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Sample records for inhalation exposure components

  1. Health Outcomes of Exposure to Biological and Chemical Components of Inhalable and Respirable Particulate Matter

    PubMed Central

    Morakinyo, Oyewale Mayowa; Mokgobu, Matlou Ingrid; Mukhola, Murembiwa Stanley; Hunter, Raymond Paul

    2016-01-01

    Particulate matter (PM) is a key indicator of air pollution and a significant risk factor for adverse health outcomes in humans. PM is not a self-contained pollutant but a mixture of different compounds including chemical and biological fractions. While several reviews have focused on the chemical components of PM and associated health effects, there is a dearth of review studies that holistically examine the role of biological and chemical components of inhalable and respirable PM in disease causation. A literature search using various search engines and (or) keywords was done. Articles selected for review were chosen following predefined criteria, to extract and analyze data. The results show that the biological and chemical components of inhalable and respirable PM play a significant role in the burden of health effects attributed to PM. These health outcomes include low birth weight, emergency room visit, hospital admission, respiratory and pulmonary diseases, cardiovascular disease, cancer, non-communicable diseases, and premature death, among others. This review justifies the importance of each or synergistic effects of the biological and chemical constituents of PM on health. It also provides information that informs policy on the establishment of exposure limits for PM composition metrics rather than the existing exposure limits of the total mass of PM. This will allow for more effective management strategies for improving outdoor air quality. PMID:27314370

  2. Inhalation exposure of animals.

    PubMed Central

    Phalen, R F

    1976-01-01

    Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed. PMID:1017420

  3. PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene

    PubMed Central

    Kim, David; Andersen, Melvin E.; Chao, Yi-Chun E.; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

    2007-01-01

    Background Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Objective Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. Methods The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. Results The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 × 10−5 cm/hr, b) permeability coefficient for the viable epidermis 3.0 × 10−3 cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers’ exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). Conclusions PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures. PMID:17589597

  4. Inhalation exposure methodology.

    PubMed Central

    Phalen, R F; Mannix, R C; Drew, R T

    1984-01-01

    Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.). PMID:6383799

  5. Assessing Inhalation Exposures Associated with ...

    EPA Pesticide Factsheets

    Journal Article This paper presents a simulation-based approach for assessing short-term, water-distribution-system-wide inhalation exposures that could result from showering and the use of humidifiers during contamination events.

  6. INHALATION EXPOSURE-RESPONSE METHODOLOGY

    EPA Science Inventory

    The Inhalation Exposure-Response Analysis Methodology Document is expected to provide guidance on the development of the basic toxicological foundations for deriving reference values for human health effects, focusing on the hazard identification and dose-response aspects of the ...

  7. INHALATION EXPOSURE-RESPONSE METHODOLOGY

    EPA Science Inventory

    The Inhalation Exposure-Response Analysis Methodology Document is expected to provide guidance on the development of the basic toxicological foundations for deriving reference values for human health effects, focusing on the hazard identification and dose-response aspects of the ...

  8. Avian inhalation exposure chamber

    DOEpatents

    Briant, J.K.; Driver, C.J.

    1992-05-05

    An exposure system is designed for delivering gaseous material ranging in particle size from 0.4 micrometers to 20.0 micrometers uniformly to the heads of experimental animals, primarily birds. The system includes a vertical outer cylinder and a central chimney with animal holding bottles connected to exposure ports on the vertical outer cylinder. 2 figs.

  9. Avian inhalation exposure chamber

    DOEpatents

    Briant, James K.; Driver, Crystal J.

    1992-01-01

    An exposure system for delivering gaseous material ranging in particle size from 0.4 micrometers to 20.0 micrometers uniformly to the heads of experimental animals, primarily birds. The system includes a vertical outer cylinder and a central chimney with animal holding bottles connected to exposure ports on the vertical outer cylinder.

  10. Whole-body nanoparticle aerosol inhalation exposures.

    PubMed

    Yi, Jinghai; Chen, Bean T; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L; Stapleton, Phoebe A; Minarchick, Valerie C; Nurkiewicz, Timothy R

    2013-05-07

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter < 200 nm and a geometric standard deviation σg < 2.5 (5). The generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size (6), which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria (5). A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m(3) whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm(3)) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m(3)). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpre and Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M

  11. Exposure levels and determinants of inhalable dust exposure in bakeries.

    PubMed

    Burstyn, I; Teschke, K; Kennedy, S M

    1997-12-01

    The study's objectives were to measure full-shift exposure to inhalable dust in bakeries and define the determinants of full-shift exposure. Inhalable dust was measured gravimetrically. Ninety-six bakery workers, employed in seven different bakeries, participated in the study. Two side-by-side full-shift inhalable dust samples were obtained from each study participant on a single occasion. Samples were collected on 18 days selected at random. During the entire sampling period, bakers were observed and information on 14 different tasks was recorded at 15 min intervals. Other production characteristics were also recorded for each sampling day. These task and production variables were used in statistical modelling to identify significant predictors of exposure. The mean full-shift inhalable dust exposure was 8.2 mg/m3 (range: 0.1-110 mg/m3). A regression model explained 79% of the variability in exposure. The model indicated that tasks such as weighing, pouring and operating dough-brakers and reversible sheeters increased the exposure, while packing, catching and decorating decreased the exposure. Bread and bun production lines were associated with increased full-shift inhalable dust exposure, while cake production and substitution of dusting with the use of divider oil were associated with decreased exposure. Production tasks and characteristics are strong predictors of personal full-shift exposures to flour dust among bakers; these can be altered to reduce exposure levels.

  12. INHALATION EXPOSURE-RESPONSE ASSESSMENTS FOR FIVE CHEMICALS

    EPA Science Inventory

    Inhalation exposure-response assessments for five chemicals (acrolein, ethylene oxide, hexachlorocyclopentadiene, hydrogen sulfide, and phosgene) for less-than-lifetime durations are being developed to inform the development of the Inhalation Exposure-Response Analysis Methodolog...

  13. INHALATION EXPOSURE-RESPONSE ASSESSMENTS FOR FIVE CHEMICALS

    EPA Science Inventory

    Inhalation exposure-response assessments for five chemicals (acrolein, ethylene oxide, hexachlorocyclopentadiene, hydrogen sulfide, and phosgene) for less-than-lifetime durations are being developed to inform the development of the Inhalation Exposure-Response Analysis Methodolog...

  14. ASSESSMENT OF DIOXIN INHALATION EXPOSURES AND ...

    EPA Pesticide Factsheets

    In the days following the September 11, 2001, terrorist attack on New York City's World Trade Center (WTC) towers, EPA, other federal agencies, and New York City and New York State public health and environmental authorities initiated numerous air monitoring activities to better understand the ongoing impact of emissions from that disaster. Using these data, EPA conducted an inhalation exposure and human health risk assessment. The overall evaluation focused on particulate matter, metals, polychlorinated biphenyls, dioxin-like compounds, asbestos, and volatile organic compounds. This paper reports on the analysis of dioxin-like compounds only.Lorber, M. 2003. Assessment of Dioxin Inhalation Exposures and Potential Health Impacts Following the Collapse of the World Trade Center Towers. Organohalogen Compounds 63 (no page numbers). journal article

  15. Pulmonary injury after ski wax inhalation exposure.

    PubMed

    Bracco, D; Favre, J B

    1998-11-01

    A wide variety of irritants can lead to respiratory failure after inhalation injuries. We present a case of adult respiratory distress syndrome after exposure to a fluorocarbon resin (PFF 1020) used as ski wax. The patient sustained a mild but prolonged exposure to this substance, which subsequently led to symptoms of severe respiratory failure over the next 24 hours. Except for hypocalcemia, there were no systemic manifestations and recovery was uneventful. Ski wax is considered to be nontoxic and there are no reported side effects of these products. Injury was related to the heated fluorocarbon particles. This case report of a severe lung inhalation injury points out the increasing risk of environmental hazards associated with the use of synthetic substances.

  16. 40 CFR 79.61 - Vehicle emissions inhalation exposure guideline.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., densities and shapes, and to predict where in the respiratory tract such particles may be deposited. It... to particles which are capable of being inhaled and may be deposited anywhere within the respiratory...) Principles and design criteria of inhalation exposure systems. Proper conduct of inhalation toxicity...

  17. Assessing inhalation exposure from airborne soil contaminants

    SciTech Connect

    Shinn, J.H.

    1998-04-01

    A method of estimation of inhalation exposure to airborne soil contaminants is presented. this method is derived from studies of airborne soil particles with radioactive tags. The concentration of contaminants in air (g/m{sup 3}) can be derived from the product of M, the suspended respirable dust mass concentration (g/m{sup 3}), S, the concentration of contaminant in the soil (g/g), and E{sub f}, an enhancement factor. Typical measurement methods and values of M, and E{sub f} are given along with highlights of experiences with this method.

  18. Conceptual model for assessment of inhalation exposure: defining modifying factors.

    PubMed

    Tielemans, Erik; Schneider, Thomas; Goede, Henk; Tischer, Martin; Warren, Nick; Kromhout, Hans; Van Tongeren, Martie; Van Hemmen, Joop; Cherrie, John W

    2008-10-01

    The present paper proposes a source-receptor model to schematically describe inhalation exposure to help understand the complex processes leading to inhalation of hazardous substances. The model considers a stepwise transfer of a contaminant from the source to the receptor. The conceptual model is constructed using three components, i.e. (i) the source, (ii) various transmission compartments and (iii) the receptor, and describes the contaminant's emission and its pattern of transport. Based on this conceptual model, a list of nine mutually independent principal modifying factors (MFs) is proposed: activity emission potential, substance emission potential, localized control, separation, segregation, dilution, worker behavior, surface contamination and respiratory protection. These MFs describe the exposure process at a high level of abstraction so that the model can be generically applicable. A list of exposure determinants underlying each of these principal MFs is proposed to describe the exposure process at a more detailed level. The presented conceptual model is developed in conjunction with an activity taxonomy as described in a separate paper. The proposed conceptual model and MFs should be seen as 'building blocks' for development of higher tier exposure models.

  19. INHALATION TOXICOLOGY METHODS: The Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

    PubMed Central

    Chen, Lung-Chi; Lippmann, Morton

    2015-01-01

    In this review, we outline the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study. We then discuss methods for: 1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; 2) their delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; 3) options for on-line functional assays during and between exposures; and 4) options for serial non-invasive assays of response. In doing so, we go beyond exposures to single agents and simple mixtures, and include methods for evaluating biological responses to complex environmental mixtures. We also emphasize that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology. PMID:25645246

  20. A novel sulfur mustard (HD) vapor inhalation exposure system for accurate inhaled dose delivery

    PubMed Central

    Perry, Mark R.; Benson, Eric M.; Kohne, Jonathon W.; Plahovinsak, Jennifer L.; Babin, Michael C.; Platoff, Gennady E.; Yeung, David T.

    2014-01-01

    Introduction A custom designed HD exposure system was used to deliver controlled inhaled doses to an animal model through an endotracheal tube. Methods Target HD vapor challenges were generated by a temperature controlled bubbler/aerosol trap, while concentration was monitored near real-time by gas chromatography. Animal breathing parameters were monitored real-time by an in-line pneumotach, pressure transducer, and Buxco pulmonary analysis computer/software. For each exposure, the challenge atmosphere was allowed to stabilize at the desired concentration while the anesthetized animal was provided humidity controlled clean air. Once the target concentration was achieved and stable, a portion of the challenge atmosphere was drawn past the endotracheal tube, where the animal inhaled the exposure ad libitum. During the exposure, HD vapor concentration and animal weight were used to calculate the needed inhaled volume to achieve the target inhaled dose (μg/kg). The exposures were halted when the inhaled volume was achieved. Results The exposure system successfully controlled HD concentrations from 22.2 to 278 mg/m3 and accurately delivered inhaled doses between 49.3 and 1120 μg/kg with actual administered doses being within 4% of the target level. Discussion This exposure system administers specific HD inhaled doses to evaluate physiological effects and for evaluation of potential medical countermeasure treatments. PMID:25291290

  1. Incinerator air emissions: Inhalation exposure perspectives

    SciTech Connect

    Rogers, H.W.

    1995-12-01

    Incineration is often proposed as the treatment of choice for processing diverse wastes, particularly hazardous wastes. Where such treatment is proposed, people are often fearful that it will adversely affect their health. Unfortunately, information presented to the public about incinerators often does not include any criteria or benchmarks for evaluating such facilities. This article describes a review of air emission data from regulatory trial burns in a large prototype incinerator, operated at design capacity by the US Army to destroy chemical warfare materials. It uses several sets of criteria to gauge the threat that these emissions pose to public health. Incinerator air emission levels are evaluated with respect to various toxicity screening levels and ambient air levels of the same pollutants. Also, emission levels of chlorinated dioxins and furans are compared with emission levels of two common combustion sources. Such comparisons can add to a community`s understanding of health risks associated with an incinerator. This article focuses only on the air exposure/inhalation pathway as related to human health. It does not address other potential human exposure pathways or the possible effects of emissions on the local ecology, both of which should also be examined during a complete analysis of any major new facility.

  2. Nicotine and Carbon Monoxide Exposure from Inhalation of Cigarillo Smoke

    PubMed Central

    Koszowski, Bartosz; Rosenberry, Zachary R.; Kanu, Alieu; Viray, Lauren C.; Potts, Jennifer L.; Pickworth, Wallace B.

    2015-01-01

    Background There has been an increase in the use of cigarillos in the US. People who smoke cigarillos typically also regularly smoke cigarettes (dual users). Methods We compared puffing topography, biomarkers of acute exposure [exhaled carbon monoxide (COex) and plasma nicotine] and physiologic effects from usual brand cigarette and Black & Mild cigarillo smoking in dual users (N=23) in two laboratory sessions. Results Participants (21 men) smoked an average of 17.5 cigarettes/day. Cigarillo consumption varied widely from as few as 1/week to daily. Participants were highly nicotine dependent (average FTND score: 6.3). There were statistically significant differences in smoking behavior between cigarette and cigarillo smoking in time to smoke, number of puffs, and total puff volume (all P<0.001). Average puff duration, interpuff interval average puff volume, and puff velocity did not differ between cigarettes and cigarillos. Nicotine boost was similar after both cigarettes and cigarillos. COex boost was significantly greater after cigarillo smoking compared to cigarette smoking (P<0.001). Conclusions The smoking pattern and exposure profile indicate that dual users inhale cigarillo smoke just as they inhale cigarette smoke thereby exposing themselves to considerable amounts of nicotine and other components of tobacco smoke. COex exposure results imply that cigarillo smoking may be associated with higher exposure to smoke-delivered volatile components of mainstream cigarillo smoke including carcinogens when compared to cigarettes. Impact The findings that cigarillos and cigarettes are smoked similarly in dual users are relevant to health and regulatory considerations on cigar products. PMID:26459155

  3. Nicotine and carbon monoxide exposure from inhalation of cigarillo smoke.

    PubMed

    Koszowski, Bartosz; Rosenberry, Zachary R; Kanu, Alieu; Viray, Lauren C; Potts, Jennifer L; Pickworth, Wallace B

    2015-12-01

    There has been an increase in the use of cigarillos in the US. People who smoke cigarillos typically also regularly smoke cigarettes (dual users). We compared puffing topography, biomarkers of acute exposure [exhaled carbon monoxide (COex) and plasma nicotine] and physiologic effects from usual brand cigarette and Black & Mild cigarillo smoking in dual users (N=23) in two laboratory sessions. Participants (21 men) smoked an average of 17.5cigarettes/day. Cigarillo consumption varied widely from as few as 1/week to daily. Participants were highly nicotine dependent (average FTND score: 6.3). There were statistically significant differences in smoking behavior between cigarette and cigarillo smoking in time to smoke, number of puffs, and total puff volume (all P<0.001). Average puff duration, interpuff interval average puff volume, and puff velocity did not differ between cigarettes and cigarillos. Nicotine boost was similar after both cigarettes and cigarillos. COex boost was significantly greater after cigarillo smoking compared to cigarette smoking (P<0.001). The smoking pattern and exposure profile indicate that dual users inhale cigarillo smoke just as they inhale cigarette smoke thereby exposing themselves to considerable amounts of nicotine and other components of tobacco smoke. COex exposure results imply that cigarillo smoking may be associated with higher exposure to smoke-delivered volatile components of mainstream cigarillo smoke including carcinogens when compared to cigarettes. The findings that cigarillos and cigarettes are smoked similarly in dual users are relevant to health and regulatory considerations on cigar products. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Respiratory disorders associated with heavy inhalation exposure to dolomite dust

    PubMed Central

    Neghab, M; Abedini, R; Soltanzadeh, A; Iloon Kashkooli, A; Ghayoomi, S M A

    2012-01-01

    Background Although dolomite is classified as a relatively non-toxic, nuisance dust, little information exists as to its potential to produce respiratory disorders following occupational exposure. The purpose of this study was, therefore, to evaluate the possible effects, if any, of heavy inhalation exposure to this chemical on the prevalence of respiratory symptoms, functional impairments and radiographic abnormalities of the lungs. Methods The study population consisted of a group of 39 exposed subjects engaged in digging and excavating activities that were in operation for building a local dam, as well as 40 healthy non-exposed employees that served as the referent group. Subjects were interviewed and respiratory symptoms questionnaires, as suggested by the American Thoracic Society (ATS), were completed for them. Thereafter, they underwent chest X-ray and lung function tests. Additionally, using routine gravimetric techniques, personal dust monitoring for airborne inhalable and respirable dust was carried out at different dusty work sites. Finally to determine the chemical composition of the dust, it was analyzed by X-ray fluorescence (XRF) technique. Results XRF revealed that the major component (50.52%) of the dust was calcium magnesium carbonate, dolomite. Additionally, levels of exposure to inhalable and respirable dust were estimated to be 51.7±24.31 and 23.0±18.11mg/m3, respectively. Statistical analysis of the data showed that symptoms such as regular cough, phlegm, wheezing, productive cough and shortness of breath were significantly (p<0.05) more prevalent among exposed workers. Similarly, the ratio of FEV1/FVC in exposed subjects was significantly different from that of non-exposed individuals. In contrast, no significant abnormalities were observed in the chest radiographs of both groups. Conclusions In conclusion, while these data cast doubt on the notion that dolomite is a harmless chemical, they provide evidence in favour of the proposition that

  5. Acute inhalation exposure of azodicarbonamide in the guinea pig.

    PubMed

    Shopp, G M; Cheng, Y S; Gillett, N A; Bechtold, W E; Medinsky, M A; Hobbs, C H; Birnbaum, L S; Mauderly, J L

    1987-02-01

    Humans have been exposed to azodicarbonamide (ADA) by inhalation where bulk quantities of ADA are handled in the workplace. Responses of some workers have led to concern for the potential irritant and sensitizing properties of inhaled ADA. This study examined the effects of inhaling ADA on lung structure and function of guinea pigs during and after an acute exposure. Groups of 20 guinea pigs were exposed to each of 3 concentrations of ADA (19, 58, and 97 mg/m3), plus air as a control, for 1 hr. Pulmonary function was measured before exposure (baseline), during exposure, immediately after exposure and 24 hr after exposure. Dynamic compliance (Cdyn), total pulmonary resistance (RL), tidal volume (VT), respiratory frequency and minute volume were measured. In addition, gross necropsies and histological examinations of respiratory tract tissues were done either immediately following the exposure or 24 hr after exposure. There were no effects of ADA exposure on gross necropsy, histology, Cdyn, or RL. Some significant, concentration-related decreases in VT, respiratory frequency and minute volume were seen. The magnitudes of these changes were small: the largest change was seen in minute volume, amounting to a 24% decrease in the high concentration group. Inhalation exposure of guinea pigs to ADA at concentrations of up to 97 mg/m3 resulted in minor changes in pulmonary function without any changes in lung histology.

  6. Pathways of inhalation exposure to manganese in children ...

    EPA Pesticide Factsheets

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation pathway model to ambient air Mn was hypothesized. Data for model evaluation were obtained from participants in the Communities Actively Researching Exposure Study (CARES). These data were collected in 2009 and included levels of Mn in residential soil and dust, levels of Mn in children's hair, information on the amount of time the child spent outside, heat and air conditioning in the home and level of parent education. Hair Mn concentration was the primary endogenous variable used to assess the theoretical inhalation exposure pathways. The model indicated that household dust Mn was a significant contributor to child hair Mn (0.37). Annual ambient air Mn concentration (0.26), time children spent outside (0.24) and soil Mn (0.24) significantly contributed to the amount of Mn in household dust. These results provide a potential framework for understanding the inhalation exposure pathway for children exposed to ambient air Mn who live in proximity to an industrial emission source. The purpose of this study was to use a structural equations modeling approach combined with exposure estimates derived from air-dispersion modeling to assess potential inhalation exposure pathways for children to a

  7. Pathways of inhalation exposure to manganese in children ...

    EPA Pesticide Factsheets

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation pathway model to ambient air Mn was hypothesized. Data for model evaluation were obtained from participants in the Communities Actively Researching Exposure Study (CARES). These data were collected in 2009 and included levels of Mn in residential soil and dust, levels of Mn in children's hair, information on the amount of time the child spent outside, heat and air conditioning in the home and level of parent education. Hair Mn concentration was the primary endogenous variable used to assess the theoretical inhalation exposure pathways. The model indicated that household dust Mn was a significant contributor to child hair Mn (0.37). Annual ambient air Mn concentration (0.26), time children spent outside (0.24) and soil Mn (0.24) significantly contributed to the amount of Mn in household dust. These results provide a potential framework for understanding the inhalation exposure pathway for children exposed to ambient air Mn who live in proximity to an industrial emission source. The purpose of this study was to use a structural equations modeling approach combined with exposure estimates derived from air-dispersion modeling to assess potential inhalation exposure pathways for children to a

  8. Inhalational and dermal exposures during spray application of biocides.

    PubMed

    Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

    2005-01-01

    Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

  9. Exposure Assessment Tools by Routes - Inhalation

    EPA Pesticide Factsheets

    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

  10. Inhalation a significant exposure route for chlorinated organophosphate flame retardants.

    PubMed

    Schreder, Erika D; Uding, Nancy; La Guardia, Mark J

    2016-05-01

    Chlorinated organophosphate flame retardants (ClOPFRs) are widely used as additive flame retardants in consumer products including furniture, children's products, building materials, and textiles. Tests of indoor media in homes, offices, and other environments have shown these compounds are released from products and have become ubiquitous indoor pollutants. In house dust samples from Washington State, U.S.A., ClOPFRs were the flame retardants detected in the highest concentrations. Two ClOPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP or TDCIPP) and tris(2-chloroethyl)phosphate (TCEP), have been designated as carcinogens, and there is growing concern about the toxicity of the homologue tris(1-chloro-2-propyl)phosphate (TCPP or TCIPP). In response to concerns about exposure to these compounds, the European Union and a number of U.S. states have taken regulatory action to restrict their use in certain product categories. To better characterize exposure to ClOPFRs, inhalation exposure was assessed using active personal air samplers in Washington State with both respirable and inhalable particulate fractions collected to assess the likelihood particles penetrate deep into the lungs. Concentrations of ∑ClOPFRs (respirable and inhalable) ranged from 97.1 to 1190 ng m(-3) (mean 426 ng m(-3)), with TCPP detected at the highest concentrations. In general, higher levels were detected in the inhalable particulate fraction. Total intake of ClOPFRs via the inhalation exposure route was estimated to exceed intake via dust ingestion, indicating that inhalation is an important route that should be taken into consideration in assessments of these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. CONTROLLED, SHORT-TERM DERMAL AND INHALATION EXPOSURE TO CHLOROFORM

    EPA Science Inventory

    Studies were conducted to determine the uptake by humans of chloroform as a result of controlled short-term dermal and inhalation exposures. The approach used continuous real-time breath analysis to determine exhaled-breath profiles and evaluate chloroform kinetics in the huma...

  12. CONTROLLED, SHORT-TERM DERMAL AND INHALATION EXPOSURE TO CHLOROFORM

    EPA Science Inventory

    Studies were conducted to determine the uptake by humans of chloroform as a result of controlled short-term dermal and inhalation exposures. The approach used continuous real-time breath analysis to determine exhaled-breath profiles and evaluate chloroform kinetics in the huma...

  13. INDOOR AIR QUALITY AND INHALATION EXPOSURE - SIMULATION TOOL KIT

    EPA Science Inventory

    A Microsoft Windows-based indoor air quality (IAQ) simulation software package is presented. Named Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short, this package complements and supplements existing IAQ simulation programs and is desi...

  14. Exposure to inhalable, respirable, and ultrafine particles in welding fume.

    PubMed

    Lehnert, Martin; Pesch, Beate; Lotz, Anne; Pelzer, Johannes; Kendzia, Benjamin; Gawrych, Katarzyna; Heinze, Evelyn; Van Gelder, Rainer; Punkenburg, Ewald; Weiss, Tobias; Mattenklott, Markus; Hahn, Jens-Uwe; Möhlmann, Carsten; Berges, Markus; Hartwig, Andrea; Brüning, Thomas

    2012-07-01

    This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m(-3) for inhalable and 1.29 mg m(-3) for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m(-3)). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements exposure to welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging.

  15. Exposure to Inhalable, Respirable, and Ultrafine Particles in Welding Fume

    PubMed Central

    Pesch, Beate

    2012-01-01

    This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m−3 for inhalable and 1.29 mg m−3 for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m−3). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements exposure to welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging. PMID:22539559

  16. INDOOR AIR QUALITY AND INHALATION EXPOSURE - SIMULATION TOOL KIT

    EPA Science Inventory

    A Microsoft Windows-based indoor air quality (IAQ) simulation software package is presented. Named Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short, this package complements and supplements existing IAQ simulation programs and is desi...

  17. Computer controlled multi-walled carbon nanotube inhalation exposure system.

    PubMed

    McKinney, Walter; Chen, Bean; Frazer, Dave

    2009-10-01

    Inhalation exposure systems are necessary tools for determining the dose-response relationship of inhaled toxicants under a variety of exposure conditions. The objective of this project was to develop an automated computer controlled system to expose small laboratory animals to precise concentrations of airborne multi-walled carbon nanotubes (MWCNT). An aerosol generator was developed which was capable of suspending a respirable fraction of multi-walled carbon nanotubes from bulk material. The output of the generator was used to expose small laboratory animals to constant aerosol concentrations up to 12 mg/m(3). Particle distribution and morphology of the MWCNT aerosol delivered to the exposure chamber were measured and compared to samples previously taken from air inside a facility that produces MWCNT. The comparison showed the MWCNT generator was producing particles similar in size and shape to those found in a work environment. The inhalation exposure system combined air flow controllers, particle monitors, data acquisition devices, and custom software with automatic feedback control to achieve constant and repeatable exposure chamber temperature, relative humidity, pressure, aerosol concentration, and particle size distribution. The automatic control algorithm was capable of maintaining the mean aerosol concentration to within 0.1 mg/m(3) of the selected target value, and it could reach 95% of the target value in less than 10 minutes during the start-up of an inhalation exposure. One of the major advantages of this system was that once the exposure parameters were selected, a minimum amount of operator intervention was required over the exposure period.

  18. Post-accident inhalation exposure and experience with plutonium

    SciTech Connect

    Shinn, J

    1998-06-01

    This paper addresses the issue of inhalation exposure immediately afterward and for a long time following a nuclear accident. For the cases where either a nuclear weapon burns or explodes prior to nuclear fission, or at locations close to a nuclear reactor accident containing fission products, a major concern is the inhalation of aerosolized plutonium (Pu) particles producing alpha-radiation. We have conducted field studies of Pu- contaminated real and simulated accident sites at Bikini, Johnston Atoll, Tonopah (Nevada), Palomares (Spain), Chernobyl, and Maralinga (Australia).

  19. An interesting case of characteristic methanol toxicity through inhalational exposure

    PubMed Central

    Kumar, Pratyush; Gogia, Atul; Kakar, Atul; Miglani, Pratyush

    2015-01-01

    Methanol poisoning is rare but carries high risk of morbidity and mortality. Most of the cases witnessed in emergency are due to consumption of adulterated alcohol. Here we are reporting a very rare case of methanol poisoning through inhalational exposure leading to putamen necrosis and decreased visual acuity. He had dyselectrolytemia and metabolic acidosis which was successfully managed with early intervention. Its importance lies in the fact that inhalational methanol poisoning is an entity which if picked up early can prevent long-term neurological sequelae. PMID:26285665

  20. Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology

    PubMed Central

    2013-01-01

    Background Dosimetry for toxicology studies involving carbon nanotubes (CNT) is challenging because of a lack of detailed occupational exposure assessments. Therefore, exposure assessment findings, measuring the mass concentration of elemental carbon from personal breathing zone (PBZ) samples, from 8 U.S.-based multi-walled CNT (MWCNT) manufacturers and users were extrapolated to results of an inhalation study in mice. Results Upon analysis, an inhalable elemental carbon mass concentration arithmetic mean of 10.6 μg/m3 (geometric mean 4.21 μg/m3) was found among workers exposed to MWCNT. The concentration equates to a deposited dose of approximately 4.07 μg/d in a human, equivalent to 2 ng/d in the mouse. For MWCNT inhalation, mice were exposed for 19 d with daily depositions of 1970 ng (equivalent to 1000 d of a human exposure; cumulative 76 yr), 197 ng (100 d; 7.6 yr), and 19.7 ng (10 d; 0.76 yr) and harvested at 0, 3, 28, and 84 d post-exposure to assess pulmonary toxicity. The high dose showed cytotoxicity and inflammation that persisted through 84 d after exposure. The middle dose had no polymorphonuclear cell influx with transient cytotoxicity. The low dose was associated with a low grade inflammatory response measured by changes in mRNA expression. Increased inflammatory proteins were present in the lavage fluid at the high and middle dose through 28 d post-exposure. Pathology, including epithelial hyperplasia and peribronchiolar inflammation, was only noted at the high dose. Conclusion These findings showed a limited pulmonary inflammatory potential of MWCNT at levels corresponding to the average inhalable elemental carbon concentrations observed in U.S.-based CNT facilities and estimates suggest considerable years of exposure are necessary for significant pathology to occur at that level. PMID:24144386

  1. U.S. EPA'S ACUTE REFERENCE EXPOSURE METHODOLOGY FOR ACUTE INHALATION EXPOSURES

    EPA Science Inventory

    The US EPA National Center for Environmental Assessment has developed a methodology to derive acute inhalation toxicity benchmarks, called acute reference exposures (AREs), for noncancer effects. The methodology provides guidance for the derivation of chemical-specific benchmark...

  2. Assessing exposures to inhaled complex mixtures.

    PubMed Central

    Leaderer, B P; Lioy, P J; Spengler, J D

    1993-01-01

    In the course of daily activities, individuals spend varying amounts of time in different spaces where they are exposed to a complex mixture of gas, vapor, and particulate contaminants. The term complex is used in this paper to refer to binary mixtures as well as truly complex mixtures of three or more constituents. The diversity of the environments where pollution may occur, the number of pollutants that may be present, and the nature of the activity in the environment combine to pose a challenge to investigators of the health effects of air pollutants. This article discusses several methods of measuring or assessing exposure to complex mixture air contaminants that include time-activity assessments, personal monitoring, biomarkers of exposure, and microenvironmental models that can be employed singly or in combination in a protocol for exposure assessment. The use of nested designs, involving more intensive data collection from samples or subjects, is also considered. PMID:8206025

  3. INHALATION EXPOSURE AND INTAKE DOSE MODEL IMPROVEMENTS

    EPA Science Inventory

    This presentation highlights recent human exposure model improvements and products developed by the EMRB in coordination with scientists in the OAQPS and provides insight into how these products are used by the OAQPS in its regulatory process. Besides providing a status report of...

  4. INHALATION EXPOSURE AND INTAKE DOSE MODEL IMPROVEMENTS

    EPA Science Inventory

    This presentation highlights recent human exposure model improvements and products developed by the EMRB in coordination with scientists in the OAQPS and provides insight into how these products are used by the OAQPS in its regulatory process. Besides providing a status report of...

  5. The validity of the EASE expert system for inhalation exposures.

    PubMed

    Cherrie, John W; Hughson, Graeme W

    2005-03-01

    Estimation and Assessment of Substance Exposure (EASE) is a computerized expert system developed by the UK Health and Safety Executive to facilitate exposure assessments in the absence of exposure measurements. The system uses a number of rules to predict a range of likely exposures or an 'end-point' for a given work situation. The purpose of this study was to identify a number of inhalation exposure measurements covering a wide range of end-points in the EASE system to compare with the predicted exposures. Occupational exposure data sets were identified from previous research projects or from consultancy work. Available information for each set of measurements was retrieved from archive storage and reviewed to ensure that it was adequate to enable EASE (version 2) predictions to be obtained. Exposure measurements and other relevant contextual data were abstracted and entered into a computer spreadsheet. EASE predictions were then obtained for each task or job and entered into the spreadsheet. In addition, we generated a random exposure range for each data set for comparison with the EASE predictions. Finally, we produced exposure assessments for a subset of the data using a structured subjective assessment method. We were able to identify approximately 4000 inhalation exposure measurements covering 52 different scenarios and 28 EASE end-points. The data included measurements of solvent vapours, non-fibrous dusts and fibres. In 62% of the end-points the EASE predictions were generally greater than the exposure measurements and in 30% of the end-points the EASE estimates were comparable with the measurements. The random allocation of exposure ranges was, as expected, less reliable than EASE, although there were still about one-third of the cases where the randomly generated exposure ranges generally agreed with the measurements. The structured subjective assessments undertaken by a human expert produced exposure estimates in better agreement with the measurements

  6. Characterization and assessment of dermal and inhalable nickel exposures in nickel production and primary user industries.

    PubMed

    Hughson, G W; Galea, K S; Heim, K E

    2010-01-01

    The aim of this study was to measure the levels of nickel in the skin contaminant layer of workers involved in specific processes and tasks within the primary nickel production and primary nickel user industries. Dermal exposure samples were collected using moist wipes to recover surface contamination from defined areas of skin. These were analysed for soluble and insoluble nickel species. Personal samples of inhalable dust were also collected to determine the corresponding inhalable nickel exposures. The air samples were analysed for total inhalable dust and then for soluble, sulfidic, metallic, and oxidic nickel species. The workplace surveys were carried out in five different workplaces, including three nickel refineries, a stainless steel plant, and a powder metallurgy plant, all of which were located in Europe. Nickel refinery workers involved with electrolytic nickel recovery processes had soluble dermal nickel exposure of 0.34 microg cm(-2) [geometric mean (GM)] to the hands and forearms. The GM of soluble dermal nickel exposure for workers involved in packing nickel salts (nickel chloride hexahydrate, nickel sulphate hexahydrate, and nickel hydroxycarbonate) was 0.61 microg cm(-2). Refinery workers involved in packing nickel metal powders and end-user powder operatives in magnet production had the highest dermal exposure (GM = 2.59 microg cm(-2) soluble nickel). The hands, forearms, face, and neck of these workers all received greater dermal nickel exposure compared with the other jobs included in this study. The soluble nickel dermal exposures for stainless steel production workers were at or slightly above the limit of detection (0.02 microg cm(-2) soluble nickel). The highest inhalable nickel concentrations were observed for the workers involved in nickel powder packing (GM = 0.77 mg m(-3)), although the soluble component comprised only 2% of the total nickel content. The highest airborne soluble nickel exposures were associated with refineries using

  7. Inhalation exposure to haloacetic acids and haloketones during showering.

    PubMed

    Xu, Xu; Weisel, Clifford P

    2003-02-01

    Inhalation exposure to haloacetic acids (HAAs) and haloketones (HKs) in contaminated drinking water occurs during showering. The size distribution of the aerosols generated by a shower was determined using an eight size-range particle counter, which measured particles from 0.1 to >2 microm. An exponential increase in aerosol numbers was observed while the shower water was on, while the aerosol numbers declined exponentially once the water was turned off. The half-lives of the shower aerosols were longer than 5 min after the shower water was turned off. Although the majority of the shower-generated aerosols were smaller than 0.3 microm, these aerosols only contributed approximately 2% to the measured total aerosol mass. The total shower-generated particulate HAA and HK concentrations collected on an open face filter were approximately 6.3 and 0.13 microg/m3, respectively, for shower water HAA and HK concentrations of 250 and 25 microg/L, respectively. The vapor-phase HK concentrations were 25-50 microg/m3. The estimate of the dose from inhalation exposure of disinfection byproducts (DBPs) in the particulate phase indicate that they represent less than 1% of the ingestion dose, so inhalation is not expected to be an important exposure route to nonvolatile water contaminants or the portion of volatile DBPs that stay in the particulate phase, unless the lung is the target organ. The vapor-phase levels of volatile HKs, though, are significantly higher and can contribute greater than 10% of the ingestion dose during a shower. Thus, risk assessment to the these DBPs needs to consider the inhalation route.

  8. Beryllium contamination and exposure monitoring in an inhalation laboratory setting.

    PubMed

    Muller, Caroline; Audusseau, Séverine; Salehi, Fariba; Truchon, Ginette; Chevalier, Gaston; Mazer, Bruce; Kennedy, Greg; Zayed, Joseph

    2010-02-01

    Beryllium (Be) is used in several forms: pure metal, beryllium oxide, and as an alloy with copper, aluminum, or nickel. Beryllium oxide, beryllium metal, and beryllium alloys are the main forms present in the workplace, with inhalation being the primary route of exposure. Cases of workers with sensitization or chronic beryllium disease challenge the scientific community for a better understanding of Be toxicity. Therefore, a toxicological inhalation study using a murine model was performed in our laboratory in order to identify the toxic effects related to different particle sizes and chemical forms of Be. This article attempts to provide information regarding the relative effectiveness of the environmental monitoring and exposure protection program that was enacted to protect staff (students and researchers) in this controlled animal beryllium inhalation exposure experiment. This includes specific attention to particle migration control through intensive housekeeping and systematic airborne and surface monitoring. Results show that the protective measures applied during this research have been effective. The highest airborne Be concentration in the laboratory was less than one-tenth of the Quebec OEL (occupational exposure limit) of 0.15 microg/m(3). Considering the protection factor of 10(3) of the powered air-purifying respirator used in this research, the average exposure level would be 0.03 x 10(- 4) microg/m(3), which is extremely low. Moreover, with the exception of one value, all average Be concentrations on surfaces were below the Quebec Standard guideline level of 3 microg/100 cm(2) for Be contamination. Finally, all beryllium lymphocyte proliferation tests for the staff were not higher than controls.

