Is Exposure to BMAA a Risk Factor for Neurodegenerative Diseases? A Response to a Critical Review of the BMAA Hypothesis

Dunlop, RA; Banack, SA; Bishop, SL; Metcalf, JS; Murch, SJ; Davis, DA; Stommel, EW; Karlsson, O; Brittebo, EB; Chatziefthimiou, AD; Tan, VX; Guillemin, GG; Cox, PA; Mash, DC; Bradley, WG
2021 | Neurotox Res | 39 (1) (81-106)
als , als/pdc , bmaa , cyanobacteria , neurodegeneration , neurodegenerative diseases
In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to beta-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer's disease, Parkinson's disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review's title which incorrectly refers to BMAA as a "non-essential" amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they are fit-for-purpose. Although there remain gaps in the literature, an increasingly large body of data from multiple independent labs using orthogonal methods provides increasing evidence that chronic exposure to BMAA may be a risk factor for neurological illness.

Polycyclic Aromatic Hydrocarbons Have Adverse Effects on Benthic Communities in the Baltic Sea: Implications for Environmental Status Assessment

Raymond, C; Gorokhova, E; Karlson, AML
2021 | Front. Environ. Sci. | 9
biodiversity , contaminants , environmental quality , hazardous substances , key-species , seafloor integrity , sediment , zoobenthos
Changes in benthic macrofaunal communities are indicative of environmental stressors, including eutrophication and hypoxia. However, some species are sensitive not only to hypoxia but also to various environmental contaminants. We tested which of the environmental predictors (sediment organic carbon, sediment concentrations of metals and polyaromatic hydrocarbons [PAHs], bottom water oxygen, salinity, temperature, and surface chlorophyll-a concentration) that best explained the following response variables: (1) macrofauna community composition, (2) abundance of a benthic sentinel species, the amphipod Monoporeia affinis; and (3) the Benthic Quality Index (BQI). All data originated from 29 reference monitoring stations in the Baltic Sea and the statistical tests included both uni- and multivariate analyses. The community composition and BQI were best explained by the same combination of salinity, depth, temperature and PAH concentrations. The abundance of M. affinis, which is sensitive to hypoxia and chemical exposure, was best explained by PAHs as a single predictor. Our findings suggest that benthic communities in the Baltic Sea are influenced by anthropogenic contaminants, which should be taken into account when benthos is used for eutrophication status assessment.

Semi-Volatile Organic Compounds in Car Dust: A Pilot Study in Jeddah, Saudi Arabia

Ali, N; Kadi, MW; Albar, HMSA; Rashid, MI; Chandrasekaran, S; Summan, AS; de Wit, CA; Malarvannan, G
2021 | Int J Environ Res Public Health | 18 (9)
aromatic-hydrocarbons pahs , brominated flame retardants , car dust , flame retardants , health , homes , house-dust , human exposure , indoor dust , metabolites , organophosphate , pahs , pcbs , phthalates , risk assessment , serum samples
People may spend a significant amount of their daily time in cars and thus be exposed to chemicals present in car dust. Various chemicals are emitted from during car use, contaminating the car dust. In this study, we compiled published and unpublished data on the occurrence of phthalates, flame retardants (FRs), polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) in Saudi car dust. Phthalates, a class of chemical commonly used as plasticizers in different car parts, were the major pollutants found in car dust, with a median value of n-ary sumation phthalates 1,279,000 ng/g. Among other chemicals, organophosphate flame retardants (OPFRs) were found to be between 1500-90,500 ng/g, which indicates their use as alternative FRs in the car industry. The daily exposure to Saudi drivers (regular and taxi drivers) was below the respective reference dose (RfD) values of the individual chemicals. However, the estimated incremental lifetime cancer risk (ILCR) values due to chronic exposure to these chemicals was >1 x 10(-5) for taxi drivers for phthalates and PAHs, indicating that the long-term exposure to these chemicals is a cause of concern for drivers who spend considerable time in cars. The study has some limitations, due to the small number of samples, lack of updated RfD values, and missing cancer slope factors for many studied chemicals. Despite these limitations, this study indicates the possible range of exposure to drivers from chemicals in car dust and warrants further extensive studies to confirm these patterns.

