Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

Energy Technology Data Exchange (ETDEWEB)

Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

2012-04-15

Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

Protecting Malaysia's aquatic resources: biomarkers of exposure and effect in resident fishes

International Nuclear Information System (INIS)

Swee Joo Teh; Hinton, D.E.

1998-01-01

Environmental regulators are increasingly looking for better, more cost-effective ways to protect biological resources from harmful consequences of pollution, and to restore the formerly contaminated watersheds. Where financial restraints are a reality, prioritization of efforts becomes necessary. Detection of harmful contaminant effects by direct analysis of fishes residing in streams and coastal waters of varying quality can yield information necessary to prioritize future efforts and to verify whether remediation has been achieved. Responses of tissues, body fluids, and cells signal exposure and these B iomarkers , on the other hand, reflect the bioavailability of contaminants, provide a rapid and inexpensive means for toxicity assessment, may serve as fingerprints of specific classes of chemicals, and serve as an early warning of population and community stress. Furthermore, biomarkers can identify early stages of disease and serve as a powerful integrator between contaminant exposure and biologic responses to xenobiotics found in the environment. This report will focus on the application of biomarkers as an indicator of xenobiotic exposure and deleterious effect and to evaluate progress of remediation efforts. Various levels of biomarker approaches, from biochemical to morphologic, which have been shown to be powerful tools for assessing environmental contamination and health, will be presented and their application for field validation will be discussed. When integrated with chemical analysis, biomarker approaches provide unique information on infaunal organisms and on the health of their ecosystems. (Author)

CHURCHILL COUNTY, NEVADA ARSENIC STUDY: WATER CONSUMPTION AND EXPOSURE BIOMARKERS

Science.gov (United States)

The US Environmental Protection Agency is required to reevaluate the Maximum Contaminant Level (MCL) for arsenic in 2006. To provide data for reducing uncertainties in assessing health risks associated with exposure to low levels (<200 g/l) of arsenic, a large scale biomarker st...

Personal exposure to PM2.5 and biomarkers of DNA damage

DEFF Research Database (Denmark)

Sørensen, Mette; Autrup, Herman; Hertel, Ole

2003-01-01

Ambient particulate air pollution assessed as outdoor concentrations of particulate matter PM(2.5)) has been associated with an increased cancer risk. However, outdoor PM(2.5) concentrations may not be the best measure of the individual particle exposure that is a sum...... of many sources besides outdoor particle levels, e.g., environmental tobacco smoke and cooking. We measured personal PM(2.5) and black smoke exposure in 50 students four times over 1 year and analyzed for biomarkers of different types of DNA damages. Ambient PM(2.5) concentrations were also measured...... collections were analyzed for 8-oxodG and 1-hydroxypyrene. Personal PM(2.5) exposure was found to be a predictor of 8-oxodG in lymphocyte DNA with an 11% increase in 8-oxodG/10 microg/m(3) increase in personal PM(2.5) exposure (P = 0.007). No other associations between exposure markers and biomarkers could...

Incorporating biomarkers in ecological risk assessment of chemical contaminants of soils

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A. J. Reinecke

2007-09-01

Full Text Available Soil is an important but complex natural resource which is increasingly used as sink for chemicals. The monitoring of soil quality and the assessment of risks posed by contaminants have become crucial. This study deals with the potential use of biomarkers in the monitoring of soils and the assessment of risk resulting from contamination. Apart from an overview of the existing literature on biomarkers, the results of various of our field experiments in South African soils are discussed. Biomarkers may have potential in the assessment of risk because they can indicate at an early stage that exposure has taken place and that a toxic response has been initiated. It is therefore expected that early biomarkers will play an increasing role as diagnostic tools for determining exposure to chemicals and the resulting effects. They may have predictive value that can assist in the prevention or minimising of risks. The aim of this study was to investigate the possibilities of using our results on biomarker responses of soil dwelling organisms to predict changes at higher organisational levels (which may have ecological implications. Our recent experimental results on the evaluation of various biomarkers in both the laboratory and the field are interpreted and placed in perspective within the broader framework of response biology. The aim was further to contribute to the development and application of biomarkers in regulatory risk assessment schemes of soils. This critical review of our own and recent literature on biomarkers in ecotoxicology leads to the conclusion that biomarkers can, under certain conditions, be useful tools in risk assessment. Clear relationships between contamination loads in soil organisms and certain biomarker responses were determined in woodlice, earthworms and terrestrial snails. Clear correlations were also established in field experiments between biomarker responses and changes at the population level. This indicated that, in

Concentrations versus amounts of biomarkers in urine: a comparison of approaches to assess pyrethroid exposure

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Bouchard Michèle

2008-11-01

Full Text Available Abstract Background Assessment of human exposure to non-persistent pesticides such as pyrethroids is often based on urinary biomarker measurements. Urinary metabolite levels of these pesticides are usually reported in volume-weighted concentrations or creatinine-adjusted concentrations measured in spot urine samples. It is known that these units are subject to intra- and inter-individual variations. This research aimed at studying the impact of these variations on the assessment of pyrethroid absorbed doses at individual and population levels. Methods Using data obtained from various adult and infantile populations, the intra and inter-individual variability in the urinary flow rate and creatinine excretion rate was first estimated. Individual absorbed doses were then calculated using volume-weighted or creatinine-adjusted concentrations according to published approaches and compared to those estimated from the amounts of biomarkers excreted in 15- or 24-h urine collections, the latter serving as a benchmark unit. The effect of the units of measurements (volume-weighted or creatinine adjusted concentrations or 24-h amounts on results of the comparison of pyrethroid biomarker levels between two populations was also evaluated. Results Estimation of daily absorbed doses of permethrin from volume-weighted or creatinine-adjusted concentrations of biomarkers was found to potentially lead to substantial under or overestimation when compared to doses reconstructed directly from amounts excreted in urine during a given period of time (-70 to +573% and -83 to +167%, respectively. It was also shown that the variability in creatinine excretion rate and urinary flow rate may introduce a bias in the case of between population comparisons. Conclusion The unit chosen to express biomonitoring data may influence the validity of estimated individual absorbed dose as well as the outcome of between population comparisons.

Carbon nanotube and nanofiber exposure and sputum and blood biomarkers of early effect among U.S. workers.

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Beard, John D; Erdely, Aaron; Dahm, Matthew M; de Perio, Marie A; Birch, M Eileen; Evans, Douglas E; Fernback, Joseph E; Eye, Tracy; Kodali, Vamsi; Mercer, Robert R; Bertke, Stephen J; Schubauer-Berigan, Mary K

2018-07-01

Carbon nanotubes and nanofibers (CNT/F) are increasingly used for diverse applications. Although animal studies suggest CNT/F exposure may cause deleterious health effects, human epidemiological studies have typically been small, confined to single workplaces, and limited in exposure assessment. We conducted an industrywide cross-sectional epidemiological study of 108 workers from 12 U.S. sites to evaluate associations between occupational CNT/F exposure and sputum and blood biomarkers of early effect. We assessed CNT/F exposure via personal breathing zone, filter-based air sampling to measure background-corrected elemental carbon (EC) (a CNT/F marker) mass and microscopy-based CNT/F structure count concentrations. We measured 36 sputum and 37 blood biomarkers. We used factor analyses with varimax rotation to derive factors among sputum and blood biomarkers separately. We used linear, Tobit, and unconditional logistic regression models to adjust for potential confounders and evaluate associations between CNT/F exposure and individual biomarkers and derived factors. We derived three sputum and nine blood biomarker factors that explained 78% and 67%, respectively, of the variation. After adjusting for potential confounders, inhalable EC and total inhalable CNT/F structures were associated with the most sputum and blood biomarkers, respectively. Biomarkers associated with at least three CNT/F metrics were 72 kDa type IV collagenase/matrix metalloproteinase-2 (MMP-2), interleukin-18, glutathione peroxidase (GPx), myeloperoxidase, and superoxide dismutase (SOD) in sputum and MMP-2, matrix metalloproteinase-9, metalloproteinase inhibitor 1/tissue inhibitor of metalloproteinases 1, 8-hydroxy-2'-deoxyguanosine, GPx, SOD, endothelin-1, fibrinogen, intercellular adhesion molecule 1, vascular cell adhesion protein 1, and von Willebrand factor in blood, although directions of associations were not always as expected. Inhalable rather than respirable CNT/F was more

Polychlorinated biphenyls pattern analysis: Potential nondestructive biomarker in vertebrates for exposure to cytochrome P450-inducing organochlorines

Energy Technology Data Exchange (ETDEWEB)

Brink, N.W. van den; Ruiter-Dijkman, E.M. De; Broekhuizen, S.; Reijnders, P.J.H.; Bosveld, A.T.C.

2000-03-01

Biomarkers are valuable instruments to assess the risks from exposure of organisms to organochlorines. In general, however, these biomarkers are either destructive to the animal of interest or extremely difficult to obtain otherwise. In this paper, the authors present a nondestructive biomarker for exposure to cytochrome P450-inducing organochlorines. This marker is based on a pattern analysis of metabolizable and nonmetabolizable polychlorinated biphenyl (PCB) congeners, which occur in several kinds of tissues (and even blood) that can be obtained without serious effects on the organism involved. The fraction of metabolizable PCB congeners is negatively correlated with exposure to PCBs, which are known to induce specific P450 isoenzymes. This relation can be modeled by a logistic curve, which can be used to define critical levels of exposure. In addition, this method creates an opportunity to analyze biomarker responses in archived tissues stored at standard freezing temperatures ({minus}20 C), at which responses to established biomarkers deteriorate. Furthermore, this method facilitates attribution of the enzyme induction to certain classes of compounds.

Capsaicinoids, chloropicrin and sulfur mustard: Possibilities for exposure biomarkers

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Maija Pesonen

2010-12-01

Full Text Available Incapacitating and irritating agents produce temporary disability persisting for hours to days after the exposure. One can be exposed to these agents occupationally in industrial or other working environments. Also general public can be exposed in special circumstances, like industrial accidents or riots. Incapacitating and irritating agents discussed in this review are chloropicrin and capsaicinoids. In addition, we include sulfur mustard, which is an old chemical warfare agent and known to cause severe long-lasting injuries or even death. Chloropicrin that was used as a warfare agent in the World War I is currently used mainly as a pesticide. Capsaicinoids, components of hot pepper plants, are used by police and other law enforcement personnel as riot control agents. Toxicity of these chemicals is associated particularly with the respiratory tract, eyes and skin. Their acute effects are relatively well known but the knowledge of putative long-term effects is almost non-existent. Also, mechanisms of effects at cellular level are not fully understood. There is a need for further research to get better idea of health risks, particularly of long-term and low-level exposures to these chemicals. For this, exposure biomarkers are essential. Validated exposure biomarkers for capsaicinoids, chloropicrin and sulfur mustard do not exist so far. Metabolites and macromolecular adducts have been suggested biomarkers for sulfur mustard and these can already be measured qualitatively, but quantitative biomarkers await further development and validation. The purpose of this review is, based on the existing mechanistic and toxicokinetic information, to shed light on the possibilities for developing biomarkers for exposure biomonitoring of these compounds. It is also of interest to find ideas for early effect biomarkers considering the need for studies on subchronic and chronic toxicity.

An ignored risk factor in toxicology: The total imprecision of exposure assessment

DEFF Research Database (Denmark)

Grandjean, Philippe; Budtz-Jørgensen, Esben

2010-01-01

twice as much for maternal hair. The total imprecision of these biomarkers much exceeded the normal laboratory variability of less than 5%. Such imprecision can cause underestimation of dose-related toxicity, and data analysis should therefore include sensitivity analyses that take this factor...... were determined in cord blood, cord tissue, and maternal hair. We determined their mutual correlations and their associations with the child's neurobehavioral effect variables at age 7 years. The exposure biomarkers correlated well with one another, but the cord blood mercury concentration showed......Quality assurance of exposure biomarkers usually focuses on laboratory performance only. Using data from a prospective birth cohort study in the Faroe Islands, we have assessed the total imprecision of exposure biomarkers. As biomarkers of prenatal methylmercury exposure, mercury concentrations...

Biomarkers of acute respiratory allergen exposure: Screening for sensitization potential

International Nuclear Information System (INIS)

Pucheu-Haston, Cherie M.; Copeland, Lisa B.; Vallanat, Beena; Boykin, Elizabeth; Ward, Marsha D.W.

2010-01-01

Effective hazard screening will require the development of high-throughput or in vitro assays for the identification of potential sensitizers. The goal of this preliminary study was to identify potential biomarkers that differentiate the response to allergens vs non-allergens following an acute exposure in naive individuals. Female BALB/c mice received a single intratracheal aspiration exposure to Metarhizium anisopliae crude antigen (MACA) or bovine serum albumin (BSA) in Hank's Balanced Salt Solution (HBSS) or HBSS alone. Mice were terminated after 1, 3, 6, 12, 18 and 24 h. Bronchoalveolar lavage fluid (BALF) was evaluated to determine total and differential cellularity, total protein concentration and LDH activity. RNA was isolated from lung tissue for microarray analysis and qRT-PCR. MACA administration induced a rapid increase in BALF neutrophils, lymphocytes, eosinophils and total protein compared to BSA or HBSS. Microarray analysis demonstrated differential expression of genes involved in cytokine production, signaling, inflammatory cell recruitment, adhesion and activation in 3 and 12 h MACA-treated samples compared to BSA or HBSS. Further analyses allowed identification of ∼ 100 candidate biomarker genes. Eleven genes were selected for further assessment by qRT-PCR. Of these, 6 demonstrated persistently increased expression (Ccl17, Ccl22, Ccl7, Cxcl10, Cxcl2, Saa1), while C3ar1 increased from 6-24 h. In conclusion, a single respiratory exposure of mice to an allergenic mold extract induces an inflammatory response which is distinct in phenotype and gene transcription from the response to a control protein. Further validation of these biomarkers with additional allergens and irritants is needed. These biomarkers may facilitate improvements in screening methods.

Development and validation of a rapid multi-biomarker liquid chromatography/tandem mass spectrometry method to assess human exposure to mycotoxins.

Science.gov (United States)

Warth, Benedikt; Sulyok, Michael; Fruhmann, Philipp; Mikula, Hannes; Berthiller, Franz; Schuhmacher, Rainer; Hametner, Christian; Abia, Wilfred Angie; Adam, Gerhard; Fröhlich, Johannes; Krska, Rudolf

2012-07-15

Mycotoxins regularly occur in food worldwide and pose serious health risks to consumers. Since individuals can be exposed to a variety of these toxic secondary metabolites of fungi at the same time, there is a demand for proper analytical methods to assess human exposure by suitable biomarkers. This study reports on the development of a liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the quantitative measurement of 15 mycotoxins and key metabolites in human urine using polarity switching. Deoxynivalenol (DON), DON-3-O-glucuronide, DON-15-O-glucuronide (D15GlcA), de-epoxy DON, nivalenol (NIV), T-2 toxin, HT-2 toxin, zearalenone, zearalenone-14-O-glucuronide, α- and β-zearalenol, fumonisins B(1) and B(2) (FB(1), FB(2)), ochratoxin A (OTA) and aflatoxin M(1) (AFM(1)) were determined without the need for any cleanup using a rapid and simple dilute and shoot approach. Validation was performed in the range of 0.005-40 µg L(-1) depending on the analyte and expected urinary concentration levels. Apparent recoveries between 78 and 119% and interday precisions of 2-17% relative standard deviation (RSD) were achieved. The applicability of the method was demonstrated by the analysis of urine samples obtained from Cameroon. In naturally contaminated urine samples up to six biomarkers of exposure (AFM(1), DON, D15GlcA, NIV, FB(1), and OTA) were detected simultaneously. We conclude that the developed LC/MS/MS method is well suited to quantify multiple mycotoxin biomarkers in human urine down to the sub-ppb range within 18 min and without any prior cleanup. The co-occurrence of several mycotoxins in the investigated samples clearly emphasizes the great potential and importance of this method to assess exposure of humans and animals to naturally occurring mycotoxins. Copyright © 2012 John Wiley & Sons, Ltd.

Urinary trans-trans muconic acid (exposure biomarker to benzene) and hippuric acid (exposure biomarker to toluene) concentrations in Mexican women living in high-risk scenarios of air pollution.

Science.gov (United States)

Pruneda-Alvarez, Lucía G; Ruíz-Vera, Tania; Ochoa-Martínez, Angeles C; Pérez-Maldonado, Iván N

2017-11-02

This study aimed to determine t,t-muconic acid (t,t-MA; exposure biomarker for benzene) and hippuric acid (HA; exposure biomarker for toluene) concentrations in the urine of women living in Mexico. In a cross-sectional study, apparently healthy women (n = 104) were voluntarily recruited from localities with a high risk of air pollution; t,t-MA and HA in urine were quantified using a high-performance liquid chromatography (HPLC) technique. Mean urinary levels of t,t-MA ranged from 680 to 1,310 μg/g creatinine. Mean values of HA ranged from 0.38 to 0.87 g/g creatinine. In conclusion, compared to data recently reported in literature, we found high urinary levels of t,t-MA and HA in assessed women participating in this study. We therefore deem the implementation of a strategy aimed at the reduction of exposure as a necessary measure for the evaluated communities.

Nutritional biomarkers for objective dietary assessment.

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Kuhnle, Gunter G C

2012-04-01

The accurate assessment of dietary exposure is important in investigating associations between diet and disease. Research in nutritional epidemiology, which has resulted in a large amount of information on associations between diet and chronic diseases in the last decade, relies on accurate assessment methods to identify these associations. However, most dietary assessment instruments rely to some extent on self-reporting, which is prone to systematic bias affected by factors such as age, gender, social desirability and approval. Nutritional biomarkers are not affected by these and therefore provide an additional, alternative method to estimate intake. However, there are also some limitations in their application: they are affected by inter-individual variations in metabolism and other physiological factors, and they are often limited to estimating intake of specific compounds and not entire foods. It is therefore important to validate nutritional biomarkers to determine specific strengths and limitations. In this perspective paper, criteria for the validation of nutritional markers and future developments are discussed. Copyright © 2012 Society of Chemical Industry.

Looking for biomarkers of Hg exposure by transcriptome analysis in the aquatic plant Elodea nuttallii

Directory of Open Access Journals (Sweden)

Regier N.

2013-04-01

Full Text Available Recently developed genomics tools have a promising potential to identify early biomarkers of exposure to toxicants. In the present work we used transcriptome analysis (RNA-seq of Elodea nuttallii –an invasive rooted macrophyte that is able to accumulate large amounts of metals- to identify biomarkers of Hg exposure. RNA-seq allowed identification of genes affected by Hg exposure and also unraveled plant response to the toxic metal: a change in energy/reserve metabolism caused by the inhibition of photosynthesis, and an adaptation of homeostasis networks to control accumulation of Hg. Data were validated by RT-qPCR and selected genes were further tested as biomarkers. Samples exposed in the field and to natural contaminated sediments clustered well with samples exposed to low metal concentrations under laboratory conditions. Our data suggest that this plant and/or this approach could be useful to develop new tests for water and sediment quality assessment.

Biomarkers for the detection of prenatal alcohol exposure (PAE)

DEFF Research Database (Denmark)

Bjerregaard, Lene Berit Skov; Bager, Heidi; Husby, Steffen

2017-01-01

Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self-reporting. However, a more objective and useful...... method is based on the use of biomarkers in biological specimens alone or in combination with maternal self-reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing...... to be applicable for detection of even low levels of alcohol exposure. Meconium is an accessible matrix for determination of FAEEs and EtG, and blood an accessible matrix for determination of PEth....

Fish bioaccumulation and biomarkers in environmental risk assessment : a review

NARCIS (Netherlands)

van der Oost, Ron; Beyer, Jonny; Vermeulen, Nico P E

In this review, a wide array of bioaccumulation markers and biomarkers, used to demonstrate exposure to and effects of environmental contaminants, has been discussed in relation to their feasibility in environmental risk assessment (ERA). Fish bioaccumulation markers may be applied in order to

A Comparison of Survey Measures and Biomarkers of Secondhand Tobacco Smoke Exposure among Nonsmokers.

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Okoli, Chizimuzo

2016-01-01

Secondhand tobacco smoke (SHS) exposure causes several adverse physical health outcomes. Conceptual differences in survey measures of 'psychosocial' (SHS exposure from smokers in an individual's life) and 'physical' (environments where an individual is exposed to SHS) SHS exposure exist. Few studies have examined the association between psychosocial and physical SHS exposures measures in comparison to biomarkers of SHS exposure. A secondary analysis of cross-sectional data was examined among a convenience sample of 20 adults. Data included survey items on SHS exposure and hair nicotine and saliva cotinine levels. Spearman analysis was used to assess correlations among variables. Medium and strong correlations were found among SHS exposure measures with the exception of saliva cotinine levels. Strong correlations were found among and between psychosocial and physical SHS exposure measures. Hair nicotine levels had medium strength associations with only perceived frequency of SHS exposure. As psychosocial measures of exposure were associated with biomarkers, such measures (particularly perceived frequency of SHS exposure) should be added to surveys in addition to physical SHS exposure measures to enhance accuracy of SHS measurement. Future explorations with robust sample sizes should further examine the strength of relationship between psychosocial and physical SHS exposure measures. © 2015 Wiley Periodicals, Inc.

Assessment of mankind's exposure through his environment: new tools and aid to decision - Colloquium report

International Nuclear Information System (INIS)

Thierry-Mieg, Morgane; Rousset, Marine; Varkados-Lemarechal, Margaret

2012-01-01

During this colloquium, the different sessions addressed environmental measurement strategies to assess mankind's exposure, the use and the interpretation of exposure bio-markers, the estimation and reconstruction of exposures (integrated modelling, model-measurement coupling), the organization and motives of dialogue between involved parties. Round tables addressed topics such as: measurement strategies and objectives, bio-availability of soil pollutants, approaches and tools for exposure assessment, new methodological strategies for the assessment of chemical exposure, interpretation of bio-markers, reference toxicological values, interest of bio-monitoring in professional environment, transcriptomic analysis, evolutions in the characterization of genotoxic hazards, a tool for the assessment of the exposure of newborn children to pesticides, and so on

Biomarkers of end of shift exposure to disinfection byproducts in nurses.

Science.gov (United States)

Ioannou, Solomon; Andrianou, Xanthi D; Charisiadis, Pantelis; Makris, Konstantinos C

2017-08-01

Increased disinfectant use commonly takes place in hospitals and other health care settings. A cross-sectional study among active nurses in two Cypriot public hospitals (n=179) was conducted to examine the prevalence of exposure to disinfection byproducts (DBPs), such as trihalomethanes (THMs) using both self-reported information and biomarker measurements. The objectives of this study were to: i) quantify the magnitude and variability of occupational exposure to disinfectants/DBPs in nurses, ii) generate job exposure matrices (JEM) and job task exposure matrices (JTEM) for disinfectants, and iii) assess the major determinants of urinary THMs in nurses. End of shift urinary total THM values showed high variability among the nurses, but did not differ between hospitals. The disinfectant group of alcohols/phenols was used by >98% of nurses, followed by octenidine (82%), iodine and chlorine (39%, each), chlorhexidine (25%), formaldehyde (12%), hydrogen peroxide (11%), and peracetic acid/ammonia/quaternary ammonium compounds (QACs), all being Nurses were exposed to nearly double the levels of TTHMs and BrTHMs (median and IQR, 1027 [560, 2475] ng/g and 323 [212, 497] ng/g, respectively) when compared to those of the general population (552 [309,989] ng/g and 152 [87,261] ng/g, respectively). This was the first occupational health dataset reporting measurements of biomarkers of end of shift exposures to disinfectants/DBPs. Copyright © 2017. Published by Elsevier B.V.

What is the best biomarker to assess arsenic exposure via drinking water?

Science.gov (United States)

Marchiset-Ferlay, Nathalie; Savanovitch, Chantal; Sauvant-Rochat, Marie-Pierre

2012-02-01

Arsenic (As) is a ubiquitous element. The current WHO guideline for As in drinking water is 10 μg/L. Furthermore, about 130 million people have only access to drinking water containing more than 10 g As/L. Although numerous studies have shown the related adverse effects of As, sensitive appropriate biomarkers are still required for studies of environmental epidemiology. A review of the literature has shown that various biomarkers are used for such research. Their limits and advantages are highlighted in this paper: (i) the detection of As or its derivatives in the blood is an indication of the dose ingested but it is not evidence of chronic intoxication. (ii) The detection of As in urine is an indispensible procedure because it is a good marker for internal dose. It has been demonstrated to correlate well for a number of chronic effects related to As levels in drinking water. However confounding factors must be taken into account to avoid misinterpretation and this may require As speciation. (iii) As in the hair and nails reflects the level of long term exposure but it is difficult to relate the level with the dose ingested. (iv) Some studies showed a correlation between urinary As and urinary and blood porphyrins. However, it is difficult to use only porphyrins as a biomarker in a population survey carried out without doing further studies. (v) Genotoxic effects are based on the characterization of these potential effects. Most studies have detected increases in DNA damage, sister chromatid exchange, micronuclei or chromosomal aberrations in populations exposed to As in drinking water. Micronuclei assay is the technique of choice to follow these populations, because it is sensitive and easy to use. To conclude, whatever epidemiological studies are, the urinary and toenail biomarkers are useful to provide indications of internal dose. Moreover, micronuclei assay can be complementary use as biomarker of early effects. Copyright © 2011 Elsevier Ltd. All rights

Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of distal airway and blood biomarkers that predict FEV1 decline

Science.gov (United States)

Weiden, Michael D.; Kwon, Sophia; Caraher, Erin; Berger, Kenneth I.; Reibman, Joan; Rom, William N.; Prezant, David J.; Nolan, Anna

2016-01-01

Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung’s normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after World Trade Center (WTC) exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1biomarkers of WTC-LI. We have identified biomarkers of Inflammation, metabolic derangement, protease/antiprotease balance and vascular injury expressed in serum within 6 months of WTC exposure that were predictive of their FEV1 up to 7 years after their WTC exposure. Predicting future risk of airway injury after particulate exposures can focus monitoring and early treatment on a subset of patients in greatest need of these services. PMID:26024341

Candidate protein biomarkers as rapid indicators of radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Horn, Simon, E-mail: sjh.horn@gmail.com [Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire OX11 0RQ (United Kingdom); Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast BT9 7BL (United Kingdom); Rothkamm, Kai [Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire OX11 0RQ (United Kingdom)

2011-09-15

For large scale exposures of the human population to ionising radiation, there is a need for cost-effective high throughput assessment of radiation exposure levels from biological samples to allow triage decisions to be made. Here we assess the usefulness of H2AX phosphorylation, 53BP1 foci formation, p53 induction and caspase activation as tools for biological dosimetry. Peripheral blood lymphocytes from healthy donors were isolated and exposed to X-rays. Cells were fixed, permeabilised and then stained with primary antibodies for {gamma}-H2AX and/or 53BP1, p53 or FLICA caspase detection kit followed by fluorescently tagged secondary antibodies. Cell nuclei were DAPI or propidium iodide counterstained for microscopy or cytometry respectively. Average {gamma}-H2AX/53BP1 foci numbers and {gamma}-H2AX fluorescence intensities increased with dose. Foci loss occurred over a period of 24 h post exposure with foci levels remaining above baseline levels for at least 24 h following exposure to 0.5 Gy or more of X-rays. p53 levels increased with dose and over time, peaking at 48 h post exposure. Apoptotic cells were highlighted with greatly increased levels of activated caspases. A single dose of 4 Gy increased the percentage of apoptotic lymphocytes to over 60% at 96 h post exposure. The finding that the biomarkers analysed here have different temporal dynamics following radiation exposure suggests that they could be combined to enable detection of exposures over a period of hours to several days after a radiation incident to help facilitate rapid triage.

Identification of urinary biomarkers of exposure to di-(2-propylheptyl) phthalate using high-resolution mass spectrometry and two data-screening approaches.

Science.gov (United States)

Shih, Chia-Lung; Liao, Pao-Mei; Hsu, Jen-Yi; Chung, Yi-Ning; Zgoda, Victor G; Liao, Pao-Chi

2018-02-01

Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer used in polyvinyl chloride and vinyl chloride copolymer that has been suggested to be a toxicant in rats and may affect human health. Because the use of DPHP is increasing, the general German population is being exposed to DPHP. Toxicant metabolism is important for human toxicant exposure assessments. To date, the knowledge regarding DPHP metabolism has been limited, and only four metabolites have been identified in human urine. Ultra-performance liquid chromatography was coupled with Orbitrap high-resolution mass spectrometry (MS) and two data-screening approaches-the signal mining algorithm with isotope tracing (SMAIT) and the mass defect filter (MDF)-for DPHP metabolite candidate discovery. In total, 13 and 104 metabolite candidates were identified by the two approaches, respectively, in in vitro DPHP incubation samples. Of these candidates, 17 were validated as tentative exposure biomarkers using a rat model, 13 of which have not been reported in the literature. The two approaches generated rather different tentative DPHP exposure biomarkers, indicating that these approaches are complementary for discovering exposure biomarkers. Compared with the four previously reported DPHP metabolites, the three tentative novel biomarkers had higher peak intensity ratios, and two were confirmed as DPHP hydroxyl metabolites based on their MS/MS product ion profiles. These three tentative novel biomarkers should be further investigated for potential application in human exposure assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fish bioaccumulation and biomarkers in environmental risk assessment: a review.

Science.gov (United States)

van der Oost, Ron; Beyer, Jonny; Vermeulen, Nico P E

2003-02-01

In this review, a wide array of bioaccumulation markers and biomarkers, used to demonstrate exposure to and effects of environmental contaminants, has been discussed in relation to their feasibility in environmental risk assessment (ERA). Fish bioaccumulation markers may be applied in order to elucidate the aquatic behavior of environmental contaminants, as bioconcentrators to identify certain substances with low water levels and to assess exposure of aquatic organisms. Since it is virtually impossible to predict the fate of xenobiotic substances with simple partitioning models, the complexity of bioaccumulation should be considered, including toxicokinetics, metabolism, biota-sediment accumulation factors (BSAFs), organ-specific bioaccumulation and bound residues. Since it remains hard to accurately predict bioaccumulation in fish, even with highly sophisticated models, analyses of tissue levels are required. The most promising fish bioaccumulation markers are body burdens of persistent organic pollutants, like PCBs and DDTs. Since PCDD and PCDF levels in fish tissues are very low as compared with the sediment levels, their value as bioaccumulation markers remains questionable. Easily biodegradable compounds, such as PAHs and chlorinated phenols, do not tend to accumulate in fish tissues in quantities that reflect the exposure. Semipermeable membrane devices (SPMDs) have been successfully used to mimic bioaccumulation of hydrophobic organic substances in aquatic organisms. In order to assess exposure to or effects of environmental pollutants on aquatic ecosystems, the following suite of fish biomarkers may be examined: biotransformation enzymes (phase I and II), oxidative stress parameters, biotransformation products, stress proteins, metallothioneins (MTs), MXR proteins, hematological parameters, immunological parameters, reproductive and endocrine parameters, genotoxic parameters, neuromuscular parameters, physiological, histological and morphological parameters

Blood-borne biomarkers and bioindicators for linking exposure to health effects in environmental health science.

Science.gov (United States)

Wallace, M Ariel Geer; Kormos, Tzipporah M; Pleil, Joachim D

2016-01-01

Environmental health science aims to link environmental pollution sources to adverse health outcomes to develop effective exposure intervention strategies that reduce long-term disease risks. Over the past few decades, the public health community recognized that health risk is driven by interaction between the human genome and external environment. Now that the human genetic code has been sequenced, establishing this "G × E" (gene-environment) interaction requires a similar effort to decode the human exposome, which is the accumulation of an individual's environmental exposures and metabolic responses throughout the person's lifetime. The exposome is composed of endogenous and exogenous chemicals, many of which are measurable as biomarkers in blood, breath, and urine. Exposure to pollutants is assessed by analyzing biofluids for the pollutant itself or its metabolic products. New methods are being developed to use a subset of biomarkers, termed bioindicators, to demonstrate biological changes indicative of future adverse health effects. Typically, environmental biomarkers are assessed using noninvasive (excreted) media, such as breath and urine. Blood is often avoided for biomonitoring due to practical reasons such as medical personnel, infectious waste, or clinical setting, despite the fact that blood represents the central compartment that interacts with every living cell and is the most relevant biofluid for certain applications and analyses. The aims of this study were to (1) review the current use of blood samples in environmental health research, (2) briefly contrast blood with other biological media, and (3) propose additional applications for blood analysis in human exposure research.

Ultra-sensitive, stable isotope assisted quantification of multiple urinary mycotoxin exposure biomarkers.

Science.gov (United States)

Šarkanj, Bojan; Ezekiel, Chibundu N; Turner, Paul C; Abia, Wilfred A; Rychlik, Michael; Krska, Rudolf; Sulyok, Michael; Warth, Benedikt

2018-08-17

There is a critical need to better understand the patterns, levels and combinatory effects of exposures we are facing through our diet and environment. Mycotoxin mixtures are of particular concern due to chronic low dose exposures caused by naturally contaminated food. To facilitate new insights into their role in chronic disease, mycotoxins and their metabolites are quantified in bio-fluids as biomarkers of exposure. Here, we describe a highly sensitive urinary assay based on ultra-high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS) and 13 C-labelled or deuterated internal standards covering the most relevant regulated and emerging mycotoxins. Utilizing enzymatic pre-treatment, solid phase extraction and UHPLC separation, the sensitivity of the method was significantly higher (10-160x lower LODs) than in a previously described method used for comparison purpose, and stable isotopes provided compensation for challenging matrix effects. This method was in-house validated and applied to re-assess mycotoxin exposure in urine samples obtained from Nigerian children, adolescent and adults, naturally exposed through their regular diet. Owing to the methods high sensitivity, biomarkers were detected in all samples. The mycoestrogen zearalenone was the most frequently detected contaminant (82%) but also ochratoxin A (76%), aflatoxin M 1 (73%) and fumonisin B 1 (71%) were quantified in a large share of urines. Overall, 57% of 120 urines were contaminated with both, aflatoxin M 1 and fumonisin B 1 , and other co-exposures were frequent. These results clearly demonstrate the advanced performance of the method to assess lowest background exposures (pg mL -1 range) using a single, highly robust assay that will allow for the systematic investigation of low dose effects on human health. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Human exposure assessment to environmental chemicals using biomonitoring.

Science.gov (United States)

Calafat, Antonia M; Ye, Xiaoyun; Silva, Manori J; Kuklenyik, Zsuzsanna; Needham, Larry L

2006-02-01

In modern societies, humans may be exposed to a wide spectrum of environmental chemicals. Although the health significance of this exposure for many chemicals is unknown, studies to investigate the prevalence of exposure are warranted because of the chemicals' potential harmful health effects, as often indicated in animal studies. Three tools have been used to assess exposure: exposure history/questionnaire information, environmental monitoring, and biomonitoring (i.e. measuring concentrations of the chemicals, their metabolites, or their adducts in human specimens). We present an overview on the use of biomonitoring in exposure assessment using phthalates, bisphenol A and other environmental phenols, and perfluorinated chemicals as examples. We discuss some factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information. The use of biomonitoring in human risk assessment is not discussed.

Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides.

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Lygia T Budnik

Full Text Available There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD but (mostly lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001. The decreased integrity of mtDNA (mtDNA-230/mtDNA-79 in exposed individuals implicates apoptotic processes (p = 0.015. The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001. Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

Assessing arsenic exposure from consumption of seafood from Vieques-Puerto Rico: a pilot biomonitoring study using different biomarkers.

Science.gov (United States)

Mansilla-Rivera, Imar; Nazario, Cruz M; Ramírez-Marrero, Farah A; Crespo, Carlos J; Rodríguez-Sierra, Carlos J

2014-02-01

The various toxic effects associated with inorganic arsenic (iAs) warrants that exposure sources be identified. This pilot study evaluated if greater seafood consumption from Vieques-Puerto Rico is associated with increased exposure to iAs. Nail, hair, and urine samples were used as biomarkers of iAs exposure in adult women and men from Vieques classified as high (n = 31) and low (n = 21) seafood consumers, who reported eating fish and/or shellfish ≥1 time per week and once per month or less, respectively. The sum of urinary iAs (As III + As V), monomethylarsonic acid (MA[V]), and dimethylarsinic acid (DMA[V]), denoted as SumAs, fluctuated from 3.3 µg/g Cr (1.2 μg/L) to 42.7 μg/g Cr (42 μg/L) (n = 52). Levels of As in nail samples (n = 49) varied from 0.04 to 0.82 μg/g dry weight (dw), whereas in hair (n = 49) As was only detected in 49 % of the samples with a maximum value of 0.95 μg/g dw. None of the biomarkers of exposure to As exceeded exposure reference values for urine (50 μg/g Cr or 50 μg/L), nails (1 μg/g), or hair (1 μg/g). However, median (10.0 μg/g Cr; 10.6 μg/L) and 95th percentile (31.9 μg/g Cr; 40.4 μg/L) of urinary SumAs were higher in Vieques samples than in the those from the general population of other countries. Among the three biomarkers of exposure, nail samples reflected better the exposure to iAs from seafood consumption with significantly higher average As concentrations in high (0.24 μg/g) than low (0.12 μg/g) seafood consumers. Multivariate results for As in nail samples (R(2) = 0.55, p < 0.0001) showed a positive association with fish consumption, particularly for men, with levels increasing with years of residency in Vieques.

Field validation of a battery of biomarkers to assess sediment quality in Spanish ports

International Nuclear Information System (INIS)

Martin-Diaz, M.L.; Blasco, J.; Sales, D.; DelValls, T.A.

2008-01-01

Two marine invertebrates, the crab Carcinus maenas and the clam Ruditapes philippinarum, were used as bioindicator species to assess contamination when exposed in situ to sediment from different sites from four Spanish ports Cadiz (SW Spain), Huelva (SW Spain), Bilbao (NE Spain) and Pasajes (NE Spain). In an attempt to determine sediments toxicity, a combination of exposure biomarkers was analyzed in both species: metallothionein-like-proteins (MTLPs), ethoxyresorufin O-deethylase (EROD), glutathione S-transferase activity (GST), glutathione peroxidase (GPX) and glutathione reductase (GR). In parallel, physical and chemical characterization of the different sediments was performed and biological responses related to the contaminants. Significant induction of MTLPs was observed when organisms were exposed to metal contaminated sediments (port of Huelva), and EROD and GPX activities after exposure to sediments containing organic compounds (port of Bilbao and Pasajes). No significant interspecies differences were observed in biomarker responses except for the GST and GR. - A battery of biomarkers shows exposure to metals and organic compounds

Field validation of a battery of biomarkers to assess sediment quality in Spanish ports

Energy Technology Data Exchange (ETDEWEB)

Martin-Diaz, M.L. [Departamento de Quimica Fisica, Facultad de Ciencias del Mar y Ambientales, Poligono Rio San Pedro s/n, 11510 Puerto Real, Cadiz (Spain); Consejo Superior de Investigaciones Cientificas, Instituto de Ciencias Marinas de Andalucia, Poligono Rio San Pedro s/n, 11510 Puerto Real, Cadiz (Spain)], E-mail: laura.martin@uca.es; Blasco, J. [Consejo Superior de Investigaciones Cientificas, Instituto de Ciencias Marinas de Andalucia, Poligono Rio San Pedro s/n, 11510 Puerto Real, Cadiz (Spain); Sales, D. [Departamento Ciencias Ambientales y Tecnologia de los Alimentos, Facultad de Ciencias del Mar y Ambientales, Poligono Rio San Pedro s/n, 11510 Puerto Real, Cadiz (Spain); DelValls, T.A. [Departamento de Quimica Fisica, Facultad de Ciencias del Mar y Ambientales, Poligono Rio San Pedro s/n, 11510 Puerto Real, Cadiz (Spain)

2008-02-15

Two marine invertebrates, the crab Carcinus maenas and the clam Ruditapes philippinarum, were used as bioindicator species to assess contamination when exposed in situ to sediment from different sites from four Spanish ports Cadiz (SW Spain), Huelva (SW Spain), Bilbao (NE Spain) and Pasajes (NE Spain). In an attempt to determine sediments toxicity, a combination of exposure biomarkers was analyzed in both species: metallothionein-like-proteins (MTLPs), ethoxyresorufin O-deethylase (EROD), glutathione S-transferase activity (GST), glutathione peroxidase (GPX) and glutathione reductase (GR). In parallel, physical and chemical characterization of the different sediments was performed and biological responses related to the contaminants. Significant induction of MTLPs was observed when organisms were exposed to metal contaminated sediments (port of Huelva), and EROD and GPX activities after exposure to sediments containing organic compounds (port of Bilbao and Pasajes). No significant interspecies differences were observed in biomarker responses except for the GST and GR. - A battery of biomarkers shows exposure to metals and organic compounds.

Assessment of mechanisms of metal-induced reproductive toxicity in aquatic species as a biomarker of exposure

International Nuclear Information System (INIS)

Anderson, M.; George, W.; Sikka, S.; Kamath, B.; Preslan, J.; Agrawal, K.; Rege, A.

1993-01-01

This project is designed to identify heavy metals and organic contaminants of concern which could impact on the biota in the Louisiana wetlands by assessment of uptake and bioaccumulation of contaminants and their effects on reproductive processes as biomarkers of exposure. Heavy metals (lead, cadmium, cobalt, and mercury) have been demonstrated to have toxic effects on reproduction in mammals and several aquatic species. Hexachlorobenzene (HCB) is an persistent environmental contaminant which has been measured in human serum, fat, semen, and follicular fluid. HCB has been shown to be a reproductive toxin in rats and primates. Polychlorinated biphenyls (PCBs) are prevalent chlorinated hydrocarbons currently contaminating our environment. PCBs resist degradation and are insoluble in water; however, they bioaccumulate in aquatic species. Disturbances of the reproductive systems are not only sensitive indicators of toxicity but threatens the propagation of a species

Urinary 1-hydroxypyrene as a biomarker to carcinogenic polycyclic aromatic hydrocarbon exposure.

Science.gov (United States)

Ifegwu, Clinton; Osunjaye, Kayode; Fashogbon, Folasade; Oke, Kolawole; Adeniyi, Afolabi; Anyakora, Chimezie

2012-01-01

In order to capture the extent of exposure to polycyclic aromatic hydrocarbons (PAHs), various biomarkers have been employed. The biomarkers employed for PAHs include PAHs genetoxic end points in lymphocytes, urinary metabolites, PAH-DNA adducts, and PAH-Protein adducts. Of these, excretory 1-hydroxypyene, a metabolite of pyrene, has been used extensively as a biological monitoring indicator of exposure to PAHs. This study attempts to assess the level of this biomarker in the body fluid of 68 exposed subjects using high performance liquid chromatography HPLC. The subjects screened included auto mechanics, drivers, and fuel attendants. 1-hydroxypyrene was extracted from the urine of the subjects using solid phase extraction method. The HPLC analysis was done in isocratic mode using water:methanol (12:88 v/v) mobile phase. The stationary phase was XBridge C18 (150 × 4.6 mm) 5 μm column. The wavelength was 250 nm at a flow rate of 1.2 mL/min. The oven temperature was 30 ºC and the injection volume was 20 μL. The run time was 3 minutes. The level of urinary 1-hydroxypyrene detected varied for the different categories of occupation studied. About 27% of sampled fuel attendants and 22% of auto mechanics had detectable 1-hydroxypyrene in their urine samples. There was no detectable 1-hydroxypyene in the urine samples of commercial drivers or in the urine samples of students used as controls. The results of this study showed that fuel attendants and auto mechanics have significant exposures to PAHs. So far, there is no established benchmark for level of PAHs in urine, but our findings indicate the possibility of future cancer cases in this population as a result of their occupational exposure. The study was not able to link the level of 1-hydroxypyene with the smoking habits of the subjects.

Urinary 1-Hydroxypyrene as a Biomarker to Carcinogenic Polycyclic Aromatic Hydrocarbon Exposure

Directory of Open Access Journals (Sweden)

Clinton Ifegwu

2012-01-01

Full Text Available In order to capture the extent of exposure to polycyclic aromatic hydrocarbons (PAHs, various biomarkers have been employed. The biomarkers employed for PAHs include PAHs genetoxic end points in lymphocytes, urinary metabolites, PAH-DNA adducts, and PAH-Protein adducts. Of these, excretory 1-hydroxypyene, a metabolite of pyrene, has been used extensively as a biological monitoring indicator of exposure to PAHs. This study attempts to assess the level of this biomarker in the body fluid of 68 exposed subjects using high performance liquid chromatography HPLC. The subjects screened included auto mechanics, drivers, and fuel attendants. 1-hydroxypyrene was extracted from the urine of the subjects using solid phase extraction method. The HPLC analysis was done in isocratic mode using water:methanol (12:88 v/v mobile phase. The stationary phase was XBridge C18 (150 × 4.6 mm 5 μm column. The wavelength was 250 nm at a flow rate of 1.2 mL/min. The oven temperature was 30 °C and the injection volume was 20 μL. The run time was 3 minutes. The level of urinary 1-hydroxypyrene detected varied for the different categories of occupation studied. About 27% of sampled fuel attendants and 22% of auto mechanics had detectable 1-hydroxypyrene in their urine samples. There was no detectable 1-hydroxypyene in the urine samples of commercial drivers or in the urine samples of students used as controls. The results of this study showed that fuel attendants and auto mechanics have significant exposures to PAHs. So far, there is no established benchmark for level of PAHs in urine, but our findings indicate the possibility of future cancer cases in this population as a result of their occupational exposure. The study was not able to link the level of 1-hydroxypyene with the smoking habits of the subjects.

Exhaled carbon monoxide: a non-invasive biomarker of short-term exposure to outdoor air pollution

Directory of Open Access Journals (Sweden)

Herve Lawin

2017-04-01

Full Text Available Abstract Background In urban settings of Africa with rapidly increasing population, traffic-related air pollution is a major contributor to outdoor air pollution (OAP. Although OAP has been identified as a leading cause of global morbidity and mortality, there is however, lack of a simple biomarker to assess levels of exposure to OAP in resource-poor settings. This study evaluated the role of exhaled carbon monoxide (exhCO as a potential biomarker of exposure to ambient carbon monoxide (ambCO from OAP. Methods This was a descriptive study conducted among male commercial motorcycle riders in Cotonou – the economic capital of Benin. The participants’ AmbCO was measured using a portable carbon monoxide (CO data logger for 8 h during the period of their shift. ExhCO was measured just before and immediately after their shift (8-h Participants were asked not to cook or to smoke during the day of the measurements. Linear regression analysis was used to assess the association between ambCO and exhCO for the last 2, 4 and 6 h of their shift. Results Of 170 participants who completed the study, their mean ± SD age was 42.2 ± 8.4 years, and their mean ± SD daily income was 7.3 ± 2.7$. Also, 95% of the participants’ used solid fuels for cooking and only 2% had ever smoked. Average exhCO increased by 5.1 ppm at the end of the shift (p = 0.004. Post-shift exhCO was significantly associated to ambCO, this association was strongest for the last 2 h of OAP exposure before exhCO measurement (β = 0.34, p < 0.001. Conclusion ExhCO level was associated with recent exposure to ambCO from OAP with measurable increase after 8 h of exposure. These findings suggest that ExhCO may be a potential biomarker of short-term exposure to OAP.

Mycotoxin exposure in rural residents in northern Nigeria: a pilot study using multi-urinary biomarkers.

Science.gov (United States)

Ezekiel, Chibundu N; Warth, Benedikt; Ogara, Isaac M; Abia, Wilfred A; Ezekiel, Victoria C; Atehnkeng, Joseph; Sulyok, Michael; Turner, Paul C; Tayo, Grace O; Krska, Rudolf; Bandyopadhyay, Ranajit

2014-05-01

A pilot, cross-sectional, correlational study was conducted in eight rural communities in northern Nigeria to investigate mycotoxin exposures in 120 volunteers (19 children, 20 adolescents and 81 adults) using a modern LC-MS/MS based multi-biomarker approach. First morning urine samples were analyzed and urinary biomarker levels correlated with mycotoxin levels in foods consumed the day before urine collection. A total of eight analytes were detected in 61/120 (50.8%) of studied urine samples, with ochratoxin A, aflatoxin M1 and fumonisin B1 being the most frequently occurring biomarkers of exposure. These mycotoxin biomarkers were present in samples from all age categories, suggestive of chronic (lifetime) exposures. Rough estimates of mycotoxin intake suggested some exposures were higher than the tolerable daily intake. Overall, rural consumer populations from Nasarawa were more exposed to several mixtures of mycotoxins in their diets relative to those from Kaduna as shown by food and urine biomarker data. This study has shown that mycotoxin co-exposure may be a major public health challenge in rural Nigeria; this calls for urgent intervention. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biological assessment of contaminated land using earthworm biomarkers in support of chemical analysis

International Nuclear Information System (INIS)

Hankard, Peter K.; Svendsen, Claus; Wright, Julian; Wienberg, Claire; Fishwick, Samantha K.; Spurgeon, David J.; Weeks, Jason M.

2004-01-01

Biological indicators can be used to assess polluted sites but their success depends on the availability of suitable assays. The aim of this study was to investigate the performance of two earthworm biomarkers, lysosomal membrane stability measured using the neutral red retention assay (NRR-T) and the total immune activity (TIA) assay, that have previously been established as responsive to chemical exposure. Responses of the two assays were measured following in situ exposure to complexly contaminated field soils at three industrial sites as well as urban and rural controls. The industrial sites were contaminated with a range of metal (cadmium, copper, lead, zinc, nickel and cobalt) and organic (including polycyclic aromatic hydrocarbons) contaminants, but at concentrations below the 'New Dutch List' Intervention concentrations. Exposed earthworms accumulated both metals and organic compounds at the contaminated sites, indicating that there was significant exposure. No effect on earthworm survival was found at any of the sites. Biomarker measurements, however, indicated significant effects, with lower NRR-T and TIA found in the contaminated soils when compared to the two controls. The results demonstrate that a comparison of soil pollutant concentrations with guideline values would not have unequivocally identified chemical exposure and toxic effect for soil organisms living in these soils. However, the earthworm biomarkers successfully identified significant exposure and biological effects caused by the mixture of chemicals present

Urinary microRNAs as potential biomarkers of pesticide exposure

International Nuclear Information System (INIS)

Weldon, Brittany A.; Shubin, Sara Pacheco; Smith, Marissa N.; Workman, Tomomi; Artemenko, Alexander; Griffith, William C.; Thompson, Beti; Faustman, Elaine M.

2016-01-01

MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response. - Highlights: • A novel method to identify microRNA biomarkers in urinary samples is proposed. • Six miRNAs have been identified as associated with occupational farm work and pesticide exposure. • An observed seasonal difference suggests transient

Urinary microRNAs as potential biomarkers of pesticide exposure

Energy Technology Data Exchange (ETDEWEB)

Weldon, Brittany A.; Shubin, Sara Pacheco; Smith, Marissa N.; Workman, Tomomi; Artemenko, Alexander; Griffith, William C. [Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA (United States); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States); Thompson, Beti [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Faustman, Elaine M., E-mail: faustman@uw.edu [Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA (United States); Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA (United States)

2016-12-01

MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farmworker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response. - Highlights: • A novel method to identify microRNA biomarkers in urinary samples is proposed. • Six miRNAs have been identified as associated with occupational farm work and pesticide exposure. • An observed seasonal difference suggests transient

Manganese accumulation in hair and teeth as a biomarker of manganese exposure and neurotoxicity in rats.

Science.gov (United States)

Liang, Guiqiang; Zhang, Li'e; Ma, Shuyan; Lv, Yingnan; Qin, Huiyan; Huang, Xiaowei; Qing, Li; Li, Qin; Chen, Kangcheng; Xiong, Feng; Ma, Yifei; Nong, Jie; Yang, Xiaobo; Zou, Yunfeng

2016-06-01

Manganese (Mn) is an essential trace element to humans. However, excessive Mn causes cognitive impairment resulting from injury to the central nervous system within the hippocampus. No ideal biomarker is currently available for evaluating Mn exposure and associated neurotoxicity in the body. Hence, this study used Mn levels in the serum (MnS), teeth (MnT), and hair (MnH) as biomarkers for evaluating the association between Mn exposure and cognitive impairment in Mn-treated rats. A total of 32 male Sprague-Dawley rats were randomly divided into four groups, received 0, 5, 10, and 20 mg/(kg day) of MnCl2·4H2O for 5 days a week for 18 weeks, respectively. Lifetime Mn cumulative dose (LMCD) was used to evaluate external Mn exposure. Hippocampus, serum, teeth, and hair specimens were collected from the rats for Mn determination by graphite furnace atomic absorption spectrometry. Learning and memory functions were assessed using the Morris water maze test. Results showed that chronic Mn exposure increased the hippocampus (MnHip), MnS, MnT, and MnH levels, as well as impaired learning and memory function in rats. MnHip, MnT, and MnH levels were positively correlated with LMCD (r = 0.759, r = 0.925, and r = 0.908, respectively; p  0.05). Thus, MnT and MnH detected long-term low-dose Mn exposure. These parameters can be reliable biomarkers for Mn exposure and associated neurotoxicity in Mn-treated rats.

Validation of biomarkers of food intake − critical assessment of candidate biomarkers

DEFF Research Database (Denmark)

Dragsted, Lars Ove; Gao, Qian; Scalbert, Augustin

2018-01-01

Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promis...

DEVELOPMENT OF BIOMARKER OF EXPOSURE TO VIRAL PATHOGENS

Science.gov (United States)

Interferon gamma (IFN-γ) was selected as a biomarker for a viral exposure study. Twelve-week-old BALB/c mice were intraperitoneally injected with 0.2ml of 104 PFU/ml of coxsackievirus B3 or B4 diluted in phosphate-buffered saline (PBS). Control mice were injected with PBS on...