  9. Modelling of occupational exposure to inhalable nickel compounds.

    PubMed

    Kendzia, Benjamin; Pesch, Beate; Koppisch, Dorothea; Van Gelder, Rainer; Pitzke, Katrin; Zschiesche, Wolfgang; Behrens, Thomas; Weiss, Tobias; Siemiatycki, Jack; Lavoué, Jerome; Jöckel, Karl-Heinz; Stamm, Roger; Brüning, Thomas

    2017-01-18

    The aim of this study was to estimate average occupational exposure to inhalable nickel (Ni) using the German exposure database MEGA. This database contains 8052 personal measurements of Ni collected between 1990 and 2009 in adjunct with information on the measurement and workplace conditions. The median of all Ni concentrations was 9 μg/m(3) and the 95th percentile was 460 μg/m(3). We predicted geometric means (GMs) for welders and other occupations centered to 1999. Exposure to Ni in welders is strongly influenced by the welding process applied and the Ni content of the used welding materials. Welding with consumable electrodes of high Ni content (>30%) was associated with 10-fold higher concentrations compared with those with a low content (<5%). The highest exposure levels (GMs ≥20 μg/m(3)) were observed in gas metal and shielded metal arc welders using welding materials with high Ni content, in metal sprayers, grinders and forging-press operators, and in the manufacture of batteries and accumulators. The exposure profiles are useful for exposure assessment in epidemiologic studies as well as in industrial hygiene. Therefore, we recommend to collect additional exposure-specific information in addition to the job title in community-based studies when estimating the health risks of Ni exposure.Journal of Exposure Science and Environmental Epidemiology advance online publication, 18 January 2017; doi:10.1038/jes.2016.80.

  10. Inhalation Exposure Input Parameters for the Biosphere Model

    SciTech Connect

    M. Wasiolek

    2006-06-05

    This analysis is one of the technical reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), referred to in this report as the biosphere model. ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. ''Inhalation Exposure Input Parameters for the Biosphere Model'' is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the biosphere model is presented in Figure 1-1 (based on BSC 2006 [DIRS 176938]). This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and how this analysis report contributes to biosphere modeling. This analysis report defines and justifies values of atmospheric mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of the biosphere model to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception. This report is concerned primarily with the

  11. EXPOSURE TO ACROLEIN BY INHALATION CAUSES PLATELET ACTIVATION

    PubMed Central

    Sithu, Srinivas D; Srivastava, Sanjay; Siddiqui, Maqsood A; Vladykovskaya, Elena; Riggs, Daniel W; Conklin, Daniel J; Haberzettl, Petra; O’Toole, Timothy E; Bhatnagar, Aruni; D’Souza, Stanley E

    2010-01-01

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption. PMID:20678513

  12. Exposure to acrolein by inhalation causes platelet activation.

    PubMed

    Sithu, Srinivas D; Srivastava, Sanjay; Siddiqui, Maqsood A; Vladykovskaya, Elena; Riggs, Daniel W; Conklin, Daniel J; Haberzettl, Petra; O'Toole, Timothy E; Bhatnagar, Aruni; D'Souza, Stanley E

    2010-10-15

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5ppm for 6h) or sub-chronic (1ppm, 6h/day for 4days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

  13. Exposure to acrolein by inhalation causes platelet activation

    SciTech Connect

    Sithu, Srinivas D.; Srivastava, Sanjay; Siddiqui, Maqsood A.; Vladykovskaya, Elena; Riggs, Daniel W.; Conklin, Daniel J.; Haberzettl, Petra; O'Toole, Timothy E.; Bhatnagar, Aruni; D'Souza, Stanley E.

    2010-10-15

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

  14. Risk Assessment of Baby Powder Exposure through Inhalation.

    PubMed

    Moon, Min Chaul; Park, Jung Duck; Choi, Byung Soon; Park, So Young; Kim, Dong Won; Chung, Yong Hyun; Hisanaga, Naomi; Yu, Il Je

    2011-09-01

    This study was conducted to assess the exposure risk through inhalation to baby powder for babies and adults under simulated conditions. Baby powder was applied to a baby doll and the amount of baby powder consumed per application was estimated. The airborne exposure to baby powder during application was then evaluated by sampling the airborne baby powder near the breathing zones of both the baby doll and the person applying the powder (the applicator). The average amount of baby powder consumed was 100 mg/application, and the average exposure concentration of airborne baby powder for the applicator and baby doll was 0.00527 mg/m(3) (range 0.00157~0.01579 mg/m(3)) and 0.02207 mg/m(3) (range 0.00780~ 0.04173 mg/m(3)), respectively. When compared with the Occupational Exposure Limit of 2 mg/m(3) set by the Korean Ministry of Labor and the Threshold Limit Value (TLV) of 2 mg/m(3) set by the ACGIH (American Conference of Governmental Industrial Hygienists), the exposure concentrations were much lower. Next, the exposure to asbestos-containing baby powder was estimated and the exposure risk was assessed based on the lung asbestos contents in normal humans. As a result, the estimated lung asbestos content resulting from exposure to asbestos-containing baby powder was found to be much lower than that of a normal Korean with no asbestos-related occupational history.

  15. Risk Assessment of Baby Powder Exposure through Inhalation

    PubMed Central

    Moon, Min Chaul; Park, Jung Duck; Choi, Byung Soon; Park, So Young; Kim, Dong Won; Chung, Yong Hyun; Hisanaga, Naomi

    2011-01-01

    This study was conducted to assess the exposure risk through inhalation to baby powder for babies and adults under simulated conditions. Baby powder was applied to a baby doll and the amount of baby powder consumed per application was estimated. The airborne exposure to baby powder during application was then evaluated by sampling the airborne baby powder near the breathing zones of both the baby doll and the person applying the powder (the applicator). The average amount of baby powder consumed was 100 mg/application, and the average exposure concentration of airborne baby powder for the applicator and baby doll was 0.00527 mg/m3 (range 0.00157~0.01579 mg/m3) and 0.02207 mg/m3 (range 0.00780~ 0.04173 mg/m3), respectively. When compared with the Occupational Exposure Limit of 2 mg/m3 set by the Korean Ministry of Labor and the Threshold Limit Value (TLV) of 2 mg/m3 set by the ACGIH (American Conference of Governmental Industrial Hygienists), the exposure concentrations were much lower. Next, the exposure to asbestos-containing baby powder was estimated and the exposure risk was assessed based on the lung asbestos contents in normal humans. As a result, the estimated lung asbestos content resulting from exposure to asbestos-containing baby powder was found to be much lower than that of a normal Korean with no asbestos-related occupational history. PMID:24278563

  16. Metabolomic Changes in Murine Serum Following Inhalation Exposure to Gasoline and Diesel Engine Emissions

    PubMed Central

    Brower, Jeremy B.; Doyle-Eisele, Melanie; Moeller, Benjamin; Stirdivant, Steven; McDonald, Jacob D.; Campen, Matthew J.

    2016-01-01

    The adverse health effects of environmental exposure to gaseous and particulate components of vehicular emissions are a major concern among urban populations. A link has been established between respiratory exposure to vehicular emissions and the development of cardiovascular disease (CVD), but the mechanisms driving this interaction remain unknown. Chronic inhalation exposure to mixed vehicle emissions has been linked to CVD in animal models. This study evaluated the temporal effects of acute exposure to mixed vehicle emissions (MVE; mixed gasoline and diesel emissions) on potentially active metabolites in the serum of exposed mice. C57Bl/6 mice were exposed to a single 6 hour exposure to filtered air (FA) or MVE (100 or 300 µg/m3) by whole body inhalation. Immediately after and 18 hours after the end of the exposure period, animals were sacrificed for serum and tissue collection. Serum was analyzed for metabolites that were differentially present between treatment groups and time points. Changes in metabolite levels suggestive of increased oxidative stress (oxidized glutathione, cysteine disulfide, taurine), lipid peroxidation (13-HODE, 9-HODE), energy metabolism (lactate, glycerate, branched chain amino acid catabolites, butrylcarnitine, fatty acids), and inflammation (DiHOME, palmitoyl ethanolamide) were observed immediately after the end of exposure in the serum of animals exposed to MVE relative to those exposed to FA. By 18 hours post exposure, serum metabolite differences between animals exposed to MVE versus those exposed to FA were less pronounced. These findings highlight complex metabolomics alterations in the circulation following inhalation exposure to a common source of combustion emissions. PMID:27017952

  17. Metabolomic changes in murine serum following inhalation exposure to gasoline and diesel engine emissions.

    PubMed

    Brower, Jeremy B; Doyle-Eisele, Melanie; Moeller, Benjamin; Stirdivant, Steven; McDonald, Jacob D; Campen, Matthew J

    2016-04-01

    The adverse health effects of environmental exposure to gaseous and particulate components of vehicular emissions are a major concern among urban populations. A link has been established between respiratory exposure to vehicular emissions and the development of cardiovascular disease (CVD), but the mechanisms driving this interaction remain unknown. Chronic inhalation exposure to mixed vehicle emissions has been linked to CVD in animal models. This study evaluated the temporal effects of acute exposure to mixed vehicle emissions (MVE; mixed gasoline and diesel emissions) on potentially active metabolites in the serum of exposed mice. C57Bl/6 mice were exposed to a single 6-hour exposure to filtered air (FA) or MVE (100 or 300 μg/m(3)) by whole body inhalation. Immediately after and 18 hours after the end of the exposure period, animals were sacrificed for serum and tissue collection. Serum was analyzed for metabolites that were differentially present between treatment groups and time points. Changes in metabolite levels suggestive of increased oxidative stress (oxidized glutathione, cysteine disulfide, taurine), lipid peroxidation (13-HODE, 9-HODE), energy metabolism (lactate, glycerate, branched chain amino acid catabolites, butrylcarnitine, fatty acids), and inflammation (DiHOME, palmitoyl ethanolamide) were observed immediately after the end of exposure in the serum of animals exposed to MVE relative to those exposed to FA. By 18 hours post exposure, serum metabolite differences between animals exposed to MVE versus those exposed to FA were less pronounced. These findings highlight complex metabolomics alterations in the circulation following inhalation exposure to a common source of combustion emissions.

  18. Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals.

    PubMed

    Adkins, B; O'Connor, R W; Dement, J M

    1987-06-01

    Laboratory animals were exposed by inhalation for 2 hr/day (acute) or 6 hr/day (four consecutive days, repeated dose) to methyl isocyanate (MIC). Exposures were conducted in stainless steel and glass inhalation exposure chambers placed in stainless steel, wire mesh cages. MIC was delivered with nitrogen via stainless steel and Teflon supply lines. Chamber concentrations ranged from 0 to 60 ppm and were monitored continuously with infrared spectrophotometers to 1 ppm and at 2-hr intervals to 20 ppb with a high performance liquid chromatograph equipped with a fluorescence detector. Other operational parameters monitored on a continuous basis included chamber temperature (20-27 degrees C), relative humidity (31-64%), static (transmural) pressure (-0.3 in.), and flow (300-500 L/min). The computer-assistance system interfaced with the inhalation exposure laboratory is described in detail, including the analytical instrumentation calibration system used throughout this investigation.

  19. Metal induced inhalation exposure in urban population: A probabilistic approach

    NASA Astrophysics Data System (ADS)

    Widziewicz, Kamila; Loska, Krzysztof

    2016-03-01

    The paper was aimed at assessing the health risk in the populations of three Silesian cities: Bielsko-Biała, Częstochowa and Katowice exposed to the inhalation intake of cadmium, nickel and arsenic present in airborne particulate matter. In order to establish how the exposure parameters affects risk a probabilistic risk assessment framework was used. The risk model was based on the results of the annual measurements of As, Cd and Ni concentrations in PM2.5 and the sets of data on the concentrations of those elements in PM10 collected by the Voivodship Inspectorate of Environmental Protection over 2012-2013 period. The risk was calculated as an incremental lifetime risk of cancer (ILCR) in particular age groups (infants, children, adults) following Monte Carlo approach. With the aim of depicting the effect the variability of exposure parameters exerts on the risk, the initial parameters of the risk model: metals concentrations, its infiltration into indoor environment, exposure duration, exposure frequency, lung deposition efficiency, daily lung ventilation and body weight were modeled as random variables. The distribution of inhalation cancer risk due to exposure to ambient metals concentrations was LN (1.80 × 10-6 ± 2.89 × 10-6) and LN (6.17 × 10-7 ± 1.08 × 10-6) for PM2.5 and PM10-bound metals respectively and did not exceed the permissible limit of the acceptable risk. The highest probability of contracting cancer was observed for Katowice residents exposed to PM2.5 - LN (2.01 × 10-6 ± 3.24 × 10-6). Across the tested age groups adults were approximately one order of magnitude at higher risk compared to infants. Sensitivity analysis showed that exposure duration (ED) and body weight (BW) were the two variables, which contributed the most to the ILCR.

  20. Inhalation Exposure Input Parameters for the Biosphere Model

    SciTech Connect

    K. Rautenstrauch

    2004-09-10

    This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling, and the plan for development of the biosphere abstraction products for TSPA, as identified in the Technical Work Plan for Biosphere Modeling and Expert Support (BSC 2004 [DIRS 169573]). This analysis report defines and justifies values of mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of ERMYN to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception.

  1. Inhalants

    MedlinePlus

    ... Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids ... Cold Medicine Abuse Electronic Cigarettes (E-cigarettes) Fentanyl Hallucinogens Heroin Inhalants Marijuana Marijuana as Medicine MDMA (Ecstasy/ ...

  2. Inhalants

    MedlinePlus

    ... place a chemical- soaked rag in their mouth. Abusers may also inhale fumes from a balloon or ... by inhalants usually lasts just a few minutes, abusers often try to prolong it by continuing to ...

  3. Inhalants

    MedlinePlus

    ... Drug Facts Chat Day: Inhalants Drug Facts Chat Day: Inhalants Print Can you get high off of ... Cool Order Free Materials National Drugs & Alcohol Chat Day Newsletter Sign up to receive National Drug & Alcohol ...

  4. Distribution of 125Iricin in mice following aerosol inhalation exposure

    SciTech Connect

    Doebler, J.A.; Wiltshire, N.D.; Mayer, T.W.; Estep, J.E.; Moeller, R.B.

    1995-12-31

    Studies were conducted to examine the uptake and redistribution of 251Iricin from the lungs of mice following nose-only aerosol inhalation exposure. Radiolabelled contents were measured in lung and various extra-pulmonary tissues 15 min through 30 h following 10 min aerosol exposures. Pharmacokinetic analyses were performed on whole organ data obtained for lungs, stomach, liver and spleen. Radioactivity within the lungs, maximal at 15 min post-exposure, was eliminated in a biexponential fashion with a long Beta half-life (approx. 40 h). Large amounts of radiolabel were also found within the gastrointestinal tract. Radiolabel within the stomach exhibited an absorption phase and two-compartment elimination. Radiolabel content of many other tissues, including known accumulation sites for intravenously administered toxin, was significantly (p < 0,05) increased (relative to 15 min post-exposure) in association with the early elimination of radiolabel from the lungs, but levels in these tissues were very low and did not increase after 4 h post-exposure. The only exception was our sample of trachea, which showed delayed elevations in radiolabel (peak at 24 h); this pattern was attributable to the contained thyroid (not removed at necropsy) and its trapping of free (125I released) upon tissue 125Iricin degradation. The overall data indicate that ricin administered by aerosol inhalation is delivered to both respiratory and gastrointestinal tracts; however, it is not extensively transported from either tract to other potential target sites. Ricin delivered to the lungs is primarily sequestered within the lungs until degradation. Only small amounts of ricin delivered to the gastrointestinal tract are absorbed into the circulation.

  5. Inhalation exposure of children to fragrances present in scented toys.

    PubMed

    Masuck, I; Hutzler, C; Jann, O; Luch, A

    2011-12-01

    When utilized in the perfuming of children's toys, fragrances capable of inducing contact allergy in human skin may also become bioavailable to children via the inhalation route. The aim of this study was to determine the area-specific emission rates of 24 fragrances from a plasticized PVC reference material that was meant to mimic a real plastic toy. This material was introduced into an emission chamber for 28 days at handling conditions or at worst-case conditions. As a result, fragrances can be separated into three categories according to their emission rates ranging from 0.0041 to 16.2 mg/m² × h, i.e., highly volatile, semivolatile, and low-volatile compounds. Compounds of the first and second categories were monitored with decreasing emission rates. Substances of the third category were detected with increasing emission rates over time. Further, higher temperatures led to higher emission rates. The emission concentration of fragrances from four real scented toys varied between 1.10 and 107 μg/m³ at day 1 in the test chamber. Therefore, short-term inhalation exposure to fragrances originating from toys was in the range of 0.53-2700 ng/kg BW/d for the children of age 1 and older. Long-term exposure to these fragrances was calculated in the range of 2.2-220 ng/kg BW/d. Besides household products and cosmetics, fragrances can be found in toys for children. Some fragrances are known contact allergens in the skin, but there is a lack of information on their effects in the human respiratory tract. Here, we analyzed and categorized fragrances present in a plasticized PVC reference material according to their emission profiles and volatility. We also demonstrate that volatile fragrances are being emitted from real toys and thus may get inhaled under consumer conditions to different extents. © 2011 John Wiley & Sons A/S.

  6. Inhalation exposure to jet fuel (JP8) among U.S. Air Force personnel.

    PubMed

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

    2010-10-01

    As jet fuel is a common occupational exposure among military and civilian populations, this study was conducted to characterize jet fuel (JP8) exposure among active duty U.S. Air Force personnel. Personnel (n = 24) were divided a priori into high, moderate, and low exposure groups. Questionnaires and personal air samples (breathing zone) were collected from each worker over 3 consecutive days (72 worker-days) and analyzed for total hydrocarbons (THC), benzene, toluene, ethylbenzene, xylenes, and naphthalene. Air samples were collected from inside the fuel tank and analyzed for the same analytes. Linear mixed-effects models were used to evaluate the exposure data. Our results show that the correlation of THC (a measure of overall JP8 inhalation exposure) with all other analytes was moderate to strong in the a priori high and moderate exposure groups combined. Inhalation exposure to all analytes varied significantly by self-reported JP8 exposure (THC levels higher among workers reporting JP8 exposure), a priori exposure group (THC levels in high group > moderate group > low group), and more specific job task groupings (THC levels among workers in fuel systems hangar group > refueling maintenance group > fuel systems office group > fuel handling group > clinic group), with task groupings explaining the most between-worker variability. Among highly exposed workers, statistically significant job task-related predictors of inhalation exposure to THC indicated that increased time in the hangar, working close to the fuel tank (inside > less than 25 ft > greater than 25 ft), primary job (entrant > attendant/runner/fireguard > outside hangar), and performing various tasks near the fuel tank, such as searching for a leak, resulted in higher JP8 exposure. This study shows that while a priori exposure groups were useful in distinguishing JP8 exposure levels, job task-based categories should be considered in epidemiologic study designs to improve exposure classification. Finally

  7. Generation and characterization of gasoline engine exhaust inhalation exposure atmospheres.

    PubMed

    McDonald, Jacob D; Barr, Edward B; White, Richard K; Kracko, Dean; Chow, Judith C; Zielinska, Barbara; Grosjean, Eric

    2008-10-01

    Exposure atmospheres for a rodent inhalation toxicology study were generated from the exhaust of a 4.3-L gasoline engine coupled to a dynamometer and operated on an adapted California Unified Driving Cycle. Exposure levels were maintained at three different dilution rates. One chamber at the lowest dilution had particles removed by filtration. Each exposure atmosphere was characterized for particle mass, particle number, particle size distribution, and detailed chemical speciation. The majority of the mass in the exposure atmospheres was gaseous carbon monoxide, nitrogen oxides, and volatile organics, with small amounts of particle-bound carbon/ions and metals. The atmospheres varied according to the cycle, with the largest spikes in volatile organic and inorganic species shown during the "cold start" portion of the cycle. Ammonia present from the exhaust and rodents interacted with the gasoline exhaust to form secondary inorganic particles, and an increase in exhaust resulted in higher proportions of secondary inorganics as a portion of the total particle mass. Particle size had a median of 10-20 nm by number and approximately 150 nm by mass. Volatile organics matched the composition of the fuel, with large proportions of aliphatic and aromatic hydrocarbons coupled to low amounts of oxygenated organics. A new measurement technique revealed organics reacting with nitrogen oxides have likely resulted in measurement bias in previous studies of combustion emissions. Identified and measured particle organic species accounted for about 10% of total organic particle mass and were mostly aliphatic acids and polycyclic aromatic hydrocarbons.

  8. Inhalation exposure to fluorotelomer alcohols yield perfluorocarboxylates in human blood?

    PubMed

    Nilsson, Helena; Kärrman, Anna; Rotander, Anna; van Bavel, Bert; Lindström, Gunilla; Westberg, Håkan

    2010-10-01

    Levels of perfluorinated carboxylates (PFCAs) in different environmental and biological compartments have been known for some time, but the routes of exposure still remain unclear. The opinions are divergent whether the exposure to general populations occurs mainly indirect through precursor compounds or direct via PFCAs. Previous results showed elevated blood levels of PFCAs in ski wax technicians compared to a general population. The objective of this follow-up study was to determine concentrations of PFCAs, perfluorosulfonates (PFSAs), and fluorotelomer alcohols (FTOHs), precursor compounds that are known to degrade to PFCAs, in air collected in the breathing zone of ski wax technicians during work. We collected air samples by using ISOLUTE ENV+ cartridges connected to portable air pumps with an air flow of 2.0 L min(-1). PFCAs C5-C11 and PFSAs C4, C6, C8, and C10 were analyzed using LC-MS/MS and FTOHs 6:2, 8:2, and 10:2 with GC-MS/MS. The results show daily inhalation exposure of 8:2 FTOH in μg/m(3) air which is up to 800 times higher than levels of PFOA with individual levels ranging between 830-255000 ng/m(3) air. This suggests internal exposure of PFOA through biotransformation of 8:2 FTOH to PFOA and PFNA in humans.

  9. LOW-DOSE AIRBORNE ENDOTOXIN EXPOSURE ENHANCES BRONCHIAL RESPONSIVENESS TO INHALED ALLERGEN IN ATOPIC ASTHMATICS

    EPA Science Inventory

    Endotoxin exposure has been associated with both protection against development of TH2-immune responses during childhood and exacerbation of asthma in persons who already have allergic airway inflammation.1 Occupational and experimental inhalation exposures to endotoxin have been...

  10. LOW-DOSE AIRBORNE ENDOTOXIN EXPOSURE ENHANCES BRONCHIAL RESPONSIVENESS TO INHALED ALLERGEN IN ATOPIC ASTHMATICS

    EPA Science Inventory

    Endotoxin exposure has been associated with both protection against development of TH2-immune responses during childhood and exacerbation of asthma in persons who already have allergic airway inflammation.1 Occupational and experimental inhalation exposures to endotoxin have been...

  11. Prenatal Inhalation Exposure to Evaporative Condensates of Gasoline with 15% Ethanol and Evaluation of Sensory Function in Adult Rat Offspring

    EPA Science Inventory

    The introduction of ethanol-blended automotive fuels has raised concerns about potential health effects from inhalation exposure to the combination of ethanol and gasoline hydrocarbon vapors. Previously, we evaluated effects of prenatal inhalation exposure to 100% ethanol (E100) ...

  12. Prenatal Inhalation Exposure to Evaporative Condensates of Gasoline with 15% Ethanol and Evaluation of Sensory Function in Adult Rat Offspring

    EPA Science Inventory

    The introduction of ethanol-blended automotive fuels has raised concerns about potential health effects from inhalation exposure to the combination of ethanol and gasoline hydrocarbon vapors. Previously, we evaluated effects of prenatal inhalation exposure to 100% ethanol (E100) ...

  13. Exposure to inhalable flour dust in Canadian flour mills.

    PubMed

    Karpinski, Eva A

    2003-12-01

    In 1999, the American Conference of Governmental Industrial Hygienists (ACGIH(R)) proposed a Threshold Limit Value (TLV(R)) of 0.5 mg/m(3) for flour dust with a sensitization notation. The Labour Program of the Department of Human Resources Development Canada (HRDC), following notice of the intention to set a TLV, conducted a study of the levels of exposure to flour dust in flour mills across Canada to verify existing conditions, as well as to decide whether to adopt the proposed TLV or reference some other value. As part of the study, a relationship between flour dust concentrations obtained by using Institute of Occupational Medicine (IOM) samplers and closed-face 37-mm cassettes was examined and the literature on the health effects of exposure to flour dust was reviewed. A total of 104 millers, packers, sweepers, bakery mix operators, and others (mixed tasks) from 14 flour mills were sampled over an 8-hour work shift using IOM samplers. The results indicate that 101 employees (97.1%) were exposed to levels exceeding 0.5 mg/m(3), 66 employees (67.3%) to levels exceeding 5 mg/m(3), and 44 employees (42.3%) to levels exceeding 10 mg/m(3). For comparison purposes, flour dust measurements were also taken in a highly automated flour mill using state-of-the-art technology. The results suggest that even with the most up-to-date technology and proper cleaning operations in place, the flour milling industry may not be able to reduce the flour dust levels to below the TLV of 0.5 mg/m(3). According to the measurements of inhalable and total dust concentrations, the IOM sampler appears to be a more efficient collector of inhalable airborne particles up to 100 microm than the closed-face 37-mm cassette.

  14. Development and characterization of a resistance spot welding aerosol generator and inhalation exposure system.

    PubMed

    Afshari, Aliakbar; Zeidler-Erdely, Patti C; McKinney, Walter; Chen, Bean T; Jackson, Mark; Schwegler-Berry, Diane; Friend, Sherri; Cumpston, Amy; Cumpston, Jared L; Leonard, H Donny; Meighan, Terence G; Frazer, David G; Antonini, James M

    2014-10-01

    Limited information exists regarding the health risks associated with inhaling aerosols that are generated during resistance spot welding of metals treated with adhesives. Toxicology studies evaluating spot welding aerosols are non-existent. A resistance spot welding aerosol generator and inhalation exposure system was developed. The system was designed by directing strips of sheet metal that were treated with an adhesive to two electrodes of a spot welder. Spot welds were made at a specified distance from each other by a computer-controlled welding gun in a fume collection chamber. Different target aerosol concentrations were maintained within the exposure chamber during a 4-h exposure period. In addition, the exposure system was run in two modes, spark and no spark, which resulted in different chemical profiles and particle size distributions. Complex aerosols were produced that contained both metal particulates and volatile organic compounds (VOCs). Size distribution of the particles was multi-modal. The majority of particles were chain-like agglomerates of ultrafine primary particles. The submicron mode of agglomerated particles accounted for the largest portion of particles in terms of particle number. Metal expulsion during spot welding caused the formation of larger, more spherical particles (spatter). These spatter particles appeared in the micron size mode and accounted for the greatest amount of particles in terms of mass. With this system, it is possible to examine potential mechanisms by which spot welding aerosols can affect health, as well as assess which component of the aerosol may be responsible for adverse health outcomes.

  15. Exposure and dose assessment to particle components among an elderly population

    NASA Astrophysics Data System (ADS)

    Almeida-Silva, M.; Almeida, S. M.; Pegas, P. N.; Nunes, T.; Alves, C. A.; Wolterbeek, H. T.

    2015-02-01

    People spend the majority of their time indoors and the composition and toxicity of indoor particles is very complex and present significant differences comparing with outdoor aerosols. Consequently, ambient particles cannot represent a real exposure. The aim of this work was to determine the daily exposure and the daily inhaled dose to particle components of elders living in Elderly Care Centers. A questionnaire was applied to 193 institutionalized elders in order to achieve their daily time pattern and to define the micro-environments where PM10 and its components (carbonaceous components and trace elements) were assessed. Daily exposure was calculated by integrating the elder's time spend in each micro-environment and the concentration of the pollutants for the period of interest. This parameter, together with the inhalation rate and the standard body weight, were used to calculate the daily inhaled dose. PM10 daily exposure and daily inhaled dose ranged between 11 - 16 μg m-3 and 20 × 10-3 - 28 × 10-3 μg kg-1, respectively. This work not only allowed a fully quantification of the magnitude of the elders exposure, but also showed that the assessment of the integrated exposure to PM components is determinant to accomplish the dose inhaled by elders living in ECCs.

  16. Assessment of relative potential for Legionella species or surrogates inhalation exposure from common water uses.

    PubMed

    Hines, Stephanie A; Chappie, Daniel J; Lordo, Robert A; Miller, Brian D; Janke, Robert J; Lindquist, H Alan; Fox, Kim R; Ernst, Hiba S; Taft, Sarah C

    2014-06-01

    The Legionella species have been identified as important waterborne pathogens in terms of disease morbidity and mortality. Microbial exposure assessment is a tool that can be utilized to assess the potential of Legionella species inhalation exposure from common water uses. The screening-level exposure assessment presented in this paper developed emission factors to model aerosolization, quantitatively assessed inhalation exposures of aerosolized Legionella species or Legionella species surrogates while evaluating two generalized levels of assumed water concentrations, and developed a relative ranking of six common in-home uses of water for potential Legionella species inhalation exposure. Considerable variability in the calculated exposure dose was identified between the six identified exposure pathways, with the doses differing by over five orders of magnitude in each of the evaluated exposure scenarios. The assessment of exposure pathways that have been epidemiologically associated with legionellosis transmission (ultrasonic and cool mist humidifiers) produced higher estimated inhalation exposure doses than pathways where epidemiological evidence of transmission has been less strong (faucet and shower) or absent (toilets and therapy pool). With consideration of the large uncertainties inherent in the exposure assessment process used, a relative ranking of exposure pathways from highest to lowest exposure doses was produced using culture-based measurement data and the assumption of constant water concentration across exposure pathways. In this ranking, the ultrasonic and cool mist humidifier exposure pathways were estimated to produce the highest exposure doses, followed by the shower and faucet exposure pathways, and then the toilet and therapy pool exposure pathways.

  17. Cerium Oxide Nanoparticle Nose-Only Inhalation Exposures ...

    EPA Pesticide Factsheets

    There is a critical need to assess the health effects associated with exposure of commercially produced NPs across the size ranges reflective of that detected in the industrial sectors that are generating, as well as incorporating, NPs into products. Generation of stable and low concentrations of size-fractionated nanoscale aerosols in nose-only chambers can be difficult, and when the aerosol agglomerates during generation, the problems are significantly increased. One problem is that many nanoscale aerosol generators have higher aerosol output and/or airflow than can be accommodated by a nose-only inhalation chamber, requiring much of the generated aerosol to be diverted to exhaust. Another problem is that mixing vessels used to modulate the fluctuating output from aerosol generators can cause substantial wall losses, consuming much of the generated aerosol. Other available aerosol generation systems can produce nanoscale aerosols from nanoparticles (NPs), however these NPs are generated in real time and do not approximate the physical and chemical characteristics of NPs that are commercially produced exposing the workers and the public. The health effects associated with exposure to commercial NP production, which are more morphologically and size heterogeneous, is required for risk assessment. To overcome these problems, a low-consumption dry-particulate nanoscale aerosol generator was developed to deliver stable concentrations in the range of 10–5000 µg

  18. Protocols of radiocontaminant air monitoring for inhalation exposure estimates

    SciTech Connect

    Shinn, J.H.

    1995-09-01

    Monitoring the plutonium and americium particle emissions from soils contaminated during atmospheric nuclear testing or due to accidental releases is important for several reasons. First, it is important to quantify the extent of potential human exposure from inhalation of alpha-emitting particles, which is the major exposure pathway from transuranic radionuclides. Second, the information provided by resuspension monitoring is the basis of criteria that determine the target soil concentrations for management and cleanup of contaminated soil sites. There are other radioactive aerosols, such as the fission products (cesium and strontium) and neutron-activation products (europium isotopes), which may be resuspended and therefore necessary to monitor as well. This Standard Protocol (SP) provides the method used for radiocontaminant air monitoring by the Health and Ecological Assessment Division (formerly Environmental Sciences Division), Lawrence Livermore National Laboratory, as developed and tested at Nevada Test Site (NTS) and in the Marshall Islands. The objective of this SP is to document the applications and methods of monitoring of all the relevant variables. This protocol deals only with measuring air concentrations of radionuclides and total suspended particulates (TSP, or {open_quotes}dust{close_quotes}). A separate protocol presents the more difficult measurements required to determine transuranic aerosol emission rates, or {open_quotes}resuspension rate{close_quotes}.

  19. Bias in air sampling techniques used to measure inhalation exposure

    SciTech Connect

    Cohen, B.S.; Harley, N.H.; Lippmann, M.

    1984-03-01

    Factors have been evaluated which contribute to the lack of agreement between inhalation exposure estimates obtained by time-weighted averaging of samples taken with mini hi-volume samplers, and those measured by time integrating, low-volume, lapel mounted, personal monitors. Measurements made with real-time aerosol monitors on workers at a Be-Cu production furnace show that part of the discrepancy results from variability of the aerosol concentration within the breathing zone. Field studies of sampler inlet bias, the influences of the electrostatic fields around polystyrene filter holders, and resuspension of dust from work clothing, were done in three areas of a Be plant. No significant differences were found in Be air concentrations measured simultaneously by open and closed face cassettes, and mini hi-volume samplers mounted on a test stand. No significant influence on Be collection was detected between either positively or negatively charged monitors and charge neutralized control monitors. The effect of contaminated work clothing on dust collection by lapel mounted monitors is most important. Beryllium release from the fabrics affected air concentrations measured by fabric mounted monitors more than it affected concentrations measured by monitors positioned above the fabrics. The latter were placed 16 cm from the vertically mounted fabrics, to simulate the position of the nose or mouth. The authors conclude that dust resuspended from work clothing is the major source of the observed discrepancy between exposures estimated from lapel mounted samplers and time-weighted averages.

  20. Inhalants

    MedlinePlus

    ... lack of coordination, euphoria (a feeling of intense happiness), and dizziness. Some users also experience lightheadedness, hallucinations ( ... on the type of inhalant used, the harmful health effects will differ. The table below lists some ...

  1. Inhalants

    MedlinePlus

    ... Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription Drugs & Cold ... Notes Articles Adolescent Cigarette, Alcohol Use Declines as Marijuana Use Rises ( February 2013 ) Program Helps Troubled Boys ...

  2. Risk Communication in EPA's Controlled Inhalation Exposure Studies and in Support.

    PubMed

    Resnik, David

    2017-01-01

    On March 28, 2017, the National Academy of Sciences, Engineering, and Medicine (NASEM) released a much-anticipated report on the Environmental Protection Agency's controlled human inhalation exposure studies. This essay reviews the ethical controversies that led to the genesis of the report, summarizes its key findings, and comments on its approach to informing human subjects about the risks of inhalation exposure studies. NASEM's report makes a valuable contribution to our understanding of the scientific and ethical issues involved in conducting human inhalation exposure studies. Its definition of "reasonably foreseeable risks" provides useful guidance to investigators, research participants, and institutional review board members.

  3. Exposure indices for the National Children's Study: application to inhalation exposures in Queens County, NY

    PubMed Central

    Isukapalli, Sastry S.; Brinkerhoff, Christopher J.; Xu, Shu; Dellarco, Michael; Landrigan, Philip J.; Lioy, Paul J.; Georgopoulos, Panos G.

    2014-01-01

    Characterization of environmental exposures to population subgroups within the National Children's Study (NCS), or other large-scale human environmental health studies is essential for developing a high-quality data platform for subsequent investigations. A computational formulation utilizing the tiered exposure ranking framework is presented for calculating inhalation exposure indices (EIs) for population subgroups. This formulation employs a probabilistic approach and combines information from diverse, publicly available exposure-relevant databases and information on biological mechanisms, for ranking study locations or population subgroups with respect to potential for specific end point-related environmental exposures. These EIs capture and summarize, within a set of numerical values/ranges, complex distributions of potential exposures to multiple airborne contaminants. These estimates capture spatial and demographic variability within each study segment, and allow for the relative comparison of study locations based on different statistical metrics of exposures. The EI formulation was applied to characterize and rank segments within Queens County, NY, which is one of the Vanguard centers for the NCS. Inhalation EI estimates relevant to respiratory outcomes, and potentially to pregnancy outcomes (low birth weight and preterm birth rates) were calculated at the study segment level. Results indicate that there is substantial variability across the study segments in Queens County, NY, and within segments, and showed an exposure gradient across the study segments that can help guide and target environmental and personal exposure sampling efforts in this county. The results also serve as an example application of the EI for use in other exposure and outcome studies. PMID:23072768

  4. STOP-EXPOSURE STUDIES OF INHALED CHLORINE PROVIDE IMPORTANT INSIGHTS ON PATHOGENESIS

    EPA Science Inventory

    As part of a project to inform approaches for risk assessment of inhaled irritants of interest to homeland security, a set of acute (Peay et aI., SOT 2010) and subacute (George et aI., SOT 2010) studies of inhaled chlorine (CI2) in female F344 rats was performed. The exposure des...

  5. STOP-EXPOSURE STUDIES OF INHALED CHLORINE PROVIDE IMPORTANT INSIGHTS ON PATHOGENESIS

    EPA Science Inventory

    As part of a project to inform approaches for risk assessment of inhaled irritants of interest to homeland security, a set of acute (Peay et aI., SOT 2010) and subacute (George et aI., SOT 2010) studies of inhaled chlorine (CI2) in female F344 rats was performed. The exposure des...

  6. Exposure to inhaled THM: comparison of continuous and event-specific exposure assessment for epidemiologic purposes.

    PubMed

    Thiriat, N; Paulus, H; Le Bot, B; Glorennec, P

    2009-10-01

    Trihalomethanes (THMs) (chloroform, bromoform, dibromochloromethane, and bromodichloromethane) are the most abundant by-products of chlorination. People are exposed to THMs through ingestion, dermal contact and inhalation. The objective of this study was to compare two methods for assessing THM inhalation: a direct method with personal monitors assessing continuous exposure and an indirect one with microenvironmental sampling and collection of time-activity data during the main event exposures: bathing, showering and swimming. This comparison was conducted to help plan a future epidemiologic study of the effects of THMs on the upper airways of children. 30 children aged from 4 to 10 years were included. They wore a 3M 3520 organic vapor monitor for 7 days. We sampled air in their bathrooms (during baths or showers) and in the indoor swimming pools they visited and recorded their time-activity patterns. We used stainless steel tubes full of Tenax to collect air samples. All analyses were performed with Gas Chromatography and Mass Spectrometry (GC-MS). Chloroform was the THM with the highest concentrations in the air of both bathrooms and indoor swimming pools. Its continuous and event exposure measurements were significantly correlated (r(s)=0.69 p<0.001). Continuous exposures were higher than event exposures, suggesting that the event exposure method does not take into account some influential microenvironments. In an epidemiologic study, this might lead to random exposure misclassification, thus underestimation of the risk, and reduced statistical power. The continuous exposure method was difficult to implement because of its poor acceptability and the fragility of the personal monitors. These two points may also reduce the statistical power of an epidemiologic study. It would be useful to test the advantages and disadvantages of a second sample in the home or of modeling the baseline concentration of THM in the home to improve the event exposure method.

  7. Pulmonary response and transmigration of inorganic fibers by inhalation exposure.

    PubMed Central

    Lee, K. P.; Barras, C. E.; Griffith, F. D.; Waritz, R. S.