Long-term exposure to particulate air pollution and black carbon in relation to natural and cause-specific mortality: a multicohort study in Sweden

Sommar, JN; Andersson, EM; Andersson, N; Sallsten, G; Stockfelt, L; Ljungman, PLS; Segersson, D; Eneroth, K; Gidhagen, L; Molnar, P; Wennberg, P; Rosengren, A; Rizzuto, D; Leander, K; Lager, A; Magnusson, PKE; Johansson, C; Barregard, L; Bellander, T; Pershagen, G; Forsberg, B
2021 | BMJ Open | 11 (9)
associations , cardiac epidemiology , cardiovascular-disease , cohorts , coupled road dust , emissions , epidemiology , goteborg , lung-cancer , matter , particles , public health , surface moisture model
Objectives To estimate concentration-response relationships for particulate matter (PM) and black carbon (BC) in relation to mortality in cohorts from three Swedish cities with comparatively low pollutant levels. Setting Cohorts from Gothenburg, Stockholm and Umea, Sweden. Design High-resolution dispersion models were used to estimate annual mean concentrations of PM with aerodynamic diameter <= 10 mu m (PM10) and <= 2.5 mu m (PM2.5), and BC, at individual addresses during each year of follow-up, 1990-2011. Moving averages were calculated for the time windows 1-5 years (lag1-5) and 6-10 years (lag6-10) preceding the outcome. Cause-specific mortality data were obtained from the national cause of death registry. Cohort-specific HRs were estimated using Cox regression models and then meta-analysed including a random effect of cohort. Participants During the study period, 7 340 cases of natural mortality, 2 755 cases of cardiovascular disease (CVD) mortality and 817 cases of respiratory and lung cancer mortality were observed among in total 68 679 individuals and 689 813 person-years of follow-up. Results Both PM10 (range: 6.3-41.9 mu g/m(3)) and BC (range: 0.2-6.8 mu g/m(3)) were associated with natural mortality showing 17% (95% CI 6% to 31%) and 9% (95% CI 0% to 18%) increased risks per 10 mu g/m(3) and 1 mu g/m(3) of lag1-5 exposure, respectively. For PM2.5 (range: 4.0-22.4 mu g/m(3)), the estimated increase was 13% per 5 mu g/m(3), but less precise (95% CI -9% to 40%). Estimates for CVD mortality appeared higher for both PM10 and PM2.5. No association was observed with respiratory mortality. Conclusion The results support an effect of long-term air pollution on natural mortality and mortality in CVD with high relative risks also at low exposure levels. These findings are relevant for future decisions concerning air quality policies.

A health economic assessment of air pollution effects under climate neutral vehicle fleet scenarios in Stockholm, Sweden

Kriit, HK; Sommar, JN; Forsberg, B; Astrom, S; Svensson, M; Johansson, C
2021 | J. Transp. Health | 22
co2 , cost , costs , disease , electric mobility , electric vehicles , emissions , exhaust , exposure , impacts , model , morbidity , mortality , non-exhaust , pm10 , pm2.5 , pollutants , qaly , quality of life , road dust , wear particles
Introduction: Electric vehicles (EVs) are heavily promoted as beneficial for climate and health. In most studies, it is assumed that EVs contribution to urban air pollution is zero due to no tailpipe emissions, ignoring the contribution of non-exhaust particles (brake, tire and road wear), which are unregulated in EU. This study of Stockholm, Sweden, aims to 1) assess how a future vehicle fleet impacts concentrations of particles of size less than 2.5 mu m (PM2.5) and evaluate the expected health outcomes economically and 2) compare this with CO2 savings. Methods: Source specific dispersion models of exhaust and non-exhaust PM2.5 was used to estimate the population weighted concentrations. Thereafter exposure differences within a business as usual (BAU2035) and a fossil free fuel (FFF2035) scenario were used to assess expected health and economic impacts. The assessment considered both exhaust and non-exhaust emissions, considering the vehicle weight and the proportion of vehicles using studded winter tires. Health economic costs were retrieved from the literature and societal willingness to pay was used to value quality-adjusted life-years lost due to morbidity and mortality. Results: The mean population weighted exhaust PM2.5 concentration decreased 0.012 mu g/m(3) (39%) in FFF2035 as compared to BAU2035. Assuming 50% higher road and tire wear PM2.5 emission because of higher weight among EVs and 30% less brake wear emissions, the estimated decrease in wear particle exposures were 0.152 (22%) and 0.014 mu g/m(3) (1.9%) for 0 and 30% use on studded winter tires, respectively. The resulting health economic costs were estimated to (sic)217M and (sic)32M, respectively. An increase by 0.079 mu g/m(3) (11%) was however estimated for 50% use of studded winter tires, corresponding to an mu 89M increase in health costs. Conclusion: Considering both exhaust and wear generated particles, it is not straight forward that an increase of EVs will decrease the negative health impacts.

