Displaying publications 1 - 20 of 37 in total

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  1. Han M, Zhu T, Liang J, Wang H, Zhu C, Lee Binti Abdullah A, et al.
    Environ Int, 2024 Jan;183:108380.
    PMID: 38141489 DOI: 10.1016/j.envint.2023.108380
    Gastrointestinal diseases exert a profound impact on global health, leading to millions of healthcare interventions and a significant number of fatalities annually. This, coupled with escalating healthcare expenditures, underscores the need for identifying and addressing potential exacerbating factors. One emerging concern is the pervasive presence of microplastics and nano-plastics in the environment, largely attributed to the indiscriminate usage of disposable plastic items. These nano-plastics, having infiltrated our food chain, pose a potential threat to gastrointestinal health. To understand this better, we co-cultured human gastric fibroblasts (HGF) with polystyrene nano-plastics (PS-NPs) of diverse sizes (80, 500, 650 nm) and meticulously investigated their cellular responses over a 24-hour period. Our findings revealed PS particles were ingested by the cells, with a notable increase in ingestion as the particle size decreased. The cellular death induced by these PS particles, encompassing both apoptosis and necrosis, showcased a clear dependence on both the particle size and its concentration. Notably, the larger PS particles manifested more potent cytotoxic effects. Further analysis indicated a concerning reduction in cellular membrane potential, alongside a marked increase in ROS levels upon PS particles exposure. This suggests a significant disruption of mitochondrial function and heightened oxidative stress. The larger PS particles were especially detrimental in causing mitochondrial dysfunction. In-depth exploration into the PS particles impact on genes linked with the permeability transition pore (PTP) elucidated that these PS particles instigated an internal calcium rush. This surge led to a compromise in the mitochondrial membrane potential, which in tandem with raised ROS levels, further catalyzed DNA damage and initiated cell death pathways. In essence, this study unveils the intricate mechanisms underpinning cell death caused by PS particles in gastric epithelial cells and highlighting the implications of PS particles on gastrointestinal health. The revelations from this research bear significant potential to shape future healthcare strategies and inform pertinent environmental policies.
  2. Li Y, Ling Ma N, Chen H, Zhong J, Zhang D, Peng W, et al.
    Environ Int, 2023 Nov;181:108279.
    PMID: 37924601 DOI: 10.1016/j.envint.2023.108279
    According to the World Health Organization, women's breast cancer is among the most common cancers with 7.8 million diagnosed cases during 2016-2020 and encompasses 15 % of all female cancer-related mortalities. These mortality events from triple-negative breast cancer are a significant health issue worldwide calling for a continuous search of bioactive compounds for better cancer treatments. Historically, plants are important sources for identifying such new bioactive chemicals for treatments. Here we use high-throughput screening and mass spectrometry analyses of extracts from 100 plant species collected in Chinese ancient forests to detect novel bioactive breast cancer phytochemicals. First, to study the effects on viability of the plant extracts, we used a MTT and CCK-8 cytotoxicity assay employing triple-negative breast cancer (TNBC) MDA-MB-231 and normal epithelial MCF-10A cell lines and cell cycle arrest to estimate apoptosis using flow cytometry for the most potent three speices. Based on these analyses, the final most potent extracts were from the Amur honeysuckle (Lonicera maackii) wood/root bark and Nigaki (Picrasma quassioides) wood/root bark. Then, 5 × 106 MDA-MB-231 cells were injected subcutaneously into the right hind leg of nude mice and a tumour was allowed to grow before treatment for seven days. Subsequently, the four exposed groups received gavage extracts from Amur honeysuckle and Nigaki (Amur honeysuckle wood distilled water, Amur honeysuckle root bark ethanol, Nigaki wood ethanol or Nigaki root bark distilled water/ethanol (1:1) extracts) in phosphate-buffered saline (PBS), while the control group received only PBS. The tumour weight of treated nude mice was reduced significantly by 60.5 % within 2 weeks, while on average killing 70 % of the MDA-MB-231 breast cancer cells after 48 h treatment (MTT test). In addition, screening of target genes using the Swiss Target Prediction, STITCH, STRING and NCBI-gene database showed that the four plant extracts possess desirable activity towards several known breast cancer genes. This reflects that the extracts may kill MBD-MB-231 breast cancer cells. This is the first screening of plant extracts with high efficiency in 2 decades, showing promising results for future development of novel cancer treatments.
