► MTT and XTT are widely used as objective indicators of cell viability in toxicology. ► Both can be reduced to their absorbant forms by superoxide. ► Nanosized TiO2 induces superoxide formation in ...different mammalian cells. ► MTT/XTT for measuring cell viability by nanosized TiO2 can yield inaccurate results.
The reduction of the tetrazolium salts, MTT and XTT, is used to estimate cell viability and proliferation. However, superoxide can also reduce tetrazolium salts to produce the absorbant formazan end products. Evidence indicates that nano-TiO2 induces superoxide formation in different mammalian cells. Therefore, studies investigating the cytological effects of nano-TiO2 may encounter misleading results when using MTT/XTT to measure viability or proliferation. In this study, cell viabilities of Chinese hamster ovary cells were assayed using MTT, XTT and the trypan blue exclusion assay following exposure to nano-TiO2. In comparison to the trypan blue exclusion assay, the MTT and XTT assays inaccurately predicted cell toxicity or overestimated cell viability respectively. XTT, in particular, appears more sensitive to superoxide than MTT. The reduction rate of XTT is 1.5 times that of MTT and SOD inhibition of XTT is less effective than that of MTT, indicating that XTT is more reactive with O2- than MTT. Therefore, using XTT or MTT for measuring cell viability or proliferation may yield inaccurate results when conditions in cultured cell increase superoxide formation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Volatile organic compounds (VOCs) represent a broad class of chemicals, many of which can be found in indoor air including residential indoor air. VOCs derive from a variety of sources including ...cleaning products, cooking practices, fragrances and fresheners, hobbies and at-home work behaviors. This study examined residential indoor air in homes (n = 99) in southeast Louisiana using passive organic vapor monitors and gas chromatography/mass spectrometry to determine if select VOCs were present, at what concentrations, and if those posed any potential long-term health risks. Twenty-nine VOCs were targeted in cross-sectional analyses using a 48-h sampling period. Twelve VOCs were detected in most of the homes sampled including xylenes, pinenes, benzene, toluene, ethylbenzene, hexane, pentane, chloroform, and carbon tetrachloride. Concentrations of alkanes and BTEX compounds were highly correlated (Spearman's r > 0.63, p < 0.0001). Using health risk measures (i.e. reference concentrations RfCs and inhalation unit risks IURs) available from the USEPA non-cancer risk assessments and cancer risk assessments were developed for some of these VOCs. Alkanes and BTEX compounds likely come from the same indoor source(s). Using existing health standards published by the USEPA, no unacceptable non-cancer risks were evident except under extremely high concentrations. Lifetime cancer risks, on the other hand, may well be considered unacceptable for chloroform and benzene (upper IUR) and for the combination of chloroform, benzene, and carbon tetrachloride. These exceeded a 1 in 10,000 cancer risk threshold in 35-50% of our simulations. Further study of residential indoor air in low-income women's homes in this area is needed. Including a larger number of VOCs may reveal yet more potential health risks.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In Suriname, mercury (Hg) use has recently increased because of gold mining, which has put fish-reliant communities (e.g., Indigenous and Tribal) at risk of enhanced Hg exposure through the riverine ...fish these communities consume. To quantify how the magnitude of these risks change according to location and time, we measured total mercury (HgT) in fish at sites downstream and upstream of an artisanal and small-scale gold mining (ASGM) operation in 2004–2005 and in 2017–2018. We tested whether fish HgT burdens over dynamic ranges were increased. Surprisingly, our findings did not support broadly increased fish Hg burden over time or that proximity to ASGM was diagnostic to fish HgT-burden. Subsequently, we elected to test the HgT stable isotope ratios on a set of freshly collected 2020 fish to determine whether differences in Hg source and delivery pathways might cofound results. We found that remote unmined sites were more susceptible to gaseous elemental Hg deposition pathways, leading to enhanced risk of contamination, whereas ASGM proximate sites were not. These results highlight that elemental mercury releases from ASGM practices may have significant impact on fish-reliant communities that are far removed from ASGM point source contamination.