    1981-01-01

    Rats, hamsters, and guinea pigs were exposed by inhalation to different concentrations of potassium octatitanate fibers. Following 3 months of exposure, the animals were sacrificed between the 15th and 24th month. The exposed animals showed dose-related dust deposition and pulmonary fibrosis mainly in the respiratory bronchiolar region. Most short fibers (less than 5 micrograms) were phagocytized by alveolar macrophages, but long fibers (greater than 10 micrograms) were phagocytized by foreign body giant cells. Dust-laden macrophages (dust cells) entered into the lumen of bronchial lymphatic or pulmonary blood vessels. Numerous dust cells were transported from the lung to the tracheobronchial and mediastinal lymph nodes where some dust cells penetrated into the blood or lymphatic circulation. Massive direct cell migration of the mediastinal adipose tissue from the lymph nodes occurred occasionally. Dust-laden giant cells were found only occasionally in the liver, and there was widespread migration of the fibers into other vital organs and tissues without any significant responses. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 PMID:7212016

  8. Air concentrations of PBDEs on in-flight airplanes and assessment of flight crew inhalation exposure.

    PubMed

    Allen, Joseph G; Sumner, Ann Louise; Nishioka, Marcia G; Vallarino, Jose; Turner, Douglas J; Saltman, Hannah K; Spengler, John D

    2013-07-01

    To address the knowledge gaps regarding inhalation exposure of flight crew to polybrominated diphenyl ethers (PBDEs) on airplanes, we measured PBDE concentrations in air samples collected in the cabin air at cruising altitudes and used Bayesian Decision Analysis (BDA) to evaluate the likelihood of inhalation exposure to result in the average daily dose (ADD) of a member of the flight crew to exceed EPA Reference Doses (RfDs), accounting for all other aircraft and non-aircraft exposures. A total of 59 air samples were collected from different aircraft and analyzed for four PBDE congeners-BDE 47, 99, 100 and 209 (a subset were also analyzed for BDE 183). For congeners with a published RfD, high estimates of ADD were calculated for all non-aircraft exposure pathways and non-inhalation exposure onboard aircraft; inhalation exposure limits were then derived based on the difference between the RfD and ADDs for all other exposure pathways. The 95th percentile measured concentrations of PBDEs in aircraft air were <1% of the derived inhalation exposure limits. Likelihood probabilities of 95th percentile exposure concentrations >1% of the defined exposure limit were zero for all congeners with published RfDs.

  9. Inhalation and Dietary Exposure to PCBs in Urban and Rural Cohorts via Congener-Specific Measurements

    PubMed Central

    2015-01-01

    Polychlorinated biphenyls (PCBs) are a group of 209 persistent organic pollutants, whose documented carcinogenic, neurological, and respiratory toxicities are expansive and growing. However, PCB inhalation exposure assessments have been lacking for North American ambient conditions and lower-chlorinated congeners. We assessed congener-specific inhalation and dietary exposure for 78 adolescent children and their mothers (n = 68) in the Airborne Exposure to Semi-volatile Organic Pollutants (AESOP) Study. Congener-specific PCB inhalation exposure was modeled using 293 measurements of indoor and outdoor airborne PCB concentrations at homes and schools, analyzed via tandem quadrupole GS-MS/MS, combined with questionnaire data from the AESOP Study. Dietary exposure was modeled using Canadian Total Diet Survey PCB concentrations and National Health and Nutrition Examination Survey (NHANES) food ingestion rates. For ∑PCB, dietary exposure dominates. For individual lower-chlorinated congeners (e.g., PCBs 40+41+71, 52), inhalation exposure was as high as one-third of the total (dietary+inhalation) exposure. ∑PCB inhalation (geometric mean (SE)) was greater for urban mothers (7.1 (1.2) μg yr–1) and children (12.0 (1.2) μg yr–1) than for rural mothers (2.4 (0.4) μg yr–1) and children (8.9 (0.3) μg yr–1). Schools attended by AESOP Study children had higher indoor PCB concentrations than did homes, and account for the majority of children’s inhalation exposure. PMID:25510359

  10. Health effects of subchronic inhalation exposure to gasoline engine exhaust.

    PubMed

    Reed, M D; Barrett, E G; Campen, M J; Divine, K K; Gigliotti, A P; McDonald, J D; Seagrave, J C; Mauderly, J L; Seilkop, S K; Swenberg, J A

    2008-10-01

    Gasoline engine emissions are a ubiquitous source of exposure to complex mixtures of particulate matter (PM) and non-PM pollutants; yet their health hazards have received little study in comparison with those of diesel emissions. As a component of the National Environmental Respiratory Center (NERC) multipollutant research program, F344 and SHR rats and A/J, C57BL/6, and BALBc mice were exposed 6 h/day, 7 days/week for 1 week to 6 months to exhaust from 1996 General Motors 4.3-L engines burning national average fuel on a simulated urban operating cycle. Exposure groups included whole exhaust diluted 1:10, 1:15, or 1:90, filtered exhaust at the 1:10 dilution, or clean air controls. Evaluations included organ weight, histopathology, hematology, serum chemistry, bronchoalveolar lavage, cardiac electrophysiology, micronuclei in circulating cells, DNA methylation and oxidative injury, clearance of Pseudomonas aeruginosa from the lung, and development of respiratory allergic responses to ovalbumin. Among the 120 outcome variables, only 20 demonstrated significant exposure effects. Several statistically significant effects appeared isolated and were not supported by related variables. The most coherent and consistent effects were those related to increased red blood cells, interpreted as likely to have resulted from exposure to 13-107 ppm carbon monoxide. Other effects supported by multiple variables included mild lung irritation and depression of oxidant production by alveolar macrophages. The lowest exposure level caused no significant effects. Because only 6 of the 20 significant effects appeared to be substantially reversed by PM filtration, the majority of effects were apparently caused by non-PM components of exhaust.

  11. Dose-Response Modeling for Inhalational Anthrax in Rabbits Following Single or Multiple Exposures.

    PubMed

    Gutting, Bradford W; Rukhin, Andrey; Marchette, David; Mackie, Ryan S; Thran, Brandolyn

    2016-11-01

    There is a need to advance our ability to characterize the risk of inhalational anthrax following a low-dose exposure. The exposure scenario most often considered is a single exposure that occurs during an attack. However, long-term daily low-dose exposures also represent a realistic exposure scenario, such as what may be encountered by people occupying areas for longer periods. Given this, the objective of the current work was to model two rabbit inhalational anthrax dose-response data sets. One data set was from single exposures to aerosolized Bacillus anthracis Ames spores. The second data set exposed rabbits repeatedly to aerosols of B. anthracis Ames spores. For the multiple exposure data the cumulative dose (i.e., the sum of the individual daily doses) was used for the model. Lethality was the response for both. Modeling was performed using Benchmark Dose Software evaluating six models: logprobit, loglogistic, Weibull, exponential, gamma, and dichotomous-Hill. All models produced acceptable fits to either data set. The exponential model was identified as the best fitting model for both data sets. Statistical tests suggested there was no significant difference between the single exposure exponential model results and the multiple exposure exponential model results, which suggests the risk of disease is similar between the two data sets. The dose expected to cause 10% lethality was 15,600 inhaled spores and 18,200 inhaled spores for the single exposure and multiple exposure exponential dose-response model, respectively, and the 95% lower confidence intervals were 9,800 inhaled spores and 9,200 inhaled spores, respectively.

  12. Developmental neurotoxicity of methanol exposure by inhalation in rats. Research report, June 1990-June 1994

    SciTech Connect

    Weiss, B.; Stern, S.; Soderholm, S.C.; Cox, C.; Sharma, A.

    1996-04-01

    The possibility of widespread methanol exposure via inhalation stemming from its adoption as an automotive fuel or fuel component arouses concern about the potential vulnerability of the fetal brain. This project was designed to help address such concerns by studying the behavior of neonate and adult Long-Evans hooded rats following perinatal exposure to methanol vapor at 4,500 ppm for six hours daily beginning on gestation day 6 with both dams and pups then being exposed through postnatal day (PND) 21. Blood methanol concentrations of the dams, measured immediately following a six-hour exposure, were approximately 500 to 800 micrograms/milliliter. Average blood methanol concentrations in the pups were about twice those of the dams. Neurotoxicity was assessed by behavioral tests used previously to reveal adverse effects following developmental exposures to ethanol, cocaine, heavy metals, and other agents. Exposure of neonates to methanol did not affect suckling latency and attachment on PND 5, or performance on the conditioned olfactory aversion test on PND 10. Exposure to methanol did alter performances in the motor activity tests. Methanol-exposed neonates were less active on PND 18, but more active on PND 25 than the equivalent control-group pups. Schedule-controlled running in adults displayed a complex interaction with treatment. Changes in performance over the course of training differed between males and females depending on exposure to methanol. The results of the complex stochastic reinforcement schedule revealed behavioral differences due to methanol exposure in adults that were relatively subtle in nature and appeared after a new pattern of contingencies was introduced.

  13. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 1 and 3 Months Post Exposure**

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rat...

  14. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 1 and 3 Months Post Exposure**

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rat...

  15. Inhalation exposure and risk from mobile source air toxics in future years.

    PubMed

    Cook, Richard; Strum, Madeleine; Touma, Jawad S; Palma, Ted; Thurman, James; Ensley, Darrell; Smith, Roy

    2007-01-01

    Modeling of inhalation exposure and risks resulting from exposure to mobile source air toxics can be used to evaluate impacts of reductions from control programs on overall risk, as well as changes in relative contributions of different source sectors to risk, changes in contributions of different pollutants to overall risk, and changes in geographic distributions of risk. Such analysis is useful in setting regulatory priorities, and informing the decision-making process. In this paper, we have conducted national-scale air quality, exposure, and risk modeling for the US in the years 2015, 2020, and 2030, using similar tools and methods as the 1999 National-Scale Air Toxics Assessment. Our results suggest that US Environmental Protection Agency emission control programs will substantially reduce average inhalation cancer risks and potential noncancer health risks from exposure to mobile source air toxics. However, cancer risk and noncancer hazard due to inhalation of air toxics will continue to be a public health concern.

  16. An in vitro approach to assess the toxicity of inhaled tobacco smoke components: nicotine, cadmium, formaldehyde and urethane.

    PubMed

    Balharry, Dominique; Sexton, Keith; BéruBé, Kelly A

    2008-02-03

    One of the first lines of defence to inhaled toxins is the barrier formed by the tracheobronchial epithelium, making this the ideal region for studying the toxicity of inhaled substances. This study utilises a highly differentiated, three-dimensional, in vitro model of human upper respiratory tract epithelium (EpiAirway-100) to measure the acute toxicological responses to well-characterised tobacco smoke components. To determine the suitability of this model for screening inhaled toxicants, the EpiAirway tissue model (ETM) was treated apically with tobacco smoke components (nicotine, formaldehyde, cadmium, urethane) which are known to induce a variety of toxic effects (e.g. cytotoxic, thrombogenic, carcinogenic). A range of concentrations were used to model different mechanisms and severity of toxicity which were then compared to known in vivo responses. Similar trends in stress response occurred, with distinct alterations to the tissue in response to all four toxins. At high concentrations, cell viability decreased and tight junctions were degraded, but at sub-toxic concentrations epithelial resistance (indicating tissue integrity) increased 20-60% from control. This peak in resistance coincided with an increase in secreted protein levels, elevated cytokine release and goblet cell hyperplasia and hypertrophy. In conclusion, acute exposure to tobacco smoke components induces measurable toxic responses within human respiratory epithelium. Sub-toxic concentrations appear to illicit a protective response by increasing mucus secretion and mediating immune responses via cytokine release. These responses are comparable to human in vivo responses, indicating potential for the ETM as a tool for screening the toxicity of inhaled compounds.

  17. Gestational Exposure to Inhaled Vapors of Ethanol and Gasoline-Ethanol Blends in Rats

    EPA Science Inventory

    The US automotive fleet is powered primarily by gasoline-ethanol fuel blends containing up to 10% ethanol (ElO). Uncertainties regarding the health risks associated with exposure to ElO prompted assessment of the effects of prenatal exposure to inhaled vapors of gasoline-ethanol ...

  18. SUBCHRONIC INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE AND AMOSITE ASBESTOS

    EPA Science Inventory

    Exposure to Libby amphibole (LA) is associated with significant increases in asbestosis, lung cancer, and mesothelioma. To support biological potency assessment and dosimetry model development, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted...

  19. Gestational Exposure to Inhaled Vapors of Ethanol and Gasoline-Ethanol Blends in Rats

    EPA Science Inventory

    The US automotive fleet is powered primarily by gasoline-ethanol fuel blends containing up to 10% ethanol (ElO). Uncertainties regarding the health risks associated with exposure to ElO prompted assessment of the effects of prenatal exposure to inhaled vapors of gasoline-ethanol ...

  20. SUBCHRONIC INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE AND AMOSITE ASBESTOS

    EPA Science Inventory

    Exposure to Libby amphibole (LA) is associated with significant increases in asbestosis, lung cancer, and mesothelioma. To support biological potency assessment and dosimetry model development, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted...

  1. Inhalation exposure systems for the development of rodent models of sulfur mustard-induced pulmonary injury.

    PubMed

    Weber, Waylon M; Kracko, Dean A; Lehman, Mericka R; Irvin, Clinton M; Blair, Lee F; White, Richard K; Benson, Janet M; Grotendorst, Gary R; Cheng, Yung-Sung; McDonald, Jacob D

    2010-01-01

    Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg x min/m(3) resulted in homogeneous lung injury with no nasal degeneration.

  2. Inhalation Exposure Systems for the Development of Rodent Models of Sulfur Mustard-Induced Pulmonary Injury

    PubMed Central

    Weber, Waylon M.; Kracko, Dean A.; Lehman, Mericka R.; Irvin, Clinton M.; Blair, Lee F.; White, Richard K.; Benson, Janet M.; Grotendorst, Gary R.; Cheng, Yung-Sung; McDonald, Jacob D.

    2011-01-01

    Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg · min/m3 resulted in homogeneous lung injury with no nasal degeneration. PMID:20025432

  3. Biodistribution of inhaled metal oxide nanoparticles mimicking occupational exposure: a preliminary investigation using enhanced darkfield microscopy.

    PubMed

    Guttenberg, Marissa; Bezerra, Leonardo; Neu-Baker, Nicole M; Del Pilar Sosa Idelchik, María; Elder, Alison; Oberdörster, Günter; Brenner, Sara A

    2016-10-01

    Inhalation exposure to engineered nanomaterials (ENMs) may result in adverse pulmonary and/or systemic health effects. In this study, enhanced darkfield microscopy (EDFM) was used as a novel approach to visualizing industrial metal oxide nanoparticles (NPs) (silica, ceria, or alumina) in multiple tissue types following inhalation in rats mimicking occupational exposures. Advantages of EDFM over electron microscopy (EM) include reduced cost, time, and ease of sample preparation and operation. Following 4-6 hour inhalation exposures at three concentrations (3.5-34.0 mg/m(3) ), lungs and secondary organs were harvested at 24 hours or 7 days post-exposure and prepared for brightfield (BF) microscopy and EDFM. NPs were visualized within the lung and associated lymphatic tissues and in major organs of excretion (liver, spleen, kidney). EDFM also revealed NPs within pulmonary blood vessels and localization within specific regions of toxicological relevance in liver and kidney, indicating pathways of excretion. Results demonstrate the utility of EDFM for rapid direct visualization of NPs in various tissue types and suggest the potential for metal oxide NPs to distribute to secondary tissues following inhalation exposure. Confirmation of the composition, distribution, and relative abundance of inhaled NPs will be pursued by combining EDFM with hyperspectral imaging (HSI) and mapping.

  4. Nonrespirability of Carbon Fibers in Rats from Repeated Inhalation Exposure

    DTIC Science & Technology

    1990-09-01

    They thank Erica R. Riley, Physics Division, CRDEC, for her SEM analysis of the generated material and Dr. Lucas Brennecke, Pathology Associates, for... Ballantyne , B., and Clary, J.J., "Subchronic Inhalation Toxicology of Carbon Fibers," J., Vol. 28, pp 373-376 (1986). 15. Guide for th,’ Care and Use

  5. Arsine toxicity is induced by inhalation but not by percutaneous exposure in hairless mice.

    PubMed

    Kato, Koichi; Yamanaka, Kenzo; Shimoda, Yasuyo; Yamano, Yuko; Nagano, Kasuke; Hata, Akihisa; Endo, Yoko; Tachikawa, Mariko; Endo, Ginji

    2014-04-01

    Arsine (AsH₃) is used in many industries, but there is insufficient knowledge about the potential for percutaneous absorption. In order to examine possible percutaneous absorption of arsine, we conducted inhalation studies. Arsine was generated by reducing arsenic trioxide with NaBH₄. Male 5-week-old Hos:HR-1 hairless mice were subjected to a single percutaneous exposure or whole-body inhalation exposure of ca. 300 ppm arsine for 5 min. The examination was performed 0-6 hr after the exposure. Total arsenic in whole blood and hematocrit (Ht) values were measured. Generation of an arsenic-hemoglobin (As-Hb) adduct in the blood was detected using high-performance liquid chromatography with an inductively coupled plasma mass spectrometer (HPLC-ICP-MS). Ht values in the inhalation group significantly decreased after 3 hr, but those in the percutaneous exposure group did not. Total arsenic in the inhalation group was 9.0-14.2 mg/l, which was significantly higher than that in the percutaneous group. The As-Hb adduct was detected only in mice in the inhalation group. Histopathological changes were noted only in the inhalation group, with marked deposition of eosinophilic globules in the proximal convoluted tubules of the kidneys, the Kupffer cells of the liver, and the red pulp in the spleen, but not in the lungs. Immunohistochemically, these eosinophilic globules were stained positively by hemoglobin (Hb) antibody. In the present study, arsine-induced hemolysis and deposition of Hb occurred in the kidney via the inhalation route but not via percutaneous exposure. The presence of As-Hb adduct may be a useful indicator for confirming arsine poisoning.

  6. Acrolein Inhalation Alters Myocardial Synchrony and Performance at and Below Exposure Concentrations that Cause Ventilatory Responses.

    PubMed

    Thompson, Leslie C; Ledbetter, Allen D; Haykal-Coates, Najwa; Cascio, Wayne E; Hazari, Mehdi S; Farraj, Aimen K

    2017-04-01

    Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we sought to better define the immediate and delayed functional cardiac effects of acrolein inhalation in vivo. We hypothesized that acrolein inhalation would increase markers of cardiac mechanical dysfunction, i.e., myocardial dyssynchrony and performance index in mice. Male C57Bl/6J mice were exposed to filtered air (FA) or acrolein (0.3 or 3.0 ppm) for 3 h in whole-body plethysmography chambers (n = 6). Echocardiographic analyses were performed 1 day before exposure and at 1 and 24 h post-exposure. Speckle tracking echocardiography revealed that circumferential strain delay (i.e., dyssynchrony) was increased at 1 and 24 h following exposure to 3.0 ppm, but not 0.3 ppm, when compared to pre-exposure and/or FA exposure. Pulsed wave Doppler of transmitral blood flow revealed that acrolein exposure at 0.3 ppm, but not 3.0 ppm, increased the Tei index of myocardial performance (i.e., decreased global heart performance) at 1 and 24 h post-exposure compared to pre-exposure and/or FA exposure. We conclude that short-term inhalation of acrolein can acutely modify cardiac function in vivo and that echocardiographic evaluation of myocardial synchrony and performance following exposure to other inhaled pollutants could provide broader insight into the health effects of air pollution.

  7. Inhalation of an essential metal: development of reference exposure levels for manganese.

    PubMed

    Winder, Bruce S; Salmon, Andrew G; Marty, Melanie A

    2010-01-01

    Exposures to high levels of manganese by ingestion or inhalation can damage the central nervous system. However, the capacity of environmental manganese to cause neurotoxicity is of most concern following inhalation exposure. Reference exposure levels (RELs) are values developed by California EPA's Office of Environmental Health Hazard Assessment (OEHHA) to protect the general public from periodic and continual exposures to airborne toxicants. The recently revised guidelines for the development of noncancer RELs encourage the use of benchmark dose methodology where appropriate, and explicitly address the potential susceptibilities associated with early-life exposures (OEHHA, 2008). This paper describes the application of those guidelines to the derivation of RELs to protect the general public from routine 8h and chronic exposures to airborne manganese. The data were amenable to benchmark analysis and the RELs derived reflect the mounting evidence that children represent a population that is differentially susceptible to manganese toxicity. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Effect of ozone exposure on airway responses to inhaled allergen in asthmatic subjects.

    PubMed

    Chen, Lisa L; Tager, Ira B; Peden, David B; Christian, Dorothy L; Ferrando, Ronald E; Welch, Barbara S; Balmes, John R

    2004-06-01

    Controlled human exposure studies have produced conflicting results regarding the effect of ozone on the early bronchoconstrictor response to inhaled allergen in specifically sensitized asthmatic subjects. Spirometric parameters do not necessarily reflect the airway inflammatory effects of inhaled ozone or allergen. This study was designed to investigate whether exposure to ozone enhances the late airway inflammatory response, as well as the early bronchoconstrictor response, to inhaled house dust mite allergen in sensitized asthmatic subjects. Randomized, counter-balanced, cross-over study. Human exposure laboratory. Fourteen subjects were exposed to 0.2 ppm O(3) or filtered air, on separate days, for 1 h during exercise. After each exposure, the subjects were challenged with doubling doses of Dermatophagoides farinae (DF) allergen (provocative concentration of DF causing a 15% decrease in FEV(1) [PC(15)]). At 6 h after allergen challenge, bronchoscopy with BAL, proximal airway lavage (PAL), and endobronchial biopsy were performed. The second exposure/allergen challenge/bronchoscopy sequence was performed at least 4 weeks after the first sequence. No significant difference in cellular or biochemical markers of the late inflammatory response after allergen was found between the ozone and air exposures (although a trend toward increased neutrophils was noted after ozone exposure in the PAL fluid, p = 0.06). For the group as a whole, no significant difference in PC(15) was demonstrated after ozone exposure compared to air exposure. However, subjects with the greatest ozone-induced decrements in FEV(1) tended to have lower PC(15) values after ozone exposure. Exposure to a relatively low-level concentration of ozone does not enhance the late inflammatory or early bronchoconstrictor response to inhaled antigen in most allergic asthmatic subjects. Our results do suggest, however, that a subgroup of asthmatics may acquire increased sensitivity to aeroallergens after

  9. Exposure to inhaled isobutyl nitrite reduces T cell-dependent responsiveness

    SciTech Connect

    Soderberg, L.S.F.; Barnett, J.B. )

    1991-03-11

    Isobutyl nitrite is a drug of abuse popular among male homosexuals and among adolescents. In order to approximate the nitrite exposures of inhalant abusers, mice were treated with 900 ppm isobutyl nitrite in an inhalation chamber for 45 min per day for 14 days. At 72 hr after the last exposure, mice were assayed for immune competence. Under these conditions, mice gained only half the weight of mice exposed to air. The spleens of nitrite exposed mice weighed 15% less and had 24% fewer cells per spleen than controls. Adjusted for equal cell numbers, T cell mitogenic and allogeneic proliferative responses were significantly reduce by 33% and 47%, respectively. Unstimulated spleen cells had elevated levels of IL-2 transcription following exposure to isobutyl nitrite suggesting that nitrite inhalation caused a nonspecific induction of T cells. In contrast, B cell proliferative responses to LPS were unaltered. Exposure to the nitrite reduced the frequency of T-dependent antibody plaque-forming cells (PFC) by 63% and the total number of reduced by 60% after as few as five daily exposures to isobutyl nitrite. Therefore, the data suggest that habitual inhalation of isobutyl nitrite impairs immune competence and that toxicity appears to be directed toward T cell functions.

  10. Respiratory exposure to components of water-miscible metalworking fluids.

    PubMed

    Suuronen, Katri; Henriks-Eckerman, Maj-Len; Riala, Riitta; Tuomi, Timo

    2008-10-01

    Water-miscible metalworking fluids (MWFs) are capable of causing respiratory symptoms and diseases. Recently, much emphasis has been put on developing new methods for assessing respiratory exposure to MWF emulsions. The air concentrations of ingredients and contaminants of MWF and inhalable dust were measured in 10 metal workshops in southern Finland. Oil mist was determined by infra red spectroscopy analysis after tetrachloroethylene extraction from the filter. Aldehydes were collected on Sep-Pak chemosorbents and analysed by liquid chromatography. Volatile organic compounds (VOCs) were collected on Tenax adsorbents and analysed by gas chromatography with mass spectrometric detection after thermal desorption. Endotoxins were collected on glass fibre filter and analysed by enzyme-based spectrophotometry, and viable microbes were collected on polycarbonate filter and cultured. Inhalable dust was collected on cellulose acetate filter and quantified gravimetrically. Associations between the different exposures were calculated with Spearman's correlations. The mean concentration of oil mist was 0.14 (range <0.010-0.60) mg m(-3). The mean total concentration of aldehydes was 0.095 (0.026-0.38) mg m(-3), with formaldehyde as the main aldehyde. The average total concentration of VOC was 1.9 (0.34-4.5) mg m(-3) consisting mainly of high-boiling aliphatic hydrocarbons. Several potential sensitizing chemicals such as terpenes were found in small quantities. The concentration of microbial contaminants was low. All the measured air concentrations were below the Finnish occupational exposure limits. The exposure in machine shops was quantitatively dominated by volatile compounds. Additional measurements of MWF components such as aldehydes, alkanolamines and VOCs are needed to get more information on the chemical composition of workshops' air. New air cleaning methods should be introduced, as oil mist separators are insufficient to clean the air of small molecular impurities.

  11. ASSESSING THE HEALTH EFFECTS AND RISKS ASSOCIATED WITH CHILDREN’S INHALATION EXPOSURES – ASTHMA AND ALLERGY

    EPA Science Inventory

    Adults and children may have different reactions to inhalation exposures, which may be the result of differences in inhaled or target tissue doses following similar exposures, and/or due to growth and development of the lung which continues postnatally in distinct stages. Because...

  12. ASSESSING THE HEALTH EFFECTS AND RISKS ASSOCIATED WITH CHILDREN’S INHALATION EXPOSURES – ASTHMA AND ALLERGY

    EPA Science Inventory

    Adults and children may have different reactions to inhalation exposures, which may be the result of differences in inhaled or target tissue doses following similar exposures, and/or due to growth and development of the lung which continues postnatally in distinct stages. Because...

  13. Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

    PubMed Central

    Barnewall, Roy E.; Comer, Jason E.; Miller, Brian D.; Gutting, Bradford W.; Wolfe, Daniel N.; Director-Myska, Alison E.; Nichols, Tonya L.; Taft, Sarah C.

    2012-01-01

    Repeated low-level exposures to biological agents could occur before or after the remediation of an environmental release. This is especially true for persistent agents such as B. anthracis spores, the causative agent of anthrax. Studies were conducted to examine aerosol methods needed for consistent daily low aerosol concentrations to deliver a low-dose (less than 106 colony forming units (CFU) of B. anthracis spores) and included a pilot feasibility characterization study, acute exposure study, and a multiple 15 day exposure study. This manuscript focuses on the state-of-the-science aerosol methodologies used to generate and aerosolize consistent daily low aerosol concentrations and resultant low inhalation doses to rabbits. The pilot feasibility characterization study determined that the aerosol system was consistent and capable of producing very low aerosol concentrations. In the acute, single day exposure experiment, targeted inhaled doses of 1 × 102, 1 × 103, 1 × 104, and 1 × 105 CFU were used. In the multiple daily exposure experiment, rabbits were exposed multiple days to targeted inhaled doses of 1 × 102, 1 × 103, and 1 × 104 CFU. In all studies, targeted inhaled doses remained consistent from rabbit-to-rabbit and day-to-day. The aerosol system produced aerosolized spores within the optimal mass median aerodynamic diameter particle size range to reach deep lung alveoli. Consistency of the inhaled dose was aided by monitoring and recording respiratory parameters during the exposure with real-time plethysmography. Overall, the presented results show that the animal aerosol system was stable and highly reproducible between different studies and over multiple exposure days. PMID:22919662

  14. Inhalable dust measurements as a first approach to assessing occupational exposure in the pharmaceutical industry.

    PubMed

    Champmartin, C; Clerc, F

    2014-01-01

    Occupational exposure to active ingredients in the pharmaceutical industry has been the subject of very few published studies. Nevertheless, operations involving active powdered drugs or dusty operations potentially lead to operator exposure. The aim of this study was to collect occupational exposure data in the pharmaceutical industry for production processes involving powdered active ingredients. While the possibility of assessing drug exposure from dust level is examined, this article focuses on inhalable dust exposure, without taking chemical risk into account. A total of 377 atmospheric (ambient and personal) samples were collected in nine drug production sites (pharmaceutical companies and contract manufacturing organizations) and the dust levels were assessed. For each sample, relevant contextual information was collected. A wide range of results was observed, both site- and operation-dependent. Exposure to inhalable dust levels varied from 0.01 mg/m(3)to 135 mg/m(3). Though restricted to dust exposure, the study highlighted some potentially critical situations or operations, in particular manual tasks (loading, unloading, mechanical actions) performed in open systems. Simple preventive measures such as ventilation, containment, and minimization of manual handling should reduce dust emissions and workers' exposure to inhalable dust.

  15. Characterization of exogeous particale content: Of canine tissue urban vs. rural inhalation exposures

    NASA Astrophysics Data System (ADS)

    Kennedy, Jamell

    Exogenous zinc (Zn) is emerging as a serious contaminant in the environment. Yearly deposition of zinc particles line heavily traveled inner city roadways and less traveled rural roadways. Particle size for zinc ranges from approximately PM10 to PM 2.5 microm or less. These fine particles contain microscopic solids or liquids that can cause serious health problems. PM10 are considered to be "thoracic" sized particles, with the mass fraction of inhaled particles penetrating beyond the larynx. Whereas, PM2.5 are considered to be "respirable" sized particles, with the mass fraction of inhaled particles penetrating to the unciliated airways. Exogenous zinc can be used as a quantifiable marker to contrast the differences in exposures in canines originating from urban and rural environments. These exposures are analyzed using a scanning electron microscope with energy dispersive X-ray spectrometry, and usage of a morphometric point counting method for a physical count and categorization of composition of inhaled retained particle content.

  16. 40 CFR 79.61 - Vehicle emissions inhalation exposure guideline.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ensure the controlled generation of the exposure atmosphere, the adequate dilution of the test emissions... systems selected to meet criteria for a given exposure study. (1) Emissions generation. Emissions shall be... delivery system is the means used to transport the emissions from the generation system to the exposure...

  17. 40 CFR 79.61 - Vehicle emissions inhalation exposure guideline.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ensure the controlled generation of the exposure atmosphere, the adequate dilution of the test emissions... systems selected to meet criteria for a given exposure study. (1) Emissions generation. Emissions shall be... delivery system is the means used to transport the emissions from the generation system to the exposure...

  18. 40 CFR 79.61 - Vehicle emissions inhalation exposure guideline.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ensure the controlled generation of the exposure atmosphere, the adequate dilution of the test emissions... systems selected to meet criteria for a given exposure study. (1) Emissions generation. Emissions shall be... delivery system is the means used to transport the emissions from the generation system to the exposure...

  19. The contributions to solvent uptake by skin and inhalation exposure

    SciTech Connect

    Daniell, W.; Stebbins, A.; Kalman, D.; O'Donnell, J.F.; Horstman, S.W. )

    1992-02-01

    Solvent exposures were assessed among 97 auto body repair workers in order to determine whether skin contact represented a significant route of exposure. Each subject's cumulative skin exposure was ranked categorically based on simple observation: 49 none, 33 incidental or low, and 15 moderate or high. The median time-weighted average air exposure to solvents was 8.4% of the American Conference of Governmental Industrial Hygienists (ACGIH) combined solvent threshold limit value (TLV) with a range of 0-62% TLV, including toluene (median 4 ppm) and xylenes (median 0.9 ppm). Urine methyl hippuric acids (MHAs, metabolites of xylenes) were low compared to the ACGIH biological exposure index (BEI) with a median of 2% and a range of 0-12% BEI but were strongly correlated with both the level of airborne xylenes and skin exposure when considered simultaneously by using analysis of covariance (R = 0.91, p less than 0.0001). MHA excretion attributable to skin exposure for 15 min or more generally was comparable to or greater than that from associated air exposure over the full work shift. This study had limited ability to assess quantitatively the contributions of toluene exposures, but there was evidence that skin exposures also contributed significantly to toluene absorption. Air sampling will substantially underestimate a worker's total solvent dose in the setting of moderate or high skin exposure. Simple observation was effective in identifying workers in this sample who appeared to have sufficient skin exposure to produce a measurable increase in solvent uptake.

  20. Modeling accumulations of particles in lung during chronic inhalation exposures that lead to impaired clearance

    SciTech Connect

    Wolff, R.K.; Griffith, W.C. Jr.; Cuddihy, R.G.; Snipes, M.B.; Henderson, R.F.; Mauderly, J.L.; McClellan, R.O. )

    1989-01-01

    Chronic inhalation of insoluble particles of low toxicity that produce substantial lung burdens of particles, or inhalation of particles that are highly toxic to the lung, can impair clearance. This report describes model calculations of accumulations in lung of inhaled low-toxicity diesel exhaust soot and high-toxicity Ga2O3 particles. Lung burdens of diesel soot were measured periodically during a 24-mo exposure to inhaled diesel exhaust at soot concentrations of 0, 0.35, 3.5, and 7 mg m-3, 7 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y after a 4-wk exposure to 23 mg Ga2O3 m-3, 2 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y both studies using inhaled radiolabeled tracer particles. Simulation models fit the observed lung burdens of diesel soot in rats exposed to the 3.5- and 7-mg m-3 concentrations of soot only if it was assumed that clearance remained normal for several months, then virtually stopped. Impaired clearance from high-toxicity particles occurred early after accumulations of a low burden, but that from low-toxicity particles was evident only after months of exposure, when high burdens had accumulated in lung. The impairment in clearances of Ga2O3 particles and radiolabeled tracers was similar, but the impairment in clearance of diesel soot and radiolabeled tracers differed in magnitude. This might have been related to differences in particle size and composition between the tracers and diesel soot. Particle clearance impairment should be considered both in the design of chronic exposures of laboratory animals to inhaled particles and in extrapolating the results to people.

  1. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure###

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rats were ex...

  2. Subchronic inhalation exposure of rats to Libby amphibole and amosite asbestos: Effects at 1 and 3 months post exposure#

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident in humans after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Ra...

  3. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rats were ex...

  4. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure###

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rats were ex...

  5. Subchronic inhalation exposure of rats to Libby amphibole and amosite asbestos: Effects at 1 and 3 months post exposure#

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident in humans after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Ra...

  6. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure

    EPA Science Inventory

    Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rats were ex...

  7. Quantitative assessment of inhalation exposure and deposited dose of aerosol from nanotechnology-based consumer sprays†

    PubMed Central

    Nazarenko, Yevgen; Lioy, Paul J.; Mainelis, Gediminas

    2015-01-01

    This study provides a quantitative assessment of inhalation exposure and deposited aerosol dose in the 14 nm to 20 μm particle size range based on the aerosol measurements conducted during realistic usage simulation of five nanotechnology-based and five regular spray products matching the nano-products by purpose of application. The products were also examined using transmission electron microscopy. In seven out of ten sprays, the highest inhalation exposure was observed for the coarse (2.5–10 μm) particles while being minimal or below the detection limit for the remaining three sprays. Nanosized aerosol particles (14–100 nm) were released, which resulted in low but measurable inhalation exposures from all of the investigated consumer sprays. Eight out of ten products produced high total deposited aerosol doses on the order of 101–103 ng kg−1 bw per application, ~85–88% of which were in the head airways, only <10% in the alveolar region and <8% in the tracheobronchial region. One nano and one regular spray produced substantially lower total deposited doses (by 2–4 orders of magnitude less), only ~52–64% of which were in the head while ~29–40% in the alveolar region. The electron microscopy data showed nanosized objects in some products not labeled as nanotechnology-based and conversely did not find nano-objects in some nano-sprays. We found no correlation between nano-object presence and abundance as per the electron microscopy data and the determined inhalation exposures and deposited doses. The findings of this study and the reported quantitative exposure data will be valuable for the manufacturers of nanotechnology-based consumer sprays to minimize inhalation exposure from their products, as well as for the regulators focusing on protecting the public health. PMID:25621175

  8. Quantitative monitoring of dermal and inhalation exposure to 1,6-hexamethylene diisocyanate monomer and oligomers.

    PubMed

    Fent, Kenneth W; Jayaraj, Karupiah; Ball, Louise M; Nylander-French, Leena A

    2008-04-01

    Respiratory sensitization and occupational asthma are associated with exposure to 1,6-hexamethylene diisocyanate (HDI) in both monomeric and oligomeric forms. The monomer and polymers of diisocyanates differ significantly in their rates of absorption into tissue and their toxicity, and hence may differ in their contribution to sensitization. We have developed and evaluated a liquid chromatography/mass spectrometry (LC-MS) method capable of quantifying HDI and its oligomers (uretidone, biuret, and isocyanurate) in air, tape-stripped skin, and paint samples collected in the automotive refinishing industry. To generate analytical standards, urea derivatives of HDI, biuret, and isocyanurate were synthesized by reaction with 1-(2-methoxyphenyl)piperazine and purified. The urea derivatives were shown to degrade on average by less than 2% per week at -20 degrees C over a 2 month period in occupational samples. The average recovery of HDI and its oligomers from tape was 100% and the limits of detection were 2 and 8 fmol microl(-1), respectively. Exposure assessments were performed on 13 automotive spray painters to evaluate the LC-MS method and the sampling methods under field conditions. Isocyanurate was the most abundant component measured in paint tasks, with median air and skin concentrations of 2.4 mg m(-3) and 4.6 microg mm(-3), respectively. Log-transformed concentrations of HDI (r = 0.79, p < 0.0001) and of isocyanurate (r = 0.71, p < 0.0001) in the skin of workers were correlated with the log-transformed product of air concentration and painting time. The other polyisocyanates were detected on skin for less than 25% of the paint tasks. This LC-MS method provides a valuable tool to investigate inhalation and dermal exposures to specific polyisocyanates and to explore relative differences in the exposure pathways.

  9. TWO-WEEK INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE (LA) AND AMOSITE ASBESTOS

    EPA Science Inventory

    The relative potency of LA compared to UICC amosite was assessed in a subacute inhalation study designed to set exposure levels for a future subchronic study. Male F344 rats (n=7/group) were exposed nose-only to air (control), 3 concentrations of LA, or I concentration of amosite...

  10. Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.