  3. Dang F, Li C, Nunes LM, Tang R, Wang J, Dong S, et al.
    Environ Int, 2023 Jun;176:107990.
    PMID: 37247467 DOI: 10.1016/j.envint.2023.107990
    Food security and sustainable development of agriculture has been a key challenge for decades. To support this, nanotechnology in the agricultural sectors increases productivity and food security, while leaving complex environmental negative impacts including pollution of the human food chains by nanoparticles. Here we model the effects of silver nanoparticles (Ag-NPs) in a food chain consisting of soil-grown lettuce Lactuca sativa and snail Achatina fulica. Soil-grown lettuce were exposed to sulfurized Ag-NPs via root or metallic Ag-NPs via leaves before fed to snails. We discover an important biomagnification of silver in snails sourced from plant root uptake, with trophic transfer factors of 2.0-5.9 in soft tissues. NPs shifts from original size (55-68 nm) toward much smaller size (17-26 nm) in snails. Trophic transfer of Ag-NPs reprograms the global metabolic profile by down-regulating or up-regulating metabolites for up to 0.25- or 4.20- fold, respectively, relative to the control. These metabolites control osmoregulation, phospholipid, energy, and amino acid metabolism in snails, reflecting molecular pathways of biomagnification and pontential adverse biological effects on lower trophic levels. Consumption of these Ag-NP contaminated snails causes non-carcinogenic effects on human health. Global public health risks decrease by 72% under foliar Ag-NP application in agriculture or through a reduction in the consumption of snails sourced from root application. The latter strategy is at the expense of domestic economic losses in food security of $177.3 and $58.3 million annually for countries such as Nigeria and Cameroon. Foliar Ag-NP application in nano-agriculture has lower hazard quotient risks on public health than root application to ensure global food safety, as brought forward by the United Nations Sustainable Development Goals.
  4. Tao H, Jawad AH, Shather AH, Al-Khafaji Z, Rashid TA, Ali M, et al.
    Environ Int, 2023 May;175:107931.
    PMID: 37119651 DOI: 10.1016/j.envint.2023.107931
    This study uses machine learning (ML) models for a high-resolution prediction (0.1°×0.1°) of air fine particular matter (PM2.5) concentration, the most harmful to human health, from meteorological and soil data. Iraq was considered the study area to implement the method. Different lags and the changing patterns of four European Reanalysis (ERA5) meteorological variables, rainfall, mean temperature, wind speed and relative humidity, and one soil parameter, the soil moisture, were used to select the suitable set of predictors using a non-greedy algorithm known as simulated annealing (SA). The selected predictors were used to simulate the temporal and spatial variability of air PM2.5 concentration over Iraq during the early summer (May-July), the most polluted months, using three advanced ML models, extremely randomized trees (ERT), stochastic gradient descent backpropagation (SGD-BP) and long short-term memory (LSTM) integrated with Bayesian optimizer. The spatial distribution of the annual average PM2.5 revealed the population of the whole of Iraq is exposed to a pollution level above the standard limit. The changes in temperature and soil moisture and the mean wind speed and humidity of the month before the early summer can predict the temporal and spatial variability of PM2.5 over Iraq during May-July. Results revealed the higher performance of LSTM with normalized root-mean-square error and Kling-Gupta efficiency of 13.4% and 0.89, compared to 16.02% and 0.81 for SDG-BP and 17.9% and 0.74 for ERT. The LSTM could also reconstruct the observed spatial distribution of PM2.5 with MapCurve and Cramer's V values of 0.95 and 0.91, compared to 0.9 and 0.86 for SGD-BP and 0.83 and 0.76 for ERT. The study provided a methodology for forecasting spatial variability of PM2.5 concentration at high resolution during the peak pollution months from freely available data, which can be replicated in other regions for generating high-resolution PM2.5 forecasting maps.
  5. Dai L, Deng L, Wang W, Li Y, Wang L, Liang T, et al.
    Environ Int, 2023 Feb;172:107775.