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•Fish mercury burdens did not noticeably increase over a 20-year delay span.•Fish mercury burdens were inconsistent with typical size-burden relationships.•Fish were increased in mercury relative to global trends even in remote areas.•Proximity to mercury-use gold mining was a poor predictor for fish mercury.•Remote intact ecosystems were more mercury sensitive than disturbed ecosystems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A long-standing challenge of untargeted metabolomic profiling by ultrahigh-performance liquid chromatography–high-resolution mass spectrometry (UHPLC–HRMS) is efficient transition from unknown mass ...spectral features to confident metabolite annotations. The compMS 2 Miner (Comprehensive MS2 Miner) package was developed in the R language to facilitate rapid, comprehensive feature annotation using a peak-picker-output and MS2 data files as inputs. The number of MS2 spectra that can be collected during a metabolomic profiling experiment far outweigh the amount of time required for pain-staking manual interpretation; therefore, a degree of software workflow autonomy is required for broad-scale metabolite annotation. CompMS 2 Miner integrates many useful tools in a single workflow for metabolite annotation and also provides a means to overview the MS2 data with a Web application GUI compMS 2 Explorer (Comprehensive MS2 Explorer) that also facilitates data-sharing and transparency. The automatable compMS 2 Miner workflow consists of the following steps: (i) matching unknown MS1 features to precursor MS2 scans, (ii) filtration of spectral noise (dynamic noise filter), (iii) generation of composite mass spectra by multiple similar spectrum signal summation and redundant/contaminant spectra removal, (iv) interpretation of possible fragment ion substructure using an internal database, (v) annotation of unknowns with chemical and spectral databases with prediction of mammalian biotransformation metabolites, wrapper functions for in silico fragmentation software, nearest neighbor chemical similarity scoring, random forest based retention time prediction, text-mining based false positive removal/true positive ranking, chemical taxonomic prediction and differential evolution based global annotation score optimization, and (vi) network graph visualizations, data curation, and sharing are made possible via the compMS 2 Explorer application. Metabolite identities and comments can also be recorded using an interactive table within compMS 2 Explorer. The utility of the package is illustrated with a data set of blood serum samples from 7 diet induced obese (DIO) and 7 nonobese (NO) C57BL/6J mice, which were also treated with an antibiotic (streptomycin) to knockdown the gut microbiota. The results of fully autonomous and objective usage of compMS 2 Miner are presented here. All automatically annotated spectra output by the workflow are provided in the Supporting Information and can alternatively be explored as publically available compMS 2 Explorer applications for both positive and negative modes (https://wmbedmands.shinyapps.io/compMS2_mouseSera_POS and https://wmbedmands.shinyapps.io/compMS2_mouseSera_NEG). The workflow provided rapid annotation of a diversity of endogenous and gut microbially derived metabolites affected by both diet and antibiotic treatment, which conformed to previously published reports. Composite spectra (n = 173) were autonomously matched to entries of the Massbank of North America (MoNA) spectral repository. These experimental and virtual (lipidBlast) spectra corresponded to 29 common endogenous compound classes (e.g., 51 lysophosphatidylcholines spectra) and were then used to calculate the ranking capability of 7 individual scoring metrics. It was found that an average of the 7 individual scoring metrics provided the most effective weighted average ranking ability of 3 for the MoNA matched spectra in spite of potential risk of false positive annotations emerging from automation. Minor structural differences such as relative carbon–carbon double bond positions were found in several cases to affect the correct rank of the MoNA annotated metabolite. The latest release and an example workflow is available in the package vignette (https://github.com/WMBEdmands/compMS2Miner) and a version of the published application is available on the shinyapps.io site (https://wmbedmands.shinyapps.io/compMS2Example).