Lockdown Measures Which Reduced Greenhouse Gas Emissions With Little Negative Impact on Quality of Life

Niemi, M; Skelton, A; Noone, K; Olsson, MJ
2021 | Earth Future | 9 (5)
covid-19 , greenhouse-gas emissions , lockdown measures , quality of life
Lockdown measures in response to the new Covid-19 virus have caused the largest ever fall of annual greenhouse gas emissions. A key question that we attempt to answer in this study is which, if any, of these measures can be productively encouraged post-lockdown in efforts to sustain at least part of this reduction in emissions. Sweden is uniquely suited for our study because the voluntary nature of lockdown in Sweden allowed us to assess the level of compliance to recommendations and its effects on greenhouse gas emissions. First, we assessed the change of perceived quality of life (QOL) among 746 individuals from Stockholm region due to adhering to lockdown measures. Second, we calculated the associated change of annual per capita greenhouse emissions. We found that avoiding travel for work, avoiding purchasing, and avoiding restaurants had the least negative effect on QOL, and at the same time the largest positive effect on carbon dioxide equivalent (CO(2)e) emission reductions. We conclude that these are potential leverage points for stimulating behavioral change that has a positive climatic impact.

Chemical speciation of mercury, sulfur and iron in a dystrophic boreal lake sediment, as controlled by the formation of mackinawite and framboidal pyrite

Skyllberg, U; Persson, A; Tjerngren, I; Kronberg, RM; Drott, A; Meili, M; Bjorn, E
2021 | Geochim. Cosmochim. Acta | 294 (106-125)
aqueous-solutions , baltic sea , boreal lake , chemical speciation , hydrogen-sulfide , iron , isotope-dilution , k-edge xanes , mackinawite , mercury , mercury biogeochemistry , metacinnabar , methyl mercury , methylmercury , organic-matter , pyrite , ray-absorption spectroscopy , sulfur , wetland soils
The chemical speciation of mercury (Hg), methyl mercury (MeHg), sulfur and iron was investigated in the sediment and porewater of Lake Angessjon, a boreal, shallow (maximum depth 2.5 m), oligo-/dystrophic lake in northern Sweden. The lake receives terrestrial stream runoff from surrounding coniferous forest soils and peatlands having a low pH (4.6) and high concentrations of dissolved organic matter (DOM, annual average: 45 mg L-1), Fe (60 mu M), sulfate (105 mu M), inorganic Hg (1200 pM) and MeHg (250 pM). Sulfur K-edge XANES and Hg L-m-edge EXAFS spectroscopic measurements were used to characterize and quantify the sulfur speciation in the lake sediment at nine occasions, covering different seasons in the years of 2007 and 2009. In the surface sediment (0-3 cm) sulfate is reduced to zero-valent S and inorganic sulfide, that in turn reacts with Fe to form FeSm (mackinawite) and FeS2 (framboidal pyrite). The latter mineral becomes increasingly dominant by depth in the sediment. Thermodynamic modeling successfully predicted measured porewater concentrations of Hg in the sediment. Metacinnabar (beta-HgS) and Hg(NOM-RS)(2) complexes (the latter formed as a reaction between Hg(II) and thiol groups associated with natural organic matter, NOM-RSH) were the dominant forms of Hg(II) in the solid phase of sediments and Hg(II)-polysulfides (aq) dominated in the porewater. We argue that FeS m is a key component that indirectly controlled the Hg (II) speciation in the sediment by keeping the aqueous phase concentration of inorganic sulfide in the 0.5-2 mu M range throughout the year. Besides providing a pool of readily soluble inorganic sulfide for formation of beta-HgS(s), as demonstrated by previously reported EXAFS experiments, we further suggest FeS m may serve as a precursor for the formation of a more crystalline (less soluble) beta-HgS(s) phase than present in environments devoid of FeSm. Support for this was provided by comparing our results with previously reported thermodynamic modelling results of Hg(II) and MeHg solubility in organic soils devoid of FeSm. In more general terms, we suggest the presence or absence of FeSm, through its influence on the chemical speciation of Hg and MeHg, may be a key factor behind the variability in rates of Hg(II) and MeHg transformation processes, such as methylation, reduction and demethylation, reported for different environmental settings. (C) 2020 The Author(s). Published by Elsevier Ltd.