    PMID: 36739854 DOI: 10.1016/j.envint.2023.107775
    There is a growing concern about human health of residents living in areas where mining and smelting occur. In order to understand the exposure to the potentially toxic elements (PTEs), we here identify and examine the cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb) and zinc (Zn) in scalp hair of residents living in the mining area (Bayan Obo, n = 76), smelting area (Baotou, n = 57) and a reference area (Hohhot, n = 61). In total, 194 hair samples were collected from the volunteers (men = 87, women = 107) aged 5-77 years old in the three areas. Comparing median PTEs levels between the young and adults, Ni levels were significantly higher in adults living in the smelting area while Cr was highest in adults from the mining area, no significant difference was found for any of the elements in the reference area. From the linear regression model, no significant relationship between PTEs concentration, log10(PTEs), and age was found. The concentrations of Ni, Cd, and Pb in hair were significantly lower in the reference area when compared to both mining and smelting areas. In addition, Cu was significantly higher in the mining area when compared to the smelting area. Factor analysis (FA) indicated that men and women from the smelting area (Baotou) and mining area (Bayan Obo), respectively, had different underlying communality of log10(PTEs), suggesting different sources of these PTEs. Multiple factor analysis quantilized the importance of gender and location when combined with PTEs levels in human hair. The results of this study indicate that people living in mining and/or smelting areas have significantly higher PTEs (Cu, Ni, Cd, and Pb) hair levels compared to reference areas, which may cause adverse health effects. Remediation should therefore be implemented to improve the health of local residents in the mining and smelting areas.
  6. Huang L, Zhu Y, Liu H, Wang Y, Allen DT, Chel Gee Ooi M, et al.
    Environ Int, 2023 Jan;171:107710.
    PMID: 36566719 DOI: 10.1016/j.envint.2022.107710
    In recent years, ozone pollution in China has been shown to increase in frequency and persistence despite the concentrations of fine particulate matter (PM2.5) decreasing steadily. Open crop straw burning (OCSB) activities are extensive in China and emit large amounts of trace gases during a short period that could lead to elevated ozone concentrations. This study addresses the impacts of OCSB emissions on ground-level ozone concentration and the associated health impact in China. Total VOCs and NOx emissions from OCSB in 2018 were 798.8 Gg and 80.6 Gg, respectively, with high emissions in Northeast China (31.7%) and North China (23.7%). Based on simulations conducted for 2018, OCSB emissions are estimated to contribute up to 0.95 µg/m3 increase in annual averaged maximum daily 8-hour (MDA8) ozone and up to 1.35 µg/m3 for the ozone season average. The significant impact of OCSB emissions on ozone is mainly characterized by localized and episodic (e.g., daily) changes in ozone concentration, up to 20 µg/m3 in North China and Yangtze River Delta region and even more in Northeast China during the burning season. With the implementation of straw burning bans, VOCs and NOx emissions from OCSB dropped substantially by 46.9%, particularly over YRD (76%) and North China (60%). Consequently, reduced OCSB emissions result in an overall decrease in annual averaged MDA8 ozone, and reductions in monthly MDA8 ozone could be over 10 µg/m3 in North China. The number of avoided premature death due to reduced OCSB emissions (considering both PM2.5 and ozone) is estimated to be 6120 (95% Confidence Interval: 5320-6800), with most health benefits gained over east and central China. Our results illustrate the effectiveness of straw burning bans in reducing ozone concentrations at annual and national scales and the substantial ozone impacts from OCSB events at localized and episodic scales.
  7. Lim KY, Foo KY
    Environ Int, 2021 12;157:106851.
    PMID: 34560322 DOI: 10.1016/j.envint.2021.106851
    The present work has been oriented to the qualitative and quantitative assessments of the aftermath effects of 2014 flood tragedy on the organic, inorganic and microbial contaminants in the floodwater, with a particular emphasis on their relative health risks and microbial infectious hazards to the flood-affected population, using average daily dose, hazard quotient, hazard index (HI), cancer risk (CR) and quantitative microbial risk assessment. Statistical comparison of the organic and inorganic contents was performed using the paired t-tests, while the predominant socio-demographic profiles and health attributes of the respondents to flood-induced health risks (HI) were verified by the chi-square test and binary logistic regression analysis. Among all, Fe, Cu, Pb, Ni, Zn, Cr, Cd, chlorpyrifos, diazinon, polycyclic aromatic hydrocarbons, estriol, 17α-ethinylestradiol, estrone, β-estradiol and bisphenol A were detected at the study area after flooding. The microbiological quality of the floodwater samples has been tracked positive for Escherichia coli, Salmonella typhimurium and Shigella flexneri, with the mean concentrations of 6500, 50 and 180 CFU/100 mL, respectively. Exposure and health risk assessments revealed that the overall HI value for organic and inorganic contaminants in the water samples was 1.19, exceeding the USEPA maximum limit of 1, after the flood incidence. The largest CR contributors were Ni, Cr and Cd, while the infection risks (Pinf,single) associated with the exposure of E. coli, Salmonella spp. and Shigella spp. were identified to be 3.1 × 10-2, 1.2 × 10-4 and 3.2 × 10-5 for incidental scenario; and 8.3 × 10-1, 3.9 × 10-1 and 1.9 × 10-1 for intentional scenario, respectively. The findings of these integrated tools are critically important to provide a more reliable quantitative assessment of human health hazards and microbial risks for different environmental settings, to safeguard water resource, and preservation of public health and the overall river ecosystem.