Low cadmium exposure in males and lactating females–estimation of biomarkers

Energy Technology Data Exchange (ETDEWEB)

Stajnko, Anja [Department of Environmental Sciences, Jožef Stefan Institute, Jamova 39, Ljubljana (Slovenia); Jožef Stefan International Postgraduate School, Jamova 39, Ljubljana (Slovenia); Falnoga, Ingrid, E-mail: ingrid.falnoga@ijs.si [Department of Environmental Sciences, Jožef Stefan Institute, Jamova 39, Ljubljana (Slovenia); Tratnik, Janja Snoj; Mazej, Darja [Department of Environmental Sciences, Jožef Stefan Institute, Jamova 39, Ljubljana (Slovenia); Jagodic, Marta [Department of Environmental Sciences, Jožef Stefan Institute, Jamova 39, Ljubljana (Slovenia); Jožef Stefan International Postgraduate School, Jamova 39, Ljubljana (Slovenia); Krsnik, Mladen [Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Njegoševa 4, Ljubljana (Slovenia); Kobal, Alfred B. [Department of Occupational Health, Idrija Mercury Mine, Arkova 43, Idrija (Slovenia); Prezelj, Marija [Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Njegoševa 4, Ljubljana (Slovenia); Kononenko, Lijana [Chemical Office of RS, Ministry of Health of RS, Ajdovščina 4, Ljubljana (Slovenia); Horvat, Milena [Department of Environmental Sciences, Jožef Stefan Institute, Jamova 39, Ljubljana (Slovenia); Jožef Stefan International Postgraduate School, Jamova 39, Ljubljana (Slovenia)

2017-01-15

Background: Urine cadmium (Cd) and renal function biomarkers, mostly analysed in urine spot samples, are well established biomarkers of occupational exposure. Their use and associations at low environmental level are common, but have recently been questioned, particularly in terms of physiological variability and normalisation bias in the case of urine spot samples. Aim: To determine the appropriateness of spot urine and/or blood Cd exposure biomarkers and their relationships with renal function biomarkers at low levels of exposure. To this end, we used data from Slovenian human biomonitoring program involving 1081 Slovenians (548 males, mean age 31 years; 533 lactating females, mean age 29 years; 2007–2015) who have not been exposed to Cd occupationally. Results: Geometric means (GMs) of Cd in blood and spot urine samples were 0.27 ng/mL (0.28 for males and 0.33 for females) and 0.19 ng/mL (0.21 for males and 0.17 for females), respectively. Differing results were obtained when contrasting normalisation by urine creatinine with specific gravity. GMs of urine albumin (Alb), alpha-1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG), and immunoglobulin G (IgG) were far below their upper reference limits. Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses with unnormalised data were taken as more valid. Relatively weak positive associations were observed between urine Cd (ng/mL) and blood Cd (β=0.11, p=0.002 for males and β=0.33, p<0.001 for females) and for females between urine NAG and blood Cd (β=0.14, p=0.04). No associations were found between other renal function biomarkers and blood Cd. Associations between Cd and renal function biomarkers in urine were stronger (p<0.05, β=0.11–0.63). Mostly, all of the associations stayed significant but weakened after normalisation for diuresis. In the case of A1M, its associations with Cd were influenced by

Low cadmium exposure in males and lactating females–estimation of biomarkers

International Nuclear Information System (INIS)

Stajnko, Anja; Falnoga, Ingrid; Tratnik, Janja Snoj; Mazej, Darja; Jagodic, Marta; Krsnik, Mladen; Kobal, Alfred B.; Prezelj, Marija; Kononenko, Lijana; Horvat, Milena

2017-01-01

Background: Urine cadmium (Cd) and renal function biomarkers, mostly analysed in urine spot samples, are well established biomarkers of occupational exposure. Their use and associations at low environmental level are common, but have recently been questioned, particularly in terms of physiological variability and normalisation bias in the case of urine spot samples. Aim: To determine the appropriateness of spot urine and/or blood Cd exposure biomarkers and their relationships with renal function biomarkers at low levels of exposure. To this end, we used data from Slovenian human biomonitoring program involving 1081 Slovenians (548 males, mean age 31 years; 533 lactating females, mean age 29 years; 2007–2015) who have not been exposed to Cd occupationally. Results: Geometric means (GMs) of Cd in blood and spot urine samples were 0.27 ng/mL (0.28 for males and 0.33 for females) and 0.19 ng/mL (0.21 for males and 0.17 for females), respectively. Differing results were obtained when contrasting normalisation by urine creatinine with specific gravity. GMs of urine albumin (Alb), alpha-1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG), and immunoglobulin G (IgG) were far below their upper reference limits. Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses with unnormalised data were taken as more valid. Relatively weak positive associations were observed between urine Cd (ng/mL) and blood Cd (β=0.11, p=0.002 for males and β=0.33, p<0.001 for females) and for females between urine NAG and blood Cd (β=0.14, p=0.04). No associations were found between other renal function biomarkers and blood Cd. Associations between Cd and renal function biomarkers in urine were stronger (p<0.05, β=0.11–0.63). Mostly, all of the associations stayed significant but weakened after normalisation for diuresis. In the case of A1M, its associations with Cd were influenced by

Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

OpenAIRE

Hecht, S

2004-01-01

Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

Biomarkers of mercury exposure in two eastern Ukraine cities

Science.gov (United States)

Gibb, H.; Haver, C.; Kozlov, K.; Centeno, J.A.; Jurgenson, V.; Kolker, A.; Conko, K.M.; Landa, E.R.; Xu, H.

2011-01-01

This study evaluates biomarkers of mercury exposure among residents of Horlivka, a city in eastern Ukraine located in an area with geologic and industrial sources of environmental mercury, and residents of Artemivsk, a nearby comparison city outside the mercury-enriched area. Samples of urine, blood, hair, and nails were collected from study participants, and a questionnaire was administered to obtain data on age, gender, occupational history, smoking, alcohol consumption, fish consumption, tattoos, dental amalgams, home heating system, education, source of drinking water, and family employment in mines. Median biomarker mercury concentrations in Artemivsk were 0.26 ??g/g-Cr (urine), 0.92 ??g/L (blood), 0.42 ??g/g (hair), 0.11 ??g/g (toenails), and 0.09 ??g/g (fingernails); median concentrations in Horlivka were 0.15 ??g/g-Cr (urine), 1.01 ??g/L (blood), 0.14 ??g/g (hair), 0.31 ??g/g (toenails), and 0.31 ??g/g (fingernails). Biomarkers of mercury exposure for study participants from Horlivka and Artemivsk are low in comparison with occupationally exposed workers at a mercury recycling facility in Horlivka and in comparison with exposures known to be associated with clinical effects. Blood and urinary mercury did not suggest a higher mercury exposure among Horlivka residents as compared with Artemivsk; however, three individuals living in the immediate vicinity of the mercury mines had elevated blood and urinary mercury, relative to overall results for either city. For a limited number of residents from Horlivka (N = 7) and Artemivsk (N = 4), environmental samples (vacuum cleaner dust, dust wipes, soil) were collected from their residences. Mercury concentrations in vacuum cleaner dust and soil were good predictors of blood and urinary mercury. Copyright ?? 2011 JOEH, LLC.

Oxidative damage to DNA and lipids as biomarkers of exposure to air pollution

DEFF Research Database (Denmark)

Møller, Peter; Loft, Steffen

2010-01-01

BACKGROUND: Air pollution is thought to exert health effects through oxidative stress, which causes damage to DNA and lipids. OBJECTIVE: We determined whether levels of oxidatively damaged DNA and lipid peroxidation products in cells or bodily fluids from humans are useful biomarkers...... of biologically effective dose in studies of the health effects of exposure to particulate matter (PM) from combustion processes. DATA SOURCES: We identified publications that reported estimated associations between environmental exposure to PM and oxidative damage to DNA and lipids in PubMed and EMBASE. We also...... identified publications from reference lists and articles cited in the Web of Science. DATA EXTRACTION: For each study, we obtained information on the estimated effect size to calculate the standardized mean difference (unitless) and determined the potential for errors in exposure assessment and analysis...

Association between a biomarker of exposure to polycyclic aromatic hydrocarbons and semen quality

Directory of Open Access Journals (Sweden)

Joanna Jurewicz

2013-10-01

Full Text Available Objectives: Growing evidence supports the reproductive and developmental toxicity of polycyclic aromatic hydrocarbons (PAHs from prenatal and postnatal exposure, but the results of epidemiological studies regarding harmful effects of PAHs exposure on male reproductive system still remain limited and inconclusive. The aim of the present study was to investigate the relationship between 1-hydroxypyrene, a biomarker of polycyclic aromatic hydrocarbons exposure and semen quality. Materials and Methods: The study population consisted of 277 men attending an infertility clinic for diagnostic purposes and having normal semen concentration of 20-300 mln/ml or slight oligozoospermia (semen concentration: 15-20 mln/ml (WHO 1999. All the men were healthy and under 45 years of age. All participants were interviewed and provided a semen sample. The interview included questions concerning demographics, socio-economic status, medical history related to past diseases which may have an impact on semen quality, lifestyle factors and occupational information. Concentrations of 1-hydroxypyrene (1-OHP in the urine samples were analyzed using high performance liquid chromatography (HPLC. Results: A positive association was found between the level of 1-OHP in urine and sperm neck abnormalities as well as the percentage of static sperm cells (p = 0.001, p = 0.018, respectively. Additionally, exposure to PAHs measured by 1-OHP in urine decreased semen volume and the percentage of motile sperm cells (p = 0.014, p = 0.0001, respectively. Conclusions: Presented findings indicate that the environmental level of PAHs exposure adversely affects male semen quality. The future large-scale studies should incorporate different biomarkers to generate a more accurate and full assessment of the effects of PAHs exposure on male fertility.

Biomarkers of Sensitivity and Exposure in Washington State Pesticide Handlers

Science.gov (United States)

Keifer, M.C.; Checkoway, H.; De Roos, A.J.; Farin, F.M.; Fenske, R.A.; Richter, R.J.; van Belle, G.; Furlong, C.E.

2011-01-01

Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are widely used in agriculture in the US and abroad. These compounds – which inhibit acetylcholinesterase (AChE) enzyme activity – continue to be responsible for a high proportion of pesticide poisonings among US agricultural workers. It is possible that some individuals may be especially susceptible to health effects related to OP/CB exposure. The paraoxonase (PON1) enzyme metabolizes the highly toxic oxon forms of some OPs, and an individual's PON1 status may be an important determinant of his or her sensitivity to these chemicals. This chapter discusses methods used to characterize individual PON1 status and reviews previous epidemiologic studies that have evaluated PON1-related sensitivity to OPs in relation to various health endpoints. It also describes an ongoing longitudinal study among OP-exposed agricultural pesticide handlers who are participating in a recently implemented cholinesterase monitoring program in Washington State. This study will evaluate handlers' PON1 status as a hypothesized determinant of butyrylcholinesterase (BuChE) inhibition. Such studies will be useful to determine how regulatory risk assessments might account for differences in PON1-related OP sensitivity when characterizing inter-individual variability in risk related to OP exposure. Recent work assessing newer and more sensitive biomarkers of OP exposure is also discussed briefly in this chapter. PMID:20221867

Household air pollution: a call for studies into biomarkers of exposure and predictors of respiratory disease.

Science.gov (United States)

Rylance, Jamie; Gordon, Stephen B; Naeher, Luke P; Patel, Archana; Balmes, John R; Adetona, Olorunfemi; Rogalsky, Derek K; Martin, William J

2013-05-01

Household air pollution (HAP) from indoor burning of biomass or coal is a leading global cause of morbidity and mortality, mostly due to its association with acute respiratory infection in children and chronic respiratory and cardiovascular diseases in adults. Interventions that have significantly reduced exposure to HAP improve health outcomes and may reduce mortality. However, we lack robust, specific, and field-ready biomarkers to identify populations at greatest risk and to monitor the effectiveness of interventions. New scientific approaches are urgently needed to develop biomarkers of human exposure that accurately reflect exposure or effect. In this Perspective, we describe the global need for such biomarkers, the aims of biomarker development, and the state of development of tests that have the potential for rapid transition from laboratory bench to field use.

Occupational Exposure to HDI: Progress and Challenges in Biomarker Analysis

OpenAIRE

Flack, Sheila L.; Ball, Louise M.; Nylander-French, Leena A.

2010-01-01

1,6-hexamethylene diisocyanate (HDI) is extensively used in the automotive repair industry and is a commonly reported cause of occupational asthma in industrialized populations. However, the exact pathological mechanism remains uncertain. Characterization and quantification of biomarkers resulting from HDI exposure can fill important knowledge gaps between exposure, susceptibility, and the rise of immunological reactions and sensitization leading to asthma. Here, we discuss existing challenge...

Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water

International Nuclear Information System (INIS)

Adair, Blakely M.; Hudgens, Edward E.; Schmitt, Michael T.; Calderon, Rebecca L.; Thomas, David J.

2006-01-01

Accurate quantitation of any contaminant of interest is critical for exposure assessment and metabolism studies that support risk assessment. A preliminary step in an arsenic exposure assessment study in Nevada quantified total arsenic (TAs) concentrations in tissues as biomarkers of exposure. Participants in this study (n=95) were at least 45 years old, had lived in the area for more than 20 years, and were exposed to a wide range of arsenic concentrations in drinking water (3-2100ppb). Concentrations of TAs in blood, urine, and toenails determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) ranged from below detection to 0.03, 0.76, and 12ppm, respectively; TAs in blood rarely exceeded the limit of detection. For comparison, TAs in toenails determined by neutron activation analysis (NAA) ranged from below detection to 16ppm. Significant (P 2 =0.3557 HG-AFS, adjusted r 2 =0.3922 NAA); TAs concentrations in urine were not described by drinking water As (adjusted r 2 =0.0170, P=0.1369). Analyses of TAs in toenails by HGAFS and NAA yielded highly concordant estimates (r=0.7977, P<0.0001). These results suggest that toenails are a better biomarker of chronic As exposure than urine in the current study, because the sequestration of As in toenails provides an integration of exposure over time that does not occur in urine

Urinary Naphthol as a Biomarker of Exposure: Results from an Oral Exposure to Carbaryl and Workers Occupationally Exposed to Naphthalene

Directory of Open Access Journals (Sweden)

Craig Sams

2017-01-01

Full Text Available Urinary naphthol is an established human biomarker used for assessing both occupational and environmental exposure. However, 1-naphthol is a metabolite of the insecticide carbaryl while both the 1- and 2-isomers are metabolites of naphthalene. Thus, urinary 1-naphthol levels will reflect combined exposure to both substances, particularly at environmental levels. The interpretation of biomarkers is aided by knowledge of levels following well-characterised exposure scenarios. This study reports urinary 1-naphthol levels in five volunteers administered an oral dose of carbaryl at the acceptable daily intake (ADI, 0.008 mg/kg. The elimination half-life was 3.6 h and the mean 1-naphthol level in 24 h total urine collections, normalised for a 70 kg individual, was 37.4 µmol/mol creatinine (range 21.3–84.3. Peak levels in spot-urine samples were around 200 µmol/mol creatinine. For comparison, 327 post-shift urine samples obtained from 90 individual workers exposed occupationally to naphthalene had 1-naphthol levels from below the limit of detection (exposure to carbaryl and naphthalene in these populations is well controlled.

Novel biomarkers of perchlorate exposure in zebrafish

Science.gov (United States)

Mukhi, S.; Carr, J.A.; Anderson, T.A.; Patino, R.

2005-01-01

Perchlorate inhibits iodide uptake by thyroid follicles and lowers thyroid hormone production. Although several effects of perchlorate on the thyroid system have been reported, the utility of these pathologies as markers of environmental perchlorate exposures has not been adequately assessed. The present study examined time-course and concentration-dependent effects of perchlorate on thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in whole-body thyroxine (T4) levels; and somatic growth and condition factor of subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring previously observed in zebrafish also were examined immunohistochemically. Three-month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to recover in clean water for 12 weeks. At two weeks of exposure, the lowest-observed-effective concentrations (LOECs) of perchlorate that induced angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131 ppb, respectively; other parameters were not affected (whole-body T4 was not determined at this time). At 12 weeks of exposure, LOECs for colloid depletion, hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11 ppb, respectively. All changes were reversible, but residual effects on angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of recovery (LOEC, 11,480 ppb). Whole-body T 4 concentration, body growth (length and weight), and condition factor were not affected by perchlorate. The sensitivity and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic vertebrates. ?? 2005 SETAC.

Exposure assessment of process-related contaminants in food by biomarker monitoring

NARCIS (Netherlands)

Rietjens, Ivonne M.C.M.; Dussort, P.; Günther, Helmut; Hanlon, Paul; Honda, Hiroshi; Mally, Angela; O’Hagan, Sue; Scholz, Gabriele; Seidel, Albrecht; Swenberg, James; Teeguarden, Justin; Eisenbrand, Gerhard

2018-01-01

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile,

Biomarcadores para avaliação da exposição humana às micotoxinas Biomarkers for assessment of human exposure to mycotoxins

Directory of Open Access Journals (Sweden)

Érika Bando

2007-06-01

of biomarkers, which elucidates the cause/effect and dose/effect relation in the evaluation of health risks for clinical and laboratory diagnostic purposes. The MEDLINE review about the use of biomarkers for assessment of aflatoxins, fumonisins, deoxynivalenol and ochratoxin A was carried out from 1981 to 2005. The biomarkers for assessment of human exposure to aflatoxins were the urinary metabolites of aflatoxin B1: aflatoxin M1, aflatoxin P1, aflatoxin Q1, the free aflatoxin in serum or plasma, the AFB-N7-guanine adducts and the albumin adducts or mutation in the tumour suppressor gene p53 present in human biological fluids. As far as fumonisins are concerned, levels of free fumonisin B1 and fumonisin B2, or levels of sphinganine and sphingosin, were quantified in blood and urine. As exposure biomarkers, deoxynivalenol has its own metabolism products and adducts (protein/DNA present in human fluids. As to ochratoxin A exposure, we measure it in biological fluids, once it enables us to prevent or minimize the incidence of deaths or illnesses provoked by chemical exposure.

Lead exposure biomarkers and mini-mental status exam scores in older men

NARCIS (Netherlands)

Wright, RO; Tsaih, SW; Schwartz, J; Spiro, A; McDonald, K; Weiss, ST; Hu, H

2003-01-01

Background: Lead is neurotoxic; yet, whether cognitive decline in older persons is associated with lead exposure is unknown. We studied whether lead exposure biomarkers are associated with cognitive test scores, as well as the modifying effects of age on the lead-cognition relationship. Methods:

Lead exposure biomarkers and mini-mental status exam scores in older men

NARCIS (Netherlands)

Wright, RO; Tsaih, SW; Schwartz, J; Spiro, A; McDonald, K; Weiss, ST; Hu, H

Background: Lead is neurotoxic; yet, whether cognitive decline in older persons is associated with lead exposure is unknown. We studied whether lead exposure biomarkers are associated with cognitive test scores, as well as the modifying effects of age on the lead-cognition relationship. Methods:

The use of biomarkers for risk assessment: Reporting from the INTARESE/ENVIRISK Workshop in Prague

Czech Academy of Sciences Publication Activity Database

Smolders, R.; Bartonova, A.; Boogaard, P. J.; Dusinska, M.; Koppen, G.; Merlo, D.F.; Šrám, Radim; Vineis, P.; Schoeters, G.

2010-01-01

Roč. 213, č. 5 (2010), s. 395-400 ISSN 1438-4639 Institutional research plan: CEZ:AV0Z50390512 Keywords : Human biomonitoring * Biomarkers of exposure * Environmental health impact assessment Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.886, year: 2010

Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to acrylamide in combination with acrylamide uptake assessment based on duplicate diets.

Science.gov (United States)

Ruenz, Meike; Bakuradze, Tamara; Eisenbrand, Gerhard; Richling, Elke

2016-04-01

The present human intervention study investigated the relation between the intake of acrylamide (AA) in diets with minimized, low, and high AA contents and the levels of urinary exposure biomarkers. As biomarkers, the mercapturic acids, N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA), and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were monitored. The study was performed with 14 healthy male volunteers over a period of 9 days, under controlled conditions excluding any inadvertent AA exposure. Dietary exposure to AA was measured by determining AA contents in duplicates of all meals consumed by the volunteers. The study design included an initial washout period of 3 days on AA-minimized diet, resulting in dietary AA exposure not exceeding 41 ng/kg bw/d. Identical washout periods of 2 days each followed the AA exposure days (day 4, low exposure, and day 7, high exposure). At the respective AA intake days, volunteers ingested 0.6-0.8 (low exposure) or 1.3-1.8 (high exposure) μg AA/kg bw/d with their food. Both low and high AA intakes resulted in an AAMA output within 72 h corresponding to 58 % of the respective AA intake. At the end of the initial 3-day washout period, an AAMA baseline level of 93 ± 31 nmol/d was recorded, suggestive for an assumed net AA baseline exposure level of 0.2-0.3 μg AA/kg bw/d.

Prevalence of prenatal exposure to substances of abuse: questionnaire versus biomarkers

OpenAIRE

Chiandetti, Antonella; Hernandez, Gimena; Mercadal-Hally, María; Alvarez, Airam; Andreu-Fernandez, Vicente; Navarro-Tapia, Elisabet; Bastons-Compta, Adriana; Garcia-Algar, Oscar

2017-01-01

Alcohol and drugs of abuse consumption in young adults, including women of childbearing age, has experienced significant increase over the past two decades. The use of questionnaires as the only measure to investigate prenatal alcohol and drugs of abuse exposure underestimates the real prevalence of exposure and could mislead to wrong conclusions. Therefore, the aim of this article was to compare reported rates of prenatal alcohol and drugs of abuse consumption with biomarkers of exposure by ...

N-alkylvaline levels in globin as a new type of biomarker in risk assessment of alkylating agents.

Science.gov (United States)

Lewalter, J

1996-01-01

Adducts with the N-terminal valine of erythrocyte globin can serve as individual biomarkers of systemic and cellular exposure to endogenous and exogenous alkylating agents. In contrast to "detoxification markers" of this kind of mecapturic acids derived from alkylation of glutathione, individual N-alkylations of valine in globin reflect the formally "toxifying" part of the stress due to alkylating agents transformed into the ultimate toxicant. Thus, in contrast to the traditional methods of biological monitoring this approach enables a better evaluation of systemic exposure to reactive agents, adapted more sensibly to the exposure situation over the whole life span of erythrocytes, and it can serve as a specific biomarker of exposure for the purpose of health surveillance in occupational medicine. An individual evaluation of exposures in comparison with the range of corresponding background levels is discussed from the point of view of supplementary risk assessment in medical surveillance of occupationally exposed persons.

A new method for generating distributions of biomonitoring equivalents to support exposure assessment and prioritization.

Science.gov (United States)

Phillips, Martin B; Sobus, Jon R; George, Barbara J; Isaacs, Kristin; Conolly, Rory; Tan, Yu-Mei

2014-08-01

Biomonitoring data are now available for hundreds of chemicals through state and national health surveys. Exposure guidance values also exist for many of these chemicals. Several methods are frequently used to evaluate biomarker data with respect to a guidance value. The "biomonitoring equivalent" (BE) approach estimates a single biomarker concentration (called the BE) that corresponds to a guidance value (e.g., Maximum Contaminant Level, Reference Dose, etc.), which can then be compared with measured biomarker data. The resulting "hazard quotient" estimates (HQ=biomarker concentration/BE) can then be used to prioritize chemicals for follow-up examinations. This approach is used exclusively for population-level assessments, and works best when the central tendency of measurement data is considered. Complementary approaches are therefore needed for assessing individual biomarker levels, particularly those that fall within the upper percentiles of measurement distributions. In this case study, probabilistic models were first used to generate distributions of BEs for perchlorate based on the point-of-departure (POD) of 7μg/kg/day. These distributions reflect possible biomarker concentrations in a hypothetical population where all individuals are exposed at the POD. A statistical analysis was then performed to evaluate urinary perchlorate measurements from adults in the 2001 to 2002 National Health and Nutrition Examination Survey (NHANES). Each NHANES adult was assumed to have experienced repeated exposure at the POD, and their biomarker concentration was interpreted probabilistically with respect to a BE distribution. The HQ based on the geometric mean (GM) urinary perchlorate concentration was estimated to be much lower than unity (HQ≈0.07). This result suggests that the average NHANES adult was exposed to perchlorate at a level well below the POD. Regarding individuals, at least a 99.8% probability was calculated for all but two NHANES adults that a higher

The use of biomonitoring data in exposure and human health risk assessment: benzene case study.

Science.gov (United States)

Arnold, Scott M; Angerer, Juergen; Boogaard, Peter J; Hughes, Michael F; O'Lone, Raegan B; Robison, Steven H; Schnatter, A Robert

2013-02-01

Abstract A framework of "Common Criteria" (i.e. a series of questions) has been developed to inform the use and evaluation of biomonitoring data in the context of human exposure and risk assessment. The data-rich chemical benzene was selected for use in a case study to assess whether refinement of the Common Criteria framework was necessary, and to gain additional perspective on approaches for integrating biomonitoring data into a risk-based context. The available data for benzene satisfied most of the Common Criteria and allowed for a risk-based evaluation of the benzene biomonitoring data. In general, biomarker (blood benzene, urinary benzene and urinary S-phenylmercapturic acid) central tendency (i.e. mean, median and geometric mean) concentrations for non-smokers are at or below the predicted blood or urine concentrations that would correspond to exposure at the US Environmental Protection Agency reference concentration (30 µg/m(3)), but greater than blood or urine concentrations relating to the air concentration at the 1 × 10(-5) excess cancer risk (2.9 µg/m(3)). Smokers clearly have higher levels of benzene exposure, and biomarker levels of benzene for non-smokers are generally consistent with ambient air monitoring results. While some biomarkers of benzene are specific indicators of exposure, the interpretation of benzene biomonitoring levels in a health-risk context are complicated by issues associated with short half-lives and gaps in knowledge regarding the relationship between the biomarkers and subsequent toxic effects.

A new approach towards biomarker selection in estimation of human exposure to chiral chemicals: a case study of mephedrone.

Science.gov (United States)

Castrignanò, Erika; Mardal, Marie; Rydevik, Axel; Miserez, Bram; Ramsey, John; Shine, Trevor; Pantoș, G Dan; Meyer, Markus R; Kasprzyk-Hordern, Barbara

2017-11-02

Wastewater-based epidemiology is an innovative approach to estimate public health status using biomarker analysis in wastewater. A new compound detected in wastewater can be a potential biomarker of an emerging trend in public health. However, it is currently difficult to select new biomarkers mainly due to limited human metabolism data. This manuscript presents a new framework, which enables the identification and selection of new biomarkers of human exposure to drugs with scarce or unknown human metabolism data. Mephedrone was targeted to elucidate the assessment of biomarkers for emerging drugs of abuse using a four-step analytical procedure. This framework consists of: (i) identification of possible metabolic biomarkers present in wastewater using an in-vivo study; (ii) verification of chiral signature of the target compound; (iii) confirmation of human metabolic residues in in-vivo/vitro studies and (iv) verification of stability of biomarkers in wastewater. Mephedrone was selected as a suitable biomarker due to its high stability profile in wastewater. Its enantiomeric profiling was studied for the first time in biological and environmental matrices, showing stereoselective metabolism of mephedrone in humans. Further biomarker candidates were also proposed for future investigation: 4'-carboxy-mephedrone, 4'-carboxy-normephedrone, 1-dihydro-mephedrone, 1-dihydro-normephedrone and 4'-hydroxy-normephedrone.

The role of toxicology to characterize biomarkers for agrochemicals with potential endocrine activities.

Science.gov (United States)

Mantovani, Alberto; Maranghi, Francesca; La Rocca, Cinzia; Tiboni, Gian Mario; Clementi, Maurizio

2008-09-01

The paper discusses current knowledge and possible research priorities on biomarkers of exposure, effect and susceptibility for potential endocrine activities of agrochemicals (dicarboximides, ethylene bisdithiocarbammates, triazoles, etc.). Possible widespread, multiple-pathway exposure to agrochemicals highlights the need to assess internal exposure of animals or humans, which is the most relevant exposure measure for hazard and risk estimation; however, exposure data should be integrated by early indicators predictive of possible health effects, particularly for vulnerable groups such as mother-child pairs. Research need include: non-invasive biomarkers for children biomonitoring; novel biomarkers of total exposure to measure whole endocrine disrupter-related burden; characterization of biomarkers of susceptibility, including the role of markers of nutritional status; anchoring early molecular markers to established toxicological endpoints to support their predictivity; integrating "omics"-based approaches in a system-toxicology framework. As biomonitoring becomes increasingly important in the environment-and-health scenario, toxicologists can substantially contribute both to the characterization of new biomarkers and to the predictivity assessment and improvement of the existing ones.

Interpretation of Urinary and Blood Benzene biomarkers of Exposure for Non-Occupationally Exposed Individuals

Science.gov (United States)

Non-occupational exposure to benzene occurs primarily through inhalation ofair impacted by motor vehicle exhaust, fuel sources, and cigarette smoke. This study relates published measurements ofbenzene biomarkers to air exposure concentrations. Benzene has three reliable biomar...

Examination of Urinary Beta-Naphthol as a Biomarker Indicative of Jet Fuel Exposures

Science.gov (United States)

2015-04-01

government or personal vehicle and what type of fuel . Flight line time Exposure to spills ( fuel ) Exposure to skin ( fuel ) Inhalation exposure (type...AFRL-RH-WP-TR-2015-0085 EXAMINATION OF URINARY β-NAPHTHOL AS A BIOMARKER INDICATIVE OF JET FUEL EXPOSURES Jeanette S. Frey Henry M... Fuel Exposures 5a. CONTRACT NUMBER 5b. GRANT NUMBER NA 5c. PROGRA7757M ELEMENT NUMBER 6. AUTHOR(S) Jeanette Frey1; Trevor J. Bihl2;Asao

Hyperspectral Imaging as an Early Biomarker for Radiation Exposure and Microcirculatory Damage

Directory of Open Access Journals (Sweden)

Michael S. Chin

2015-10-01

Full Text Available BACKGROUND: Radiation exposure can lead to detrimental effects in skin microcirculation. The precise relationship between radiation dose received and its effect on cutaneous perfusion still remains controversial. Previously, we have shown that hyperspectral imaging (HSI is able to demonstrate long-term reductions in cutaneous perfusion secondary to chronic microvascular injury. This study characterizes the changes in skin microcirculation in response to varying doses of ionizing radiation and investigates these microcirculatory changes as a possible early non-invasive biomarker that may correlate with the extent of long-term microvascular damage.METHODS: Immunocompetent hairless mice (n=66 were exposed to single fractions of superficial beta-irradiation in doses of 0, 5, 10, 20, 35, or 50 Gy. A HSI device was utilized to measure deoxygenated hemoglobin levels in irradiated and control areas. HSI measurements were performed at baseline before radiation exposure and for the first three days post-irradiation. Maximum macroscopic skin reactions were graded, and histological assessment of cutaneous microvascular densities at four weeks post-irradiation was performed in harvested tissue by CD31 immunohistochemistry.RESULTS: CD31 immunohistochemistry demonstrated a significant correlation (r=0.90, p<0.0001 between dose and vessel density reduction at four weeks. Using HSI analysis, early changes in deoxygenated hemoglobin levels were observed during the first three days post-irradiation in all groups. These deoxygenated hemoglobin changes varied proportionally with dose (r=0.98, p<0.0001 and skin reactions (r=0.98, p<0.0001. There was a highly significant correlation (r= 0.91, p<0.0001 between these early changes in deoxygenated hemoglobin and late vascular injury severity assessed at the end of four weeks.CONCLUSIONS: Radiation dose is directly correlated with cutaneous microvascular injury severity at four weeks in our model. Early post-exposure

Dietary exposure to aflatoxin and fumonisin among Tanzanian children as determined using biomarkers of exposure

Science.gov (United States)

Shirima, Candida P.; Kimanya, Martin E.; Kinabo, Joyce L.; Routledge, Michael N.; Srey, Chou; Wild, Christopher P.; Gong, Yun Yun

2014-01-01

Scope The study aims to evaluate the status of dietary exposure to aflatoxin and fumonisin in young Tanzanian children, using previously validated biomarkers of exposure. Methods and results A total of 148 children aged 12 to 22 months, were recruited from three geographically distant villages in Tanzania; Nyabula, Kigwa and Kikelelwa. Plasma aflatoxin-albumin adducts (AF-alb) and urinary fumonisin B1 (UFB1) were measured by ELISA and LC-MS, respectively. AF-alb was detectable in 84% of children, was highest in fully weaned children (pfumonisin through contaminated diet, although the level of exposure varies markedly between the three villages studied. PMID:23776058

Biomarkers of methylmercury exposure immunotoxicity among fish consumers in Amazonian Brazil.

Science.gov (United States)

Nyland, Jennifer F; Fillion, Myriam; Barbosa, Fernando; Shirley, Devon L; Chine, Chiameka; Lemire, Melanie; Mergler, Donna; Silbergeld, Ellen K

2011-12-01

Mercury (Hg) is a ubiquitous environmental contaminant with neurodevelopmental and immune system effects. An informative biomarker of Hg-induced immunotoxicity could aid studies on the potential contribution to immune-related health effects. Our objectives were to test the hypothesis that methylmercury (MeHg) exposures affect levels of serum biomarkers and to examine interactions between Hg and selenium (Se) in terms of these responses. This cross-sectional epidemiological study assessed adults living along the Tapajós River, a system long affected by MeHg. We measured antinuclear (ANA) and antinucleolar (ANoA) autoantibody levels and eight cytokines in serum samples (n = 232). Total Hg (including MeHg) and Se were measured in blood, plasma, hair, and urine. The median (range) total Hg concentrations were 14.1 μg/g (1.1-62.4), 53.5 μg/L (4.3-288.9), 8.8 μg/L (0.2-40), and 3.0 μg/L (0.2-16.1) for hair, blood, plasma, and urine, respectively. Elevated titers of ANA (but not ANoA) were positively associated with MeHg exposure (log-transformed, for blood and plasma), unadjusted [odds ratio (OR) = 2.6; 95% confidence interval (CI): 1.1, 6.2] and adjusted for sex and age (OR = 2.9; 95% CI: 1.1, 7.5). Proinflammatory [interleukin (IL)-6 and interferon (IFN)-γ], anti-inflammatory (IL-4), and IL-17 cytokine levels were increased with MeHg exposure; however, in the subset of the population with elevated ANA, proinflammatory IL-1β, IL-6, IFN-γ, and tumor necrosis factor (TNF)-α and anti-inflammatory (IL-4) cytokine levels were decreased with MeHg exposure. Although Se status was associated with MeHg level (correlation coefficient = 0.86; 95% CI: 0.29, 1.43), Se status was not associated with any changes in ANA and did not modify associations between Hg and ANA titers. MeHg exposure was associated with an increased ANA and changes in serum cytokine profile. Moreover, alterations in serum cytokine profiles differed based on ANA response, suggesting a specific phenotype

Increased levels of etheno-DNA adducts and genotoxicity biomarkers of long-term exposure to pure diesel engine exhaust.

Science.gov (United States)

Shen, Meili; Bin, Ping; Li, Haibin; Zhang, Xiao; Sun, Xin; Duan, Huawei; Niu, Yong; Meng, Tao; Dai, Yufei; Gao, Weimin; Yu, Shanfa; Gu, Guizhen; Zheng, Yuxin

2016-02-01

Etheno-DNA adducts are biomarkers for assessing oxidative stress. In this study, the aim was to detect the level of etheno-DNA adducts and explore the relationship between the etheno-DNA adducts and genotoxicity biomarkers of the diesel engine exhaust (DEE)-exposed workers. We recruited 86 diesel engine testing workers with long-term exposure to DEE and 99 non-DEE-exposed workers. The urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and etheno-DNA adducts (εdA and εdC) were detected by HPLC-MS/MS and UPLC-MS/MS, respectively. Genotoxicity biomarkers were also evaluated by comet assay and cytokinesis-block micronucleus assay. The results showed that urinary εdA was significantly higher in the DEE-exposed workers (p<0.001), exhibited 2.1-fold increase compared with the non-DEE-exposed workers. The levels of urinary OH-PAHs were positively correlated with the level of εdA among all the study subjects (p<0.001). Moreover, we found that the increasing level of εdA was significantly associated with the increased olive tail moment, percentage of tail DNA, or frequency of micronucleus in the study subjects (p<0.01). No significant association was observed between the εdC level and any measured genotoxicity biomarkers. In summary, εdA could serve as an indicator for DEE exposure in the human population. Copyright © 2015 Elsevier B.V. All rights reserved.

Bio-monitoring of mycotoxin exposure in Cameroon using a urinary multi-biomarker approach.

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Abia, Wilfred A; Warth, Benedikt; Sulyok, Michael; Krska, Rudolf; Tchana, Angele; Njobeh, Patrick B; Turner, Paul C; Kouanfack, Charles; Eyongetah, Mbu; Dutton, Mike; Moundipa, Paul F

2013-12-01

Bio-monitoring of human exposure to mycotoxin has mostly been limited to a few individually measured mycotoxin biomarkers. This study aimed to determine the frequency and level of exposure to multiple mycotoxins in human urine from Cameroonian adults. 175 Urine samples (83% from HIV-positive individuals) and food frequency questionnaire responses were collected from consenting Cameroonians, and analyzed for 15 mycotoxins and relevant metabolites using LC-ESI-MS/MS. In total, eleven analytes were detected individually or in combinations in 110/175 (63%) samples including the biomarkers aflatoxin M1, fumonisin B1, ochratoxin A and total deoxynivalenol. Additionally, important mycotoxins and metabolites thereof, such as fumonisin B2, nivalenol and zearalenone, were determined, some for the first time in urine following dietary exposures. Multi-mycotoxin contamination was common with one HIV-positive individual exposed to five mycotoxins, a severe case of co-exposure that has never been reported in adults before. For the first time in Africa or elsewhere, this study quantified eleven mycotoxin biomarkers and bio-measures in urine from adults. For several mycotoxins estimates indicate that the tolerable daily intake is being exceeded in this study population. Given that many mycotoxins adversely affect the immune system, future studies will examine whether combinations of mycotoxins negatively impact Cameroonian population particularly immune-suppressed individuals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan

International Nuclear Information System (INIS)

Chen, C.-J.; Hsu, L.-I; Wang, C.-H.

2005-01-01

Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress

Toxicity assessment of unintentional exposure to multiple chemicals

International Nuclear Information System (INIS)

Mumtaz, M.M.; Ruiz, P.; De Rosa, C.T.

2007-01-01

Typically exposure to environmental chemicals is unintentional, and often the exposure is to chemical mixtures, either simultaneously or sequentially. When exposure occurs, in public health practice, it is prudent to ascertain if thresholds for harmful health effects are exceeded, whether by individual chemicals or by chemicals in combination. Three alternative approaches are available for assessing the toxicity of chemical mixtures. Each approach, however, has shortcomings. As the procedures of each approach are described in this paper, at various steps research needs are identified. Recently, reliance has increased on computational toxicology methods for predicting toxicological effects when data are limited. Advances in molecular biology, identification of biomarkers, and availability of accurate and sensitive methods allow us to more precisely define the relationships between multiple chemical exposures and health effects, both qualitatively and quantitatively. Key research needs are best fulfilled through collaborative research. It is through such collaborations that resources are most effectively leveraged to further develop and apply toxicity assessment methods that advance public health practices in vulnerable communities

Using Spot Biomarker Data to Inform Chronic Exposure and Health Risk

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The U.S. NHANES and other health surveys frequently collect and analyze spot biological specimens to inform chemical exposures. These spot measurements can be compared to biomarker-based reference levels, such as “Biomonitoring Equivalents” (BEs), to evaluate health r...

Assessment of workers’ exposure to Aflatoxin B1 in a Portuguese waste industry

OpenAIRE

Viegas, Susana; Veiga, Luísa; Figueredo, Paula; Almeida, Ana; Carolino, Elisabete; Viegas, Carla

2015-01-01

Aflatoxin B1 (AFB1) is considered by different International Agencies as a genotoxic and potent hepatocarcinogen. However, despite the fact that the fungi producing this compound are detected in some work environments, AFB1 is rarely monitored in occupational settings. The aim of the present investigation was to assess exposure to AFB1 of workers from one Portuguese waste company located in the outskirt of Lisbon. Occupational exposure assessment to AFB1 was done with a biomarker of internal ...

Urinary biomarkers of occupational jet fuel exposure among Air Force personnel.

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Smith, Kristen W; Proctor, Susan P; Ozonoff, A L; McClean, Michael D

2012-01-01

There is a potential for widespread occupational exposure to jet fuel among military and civilian personnel. Urinary metabolites of naphthalene have been suggested for use as short-term biomarkers of exposure to jet fuel (jet propulsion fuel 8 (JP8)). In this study, urinary biomarkers of JP8 were evaluated among US Air Force personnel. Personnel (n=24) were divided a priori into high, moderate, and low exposure groups. Pre- and post-shift urine samples were collected from each worker over three workdays and analyzed for metabolites of naphthalene (1- and 2-naphthol). Questionnaires and breathing-zone naphthalene samples were collected from each worker during the same workdays. Linear mixed-effects models were used to evaluate the exposure data. Post-shift levels of 1- and 2-naphthol varied significantly by a priori exposure group (levels in high group>moderate group>low group), and breathing-zone naphthalene was a significant predictor of post-shift levels of 1- and 2-naphthol, indicating that for every unit increase in breathing-zone naphthalene, there was an increase in naphthol levels. These results indicate that post-shift levels of urinary 1- and 2-naphthol reflect JP8 exposure during the work-shift and may be useful surrogates of JP8 exposure. Among the high exposed workers, significant job-related predictors of post-shift levels of 1- and 2-naphthol included entering the fuel tank, repairing leaks, direct skin contact with JP8, and not wearing gloves during the work-shift. The job-related predictors of 1- and 2-naphthol emphasize the importance of reducing inhalation and dermal exposure through the use of personal protective equipment while working in an environment with JP8.

The use of biomonitoring data in exposure and human health risk assessment: benzene case study

Science.gov (United States)

Angerer, Juergen; Boogaard, Peter J.; Hughes, Michael F.; O’Lone, Raegan B.; Robison, Steven H.; Robert Schnatter, A.

2013-01-01

A framework of “Common Criteria” (i.e. a series of questions) has been developed to inform the use and evaluation of biomonitoring data in the context of human exposure and risk assessment. The data-rich chemical benzene was selected for use in a case study to assess whether refinement of the Common Criteria framework was necessary, and to gain additional perspective on approaches for integrating biomonitoring data into a risk-based context. The available data for benzene satisfied most of the Common Criteria and allowed for a risk-based evaluation of the benzene biomonitoring data. In general, biomarker (blood benzene, urinary benzene and urinary S-phenylmercapturic acid) central tendency (i.e. mean, median and geometric mean) concentrations for non-smokers are at or below the predicted blood or urine concentrations that would correspond to exposure at the US Environmental Protection Agency reference concentration (30 µg/m3), but greater than blood or urine concentrations relating to the air concentration at the 1 × 10−5 excess cancer risk (2.9 µg/m3). Smokers clearly have higher levels of benzene exposure, and biomarker levels of benzene for non-smokers are generally consistent with ambient air monitoring results. While some biomarkers of benzene are specific indicators of exposure, the interpretation of benzene biomonitoring levels in a health-risk context are complicated by issues associated with short half-lives and gaps in knowledge regarding the relationship between the biomarkers and subsequent toxic effects. PMID:23346981

Hemopexin as biomarkers for analyzing the biological responses associated with exposure to silica nanoparticles

Science.gov (United States)

Higashisaka, Kazuma; Yoshioka, Yasuo; Yamashita, Kohei; Morishita, Yuki; Pan, Huiyan; Ogura, Toshinobu; Nagano, Takashi; Kunieda, Akiyoshi; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

2012-10-01

Practical uses of nanomaterials are rapidly spreading to a wide variety of fields. However, potential harmful effects of nanomaterials are raising concerns about their safety. Therefore, it is important that a risk assessment system is developed so that the safety of nanomaterials can be evaluated or predicted. Here, we attempted to identify novel biomarkers of nanomaterial-induced health effects by a comprehensive screen of plasma proteins using two-dimensional differential in gel electrophoresis (2D-DIGE) analysis. Initially, we used 2D-DIGE to analyze changes in the level of plasma proteins in mice after intravenous injection via tail veins of 0.8 mg/mouse silica nanoparticles with diameters of 70 nm (nSP70) or saline as controls. By quantitative image analysis, protein spots representing >2.0-fold alteration in expression were found and identified by mass spectrometry. Among these proteins, we focused on hemopexin as a potential biomarker. The levels of hemopexin in the plasma increased as the silica particle size decreased. In addition, the production of hemopexin depended on the characteristics of the nanomaterials. These results suggested that hemopexin could be an additional biomarker for analyzing the biological responses associated with exposure to silica nanoparticles. We believe that this study will contribute to the development of biomarkers to ensure the safety of silica nanoparticles.

Assessment of human dietary exposure to arsenic through rice.

Science.gov (United States)

Davis, Matthew A; Signes-Pastor, Antonio J; Argos, Maria; Slaughter, Francis; Pendergrast, Claire; Punshon, Tracy; Gossai, Anala; Ahsan, Habibul; Karagas, Margaret R

2017-05-15

Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Toenail as a biomarker of heavy metal exposure via drinking water: a systematic review.

Science.gov (United States)

Ab Razak, Nurul Hafiza; Praveena, Sarva Mangala; Hashim, Zailina

2015-01-01

Toenail is metabolic end product of the skin, which can provide information about heavy metal accumulation in human cells. Slow growth rates of toenail can represent heavy metal exposure from 2 to 12 months before the clipping. The toenail is a non-invasive biomarker that is easy to collect and store and is stable over time. In this systematic review, the suitability of toenail as a long-term biomarker was reviewed, along with the analysis and validation of toenail and confounders to heavy metal. This systematic review has included 30 articles chosen from a total of 132 articles searched from online electronic databases like Pubmed, Proquest, Science Direct, and SCOPUS. Keywords used in the search included "toenail", "biomarker", "heavy metal", and "drinking water". Heavy metal in toenail can be accurately analyzed using an ICP-MS instrument. The validation of toenail heavy metal concentration data is very crucial; however, the Certified Reference Material (CRM) for toenail is still unavailable. Usually, CRM for hair is used in toenail studies. Confounders that have major effects on heavy metal accumulation in toenail are dietary intake of food and supplement, smoking habit, and overall health condition. This review has identified the advantages and limitations of using toenail as a biomarker for long-term exposure, which can help future researchers design a study on heavy metal exposure using toenail.

1-Hydroxypyrene as a biomarker of PAH exposure in the marine polychaete Nereis diversicolor

DEFF Research Database (Denmark)

Tairova, Zhanna; Giessing, Anders; Hansen, Rikke

2009-01-01

The possibility of using the pyrene metabolite I-hydroxypyrene as a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure was investigated by exposure of the marine polychaete Nereis diversicolor to several PAHs in the laboratory. Animals were exposed to pyrene alone and to five different...

A brief review and evaluation of earthworm biomarkers in soil pollution assessment.

Science.gov (United States)

Shi, Zhiming; Tang, Zhiwen; Wang, Congying

2017-05-01

Earthworm biomarker response to pollutants has been widely investigated in the assessment of soil pollution. However, whether and how the earthworm biomarker-approach can be actually applied to soil pollution assessment is still a controversial issue. This review is concerned about the following points: 1. Despite much debate, biomarker is valuable to ecotoxicology and biomarker approach has been properly used in different fields. Earthworm biomarker might be used in different scenarios such as large-scale soil pollution survey and soil pollution risk assessment. Compared with physicochemical analysis, they can provide more comprehensive and straightforward information about soil pollution at low cost. 2. Although many earthworm species from different ecological categories have been tested, Eisenia fetida/andrei is commonly used. Many earthworm biomarkers have been screened from the molecular to the individual level, while only a few biomarkers, such as avoidance behavior and lysosomal membrane stability, have been focused on. Other aspects of the experimental design were critically reviewed. 3. More studies should focus on determining the reliability of various earthworm biomarkers in soil pollution assessment in future research. Besides, establishing a database of a basal level of each biomarker, exploring biomarker response in different region/section/part of earthworm, and other issues are also proposed. 4. A set of research guideline for earthworm biomarker studies was recommended, and the suitability of several earthworm biomarkers was briefly evaluated with respect to their application in soil pollution assessment. This review will help to promote further studies and practical application of earthworm biomarker in soil pollution assessment.

Biomarkers, lactate, and clinical scores as outcome predictors in systemic poisons exposures.

Science.gov (United States)

Lionte, C; Sorodoc, V; Tuchilus, C; Cimpoiesu, D; Jaba, E

2017-07-01

Acute exposure to systemic poisons represents an important challenge in clinical toxicology. We aimed to analyze the potential role of cardiac biomarkers, routine laboratory tests, and clinical scores as morbidity and in-hospital mortality predictors in patients intoxicated with various systemic poisons. We conducted a prospective study on adults acutely exposed to systemic poisons. We determined the PSS, Glasgow Coma Scale (GCS), and we performed electrocardiogram, laboratory tests, lactate and cardiac biomarkers (which were reassessed 4 h, respectively 6 h later). Of 120 patients included, 45% developed complications, 19.2% had a poor outcome, and 5% died. Multivariate logistic regression sustained lactate (odds ratio (OR) 1.58; confidence interval (CI) 95%: 0.97-2.59; p 0.066), MB isoenzyme of creatine kinase (6h-CKMB; OR 1.08; CI 95%: 1.02-1.16; p 0.018) as predictors for a poor outcome. A GCS poisons exposure. Receiver operating characteristic analysis showed that brain natriuretic peptide (area under the curve (AUC), 0.96; CI 95%: 0.92-0.99; p poisons exposure.

Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons and Cognitive Function among Elderly in the United States (National Health and Nutrition Examination Survey: 2001-2002)

Science.gov (United States)

Best, Elizabeth A.; Juarez-Colunga, Elizabeth; James, Katherine; LeBlanc, William G.; Serdar, Berrin

2016-01-01

Recent studies report a link between common environmental exposures, such as particulate matter air pollution and tobacco smoke, and decline in cognitive function. The purpose of this study was to assess the association between exposure to polycyclic aromatic hydrocarbons (PAHs), a selected group of chemicals present in particulate matter and tobacco smoke, and measures of cognitive performance among elderly in the general population. This cross-sectional analysis involved data from 454 individuals aged 60 years and older from the 2001–2002 National Health and Nutrition Examination Survey. The association between PAH exposures (as measured by urinary biomarkers) and cognitive function (digit symbol substitution test (DSST)) was assessed using multiple linear regression analyses. After adjusting for age, socio-economic status and diabetes we observed a negative association between urinary 1-hydroxypyrene, the gold standard of PAH exposure biomarkers, and DSST score. A one percent increase in urinary 1-hydroxypyrene resulted in approximately a 1.8 percent poorer performance on the digit symbol substitution test. Our findings are consistent with previous publications and further suggest that PAHs, at least in part may be responsible for the adverse cognitive effects linked to tobacco smoke and particulate matter air pollution. PMID:26849365

Functional, Structural, and Neurotoxicity Biomarkers in Integrative Assessment of Concussions

Directory of Open Access Journals (Sweden)

Svetlana A Dambinova

2016-10-01

Full Text Available Concussion is a complex, heterogenous process affecting the brain. Accurate assessment and diagnosis and appropriate management of concussion are essential to ensure athletes do not prematurely return to play or others to work or active military duty, risking re-injury. To date, clinical diagnosis relies primarily on evaluating subjects for functional impairment using instruments that include neurocognitive testing, subjective symptom report, and neurobehavioral assessments, such as balance and vestibular-ocular reflex testing. Structural biomarkers, defined as advanced neuroimaging techniques and biomarkers assessing neurotoxicity and immunoexcitotoxicity may complement the use of functional biomarkers. We hypothesize that neurotoxicity AMPA, NMDA, and kainite receptor biomarkers might be utilized as a part of comprehensive approach to concussion evaluations, with the goal of increasing diagnostic accuracy and facilitating treatment planning and prognostic assessment.

Inflammatory Biomarkers Predict Airflow Obstruction After Exposure to World Trade Center Dust

Science.gov (United States)

Nolan, Anna; Naveed, Bushra; Comfort, Ashley L.; Ferrier, Natalia; Hall, Charles B.; Kwon, Sophia; Kasturiarachchi, Kusali J.; Cohen, Hillel W.; Zeig-Owens, Rachel; Glaser, Michelle S.; Webber, Mayris P.; Aldrich, Thomas K.; Rom, William N.; Kelly, Kerry; Prezant, David J.

2012-01-01

Background: The World Trade Center (WTC) collapse on September 11, 2001, produced airflow obstruction in a majority of firefighters receiving subspecialty pulmonary evaluation (SPE) within 6.5 years post-September 11, 2001. Methods: In a cohort of 801 never smokers with normal pre-September 11, 2001, FEV1, we correlated inflammatory biomarkers and CBC counts at monitoring entry within 6 months of September 11, 2001, with a median FEV1 at SPE (34 months; interquartile range, 25-57). Cases of airflow obstruction had FEV1 less than the lower limit of normal (LLN) (100 of 801; 70 of 100 had serum), whereas control subjects had FEV1 greater than or equal to LLN (153 of 801; 124 of 153 had serum). Results: From monitoring entry to SPE years later, FEV1 declined 12% in cases and increased 3% in control subjects. Case subjects had elevated serum macrophage derived chemokine (MDC), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor, and interferon inducible protein-10 levels. Elevated GM-CSF and MDC increased the risk for subsequent FEV1 less than LLN by 2.5-fold (95% CI, 1.2-5.3) and 3.0-fold (95% CI, 1.4-6.1) in a logistic model adjusted for exposure, BMI, age on September 11, 2001, and polymorphonuclear neutrophils. The model had sensitivity of 38% (95% CI, 27-51) and specificity of 88% (95% CI, 80-93). Conclusions: Inflammatory biomarkers can be risk factors for airflow obstruction following dust and smoke exposure. Elevated serum GM-CSF and MDC levels soon after WTC exposure were associated with increased risk of airflow obstruction in subsequent years. Biomarkers of inflammation may help identify pathways producing obstruction after irritant exposure. PMID:21998260

Detection of Radiation-Exposure Biomarkers by Differential Mobility Prefiltered Mass Spectrometry (DMS-MS).

Science.gov (United States)

Coy, Stephen L; Krylov, Evgeny V; Schneider, Bradley B; Covey, Thomas R; Brenner, David J; Tyburski, John B; Patterson, Andrew D; Krausz, Kris W; Fornace, Albert J; Nazarov, Erkinjon G

2010-04-15

Technology to enable rapid screening for radiation exposure has been identified as an important need, and, as a part of a NIH / NIAD effort in this direction, metabolomic biomarkers for radiation exposure have been identified in a recent series of papers. To reduce the time necessary to detect and measure these biomarkers, differential mobility spectrometry - mass spectrometry (DMS-MS) systems have been developed and tested. Differential mobility ion filters preselect specific ions and also suppress chemical noise created in typical atmospheric-pressure ionization sources (ESI, MALDI, and others). Differential-mobility-based ion selection is based on the field dependence of ion mobility, which, in turn, depends on ion characteristics that include conformation, charge distribution, molecular polarizability, and other properties, and on the transport gas composition which can be modified to enhance resolution. DMS-MS is able to resolve small-molecule biomarkers from nearly-isobaric interferences, and suppresses chemical noise generated in the ion source and in the mass spectrometer, improving selectivity and quantitative accuracy. Our planar DMS design is rapid, operating in a few milliseconds, and analyzes ions before fragmentation. Depending on MS inlet conditions, DMS-selected ions can be dissociated in the MS inlet expansion, before mass analysis, providing a capability similar to MS/MS with simpler instrumentation. This report presents selected DMS-MS experimental results, including resolution of complex test mixtures of isobaric compounds, separation of charge states, separation of isobaric biomarkers (citrate and isocitrate), and separation of nearly-isobaric biomarker anions in direct analysis of a bio-fluid sample from the radiation-treated group of a mouse-model study. These uses of DMS combined with moderate resolution MS instrumentation indicate the feasibility of field-deployable instrumentation for biomarker evaluation.

Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

Science.gov (United States)

Dixon, C. Edward

2011-06-01

Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

Occupational exposure to HDI: progress and challenges in biomarker analysis.