Suspect and non-target screening of ovarian follicular fluid and serum – identification of anthropogenic chemicals and investigation of their association to fertility

Hallberg, I; Plassmann, M; Olovsson, M; Holte, J; Damdimopoulou, P; Sjunnesson, YCB; Benskin, JP; Persson, S
2021 | Environ. Sci.-Process Impacts | 23 (10) (1578-1588)
bisphenol-a concentrations , contaminants , embryo score , exposure , infertility , mass spectrometry , perfluorinated chemicals , perfluoroalkyl , polychlorinated biphenyls , women
In this work, ultra-high performance liquid chromatography-high resolution (Orbitrap) mass spectrometry-based suspect and non-target screening was applied to follicular fluid (n = 161) and serum (n = 116) from women undergoing in vitro fertilization in order to identify substances that may be associated with decreased fertility. Detected features were prioritized for identification based on (i) hazard/exposure scores in a database of chemicals on the Swedish market and an in-house database on per- and polyfluoroalkyl substances (PFAS); (ii) enrichment in follicular fluid relative to serum; and (iii) association with treatment outcomes. Non-target screening detected 20 644 features in follicular fluid and 13 740 in serum. Two hundred and sixty-two features accumulated in follicular fluid (follicular fluid: serum ratio >20) and another 252 features were associated with embryo quality. Standards were used to confirm the identities of 21 compounds, including 11 PFAS. 6-Hydroxyindole was associated with lower embryo quality and 4-aminophenol was associated with higher embryo quality. Overall, we show the complexity of follicular fluid and the applicability of suspect and non-target screening for discovering both anthropogenic and endogenous substances, which may play a role in fertility in women.

Permafrost Thaw Increases Methylmercury Formation in Subarctic Fennoscandia

Tarbier, B; Hugelius, G; Sannel, ABK; Baptista-Salazar, C; Jonsson, S
2021 | Environ. Sci. Technol. | 55 (10) (6710-6717)
availability , carbon , holocene development , mercury distribution , methylation rates , peatlands , pollution , ponds , stocks , tracer
Methylmercury (MeHg) forms in anoxic environments and can bioaccumulate and biomagnify in aquatic food webs to concentrations of concern for human and wildlife health. Mercury (Hg) pollution in the Arctic environment may worsen as these areas warm and Hg, currently locked in permafrost soils, is remobilized. One of the main concerns is the development of Hg methylation hotspots in the terrestrial environment due to thermokarst formation. The extent to which net methylation of Hg is enhanced upon thaw is, however, largely unknown. Here, we have studied the formation of Hg methylation hotspots using existing thaw gradients at five Fennoscandian permafrost peatland sites. Total Hg (HgT) and MeHg concentrations were analyzed in 178 soil samples from 14 peat cores. We observed 10 times higher concentrations of MeHg and 13 times higher %MeHg in the collapse fen (representing thawed conditions) as compared to the peat plateau (representing frozen conditions). This suggests significantly greater net methylation of Hg when thermokarst wetlands are formed. In addition, we report HgT to soil organic carbon ratios representative of Fennoscandian permafrost peatlands (median and interquartile range of 0.09 +/- 0.07 mu g HgT g(-1) C) that are of value for future estimates of circumpolar HgT stocks.