  8. French MA, Fiona Barker S, Taruc RR, Ansariadi A, Duffy GA, Saifuddaolah M, et al.
    Environ Int, 2021 10;155:106679.
    PMID: 34126296 DOI: 10.1016/j.envint.2021.106679
    BACKGROUND: The intense interactions between people, animals and environmental systems in urban informal settlements compromise human and environmental health. Inadequate water and sanitation services, compounded by exposure to flooding and climate change risks, expose inhabitants to environmental contamination causing poor health and wellbeing and degrading ecosystems. However, the exact nature and full scope of risks and exposure pathways between human health and the environment in informal settlements are uncertain. Existing models are limited to microbiological linkages related to faecal-oral exposures at the individual level, and do not account for a broader range of human-environmental variables and interactions that affect population health and wellbeing.

    METHODS: We undertook a 12-month health and environmental assessment in 12 flood-prone informal settlements in Makassar, Indonesia. We obtained caregiver-reported health data, anthropometric measurements, stool and blood samples from children 

  9. Lam SS, Tjørnløv RS, Therkildsen OR, Christensen TK, Madsen J, Daugaard-Petersen T, et al.
    Environ Int, 2020 09;142:105873.
    PMID: 32585505 DOI: 10.1016/j.envint.2020.105873
    Blood plasma was collected during 2016-2018 from healthy incubating eiders (Somateria molissima, n = 183) in three Danish colonies, and healthy migrating pink-footed geese (Anser brachyrhynchus, n = 427) at their spring roost in Central Norway (Svalbard breeding population) and their novel flyway through the Finnish Baltic Sea (Russian breeding population). These species and flyways altogether represent terrestrial, brackish and marine ecosystems spanning from the Western to the Eastern and Northern part of the Baltic Sea. Plasma of these species was analysed for seroprevalence of specific avian influenza A (AI) antibodies to obtain information on circulating AI serotypes and exposure. Overall, antibody prevalence was 55% for the eiders and 47% for the pink-footed geese. Of AI-antibody seropositive birds, 12% (22/183) of the eiders and 3% (12/427) of the pink-footed geese had been exposed to AI of the potentially zoonotic serotypes H5 and/or H7 virus. AI seropositive samples selected at random (n = 33) showed a low frequency of serotypes H1, H6 and H9. Future projects should aim at sampling and isolating AI virus to characterize dominant serotypes and virus strains (PCR). This will increase our understanding of how AI exposure may affect health, breeding and population viability of Baltic common eiders and pink-footed geese as well as the potential spill-over to humans (zoonotic potential).
  10. Ma NL, Hansen M, Roland Therkildsen O, Kjær Christensen T, Skjold Tjørnløv R, Garbus SE, et al.
    Environ Int, 2020 09;142:105866.
    PMID: 32590281 DOI: 10.1016/j.envint.2020.105866
    The Baltic/Wadden Sea Flyway of common eiders has declined over the past three decades. Multiple factors such as contaminant exposure, global warming, hunting, white-tailed eagle predation, decreased agricultural eutrophication and infectious diseases have been suggested to explain the decline. We collected information on body mass, mercury (Hg) concentration, biochemistry and untargeted metabolomics of incubating birds in two colonies in the Danish Straits (Hov Røn, n = 100; Agersø, n = 29) and in one colony in the Baltic proper (Christiansø, n = 23) to look into their metabolisms and energy balance. Body mass was available from early and late incubation for Hov Røn and Christiansø, showing a significant decline (25-30%) in both colonies with late body mass at Christiansø being the lowest. Whole blood concentrations of total mercury Hg were significantly higher in birds at Christiansø in the east compared to Hov Røn in the west. All birds in the three colonies had Hg concentrations in the range of ≤1.0 μg/g ww, which indicates that the risk of effects on reproduction is in the no to low risk category for wild birds. Among the biochemical measures, glucose, fructosamine, amylase, albumin and protein decreased significantly from early to late incubation at Hov Røn and Christiansø, reflecting long-term fastening as supported by the decline in body mass. Untargeted metabolomics performed on Christiansø eiders revealed presence of 8,433 plasma metabolites. Of these, 3,179 metabolites changed significantly (log2-fold change ≥1, p ≤ 0.05) from the early to late incubation. For example, smaller peptides and vitamin B2 (riboflavin) were significantly down-regulated while 11-deoxycorticosterone and palmitoylcarnitine were significantly upregulated. These results show that cumulative stress including fasting during incubation affect the eiders' biochemical profile and energy metabolism and that this may be most pronounced for the Christiansø colony in the Baltic proper. This amplify the events of temperature increases and food web changes caused by global warming that eventually accelerate the loss in body weight. Future studies should examine the relationship between body condition, temperature and reproductive outcomes and include mapping of food web contaminant, energy and nutrient content to better understand, manage and conserve the populations.