Science.gov (United States)

Flack, Sheila L; Ball, Louise M; Nylander-French, Leena A

2010-10-01

1,6-Hexamethylene diisocyanate (HDI) is extensively used in the automotive repair industry and is a commonly reported cause of occupational asthma in industrialized populations. However, the exact pathological mechanism remains uncertain. Characterization and quantification of biomarkers resulting from HDI exposure can fill important knowledge gaps between exposure, susceptibility, and the rise of immunological reactions and sensitization leading to asthma. Here, we discuss existing challenges in HDI biomarker analysis including the quantification of N-acetyl-1,6-hexamethylene diamine (monoacetyl-HDA) and N,N'-diacetyl-1,6-hexamethylene diamine (diacetyl-HDA) in urine samples based on previously established methods for HDA analysis. In addition, we describe the optimization of reaction conditions for the synthesis of monoacetyl-HDA and diacetyl-HDA, and utilize these standards for the quantification of these metabolites in the urine of three occupationally exposed workers. Diacetyl-HDA was present in untreated urine at 0.015-0.060 μg/l. Using base hydrolysis, the concentration range of monoacetyl-HDA in urine was 0.19-2.2 μg/l, 60-fold higher than in the untreated samples on average. HDA was detected only in one sample after base hydrolysis (0.026 μg/l). In contrast, acid hydrolysis yielded HDA concentrations ranging from 0.36 to 10.1 μg/l in these three samples. These findings demonstrate HDI metabolism via N-acetylation metabolic pathway and protein adduct formation resulting from occupational exposure to HDI. Copyright © 2010 Elsevier B.V. All rights reserved.

The use of biomarkers in occupational health research, practice, and policy.

Science.gov (United States)

Schulte, P A; Hauser, J E

2012-08-13

Biomarkers are potentially useful tools for occupational health and safety research, practice, and policy. However, the full realization of this potential has not been achieved. In this paper, the progress made in these three usage areas is reviewed to identify what efforts can be taken to realize the full promise of biomarkers. Biomarker uses are described by a diverse taxonomy that builds on the categories of exposure, effect and susceptibility, and the continuum between exposure and disease prognosis. The most significant uses of biomarkers in occupational health have been in biological monitoring of workers. Other important uses have been in enhancing research and assessing mechanisms of action of occupational toxicants at low exposures. Seven critical areas will influence the extent to which the potential of biomarkers in occupational health and safety is realized. These include: (1) adequate investment in validation; (2) obtaining international agreement on exposure guidelines; (3) exploring the utility of biomarkers in regulation; (4) applying biomarkers to critical occupational safety and health questions; (5) developing the exposome; (6) utilizing biomarkers to address emerging occupational health issues; and (7) continuing to address the ethical and social justice issues related to biomarkers. Overall, if biomarkers are to make a major contribution to occupational health and safety then a more holistic approach to bringing them from the laboratory to practice will be needed. Published by Elsevier Ireland Ltd.

Biomonitoring of the mycotoxin Zearalenone: current state-of-the art and application to human exposure assessment.

Science.gov (United States)

Mally, Angela; Solfrizzo, Michele; Degen, Gisela H

2016-06-01

Zearalenone (ZEN), a mycotoxin with high estrogenic activity in vitro and in vivo, is a widespread food contaminant that is commonly detected in maize, wheat, barley, sorghum, rye and other grains. Human exposure estimates based on analytical data on ZEN occurrence in various food categories and food consumption data suggest that human exposure to ZEN and modified forms of ZEN may be close to or even exceed the tolerable daily intake (TDI) derived by the European Food Safety Authority (EFSA) for some consumer groups. Considering the inherent uncertainties in estimating dietary intake of ZEN that may lead to an under- or overestimation of ZEN exposure and consequently human risk and current lack of data on vulnerable consumer groups, there is a clear need for more comprehensive and reliable exposure data to refine ZEN risk assessment. Human biomonitoring (HBM) is increasingly being recognized as an efficient and cost-effective way of assessing human exposure to food contaminants, including mycotoxins. Based on animal and (limited) human data on the toxicokinetics of ZEN, it appears that excretion of ZEN and its major metabolites may present suitable biomarkers of ZEN exposure. In view of the limitations of available dietary exposure data on ZEN and its modified forms, the purpose of this review is to provide an overview of recent studies utilizing HBM to monitor and assess human exposure to ZEN. Considerations are given to animal and human toxicokinetic data relevant to HBM, analytical methods, and available HBM data on urinary biomarkers of ZEN exposure in different cohorts.

Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure

Science.gov (United States)

Deng, Yongfeng; Zhang, Yan; Lemos, Bernardo; Ren, Hongqiang

2017-04-01

Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5 μm and 20 μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs.

Cocktail effects on biomarker responses in fish

Energy Technology Data Exchange (ETDEWEB)

Celander, Malin C., E-mail: malin.celander@zool.gu.se [University of Gothenburg, Department of Zoology, Box 463, SE-405 30 Gothenburg (Sweden)

2011-10-15

One of today's greatest challenges in environmental toxicology is to understand effects of mixture toxicity, commonly referred to as cocktail effects, in humans and in wildlife. Biomarker responses in fish are routinely used to assess exposure of anthropogenic chemicals in the aquatic environment. However, little is known about how cocktail effects affect these biomarker responses. For this reason, there is an obvious risk for misinterpretation of biomarker-data and this can have profound negative effects on stakeholder's decisions and actions, as well as on legislations and remediation-plans initiated in order to reduce exposure to certain chemicals. Besides, chemical safety-levels are traditionally based on experiences from lab-studies with single chemicals, which is unfortunate as a chemical can be more toxic when it is mixed with other chemicals, because of the cocktail effect. This review focuses on pharmacokinetic interactions between different classes of pollutants on detoxification mechanisms and how that affects two commonly used biomarkers in the aquatic environment: (1) induction of cytochrome P450 1A (CYP1A) that is mediated via activation of the arylhydrocarbon receptor (AhR), used to assess exposure to aromatic hydrocarbons; (2) induction of vitellogenin (VTG) that is mediated via activation of the estrogen receptor (ER), used to assess exposure to estrogenic chemicals. These responses can be either directly or indirectly affected by the presence of other classes of pollutants as a result of cocktail effects. For example, chemicals that inhibit the function of key metabolic enzymes and transporter pumps that are involved in elimination of AhR- and ER agonists, can result in bioaccumulation of aromatic hydrocarbons and estrogenic chemicals resulting in increased biomarker responses. This cocktail effect can lead to overestimation of the actual exposure pressure. On the contrary, induction of expression of key metabolic enzymes and transporter

Fibrosis biomarkers in workers exposed to MWCNTs

International Nuclear Information System (INIS)

Fatkhutdinova, Liliya M.; Khaliullin, Timur O.; Vasil'yeva, Olga L.; Zalyalov, Ramil R.; Mustafin, Ilshat G.; Kisin, Elena R.; Birch, M. Eileen; Yanamala, Naveena; Shvedova, Anna A.

2016-01-01

Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. - Highlights: • The effects of MWCNT exposure in humans remain unclear. • We found increased KL-6/TGF-β levels in the biofluids of MWCNT-exposed workers. �

Fibrosis biomarkers in workers exposed to MWCNTs

Energy Technology Data Exchange (ETDEWEB)

Fatkhutdinova, Liliya M., E-mail: liliya.fatkhutdinova@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Khaliullin, Timur O., E-mail: Khaliullin.40k@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Department of Physiology & Pharmacology, WVU, Morgantown, WV (United States); Vasil' yeva, Olga L., E-mail: volgaleon@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Zalyalov, Ramil R., E-mail: zalyalov.ramil@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Mustafin, Ilshat G., E-mail: ilshat64@mail.ru [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Kisin, Elena R., E-mail: edk8@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Birch, M. Eileen, E-mail: mib2@cdc.gov [National Institute for Occupational Safety and Health, Cincinnati, OH (United States); Yanamala, Naveena, E-mail: wqu1@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Shvedova, Anna A., E-mail: ats1@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Department of Physiology & Pharmacology, WVU, Morgantown, WV (United States)

2016-05-15

Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. - Highlights: • The effects of MWCNT exposure in humans remain unclear. • We found increased KL-6/TGF-β levels in the biofluids of MWCNT-exposed workers. �

Lipid and Creatinine Adjustment to Evaluate Health Effects of Environmental Exposures.

Science.gov (United States)

O'Brien, Katie M; Upson, Kristen; Buckley, Jessie P

2017-03-01

Urine- and serum-based biomarkers are useful for assessing individuals' exposure to environmental factors. However, variations in urinary creatinine (a measure of dilution) or serum lipid levels, if not adequately corrected for, can directly impact biomarker concentrations and bias exposure-disease association measures. Recent methodological literature has considered the complex relationships between creatinine or serum lipid levels, exposure biomarkers, outcomes, and other potentially relevant factors using directed acyclic graphs and simulation studies. The optimal measures of urinary dilution and serum lipids have also been investigated. Existing evidence supports the use of covariate-adjusted standardization plus creatinine adjustment for urinary biomarkers and standardization plus serum lipid adjustment for lipophilic, serum-based biomarkers. It is unclear which urinary dilution measure is best, but all serum lipid measures performed similarly. Future research should assess methods for pooled biomarkers and for studying diseases and exposures that affect creatinine or serum lipids directly.

Blood arsenic as a biomarker of arsenic exposure: Results from a prospective study

International Nuclear Information System (INIS)

Hall, Marni; Chen Yu; Ahsan, Habibul; Slavkovich, Vesna; Geen, Alexander van; Parvez, Faruque; Graziano, Joseph

2006-01-01

Exposure to arsenic (As)-contaminated drinking water affects millions of people worldwide. Arsenic exposure is associated with skin lesions, skin, lung, kidney and liver cancers, neurologic and cardiovascular effects. Past studies involving biomarkers of As exposure have typically examined urinary As (UAs) (adjusted for urinary creatinine), hair or toenail As, but not blood As (BAs) since blood concentrations are exceedingly low and are not detectable by conventional atomic absorption spectrophotometric techniques. In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the health effects of as longitudinal study (HEALS) in Araihazar, Bangladesh, we measured blood, urine and water As concentrations, and examined their associations with each other, and with the risk for skin lesions. BAs concentrations were highly correlated with creatinine-adjusted UAs concentrations (r = 0.85) and with water As (WAs) (r = 0.75). We observed consistent dose-response relationships between the risk of skin lesions and all the measures of As exposure. Rate ratios (RRs) for skin lesions by quintile of As exposure, adjusted for age and gender, revealed that the two highest quintiles were significantly related to an increased risk of skin lesions for each measure of exposure: BAs, UAs, WAs and a time-weighted water As variable. This prospective study confirms the increased risk of skin lesions in relation to As concentrations in blood, urine and water and also establishes that BAs is a useful biomarker of As exposure in this study population

Toxicity assessment of simulated urban runoff containing polycyclic musks and cadmium in Carassius auratus using oxidative stress biomarkers

International Nuclear Information System (INIS)

Chen Fang; Gao Jie; Zhou Qixing

2012-01-01

The objective of this study was to assess potential toxic effects of simulated urban runoff on Carassius auratus using oxidative stress biomarkers. The activity of antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and the content of malondialdehyde (MDA) in the liver of C. auratus were analyzed after a 7-, 14- and 21-day exposure to simulated urban runoff containing galaxolide (HHCB) and cadmium (Cd). The results showed that the activity of antioxidant enzymes and the content of MDA increased significantly exposed to the simulated urban runoff containing HHCB alone or mixture of HHCB and Cd. The activity of the investigated enzymes and the content of MDA then returned to the blank level over a longer period of exposure. The oxidative stress could be obviously caused in the liver of C. auratus under the experimental conditions. This could provide useful information for toxic risk assessment of urban runoff. - Highlights: ► We assessed potential toxicity of urban runoff containing HHCB and Cd. ► Exposure of simulated urban runoff can caused oxidative stress in C. auratus liver. ► SOD and CAT are more sensitive than POD and more suitable for indicating the toxicity of urban runoff. ► The present study using oxidative stress biomarkers could provide useful information for toxic risk assessment of urban runoff. - Simulated urban runoff containing HHCB and Cd could cause oxidative stress on the liver of Carassius auratus, which could provide useful information for toxic risk assessment of urban runoff.

Analyzing the effectiveness of using branchial NKA activity as a biomarker for assessing waterborne copper toxicity in tilapia (Oreochromis mossambicus): A damage-based modeling approach.

Science.gov (United States)

Wu, Su-Mei; Tsai, Jeng-Wei; Tzeng, Wen-Nan; Chen, Wei-Yu; Shih, Wan-Yu

2015-06-01

Branchial Na(＋)-K(＋)-ATPase (NKA) activity has been suggested as a promising biomarker for assessing metal stress in aquatic organisms. However, studies that systematically show the effectiveness of using NKA activity to detect metal exposure and toxicity at the individual level are limited. In this study, we aimed to determine whether branchial NKA activity mechanistically responds to the accumulation of waterborne copper (Cu) and accounts for observed toxicity over time under environmentally-relevant and aquafarming Cu exposure levels (0.2, 1 and 2 mg L(-1)). Temporal trends in Cu accumulation and the corresponding responses of branchial NKA activity resulting from Cu exposure were investigated in laboratory experiments conducted on juvenile tilapia (Oreochromis mossambicus), a freshwater teleost that shows potential as a bioindicator of real-time and historical metal pollution. We used the process-based damage assessment model (DAM) to inspect the time course of Cu toxicity by integrating the compensation process between Cu-induced inhibition and repair of branchial NKA activity. NKA activity acted as a sensitive biomarker for Cu exposure and accumulation in tilapia, which showed induced impairment of osmoregulation and lethality when they were exposed to environmentally relevant levels (0.2 mg L(-1)), but not to higher exposure levels (1 and 2 mg L(-1)) in aquaculture farms or contaminated aquatic ecosystems. This study highlights the benefits and limitations of using branchial NKA activity as a sensitive biomarker to assess the health status of a fish population and its ecosystem. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of coexposure on toluene biomarkers in rats.

Science.gov (United States)

Cosnier, Frédéric; Nunge, Hervé; Brochard, Céline; Burgart, Manuella; Rémy, Aurélie; Décret, Marie-Josèphe; Cossec, Benoît; Campo, Pierre

2014-03-01

1. Toluene (TOL) is widely used in industry. Occupational exposure to TOL is commonly assessed using TOL in blood, hippuric acid and ortho-cresol. Levels of these biomarkers may depend on factors potentially interfering with TOL biotransformation, such as the presence of other solvents in the workplace. Mercapturic acids (MAs) could be an alternative to the "traditional" TOL biomarkers. 2. This study aims (1) to investigate in rat the effects of an exposure to vapours mixtures on the TOL metabolism, and (2) to assess how well MAs performed in these contexts compared to the traditional TOL biomarkers. 3. Rats were exposed by inhalation to binary mixtures of TOL with n-butanol (BuOH), ethyl acetate (EtAc), methyl ethyl ketone (MEK) or xylenes (XYLs); biological exposure indicators were then measured. 4. Depending on the compounds in the mixture and their concentrations, TOL metabolism was accelerated (with BuOH), unchanged (with EtAc) or inhibited (with XYLs and MEK). Inhibition leads to an increase in blood TOL concentrations, even at authorized atmospheric concentrations, which may potentiate the effect of TOL. 5. MAs excretions are little affected by coexposure scenarios, their levels correlating well with atmospheric TOL levels. They could thus be suitable bioindicators of atmospheric TOL exposure.

Seasonal effect on biomarkers of exposure to petroleum hydrocarbons in fish from Kuwait's marine area.

Science.gov (United States)

Beg, M U; Al-Subiai, S N; Al-Jandal, N; Butt, S A; Beg, K R; Al-Husaini, M

2015-11-30

The aquatic biota of the Arabian Gulf deals with exposure to chronic oil pollution, several constituents of which cause induction of Cytochrome P450 1A that serves as a biomarker of AhR ligand exposure. In this study, fluorescent aromatic compounds (FACs) in bile and 7-ethoxyresorufin-o-deethylase (EROD) catalytic activity were determined as a measure of exposure biomarkers in two fish species, yellow fin seabream (Acanthopagrus latus) and tonguesole (Cynoglossus arel) captured from Kuwait Bay and outside the Bay area. FACs in fish bile determined by using fixed-wavelength fluorescence (FF) showed high fluorescence ratios between FF290/335 and FF380/430 indicating predominant exposure to low molecular weight, naphthalene-rich petroleum products (375±91.0 pg ml(-1)). Exposures to benzo(a)pyrene-type high-molecular weight polycyclic aromatic hydrocarbons (PAHs) originating from burnt fuel were also present in appreciable concentration in the bile. The ratio of petrogenic to pyrogenic hydrocarbon was twofold higher in winter compared to summer months in both species. Seasonal effect on EROD was significant in tonguesole in Auha site (Ppollution in Kuwait Bay area. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gold Nanoparticles for the Detection of DNA Adducts as Biomarkers of Exposure to Acrylamide

Science.gov (United States)

Larguinho, Miguel Angelo Rodrigues

The main objective of this thesis was the development of a gold nanoparticle-based methodology for detection of DNA adducts as biomarkers, to try and overcome existing drawbacks in currently employed techniques. For this objective to be achieved, the experimental work was divided in three components: sample preparation, method of detection and development of a model for exposure to acrylamide. Different techniques were employed and combined for de-complexation and purification of DNA samples (including ultrasonic energy, nuclease digestion and chromatography), resulting in a complete protocol for sample treatment, prior to detection. The detection of alkylated nucleotides using gold nanoparticles was performed by two distinct methodologies: mass spectrometry and colorimetric detection. In mass spectrometry, gold nanoparticles were employed for laser desorption/ionisation instead of the organic matrix. Identification of nucleotides was possible by fingerprint, however no specific mass signals were denoted when using gold nanoparticles to analyse biological samples. An alternate method using the colorimetric properties of gold nanoparticles was employed for detection. This method inspired in the non-cross-linking assay allowed the identification of glycidamide-guanine adducts and DNA adducts generated in vitro. For the development of a model of exposure, two different aquatic organisms were studies: a goldfish and a mussel. Organisms were exposed to waterborne acrylamide, after which mortality was recorded and effect concentrations were estimated. In goldfish, both genotoxicity and metabolic alterations were assessed and revealed dose-effect relationships of acrylamide. Histopathological alterations were verified primarily in pancreatic cells, but also in hepatocytes. Mussels showed higher effect concentrations than goldfish. Biomarkers of oxidative stress, biotransformation and neurotoxicity were analysed after prolonged exposure, showing mild oxidative stress in

A study on some enzymes in rice field fish as biomarkers for pesticide exposure

International Nuclear Information System (INIS)

Juzu Hayati Arshad; Mazlina Muhammad; Salmijah Surif; Abdul Manan Mat Jais

2002-01-01

A study was carried out on three enzymes in rice field fish which can be used as possible biomarkers for pesticide exposure. The results obtained showed that the activity of the enzyme EROD (ethoxyresorufin-o-deethylase) increased between 1.5-2.2 fold in snakehead or haruan (Channa striata) sampled from the pesticide polluted areas, particularly the recycled areas and only a slight increase in EROD activity in climbing perch or puyu (Anabas testudineus). Increase in the activity of carboxylesterase was also noted. The percentage inhibition of acety1cholinesterase ranges from 18.4%-57.4% and 2.5%-34.2% for Channa striata and Anabas testudineus, respectively. Generally, a higher percentage of acety1cholinesterase inhibition was noted for those fish sampled from the recycled areas. The noted changes in the activity of these enzymes suggest exposure of rice field fish to foreign compounds, possibly pesticides, which are known to induce EROD activity and inhibit acety1cholinesterase activity. Therefore it may be possible to use these enzymes as biomarkers for pesticide exposure. (Author)

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

International Nuclear Information System (INIS)

Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A.

2016-01-01

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. - Highlights: • To define susceptible populations is important for risk assessment and management; • Genetic susceptibility may influence the individual response to nanomaterial exposure; • Susceptibility factors in workplace settings have both scientific and ethical issues.

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

Energy Technology Data Exchange (ETDEWEB)

Iavicoli, Ivo, E-mail: ivo.iavicoli@unina.it [Department of Public Health, Division of Occupational Medicine, University of Naples Federico II, Via S. Pansini 5, 80131 Naples (Italy); Leso, Veruscka, E-mail: veruscka@email.it [Institute of Public Health, Section of Occupational Medicine, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome (Italy); Schulte, Paul A., E-mail: pas4@cdc.gov [National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 4676 Columbia Parkway, MS C-14, Cincinnati, OH 45226 (United States)

2016-05-15

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. - Highlights: • To define susceptible populations is important for risk assessment and management; • Genetic susceptibility may influence the individual response to nanomaterial exposure; • Susceptibility factors in workplace settings have both scientific and ethical issues.

Biomarker responsiveness in different tissues of caged Ruditapes philippinarum and its use within an integrated sediment quality assessment

Energy Technology Data Exchange (ETDEWEB)

Ramos-Gomez, Julia, E-mail: julia.ramosgomez@uca.es [UNITWIN/UNESCO/WiCoP, Departamento de Quimica Fisica, Universidad de Cadiz, Facultad de Ciencias del Mar y Ambientales, Campus Universitario de Puerto Real, 11510 Puerto Real, Cadiz (Spain); Coz, Alberto; Viguri, Javier R. [Dpto. Ingenieria Quimica y Quimica Inorganica, ETSIIT, Universidad de Cantabria, Avda. los Castros, s/n 39005 Santander (Spain); Luque, Angel [Departamento de Biologia, Universidad de Las Palmas de Gran Canaria, 35017 Las Palmas de Gran Canaria, Gran Canaria, The Canary Islands (Spain); Martin-Diaz, M. Laura [UNITWIN/UNESCO/WiCoP, Departamento de Quimica Fisica, Universidad de Cadiz, Facultad de Ciencias del Mar y Ambientales, Campus Universitario de Puerto Real, 11510 Puerto Real, Cadiz (Spain); Centro Andaluz de Ciencia y Tecnologia Marinas (CACYTMAR), Universidad de Cadiz, Campus Universitario de Puerto Real, 11510 Puerto Real, Cadiz (Spain); DelValls, T. Angel [UNITWIN/UNESCO/WiCoP, Departamento de Quimica Fisica, Universidad de Cadiz, Facultad de Ciencias del Mar y Ambientales, Campus Universitario de Puerto Real, 11510 Puerto Real, Cadiz (Spain)

2011-07-15

Biomarkers comprising activities of biotransformation enzymes (ethoxyresorufin-O-deethylase -EROD-, dibenzylfluorescein dealkylase -DBF-, glutathione S-transferase -GST), antioxidant enzymes (glutathione reductase -GR- and glutathione peroxidase -GPX), lipid peroxidation -LPO- and DNA strand breaks were analyzed in the clam Ruditapes philippinarum caged at Cadiz Bay, Santander Bay and Las Palmas de Gran Canaria (LPGC) Port (Spain). Sediments were characterized. Digestive gland was the most sensitive tissue to sediment contamination. In Cadiz Bay, changes in LPO regarding day 0 were related with metals. In LPGC Port, DBF, EROD, and GST activity responses suggested the presence of undetermined contaminants which might have led to DNA damage. In Santander Bay, PAHs were related with EROD activity, organic and metal contamination was found to be associated with GR and GST activities and DNA damage presented significant (p < 0.05) induction. R. philippinarum was sensitive to sediment contamination at biochemical level. Biomarkers allowed chemical exposure and sediment quality assessment. - Highlights: > Ruditapes philippinarum is sensitive to sediment contamination at biochemical level. > Digestive gland biomarkers showed the best correlations with sediment contaminants. > Presence of potentially toxic chemicals not analyzed in this research was unmasked. > Multivariate analysis allowed the identification of toxic xenobiotic and possible sources. > Inner area of Santander Bay presented the highest sediment toxicity. - Integration of Ruditapes philippinarum biomarker results and sediment chemistry distinguished xenobiotic exposure and sediment toxicity in coastal areas of Spain.

Chemical and biochemical tools to assess pollution exposure in cultured fish

International Nuclear Information System (INIS)

Fernandes, Denise; Zanuy, Silvia; Bebianno, Maria Joao; Porte, Cinta

2008-01-01

There is little information regarding pollutant levels in farmed fish, and the risks associated to consumption. This study was designed to assess levels of exposure to metals, organochlorinated compounds, polycyclic aromatic hydrocarbons (PAHs) and alkylphenols (APEs) in farmed sea bass Dicentrarchus labrax from five aquacultures located in Southern Europe. Additionally, several biochemical responses (metallothionein, 7-ethoxyresorufin O-deethylase, vitellogenin) were determined as complementary tools. The obtained data indicate that pollutants exposure in farmed fish is similar to the levels reported in wild specimens from the area. Nonetheless, some biochemical responses were observed in the studied organisms, viz. metallothionein induction in Cu exposed organisms, and 7-ethoxyresorufin O-deethylase (EROD) and vitellogenin induction in PAHs and APEs exposed ones. The study further supports the usefulness of the biomarker approach as a first screening method to discriminate between basal and high levels of exposure in cultured fish. - Pollution assessment in cultured fish: chemical and biochemical tools

Effects of a powered air-purifying respirator intervention on indium exposure reduction and indium related biomarkers among ITO sputter target manufacturing workers.

Science.gov (United States)

Liu, Hung-Hsin; Chen, Chang-Yuh; Lan, Cheng-Hang; Chang, Cheng-Ping; Peng, Chiung-Yu

2016-01-01

This study aimed to evaluate the efficacy of powered air-purifying respirators (PAPRs) worn by the workers, and to investigate the effect of this application on exposure and preclinical effects in terms of workplace measuring and biomarker monitoring in ITO sputter target manufacturing plants and workers, respectively. Fifty-four workers were recruited and investigated from 2010-2012, during which PAPRs were provided to on-site workers in September 2011. Each worker completed questionnaires and provided blood and urine samples for analysis of biomarkers of indium exposure and preclinical effects. Area and personal indium air samples were randomly collected from selected worksites and from participants. The penetration percentage of the respirator (concentration inside respirator divided by concentration outside respirator) was 6.6%. Some biomarkers, such as S-In, SOD, GPx, GST, MDA, and TMOM, reflected the decrease in exposure and showed lower levels, after implementation of PAPRs. This study is the first to investigate the efficacy of PAPRs for reducing indium exposure. The measurement results clearly showed that the implementation of PAPRs reduces levels of indium-related biomarkers. These findings have practical applications for minimizing occupational exposure to indium and for managing the health of workers exposed to indium.

Moesin Is a Biomarker for the Assessment of Genotoxic Carcinogens in Mouse Lymphoma

Science.gov (United States)

Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

2012-01-01

1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. PMID:22358511

DNA mismatch repair related gene expression as potential biomarkers to assess cadmium exposure in Arabidopsis seedlings

International Nuclear Information System (INIS)

Liu Wan; Zhou Qixing; Li Peijun; Gao Hairong; Han, Y.P.; Li, X.J.; Yang, Y.S.; Li Yanzhi

2009-01-01

In the current study, Arabidopsis seedlings were hydroponically grown on MS media containing cadmium (Cd) of 0-2.0 mg L -1 for 60 h of treatment. Gene expression profiles were used to relate exposure to Cd with some altered biological responses and/or specific growth effects. RT-PCR analysis was used to quantitate mRNA expression for seven genes known to be involved in DNA mismatch repair (MMR) system and cell division. Results indicated that Cd concentrations of 0.25-2.0 mg L -1 cause increased total soluble protein levels in shoots of Arabidopsis seedlings in an inverted U-shaped dose-response manner. Exposure to 0.25 and 0.5 mg L -1 of Cd dramatically induced expression of four genes (i.e. proliferating cell nuclear antigen 2 (atPCNA 2), MutL1 homolog (atMLH1), MutS 2 homolog (atMSH2) and atMSH3) and five genes (i.e. atPCNA1,2, atMLH1 and atMSH2,7), respectively, in shoots of Arabidopsis seedlings; Exposure to 1.0 mg L -1 of Cd significantly elevated expression of only two genes (atMSH6,7), but caused prominent inhibition in expression of three genes (atPCNA2, atMLH1 and atMSH3) in shoots of Arabidopsis seedlings. The expression alterations of the above genes were independent of any biological effects such as survival, fresh weight and chlorophyll level of shoots. However, shoots of Arabidopsis seedlings exposed to 2.0 mg L -1 of Cd exhibited statistically prominent repression in expression of these seven genes, and showed incipient reduction of fresh weight and chlorophyll level. This research provides data concerning sensitivity of expression profiles of atMLH1, atMSH2,3,6,7 and atPCNA1,2 genes in Arabidopsis seedlings to Cd exposure, as well as the potential use of these gene expression patterns as representative molecular biomarkers indicative of Cd exposure and related biological effects.

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure

Science.gov (United States)

Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Mahon, Sari B.; Kim, Sonia; Ryu, Justine H.; Werdich, Andreas; Januzzi, James L.; Boss, Gerry R.; Rockwood, Gary A.; MacRae, Calum A.; Brenner, Matthew; Gerszten, Robert E.; Peterson, Randall T.

2013-01-01

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.—Nath, A. K., Roberts, L. D., Liu, Y., Mahon, S. B., Kim, S., Ryu, J. H., Werdich, A., Januzzi, J. L., Boss, G. R., Rockwood, G. A., MacRae, C. A., Brenner, M., Gerszten, R. E., Peterson, R. T. Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. PMID:23345455

An integrated biomarker response index for the mussel Mytilus edulis based on laboratory exposure to anthracene and field transplantation experiments

Science.gov (United States)

Yuan, Mengqi; Wang, You; Zhou, Bin; Jian, Xiaoyang; Dong, Wenlong; Tang, Xuexi

2017-09-01

Organic pollution is a serious environmental problem in coastal areas and it is important to establish quantitative methods for monitoring this pollution. This study screened a series of sensitive biomarkers to construct an integrated biomarker response (IBR) index using Mytilus edulis. Mussels were exposed to the polycyclic aromatic hydrocarbon anthracene under controlled laboratory conditions and the activities of components of the glutathione antioxidant system, and the concentrations of oxidative-damage markers, were measured in the gills and digestive glands. Anthracene exposure resulted in increased levels of malondialdehyde (MDA) and superoxide radicals (O 2 • ), indicating that oxidative damage had occurred. Correspondingly, anthracene exposure induced increased activities of glutathione S-transferase (GST), glutathione peroxidase (GPx) and reduced glutathione (GSH) in digestive glands, and GPx and glutathione reductase (GR) in gills, consistent with stimulation of the antioxidant system. A field experiment was set up, in which mussels from a relatively clean area were transplanted to a contaminated site. One month later, the activities of GST, GPx and GR had increased in several tissues, particularly in the digestive glands. Based on the laboratory experiment, an IBR, which showed a positive relationship with anthracene exposure, was constructed. The IBR is suggested to be a potentially useful tool for assessing anthracene pollution.

1-hydroxypyrene as a biomarker of PAH exposure in the marine invertebrates N. diversicolor

DEFF Research Database (Denmark)

Tairova, Zhanna; Giessing, Anders; Hansen, Rikke

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, persistent and toxic contaminants in the marine environment. Uptake of PAHs by marine deposit-feeding invertebrates can be determined by screening for PAH-derived metabolites. Methods for detection and quantification of PAH metabolites may...... invertebrates is on the other hand practically non-existing. The present study investigated formation of pyrene metabolites in the marine polychaete Nereis diversicolor, with special attention given to the detection of 1-hydroxypyrene. 1-hydroxypyrene was identified in tissues of Nereis diversicolor exposed...... this context the usefulness of SFS for identification and quantification was explored. Considering the complex composition of environmental PAH pollution, before the 1-hydoxypyrene in tissues of exposed marine invertebrates can be regarded as a suitable biomarker for assessing total PAH exposure...

Biomarker-Based Approaches for Assessing Alcohol Use Disorders

Directory of Open Access Journals (Sweden)

Onni Niemelä

2016-01-01

Full Text Available Although alcohol use disorders rank among the leading public health problems worldwide, hazardous drinking practices and associated morbidity continue to remain underdiagnosed. It is postulated here that a more systematic use of biomarkers improves the detection of the specific role of alcohol abuse behind poor health. Interventions should be initiated by obtaining information on the actual amounts of recent alcohol consumption through questionnaires and measurements of ethanol and its specific metabolites, such as ethyl glucuronide. Carbohydrate-deficient transferrin is a valuable tool for assessing chronic heavy drinking. Activities of common liver enzymes can be used for screening ethanol-induced liver dysfunction and to provide information on the risk of co-morbidities including insulin resistance, metabolic syndrome and vascular diseases. Conventional biomarkers supplemented with indices of immune activation and fibrogenesis can help to assess the severity and prognosis of ethanol-induced tissue damage. Many ethanol-sensitive biomarkers respond to the status of oxidative stress, and their levels are modulated by factors of life style, including weight gain, physical exercise or coffee consumption in an age- and gender-dependent manner. Therefore, further attention should be paid to defining safe limits of ethanol intake in various demographic categories and establishing common reference intervals for biomarkers of alcohol use disorders.

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes.

Science.gov (United States)

Baumann, R; Gube, M; Markert, A; Davatgarbenam, S; Kossack, V; Gerhards, B; Kraus, T; Brand, P

2018-01-01

Zinc- and copper-containing welding fumes increase systemic C-reactive protein (CRP). The aim of this study was to investigate the performance of the biomarkers serum amyloid A (SAA) and soluble vascular cell adhesion molecule-1 (VCAM-1) in this regard. Fifteen male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc for 6 h. Plasma samples were collected before, 6 and 24 h after start of exposure and biomarkers therein were measured by electrochemiluminescent assay. For each exposure, systemic concentrations of systemic SAA, but not VCAM-1, increased significantly at 24 h after exposure start compared with baseline ("copper only": P=0.0005, "zinc only": P=0.027, "copper and zinc": P=0.001). SAA showed a wider range of concentrations than did CRP and its levels increased up to 19-fold after welding fume exposure. The recognition of copper as a potential harmful component in welding fumes, also independent from zinc, deserves further consideration. SAA might represent a new sensitive biomarker for potential subclinical sterile inflammation after inhalation of copper- and/or zinc-containing welding fumes. As elevations of CRP and SAA protein have both been linked to a higher risk for cardiovascular disease, these findings might particularly be important for long-term welders.

Biomarkers of oxidative stress study V: ozone exposure of rats and its effect on lipids, proteins, and DNA in plasma and urine.

Science.gov (United States)

Kadiiska, Maria B; Basu, Samar; Brot, Nathan; Cooper, Christopher; Saari Csallany, A; Davies, Michael J; George, Magdalene M; Murray, Dennis M; Jackson Roberts, L; Shigenaga, Mark K; Sohal, Rajindar S; Stocker, Roland; Van Thiel, David H; Wiswedel, Ingrid; Hatch, Gary E; Mason, Ronald P

2013-08-01

Ozone exposure effect on free radical-catalyzed oxidation products of lipids, proteins, and DNA in the plasma and urine of rats was studied as a continuation of the international Biomarker of Oxidative Stress Study (BOSS) sponsored by NIEHS/NIH. The goal was to identify a biomarker for ozone-induced oxidative stress and to assess whether inconsistent results often reported in the literature might be due to the limitations of the available methods for measuring the various types of oxidative products. The time- and dose-dependent effects of ozone exposure on rat plasma lipid hydroperoxides, malondialdehyde, F2-isoprostanes, protein carbonyls, methionine oxidation, and tyrosine- and phenylalanine oxidation products, as well as urinary malondialdehyde and F2-isoprostanes were investigated with various techniques. The criterion used to recognize a marker in the model of ozone exposure was that a significant effect could be identified and measured in a biological fluid seen at both doses at more than one time point. No statistically significant differences between the experimental and the control groups at either ozone dose and time point studied could be identified in this study. Tissue samples were not included. Despite all the work accomplished in the BOSS study of ozone, no available product of oxidation in biological fluid has yet met the required criteria of being a biomarker. The current negative findings as a consequence of ozone exposure are of great importance, because they document that in complex systems, as the present in vivo experiment, the assays used may not provide meaningful data of ozone oxidation, especially in human studies. Published by Elsevier Inc.

Is acetylcholinesterase a biomarker of susceptibility in Daphnia magna (Crustacea, Cladocera) after deltamethrin exposure?

Science.gov (United States)

Toumi, Héla; Boumaiza, Moncef; Millet, Maurice; Radetski, Claudemir Marcos; Felten, Vincent; Férard, Jean François

2015-02-01

In the present study, we explored the possibility of using the acetylcholinesterase (AChE) as a biomarker after deltamethrin (pyrethroid insecticide) exposure with three strains of the cladoceran Daphnia magna. Four calculated time-weighted deltamethrin concentrations (20.1, 40.3, 80.6 and 161.3 ng L(-1)) were compared against control acetylcholinesterase activity. Our results showed that after 48 h of deltamethrin exposure, all treatments induced a significant decrease of AChE activities whatever the three considered strains. However, diverse responses were registered in terms of lowest observed effect concentrations (LOEC: 80.6 ng L(-1) for strain 1 and 20.1 ng L(-1) for strains 2 and 3) revealing differences in sensitivity among the three tested strains of D. magna. Our results suggest that after deltamethrin exposure, the AChE activity responses can be also used as a biomarker of susceptibility (i.e., variation of strain specific response). Moreover, our results show that strain 1 is the less sensitive in terms of IC50-48 h of AChE, whereas it became the most sensitive when considering the EC50-48 h estimated in the standard ecotoxicity test. Copyright © 2014 Elsevier Ltd. All rights reserved.

Application of biomarkers to assess the condition of European Marine Sites

Energy Technology Data Exchange (ETDEWEB)

Hagger, Josephine A., E-mail: j.hagger@exeter.ac.u [School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS (United Kingdom); Galloway, Tamara S. [School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS (United Kingdom); Langston, William J. [Marine Biological Association, Citadel Hill, Plymouth PL1 2PB, Devon (United Kingdom); Jones, Malcolm B. [School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA, Devon (United Kingdom)

2009-07-15

A series of European Marine Sites has been designated as Special Areas of Conservation (SAC) in England. The aim of this study was to develop a practical methodology to assess the condition of SACs by applying a suite of biomarkers. Biomarkers were applied to the blue mussel Mytilus edulis and the shore crab Carcinus maenas from the Fal and Helford SAC (Cornwall). Individual biomarkers provided useful diagnostic information on the activity of certain classes of contaminants and an integrated Biomarker Response Index (BRI) was used to achieve a more holistic understanding of the condition of the SAC. The BRI indicated that the general health of both organisms was impacted in the upper part of the SAC (Fal Estuary) which correlated well with known chemical hotspots and sources of contamination. The BRI allows a pragmatic way to prioritise SAC sites that may require further investigative studies. - A suite of biomarkers was successfully used to create a Biomarker Response Index to assess the health of aquatic organisms from European Marine Sites.

Application of biomarkers to assess the condition of European Marine Sites

International Nuclear Information System (INIS)

Hagger, Josephine A.; Galloway, Tamara S.; Langston, William J.; Jones, Malcolm B.

2009-01-01

A series of European Marine Sites has been designated as Special Areas of Conservation (SAC) in England. The aim of this study was to develop a practical methodology to assess the condition of SACs by applying a suite of biomarkers. Biomarkers were applied to the blue mussel Mytilus edulis and the shore crab Carcinus maenas from the Fal and Helford SAC (Cornwall). Individual biomarkers provided useful diagnostic information on the activity of certain classes of contaminants and an integrated Biomarker Response Index (BRI) was used to achieve a more holistic understanding of the condition of the SAC. The BRI indicated that the general health of both organisms was impacted in the upper part of the SAC (Fal Estuary) which correlated well with known chemical hotspots and sources of contamination. The BRI allows a pragmatic way to prioritise SAC sites that may require further investigative studies. - A suite of biomarkers was successfully used to create a Biomarker Response Index to assess the health of aquatic organisms from European Marine Sites.

Lysosomal membrane stability of the mussel, Mytilus galloprovincialis (L.), as a biomarker of tributyltin exposure.

Science.gov (United States)

Okoro, Hussein K; Snyman, Reinette G; Fatoki, Olalekan S; Adekola, Folahan A; Ximba, Bhekumusa J; Slabber, Michelle Y

2015-05-01

The effect of tributyltin (TBT) on the stability of hemocytic lysosome membranes of the mussel, Mytilus galloprovincialis, and the use thereof as a biomarker of TBT-induced stress, was investigated. Mussels were exposed to 0.1 and 1.0 µg/L tributyltin respectively for 4 weeks. Lysosomal membrane stability of hemocytes was tested weekly by means of the neutral red retention time (NRRT) assay, after which the mussel samples were analyzed for TBT content. The two exposed groups exhibited significantly increased (p < 0.05) whole body TBT concentrations with concomitant significant decreases (p < 0.05) in NRRT (R(2) values of 0.85 and 0.971 for lower and higher exposure groups, respectively). The higher exposure group showed a typical dose-response curve. For the control, no TBT was detected and NRRT remained stable. It was concluded that the NRRT assay could be considered as a useful technique, and lysosomal membrane destabilization a useful early warning and cellular biomarker of stress due to TBT exposure in M. galloprovincialis.

Biomarker responsiveness in different tissues of caged Ruditapes philippinarum and its use within an integrated sediment quality assessment

International Nuclear Information System (INIS)

Ramos-Gomez, Julia; Coz, Alberto; Viguri, Javier R.; Luque, Angel; Martin-Diaz, M. Laura; DelValls, T. Angel

2011-01-01

Biomarkers comprising activities of biotransformation enzymes (ethoxyresorufin-O-deethylase -EROD-, dibenzylfluorescein dealkylase -DBF-, glutathione S-transferase -GST), antioxidant enzymes (glutathione reductase -GR- and glutathione peroxidase -GPX), lipid peroxidation -LPO- and DNA strand breaks were analyzed in the clam Ruditapes philippinarum caged at Cadiz Bay, Santander Bay and Las Palmas de Gran Canaria (LPGC) Port (Spain). Sediments were characterized. Digestive gland was the most sensitive tissue to sediment contamination. In Cadiz Bay, changes in LPO regarding day 0 were related with metals. In LPGC Port, DBF, EROD, and GST activity responses suggested the presence of undetermined contaminants which might have led to DNA damage. In Santander Bay, PAHs were related with EROD activity, organic and metal contamination was found to be associated with GR and GST activities and DNA damage presented significant (p < 0.05) induction. R. philippinarum was sensitive to sediment contamination at biochemical level. Biomarkers allowed chemical exposure and sediment quality assessment. - Highlights: → Ruditapes philippinarum is sensitive to sediment contamination at biochemical level. → Digestive gland biomarkers showed the best correlations with sediment contaminants. → Presence of potentially toxic chemicals not analyzed in this research was unmasked. → Multivariate analysis allowed the identification of toxic xenobiotic and possible sources. → Inner area of Santander Bay presented the highest sediment toxicity. - Integration of Ruditapes philippinarum biomarker results and sediment chemistry distinguished xenobiotic exposure and sediment toxicity in coastal areas of Spain.

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

Science.gov (United States)

Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A.

2016-01-01

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. PMID:26724381

A randomised, controlled, two-Centre open-label study in healthy Japanese subjects to evaluate the effect on biomarkers of exposure of switching from a conventional cigarette to a tobacco heating product

Directory of Open Access Journals (Sweden)

Nathan Gale

2017-08-01

Full Text Available Abstract Background Smoking is a leading cause of numerous human disorders including lung cancer, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease. The development of modified risk tobacco products (MRTPs has been suggested as a possible way to reduce the risks of tobacco smoking by reducing exposure to cigarette smoke toxicants. This study is designed to investigate whether biomarkers of such exposure are reduced when smokers switch from smoking commercial cigarettes to using either a novel or a commercially-available tobacco heating product (THP. Design and Methods This study will assess biomarkers of exposure in current smokers who either remain smoking, switch to THP use, or quit all tobacco use completely, for 5 days. The study is an in-clinic (confinement two-centre, randomised controlled clinical study with a forced-switching design. Subjects of either gender will be aged 23–55 years (minimum legal smoking age plus 3 years, of Japanese origin and with a verified smoking status (assessed by exhaled breath carbon monoxide and urinary cotinine levels. Subjects will have a usual brand cigarette within the International Organisation for Standardisation (ISO tar band of 6-8 mg and will be judged to be healthy by medical history, physical examination, vital signs, electrocardiography (ECG, clinical biochemistry and lung function tests. The primary objective of this study is to assess changes within groups in selected biomarkers of exposure (BoE and of biological effect (BoBE after a forced switch from a commercial control cigarette to either a menthol or a non-menthol THP. Secondary objectives are to assess between-group differences, to determine nicotine pharmacokinetics for cigarettes and THPs, to assess subject’s satisfaction with the study products, and to monitor additional endpoints related to safety and product use. Discussion Data from this study will advance our scientific understanding of the

HISTORICAL MONITORING OF BIOMARKERS OF PAH EXPOSURE OF BROWN BULLHEAD IN THE REMEDIATED BLACK RIVER AND THE CUYAHOGA RIVER, OHIO

Science.gov (United States)

Biomarkers of exposure to chemical contamination were measured in brown bullhead from a heavily PAH contaminated section of the Black River, Ohio, during and immediately after remedial sediment dredging in 1990-1991, and in follow-up visits in 1993 and 1998. Biomarker levels of ...

Toenail as Non-invasive Biomarker in Metal Toxicity Measurement of Welding Fumes Exposure - A Review

Science.gov (United States)

Bakri, S. F. Z.; Hariri, A.; Ma'arop, N. F.; Hussin, N. S. A. W.

2017-01-01

Workers are exposed to a variety of heavy metal pollutants that are released into the environment as a consequence of workplace activities. This chemical pollutants are incorporated into the human by varies of routes entry and can then be stored and distributed in different tissues, consequently have a potential to lead an adverse health effects and/or diseases. As to minimize the impact, a control measures should be taken to avoid these effects and human biological marker is a very effective tool in the assessment of occupational exposure and potential related risk as the results is normally accurate and reproducible. Toenail is the ideal matrix for most common heavy metals due to its reliability and practicality compared to other biological samples as well as it is a non-invasive and this appears as a huge advantage of toenail as a biomarker. This paper reviews studies that measure the heavy metals concentration in toenail as non-invasive matrix which later may adapt in the investigation of metal fume emitted from welding process. The development of new methodology and modern analytical techniques has allowed the use of toenail as non-invasive approach. The presence of a heavy metal in this matrix reflects an exposure but the correlations between heavy metal levels in the toenail must be established to ensure that these levels are related to the total body burden. These findings suggest that further studies on interactions of these heavy metals in metal fumes utilizing toenail biomarker endpoints are highly warranted especially among welders.

Can the integration of multiple biomarkers and sediment geochemistry aid solving the complexity of sediment risk assessment? A case study with a benthic fish

International Nuclear Information System (INIS)

Costa, Pedro M.; Caeiro, Sandra; Vale, Carlos; DelValls, T. Àngel; Costa, Maria H.

2012-01-01

Surveying toxicity of complex geochemical media as aquatic sediments often yields results that are either difficult to interpret or even contradictory to acknowledged theory. Multi-level biomarkers were investigated in a benthic fish exposed to estuarine sediments through laboratory and in situ bioassays, to evaluate their employment either in ecological risk assessment or in more mechanistic approaches to assess sediment-bound toxicity. Biomarkers reflecting lesions (such as genotoxicity or histopathology), regardless of their low or absent specificity to contaminants, are efficient in segregating exposure to contaminated from uncontaminated sediments even when classical biomarkers like CYP1A and metallothionein induction are inconclusive. Conversely, proteomics and gene transcription analyses provided information on the mechanics of toxicity and aided explaining response variation as a function of metabolic imbalance and impairment of defences against insult. In situ bioassays, although less expedite and more affected by confounding factors, produced data better correlated to overall sediment contamination. Highlights: ► Sediment-bound contaminant mixtures can yield unexpected biomarker responses in fish. ► Biomarkers reflecting lesions are sturdier predictors of pollution by mixed xenobiotics. ► Proteomics and gene transcription analyses disclosed the existence of complex patterns of response to toxicity. ► Laboratory bioassays are less impacted by noise variables but tend to lose ecological relevance. - Evaluation of multi-level biomarker responses in fish for ecological risk assessment

The Alberta Oil Sands Community Exposure and Health Effects Assessment Program : methods report

International Nuclear Information System (INIS)

2000-01-01

The Alberta Oil Sands Community Exposure and Health Effects Assessment Program involved the development of a holistic approach to the study of personal exposure and the potential health impacts of airborne contaminants including volatile organic compounds (VOCs), sulphur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), ozone (O 3 ) and particulates (both PM10 and PM2.5). Volunteer residents from Fort McMurray, Alberta were recruited to participate in neurocognitive tests and a health and nutrition survey. In addition, the local community identified several priority contaminants which were highlighted during a public hearing of the Alberta Energy and Utilities Board in relation to Syncrude's Mildred Lake Development Project. The approach to the study was based on the direct measurement of all routes of exposure to the contaminants (breathing, ingestion and skin contact), direct measurement of biomarkers, and daily logs of participant's activities. The choice of biomarkers was based on the ability of the laboratory to measure low levels of relevant biological markers, the most appropriate media for measuring the markers, and the burden placed on each volunteer. The final set of biological measures of exposure included trace metals (arsenic, cadmium, lead and uranium) nicotine, and metabolites of the BTEX compounds (benzene, toluene, ethylbenzene, and xylenes). The objective was to determine if chronic or occupational exposure to these contaminants cause structural alterations in the respiratory system that compromise oxygen absorption and lung elasticity. 82 refs., 14 tabs., 15 figs., 3 appendices

A critical assessment of some biomarker approaches linked with dietary intake

DEFF Research Database (Denmark)

Crews, H.; Alink, G.; Andersen, Rikke

2001-01-01

interactions and the role of measuring total antioxidant capacity is considered in some detail. In contrast to most nutrients, there is a marked lack of biomarkers of either exposure or effect for most non-nutrients. The role of biological effect monitoring is considered for dietary contaminants, fumonisins...

Relation between dietary cadmium intake and biomarkers of cadmium exposure in premenopausal women accounting for body iron stores

Directory of Open Access Journals (Sweden)

Julin Bettina

2011-12-01

Full Text Available Abstract Background Cadmium is a widespread environmental pollutant with adverse effects on kidneys and bone, but with insufficiently elucidated public health consequences such as risk of end-stage renal diseases, fractures and cancer. Urinary cadmium is considered a valid biomarker of lifetime kidney accumulation from overall cadmium exposure and thus used in the assessment of cadmium-induced health effects. We aimed to assess the relationship between dietary cadmium intake assessed by analyses of duplicate food portions and cadmium concentrations in urine and blood, taking the toxicokinetics of cadmium into consideration. Methods In a sample of 57 non-smoking Swedish women aged 20-50 years, we assessed Pearson's correlation coefficients between: 1 Dietary intake of cadmium assessed by analyses of cadmium in duplicate food portions collected during four consecutive days and cadmium concentrations in urine, 2 Partial correlations between the duplicate food portions and urinary and blood cadmium concentrations, respectively, and 3 Model-predicted urinary cadmium concentration predicted from the dietary intake using a one-compartment toxicokinetic model (with individual data on age, weight and gastrointestinal cadmium absorption and urinary cadmium concentration. Results The mean concentration of cadmium in urine was 0.18 (+/- s.d.0.12 μg/g creatinine and the model-predicted urinary cadmium concentration was 0.19 (+/- s.d.0.15 μg/g creatinine. The partial Pearson correlations between analyzed dietary cadmium intake and urinary cadmium or blood concentrations were r = 0.43 and 0.42, respectively. The correlation between diet and urinary cadmium increased to r = 0.54 when using a one-compartment model with individual gastrointestinal cadmium absorption coefficients based on the women's iron status. Conclusions Our results indicate that measured dietary cadmium intake can reasonably well predict biomarkers of both long-term kidney accumulation

Biomarkers in Prostate Cancer Epidemiology

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Mudit Verma

2011-09-01

Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

Effect of vitamin levels on biomarkers of exposure and oxidative damage – The EXPAH study

Czech Academy of Sciences Publication Activity Database

Šrám, Radim; Farmer, P.; Singh, R.; Garte, S.; Kalina, I.; Popov, T. A.; Binková, Blanka; Ragin, C.; Taioli, E.

2009-01-01

Roč. 672, č. 2 (2009), s. 129-134 ISSN 1383-5718 Institutional research plan: CEZ:AV0Z50390512 Keywords : molecular epidemiology * cross-sectional study * biomarkers of exposure Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.552, year: 2009

Biomarkers in an invasive fish species, Oreochromis niloticus, to assess the effects of pollution in a highly degraded Brazilian River.

Science.gov (United States)

Linde-Arias, Ana Rosa; Inácio, Alan F; de Alburquerque, Carla; Freire, Marina M; Moreira, Josino C

2008-07-25

Paraiba do Sul watershed is one of the most important Brazilian water bodies (5.5 million people depend on the river). It is in a critical environmental situation, polluted by industrial discharges, non-treated urban wastes, and pesticides, which have had cumulatively negative effects. This study analyzes the effects of pollution, with a biomarker approach, by using the invasive fish species, Oreochromis niloticus, as a sentinel species. The approach comprehends a general biomarker of the health of individual fish, the condition factor, a biomarker of genotoxicity, the micronuclei test; and specific biomarkers of contaminant exposure such as metallothionein (MT) and acetylcholinesterase (AChE) activity. The results revealed different effects in fish from diverse locations with varying degrees of pollution. Low AChE activities were found in fish from the region with strong agriculture activity, showing the effects of pesticides. Fish from an industrialized and heavily environmentally degraded area presented high levels of MT and low AChE activities, indicating an intricate polluted condition. It is noteworthy that fish located just upstream of the main water-treatment plant of the metropolitan area Rio de Janeiro presented high levels of MT, showing to be affected by metals. This can be an alert to public health officials. O. niloticus has proven a suitable sentinel species to assess the effects of pollutions in an aquatic system with a complex and serious polluted situation. The present study also shows the usefulness of integrating a set of biomarkers to define the exposure and the effects of anthropogenic inputs among impacted and reference sites in this water body.

Exposure to asbestos and levels of selected tumor biomarkers

International Nuclear Information System (INIS)

Krajewska, B.; Lutz, W.; Pilacik, B.

1996-01-01

Occupational exposure to asbestos, a recognised carcinogen, poses a risk for such diseases as asbestosis, lung cancer and mesothelioma. It is thought that asbestos fibres may damage microphages which undergo neoplastic transformation as well as fibroblast, while partial phagocytosis may generate free oxygenic radicals which induce cellular peroxidase and damage macromolecules. Neoplastic biomarkers such as tissue polypeptide antigen (TPA) or carcinoembryonic antigen (CEA) are now used for this purpose. The aim of the work was to identify workers exposed to asbestos in the population, especially high risk groups neoplastic diseases and to evaluate the usefulness of TPA and CEA determinations. The study covered a group of asbestos exposed workers (n = 4000 and the control group of workers (n = 135) nonexposed to any toxic factor at work. Age, exposure time, smoking habits and workpost characteristics were taken into consideration in the analysis of the results. It was revealed that in 38 persons exposed to asbestos, TPA values were above the concentration limit set on the basis of studies carried out in the control group, and elevated CEA values applied to 13 persons. Significant differences between groups under study were found in the proportion of pathological TPA values. Such a relationship was not observed in regard to CEA values. In the exposed group the results also indicated an evident effect of age and exposure time on the number of persons with TPA values above concentration limit. The effect of smoking on the frequency of pathological TPA values was also clear-cut in workers exposed to asbestos. Taking into account three types of employment, the analysis indicated significant differences in TPA values between blue collar workers and other personnel; and between white collar workers and other personnel. This means a similar percentage of pathological TPA values in the group of blue collar and white collar workers. The study carried out allowed to identify

Benzene exposure assessed by metabolite excretion in Estonian oil shale mineworkers: influence of glutathione s-transferase polymorphisms

DEFF Research Database (Denmark)

Sørensen, Mette; Poole, Jason; Autrup, Herman

2004-01-01

Measurement of urinary excretion of the benzene metabolites S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) has been proposed for assessing benzene exposure, in workplaces with relatively high benzene concentrations. Excretion of S-PMA and t,t-MA in underground workers...... the last shift of the week. Personal benzene exposure was 114 +/- 35 mug/m(3) in surface workers (n = 15) and 190 +/- 50 mug/m(3) in underground workers (n = 15) in measurements made prior to the study. We found t,t-MA excretion to be significantly higher in underground workers after the end of shifts 1...... of benzene metabolites as biomarkers for assessment of exposure at modest levels and warrant for further investigations of health risks of occupational benzene exposure in shale oil mines....