    PubMed

    Fabian, E; Bordag, N; Herold, M; Kamp, H; Krennrich, G; Looser, R; Ma-Hock, L; Mellert, W; Montoya, G; Peter, E; Prokudin, A; Spitzer, M; Strauss, V; Walk, T; Zbranek, R; van Ravenzwaay, B

    2016-07-25

    The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. TWO-WEEK INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE (LA) AND AMOSITE ASBESTOS

    EPA Science Inventory

    The relative potency of LA compared to UICC amosite was assessed in a subacute inhalation study designed to set exposure levels for a future subchronic study. Male F344 rats (n=7/group) were exposed nose-only to air (control), 3 concentrations of LA, or I concentration of amosite...

  12. Analysis of Exposure-Dose Variation of Inhaled Particles in Adult Subjects.

    EPA Science Inventory

    Although internal dose is a key factor for determining the health risk of inhaled pollutant particles, available dose information is largely limited to young healthy adults under a few typical exposure conditions. Extrapolation of the limited dose information to different populat...

  13. POTENTIAL INHALATION EXPOSURE TO VOLATILE CHEMICALS IN WATER-BASED HARD-SURFACE CLEANERS

    EPA Science Inventory

    Potential inhalation exposure of building occupants to volatile chemicals in water-based hard-surface cleaners was evaluated by analyzing 267 material safety data sheets (MSDSs). Among the 154 chemicals reported, 44 are volatile or semi-volatile. Hazardous air pollutants (HAPs) r...

  14. Analysis of Exposure-Dose Variation of Inhaled Particles in Adult Subjects.

    EPA Science Inventory

    Although internal dose is a key factor for determining the health risk of inhaled pollutant particles, available dose information is largely limited to young healthy adults under a few typical exposure conditions. Extrapolation of the limited dose information to different populat...

  15. POTENTIAL INHALATION EXPOSURE TO VOLATILE CHEMICALS IN WATER-BASED HARD-SURFACE CLEANERS

    EPA Science Inventory

    Potential inhalation exposure of building occupants to volatile chemicals in water-based hard-surface cleaners was evaluated by analyzing 267 material safety data sheets (MSDSs). Among the 154 chemicals reported, 44 are volatile or semi-volatile. Hazardous air pollutants (HAPs) r...

  16. INHALATION EXPOSURE TO CARBON NANOTUBES (CNT) AND CARBON NANOFIBERS (CNF): METHODOLOGY AND DOSIMETRY

    PubMed Central

    Oberdörster, Günter; Castranova, Vincent; Asgharian, Bahman; Sayre, Phil

    2015-01-01

    Carbon nanotubes (CNT) and nanofibers (CNF) are used increasingly in a broad array of commercial products. Given current understandings, the most significant life-cycle exposures to CNT/CNF occur from inhalation when they become airborne at different stages of their life cycle, including workplace, use, and disposal. Increasing awareness of the importance of physicochemical properties as determinants of toxicity of CNT/CNF and existing difficulties in interpreting results of mostly acute rodent inhalation studies to date necessitate a reexamination of standardized inhalation testing guidelines. The current literature on pulmonary exposure to CNT/CNF and associated effects is summarized; recommendations and conclusions are provided that address test guideline modifications for rodent inhalation studies that will improve dosimetric extrapolation modeling for hazard and risk characterization based on the analysis of exposure-dose-response relationships. Several physicochemical parameters for CNT/CNF, including shape, state of agglomeration/aggregation, surface properties, impurities, and density, influence toxicity. This requires an evaluation of the correlation between structure and pulmonary responses. Inhalation, using whole-body exposures of rodents, is recommended for acute to chronic pulmonary exposure studies. Dry powder generator methods for producing CNT/CNF aerosols are preferred, and specific instrumentation to measure mass, particle size and number distribution, and morphology in the exposure chambers are identified. Methods are discussed for establishing experimental exposure concentrations that correlate with realistic human exposures, such that unrealistically high experimental concentrations need to be identified that induce effects under mechanisms that are not relevant for workplace exposures. Recommendations for anchoring data to results seen for positive and negative benchmark materials are included, as well as periods for postexposure observation

  17. Combustion-derived nanoparticles: A review of their toxicology following inhalation exposure

    PubMed Central

    Donaldson, Ken; Tran, Lang; Jimenez, Luis Albert; Duffin, Rodger; Newby, David E; Mills, Nicholas; MacNee, William; Stone, Vicki

    2005-01-01

    This review considers the molecular toxicology of combustion-derived nanoparticles (CDNP) following inhalation exposure. CDNP originate from a number of sources and in this review we consider diesel soot, welding fume, carbon black and coal fly ash. A substantial literature demonstrates that these pose a hazard to the lungs through their potential to cause oxidative stress, inflammation and cancer; they also have the potential to redistribute to other organs following pulmonary deposition. These different CDNP show considerable heterogeneity in composition and solubility, meaning that oxidative stress may originate from different components depending on the particle under consideration. Key CDNP-associated properties of large surface area and the presence of metals and organics all have the potential to produce oxidative stress. CDNP may also exert genotoxic effects, depending on their composition. CDNP and their components also have the potential to translocate to the brain and also the blood, and thereby reach other targets such as the cardiovascular system, spleen and liver. CDNP therefore can be seen as a group of particulate toxins unified by a common mechanism of injury and properties of translocation which have the potential to mediate a range of adverse effects in the lungs and other organs and warrant further research. PMID:16242040

  18. Computer-automated silica aerosol generator and animal inhalation exposure system.

    PubMed

    McKinney, Walter; Chen, Bean; Schwegler-Berry, Diane; Frazer, Dave G

    2013-06-01

    Inhalation exposure systems are necessary tools for determining the dose response relationship of inhaled toxicants under a variety of exposure conditions. The objective of this study was to develop an automated computer controlled system to expose small laboratory animals to precise concentrations of uniformly dispersed airborne silica particles. An acoustical aerosol generator was developed which was capable of re-suspending particles from bulk powder. The aerosolized silica output from the generator was introduced into the throat of a venturi tube. The turbulent high-velocity air stream within the venturi tube increased the dispersion of the re-suspended powder. That aerosol was then used to expose small laboratory animals to constant aerosol concentrations, up to 20 mg/m(3), for durations lasting up to 8 h. Particle distribution and morphology of the silica aerosol delivered to the exposure chamber were characterized to verify that a fully dispersed and respirable aerosol was being produced. The inhalation exposure system utilized a combination of airflow controllers, particle monitors, data acquisition devices and custom software with automatic feedback control to achieve constant and repeatable exposure environments. The automatic control algorithm was capable of maintaining median aerosol concentrations to within ±0.2 mg/m(3) of a user selected target concentration during exposures lasting from 2 to 8 h. The system was able to reach 95% of the desired target value in <10 min during the beginning phase of an exposure. This exposure system provided a highly automated tool for conducting inhalation toxicology studies involving silica particles.

  19. Occupational exposure to inhaled anesthetic. Is it a concern for pregnant women?

    PubMed Central

    Shuhaiber, S.; Koren, G.

    2000-01-01

    QUESTION: Two of my pregnant patients are exposed to inhaled anesthetic on the job. One is an anesthetist, and the other is a veterinarian. They have both expressed concern about this exposure. How should I advise them? ANSWER: Occupational exposure to waste anesthetic gas is not associated with increased risk of major malformations. Risk of spontaneous abortion might be slightly increased, however. This risk can be reduced, if not eliminated, by good gas scavenging systems. PMID:11153403

  20. Computer-automated silica aerosol generator and animal inhalation exposure system

    PubMed Central

    McKinney, Walter; Chen, Bean; Schwegler-Berry, Diane; Frazer, Dave G.

    2015-01-01

    Inhalation exposure systems are necessary tools for determining the dose response relationship of inhaled toxicants under a variety of exposure conditions. The objective of this study was to develop an automated computer controlled system to expose small laboratory animals to precise concentrations of uniformly dispersed airborne silica particles. An acoustical aerosol generator was developed which was capable of re-suspending particles from bulk powder. The aerosolized silica output from the generator was introduced into the throat of a venturi tube. The turbulent high-velocity air stream within the venturi tube increased the dispersion of the re-suspended powder. That aerosol was then used to expose small laboratory animals to constant aerosol concentrations, up to 20mg/m3, for durations lasting up to 8h. Particle distribution and morphology of the silica aerosol delivered to the exposure chamber were characterized to verify that a fully dispersed and respirable aerosol was being produced. The inhalation exposure system utilized a combination of airflow controllers, particle monitors, data acquisition devices and custom software with automatic feedback control to achieve constant and repeatable exposure environments. The automatic control algorithm was capable of maintaining median aerosol concentrations to within ±0.2 mg/m3 of a user selected target concentration during exposures lasting from 2 to 8 h. The system was able to reach 95% of the desired target value in <10min during the beginning phase of an exposure. This exposure system provided a highly automated tool for conducting inhalation toxicology studies involving silica particles. PMID:23796015

  1. Acute respiratory toxicity following inhalation exposure to soman in guinea pigs

    SciTech Connect

    Perkins, Michael W.; Pierre, Zdenka; Rezk, Peter; Sabnekar, Praveena; Sciuto, Alfred M.; Nambiar, Madhusoodana P.

    2010-06-01

    Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m{sup 3} concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m{sup 3} soman survived, while animals exposed to 841, and 1121 mg/m{sup 3} resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt{sub 50} for soman determined by probit analysis was 827.2 mg/m{sup 3}. A majority of the animals that died at 1121 mg/m{sup 3} developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.

  2. Comparison of sarin and cyclosarin toxicity by subcutaneous, intravenous and inhalation exposure in Gottingen minipigs.

    PubMed

    Hulet, Stanley W; Sommerville, Douglas R; Miller, Dennis B; Scotto, Jacqueline A; Muse, William T; Burnett, David C

    2014-02-01

    Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB and GF vapor via whole-body inhalation exposures or to liquid GB or GF via intravenous or subcutaneous injections. Vapor inhalation exposures were for 10, 60 or 180 min. Maximum likelihood estimation was used to calculate the median effect levels for severe effects (ECT50 and ED50) and lethality (LCT50 and LD50). Ordinal regression was used to model the concentration × time profile of the agent toxicity. Contrary to that predicted by Haber's rule, LCT50 values increased as the duration of the exposures increased for both nerve agents. The toxic load exponents (n) were calculated to be 1.38 and 1.28 for GB and GF vapor exposures, respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GB in male minipigs were 73, 106 and 182 mg min/m(3), respectively. LCT50 values for 10-, 60 - and 180-min exposures to vapor GB in female minipigs were 87, 127 and 174 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GF in male minipigs were 218, 287 and 403 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures in female minipigs were 183, 282 and 365 mg min/m(3), respectively. For GB vapor exposures, there was a tenuous gender difference which did not exist for vapor GF exposures. Surprisingly, GF was 2-3 times less potent than GB via the inhalation route of exposure regardless of exposure duration. Additionally GF was found to be less potent than GB by intravenous and subcutaneous routes.

  3. Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

    SciTech Connect

    Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

    2016-12-08

    When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and the volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. In conclusion, given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted.

  4. Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

    DOE PAGES

    Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

    2016-12-08

    When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and themore » volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. In conclusion, given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted.« less

  5. Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

    PubMed Central

    Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

    2016-01-01

    When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and the volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. Given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted. PMID:27930709

  6. The impact of a change to inhalable occupational exposure limits: strontium chromate exposure in the U.S. Air Force.

    PubMed

    Carlton, Gary N

    2003-01-01

    The American Conference of Governmental Industrial Hygienists has announced its intention to replace all total particulate threshold limit values (TLVs) with size-selective TLVs. Because the U.S. Air Force has adopted the TLVs as its occupational exposure limits, the impact of this change is of interest, specifically for hexavalent chromium. This article reviews historical strontium chromate sampling data in the Air Force and the impact of its reinterpretation in comparison to an inhalable TLV. Based on the measured conversion factor between the 37-mm cassette and the IOM inhalable sampler, inhalable strontium chromate exposures will continue to exceed the TLV during all aircraft priming and most sanding procedures. In addition, inhalable exposures are expected to exceed 1000 times the TLV, greater than the highest currently assigned protection factor for airline respirators, during 25% of priming procedures. Without a change in the value of the current TLV time-weighted average of 0.5 microg/m(3), the Air Force will need to reduce strontium chromate levels, either by incorporating work practices that decrease worker productivity or considering a change to nonchromated primers.

  7. MODELING INHALATION AND MULTIMEDIA MULTIPATHWAY HUMAN EXPOSURES TO ENVIRONMENTAL POLLUTANTS

    EPA Science Inventory

    Estimation of exposures of children and adults to air toxics or multimedia pollutants require careful consideration of sources and concentrations of pollutants that may be present in different media, as well as various routes and pathways of exposures associated with age-specif...

  8. MODELING INHALATION AND MULTIMEDIA MULTIPATHWAY HUMAN EXPOSURES TO ENVIRONMENTAL POLLUTANTS

    EPA Science Inventory

    Estimation of exposures of children and adults to air toxics or multimedia pollutants require careful consideration of sources and concentrations of pollutants that may be present in different media, as well as various routes and pathways of exposures associated with age-specif...

  9. Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs

    SciTech Connect

    Che, Magnus M.; Conti, Michele; Boylan, Megan; Sabnekar, Praveena; Rezk, Peter; Sciuto, Alfred M.; Doctor, Bhupendra P.; Nambiar, Madhusoodana P.

    2009-09-15

    We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m{sup 3} sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.

  10. Post-exposure treatment with nasal atropine methyl bromide protects against microinstillation inhalation exposure to sarin in guinea pigs.

    PubMed

    Che, Magnus M; Conti, Michele; Chanda, Soma; Boylan, Megan; Sabnekar, Praveena; Rezk, Peter; Amari, Ethery; Sciuto, Alfred M; Gordon, Richard K; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2009-09-15

    We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m(3) sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarin exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.

  11. Organic Dust, Lipopolysaccharide, and Peptidoglycan Inhalant Exposures Result in Bone Loss/Disease

    PubMed Central

    Dusad, Anand; Thiele, Geoff M.; Klassen, Lynell W.; Gleason, Angela M.; Bauer, Christopher; Mikuls, Ted R.; Duryee, Michael J.; West, William W.; Romberger, Debra J.

    2013-01-01

    Skeletal health consequences associated with chronic inflammatory respiratory disease, and particularly chronic obstructive pulmonary disease (COPD), contribute to overall disease morbidity. Agricultural environmental exposures induce significant airway diseases, including COPD. However, animal models to understand inhalant exposure–induced lung injury and bone disease have not been described. Using micro–computed tomography (micro-CT) imaging technology and histology, bone quantity and quality measurements were investigated in mice after repetitive intranasal inhalation exposures to complex organic dust extracts (ODEs) from swine confinement facilities. Comparison experiments with LPS and peptidoglycan (PGN) alone were also performed. After 3 weeks of repetitive ODE inhalation exposure, significant loss of bone mineral density and trabecular bone volume fraction was evident, with altered morphological microarchitecture changes in the trabecular bone, compared with saline-treated control animals. Torsional resistance was also significantly reduced. Compared with saline treatment, ODE-treated mice demonstrated decreased collagen and proteoglycan content in their articular cartilage, according to histopathology. Significant bone deterioration was also evident after repetitive intranasal inhalant treatment with LPS and PGN. These findings were not secondary to animal distress, and not entirely dependent on the degree of induced lung parenchymal inflammation. Repetitive LPS treatment demonstrated the most pronounced changes in bone parameters, and PGN treatment resulted in the greatest lung parenchymal inflammatory changes. Collectively, repetitive inhalation exposures to noninfectious inflammatory agents such as complex organic dust, LPS, and PGN resulted in bone loss. This animal model may contribute to efforts toward understanding the mechanisms and evaluating the therapeutics associated with adverse skeletal health consequences after subchronic airway injury

  12. A dynamic exposure system: Concurrent toluene inhalation and fixed ratio performance in mice

    SciTech Connect

    Tegeris, J.S.; Knisely, J.S.; Balster, R.L. )

    1990-02-26

    The potential for occupational exposure to acute high doses of solvents, coupled with the rising incidence of inhalant abuse, necessitates the need to better characterize the behavioral effects of solvents. Vapor exposure was accomplished with a computer-controlled mass flow system where exposure levels were monitored by infrared spectroscopy. Twelve food-deprived CFW male mice were shaped to lever press for milk reinforcement under a FR20 schedule. Within-session concentration-effect relationships for toluene were determined by successive 5-minute exposures to 5 successively increasing concentrations, preceded by 5 minutes of air exposure. These results were compared to concentration-effect relationships determined by single concentration test sessions, utilizing 20-minute exposures, preceded and followed by 5 minutes of air exposure. Under the within-session method, very similar concentration related decreases in response rates were produced, regardless of whether the concentration range examined was 500-6,000 ppm or 125-2,000 ppm. Effects of toluene based upon exposure to single concentrations yielded a less sensitive effect for the concentration range 125-2,000 ppm. Return to baseline response rates were rapid, correlating well with the rapid rate of clearance classically exhibited by solvents. These results indicate that this dynamic mass flow system provides a sensitive and consistent means by which to measure the behavioral effects of inhalants and allows for a great deal of flexibility for rapid alteration of exposure conditions.

  13. Bioavailability of octamethylcyclotetrasiloxane (D(4)) after exposure to silicones by inhalation and implantation.

    PubMed Central

    Luu, H M; Hutter, J C

    2001-01-01

    We developed a physiologically based pharmacokinetic (PBPK) model to predict the target organ doses of octamethylcyclotetrasiloxane (D(4)) after intravenous (IV), inhalation, or implantation exposures. The model used (14)C-D(4) IV disposition data in rats to estimate tissue distribution coefficients, metabolism, and excretion parameters. We validated the model by comparing the predicted blood and tissues concentrations of D(4) after inhalation to experimental results in both rats and humans. We then used the model to simulate D(4) kinetics after single and/or repeated D(4) exposures in rats and humans. The model predicted bioaccumulation of D(4) in fatty tissues (e.g., breast), especially in women. Because of its high lipid solubility (Log P(oct/water) = 5.1), D(4) persisted in fat with a half life of 11.1 days after inhalation and 18.2 days after breast implant exposure. Metabolism and excretion remained constant with repeated exposures, larger doses, and/or different routes of exposure. The accumulation of D(4) in fatty tissues should play an important role in the risk assessment of D(4) especially in women exposed daily to multiple personal care products and silicone breast implants. PMID:11712992

  14. Toluene diisocyanate: an assessment of carcinogenic risk following oral and inhalation exposure.

    PubMed

    Doe, J E; Hoffmann, H D

    1995-01-01

    Although respiratory sensitization and pulmonary irritation have been the subject of particular studies with toluene diisocyanate (TDI), in recent years the potential carcinogenicity of TDI has been a reason for concern and speculation. This has arisen from the expectation that following exposure to TDI the chemical would hydrolyze at aqueous tissue surfaces to give rise to toluene diamine (TDA), a mutagen and rodent carcinogen. The chemistry of TDI suggests that the reaction with biological NH2 groups such as those on proteins, and polymerization to oligoureas, will compete with the hydrolysis reaction. This has been shown with results of in vitro studies where conjugation to protein occurs without detectable formation of TDA when protein solutions in saline are exposed to TDI vapor. Lower pH levels leading to high protonation of biological NH2 groups facilitate hydrolysis of TDI to TDA and subsequent formation of polyureas. These observations are consistent with comparative toxicokinetic studies in rats, which demonstrate significant levels of TDA following oral dosing with TDI--due to the acidic environment in the stomach--but not after inhalation. These results provide an explanation for the tumors observed in rodents after oral dosing of TDI in corn oil, but not after inhalation. Inhalation is the relevant route of human exposure for TDI and the toxicokinetics of TDI exposure at occupational exposure limits have been studied. These data provide a means by which quantitative estimates of the risk of carcinogenicity possibly resulting from the intermediate formation of TDA during TDI exposure can be obtained. Several calculations have been made, all of which lead to the conclusion that TDI exposure by inhalation at the recommended occupational limits will not give rise to significant carcinogenic risk.

  15. Exposures to inhalable and "total" oil mist aerosol by metal machining shop workers.

    PubMed

    Wilsey, P W; Vincent, J H; Bishop, M J; Brosseau, L M; Greaves, I A

    1996-12-01

    Several recent studies have compared worker personal aerosol exposures as measured by the current method with those obtained by a new approach based on collecting the inhalable fraction, intended to represent all the particles that are capable of entering through the nose and/or mouth during breathing. The present study investigated this relationship for a metal machining facility where aerosols were generated from severely refined, nonaqueous ("straight") cutting oils used during the lathe working of metal rod stock. Workers (n = 23) wore two personal aerosol samplers simulataneously, one of the 37-mm type (for "total" aerosol exposure, E37) and the other of the Institute of Occupational Medicine (IOM) type (for inhalable aerosol exposure, EIOM). The data were analyzed by weighted least squares linear regression to determine the coefficient S in the relation EIOM = S.E37. It was found that S = 2.96 +/- 0.60. This ratio-in which exposure to inhalable aerosol was greater than to "total" aerosol-is consistent with previous observations in other industries. The relative coarsenss of the oil mist aerosol, as estimated by cascade impactor measurements, probably explains the difference between the sampling methods. The collection of large "splash" droplets, may also contribute. Future occupational aerosol standards for metalworking fluids will be based on the new, health-related criteria, and exposures will be assessed on the basis of the inhalable fraction. Results of studies like that described here will enable assessment of the impact on future workplace aerosol exposure assessments of introducing new standards.

  16. Range-Finding Risk Assessment of Inhalation Exposure to Nanodiamonds in a Laboratory Environment

    PubMed Central

    Koivisto, Antti J.; Palomäki, Jaana E.; Viitanen, Anna-Kaisa; Siivola, Kirsi M.; Koponen, Ismo K.; Yu, Mingzhou; Kanerva, Tomi S.; Norppa, Hannu; Alenius, Harri T.; Hussein, Tareq; Savolainen, Kai M.; Hämeri, Kaarle J.

    2014-01-01

    This study considers fundamental methods in occupational risk assessment of exposure to airborne engineered nanomaterials. We discuss characterization of particle emissions, exposure assessment, hazard assessment with in vitro studies, and risk range characterization using calculated inhaled doses and dose-response translated to humans from in vitro studies. Here, the methods were utilized to assess workers’ risk range of inhalation exposure to nanodiamonds (NDs) during handling and sieving of ND powder. NDs were agglomerated to over 500 nm particles, and mean exposure levels of different work tasks varied from 0.24 to 4.96 µg·m−3 (0.08 to 0.74 cm−3). In vitro-experiments suggested that ND exposure may cause a risk for activation of inflammatory cascade. However, risk range characterization based on in vitro dose-response was not performed because accurate assessment of delivered (settled) dose on the cells was not possible. Comparison of ND exposure with common pollutants revealed that ND exposure was below 5 μg·m−3, which is one of the proposed exposure limits for diesel particulate matter, and the workers’ calculated dose of NDs during the measurement day was 74 ng which corresponded to 0.02% of the modeled daily (24 h) dose of submicrometer urban air particles. PMID:24840353

  17. Healthy hire effect, job selection and inhalation exposure among young adults with asthma.

    PubMed

    Olivieri, M; Mirabelli, M C; Plana, E; Radon, K; Antó, J M; Bakke, P; Benke, G; D'Errico, A; Henneberger, P; Kromhout, H; Norbäck, D; Torén, K; van Sprundel, M; Villani, S; Wieslander, G; Zock, J-P; Kogevinas, M

    2010-09-01

    The aim of the present study was to assess whether asthma onset prior to entering the workforce influences whether a person holds a subsequent job with asthma-related inhalation exposures. The data of 19,784 adults from the European Community Respiratory Health Survey were analysed. For each respondent, a current or previously held job was linked to a job exposure matrix assigning high, low or no exposure to dust, gases or fumes. Jobs were also categorised according to the risk of exposures related to occupational asthma. Associations between asthma and subsequent occupational exposures were assessed using logistic regression models, with a random intercept for study centre and fixed adjustment for age, sex, type of study sample and smoking status. Of the respondents, 8% (n = 1,619) reported asthma with onset before completion of full-time education. This population was at decreased risk of having a job with high (odds ratio 0.79; 95% confidence interval 0.68-0.92) or low (0.91; 0.80-1.03) exposure to dust, gases or fumes. The associations were consistent across exposure types (dusts, gases or fumes) and for jobs with a high risk of occupational asthma. Adults with asthma onset prior to entering the workforce may be less likely to hold jobs involving inhalation exposures.

  18. Healthy hire effect, job selection and inhalation exposure among young adults with asthma

    PubMed Central

    Olivieri, M.; Mirabelli, M.C.; Plana, E.; Radon, K.; Antó, J.M.; Bakke, P.; Benke, G.; D’Errico, A.; Henneberger, P.; Kromhout, H.; Norbäck, D.; Torén, K.; van Sprundel, M.; Villani, S.; Wieslander, G.; Zock, J-P.; Kogevinas, M.

    2015-01-01

    The aim of the present study was to assess whether asthma onset prior to entering the workforce influences whether a person holds a subsequent job with asthma-related inhalation exposures. The data of 19,784 adults from the European Community Respiratory Health Survey were analysed. For each respondent, a current or previously held job was linked to a job exposure matrix assigning high, low or no exposure to dust, gases or fumes. Jobs were also categorised according to the risk of exposures related to occupational asthma. Associations between asthma and subsequent occupational exposures were assessed using logistic regression models, with a random intercept for study centre and fixed adjustment for age, sex, type of study sample and smoking status. Of the respondents, 8% (n=1,619) reported asthma with onset before completion of full-time education. This population was at decreased risk of having a job with high (odds ratio 0.79; 95% confidence interval 0.68–0.92) or low (0.91; 0.80–1.03) exposure to dust, gases or fumes. The associations were consistent across exposure types (dusts, gases or fumes) and for jobs with a high risk of occupational asthma. Adults with asthma onset prior to entering the workforce may be less likely to hold jobs involving inhalation exposures. PMID:20185427

  19. Acute microinstillation inhalation exposure to sarin induces changes in respiratory dynamics and functions in guinea pigs.

    PubMed

    Conti, Michele L; Che, Magnus M; Boylan, Megan; Sciuto, Alfred M; Gordon, Richard K; Nambiar, Madhusoodana P

    2009-01-01

    This study investigates the toxic effects of sarin on respiratory dynamics following microinstillation inhalation exposure in guinea pigs. Animals are exposed to sarin for 4 minutes, and respiratory functions are monitored at 4 hours and 24 hours by whole-body barometric plethysmography. Data show significant changes in respiratory dynamics and function following sarin exposure. An increase in respiratory frequency is observed at 4 hours post exposure compared with saline controls. Tidal volume and minute volume are also increased in sarin-exposed animals 4 hours after exposure. Peak inspiratory flow increases, whereas peak expiratory flow increases at 4 hours and is erratic following sarin exposure. Animals exposed to sarin show a significant decrease in expiratory time and inspiratory time. End-inspiratory pause is unchanged whereas end-expiratory pause is slightly decreased 24 hours after sarin exposure. These results indicate that inhalation exposure to sarin alters respiratory dynamics and function at 4 hours, with return to normal levels at 24 hours post exposure.

  20. Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

    PubMed Central

    Kuempel, Eileen D.; Sweeney, Lisa M.; Morris, John B.; Jarabek, Annie M.

    2015-01-01

    The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose-response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates. PMID:26551218

  1. Ethanol toxicokinetics resulting from inhalation exposure in human volunteers and toxicokinetic modeling.

    PubMed

    Dumas-Campagna, Josée; Tardif, Robert; Charest-Tardif, Ginette; Haddad, Sami

    2014-02-01

    Uncertainty exists regarding the validity of a previously developed physiologically-based pharmacokinetic model (PBPK) for inhaled ethanol in humans to predict the blood levels of ethanol (BLE) at low level exposures (<1000 ppm). Thus, the objective of this study is to document the BLE resulting from low levels exposures in order to refine/validate this PBPK model. Human volunteers were exposed to ethanol vapors during 4 h at 5 different concentrations (125-1000 ppm), at rest, in an inhalation chamber. Blood and exhaled air were sampled. Also, the impact of light exercise (50 W) on the BLE was investigated. There is a linear relationship between the ethanol concentrations in inhaled air and (i) BLE (women: r²= 0.98/men: r²= 0.99), as well as (ii) ethanol concentrations in the exhaled air at end of exposure period (men: r²= 0.99/women: r²= 0.99). Furthermore, the exercise resulted in a net and significant increase of BLE (2-3 fold). Overall, the original model predictions overestimated the BLE for all low exposures performed in this study. To properly simulate the toxicokinetic data, the model was refined by adding a description of an extra-hepatic biotransformation of high affinity and low capacity in the richly perfused tissues compartment. This is based on the observation that total clearance observed at low exposure levels was much greater than liver blood flow. The results of this study will facilitate the refinement of the risk assessment associated with chronic inhalation of low levels of ethanol in the general population and especially among workers.

  2. Occupational inhalational exposure and serum GM-CSF autoantibody in pulmonary alveolar proteinosis.

    PubMed

    Xiao, Yong-Long; Xu, Kai-Feng; Li, Yan; Li, Yan; Li, Hui; Shi, Bin; Zhou, Ke-Feng; Zhou, Zheng-Yang; Cai, Hou-Rong

    2015-07-01

    Although the serum granulocyte-macrophage colony stimulating factor autoantibody (GMAb) levels have been recognised as a diagnostic marker in primary pulmonary alveolar proteinosis (PAP), their role in PAP with occupational inhalational exposure (PAPo) remains unclear. Forty-five consecutive patients with PAP were enrolled. Each patient with PAP was assessed for baseline clinical characteristics, chest high-resolution CT (HRCT), serum GMAb and occupational exposure. Fifty healthy controls were included to define normal ranges for GMAb levels. Ninety-seven hospital controls with other respiratory diseases were included to establish prevalence of a history of occupational inhalation exposure. According to the serum GMAb cut-off value of 2.39 μg/mL, 84.4% of the recruited patients with PAP had positive serum GMAb with a median level of 28.7 μg/mL, defined as autoimmune PAP, and the remaining 15.6% had negative serum GMAb with a median level of 0.16 μg/mL, defined as non-autoimmune PAP. Also, 34.2% of patients with autoimmune PAP had a history of occupational inhalational exposure, which was not significantly higher than that of hospital controls (34.2% vs 19.6%, p=0.072). Four patients with PAPo showed negative GMAb. Their arterial oxygen tension, pulmonary function parameters and chest HRCT features were significantly different when compared with patients with autoimmune PAP (p<0.05). These four non-autoimmune occupational lung disease cases culminated in 3 deaths and a lung transplant. A number of patients with PAP who may have occupational inhalational exposure and negative serum GMAb represent a high possibility of silicoproteinosis and very poor survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Behavioral evaluation of rats following low-level inhalation exposure to sarin.

    PubMed

    Genovese, Raymond F; Mioduszewski, Robert J; Benton, Bernard J; Pare, Matthew A; Cooksey, Jessica A

    2009-02-01

    We evaluated the effects, in rats, of single and multiple low-level inhalation exposures to sarin. Rats were trained on a variable-interval, 56 s (VI56) schedule of food reinforcement and then exposed to sarin vapor (1.7-4.0 mg/m(3) x 60 min) or air control. The exposures did not produce clinical signs of toxicity other than miosis. Subsequently, performance on the VI56 and acquisition of a radial-arm maze spatial memory task was evaluated over approximately 11 weeks. Single exposures did not affect performance on the VI56 and had little effect on acquisition of the radial-arm maze task. Multiple exposures (4.0 mg/m(3) x 60 min/day x 3) disrupted performance on the VI56 schedule during the initial post-exposure sessions. The disruption, however, resolved after several days. Multiple exposures also produced a deficit on the radial-arm maze task in that sarin-exposed rats tended to take it longer to complete the maze and to make more errors. The deficit, however, resolved during the first three weeks of acquisition. These results demonstrate that in rats, inhalation exposure to sarin at levels below those causing overt signs of clinical toxicity can produce cognitive and performance deficits. Furthermore, the observed deficits do not appear to be persistent.

  4. Adverse respiratory effects in rats following inhalation exposure to ammonia: respiratory dynamics and histopathology.

    PubMed

    Perkins, Michael W; Wong, Benjamin; Tressler, Justin; Rodriguez, Ashley; Sherman, Katherine; Andres, Jaclynn; Devorak, Jennifer; L Wilkins, William; Sciuto, Alfred M

    2017-01-01

    Acute respiratory dynamics and histopathology of the lungs and trachea following inhaled exposure to ammonia were investigated. Respiratory dynamic parameters were collected from male Sprague-Dawley rats (300-350 g) during (20 min) and 24 h (10 min) after inhalation exposure for 20 min to 9000, 20,000, and 23,000 ppm of ammonia in a head-only exposure system. Body weight loss, analysis of blood cells, and lungs and trachea histopathology were assessed 1, 3, and 24 h following inhalation exposure to 20,000 ppm of ammonia. Prominent decreases in minute volume (MV) and tidal volume (TV) were observed during and 24 h post-exposure in all ammonia-exposed animals. Inspiratory time (IT) and expiratory time (ET) followed similar patterns and decreased significantly during the exposure and then increased at 24 h post-exposure in all ammonia-exposed animals in comparison to air-exposed controls. Peak inspiratory (PIF) and expiratory flow (PEF) significantly decreased during the exposure to all ammonia doses, while at 24 h post-exposure they remained significantly decreased following exposure to 20,000 and 23,000 ppm. Exposure to 20,000 ppm of ammonia resulted in body weight loss at 1 and 3 h post-exposure; weight loss was significant at 24 h compared to controls. Exposure to 20,000 ppm of ammonia for 20 min resulted in increases in the total blood cell counts of white blood cells, neutrophils, and platelets at 1, 3, and 24 h post-exposure. Histopathologic evaluation of the lungs and trachea tissue of animals exposed to 20,000 ppm of ammonia at 1, 3, and 24 h post-exposure revealed various morphological changes, including alveolar, bronchial, and tracheal edema, epithelial necrosis, and exudate consisting of fibrin, hemorrhage, and inflammatory cells. The various alterations in respiratory dynamics and damage to the respiratory system observed in this study further emphasize ammonia-induced respiratory toxicity and the relevance of

  5. Immune activation and autoantibodies in humans with long-term inhalation exposure to formaldehyde

    SciTech Connect

    Thrasher, J.D.; Broughton, A.; Madison, R. )

    1990-07-01

    Four groups of patients with long-term inhalation exposure to formaldehyde (HCHO) were compared with controls who had short-term periodic exposure to HCHO. The following were determined for all groups: total white cell, lymphocyte, and T cell counts; T helper/suppressor ratios; total Ta1+, IL2+, and B cell counts; antibodies to formaldehyde-human serum albumin (HCHO-HSA) conjugate and autoantibodies. When compared with the controls, the patients had significantly higher antibody titers to HCHO-HSA. In addition, significant increases in Ta1+, IL2+, and B cells and autoantibodies were observed. Immune activation, autoantibodies, and anti-HCHO-HSA antibodies are associated with long-term formaldehyde inhalation.

  6. Longitudinal distribution of ozone absorption in the lung: Effect of continuous inhalation exposure

    SciTech Connect

    Asplund, P.T.; Rigas, M.L.; Ultman, J.S.; Ben-Jebria, A. |

    1996-11-01

    The effect of continuous exposure to ozone on the absorption of ozone in the conducting airways of human lungs was investigated with a bolus-response method. Eleven healthy nonsmoking college students (8 males, 3 females) were exposed at rest for 2 h on 3 separate days to air containing 0 ppm, 0.12 ppm, and 0.36 ppm ozone. A personal inhalation chamber equipped with a head-only clear plastic dome was used for exposure. Every 30 min a subject removed the dome and orally inhaled a series of five ozone-air boluses, each in a separate breath. Penetration of the boluses distal to the lips was targeted in the range of 70-120 ml (corresponding to the central conducting airways). By integrating the inhaled and exhaled-ozone concentration curves, we obtained the absorbed fraction {Lambda} and the dispersion ({sigma}{sup 2}) of the ozone bolus for each test breath. In addition, the subtraction of baseline measurements made just before exposure enabled us to determine the changes in absorbed fraction ({Delta}{Lambda}) and in dispersion ({Delta}{sigma}{sup 2}) that resulted from exposure alone. Absorbed fraction decreased, but {sigma}{sup 2} increased during O{sub 3} exposure, and the differences in {Delta}{Lambda} and in {Delta}{sigma}{sup 2} between breathing air and exposure to either 0.12 ppm or 0.36 ppm O{sub 3} were significant. We concluded that exposure of the conducting airways to O{sub 3} reduced their capacity to absorb O{sub 3}, possibly by the depletion of biochemical substrates that are normally oxidized by O{sub 3}. 20 refs., 9 figs.

  7. A Murine Inhalation Model to Characterize Pulmonary Exposure to Dry Aspergillus fumigatus Conidia

    PubMed Central

    Buskirk, Amanda D.; Green, Brett J.; Lemons, Angela R.; Nayak, Ajay P.; Goldsmith, W. Travis; Kashon, Michael L.; Anderson, Stacey E.; Hettick, Justin M.; Templeton, Steven P.; Germolec, Dori R.; Beezhold, Donald H.

    2014-01-01

    Most murine models of fungal exposure are based on the delivery of uncharacterized extracts or liquid conidia suspensions using aspiration or intranasal approaches. Studies that model exposure to dry fungal aerosols using whole body inhalation have only recently been described. In this study, we aimed to characterize pulmonary immune responses following repeated inhalation of conidia utilizing an acoustical generator to deliver dry fungal aerosols to mice housed in a nose only exposure chamber. Immunocompetent female BALB/cJ mice were exposed to conidia derived from Aspergillus fumigatus wild-type (WT) or a melanin-deficient (Δalb1) strain. Conidia were aerosolized and delivered to mice at an estimated deposition dose of 1×105 twice a week for 4 weeks (8 total). Histopathological and immunological endpoints were assessed 4, 24, 48, and 72 hours after the final exposure. Histopathological analysis showed that conidia derived from both strains induced lung inflammation, especially at 24 and 48 hour time points. Immunological endpoints evaluated in bronchoalveolar lavage fluid (BALF) and the mediastinal lymph nodes showed that exposure to WT conidia led to elevated numbers of macrophages, granulocytes, and lymphocytes. Importantly, CD8+ IL17+ (Tc17) cells were significantly higher in BALF and positively correlated with germination of A. fumigatus WT spores. Germination was associated with specific IgG to intracellular proteins while Δalb1 spores elicited antibodies to cell wall hydrophobin. These data suggest that inhalation exposures may provide a more representative analysis of immune responses following exposures to environmentally and occupationally prevalent fungal contaminants. PMID:25340353

  8. Commuter exposure to inhalable, thoracic and alveolic particles in various transportation modes in Delhi.

    PubMed

    Kumar, Pramod; Gupta, N C

    2016-01-15

    A public health concern is to understand the linkages between specific pollution sources and adverse health impacts. Commuting can be viewed as one of the significant-exposure activity in high-vehicle density areas. This paper investigates the commuter exposure to inhalable, thoracic and alveolic particles in various transportation modes in Delhi, India. Air pollution levels are significantly contributed by automobile exhaust and also in-vehicle exposure can be higher sometime than ambient levels. Motorcycle, auto rickshaw, car and bus were selected to study particles concentration along two routes in Delhi between Kashmere Gate and Dwarka. The bus and auto rickshaw were running on compressed natural gas (CNG) while the car and motorcycle were operated on gasoline fuel. Aerosol spectrometer was employed to measure inhalable, thoracic and alveolic particles during morning and evening rush hours for five weekdays. From the study, we observed that the concentration levels of these particles were greatly influenced by transportation modes. Concentrations of inhalable particles were found higher during morning in auto rickshaw (332.81 ± 90.97 μg/m(3)) while the commuter of bus exhibited higher exposure of thoracic particles (292.23 ± 110.45 μg/m(3)) and car commuters were exposed to maximum concentrations of alveolic particles (222.37 ± 26.56 μg/m(3)). We observed that in evening car commuters experienced maximum concentrations of all sizes of particles among the four commuting modes. Interestingly, motorcycle commuters were exposed to lower levels of inhalable and thoracic particles during morning and evening hours as compared to other modes of transport. The mean values were found greater than the median values for all the modes of transport suggesting that positive skewed distributions are characteristics of naturally occurring phenomenon.