Fate of active pharmaceutical ingredients in a northern high-rate algal pond fed with municipal wastewater

Lindberg, RH; Namazkar, S; Lage, S; Ostman, M; Gojkovic, Z; Funk, C; Gentili, FG; Tysklind, M
2021 | Chemosphere | 271
algal biomass , alternative green treatment techniques , hydrophobicity driven removal , removal mechanisms
Active pharmaceutical ingredients (APIs) are vital to human health and welfare, but following therapeutic use, they may pose a potential ecological risk if discharged into the environment. Today's conventional municipal wastewater treatment plants are not designed to remove APIs specifically, and various techniques, preferably cost-effective and environmentally friendly, are being developed and evaluated. Microalgae-based treatment of wastewater is a sustainable and low-cost approach to remove nutrients and emerging contaminants. In this study, a North Sweden high-rate algal pond (HRAP) using municipal untreated wastewater as medium, was investigated in terms of API distribution and fate. Three six-day batches were prepared during 18 days and a total of 36 APIs were quantified within the HRAP of which 14 were removed from the aqueous phase above 50% and seven removed above 90% of their initial concentrations. Twelve APIs of a hydrophobic nature were mostly associated with the algal biomass that was harvested at the end of each batch. HRAPs treatment successfully removed 69% of studied APIs (25 of 36 studied) in six day time. The distribution of various APIs between the aqueous phase and biomass suggested that several removal mechanisms may occur, such as hydrophobicity driven removal, passive biosorption and active bioaccumulation. (C) 2021 Elsevier Ltd. All rights reserved.

The Baltic Sea: An ecosystem with multiple stressors

Dietz, R; Sonne, C; Jenssen, BM; Das, K; de Wit, CA; Harding, KC; Siebert, U; Olsen, MT
2021 | Environ Int | 147
baltic , biomarkers , health effects , mercury , pops
This introductory chapter to our Environment International VSI does not need an abstract and therefore we just include our recommendations below in order to proceed with the resubmission. Future work should examine waterbirds as food web sentinels of multiple stressors as well as Baltic Sea food web dynamics of hazardous substances and how climate change may modify it. Also, future work should aim at further extending the new frameworks developed within BALTHEALTH for energy and contaminant transfer at the population level (Des forges et al., 2018, Cervin et al., 2020/this issue Silva et al., 2020/this issue) and their long term effects on Baltic Sea top predators, such as harbour porpoises, grey seals ringed seals, and white-tailed eagles. Likewise, the risk evaluation conducted for PCB in connection with mercury on Arctic wildlife (Dietz et al., 2019, not a BONUS BALTHEALTH product) could be planned for Baltic Sea molluscs, fish, bird and marine mammals in the future. Finally, future efforts could include stressors not covered by the BONUS BALTHEALTH project, such as food web fluxes, overexploitation, bycatches, eutrophication and underwater noise.

Combining Headspace Solid-Phase Microextraction with Internal Benchmarking to Determine the Elimination Kinetics of Hydrophobic UVCBs

Suhring, R; Sjoholm, KK; Mayer, P; MacLeod, M
2021 | Environ. Sci. Technol. | 55 (16) (11125-11132)
chemical activity , equilibrium sampling , exposure , hs-spme , internal benchmarking , kinetic bcf , mixture analysis , suspect-screening analysis
Substances classified as unknown or variable composition, complex reaction products or biological origin (UVCB) present a challenge for environmental hazard and risk assessment. Here, we present a novel approach for whole-substance bioconcentration testing applied to cedarwood oil-an essential oil composed of volatile, hydrophobic organic chemicals. The method yields whole-body elimination rate constants for a mixture of constituents. Our approach combines in vivo dietary fish exposure with internal benchmarking and headspace solid-phase micro-extraction (HS-SPME) equilibrium sampling followed by suspect-screening analysis. We quantified depuration rate constants of 13 individual cedarwood oil constituents based on relative peak areas using gas chromatography (GC) coupled with Orbitrap-mass spectrometry (MS) and GC triple-quadrupole (QqQ)-MS. For seven constituents with available analytical standards, we compared the rate constants to the results obtained from solvent extraction, clean-up, and targeted GC-MS analysis. The HS-SPME sampling approach allowed for automated sample extraction and analyte enrichment while minimizing evaporative losses of the volatile target analytes and reducing matrix interferences from low-volatility organics. The suspect-screening analysis enabled the quantification of constituents without available analytical standards, while the internal benchmarking significantly reduced variability from differences in delivered dose and analytical variability between the samples.

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