on neurodevelopment of 2-year-olds in the APrON cohort

Liu, JY; Martin, LJ; Dinu, I; Field, CJ; Dewey, D; Martin, JW
2021 | Environ Int | 155
a exposure , behavior , bisphenol a , bisphenol s , bpa , early-childhood , heavy metals , inner-city children , maternal nutrients , neurodevelopment , oxidative stress , samples , selenium , united-states
Background: Epidemiological studies suggest that Bisphenol-A (BPA) is a developmental neurotoxicant, but the modifying effects of maternal nutrient status or neurotoxicant metal co-exposures have not been reported. Bisphenol-S (BPS) is being used as a BPA-alternative, but few epidemiological studies have evaluated its effects. Objectives: To examine if prenatal maternal BPA or BPS exposure are associated with children's neurodevelopment at two years of age while adjusting for effect-measure modification by sex, maternal nutrients, and co-exposure to neurotoxic metals. Methods: Total BPA and BPS concentrations were analyzed in spot maternal urine from the second trimester; metals and maternal nutrient status were analyzed in blood. Child neurodevelopment was evaluated with the Bayley Scales of Infant Development-III (Bayley-III) at age 2 (394 maternal-child pairs) and linear regression was used to investigate associations. Results: Among nutrients and neurotoxic metals, selenium (Se) and cadmium (Cd) were the most significant predictors of Bayley-III scale scores. Higher maternal Cd was significantly correlated with poorer motor performance (p < 0.01), and higher levels of maternal Se were significantly associated with poorer performance on the cognitive, motor, and adaptive behavior scales (p < 0.05). While maternal Cd did not modify relationships between bisphenol exposures and Bayley-III scores, both maternal Se and child sex were significant effectmeasure modifiers. Associations between BPA exposure and social emotional scores were negative for boys (p = 0.056) but positive for girls (p = 0.046). Higher exposure to bisphenols was associated with lower motor scores among children with lower levels of maternal Se. Conclusion: Higher maternal Cd was associated with poorer motor development, but it was not an effect-measure modifier of bisphenols' effects on motor development. Maternal Se may be protective against adverse effects of bisphenols, and additional nutrient-bisphenol interaction studies examining sex-specific effects of BPA and BPS on child development are warranted.

Nontarget analysis reveals gut microbiome-dependent differences in the fecal PCB metabolite profiles of germ-free and conventional mice

Li, XS; Liu, YN; Martin, JW; Cui, JY; Lehmler, HJ
2021 | Environ. Pollut. | 268
2,4',5-trichlorobiphenyl , chlorinated biphenyl , drug-processing genes , enterotype , excretion , feces , glucuronidation , hydroxylated polychlorinated-biphenyls , identification , mechanisms , mixture , mus musculus , nontarget high-resolution mass spectrometry , pcb metabolites , rats
Mammalian polychlorinated biphenyl (PCB) metabolism has not been systematically explored with nontarget high-resolution mass spectrometry (Nt-HRMS). Here we investigated the importance of the gut microbiome in PCB biotransformation by Nt-HRMS analysis of feces from conventional (CV) and germ-free (GF) adult female mice exposed to a single oral dose of an environmental PCB mixture (6 mg/kg or 30 mg/kg in corn oil). Feces were collected for 24 h after PCB administration, PCB metabolites were extracted from pooled samples, and the extracts were analyzed by Nt-HRMS. Twelve classes of PCB metabolites were detected in the feces from CV mice, including PCB sulfates, hydroxylated PCB sulfates (OH-PCB sulfates), PCB sulfonates, and hydroxylated methyl sulfone PCBs (OH-MeSO2-PCBs) reported previously. We also observed eight additional PCB metabolite classes that were tentatively identified as hydroxylated PCBs (OH-PCBs), dihydroxylated PCBs (DiOH-PCBs), monomethoxylated dihydroxylated PCBs (MeO-OH-PCBs), methoxylated PCB sulfates (MeO-PCB sulfates), mono-to tetra-hydroxylated PCB quinones ((OH)(x)-quinones, x = 1-4), and hydroxylated polychlorinated benzofurans (OH-PCDF). Most metabolite classes were also detected in the feces from GF mice, except for MeO-OH-PCBs, OH-MeSO2-PCBs, and OH-PCDFs. Semi-quantitative analyses demonstrate that relative PCB metabolite levels increased with increasing dose and were higher in CV than GF mice, except for PCB sulfates and MeO-PCB sulfates, which were higher in GF mice. These findings demonstrate that the gut microbiome plays a direct or indirect role in the absorption, distribution, metabolism, or excretion of PCB metabolites, which in turn may affect toxic outcomes following PCB exposure. (C) 2020 Elsevier Ltd. All rights reserved.