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IJS, KILJ, NUK, PNG, UL, UM
Environmental health literacy (EHL) involves understanding and using environmental information to make decisions about health. This study developed a validated survey instrument with four scales for ...assessing media-specific (i.e., air, food, water) and general EHL. The four scales were created as follows: 1) item generation: environmental health scientists and statisticians developed an initial set of items in three domains: knowledge, attitudes, and behaviors; 2) item review: items were reviewed for face validity; 3) validation: 174 public health students, the exploratory sample, and 98 community members, the test sample, validated the scales. The scales' factor structure was based on exploratory factor analysis (EFA) and model fit was assessed through confirmatory factor analysis (CFA). For each scale, the final EFA resulted in an independent three-factor solution for knowledge, attitudes, and behaviors. Good fit for the three-factor structure was observed. Model fit for CFA was generally confirmed with fit indices. The scales showed internal consistency with Cronbach's alpha from 0.63 to 0.70. The 42-item instrument represents an important contribution towards assessing EHL and is designed to enable meaningful engagement between researchers and community members about environmental health. The intended outcome is sustained community-academic partnerships benefiting research design, implementation, translation, dissemination, and community action.
The Deepwater Horizon oil spill of 2010 prompted concern about health risks among seafood consumers exposed to polycyclic aromatic hydrocarbons (PAHs) via consumption of contaminated seafood.
The ...objective of this study was to conduct population-specific probabilistic health risk assessments based on consumption of locally harvested white shrimp (Litopenaeus setiferus) among Vietnamese Americans in southeast Louisiana.
We conducted a survey of Vietnamese Americans in southeast Louisiana to evaluate shrimp consumption, preparation methods, and body weight among shrimp consumers in the disaster-impacted region. We also collected and chemically analyzed locally harvested white shrimp for 81 individual PAHs. We combined the PAH levels (with accepted reference doses) found in the shrimp with the survey data to conduct Monte Carlo simulations for probabilistic noncancer health risk assessments. We also conducted probabilistic cancer risk assessments using relative potency factors (RPFs) to estimate cancer risks from the intake of PAHs from white shrimp.
Monte Carlo simulations were used to generate hazard quotient distributions for noncancer health risks, reported as mean ± SD, for naphthalene (1.8 × 10-4 ± 3.3 × 10-4), fluorene (2.4 × 10-5 ± 3.3 × 10-5), anthracene (3.9 × 10-6 ± 5.4 × 10-6), pyrene (3.2 × 10-5 ± 4.3 × 10-5), and fluoranthene (1.8 × 10-4 ± 3.3 × 10-4). A cancer risk distribution, based on RPF-adjusted PAH intake, was also generated (2.4 × 10-7 ± 3.9 × 10-7).
The risk assessment results show no acute health risks or excess cancer risk associated with consumption of shrimp containing the levels of PAHs detected in our study, even among frequent shrimp consumers.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The disparate measurement protocols used to collect study data are an intrinsic barrier to combining information from environmental health studies. Using standardized measurement protocols and data ...standards for environmental exposures addresses this gap by improving data collection quality and consistency. To assess the prevalence of environmental exposures in National Institutes of Health (NIH) public data repositories and resources and to assess the commonality of the data elements, we analyzed clinical measures and exposure assays by comparing the Caribbean Consortium for Research in Environmental and Occupational Health study with selected NIH environmental health resources and studies. Our assessment revealed that (1) environmental assessments are widely collected in these resources, (2) biological assessments are less prevalent, and (3) NIH resources can help identify common data for meta-analysis. We highlight resources to help link environmental exposure data across studies to support data sharing. Including NIH data standards in environmental health research facilitates comparing and combining study data, and the use of NIH resources and adoption of standard measures will allow integration of multiple studies and increase the scientific impact of individual studies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Metals, stress, and sociodemographics are commonly studied separately for their effects on birth outcomes, yet often jointly contribute to adverse outcomes. This study analyzes two methods for ...measuring cumulative risk to understand how maternal chemical and nonchemical stressors may contribute to small for gestational age (SGA). SGA was calculated using sex-specific fetal growth curves for infants of pregnant mothers (
= 2562) enrolled in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. The exposures (maternal lead, mercury, cadmium, Cohen's perceived stress, Edinburgh depression scores, race/ethnicity, income, and education) were grouped into three domains: metals, psychosocial stress, and sociodemographics. In Method 1 we created cumulative risk scores using tertiles. Method 2 employed weighted quantile sum (WQS) regression. For each method, logistic models were built with three exposure domains individually and race/ethnicity, adjusting for age, parity, pregnancy weight gain, and marital status. The adjusted effect of overall cumulative risk with three domains, was also modeled using each method. Sociodemographics was the only exposure associated with SGA in unadjusted models ((odds ratio) OR: 1.35, 95% (confidence interval) CI: 1.08, 1.68). The three cumulative variables in adjusted models were not significant individually, but the overall index was associated with SGA (OR: 1.17, 95% CI: 1.02, 1.35). In the WQS model, only the sociodemographics domain was significantly associated with SGA. Sociodemographics tended to be the strongest risk factor for SGA in both risk score and WQS models.