  11. Sonne C, Siebert U, Gonnsen K, Desforges JP, Eulaers I, Persson S, et al.
    Environ Int, 2020 06;139:105725.
    PMID: 32311628 DOI: 10.1016/j.envint.2020.105725
    Here we review contaminant exposure and related health effects in six selected Baltic key species. Sentinel species included are common eider, white-tailed eagle, harbour porpoise, harbour seal, ringed seal and grey seal. The review represents the first attempt of summarizing available information and baseline data for these biomonitoring key species exposed to industrial hazardous substances focusing on anthropogenic persistent organic pollutants (POPs). There was only limited information available for white-tailed eagles and common eider while extensive information exist on POP exposure and health effects in the four marine mammal species. Here we report organ-tissue endpoints (pathologies) and multiple biomarkers used to evaluate health and exposure of key species to POPs, respectively, over the past several decades during which episodes of significant population declines have been reported. Our review shows that POP exposure affects the reproductive system and survival through immune suppression and endocrine disruption, which have led to population-level effects on seals and white-tailed eagles in the Baltic. It is notable that many legacy contaminants, which have been banned for decades, still appear to affect Baltic wildlife. With respect to common eiders, changes in food composition, quality and contaminant exposure seem to have population effects which need to be investigated further, especially during the incubation period where the birds fast. Since new industrial contaminants continuously leak into the environment, we recommend continued monitoring of them in sentinel species in the Baltic, identifying possible effects linked to climate change, and modelling of population level effects of contaminants and climate change.
  12. Fu X, Norbäck D, Yuan Q, Li Y, Zhu X, Hashim JH, et al.
    Environ Int, 2020 05;138:105664.
    PMID: 32200316 DOI: 10.1016/j.envint.2020.105664
    Indoor microbial diversity and composition are suggested to affect the prevalence and severity of asthma by previous home microbiome studies, but no microbiome-health association study has been conducted in a school environment, especially in tropical countries. In this study, we collected floor dust and environmental characteristics from 21 classrooms, and health data related to asthma symptoms from 309 students, in junior high schools in Johor Bahru, Malaysia. The bacterial and fungal composition was characterized by sequencing 16s rRNA gene and internal transcribed spacer (ITS) region, and the absolute microbial concentration was quantified by qPCR. In total, 326 bacterial and 255 fungal genera were characterized. Five bacterial (Sphingobium, Rhodomicrobium, Shimwellia, Solirubrobacter, Pleurocapsa) and two fungal (Torulaspora and Leptosphaeriaceae) taxa were protective for asthma severity. Two bacterial taxa, Izhakiella and Robinsoniella, were positively associated with asthma severity. Several protective bacterial taxa including Rhodomicrobium, Shimwellia and Sphingobium have been reported as protective microbes in previous studies, whereas other taxa were first time reported. Environmental characteristics, such as age of building, size of textile curtain per room volume, occurrence of cockroaches, concentration of house dust mite allergens transferred from homes by the occupants, were involved in shaping the overall microbial community but not asthma-associated taxa; whereas visible dampness and mold, which did not change the overall microbial community for floor dust, was negatively associated with the concentration of protective bacteria Rhodomicrobium (β = -2.86, p = 0.021) of asthma. The result indicates complex interactions between microbes, environmental characteristics and asthma symptoms. Overall, this is the first indoor microbiome study to characterize the asthma-associated microbes and their environmental determinant in the tropical area, promoting the understanding of microbial exposure and respiratory health in this region.