Biomarkers for Exposure to Ambient Air Pollution - Comparison of Carcinogen-DNA Adduct Levels with Other Exposure Markers and Markers for Oxidative Stress

DEFF Research Database (Denmark)

Autrup, Herman; Daneshvar, Bahram; Dragsted, Lars Ove

1999-01-01

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts....../10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96...... nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative...

III: Use of biomarkers as Risk Indicators in Environmental Risk Assessment of oil based discharges offshore.

Science.gov (United States)

Sanni, Steinar; Lyng, Emily; Pampanin, Daniela M

2017-06-01

Offshore oil and gas activities are required not to cause adverse environmental effects, and risk based management has been established to meet environmental standards. In some risk assessment schemes, Risk Indicators (RIs) are parameters to monitor the development of risk affecting factors. RIs have not yet been established in the Environmental Risk Assessment procedures for management of oil based discharges offshore. This paper evaluates the usefulness of biomarkers as RIs, based on their properties, existing laboratory biomarker data and assessment methods. Data shows several correlations between oil concentrations and biomarker responses, and assessment principles exist that qualify biomarkers for integration into risk procedures. Different ways that these existing biomarkers and methods can be applied as RIs in a probabilistic risk assessment system when linked with whole organism responses are discussed. This can be a useful approach to integrate biomarkers into probabilistic risk assessment related to oil based discharges, representing a potential supplement to information that biomarkers already provide about environmental impact and risk related to these kind of discharges. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of biomonitoring data from the CDC National Exposure Report in a risk assessment context: perspectives across chemicals.

Science.gov (United States)

Aylward, Lesa L; Kirman, Christopher R; Schoeny, Rita; Portier, Christopher J; Hays, Sean M

2013-03-01

Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals [NER; Centers for Disease Control and Prevention (2012)] provide information on the presence and concentrations of > 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment-based values now allow interpretation of these biomonitoring data in a public health risk context. We compared the measured biomarker concentrations in the NER with BEs and similar risk assessment values to provide an across-chemical risk assessment perspective on the measured levels for approximately 130 analytes in the NER. We identified available risk assessment-based biomarker screening values, including BEs and Human Biomonitoring-I (HBM-I) values from the German Human Biomonitoring Commission. Geometric mean and 95th percentile population biomarker concentrations from the NER were compared to the available screening values to generate chemical-specific hazard quotients (HQs) or cancer risk estimates. Most analytes in the NER show HQ values of chemicals, benzene, xylene, several metals, di-2(ethylhexyl)phthalate, and some legacy organochlorine pesticides) approach or exceed HQ values of 1 or cancer risks of > 1 × 10-4 at the geometric mean or 95th percentile, suggesting exposure levels may exceed published human health benchmarks. This analysis provides for the first time a means for examining population biomonitoring data for multiple environmental chemicals in the context of the risk assessments for those chemicals. The results of these comparisons can be used to focus more detailed chemical-specific examination of the data and inform priorities for chemical risk management and research.

Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow

International Nuclear Information System (INIS)

Kulkarni, Shilpa; Koller, Antonius; Mani, Kartik M.; Wen, Ruofeng; Alfieri, Alan; Saha, Subhrajit; Wang, Jian; Patel, Purvi; Bandeira, Nuno; Guha, Chandan

2016-01-01

Purpose: Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). Methods and Materials: For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24 and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. Results: A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Conclusions: Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially secreted

Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow

Energy Technology Data Exchange (ETDEWEB)

Kulkarni, Shilpa [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Koller, Antonius [Proteomics Center, Stony Brook University School of Medicine, Stony Brook, New York (United States); Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, New York, New York (United States); Mani, Kartik M. [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Wen, Ruofeng [Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York (United States); Alfieri, Alan; Saha, Subhrajit [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Wang, Jian [Center for Computational Mass Spectrometry, University of California, San Diego, California (United States); Department of Computer Science and Engineering, University of California, San Diego, California (United States); Patel, Purvi [Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, New York, New York (United States); Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York (United States); Bandeira, Nuno [Center for Computational Mass Spectrometry, University of California, San Diego, California (United States); Department of Computer Science and Engineering, University of California, San Diego, California (United States); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California (United States); Guha, Chandan, E-mail: cguha@montefiore.org [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); and others

2016-11-01

Purpose: Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). Methods and Materials: For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24 and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. Results: A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Conclusions: Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially secreted

Using a novel "Integrated Biomarker Proteomic" index to assess the effects of freshwater pollutants in European eel peripheral blood mononuclear cells.

Science.gov (United States)

Roland, Kathleen; Kestemont, Patrick; Dieu, Marc; Raes, Martine; Silvestre, Frédéric

2016-03-30

Using proteomic data as biomarkers of environmental pollution has the potential to be of a great interest in ecological risk assessment as they constitute early warning indicators of ecologically relevant effects on biological systems. To develop such specific and sensitive biomarkers, the use of a set of proteins is required and the identification of protein expression signatures (PES) may reflect the exposure to specific classes of pollutants. Using 2D-DIGE (Differential in Gel Electrophoresis) methodology, this study aimed at identifying specific PES on European eel (Anguilla anguilla) peripheral blood mononuclear cells (PBMC) after 48 h in vitro exposure to two sublethal concentrations of dichlorodiphenyltrichloroethane (p,p'-DDT) (10 μg/L and 1mg/L) or cadmium (Cd) (1 μg/L and 100 μg/L). The present results have been supplemented with data of a first in vitro study on cells exposed to perfluorooctane sulfonate (PFOS) (10 μg/L and 1mg/L). A total of thirty-four protein spots, belonging to 18 different identified proteins found in all conditions, have been selected as possible biomarkers to develop a synthetic Integrated Biomarker Proteomic (IBP) index. IBP follows a dose-response relationship with higher values at the highest tested concentration for each pollutant (Cd: 9.96; DDT: 7.44; PFOS: 7.94) compared to the lowest tested concentration (Cd: 3.81; DDT: 2.91; PFOS: 2.06). In a second step, star plot graphs have been applied to proteomic data in order to allow visual integration of a set of early warning responses measured with protein biomarkers. Such star plots permit to discriminate the type of pollutant inducing a proteomic response. We conclude that using IBP is relevant in environmental risk assessment, giving to this index the potential to be applied as a global index of proteome alteration in endangered species such as the European eel. In this study, 34 protein spots have been selected as possible biomarkers to develop a synthetic Integrated

The colloidal thyroxine (T4) ring as a novel biomarker of perchlorate exposure in the African clawed frog Xenopus laevis

Science.gov (United States)

Hu, F.; Sharma, Bibek; Mukhi, S.; Patino, R.; Carr, J.A.

2006-01-01

The purpose of this study was to determine if changes in colloidal thyroxine (T4) immunoreactivity can be used as a biomarker of perchlorate exposure in amphibian thyroid tissue. Larval African clawed frogs (Xenopus laevis) were exposed to 0, 1, 8, 93, and 1131 ??g perchlorate/l for 38 and 69 days to cover the normal period of larval development and metamorphosis. The results of this study confirmed the presence of an immunoreactive colloidal T4 ring in thyroid follicles of X. laevis and demonstrated that the intensity of this ring is reduced in a concentration-dependent manner by perchlorate exposure. The smallest effective concentration of perchlorate capable of significantly reducing colloidal T4 ring intensity was 8 ??g perchlorate/l. The intensity of the immunoreactive colloidal T4 ring is a more sensitive biomarker of perchlorate exposure than changes in hind limb length, forelimb emergence, tail resorption, thyrocyte hypertrophy, or colloid depletion. We conclude that the colloidal T4 ring can be used as a sensitive biomarker of perchlorate-induced thyroid disruption in amphibians. ?? Copyright 2006 Oxford University Press.

Gene transcription and biomarker responses in the clam Ruditapes philippinarum after exposure to ibuprofen

Energy Technology Data Exchange (ETDEWEB)

Milan, Massimo; Pauletto, Marianna; Patarnello, Tomaso; Bargelloni, Luca [Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell' Universita 16, Legnaro (Padova) (Italy); Marin, Maria Gabriella [Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova (Italy); Matozzo, Valerio, E-mail: matozzo@bio.unipd.it [Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova (Italy)

2013-01-15

Pharmaceuticals are a class of emerging environmental contaminants that continuously enter aquatic environments. Presently, little information is available about the effects of these substances on non-target organisms, such as bivalves. We investigated the effects of ibuprofen (IBU) on the clam Ruditapes philippinarum. Clams were exposed for 1, 3, 5 and 7 days to 0, 100 and 1000 {mu}g IBU/L, and established biomarker responses (haemolymph lysozyme, gill acetylcholinesterase and digestive gland superoxide dismutase activities) as well as digestive gland transcriptome were evaluated. A two-way ANOVA revealed significant effects of both 'IBU concentration' and 'exposure duration' on biomarker responses. Overall, the enzyme activities were generally lower in IBU-exposed clams than in controls. Although limited knowledge of the mollusc transcriptome makes it difficult to interpret the effects of IBU on clams, the gene transcription analysis using DNA microarrays enabled the identification of the putative molecular mode of action of the IBU. The functional analysis of differentially transcribed genes suggests that IBU can interfere with various signalling pathways in clams, such as arachidonic acid metabolism, apoptosis, peroxisomal proliferator-activated receptors, and nuclear factor-kappa B. In addition, several genes involved in the metabolism of xenobiotics (e.g., glutathione S-transferase, sulfotransferase, cytochrome P450) were also found to be significantly affected by IBU exposure. In summary, the integrated approach of gene transcription analysis and biomarker responses facilitated the elucidation of the putative mechanisms of action of IBU in non-target species.

Gene transcription and biomarker responses in the clam Ruditapes philippinarum after exposure to ibuprofen

International Nuclear Information System (INIS)

Milan, Massimo; Pauletto, Marianna; Patarnello, Tomaso; Bargelloni, Luca; Marin, Maria Gabriella; Matozzo, Valerio

2013-01-01

Pharmaceuticals are a class of emerging environmental contaminants that continuously enter aquatic environments. Presently, little information is available about the effects of these substances on non-target organisms, such as bivalves. We investigated the effects of ibuprofen (IBU) on the clam Ruditapes philippinarum. Clams were exposed for 1, 3, 5 and 7 days to 0, 100 and 1000 μg IBU/L, and established biomarker responses (haemolymph lysozyme, gill acetylcholinesterase and digestive gland superoxide dismutase activities) as well as digestive gland transcriptome were evaluated. A two-way ANOVA revealed significant effects of both “IBU concentration” and “exposure duration” on biomarker responses. Overall, the enzyme activities were generally lower in IBU-exposed clams than in controls. Although limited knowledge of the mollusc transcriptome makes it difficult to interpret the effects of IBU on clams, the gene transcription analysis using DNA microarrays enabled the identification of the putative molecular mode of action of the IBU. The functional analysis of differentially transcribed genes suggests that IBU can interfere with various signalling pathways in clams, such as arachidonic acid metabolism, apoptosis, peroxisomal proliferator-activated receptors, and nuclear factor-kappa B. In addition, several genes involved in the metabolism of xenobiotics (e.g., glutathione S-transferase, sulfotransferase, cytochrome P450) were also found to be significantly affected by IBU exposure. In summary, the integrated approach of gene transcription analysis and biomarker responses facilitated the elucidation of the putative mechanisms of action of IBU in non-target species.

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials.

Science.gov (United States)

Iavicoli, Ivo; Leso, Veruscka; Schulte, Paul A

2016-05-15

Rapid advances and applications in nanotechnology are expected to result in increasing occupational exposure to nano-sized materials whose health impacts are still not completely understood. Scientific efforts are required to identify hazards from nanomaterials and define risks and precautionary management strategies for exposed workers. In this scenario, the definition of susceptible populations, which may be at increased risk of adverse effects may be important for risk assessment and management. The aim of this review is to critically examine available literature to provide a comprehensive overview on susceptibility aspects potentially affecting heterogeneous responses to nanomaterials workplace exposure. Genetic, genotoxic and epigenetic alterations induced by nanomaterials in experimental studies were assessed with respect to their possible function as determinants of susceptibility. Additionally, the role of host factors, i.e. age, gender, and pathological conditions, potentially affecting nanomaterial toxicokinetic and health impacts, were also analysed. Overall, this review provides useful information to obtain insights into the nanomaterial mode of action in order to identify potentially sensitive, specific susceptibility biomarkers to be validated in occupational settings and addressed in risk assessment processes. The findings of this review are also important to guide future research into a deeper characterization of nanomaterial susceptibility in order to define adequate risk communication strategies. Ultimately, identification and use of susceptibility factors in workplace settings has both scientific and ethical issues that need addressing. Copyright © 2015 Elsevier Inc. All rights reserved.

Human Biomonitoring of Engineered Nanoparticles: An Appraisal of Critical Issues and Potential Biomarkers

Directory of Open Access Journals (Sweden)

Enrico Bergamaschi

2012-01-01

Full Text Available The present paper deals with the applicability of biological monitoring to the assessment of exposure and possible effects deriving from exposure to engineered nanomaterials (NM. After establishing a conceptual framework in which human biomonitoring should be placed, the paper reviews the critical issues related to the unusual properties of NM affecting the implementation of biomonitoring activities for this new class of chemicals. Relying on the recent advances in the toxicogenomic, it is possible to assess whether specific biological pathways are activated or perturbed by specific NM. However, to evaluate if quantitative changes in these biomarkers can be used as indicators or predictors for toxicity in humans, validation on well characterised groups of exposed people is needed. At present, it appears more pragmatic to evolve NM-associated biomarker identification considering relevant biological responses found in environmental and occupational studies and assessing the early events associated with exposure to these NM. The battery of biochemical markers includes soluble molecules, antioxidant capacity, peroxidated lipids and carbonyl groups in serum proteins as a biomarkers of systemic inflammation and vascular adhesion molecules to assess endothelial activation/damage. Abnormalities in exhaled breath condensate chemistry reflecting intrinsic changes in the airway lining fluid and lung inflammation seem promising tools suitable for BM studies and are broadly discussed.

Characterisation of esterases as potential biomarkers of pesticide exposure in the lugworm Arenicola marina (Annelida: Polychaeta)

International Nuclear Information System (INIS)

Hannam, Marie L.; Hagger, Josephine A.; Jones, Malcolm B.; Galloway, Tamara S.

2008-01-01

Here, we identify and characterise cholinesterase (ChE) and carboxylesterase (CbE) activities in the body tissues of the sediment dwelling worm Arenicola marina. Exposure to the organophosphorus pesticide azamethiphos yielded an in vitro IC 50 of 5 μg l -1 for propionylcholinesterase (PChE). PChE was significantly inhibited in vivo after a 10 day exposure to 100 μg l -1 azamethiphos, equivalent to the recommended aquatic application rate (ANOVA; F = 2.75, P = 0.033). To determine sensitivity to environmental conditions, A. marina were exposed for 10 days to field collected sediments. PChE activity was significantly lower in worms exposed to sediments from an estuary classified to be at high risk from point source pollution by the UK Environment Agency (ANOVA; F = 15.33, P < 0.001). Whilst causality cannot be directly attributed from these latter exposures, they provide an important illustration of the potential utility of esterase activity as a biomarker of environmental quality in this ecologically relevant sentinel species. - This paper provides a preliminary characterisation of esterase enzyme activities in the tissues and body fluids of the sediment dwelling worm Arenicola marina and explores their potential use as biomarkers of organophosphorus pesticide exposure in the marine environment

Characterisation of esterases as potential biomarkers of pesticide exposure in the lugworm Arenicola marina (Annelida: Polychaeta)

Energy Technology Data Exchange (ETDEWEB)

Hannam, Marie L. [Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth, Devon, PL4 8AA (United Kingdom)], E-mail: marie.hannam@plymouth.ac.uk; Hagger, Josephine A.; Jones, Malcolm B.; Galloway, Tamara S. [Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth, Devon, PL4 8AA (United Kingdom)

2008-03-15

Here, we identify and characterise cholinesterase (ChE) and carboxylesterase (CbE) activities in the body tissues of the sediment dwelling worm Arenicola marina. Exposure to the organophosphorus pesticide azamethiphos yielded an in vitro IC{sub 50} of 5 {mu}g l{sup -1} for propionylcholinesterase (PChE). PChE was significantly inhibited in vivo after a 10 day exposure to 100 {mu}g l{sup -1} azamethiphos, equivalent to the recommended aquatic application rate (ANOVA; F = 2.75, P = 0.033). To determine sensitivity to environmental conditions, A. marina were exposed for 10 days to field collected sediments. PChE activity was significantly lower in worms exposed to sediments from an estuary classified to be at high risk from point source pollution by the UK Environment Agency (ANOVA; F = 15.33, P < 0.001). Whilst causality cannot be directly attributed from these latter exposures, they provide an important illustration of the potential utility of esterase activity as a biomarker of environmental quality in this ecologically relevant sentinel species. - This paper provides a preliminary characterisation of esterase enzyme activities in the tissues and body fluids of the sediment dwelling worm Arenicola marina and explores their potential use as biomarkers of organophosphorus pesticide exposure in the marine environment.

Assessing exposure and health consequences of chemicals in drinking water: current state of knowledge and research needs.

Science.gov (United States)

Villanueva, Cristina M; Kogevinas, Manolis; Cordier, Sylvaine; Templeton, Michael R; Vermeulen, Roel; Nuckols, John R; Nieuwenhuijsen, Mark J; Levallois, Patrick

2014-03-01

Safe drinking water is essential for well-being. Although microbiological contamination remains the largest cause of water-related morbidity and mortality globally, chemicals in water supplies may also cause disease, and evidence of the human health consequences is limited or lacking for many of them. We aimed to summarize the state of knowledge, identify gaps in understanding, and provide recommendations for epidemiological research relating to chemicals occurring in drinking water. Assessing exposure and the health consequences of chemicals in drinking water is challenging. Exposures are typically at low concentrations, measurements in water are frequently insufficient, chemicals are present in mixtures, exposure periods are usually long, multiple exposure routes may be involved, and valid biomarkers reflecting the relevant exposure period are scarce. In addition, the magnitude of the relative risks tends to be small. Research should include well-designed epidemiological studies covering regions with contrasting contaminant levels and sufficient sample size; comprehensive evaluation of contaminant occurrence in combination with bioassays integrating the effect of complex mixtures; sufficient numbers of measurements in water to evaluate geographical and temporal variability; detailed information on personal habits resulting in exposure (e.g., ingestion, showering, swimming, diet); collection of biological samples to measure relevant biomarkers; and advanced statistical models to estimate exposure and relative risks, considering methods to address measurement error. Last, the incorporation of molecular markers of early biological effects and genetic susceptibility is essential to understand the mechanisms of action. There is a particular knowledge gap and need to evaluate human exposure and the risks of a wide range of emerging contaminants. Villanueva CM, Kogevinas M, Cordier S, Templeton MR, Vermeulen R, Nuckols JR, Nieuwenhuijsen MJ, Levallois P. 2014. Assessing

Novel exposure biomarkers of N,N-diethyl-m-toluamide (DEET): Data from the 2007-2010 National Health and Nutrition Examination Survey.

Science.gov (United States)

Calafat, Antonia M; Baker, Samuel E; Wong, Lee-Yang; Bishop, Amanda M; Morales-A, Pilar; Valentin-Blasini, Liza

2016-01-01

N,N-diethyl-m-toluamide (DEET) is a widely used insect repellent in the United States. To assess exposure to DEET in a representative sample of persons 6years and older in the U.S. general population from the 2007-2010 National Health and Nutrition Examination Survey. We analyzed 5348 urine samples by using online solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. We used regression models to examine associations of various demographic parameters with urinary concentrations of DEET biomarkers. We detected DEET in ~3% of samples and at concentration ranges (>0.08μg/L-45.1μg/L) much lower than those of 3-(diethylcarbamoyl)benzoic acid (DCBA) (>0.48μg/L-30,400μg/L) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB) (>0.09μg/L-332μg/L). DCBA was the most frequently detected metabolite (~84%). Regardless of survey cycle and the person's race/ethnicity or income, adjusted geometric mean concentrations of DCBA were higher in May-Sep than in Oct-Apr. Furthermore, non-Hispanic whites in the warm season were more likely than in the colder months [adjusted odds ratio (OR)=10.83; 95% confidence interval (CI), 3.28-35.79] and more likely than non-Hispanic blacks (OR=3.45; 95% CI, 1.51-7.87) to have DCBA concentrations above the 95th percentile. The general U.S. population, including school-age children, is exposed to DEET. However, reliance on DEET as the sole urinary biomarker would likely underestimate the prevalence of exposure. Instead, oxidative metabolites of DEET are the most adequate exposure biomarkers. Differences by season of the year based on demographic variables including race/ethnicity likely reflect different lifestyle uses of DEET-containing products. Published by Elsevier Ltd.

Evaluation of a biomarker of Cd(II) exposure on Limnoperna fortunei

International Nuclear Information System (INIS)

Mariano, Belaich; Cristian, Oliver; Marcela, Pilloff; Porta, Andres

2006-01-01

The use of organisms to monitor contamination allows the access to information that cannot be acquired by chemical methods. Limnoperna fortunei, mussel frequently found in Rio de la Plata estuary, fulfils the requirements to be used as a biomonitoring organism. In this work we report that a polypeptide of 22 kDa of molecular weight (LF22) is induced when L. fortunei is exposed to Cd (II), Cu(II) and Hg(II) sublethal levels. To characterize LF22, mussels were sampled from a non-polluted region and whole soft tissue was homogenized, with and without previous exposure to 100 μg/L of Cd(II). The cytosolic proteins were evaluated by mono and bidimensional SDS-PAGE, and size exclusion chromatography. All the methods showed that LF22 triples its concentration in presence of Cd(II). Purification of LF22 was achieved by fractioned precipitation, salting-out, ionic exchange and size exclusion chromatography. We conclude that LF22 is a useful biomarker of heavy metal exposure. - Limnoperna fortunei induces a 22 kDa polypeptide in sublethal exposure to Cd(II)

Longitudinal study of long-term smoking behaviour by biomarker-supported determination of exposure to smoke.

Science.gov (United States)

Cunningham, Anthony; Sommarström, Johan; Sisodiya, Ajit S; Errington, Graham; Prasad, Krishna

2014-04-12

Long-term studies of smokers who switch to lower nicotine yield cigarettes have been identified by the World Health Organization Study Group TobReg and the US Food and Drug Administration as one key area where new knowledge is required to guide science based regulation. The limited number of long-term switching studies have concluded that smokers who switch to lower nicotine yield cigarettes show evidence of partial compensation. Since the European Union tobacco product directive of 2001 introduced tar and nicotine yield ceilings, there has been no long-term observational switching study. To address the limitations of previous studies where smokers were forced switched for relatively short durations, we plan to undertake a long-term study of spontaneous switching which is appropriately powered and includes non-switchers as a control group. Healthy adult smokers aged 21-64 years will be enrolled into this 5-year non-residential, multicentre study across 10 cities in Germany. They will be assessed at 10 timepoints with 6 month intervals during which inclusion criteria will be reassessed and spent cigarette filter tips, saliva and 24 h urine samples will be collected. These samples will be used to determine average daily cigarette consumption, estimate mouth-level exposure to tar and nicotine and measure selected biomarkers of exposure, respectively. Spontaneous changes in subjects' preferred cigarette products and any consequent change in tar or nicotine yield will be monitored. Subjects will be required to complete questionnaires on quality of life, smoking behaviours, smoking-related sensory attributes and recent life changes. The planned study is anticipated to contribute to understanding smokers' behaviours and their consequent exposure to smoke constituents. It will also allow assessment of compensatory changes in their behaviour following spontaneous switching of cigarette product smoked. Data from this study are expected to provide insights into study design

Health and household air pollution from solid fuel use: the need for improved exposure assessment.

Science.gov (United States)

Clark, Maggie L; Peel, Jennifer L; Balakrishnan, Kalpana; Breysse, Patrick N; Chillrud, Steven N; Naeher, Luke P; Rodes, Charles E; Vette, Alan F; Balbus, John M

2013-10-01

Nearly 3 billion people worldwide rely on solid fuel combustion to meet basic household energy needs. The resulting exposure to air pollution causes an estimated 4.5% of the global burden of disease. Large variability and a lack of resources for research and development have resulted in highly uncertain exposure estimates. We sought to identify research priorities for exposure assessment that will more accurately and precisely define exposure-response relationships of household air pollution necessary to inform future cleaner-burning cookstove dissemination programs. As part of an international workshop in May 2011, an expert group characterized the state of the science and developed recommendations for exposure assessment of household air pollution. The following priority research areas were identified to explain variability and reduce uncertainty of household air pollution exposure measurements: improved characterization of spatial and temporal variability for studies examining both short- and long-term health effects; development and validation of measurement technology and approaches to conduct complex exposure assessments in resource-limited settings with a large range of pollutant concentrations; and development and validation of biomarkers for estimating dose. Addressing these priority research areas, which will inherently require an increased allocation of resources for cookstove research, will lead to better characterization of exposure-response relationships. Although the type and extent of exposure assessment will necessarily depend on the goal and design of the cookstove study, without improved understanding of exposure-response relationships, the level of air pollution reduction necessary to meet the health targets of cookstove interventions will remain uncertain.

Host Response to Environmental Hazards: Using Literature, Bioinformatics, and Computation to Derive Candidate Biomarkers of Toxic Industrial Chemical Exposure

Science.gov (United States)

2015-10-01

military threat chemicals with adverse health effects and clinical outcomes to improve diagnostic potential after exposure to toxic industrial...end organ injury following chemical exposures in the field. Markers of end-organ injury and toxicity and other health effects markers, particularly...Biomarkers of Toxic Industrial Chemical Exposure Major Jonathan D. Stallings *1 , Danielle L. Ippolito 1 , Anders Wallqvist 2 , B. Claire McDyre 3 , and

Maternal Arsenic Exposure, Arsenic Methylation Efficiency, and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico

Science.gov (United States)

Laine, Jessica E.; Bailey, Kathryn A.; Rubio-Andrade, Marisela; Olshan, Andrew F.; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H.; Stýblo, Miroslav; García-Vargas, Gonzalo G.

2014-01-01

Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. Results: DW-iAs for the study subjects ranged from iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations. Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192; http://dx.doi.org/10.1289/ehp.1307476 PMID:25325819

Biosensor Detection of Neuropathy Target Esterase in Whole Blood as a Biomarker of Exposure to Neuropathic Organophosphorus Compounds

National Research Council Canada - National Science Library

Makhaeva, Galina F; Sigolaeva, Larisa V; Zhuravleva, Lyudmila Z; Eremenko, Arkady V; Kurochkin, Ilya N; Malygin, Vladimir V; Richardson, Rudy J

2002-01-01

.... Lymphocyte NTE has also found use as a biomarker of human exposure to neuropathic OPs. Recently, a sensitive NTE biosensor was developed using a tyrosinase carbon-paste electrode for amperometric (Amp...

Biomarkers of PTSD: military applications and considerations.

Science.gov (United States)

Lehrner, Amy; Yehuda, Rachel

2014-01-01

Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment.

Science.gov (United States)

Chaudhari, Umesh; Nemade, Harshal; Wagh, Vilas; Gaspar, John Antonydas; Ellis, James K; Srinivasan, Sureshkumar Perumal; Spitkovski, Dimitry; Nguemo, Filomain; Louisse, Jochem; Bremer, Susanne; Hescheler, Jürgen; Keun, Hector C; Hengstler, Jan G; Sachinidis, Agapios

2016-11-01

The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming and are often insufficient to predict human relevant cardiotoxicity. The purpose of this study was to develop an in vitro repeated exposure toxicity methodology allowing the identification of predictive genomics biomarkers of functional relevance for drug-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The hiPSC-CMs were incubated with 156 nM doxorubicin, which is a well-characterized cardiotoxicant, for 2 or 6 days followed by washout of the test compound and further incubation in compound-free culture medium until day 14 after the onset of exposure. An xCELLigence Real-Time Cell Analyser was used to monitor doxorubicin-induced cytotoxicity while also monitoring functional alterations of cardiomyocytes by counting of the beating frequency of cardiomyocytes. Unlike single exposure, repeated doxorubicin exposure resulted in long-term arrhythmic beating in hiPSC-CMs accompanied by significant cytotoxicity. Global gene expression changes were studied using microarrays and bioinformatics tools. Analysis of the transcriptomic data revealed early expression signatures of genes involved in formation of sarcomeric structures, regulation of ion homeostasis and induction of apoptosis. Eighty-four significantly deregulated genes related to cardiac functions, stress and apoptosis were validated using real-time PCR. The expression of the 84 genes was further studied by real-time PCR in hiPSC-CMs incubated with daunorubicin and mitoxantrone, further anthracycline family members that are also known to induce cardiotoxicity. A panel of 35 genes was deregulated by all three anthracycline family members and can therefore be expected to predict the cardiotoxicity of compounds acting by similar mechanisms as doxorubicin, daunorubicin or mitoxantrone. The identified gene panel can be applied in the safety

Identification of Biomarkers of Exposure to FTOHs and PAPs in Humans Using a Targeted and Nontargeted Analysis Approach.

Science.gov (United States)

Dagnino, Sonia; Strynar, Mark J; McMahen, Rebecca L; Lau, Christopher S; Ball, Carol; Garantziotis, Stavros; Webster, Thomas F; McClean, Michael D; Lindstrom, Andrew B

2016-09-20

Although historic perfluorinated compounds are currently under scrutiny and growing regulatory control in the world, little is known about human exposure to other polyfluorinated compounds presently in use. Fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are known to degrade to terminal perfluorinated acids and toxic reactive intermediates through metabolic pathways. Therefore, it is important to characterize their human exposure by the identification of unique biomarkers. With the use of liquid chromatography-mass spectrometry-time-of-flight analysis (LC-MS-TOF), we developed a workflow for the identification of metabolites for the 8:2 FTOH and 8:2 diPAP. Analysis of serum and urine of dosed rats indicated the 8:2 FTOH-sulfate and the 8:2 diPAP as potential biomarkers. These compounds, as well as 25 other fluorinated compounds and metabolites, were analyzed in human serum and urine samples from the general population (n = 100) and office workers (n = 30). The 8:2 FTOH-sulfate was measured for the first time in human samples in 5 to 10% of the serum samples, ranging from 50 to 80 pg/mL. The 8:2 diPAP was measured in 58% of the samples, ranging from 100 to 800 pg/mL. This study indicates the FTOH-sulfate conjugate as a biomarker of exposure to FTOHs and PAPs in humans.

On the assessment of the added value of new predictive biomarkers.

Science.gov (United States)

Chen, Weijie; Samuelson, Frank W; Gallas, Brandon D; Kang, Le; Sahiner, Berkman; Petrick, Nicholas

2013-07-29

The surge in biomarker development calls for research on statistical evaluation methodology to rigorously assess emerging biomarkers and classification models. Recently, several authors reported the puzzling observation that, in assessing the added value of new biomarkers to existing ones in a logistic regression model, statistical significance of new predictor variables does not necessarily translate into a statistically significant increase in the area under the ROC curve (AUC). Vickers et al. concluded that this inconsistency is because AUC "has vastly inferior statistical properties," i.e., it is extremely conservative. This statement is based on simulations that misuse the DeLong et al. method. Our purpose is to provide a fair comparison of the likelihood ratio (LR) test and the Wald test versus diagnostic accuracy (AUC) tests. We present a test to compare ideal AUCs of nested linear discriminant functions via an F test. We compare it with the LR test and the Wald test for the logistic regression model. The null hypotheses of these three tests are equivalent; however, the F test is an exact test whereas the LR test and the Wald test are asymptotic tests. Our simulation shows that the F test has the nominal type I error even with a small sample size. Our results also indicate that the LR test and the Wald test have inflated type I errors when the sample size is small, while the type I error converges to the nominal value asymptotically with increasing sample size as expected. We further show that the DeLong et al. method tests a different hypothesis and has the nominal type I error when it is used within its designed scope. Finally, we summarize the pros and cons of all four methods we consider in this paper. We show that there is nothing inherently less powerful or disagreeable about ROC analysis for showing the usefulness of new biomarkers or characterizing the performance of classification models. Each statistical method for assessing biomarkers and

Is plasma β-glucuronidase a novel human biomarker for monitoring anticholinesterase pesticides exposure? A Malaysian experience

International Nuclear Information System (INIS)

Inayat-Hussain, Salmaan H.; Lubis, Syarif Husin; Sakian, Noor Ibrahim Mohamed; Ghazali, Ahmad Rohi; Ali, Noor Suhailah; El Sersi, Magdi; Toong, Lee Mun; Zainal, Awang Mat; Hashim, Suhaimi; Ghazali, Mohd Shariman; Saidin, Mohd Nazri; Rahman, Ab Razak Ab; Rafaai, Mohd Jamil Mohd; Omar, Sollahudin; Rapiai, Rafiah; Othman, Radziah; Chan, Lee Tiong; Johari, Amran; Soon, Wong Hing; Salleh, Abdul Rahim; Satoh, Tetsuo

2007-01-01

A cross-sectional study was conducted to investigate the effects of acute and chronic pesticide exposure on the plasma β-glucuronidase enzyme activity among five patients of acute pesticide poisoning in Tengku Ampuan Rahimah Hospital, Klang, 230 farmers in the MADA area, Kedah and 49 fishermen in Setiu, Terengganu. The duration of pesticide exposure among the patients was unknown, but the plasma samples from patients were collected on day one in the hospital. The duration of pesticide exposure among the farmers was between 1 and 45 years. The β-glucuronidase activity was compared with plasma cholinesterase activity in the same individual. The plasma cholinesterase activity was measured using Cholinesterase (PTC) Reagent set kit (Teco Diagnostics, UK) based on colorimetric method, while the plasma β-glucuronidase activity was measured fluorometrically based on β-glucuronidase assay. The plasma cholinesterase activity was significantly reduced (p 0.05). The plasma β-glucuronidase activity among the farmers was significantly elevated (p 0.05). The plasma cholinesterase activity was positively correlated with the plasma β-glucuronidase activity among the farmers (r = 0.205, p 0.05). Thus, plasma β-glucuronidase enzyme activity can be measured as a biomarker for the chronic exposure of pesticide. However, further studies need to be performed to confirm whether plasma β-glucuronidase can be a sensitive biomarker for anticholinesterase pesticide poisoning

Latent class models for joint analysis of disease prevalence and high-dimensional semicontinuous biomarker data.

Science.gov (United States)

Zhang, Bo; Chen, Zhen; Albert, Paul S

2012-01-01

High-dimensional biomarker data are often collected in epidemiological studies when assessing the association between biomarkers and human disease is of interest. We develop a latent class modeling approach for joint analysis of high-dimensional semicontinuous biomarker data and a binary disease outcome. To model the relationship between complex biomarker expression patterns and disease risk, we use latent risk classes to link the 2 modeling components. We characterize complex biomarker-specific differences through biomarker-specific random effects, so that different biomarkers can have different baseline (low-risk) values as well as different between-class differences. The proposed approach also accommodates data features that are common in environmental toxicology and other biomarker exposure data, including a large number of biomarkers, numerous zero values, and complex mean-variance relationship in the biomarkers levels. A Monte Carlo EM (MCEM) algorithm is proposed for parameter estimation. Both the MCEM algorithm and model selection procedures are shown to work well in simulations and applications. In applying the proposed approach to an epidemiological study that examined the relationship between environmental polychlorinated biphenyl (PCB) exposure and the risk of endometriosis, we identified a highly significant overall effect of PCB concentrations on the risk of endometriosis.

The use of discriminant analysis for evaluation of early-response multiple biomarkers of radiation exposure using non-human primate 6-Gy whole-body radiation model

Energy Technology Data Exchange (ETDEWEB)

Ossetrova, N.I. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: ossetrova@afrri.usuhs.mil; Farese, A.M.; MacVittie, T.J. [Marlene and Stewart Greenebaum Cancer Center, Bressler Research Building, Room 7-039, University of Maryland-Baltimore, 655 West Baltimore Street, Baltimore, MD 21201 (United States); Manglapus, G.L.; Blakely, W.F. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

2007-07-15

The present need to rapidly identify severely irradiated individuals in mass-casualty and population-monitoring scenarios prompted an evaluation of potential protein biomarkers to provide early diagnostic information after exposure. The level of specific proteins measured using immunodiagnostic technologies may be useful as protein biomarkers to provide early diagnostic information for acute radiation exposures. Herein we present results from on-going studies using a non-human primate (NHP) 6-Gy X-rays ( 0.13Gymin{sup -1}) whole-body radiation model. Protein targets were measured by enzyme-linked immunosorbent assay (ELISA) in blood plasma before, 1, and 2 days after exposure. Exposure of 10 NHPs to 6 Gy resulted in the up-regulation of plasma levels of (a) p21 WAF1/CIP1, (b) interleukin 6 (IL-6), (c) tissue enzyme salivary {alpha}-amylase, and (d) C-reactive protein. Data presented show the potential utility of protein biomarkers selected from distinctly different pathways to detect radiation exposure. A correlation analysis demonstrated strong correlations among different combinations of four candidate radiation-responsive blood protein biomarkers. Data analyzed with use of multivariate discriminant analysis established very successful separation of NHP groups: 100% discrimination power for animals with correct classification for separation between groups before and 1 day after irradiation, and 95% discrimination power for separation between groups before and 2 days after irradiation. These results also demonstrate proof-in-concept that multiple protein biomarkers provide early diagnostic information to the medical community, along with classical biodosimetric methodologies, to effectively manage radiation casualty incidents.

The Role of Urinary Biomarker Levels in Assessing the Presence and Severity of Ureteropelvic Junction Obstruction in Children: A Systematic Review and Meta-Analysis

Directory of Open Access Journals (Sweden)

Abbas Alipour

2016-07-01

Full Text Available Context Ureteropelvic junction obstruction (UPJO is the most common obstructive disease of the urinary tract in infancy and childhood with a prevalence of 15% - 45% in neonates with antenatal hydronephrosis. The diagnosis of UPJO should be confirmed by imaging studies - most of which have a propensity to radiation exposure. Objectives The current study aimed to present a review protocol to assess the role of measuring urinary biomarkers to distinguish severe UPJO from milder forms of the disease. Data Sources The database of UPJO studies was searched and studies that compared the levels of urinary biomarkers with the gold standard (i e, dynamic renal scans for UPJO diagnosis were selected. Severity assessment was done quantitatively. Study Selection Three hundred fifty-eight articles were identified across the electronic databases. Twenty-seven articles were selected for the final analyses. Data Extraction Data were extracted independently by three reviewers and analyzed using STATA software version 12. Results Meta-analysis of studies showed that patients with severe UPJO had significantly higher biomarker levels than those with mild to moderate obstruction, with a pooled standardized mean difference (SMD of 0.5 (confidence interval (CI 95%, 0.34 - 0.67; P < 0.001; and significantly higher biomarker standardized to urinary creatinine levels than those with mild to moderate obstruction, with a pooled SMD of 1.02 (95% CI, 0.88 - 1.16; P < 0.001. Meta-analysis showed that patients with severe UPJO had significantly higher biomarker levels than healthy children, with a pooled SMD of 1.27 (CI 95%, 1.16 - 1.39; P < 0.001; and significantly higher biomarker standardized to urinary creatinine levels than healthy children, with a pooled SMD of 1.14 (CI 95%, 0.95 - 1.32; P < 0.001. Conclusions The assessment of urinary biomarkers is a helpful tool to assess the presence and severity of UPJO, but there is little published data on each of the studied

Serum metabolome biomarkers associate low-level environmental perfluorinated compound exposure with oxidative /nitrosative stress in humans.

Science.gov (United States)

Wang, Xiaofei; Liu, Liangpo; Zhang, Weibing; Zhang, Jie; Du, Xiaoyan; Huang, Qingyu; Tian, Meiping; Shen, Heqing

2017-10-01

Previous in vivo and in vitro studies have linked perfluorinated compound (PFC) exposure with metabolic interruption, but the inter-species difference and high treatment doses usually make the results difficult to be extrapolated to humans directly. The best strategy for identifying the metabolic interruption may be to establish the direct correlations between monitored PFCs data and metabolic data on human samples. In this study, serum metabolome data and PFC concentrations were acquired for a Chinese adult male cohort. The most abundant PFCs are PFOA and PFOS with concentration medians 7.56 and 12.78 nM, respectively; in together they count around 81.6% of the total PFCs. PFC concentration-related serum metabolic profile changes and the related metabolic biomarkers were explored by using partial least squares-discriminant analysis (PLS-DA). Respectively taking PFOS, PFOA and total PFC as the classifiers, serum metabolome can be differentiated between the lowest dose group (1st quartile PFCs) and the highest PFC dose group (4th quartile PFCs). Ten potential PFC biomarkers were identified, mainly involving in pollutant detoxification, antioxidation and nitric oxide (NO) signal pathways. These suggested that low-level environmental PFC exposure has significantly adverse impacts on glutathione (GSH) cycle, Krebs cycle, nitric oxide (NO) generation and purine oxidation in humans. To the best of our knowledge, this is the first report investigating the association of environmental PFC exposure with human serum metabolome alteration. Given the important biological functions of the identified biomarkers, we suggest that PFC could increase the metabolism syndromes risk including diabetes and cardiovascular diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

TSPY4 is a novel sperm-specific biomarker of semen exposure in human cervicovaginal fluids; potential use in HIV prevention and contraception studies.

Science.gov (United States)

Jacot, Terry A; Zalenskaya, Irina; Mauck, Christine; Archer, David F; Doncel, Gustavo F

2013-09-01

Developing an objective, reliable method to determine semen exposure in cervicovaginal fluids is important for accurately studying the efficacy of vaginal microbicides and contraceptives. Y-chromosome biomarkers offer better stability, sensitivity, and specificity than protein biomarkers. TSPY4 belongs to the TSPY (testis-specific protein Y-encoded) family of homologous genes on the Y-chromosome. Using a multiplex PCR amplifying TSPY4, amelogenin, and Sex-determining region in the Y chromosome (SRY), our objective was to determine whether a gene in the TSPY family was a more sensitive marker of semen exposure in cervicovaginal fluids than SRY. The multiplex polymerase chain reaction (PCR) was developed using sperm and vaginal epithelial (female) DNA. Diluted sperm DNA and mixed male/female DNA was used to determine the sensitivity of the multiplex PCR. Potential interference of TSPY4 amplification by components in cervicovaginal and seminal fluids was determined. TSPY4 and SRY amplification was also investigated in women participating in a separate IRB-approved clinical study in which cervicovaginal swab DNA was collected before semen exposure and at various time points after exposure. TSPY4, SRY, and amelogenin were amplified in sperm DNA, but only amelogenin in female DNA. The limit of sperm DNA from which TSPY4 could be amplified was lower than SRY (4 pg vs 80 pg). TSPY4 could also be amplified from mixed male/female DNA. Amplification was not affected by cervicovaginal and seminal components. Using cervicovaginal swab DNA from three women before and after semen exposure, TSPY4 was detected up to 72 h post exposure while SRY detection was observed up to 24-48 h. TSPY4 was detected up to 7 days post exposure in one out of three women. We have demonstrated that TSPY4 is a new sensitive, and sperm-specific biomarker. The multiplex PCR incorporating this new biomarker has potential to be an objective measure for determining semen exposure in clinical trials of

Measuring urinary N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (IPMA3) as a potential biomarker of isoprene exposure.

Science.gov (United States)

Alwis, K Udeni; Bailey, T Liz; Patel, Dhrusti; Wang, Liqun; Blount, Benjamin C

2016-10-19

Isoprene, the 2-methyl analog of 1,3-butadiene, is identified as a possible human carcinogen by the International Agency for Research on Cancer (IARC). Isoprene is ubiquitous in the environment with numerous natural and anthropogenic sources. Tobacco smoke is the main exogenous source of isoprene exposure in indoor environments. Among smoke constituents, isoprene is thought to contribute significantly to cancer risk; however, no selective urinary biomarkers of isoprene exposure have been identified for humans. In this manuscript, we measured the minor isoprene metabolite IPMA1 (mixture of N-acetyl-S-(1-[hydroxymethyl]-2-methyl-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3-methyl-3-buten-1-yl)-L-cysteine), and we identified IPMA3 (N-acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine) as a major isoprene metabolite and novel isoprene exposure biomarker for humans. Urinary isoprene metabolites were measured using ultra high performance liquid chromatography coupled with electrospray ionization triple quad tandem mass spectrometry (UPLC/ESI-MSMS). The detection rates of IPMA1 and IPMA3 are <20% and 82%, respectively. The selectivity and abundance of IPMA3 make it a useful urinary biomarker of isoprene exposure. The limit of detection of IPMA3 in urine was 0.5 ng mL -1 . IPMA3 was stable under different storage temperatures and following ten freeze-thaw cycles. The average recovery of urine spiked with IPMA3 at three different levels was 99%. IPMA3 was measured in urine samples received from 75 anonymous subjects; the median (25th percentile, 75th percentile) IPMA3 level in smokers was 36.2 (18.2, 56.8) ng mL -1 and non-smokers 2.31 (2.31, 4.38) ng mL -1 . Application of this method to large population studies will help to characterize isoprene exposure and assess potential health impact. Published by Elsevier B.V.

Biomarkers of intermediate endpoints in environmental and occupational health

DEFF Research Database (Denmark)

Knudsen, Lisbeth E; Hansen, Ase M

2007-01-01

The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

Exposure to organophosphate flame retardants in spray polyurethane foam applicators: Role of dermal exposure.

Science.gov (United States)

Bello, Anila; Carignan, Courtney C; Xue, Yalong; Stapleton, Heather M; Bello, Dhimiter

2018-04-01

Spray polyurethane foam (SPF) is a highly effective thermal insulation material that has seen considerable market growth in the past decade. Organophosphate flame retardants (PFRs) are added to SPF formulations to meet fire code requirements. A common flame retardant used in SPF formulations is tris 1-chloro 2-propyl phosphate (TCIPP), a suspected endocrine disruptor. Exposure monitoring efforts during SPF applications have focused primarily on the isocyanate component, a potent respiratory and dermal sensitizer. However, to our knowledge, there is no monitoring data for TCIPP. To characterize occupational exposures to TCIPP and other flame retardants during SPF insulation. Workers at four SPF insulation sites and one foam removal site (total n = 14) were recruited as part of this pilot study. Personal inhalation exposure to TCIPP was monitored with a CIP-10MI inhalable sampler and potential dermal exposure was assessed through the use of a glove dosimeter. Biomarkers of TCIPP and three other PFRs were measured in urine collected from workers pre-and post-shift. Linear mixed effect models were used to analyze associations of urinary biomarkers with inhalation and dermal exposures and paired t-tests were used to examine the difference on the means of urinary biomarkers pre-and post-shift. Chemical analysis of all species was performed with liquid chromatography-electrospray ionization tandem mass spectrometry. Geometric mean (GM) concentrations of TCIPP in personal air monitors and glove dosimeters collected from SPF applicators, 294.7 μg/m 3 and 18.8 mg/pair respectively. Overall, GM concentrations of the two TCIPP urinary biomarkers BCIPP and BCIPHIPP and (6.2 and 88.8 μg/mL) were 26-35 times higher than reported in the general population. Post-shift levels of TCIPP biomarkers were higher than pre-shift even though workers at insulation sites wore supplied air respirators, gloves and coveralls. The urinary biomarkers for the other PFRs were not

Calcium-deficiency assessment and biomarker identification by an integrated urinary metabonomics analysis

Science.gov (United States)

2013-01-01

Background Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. Methods The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. Results Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson

Integrated Environmental Assessment Part III: ExposureAssessment

Energy Technology Data Exchange (ETDEWEB)

McKone, Thomas E.; Small, Mitchell J.

2006-06-01

Human exposure assessment is a key step in estimating the environmental and public health burdens that result chemical emissions in the life cycle of an industrial product or service. This column presents the third in a series of overviews of the state of the art in integrated environmental assessment - earlier columns described emissions estimation (Frey and Small, 2003) and fate and transport modeling (Ramaswami, et al., 2004). When combined, these first two assessment elements provide estimates of ambient concentrations in the environment. Here we discuss how both models and measurements are used to translate ambient concentrations into metrics of human and ecological exposure, the necessary precursors to impact assessment. Exposure assessment is the process of measuring and/or modeling the magnitude, frequency and duration of contact between a potentially harmful agent and a target population, including the size and characteristics of that population (IPCS, 2001; Zartarian, et al., 2005). Ideally the exposure assessment process should characterize the sources, routes, pathways, and uncertainties in the assessment. Route of exposure refers to the way that an agent enters the receptor during an exposure event. Humans contact pollutants through three routes--inhalation, ingestion, and dermal uptake. Inhalation occurs in both outdoor environments and indoor environments where most people spend the majority of their time. Ingestion includes both water and food, as well as soil and dust uptake due to hand-to-mouth activity. Dermal uptake occurs through contacts with consumer products; indoor and outdoor surfaces; the water supply during washing or bathing; ambient surface waters during swimming or boating; soil during activities such as work, gardening, and play; and, to a lesser extent, from the air that surrounds us. An exposure pathway is the course that a pollutant takes from an ambient environmental medium (air, soil, water, biota, etc), to an exposure medium

Future research needs associated with the assessment of potential human health risks from exposure to toxic ambient air pollutants

DEFF Research Database (Denmark)

Möller, Lennart; Schuetzle, Dennis; Autrup, Herman

1994-01-01

of identification and quantification of toxics in source emissions and ambient air, atmospheric transport and chemistry, exposure level assessment, the development of improved in vitro bioassays, biomarker development, the development of more accurate epidemiological methodologies, and risk quantification......This paper presents key conclusions and future research needs from a Workshop on the Risk Assessment of Urban Air, Emissions, Exposure, Risk Identification, and Quantification, which was held in Stockholm during June 1992 by 41 participants from 13 countries. Research is recommended in the areas...... techniques. Studies are described that will be necessary to assess and reduce the level of uncertainties associated with each step of the risk assessment process. International collaborative research efforts between industry and government organizations are recommended as the most effective way to carry out...

Biomarkers of PTSD: military applications and considerations

Directory of Open Access Journals (Sweden)

Amy Lehrner

2014-08-01

Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

Roles of biomarkers in evaluating interactions among mixtures of lead, cadmium and arsenic

International Nuclear Information System (INIS)

Wang Gensheng; Fowler, Bruce A.

2008-01-01

Human exposure to environmental chemicals is most correctly characterized as exposure to mixtures of these agents. The metals/metalloids, lead (Pb), cadmium (Cd), and arsenic (As), are among the leading toxic agents detected in the environment. Exposure to these elements, particularly at chronic low dose levels, is still a major public health concern. Concurrent exposure to Pb, Cd, or As may produce additive or synergistic interactions or even new effects that are not seen in single component exposures. Evaluating these interactions on a mechanistic basis is essential for risk assessment and management of metal/metalloid mixtures. This paper will review a number of individual studies that addressed interactions of these metals/metalloids in both experimental and human exposure studies with particular emphasis on biomarkers. In general, co-exposure to metal/metalloid mixtures produced more severe effects at both relatively high dose and low dose levels in a biomarker-specific manner. These effects were found to be mediated by dose, duration of exposure and genetic factors. While traditional endpoints, such as morphological changes and biochemical parameters for target organ toxicity, were effective measures for evaluating the toxicity of high dose metal/metalloid mixtures, biomarkers for oxidative stress, altered heme biosynthesis parameters, and stress proteins showed clear responses in evaluating toxicity of low dose metal/metalloid mixtures. Metallothionein, heat shock proteins, and glutathione are involved in regulating interactive effects of metal/metalloid mixtures at low dose levels. These findings suggest that further studies on interactions of these metal/metalloid mixtures utilizing biomarker endpoints are highly warranted

Human biomonitoring after chemical incidents and during short-term maintenance work as a tool for exposure analysis and assessment.

Science.gov (United States)

Bader, M; Van Weyenbergh, T; Verwerft, E; Van Pul, J; Lang, S; Oberlinner, C

2014-12-15

Human biomonitoring (HBM) is frequently used for the analysis and assessment of exposure to chemicals under routine working conditions. In recent years, HBM has also been applied to monitor the exposure of the general population, and of emergency responders in the aftermath of chemical incidents. Two examples of targeted HBM programs in the chemical industry are described and discussed in this paper: (1) analysis and assessment of the exposure of firefighters and chemical workers after the spill of p-chloroaniline from a burning chemical barrel, and (2) biomonitoring of maintenance workers potentially exposed to benzene during regular turnarounds. The results of these investigations underline that human biomonitoring contributes substantially to comprehensive exposure analyses, human health risk assessments and communication. In addition, regular HBM surveillance and feedback can assist in the continuous improvement of workplace safety measures and exposure control. In conclusion, data on accidental or short-term exposure to hazardous chemicals are an important source of information for the further development of limit and assessment values, the validation of biomarkers and of targeted HBM programs for both routine monitoring and disaster management. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Assessment of human exposures

Energy Technology Data Exchange (ETDEWEB)

Lebret, E. [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

1995-12-31

This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

Assessment of human exposures

Energy Technology Data Exchange (ETDEWEB)

Lebret, E [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

1996-12-31

This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity?

Science.gov (United States)

Mohan, Chandra; Assassi, Shervin

2015-11-26

Serological and proteomic biomarkers can help clinicians diagnose rheumatic diseases earlier and assess disease activity more accurately. These markers have been incorporated into the recently revised classification criteria of several diseases to enable early diagnosis and timely initiation of treatment. Furthermore, they also facilitate more accurate subclassification and more focused monitoring for the detection of certain disease manifestations, such as lung and renal involvement. These biomarkers can also make the assessment of disease activity and treatment response more reliable. Simultaneously, several new serological and proteomic biomarkers have become available in the routine clinical setting--for example, a protein biomarker panel for rheumatoid arthritis and a myositis antibody panel for dermatomyositis and polymyositis. This review will focus on commercially available antibody and proteomic biomarkers in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis and polymyositis, and axial spondyloarthritis (including ankylosing spondylitis). It will discuss how these markers can facilitate early diagnosis as well as more accurate subclassification and assessment of disease activity in the clinical setting. The ultimate goal of current and future biomarkers in rheumatic diseases is to enable early detection of these diseases and their clinical manifestations, and to provide effective monitoring and treatment regimens that are tailored to each patient's needs and prognosis. © BMJ Publishing Group Ltd 2015.

Future research needs associated with the assessment of potential human health risks from exposure to toxic ambient air pollutants

DEFF Research Database (Denmark)

Möller, Lennart; Schuetzle, Dennis; Autrup, Herman

1994-01-01

of identification and quantification of toxics in source emissions and ambient air, atmospheric transport and chemistry, exposure level assessment, the development of improved in vitro bioassays, biomarker development, the development of more accurate epidemiological methodologies, and risk quantification...... techniques. Studies are described that will be necessary to assess and reduce the level of uncertainties associated with each step of the risk assessment process. International collaborative research efforts between industry and government organizations are recommended as the most effective way to carry out...