Effects of prenatal exposure and co-exposure to metallic or metalloid elements on early infant neurodevelopmental outcomes in areas with small-scale gold mining activities in Northern Tanzania

Nyanza, EC; Bernier, FP; Martin, JW; Manyama, M; Hatfield, J; Dewey, D
2021 | Environ Int | 149
arsenic , artisanal and small-scale gold mining , cadmium , co-exposure , lead,mercury , neurodevelopmental impairment
Background: Artisanal and small-scale gold mining (ASGM) is associated with release of neurotoxic metallic or metalloid chemical elements including lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As). Objective: To examine associations between prenatal exposure and co-exposure to total lead (T-Pb), total mercury (T-Hg), total cadmium (T-Cd) and total arsenic (T-As) and infant neurodevelopment at 6 to 12 months of age in areas with ASGM activities in Tanzania. Methods: Women in their second trimester of pregnancy who resided in ASGM areas were enrolled from 2015 to 2017 (n = 883). At 6 to 12 months of age, children were assessed with the Malawi Developmental Assessment Tool (MDAT) (n = 439). We measured T-Pb, T-Hg, and T-Cd in maternal dried blood spots and T-As in maternal urines. Poisson regression was used to examine associations between prenatal concentrations of these elements and neurodevelopmental outcomes. Results: Prenatal T-Hg concentration was associated with global neurodevelopment status (aPR 1.03, CI:1.01-1.04; p < 0.001) and language impairment (aPR 1.05, CI:1.03-1.07; p < 0.001) on the MDAT. When prenatal T-Hg and T-As values were at or above the human biomonitoring reference values (>= 95%) of the German Environmental Survey for Human Biomonitoring, that is 0.80 mu g/L and 15 mu g/L, respectively, the prevalence ratio of global neurodevelopmental impairment was two times higher (aPR 2.1, CI:1.0-4.3; p = 0.034). There was a 40% increase in the prevalence ratio of global neurodevelopmental impairment (aPR 1.4, CI:0.90-2.10, p = 0.027), when prenatal T-Hg was at or above the reference value of 0.80 mu g/L and T-Pb was at or above the reference value of 35 mu g/L. When prenatal T-Hg was at or above the reference value of 0.80 mu g/L and T-As was at or above the reference value of 15 mu g/L, the prevalence ratio of global neurodevelopmental impairment was two times higher (aPR 2.1, CI:1.0-4.3; p < 0.034). Discussion: Infants born to women in areas with ASGM activities are at significant risk for neurodevelopmental impairment and this is associated with exposure to higher concentrations of Hg prenatally. Co-exposure to high concentrations of Hg and Pb, or Hg and As appeared to have negative potentiated effects on infants' neurodevelopment.

Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

Zhang, P; Carlsten, C; Chaleckis, R; Hanhineva, K; Huang, MN; Isobe, T; Koistinen, VM; Meister, I; Papazian, S; Sdougkou, K; Xie, HY; Martin, JW; Rappaport, SM; Tsugawa, H; Walker, DI; Woodruff, TJ; Wright, RO; Wheelock, CE
2021 | Environ. Sci. Technol. Lett. | 8 (10) (839-852)
air pollution , cancer , dietary , disease , environment , exposure , high-resolution metabolomics , ion mobility spectrometry , mass spectrometry , mortality
The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics.

Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

Zhang, P; Carlsten, C; Chaleckis, R; Hanhineva, K; Huang, MN; Isobe, T; Koistinen, VM; Meister, I; Papazian, S; Sdougkou, K; Xie, HY; Martin, JW; Rappaport, SM; Tsugawa, H; Walker, DI; Woodruff, TJ; Wright, RO; Wheelock, CE
2021 | Environ. Sci. Technol. Lett. | 8 (10) (839-852)
air pollution , cancer , dietary , disease , environment , exposure , high-resolution metabolomics , ion mobility spectrometry , mass spectrometry , mortality
The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics.

Neurodevelopmental and Metabolomic Responses from Prenatal Coexposure to Perfluorooctanesulfonate (PFOS) and Methylmercury (MeHg) in Sprague-Dawley Rats

Reardon, AJF; Karathra, J; Ribbenstedt, A; Benskin, JP; MacDonald, AM; Kinniburgh, DW; Hamilton, TJ; Fouad, K; Martin, JW
2019 | Chem. Res. Toxicol. | 32 (8) (1656-1669)
adult-blood donors , attention deficit/hyperactivity disorder , developmental exposure , fish consumption , lactational exposure , locomotor-activity , perfluorinated compounds , perfluoroalkyl acids , persistent organic pollutants , polychlorinated biphenyls
Methylmercury (MeHg) and perfluoro-octanesulfonate (PFOS) are major contaminants of human blood that are both common in dietary fish, thereby raising questions about their combined impact on human development. Here, pregnant Sprague-Dawley rats ingested a daily dose, from gestational day 1 through to weaning, of either 1 mg/kg bw PFOS (PFOS-only), 1 mg/kg MeHg (MeHg-only), a mixture of 0.1 mg/kg PFOS and 1 mg/kg MeHg (Low-Mix), or of 1 mg/kg of PFOS and 1 mg/kg MeHg (High-Mix). Newborns were monitored for physical milestones and reflexive developmental responses, and in juveniles the spontaneous activity, anxiety, memory, and cognition were assessed. Targeted metabolomics of 199 analytes was applied to sectioned brain regions of juvenile offspring. Newborns in the High-Mix group had decreased weight gain as well as delayed reflexes and innate behavioral responses compared to controls and individual chemical groups indicating a toxicological interaction on early development. In juveniles, cumulative mixture effects increased in a dose-dependent manner in tests of anxiety-like behavior. However, other developmental test results suggested antagonism, as PFOS-only and MeHg-only juveniles had increased hyperactivity and thigmotaxic behavior, respectively, but fewer effects in Low-Mix and High-Mix groups. Consistent with these behavioral observations, a pattern of antagonism was also observed in neurochemicals measured in rat cortex, as PFOS-only and MeHg-only juveniles had altered concentrations of metabolites (e.g., lipids, amino acids, and biogenic amines), while no changes were evident in the combined exposures. The cortical metabolites altered in PFOS-only and MeHg-only exposed groups are involved in inhibitory and excitatory neurotransmission. These proof-of-principle findings at relatively high doses indicate the potential for toxicological interaction between PFOS and MeHg, with developmental-stage specific effects. Future mixture studies at lower doses are warranted, and prospective human birth cohorts should consider possible confounding effects from PFOS and mercury exposure on neurodevelopment.

High-resolution mass spectrometry (HRMS) methods for nontarget discovery and characterization of poly- and per-fluoroalkyl substances (PFASs) in environmental and human samples