  9. Inflammatory Cytokines and White Blood Cell Counts Response to Environmental Levels of Diesel Exhaust and Ozone Inhalation Exposures

    EPA Science Inventory

    Epidemiological observations of urban inhalation exposures to diesel exhaust (DE) and ozone (O3) have shown pre-clinical cardiopulmonary responses in humans. Identifying the key biological mechanisms that initiate these health bioindicators is difficult due to variability in envi...

  10. Exposure versus internal dose: Respiratory tract deposition modeling of inhaled asbestos fibers in rats and humans (Presentation Poster)

    EPA Science Inventory

    Exposure to asbestos is associated with respiratory diseases, including asbestosis, lung cancer and mesothelioma. Internal fiber dose depends on fiber inhalability and orientation, fiber density, length and width, and various deposition mechanisms (DM). Species-specific param...

  11. Increased Non-conducted P-wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

    EPA Science Inventory

    Exposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that ar...

  12. Exposure versus internal dose: Respiratory tract deposition modeling of inhaled asbestos fibers in rats and humans (Presentation Poster)

    EPA Science Inventory

    Exposure to asbestos is associated with respiratory diseases, including asbestosis, lung cancer and mesothelioma. Internal fiber dose depends on fiber inhalability and orientation, fiber density, length and width, and various deposition mechanisms (DM). Species-specific param...

  13. Inflammatory Cytokines and White Blood Cell Counts Response to Environmental Levels of Diesel Exhaust and Ozone Inhalation Exposures

    EPA Science Inventory

    Epidemiological observations of urban inhalation exposures to diesel exhaust (DE) and ozone (O3) have shown pre-clinical cardiopulmonary responses in humans. Identifying the key biological mechanisms that initiate these health bioindicators is difficult due to variability in envi...

  14. Increased Non-conducted P-wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

    EPA Science Inventory

    Exposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that ar...

  15. Inhalation toxicity of 4-ethoxyaniline (p-phenetidine): critical analysis of results of subacute inhalation exposure studies in rats.

    PubMed

    Pauluhn, J; Mohr, U

    2001-11-01

    This article addresses results from a single 4-h and repeated 1- and 4-wk inhalation exposure studies in Wistar rats with vapor and/or aerosol atmospheres of 4-ethoxyaniline (p-phenetidine). Groups of 10 rats/sex were exposed nose-only to mean analytical concentrations of 11.1, 86.2, and 882.6 mg p-phenetidine/m(3) using an exposure regimen of 6 h/day, 5 days/wk for 4 wk. Concentrations were selected based on results from a pilot study in which rats were exposed under identical conditions on 5 consecutive days for 6 h/day to mean analytical concentrations of 38.2, 133.0, and 1247.6 mg/m(3). In repeated exposure studies, the focus of endpoints was on hematotoxicity. The LC50 was not determined, but no rats died following a single 4-h exposure to 5085 mg/m(3) as a mixture of vapor and aerosol. No mortality was observed either in the 1- or 4-wk studies. Rats exposed to 882.6 mg/m(3) and above evoked characteristic signs of toxicity that included cyanosis, with no apparent progression of findings during the exposure period. Animals exposed to 86.2 mg/m(3) and above exhibited a concentration-dependent, significant increase in blood methemoglobin and reticulocyte counts as well as a significant decrease in hemoglobin, hematocrit, and red blood cell counts. Spleen weights were significantly increased in groups exposed to 133.0 mg/m(3) and above. Microscopic changes demonstrated an increased hematopoiesis (bone marrow smears) and splenic hemosiderosis at 86.2 and 882.6 mg/m(3) and a hepatic hemosiderosis only at 882.6 mg/m(3). These data suggest that the toxicity of p-phenetidine is similar to that of its structural analog aniline. Based on the erythrocytotoxicity occurring at 86.2 mg/m(3) and above, including the apparent reactive changes in bone marrow (increased erythropoiesis) and spleen (increased erythroclasia), the no-observed-adverse-effect level (NOAEL) of the 4-wk study was 11.1 mg/m(3) air and that of the 1-wk study was 38.2 mg/m(3) air. This difference in

  16. Exposure and inhalation risk assessment in an aluminium cast-house.

    PubMed

    Godderis, L; Vanderheyden, W; Van Geel, J; Moens, G; Masschelein, R; Veulemans, H

    2005-12-01

    To date the exposure, absorption and respiratory health effects of cast-house workers have not been described since most studies performed in the aluminium industry are focused on exposure and health effects of potroom personnel. In the present study, we assessed the external exposure and the absorbed dose of metals in personnel from the aluminium cast house. This was combined with an evaluation of respiratory complaints and the lung function of the personnel. 30 workers from an aluminium casting plant participated and 17 individuals of the packaging and distribution departments were selected as controls. The exposure was assessed by the quantification of total inhalable fume with metal fraction and by the determination of urinary aluminium, chromium, beryllium, manganese and lead concentration. Carbon monoxide (CO), carbon dioxide (CO2), aldehydes and polyaromatic hydrocarbons and man-made mineral fibres concentration were assessed as well. In order to evaluate their respiratory status each participant filled out a questionnaire and their lung function was tested by forced spirometry. Total inhalable fume exposure was maximum 4.37 mg m(-3). Exposure to the combustion gases, man-made mineral fibres and metal fume was well below the exposure limits. Beryllium could not be detected in the urine. The values of aluminium, manganese and lead in the urine were all under the respective reference value. One individual had a urinary chromium excretion above the ACGIH defined biological exposure index (BEI) of 30 microg g(-1) creatinine. There was no significant difference in any of the categories of the respiratory questionnaire and in the results of the spirometry between cast house personnel and referents (Chi-square, all p > 0.05). Exposure in cast houses seem to be acceptable under these conditions. However, peak exposure to fumes cannot be excluded and the potential risk of chromium and beryllium exposure due to the recycling of aluminium requires further attention.

  17. Applicability of a modified MCE filter method with Button Inhalable Sampler for monitoring personal bioaerosol inhalation exposure.

    PubMed

    Xu, Zhenqiang; Xu, Hong; Yao, Maosheng

    2013-05-01

    In this study, a "modified" mixed cellulose ester (MCE) filter culturing method (directly placing filter on agar plate for culturing without extraction) was investigated in enumerating airborne culturable bacterial and fungal aerosol concentration and diversity both in different environments. A Button Inhalable Sampler loaded with a MCE filter was operated at a flow rate of 5 L/min to collect indoor and outdoor air samples using different sampling times: 10, 20, and 30 min in three different time periods of the day. As a comparison, a BioStage impactor, regarded as the gold standard, was operated in parallel at a flow rate of 28.3 L/min for all tests. The air samples collected by the Button Inhalable Sampler were directly placed on agar plates for culturing, and those collected by the BioStage impactor were incubated directly at 26 °C. The colony forming units (CFUs) were manually counted and the culturable concentrations were calculated both for bacterial and fungal aerosols. The bacterial CFUs developed were further washed off and subjected to polymerase chain reaction-denaturing gradient gel electrophoresis (DGGE) for diversity analysis. For fungal CFUs, microscopy method was applied to studying the culturable fungal diversity obtained using different methods. Experimental results showed that the performance of two investigated methods varied with sampling environments and microbial types (culturable bacterial and fungal aerosols). For bacterial aerosol sampling, both methods were shown to perform equally well, and in contrast the "modified" MCE filter method was demonstrated to enumerate more culturable fungal aerosols than the BioStage impactor. In general, the microbial species richness (number of gel bands) was observed to increase with increasing collection time. For both methods, the DGGE gel patterns were observed to vary with sampling time and environment despite of similar number of gel bands. In addition, an increase in sampling time from 20 to 30 min

  18. Risk assessment of inhalation exposure to Particulate Polycyclic Aromatic Hydrocarbons in school children

    NASA Astrophysics Data System (ADS)

    Jyethi, D. S.; Khillare, P. S.; Sarkar, S.

    2013-12-01

    Polycyclic aromatic hydrocarbons (PAHs) associated with the inhalable fraction of particulate matter were determined for one year (2009-10) at an urban site located in proximity of industrial and heavy traffic roads in Delhi, India. PM10 (aerodynamic diameter ≤10 μm) levels were ~11.6 times the World Health Organization standard. Vehicular (59.5%) and coal combustion (40.5%) sources accounted for the high levels of PAHs (range 38.1 ng m-3 - 217.3 ng m-3) with four and five ring PAHs having ~80 % contribution. Atmospheric distribution of total PAHs were heavily influenced (~75%) by the carcinogenic species and the B[a]P equivalent concentrations, through both TEF and MEF approach, exhibited highest exposure risks during winter. Extremely high daily inhalation exposure of PAHs was observed during winter (439.43 ng day-1) followed by monsoon (232.59 ng day-1) and summer (171.08 ng day-1). Daily inhalation exposure of PAHs to school children during a day exhibited the trend: school hours>commuting to school>resting period, in all the seasons. Vehicular source contributions to daily PAH levels were significantly correlated (r=0.94, p<0.001) with the daily inhalation exposure level of school children. It is important to note that health hazards posed by vehicular pollution are born disproportionately by children attending certain schools based on the location of the school. Interestingly, since India is a tropical country, most of the buildings are naturally ventilated and their air exchange rates are higher than heating, ventilation, and air conditioning (HVAC)-equipped buildings, resulting into a significant impact of outdoor air on indoor air quality. In the apparent absence of any indoor PAH sources, outdoor concentrations and in turn air exchange rates (that are specific for infiltration and natural ventilation pathways) play a key role in assessing PAH exposure. A conservative estimate of ~11 excess cancer cases in children during childhood and ~ 652 cases for a

  19. [The risk of inhalable wood dust: assessment of workers exposure wood working factories].

    PubMed

    Zakrzewska, M; Tarzia, V; Iannò, A; Capone, P P; Campopiano, A; Giardino, R; Villella, E

    2007-01-01

    The International Agency for Research on Cancer RC) has classified wood dust as carcinogenic to humans based on demiological and experimental evidence. Exposure to wood dust may use respiratory and dermal symptoms and diseases. The aim of this work was to estimate occupational exposure to inhalable wood dust adopting the formal procedure described by UNI EN 689/97. The exposure of 23 workers in three different working day was measured. In total, 69 personal air samplings were carried out at five wood working factories. Inhalable fraction of airborne dust was collected on 5 microm pore size, 25 mm diameter PVC filters utilizing the IOM samplers. The quantity of the wood dust was determined with gravimetric method. The results show that about 13% of the exposure values exceed the limit of 5 mg/m3 specified by the Italian Law Decree 66/2000 and about 48% of personal exposures are lower then the limit value. Prevention measures, technological solutions and personal protection equipment should be adopted in order to reduce worker's exposure.

  20. Characterization of inhalation exposure to jet fuel among U.S. Air Force personnel.

    PubMed

    Merchant-Borna, Kian; Rodrigues, Ema G; Smith, Kristen W; Proctor, Susan P; McClean, Michael D

    2012-07-01

    Jet propulsion fuel-8 (JP-8) is the primary jet fuel used by the US military, collectively consuming ~2.5 billion gallons annually. Previous reports suggest that JP-8 is potentially toxic to the immune, respiratory, and nervous systems. The objectives of this study were to evaluate inhalation exposure to JP-8 constituents among active duty United States Air Force (USAF) personnel while performing job-related tasks, identify significant predictors of inhalation exposure to JP-8, and evaluate the extent to which surrogate exposure classifications were predictive of measured JP-8 exposures. Seventy-three full-time USAF personnel from three different air force bases were monitored during four consecutive workdays where personal air samples were collected and analyzed for benzene, ethylbenzene, toluene, xylenes, total hydrocarbons (THC), and naphthalene. The participants were categorized a priori into high- and low-exposure groups, based on their exposure to JP-8 during their typical workday. Additional JP-8 exposure categories included job title groups and self-reported exposure to JP-8. Linear mixed-effects models were used to evaluate predictors of personal air concentrations. The concentrations of THC in air were significantly different between a priori exposure groups (2.6 mg m(-3) in high group versus 0.5 mg m(-3) in low, P < 0.0001), with similar differences observed for other analytes in air. Naphthalene was strongly correlated with THC (r = 0.82, P < 0.0001) and both were positively correlated with the relative humidity of the work environment. Exposures to THC and naphthalene varied significantly by job categories based on USAF specialty codes and were highest among personnel working in fuel distribution/maintenance, though self-reported exposure to JP-8 was an even stronger predictor of measured exposure in models that explained 72% (THC) and 67% (naphthalene) of between-worker variability. In fact, both self-report JP-8 exposure and a priori exposure groups

  1. Lung carcinogenesis in rats after inhalation exposure to (237)NpO2.

    PubMed

    Dudoignon, N; Guézingar-Liébard, F; Guillet, K; L'Hullier, I; Rateau, G; Monchaux, G; Fritsch, P

    1999-12-01

    The results of several studies of experimental carcinogenesis suggest that, after inhalation of alpha-particle emitters, lung tumor incidence varies depending on the exposure rate and dose distribution in the tissue. In the case of transuranics, the main influencing factor would be the specific alpha-particle activity of the inhaled actinide. To confirm these results, long-term studies were performed using male Sprague-Dawley rats exposed to (237)NpO(2) by inhalation. The initial lung burdens of the animals ranged from 0. 1 to about 7 kBq. The rats were followed during their life span and weighed regularly, and their lung burdens were determined in vivo and at death to estimate the lung dose. At death, the incidence of lung tumors and their malignancy and histological types were analyzed. The analysis revealed a typically linear-quadratic dose response for incidence of malignant lung neoplasm and a differential dose response for various types of tumors. Although these results confirm the influence of the activity of the inhaled actinide oxide, further experiments are needed to be able to compare a more homogeneous population of animals.

  2. Kinetics of deposition and clearance of inhaled mineral dusts during chronic exposure.

    PubMed Central

    Vincent, J H; Johnston, A M; Jones, A D; Bolton, R E; Addison, J

    1985-01-01

    New inhalation studies have been carried out with rats exposed to UICC (Union International Contre le Cancer) amosite asbestos, with the main aim of further elucidating the factors the influence the accumulation of dust in the lung during prolonged chronic exposure. The results show that, for exposure times beyond a few weeks, the lung burden rises linearly and does not level off as predicted by simple models based on ideas taken from the 1966 report of the Task Group on Lung Dynamics. Furthermore, the lung burden is found to scale directly in proportion to the exposure concentration in a way that seems to contradict the overload hypothesis stated earlier. Nevertheless, the general pattern exhibited by our results for asbestos is markedly similar to that found elsewhere for rats inhaling diesel fume, leading to the suggestion that it is general (and not specific to fibrous dust); and the hypothesis that, whereas overload of clearance can take place at high lung burdens after exposure has ceased, it is cancelled by the sustained stimulus to clearance mechanisms provided by the continuous challenge of chronic exposure. The linearity of the increase in lung burden is explained in terms of a kinetic model involving sequestration of some inhaled material to parts of the lung where it is difficult to clear. The particular sequestration model favoured is one where, the longer a particle remains in the lung without being cleared, the more likely it will be sequestrated (and therefore less likely cleared). It is believed that such ideas may eventually be useful in forming exposure-dose relations for epidemiology. PMID:2864076

  3. Increased susceptibility to RSV infection by exposure to inhaled diesel engine emissions.

    PubMed

    Harrod, Kevin S; Jaramillo, Richard J; Rosenberger, Cynthia L; Wang, Shan-Ze; Berger, Jennifer A; McDonald, Jacob D; Reed, Matthew D

    2003-04-01

    Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection in humans, the underlying cellular and molecular mechanisms have not been well studied in experimental systems. The current study assessed the impact of inhaled diesel engine emissions (DEE) on the host response in vivo to a common pediatric respiratory pathogen, respiratory syncytial virus (RSV). Using a relatively resistant mouse model of RSV infection, prior exposure to either 30 microg/m3 particulate matter (PM) or 1,000 microg/m3 PM of inhaled DEE (6 h/d for seven consecutive days) increased lung inflammation to RSV infection as compared with air-exposed RSV-infected C57Bl/6 mice. Inflammatory cells in bronchoalveolar lavage fluid were increased in a dose-dependent manner with regard to the level of DEE exposure, concomitant with increased levels of inflammatory mediators. Lung histology analysis indicated pronounced peribronchial and peribronchiolar inflammation concordant with the level of DEE exposure during infection. Mucous cell metaplasia was markedly increased in the airway epithelium of DEE-exposed mice following RSV infection. Interestingly, both airway and alveolar host defense and immunomodulatory proteins were attenuated during RSV infection by prior DEE exposure. DEE-induced changes in inflammatory and lung epithelial responses to infection were associated with increased RSV gene expression in the lungs following DEE exposure. These findings are consistent with the concept that DEE exposure modulates the lung host defense to respiratory viral infections and may alter the susceptibility to respiratory infections leading to increased lung disease.

  4. Maternal and Fetal Blood and Organ Toluene Levels in Rats Following Acute and Repeated Binge Inhalation Exposure

    PubMed Central

    Bowen, Scott E.; Hannigan, John H.; Irtenkauf, Susan

    2007-01-01

    Inhalation of organic solvents is a persistent form of drug abuse with particular concern being the abuse of inhalants by women of child-bearing age. While studies have begun assessing postnatal outcomes of offspring exposed prenatally to inhalants, relatively little is known about the distribution of toluene in blood and body tissues of pregnant, inhalant-abusing women, or in the fetuses. The present study assessed the tissue toluene levels attained following brief toluene exposures using a pre-clinical rat model of maternal inhalant abuse. Timed-pregnant Sprague-Dawley rats were exposed to toluene at 8,000 or 12,000 parts per million (ppm) for 15, 30 or 45 min/exposure. Exposures occurred twice each day from gestational day 8 (GD8) through GD20. Immediately following the second exposure on GD8, GD14 and GD20 blood was taken from the saphenous vein of the dams. Following saphenous vein blood collection on GD20, dams were sacrificed and trunk blood was collected along with maternal tissue specimens from cerebellum, heart, lung, kidney and liver. The placenta, amniotic fluid and fetal brain were also collected. Results demonstrated that maternal saphenous blood toluene levels increased as the inhaled concentration of toluene and duration of exposure increased. The maternal cerebellum, heart, kidney and liver appeared to be saturated after 30 min on GD20 such that toluene levels in those organs were equivalent across all ambient concentrations of inhaled toluene. Toluene levels also increased in fetal brain as the inhaled concentration of toluene increased and in placenta and amniotic fluid as the duration of exposure increased. Toluene levels in all tissues at GD20, except maternal lung and amniotic fluid, were higher than in maternal saphenous blood suggesting that toluene concentrated in those organs. Measurement of toluene levels in blood and other tissues following repeated toluene exposure demonstrated that toluene readily reaches a variety of potential sites

  5. Evaluation of newly developed nose-only inhalation exposure chamber for nanoparticles.

    PubMed

    Jeon, KiSoo; Yu, Il Je; Ahn, Kang-Ho

    2012-08-01

    In this study, a direct-flow-type nose-only exposure chamber developed for inhalation toxicity experiments using a numerical analysis and experiments is evaluated. Maintaining a uniform flow rate and test article concentration are the critical factors when designing an inhalation exposure chamber. Therefore, this study evaluated whether the flow rate and particle size distribution at the injection nozzles at each port could be maintained with a deviation below 10%. To achieve this requirement, a nose-only exposure chamber flow field was simulated using a numerical analysis method, i.e. computational fluid dynamics (CFD) code FLUENT 6.3.26. Based on the simulation results, a test chamber was built and tested. The flow velocity was measured at the injection nozzle of the chamber and the aerosol particle size distribution was also measured at each port while inserting the test material into the exposure chamber. The results indicated that a uniform flow field distribution at each stage and port, the deviation of the flow velocity, and particle size distribution were all within 10%. Thus, the resulting nose-only exposure chamber could be described as well-designed.

  6. A Novel System to Generate WTC Dust Particles for Inhalation Exposures

    PubMed Central

    Vaughan, Joshua M.; Garrett, Brittany; Prophete, Colette; Horton, Lori; Sisco, Maureen; Soukup, Joleen M.; Zelikoff, Judith; Ghio, Andrew; Peltier, Richard E.; Asgharian, Bahman; Chen, Lung-Chi; Cohen, Mitchell D.

    2014-01-01

    First Responders (FR) present at Ground Zero within the first 72-hr after the WTC (World Trade Center) collapse have progressively exhibited significant respiratory injury. The majority (>96%) of WTC dusts were >10 μm and no studies have examined potential health effects of this size fraction. This study sought to develop a system to generate and deliver supercoarse (10–53 μm) WTC particles to a rat model in a manner that mimicked FR exposure scenarios. A modified Fishing Line generator was integrated onto an intratracheal inhalation (ITIH) system that allowed for a bypassing of the nasal passages so as to mimic FR exposures. Dust concentrations were measured gravimetrically; particle size distribution was measured via elutriation. Results indicate that the system could produce dusts with 23 μm MMAD at levels up to ≥ 1200 mg/m3. To validate system utility, F344 rats were exposed for 2-hr to ≈100 mg WTC dust/m3. Exposed rats had significantly increased lung weight and levels of select tracer metals 1-hr post-exposure. Using this system, it is now possible to conduct relevant inhalation exposures to determine adverse WTC dusts impacts on the respiratory system. Furthermore, this novel integrated Fishing Line-ITIH system could potentially be used in the analyses of a wide spectrum of other dusts/pollutants of sizes previously untested or delivered to the lungs in ways that did not reflect realistic exposure scenarios. PMID:24220216

  7. Proposal for reference concentrations (RfC) for inhalation exposure to methanol.

    PubMed

    Vyskocil; Viau

    2000-12-01

    A tentative reference concentration (RfC) for methanol in ambient air, i.e. an exposure concentration below which adverse effects are not expected to occur, was derived from the analysis of the toxicological data available in the literature. Well-documented studies that correlate environmental levels of methanol with observed toxic effects have not been found in the literature, nor have any long-term epidemiological studies of chronic low-level occupational exposure been found. Assessment of RfC for acute inhalation exposure is based on a human study (n=26 subjects) with a 'tentative' NOAEL of 262 mg/m(3). The calculated RfC for 1 h exposure is 104.8 mg/m(3). The RfC is given a low confidence rating as there was only one methanol concentration used. A well designed study on monkeys served as the basis for the assessment of RfC for chronic inhalation exposure. In this study, 13.1 and 131 mg/m(3) were considered as NOAEL and LOAEL, respectively. The calculated RfC is 0.38 mg/m(3). The overall database is weak, lacking data on reproductive and developmental endpoints in human or non-human primates. Nevertheless, the RfC is given a medium confidence rating because of the strength of the principal study.

  8. Early intrauterine exposure to tobacco-inhaled products and obesity.

    PubMed

    Toschke, A M; Montgomery, S M; Pfeiffer, U; von Kries, R

    2003-12-01

    An association between maternal smoking during pregnancy and offspring obesity has been reported. This study assessed the impact of maternal smoking during the first trimester. Data on 4,974 German children aged 5-6 years were obtained at school entry health examinations in 2001-2002 in Bavaria. Obesity was defined by body mass index using International Obesity Task Force cutpoints. Prevalence of obesity was 1.9% (95% confidence interval (CI): 1.5, 2.4) in offspring of never smokers, 4.5% (95% CI: 2.9, 6.7) for maternal smoking during the first trimester only, and 5.9% (95% CI: 3.8, 8.7) for maternal smoking throughout pregnancy. Unadjusted odds ratios were higher for maternal smoking throughout pregnancy (odds ratio = 3.23, 95% CI: 2.00, 5.21) compared with the first trimester only (odds ratio = 2.41, 95% CI: 1.49, 3.91). Adjusted odds ratios were similar: 1.70 (95% CI: 1.02, 2.87) for maternal smoking throughout pregnancy and 2.22 (95% CI: 1.33, 3.69) for maternal smoking in the first trimester only. When modeled together, no statistically significant difference in obesity risk was found between maternal smoking in the first trimester compared with throughout pregnancy. The effect of intrauterine tobacco exposure on childhood obesity may depend largely on cigarette smoking during the first trimester, whereas the additional impact of smoking throughout pregnancy might be due to confounding by sociodemographics. Women should be encouraged to quit smoking prior to conception.

  9. Health Risk Assessment of Inhalation Exposure to Formaldehyde and Benzene in Newly Remodeled Buildings, Beijing

    PubMed Central

    Huang, Lihui; Mo, Jinhan; Sundell, Jan; Fan, Zhihua; Zhang, Yinping

    2013-01-01

    Objective To assess health risks associated with inhalation exposure to formaldehyde and benzene mainly emitted from building and decoration materials in newly remodeled indoor spaces in Beijing. Methods We tested the formaldehyde and benzene concentrations in indoor air of 410 dwellings and 451 offices remodeled within the past year, in which the occupants had health concerns about indoor air quality. To assess non-carcinogenic health risks, we compared the data to the health guidelines in China and USA, respectively. To assess carcinogenic health risks, we first modeled indoor personal exposure to formaldehyde and benzene using the concentration data, and then estimated the associated cancer risks by multiplying the indoor personal exposure by the Inhalation Unit Risk values (IURs) provided by the U.S. EPA Integrated Risk Information System (U.S. EPA IRIS) and the California Office of Environmental Health Hazard Assessment (OEHHA), respectively. Results (1) The indoor formaldehyde concentrations of 85% dwellings and 67% offices were above the acute Reference Exposure Level (REL) recommended by the OEHHA and the concentrations of all tested buildings were above the chronic REL recommended by the OEHHA; (2) The indoor benzene concentrations of 12% dwellings and 32% offices exceeded the reference concentration (RfC) recommended by the U.S. EPA IRIS; (3) The median cancer risks from indoor exposure to formaldehyde and benzene were 1,150 and 106 per million (based on U.S. EPA IRIS IURs), 531 and 394 per million (based on OEHHA IURs). Conclusions In the tested buildings, formaldehyde exposure may pose acute and chronic non-carcinogenic health risks to the occupants, whereas benzene exposure may pose chronic non-carcinogenic risks to the occupants. Exposure to both compounds is associated with significant carcinogenic risks. Improvement in ventilation, establishment of volatile organic compounds (VOCs) emission labeling systems for decorating and refurbishing materials

  10. NEUROTOXICITY FOLLOWING ACUTE INHALATION EXPOSURE TO THE OIL DISPERSANT COREXIT EC9500A

    PubMed Central

    Sriram, Krishnan; Lin, Gary X.; Jefferson, Amy M.; Goldsmith, William T.; Jackson, Mark; McKinney, Walter; Frazer, David G.; Robinson, Victor A.; Castranova, Vincent

    2015-01-01

    Consequent to the 2010 Deepwater Horizon oil spill in the Gulf of Mexico, there is an emergent concern about the short- and long-term adverse health effects of exposure to crude oil, weathered-oil products, and oil dispersants among the workforce employed to contain and clean up the spill. Oil dispersants typically comprise of a mixture of solvents and surfactants that break down floating oil to micrometer-sized droplets within the water column, thus preventing it from reaching the shorelines. As dispersants are generally sprayed from the air, workers are at risk for exposure primarily via inhalation. Such inhaled fractions might potentially permeate or translocate to the brain via olfactory or systemic circulation, producing central nervous system (CNS) abnormalities. To determine whether oil dispersants pose a neurological risk, male Sprague-Dawley rats were exposed by whole-body inhalation exposure to a model oil dispersant, COREXIT EC9500A (CE; approximately 27 mg/m3 × 5 h/d × 1 d), and various molecular indices of neural dysfunction were evaluated in discrete brain areas, at 1 or 7 d postexposure. Exposure to CE produced partial loss of olfactory marker protein in the olfactory bulb. CE also reduced tyrosine hydroxylase protein content in the striatum. Further, CE altered the levels of various synaptic and neuronal intermediate filament proteins in specific brain areas. Reactive astrogliosis, as evidenced by increased expression of glial fibrillary acidic protein, was observed in the hippocampus and frontal cortex following exposure to CE. Collectively, these findings are suggestive of disruptions in olfactory signal transduction, axonal function, and synaptic vesicle fusion, events that potentially result in an imbalance in neurotransmitter signaling. Whether such acute molecular aberrations might persist and produce chronic neurological deficits remains to be ascertained. PMID:21916746

  11. Neurotoxicity following acute inhalation exposure to the oil dispersant COREXIT EC9500A.

    PubMed

    Sriram, Krishnan; Lin, Gary X; Jefferson, Amy M; Goldsmith, William T; Jackson, Mark; McKinney, Walter; Frazer, David G; Robinson, Victor A; Castranova, Vincent

    2011-01-01

    Consequent to the 2010 Deepwater Horizon oil spill in the Gulf of Mexico, there is an emergent concern about the short- and long-term adverse health effects of exposure to crude oil, weathered-oil products, and oil dispersants among the workforce employed to contain and clean up the spill. Oil dispersants typically comprise of a mixture of solvents and surfactants that break down floating oil to micrometer-sized droplets within the water column, thus preventing it from reaching the shorelines. As dispersants are generally sprayed from the air, workers are at risk for exposure primarily via inhalation. Such inhaled fractions might potentially permeate or translocate to the brain via olfactory or systemic circulation, producing central nervous system (CNS) abnormalities. To determine whether oil dispersants pose a neurological risk, male Sprague-Dawley rats were exposed by whole-body inhalation exposure to a model oil dispersant, COREXIT EC9500A (CE; approximately 27 mg/m(3) × 5 h/d × 1 d), and various molecular indices of neural dysfunction were evaluated in discrete brain areas, at 1 or 7 d postexposure. Exposure to CE produced partial loss of olfactory marker protein in the olfactory bulb. CE also reduced tyrosine hydroxylase protein content in the striatum. Further, CE altered the levels of various synaptic and neuronal intermediate filament proteins in specific brain areas. Reactive astrogliosis, as evidenced by increased expression of glial fibrillary acidic protein, was observed in the hippocampus and frontal cortex following exposure to CE. Collectively, these findings are suggestive of disruptions in olfactory signal transduction, axonal function, and synaptic vesicle fusion, events that potentially result in an imbalance in neurotransmitter signaling. Whether such acute molecular aberrations might persist and produce chronic neurological deficits remains to be ascertained.

  12. Exposure to inhalable dust, wheat flour and alpha-amylase allergens in industrial and traditional bakeries.

    PubMed

    Bulat, Petar; Myny, Katrien; Braeckman, Lutgart; van Sprundel, Marc; Kusters, Edouard; Doekes, Gert; Pössel, Kerstin; Droste, Jos; Vanhoorne, Michel

    2004-01-01

    This study was designed to characterize exposure to inhalable dust, wheat flour and alpha-amylase allergens in industrial and traditional bakeries. The study included 70 bakeries from the northern part of Belgium. Based on the degree of automation and a clear division of individual job tasks, four bakeries were identified as industrial and the remaining 66 were identified as traditional ones. Personal, as well as stationary, samples of inhalable dust were collected during full shift periods, usually 5-7 h. The portable pumps aspirated 2 l/min through Teflon personal dust samplers (Millipore, pore size 1.0 microm) mounted in PAS-6 sampling heads. In the collected samples the inhalable dust, wheat flour and alpha-amylase allergens were determined. Wheat flour allergens were measured using enzyme-linked immunosorbent assay inhibition and an antiwheat IgG4 serum pool. The alpha-amylase allergens were measured using a sandwich enzyme immunoassay with affinity-purified polyclonal rabbit IgG antibodies. In total, 440 samples (300 personal and 140 stationary) were processed. The highest inhalable dust exposure was observed in traditional bakeries among bread [geometric mean (GM) 2.10 mg/m3] and bread and pastry workers (GM 1.80 mg/m3). In industrial bakeries the highest dust exposure was measured in bread-producing workers (GM 1.06 mg/m3). Similar relations were observed for wheat flour and alpha-amylase allergens. Bread baking workers in traditional bakeries had the highest exposure to both allergens (wheat flour GM 22.33 microg/m(3), alpha-amylase GM 0.61 ng/m3). The exposure to wheat flour and alpha-amylase allergens in industrial bakeries was higher in bread baking workers (wheat flour GM 6.15 microg/m3, alpha-amylase GM 0.47 ng/m3) than in bread packing workers (wheat flour GM 2.79 microg/m3, alpha-amylase GM 0.15 ng/m3). The data presented suggest that, on average, exposure in the Belgium bakeries studied-industrial as well as traditional-is lower than or similar to

  13. Case Study: Three Acute 241Am Inhalation Exposures with DTPA Therapy

    SciTech Connect

    Carbaugh, Eugene H.; Lynch, Timothy P.; Cannon, Curt; Lewis, Loren L.

    2010-10-01

    Three workers incurred inhalation exposures to 241Am oxide as a result of waste sorting and compaction activities. The magnitudes of the exposures were not fully recognized until the following day when an in vivo chest count identified a significant lung deposition of 241Am in a male worker, and DTPA chelation therapy was initiated. Two additional workers (one female and one male) were then identified as sufficiently exposed to also warrant therapy. In vivo bioassay measurements were performed over the ensuing 6 months to quantify the 241Am activity in the lungs, liver, and skeleton. Urine and fecal samples were collected and showed readily detectable 241Am. Clinical lab tests and medical evaluations all showed normal results. There were no significant adverse clinical health effects from the therapy. The estimated 241Am inhalation intakes for the three workers were 1800 Bq, 630 Bq, and 150 Bq. Lung retention showed somewhat longer pulmonary clearance half-times than standard inhalation class W or absorption Type M assumptions. The three underwent slightly different therapy regimes, with therapy effectiveness factors (defined as the ratio of the reference doses without therapy relative to the final assessed doses) of 4.65, 1.93, and 1.67, respectively.

  14. Source identification of ambient PM 2.5 during summer inhalation exposure studies in Detroit, MI

    NASA Astrophysics Data System (ADS)

    Morishita, Masako; Keeler, Gerald J.; Wagner, James G.; Harkema, Jack R.

    Particulate air pollution is associated with cardiopulmonary morbidity and mortality in heavily populated urban centers of the United States. Because ambient fine particulate matter (aerodynamic diameter ⩽2.5 μm; PM 2.5) is a complex mixture resulting from multiple sources and variable atmospheric conditions, it is difficult to identify specific components of PM 2.5 that are responsible for adverse health effects. During four consecutive summers from 2000 to 2003 we characterized the ambient gaseous and PM 2.5 air quality in an urban southwest Detroit community where childhood asthma hospitalization rates are more than twice the statewide average. Both integrated and continuous PM measurements together with gaseous air pollution measurements were performed using a mobile air research facility, AirCARE1, in which concurrent toxicological studies were being conducted. Chemical and physical characterizations of PM 2.5 as well as receptor modeling using positive matrix factorization (PMF) were completed. Results from PMF indicated that six major sources contributed to the observed ambient PM 2.5 mass during the summer months. Primary sources included (1) coal combustion/secondary sulfate aerosol, (2) motor vehicle/urban road dust, (3) municipal waste incinerators, (4) oil combustion/refineries, (5) sewage sludge incinerators, and (6) iron/steel manufacturing. Although the contribution of the coal/secondary sulfate aerosol source was greater than other factors, increased levels of urban PM 2.5 from local combustion sources were also observed. In addition to characterization of ambient PM 2.5 and their sources in southwest Detroit, this paper discusses possible associations of ambient PM 2.5 from local combustion sources, specifically incinerator and refinery emissions and the observed adverse health effects during the inhalation exposure campaigns.

  15. 5-Day repeated inhalation and 28-day post-exposure study of graphene.

    PubMed

    Shin, Jae Hoon; Han, Sung Gu; Kim, Jin Kwon; Kim, Boo Wook; Hwang, Joo Hwan; Lee, Jong Seong; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Keun Soo; Lee, Heon Sang; Song, Nam Woong; Ahn, Kangho; Yu, Il Je

    2015-01-01

    Graphene has recently been attracting increasing attention due to its unique electronic and chemical properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats. A total of three groups (20 rats per group) were compared: (1) control (ambient air), (2) low concentration (0.68 ± 0.14 mg/m(3) graphene) and (3) high concentration (3.86 ± 0.94 mg/m(3) graphene). The rats were exposed to graphene for 6 h/day for 5 days, followed by recovery for 1, 3, 7 or 28 days. The bioaccumulation and macrophage ingestion of the graphene were evaluated in the rat lungs. The exposure to graphene did not change the body weights or organ weights of the rats after the 5-day exposure and during the recovery period. No statistically significant difference was observed in the levels of lactate dehydrogenase, protein and albumin between the exposed and control groups. However, graphene ingestion by alveolar macrophages was observed in the exposed groups. Therefore, these results suggest that the 5-day repeated exposure to graphene only had a minimal toxic effect at the concentrations and time points used in this study.