Determination of Phthalate Metabolites in Human Serum and Urine as Biomarkers for Phthalate Exposure Using Column-Switching LC-MS/MS

Directory of Open Access Journals (Sweden)

Jee Yeon Jeong

2011-03-01

Conclusion:The accuracy and precision of the analytical method indicate that urinary metabolite determination can be a more acceptable biomarker for studying phthalate exposure and adverse health outcomes.

Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

International Nuclear Information System (INIS)

LaCourse, E. James; Hernandez-Viadel, Mariluz; Jefferies, James R.; Svendsen, Claus; Spurgeon, David J.; Barrett, John; John Morgan, A.; Kille, Peter; Brophy, Peter M.

2009-01-01

The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

Energy Technology Data Exchange (ETDEWEB)

LaCourse, E. James, E-mail: james.la-course@liverpool.ac.u [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Hernandez-Viadel, Mariluz; Jefferies, James R. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Svendsen, Claus; Spurgeon, David J. [Centre for Ecology and Hydrology, Huntingdon PE28 2LS (United Kingdom); Barrett, John [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); John Morgan, A.; Kille, Peter [Biosciences, University of Cardiff, Cardiff CF10 3TL (United Kingdom); Brophy, Peter M. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom)

2009-08-15

The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

Identification of new biomarker of radiation exposure for establishing rapid, simplified biodosimetric method

International Nuclear Information System (INIS)

Iizuka, Daisuke; Kawai, Hidehiko; Kamiya, Kenji; Suzuki, Fumio; Izumi, Shunsuke

2014-01-01

Until now, counting chromosome aberration is the most accurate method for evaluating radiation doses. However, this method is time consuming and requires skills for evaluating chromosome aberrations. It could be difficult to apply this method to majority of people who are expected to be exposed to ionizing radiation. In this viewpoint, establishment of rapid, simplified biodosimetric methods for triage will be anticipated. Due to the development of mass spectrometry method and the identification of new molecules such as microRNA (miRNA), it is conceivable that new molecular biomarker of radiation exposure using some newly developed mass spectrometry. In this review article, the part of our results including the changes of protein (including the changes of glycosylation), peptide, metabolite, miRNA after radiation exposure will be shown. (author)

Biomarker analysis of American toad (Anaxyrus americanus) and grey tree frog (Hyla versicolor) tadpoles following exposure to atrazine.

Science.gov (United States)

The objective of the current study was to use a biomarker-based approach to investigate the influence of atrazine exposure on American toad (Anaxyrus americanus) and grey tree frog (Hyla versicolor) tadpoles. Atrazine is one of the most frequently detected herbicides in environme...

Effects of electromagnetic fields exposure on plasma hormonal and inflammatory pathway biomarkers in male workers of a power plant

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhaopin; Fei, Ying; Liu, Hui [Zhejiang Univ., Hangzhou (China). Dept. of Epidemiology and Health Statistics; Zhejiang Univ., Hangzhou (China). Chronic Disease Research Inst.; and others

2016-01-15

The potential health risks of electromagnetic fields (EMFs) have currently raised considerable public concerns. The aim of this study was to evaluate the effects of EMF exposure on levels of plasma hormonal and inflammatory pathway biomarkers in male workers of an electric power plant. Seventy-seven male workers with high occupational EMF exposure and 77 male controls with low exposure, matched by age, were selected from a cross-sectional study. Moreover, high EMF exposure group was with walkie-talkies usage and exposed to power frequency EMF at the work places for a longer duration than control group. A questionnaire was applied to obtain relevant information, including sociodemographic characteristics, lifestyle factors, and EMF exposures. Plasma levels of testosterone, estradiol, melatonin, NF-KB, heat-shock protein (HSP) 70, HSP27, and TET1 were determined by an enzyme-linked immunosorbent assay. EMF exposure group had statistically significantly lower levels of testosterone (β = -0.3 nmol/L, P = 0.015), testosterone/estradiol (T/E2) ratio (β = -15.6, P = 0.037), and NF-KB (β = -20.8 ng/L, P = 0.045) than control group. Moreover, joint effects between occupational EMF exposure and employment duration, mobile phone fees, years of mobile phone usage, and electric fees on levels of testosterone and T/E2 ratio were observed. Nevertheless, no statistically significant associations of EMF exposures with plasma estradiol, melatonin, HSP70, HSP27, and TET1 were found. The findings showed that chronic exposure to EMF could decrease male plasma testosterone and T/E2 ratio, and it might possibly affect reproductive functions in males. No significant associations of EMF exposure with inflammatory pathway biomarkers were found.

The Aggregate Exposure Pathway (AEP): A conceptual framework for advancing exposure science research and applications

Science.gov (United States)

Historically, risk assessment has relied upon toxicological data to obtain hazard-based reference levels, which are subsequently compared to exposure estimates to determine whether an unacceptable risk to public health may exist. Recent advances in analytical methods, biomarker ...

The Aggregate Exposure Pathway (AEP): A conceptual framework for advancing exposure science research and transforming risk assessment

Science.gov (United States)

Recent advances in analytical methods, biomarker discovery, cell-based assay development, computational tools, sensor/monitor, and omics technology have enabled new streams of exposure and toxicity data to be generated at higher volumes and speed. These new data offer the opport...

The role of biomarkers in evaluating human health concerns from fungal contaminants in food.

Science.gov (United States)

Turner, Paul C; Flannery, Brenna; Isitt, Catherine; Ali, Mariyam; Pestka, James

2012-06-01

Mycotoxins are toxic secondary metabolites that globally contaminate an estimated 25 % of cereal crops and thus exposure is frequent in many populations. Aflatoxins, fumonisins and deoxynivalenol are amongst those mycotoxins of particular concern from a human health perspective. A number of risks to health are suggested including cancer, growth faltering, immune suppression and neural tube defects; though only the demonstrated role for aflatoxin in the aetiology of liver cancer is widely recognised. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates; instead biomarkers provide better tools for informing epidemiological investigations. Validated exposure biomarkers for aflatoxin (urinary aflatoxin M(1), aflatoxin-N7-guaunine, serum aflatoxin-albumin) were established almost 20 years ago and were critical in confirming aflatoxins as potent liver carcinogens. Validation has included demonstration of assay robustness, intake v. biomarker level, and stability of stored samples. More recently, aflatoxin exposure biomarkers are revealing concerns of growth faltering and immune suppression; importantly, they are being used to assess the effectiveness of intervention strategies. For fumonisins and deoxynivalenol these steps of development and validation have significantly advanced in recent years. Such biomarkers should better inform epidemiological studies and thus improve our understanding of their potential risk to human health.

Comparison of Biomarkers of Tobacco Exposure between Premium and Discount Brand Cigarette Smokers in the NHANES 2011-2012 Special Sample.

Science.gov (United States)

Wasserman, Emily J; Reilly, Samantha M; Goel, Reema; Foulds, Jonathan; Richie, John P; Muscat, Joshua E

2018-05-01

Background: Increased cigarette costs have inadvertently strengthened the appeal of discounted brands to price-sensitive smokers. Although smokers perceive discounted brands as having poorer quality, little is known about their delivery of toxic tobacco smoke constituents compared with premium-branded tobacco products. Methods: We investigated the differences between discount and premium brand smokers using the National Health and Nutrition Examination Survey 2011-2012 Special Smoker Sample. Our analyses focused on demographic differences and 27 biomarkers of harmful and potentially harmful constituents (HPHC) listed by the FDA, including volatile organic compounds, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronide; reported as total NNAL (tNNAL)], metals, and polycyclic aromatic hydrocarbons (PAHs). Data were analyzed using linear regression models adjusting for potential confounders. Results: A total of 976 non-tobacco users and 578 recent cigarette smokers were eligible for analysis, of which 141 (26.0% weighted) smoked discount brand cigarettes and 437 (74.0% weighted) smoked premium. Discount brand smokers were older, predominantly non-Hispanic white, and had higher serum cotinine. Discount brand smokers had significantly higher levels of 13 smoking-related biomarkers, including tNNAL, uranium, styrene, xylene, and biomarkers of exposure to PAHs (naphthalene, fluorene, and phenanthrene), compared with premium brand smokers. Conclusions: These findings suggest that discount cigarette use is associated with higher exposure to several carcinogenic and toxic HPHCs. Impact: These results may have important regulatory implications for product standards, as higher exposures could lead to a greater degree of harm. Cancer Epidemiol Biomarkers Prev; 27(5); 601-9. ©2018 AACR . ©2018 American Association for Cancer Research.

Short-Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study.

Science.gov (United States)

Li, Wenyuan; Wilker, Elissa H; Dorans, Kirsten S; Rice, Mary B; Schwartz, Joel; Coull, Brent A; Koutrakis, Petros; Gold, Diane R; Keaney, John F; Lin, Honghuang; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A

2016-04-28

Short-term exposure to elevated air pollution has been associated with higher risk of acute cardiovascular diseases, with systemic oxidative stress induced by air pollution hypothesized as an important underlying mechanism. However, few community-based studies have assessed this association. Two thousand thirty-five Framingham Offspring Cohort participants living within 50 km of the Harvard Boston Supersite who were not current smokers were included. We assessed circulating biomarkers of oxidative stress including blood myeloperoxidase at the seventh examination (1998-2001) and urinary creatinine-indexed 8-epi-prostaglandin F2α (8-epi-PGF2α) at the seventh and eighth (2005-2008) examinations. We measured fine particulate matter (PM2.5), black carbon, sulfate, nitrogen oxides, and ozone at the Supersite and calculated 1-, 2-, 3-, 5-, and 7-day moving averages of each pollutant. Measured myeloperoxidase and 8-epi-PGF2α were loge transformed. We used linear regression models and linear mixed-effects models with random intercepts for myeloperoxidase and indexed 8-epi-PGF2α, respectively. Models were adjusted for demographic variables, individual- and area-level measures of socioeconomic position, clinical and lifestyle factors, weather, and temporal trend. We found positive associations of PM2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2- to 7-day moving averages of PM2.5 and sulfate were consistently positively associated with 8-epi-PGF2α. Stronger positive associations of black carbon and sulfate with myeloperoxidase were observed among participants with diabetes than in those without. Our community-based investigation supports an association of select markers of ambient air pollution with circulating biomarkers of oxidative stress. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The effects of methylmercury exposure on behavior and biomarkers of oxidative stress in adult mice.

Science.gov (United States)

Kirkpatrick, Meg; Benoit, Janina; Everett, Wyll; Gibson, Jennifer; Rist, Michael; Fredette, Nicholas

2015-09-01

Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies (in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5 mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined Toxic Exposures and Human Health: Biomarkers of Exposure and Effect

Directory of Open Access Journals (Sweden)

Johan Högberg

2011-02-01

Full Text Available Procedures for risk assessment of chemical mixtures, combined and cumulative exposures are under development, but the scientific database needs considerable expansion. In particular, there is a lack of knowledge on how to monitor effects of complex exposures, and there are few reviews on biomonitoring complex exposures. In this review we summarize articles in which biomonitoring techniques have been developed and used. Most examples describe techniques for biomonitoring effects which may detect early changes induced by many chemical stressors and which have the potential to accelerate data gathering. Some emphasis is put on endocrine disrupters acting via epigenetic mechanisms and on carcinogens. Solid evidence shows that these groups of chemicals can interact and even produce synergistic effects. They may act during sensitive time windows and biomonitoring their effects in epidemiological studies is a challenging task.

Biomarkers of PAH exposure and hematologic effects in subjects exposed to combustion emission during residential (and professional) cooking practices in Pakistan.

Science.gov (United States)

Kamal, Atif; Cincinelli, Alessandra; Martellini, Tania; Malik, Riffat Naseem

2016-01-01

The aim of this study was to evaluate and compare the exposure of household women and professional male workers to combustion emission in the indoor and semi-outdoor environments, respectively, by using biochemical parameters and the biomarkers of exposure to polycyclic aromatic hydrocarbon (PAH). Female (WR n = 60) and male "cooks" (WC n = 60) exposed to the combustion emission of fuel wood and coal in rural/suburban areas of Pakistan were recruited in this study and compared to non-exposed female (CF) and male (CM) groups (n = 32 and 34, respectively). Urinary biomarkers of PAH exposure including 1-hyroxypyrene (1-OHPyr), α-naphthol, and β-naphthol were analyzed together with the biomarkers of effect, including the serum c-reactive proteins (CRP), white blood cells (WBCs), hemoglobin (Hb), red blood cells (RBC), and platelet (PLT) count. In addition, blood superoxide dismutase (SOD) and urinary level of 8-hydroxydeoxyguanosine (8-OHdG) were evaluated to determine the oxidative stress and DNA damage, respectively. A questionnaire was used to document demographic-, health-, and exposure-related information. The results showed that urinary β-naphthol was almost 44% higher in WR subjects than WC (median 7.69 vs. 3.39 μmol/mol-Cr, respectively; p = 0.01) and respective controls (CF). Higher urinary 8-OHdG were observed in WR (71.1 ng/mg-Cr) than WC (56.37 ng/mg-Cr) (p cooking (due to occupational requirement) than WR.

Evaluation of Serum and Urinary Neopterin Levels as a Biomarker ...

African Journals Online (AJOL)

Background: Crystalline silica is a commonly used mineral in various industries and construction activities, and it is so important introducing potential biomarkers to identify early indicators of biological effects in its high‑risk occupational exposures. Aim: The present study was aimed to assess the blood and urinary neopterin ...

Telomere Length – a New Biomarker in Medicine

Directory of Open Access Journals (Sweden)

Agnieszka Kozłowska

2015-12-01

Full Text Available A number of xenobiotics in the environment and workplace influences on our health and life. Biomarkers are tools for measuring such exposures and their effects in the organism. Nowadays, telomere length, epigenetic changes, mutations and changes in gene expression pattern have become new molecular biomarkers. Telomeres play the role of molecular clock, which influences on expectancy of cell life and thus aging, the formation of damages, development diseases and carcinogenesis. The telomere length depends on mechanisms of replication and the activity of telomerase. Telomere length is currently used as a biomarker of susceptibility and/or exposure. This paper describes the role of telomere length as a biomarker of aging cells, oxidative stress, a marker of many diseases including cancer, and as a marker of environmental and occupational exposure.

Assessment of Human Exposure to ENMs.

Science.gov (United States)

Jiménez, Araceli Sánchez; van Tongeren, Martie

2017-01-01

Human exposure assessment of engineered nanomaterials (ENMs) is hampered, among other factors, by the difficulty to differentiate ENM from other nanomaterials (incidental to processes or naturally occurring) and the lack of a single metric that can be used for health risk assessment. It is important that the exposure assessment is carried out throughout the entire life-cycle as releases can occur at the different stages of the product life-cycle, from the synthesis, manufacture of the nano-enable product (occupational exposure) to the professional and consumer use of nano-enabled product (consumer exposure) and at the end of life.Occupational exposure surveys should follow a tiered approach, increasing in complexity in terms of instruments used and sampling strategy applied with higher tiers in order tailor the exposure assessment to the specific materials used and workplace exposure scenarios and to reduce uncertainty in assessment of exposure. Assessment of consumer exposure and of releases from end-of-life processes currently relies on release testing of nano-enabled products in laboratory settings.

Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

International Nuclear Information System (INIS)

Bugel, Sean M.; Bonventre, Josephine A.; White, Lori A.; Tanguay, Robert L.; Cooper, Keith R.

2014-01-01

Highlights: • Reproductive biomarker genes in Newark Bay killifish are desensitized to estrogen. • Gene desensitization indicates pre-transcriptional effects on estrogen signaling. • Desensitization does not have a metabolic or epigenetic basis (gene methylation). • Modulation of vitellogenin and choriogenin genes correlates with reproductive impacts. • Choriogenin L appears less prone to false negatives and may be a sensitive biomarker. - Abstract: Reproductive and endocrine disruption is commonly reported in aquatic species exposed to complex contaminant mixtures. We previously reported that Atlantic killifish (Fundulus heteroclitus) from the chronically contaminated Newark Bay, NJ, exhibit multiple endocrine disrupting effects, including inhibition of vitellogenesis (yolk protein synthesis) in females and false negative vitellogenin biomarker responses in males. Here, we characterized the effects on estrogen signaling and the transcriptional regulation of estrogen-responsive genes in this model population. First, a dose–response study tested the hypothesis that reproductive biomarkers (vtg1, vtg2, chg H, chg Hm, chg L) in Newark Bay killifish are relatively less sensitive to 17β-estradiol at the transcriptional level, relative to a reference (Tuckerton, NJ) population. The second study assessed expression for various metabolism (cyp1a, cyp3a30, mdr) and estrogen receptor (ER α, ER βa, ER βb) genes under basal and estrogen treatment conditions in both populations. Hepatic metabolism of 17β-estradiol was also evaluated in vitro as an integrated endpoint for adverse effects on metabolism. In the third study, gene methylation was evaluated for promoters of vtg1 (8 CpGs) and vtg2 (10 CpGs) in both populations, and vtg1 promoter sequences were examined for single nucleotide polymorphism (SNPs). Overall, these studies show that multi-chemical exposures at Newark Bay have desensitized all reproductive biomarkers tested to estrogen. For example, at 10 ng

Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

Energy Technology Data Exchange (ETDEWEB)

Bugel, Sean M., E-mail: Sean.Bugel@oregonstate.edu [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Bonventre, Josephine A. [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); White, Lori A. [Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 (United States); Tanguay, Robert L. [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Cooper, Keith R. [Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 (United States)

2014-07-01

Highlights: • Reproductive biomarker genes in Newark Bay killifish are desensitized to estrogen. • Gene desensitization indicates pre-transcriptional effects on estrogen signaling. • Desensitization does not have a metabolic or epigenetic basis (gene methylation). • Modulation of vitellogenin and choriogenin genes correlates with reproductive impacts. • Choriogenin L appears less prone to false negatives and may be a sensitive biomarker. - Abstract: Reproductive and endocrine disruption is commonly reported in aquatic species exposed to complex contaminant mixtures. We previously reported that Atlantic killifish (Fundulus heteroclitus) from the chronically contaminated Newark Bay, NJ, exhibit multiple endocrine disrupting effects, including inhibition of vitellogenesis (yolk protein synthesis) in females and false negative vitellogenin biomarker responses in males. Here, we characterized the effects on estrogen signaling and the transcriptional regulation of estrogen-responsive genes in this model population. First, a dose–response study tested the hypothesis that reproductive biomarkers (vtg1, vtg2, chg H, chg Hm, chg L) in Newark Bay killifish are relatively less sensitive to 17β-estradiol at the transcriptional level, relative to a reference (Tuckerton, NJ) population. The second study assessed expression for various metabolism (cyp1a, cyp3a30, mdr) and estrogen receptor (ER α, ER βa, ER βb) genes under basal and estrogen treatment conditions in both populations. Hepatic metabolism of 17β-estradiol was also evaluated in vitro as an integrated endpoint for adverse effects on metabolism. In the third study, gene methylation was evaluated for promoters of vtg1 (8 CpGs) and vtg2 (10 CpGs) in both populations, and vtg1 promoter sequences were examined for single nucleotide polymorphism (SNPs). Overall, these studies show that multi-chemical exposures at Newark Bay have desensitized all reproductive biomarkers tested to estrogen. For example, at 10 ng

Assessment of Urinary Deoxynivalenol Biomarkers in UK Children and Adolescents

Directory of Open Access Journals (Sweden)

Maria Papageorgiou

2018-01-01

Full Text Available Deoxynivalenol (DON, the mycotoxin produced mainly by Fusarium graminearum and found in contaminated cereal-based foodstuff, has been consistently detected in body fluids in adults. Available data in children and adolescents are scarce. This study assessed urinary DON concentrations in children aged 3–9 years (n = 40 and adolescents aged 10–17 years (n = 39 in the UK. Morning urine samples were collected over two consecutive days and analysed for free DON (un-metabolised form, DON-glucuronides (DON-GlcA, deepoxy deoxynivalenol (DOM-1, and total DON (sum of free DON, DON-GlcA, and DOM-1. Total DON was detected in the urine of >95% of children and adolescents on both days. Mean total DON concentrations (ng/mg creatinine were 41.6 and 21.0 for children and adolescents, respectively. The greatest total DON levels were obtained in female children on both days (214 and 219 ng/mg creatinine on days 1 and 2, respectively. Free DON and DON-GlcA were detected in most urine specimens, whereas DOM-1 was not present in any sample. Estimation of dietary DON exposure suggested that 33–63% of children and 5–46% of adolescents exceeded current guidance regarding the maximum provisional tolerable daily intake (PMTDI for DON. Although moderate mean urinary DON concentrations were shown, the high detection frequency of urinary DON, the maximum biomarker concentrations, and estimated dietary DON exposure are concerning.

Toxicity of Lunar Dust in Lungs Assessed by Examining Biomarkers in Exposed Mice

Science.gov (United States)

Lam, C.-W.; James, J. T.; Zeidler-Erdely, P. C.; Castranova, V.; Young, S. H.; Quan, C. L.; Khan-Mayberry, N.; Taylor, L. A.

2010-01-01

NASA is contemplating to build an outpost on the Moon for prolonged human habitation and research. The lunar surface is covered by a layer of soil, of which the finest portion is highly reactive dust. Dust samples of respirable sizes were aerodynamically isolated from two lunar soil samples of different maturities (cosmic exposure ages) collected during the Apollo 16 mission. The lunar dust samples, TiO2, or quartz, suspended in normal saline were given to groups of 5 C57 male mice by intrapharyngeal aspiration at 0. 1, 0.3, or 1.0 mg/mouse. Because lunar dust aggregates rapidly in aqueous media, some tests were conducted with dusts suspended in Survanta/saline (1:1). The mice were euthanized 7 or 30 days later, and their lungs were lavaged to assess the presence of toxicity biomarkers in bronchioalveolar lavage fluids. The overall results showed that the two lunar dust samples were similar in toxicity, they were more toxic than T102 , but less toxic than quartz. This preliminary study is a part of the large study to obtain data for setting exposure limits for astronauts living on the Moon

In situ biomonitoring of juvenile Chinook salmon (Onchorhynchus tshawytscha) using biomarkers of chemical exposures and effects in a partially remediated urbanized waterway of the Puget Sound, WA

Energy Technology Data Exchange (ETDEWEB)

Browne, Eva [Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way Northeast, Suite 100, Seattle, WA 98105-6099 (United States); Kelley, Matthew; Zhou, Guo-Dong; He, Ling Yu; McDonald, Thomas; Wang, Shirley [Department of Environmental and Occupational Health, Texas A and M Health Science Center, College Station, TX 77843-1266 (United States); Duncan, Bruce [US Environmental Protection Agency, Region 10, 1200 Sixth Avenue, Seattle, WA 98101 (United States); Meador, James [Ecotoxicology Division, National Marine Fisheries Service, Seattle, WA 98105 (United States); Donnelly, Kirby [Department of Environmental and Occupational Health, Texas A and M Health Science Center, College Station, TX 77843-1266 (United States); Gallagher, Evan, E-mail: evang3@u.washington.edu [Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way Northeast, Suite 100, Seattle, WA 98105-6099 (United States)

2010-10-15

In situ biomonitoring has been used to assess the effects of pollution on aquatic species in heavily polluted waterways. In the current study, we used in situ biomonitoring in conjunction with molecular biomarker analysis to determine the effects of pollutant exposure in salmon caged in the Duwamish waterway, a Pacific Northwest Superfund site that has been subject to remediation. The Duwamish waterway is an important migratory route for Pacific salmon and has received historic inputs of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Juvenile pre-smolt Chinook salmon (Oncorhynchus tshawytscha) caged for 8 days in the three contaminated sites in close proximity within the Duwamish were analyzed for steady state hepatic mRNA expression of 7 exposure biomarker genes encompassing several gene families and known to be responsive to pollutants, including cytochrome P4501A (CYP1A) and CYP2K1, glutathione S-transferase {pi} class (GST-{pi}), microsomal GST (mGST), glutamylcysteine ligase catalytic subunit (GCLC), UDP-glucuronyltransferase family 1 (UDPGT), and type 2 deiodinase (type 2 DI, or D2). Quantitation of gene expression was accomplished by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in assays developed specifically for Chinook salmon genes. Gill PAH-DNA adducts were assessed as a chemical effects biomarker using {sup 32}P-postlabeling. The biomarkers in the field-caged fish were analyzed with respect to caged animals maintained at the hatchery receiving flow-through water. Chemical analysis of sediment samples from three field sampling sites revealed relatively high concentrations of total PAHs in one site (site B2, 6711 ng/g dry weight) and somewhat lower concentrations of PAHs in two adjacent sites (sites B3 and B4, 1482 and 1987 ng/g, respectively). In contrast, waterborne PAHs at all of the sampling sites were relatively low (<1 ng/L). Sediment PCBs at the sites ranged from a low of 421 ng/g at site B3

Chromosome translocations measured by fluorescence in-situ hybridization: A promising biomarker

International Nuclear Information System (INIS)

Lucas, J.N.; Straume, T.

1995-10-01

A biomarker for exposure and risk assessment would be most useful if it employs an endpoint that is highly quantitative, is stable with time, and is relevant to human risk. Recent advances in chromosome staining using fluorescence in situ hybridization (FISH) facilitate fast and reliable measurement of reciprocal translocations, a kind of DNA damage linked to both prior exposure and risk. In contrast to other biomarkers available, the frequency of reciprocal translocations in individuals exposed to whole-body radiation is stable with time post exposure, has a rather small inter-individual variability, and can be measured accurately at the low levels. Here, the authors discuss results from their studies demonstrating that chromosome painting can be used to reconstruct radiation dose for workers exposed within the dose limits, for individuals exposed a long time ago, and even for those who have been diagnosed with leukemia but not yet undergone therapy

An Investigation of Modifying Effects of Metallothionein Single-Nucleotide Polymorphisms on the Association between Mercury Exposure and Biomarker Levels

Science.gov (United States)

Wang, Yi; Goodrich, Jaclyn M.; Gillespie, Brenda; Werner, Robert; Basu, Niladri

2012-01-01

Background: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. Objective: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure–biomarker relationships. Methods: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methylmercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. Results: The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the U.S. general population (0.95 μg/L and 0.47 μg/g, respectively). The mean estimated daily MeHg intake was 0.084 μg/kg/day (range, 0–0.98 μg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 μg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270837) AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1M TC and CC genotypes (n = 15), respectively. Conclusion: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general

Ionizing radiation biomarkers for potential use in epidemiological studies

International Nuclear Information System (INIS)

Pernot, Eileen; Cardis, Elisabeth; Hall, Janet; Baatout, Sarah; El Saghire, Houssein; Mohammed Abderrafi Benotmane; Roel Quintens; Blanchardon, Eric; Bouffler, Simon; Gomolka, Maria; Guertler, Anne; Kreuzer, Michaela; Harms-Ringdahl, Mats; Jeggo, Penny; Laurier, Dominique; Lindholm, Carita; Mkacher, Radhia; Sabatier, Laure; Tapio, Soile; De Vathaire, Florent

2012-01-01

Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100 mSv and/or 0.1 mSv min -1 ) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of

Challenges and perspectives of nanoparticle exposure assessment.

Science.gov (United States)

Lee, Ji Hyun; Moon, Min Chaul; Lee, Joon Yeob; Yu, Il Je

2010-06-01

Nanoparticle exposure assessment presents a unique challenge in the field of occupational and environmental health. With the commercialization of nanotechnology, exposure usually starts from the workplace and then spreads to environment and consumer exposure. This report discusses the current trends of nanoparticle exposure assessment, including the definition of nanotechnology relevant terms, essential physicochemical properties for nanomaterial characterization, current international activities related nanomaterial safety, and exposure assessment standard development for nanotechnology. Further this report describes challenges of nanoparticle exposure assessment such as background measurement, metrics of nanoparticle exposure assessment and personal sampling.

Biomarkers of Nutrition for Development—Iodine Review1234

Science.gov (United States)

Rohner, Fabian; Zimmermann, Michael; Jooste, Pieter; Pandav, Chandrakant; Caldwell, Kathleen; Raghavan, Ramkripa; Raiten, Daniel J.

2014-01-01

The objective of the Biomarkers of Nutrition for Development (BOND) project is to provide state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. Specifically, the BOND project seeks to develop consensus on accurate assessment methodologies that are applicable to researchers (laboratory/clinical/surveillance), clinicians, programmers, and policy makers (data consumers). The BOND project is also intended to develop targeted research agendas to support the discovery and development of biomarkers through improved understanding of nutrient biology within relevant biologic systems. In phase I of the BOND project, 6 nutrients (iodine, vitamin A, iron, zinc, folate, and vitamin B-12) were selected for their high public health importance because they typify the challenges faced by users in the selection, use, and interpretation of biomarkers. For each nutrient, an expert panel was constituted and charged with the development of a comprehensive review covering the respective nutrient’s biology, existing biomarkers, and specific issues of use with particular reference to the needs of the individual user groups. In addition to the publication of these reviews, materials from each will be extracted to support the BOND interactive Web site (http://www.nichd.nih.gov/global_nutrition/programs/bond/pages/index.aspx). This review represents the first in the series of reviews and covers all relevant aspects of iodine biology and biomarkers. The article is organized to provide the reader with a full appreciation of iodine’s background history as a public health issue, its biology, and an overview of available biomarkers and specific considerations for the use and interpretation of iodine biomarkers across a range of clinical and population-based uses. The review also includes a detailed research agenda to address priority gaps in our understanding of iodine biology and assessment

Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

Science.gov (United States)

Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

2016-05-01

The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biomarkers for exposure to ambient air pollution - Comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress

DEFF Research Database (Denmark)

Autrup, Herman; Daneshvar, Bahram; Dragsted, Lars Ove

1999-01-01

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts...... correlations were observed between bulky carcinogen-DNA adduct and PAM-albumin levels (p = 0.005), and between DNA adduct and gamma-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAM-albumin adducts and AAS in plasma (r = 0.001) and GGS in hemoglobin (p...... in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAM-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, bur not in the workers who were homozygotes or heterozygotes for GSTM1. Our...

Biomarkers of mercury exposure at a mercury recycling facility in Ukraine.

Science.gov (United States)

Gibb, Herman Jones; Kozlov, Kostj; Buckley, Jessie Poulin; Centeno, Jose; Jurgenson, Vera; Kolker, Allan; Conko, Kathryn; Landa, Edward; Panov, Boris; Panov, Yuri; Xu, Hanna

2008-08-01

This study evaluates biomarkers of occupational mercury exposure among workers at a mercury recycling operation in Gorlovka, Ukraine. The 29 study participants were divided into three occupational categories for analysis: (1) those who worked in the mercury recycling operation (Group A, n = 8), (2) those who worked at the facility but not in the yard where the recycling was done (Group B, n = 14), and (3) those who did not work at the facility (Group C, n = 7). Urine, blood, hair, and nail samples were collected from the participants, and a questionnaire was administered to obtain data on age, gender, occupational history, smoking, alcohol consumption, fish consumption, tattoos, dental amalgams, home heating system, education, source of drinking water, and family employment in the former mercury mine/smelter located on the site of the recycling facility. Each factor was tested in a univariate regression with total mercury in urine, blood, hair, and nails. Median biomarker concentrations were 4.04 microg/g-Cr (urine), 2.58 microg/L (blood), 3.95 microg/g (hair), and 1.16 microg/g (nails). Occupational category was significantly correlated (p recycling operation had the highest blood and urinary mercury levels. Those who worked at the facility but were not directly involved with the recycling operation had higher levels than those who did not work at the facility.

Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure

Directory of Open Access Journals (Sweden)

Craig Sams

2016-05-01

Full Text Available Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i develop a robust analytical method, ii determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54% in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended.

Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

Directory of Open Access Journals (Sweden)

Natalie Turner

2014-03-01

Full Text Available Circulating tumor cell (CTC count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

Biomarkers of Immunotoxicity for Environmental and Public Health Research

Directory of Open Access Journals (Sweden)

Nina T. Holland

2011-05-01

Full Text Available The immune response plays an important role in the pathophysiology of numerous diseases including asthma, autoimmunity and cancer. Application of biomarkers of immunotoxicity in epidemiology studies and human clinical trials can improve our understanding of the mechanisms that underlie the associations between environmental exposures and development of these immune-mediated diseases. Immunological biomarkers currently used in environmental health studies include detection of key components of innate and adaptive immunity (e.g., complement, immunoglobulin and cell subsets as well as functional responses and activation of key immune cells. The use of high-throughput assays, including flow cytometry, Luminex, and Multi-spot cytokine detection methods can further provide quantitative analysis of immune effects. Due to the complexity and redundancy of the immune response, an integrated assessment of several components of the immune responses is needed. The rapidly expanding field of immunoinformatics will also aid in the synthesis of the vast amount of data being generated. This review discusses and provides examples of how the identification and development of immunological biomarkers for use in studies of environmental exposures and immune-mediated disorders can be achieved.

Biomarkers of Immunotoxicity for Environmental and Public Health Research

Science.gov (United States)

Duramad, Paurene; Holland, Nina T.

2011-01-01

The immune response plays an important role in the pathophysiology of numerous diseases including asthma, autoimmunity and cancer. Application of biomarkers of immunotoxicity in epidemiology studies and human clinical trials can improve our understanding of the mechanisms that underlie the associations between environmental exposures and development of these immune-mediated diseases. Immunological biomarkers currently used in environmental health studies include detection of key components of innate and adaptive immunity (e.g., complement, immunoglobulin and cell subsets) as well as functional responses and activation of key immune cells. The use of high-throughput assays, including flow cytometry, Luminex, and Multi-spot cytokine detection methods can further provide quantitative analysis of immune effects. Due to the complexity and redundancy of the immune response, an integrated assessment of several components of the immune responses is needed. The rapidly expanding field of immunoinformatics will also aid in the synthesis of the vast amount of data being generated. This review discusses and provides examples of how the identification and development of immunological biomarkers for use in studies of environmental exposures and immune-mediated disorders can be achieved. PMID:21655126

Assessment of potential biomarkers, metallothionein and vitellogenin mRNA expressions in various chemically exposed benthic Chironomus riparius larvae

Science.gov (United States)

Park, Kiyun; Kwak, Inn-Sil

2012-12-01

The objective of this study was conducted to identify the possibility of using Chironomus metallothionein (MT) and vitellogenin (VTG) as biomarkers of stress caused by endocrinedisrupting chemicals (EDCs), heavy metals, herbicides and veterinary antibiotics. We characterized the MT and VTG cDNA in Chironomus riparius and evaluated their mRNA expression profiles following exposure to different environmental pollutants. The gene expression analysis showed that the MT mRNA levels increased significantly after long-term exposure to cadmium (Cd), copper (Cu), Lead (Pb), di(2-ethylhexyl) phthalate (DEHP), and 2,4-dichlorophenoxyacetic acid (2,4-D). Moreover, the VTG mRNA expression increased significantly in C. riparius larvae exposed to BPA, NP, DEHP, Cd, 2,4-D and fenbendazole. Evaluation of the long-term effects of environmental pollutants revealed up regulation of Chironomus MT mRNA in response to DEHP exposure among EDCs, and the level of the VTG mRNA was increased significantly following treatment with Cd and herbicide 2,4-D at all concentrations in a dose-dependent manner. These results indicate that VTG could be used as a potential biomarker of herbicide and Cd as well as EDCs, while MT was a potential biomarker of heavy metals such as Cd, Cu, and Pb in aquatic environments.

A general framework for the regression analysis of pooled biomarker assessments.

Science.gov (United States)

Liu, Yan; McMahan, Christopher; Gallagher, Colin

2017-07-10

As a cost-efficient data collection mechanism, the process of assaying pooled biospecimens is becoming increasingly common in epidemiological research; for example, pooling has been proposed for the purpose of evaluating the diagnostic efficacy of biological markers (biomarkers). To this end, several authors have proposed techniques that allow for the analysis of continuous pooled biomarker assessments. Regretfully, most of these techniques proceed under restrictive assumptions, are unable to account for the effects of measurement error, and fail to control for confounding variables. These limitations are understandably attributable to the complex structure that is inherent to measurements taken on pooled specimens. Consequently, in order to provide practitioners with the tools necessary to accurately and efficiently analyze pooled biomarker assessments, herein, a general Monte Carlo maximum likelihood-based procedure is presented. The proposed approach allows for the regression analysis of pooled data under practically all parametric models and can be used to directly account for the effects of measurement error. Through simulation, it is shown that the proposed approach can accurately and efficiently estimate all unknown parameters and is more computational efficient than existing techniques. This new methodology is further illustrated using monocyte chemotactic protein-1 data collected by the Collaborative Perinatal Project in an effort to assess the relationship between this chemokine and the risk of miscarriage. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Assessment of Exposure to VOCs among Pregnant Women in the National Children's Study.

Science.gov (United States)

Boyle, Elizabeth Barksdale; Viet, Susan M; Wright, David J; Merrill, Lori S; Alwis, K Udeni; Blount, Benjamin C; Mortensen, Mary E; Moye, John; Dellarco, Michael

2016-03-29

Epidemiologic studies can measure exposure to volatile organic compounds (VOCs) using environmental samples, biomarkers, questionnaires, or observations. These different exposure assessment approaches each have advantages and disadvantages; thus, evaluating relationships is an important consideration. In the National Children's Vanguard Study from 2009 to 2010, participants completed questionnaires and data collectors observed VOC exposure sources and collected urine samples from 488 third trimester pregnant women at in-person study visits. From urine, we simultaneously quantified 28 VOC metabolites of exposure to acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, 1,3-butadiene, carbon disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and xylene exposures using ultra high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS) method. Urinary thiocyanate was measured using an ion chromatography coupled with an electrospray ionization tandem mass spectrometry method (IC-ESI/MSMS). We modeled the relationship between urinary VOC metabolite concentrations and sources of VOC exposure. Sources of exposure were assessed by participant report via questionnaire (use of air fresheners, aerosols, paint or varnish, organic solvents, and passive/active smoking) and by observations by a trained data collector (presence of scented products in homes). We found several significant (p < 0.01) relationships between the urinary metabolites of VOCs and sources of VOC exposure. Smoking was positively associated with metabolites of the tobacco constituents acrolein, acrylamide, acrylonitrile, 1,3-butadiene, crotonaldehyde, cyanide, ethylene oxide, N,N-dimethylformamide, propylene oxide, styrene, and xylene. Study location was negatively associated with the toluene metabolite N

Quantifying Treatment Benefit in Molecular Subgroups to Assess a Predictive Biomarker.

Science.gov (United States)

Iasonos, Alexia; Chapman, Paul B; Satagopan, Jaya M

2016-05-01

An increased interest has been expressed in finding predictive biomarkers that can guide treatment options for both mutation carriers and noncarriers. The statistical assessment of variation in treatment benefit (TB) according to the biomarker carrier status plays an important role in evaluating predictive biomarkers. For time-to-event endpoints, the hazard ratio (HR) for interaction between treatment and a biomarker from a proportional hazards regression model is commonly used as a measure of variation in TB. Although this can be easily obtained using available statistical software packages, the interpretation of HR is not straightforward. In this article, we propose different summary measures of variation in TB on the scale of survival probabilities for evaluating a predictive biomarker. The proposed summary measures can be easily interpreted as quantifying differential in TB in terms of relative risk or excess absolute risk due to treatment in carriers versus noncarriers. We illustrate the use and interpretation of the proposed measures with data from completed clinical trials. We encourage clinical practitioners to interpret variation in TB in terms of measures based on survival probabilities, particularly in terms of excess absolute risk, as opposed to HR. Clin Cancer Res; 22(9); 2114-20. ©2016 AACR. ©2016 American Association for Cancer Research.

Human Exposure Assessment for Air Pollution.

Science.gov (United States)

Han, Bin; Hu, Li-Wen; Bai, Zhipeng

2017-01-01

Assessment of human exposure to air pollution is a fundamental part of the more general process of health risk assessment. The measurement methods for exposure assessment now include personal exposure monitoring, indoor-outdoor sampling, mobile monitoring, and exposure assessment modeling (such as proximity models, interpolation model, air dispersion models, and land-use regression (LUR) models). Among these methods, personal exposure measurement is considered to be the most accurate method of pollutant exposure assessment until now, since it can better quantify observed differences and better reflect exposure among smaller groups of people at ground level. And since the great differences of geographical environment, source distribution, pollution characteristics, economic conditions, and living habits, there is a wide range of differences between indoor, outdoor, and individual air pollution exposure in different regions of China. In general, the indoor particles in most Chinese families comprise infiltrated outdoor particles, particles generated indoors, and a few secondary organic aerosol particles, and in most cases, outdoor particle pollution concentrations are a major contributor to indoor concentrations in China. Furthermore, since the time, energy, and expense are limited, it is difficult to measure the concentration of pollutants for each individual. In recent years, obtaining the concentration of air pollutants by using a variety of exposure assessment models is becoming a main method which could solve the problem of the increasing number of individuals in epidemiology studies.

Semen says: assessing the accuracy of adolescents' self-reported sexual abstinence using a semen Y-chromosome biomarker.

Science.gov (United States)

Rosenbaum, Janet E; Zenilman, Jonathan M; Rose, Eve; Wingood, Gina M; DiClemente, Ralph J

2017-03-01

Researchers often assess condom use only among participants who report recent sexual behaviour, excluding participants who report no recent vaginal sex or who did not answer questions about their sexual behaviour, but self-reported sexual behaviour may be inaccurate. This study uses a semen Y-chromosome biomarker to assess semen exposure among participants who reported sexual abstinence or did not report their sexual behaviour. This prospective cohort study uses data from 715 sexually active African-American female adolescents in Atlanta, surveyed at baseline, 6 months and 12 months. Participants completed a 40 min interview and were tested for semen Y-chromosome with PCR from a self-administered vaginal swab. We predicted Y-chromosome test results from self-reported sexual behaviour using within-subject panel regression. Among the participants who reported abstinence from vaginal sex in the past 14 days, 9.4% tested positive for semen Y-chromosome. Among item non-respondents, 6.3% tested positive for semen Y-chromosome. Women who reported abstinence and engaged in item non-response regarding their sexual behaviour had respectively 62% and 78% lower odds of testing positive for Y-chromosome (OR 0.38 (0.21 to 0.67), OR 0.22 (0.12 to 0.40)), controlling for smoking, survey wave and non-coital sexual behaviours reported during abstinence. Adolescents who report sexual abstinence under-report semen exposure. Research should validate self-reported sexual behaviour with biomarkers. Adolescents who engage in item non-response regarding vaginal sex test positive for semen Y-chromosome at similar rates, which supports the practice of grouping non-respondents with adolescents reporting abstinence in statistical analysis. NCT00633906. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Influence of Machine-Derived Smoke Yields on Biomarker of Exposure (BOE Levels in Cigarette Smokers*

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Scherer Gerhard

2015-01-01

Full Text Available Individual uptake of tobacco smoke constituents by smoking is highly variable in cigarette smokers and cannot be predicted by smoking behaviour variables and machine-derived smoke yields. It is well established that uptake of smoke constituents is best described by a series of bio-markers of exposure (BOEs such as metabolites of nico-tine, tobacco-specific nitrosamines (TSNAs, polycyclic aromatic hydrocarbons (PAHs, aromatic amines, benzene, 1,3-butadiene, acrolein, hydrogen cyanide, 2,5-dimethyl-furan and other smoke constituents.

Composite biomarkers for assessing Duchenne muscular dystrophy: an initial assessment.

Science.gov (United States)

Shklyar, Irina; Pasternak, Amy; Kapur, Kush; Darras, Basil T; Rutkove, Seward B

2015-02-01

Compared with individual parameters, composite biomarkers may provide a more effective means for monitoring disease progression and the effects of therapy in clinical trials than single measures. In this study, we built composite biomarkers for use in Duchenne muscular dystrophy by combining values from two objective measures of disease severity: electrical impedance myography and quantitative ultrasound and evaluating how well they correlated to standard functional measures. Using data from an ongoing study of electrical impedance myography and quantitative ultrasound in 31 Duchenne muscular dystrophy and 26 healthy boys aged 2-14 years, we combined data sets by first creating z scores based on the normal subject data and then using simple mathematical operations (addition and multiplication) to create composite measures. These composite scores were then correlated to age and standard measures of function including the 6-minute walk test, the North Star Ambulatory Assessment, and handheld dynamometry. Combining data sets resulted in stronger correlations with all four outcomes than for either electrical impedance myography or quantitative ultrasound alone in six of eight instances. These improvements reached statistical significance (P Duchenne muscular dystrophy clinical trials is warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of biomarker development on drug safety assessment

International Nuclear Information System (INIS)

Marrer, Estelle; Dieterle, Frank

2010-01-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

CYP1A1 and CYP1B1 in human lymphocytes as biomarker of exposure: effect of dioxin exposure and polymorphisms

Energy Technology Data Exchange (ETDEWEB)

Duursen, M. van; Sanderson, T.; Berg, M. van den [Inst. for Risk Assessment Sciences, Utrecht (Netherlands)

2004-09-15

There are several known genetic polymorphisms of the CYP1A1 and CYP1B1 genes. A polymorphism in the 3'-untranslated region of the CYP1A1 gene (CYP1A1 MspI or CYP1A1 m1) is often studied in relation with breast or lung cancer, but little is known about the functional effect of this polymorphism. An amino acid substitution in codon 432 (Val to Leu) of the CYP1B1 gene is associated with a lower catalytic activity of the enzyme. However, the involvement of these polymorphisms on the inducibility of CYP1A1 and CYP1B1 gene expression is unclear. CYP1A1 and CYP1B1 mRNA expression levels can be determined in peripheral blood lymphocytes. This makes them potential candidates for use as biomarker of exposure to environmental compounds. Interindividual variations in mRNA expression patterns, catalytic activity and polymorphisms are very important factors when CYP1A1 and CYP1B1 expression patterns are used as biomarker of exposure, but little is known about it. Spencer et al. showed a concentration-dependent increase of CYP1B1 mRNA in lymphocytes upon exposure in vitro to 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD), the most potent dioxin. Yet, only a few studies describe the in vivo correlation between polymorphisms, mRNA expression level and exposure to environmental factors. In this study, we wanted to obtain a better insight in the CYP1A1 and CYP1B1 mRNA expression and enzyme activity in human lymphocytes. We determined the constitutive CYP1A1 and CYP1B1 mRNA expression in lymphocytes of ten healthy volunteers and the variability in sensitivity toward enzyme induction by TCDD. Further, the CYP1A1 m1 and CYP1B1 Val432Leu polymorphisms were determined.

Integrative assessment of biomarker responses in teleostean fishes exposed to glyphosate-based herbicide (Excel Mera 71

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Sukhendu Dey

2016-12-01

Full Text Available Present study deals with the effects of glyphosate-based herbicide, Excel Mera 71 on Anabas testudineus, Heteropnestes fossilis and Oreochromis niloticus in field conditions (1.85 kg/ha based on anti-oxidative, metabolic and digestive responses. For this study following biomarkers viz., acetylcholinesterase (AChE, lipid peroxidation (LPO, catalase (CAT, glutathione-S-transferase (GST, alkaline phosphatase (ALP, aspartate aminotransferase (AST, alanine aminotransferase (ALT, amylase, lipase and protease were investigated in gill, stomach, intestine, liver, kidney, brain, muscle and spinal cord of the concerned fish species. Enzyme activities were significantly altered by glyphosate exposure after 30 days, these activities were tissue as well as species specific. The results suggested that these biomarkers could be used to assess the ecological risks of glyphosate on fish. Bioaccumulation factor (BAF studied in different aquatic natural macrophytes showed order of Alternanthera philoxeroides > Azolla pinnata > Lemna sp. (Minor > Lemna sp. (Major > Pistia stratiotes, while transfer factor (TF showed the order of Pistia stratiotes > Alternanthera philoxeroides > Lemna sp. Bioconcentration factor (BCF study showed maximum accumulation of glyphosate in liver, kidney or intestine, and minimum either in bone or stomach irrespective of fish species. An integrated biomarker response (IBR, which uses a battery of biomarkers to calculate the standardized scores for each biomarker responses ranging from physiological to biochemical/molecular responses, was evaluated by combining the multiple biomarkers into a single value to evaluate quantitatively the toxicological effects of glyphosate. In general, the multiple indices exhibited variations and A. testudineus was more affected than other fish species; maximum IBR value was observed for LPO and minimum in case of ALT. The order of integrated biomarkers caused by glyphosate treatment was

Utility and Cutoff Value of Hair Nicotine as a Biomarker of Long-Term Tobacco Smoke Exposure, Compared to Salivary Cotinine

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Sungroul Kim

2014-08-01

Full Text Available While hair samples are easier to collect and less expensive to store and transport than biological fluids, and hair nicotine characterizes tobacco exposure over a longer time period than blood or urine cotinine, information on its utility, compared with salivary cotinine, is still limited. We conducted a cross-sectional study with 289 participants (107 active smokers, 105 passive smokers with self-reported secondhand smoke (SHS exposure, and 77 non-smokers with no SHS exposure in Baltimore (Maryland, USA. A subset of the study participants (n = 52 were followed longitudinally over a two-month interval.  Median baseline hair nicotine concentrations for active, passive and non-smokers were 16.2, 0.36, and 0.23 ng/mg, respectively, while those for salivary cotinine were 181.0, 0.27, and 0.27 ng/mL, respectively. Hair nicotine concentrations for 10% of passive or non-smokers were higher than the 25th percentile value for active smokers while all corresponding salivary cotinine concentrations for them were lower than the value for active smokers. This study showed that hair nicotine concentration values could be used to distinguish active or heavy passive adult smokers from non-SHS exposed non-smokers. Our results indicate that hair nicotine is a useful biomarker for the assessment of long-term exposure to tobacco smoke.

Effect of uranium chronic exposure on the moult in crayfish

International Nuclear Information System (INIS)

Simon, O.; Camilleri, V.; Garnier-Laplace, J.

2004-01-01

Throughout any ecological risk assessment, one can try to establish a link between pollutant in the ecosystem and adverse biological effects. A number of methodological approaches are based on the development of the use of bio-markers such as the enzyme activity measurements (biotransformation enzymes, antioxidant enzymes) and/or bioaccumulation markers (metal in target-organs). These data allow obtaining an early-warning signal of exposure and potential involved effects and help risk management. However, the effects at higher hierarchical levels (organism or population) are not frequently considered because they tend to occur after longer exposure periods. On the basis of previous results obtained to quantify uranium biokinetics in the crayfish Orconectes limosus and to understand the influence of the exposure pathway, a chronic exposure experiment was performed for 100 days at an environmentally relevant uranium concentration in water (low level concentration ranging from?? to 100 nM). The main effect studied was focused on the moult; moulted animals being the most sensitive to pollutants. Effects on the moult process were assessed in terms of occurrence, delay, and success. Preliminary results that indicated no induction of the moult by U exposure and better survival rate to uranium exposure must be confirmed. Simultaneously, both enzymatic bio-markers of effect quantifying the oxidative status (catalase, superoxide dismutase and glutathione peroxidases) and markers of exposure (uranium distribution at organs and cellular levels and MET observations) were studied. Results obtained from complementary experiments on the uranium fluxes all over moult states were used to discuss the link between bio-markers responses and observed effects on the moult. (author)

Effect of uranium chronic exposure on the moult in crayfish

Energy Technology Data Exchange (ETDEWEB)

Simon, O.; Camilleri, V.; Garnier-Laplace, J. [CEA Cadarache (DEI/SECRE/LRE), Laboratory of Radioecology and Ecotoxicology, Institute for Radioprotection and Nuclear Safety, 13 - Saint-Paul-lez-Durance (France)

2004-07-01

Throughout any ecological risk assessment, one can try to establish a link between pollutant in the ecosystem and adverse biological effects. A number of methodological approaches are based on the development of the use of bio-markers such as the enzyme activity measurements (biotransformation enzymes, antioxidant enzymes) and/or bioaccumulation markers (metal in target-organs). These data allow obtaining an early-warning signal of exposure and potential involved effects and help risk management. However, the effects at higher hierarchical levels (organism or population) are not frequently considered because they tend to occur after longer exposure periods. On the basis of previous results obtained to quantify uranium biokinetics in the crayfish Orconectes limosus and to understand the influence of the exposure pathway, a chronic exposure experiment was performed for 100 days at an environmentally relevant uranium concentration in water (low level concentration ranging from?? to 100 nM). The main effect studied was focused on the moult; moulted animals being the most sensitive to pollutants. Effects on the moult process were assessed in terms of occurrence, delay, and success. Preliminary results that indicated no induction of the moult by U exposure and better survival rate to uranium exposure must be confirmed. Simultaneously, both enzymatic bio-markers of effect quantifying the oxidative status (catalase, superoxide dismutase and glutathione peroxidases) and markers of exposure (uranium distribution at organs and cellular levels and MET observations) were studied. Results obtained from complementary experiments on the uranium fluxes all over moult states were used to discuss the link between bio-markers responses and observed effects on the moult. (author)

Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes

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Carl D. D’Ruiz

2016-07-01

Full Text Available Abstract Background Electronic cigarettes (e-cigarettes are popular alternatives to conventional cigarettes among adult smokers wishing to reduce their exposure to harmful smoke constituents. However, little information exists on the relative internal exposures resulting from the exclusive or dual use of e-cigarettes. Methods Measurements of product use; adverse events; changes in smoking urge; and blood, urine and exhaled breath biomarkers of exposure (BoE representing toxicants believed to contribute to smoking related diseases were made at baseline and after five days of product use in 105 clinically-confined smokers randomized into groups that partially or completely substituted their usual brand combustible cigarette with commercial e-cigarettes, or discontinued all nicotine and tobacco products. Results Subjects switching to e-cigarettes had significantly lower levels (29 %–95 % of urinary BoEs after 5 days. Nicotine equivalents declined by 25 %–40 %. Dual users who substituted half of their self-reported daily cigarette consumption with e-cigarettes experienced 7 %–38 % reductions, but had increases (1 %–20 % in nicotine equivalents. Blood nicotine biomarker levels were lower in the cessation (75 %–96 % and e-cigarette use groups (11 %–83 %; dual users had no significant reductions. All groups experienced significant decreases in exhaled CO (27 %–89 %. Exhaled NO increases (46 %–63 % were observed in the cessation and e-cigarette use groups; dual users had minimal changes. By Day 5, all groups had greater reductions in smoking urge compared to cessation. However, reductions were larger in the dual use group. No serious adverse events were observed. Conclusions Exposures to harmful smoke toxicants were observed to be lower in smokers who completely or partially replaced their cigarettes with e-cigarettes over five days.

Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes.