Liu, YN; D'Agostino, LA; Qu, GB; Jiang, GB; Martin, JW
2019 | Trac-Trends Anal. Chem. | 121
acids , chromatography , drinking water , fluorinated alternatives , high-resolution mass spectrometry (hrms) , identification , nontarget discovery , perfluorinated compounds , perfluoroalkyl substances , perfluorooctane sulfonate , pfas-feature identification , poly-/per-fluoroalkyl substances (pfass) , polyfluoroalkyl substances , precursors , suspect screening
Widespread environmental contamination of legacy long-chain poly- and per-fluoroalkyl substances (PFASs) has triggered chemical regulatory action and a global transitioning to alternative PFASs. More than 5000 PFASs are now recognized on various lists, but few have been monitored despite ample evidence of unidentified organic fluorine in human and environmental samples. Nevertheless, our review of the literature indicates that nontarget analytical methods based on high-resolution mass spectrometry have been used to discover more than 750 PFASs, belonging to more than 130 diverse classes, in strategically selected environmental samples, biofluids or commercial products. Among these reports, we summarize the analytical and data-processing strategies for nontarget PFAS discovery, identify knowledge gaps and propose new areas for method development. Discovery of emerging PFASs before they are global contaminants could mitigate future contamination if strategic techniques can be developed to prioritize some of these substances for synthesis and confirmation, further monitoring, source elucidation and hazard characterization. (c) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Longitudinal analysis reveals early-pregnancy associations between perfluoroalkyl sulfonates and thyroid hormone status in a Canadian prospective birth cohort

Reardon, AJF; Moez, EK; Dinu, I; Goruk, S; Field, CJ; Kinniburgh, DW; MacDonald, AM; Martin, JW
2019 | Environ Int | 129 (389-399)
child-development , free-thyroxine , longitudinal study design , neuropsychological development , perfluorinated acid isomers , perfluoroalkyl acids , perfluoroalkyl carboxylates , perfluoroalkyl sulfonates , perfluorooctane sulfonate , peroxidase antibodies , polyfluoroalkyl substances , pregnancy , serum concentrations , sprague-dawley rats , subclinical hypothyroidism , thyroid hormones
Serum perfluoroalkyl acids (PFAAs) have been linked to disruption of maternal thyroid hormone homeostasis, but results have varied between studies which we hypothesized was due to timing of the thyroid hormone measurements, variability in PFAA isomer patterns, or presence of other stressors. In a longitudinal study design, we investigated the time-dependency of associations between PFAA isomers and thyroid hormones during pregnancy and post-partum while considering thyroid peroxidase antibody (TPOAb) status and mercury (Hg) co-exposure. In participants of a prospective Canadian birth cohort (n = 494), free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH) and TPOAb were quantified in maternal plasma collected in each trimester and 3-months postpartum, and 25 PFAAs (15 linear and 10 branched) and Hg were quantified in samples collected during the second trimester. Perfluorohexane sulfonate (PFHxS) and total branched isomers of perfluorooctane sulfonate (PFOS) were positively associated with TSH in mixed-effect models, with strongest associations early in gestation. Throughout pregnancy and post-partum, PFHxS was inversely associated with FT4, consistent with elevated TSH, while Hg was inversely associated with FT3. In TPOAb-positive women, negative associations were found between PFUnA and FT4, and 1m-PFOS and TSH, supporting previous studies that thyroid disorder could increase susceptibility to PFAA-mediated hormone dysregulation. Hg did not confound associations but was a significant interaction term, revealing further positive associations between PFOS isomers (Sigma 3m + 4m-PFOS) and TSH. Higher perfluoroalkyl sulfonate exposures were associated with higher TSH and/or lower FT4, strongly suggestive that PFHxS and branched PFOS isomers are risk factors for subclinical maternal hypothyroidism. Isomer-specific analysis is important in future studies, as crude measures of 'totalPFOS' masked the associations of branched isomers. A concerning result was for PFHxS which had consistent negative associations with FT4 at all time points and a positive association with TSH in early pregnancy when fetal development is most sensitive to disruption.

Letter to the Editor: Optimism for Nontarget Analysis in Environmental Chemistry

Samanipour, S; Martin, JW; Lamoree, MH; Reid, MJ; Thomas, KV
2019 | Environ. Sci. Technol. | 53 (10) (5529-5530)

Hundreds of Unrecognized Halogenated Contaminants Discovered in Polar Bear Serum

Liu Y; Richardson ES; Derocher AE; Lunn NJ; Lehmler H-J; Li X; Zhang Y; Yue Cui J; Cheng L; Martin JW
2018 | Angew. Chem. Int. Ed. Engl. | 57 (50) (16401-16406)

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