  16. An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO₂ inhalation exposures.

    PubMed

    Demokritou, Philip; Gass, Samuel; Pyrgiotakis, Georgios; Cohen, Joel M; Goldsmith, William; McKinney, Walt; Frazer, David; Ma, Jane; Schwegler-Berry, Diane; Brain, Joseph; Castranova, Vincent

    2013-12-01

    Nanoscale CeO₂ is increasingly used for industrial and commercial applications, including catalysis, UV-shielding and as an additive in various nanocomposites. Because of its increasing potential for consumer and occupational exposures, a comprehensive toxicological characterisation of this nanomaterial is needed. Preliminary results from intratracheal instillation studies in rats point to cytotoxicity and inflammation, though these studies may not accurately use realistic nanoscale exposure profiles. By contrast, published in vitro cellular studies have reported limited toxicological outcomes for the case of nano-ceria. Here, the authors present an integrative study evaluating the toxicity of nanoscale CeO₂ both in vitro, using the A549 lung epithelial cell line, and in vivo using an intact rat model. Realistic nano-ceria exposure atmospheres were generated using the Harvard Versatile Engineered Nanomaterial Generation System (VENGES), and rats were exposed via inhalation. Finally, the use of a nanothin amorphous SiO₂ encapsulation coating as a means of mitigating CeO₂ toxicity was assessed. Results from the inhalation experiments show lung injury and inflammation with increased PMN and LDH levels in the bronchoalveolar lavage fluid of the CeO₂-exposed rats. Moreover, exposure to SiO₂-coated CeO₂ did not induce any pulmonary toxicity to the animals, representing clear evidence for the safe by design SiO₂-encapsualtion concept.

  17. Toxicological response of Sprague Dawley rats from inhalation exposure to perfluorooctane sulfonyl fluoride (POSF).

    PubMed

    Butenhoff, John L; Olsen, Geary W; Chang, Sue

    2017-04-05

    Perfluorooctane sulfonyl fluoride (POSF) was a volatile starting material in the production of perfluorooctane sulfonate (PFOS), a stable surfactant that has been extensively studied due to its ubiquitous environmental distribution and slow clearance in humans. Because the inhalation toxicity of POSF on repeated exposure has not been previously reported, the current study evaluated the inhalation toxicity of POSF at 30, 100, and 300ppm (v/v) in rats for up to 13 weeks with a four-week recovery period. The extent of PFOS formation was also measured because POSF hydrolyzed to form PFOS. In addition, detailed urinalysis and examination of the urinary bladder were included to determine if factors associated with the development of bladder cancer were present. Exposure to POSF at 300ppm was associated with reduction in body weight-gain, necrosis of laryngeal cartilage, increased lung and bronchi weight with septal thickening, and changes in alveolar macrophages. The microscopic observations in larynx and lung are consistent with likely hydrolysis of POSF to form hydrogen fluoride (HF). Exposure to POSF at 100 and 300ppm was associated with increased relative liver weight, hepatocellular hypertrophy (except for females exposed to 100ppm POSF), and lowering of serum cholesterol (male only). After 13 weeks of exposure to 30, 100, or 300ppm POSF, serum PFOS concentration approximated 7, 35, or 100μg/mL, respectively. Approximately 0.1% of inhaled POSF was converted to PFOS. No changes indicative of bladder effects were observed in these rats exposed to POSF at any dose.

  18. Acute Inhalation Exposure to Vaporized Methamphetamine Causes Lung Injury in Mice

    PubMed Central

    Wells, Sandra M.; Buford, Mary C.; Braseth, Sarah N.; Hutchison, James D.; Holian, Andrij

    2009-01-01

    Methamphetamine (MA) is currently the most widespread illegally used stimulant in the United States. Use of MA by smoking is the fastest growing mode of administration, which increases concerns about potential pulmonary and other medical complications. A murine exposure system was developed to study the pulmonary affects of inhaled MA. Mice were exposed to 25–100 mg vaporized MA and assessments were made 3 h following initiation of exposure to model acute lung injury. Inhalation of MA vapor resulted in dose-dependent increases in MA plasma levels that were in the range of those experienced by MA users. At the highest MA dose, histological changes were observed in the lung and small but significant increases in lung wet weight to body weight ratios (5.656 ± 0.176 mg/g for the controls vs. 6.706± 0.135 mg/g for the 100 mg MA-exposed mice) were found. In addition, there was 53% increase in total protein in bronchoalveolar lavage (BAL) fluid, greater than 20% increase in albumin levels in the BAL fluid, greater than 2.5-fold increase in lactate dehydrogenase levels in the BAL fluid, and reduced total BAL cell numbers (approximately 77% of controls). Levels of the early response cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 were dose-dependently increased in BAL fluid of MA-exposed mice. Exposure to 100 mg MA significantly increased free radical generation in the BAL cells to 107–146% of controls and to approximately 135% of the controls in lung tissue in situ. Together, these data show that acute inhalation exposure to relevant doses of volatilized MA is associated with elevated free radical formation and significant lung injury. PMID:18645723

  19. Biological effects of short-term, high-concentration exposure to methyl isocyanate. I. Study objectives and inhalation exposure design

    SciTech Connect

    Dodd, D.E.; Frank, F.R.; Fowler, E.H.; Troup, C.M.; Milton, R.M.

    1987-06-01

    Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC). Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations. The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage. All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration. MIC vapors were statically generated in a double chamber exposure design. Precautionary measures taken during exposures are discussed. Guinea pigs were more susceptible than rats to MIC exposure-related early mortality. A greater than one order of magnitude difference was observed between an MIC concentration that caused no early mortality in rats (3506 ppm) and an MIC concentration that caused partial (6%) early mortality in guinea pigs (225 ppm) for exposures of 10 to 15 min duration. For both species, the most noteworthy clinical signs during exposure were lacrimation, blepharospasm, and mouth breathing. Fifteen minute LC/sub 50/ tests with 14-day postexposure follow-up were conducted, and the LC/sub 50/ (95% confidence limit) values were 171 (114-256) ppm for rats and 112 (61-204) ppm for guinea pigs. Target exposure concentrations for the toxicologic investigations of MIC-induced early mortality were established. A short summary of pertinent results of Union Carbide Corporation's post-Bhopal toxicologic investigations is presented.

  20. Behavior of rock wool in rat lungs after exposure by nasal inhalation.

    PubMed

    Kudo, Yuichiro; Kohyama, Norihiko; Satoh, Toshihiko; Konishi, Yoshihito; Aizawa, Yoshiharu

    2006-11-01

    To evaluate the safety of rock wool (RW) fibers, we examined the biopersistence of RW fibers in the lungs of rats, based on the changes of fiber number and fiber size in the length and width, in a nose-only inhalation exposure study. Twenty male Fischer 344 rats (6 to 10 wk old) were exposed to RW fibers at a fiber concentration of 70.6 (20.4) fiber/m(3) and a dispersion density of 30.4 (6.6) mg/m(3) [arithmetic mean (SD)] continuously for 3 h daily for 5 consecutive days. Five rats each were sacrificed shortly after exposure ended (baseline group) and at 1, 2, and 4 wk after exposure, and their lung tissues were ashed by a low temperature plasma-asher. The numbers and sizes of fibers in the ash samples were determined using a phase contrast microscope and a computed image analyzer. The fiber numbers in the lungs at 4 wk after exposure had significantly decreased from the baseline value, i. e. shortly after exposure (p<0.05). The half-lives of RW fibers calculated using the one-compartment model were 32 d for total fibers and 10 d for fibers longer than 20 microm in length. Fiber number was 53.6% of the baseline at 4 wk after exposure (baseline group=100%). Likewise, fiber sizes had significantly decreased at 4 wk after exposure (p<0.05), probably because fibers had been dissolved in body fluid, phagocytosed by alveolar macrophages or discharged from the body by mucociliary movement. In future studies, it will be necessary to examine the carcinogenicity of RW fibers through long-term inhalation studies.

  1. Nanomaterial inhalation exposure from nanotechnology-based cosmetic powders: a quantitative assessment

    PubMed Central

    Nazarenko, Yevgen; Zhen, Huajun; Han, Taewon; Lioy, Paul J.

    2012-01-01

    In this study we quantified exposures to airborne particles ranging from 14 nm to 20 µm due to the use of nanotechnology-based cosmetic powders. Three nanotechnology-based and three regular cosmetic powders were realistically applied to a mannequin’s face while measuring the concentration and size distribution of inhaled aerosol particles. Using these data we calculated that the highest inhaled particle mass was in the coarse aerosol fraction (2.5–10 µm), while particles <100 nm made minimal contribution to the inhaled particle mass. For all powders, 85–93 % of aerosol deposition occurred in the head airways, while <10 % deposited in the alveolar and <5 % in the tracheobronchial regions. Electron microscopy data suggest that nanomaterials were likely distributed as agglomerates across the entire investigated aerosol size range (14 nm–20 µm). Thus, investigation of nanoparticle health effects should consider not only the alveolar region, but also other respiratory system regions where substantial nanomaterial deposition during the actual nanotechnology-based product use would occur. PMID:23175627

  2. Hepatotumorigenicity of ethyl tertiary-butyl ether with 2-year inhalation exposure in F344 rats.

    PubMed

    Saito, Arata; Sasaki, Toshiaki; Kasai, Tatuya; Katagiri, Taku; Nishizawa, Tomoshi; Noguchi, Tadashi; Aiso, Shigetoshi; Nagano, Kasuke; Fukushima, Shoji

    2013-05-01

    Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1,500 or 5,000 ppm (v/v) in whole-body inhalation chambers for 6 h/day, 5 days/week for 104 weeks. A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5,000 ppm, but not in females at any concentration. In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5,000 ppm. Regarding non-neoplastic lesions, rat-specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5,000 ppm. Increased incidences of urothelial hyperplasia of the pelvis were observed at 1,500 ppm and above, and mineral deposition was apparent in the renal papilla at 5,000 ppm in males. There were no treatment-related histopathological changes observed in any other organs or tissues in either sex. The present 2-year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats.

  3. Lung injury via oxidative stress in mice induced by inhalation exposure to rocket kerosene.

    PubMed

    Xu, Bingxin; Li, Chenglin; Wang, Jianying; Wu, Jihua; Si, Shaoyan; Liu, Zhiguo; Li, Jianzhong; Zhang, Jianzhong; Cui, Yan

    2015-01-01

    Rocket kerosene (RK) is a new rocket propellant. Toxicity occurs if a high level of RK is inhaled. To study the toxicity of RK in lung and the mechanisms of RK-induced lung jury, a total of 72 male ICR mice (1.5 months, adult) were randomly assigned to the RK exposure group (RKEG) and normal control group (NCG). Mice were whole-body exposed to room air or aerosol of 18000 mg/m3 RK for 4 hours. Histopathological analysis was performed to evaluate the pulmonary lesions. Oxidative stress was assessed by assay of MDA, SOD, GSH-PX and TAOC. Inflammatory response was estimated by detecting inflammatory cell counts, TNF-α and IL-6 protein levels in serum. The results showed that after 2 to 6 hours of RK exposure, pulmonary vascular dilatation, congestion and edematous widening of the alveolar septum were noted. After 12 to 24 hours post-exposure, diffuse hemorrhage in alveolar space were found, along with the progressive pulmonary vascular dilatation and edematous widening of alveolar septum. During 3 to 7 days of RK-exposure, inflammatory cells were scattered in the lung tissue. The pathological alterations of the lung were alleviated after 14 days post-exposure, and showed significant improvement after 21 days post-exposure. After 30 days of RK exposure, the pathological changes in the lung tissue were nearly recovered except the local thickening of the alveolar wall. Compared with NCG, RK inhalation produced a significant increase of MDA levels and a significant decrease of SOD, GSH-Px and TAOC activity in the lung after 2 hours post-exposure (P<0.05). There were significant increases of TNF-α and IL-6 protein levels in serum of mice in RKEG after 2, 6 and 12 hours and 1, 4 and 7 days post-exposure compared with NCG (P<0.05). TNF-α protein levels had a sharp increase after 4 days of exposure. IL-6 protein level was increased at early phase of experiment and then gradually decreased along with the prolonged course of exposure. Considering that the RK-induced lung

  4. Lung injury via oxidative stress in mice induced by inhalation exposure to rocket kerosene

    PubMed Central

    Xu, Bingxin; Li, Chenglin; Wang, Jianying; Wu, Jihua; Si, Shaoyan; Liu, Zhiguo; Li, Jianzhong; Zhang, Jianzhong; Cui, Yan

    2015-01-01

    Rocket kerosene (RK) is a new rocket propellant. Toxicity occurs if a high level of RK is inhaled. To study the toxicity of RK in lung and the mechanisms of RK-induced lung jury, a total of 72 male ICR mice (1.5 months, adult) were randomly assigned to the RK exposure group (RKEG) and normal control group (NCG). Mice were whole-body exposed to room air or aerosol of 18000 mg/m3 RK for 4 hours. Histopathological analysis was performed to evaluate the pulmonary lesions. Oxidative stress was assessed by assay of MDA, SOD, GSH-PX and TAOC. Inflammatory response was estimated by detecting inflammatory cell counts, TNF-α and IL-6 protein levels in serum. The results showed that after 2 to 6 hours of RK exposure, pulmonary vascular dilatation, congestion and edematous widening of the alveolar septum were noted. After 12 to 24 hours post-exposure, diffuse hemorrhage in alveolar space were found, along with the progressive pulmonary vascular dilatation and edematous widening of alveolar septum. During 3 to 7 days of RK-exposure, inflammatory cells were scattered in the lung tissue. The pathological alterations of the lung were alleviated after 14 days post-exposure, and showed significant improvement after 21 days post-exposure. After 30 days of RK exposure, the pathological changes in the lung tissue were nearly recovered except the local thickening of the alveolar wall. Compared with NCG, RK inhalation produced a significant increase of MDA levels and a significant decrease of SOD, GSH-Px and TAOC activity in the lung after 2 hours post-exposure (P < 0.05). There were significant increases of TNF-α and IL-6 protein levels in serum of mice in RKEG after 2, 6 and 12 hours and 1, 4 and 7 days post-exposure compared with NCG (P < 0.05). TNF-α protein levels had a sharp increase after 4 days of exposure. IL-6 protein level was increased at early phase of experiment and then gradually decreased along with the prolonged course of exposure. Considering that the RK-induced lung

  5. Most cancer in firefighters is due to radio-frequency radiation exposure not inhaled carcinogens.

    PubMed

    Milham, S

    2009-11-01

    Recent reviews and reports of cancer incidence and mortality in firefighters conclude that they are at an increased risk of a number of cancers. These include leukemia, multiple myeloma, non-Hodgkin's lymphoma, male breast cancer, malignant melanoma, and cancers of the brain, stomach, colon, rectum, prostate, urinary bladder, testes, and thyroid. Firefighters are exposed to a long list of recognized or probable carcinogens in combustion products and the presumed route of exposure to these carcinogens is by inhalation. Curiously, respiratory system cancers and diseases are usually not increased in firefighters as they are in workers exposed to known inhaled carcinogens. The list of cancers with increased risk in firefighters strongly overlaps the list of cancers at increased risk in workers exposed to electromagnetic fields (EMF) and radiofrequency radiation (RFR). Firefighters have increased exposure to RFR in the course of their work, from the mobile two-way radio communications devices which they routinely use while fighting fires, and at times from firehouse and fire vehicle radio transmitters. I suggest that some of the increased cancer risk in firefighters is caused by RFR exposure, and is therefore preventable. The precautionary principle should be applied to reduce the risk of cancer in firefighters, and workman's compensation rules will necessarily need to be modified.

  6. Determination of the toxicity of cyclotriphosphazene hydraulic fluid by 21-day repeated inhalation and dermal exposure.

    PubMed

    Kinkead, E; Kimmel, E; Wall, H; Grabau, J

    1990-11-01

    Cyclotriphosphazene (CTP) ester is one of a series of compounds developed for use as a fire-resistant hydraulic fluid. The most significant routes of industrial exposure to hydraulic fluids are dermal, because of spills or leaks, and aerosol inhalation from pressurized system leaks. This study was designed to evaluate the toxic effects associated with repeated or continuous exposure to CTP by both dermal and inhalation routes. Male and female Fischer 344 (F-344) rats were exposed for 3 weeks to air alone, or to 0.25, 0.50, or 1.00 mg CTP/L. No deaths or signs of toxic stress occurred during the exposure period. A depression in mean body weight gain and increases in numbers of pulmonary alveolar macrophages and renal hyaline droplets were noted in both genders. Male and female New Zealand White (NZW) rabbits were treated dermally for 3 weeks with mineral oil, or 0.25, 0.50, or 1.00 g CTP/kg. No toxic effects were noted in either gender of rabbits.

  7. Assessment of the genotoxicity of trichloroethylene in the in vivo micronucleus assay by inhalation exposure.

    PubMed

    Wilmer, J W; Spencer, P J; Ball, N; Bus, J S

    2014-05-01

    The in vivo genotoxic potential of trichloroethylene (TCE) was evaluated by examining the incidence of micronucleated polychromatic erythrocytes (MN-PCEs) in the bone marrow. Groups of male CD rats were exposed by inhalation to targeted concentrations of 0 (negative control), 50, 500, 2500 or 5000 ppm for 6 consecutive hours on a single day. The exposure concentrations were selected to overlap those employed by a published study that reported a 2- to 3-fold increase in the frequency of micronuclei in male rats following a single inhalation exposure to 5, 500 and 5000 ppm TCE for 6h but not following repeated exposure to similar concentrations. In addition, any treatment-related findings were assessed in the context of potential TCE-induced hypothermia. Clinical signs consistent with marked TCE-induced sedation were observed in rats exposed to 5000 ppm and subsequently three rats died prior to the end of the 6h exposure period. No remarkable changes in body temperature were observed in surviving animals monitored with transponders before and after exposures. There were no statistically significant increases in the frequencies of MN-PCEs in groups treated with the test material as compared to the negative controls. The positive control animals showed a significant increase in the frequency of MN-PCEs and a decrease in the relative proportion of PCEs among erythrocytes as compared to the negative control animals. There were no statistically significant differences in the per cent PCEs in groups treated with the test material. As no increase in the incidence of micronuclei was observed in any of the TCE exposure groups, kinetochore analyses were not performed. Under the experimental conditions used, TCE was considered to be negative in the rat bone marrow micronucleus test.

  8. Blood and bronchoalveolar lavage fluid acetylcholinesterase levels following microinstillation inhalation exposure to sarin in Guinea pigs.

    PubMed

    Che, Magnus M; Conti, Michele; Boylan, Megan; Sciuto, Alfred M; Gordon, Richard K; Nambiar, Madhusoodana P

    2008-07-01

    We determined acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition in the bronchoalveolar lavage fluid (BALF) following inhalation exposure to chemical threat nerve agent (CTNA) sarin. Age- and weight-matched male guinea pigs were exposed to five different doses of sarin (169.3, 338.7, 508, 677.4, and 846.5 mg/m(3)) using a microinstillation inhalation exposure technique for 4 min. The technique involves aerosolization of the agent in the trachea using a microcatheter with a center hole that delivers the agent and multiple peripheral holes that pumps air to aerosolize the agent at the tip. Animals exposed to higher doses of sarin occasionally developed seizures and succumbed to death within 15 min after exposure. The LCt(50) for sarin using the microinstillation technique was determined to be close to 677.4 mg/m(3). Ear blood AChE activity showed a dose-dependent inhibition at 15 min postexposure. The inhibition of blood AChE remained constant over 35 and 55 min after sarin exposure indicating that there was no lung depot effect. Cardiac blood AChE and butyrylcholinesterase (BChE) activity in surviving animals euthanized at 24 h postexposure showed a dose-dependent inhibition with an inhibition of 60% at 677.4 and 846.5 mg/m(3) sarin exposure. AChE and BChE activity in bronchoalveolar lavage fluid (BALF) showed a slight increase at 338.7 to 677.4 mg/m(3) sarin exposure but a marginal inhibition at 169.3 mg/m(3). In contrast, the AChE protein levels determined by immunoblotting showed an increase at 169.3 mg/m(3) in the BALF. The BALF protein level, a biomarker of lung injury, was increased maximally at 338.7 mg/m(3) and that increase was dropped with an increase in the dose of sarin. The BALF protein levels correlated with the AChE and BChE activity. These data suggest that sarin microinstillation inhalation exposure results in respiratory toxicity and lung injury characterized by changes in lavage AChE, BChE, and protein levels.

  9. Inhalation exposure in the home to volatile organic contaminants of drinking water.

    PubMed

    Andelman, J B

    1985-12-01

    Our field studies show that indoor air concentrations of volatilized trichloroethylene (TCE) can be substantial when TCE-contaminated water is used domestically. Using a model shower, increases in TCE water concentrations, water temperature and drop path (time) increased the steady-state air TCE concentrations. Volatilization was incomplete and the rates were comparable to predicted ones. Indoor air models show that the inhalation route of exposure for such chemicals has the potential for being much greater than by direct ingestion. This should be considered in developing regulations to limit adverse health impacts from contaminants of potable water.

  10. A Comparison of "Total Dust" and Inhalable Personal Sampling for Beryllium Exposure

    SciTech Connect

    Carter, Colleen M.

    2012-05-09

    In 2009, the American Conference of Governmental Industrial Hygienists (ACGIH) reduced the Beryllium (Be) 8-hr Time Weighted Average Threshold Limit Value (TLV-TWA) from 2.0 μg/m3 to 0.05 μg/m3 with an inhalable 'I' designation in accordance with ACGIH's particle size-selective criterion for inhalable mass. Currently, per the Department of Energy (DOE) requirements, the Lawrence Livermore National Laboratory (LLNL) is following the Occupational Health and Safety Administration (OSHA) Permissible Exposure Limit (PEL) of 2.0 μg/m3 as an 8-hr TWA, which is also the 2005 ACGIH TLV-TWA, and an Action Level (AL) of 0.2 μg/m3 and sampling is performed using the 37mm (total dust) sampling method. Since DOE is considering adopting the newer 2009 TLV guidelines, the goal of this study was to determine if the current method of sampling using the 37mm (total dust) sampler would produce results that are comparable to what would be measured using the IOM (inhalable) sampler specific to the application of high energy explosive work at LLNL's remote experimental test facility at Site 300. Side-by-side personal sampling using the two samplers was performed over an approximately two-week period during chamber re-entry and cleanup procedures following detonation of an explosive assembly containing Beryllium (Be). The average ratio of personal sampling results for the IOM (inhalable) vs. 37-mm (total dust) sampler was 1.1:1 with a P-value of 0.62, indicating that there was no statistically significant difference in the performance of the two samplers. Therefore, for the type of activity monitored during this study, the 37-mm sampling cassette would be considered a suitable alternative to the IOM sampler for collecting inhalable particulate matter, which is important given the many practical and economic advantages that it presents. However, similar comparison studies would be necessary for this conclusion to be applied to other types of

  11. Selective cognitive deficits in adult rats after prenatal exposure to inhaled ethanol.

    PubMed

    Oshiro, W M; Beasley, T E; McDaniel, K L; Taylor, M M; Evansky, P; Moser, V C; Gilbert, M E; Bushnell, P J

    2014-01-01

    Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by inhalation, the most likely route of exposure from gasoline-ethanol fuel blends. We evaluated the potential cognitive consequences of ethanol inhalation by exposing pregnant Long Evans rats to clean air or ethanol vapor from gestational days 9-20, a critical period of neuronal development. Concentrations of inhaled ethanol (5000, 10,000, or 21,000 ppm for 6.5h/day) produced modeled peak blood ethanol concentrations (BECs) in exposed dams of 2.3, 6.8, and 192 mg/dL, respectively. In offspring, no dose-related impairments were observed on spatial learning or working memory in the Morris water maze or in operant delayed match-to-position tests. Two measures showed significant effects in female offspring at all ethanol doses: 1) impaired cue learning after trace fear conditioning, and 2) an absence of bias for the correct quadrant after place training during a reference memory probe in the Morris water maze. In choice reaction time tests, male offspring (females were not tested) from the 5000 and 10,000 ppm groups showed a transient increase in decision times. Also, male offspring from the 21,000 ppm group made more anticipatory responses during a preparatory hold period, suggesting a deficit in response inhibition. The increase in anticipatory responding during the choice reaction time test shows that inhaled ethanol yielding a peak BEC of ~200mg/dL can produce lasting effects in the offspring. The lack of a dose-related decrement in the effects observed in females on cue learning and a reference memory probe may reflect confounding influences in the exposed offspring possibly related to maternal care or altered anxiety levels in females. The surprising lack of more pervasive cognitive deficits

  12. Pathways of inhalation exposure to manganese in children living near a ferromanganese refinery: A structural equation modeling approach

    EPA Science Inventory

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation ...

  13. Pathways of inhalation exposure to manganese in children living near a ferromanganese refinery: A structural equation modeling approach

    EPA Science Inventory

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation ...

  14. A novel system to generate WTC dust particles for inhalation exposures.

    PubMed

    Vaughan, Joshua M; Garrett, Brittany J; Prophete, Colette; Horton, Lori; Sisco, Maureen; Soukup, Joleen M; Zelikoff, Judith T; Ghio, Andrew; Peltier, Richard E; Asgharian, Bahman; Chen, Lung-Chi; Cohen, Mitchell D

    2014-01-01

    First responders (FRs) present at Ground Zero within the critical first 72 h after the World Trade Center (WTC) collapse have progressively exhibited significant respiratory injury. The majority (>96%) of WTC dusts were >10 μm and no studies have examined potential health effects of this size fraction. This study sought to develop a system to generate and deliver supercoarse (10-53 μm) WTC particles to a rat model in a manner that mimicked FR exposure scenarios. A modified Fishing Line generator was integrated onto an intratracheal inhalation (ITIH) system that allowed for a bypassing of the nasal passages so as to mimic FR exposures. Dust concentrations were measured gravimetrically; particle size distribution was measured via elutriation. Results indicate that the system could produce dusts with 23 μm mass median aerodynamic diameter (MMAD) at levels up to ≥1200 mg/m(3). To validate system utility, F344 rats were exposed for 2 h to ≈100 mg WTC dust/m(3). Exposed rats had significantly increased lung weight and levels of select tracer metals 1 h after exposure. Using this system, it is now possible to conduct relevant inhalation exposures to determine adverse WTC dusts impacts on the respiratory system. Furthermore, this novel integrated Fishing Line-ITIH system could potentially be used in the analyses of a wide spectrum of other dusts/pollutants of sizes previously untested or delivered to the lungs in ways that did not reflect realistic exposure scenarios.

  15. Effects of exercise exposure on toxic interactions between inhaled oxidant and aldehyde air pollutants

    SciTech Connect

    Mautz, W.J.; Kleinman, M.T.; Phalen, R.F.; Crocker, T.T.

    1988-01-01

    Respiratory tract injury resulting from inhalation of mixtures of ozone (O3) and nitrogen dioxide (NO2) and of O3 and formaldehyde (HCHO) was studied in Sprague-Dawley rats under exposure conditions of rest and exercise. Focal inflammatory injury induced in lung parenchyma by O3 exposure was measured morphometrically and HCHO injury to the nasal respiratory epithelium was measured by cell turnover using tritium-labeled thymidine. Mixtures of O3 (0.35 or 0.6 ppm) with NO2 (respectively 0.6 or 2.5 ppm) doubled the level of lung injury produced by O3 alone in resting exposures to the higher concentrations and in exercising exposures to the lower concentrations. Formaldehyde (10 ppm) mixed with O3 (0.6 ppm) resulted in reduced lung injury compared to O3 alone in resting exposures, but exercise exposure to the mixture did not show an antagonistic interaction. Nasal epithelial injury from HCHO exposure was enhanced when O3 was present in a mixture. Mixtures of O3 and NO2 at high and low concentrations formed respectively 0.73 and 0.02 ppm nitric acid (HNO3) vapor. Chemical interactions among the oxidants, HNO3, and other reaction products (N2O5 and nitrate radical) and lung tissue may be the basis for the O3-NO2 synergism. Increased dose and dose rate associated with exercise exposure may explain the presence of synergistic interaction at lower concentrations than observed in resting exposure. No oxidation products were detected in O3-HCHO mixtures, and the antagonistic interaction observed in lung tissue during resting exposure may result from irritant breathing pattern interactions.

  16. Effects of arsenic trioxide inhalation exposure on pulmonary antibacterial defenses in mice

    SciTech Connect

    Aranyi, C.; Bradof, J.N.; O'Shea, W.J.; Graham, J.A.; Miller, F.J.

    1985-01-01

    The effects of single and multiple (5 and 20) 3-h inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0. 4 micron mass median aerodynamic diameter. Aerosol mass concentration ranged from 125 to 1000 micrograms As/m3. Effects of the exposures were evaluated by determination of changes in susceptibility to experimentally induced streptococcal aerosol infection and in pulmonary bactericidal activity to /sup 35/S-labeled Klebsiella pneumoniae. Significant increases in mortality due to the infectious challenge and decreases in bactericidal activity were seen after single 3-h exposures to 270, 500, and 940 micrograms As/m3. Similarly, 5 or 20 multiple 3-h exposures to 500 micrograms As/m3 produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity. At 125 or 250 micrograms As/m3, a decrease in bactericidal activity was seen only after 20 exposures to 250 micrograms/m3. Results from earlier studies with an arsenic-containing copper smelter dust were compared to these data. The possibility of the development of adaptation during multiple exposures to arsenic trioxide is also considered.

  17. Recombinant paraoxonase 1 protects against sarin and soman toxicity following microinstillation inhalation exposure in guinea pigs.

    PubMed

    Valiyaveettil, Manojkumar; Alamneh, Yonas; Rezk, Peter; Perkins, Michael W; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2011-05-10

    To explore the efficacy of paraoxonase 1 (PON1) as a catalytic bioscavenger, we evaluated human recombinant PON1 (rePON1) expressed in Trichoplusia ni larvae against sarin and soman toxicity using microinstillation inhalation exposure in guinea pigs. Animals were pretreated intravenously with catalytically active rePON1, followed by exposure to 1.2 X LCt₅₀ sarin or soman. Administration of 5 units of rePON1 showed mild increase in the blood activity of the enzyme after 30 min, but protected the animals with a significant increase in survival rate along with minimal signs of nerve agent toxicity. Recombinant PON1 pretreated animals exposed to sarin or soman prevented the reduction of blood O₂ saturation and pulse rate observed after nerve agent exposure. In addition, rePON1 pretreated animals showed significantly higher blood PON1, acetylcholinesterase (AChE), and butyrylcholinesterase activity after nerve agent exposure compared to the respective controls without treatments. AChE activity in different brain regions of rePON1 pretreated animals exposed to sarin or soman were also significantly higher than respective controls. The remaining activity of blood PON1, cholinesterases and brain AChE in PON1 pretreated animals after nerve agent exposure correlated with the survival rate. In summary, these data suggest that human rePON1 protects against sarin and soman exposure in guinea pigs.

  18. Characterization of an inhaled toluene drug discrimination in mice: effect of exposure conditions and route of administration.

    PubMed

    Shelton, Keith L; Slavova-Hernandez, Galina

    2009-06-01

    The drug discrimination procedure in animals has been extensively utilized to model the abuse related, subjective effects of drugs in humans, but it has seldom been used to examine abused volatile inhalants like toluene. The present study sought to characterize the temporal aspects of toluene's discriminative stimulus as well assess toluene blood concentrations under identical exposure conditions. B6SJLF1/J mice were trained to discriminate 10 min of exposure to 6000 ppm inhaled toluene vapor from air. Toluene vapor concentration dependently substituted for the training exposure condition with longer exposures to equivalent concentrations producing greater substitution than shorter exposures. Toluene's discriminative stimulus effects dissipated completely by 60 min after the cessation of exposure. Injected liquid toluene dose-dependently substituted for toluene vapor as well as augmenting the discriminative stimulus effects of inhaled toluene. Toluene blood concentrations measured under several exposure conditions which produced full substitution were all nearly identical suggesting that the concentration of toluene in the animal tissues at the time of testing determined discriminative performance. These results indicate that the discriminative stimulus effects of inhaled toluene vapor are likely mediated by CNS effects rather than by its pronounced peripheral stimulus effects.

  19. Characterization of an inhaled toluene drug discrimination in mice: effect of exposure conditions and route of administration

    PubMed Central

    Shelton, Keith L.; Slavova-Hernandez, Galina

    2009-01-01

    The drug discrimination procedure in animals has been extensively utilized to model the abuse related, subjective effects of drugs in humans, but it has seldom been used to examine abused volatile inhalants like toluene. The present study sought to characterize the temporal aspects of toluene's discriminative stimulus as well assess toluene blood concentrations under identical exposure conditions. B6SJLF1/J mice were trained to discriminate 10 min of exposure to 6000 ppm inhaled toluene vapor from air. Toluene vapor concentration dependently substituted for the training exposure condition with longer exposures to equivalent concentrations producing greater substitution than shorter exposures. Toluene's discriminative stimulus effects dissipated completely by 60 min after the cessation of exposure. Injected liquid toluene dose-dependently substituted for toluene vapor as well as augmenting the discriminative stimulus effects of inhaled toluene. Toluene blood concentrations measured under several exposure conditions which produced full substitution were all nearly identical suggesting that the concentration of toluene in the animals tissues at the time of testing determined discriminative performance. These results indicate that the discriminative stimulus effects of inhaled toluene vapor are likely mediated by CNS effects rather than by it's pronounced peripheral stimulus effects. PMID:19268500

  20. Repeated Iron-Soot Exposure and Nose-to-brain Transport of Inhaled Ultrafine Particles.

    PubMed

    Hopkins, Laurie E; Laing, Emilia A; Peake, Janice L; Uyeminami, Dale; Mack, Savannah M; Li, Xueting; Smiley-Jewell, Suzette; Pinkerton, Kent E

    2017-01-01

    Particulate exposure has been implicated in the development of a number of neurological maladies such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, and idiopathic Parkinson's disease. Only a few studies have focused on the olfactory pathway as a portal through which combustion-generated particles may enter the brain. The primary objective of this study was to define the deposition, uptake, and transport of inhaled ultrafine iron-soot particles in the nasal cavities of mice to determine whether combustion-generated nanoparticles reach the olfactory bulb via the olfactory epithelium and nerve fascicles. Adult female C57B6 mice were exposed to iron-soot combustion particles at a concentration of 200 μg/m(3), which included 40 μg/m(3) of iron oxide nanoparticles. Mice were exposed for 6 hr/day, 5 days/week for 5 consecutive weeks (25 total exposure days). Our findings visually demonstrate that inhaled ultrafine iron-soot reached the brain via the olfactory nerves and was associated with indicators of neural inflammation.

  1. Lung changes in rats following inhalation exposure to volcanic ash for two years

    SciTech Connect

    Wehner, A.P.; Dagle, G.E.; Clark, M.L.; Buschbom, R.L.

    1986-08-01

    Rats were exposed by inhalation to 5 or 50 mg/m/sup 3/ Mount St. Helens volcanic ash, to 50 mg/m/sup 3/ quartz (positive controls), or to filtered room air (sham-exposed controls), for 6 hr/day, 5 days/week, for up to 24 months to investigate biological effects of chronic inhalation exposure to volcanic ash under controlled laboratory conditions. Exposure-related lung changes comprised accelerated respiratory frequency; alveolar macrophage accumulation; interstitial reaction; lymphoreticular reaction in peribronchiolar regions and in mediastinal lymph nodes; alveolar proteinosis in the 50- mg/m/sup 3/ ash- or quartz-exposed groups; increase in fresh lung weights; decreased body weight and increased mortality in the quartz-exposed group; and epidermoid carcinomas especially in the quartz-exposed females and, to a lesser extent, in the 50-mg/m/sup 3/ ash-exposed females. The observed changes reflect significant dose-response and agent-response relationships.

  2. Inhalational exposure to dimethyl sulfate vapor followed by reactive airway dysfunction syndrome

    PubMed Central

    Aghabiklooei, Abbas; Zamani, Nasim; Shiva, Hamidreza; Rezaei, Nader

    2010-01-01

    Dimethyl sulfate (DMS) is an oily liquid used as a solvent, stabilizer, sulfonation agent, and catalyst. Exposure to DMS primarily happens in the workplace via inhalational contact and damages the upper and lower airways. Our manuscript reports a case of DMS-related reactive airway dysfunction syndrome (RADS). The patient was a healthy 29-year-old man who was referred to our ER after accidental exposure to the vapor of DMS with the complaint of dyspnea, dry cough, photophobia, and hoarseness. His vital signs were normal except for a low-grade fever. Redness of the pharynx, conjunctivitis, and cholinergic signs and symptoms were present. Conservative management with O2 and fluid therapy was initiated. Twenty hours later, the patient became drowsy and his respiratory symptoms exacerbated; chest X-ray revealed haziness in the base of the right lung and prominence of the vessels of the lung hillum. After 1 week, the liver transaminases rose and C-reactive protein elevated (2+). The patient got better with conservative treatment and was discharged after 9 days; however, exertional dyspnea, wheezing, and thick white sputum persisted and therefore, reactive airway dysfunction syndrome (RADS) related to DMS vapor was confirmed which was treated by prednisolone. Exertional dyspnea continued up to 10 months. Hoarseness lasted for 6 months. This case shows that DMS vapor inhalation can cause RADS especially in the chemical workers who continue working in the contaminated place despite the relatively good air conditioning. PMID:21461165

  3. Improved inhalation technology for setting safe exposure levels for workplace chemicals

    NASA Technical Reports Server (NTRS)

    Stuart, Bruce O.

    1993-01-01

    Threshold Limit Values recommended as allowable air concentrations of a chemical in the workplace are often based upon a no-observable-effect-level (NOEL) determined by experimental inhalation studies using rodents. A 'safe level' for human exposure must then be estimated by the use of generalized safety factors in attempts to extrapolate from experimental rodents to man. The recent development of chemical-specific physiologically-based toxicokinetics makes use of measured physiological, biochemical, and metabolic parameters to construct a validated model that is able to 'scale-up' rodent response data to predict the behavior of the chemical in man. This procedure is made possible by recent advances in personal computer software and the emergence of appropriate biological data, and provides an analytical tool for much more reliable risk evaluation and airborne chemical exposure level setting for humans.

  4. Acute inhalation injury with evidence of diffuse bronchiolitis following chlorine gas exposure at a swimming pool.

    PubMed

    Parimon, Tanyalak; Kanne, Jeffrey P; Pierson, David J

    2004-03-01

    A previously healthy 23-year-old man with nonproductive cough and sore throat presented to the hospital a few hours after chlorine gas exposure at a fitness center swimming pool. Initial physical examination and chest radiograph were normal. Thirty-six hours later he developed worsening dyspnea and cough, with development of blood-tinged sputum. Arterial blood gas analysis showed mild hypoxemia and a subsequent chest radiograph demonstrated diffuse tiny nodular opacities. Findings on a thin-section computed tomogram of the chest were consistent with diffuse bronchiolitis. Pulmonary function tests showed a mild obstructive abnormality and he demonstrated substantial bronchodilator response. The patient was treated with oral corticosteroids and an inhaled beta(2) agonist, to which he responded well, with full clinical recovery occurring over 5 months. This manifestation of chlorine gas exposure at a swimming pool is unusual.

  5. [Exposure of the pediatric surgeon to inhalation-anesthetic during pediatric bronchoscopy procedures].