Science.gov (United States)

D'Ruiz, Carl D; Graff, Donald W; Robinson, Edward

2016-07-11

Electronic cigarettes (e-cigarettes) are popular alternatives to conventional cigarettes among adult smokers wishing to reduce their exposure to harmful smoke constituents. However, little information exists on the relative internal exposures resulting from the exclusive or dual use of e-cigarettes. Measurements of product use; adverse events; changes in smoking urge; and blood, urine and exhaled breath biomarkers of exposure (BoE) representing toxicants believed to contribute to smoking related diseases were made at baseline and after five days of product use in 105 clinically-confined smokers randomized into groups that partially or completely substituted their usual brand combustible cigarette with commercial e-cigarettes, or discontinued all nicotine and tobacco products. Subjects switching to e-cigarettes had significantly lower levels (29 %-95 %) of urinary BoEs after 5 days. Nicotine equivalents declined by 25 %-40 %. Dual users who substituted half of their self-reported daily cigarette consumption with e-cigarettes experienced 7 %-38 % reductions, but had increases (1 %-20 %) in nicotine equivalents. Blood nicotine biomarker levels were lower in the cessation (75 %-96 %) and e-cigarette use groups (11 %-83 %); dual users had no significant reductions. All groups experienced significant decreases in exhaled CO (27 %-89 %). Exhaled NO increases (46 %-63 %) were observed in the cessation and e-cigarette use groups; dual users had minimal changes. By Day 5, all groups had greater reductions in smoking urge compared to cessation. However, reductions were larger in the dual use group. No serious adverse events were observed. Exposures to harmful smoke toxicants were observed to be lower in smokers who completely or partially replaced their cigarettes with e-cigarettes over five days.

One week's holiday sun exposure induces expression of photoaging biomarkers.

Science.gov (United States)

Lesiak, Aleksandra; Rogowski-Tylman, Michal; Danilewicz, Marian; Wozniacka, Anna; Narbutt, Joanna

2016-01-01

Skin aging is accompanied by the upregulation of the expression of various matrix metalloproteinases (MMPs). It was shown that exposure to ultraviolet radiation (UVR) may induce skin expression of MMPs and dysregulation of the transforming growth factor beta (TGF-β)/Smad pathway. The aim of our study was to compare the effects of short holiday UVR exposure and lifetime UVR exposure, on the expression of MMP-8, TGF-β1, and Smad2 in human skin biopsies. Skin biopsies were taken from the outer upper arm of 15 elderly people with significant photoaging (mean age 64.1 years) (Group 1) and from 15 healthy young adult volunteers (mean age 24.1 y) who participated in a six-day sun holiday. Biopsies were taken twice: 24 hours before leaving for holiday (Group 2a) and 24 hours after returning (Group 2b). The expression of TGF-β1, Smad2, and MMP-8 was examined by immunochemistry and measured semiquantitatively by two independent pathologists. The mean expression of TGF-β1 in dermal fibroblasts and keratinocytes in Group 1 and Group 2b was significantly lower than in Group 2a (0.54% ± 0.44% and 0.48% ± 0.51% vs. 1.48% ± 0.72%, respectively). The percentage of Smad2 (+) cells in Group 1 and Group 2b was lower than in Group 2a (2.13% ± 1.39% and 1.81% ± 1.16% vs. 4.13% ± 1.58%, respectively). The MMP-8 expression in Group 2b was 1.36% ± 0.68% and was significantly higher than in Group 1 (0.34% ± 0.42%) and Group 2a in which the protein was not detected (p < 0.001). We conclude that the decrease in the expression of TGF-β1 and Smad2 is a persistent biomarker of skin photoaging, while the increased expression of MMP-8 in keratinocytes can be regarded as a marker of acute sun exposure.

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities.

Science.gov (United States)

Helb, Danica A; Tetteh, Kevin K A; Felgner, Philip L; Skinner, Jeff; Hubbard, Alan; Arinaitwe, Emmanuel; Mayanja-Kizza, Harriet; Ssewanyana, Isaac; Kamya, Moses R; Beeson, James G; Tappero, Jordan; Smith, David L; Crompton, Peter D; Rosenthal, Philip J; Dorsey, Grant; Drakeley, Christopher J; Greenhouse, Bryan

2015-08-11

Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates of Pf exposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf antigens by protein microarray in 186 Ugandan children, for whom detailed Pf exposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual's recent exposure. Responses to three novel Pf antigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86-0.93), whereas responses to six antigens accurately estimated an individual's malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs.

Estimating central tendency from a single spot measure: A closed-form solution for lognormally distributed biomarker data for risk assessment at the individual level.

Science.gov (United States)

Pleil, Joachim D; Sobus, Jon R

2016-01-01

Exposure-based risk assessment employs large cross-sectional data sets of environmental and biomarker measurements to predict population statistics for adverse health outcomes. The underlying assumption is that long-term (many years) latency health problems including cancer, autoimmune and cardiovascular disease, diabetes, and asthma are triggered by lifetime exposures to environmental stressors that interact with the genome. The aim of this study was to develop a specific predictive method that provides the statistical parameters for chronic exposure at the individual level based upon a single spot measurement and knowledge of global summary statistics as derived from large data sets. This is a profound shift in exposure and health statistics in that it begins to answer the question "How large is my personal risk?" rather than just providing an overall population-based estimate. This approach also holds value for interpreting exposure-based risks for small groups of individuals within a community in comparison to random individuals from the general population.

An Exposure Assessment of Polybrominated Diphenyl Ethers ...

Science.gov (United States)

EPA announced the availability of the final report, An Exposure Assessment of Polybrominated Diphenyl Ethers. This report provides a comprehensive assessment of the exposure of Americans to this class of persistent organic pollutants. Individual chapters in this document address: the production, use, and lifecycle of PBDEs; environmental fate; environmental levels; and human exposure. This final report addresses the exposure assessment needs identified in the OPBDE Workgroup project plan. It provides a comprehensive assessment of the exposure of Americans to this class of persistent organic pollutants. Individual chapters in this document address: the production, use, and lifecycle of PBDEs; environmental fate; environmental levels; and human exposure.

Aflatoxin exposure during the first 1000 days of life in rural South Asia assessed by aflatoxin B₁-lysine albumin biomarkers.

Science.gov (United States)

Groopman, John D; Egner, Patricia A; Schulze, Kerry J; Wu, Lee S-F; Merrill, Rebecca; Mehra, Sucheta; Shamim, Abu A; Ali, Hasmot; Shaikh, Saijuddin; Gernand, Alison; Khatry, Subarna K; LeClerq, Steven C; West, Keith P; Christian, Parul

2014-12-01

Aflatoxin B1 is a potent carcinogen, occurring from mold growth that contaminates staple grains in hot, humid environments. In this investigation, aflatoxin B1-lysine albumin biomarkers were measured by mass spectrometry in rural South Asian women, during the first and third trimester of pregnancy, and their children at birth and at two years of age. These subjects participated in randomized community trials of antenatal micronutrient supplementation in Sarlahi District, southern Nepal and Gaibandha District in northwestern Bangladesh. Findings from the Nepal samples demonstrated exposure to aflatoxin, with 94% detectable samples ranging from 0.45 to 2939.30 pg aflatoxin B1-lysine/mg albumin during pregnancy. In the Bangladesh samples the range was 1.56 to 63.22 pg aflatoxin B1-lysine/mg albumin in the first trimester, 3.37 to 72.8 pg aflatoxin B1-lysine/mg albumin in the third trimester, 4.62 to 76.69 pg aflatoxin B1-lysine/mg albumin at birth and 3.88 to 81.44 pg aflatoxin B1-lysine/mg albumin at age two years. Aflatoxin B1-lysine adducts in cord blood samples demonstrated that the fetus had the capacity to convert aflatoxin into toxicologically active compounds and the detection in the same 2-year-old children illustrates exposure over the first 1000 days of life. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessment of Exposure to VOCs among Pregnant Women in the National Children’s Study

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Elizabeth Barksdale Boyle

2016-03-01

Full Text Available Epidemiologic studies can measure exposure to volatile organic compounds (VOCs using environmental samples, biomarkers, questionnaires, or observations. These different exposure assessment approaches each have advantages and disadvantages; thus, evaluating relationships is an important consideration. In the National Children’s Vanguard Study from 2009 to 2010, participants completed questionnaires and data collectors observed VOC exposure sources and collected urine samples from 488 third trimester pregnant women at in-person study visits. From urine, we simultaneously quantified 28 VOC metabolites of exposure to acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, 1,3-butadiene, carbon disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and xylene exposures using ultra high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS method. Urinary thiocyanate was measured using an ion chromatography coupled with an electrospray ionization tandem mass spectrometry method (IC-ESI/MSMS. We modeled the relationship between urinary VOC metabolite concentrations and sources of VOC exposure. Sources of exposure were assessed by participant report via questionnaire (use of air fresheners, aerosols, paint or varnish, organic solvents, and passive/active smoking and by observations by a trained data collector (presence of scented products in homes. We found several significant (p < 0.01 relationships between the urinary metabolites of VOCs and sources of VOC exposure. Smoking was positively associated with metabolites of the tobacco constituents acrolein, acrylamide, acrylonitrile, 1,3-butadiene, crotonaldehyde, cyanide, ethylene oxide, N,N-dimethylformamide, propylene oxide, styrene, and xylene. Study location was negatively associated with the toluene metabolite

Assessment of Exposure to VOCs among Pregnant Women in the National Children’s Study

Science.gov (United States)

Boyle, Elizabeth Barksdale; Viet, Susan M.; Wright, David J.; Merrill, Lori S.; Alwis, K. Udeni; Blount, Benjamin C.; Mortensen, Mary E.; Moye, John; Dellarco, Michael

2016-01-01

Epidemiologic studies can measure exposure to volatile organic compounds (VOCs) using environmental samples, biomarkers, questionnaires, or observations. These different exposure assessment approaches each have advantages and disadvantages; thus, evaluating relationships is an important consideration. In the National Children’s Vanguard Study from 2009 to 2010, participants completed questionnaires and data collectors observed VOC exposure sources and collected urine samples from 488 third trimester pregnant women at in-person study visits. From urine, we simultaneously quantified 28 VOC metabolites of exposure to acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, 1,3-butadiene, carbon disulfide, crotonaldehyde, cyanide, N,N-dimethylformamide, ethylbenzene, ethylene oxide, propylene oxide, styrene, tetrachloroethylene, toluene, trichloroethylene, vinyl chloride, and xylene exposures using ultra high performance liquid chromatography coupled with an electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS) method. Urinary thiocyanate was measured using an ion chromatography coupled with an electrospray ionization tandem mass spectrometry method (IC-ESI/MSMS). We modeled the relationship between urinary VOC metabolite concentrations and sources of VOC exposure. Sources of exposure were assessed by participant report via questionnaire (use of air fresheners, aerosols, paint or varnish, organic solvents, and passive/active smoking) and by observations by a trained data collector (presence of scented products in homes). We found several significant (p < 0.01) relationships between the urinary metabolites of VOCs and sources of VOC exposure. Smoking was positively associated with metabolites of the tobacco constituents acrolein, acrylamide, acrylonitrile, 1,3-butadiene, crotonaldehyde, cyanide, ethylene oxide, N,N-dimethylformamide, propylene oxide, styrene, and xylene. Study location was negatively associated with the toluene metabolite N

Review of the state of the art of human biomonitoring for chemical substances and its application to human exposure assessment for food safety

DEFF Research Database (Denmark)

Choi, Judy; Mørck, Thit Aarøe; Polcher, Alexandra

2015-01-01

Human biomonitoring (HBM) measures the levels of substances in body fluids and tissues. Many countries have conducted HBM studies, yet little is known about its application towards chemical risk assessment, particularly in relation to food safety. Therefore a literature search was performed...... in several databases and conference proceedings for 2002 – 2014. Definitions of HBM and biomarkers, HBM techniques and requirements, and the possible application to the different steps of risk assessment were described. The usefulness of HBM for exposure assessment of chemical substances from food source...... safety areas (namely exposure assessment), and for the implementation of a systematic PMM approach. But further work needs to be done to improve usability. Major deficits are the lack of HBM guidance values on a considerable number of substance groups, for which health based guidance values (HBGVs) have...

Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

Energy Technology Data Exchange (ETDEWEB)

Cazenave, Jimena, E-mail: jcazenave@inali.unl.edu.a [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Bacchetta, Carla; Parma, Maria J.; Scarabotti, Pablo A. [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Wunderlin, Daniel A. [Dto. Bioquimica Clinica-CIBICI-CONICET, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre esq Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

2009-11-15

This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems. - A battery of biomarkers was successfully applied to assess the health of the fish Prochilodus lineatus from Salado River basin.

Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

International Nuclear Information System (INIS)

Cazenave, Jimena; Bacchetta, Carla; Parma, Maria J.; Scarabotti, Pablo A.; Wunderlin, Daniel A.

2009-01-01

This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems. - A battery of biomarkers was successfully applied to assess the health of the fish Prochilodus lineatus from Salado River basin.

Validation of the Brazilian Healthy Eating Index-Revised Using Biomarkers in Children and Adolescents

Directory of Open Access Journals (Sweden)

Roseli B. D. Toffano

2018-01-01

Full Text Available The Brazilian Healthy Eating Index-Revised (BHEI-R can be used to determine overall dietary patterns. We assessed the BHEI-R scores in children and adolescents, aged from 9 to 13 years old, and associated its component scores with biomarkers of health and dietary exposure. Three 24-h recalls were used to generate BHEI-R. Biomarkers were analyzed in plasma and red blood cells. Correlation tests, agreement, and covariance analyses were used to associate BHEI-R components with biomarkers. Data from 167 subjects were used. The strongest correlations were between fruits, vegetables and legumes with omega-6 and omega-3 fatty acids, and β-carotene intakes. Milk and dairy correlated with plasma retinol and pyridoxine. All components rich in vegetable and animal protein sources correlated with plasma creatine. Total BHEI-R scores were positively associated with intakes of omega-6, omega-3, fiber and vitamin C, and inversely associated with energy and saturated fat intakes of individuals. Plasma β-carotene and riboflavin biomarkers were positively associated with total BHEI-R. An inadequate food consumption pattern was captured by both biomarkers of health and dietary exposure. BHEI-R was validated for the above dietary components and can be associated with metabolomics and nutritional epidemiological data in future pediatric studies.

Biomarkers for Pulmonary Inflammation and Fibrosis and Lung Ventilation Function in Chinese Occupational Refractory Ceramic Fibers-Exposed Workers.

Science.gov (United States)

Zhu, Xiaojun; Gu, Yishuo; Ma, Wenjun; Gao, Panjun; Liu, Mengxuan; Xiao, Pei; Wang, Hongfei; Chen, Juan; Li, Tao

2017-12-27

Refractory ceramic fibers (RCFs) can cause adverse health effects on workers' respiratory system, yet no proper biomarkers have been used to detect early pulmonary injury of RCFs-exposed workers. This study assessed the levels of two biomarkers that are related to respiratory injury in RCFs-exposed workers, and explored their relations with lung function. The exposure levels of total dust and respirable fibers were measured simultaneously in RCFs factories. The levels of TGF-β1 and ceruloplasmin (CP) increased with the RCFs exposure level ( p relations were found between the concentrations of CP and FVC (B = -0.423, p = 0.025), or FEV₁ (B = -0.494, p = 0.014). The concentration of TGF-β1 (B = 0.103, p = 0.001) and CP (B = 8.027, p = 0.007) were associated with respirable fiber exposure level. Occupational exposure to RCFs can impair lung ventilation function and may have the potential to cause pulmonary inflammation and fibrosis. TGF-β1 and CP might be used as sensitive and noninvasive biomarkers to detect lung injury in occupational RCFs-exposed workers. Respirable fiber concentration can better reflect occupational RCFs exposure and related respiratory injuries.

Effects of low-level exposure to xenobiotics present in paints on oxidative stress in workers.

Science.gov (United States)

Moro, Angela M; Charão, Mariele; Brucker, Natália; Bulcão, Rachel; Freitas, Fernando; Guerreiro, Gilian; Baierle, Marília; Nascimento, Sabrina; Waechter, Fernanda; Hirakata, Vânia; Linden, Rafael; Thiesen, Flávia V; Garcia, Solange Cristina

2010-09-15

Paints are composed of an extensive variety of hazardous substances, such as organic solvents and heavy metals. Biomonitoring is an essential tool for assessing the risk to occupational health. Thus, this study analyzed the levels of biomarkers of exposure for toluene, xylene, styrene, ethylbenzene, and lead, as well as the oxidative stress biomarker alterations in painters of an industry. Lipid peroxidation biomarker (MDA), delta-aminolevulinate dehydratase (ALA-D), nonprotein thyol groups, superoxide dismutase and catalase (CAT) were analyzed in exposed and nonexposed subjects. We estimated which of the paint constituents have the greatest influence on the changes in the biomarkers of oxidative stress in this case of co-exposure. The results demonstrated that despite the fact that all the biomarkers of exposure were below the biological exposure limits, the MDA levels and antioxidant enzyme activities were increased, while nonprotein thyol groups and ALA-D levels were decreased in painters when compared with nonexposed subjects. After statistic test, toluene could be suggested as the principal factor responsible for increased lipid peroxidation and inhibition of ALA-D enzyme; however, further studies on the inhibition of ALA-D enzyme by toluene are necessary. Copyright 2010 Elsevier B.V. All rights reserved.

Quantitative imaging biomarkers: a review of statistical methods for technical performance assessment.

Science.gov (United States)

Raunig, David L; McShane, Lisa M; Pennello, Gene; Gatsonis, Constantine; Carson, Paul L; Voyvodic, James T; Wahl, Richard L; Kurland, Brenda F; Schwarz, Adam J; Gönen, Mithat; Zahlmann, Gudrun; Kondratovich, Marina V; O'Donnell, Kevin; Petrick, Nicholas; Cole, Patricia E; Garra, Brian; Sullivan, Daniel C

2015-02-01

Technological developments and greater rigor in the quantitative measurement of biological features in medical images have given rise to an increased interest in using quantitative imaging biomarkers to measure changes in these features. Critical to the performance of a quantitative imaging biomarker in preclinical or clinical settings are three primary metrology areas of interest: measurement linearity and bias, repeatability, and the ability to consistently reproduce equivalent results when conditions change, as would be expected in any clinical trial. Unfortunately, performance studies to date differ greatly in designs, analysis method, and metrics used to assess a quantitative imaging biomarker for clinical use. It is therefore difficult or not possible to integrate results from different studies or to use reported results to design studies. The Radiological Society of North America and the Quantitative Imaging Biomarker Alliance with technical, radiological, and statistical experts developed a set of technical performance analysis methods, metrics, and study designs that provide terminology, metrics, and methods consistent with widely accepted metrological standards. This document provides a consistent framework for the conduct and evaluation of quantitative imaging biomarker performance studies so that results from multiple studies can be compared, contrasted, or combined. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study.

Directory of Open Access Journals (Sweden)

Kathleen D Liu

Full Text Available Although stored urine samples are often used in biomarker studies focused on acute and chronic kidney disease, how storage time impacts biomarker levels is not well understood.866 subjects enrolled in the NIDDK-sponsored ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI Study were included. Samples were processed under standard conditions and stored at -70°C until analyzed. Kidney injury molecule-1 (KIM-1, neutrophil gelatinase-associated lipocalin (NGAL, interleukin-18 (IL-18, and liver fatty acid binding protein (L-FABP were measured in urine samples collected during the index hospitalization or an outpatient visit 3 months later. Mixed effects models were used to determine the effect of storage time on biomarker levels and stratified by visit.Median storage was 17.8 months (25-75% IQR 10.6-23.7 for samples from the index hospitalization and 14.6 months (IQR 7.3-20.4 for outpatient samples. In the mixed effects models, the only significant association between storage time and biomarker concentration was for KIM-1 in outpatient samples, where each month of storage was associated with a 1.7% decrease (95% CI -3% to -0.3%. There was no relationship between storage time and KIM-1 levels in samples from the index hospitalization.There was no significant impact of storage time over a median of 18 months on urine KIM-1, NGAL, IL-18 or L-FABP in hospitalized samples; a statistically significant effect towards a decrease over time was noted for KIM-1 in outpatient samples. Additional studies are needed to determine whether longer periods of storage at -70°C systematically impact levels of these analytes.

Assessment of mercury exposure among small-scale gold miners using mercury stable isotopes

International Nuclear Information System (INIS)

Sherman, Laura S.; Blum, Joel D.; Basu, Niladri; Rajaee, Mozhgon; Evers, David C.; Buck, David G.; Petrlik, Jindrich; DiGangi, Joseph

2015-01-01

Total mercury (Hg) concentrations in hair and urine are often used as biomarkers of exposure to fish-derived methylmercury (MeHg) and gaseous elemental Hg, respectively. We used Hg stable isotopes to assess the validity of these biomarkers among small-scale gold mining populations in Ghana and Indonesia. Urine from Ghanaian miners displayed similar Δ 199 Hg values to Hg derived from ore deposits (mean urine Δ 199 Hg=0.01‰, n=6). This suggests that urine total Hg concentrations accurately reflect exposure to inorganic Hg among this population. Hair samples from Ghanaian miners displayed low positive Δ 199 Hg values (0.23–0.55‰, n=6) and low percentages of total Hg as MeHg (7.6–29%, n=7). These data suggest that the majority of the Hg in these miners' hair samples is exogenously adsorbed inorganic Hg and not fish-derived MeHg. Hair samples from Indonesian gold miners who eat fish daily displayed a wider range of positive Δ 199 Hg values (0.21–1.32‰, n=5) and percentages of total Hg as MeHg (32–72%, n=4). This suggests that total Hg in the hair samples from Indonesian gold miners is likely a mixture of ingested fish MeHg and exogenously adsorbed inorganic Hg. Based on data from both populations, we suggest that total Hg concentrations in hair samples from small-scale gold miners likely overestimate exposure to MeHg from fish consumption. - Highlights: • Mercury isotopes were measured in hair and urine from small-scale gold miners. • Mercury isotopes indicate that Hg in urine comes from mining activity. • Mercury isotopes suggest Hg in hair is a mixture of fish MeHg and inorganic Hg. • A large percentage of Hg in miner’s hair is released during amalgam burning and adsorbed

Assessing Smoking Behaviour and Tobacco Smoke Exposure: Definitions and Methods

Directory of Open Access Journals (Sweden)

Gregg E

2014-12-01

Full Text Available In recent years, the increased availability of tobacco products other than conventional cigarettes, the use of puffing topography devices for smoking behaviour studies and the use of biomarkers to study smoke constituents exposure have generated the need for a more comprehensive set of definitions concerning smoking behaviour and exposure to smoke. The definitions offered in this paper are based on many years of practical experience and on consensus within a broad group of scientists working in these areas. It is intended that, with wider and more consistent usage, these definitions should reduce any misunderstandings and facilitate interpretation of future studies.

mRNA expression of a cadmium-responsive gene is a sensitive biomarker of cadmium exposure in the soil collembolan Folsomia candida

International Nuclear Information System (INIS)

Nakamori, Taizo; Fujimori, Akira; Kinoshita, Keiji; Ban-nai, Tadaaki; Kubota, Yoshihisa; Yoshida, Satoshi

2010-01-01

The gene expression of environmental organisms is useful as a biomarker of environmental pollution. One of its advantages is high sensitivity. We identified the cDNA of a novel cadmium-responsive gene in the soil collembolan Folsomia candida. The deduced protein, designated 'metallothionein-like motif containing protein' (MTC), was cysteine-rich and contained a metallothionein-like motif with similarity to metallothionein, but had a much longer sequence than metallothionein and contained repeated sequences of amino acids. Expression of MTC mRNA was sensitively induced by cadmium exposure at 0.3 mg/kg of dry food, a concentration at which toxic effects are not observed, but expression was not affected by γ-ray exposure (an inducer of oxidative stress). These findings suggest that MTC is involved in cadmium-binding processes rather than in oxidative-stress responses. In conclusion, we suggest that gene expression of MTC may be a candidate biomarker for detecting low levels of cadmium contamination in soil. - The mRNA expression of a gene potentially encoding a metallothionein-like motif containing protein is sensitively induced by cadmium exposure in the soil collembolan Folsomia candida.

mRNA expression of a cadmium-responsive gene is a sensitive biomarker of cadmium exposure in the soil collembolan Folsomia candida

Energy Technology Data Exchange (ETDEWEB)

Nakamori, Taizo, E-mail: taizo@ynu.ac.j [Environmental Radiation Effects Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Fujimori, Akira [Heavy-Ion Radiobiology Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Kinoshita, Keiji [Nagoya University Avian Bioscience Research Centre, Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Ban-nai, Tadaaki; Kubota, Yoshihisa; Yoshida, Satoshi [Environmental Radiation Effects Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

2010-05-15

The gene expression of environmental organisms is useful as a biomarker of environmental pollution. One of its advantages is high sensitivity. We identified the cDNA of a novel cadmium-responsive gene in the soil collembolan Folsomia candida. The deduced protein, designated 'metallothionein-like motif containing protein' (MTC), was cysteine-rich and contained a metallothionein-like motif with similarity to metallothionein, but had a much longer sequence than metallothionein and contained repeated sequences of amino acids. Expression of MTC mRNA was sensitively induced by cadmium exposure at 0.3 mg/kg of dry food, a concentration at which toxic effects are not observed, but expression was not affected by gamma-ray exposure (an inducer of oxidative stress). These findings suggest that MTC is involved in cadmium-binding processes rather than in oxidative-stress responses. In conclusion, we suggest that gene expression of MTC may be a candidate biomarker for detecting low levels of cadmium contamination in soil. - The mRNA expression of a gene potentially encoding a metallothionein-like motif containing protein is sensitively induced by cadmium exposure in the soil collembolan Folsomia candida.

Impact of the Improved Patsari Biomass Stove on Urinary Polycyclic Aromatic Hydrocarbon Biomarkers and Carbon Monoxide Exposures in Rural Mexican Women

Science.gov (United States)

Riojas-Rodriguez, Horacio; Schilmann, Astrid; Marron-Mares, Adriana Teresa; Masera, Omar; Li, Zheng; Romanoff, Lovisa; Sjödin, Andreas; Rojas-Bracho, Leonora; Needham, Larry L.

2011-01-01

Background: Cooking with biomass fuels on open fires results in exposure to health-damaging pollutants such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), and particulate matter. Objective: We compared CO exposures and urinary PAH biomarkers pre- and postintervention with an improved biomass stove, the Patsari stove. Methods: In a subsample of 63 women participating in a randomized controlled trial in central Mexico, we measured personal CO exposure for 8 hr during the day using continuous monitors and passive samplers. In addition, first-morning urine samples obtained the next day were analyzed for monohydroxylated PAH metabolites by gas chromatography/isotope dilution/high-resolution mass spectrometry. Exposure data were collected during the use of an open fire (preintervention) and after installation of the improved stove (postintervention) for 47 women, enabling paired comparisons. Results: Median pre- and postintervention values were 4 and 1 ppm for continuous personal CO and 3 and 1 ppm for passive sampler CO, respectively. Postintervention measurements indicated an average reduction of 42% for hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene on a whole-weight concentration basis (micrograms per liter of urine), and a 34% reduction on a creatinine-adjusted basis (micrograms per gram of creatinine). Pre- and postintervention geometric mean values for 1-hydroxypyrene were 3.2 and 2.0 μg/g creatinine, respectively. Conclusion: Use of the Patsari stove significantly reduced CO and PAH exposures in women. However, levels of many PAH biomarkers remained higher than those reported among smokers. PMID:21622083

Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

International Nuclear Information System (INIS)

Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés

2017-01-01

Highlights: • Arsenic early induces MAPK pathway in R. arenarum embryos and larvae. • The MAPKs MEK-ERK in turn upregulate the transcription factors c-FOS and c-JUN. • SOD, CAT and GST would be affected by ROS at synthesis and degradation level. • Low As levels inducing molecular biomarkers have high probabilities of exceedence. • Molecular biomarkers are most adequate to ascertain As impact in R. arenarum. - Abstract: Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15 mg L"–"1. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of

Molecular effectors in the chronic exposure to arsenic as early and sensitive biomarkers in developing Rhinella arenarum toads

Energy Technology Data Exchange (ETDEWEB)

Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés, E-mail: a.venturino@conicet.gov.ar

2017-05-15

Highlights: • Arsenic early induces MAPK pathway in R. arenarum embryos and larvae. • The MAPKs MEK-ERK in turn upregulate the transcription factors c-FOS and c-JUN. • SOD, CAT and GST would be affected by ROS at synthesis and degradation level. • Low As levels inducing molecular biomarkers have high probabilities of exceedence. • Molecular biomarkers are most adequate to ascertain As impact in R. arenarum. - Abstract: Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15 mg L{sup –1}. The Argentinean autochthonous toad Rhinella arenarum was selected to study the molecular mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of

Pb enamel biomarker: Deposition of pre- and postnatal Pb isotope injection in reconstructed time points along rat enamel transect

International Nuclear Information System (INIS)

Rinderknecht, A.L.; Kleinman, M.T.; Ericson, J.E.

2005-01-01

Exposure to lead (Pb) as well as other heavy metals in the environment is still a matter of public health concern. The development of the enamel biomarker for heavy metal exposure assessment is designed to improve studies of dose-effect relationships to developmental anomalies, particularly embryonic dysfunctions, and to provide a time-specific recount of past exposures. The work presented in this paper demonstrates maternal transfer across the placental barrier of the enriched isotope 206 Pb tracer to the enamel of the rat pup. Likewise, injections of 204 Pb-enriched tracer in the neonate rat resulted in deposition of the tracer in the enamel histology as measured by secondary ion microprobe spectrometry. Through enamel, we were able to observe biological removal and assimilation of prenatal and postnatal tracers, respectively. This research demonstrates that enamel can be used as a biomarker of exposure to Pb and may illustrate the toxicokinetics of incorporating Pb into fetal and neonatal steady-state system processes. The biomarker technique, when completely developed, may be applied to cross-sectional and longitudinal epidemiological research

A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the correlation between serum and meconium and their association with infant birth weight

Directory of Open Access Journals (Sweden)

Braun Joe M

2010-08-01

Full Text Available Abstract Background The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure. Methods We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'-hydroxycotinine concentrations and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression. Results We detected nicotine (80%, cotinine (69%, and trans-3'-hydroxycotinine (57% in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight. Conclusions Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.

Combining traditional dietary assessment methods with novel metabolomics techniques : present efforts by the Food Biomarker Alliance

NARCIS (Netherlands)

Brouwer-Brolsma, Elske M.; Brennan, Lorraine; Drevon, Christian A.; van Kranen, Henk; Manach, Claudine; Dragsted, Lars Ove; Roche, Helen M.; Andres-Lacueva, Cristina; Bakker, Stephan J. L.; Bouwman, Jildau; Capozzi, Francesco; De Saeger, Sarah; Gundersen, Thomas E.; Kolehmainen, Marjukka; Kulling, Sabine E.; Landberg, Rikard; Linseisen, Jakob; Mattivi, Fulvio; Mensink, Ronald P.; Scaccini, Cristina; Skurk, Thomas; Tetens, Inge; Vergeres, Guy; Wishart, David S.; Scalbert, Augustin; Feskens, Edith J. M.

FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently

Exploring Global Exposure Factors Resources for Use in Consumer Exposure Assessments

Science.gov (United States)

Zaleski, Rosemary T.; Egeghy, Peter P.; Hakkinen, Pertti J.

2016-01-01

This publication serves as a global comprehensive resource for readers seeking exposure factor data and information relevant to consumer exposure assessment. It describes the types of information that may be found in various official surveys and online and published resources. The relevant exposure factors cover a broad range, including general exposure factor data found in published compendia and databases and resources about specific exposure factors, such as human activity patterns and housing information. Also included are resources on exposure factors related to specific types of consumer products and the associated patterns of use, such as for a type of personal care product or a type of children’s toy. Further, a section on using exposure factors for designing representative exposure scenarios is included, along with a look into the future for databases and other exposure science developments relevant for consumer exposure assessment. PMID:27455300

Asbestos Exposure Assessment Database

Science.gov (United States)

Arcot, Divya K.

2010-01-01

Exposure to particular hazardous materials in a work environment is dangerous to the employees who work directly with or around the materials as well as those who come in contact with them indirectly. In order to maintain a national standard for safe working environments and protect worker health, the Occupational Safety and Health Administration (OSHA) has set forth numerous precautionary regulations. NASA has been proactive in adhering to these regulations by implementing standards which are often stricter than regulation limits and administering frequent health risk assessments. The primary objective of this project is to create the infrastructure for an Asbestos Exposure Assessment Database specific to NASA Johnson Space Center (JSC) which will compile all of the exposure assessment data into a well-organized, navigable format. The data includes Sample Types, Samples Durations, Crafts of those from whom samples were collected, Job Performance Requirements (JPR) numbers, Phased Contrast Microscopy (PCM) and Transmission Electron Microscopy (TEM) results and qualifiers, Personal Protective Equipment (PPE), and names of industrial hygienists who performed the monitoring. This database will allow NASA to provide OSHA with specific information demonstrating that JSC s work procedures are protective enough to minimize the risk of future disease from the exposures. The data has been collected by the NASA contractors Computer Sciences Corporation (CSC) and Wyle Laboratories. The personal exposure samples were collected from devices worn by laborers working at JSC and by building occupants located in asbestos-containing buildings.

Model-based analysis of thromboxane B2 and prostaglandin E2 as biomarkers in the safety evaluation of naproxen

International Nuclear Information System (INIS)

Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert; Della Pasqua, Oscar

2014-01-01

The assessment of safety in traditional toxicology protocols relies on evidence arising from observed adverse events (AEs) in animals and on establishing their correlation with different measures of drug exposure (e.g., C max and AUC). Such correlations, however, ignore the role of biomarkers, which can provide further insight into the underlying pharmacological mechanisms. Here we use naproxen as a paradigm drug to explore the feasibility of a biomarker-guided approach for the prediction of AEs in humans. A standard toxicology protocol was set up for the evaluation of effects of naproxen in rat, in which four doses were tested (7.5, 15, 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of exposure, thromboxane B 2 and prostaglandin E 2 were also collected in satellite groups. Nonlinear mixed effects modelling was used to evaluate the predictive performance of the approach. A one-compartmental model with first order absorption was found to best describe the pharmacokinetics of naproxen. A nonlinear relationship between dose and bioavailability was observed which leads to a less than proportional increase in naproxen concentrations with increasing doses. The pharmacodynamics of TXB 2 and PGE 2 was described by direct inhibition models with maximum pharmacological effects achieved at doses > 7.5 mg/kg. The predicted PKPD relationship in humans was within 10-fold of the values previously published. Moreover, our results indicate that biomarkers can be used to assess interspecies differences in PKPD and extrapolated data from animals to humans. Biomarker sampling should be used systematically in general toxicity studies. - Highlights: • Prediction of a drug's safety profile from preclinical protocols remains challenging. • Pharmacokinetic measures of safe exposure (e.g., AUC) ignore the role of biomarkers. • PKPD relationships enable the evaluation of adverse events in a mechanistic manner. • Major differences exist between rats and

Cellular Models for Environmental Toxicant Biomarker Discovery

National Research Council Canada - National Science Library

Halverson, Kelly M; Lewsis, John A; Jackson, David A; Dennis, William; Brennan, Linda; Krakaner, Teresa

2006-01-01

...) is the development of biomarkers of exposure, effect, and susceptibility. As exposure monitoring using environmental sampling equipment can be impractical and doesn't account for differences in individual responses, new methodologies must be sought...

Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study

Science.gov (United States)

Liu, Kathleen D.; Siew, Edward D.; Reeves, W. Brian; Himmelfarb, Jonathan; Go, Alan S.; Hsu, Chi-yuan; Bennett, Michael R.; Devarajan, Prasad; Ikizler, T. Alp; Kaufman, James S.; Kimmel, Paul L.; Chinchilli, Vernon M.; Parikh, Chirag R.

2016-01-01

Background Although stored urine samples are often used in biomarker studies focused on acute and chronic kidney disease, how storage time impacts biomarker levels is not well understood. Methods 866 subjects enrolled in the NIDDK-sponsored ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study were included. Samples were processed under standard conditions and stored at -70°C until analyzed. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and liver fatty acid binding protein (L-FABP) were measured in urine samples collected during the index hospitalization or an outpatient visit 3 months later. Mixed effects models were used to determine the effect of storage time on biomarker levels and stratified by visit. Results Median storage was 17.8 months (25–75% IQR 10.6–23.7) for samples from the index hospitalization and 14.6 months (IQR 7.3–20.4) for outpatient samples. In the mixed effects models, the only significant association between storage time and biomarker concentration was for KIM-1 in outpatient samples, where each month of storage was associated with a 1.7% decrease (95% CI -3% to -0.3%). There was no relationship between storage time and KIM-1 levels in samples from the index hospitalization. Conclusion There was no significant impact of storage time over a median of 18 months on urine KIM-1, NGAL, IL-18 or L-FABP in hospitalized samples; a statistically significant effect towards a decrease over time was noted for KIM-1 in outpatient samples. Additional studies are needed to determine whether longer periods of storage at -70°C systematically impact levels of these analytes. PMID:27788160

Children's exposure to environmental pollutants and biomarkers of genetic damage. II. Results of a comprehensive literature search and meta-analysis

DEFF Research Database (Denmark)

Neri, Monica; Ugolini, Donatella; Bonassi, Stefano

2005-01-01

The present review is based on findings from 178 publications retrieved through an extensive search of the MedLine/PubMed database for a 25 years time period (1980-2004) and 10 manually identified papers. Among the cytogenetic biomarkers that are frequently used in field studies, chromosome...... pollutants, soil and drinking water contaminants, mostly increased CA and, to a lesser extent, MN levels in children. The effect of exposure to airborne urban pollutants was consistently reported by field studies measuring DNA, albumin and hemoglobin adducts. Prenatal (in utero) and postnatal exposure...

Exposure Assessment Tools by Chemical Classes - Nanomaterials

Science.gov (United States)

EPA ExpoBox is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases

Exposure Assessment Tools by Tiers and Types - Deterministic and Probabilistic Assessments

Science.gov (United States)

EPA ExpoBox is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases

Determinants of Dermal Exposure Relevant for Exposure Modelling in Regulatory Risk Assessment

NARCIS (Netherlands)

Marquart, J.; Brouwer, D.H.; Gijsbers, J.H.J.; Links, I.H.M.; Warren, N.; Hemmen, J.J. van

2003-01-01

Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European

Human exposure, biomarkers, and fate of organotins in the environment.

Science.gov (United States)

Okoro, Hussein K; Fatoki, Olalekan S; Adekola, Folahan A; Ximba, Bhekumusa J; Snyman, Reinette G; Opeolu, Beatrice

2011-01-01

organotins and the consequences of exposure to them are needed. In particular, we believe the following areas need attention: expanded toxicity testing in aquatic species, human exposure, human body burdens, and the research to identify biomarkers for testing the toxicity of the organotins to marine invertebrates.

Comparative Probabilistic Assessment of Occupational Pesticide Exposures Based on Regulatory Assessments

Science.gov (United States)

Pouzou, Jane G.; Cullen, Alison C.; Yost, Michael G.; Kissel, John C.; Fenske, Richard A.

2018-01-01

Implementation of probabilistic analyses in exposure assessment can provide valuable insight into the risks of those at the extremes of population distributions, including more vulnerable or sensitive subgroups. Incorporation of these analyses into current regulatory methods for occupational pesticide exposure is enabled by the exposure data sets and associated data currently used in the risk assessment approach of the Environmental Protection Agency (EPA). Monte Carlo simulations were performed on exposure measurements from the Agricultural Handler Exposure Database and the Pesticide Handler Exposure Database along with data from the Exposure Factors Handbook and other sources to calculate exposure rates for three different neurotoxic compounds (azinphos methyl, acetamiprid, emamectin benzoate) across four pesticide-handling scenarios. Probabilistic estimates of doses were compared with the no observable effect levels used in the EPA occupational risk assessments. Some percentage of workers were predicted to exceed the level of concern for all three compounds: 54% for azinphos methyl, 5% for acetamiprid, and 20% for emamectin benzoate. This finding has implications for pesticide risk assessment and offers an alternative procedure that may be more protective of those at the extremes of exposure than the current approach. PMID:29105804

Comparative Probabilistic Assessment of Occupational Pesticide Exposures Based on Regulatory Assessments.

Science.gov (United States)

Pouzou, Jane G; Cullen, Alison C; Yost, Michael G; Kissel, John C; Fenske, Richard A

2017-11-06

Implementation of probabilistic analyses in exposure assessment can provide valuable insight into the risks of those at the extremes of population distributions, including more vulnerable or sensitive subgroups. Incorporation of these analyses into current regulatory methods for occupational pesticide exposure is enabled by the exposure data sets and associated data currently used in the risk assessment approach of the Environmental Protection Agency (EPA). Monte Carlo simulations were performed on exposure measurements from the Agricultural Handler Exposure Database and the Pesticide Handler Exposure Database along with data from the Exposure Factors Handbook and other sources to calculate exposure rates for three different neurotoxic compounds (azinphos methyl, acetamiprid, emamectin benzoate) across four pesticide-handling scenarios. Probabilistic estimates of doses were compared with the no observable effect levels used in the EPA occupational risk assessments. Some percentage of workers were predicted to exceed the level of concern for all three compounds: 54% for azinphos methyl, 5% for acetamiprid, and 20% for emamectin benzoate. This finding has implications for pesticide risk assessment and offers an alternative procedure that may be more protective of those at the extremes of exposure than the current approach. © 2017 Society for Risk Analysis.

Assessment of biological effects of pollutants in a hyper eutrophic tropical water body, Lake Beira, Sri Lanka using multiple biomarker responses of resident fish, Nile tilapia (Oreochromis niloticus).

Science.gov (United States)

Pathiratne, Asoka; Pathiratne, K A S; De Seram, P K C

2010-08-01

Biomarkers measured at the molecular and cellular level in fish have been proposed as sensitive "early warning" tools for biological effect measurements in environmental quality assessments. Lake Beira is a hypertrophic urban water body with a complex mixture of pollutants including polycyclic aromatic hydrocarbons (PAHs) and Microcystins. In this study, a suite of biomarker responses viz. biliary fluorescent aromatic compounds (FACs), hepatic ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST), brain and muscle cholinesterases (ChE), serum sorbitol dehydrogenase (SDH), and liver histology of Oreochromis niloticus, the dominant fish inhabiting this tropical Lake were evaluated to assess the pollution exposure and biological effects. Some fish sampled in the dry periods demonstrated prominent structural abnormalities in the liver and concomitant increase in serum SDH and reduction in hepatic GST activities in comparison to the control fish and the fish sampled in the rainy periods. The resident fish with apparently normal liver demonstrated induction of hepatic EROD and GST activities and increase in biliary FACs irrespective of the sampling period indicating bioavailability of PAHs. Muscle ChE activities of the resident fish were depressed significantly indicating exposure to anticholinesterase substances. The results revealed that fish populations residing in this Lake is under threat due to the pollution stress. Hepatic abnormalities in the fish may be mainly associated with the pollution stress due to recurrent exposure to PAHs and toxigenic Microcystis blooms in the Lake.

Mercury levels assessment and its relationship with oxidative stress biomarkers in children from three localities in Yucatan, Mexico.

Science.gov (United States)

Rangel-Méndez, Jorge A; Arcega-Cabrera, Flor E; Fargher, Lane F; Moo-Puc, Rosa E

2016-02-01

Mercury (Hg) is a global pollutant that is released into the environment from geologic and anthropogenic sources. Once it enters an organism, it generates several toxicity mechanisms and oxidative stress has been proposed as the main one. Metal susceptibility is greater in children, which is a result of their physiology and behavior. In Yucatan, Mexico, burning of unregulated garbage dumps and household trash, ingestion of top marine predators, and pottery manufacturing are among the conditions that could promote Hg exposure. However, for Yucatan, there are no published studies that report Hg levels and associated oxidative stress status in children. Therefore, this study aimed to assess Hg levels in blood and urine and oxidative stress biomarkers levels in a sample of 107 healthy children from three localities in Yucatan, Mexico, as well as investigate the relationship between these parameters. Hg was detected in 11 (10.28%) of blood samples and 38 (35.51%) of urine samples collected from the participating children. Fourteen subjects showed Hg above recommended levels. The oxidative stress biomarkers were slightly elevated in comparison with other studies and were statistically different between the sampling sites. No linear correlation between Hg levels and oxidative stress biomarkers was found. Nevertheless, exploratory univariate and multivariate analysis showed non-linear relations among the measured variables. Globally, the study provides, for the first time, information regarding Hg levels and their relationship with oxidative stress biomarkers in a juvenile population from Mexico's southeast (Yucatan) region. In agreement with worldwide concern about Hg, this study should stimulate studies on metal monitoring in humans (especially children) among scientists working in Mexico, the establishment of polices for its regulation, and the reduction of human health risks. Copyright © 2015 Elsevier B.V. All rights reserved.

Challenges and Perspectives of Nanoparticle Exposure Assessment

OpenAIRE

Lee, Ji Hyun; Moon, Min Chaul; Lee, Joon Yeob; Yu, Il Je

2010-01-01

Nanoparticle exposure assessment presents a unique challenge in the field of occupational and environmental health. With the commercialization of nanotechnology, exposure usually starts from the workplace and then spreads to environment and consumer exposure. This report discusses the current trends of nanoparticle exposure assessment, including the definition of nanotechnology relevant terms, essential physicochemical properties for nanomaterial characterization, current international activi...

Assessing population exposures to motor vehicle exhaust.

Science.gov (United States)

Van Atten, Chris; Brauer, Michael; Funk, Tami; Gilbert, Nicolas L; Graham, Lisa; Kaden, Debra; Miller, Paul J; Bracho, Leonora Rojas; Wheeler, Amanda; White, Ronald H

2005-01-01

The need is growing for a better assessment of population exposures to motor vehicle exhaust in proximity to major roads and highways. This need is driven in part by emerging scientific evidence of adverse health effects from such exposures and policy requirements for a more targeted assessment of localized public health impacts related to road expansions and increasing commercial transportation. The momentum for improved methods in measuring local exposures is also growing in the scientific community, as well as for discerning which constituents of the vehicle exhaust mixture may exert greater public health risks for those who are exposed to a disproportionate share of roadway pollution. To help elucidate the current state-of-the-science in exposure assessments along major roadways and to help inform decision makers of research needs and trends, we provide an overview of the emerging policy requirements, along with a conceptual framework for assessing exposure to motor-vehicle exhaust that can help inform policy decisions. The framework includes the pathway from the emission of a single vehicle, traffic emissions from multiple vehicles, atmospheric transformation of emissions and interaction with topographic and meteorologic features, and contact with humans resulting in exposure that can result in adverse health impacts. We describe the individual elements within the conceptual framework for exposure assessment and discuss the strengths and weaknesses of various approaches that have been used to assess public exposures to motor vehicle exhaust.

Occupational Exposure to Alcohol-Based Hand Sanitizers: The Diagnostic Role of Alcohol Biomarkers in Hair.

Science.gov (United States)

Salomone, A; Bozzo, A; Di Corcia, D; Gerace, E; Vincenti, M

2018-04-01

Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) in hair are effective direct biomarkers of ethanol ingestion, whose analytical determination can be used to discriminate between chronic and occasional ethanol intake. Ethanol is a compound widely used in some workplaces (e.g., clinics, hospitals) and is present in considerable amounts in mouthwash for oral cleaning, medications, cosmetic products, hydro-alcoholic disinfectants and antiseptics for hands. This study examined the ethyl alcohol exposure derived from hand disinfectants (in gel form) by simulating the typical occupational situation of medical-health workers (healthcare workers, nurses, surgeons, etc.) who frequently wash their hands with antiseptic sanitizer. Two types of hand disinfectants with 62% w/w of ethanol content were daily applied to the hands of a teetotaler for 20 times a day, for 4 consecutive weeks, thus simulating a typical workplace situation and a cumulative dermal exposure to ethanol of ~1,100 g. Different matrices (head, chest and beard hair, urine) were regularly sampled and analyzed using a ultra high-performance liquid chromatography tandem massspectrometry validated method for EtG and a (HS)SPME-GC-MS validated technique for FAEEs. The data obtained showed that a significant dermal absorption and/or inhalation of ethanol occurred, and that the use of detergents produce urinary EtG concentrations both higher than the cut-offs normally used for clinical and forensic analyses (either 100 and 500 ng/mL, depending on the context). The concentrations of the ethanol metabolites in the keratin matrices were, respectively, below the cut-off of 7 pg/mg for EtG and below 0.5 ng/mg for FAAEs (0.35 ng/mg for ethyl palmitate). In conclusion, the regular use of alcohol-based hand sanitizers can affect the concentration of urinary EtG and lead to positive analytical results, particularly when specimens are obtained shortly after sustained use of ethanol-containing hand sanitizer. On the

Multiple protein biomarker assessment for recombinant bovine somatotropin (rbST abuse in cattle.

Directory of Open Access Journals (Sweden)

Susann K J Ludwig

Full Text Available Biomarker profiling, as a rapid screening approach for detection of hormone abuse, requires well selected candidate biomarkers and a thorough in vivo biomarker evaluation as previously done for detection of growth hormone doping in athletes. The bovine equivalent of growth hormone, called recombinant bovine somatotropin (rbST is (illegally administered to enhance milk production in dairy cows. In this study, first a generic sample pre-treatment and 4-plex flow cytometric immunoassay (FCIA were developed for simultaneous measurement of four candidate biomarkers selected from literature: insulin-like growth factor 1 (IGF-1, its binding protein 2 (IGFBP2, osteocalcin and endogenously produced antibodies against rbST. Next, bovine serum samples from two extensive controlled rbST animal treatment studies were used for in vivo validation and biomarker evaluation. Finally, advanced statistic tools were tested for the assessment of biomarker combination quality aiming to correctly identify rbST-treated animals. The statistical prediction tool k-nearest neighbours using a combination of the biomarkers osteocalcin and endogenously produced antibodies against rbST proved to be very reliable and correctly predicted 95% of the treated samples starting from the second rbST injection until the end of the treatment period and even thereafter. With the same biomarker combination, only 12% of untreated animals appeared false-positive. This reliability meets the requirements of Commission Decision 2002/657/EC for screening methods in veterinary control. From the results of this multidisciplinary study, it is concluded that the osteocalcin - anti-rbST-antibodies combination represent fit-for-purpose biomarkers for screening of rbST abuse in dairy cattle and can be reliably measured in both the developed 4-plex FCIA as well as in a cost-effective 2-plex microsphere-based binding assay. This screening method can be incorporated in routine veterinary monitoring

Drinking water studies: a review on heavy metal, application of biomarker and health risk assessment (a special focus in Malaysia).

Science.gov (United States)

Ab Razak, Nurul Hafiza; Praveena, Sarva Mangala; Aris, Ahmad Zaharin; Hashim, Zailina

2015-12-01

Malaysia has abundant sources of drinking water from river and groundwater. However, rapid developments have deteriorated quality of drinking water sources in Malaysia. Heavy metal studies in terms of drinking water, applications of health risk assessment and bio-monitoring in Malaysia were reviewed from 2003 to 2013. Studies on heavy metal in drinking water showed the levels are under the permissible limits as suggested by World Health Organization and Malaysian Ministry of Health. Future studies on the applications of health risk assessment are crucial in order to understand the risk of heavy metal exposure through drinking water to Malaysian population. Among the biomarkers that have been reviewed, toenail is the most useful tool to evaluate body burden of heavy metal. Toenails are easy to collect, store, transport and analysed. This review will give a clear guidance for future studies of Malaysian drinking water. In this way, it will help risk managers to minimize the exposure at optimum level as well as the government to formulate policies in safe guarding the population. Copyright © 2015 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Model-based analysis of thromboxane B{sub 2} and prostaglandin E{sub 2} as biomarkers in the safety evaluation of naproxen

Energy Technology Data Exchange (ETDEWEB)

Sahota, Tarjinder; Sanderson, Ian; Danhof, Meindert [Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden (Netherlands); Della Pasqua, Oscar [Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden (Netherlands); Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, Uxbridge (United Kingdom)

2014-08-01

The assessment of safety in traditional toxicology protocols relies on evidence arising from observed adverse events (AEs) in animals and on establishing their correlation with different measures of drug exposure (e.g., C{sub max} and AUC). Such correlations, however, ignore the role of biomarkers, which can provide further insight into the underlying pharmacological mechanisms. Here we use naproxen as a paradigm drug to explore the feasibility of a biomarker-guided approach for the prediction of AEs in humans. A standard toxicology protocol was set up for the evaluation of effects of naproxen in rat, in which four doses were tested (7.5, 15, 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of exposure, thromboxane B{sub 2} and prostaglandin E{sub 2} were also collected in satellite groups. Nonlinear mixed effects modelling was used to evaluate the predictive performance of the approach. A one-compartmental model with first order absorption was found to best describe the pharmacokinetics of naproxen. A nonlinear relationship between dose and bioavailability was observed which leads to a less than proportional increase in naproxen concentrations with increasing doses. The pharmacodynamics of TXB{sub 2} and PGE{sub 2} was described by direct inhibition models with maximum pharmacological effects achieved at doses > 7.5 mg/kg. The predicted PKPD relationship in humans was within 10-fold of the values previously published. Moreover, our results indicate that biomarkers can be used to assess interspecies differences in PKPD and extrapolated data from animals to humans. Biomarker sampling should be used systematically in general toxicity studies. - Highlights: • Prediction of a drug's safety profile from preclinical protocols remains challenging. • Pharmacokinetic measures of safe exposure (e.g., AUC) ignore the role of biomarkers. • PKPD relationships enable the evaluation of adverse events in a mechanistic manner. • Major

Global DNA methylation and oxidative stress biomarkers in workers exposed to metal oxide nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Liou, Saou-Hsing; Wu, Wei-Te; Liao, Hui-Yi [National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China); Chen, Chao-Yu; Tsai, Cheng-Yen; Jung, Wei-Ting [Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan (China); Lee, Hui-Ling, E-mail: huilinglee3573@gmail.com [Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan (China)

2017-06-05

Highlights: • Global methylation and oxidative DNA damage levels in nanomaterial handling workers were assessed. • 8-isoprostane in exhaled breath condensate of workers exposed to nanoparticles was higher. • 8-OHdG was negatively correlated with global methylation. • Exposure to metal oxide nanoparticles may lead to global methylation and DNA oxidative damage. - Abstract: This is the first study to assess global methylation, oxidative DNA damage, and lipid peroxidation in workers with occupational exposure to metal oxide nanomaterials (NMs). Urinary and white blood cell (WBC) 8-hydroxydeoxyguanosine (8-OHdG), and exhaled breath condensate (EBC) 8-isoprostane were measured as oxidative stress biomarkers. WBC global methylation was measured as an epigenetic alteration. Exposure to TiO{sub 2}, SiO{sub 2,} and indium tin oxide (ITO) resulted in significantly higher oxidative biomarkers such as urinary 8-OHdG and EBC 8-isoprostane. However, significantly higher WBC 8-OHdG and lower global methylation were only observed in ITO handling workers. Significant positive correlations were noted between WBC and urinary 8-OHdG (Spearman correlation r = 0.256, p = 0.003). Furthermore, a significant negative correlation was found between WBC 8-OHdG and global methylation (r = −0.272, p = 0.002). These results suggest that exposure to metal oxide NMs may lead to global methylation, DNA oxidative damage, and lipid peroxidation.

Health Status of Sand Flathead (Platycephalus bassensis, Inhabiting an Industrialised and Urbanised Embayment, Port Phillip Bay, Victoria as Measured by Biomarkers of Exposure and Effects.