  13. Lam SS, McPartland M, Noori B, Garbus SE, Lierhagen S, Lyngs P, et al.
    Environ Int, 2020 04;137:105582.
    PMID: 32086081 DOI: 10.1016/j.envint.2020.105582
    Here we investigate if lead may be a contributing factor to the observed population decline in a Baltic colony of incubating eiders (Somateria mollissima). Body mass and blood samples were obtained from 50 incubating female eiders at the Baltic breeding colony on Christiansø during spring 2017 (n = 27) and 2018 (n = 23). All the females were sampled twice during early (day 4) and late (day 24) incubation. The full blood was analysed for lead to investigate if the concentrations exceeded toxic thresholds or changed over the incubation period due to remobilisation from bones and liver tissue. Body mass, hatch date and number of chicks were also analysed with respect to lead concentrations. The body mass (mean ± SD g) increased significantly in the order: day 24 in 2018 (1561 ± 154 g) 
  14. Choi D, Oh JI, Lee J, Park YK, Lam SS, Kwon EE
    Environ Int, 2019 11;132:105037.
    PMID: 31437646 DOI: 10.1016/j.envint.2019.105037
    In an effort to seek a new technical platform for disposal of drinking water treatment sludge (DWTS: alum sludge), pyrolysis of DWTS was mainly investigated in this study. To establish a more sustainable thermolytic platform for DWTS, this study particularly employed CO2 as reactive gas medium. Thus, this study laid great emphasis on elucidating the mechanistic roles of CO2 during the thermolysis of DWTS. A series of the TGA tests of DWTS in CO2 in reference to N2 revealed no occurrence of the heterogeneous reaction between CO2 and the sample surface of DWTS. As such, at the temperature regime before initiating the Boudouard reaction (i.e., ≥700 °C), the mass decay patterns of DWTS in N2 and CO2 were nearly identical. However, the gaseous effluents from lab-scale pyrolysis of DWTS in CO2 in reference to N2 were different. In sum, the homogeneous reactions between CO2 and volatile matters (VMs) evolved from the thermolysis of DWTS led to the enhanced generation of CO. Also, CO2 suppressed dehydrogenation of VMs. Such the genuine mechanistic roles of CO2 in the thermolysis of DWTS subsequently led to the compositional modifications of the chemical species in pyrolytic oil. Furthermore, the biochar composite was obtained as byproduct of pyrolysis of DWTS. Considering that the high content of Al2O3 and Fe-species in the biochar composite imparts a strong affinity for As(V), the practical use of the biochar composite as a sorptive material for arsenic (V) was evaluated at the fundamental levels. This work reported that adsorption of As(V) onto the biochar composite followed the pseudo-second order model and the Freundlich isotherm model.
  15. Alofe O, Kisanga E, Inayat-Hussain SH, Fukumura M, Garcia-Milian R, Perera L, et al.
    Environ Int, 2019 10;131:104969.
    PMID: 31310931 DOI: 10.1016/j.envint.2019.104969
    Environmental and occupational exposure to industrial chemicals has been linked to toxic and carcinogenic effects in animal models and human studies. However, current toxicology testing does not thoroughly explore the endocrine disrupting effects of industrial chemicals, which may have low dose effects not predicted when determining the limit of toxicity. The objective of this study was to evaluate the endocrine disrupting potential of a broad range of chemicals used in the petrochemical sector. Therefore, 139 chemicals were classified for reproductive toxicity based on the United Nations Globally Harmonized System for hazard classification. These chemicals were evaluated in PubMed for reported endocrine disrupting activity, and their endocrine disrupting potential was estimated by identifying chemicals with active nuclear receptor endpoints publicly available databases. Evaluation of ToxCast data suggested that these chemicals preferentially alter the activity of the estrogen receptor (ER). Four chemicals were prioritized for in vitro testing using the ER-positive, immortalized human uterine Ishikawa cell line and a range of concentrations below the reported limit of toxicity in humans. We found that 2,6-di-tert-butyl-p-cresol (BHT) and diethanolamine (DEA) repressed the basal expression of estrogen-responsive genes PGR, NPPC, and GREB1 in Ishikawa cells, while tetrachloroethylene (PCE) and 2,2'-methyliminodiethanol (MDEA) induced the expression of these genes. Furthermore, low-dose combinations of PCE and MDEA produced additive effects. All four chemicals interfered with estradiol-mediated induction of PGR, NPPC, and GREB1. Molecular docking demonstrated that these chemicals could bind to the ligand binding site of ERα, suggesting the potential for direct stimulatory or inhibitory effects. We found that these chemicals altered rates of proliferation and regulated the expression of cell proliferation associated genes. These findings demonstrate previously unappreciated endocrine disrupting effects and underscore the importance of testing the endocrine disrupting potential of chemicals in the future to better understand their potential to impact public health.