    PubMed

    Westphal, K; Lischke, V; Aybeck, T; Kessler, P

    1997-12-01

    General anaesthetic agents are frequently used for paediatric bronchoscopy. A disadvantage of this open system anaesthesia seems to be the contamination of the working environment. The aim of this study was to determine the exposure of the endoscopist during paediatric bronchoscopy under general anaesthesia in different working environments and to compare these measurements with the currently valid international threshold limit values. 25 children (ASA I-III) scheduled for diagnostic bronchoscopy were included in the study. After inhalational induction all children were intubated with a nonflexible bronchoscope and manually ventilated through a side arm of the bronchoscope. Maintenance of anaesthesia was achieved with sevoflurane (2-3 vol%) in 80% oxygen. Trace concentrations were measured every 90 seconds in the breathing zones of the paediatrician by means of a highly sensitive direct-reading instrument (Brüel & Kjaer 1302). The lower detection limit was 0.02 ppm. The investigation was done in an OT with and without air conditioning and scavening system. The mean age of the children was 50.3 months (range: 3-109 months). Ventilation and oxygenation were stable throughout the bronchoscopic procedure. Mean exposure of the paediatrician without air-conditioning and scavening system to sevoflurane was over 50 ppm for the endoscopist. All international threshold limit values were exceeded. Peak concentrations higher than 100 ppm sevoflurane were detected repeatedly in 40% of anaesthesias. During bronchoscopy in the operating room equipped with laminar air flow (20.2 air exchanges per hour) and narcotic gas evacuation (30 l/min) the mean exposure of the paediatrician was 26.4 ppm sevoflurane. The main finding of the present study is that under inhalation anaesthesia with sevoflurane for paediatric bronchoscopy occupation exposure is higher than the limits stated in all known health regulation guidelines. Therefore, in case of such working conditions, the use of total

  6. Effects of Didecyldimethylammonium Chloride (DDAC) on Sprague-Dawley Rats after 13 Weeks of Inhalation Exposure

    PubMed Central

    Kim, Yong-Soon; Lee, Sung-Bae; Lim, Cheol-Hong

    2017-01-01

    Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were 0.63 μm, 0.81 μm, and 1.65 μm, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low (0.11 ± 0.06 mg/m3), the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high (1.41 ± 0.71 mg/m3) male group and 15% lower in the high (1.41 ± 0.71 mg/m3) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is 0.11 mg/m3. PMID:28133508

  7. Quantitative health risk assessment of inhalation exposure to polycyclic aromatic hydrocarbons on citizens in Tianjin, China.

    PubMed

    Bai, Zhipeng; Hu, Yandi; Yu, Huan; Wu, Nan; You, Yan

    2009-08-01

    Considering the large amounts of PAHs emitted into the ambient air in China, it is urgent to take preliminary health risk assessment of citizens through inhalation exposure to PAHs in China. The incremental lifetime cancer risk (ILCR) model was used to get the risk level of Tianjin citizens as an example, and Monte Carlo simulation was adopted to deal with the uncertainty. Exposure analysis found that the average values of B[a]P equivalent (B[a]Peq) daily exposure doses for children in the indoor, traffic and outdoor settings were estimated to be 2,446.8, 478.4, and 321.6 ng day(-1), respectively. And those for adults were 3,344.1, 794.9, and 519.0 ng day(-1), respectively. Much attention must be paid to indoor exposure, as it contributes more than 70% of the B[a]Peq daily exposure dose. ILCR falls within the range of 10(-5)-10(-3), which is higher than the acceptable risk level of 10(-6), and lower than the priority risk level (10(-3)). So this risk should be compared with those of other public health issues in the purpose of risk management. Sensitivity analysis found that the two variables, indoor air PAHs concentration distribution and the cancer slope factor (CSF) of BaP, contribute about 89% of the total risk uncertainty. Thus they are considered as the two main factors influencing the accuracy of the PAHs health risk assessment.

  8. Source-to-receptor pathways of anthropogenic PM 2.5 in Detroit, Michigan: Comparison of two inhalation exposure studies

    NASA Astrophysics Data System (ADS)

    Morishita, Masako; Keeler, Gerald J.; McDonald, Jacob D.; Wagner, James G.; Young, Li-Hao; Utsunomiya, Satoshi; Ewing, Rodney C.; Harkema, Jack R.

    Recent studies have attributed toxic effects of ambient fine particulate matter (aerodynamic diameter ≤ 2.5 μm; PM 2.5) to physical and/or chemical properties rather than total mass. However, identifying specific components or sources of a complex mixture of ambient PM 2.5 that are responsible for adverse health effects is still challenging. In order to improve our understanding of source-to-receptor pathways for ambient PM 2.5 (links between sources of ambient PM 2.5 and measures of biologically relevant dose), integrated inhalation toxicology studies using animal models and concentrated air particles (CAPs) were completed in southwest Detroit, a community where the pediatric asthma rate is more than twice the national average. Ambient PM 2.5 was concentrated with a Harvard fine particle concentrator housed in AirCARE1, a mobile air research laboratory which facilitates inhalation exposure studies in real-world settings. Detailed characterizations of ambient PM 2.5 and CAPs, identification of major emission sources of PM 2.5, and quantification of trace elements in the lung tissues of laboratory rats that were exposed to CAPs for two distinct 3-day exposure periods were completed. This paper describes the physical/chemical properties and sources of PM 2.5, pulmonary metal concentrations and meteorology from two different 3-day exposure periods—both conducted at the southwest Detroit location in July 2003—which resulted in disparate biological effects. More specifically, during one of the exposure periods, ambient PM 2.5-derived trace metals were recovered from lung tissues of CAPs-exposed animals, and these metals were linked to local combustion point sources in southwest Detroit via receptor modeling and meteorology; whereas in the other exposure period, no such trace metals were observed. By comparing these two disparate results, this investigation was able to define possible links between PM 2.5 emitted from refineries and incinerators and biologically

  9. Subchronic inhalation exposure study of an airborne polychlorinated biphenyl mixture resembling the Chicago ambient air congener profile.

    PubMed

    Hu, Xin; Adamcakova-Dodd, Andrea; Lehmler, Hans-Joachim; Hu, Dingfei; Hornbuckle, Keri; Thorne, Peter S

    2012-09-04

    Although inhalation of atmospheric polychlorinated biphenyls (PCBs) is the most universal exposure route and has become a substantial concern in urban areas, research is lacking to determine the body burden of inhaled PCBs and consequent health effects. To reflect the Chicago airshed environment and mimic the PCB profile in Chicago air, we generated vapors from a Chicago air mixture (CAM). Sprague-Dawley rats were exposed to the CAM vapor for 1.6 h/day via nose-only inhalation for 4 weeks, 520 ± 10 μg/m(3). Congener-specific quantification in tissue and air samples was performed by gas chromatography-tandem mass spectrometry (GC/MS/MS). In contrast to the lower-chlorinated congener-enriched vapor, body tissues mainly contained tri- to hexachlorobiphenyls. Congener profiles varied between vapor and tissues and among different organs. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) were also investigated for tissue distribution. We evaluated a variety of end points to catalogue the effects of long-term inhalation exposure, including immune responses, enzyme induction, cellular toxicity, and histopathologic abnormalities. Glutathione oxidized/reduced ratio (GSSG/GSH) was increased in the blood of exposed animals, accompanied by elevation of hematocrit. This study demonstrated that inhalation contributed to the body burden of mostly tri- to hexachlorobiphenyls and produced a distinct profile of congeners in tissue, yet minimal toxicity was found at this exposure dose, estimated at 134 μg/rat.

  10. Subchronic inhalation exposure study of an airborne polychlorinated biphenyl (PCB) mixture resembling the Chicago ambient air congener profile

    PubMed Central

    Hu, Xin; Adamcakova-Dodd, Andrea; Lehmler, Hans-Joachim; Hu, Dingfei; Hornbuckle, Keri; Thorne, Peter S

    2013-01-01

    Although inhalation of atmospheric PCBs is the most universal exposure route and has become a substantial concern in urban areas, research is lacking to determine the body burden of inhaled PCBs and consequent health effects. To reflect the Chicago airshed environment and mimic the PCB profile in Chicago air, we generated vapors from a Chicago Air Mixture (CAM). Sprague-Dawley rats were exposed to the CAM vapor for 1.6 hr/day via nose-only inhalation for 4 wks, 520±10 μg/m3. Congener-specific quantification in tissue and air samples was performed by GC/MS/MS. In contrast to the lower-chlorinated congener enriched vapor, body tissues mainly contained tri- to hexachlorobiphenyls. Congener profiles varied between vapor and tissues, and among different organs. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) were also investigated for tissue distribution. We evaluated a variety of endpoints to catalog the effects of long-term inhalation exposure, including immune responses, enzyme induction, cellular toxicity and histopathologic abnormalities. GSSG/GSH ratio was increased in blood of exposed animals, accompanied by elevation of hematocrit. This study demonstrated that inhalation contributed to the body burden of mostly tri- to hexachlorobiphenyls and produced a distinct profile of congeners in tissue, yet minimal toxicity was found at this exposure dose estimated at 134 μg/rat. PMID:22846166

  11. Effect of 4-week inhalation exposure to 1-bromopropane on blood pressure in rats.

    PubMed

    Huang, Fen; Ichihara, Sahoko; Yamada, Yuki; Banu, Shameema; Ichihara, Gaku

    2017-03-01

    The pathophysiology of hypertension is complex and multifactorial, and includes exposure to various chemical substances. Several recent studies have documented the reproductive and neurological toxicities of 1-bromopropane (1-BP). Given that 1-BP increased reactive oxygen species in the brain of rats, we hypothesized that 1-BP also has cardiovascular toxicity through increased oxidative stress. To test this hypothesis, male F344 and Wistar Nagoya rats (n = 7-8 per group per test) were exposed to 0 or 1000 ppm of 1-BP via inhalation for 4 weeks (8 h per day, 7 days per week). The exposure to 1-BP increased systolic blood pressure. This effect was associated with a significant decrease in the reduced/oxidized glutathione ratio. A significant increase in nitrotyrosine levels, activation of the NADPH oxidase pathway, which was evidenced by upregulation of gp91phox, a NADPH oxidase subunit, and significant decreases in the expressions of antioxidant molecules such as Cu/Zn- and Mn-superoxide dismutase catalase, and nuclear factor erythroid 2-related factor 2, were observed in the aortas of Wistar Nagoya rats exposed to 1-BP. Our results indicate that subacute (4-week) inhalation exposure to 1-BP increases blood pressure and suggest that this cardiovascular toxic effect is due, at least in part, to increased oxidative stress mediated through activation of the NADPH oxidase pathway. Further study is needed to assess whether NADPH oxidase activation causes the increase in blood pressure in the rats exposed to 1-BP. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Acute lung injury following inhalation exposure to nerve agent VX in guinea pigs.

    PubMed

    Wright, Benjamin S; Rezk, Peter E; Graham, Jacob R; Steele, Keith E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2006-05-01

    A microinstillation technique of inhalation exposure was utilized to assess lung injury following chemical warfare nerve agent VX [methylphosphonothioic acid S-(2-[bis(1-methylethyl)amino]ethyl) O-ethyl ester] exposure in guinea pigs. Animals were anesthetized using Telazol-meditomidine, gently intubated, and VX was aerosolized using a microcatheter placed 2 cm above the bifurcation of the trachea. Different doses (50.4 microg/m3, 70.4 micro g/m(m3), 90.4 microg/m(m3)) of VX were administered at 40 pulses/min for 5 min. Dosing of VX was calculated by the volume of aerosol produced per 200 pulses and diluting the agent accordingly. Although the survival rate of animals exposed to different doses of VX was similar to the controls, nearly a 20% weight reduction was observed in exposed animals. After 24 h of recovery, the animals were euthanized and bronchoalveolar lavage (BAL) was performed with oxygen free saline. BAL was centrifuged and separated into BAL fluid (BALF) and BAL cells (BALC) and analyzed for indication of lung injury. The edema by dry/wet weight ratio of the accessory lobe increased 11% in VX-treated animals. BAL cell number was increased in VX-treated animals compared to controls, independent of dosage. Trypan blue viability assay indicated an increase in BAL cell death in 70.4 microg/m(m3) and 90.4 microg/m(m3) VX-exposed animals. Differential cell counting of BALC indicated a decrease in macrophage/monocytes in VX-exposed animals. The total amount of BAL protein increased gradually with the exposed dose of VX and was highest in animals exposed to 90.4 microg/m(m3), indicating that this dose of VX caused lung injury that persisted at 24 h. In addition, histopathology results also suggest that inhalation exposure to VX induces acute lung injury.

  13. Assessments of lung toxicity to Acrawax C following acute inhalation exposure.

    PubMed

    Warheit, D B; Carakostas, M C; Hartsky, M A

    1990-01-01

    Acrawax is a trademark for a series of synthetic waxes which are used as flatteners in paint, and lubricants in plastics, and these materials have been routinely regarded as nuisance dusts. Due to a paucity of information regarding the pulmonary toxicity of this material, we investigated the effects of acute inhalation of Acrawax C in rats. CD rats were exposed to aerosols of Acrawax C for 6 hours at 112 mg/m3. Fluids and cells from sham and exposed animals were recovered by bronchoalveolar lavage (BAL) and measured for cellular and biochemical parameters at 0, 24, 48, 172 hrs (8 days), and 1 month postexposure. Pulmonary macrophages (PM) were cultured and studied for in vitro and in vivo phagocytosis, as well as surface morphology. The lungs of additional animals exposed to Acrawax were fixed for assessment by histopathology, and transmission electron microscopy. Our results showed that Acrawax C exposure produced a mild inflammatory response at 24 hours postexposure, but cell differentials were not significantly different from controls at 48 hrs after exposure. BAL levels of lactate dehydrogenase, alkaline phosphatase and protein were slightly different from controls only at 8 days postexposure, and had returned to control values by 1 month of recovery. Acrawax exposure had no adverse effects on either morphology or the phagocytic capacity of pulmonary macrophages recovered from exposed animals. Histopathologic analysis of lung tissue from Acrawax C-exposed rats revealed normal lung architecture. Based on acute studies, our results suggest that the response to inhaled Acrawax C is not substantially different from the response to other nuisance dusts such as carbonyl iron and titanium dioxide.

  14. In utero smoke exposure and impaired response to inhaled corticosteroids in children with asthma.

    PubMed

    Cohen, Robyn T; Raby, Benjamin A; Van Steen, Kristel; Fuhlbrigge, Anne L; Celedón, Juan C; Rosner, Bernard A; Strunk, Robert C; Zeiger, Robert S; Weiss, Scott T

    2010-09-01

    Few studies have examined the effects of in utero smoke exposure (IUS) on lung function in children with asthma, and there are no published data on the impact of IUS on treatment outcomes in children with asthma. To explore whether IUS exposure is associated with increased airway responsiveness among children with asthma and whether IUS modifies the response to treatment with inhaled corticosteroids (ICSs). To assess the impact of parent-reported IUS exposure on airway responsiveness in childhood asthma, we performed a repeated-measures analysis of methacholine PC(20) data from the Childhood Asthma Management Program, a 4-year, multicenter, randomized, double-masked, placebo-controlled trial of 1041 children age 5 to 12 years comparing the long-term efficacy of ICS with mast cell stabilizing agents or placebo. Although improvement was seen in both groups, children with asthma and IUS exposure had on average 26% less of an improvement in airway responsiveness over time compared with unexposed children (P = .01). Moreover, while children who were not exposed to IUS who received budesonide experienced substantial improvement in PC(20) compared with untreated children (1.25-fold increase; 95% CI, 1.03-1.50; P = .02), the beneficial effects of budesonide were attenuated among children with a history of IUS exposure (1.04-fold increase, 95% CI, 0.65-1.68; P = .88). In utero smoke exposure reduces age-related improvements in airway responsiveness among children with asthma. Moreover, IUS appears to blunt the beneficial effects of ICS use on airways responsiveness. These results emphasize the importance of preventing this exposure through smoking cessation counseling efforts with pregnant women. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. Gastrointestinal acetylcholinesterase activity following endotracheal microinstillation inhalation exposure to sarin in guinea pigs.

    PubMed

    Chanda, Soma; Song, Jian; Rezk, Peter; Sabnekar, Praveena; Doctor, Bhupendra P; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2010-09-06

    The goal of this study was to assess acetylcholinesterase (AChE) inhibition at different regions of the gastrointestinal (GI) tract following inhalation exposure to nerve agent sarin. Seven major regions of the GI tract were removed from saline control animals (n=3) and 677.4 mg/m(3) sarin-exposed animals at 4h (n=4) and 24h (n=4) post-exposure. AChE activity was determined in blood and homogenized tissue supernatant by specific Ellman's assay using Iso-OMPA, a BChE inhibitor, and expressed as activity/optical density of hemoglobin for blood and activity/mg protein for tissues. Our data showed that the AChE activity was significantly decreased for groups both 4h and 24h post-sarin exposure. Among the seven chosen regions of the guinea pig GI tract, duodenum showed the highest AChE activity in control animals. The AChE activity was significantly decreased in the stomach (p=0.03), duodenum (p=0.029), jejunum (p=0.006), and ileum (p=0.006) 4h following sarin exposure. At 24h post-sarin exposure the AChE activity of duodenum (p=0.029) and ileum (p=0.006) was significantly inhibited. Esophagus showed no inhibition following sarin exposure at both 4h and 24h groups. These results suggest that the AChE activity is different in different regions of the GI tract and highest levels of AChE inhibition following sarin exposure were seen in regions exhibiting higher overall AChE activity and cholinergic function.

  16. Inhaled Nitric Oxide Decreases Leukocyte Trafficking in the Neonatal Mouse Lung During Exposure to >95% Oxygen

    PubMed Central

    Rose, Melissa J.; Stenger, Michael R.; Joshi, Mandar S.; Welty, Stephen E.; Bauer, John Anthony; Nelin, Leif D.

    2010-01-01

    Chronic lung injury in the neonate is termed bronchopulmonary dysplasia (BPD). These patients generally require supplemental oxygen therapy, and hyperoxia has been implicated in the pathogenesis of BPD. The concomitant use of oxygen and inhaled nitric oxide (iNO) may result in the generation of reactive nitrogen species, or may have an anti-inflammatory effect in the neonatal lung. We tested the hypothesis that exposure to >95% O2 in neonatal mice would increase trafficking of leukocytes into the lung, and that the addition of iNO to >95% O2 would decrease this leukocyte trafficking. Hyperoxia resulted in fewer alveoli, increased presence of neutrophils and macrophages, and decreased number of mast cells within the lung parenchyma. Adding iNO to hyperoxia prevented the hyperoxia-induced changes and resulted in the numbers of alveoli, neutrophils, macrophages, and mast cells approximating those found in controls (room air exposure). Intercellular adhesion molecule (ICAM) and monocyte chemotactic protein-1 (MCP-1), two factors responsible for leukocyte recruitment, were upregulated by hyperoxic exposure, but the addition of iNO to the hyperoxic exposure prevented the hyperoxia-induced upregulation of ICAM and MCP-1. These data demonstrate that iNO alters the hyperoxia-induced recruitment of leukocytes into the lung. PMID:19915514

  17. Benzothiazoles in indoor air from Albany, New York, USA, and its implications for inhalation exposure.

    PubMed

    Wan, Yanjian; Xue, Jingchuan; Kannan, Kurunthachalam

    2016-07-05

    Benzothiazole and its derivatives (collectively referred to BTHs) are used widely in many consumer (e.g., textiles) and industrial (e.g., rubber) products. Very little is known about the occurrence of BTHs in indoor air and the inhalation exposure of humans to these substances. In this study, 81 indoor air samples collected from various locations in Albany, New York, USA, in 2014 were analyzed for BTHs by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BTHs were found in all indoor air samples, and the overall concentrations in bulk air (vapor plus particulate phases) were in the range of 4.36-2229 ng/m(3) (geometric mean: 32.7 ng/m(3)). The highest concentrations (geometric mean: 148 ng/m(3)) were found in automobiles, followed by homes (49.5)>automobile garages (46.0)>public places, e.g., shopping malls (24.2)>barbershops (18.9) >offices (18.8)>laboratories (15.1). The estimated geometric mean daily intake (EDI) of BTHs for infants, toddlers, children, teenagers, and adults through indoor air inhalation from homes was 27.7, 26.3, 17.9, 10.5, and 7.77 ng/kg-bw/day, respectively. The estimated contribution of indoor air to total BTHs intake was approximately 10%. This is the first study on the occurrence of BTHs in indoor air. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Inhalation exposure to ethylene induces eosinophilic rhinitis and nasal epithelial remodeling in Fischer 344 rats.

    PubMed

    Brandenberger, Christina; Hotchkiss, Jon A; Krieger, Shannon M; Pottenger, Lynn H; Harkema, Jack R

    2015-11-05

    This study investigated the time- and concentration-dependent effects of inhaled ethylene on eosinophilic rhinitis and nasal epithelial remodeling in Fisher 344 rats exposed to 0, 10, 50, 300, or 10,000 ppm ethylene, 6 h/day, 5 days/week for up to 4 weeks. Morphometric quantitation of eosinophilic inflammation and mucous cell metaplasia/hyperplasia (MCM) and nasal mucosal gene expression were evaluated at anatomic sites previously shown to undergo ethylene-induced epithelial remodeling. Serum levels of total IgE, IgG1 and IgG2a were measured to determine if ethylene exposure increased the expression of Th2-associated (IgE and IgG1) relative to Th1-associated (IgG2a) antibody isotypes. Rats exposed to 0 or 10,000 ppm for 1, 3, 5, 10, or 20 days were analyzed to assess the temporal pattern of ethylene-induced alterations in nasal epithelial cell proliferation, morphology and gene expression. Rats exposed to 0, 10, 50, 300, and 10,000 ppm ethylene for 20 days were analyzed to assess concentration-dependent effects on lesion development. Additional rats exposed 4 weeks to 0, 300, or 10,000 ppm ethylene were held for 13 weeks post-exposure to examine the persistence of ethylene-induced mucosal alterations. The data indicate that cell death and reparative cell proliferation were not a part of the pathogenesis of ethylene-induced nasal lesions. Enhanced gene expression of Th2 cytokines (e.g., IL-5, IL-13) and chitinase (YM1/2) in the nasal mucosa was much greater than that of Th1 cytokines (e.g., IFNγ) after ethylene exposure. A significant increase in MCM was measured after 5 days of exposure to 10,000 ppm ethylene and after 20 days of exposure 10 ppm ethylene. Ethylene-induced MCM was reversible after cessation of exposure. No increase in total serum IgE, IgG1 or IgG2a was measured in any ethylene-exposed group. These data do not support involvement of an immune-mediated allergic mechanism in the pathogenesis of ethylene-induced nasal lesions in rats. Repeated

  19. Component-specific toxic concerns of the inhalable fraction of urban road dust.

    PubMed

    Potgieter-Vermaak, S; Rotondo, G; Novakovic, V; Rollins, S; Van Grieken, R

    2012-12-01

    Continuous global urbanisation causes an ever-growing ecological footprint of pollution. Road dust (RD), one of these pollutants, poses a health concern due to carcinogenic and toxic components potentially present in the micron-sized fractions. The literature reports on the concentrations of trace, toxic metals and metalloids present in RD (Hooker and Nathanail in Chem Geol 226:340-351, 2006), but the literature on its molecular composition is limited. Recent reports on the bioaccessibility of platinum group metals are also reported (Colombo et al. in Chem Geol 226:340-351, 2008). In vitro and animal toxicological studies confirmed that the chemical composition of inhaled particles plays a major role in its toxic, genotoxic and carcinogenic mechanisms, but the component-specific toxic effects are still not understood. Particle-bound airborne transition metals can also lead to the production of reactive oxygen species in lung tissue; a special concern amongst particularly susceptible cohorts (children and elderly). The characterisation of the molecular composition of the fine fraction is evidently of importance for public health. During a pilot study, partially characterised size-fractioned RD samples (Barrett et al. in Eviron Sci Technol 44:2940-2946, 2010) were analysed for their elemental concentration using X-ray fluorescence spectrometry and inductively coupled plasma mass spectrometry. In addition, separately dispersed particles (200 particles per size fraction) were analysed individually by means of computer-controlled electron probe X-ray micro-analysis (CC-EPXMA) and their molecular structure probed by studying elemental associations. These were correlated with micro-Raman spectroscopy (MRS) results. It was found that the fine fraction (<38 μm) had the highest Pb (238 ppm) and Cr (171 ppm) concentrations. The CC-EPXMA data showed >50 % association of Cr-rich particles with Pb, and the MRS data showed that the Cr was mostly present as lead chromate and

  20. ACUTE NEUROTOXIC EFFECTS OF INHALED PERCHLOROETHYLENE ON PATTERN VISUAL EVOKED POTENTIALS AS A FUNCTION OF EXPOSURE AND ESTIMATED BLOOD AND BRAIN CONCENTRATION.

    EPA Science Inventory

    Previous experiments have shown the effects of acute inhalation exposure to trichloroethylene (TCE) and toluene are related to the target tissue concentration at the time of testing. The current studies examined exposure to another volatile organic compound, perchloroethylene (P...

  1. ACUTE NEUROTOXIC EFFECTS OF INHALED PERCHLOROETHYLENE ON PATTERN VISUAL EVOKED POTENTIALS AS A FUNCTION OF EXPOSURE AND ESTIMATED BLOOD AND BRAIN CONCENTRATION.

    EPA Science Inventory

    Previous experiments have shown the effects of acute inhalation exposure to trichloroethylene (TCE) and toluene are related to the target tissue concentration at the time of testing. The current studies examined exposure to another volatile organic compound, perchloroethylene (P...

  2. Acute inhalational exposure to chlorodifluoromethane (freon-22): a report of 43 cases.

    PubMed

    Kubota, Takeshi; Miyata, Akimasa

    2005-01-01

    We report 43 cases of chlorodifluoromethane (Freon-22) intoxication that occurred on August 5, 2003 when a freezer in a seafood factory exploded. In this accident, 80 workers were exposed to Freon-22 gas and 43 workers developed symptoms and were transferred to six hospitals. Neurological symptoms including dizziness, headache, and nausea were most frequently observed (40 of 43 patients). One patient was comatose but recovered within 1 h with oxygen inhalation. Airway and respiratory symptoms including dysesthesia of the tongue, pharyngitis, and shortness of breath were also frequently observed (26 of 43 patients). These symptoms disappeared within a few days in all patients. There were no fatalities. Although Freon-22 has been considered to be a chlorofluorocarbon of relatively low toxicity, this incident suggests that potentially significant toxic effects may occur following large exposures.

  3. In Utero Smoke Exposure and Impaired Response to Inhaled Corticosteroids in Children with Asthma

    PubMed Central

    Cohen, Robyn T.; Raby, Benjamin A.; Van Steen, Kristel; Fuhlbrigge, Anne L.; Celedón, Juan C.; Rosner, Bernard A.; Strunk, Robert C.; Zeiger, Robert S.; Weiss, Scott T.

    2010-01-01

    Background Few studies have examined the effects of in utero smoke exposure (IUS) on lung function in children with asthma, and there are no published data on the impact of IUS on treatment outcomes in asthmatic children. Objectives To explore whether IUS exposure is associated with increased airway responsiveness among children with asthma, and whether IUS modifies the response to treatment with inhaled corticosteroids (ICS). Methods To assess the impact of parent-reported IUS exposure on airway responsiveness in childhood asthma we performed a repeated-measures analysis of methacholine PC20 data from the Childhood Asthma Management Program (CAMP), a four-year, multicenter, randomized double masked placebo controlled trial of 1041 children ages 5–12 comparing the long term efficacy of ICS with mast cell stabilizing agents or placebo. Results Although improvement was seen in both groups, asthmatic children with IUS exposure had on average 26% less of an improvement in airway responsiveness over time compared to unexposed children (p=.01). Moreover, while children who were not exposed to IUS who received budesonide experienced substantial improvement in PC20 compared to untreated children (1.25 fold-increase, 95% CI 1.03, 1.50, p=.02) the beneficial effects of budesonide were attenuated among children with a history of IUS exposure (1.04 fold-increase, 95% CI 0.65, 1.68, p=.88). Conclusions IUS reduces age-related improvements in airway responsiveness among asthmatic children. Moreover, IUS appears to blunt the beneficial effects of ICS use on airways responsiveness. These results emphasize the importance of preventing this exposure through smoking cessation counseling efforts with pregnant women. PMID:20673983

  4. Behavior of rock wool in lungs after exposure by nasal inhalation in rats.

    PubMed

    Kudo, Yuichiro; Aizawa, Yoshiharu

    2009-07-01

    To evaluate the safety of rock wool (RW fibers), we examined the biopersistence of a RW sample in the lungs of rats, based on the changes of fiber number and fiber size in terms of length and width, by a nose-only inhalation exposure study. Twenty male Fischer 344 rats (6-10 weeks old) were exposed to RW fibers at a concentration of 70 (21) fiber/m(3) and 30 (6.6) mg/m(3), arithmetic mean (geometric standard deviation), continuously for 3 h daily for five consecutive days. Five rats each were sacrificed shortly and at 1, 2, and 4 weeks after exposure, and their lung tissues were ashed by a low-temperature plasma-asher. Then, the numbers and sizes of fibers in the ashed samples were determined using phase-contrast microscope and computed image analyzer. The fiber numbers in the lungs 4 weeks after exposure significantly decreased from the baseline value, i.e., shortly after exposure (P < 0.05). The half-lives of RW fibers calculated from the one-compartment model were 32 days for total fibers and 10 days for fibers longer than 20 mum. The decrease of fiber number was 53.6% by 4 weeks after exposure (baseline group = 100%). Likewise, fiber sizes significantly decreased by 4 weeks after exposure (P < 0.05), probably because fibers were dissolved in body fluid, ingested by alveolar macrophages or discharged to outside of the body by mucociliary movement. In future studies, it is necessary to examine the long-term persistence of RW fibers in the lungs.

  5. SIMULATION TOOL KIT FOR INDOOR AIR QUALITY AND INHALATION EXPOSURE (IAQX) VERSION 1.0 USER'S GUIDE

    EPA Science Inventory

    The User's Guide describes a Microsoft Windows-based indoor air quality (IAQ) simulation software package designed Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short. This software complements and supplements existing IAQ simulation programs and...

  6. SIMULATION TOOL KIT FOR INDOOR AIR QUALITY AND INHALATION EXPOSURE (IAQX) VERSION 1.0 USER'S GUIDE

    EPA Science Inventory

    The User's Guide describes a Microsoft Windows-based indoor air quality (IAQ) simulation software package designed Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short. This software complements and supplements existing IAQ simulation programs and...

  7. Inhalation exposure during spray application and subsequent sanding of a wood sealant containing zinc oxide nanoparticles.

    PubMed

    Cooper, Michael R; West, Gavin H; Burrelli, Leonard G; Dresser, Daniel; Griffin, Kelsey N; Segrave, Alan M; Perrenoud, Jon; Lippy, Bruce E

    2017-07-01

    Nano-enabled construction products have entered into commerce. There are concerns about the safety of manufactured nanomaterials, and exposure assessments are needed for a more complete understanding of risk. This study assessed potential inhalation exposure to ZnO nanoparticles during spray application and power sanding of a commercially available wood sealant and evaluated the effectiveness of local exhaust ventilation in reducing exposure. A tradesperson performed the spraying and sanding inside an environmentally-controlled chamber. Dust control methods during sanding were compared. Filter-based sampling, electron microscopy, and real-time particle counters provided measures of exposure. Airborne nanoparticles above background levels were detected by particle counters for all exposure scenarios. Nanoparticle number concentrations and particle size distributions were similar for sanding of treated versus untreated wood. Very few unbound nanoparticles were detected in aerosol samples via electron microscopy, rather nano-sized ZnO was contained within, or on the surface of larger airborne particles. Whether the presence of nanoscale ZnO in these aerosols affects toxicity merits further investigation. Mass-based exposure measurements were below the NIOSH Recommended Exposure Limit for Zn, although there are no established exposure limits for nanoscale ZnO. Local exhaust ventilation was effective, reducing airborne nanoparticle number concentrations by up to 92% and reducing personal exposure to total dust by at least 80% in terms of mass. Given the discrepancies between the particle count data and electron microscopy observations, the chemical identity of the airborne nanoparticles detected by the particle counters remains uncertain. Prior studies attributed the main source of nanoparticle emissions during sanding to copper nanoparticles generated from electric sander motors. Potentially contrary results are presented suggesting the sander motor may not have been

  8. Behavioral and biochemical evaluation of sub-lethal inhalation exposure to VX in rats.

    PubMed

    Genovese, Raymond F; Benton, Bernard J; Lee, Esther H; Shippee, Sara J; Jakubowski, E Michael

    2007-03-22

    We evaluated the effects of low-level inhalation exposures (whole body, 60min duration) to the chemical warfare nerve agent VX (0.016, 0.15, 0.30 or 0.45mg/m(3)) in rats. The range of concentrations was approximately equivalent to 0.02-0.62 times 1.0 LC50. Biochemical effects were assessed by evaluating blood acetylcholinesterase (AChE) activity and by a regeneration assay that quantified the amount of VX (as the G analog) present in blood. Behavioral effects were assessed using a variable-interval 56-s schedule of reinforcement (VI56), in which rats were trained to press a lever to receive a food reward. VI56 training was established before exposure and evaluations continued after exposure. Additionally, after exposure, acquisition and maintenance of an eight-arm radial maze (RAM) task was evaluated in which rats learned to locate the four arms of the maze that presented a single food pellet reward. Behavioral assessments were conducted over approximately 3 months following exposure. Transient miosis was observed following exposure to all concentrations of VX and exposures to the 0.45mg/m(3) concentration also produced mild and temporary signs of toxicity (i.e., slight tremor and ataxia) in some subjects. All concentrations of VX also inhibited circulating AChE and the highest concentration inhibited AChE activity to less than 10% of pre-exposure values. Regenerated VX-G was found in red blood cell (RBC) and plasma blood fractions. In this respect, more VX-G was seen in plasma than RBC. Only small disruptions were observed on the VI56 or RAM following some VX exposures. In general, however, behavioral effects were minor and not clearly systematic. Taken together these results demonstrate that largely asymptomatic exposures to VX vapors in rats can produce substantial biochemical effects while having only minor performance effects on a previously learned behavioral task and on the acquisition of a new behavioral task.

  9. Exposure to inhalable dust and endotoxin among Danish pig farmers affected by work tasks and stable characteristics.

    PubMed

    Basinas, Ioannis; Schlünssen, Vivi; Takai, Hisamitsu; Heederik, Dick; Omland, Øyvind; Wouters, Inge M; Sigsgaard, Torben; Kromhout, Hans

    2013-10-01

    To identify working tasks and stable characteristics that determine intensity and variability of personal exposure to dust and endotoxin among pig farmers. Three hundred fifty-four personal full-shift measurements were performed in 231 farmers employed in 53 Danish pig farms. Filters were gravimetrically analysed for inhalable dust and for endotoxin by the Limulus amebocyte lysate assay. Information on working tasks and stable characteristics were collected using self-reported activity diaries and walk-through surveys performed in conjunction with the measurements. Associations between log-transformed dust and endotoxin exposure and working tasks and stable characteristics were examined using linear mixed-effects analysis. In these models, worker and farm identity were treated as random effects and working tasks and stable characteristics as fixed effects. Both separate and combined models for tasks and stable characteristics were elaborated. Inhalable dust concentrations ranged between 0.1 and 48 mg m(-3) and endotoxin concentrations varied between 9.2 and 370,000 EU m(-3). Field work activities played a dominant role on the exposure variability. Indoor working tasks with intense animal activity or handling of feed materials increased exposure concentrations, whereas engagement in field work was associated with lower exposure concentrations. High-pressure water cleaning increased endotoxin exposure but did not affect exposure to inhalable dust. Stable characteristics related to feeding practices and type of ventilation were determinants of exposure to inhalable dust. For endotoxin, the most important determinants were use of dry feed and slatted floor coverage. Feeding practices solely explained all between-farms variability in exposure to inhalable dust and endotoxin. These findings suggest feeding systems, flooring and ventilation to be potential areas where improved methods can reduce exposure to dust and endotoxin among pig farmers. Further, they highlight

  10. Determinants of exposure to inhalable particulate, wood dust, resin acids, and monoterpenes in a lumber mill environment.

    PubMed

    Teschke, K; Demers, P A; Davies, H W; Kennedy, S M; Marion, S A; Leung, V

    1999-05-01

    In a lumber mill in the northern inland region of British Columbia, Canada, we measured inhalable particulate, resin acid, and monoterpene exposures, and estimated wood dust exposures. Potential determinants of exposure were documented concurrently, including weather conditions, tree species, wood conditions, jobs, tasks, equipment used, and certain control measures. Over 220 personal samples were taken for each contaminant. Geometric mean concentrations were 0.98 mg/m3 for inhalable particulate, 0.49 mg/m3 for estimated wood dust, 8.04 micrograms/m3 for total resin acids, and 1.11 mg/m3 for total monoterpenes. Multiple regression models for all contaminants indicated that spruce and pine produced higher exposures than alpine fir or mixed tree species, cleaning up sawdust increased exposures, and personnel enclosure was an effective means of reducing exposures. Sawing wood in the primary breakdown areas of the mill was the main contributor to monoterpene exposures, so exposures were highest for the barker operator, the head rig operator, the canter operator, the board edgers, and a roving utility worker in the sawmill, and lowest in the planer mills (after kiln drying of the lumber) and yard. Cleaning up sawdust, planing kiln-dried lumber, and driving mobile equipment in the yard substantially increased exposures to both inhalable particulate and estimated wood dust. Jobs at the front end of the sawmill where primary breakdown of the logs takes place had lower exposures. Resin acid exposures followed a similar pattern, except that yard driving jobs did not increase exposures.

  11. Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats.

    PubMed

    Peng, Xinqi; Perkins, Michael W; Simons, Jannitt; Witriol, Alicia M; Rodriguez, Ashley M; Benjamin, Brittany M; Devorak, Jennifer; Sciuto, Alfred M

    2014-06-01

    This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250-300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m³ or 0.2, 0.5 and 0.8 LCt₅₀, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m³ VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.

  12. Kinetics of sarin (GB) following a single sublethal inhalation exposure in the guinea pig.

    PubMed

    Whalley, Christopher E; McGuire, Jeffrey M; Miller, Dennis B; Jakubowski, Edward M; Mioduszewski, Robert J; Thomson, Sandra A; Lumley, Lucille A; McDonough, John H; Shih, Tsung-Ming A

    2007-06-01

    To improve toxicity estimates from sublethal exposures to chemical warfare nerve agents (CWNA), it is necessary to generate mathematical models of the absorption, distribution, and elimination of nerve agents. However, current models are based on representative data sets generated with different routes of exposure and in different species and are designed to interpolate between limited laboratory data sets to predict a wide range of possible human exposure scenarios. This study was performed to integrate CWNA sublethal toxicity data in male Duncan Hartley guinea pigs. Specific goal was to compare uptake and clearance kinetics of different sublethal doses of sarin (either 0.1 x or 0.4 x LC50) in blood and tissues of guinea pigs exposed to agent by acute whole-body inhalation exposure after the 60-min LC50 was determined. Arterial catheterization allowed repeated blood sampling from the same animal at various time periods. Blood and tissue levels of acetylcholinesterase, butyrylcholinesterase, and regenerated sarin (rGB) were determined at various time points during and following sarin exposure. The following pharmacokinetic parameters were calculated from the graph of plasma or RBC rGB concentration versus time: time to reach the maximal concentration; maximal concentration; mean residence time; clearance; volume of distribution at steady state; terminal elimination-phase rate constant; and area under plasma concentration time curve extrapolated to infinity using the WinNonlin analysis program 5.0. Plasma and RBC t(1/2) for rGB was also calculated. Data will be used to develop mathematical model of absorption and distribution of sublethal sarin doses into susceptible tissues.