Directory of Open Access Journals (Sweden)

Jarrad K Baker

Full Text Available Port Phillip Bay, Australia, is a large semi-closed bay with over four million people living in its catchment basin. The Bay receives waters from the Yarra River which drains the city of Melbourne, as well as receiving the discharges of sewage treatment plants and petrochemical and agricultural chemicals. A 1999 study demonstrated that fish inhabiting Port Phillip Bay showed signs of effects related to pollutant exposure despite pollution management practices having been implemented for over a decade. To assess the current health status of the fish inhabiting the Bay, a follow up survey was conducted in 2015. A suite of biomarkers of exposure and effects were measured to determine the health status of Port Phillip Bay sand flathead (Platycephalus bassensis, namely ethoxyresorufin-O-deethylase (EROD activity, polycyclic aromatic hydrocarbons (PAH biliary metabolites, carboxylesterase activity (CbE and DNA damage (8-oxo-dG. The reduction in EROD activity in the present study suggests a decline in the presence of EROD activity-inducing chemicals within the Bay since the 1990s. Fish collected in the most industrialised/urbanised sites did not display higher PAH metabolite levels than those in less developed areas of the Bay. Ratios of PAH biliary metabolite types were used to indicate PAH contaminant origin. Ratios indicated fish collected at Corio Bay and Hobsons Bay were subjected to increased low molecular weight hydrocarbons of petrogenic origin, likely attributed to the close proximity of these sites to oil refineries, compared to PAH biliary metabolites in fish from Geelong Arm and Mordialloc. Quantification of DNA damage indicated a localised effect of exposure to pollutants, with a 10-fold higher DNA damage level in fish sampled from the industrial site of Corio Bay relative to the less developed site of Sorrento. Overall, integration of biomarkers by multivariate analysis indicated that the health of fish collected in industrialised areas

Health risk assessment of exposure to ionizing radiation

International Nuclear Information System (INIS)

Ogata, Hiromitsu

2011-01-01

Risk assessment is an essential process for evaluating the human health effects of exposure to ionizing radiation and for determining acceptable levels of exposure. There are two major components of radiation risk assessment: a measure of exposure level and a measure of disease occurrence. For quantitative estimation of health risks, it is important to evaluate the association between exposure and disease occurrence using epidemiological or experimental data. In these approaches, statistical risk models are used particularly for estimating cancer risks related to exposure to low levels of radiation. This paper presents a summary of basic models and methods of risk assessment for studying exposure-risk relationships. Moreover, quantitative risk estimates are subject to several sources of uncertainty due to inherent limitations in risk assessment studies. This paper also discusses the limitations of radiation risk assessment. (author)

Molecular Biomarkers: Their significance and application in marine pollution monitoring

Digital Repository Service at National Institute of Oceanography (India)

Sarkar, A.; Ray, D.; Shrivastava, A.N.; Sarkar, S.

worldwide. Among the various types of biomarkers, the following have received special attention: cytochrome P4501A induction, DNA integrity, acetylcholinesterase activity and metallothionein induction. These biomarkers are being used to evaluate exposure...

Use of urinary biomarkers to characterize occupational exposure to BTEX in healthcare waste autoclave operators.

Science.gov (United States)

Rafiee, Ata; Delgado-Saborit, Juana Maria; Gordi, Elham; Quémerais, Bernadette; Kazemi Moghadam, Vahid; Lu, Wenjing; Hashemi, Fallah; Hoseini, Mohammad

2018-08-01

Urinary benzene, toluene, ethylbenzene, and xylenes (BTEX) can be used as a reliable biomarker of exposure to these pollutants. This study was aimed to investigate the urinary BTEX concentration in operators of healthcare waste (HCW) autoclaves. This cross-sectional study was conducted in selected hospitals in Tehran, Iran between April and June 2017. Twenty operators (as the case group) and twenty control subjects were enrolled in the study. Personal urine samples were collected at the beginning and end of the work shift. Urinary BTEX were measured by a headspace gas chromatography-mass spectrometry (GC/MS). A detailed questionnaire was used to gather information from subjects. Results showed that the median of urinary benzene, toluene, ethylbenzene, m-p xylene, and o-xylene levels in the exposed group were 3.26, 3.36, 0.84, 3.94 and 4.48 μg/L, respectively. With the exception of ethylbenzene, subjects in the exposed group had significantly higher urinary BTEX levels than control group (p autoclave used were also identified as predictors of urinary BTEX concentrations. The healthcare waste treatment autoclaves can be considered as a significant BTEX exposure source for operators working with these treatment facilities. The appropriate personal protection equipment and control measures capable in reducing BTEX exposure should be provided to HCW workers to reduce their exposures to BTEX. Copyright © 2018 Elsevier B.V. All rights reserved.

Active biomonitoring in freshwater environments: early warning signals from biomarkers in assessing biological effects of diffuse sources of pollutants

Science.gov (United States)

Wepener, V.; van Vuren, J. H. J.; Chatiza, F. P.; Mbizi, Z.; Slabbert, L.; Masola, B.

Effluents are a main source of direct and continuous input of pollutants in aquatic ecosystems. Relating observed effects to specific pollutants or even classes of pollutants remains a very difficult task due to the usually unknown, complex and often highly variable composition of effluents. It is recognized that toxicants interfere with organism integrity at the biochemical level and give rise to effects at the individual level and is manifested in reduced ecologically relevant characteristics such as growth, reproduction and survival, and ultimately at the ecosystem level. By integrating multiple endpoints at different ecologically relevant levels of organization within one test organism, it should be possible to gain understanding in how different levels of organization within this organism respond to toxic exposure and how responses at these different levels are interrelated. This paper presents results from a field study in the Rietvlei Wetland system, Gauteng, South Africa using the freshwater mollusk ( Melanoides tuberculata) and freshwater fish ( Oreochromis mossambicus) as bioindicator organisms. Active biomonitoring (ABM) exposures were conducted where organisms were exposed for 28 days in an effluent dominated river during high flow conditions in April 2003. The river receives effluent from a wastewater treatment plant and an industrial complex, so that up to 75% of the total flow of the river is effluent-based. Effects of field exposure were determined using cellular biomarkers e.g. DNA damage, HSP 70, metallothionein, acetylcholine esterase, lactate dehydrogenase and ethoxyresorufin-o-deethylase activity. The results clearly indicate that although the traditional mortality-based whole effluent toxicity testing did not indicate any toxicity, the in situ exposed organisms were stressed. A multivariate statistical approach was particularly useful for integrating the biomarker responses and highlighting sites at which more detailed analysis of chemical

Biomarkers of kidney integrity in children and adolescents with dental amalgam mercury exposure: Findings from the Casa Pia children's amalgam trial

International Nuclear Information System (INIS)

Woods, James S.; Martin, Michael D.; Leroux, Brian G.; DeRouen, Timothy A.; Bernardo, Mario F.; Luis, Henrique S.; Leitao, Jorge G.; Kushleika, John V.; Rue, Tessa C.; Korpak, Anna M.

2008-01-01

Mercury is toxic to the kidney, and dental amalgam is a source of mercury exposure. Few studies have evaluated the effects of dental amalgam on kidney function in a longitudinal context in children. Here, we evaluated urinary concentrations of glutathione S-transferases (GSTs) α and π as biomarkers of renal proximal and distal tubular integrity, respectively, and albumin as a biomarker of glomerular integrity in children and adolescents 8-18 years of age over a 7-year course of dental amalgam treatment. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral and renal effects of dental amalgam in children. Subjects were randomized to either dental amalgam or resin composite treatments. Urinary GSTs α and π, albumin, and creatinine concentrations were measured at baseline and annually in all subjects. Results were evaluated using linear regression analysis. GST-α concentrations were similar between treatment groups and in each sex and race (white vs. non-white) group in each follow-up year. GST-π levels tended upward over the course of follow-up by four- to six-fold. This increase was seen in all groups irrespective of the treatment, race, or gender. Females had GST-π levels approximately twice those of males at all ages. Albumin concentrations were constant throughout the follow-up period and did not differ by treatment, although females had 39% higher albumin levels than males. Additionally, we found no significant effects of amalgam treatment on the proportion of children with microalbuminuria (>30 mg/g creatinine). These findings are relevant within the context of children's health risk assessment as relates to the safety of mercury exposure from dental amalgam on kidney function. These data also provide normative values for sensitive indices of renal functional integrity that may serve in the evaluation of children and adolescents with renal disorders

Ambient Air Pollution and Biomarkers of Health Effect.

Science.gov (United States)

Yang, Di; Yang, Xuan; Deng, Furong; Guo, Xinbiao

2017-01-01

Recently, the air pollution situation of our country is very serious along with the development of urbanization and industrialization. Studies indicate that the exposure of air pollution can cause a rise of incidence and mortality of many diseases, such as chronic obstructive pulmonary disease (COPD), asthma, myocardial infarction, and so on. However, there is now growing evidence showing that significant air pollution exposures are associated with early biomarkers in various systems of the body. In order to better prevent and control the damage effect of air pollution, this article summarizes comprehensively epidemiological studies about the bad effects on the biomarkers of respiratory system, cardiovascular system, and genetic and epigenetic system exposure to ambient air pollution.

Cigarettes with different nicotine levels affect sensory perception and levels of biomarkers of exposure in adult smokers.

Science.gov (United States)

McKinney, Diana L; Frost-Pineda, Kimberly; Oldham, Michael J; Fisher, Michael T; Wang, Jingzhu; Gogova, Maria; Kobal, Gerd

2014-07-01

Few clinical studies involving cigarettes have provided a comprehensive picture of smoke exposure, test article characterization, and insights into sensory properties combined. The purpose of these pilot studies was to determine whether cigarettes with different levels of nicotine but similar tar levels would affect sensory experience or smoking behavior so as to significantly alter levels of selected biomarkers of exposure (BOE). In 2 confined, double-blind studies, 120 adult smokers switched from Marlboro Gold cigarettes at baseline to either 1 of 2 lower nicotine cigarettes or 1 of 2 higher nicotine cigarettes and then to the other cigarette after 5 days. Urinary excretion of exposure biomarkers (nicotine equivalents [NE], total and free 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL], 1-hydroxypyrene, and 3-hydroxypropyl mercapturic acid) as well as carboxyhemoglobin and plasma cotinine were measured at baseline, Day 5, and Day 10. Daily cigarette consumption was monitored and sensory characteristics were rated for each cigarette. With higher nicotine yield, urine NE, urine total NNAL, and plasma cotinine increased while nonnicotine BOE decreased without changes in cigarette consumption. In contrast, with lower nicotine yield, urine NE, urine total NNAL, and plasma cotinine dropped while nonnicotine BOE and cigarettes per day increased. Higher nicotine cigarettes were rated harsher and stronger than at baseline while lower nicotine cigarettes were less strong. All 4 test cigarettes were highly disliked. These studies demonstrate that abrupt increases or decreases in nicotine and the resulting sensory changes impact BOE through changes in intensity or frequency of smoking. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biomarkers of air pollution exposure

Czech Academy of Sciences Publication Activity Database

Šrám, Radim; Binková, Blanka; Beskid, Olena; Biroš, Erik; Chvátalová, Irena; Stávková, Zdena; Milcová, Alena; Rössner, P.; Šmerhovský, Zdeněk

93(1) (2003), s. 16 ISSN 0901-9928. [Nordic Conference of the Nordic Societies of Toxicology and Environmental Mutagenesis /7./. 15.06.2003-18.06.2003, Bornholm] Grant - others:EC IC(XE) QLRT-2000-00091 Institutional research plan: CEZ:AV0Z5039906 Keywords : polycyclic aromatic hydrocarbons * occupational exposure * environmental exposure Subject RIV: EB - Genetics ; Molecular Biology

Assessment of mercury exposure among small-scale gold miners using mercury stable isotopes

Energy Technology Data Exchange (ETDEWEB)

Sherman, Laura S., E-mail: lsaylors@umich.edu [University of Michigan, Department of Earth and Environmental Sciences, 1100 North University Avenue, Ann Arbor, MI 48109 (United States); Blum, Joel D. [University of Michigan, Department of Earth and Environmental Sciences, 1100 North University Avenue, Ann Arbor, MI 48109 (United States); Basu, Niladri [McGill University, Faculty of Agricultural and Environmental Sciences, 21,111 Lakeshore Road, Ste. Anne de Bellevue, Quebec, Canada H9X3V9 (Canada); Rajaee, Mozhgon [University of Michigan, Department of Environmental Health Sciences, 1415 Washington Heights, Ann Arbor, MI 48109 (United States); Evers, David C.; Buck, David G. [Biodiversity Research Institute, 19 Flaggy Meadow Road, Gorham, ME 04038 (United States); Petrlik, Jindrich [Arnika Association, Chlumova 17, Prague 3 (Czech Republic); DiGangi, Joseph [IPEN, Box 7256, SE-402 35 Gothenburg (Sweden)

2015-02-15

Total mercury (Hg) concentrations in hair and urine are often used as biomarkers of exposure to fish-derived methylmercury (MeHg) and gaseous elemental Hg, respectively. We used Hg stable isotopes to assess the validity of these biomarkers among small-scale gold mining populations in Ghana and Indonesia. Urine from Ghanaian miners displayed similar Δ{sup 199}Hg values to Hg derived from ore deposits (mean urine Δ{sup 199}Hg=0.01‰, n=6). This suggests that urine total Hg concentrations accurately reflect exposure to inorganic Hg among this population. Hair samples from Ghanaian miners displayed low positive Δ{sup 199}Hg values (0.23–0.55‰, n=6) and low percentages of total Hg as MeHg (7.6–29%, n=7). These data suggest that the majority of the Hg in these miners' hair samples is exogenously adsorbed inorganic Hg and not fish-derived MeHg. Hair samples from Indonesian gold miners who eat fish daily displayed a wider range of positive Δ{sup 199}Hg values (0.21–1.32‰, n=5) and percentages of total Hg as MeHg (32–72%, n=4). This suggests that total Hg in the hair samples from Indonesian gold miners is likely a mixture of ingested fish MeHg and exogenously adsorbed inorganic Hg. Based on data from both populations, we suggest that total Hg concentrations in hair samples from small-scale gold miners likely overestimate exposure to MeHg from fish consumption. - Highlights: • Mercury isotopes were measured in hair and urine from small-scale gold miners. • Mercury isotopes indicate that Hg in urine comes from mining activity. • Mercury isotopes suggest Hg in hair is a mixture of fish MeHg and inorganic Hg. • A large percentage of Hg in miner’s hair is released during amalgam burning and adsorbed.

Biomarkers of mercury exposure at a mercury recycling facility in Ukraine

Science.gov (United States)

Gibb, H.J.; Kozlov, K.; Buckley, J.P.; Centeno, J.; Jurgenson, V.; Kolker, A.; Conko, K.; Landa, E.; Panov, B.; Panov, Y.; Xu, H.

2008-01-01

This study evaluates biomarkers of occupational mercury exposure among workers at a mercury recycling operation in Gorlovka, Ukraine. The 29 study participants were divided into three occupational categories for analysis: (1) those who worked in the mercury recycling operation (Group A, n = 8), (2) those who worked at the facility but not in the yard where the recycling was done (Group B, n = 14), and (3) those who did not work at the facility (Group C, n = 7). Urine, blood, hair, and nail samples were collected from the participants, and a questionnaire was administered to obtain data on age, gender, occupational history, smoking, alcohol consumption, fish consumption, tattoos, dental amalgams, home heating system, education, source of drinking water, and family employment in the former mercury mine/smelter located on the site of the recycling facility. Each factor was tested in a univariate regression with total mercury in urine, blood, hair, and nails. Median biomarker concentrations were 4.04 ??g/g-Cr (urine), 2.58 ??g/L (blood), 3.95 ??g/g (hair), and 1.16 ??g/g (nails). Occupational category was significantly correlated (p < 0.001) with both blood and urinary mercury concentrations but not with hair or nail mercury. Four individuals had urinary mercury concentrations in a range previously found to be associated with subtle neurological and subjective symptoms (e.g., fatigue, loss of appetite, irritability), and one worker had a urinary mercury concentration in a range associated with a high probability of neurological effects and proteinuria. Comparison of results by occupational category found that workers directly involved with the recycling operation had the highest blood and urinary mercury levels. Those who worked at the facility but were not directly involved with the recycling operation had higher levels than those who did not work at the facility. Copyright ?? 2008 JOEH, LLC.

Opportunities for using spatial property assessment data in air pollution exposure assessments

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Keller C Peter

2005-10-01

Full Text Available Abstract Background Many epidemiological studies examining the relationships between adverse health outcomes and exposure to air pollutants use ambient air pollution measurements as a proxy for personal exposure levels. When pollution levels vary at neighbourhood levels, using ambient pollution data from sparsely located fixed monitors may inadequately capture the spatial variation in ambient pollution. A major constraint to moving toward exposure assessments and epidemiological studies of air pollution at a neighbourhood level is the lack of readily available data at appropriate spatial resolutions. Spatial property assessment data are widely available in North America and may provide an opportunity for developing neighbourhood level air pollution exposure assessments. Results This paper provides a detailed description of spatial property assessment data available in the Pacific Northwest of Canada and the United States, and provides examples of potential applications of spatial property assessment data for improving air pollution exposure assessment at the neighbourhood scale, including: (1 creating variables for use in land use regression modelling of neighbourhood levels of ambient air pollution; (2 enhancing wood smoke exposure estimates by mapping fireplace locations; and (3 using data available on individual building characteristics to produce a regional air pollution infiltration model. Conclusion Spatial property assessment data are an extremely detailed data source at a fine spatial resolution, and therefore a source of information that could improve the quality and spatial resolution of current air pollution exposure assessments.

A novel immunochromatographic electrochemical biosensor for highly sensitive and selective detection of trichloropyridinol, a biomarker of exposure to chlorpyrifos.

Science.gov (United States)

Wang, Limin; Lu, Donglai; Wang, Jun; Du, Dan; Zou, Zhexiang; Wang, Hua; Smith, Jordan N; Timchalk, Charles; Liu, Fengquan; Lin, Yuehe

2011-02-15

We present a novel portable immunochromatographic electrochemical biosensor (IEB) for simple, rapid, and sensitive biomonitoring of trichloropyridinol (TCP), a metabolite biomarker of exposure to organophosphorus insecticides. Our new approach takes the advantage of immunochromatographic test strip for a rapid competitive immunoreaction and a disposable screen-printed carbon electrode for a rapid and sensitive electrochemical analysis of captured HRP labeling. Several key experimental parameters (e.g. immunoreaction time, the amount of HRP labeled TCP, concentration of the substrate for electrochemical measurements, and the blocking agents for the nitrocellulose membrane) were optimized to achieve a high sensitivity, selectivity and stability. Under optimal conditions, the IEB has demonstrated a wide linear range (0.1-100 ng/ml) with a detection limit as low as 0.1 ng/ml TCP. Furthermore, the IEB has been successfully applied for biomonitoring of TCP in the rat plasma samples with in vivo exposure to organophosphorus insecticides like Chlorpyrifos-oxon (CPF-oxon). The IEB thus opens up new pathways for designing a simple, rapid, clinically accurate, and quantitative tool for TCP detection, as well as holds a great promise for in-field screening of metabolite biomarkers, e.g., TCP, for humans exposed to organophosphorus insecticides. Copyright © 2010 Elsevier B.V. All rights reserved.

The Biomonitoring, Environmental Epidemiology, and Short-Lived Chemicals (BEES-C) Instrument for Assessing Study Quality

Science.gov (United States)

Environmental epidemiology studies can be an effective means to assess impacts on human health from exposure to environmental stressors. Exposure scenarios are often extremely complex and proper assessment is critical for interpreting epidemiological study results. Biomarkers are...

Associations between Urinary Excretion of Cadmium and Renal Biomarkers in Nonsmoking Females: A Cross-Sectional Study in Rural Areas of South China

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Yun-rui Zhang

2015-09-01

Full Text Available Objectives: The aim of this study was to systematically evaluate the relationship between urinary excretion of cadmium (U-Cd and biomarkers of renal dysfunction. Methods: One hundred eighty five non-smoking female farmers (aged from 44 to 71 years were recruited from two rural areas with different cadmium levels of exposure in southern China. Morning spot urine samples were collected for detecting U-Cd, urinary creatinine (U-cre, β2-microglobulin (β2-MG, α1-microglobulin (α1-MG, metallothionein (MT, retinol binding protein (RBP, albumin (AB, N-acetyl-β-D-glucosaminidase (NAG, alkaline phosphatase (ALP, γ-glutamyl transpeptidase (GGT and kidney injury molecule-1 (KIM-1. Spearman’s rank correlation was carried out to assess pairwise bivariate associations between continuous variables. Three different models of multiple linear regression (the cre-corrected, un-corrected and cre-adjusted model were used to model the dose-response relationships between U-Cd and nine urine markers. Results: Spearman’s rank correlation showed that NAG, ALP, RBP, β2-MG and MT were significantly associated with U-Cd for both cre-corrected and observed data. Generally, NAG correlated best with U-Cd among the nine biomarkers studied, followed by ALP and MT. In the un-corrected model and cre-adjusted model, the regression coefficients and R2 of nine biomarkers were larger than the corresponding values in the cre-corrected model, indicating that the use of observed data was better for investigating the relationship between biomarkers and U-Cd than cre-corrected data. Conclusions: Our results suggest that NAG, MT and ALP in urine were better biomarkers for long-term environmental cadmium exposure assessment among the nine biomarkers studied. Further, data without normalization with creatinine show better relationships between cadmium exposure and renal dysfunction.

Using multiple biomarkers and determinants to obtain a better measurement of oxidative stress: a latent variable structural equation model approach.

Science.gov (United States)

Eldridge, Ronald C; Flanders, W Dana; Bostick, Roberd M; Fedirko, Veronika; Gross, Myron; Thyagarajan, Bharat; Goodman, Michael

2017-09-01

Since oxidative stress involves a variety of cellular changes, no single biomarker can serve as a complete measure of this complex biological process. The analytic technique of structural equation modeling (SEM) provides a possible solution to this problem by modelling a latent (unobserved) variable constructed from the covariance of multiple biomarkers. Using three pooled datasets, we modelled a latent oxidative stress variable from five biomarkers related to oxidative stress: F 2 -isoprostanes (FIP), fluorescent oxidation products, mitochondrial DNA copy number, γ-tocopherol (Gtoc) and C-reactive protein (CRP, an inflammation marker closely linked to oxidative stress). We validated the latent variable by assessing its relation to pro- and anti-oxidant exposures. FIP, Gtoc and CRP characterized the latent oxidative stress variable. Obesity, smoking, aspirin use and β-carotene were statistically significantly associated with oxidative stress in the theorized directions; the same exposures were weakly and inconsistently associated with the individual biomarkers. Our results suggest that using SEM with latent variables decreases the biomarker-specific variability, and may produce a better measure of oxidative stress than do single variables. This methodology can be applied to similar areas of research in which a single biomarker is not sufficient to fully describe a complex biological phenomenon.

The use of biomarkers to assess the health of aquatic ecosystems in Brazil: a review

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Thaís Dalzochio

2016-11-01

Full Text Available Abstract Organisms in polluted environments are typically exposed to a complex mixture of chemical contaminants. The great concern about the health of aquatic ecosystems has led to the increased use of biomarkers over the past years. The aim of this work was to review the papers published from 2000 to 2015, which used biomarkers to assess the health of aquatic ecosystems in Brazil. A research resulted in 99 eligible papers. More than 80% of studies were conducted in the states of São Paulo and Rio Grande do Sul. Approximately 63% of studies used fish as bioindicator, whereas the micronucleus test and biochemical analyses were the most used biomarkers. A multibiomarker approach was used by 60.6% of studies, while 39.4% used one single biomarker. Furthermore, 68% were field studies and more than 75% of these used control animals sampled at reference sites. A relationship between the biomarker responses and pollution was reported by 87% of studies; however, 43.4% of studies analyzed only one sampling period, limiting comparisons and comprehension about possible seasonal variations. This review evidenced some weak points in studies using biomarkers in Brazil, especially related to the lack of studies in two important biomes (the Pantanal and the Amazon Rainforest and experimental designs (small sample size, sampling in one single period, use of one single biomarker. Thus, future studies should consider mainly the use of multiple biomarkers, greater sample size, seasonal sampling and water physicochemical parameters to better diagnose the health of aquatic ecosystems.

An efficient analytical method for determination of S-phenylmercapturic acid in urine by HPLC fluorimetric detector to assessing benzene exposure.

Science.gov (United States)

Mendes, Michele P Rocha; Silveira, Josianne Nicácio; Andre, Leiliane Coelho

2017-09-15

Benzene is an important occupational and environmental contaminant, naturally present in petroleum and as by-product in the steel industry. Toxicological studies showed pronounced myelotoxic action, causing leukemic and others blood cells disorders. Assessing of benzene exposure is performed by biomarkers as trans, trans-muconic acid (AttM) and S-phenylmercapturic acid (S-PMA) in urine. Due to specificity of S-PMA, this biomarker has been proposed to asses lower levels of benzene in air. The aim of this study was to validate an analytical method for the quantification of S-PMA by High-Performance Liquid Chromatography with fluorometric detector. The development of an analytical method of S-PMA in urine was carried out by solid phase extraction (SPE) using C-18 phase. The eluated were submitted to water bath at 75°C and nitrogen to analyte concentration, followed by alkaline hydrolysis and derivatization with monobromobimane. The chromatography conditions were reverse phase C-18 column (240mm, 4mm and 5μm) at 35°C; acetonitrile and 0.5% acetic acid (50:50) as mobile phase with a flow of 0.8mL/min. The limits of detection and quantification were 0.22μg/L and 0.68μg/L, respectively. The linearity was verified by simple linear regression, and the method exhibited good linearity in the range of 10-100μg/L. There was no matrix effect for S-PMA using concentrations of 40, 60, 80 and 100μg/L. The intra- and interassay precision showed coefficient of variation of less than 10% and the recovery ranged from 83.4 to 102.8% with an average of 94.4%. The stability of S-PMA in urine stored at -20°C was of seven weeks. The conclusion is that this method presents satisfactory results per their figures of merit. This proposed method for determining urinary S-PMA showed adequate sensitivity for assessment of occupational and environmental exposure to benzene using S-PMA as biomarker of exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

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Kjell Oberg

2016-09-01

Full Text Available The complexity of the clinical management of neuroendocrine neoplasia (NEN is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin; monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33 assessed current imaging strategies and biomarkers in NEN management. Consensus (>75% was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

Radioactively contaminated areas: Bioindicator species and biomarkers of effect in an early warning scheme for a preliminary risk assessment

Energy Technology Data Exchange (ETDEWEB)

Lourenço, Joana, E-mail: joanalourenco@ua.pt [Department of Biology & CESAM, University of Aveiro, Campus Universitário de Santiago, Aveiro (Portugal); Mendo, Sónia [Department of Biology & CESAM, University of Aveiro, Campus Universitário de Santiago, Aveiro (Portugal); Pereira, Ruth [Department of Biology, Faculty of Sciences of the University of Porto & CIIMAR – Interdisciplinary Centre of Marine and Environmental Research & GreenUP/CITAB-UP, Porto (Portugal)

2016-11-05

Highlights: • Knowing the most used biomarkers and bioindicators used in radioactive areas. • Understanding of the response similarities between human and non-human biota. • Identifying the knowledge gaps. • Proposing an early warning scheme, to perform a screening evaluation of radioactive areas. • Permitting routine assessments without disturbing and alarming local populations. - Abstract: Concerns about the impacts on public health and on the natural environment have been raised regarding the full range of operational activities related to uranium mining and the rest of the nuclear fuel cycle (including nuclear accidents), nuclear tests and depleted uranium from military ammunitions. However, the environmental impacts of such activities, as well as their ecotoxicological/toxicological profile, are still poorly studied. Herein, it is discussed if organisms can be used as bioindicators of human health effects, posed by lifetime exposure to radioactively contaminated areas. To do so, information was gathered from several studies performed on vertebrates, invertebrate species and humans, living in these contaminated areas. The retrieved information was compared, to determine which are the most used bioindicators and biomarkers and also the similarities between human and non-human biota responses. The data evaluated are used to support the proposal for an early warning scheme, based on bioindicator species and on the most sensitive and commonly shared biomarkers, to perform a screening evaluation of radioactively contaminated sites. This scheme could be used to support decision-making for a deeper evaluation of risks to human health, making it possible to screen a large number of areas, without disturbing and alarming local populations.

QQ-plots for assessing distributions of biomarker measurements and generating defensible summary statistics

Science.gov (United States)

One of the main uses of biomarker measurements is to compare different populations to each other and to assess risk in comparison to established parameters. This is most often done using summary statistics such as central tendency, variance components, confidence intervals, excee...

Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke.

Science.gov (United States)

Scherer, Gerhard; Urban, Michael; Hagedorn, Heinz-Werner; Serafin, Richard; Feng, Shixia; Kapur, Sunil; Muhammad, Raheema; Jin, Yan; Sarkar, Mohamadi; Roethig, Hans-Juergen

2010-10-01

Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of methylmercapturic acid (MMA, biomarker for methylating agents such as NDMA and NNK), 2-hydroxyethylmercapturic acid (HEMA, biomarker for ethylene oxide) and 2-cyanoethylmercapturic acid (CEMA, biomarker for acrylonitrile) in human urine using deuterated internal standards of each compound. The method involves liquid/liquid extraction of the urine sample, solid phase extraction on anion exchange cartridges, derivatization with pentafluorobenzyl bromide (PFBBr), liquid/liquid extraction of the reaction mixture and LC-MS/MS analysis with positive electrospray ionization. The method was linear in the ranges of 5.00-600, 1.00-50.0 and 1.50-900 ng/ml for MMA, HEMA and CEMA, respectively. The method was applied to two clinical studies in adult smokers of conventional cigarettes who either continued smoking conventional cigarettes, were switched to test cigarettes consisting of either an electrically heated cigarette smoking system (EHCSS) or having a highly activated carbon granule filter that were shown to have reduced exposure to specific smoke constituents, or stopped smoking. Urinary excretion of MMA was found to be unaffected by switching to the test cigarettes or stop smoking. Urinary HEMA excretion decreased by 46 to 54% after switching to test cigarettes and by approximately 74% when stopping smoking. Urinary CEMA excretion decreased by 74-77% when switching to test cigarettes and by approximately 90% when stopping smoking. This validated method for urinary alkylmercapturic acids is suitable to distinguish differences in exposure not only between smokers and nonsmokers but also between smoking of conventional and

Assessing Sources of Stress to Aquatic Ecosystems: Using Biomarkers and Bioindicators to Characterize Exodure-Response Profiles of Anthropogenic Activities

Energy Technology Data Exchange (ETDEWEB)

Adams, S.M.

1999-03-29

Establishing causal relationships between sources of environmental stressors and aquatic ecosystem health if difficult because of the many biotic and abiotic factors which can influence or modify responses of biological systems to stress, the orders of magnitude involved in extrapolation over both spatial and temporal scales, and compensatory mechanisms such as density-dependent responses that operate in populations. To address the problem of establishing causality between stressors and effects on aquatic systems, a diagnostic approach, based on exposure-response profiles for various anthropogenic activities, was developed to help identify sources of stress responsible for effects on aquatic systems at ecological significant levels of biological organization (individual, population, community). To generate these exposure-effects profiles, biomarkers of exposure were plotted against bioindicators of corresponding effects for several major anthropogenic activities including petrochemical , pulp and paper, domestic sewage, mining operations, land-development activities, and agricultural activities. Biomarkers of exposure to environmental stressors varied depending on the type of anthropogenic activity involved. Bioindicator effects, however, including histopathological lesions, bioenergetic status, individual growth, reproductive impairment, and community-level responses were similar among many of the major anthropogenic activities. This approach is valuable to help identify and diagnose sources of stressors in environments impacted by multiple stressors. By identifying the types and sources of environmental stressors, aquatic ecosystems can be more effectively protected and managed to maintain acceptable levels of environmental quality and ecosystem fitness.

DNA Methylation Biomarkers: Cancer and Beyond

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Thomas Mikeska

2014-09-01

Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

Determinants of dermal exposure relevant for exposure modelling in regulatory risk assessment.

Science.gov (United States)

Marquart, J; Brouwer, D H; Gijsbers, J H J; Links, I H M; Warren, N; van Hemmen, J J

2003-11-01

Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European research programme, an analysis of potential dermal exposure determinants was made based on the available studies and models and on the expert judgement of the authors of this publication. Only a few potential determinants appear to have been studied in depth. Several studies have included clusters of determinants into vaguely defined parameters, such as 'task' or 'cleaning and maintenance of clothing'. Other studies include several highly correlated parameters, such as 'amount of product handled', 'duration of task' and 'area treated', and separation of these parameters to study their individual influence is not possible. However, based on the available information, a number of determinants could clearly be defined as proven or highly plausible determinants of dermal exposure in one or more exposure situation. This information was combined with expert judgement on the scientific plausibility of the influence of parameters that have not been extensively studied and on the possibilities to gather relevant information during a risk assessment process. The result of this effort is a list of determinants relevant for dermal exposure models in the scope of regulatory risk assessment. The determinants have been divided into the major categories 'substance and product characteristics', 'task done by the worker', 'process technique and equipment', 'exposure control measures', 'worker characteristics and habits' and 'area and situation'. To account for the complex nature of the dermal exposure processes, a further subdivision was made into the three major processes 'direct contact', 'surface contact' and 'deposition'.

Probabilistic mercury multimedia exposure assessment in small children and risk assessment.

Science.gov (United States)

Morisset, Typhaine; Ramirez-Martinez, Alejandra; Wesolek, Nathalie; Roudot, Alain-Claude

2013-09-01

Emissions of mercury in the environment have been decreasing for several years. However, mercury species are still found in different media (food, water, air and breast-milk). Due to mercury toxicity and typical behaviour in children, we have conducted a mercury exposure assessment in French babies, and small children aged 0 to 36months. Consumption and mercury concentration data were chosen for the exposure assessment. The Monte Carlo technique has been used to calculate the weekly exposure dose in order to integrate inter-individual variability and parameter uncertainty. Exposure values have been compared to toxicological reference values for health risk assessment. Inorganic mercury median exposure levels ranged from 0.160 to 1.649μg/kg of body weight per week (95th percentile (P95): 0.298-2.027µg/kg bw/week); elemental mercury median exposure level in children was 0.11ng/kg bw/week (P95: 28ng/kg bw/week); and methylmercury median exposure level ranged from 0.247 to 0.273µg/kg bw/week (P95: 0.425-0.463µg/kg bw/week). Only elemental mercury by inhalation route (indoor air) and methylmercury by ingestion (fish and breast-milk) seem to lead to a health risk in small children. These results confirm the importance of assessing total mercury concentration in media like breast-milk, indoor air and dust and methylmercury level in food, other than fish and seafood. In this way, informed monitoring plan and risk assessment in an at-risk sub-population can be set. © 2013 Elsevier Ltd. All rights reserved.

Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity.

Science.gov (United States)

Roels, H A; Bowler, R M; Kim, Y; Claus Henn, B; Mergler, D; Hoet, P; Gocheva, V V; Bellinger, D C; Wright, R O; Harris, M G; Chang, Y; Bouchard, M F; Riojas-Rodriguez, H; Menezes-Filho, J A; Téllez-Rojo, Martha Maria

2012-08-01

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age. Copyright © 2012 Elsevier Inc. All rights reserved.

Cardiovascular health effects following exposure of human volunteers during fire extinction exercises

DEFF Research Database (Denmark)

Andersen, Maria Helena Guerra; Saber, Anne Thoustrup; Pedersen, Peter Bøgh

2017-01-01

Background: Firefighters have increased risk of cardiovascular disease and of sudden death from coronary heart disease on duty while suppressing fires. This study investigated the effect of firefighting activities, using appropriate personal protective equipment (PPE), on biomarkers...... firefighting exercises in a constructed firehouse and flashover container. The subjects were instructed to extinguish fires of either wood or wood with electrical cords and mattresses. The exposure to particulate matter ( PM) was assessed at various locations and personal exposure was assessed by portable PM...

Biomarkers specific to densely-ionising (high LET) radiations

International Nuclear Information System (INIS)

Brenner, D.J.; Okladnikova, N.; Hande, P.; Burak, L.; Geard, C.R.; Azizova, T.

2001-01-01

There have been several suggestions of biomarkers that are specific to high LET radiation. Such a biomarker could significantly increase the power of epidemiological studies of individuals exposed to densely-ionising radiations such as alpha particles (e.g. radon, plutonium workers, individuals exposed to depleted uranium) or neutrons (e.g. radiation workers, airline personnel). We discuss here a potentially powerful high LET biomarker (the H value) which is the ratio of induced inter-chromosomal aberrations to intra-arm aberrations. Both theoretical and experimental studies have suggested that this ratio should differ by a factor of about three between high LET radiation and any other likely clastogen, and will yield more discrimination than the previously suggested F value (ratio of inter-chromosomal aberrations to intra-chromosomal inter-arm aberrations). Evidence of the long-term stability of such chromosomal biomarkers has also been generated. Because these stable intra-arm and inter-chromosomal aberrations are (1) frequent and (2) measurable at long times after exposure, this H value appears to be a practical biomarker of high LET exposure, and several in vitro studies have confirmed the approach for unstable aberrations. The approach is currently being tested in a population of Russian radiation workers exposed several decades ago to high- or low LET radiation. (author)

Gene-Expression Biomarkers for Application to High-Throughput Radiation Biodosimetry

National Research Council Canada - National Science Library

Grace, M. B; Salter, C. A; Bullard, J. R; Prasanna, P. G; Manglapus, G. L; Blakely, W. F

2005-01-01

.... Even with the delayed onset of symptoms, sometimes several days after exposure, gene-expression biomarkers can identify these exposed individuals very early after exposure, allowing for prompt medical intervention...

Prenatal phthalate exposures and child temperament at 12 and 24 months.

Science.gov (United States)

Singer, Alison B; Wolff, Mary S; Silva, Manori J; Calafat, Antonia M; Engel, Stephanie M

2017-09-01

Gestational phthalate exposures have been adversely associated with attention, externalizing, and internalizing behaviors in childhood. Early childhood temperament may be a marker of later behavioral patterns. We therefore sought to determine whether gestational phthalate exposures were associated with infant and toddler temperament. The Mount Sinai Children's Environmental Health Study is a prospective cohort study of children born between May 1998 and July 2001 in New York City (N=404). Phthalate metabolites were measured in spot urine samples collected from pregnant women in their third trimester. Child temperament was assessed by parental report at 12-months using the Infant Behavior Questionnaire (IBQ) (N=204) and at 24-months using the Toddler Behavior Assessment Questionnaire (TBAQ) (N=279). We used multiple linear regression to evaluate associations between urinary phthalate metabolites and eleven temperament domains. Phthalate biomarker concentrations were weakly associated with lower gross motor activity levels as well as higher duration of orienting at the 12-month assessment. Mono(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP) and the sum of metabolites of di(2-ethylhexyl) phthalate (∑DEHP) were associated with lower levels of smiling and laughing at 12 months. At 24-months, social fear and lower pleasure was linked to higher concentrations of MCPP and MBzP, and higher ∑DEHP was weakly associated with increased anger levels at 24-months. Though we observed some weak associations between biomarkers of prenatal exposure to phthalates and temperament at 12- and 24-months, overall phthalates biomarkers were not strongly associated with alterations in temperament. Copyright © 2017. Published by Elsevier B.V.

Formal recycling of e-waste leads to increased exposure to toxic metals: an occupational exposure study from Sweden.

Science.gov (United States)

Julander, Anneli; Lundgren, Lennart; Skare, Lizbet; Grandér, Margaretha; Palm, Brita; Vahter, Marie; Lidén, Carola

2014-12-01

Electrical and electronic waste (e-waste) contains multiple toxic metals. However, there is currently a lack of exposure data for metals on workers in formal recycling plants. The objective of this study was to evaluate workers' exposure to metals, using biomarkers of exposure in combination with monitoring of personal air exposure. We assessed exposure to 20 potentially toxic metals among 55 recycling workers and 10 office workers at three formal e-waste recycling plants in Sweden. Workers at two of the plants were followed-up after 6 months. We collected the inhalable fraction and OFC (37-mm) fraction of particles, using personal samplers, as well as spot samples of blood and urine. We measured metal concentrations in whole blood, plasma, urine, and air filters using inductively coupled plasma-mass spectrometry following acid digestion. The air sampling indicated greater airborne exposure, 10 to 30 times higher, to most metals among the recycling workers handling e-waste than among the office workers. The exposure biomarkers showed significantly higher concentrations of chromium, cobalt, indium, lead, and mercury in blood, urine, and/or plasma of the recycling workers, compared with the office workers. Concentrations of antimony, indium, lead, mercury, and vanadium showed close to linear associations between the inhalable particle fraction and blood, plasma, or urine. In conclusion, our study of formal e-waste recycling shows that workers performing recycling tasks are exposed to multiple toxic metals. Copyright © 2014. Published by Elsevier Ltd.

USE OF MULTIPARAMETER ANALYSIS OF LABORATORY BIOMARKERS TO ASSESS RHEUMATOID ARTHRITIS ACTIVITY

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A. A. Novikov

2015-01-01

Full Text Available The key component in the management of patients with rheumatoid arthritis (RA is regular control of RA activity. The quantitative assessment of a patient’s status allows the development of standardized indications for anti-rheumatic therapy.Objective: to identify the laboratory biomarkers able to reflect RA activity.Subjects and methods. Fifty-eight patients with RA and 30 age- and sex-matched healthy donors were examined. The patients were divided into high/moderate and mild disease activity groups according to DAS28. The serum concentrations of 30 biomarkers were measured using immunonephelometric assay, enzyme immunoassay, and xMAP technology.Results and discussion. Multivariate analysis could identify the factors mostly related to high/moderate RA activity according to DAS28, such as fibroblast growth factor-2, monocyte chemoattractant protein-1, interleukins (IL 1α, 6, and 15, and tumor necrosis factor-α and could create a prognostic model for RA activity assessment. ROC analysis has shown that this model has excellent diagnostic efficiency in differentiating high/moderate versus low RA activity.Conclusion. To create a subjective assessment-independent immunological multiparameter index of greater diagnostic accuracy than the laboratory parameters routinely used in clinical practice may be a qualitatively new step in assessing and monitoring RA activity.

Cognitive decline, mortality, and organophosphorus exposure in aging Mexican Americans.

Science.gov (United States)

Paul, Kimberly C; Ling, Chenxiao; Lee, Anne; To, Tu My; Cockburn, Myles; Haan, Mary; Ritz, Beate

2018-01-01

Cognitive impairment is a major health concern among older Mexican Americans, associated with significant morbidity and mortality, and may be influenced by environmental exposures. To investigate whether agricultural based ambient organophosphorus (OP) exposure influences 1) the rate of cognitive decline and mortality and 2) whether these associations are mediated through metabolic or inflammatory biomarkers. In a subset of older Mexican Americans from the Sacramento Area Latino Study on Aging (n = 430), who completed modified mini-mental state exams (3MSE) up to 7 times (1998-2007), we examined the relationship between estimated ambient OP exposures and cognitive decline (linear repeated measures model) and time to dementia or being cognitively impaired but not demented (CIND) and time to mortality (cox proportional hazards model). We then explored metabolic and inflammatory biomarkers as potential mediators of these relationships (additive hazards mediation). OP exposures at residential addresses were estimated with a geographic information system (GIS) based exposure assessment tool. Participants with high OP exposure in the five years prior to baseline experienced faster cognitive decline (β = 0.038, p = 0.02) and higher mortality over follow-up (HR = 1.91, 95% CI = 1.12, 3.26). The direct effect of OP exposure was estimated at 241 (95% CI = 27-455) additional deaths per 100,000 person-years, and the proportion mediated through the metabolic hormone adiponectin was estimated to be 4% 1.5-19.2). No other biomarkers were associated with OP exposure. Our study provides support for the involvement of OP pesticides in cognitive decline and mortality among older Mexican Americans, possibly through biologic pathways involving adiponectin. Copyright © 2017 Elsevier Inc. All rights reserved.

Monitoring OH-PCBs in PCB transport worker's urine as a non-invasive exposure assessment tool.

Science.gov (United States)

Haga, Yuki; Suzuki, Motoharu; Matsumura, Chisato; Okuno, Toshihiro; Tsurukawa, Masahiro; Fujimori, Kazuo; Kannan, Narayanan; Weber, Roland; Nakano, Takeshi

2018-04-14

In this study, we analyzed hydroxylated polychlorinated biphenyls (OH-PCBs) in urine of both PCB transport workers and PCB researchers. A method to monitor OH-PCB in urine was developed. Urine was solid-phase extracted with 0.1% ammonia/ methanol (v/v) and glucuronic acid/sulfate conjugates and then decomposed using β-glucuronidase/arylsulfatase. After alkaline digestion/derivatization, the concentration of OH-PCBs was determined by HRGC/HRMS-SIM. In the first sampling campaign, the worker's OH-PCB levels increased several fold after the PCB waste transportation work, indicating exposure to PCBs. The concentration of OH-PCBs in PCB transport workers' urine (0.55~11 μg/g creatinine (Cre)) was higher than in PCB researchers' urine (PCB storage area. In the second sampling, after recommended PCB exposure reduction measures had been enacted, the worker's PCB levels did not increase during handling of PCB equipment. This suggests that applied safety measures improved the situation. Hydroxylated trichlorobiphenyls (OH-TrCBs) were identified as a major homolog of OH-PCBs in urine. Also, hydroxylated tetrachlorobiphenyls (OH-TeCBs) to hydroxylated hexachlorobiphenyls (OH-HxCBs) were detected. For the sum of ten selected major indicators, a strong correlation to total OH-PCBs were found and these can possibly be used as non-invasive biomarkers of PCB exposure in workers managing PCB capacitors and transformer oils. We suggest that monitoring of OH-PCBs in PCB management projects could be considered a non-invasive way to detect exposure. It could also be used as a tool to assess and improve PCB management. This is highly relevant considering the fact that in the next 10 years, approx. 14 million tons of PCB waste need to be managed. Also, the selected populations could be screened to assess whether exposure at work, school, or home has taken place.

Human Antibody Response to Aedes aegypti Saliva in an Urban Population in Bolivia: A New Biomarker of Exposure to Dengue Vector Bites

Science.gov (United States)

Doucoure, Souleymane; Mouchet, François; Cournil, Amandine; Le Goff, Gilbert; Cornelie, Sylvie; Roca, Yelin; Giraldez, Mabel Guerra; Simon, Zaira Barja; Loayza, Roxanna; Misse, Dorothée; Flores, Jorge Vargas; Walter, Annie; Rogier, Christophe; Herve, Jean Pierre; Remoue, Franck

2012-01-01

Aedes mosquitoes are important vectors of re-emerging diseases in developing countries, and increasing exposure to Aedes in the developed world is currently a source of concern. Given the limitations of current entomologic methods, there is a need for a new effective way for evaluating Aedes exposure. Our objective was to evaluate specific antibody responses to Aedes aegypti saliva as a biomarker for vector exposure in a dengue-endemic urban area. IgG responses to saliva were strong in young children and steadily waned with age. Specific IgG levels were significantly higher in persons living in sites with higher Ae. aegypti density, as measured by using entomologic parameters. Logistic regression showed a significant correlation between IgG to saliva and exposure level, independently of either age or sex. These results suggest that antibody responses to saliva could be used to monitor human exposure to Aedes bites. PMID:22848099

Assessing relationships between chemical exposure, parasite infection, fish health, and fish ecological status: a case study using chub (Leuciscus cephalus) in the Bílina River, Czech Republic

Czech Academy of Sciences Publication Activity Database

Wenger, M.; Ondračková, Markéta; Machala, M.; Neča, J.; Hyršl, P.; Šimková, A.; Jurajda, Pavel; von der Ohe, P.; Segner, H.

2010-01-01

Roč. 29, č. 2 (2010), s. 453-466 ISSN 0730-7268 R&D Projects: GA MŠk LC522 Grant - others:6th Framework Programme EC(XE) MODELKEY (511237-GOCE) Institutional research plan: CEZ:AV0Z60930519 Keywords : multiple stressors * environmental risk assessment * exposure biomarkers * parasites * fish health Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 3.026, year: 2010

Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen.

Science.gov (United States)

Thompson, Aaron M S; Zanobetti, Antonella; Silverman, Frances; Schwartz, Joel; Coull, Brent; Urch, Bruce; Speck, Mary; Brook, Jeffrey R; Manno, Michael; Gold, Diane R

2010-01-01

Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardio-vascular disease. We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter pollutants on systemic IL-6 and fibrinogen. Effect modification by season was considered. We observed a positive association between IL-6 and O3 [0.31 SD per O3 interquartile range (IQR); 95% confidence interval (CI), 0.080.54] and between IL-6 and SO2 (0.25 SD per SO2 IQR; 95% CI, 0.060.43). We observed the strongest effects using 4-day moving averages. Responses to pollutants varied by season and tended to be higher in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with pollution. This study demonstrates a significant association between ambient pollutant levels and baseline levels of systemic IL-6. These findings have potential implications for controlled human exposure studies. Future research should consider whether ambient pollution exposure before chamber exposure modifies IL-6 response.

Effects of chronic exposure to cadmium and temperature, alone or combined, on the threespine stickleback (Gasterosteus aculeatus): Interest of digestive enzymes as biomarkers.

Science.gov (United States)

Hani, Younes Mohamed Ismail; Turies, Cyril; Palluel, Olivier; Delahaut, Laurence; Gaillet, Véronique; Bado-Nilles, Anne; Porcher, Jean-Marc; Geffard, Alain; Dedourge-Geffard, Odile

2018-06-01

The development of predictive, sensitive and reliable biomarkers is of crucial importance for aquatic biomonitoring to assess the effects of chemical substances on aquatic organisms, especially when it comes to combined effects with other stressors (e.g. temperature). The first purpose of the present study was to evaluate the single and combined effects of 90 days of exposure to an environmental cadmium concentration (0.5 μg L -1 ) and two water temperatures (16 and 21 °C) on different parameters. These parameters are involved in (i) the antioxidant system (superoxide dismutase activity -SOD- and total glutathione levels -GSH-), (ii) the energy metabolism, i.e. energy reserves (glycogen, lipids, proteins) and digestive enzymes (trypsin, amylase, intestinal alkaline phosphatase -IAP-), and (iii) biometric parameters (weight, length, Fulton's condition factor, and the gonadosomatic index -GSI-) of threespine stickleback (Gasterosteus aculeatus). The second purpose was to determine the interest of the three digestive enzymes as biomarkers in comparison with the other parameters. The higher temperature (21 °C) impacted the anti-oxidant and energy reserve parameters. In liver, GSH levels increased on day 60, while SOD decreased on days 15 and 90, with a significant decrease of protein and lipid energy reserves on day 90. In muscle, the higher temperature decreased SOD activity only on day 90. G. aculeatus biometric parameters were also impacted by the higher temperature, which limited stickleback growth after 90 days of exposure. In female sticklebacks, the GSI peaked on day 60 and decreased sharply on day 90, while the highest values were reached at day 90 in the control groups, suggesting impaired reproduction in sticklebacks raised at 21 °C. These results suggest that 21 °C is an upper-limit temperature for long-term physiological processes in sticklebacks. In contrast, very low-concentration cadmium exposure had no effect on classical biomarkers

IWGT report on quantitative approaches to genotoxicity risk assessment II. Use of point-of-departure (PoD) metrics in defining acceptable exposure limits and assessing human risk.

Science.gov (United States)

MacGregor, James T; Frötschl, Roland; White, Paul A; Crump, Kenny S; Eastmond, David A; Fukushima, Shoji; Guérard, Melanie; Hayashi, Makoto; Soeteman-Hernández, Lya G; Johnson, George E; Kasamatsu, Toshio; Levy, Dan D; Morita, Takeshi; Müller, Lutz; Schoeny, Rita; Schuler, Maik J; Thybaud, Véronique

2015-05-01

This is the second of two reports from the International Workshops on Genotoxicity Testing (IWGT) Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment (the QWG). The first report summarized the discussions and recommendations of the QWG related to the need for quantitative dose-response analysis of genetic toxicology data, the existence and appropriate evaluation of threshold responses, and methods to analyze exposure-response relationships and derive points of departure (PoDs) from which acceptable exposure levels could be determined. This report summarizes the QWG discussions and recommendations regarding appropriate approaches to evaluate exposure-related risks of genotoxic damage, including extrapolation below identified PoDs and across test systems and species. Recommendations include the selection of appropriate genetic endpoints and target tissues, uncertainty factors and extrapolation methods to be considered, the importance and use of information on mode of action, toxicokinetics, metabolism, and exposure biomarkers when using quantitative exposure-response data to determine acceptable exposure levels in human populations or to assess the risk associated with known or anticipated exposures. The empirical relationship between genetic damage (mutation and chromosomal aberration) and cancer in animal models was also examined. It was concluded that there is a general correlation between cancer induction and mutagenic and/or clastogenic damage for agents thought to act via a genotoxic mechanism, but that the correlation is limited due to an inadequate number of cases in which mutation and cancer can be compared at a sufficient number of doses in the same target tissues of the same species and strain exposed under directly comparable routes and experimental protocols. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

The current status of biomarkers for predicting toxicity

Science.gov (United States)

Campion, Sarah; Aubrecht, Jiri; Boekelheide, Kim; Brewster, David W; Vaidya, Vishal S; Anderson, Linnea; Burt, Deborah; Dere, Edward; Hwang, Kathleen; Pacheco, Sara; Saikumar, Janani; Schomaker, Shelli; Sigman, Mark; Goodsaid, Federico

2013-01-01

Introduction There are significant rates of attrition in drug development. A number of compounds fail to progress past preclinical development due to limited tools that accurately monitor toxicity in preclinical studies and in the clinic. Research has focused on improving tools for the detection of organ-specific toxicity through the identification and characterization of biomarkers of toxicity. Areas covered This article reviews what we know about emerging biomarkers in toxicology, with a focus on the 2012 Northeast Society of Toxicology meeting titled ‘Translational Biomarkers in Toxicology.’ The areas covered in this meeting are summarized and include biomarkers of testicular injury and dysfunction, emerging biomarkers of kidney injury and translation of emerging biomarkers from preclinical species to human populations. The authors also provide a discussion about the biomarker qualification process and possible improvements to this process. Expert opinion There is currently a gap between the scientific work in the development and qualification of novel biomarkers for nonclinical drug safety assessment and how these biomarkers are actually used in drug safety assessment. A clear and efficient path to regulatory acceptance is needed so that breakthroughs in the biomarker toolkit for nonclinical drug safety assessment can be utilized to aid in the drug development process. PMID:23961847

The Biomarkers of Exposure and Effect in Agriculture (BEEA) Study: Rationale, Design, Methods, and Participant Characteristics.

Science.gov (United States)

Hofmann, Jonathan N; Beane Freeman, Laura E; Lynch, Charles F; Andreotti, Gabriella; Thomas, Kent W; Sandler, Dale P; Savage, Sharon A; Alavanja, Michael C

2015-01-01

Agricultural exposures including pesticides, endotoxin, and allergens have been associated with risk of various cancers and other chronic diseases, although the biological mechanisms underlying these associations are generally unclear. To facilitate future molecular epidemiologic investigations, in 2010 the study of Biomarkers of Exposure and Effect in Agriculture (BEEA) was initiated within the Agricultural Health Study, a large prospective cohort in Iowa and North Carolina. Here the design and methodology of BEEA are described and preliminary frequencies for participant characteristics and current agricultural exposures are reported. At least 1,600 male farmers over 50 years of age will be enrolled in the BEEA study. During a home visit, participants are asked to complete a detailed interview about recent agricultural exposures and provide samples of blood, urine, and (since 2013) house dust. As of mid-September 2014, in total, 1,233 participants have enrolled. Most of these participants (83%) were still farming at the time of interview. Among those still farming, the most commonly reported crops were corn (81%) and soybeans (74%), and the most frequently noted animals were beef cattle (35%) and hogs (13%). There were 861 (70%) participants who reported occupational pesticide use in the 12 months prior to interview; among these participants, the most frequently noted herbicides were glyphosate (83%) and 2,4-D (72%), and most commonly reported insecticides were malathion (21%), cyfluthrin (13%), and permethrin (12%). Molecular epidemiologic investigations within BEEA have the potential to yield important new insights into the biological mechanisms through which these or other agricultural exposures influence disease risk.