  16. Adeel M, Lee JY, Zain M, Rizwan M, Nawab A, Ahmad MA, et al.
    Environ Int, 2019 06;127:785-800.
    PMID: 31039528 DOI: 10.1016/j.envint.2019.03.022
    BACKGROUND: Rare earth elements (REEs) are gaining attention due to rapid rise of modern industries and technological developments in their usage and residual fingerprinting. Cryptic entry of REEs in the natural resources and environment is significant; therefore, life on earth is prone to their nasty effects. Scientific sectors have expressed concerns over the entry of REEs into food chains, which ultimately influences their intake and metabolism in the living organisms.

    OBJECTIVES: Extensive scientific collections and intensive look in to the latest explorations agglomerated in this document aim to depict the distribution of REEs in soil, sediments, surface waters and groundwater possibly around the globe. Furthermore, it draws attention towards potential risks of intensive industrialization and modern agriculture to the exposure of REEs, and their effects on living organisms. It also draws links of REEs usage and their footprints in natural resources with the major food chains involving plants, animals and humans.

    METHODS: Scientific literature preferably spanning over the last five years was obtained online from the MEDLINE and other sources publishing the latest studies on REEs distribution, properties, usage, cycling and intrusion in the environment and food-chains. Distribution of REEs in agricultural soils, sediments, surface and ground water was drawn on the global map, together with transport pathways of REEs and their cycling in the natural resources.

    RESULTS: Fourteen REEs (Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Sm, Tb, Th and Yb) were plighted in this study. Wide range of their concentrations has been detected in agricultural soils (<15.9-249.1 μg g-1) and in groundwater (<3.1-146.2 μg L-1) at various sites worldwide. They have strong tendency to accumulate in the human body, and thus associated with kidney stones. The REEs could also perturb the animal physiology, especially affecting the reproductive development in both terrestrial and aquatic animals. In plants, REEs might affect the germination, root and shoot development and flowering at concentration ranging from 0.4 to 150 mg kg-1.

    CONCLUSIONS: This review article precisely narrates the current status, sources, and potential effects of REEs on plants, animals, humans health. There are also a few examples where REEs have been used to benefit human health. However, still there is scarce information about threshold levels of REEs in the soil, aquatic, and terrestrial resources as well as living entities. Therefore, an aggressive effort is required for global action to generate more data on REEs. This implies we prescribe an urgent need for inter-disciplinary studies about REEs in order to identify their toxic effects on both ecosystems and organisms.

  17. Inayat-Hussain SH, Fukumura M, Muiz Aziz A, Jin CM, Jin LW, Garcia-Milian R, et al.
    Environ Int, 2018 08;117:348-358.
    PMID: 29793188 DOI: 10.1016/j.envint.2018.05.010
    BACKGROUND: Recent trends have witnessed the global growth of unconventional oil and gas (UOG) production. Epidemiologic studies have suggested associations between proximity to UOG operations with increased adverse birth outcomes and cancer, though specific potential etiologic agents have not yet been identified. To perform effective risk assessment of chemicals used in UOG production, the first step of hazard identification followed by prioritization specifically for reproductive toxicity, carcinogenicity and mutagenicity is crucial in an evidence-based risk assessment approach. To date, there is no single hazard classification list based on the United Nations Globally Harmonized System (GHS), with countries applying the GHS standards to generate their own chemical hazard classification lists. A current challenge for chemical prioritization, particularly for a multi-national industry, is inconsistent hazard classification which may result in misjudgment of the potential public health risks. We present a novel approach for hazard identification followed by prioritization of reproductive toxicants found in UOG operations using publicly available regulatory databases.

    METHODS: GHS classification for reproductive toxicity of 157 UOG-related chemicals identified as potential reproductive or developmental toxicants in a previous publication was assessed using eleven governmental regulatory agency databases. If there was discordance in classifications across agencies, the most stringent classification was assigned. Chemicals in the category of known or presumed human reproductive toxicants were further evaluated for carcinogenicity and germ cell mutagenicity based on government classifications. A scoring system was utilized to assign numerical values for reproductive health, cancer and germ cell mutation hazard endpoints. Using a Cytoscape analysis, both qualitative and quantitative results were presented visually to readily identify high priority UOG chemicals with evidence of multiple adverse effects.