Currently, the effects of chronic, continuous low dose environmental irradiation on the mitochondrial genome of resident small mammals are unknown. Using the bank vole (Myodes glareolus) as a model ...system, we tested the hypothesis that approximately 50 generations of exposure to the Chernobyl environment has significantly altered genetic diversity of the mitochondrial genome. Using deep sequencing, we compared mitochondrial genomes from 131 individuals from reference sites with radioactive contamination comparable to that present in northern Ukraine before the 26 April 1986 meltdown, to populations where substantial fallout was deposited following the nuclear accident. Population genetic variables revealed significant differences among populations from contaminated and uncontaminated localities. Therefore, we rejected the null hypothesis of no significant genetic effect from 50 generations of exposure to the environment created by the Chernobyl meltdown. Samples from contaminated localities exhibited significantly higher numbers of haplotypes and polymorphic loci, elevated genetic diversity, and a significantly higher average number of substitutions per site across mitochondrial gene regions. Observed genetic variation was dominated by synonymous mutations, which may indicate a history of purify selection against nonsynonymous or insertion/deletion mutations. These significant differences were not attributable to sample size artifacts. The observed increase in mitochondrial genomic diversity in voles from radioactive sites is consistent with the possibility that chronic, continuous irradiation resulting from the Chernobyl disaster has produced an accelerated mutation rate in this species over the last 25 years. Our results, being the first to demonstrate this phenomenon in a wild mammalian species, are important for understanding genetic consequences of exposure to low‐dose radiation sources.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Following oil spills such as the Deepwater Horizon accident (DWH), contamination of seafood resources and possible increased health risks attributable to consumption of seafood in spill areas are ...major concerns. In this study, locally harvested finfish and shrimp were collected from research participants in southeast Louisiana and analyzed for polycyclic aromatic hydrocarbons (PAHs). PAHs are some of the most important chemicals of concern regarding oil‐spill‐contaminated seafood resources during and following oil spills. Some PAHs are considered carcinogens for risk assessment purposes, and currently, seven of these can be combined in lifetime cancer risk assessments using EPA approaches. Most PAHs were not detected in these samples (minimum detection limits ranged from 1.2 to 2.1 PPB) and of those that were detected, they were generally below 10 PPB. The pattern of detected PAHs suggested that the source of these chemicals in these seafood samples was not a result of direct contact with crude oil. Lifetime cancer risks were assessed using conservative assumptions and models in a probabilistic framework for the seven carcinogenic PAHs. Lifetime health risks modeled using this framework did not exceed a 1/10,000 cancer risk threshold. Conservative, health‐protective deterministic estimates of the levels of concern for PAH chemical concentration and seafood intake rates were above the concentrations and intake rates modeled under this probabilistic framework. Taken together, consumption of finfish and shrimp harvested from southeast Louisiana following the DWH does not pose unacceptable lifetime cancer risks from these seven carcinogenic PAHs even for the heaviest possible consumers.
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BFBNIB, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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