Association between biomarkers and clinical characteristics in chronic subdural hematoma patients assessed with lasso regression.

Directory of Open Access Journals (Sweden)

Are Hugo Pripp

Full Text Available Chronic subdural hematoma (CSDH is characterized by an "old" encapsulated collection of blood and blood breakdown products between the brain and its outermost covering (the dura. Recognized risk factors for development of CSDH are head injury, old age and using anticoagulation medication, but its underlying pathophysiological processes are still unclear. It is assumed that a complex local process of interrelated mechanisms including inflammation, neomembrane formation, angiogenesis and fibrinolysis could be related to its development and propagation. However, the association between the biomarkers of inflammation and angiogenesis, and the clinical and radiological characteristics of CSDH patients, need further investigation. The high number of biomarkers compared to the number of observations, the correlation between biomarkers, missing data and skewed distributions may limit the usefulness of classical statistical methods. We therefore explored lasso regression to assess the association between 30 biomarkers of inflammation and angiogenesis at the site of lesions, and selected clinical and radiological characteristics in a cohort of 93 patients. Lasso regression performs both variable selection and regularization to improve the predictive accuracy and interpretability of the statistical model. The results from the lasso regression showed analysis exhibited lack of robust statistical association between the biomarkers in hematoma fluid with age, gender, brain infarct, neurological deficiencies and volume of hematoma. However, there were associations between several of the biomarkers with postoperative recurrence requiring reoperation. The statistical analysis with lasso regression supported previous findings that the immunological characteristics of CSDH are local. The relationship between biomarkers, the radiological appearance of lesions and recurrence requiring reoperation have been inclusive using classical statistical methods on these data

Assessment of xenoestrogenic exposure by a biomarker approach: application of the E-Screen bioassay to determine estrogenic response of serum extracts

Directory of Open Access Journals (Sweden)

Weihe Pal

2003-10-01

Full Text Available Abstract Background Epidemiological documentation of endocrine disruption is complicated by imprecise exposure assessment, especially when exposures are mixed. Even if the estrogenic activity of all compounds were known, the combined effect of possible additive and/or inhibiting interaction of xenoestrogens in a biological sample may be difficult to predict from chemical analysis of single compounds alone. Thus, analysis of mixtures allows evaluation of combined effects of chemicals each present at low concentrations. Methods We have developed an optimized in vitro E-Screen test to assess the combined functional estrogenic response of human serum. The xenoestrogens in serum were separated from endogenous steroids and pharmaceuticals by solid-phase extraction followed by fractionation by high-performance liquid chromatography. After dissolution of the isolated fraction in ethanol-DMSO, the reconstituted extract was added with estrogen-depleted fetal calf serum to MCF-7 cells, the growth of which is stimulated by estrogen. After a 6-day incubation on a microwell plate, cell proliferation was assessed and compared with the effect of a 17-beta-estradiol standard. Results and conclusions To determine the applicability of this approach, we assessed the estrogenicity of serum samples from 30 pregnant and 60 non-pregnant Danish women thought to be exposed only to low levels of endocrine disruptors. We also studied 211 serum samples from pregnant Faroese women, whose marine diet included whale blubber that contain a high concentration of persistent halogenated pollutants. The estrogenicity of the serum from Danish controls exceeded the background in 22.7 % of the cases, while the same was true for 68.1 % of the Faroese samples. The increased estrogenicity response did not correlate with the lipid-based concentrations of individual suspected endocrine disruptors in the Faroese samples. When added along with the estradiol standard, an indication of an

Retrospective Occupational Exposure Assessment in Community-Based Studies Made Easier

International Nuclear Information System (INIS)

Fritschi, L.; Girschik, J.; Friesen, M.C.; Glass, D.; Monash, G.B.; Sadkowsky, T.

2010-01-01

Occ DEAS Assessing occupational exposure in retrospective community-based case-control studies is difficult as measured exposure data are very seldom available. The expert assessment method is considered the most accurate way to attribute exposure but it is a time consuming and expensive process and may be seen as subjective, non reproducible, and non transparent. In this paper, we describe these problems and outline our solutions as ope rationalized in a web-based software application (Occ DEAS). The novel aspects of Occ DEAS are combining all steps in the assessment into one software package; enmeshing the process of assessment into the development of questionnaires; selecting the exposure(s) of interest; specifying rules for exposure assignment; allowing manual or automatic assessments; ensuring that circumstances in which exposure is possible for an individual are highlighted for review; providing reports to ensure consistency of assessment. Development of this application has the potential to make high-quality occupational assessment more efficient and accessible for epidemiological studies

Assessment of predictive dermal exposure to chemicals in the work environment

Directory of Open Access Journals (Sweden)

Agnieszka Jankowska

2017-08-01

Full Text Available Assessment of dermal exposure to chemicals in the work environment is problematic, mainly as a result of the lack of measurement data on occupational exposure to chemicals. Due to common prevalence of occupational skin exposure and its health consequences it is necessary to look for efficient solutions allowing for reliable exposure assessment. The aim of the study is to present predictive models used to assess non-measured dermal exposure, as well as to acquaint Polish users with the principles of the selected model functioning. This paper presents examples of models to assist the employer in the the assessment of occupational exposure associated with the skin contact with chemicals, developed in European Union (EU countries, as well as in countries outside the EU. Based on the literature data dermal exposure models EASE (Estimation and Assessment of Substance Exposure, COSHH Essentials (Control of Substances Hazardous to Health Regulations, DREAM (Dermal Exposure Assessment Method, Stoffenmanager , ECETOC TRA (European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment, MEASE (Metal’s EASE, PHED (Pesticide Handlers Exposure Database, DERM (Dermal Exposure Ranking Method and RISKOFDERM (Risk Assessment of Occupational Dermal Exposure to Chemicals were briefly described. Moreover the characteristics of RISKOFDERM, guidelines for its use, information on input and output data were further detailed. Problem of full work shift dermal exposure assessment is described. An example of exposure assessment using RISKOFDERM and effectiveness evaluation to date were also presented. When no measurements are available, RISKOFDERM allows dermal exposure assessment and thus can improve the risk assessment quality and effectiveness of dermal risk management. Med Pr 2017;68(4:557–569

The alkaline comet assay as a biomarker of primary DNA damage in peripheral blood leukocytes of nuclear medicine personnel

International Nuclear Information System (INIS)

Kopjar, N.; Garaj-Vrhovac, V.

2003-01-01

The aim of this study was to assess whether occupational exposure to chronic low doses of ionizing radiation in nuclear medicine departments may lead to genotoxicity. The alkaline comet assay was selected as a bio-marker of exposure to evaluate the levels of primary DNA damage in peripheral blood leukocytes of exposed and corresponding control subjects. Statistically significant differences were found between comet tail length and tail moment values measured in leukocytes from the exposed and control groups. Within exposed group significant inter-individual differences in DNA damage were assessed, indicating different genome sensitivity. In majority of exposed subjects the levels of DNA damage were in positive correlation with the duration of occupational exposure, while the influences of age and dosimeter readings could be excluded. However, the levels of primary DNA damage detected both in control and exposed subjects were significantly influenced by smoking. The present study indicates the possibility of genotoxic risks related to occupational exposure in nuclear medicine departments. Therefore, the exposed personnel should carefully apply the radiation protection procedures to minimize, as low as possible, radiation exposure to avoid possible genotoxic effects. According to results obtained, the alkaline comet assay could be usefully applied as a sensitive additional bio-marker in the regular health screening of workers occupationally exposed to low doses of ionizing radiation. (authors)

Short-Term Changes in Respiratory Biomarkers after Swimming in a Chlorinated Pool

OpenAIRE

Font-Ribera, Laia; Kogevinas, Manolis; Zock, Jan-Paul; G?mez, Federico P.; Barreiro, Esther; Nieuwenhuijsen, Mark J.; Fernandez, Pilar; Lourencetti, Carolina; P?rez-Olabarr?a, Maitane; Bustamante, Mariona; Marcos, Ricard; Grimalt, Joan O.; Villanueva, Cristina M.

2010-01-01

Background Swimming in chlorinated pools involves exposure to disinfection by-products (DBPs) and has been associated with impaired respiratory health. Objectives We evaluated short-term changes in several respiratory biomarkers to explore mechanisms of potential lung damage related to swimming pool exposure. Methods We measured lung function and biomarkers of airway inflammation [fractional exhaled nitric oxide (FeNO), eight cytokines, and vascular endothelial growth factor (VEGF) in exhaled...

The role of non-invasive biomarkers in detecting acute respiratory effects of traffic-related air pollution.

Science.gov (United States)

Scarpa, M C; Kulkarni, N; Maestrelli, P

2014-09-01

The role of non-invasive methods in the investigation of acute effects of traffic-related air pollution is not clearly established. We evaluated the usefulness of non-invasive biomarkers in detecting acute air pollution effects according to the age of participants, the disease status, their sensitivity compared with lung function tests and their specificity for a type of pollutant. Search terms lead to 535 titles, among them 128 had potentially relevant abstracts. Sixtynine full papers were reviewed, while 59 articles were excluded as they did not meet the selection criteria. Methods used to assess short-term effects of air pollution included analysis of nasal lavage (NAL) for the upper airways, and induced sputum (IS), exhaled breath condensate (EBC) and exhaled nitric oxide (FeNO) for central and lower airways. There is strong evidence that FeNO evaluation is useful independently from subject age, while IS analysis is suitable almost for adults. Biomarker changes are generally observed upon pollutant exposure irrespective of the disease status of the participants. None of the biomarkers identified are specific for a type of pollutant exposure. Based on experimental exposure studies, there is moderate evidence that IS analysis is more sensitive than lung function tests, whereas this is not the case for biomarkers obtained by NAL or EBC. Cells and some cytokines (IL-6, IL-8 and myeloperoxidase) have been measured both in the upper respiratory tract (NAL) and in the lower airways (IS). Overall, the response to traffic exposure seems different in the two compartments. In conclusion, this survey of current literature displays the complexity of this research field, highlights the significance of short-term studies on traffic pollution and gives important tips when planning studies to detect acute respiratory effects of air pollution in a non-invasive way. © 2014 John Wiley & Sons Ltd.

Biomarkers for Pulmonary Inflammation and Fibrosis and Lung Ventilation Function in Chinese Occupational Refractory Ceramic Fibers-Exposed Workers

Directory of Open Access Journals (Sweden)

Xiaojun Zhu

2017-12-01

Full Text Available Refractory ceramic fibers (RCFs can cause adverse health effects on workers’ respiratory system, yet no proper biomarkers have been used to detect early pulmonary injury of RCFs-exposed workers. This study assessed the levels of two biomarkers that are related to respiratory injury in RCFs-exposed workers, and explored their relations with lung function. The exposure levels of total dust and respirable fibers were measured simultaneously in RCFs factories. The levels of TGF-β1 and ceruloplasmin (CP increased with the RCFs exposure level (p < 0.05, and significantly increased in workers with high exposure level (1.21 ± 0.49 ng/mL, 115.25 ± 32.44 U/L when compared with the control group (0.99 ± 0.29 ng/mL, 97.90 ± 35.01 U/L (p < 0.05. The levels of FVC and FEV1 were significantly decreased in RCFs exposure group (p < 0.05. Negative relations were found between the concentrations of CP and FVC (B = −0.423, p = 0.025, or FEV1 (B = −0.494, p = 0.014. The concentration of TGF-β1 (B = 0.103, p = 0.001 and CP (B = 8.027, p = 0.007 were associated with respirable fiber exposure level. Occupational exposure to RCFs can impair lung ventilation function and may have the potential to cause pulmonary inflammation and fibrosis. TGF-β1 and CP might be used as sensitive and noninvasive biomarkers to detect lung injury in occupational RCFs-exposed workers. Respirable fiber concentration can better reflect occupational RCFs exposure and related respiratory injuries.

Wishful Thinking? Inside the Black Box of Exposure Assessment.

Science.gov (United States)

Money, Annemarie; Robinson, Christine; Agius, Raymond; de Vocht, Frank

2016-05-01

Decision-making processes used by experts when undertaking occupational exposure assessment are relatively unknown, but it is often assumed that there is a common underlying method that experts employ. However, differences in training and experience of assessors make it unlikely that one general method for expert assessment would exist. Therefore, there are concerns about formalizing, validating, and comparing expert estimates within and between studies that are difficult, if not impossible, to characterize. Heuristics on the other hand (the processes involved in decision making) have been extensively studied. Heuristics are deployed by everyone as short-cuts to make the often complex process of decision-making simpler, quicker, and less burdensome. Experts' assessments are often subject to various simplifying heuristics as a way to reach a decision in the absence of sufficient data. Therefore, investigating the underlying heuristics or decision-making processes involved may help to shed light on the 'black box' of exposure assessment. A mixed method study was conducted utilizing both a web-based exposure assessment exercise incorporating quantitative and semiqualitative elements of data collection, and qualitative semi-structured interviews with exposure assessors. Qualitative data were analyzed using thematic analysis. Twenty-five experts completed the web-based exposure assessment exercise and 8 of these 25 were randomly selected to participate in the follow-up interview. Familiar key themes relating to the exposure assessment exercise emerged; 'intensity'; 'probability'; 'agent'; 'process'; and 'duration' of exposure. However, an important aspect of the detailed follow-up interviews revealed a lack of structure and order with which participants described their decision making. Participants mostly described some form of an iterative process, heavily relying on the anchoring and adjustment heuristic, which differed between experts. In spite of having undertaken

A multiple biomarker assay for quality assessment of botanical drugs using a versatile microfluidic chip.

Science.gov (United States)

Li, Zhen-Hao; Ai, Ni; Yu, Lawrence X; Qian, Zhong-Zhi; Cheng, Yi-Yu

2017-09-25

Quality control is critical for ensuring the safety and effectiveness of drugs. Current quality control method for botanical drugs is mainly based on chemical testing. However, chemical testing alone may not be sufficient as it may not capture all constituents of botanical drugs. Therefore, it is necessary to establish a bioassay correlating with the drug's known mechanism of action to ensure its potency and activity. Herein we developed a multiple biomarker assay to assess the quality of botanicals using microfluidics, where enzyme inhibition was employed to indicate the drug's activity and thereby evaluate biological consistency. This approach was exemplified on QiShenYiQi Pills using thrombin and angiotensin converting enzyme as "quality biomarkers". Our results demonstrated that there existed variations in potency across different batches of the intermediates and preparations. Compared with chromatographic fingerprinting, the bioassay provided better discrimination ability for some abnormal samples. Moreover, the chip could function as "affinity chromatography" to identify bioactive phytochemicals bound to the enzymes. This work proposed a multiple-biomarker strategy for quality assessment of botanical drugs, while demonstrating for the first time the feasibility of microfluidics in this field.

Evaluation of inflammatory biomarkers associated with oxidative stress and histological assessment of magnetic therapy on experimental myopathy in rats.

Science.gov (United States)

Vignola, María Belén; Dávila, Soledad; Cremonezzi, David; Simes, Juan C; Palma, José A; Campana, Vilma R

2012-12-01

The effect of pulsed electromagnetic field (PEMF) therapy, also called magnetic therapy, upon inflammatory biomarkers associated with oxidative stress plasma fibrinogen, nitric oxide (NO), L-citrulline, carbonyl groups, and superoxide dismutase (SOD) was evaluated through histological assessment, in rats with experimental myopathy. The groups studied were: (A) control (intact rats that received PEMF sham exposures); (B) rats with myopathy and sacrificed 24 h later; (C) rats with myopathy; (D) rats with myopathy and treated with PEMF; and (E) intact rats treated with PEMF. Groups A, C, D, and E were sacrificed 8 days later. Myopathy was induced by injecting 50 μl of 1% carrageenan λ (type IV) once sub-plantar. Treatment was carried out with PEMF emitting equipment with two flat solenoid disks for 8 consecutive days in groups D and E, at 20 mT and 50 Hz for 30 min/day/rat. The biomarkers were determined by spectrophotometry. The muscles (5/8) were stained with Hematoxylin-Eosin and examined by optic microscopy. Quantitative variables were statistically analyzed by the Fisher test, and categorical applying Pearson's Chi Squared test at p < 0.05 for all cases. In Groups B and C, the biomarkers were significantly increased compared to A, D, and E groups: fibrinogen (p < 0.001); NO, L-citrulline and carbonyl groups (p < 0.05); SOD (p < 0.01) as well as the percentage of area with inflammatory infiltration (p < 0.001). PEMF caused decreased levels of fibrinogen, L-citrulline, NO, SOD, and carbonyl groups and significant muscle recovery in rats with experimental myopathies.

Perspectives for integrating human and environmental exposure assessments.

Science.gov (United States)

Ciffroy, P; Péry, A R R; Roth, N

2016-10-15

Integrated Risk Assessment (IRA) has been defined by the EU FP7 HEROIC Coordination action as "the mutual exploitation of Environmental Risk Assessment for Human Health Risk Assessment and vice versa in order to coherently and more efficiently characterize an overall risk to humans and the environment for better informing the risk analysis process" (Wilks et al., 2015). Since exposure assessment and hazard characterization are the pillars of risk assessment, integrating Environmental Exposure assessment (EEA) and Human Exposure assessment (HEA) is a major component of an IRA framework. EEA and HEA typically pursue different targets, protection goals and timeframe. However, human and wildlife species also share the same environment and they similarly inhale air and ingest water and food through often similar overlapping pathways of exposure. Fate models used in EEA and HEA to predict the chemicals distribution among physical and biological media are essentially based on common properties of chemicals, and internal concentration estimations are largely based on inter-species (i.e. biota-to-human) extrapolations. Also, both EEA and HEA are challenged by increasing scientific complexity and resources constraints. Altogether, these points create the need for a better exploitation of all currently existing data, experimental approaches and modeling tools and it is assumed that a more integrated approach of both EEA and HEA may be part of the solution. Based on the outcome of an Expert Workshop on Extrapolations in Integrated Exposure Assessment organized by the HEROIC project in January 2014, this paper identifies perspectives and recommendations to better harmonize and extrapolate exposure assessment data, models and methods between Human Health and Environmental Risk Assessments to support the further development and promotion of the concept of IRA. Ultimately, these recommendations may feed into guidance showing when and how to apply IRA in the regulatory decision

Biomarker assessment of the effects of strip mine contamination on channel catfish

International Nuclear Information System (INIS)

Martin, L.K. Jr.; Black, M.C.

1994-01-01

A suite of biomarkers were used to evaluate acute (1 day) to semi-chronic (3 month) heavy metal-induced toxicity in channel catfish, Ictalurus punctatus, caged at an abandoned strip mine and a noncontaminated reference site. Assays performed include indicators of metabolic, hematological, osmoregulatory, and genotoxic stress. Two cage designs were utilized to evaluate the importance of exposure routes; one allowing exclusive contact with the water column and the other allowing contact with water and sediments. Significant DNA strand breakage was observed in catfish exposed in both regimes, but DNA repair was observed only in water-exposed catfish. Transient increases in hemoglobin, ALAD, and hematocrit levels were observed at 1 month for both exposure regimes, followed by a return to control levels for the duration of the study. Environmental conditions (i.e., changes in water quality and temperature) may have contributed to the variable plasma chloride and glucose levels observed in all catfish exposed to strip mine wastes. Further analysis of the data with non-metric clustering techniques and correlations with tissue metal residues may yield more insights into causal relationships

Exposure Assessment Tools by Lifestages and Populations - General Population

Science.gov (United States)

EPA ExpoBox is a toolbox for exposure assessors. Its purpose is to provide a compendium of exposure assessment and risk characterization tools that will present comprehensive step-by-step guidance and links to relevant exposure assessment data bases

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

International Nuclear Information System (INIS)

Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

2013-01-01

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH 1–34 or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and

Biomarker assessment and molecular testing for prognostication in breast cancer.

Science.gov (United States)

Kos, Zuzana; Dabbs, David J

2016-01-01

Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures. © 2015 John Wiley & Sons Ltd.

Responses of biomarkers of a standardized (Cyprinus carpio) and a native (Pimelodella laticeps) fish species after in situ exposure in a periurban zone of Luján river (Argentina).

Science.gov (United States)

Scarcia, Paola; Calamante, Gabriela; de la Torre, Fernando

2014-05-01

The Luján River basin, which is located in the northwest area of the province of Buenos Aires, Argentina, receives different anthropogenic inputs before reaching the Río de la Plata estuary. The aim of this study was to assess the adverse impact of the river in the middle part of the basin. To this end, an in situ cage assay was conducted in two sites of the river (S1 and S2) near Luján city, and the responses of hepatic biomarkers of both a standardized (Cyprinus carpio) and a native (Pimelodella laticeps) species were evaluated. The biomarkers studied were the condition factor and liver somatic indices (LSI), the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST), lipid peroxidation levels (thiobarbituric acid reactive substances, TBARS) and the induction of hepatic cytochrome P450 1A (CYP1A) and vitellogenin (Vtg) proteins. After 14 days, LSI and GST activity increased, and TBARS levels decreased in both species exposed at S1 and S2. In addition, exposure at both sites promoted an increase in SOD activity and CYP1A induction in C. carpio, while Vtg expression was observed only at S1. A shorter exposure period (7 days) caused an initial response only at S2 mediated only by CAT in P. laticeps. Finally, our results demonstrate that a 14-day period of in situ exposure in Luján River could lead to antioxidant and biotransformation processes in C. carpio and to phase II biotransformation responses in P. laticeps. Copyright © 2012 Wiley Periodicals, Inc.

Safety assessments for potential exposures

International Nuclear Information System (INIS)

Dunn, D.I.

2012-04-01

Safety Assessment of potential exposures have been carried out in major practices, namely: industrial radiography, gamma irradiators and electron accelerators used in industry and research, and radiotherapy. This paper focuses on reviewing safety assessment methodologies and using developed software to analyse radiological accidents, also review, and discuss these past accidents.The primary objective of the assessment is to assess the adequacy of planned or existing measures for protection and safety and to identify any additional measures that should be put in place. As such, both routine use of the source and the probability and magnitude of potential exposures arising from accidents or incidents should be considered. Where the assessment indicates that there is a realistic possibility of an accident affecting workers or members of the public or having consequences for the environment, the registrant or licensee should prepare a suitable emergency plan. A safety assessment for normal operation addresses all the conditions under which the radiation source operates as expected, including all phases of the lifetime of the source. Due account needs to be taken of the different factors and conditions that will apply during non-operational phases, such as installation, commissioning and maintenance. (author)

Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo.

Science.gov (United States)

Brillant, Nathalie; Elmasry, Mohamed; Burton, Neal C; Rodriguez, Josep Monne; Sharkey, Jack W; Fenwick, Stephen; Poptani, Harish; Kitteringham, Neil R; Goldring, Christopher E; Kipar, Anja; Park, B Kevin; Antoine, Daniel J

2017-10-01

The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention. Perturbation of liver function and cellular viability was assessed in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122, HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a 60% partial hepatectomy model as a situation of defined hepatic functional mass loss to compared acetaminophen-induced changes to. Integration of these mechanistic markers correlated with histological features of APAP hepatotoxicity in a time-dependent manner. They accurately reflected the onset and recovery from hepatotoxicity compared to traditional biomarkers and also reported the efficacy of NAC with high sensitivity. ICG clearance kinetics correlated with histological scores for acute liver damage for APAP (i.e. 3h timepoint; r=0.90, P<0.0001) and elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6h timepoint; r=0.70, P=0.005) and HMGB1 (e.g. 6h timepoint; r=0.56, P=0.04). For the first time we report the utility of this non-invasive longitudinal imaging approach to provide direct visualisation of the liver function coupled with mechanistic biomarkers, in the same animal, allowing the investigation of the toxicological and pharmacological aspects of APAP-ILI and hepatic regeneration. Copyright © 2017

Short-Term Exposure to Ambient Air Pollution and Biomarkers of Systemic Inflammation: The Framingham Heart Study.

Science.gov (United States)

Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H; Rice, Mary B; Ljungman, Petter L; Schwartz, Joel D; Coull, Brent A; Koutrakis, Petros; Gold, Diane R; Keaney, John F; Vasan, Ramachandran S; Benjamin, Emelia J; Mittleman, Murray A

2017-09-01

The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area. We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameterpollution was associated with higher levels of C-reactive protein, interleukin-6, and tumor necrosis factor receptor 2 but not fibrinogen or tumor necrosis factor α in individuals residing in the greater Boston area. © 2017 American Heart Association, Inc.

Specificity and sensitivity of NMR based urinary metabolic biomarker for radiation injury

International Nuclear Information System (INIS)

Tyagi, Ritu; Watve, Apurva; Khushu, Subash; Rana, Poonam

2016-01-01

Increasing burden of natural background radiation and terrestrial radionuclides is a big threat of radiation exposure to the population at large. It is necessary to develop biomarker of ionizing radiation exposure that can be used for mass screening in the event of a radiological mass casualty incident. Metabolomics has already been proven as an excellent developing prospect for capturing diseases specific metabolic signatures as possible biomarkers. The aim of the present study is to evaluate the sensitivity and specificity of the urinary metabolites after whole body radiation exposure which can further be used as early predictive marker. The PLS-DA based ROC curve depicted taurine as a biomarker of early radiation injury. This study along with other 'omics' technique will be useful to help design strategies for non-invasive radiation biodosimetry through metabolomics in human populations

Quality assurance in biomarker measurement.

Science.gov (United States)

Aitio, A; Apostoli, P

1995-05-01

Quality assurance (QA) concerns the validity of all the analytical processes (from collection of the samples to interpretation of the results). It is not an abstract concept but must be adapted to the different situations such as the different exposure levels, the different analytical methods, and the context of use (risk assessment procedures, research, routine determinations). The main requirements in QA programmes regard the control of all the known sources of preanalytical and analytical variations, while the instruments with which adequate QA can be implemented are the certified materials and the quality control programmes (quality manual, internal and external quality controls). Another important concept in QA is that measurements must be placed a different metrological levels: at the highest there are the methods (definitive, reference) to be used for assessing accuracy of routine methods. QA programmes should enable a grading of biomarkers (from experimental only to full evaluated) and of the laboratories in order to identify the significance of the test and to assess the level at which a laboratory could operate.

Measuring tobacco smoke exposure: quantifying nicotine/cotinine concentration in biological samples by colorimetry, chromatography and immunoassay methods.

Science.gov (United States)

Dhar, Preeti

2004-04-01

Procedures to assess tobacco smoke exposure are reviewed and biomarkers used for determining the smoking status of an individual are compared. Methods used to extract these biomarkers from saliva, urine, and blood and the advantages and disadvantages of the assays are discussed. Finally, the procedures used to measure the levels of cortisol, a stress hormone speculated to be linked to nicotine metabolism, are discussed.

Toxicity of lunar dust assessed in inhalation-exposed rats.

Science.gov (United States)

Lam, Chiu-wing; Scully, Robert R; Zhang, Ye; Renne, Roger A; Hunter, Robert L; McCluskey, Richard A; Chen, Bean T; Castranova, Vincent; Driscoll, Kevin E; Gardner, Donald E; McClellan, Roger O; Cooper, Bonnie L; McKay, David S; Marshall, Linda; James, John T

2013-10-01

Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m(3). This 4-week exposure study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats.

Placental biomarkers of PAH exposure and glutathione-S-transferase biotransformation enzymes in an obstetric population from Tijuana, Baja California, Mexico

Energy Technology Data Exchange (ETDEWEB)

Dodd-Butera, Teresa, E-mail: tdbutera@csusb.edu [California State University San Bernardino, Department of Nursing, 5500 University Parkway, San Bernardino, CA 92407 (United States); San Diego State University, Graduate School of Public Health, San Diego, CA (United States); Union Institute & University, Cincinnati, OH (United States); Quintana, Penelope J.E., E-mail: jquintan@mail.sdsu.edu [San Diego State University, Graduate School of Public Health, San Diego, CA (United States); Ramirez-Zetina, Martha, E-mail: martharz8@hotmail.com [Instituto Mexicano del Seguro Social Tijuana, BC (Mexico); Batista-Castro, Ana C., E-mail: anabatista101@hotmail.com [Instituto Mexicano del Seguro Social Tijuana, BC (Mexico); Hospital General de Tijuana, Tijuana (Mexico); Sierra, Maria M., E-mail: sierramer@gmail.com [San Diego State University, Graduate School of Public Health, San Diego, CA (United States); Shaputnic, Carolyn, E-mail: cshaputnic@ucsd.edu [San Diego State University, Graduate School of Public Health, San Diego, CA (United States); University of California, San Diego, Western FASD Practice and Implementation Center, Department of Pediatrics, Division of Dysmorphology-Teratology, San Diego, CA (United States); Garcia-Castillo, Maura, E-mail: mauragarcia@gmail.com [Xochicalco Universidad Escuela de Medicina, BC (Mexico); Institute for Public Health, San Diego State University, San Diego, CA (United States); Ingmanson, Sonja, E-mail: sonejah@yahoo.com [San Diego State University, Graduate School of Public Health, San Diego, CA (United States); Hull, Stacy, E-mail: hulst74@hotmail.com [San Diego State University, Graduate School of Public Health, San Diego, CA (United States)

2017-01-15

Environmental exposures along the US-Mexico border have the potential to adversely affect the maternal-fetal environment. The purpose of this study was to assess placental biomarkers of environmental exposures in an obstetric population at the California-Baja California border in relation to detoxifying enzymes in the placenta and nutritional status. This study was conducted on consenting, full-term, obstetric patients (n=54), delivering in a hospital in Tijuana, Baja California (BC), Mexico. Placental polyaromatic hydrocarbon (PAH)-DNA adducts were measured in addition to placental glutathione-S-transferase (GST) activity and genotype, maternal serum folate, and maternal and umbilical cord blood lead and cadmium levels. A questionnaire was administered to the mothers to determine maternal occupation in a maquiladora, other exposures, and obstetric indicators. In univariate analysis, maternal serum folate levels were inversely correlated with total PAH-DNA adducts (rho=−0.375, p=0.007); adduct #1 (rho=−0.388, p=0.005); and adduct #3 (rho =−0.430, p=0.002). Maternal lead levels were significantly positively correlated with cord blood lead levels (rho=0.512, p<0.001). Cadmium levels were generally very low but significantly higher in mothers exposed to environmental tobacco smoke (ETS) (either at work or at home, n=10). In multivariate analysis, only maternal serum folate levels remained as a significant negative predictor of total DNA-PAH adducts levels in placenta. These findings affirm that placental tissue is a valuable and readily available source of human tissue for biomonitoring; and indicate that further study of the role of nutrition in detoxification and mitigation of environmental exposures in pregnant women is warranted. - Highlights: • Maternal-fetal environment susceptible to toxic exposures at US-Mexico border. • Lower serum folate was correlated with higher PAH-DNA adduct levels at birth. • Placental DNA adducts in GST mu (-) cord blood

Placental biomarkers of PAH exposure and glutathione-S-transferase biotransformation enzymes in an obstetric population from Tijuana, Baja California, Mexico

International Nuclear Information System (INIS)

Dodd-Butera, Teresa; Quintana, Penelope J.E.; Ramirez-Zetina, Martha; Batista-Castro, Ana C.; Sierra, Maria M.; Shaputnic, Carolyn; Garcia-Castillo, Maura; Ingmanson, Sonja; Hull, Stacy

2017-01-01

Environmental exposures along the US-Mexico border have the potential to adversely affect the maternal-fetal environment. The purpose of this study was to assess placental biomarkers of environmental exposures in an obstetric population at the California-Baja California border in relation to detoxifying enzymes in the placenta and nutritional status. This study was conducted on consenting, full-term, obstetric patients (n=54), delivering in a hospital in Tijuana, Baja California (BC), Mexico. Placental polyaromatic hydrocarbon (PAH)-DNA adducts were measured in addition to placental glutathione-S-transferase (GST) activity and genotype, maternal serum folate, and maternal and umbilical cord blood lead and cadmium levels. A questionnaire was administered to the mothers to determine maternal occupation in a maquiladora, other exposures, and obstetric indicators. In univariate analysis, maternal serum folate levels were inversely correlated with total PAH-DNA adducts (rho=−0.375, p=0.007); adduct #1 (rho=−0.388, p=0.005); and adduct #3 (rho =−0.430, p=0.002). Maternal lead levels were significantly positively correlated with cord blood lead levels (rho=0.512, p<0.001). Cadmium levels were generally very low but significantly higher in mothers exposed to environmental tobacco smoke (ETS) (either at work or at home, n=10). In multivariate analysis, only maternal serum folate levels remained as a significant negative predictor of total DNA-PAH adducts levels in placenta. These findings affirm that placental tissue is a valuable and readily available source of human tissue for biomonitoring; and indicate that further study of the role of nutrition in detoxification and mitigation of environmental exposures in pregnant women is warranted. - Highlights: • Maternal-fetal environment susceptible to toxic exposures at US-Mexico border. • Lower serum folate was correlated with higher PAH-DNA adduct levels at birth. • Placental DNA adducts in GST mu (-) cord blood

Biomarker Identification Using Text Mining

Directory of Open Access Journals (Sweden)

Hui Li

2012-01-01

Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

Biomarker responses and contamination levels in the clam Ruditapes philippinarum for biomonitoring the Lagoon of Venice (Italy).

Science.gov (United States)

Matozzo, Valerio; Binelli, Andrea; Parolini, Marco; Locatello, Lisa; Marin, Maria Gabriella

2010-03-01

A multibiomarker approach was used to assess effects of environmental contaminants in the clam Ruditapes philippinarum from the Lagoon of Venice. Bivalves were collected in 8 sites of the Lagoon (Campalto, Marghera, Palude del Monte, Valle di Brenta, Cà Roman, San Servolo, Fusina and Canale Dese), differently influenced by both anthropogenic impact and natural conditions. The following biomarkers were chosen: total haemocyte count and lysozyme activity in cell-free haemolymph as immunomarkers, acetylcholinesterase activity in gills as a biomarker of exposure to neurotoxic compounds, vitellogenin-like protein levels in both digestive gland and cell-free haemolymph as a biomarker of exposure to estrogenic compounds, and survival-in-air widely used to evaluate general stress conditions in clams. In addition, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its breakdown products (DDE, DDD), hexachlorobenzene (HCB) and hexachlorocyclohexane (HCH) were measured in clams. Results demonstrated that the integrated approach between biomarkers and chemical analyses in R. philippinarum is a useful tool in biomonitoring the Lagoon of Venice. The biomarker responses suggested quite similar contamination levels in the entire Lagoon, although the relative impact of differing classes of pollutants changed among sites according to potential sources, as chemical analyses demonstrated. Overall, among the sampling sites investigated, Palude del Monte can represent an environmental risk area, bearing in mind its peculiar use for clam culture.

Profiling of Biomarkers for the Exposure of Polycyclic Aromatic Hydrocarbons: Lamin-A/C Isoform 3, Poly[ADP-ribose] Polymerase 1, and Mitochondria Copy Number Are Identified as Universal Biomarkers

Directory of Open Access Journals (Sweden)

Hwan-Young Kim

2014-01-01

Full Text Available This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH- induced genotoxicity in cell lines and zebrafish. Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA copy number was dramatically elevated after 5-day treatment of fluoranthene and pyrene. The notable deregulated proteins for PAHs exposure were displayed as follows: lamin-A/C isoform 3 and annexin A1 for benzopyrene; lamin-A/C isoform 3 and DNA topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1 for fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities including curved backbone and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM of benzopyrene. In conclusion, the change of mitochondrial genome (increased mtDNA copy number was closely associated with PAH exposure in cell lines and mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitable in vivo model for monitoring PAHs exposure to hematopoietic tissue and other organs.

Dietary and health biomarkers-time for an update

NARCIS (Netherlands)

Dragsted, L.O.; Gao Qizian,; Praticò, G.; Manach, Claudine; Wishart, D.S.; Scalbert, A.; Feskens, E.J.M.

2017-01-01

In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health.

Oxyfluorfen toxic effect on S. obliquus evaluated by different photosynthetic and enzymatic biomarkers.

Science.gov (United States)

Geoffroy, L; Dewez, D; Vernet, G; Popovic, R

2003-11-01

The effect of oxyfluorfen was investigated when alga Scenedesmus obliquus has been exposed to different concentrations (7.5, 15, and 22.5 microg x L(-1)) at 12, 24, and 48 hours of exposure. Toxicity test was done by using 13 biomarkers concerning growth rate, chlorophyll content and indicators of photosynthetic and antioxidant enzyme activities. The change of the 13 parameters showed a great variation of sensitivity indicating differences in parameters' suitability to be used as biomarkers when alga culture was exposed to oxyfluorfen toxicity. The order of sensitivity between those biomarkers was: Antenna size (ABS/RC) > Chlorophyll content > Catalase (CAT) > Operational PSII quantum yield (phiS(PSII)) > Glutathione S-transferase (GST) > Functional plastoquinone pool (Q(PQ)) > Glutathione reductase (GR) > Growth rate > Nonphotochemical quenching (QN) > Proton gradient quenching (Q(Emax)) > Ascorbate peroxidase (APX) > Photochemical quenching (Q(p)) > Maximum PSII quantum yield (Phi(PSII)). The effect of oxyfluorfen on the changes of those parameters was interpreted as a result of herbicide mode of action at molecular level of alga cellular system. This study indicated for some photosynthetic and enzymatic biomarkers to be useful indicators of toxicity effect induced in non-target alga species. Determination of biomarkers' sensitivity order may facilitate their selection to be used in environmental risk assessment of polluted water.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

Energy Technology Data Exchange (ETDEWEB)

Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

2015-09-01

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

Methylmercury Exposure and Incident Diabetes in U.S. Men and Women in Two Prospective Cohorts

DEFF Research Database (Denmark)

Mozaffarian, Dariush; Shi, Peilin; Morris, J Steven

2013-01-01

compared, and in analyses stratified by fish or omega-3 consumption, BMI, and age.CONCLUSIONSThese findings from two separate large prospective cohorts do not support adverse effects of methylmercury on development of diabetes in men or women at usual levels of exposure seen in these populations.......OBJECTIVEEmerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively determine associations of mercury exposure, as assessed by biomarker measurement, with incident diabetes.RESEARCH DESIGN...... AND METHODSWe used neutron activation analysis to measure toenail mercury, an objective biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline in two separate U.S. prospective cohorts. Incident diabetes was identified from biennial questionnaires and confirmed by validated...

Values of iodine metabolism biomarkers in assessing the iodine nutrition status in surgically treated patients with thyroid disease.

Science.gov (United States)

Han, Jian-hua; Wu, Lian; Yu, Song-lin; Fang, Hui-ling; Kamg, Wei-ming; Cheng, Xin-qi; Lu, Jie; Yu, Jian-chun; Qiu, Ling

2015-04-01

To assess the clinical application value of iodine metabolism biomarkers in assessing iodine nutrition status in surgically treated patients with thyroid disease. Blood,morning urine and 24-hour urine samples were collected in 31 healthy volunteers and in 30 surgically treated patients with thyroid disease before and after surgery. Iodine concentration was analyzed by inductively coupled plasma mass spectrometry. The iodine metabolism biomarkers including serum iodine (SI), morning urine iodine(UI), morning urine iodine/urine creatinine ratio (UI/UCr), 24-hour urine iodine (24 h UI), and 24-hour urine iodine excretion (24 h UIE) were evaluated in these two groups. In addition, the validation coincidence rate of iodine metabolism biomarkers in healthy volunteers to different reference ranges including World Health Organization, Mayo Clinic, and Quest Diagnostics were calculated. The UI/UCr ratio of pre-operative thyroid disease patients was significantly lower than that of healthy volunteers (P0.05) between these two groups. The SI, UI ,and 24 h UI in postoperative thyroid disease patients were significantly higher than those of the pre-operative patients (all Piodine metabolism biomarkers. The UI/UCr ratio may be used for iodine nutrition evaluation in surgically treated patients with thyroid disease.

Increasing fine particulate air pollution in China and the potential use of exposure and biomarker data in disease prevention.

Science.gov (United States)

Wendt, Chris H; Ramachandran, Gurumurthy; Lo, Charles; Hertz, Marshall; Mandel, Jeffrey H

2015-03-16

Increased industrialization and urbanization have led to marked increases in air pollutants in China over the last decade. Pollutant levels in the north and eastern regions are often four times higher than current daily levels in the United States. Recent reports indicate a higher incidence of lung cancer and mortality in men and urban dwellers, but the contribution of air pollution to these findings remains unknown. Future studies that define individual exposures, combined with biomarkers linked to disease, will be essential to the understanding of risk posed by air pollution in China.

Carcinogen biomonitoring in human exposures and laboratory research: validation and application to human occupational exposures.

Science.gov (United States)

Talaska, Glenn; Maier, Andrew; Henn, Scott; Booth-Jones, Angela; Tsuneoka, Yutaka; Vermeulen, Roel; Schumann, Brenda L

2002-08-05

A multiple biomarker approach is required to integrate for metabolism, temporal response and exposure-response kinetics, biological relevance, and positive predictive value. Carcinogen DNA adduct analysis can be used in animal and in vitro studies to detect absorption permutations caused by mixture interactions, and to control metabolic variation when specific CYP450 genes (1A1 or 1A2) are knocked out. These enzymes are not critical to the metabolic activation of model Polycyclic Aromatic Compounds (PAC) and aromatic amines, respectively, as suggested by in vitro analysis. Several human studies have been carried out where multiple biomarkers have been measured. In a study of benzidine workers, the similarities in elimination kinetics between urinary metabolites and mutagenicity is likely responsible for a better correlation between these markers than to BZ-DNA adducts in exfoliated cells. In a study of rubber workers, the relationship between specific departments, urinary 1 HP and DNA adducts in exfoliated cells coincided with the historical urinary bladder cancer risk in these departments; the same relationship did not hold for urinary mutagenicity. In a study of automotive mechanics, biomarkers were used to monitor the effectiveness of exposure interventions. These data reinforce the notion that carcinogen biomarkers are useful to monitor exposure, but that a complementary approaches involving effect and perhaps susceptibility biomarkers is necessary to obtain the necessary information.

Mus musculus bone fluoride concentration as a useful biomarker for risk assessment of skeletal fluorosis in volcanic areas.

Science.gov (United States)

Linhares, Diana; Camarinho, Ricardo; Garcia, Patrícia Ventura; Rodrigues, Armindo Dos Santos

2018-08-01

Fluoride is often found in elevated concentrations in volcanic areas due to the release of magmatic fluorine as hydrogen fluorine through volcanic degassing. The exposure to high levels of fluoride can affect the processes of bone formation and resorption causing skeletal fluorosis, a pathology that can easily be mistaken for other skeletal diseases. In this study, we aimed to determine if fluoride concentration in the femoral bone of wild populations of the house mouse (Mus musculus) is a good biomarker of exposure to active volcanic environments naturally enriched in fluoride, allowing their use in biomonitoring programs. The fluoride concentration of the whole femoral bone of 9 mice from Furnas (5 males and 4 females) and 33 mice from Rabo de Peixe (16 males and 17 females) was measured by the potentiometric method with a fluoride ion selective electrode. Fluoride in bones was significantly higher in the mice from Furnas when compared with the mice from Rabo de Peixe (616.5 ± 129.3 μg F/g vs. 253.8 ± 10.5 μg F/g). Accumulation rates were also significantly higher in the mice collected in Furnas when compared with Rabo de Peixe individuals (3.84 ± 0.52 μg F/day vs. 1.22 ± 0.06 μg F/day). The results demonstrate a significant association between exposure to fluoride in the active volcanic environment and fluoride content in bone, revealing that bone fluoride concentration is a suitable biomarker of chronic environmental exposure to fluoride. Copyright © 2018 Elsevier Ltd. All rights reserved.

Use of a urinary sugars biomarker to assess measurement error in self-reported sugars intake in the Nutrition and Physical Activity Assessment Study (NPAAS)

Science.gov (United States)

Tasevska, Natasha; Midthune, Douglas; Tinker, Lesley F.; Potischman, Nancy; Lampe, Johanna W.; Neuhouser, Marian L.; Beasley, Jeannette M.; Van Horn, Linda; Prentice, Ross L.; Kipnis, Victor

2014-01-01

Background Measurement error (ME) in self-reported sugars intake may be obscuring the association between sugars and cancer risk in nutritional epidemiologic studies. Methods We used 24-hour urinary sucrose and fructose as a predictive biomarker for total sugars, to assess ME in self-reported sugars intake. The Nutrition and Physical Activity Assessment Study (NPAAS) is a biomarker study within the Women’s Health Initiative (WHI) Observational Study, that includes 450 post-menopausal women aged 60–91. Food Frequency Questionnaires (FFQ), 4-day food records (4DFR) and three 24-h dietary recalls (24HRs) were collected along with sugars and energy dietary biomarkers. Results Using the biomarker, we found self-reported sugars to be substantially and roughly equally misreported across the FFQ, 4DFR and 24HR. All instruments were associated with considerable intake- and person-specific bias. Three 24HRs would provide the least attenuated risk estimate for sugars (attenuation factor, AF=0.57), followed by FFQ (AF=0.48), and 4DFR (AF=0.32), in studies of energy-adjusted sugars and disease risk. In calibration models, self-reports explained little variation in true intake (5–6% for absolute sugars; 7–18% for sugars density). Adding participants’ characteristics somewhat improved the percentage variation explained (16–18% for absolute sugars; 29–40% for sugars density). Conclusions None of the self-report instruments provided a good estimate of sugars intake, although overall 24HRs seemed to perform the best. Impact Assuming the calibrated sugars biomarker is unbiased, this analysis suggests that, measuring the biomarker in a subsample of the study population for calibration purposes may be necessary for obtaining unbiased risk estimates in cancer association studies. PMID:25234237

Amylase and blood cell-count hematological radiation-injury biomarkers in a rhesus monkey radiation model-use of multiparameter and integrated biological dosimetry

Energy Technology Data Exchange (ETDEWEB)

Blakely, W.F. [Uniformed Services University, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: blakely@afrri.usuhs.mil; Ossetrova, N.I.; Manglapus, G.L.; Salter, C.A.; Levine, I.H.; Jackson, W.E.; Grace, M.B.; Prasanna, P.G.S.; Sandgren, D.J.; Ledney, G.D. [Uniformed Services University, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

2007-07-15

Effective medical management of suspected radiation exposure incidents requires the recording of dynamic medical data (clinical signs and symptoms), biological assessments of radiation exposure, and physical dosimetry in order to provide diagnostic information to the treating physician and dose assessment for personnel radiation protection records. The need to rapidly assess radiation dose in mass-casualty and population-monitoring scenarios prompted an evaluation of suitable biomarkers that can provide early diagnostic information after exposure. We investigated the utility of serum amylase and hematological blood-cell count biomarkers to provide early assessment of severe radiation exposures in a non-human primate model (i.e., rhesus macaques; n=8) exposed to whole-body radiation of {sup 60}Co-gamma rays (6.5 Gy, 40cGymin{sup -1}). Serum amylase activity was significantly elevated (12.3{+-}3.27- and 2.6{+-}0.058-fold of day zero samples) at 1 and 2-days, respectively, after radiation. Lymphocyte cell counts decreased ({<=}15% of day zero samples) 1 and 2 days after radiation exposure. Neutrophil cell counts increased at day one by 1.9({+-}0.38)-fold compared with levels before irradiation. The ratios of neutrophil to lymphocyte cell counts increased by 13({+-}2.66)- and 4.23({+-}0.95)-fold at 1 and 2 days, respectively, after irradiation. These results demonstrate that increases in serum amylase activity along with decreases of lymphocyte counts, increases in neutrophil cell counts, and increases in the ratio of neutrophil to lymphocyte counts 1 day after irradiation can provide enhanced early triage discrimination of individuals with severe radiation exposure and injury. Use of the biodosimetry assessment tool (BAT) application is encouraged to permit dynamic recording of medical data in the management of a suspected radiological casualty.

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study

OpenAIRE

Mastrangelo, Giuseppe; Carta, Angela; Arici, Cecilia; Pavanello, Sofia; Porru, Stefano

2017-01-01

Background No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines. Methods Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; th...

Progress in human exposure assessment for biocidal products

NARCIS (Netherlands)

Hemmen, J.J. van

2004-01-01

An important shortcoming in our present knowledge required for risk assessment of biocidal products is the assessment of human exposure. This knowledge gap has been filled in a preliminary fashion with the TNsG on human exposure to biocidal products (available from the ECB website). Explicit User

Assessment of chemical exposures: calculation methods for environmental professionals

National Research Council Canada - National Science Library

Daugherty, Jack E

1997-01-01

... on by scientists, businessmen, and policymakers. Assessment of Chemical Exposures: Calculation Methods for Environmental Professionals addresses the expanding scope of exposure assessments in both the workplace and environment...

Risk assessment and management of radiofrequency radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Dabala, Dana [Railways Medical Clinic Cluj-Napoca, Occupational Medicine Department, 16-20 Bilascu Gheorghe St., 400015 Cluj-Napoca (Romania); Surducan, Emanoil; Surducan, Vasile; Neamtu, Camelia [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath St., 400293 Cluj-Napoca (Romania)

2013-11-13

Radiofrequency radiation (RFR) industry managers, occupational physicians, security department, and other practitioners must be advised on the basic of biophysics and the health effects of RF electromagnetic fields so as to guide the management of exposure. Information on biophysics of RFR and biological/heath effects is derived from standard texts, literature and clinical experiences. Emergency treatment and ongoing care is outlined, with clinical approach integrating the circumstances of exposure and the patient's symptoms. Experimental risk assessment model in RFR chronic exposure is proposed. Planning for assessment and monitoring exposure, ongoing care, safety measures and work protection are outlining the proper management.

Risk assessment and management of radiofrequency radiation exposure

International Nuclear Information System (INIS)

Dabala, Dana; Surducan, Emanoil; Surducan, Vasile; Neamtu, Camelia

2013-01-01

Radiofrequency radiation (RFR) industry managers, occupational physicians, security department, and other practitioners must be advised on the basic of biophysics and the health effects of RF electromagnetic fields so as to guide the management of exposure. Information on biophysics of RFR and biological/heath effects is derived from standard texts, literature and clinical experiences. Emergency treatment and ongoing care is outlined, with clinical approach integrating the circumstances of exposure and the patient's symptoms. Experimental risk assessment model in RFR chronic exposure is proposed. Planning for assessment and monitoring exposure, ongoing care, safety measures and work protection are outlining the proper management

Validation of fumonisin biomarkers in F344 rats

International Nuclear Information System (INIS)

Cai Qingsong; Tang Lili; Wang Jiasheng

2007-01-01

Fumonisins (FNs) are ubiquitous contaminants of cereal grains. Fumonisin B 1 (FB 1 ) was linked to several animal and human diseases. To validate FB 1 biomarkers for studying human disease risks, F344 rats were administered by gavage with either a single dose of 0, 10 or 25 mg FB 1 /kg body weight (BW) or repeated doses of 0, 1.0, or 2.5 mg FB 1 /kg BW/day for 5 weeks. FB 1 excretion and FB 1 -induced metabolic alterations of sphingolipids in rat urine, feces and serum were assessed. Dose-dependent urinary and fecal excretion of free FB 1 were found in both single-dose- and repeat-dose-treated rats. In the single-dose study, urinary sphinganine (Sa) to sphingosine (So) ratio (Sa/So) reached a maximum at day 7 for the high-dose group and at day 5 for the low-dose group, whereas serum Sa/So showed only marginal changes. In the repeat-dose study, urinary Sa/So was persistently elevated at 2 weeks, while serum Sa/So was unchanged. Time course changes of sphinganine 1-phosphate (SaP) and sphingosine 1-phosphate (SoP) were also examined. Although serum Sa/So and SaP/SoP ratios showed no signs of time- or dose-dependent changes, a 10-fold increase in urinary SaP/SoP was observed, suggesting that urinary SaP/SoP is a more sensitive biomarker for FB 1 exposure. The accumulation of SaP and SoP was evident in the time course of SaP/Sa and SoP/So, which may reflect activity changes of enzymes closely related to the metabolism and catabolism of SaP and SoP. These results provide concrete evidence towards the practical use of excreted FB 1 , Sa/So and SaP/SoP as biomarkers of exposure to FNs

Blood miRNAs as sensitive and specific biological indicators of environmental and occupational exposure to volatile organic compound (VOC).

Science.gov (United States)

Song, Mi-Kyung; Ryu, Jae-Chun

2015-10-01

To date, there is still shortage of highly sensitive and specific minimally invasive biomarkers for assessment of environmental toxicants exposure. Because of the significance of microRNA (miRNA) in various diseases, circulating miRNAs in blood may be unique biomarkers for minimally invasive prediction of toxicants exposure. We identified and validated characteristic miRNA expression profiles of human whole blood in workers exposed to volatile organic compounds (VOCs) and compared the usefulness of miRNA indicator of VOCs with the effectiveness of the already used urinary biomarkers of occupational exposure. Using a microarray based approach we screened and detected deregulated miRNAs in their expression in workers exposed to VOCs (toluene [TOL], xylene [XYL] and ethylbenzene [EBZ]). Total 169 workers from four dockyards were enrolled in current study, and 50 subjects of them were used for miRNA microarray analysis. We identified 467 miRNAs for TOL, 211 miRNAs for XYL, and 695 miRNAs for XYL as characteristic discernible exposure indicator, which could discerned each VOC from the control group with higher accuracy, sensitivity, and specificity than urinary biomarkers. Current observations from this study point out that the altered levels of circulating miRNAs can be a reliable novel, minimally invasive biological indicator of occupational exposure to VOCs. Copyright © 2015 Elsevier GmbH. All rights reserved.

Human exposure to bisphenol A by biomonitoring: Methods, results and assessment of environmental exposures

International Nuclear Information System (INIS)

Dekant, Wolfgang; Voelkel, Wolfgang

2008-01-01

Human exposure to bisphenol A is controversially discussed. This review critically assesses methods for biomonitoring of bisphenol A exposures and reported concentrations of bisphenol A in blood and urine of non-occupationally ('environmentally') exposed humans. From the many methods published to assess bisphenol A concentrations in biological media, mass spectrometry-based methods are considered most appropriate due to high sensitivity, selectivity and precision. In human blood, based on the known toxicokinetics of bisphenol A in humans, the expected very low concentrations of bisphenol A due to rapid biotransformation and the very rapid excretion result in severe limitations in the use of reported blood levels of bisphenol A for exposure assessment. Due to the rapid and complete excretion of orally administered bisphenol A, urine samples are considered as the appropriate body fluid for bisphenol A exposure assessment. In urine samples from several cohorts, bisphenol A (as glucuronide) was present in average concentrations in the range of 1-3 μg/L suggesting that daily human exposure to bisphenol A is below 6 μg per person (< 0.1 μg/kg bw/day) for the majority of the population

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

Science.gov (United States)

Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

2015-05-01

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Resuspended contaminated sediments cause sublethal stress to oysters: A biomarker differentiates total suspended solids and contaminant effects.