    RESULTS: We observed substantial inconsistencies in classification among the 11 databases. By adopting the most stringent classification within and across countries, 43 chemicals were classified as known or presumed human reproductive toxicants (GHS Category 1), while 31 chemicals were classified as suspected human reproductive toxicants (GHS Category 2). The 43 reproductive toxicants were further subjected to analysis for carcinogenic and mutagenic properties. Calculated hazard scores and Cytoscape visualization yielded several high priority chemicals including potassium dichromate, cadmium, benzene and ethylene oxide.

    CONCLUSIONS: Our findings reveal diverging GHS classification outcomes for UOG chemicals across regulatory agencies. Adoption of the most stringent classification with application of hazard scores provides a useful approach to prioritize reproductive toxicants in UOG and other industries for exposure assessments and selection of safer alternatives.

  18. Barnett-Itzhaki Z, Esteban López M, Puttaswamy N, Berman T
    Environ Int, 2018 07;116:156-164.
    PMID: 29684824 DOI: 10.1016/j.envint.2018.03.046
    Rapid development and industrialization in Southeast (SE) Asia has led to environmental pollution, potentially exposing the general population to environmental contaminants. Human biomonitoring (HBM), measurement of chemical and/or their metabolites in human tissues and fluids, is an important tool for assessing cumulative exposure to complex mixtures of chemicals and for monitoring chemical exposures in the general population. While there are national HBM programs in several developed countries, there are no such national programs in most of the SE Asian countries. However, in recent years there has been progress in the field of HBM in many of the SE Asian countries. In this review, we present recent HBM studies in five selected SE Asian countries: Bangladesh, Indonesia, Malaysia, Myanmar and Thailand. While there is extensive HBM research in several SE Asian countries, such as Thailand, in other countries HBM studies are limited and focus on traditional environmental pollutants (such as lead, arsenic and mercury). Further development of this field in SE Asia would be benefited by establishment of laboratory capacity, improving quality control and assurance, collaboration with international experts and consortiums, and sharing of protocols and training both for pre-analytical and analytical phases. This review highlights the impressive progress in HBM research in selected SE Asian countries and provides recommendations for development of this field.
  19. Plusquin M, Guida F, Polidoro S, Vermeulen R, Raaschou-Nielsen O, Campanella G, et al.
    Environ Int, 2017 11;108:127-136.
    PMID: 28843141 DOI: 10.1016/j.envint.2017.08.006
    Long-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes. This study included blood-derived DNA methylation (Illumina-HM450 methylation) for 454 Italian and 159 Dutch participants from the European Prospective Investigation into Cancer and Nutrition (EPIC). Long-term air pollution exposure levels, including NO2, NOx, PM2.5, PMcoarse, PM10, PM2.5 absorbance (soot) were estimated using models developed within the ESCAPE project, and back-extrapolated to the time of sampling when possible. We meta-analysed the associations between the air pollutants and global DNA methylation, methylation in functional regions and epigenome-wide methylation. CpG sites found differentially methylated with air pollution were further investigated for functional interpretation in an independent population (EnviroGenoMarkers project), where (N=613) participants had both methylation and gene expression data available. Exposure to NO2 was associated with a significant global somatic hypomethylation (p-value=0.014). Hypomethylation of CpG island's shores and shelves and gene bodies was significantly associated with higher exposures to NO2 and NOx. Meta-analysing the epigenome-wide findings of the 2 cohorts did not show genome-wide significant associations at single CpG site level. However, several significant CpG were found if the analyses were separated by countries. By regressing gene expression levels against methylation levels of the exposure-related CpG sites, we identified several significant CpG-transcript pairs and highlighted 5 enriched pathways for NO2 and 9 for NOx mainly related to the immune system and its regulation. Our findings support results on global hypomethylation associated with air pollution, and suggest that the shores and shelves of CpG islands and gene bodies are mostly affected by higher exposure to NO2 and NOx. Functional differences in the immune system were suggested by transcriptome analyses.
  20. Wee SY, Aris AZ
    Environ Int, 2017 09;106:207-233.
    PMID: 28552550 DOI: 10.1016/j.envint.2017.05.004
    To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water.
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