  13. Depleted uranium contamination by inhalation exposure and its detection after approximately 20 years: implications for human health assessment.

    PubMed

    Parrish, Randall R; Horstwood, Matthew; Arnason, John G; Chenery, Simon; Brewer, Tim; Lloyd, Nicholas S; Carpenter, David O

    2008-02-01

    Inhaled depleted uranium (DU) aerosols are recognised as a distinct human health hazard and DU has been suggested to be responsible in part for illness in both military and civilian populations that may have been exposed. This study aimed to develop and use a testing procedure capable of detecting an individual's historic milligram-quantity aerosol exposure to DU up to 20 years after the event. This method was applied to individuals associated with or living proximal to a DU munitions plant in Colonie New York that were likely to have had a significant DU aerosol inhalation exposure, in order to improve DU-exposure screening reliability and gain insight into the residence time of DU in humans. We show using sensitive mass spectrometric techniques that when exposure to aerosol has been unambiguous and in sufficient quantity, urinary excretion of DU can be detected more than 20 years after primary DU inhalation contamination ceased, even when DU constitutes only approximately 1% of the total excreted uranium. It seems reasonable to conclude that a chronically DU-exposed population exists within the contamination 'footprint' of the munitions plant in Colonie, New York. The method allows even a modest DU exposure to be identified where other less sensitive methods would have failed entirely. This should allow better assessment of historical exposure incidence than currently exists.

  14. Reproductive and offspring developmental effects following maternal inhalation exposure to methanol in nonhuman primates.

    PubMed

    Burbacher, T; Shen, D; Grant, K; Sheppard, L; Damian, D; Ellis, S; Liberato, N

    1999-10-01

    In an effort to improve air quality and decrease dependence on petroleum, the federal government, industry, and other groups have encouraged development of alternative fuels such as methanol to substitute for gasoline or diesel fuel. Methanol is also a candidate to provide the hydrogen for fuel cells, which are being developed for a variety of power sources (including motor vehicle engines). Before people are exposed to increased concentrations of methanol, the potential health effects of such exposures require study. Methanol, a simple alcohol containing one carbon atom, occurs naturally in plants and animals and participates in human metabolism. People regularly consume low doses of methanol in fruits, vegetables, and fermented beverages as well as soft drinks and foods sweetened with aspartame (which breaks down to methanol in the gastrointestinal tract). Despite its ubiquitous presence, methanol can be highly toxic if sufficient quantities are consumed. Ingestion of methanol (usually in the form of wood alcohol or tainted alcoholic beverages) can result in metabolic acidosis, blindness, and even death. Although the body has the capacity to metabolize the low doses of methanol to which people are regularly exposed, it cannot handle high doses because too much methanol overwhelms the body's ability to remove a toxic metabolite (formate). When formate accumulates, methanol poisoning occurs. One factor that regulates the rate at which formate is removed is the liver level of a derivative of the vitamin folic acid. People who are deficient in folic acid (including 15% to 30% of pregnant women) may be particularly susceptible to the toxic effects of methanol. If methanol were to be widely adopted as a fuel, environmental exposures would increase through ingestion of contaminated drinking water, inhalation of vapors from evaporative and other emissions, and dermal contact. Current concentrations of methanol in ambient air are very low, 1 to 30 parts per billion (ppb

  15. Characterisation of urban inhalation exposures to benzene, formaldehyde and acetaldehyde in the European Union: comparison of measured and modelled exposure data.

    PubMed

    Bruinen de Bruin, Yuri; Koistinen, Kimmo; Kephalopoulos, Stylianos; Geiss, Otmar; Tirendi, Salvatore; Kotzias, Dimitrios

    2008-07-01

    All across Europe, people live and work in indoor environments. On average, people spend around 90% of their time indoors (homes, workplaces, cars and public transport means, etc.) and are exposed to a complex mixture of pollutants at concentration levels that are often several times higher than outdoors. These pollutants are emitted by different sources indoors and outdoors and include volatile organic compounds (VOCs), carbonyls (aldehydes and ketones) and other chemical substances often adsorbed on particles. Moreover, legal obligations opposed by legislations, such as the European Union's General Product Safety Directive (GPSD) and Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), increasingly require detailed understanding of where and how chemical substances are used throughout their life-cycle and require better characterisation of their emissions and exposure. This information is essential to be able to control emissions from sources aiming at a reduction of adverse health effects. Scientifically sound human risk assessment procedures based on qualitative and quantitative human exposure information allows a better characterisation of population exposures to chemical substances. In this context, the current paper compares inhalation exposures to three health-based EU priority substances, i.e. benzene, formaldehyde and acetaldehyde. Distributions of urban population inhalation exposures, indoor and outdoor concentrations were created on the basis of measured AIRMEX data in 12 European cities and compared to results from existing European population exposure studies published within the scientific literature. By pooling all EU city personal exposure, indoor and outdoor concentration means, representative EU city cumulative frequency distributions were created. Population exposures were modelled with a microenvironment model using the time spent and concentrations in four microenvironments, i.e. indoors at home and at work, outdoors

  16. Analysis of exposure due to work on activated components

    SciTech Connect

    Cossairt, J.D.

    1987-09-01

    In this brief note the author summarized analysis of the exposure incurred in various maintenance jobs involving activated accelerator and beam line components at Fermilab. A tabulation was made of parameters associated with each job. Included are rather terse descriptions of the various tasks. The author presented various plots of the quantities in the table. All exposure rates are mR/hr while all exposures accumulated are mR. The exposure rates were generally measured at the Fermilab standard one foot distance from the activated component. Accumulated exposures are taken from the self-reading pocket dosimeter records maintained by the radiation control technicians.

  17. The Air Pollution Exposure Laboratory (APEL) for controlled human exposure to diesel exhaust and other inhalants: characterization and comparison to existing facilities.

    PubMed

    Birger, Nicholas; Gould, Timothy; Stewart, James; Miller, Mark R; Larson, Timothy; Carlsten, Chris

    2011-03-01

    The Air Pollution Exposure Laboratory (APEL) was designed for the controlled inhalation of human subjects to aged and diluted diesel exhaust (DE) to mimic "real-world" occupational and environmental conditions. An EPA Tier 3-compliant, 6.0 kW diesel generator is operated under discrete cyclic loads to simulate diesel on-road emissions. The engine accepts standard ultra-low sulfur diesel or a variety of alternative fuels (such as biodiesel) via a partitioned tank. A portion of raw exhaust is drawn into the primary dilution system and is diluted 9:1 with compressed air at standard temperature (20°C) and humidity (40%) levels. The exhaust is further diluted approximately 25:1 by high efficiency particulate air (HEPA)-filtered air (FA) and then aged for 4 min before entering the 4 × 6 × 7-foot exposure booth. An optional HEPA filter path immediately proximal to the booth can generate a particle-reduced (gas-enriched) exposure. In-booth particulate is read by a nephelometer to provide an instantaneous light scattering coefficient for closed-loop system control. A Scanning Mobility Particle Sizer and multi-stage impactor measures particle size distribution. Filter sampling allows determination of sessional average concentrations of size-fractionated and unfractionated particulate oxidative potential, elemental carbon, organic carbon and trace elements. Approximately 300 μg/m(3) PM(2.5) is routinely achievable at APEL and is well characterized in terms of oxidative potential and elemental components. APEL efficiently creates fresh DE, appropriately aged and diluted for human experimentation at safe yet realistic concentrations. Description of exposure characteristics allows comparison to other international efforts to deepen the current evidence base regarding the health effects of DE.

  18. Altered Methylation in Tandem Repeat Element and Elemental Component Levels in Inhalable Air Particles

    PubMed Central

    Hou, Lifang; Zhang, Xiao; Zheng, Yinan; Wang, Sheng; Dou, Chang; Guo, Liqiong; Byun, Hyang-Min; Motta, Valeria; McCracken, John; Díaz, Anaité; Kang, Choong-Min; Koutrakis, Petros; Bertazzi, Pier Alberto; Li, Jingyun; Schwartz, Joel; Baccarelli, Andrea A.

    2014-01-01

    Exposure to particulate matter (PM) has been associated with lung cancer risk in epidemiology investigations. Elemental components of PM have been suggested to have critical roles in PM toxicity, but the molecular mechanisms underlying their association with cancer risks remain poorly understood. DNA methylation has emerged as a promising biomarker for environmental-related diseases, including lung cancer. In this study, we evaluated the effects of PM elemental components on methylation of three tandem repeats in a highly-exposed population in Beijing, China. The Beijing Truck Driver Air Pollution Study was conducted shortly before the 2008 Beijing Olympic Games (June 15-July 27, 2008) and included 60 truck drivers and 60 office workers. On two days separated by 1-2 weeks, we measured blood DNA methylation of SATα, NBL2, D4Z4, and personal exposure to eight elemental components in PM2.5, including aluminum (Al), silicon (Si), sulfur (S), potassium (K), calcium (Ca) titanium (Ti), iron (Fe), and zinc (Zn). We estimated the associations of individual elemental component with each tandem repeat methylation in generalized estimating equations (GEE) models adjusted for PM2.5 mass and other covariates. Out of the eight examined elements, NBL2 methylation was positively associated with concentrations of Si (0.121, 95%CI: 0.030; 0.212, FDR=0.047) and Ca (0.065, 95%CI: 0.014; 0.115, FDR=0.047) in truck drivers. In office workers, SATα methylation was positively associated with concentrations of S (0.115, 95%CI: 0.034; 0.196, FDR=0.042). PM-associated differences in blood tandem-repeat methylation may help detect biological effects of the exposure and identify individuals who may eventually experience higher lung cancer risk. PMID:24273195

  19. Assessment of inhalation exposure to indoor air pollutants: Screening for health risks of multiple pollutants in Japanese dwellings.

    PubMed

    Azuma, Kenichi; Uchiyama, Iwao; Uchiyama, Shigehisa; Kunugita, Naoki

    2016-02-01

    Over the past few decades, multiple low level indoor pollutants have been found in domestic dwellings. The types and concentrations of these indoor pollutants have not been consistent over time and have changed with alterations in lifestyle, the development of novel products used in housing, and the development of new measurement technologies. To clarify the highest risk pollutants for which health risks should be reduced, we conducted a health risk assessment of 49 indoor air pollutants measured in 602 houses during winter and summer from 2012 to 2014. Inhalation reference concentrations were determined, and the margins of exposure were estimated for each indoor pollutant from measured indoor air concentrations. Health risks due to ammonia and acidic gases, including formic acid, acetic acid, and hydrogen chloride, were also assessed. Overall, during both winter and summer, the highest risk pollutants were acrolein, nitrogen dioxide, benzene, formic acid, and hydrogen chloride. The health risks of propanal, acetaldehyde, and 1,4-dichlorobenzene were also high. Principal component analysis (PCA) suggested an independent principal component for 1,4-dichlorobenzene. The primary source of exposure to 1,4-dichlorobenzene in Japan is an indoor household insect repellent. The improvement of individual lifestyle and housing may be appropriate targets for reducing the risk associated with this compound. The provision of further information on the risk to consumers and promotion of changes in consumer consciousness are needed. PCA suggested that the health risks of indoor air pollutants are amalgamated into similar chemical families, such as aldehydes, aliphatic hydrocarbons, aromatic hydrocarbons, or acetic esters. Our results suggest that health-based guidelines or source control measures, based on these chemical families and similar health endpoints, are appropriate for reducing total health risk due to multiple low level indoor pollutants. Copyright © 2015 Elsevier Inc

  20. Exposure to airborne microbial components in autumn and spring during work at Danish biofuel plants.

    PubMed

    Madsen, A M

    2006-11-01

    Exposure to microbial components can cause respiratory problems. The exposure levels to microbial components at biofuel plants are not known. Therefore, exposure to inhalable airborne fungi, bacteria, actinomycetes, endotoxin and NAGase was measured using personal and stationary samplers at five Danish biofuel plants in autumn and spring. The personal exposure levels to endotoxin (median=55 EU m-3), thermophilic actinomycetes (median=1.3x10(4) colony forming units (cfu) m-3), total bacteria (median=48x10(4) cells m-3) and total fungi (median=21x10(4) spores m-3) were, in general, high at the five biofuel plants. At straw reception areas, higher exposure to most microbial components was found in spring than in autumn. Endotoxin was found in higher concentrations at straw plants than at wood-chip plants, while the opposite was measured for Aspergillus fumigatus. Some tasks were associated with exposures to microorganisms and endotoxins at much higher levels than the suggested occupational exposure limits. For example, people working with a straw shredder for at least 30 min during a working day were exposed to a median endotoxin exposure of 23,775 endotoxin units (EU) m-3. People working with estimating the water content in wood chips and repairing the chips cranes for at least 30 min during a working day were exposed to a median value of A. fumigatus of 6.7x10(4) cfu m-3 and a median value of fungi of 70x10(4) spores m-3. Consequently, this working environment may cause respiratory disorders in the people working at the plant. Differences in exposure levels were seen between the plants and this may partly be due to differences of the process equipment, tasks and the biofuel handled.

  1. Estimated rate of fatal automobile accidents attributable to acute solvent exposure at low inhaled concentrations.

    PubMed

    Benignus, Vernon A; Bushnell, Philip J; Boyes, William K

    2011-12-01

    Acute solvent exposures may contribute to automobile accidents because they increase reaction time and decrease attention, in addition to impairing other behaviors. These effects resemble those of ethanol consumption, both with respect to behavioral effects and neurological mechanisms. These observations, along with the extensive data on the relationship between ethanol consumption and fatal automobile accidents, suggested a way to estimate the probability of fatal automobile accidents from solvent inhalation. The problem can be approached using the logic of the algebraic transitive postulate of equality: if A=B and B=C, then A=C. We first calculated a function describing the internal doses of solvent vapors that cause the same magnitude of behavioral impairment as ingestion of ethanol (A=B). Next, we fit a function to data from the literature describing the probability of fatal car crashes for a given internal dose of ethanol (B=C). Finally, we used these two functions to generate a third function to estimate the probability of a fatal car crash for any internal dose of organic solvent vapor (A=C). This latter function showed quantitatively (1) that the likelihood of a fatal car crash is increased by acute exposure to organic solvent vapors at concentrations less than 1.0 ppm, and (2) that this likelihood is similar in magnitude to the probability of developing leukemia from exposure to benzene. This approach could also be applied to other potentially adverse consequences of acute exposure to solvents (e.g., nonfatal car crashes, property damage, and workplace accidents), if appropriate data were available.

  2. Single inhalation exposure to 90SrCl2 in the beagle dog: hematological effects

    SciTech Connect

    Gillett, N.A.; Muggenburg, B.A.; Boecker, B.B.; Hahn, F.F.; Seiler, F.A.; Rebar, A.H.; Jones, R.K.; McClellan, R.O.

    1987-05-01

    The toxicity of /sup 90/Sr administered by the inhalation route was studied in young adult Beagle dogs exposed once to aerosols containing /sup 90/SrCl/sub 2/. Due to its relatively soluble chemical form, /sup 90/Sr was rapidly translocated from lung to bone where a substantial portion was retained for a long period of time. This resulted in only a brief radiation exposure of the respiratory tract and a protracted exposure of the skeleton. The long-term retained burdens ranged from 0.037 to 4.4 MBq /sup 90/Sr/kg body wt. Dogs were subsequently observed throughout their life span. Six dogs with long-term retained burdens of 1.7 to 4.1 MBq /sup 90/Sr/kg died at less than 32 days after exposure from radiation-induced bone marrow hypoplasia. Review of hematological parameters of all dogs showed a similar, consistent, and dose-related pancytopenia in those animals having a long-term retained burden of greater than 0.37 MBq /sup 90/Sr/kg. Thrombocytopenia and neutropenia persisted in all exposed dogs through 1000 days after exposure. For reference purposes, a burden of 0.37 MBq /sup 90/Sr/kg is calculated to deliver an average radiation dose to the skeleton over 30, 100, and 1000 days after intake of 1.0, 2.8, and 17 Gy, respectively. The hematologic changes were similar to those seen in people exposed to high doses of whole-body external radiation.

  3. Treatment with endotracheal therapeutics after sarin microinstillation inhalation exposure increases blood cholinesterase levels in guinea pigs.

    PubMed

    Che, Magnus M; Song, Jian; Oguntayo, Samuel; Doctor, Bhupendra P; Rezk, Peter; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2012-05-01

    Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in the blood and tissues of animals that are treated with a number of endotracheally aerosolized therapeutics for protection against inhalation toxicity to sarin. Therapeutics included, aerosolized atropine methyl bromide (AMB), scopolamine or combination of AMB with salbutamol, sphingosine 1-phosphate, keratinocyte growth factor, adenosine A1 receptor antisense oligonucleotide (EPI2010), 2,3-diacetyloxybenzoic acid (2,3 DABA), oxycyte, and survanta. Guinea pigs exposed to 677.4 mg/m(3) or 846.5 mg/m(3) (1.2 LCt(50)) sarin for 4 min using a microinstillation inhalation exposure technique and treated 1 min later with the aerosolized therapeutics. Treatment with all therapeutics significantly increased the survival rate with no convulsions throughout the 24 h study period. Blood AChE activity determined using acetylthiocholine as substrate showed 20% activity remaining in sarin-exposed animals compare to controls. In aerosolized AMB and scopolamine-treated animals the remaining AChE activity was significantly higher (45-60%) compared to sarin-exposed animals (p < 0.05). Similarly, treatment with all the combination therapeutics resulted in significant increase in blood AChE activity in comparison to sarin-exposed animals although the increases varied between treatments (p < 0.05). BChE activity was increased after treatment with aerosolized therapeutics but was lesser in magnitude compared to AChE activity changes. Various tissues showed elevated AChE activity after therapeutic treatment of sarin-exposed animals. Increased AChE and BChE activities in animals treated with nasal therapeutics suggest that enhanced breathing and reduced respiratory toxicity/lung injury possibly contribute to rapid normalization of chemical warfare nerve agent inhibited cholinesterases.

  4. Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge

    PubMed Central

    He, Rui; Oyoshi, Michiko K.; Jin, Haoli; Geha, Raif S.

    2007-01-01

    IL-17 has been implicated in a number of inflammatory diseases, but the conditions of antigen exposure that drive the generation of Th17 responses have not been well defined. Epicutaneous (EC) immunization of mice with ovalbumin (OVA), which causes allergic skin inflammation with many characteristics of the skin lesions of atopic dermatitis, was found to also drive IL-17 expression in the skin. EC, but not i.p., immunization of mice with OVA drove the generation of IL-17-producing T cells in draining lymph nodes and spleen and increased serum IL-17 levels. OVA inhalation by EC-sensitized mice induced IL-17 and CXCL2 expression and neutrophil influx in the lung along with bronchial hyperreactivity, which were reversed by IL-17 blockade. Dendritic cells trafficking from skin to lymph nodes expressed more IL-23 and induced more IL-17 secretion by naïve T cells than splenic dendritic cells. This was inhibited by neutralizing IL-23 in vitro and by intradermal injection of anti-TGFβ neutralizing antibody in vivo. Our findings suggest that initial cutaneous exposure to antigens in patients with atopic dermatitis may selectively induce the production of IL-17, which, in turn, drives inflammation of their airways. PMID:17893340

  5. Potential for Inhalation Exposure to Engineered Nanoparticles from Nanotechnology-Based Cosmetic Powders

    PubMed Central

    Nazarenko, Yevgen; Zhen, Huajun; Han, Taewon; Lioy, Paul J.

    2012-01-01

    Background: The market of nanotechnology-based consumer products is rapidly expanding, and the lack of scientific evidence describing the accompanying exposure and health risks stalls the discussion regarding its guidance and regulation. Objectives: We investigated the potential for human contact and inhalation exposure to nanomaterials when using nanotechnology-based cosmetic powders and compare them with analogous products not marketed as nanotechnology based. Methods: We characterized the products using transmission electron microscopy (TEM) and laser diffraction spectroscopy and found nanoparticles in five of six tested products. TEM photomicrographs showed highly agglomerated states of nanoparticles in the products. We realistically simulated the use of cosmetic powders by applying them to the face of a human mannequin head while simultaneously sampling the released airborne particles through the ports installed in the mannequin’s nostrils. Results: We found that a user would be exposed to nanomaterial predominantly through nanoparticle-containing agglomerates larger than the 1–100-nm aerosol fraction. Conclusions: Predominant deposition of nanomaterial(s) will occur in the tracheobronchial and head airways—not in the alveolar region as would be expected based on the size of primary nanoparticles. This could potentially lead to different health effects than expected based on the current understanding of nanoparticle behavior and toxicology studies for the alveolar region. PMID:22394622

  6. Potential for inhalation exposure to engineered nanoparticles from nanotechnology-based cosmetic powders.

    PubMed

    Nazarenko, Yevgen; Zhen, Huajun; Han, Taewon; Lioy, Paul J; Mainelis, Gediminas

    2012-06-01

    The market of nanotechnology-based consumer products is rapidly expanding, and the lack of scientific evidence describing the accompanying exposure and health risks stalls the discussion regarding its guidance and regulation. We investigated the potential for human contact and inhalation exposure to nanomaterials when using nanotechnology-based cosmetic powders and compare them with analogous products not marketed as nanotechnology based. We characterized the products using transmission electron microscopy (TEM) and laser diffraction spectroscopy and found nanoparticles in five of six tested products. TEM photomicrographs showed highly agglomerated states of nanoparticles in the products. We realistically simulated the use of cosmetic powders by applying them to the face of a human mannequin head while simultaneously sampling the released airborne particles through the ports installed in the mannequin's nostrils. We found that a user would be exposed to nanomaterial predominantly through nanoparticle-containing agglomerates larger than the 1-100-nm aerosol fraction. Predominant deposition of nanomaterial(s) will occur in the tracheobronchial and head airways--not in the alveolar region as would be expected based on the size of primary nanoparticles. This could potentially lead to different health effects than expected based on the current understanding of nanoparticle behavior and toxicology studies for the alveolar region.

  7. Pathways of inhalation exposure to manganese in children living near a ferromanganese refinery: A structural equation modeling approach.

    PubMed

    Fulk, Florence; Succop, Paul; Hilbert, Timothy J; Beidler, Caroline; Brown, David; Reponen, Tiina; Haynes, Erin N

    2017-02-01

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation pathway model to ambient air Mn was hypothesized. Data for model evaluation were obtained from participants in the Communities Actively Researching Exposure Study (CARES). These data were collected in 2009 and included levels of Mn in residential soil and dust, levels of Mn in children's hair, information on the amount of time the child spent outside, heat and air conditioning in the home and level of parent education. Hair Mn concentration was the primary endogenous variable used to assess the theoretical inhalation exposure pathways. The model indicated that household dust Mn was a significant contributor to child hair Mn (0.37). Annual ambient air Mn concentration (0.26), time children spent outside (0.24) and soil Mn (0.24) significantly contributed to the amount of Mn in household dust. These results provide a potential framework for understanding the inhalation exposure pathway for children exposed to ambient air Mn who live in proximity to an industrial emission source.

  8. Pulmonary toxicity in mice by 2- and 13-week inhalation exposures to indium-tin oxide and indium oxide aerosols.

    PubMed

    Nagano, Kasuke; Nishizawa, Tomoshi; Eitaki, Yoko; Ohnishi, Makoto; Noguchi, Tadashi; Arito, Heihachiro; Fukushima, Shoji

    2011-01-01

    Inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) in mice were characterized in comparison with those previously reported in rats. B6C3F(1) mice of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m(3) or 13 wk at 0, 0.1or 1 mg/m(3). ITO and IO particles were deposited in the lung, mediastinal lymph node (MLN) and nasal-associated lymphoid tissue. Alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and increased lung weight were induced by 2- and 13-week exposures to ITO and IO, while alveolar epithelial hyperplasia occurred only in the 2-week exposures. Thickened pleural wall, hyperplastic MLN, extramedullary hematopoiesis in the spleen and increased levels of erythrocyte parameters were induced by 13-week exposure to ITO. The ITO- and IO-induced pulmonary lesions were milder in mice than those previously reported in rats, and the fibrotic lesions were different between these two species. Indium levels in the lung and pooled blood were analyzed in the mice exposed to ITO and IO for 13 wk. In the 13-week inhalation exposure of mice to ITO, alveolar proteinosis and significantly increased lung weight were induced at the same exposure concentration as the current threshold limit value for indium and its compounds.

  9. Assessment of the mode of action for hexavalent chromium-induced lung cancer following inhalation exposures.

    PubMed

    Proctor, Deborah M; Suh, Mina; Campleman, Sharan L; Thompson, Chad M

    2014-11-05

    Inhalation of hexavalent chromium [Cr(VI)] is associated with increased lung cancer risk among workers in several industries, most notably chromate production workers exposed to high concentrations of Cr(VI) (≥100 μg/m(3)), for which clear exposure-response relationships and respiratory irritation and tissue damage have been reported. Data from this industry are used to assess lung cancer risk associated with environmental and current occupational exposures, occurring at concentrations that are significantly lower. There is considerable uncertainty in the low dose extrapolation of historical occupational epidemiology data to assess risk at current exposures because no published or well recognized mode of action (MOA) for Cr(VI)-induced lung tumors exists. We conducted a MOA analysis for Cr(VI)-induced lung cancer evaluating toxicokinetic and toxicological data in humans and rodents and mechanistic data to assess plausibility, dose-response, and temporal concordance for potential MOAs. Toxicokinetic data support that extracellular reduction of Cr(VI), which limits intracellular absorption of Cr(VI) and Cr(VI)-induced toxicity, can be overwhelmed at high exposure levels. In vivo genotoxicity and mutagenicity data are mostly negative and do not support a mutagenic MOA. Further, both chronic bioassays and the epidemiologic literature support that lung cancer occurs at exposures that cause tissue damage. Based on this MOA analysis, the overall weight of evidence supports a MOA involving deposition and accumulation of particulate chromium in the bifurcations of the lung resulting in exceedance of clearance mechanisms and cellular absorption of Cr(VI). Once inside the cell, reduction of Cr(VI) results in oxidative stress and the formation of Cr ligands. Subsequent protein and DNA damage lead to tissue irritation, inflammation, and cytotoxicity. These effects, concomitant with increased cell proliferation, result in changes to DNA sequences and/or methylation status

  10. Exposure to grain dust and microbial components in the Norwegian grain and compound feed industry.

    PubMed

    Halstensen, Anne Straumfors; Heldal, Kari Kulvik; Wouters, Inge M; Skogstad, Marit; Ellingsen, Dag G; Eduard, Wijnand

    2013-11-01

    The aim of this study was to extensively characterize grain workers' personal exposure during work in Norwegian grain elevators and compound feed mills, to identify differences in exposures between the workplaces and seasons, and to study the correlations between different microbial components. Samples of airborne dust (n = 166) were collected by full-shift personal sampling during work in 20 grain elevators and compound feed mills during one autumn season and two winter seasons. The personal exposure to grain dust, endotoxins, β-1→3-glucans, bacteria, and fungal spores was quantified. Correlations between dust and microbial components and differences between workplaces and seasons were investigated. Determinants of endotoxin and β-1→3-glucan exposure were evaluated by linear mixed-effect regression modeling. The workers were exposed to an overall geometric mean of 1.0mg m(-3) inhalable grain dust [geometric standard deviation (GSD) = 3.7], 628 endotoxin units m(-3) (GSD = 5.9), 7.4 µg m(-3) of β-1→3-glucan (GSD = 5.6), 21 × 10(4) bacteria m(-3) (GSD = 7.9) and 3.6 × 10(4) fungal spores m(-3) (GSD = 3.4). The grain dust exposure levels were similar across workplaces and seasons, but the microbial content of the grain dust varied substantially between workplaces. Exposure levels of all microbial components were significantly higher in grain elevators compared with all other workplaces. The grain dust exposure was significantly correlated (Pearson's r) with endotoxin (rp = 0.65), β-1→3-glucan (rp = 0.72), bacteria (rp = 0.44) and fungal spore (rp = 0.48) exposure, whereas the explained variances were strongly dependent on the workplace. Bacteria, grain dust, and workplace were important determinants for endotoxin exposure, whereas fungal spores, grain dust, and workplace were important determinants for β-1→3-glucan exposure. Although the workers were exposed to a relatively low mean dust level, the microbial exposure was high. Furthermore, the

  11. Inhalation exposures to particulate matter and carbon monoxide during Ethiopian coffee ceremonies in Addis Ababa: a pilot study.

    PubMed

    Keil, Chris; Kassa, Hailu; Brown, Alexander; Kumie, Abera; Tefera, Worku

    2010-01-01

    The unique Ethiopian cultural tradition of the coffee ceremony increases inhalation exposures to combustion byproducts. This pilot study evaluated exposures to particulate matter and carbon monoxide in ten Addis Ababa homes during coffee ceremonies. For coffee preparers the geometric mean (57 μg/m³) and median (72 μg/m³) contributions to an increase in a 24-hour time-weighted average exposure were above World Health Organization (WHO) guidelines. At 40% of the study sites the contribution to the 24-hour average exposure was greater than twice the WHO guideline. Similar exposure increases existed for ceremony participants. Particulate matter concentrations may be related to the use of incense during the ceremony. In nearly all homes the WHO guideline for a 60-minute exposure to carbon monoxide was exceeded. Finding control measures to reduce these exposures will be challenging due to the deeply engrained nature of this cultural practice and the lack of availability of alternative fuels.

  12. Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes

    PubMed Central

    2014-01-01

    Background Engineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNT (5 mg/m3, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation. Results Twenty-three percent of the filtered air controls, 26.5% of the MWCNT-exposed, and 51.9% of the MCA-exposed mice, had lung bronchiolo-alveolar adenomas and lung adenocarcinomas. The average number of tumors per mouse was 0.25, 0.81 and 0.38 respectively. By contrast, 90.5% of the mice which received MCA followed by MWCNT had bronchiolo-alveolar adenomas and adenocarcinomas with an average of 2.9 tumors per mouse 17months after exposure. Indeed, 62% of the mice exposed to MCA followed by MWCNT had bronchiolo-alveolar adenocarcinomas compared to 13% of the mice that received filtered air, 22% of the MCA-exposed, or 14% of the MWCNT-exposed. Mice with early morbidity resulting in euthanasia had the highest rate of metastatic disease. Three mice exposed to both MCA and

  13. Trichloroethene levels in human blood and exhaled breath from controlled inhalation exposure.

    PubMed Central

    Pleil, J D; Fisher, J W; Lindstrom, A B

    1998-01-01

    (SE) = 0.12 across all subjects. blood/breath comparisons at equilibrium resulted in calculated in vivo partition coefficients with a mean of 10.8 and SE = 0.60 across all subjects and experiments and 9.69 with SE = 0.93 for elimination-only experiments. We found that about 78% of trichloroethene entering the body during inhalation exposure is metabolized, stored, or excreted through routes other than exhalation. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9721257

  14. Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats.

    PubMed

    Shim, Ilseob; Seo, Gyun-Baek; Oh, Eunha; Lee, Mimi; Kwon, Jung-Taek; Sul, Donggeun; Lee, Byung-Woo; Yoon, Byung-Il; Kim, Pilje; Choi, Kyunghee; Kim, Hyun-Mi

    2013-01-01

    Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.

  15. Lung cancer risk from exposure to alpha particles and inhalation of other pollutants in rats

    SciTech Connect

    Burns, F.J.

    1990-01-01

    The goal of these experiments is to establish a quantitative correlation between early DNA damage and cancer incidence in a way that would be helpful for assessing the carcinogenic risk of radon alone or in combination with specific indoor pollutants. Rat tracheal epithelium has been exposed in vivo to {sup 210}Po alpha particles in the presence and absence of NO{sub 2} or cigarette smoke. The major accomplishments so far are: the design and implementation of a tracheal implant to simulate radon alpha particle exposure, the measurement of DNA breaks in a small 7.0 mm segment of the trachea exposed to external x-irradiation, the measurement of the rate of repair of the x-ray induced tracheal DNA strand breaks, the measurement of DNA strand breaks following inhalation of cigarette smoke or NO{sub 2}, the measurement of tracheal DNA stand breaks following exposure to high doses {sup 210}Po alpha particle radiation, the assessment of the amount of mucous in the goblet cells and in the underlying mucous glands. So far we have been unable to detect DNA strand breaks in the tracheal epithelium as a result of exposure to NO{sub 2} cigarette smoke or {sup 210}Po alpha particles. We have developed a simple artificial' trachea consisting of rat tracheal epithelial cells growing on a basement membrane coated millipore filter. Experiments are proposed to utilize these artificial tracheas to eliminate the potential interference of increased mucous secretion and/or inflammation that can significantly affect the radiation dose from the alpha particles. 61 refs., 17 figs.

  16. Three cases of sudden death due to butane or propane gas inhalation: analysis of tissues for gas components.

    PubMed

    Sugie, Hideaki; Sasaki, Chizuko; Hashimoto, Chikako; Takeshita, Hiroshi; Nagai, Tomonori; Nakamura, Shigeki; Furukawa, Masataka; Nishikawa, Takashi; Kurihara, Katsuyoshi

    2004-07-16

    We report three cases of sudden death due to inhalation of portable cooking stove fuel (case 1), cigarette lighter fuel (case 2), and liquefied petroleum gas (LPG) (case 3). Specimens of blood, urine, stomach contents, brain, heart, lung, liver, kidney, and fat were collected and analyzed for propylene, propane, isobutane, and n-butane by headspace gas chromatography. n-Butane was the major substance among the volatiles found in the tissues of cases 1 and 2, and propane was the major substance in case 3. A combination of the autopsy findings and the gas analysis results revealed that the cause of death was ventricular fibrillation induced by hard muscle exercise after gas inhalation in cases 1 and 2, and that the cause of death in case 3 might be hypoxia. It is possible that the victim in case 3 was under anesthetic toxicity of accumulated isobutane which is a minor component of liquefied petroleum gas.

  17. Occurrence, seasonal variation and inhalation exposure of atmospheric organophosphate and pyrethroid pesticides in an urban community in South China.

    PubMed

    Li, Huizhen; Ma, Hongzhu; Lydy, Michael J; You, Jing

    2014-01-01

    The shift in pesticide usage patterns demands a better understanding of the occurrence, fate and exposure risk of atmospheric current-use pesticides (CUPs). Air samples collected in different seasons from an urban community in Guangzhou, China were analyzed to investigate seasonal variation, gas-particle partitioning and inhalation exposure of atmospheric organophosphate and pyrethroid pesticides. Chlorpyrifos and eight pyrethroids were detected in the air samples and the total concentrations of the nine CUPs ranged from 150 to 3816 pg m(-3). Chlorpyrifos and cypermethrin were the most dominant CUPs detected in the atmosphere, accounting for 68% and 15% of the total CUPs, respectively. Seasonal variation in concentration was observed for most CUPs, with peak concentrations occurring in summer and fall, which was consistent with their application patterns. Partitioning of chlorpyrifos between gas and particle phases was also seasonally-dependent, with more chlorpyrifos found in the gas phase in summer and fall. Additionally, gas-particle partitioning analysis suggested that chlorpyrifos might experience long-range transport. Evaluation of potential exposure from inhalation of atmospheric CUPs suggested that children, toddlers and infants had the highest exposure, but the risk quotients were low for all age groups when annual average concentrations were used as exposure metrics. Exposure risk was higher in summer and fall than the annual average level due to higher atmospheric pesticide concentrations, longer exposure times and more pesticides being in the gaseous form. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Quantifying the distribution of inhalation exposure in human populations: Distribution of minute volumes in adults and children

    SciTech Connect

    Beals, J.A.J.; Funk, L.M.; Fountain, R.; Sedman, R.

    1996-09-01

    Assessments of inhalation exposure to environmental agents necessitate quantitative estimates of pulmonary ventilation rates. Estimating a range of exposures in a given population requires an understanding of the variability of ventilation rates in the population. Distribution of ventilation rates (Ve) were described based on the results of a large study where Ve were measured while subjects performed a variety of physical tasks. Three distinct ventilation levels were identified using cluster analyses of the mean Ve and then various activities were assigned to the three levels using a k-means procedure. Separate distributions were identified for the three Ve levels for adult males, adult females, and children. The variability of Ve was consistent with a lognormal distribution for all groups. An aggregate daily inhalation rate can be estimated based on the distributions of Ve. 41 refs., 1 fig., 5 tabs.

  19. Fractional Exhaled Nitric Oxide (FeNO) and Spirometry as Indicators of Inhalation Exposure to Chemical Agents in Pathology Workers.

    PubMed

    Suzuki, Ritsuko Arakawa; Irokawa, Toshiya; Ogawa, Hiromasa; Ohkouchi, Shinya; Tabata, Masao; Togashi, Susumu; Nakamura, Takeshi; Ohisa, Noriko; Nikkuni, Etsuhiro; Miura, Emiri; Yoshida, Kaoru; Inomata, Hiroshi; Kurosawa, Hajime

    2017-05-01

    The objective of this study was to examine whether fractional exhaled nitric oxide (FeNO) and spirometry can be used as indices to evaluate adverse health effects of low-concentrated chemical inhalation exposure, mainly to formaldehyde. Thirty-three subjects (pathology technicians) and 30 controls (workers without handling any chemicals in the same hospitals) participated in this study. All participants underwent FeNO measurement and spirometry before and after 5 days of work. FeNO significantly increased in the subjects with a history of asthma (P < 0.05), whereas forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) decreased in the subjects (P < 0.05). Furthermore, work duration and pre-work levels of FEV1 in the subjects had a significant association. The results suggest that FeNO, FVC, and FEV1 represent effective health-effect indices of low-concentrated chemical inhalation exposure.

  20. Endotoxins: The Critical Risk Factor in Reclaimed Water via Inhalation Exposure.

    PubMed

    Xue, Jinling; Zhang, Jinshan; Xu, Bi; Xie, Jiani; Wu, Wenzhao; Lu, Yun

    2016-11-01

    The use of reclaimed water for nonpotable uses requires consideration of potential adverse health effects. Considering that inhalation can be a significant route of transmission of microorganisms and inflammatory agents, this study used a mouse model to test the possible adverse effects of reclaimed water use during car washing where aerosols are generated. Intensive innate immune responses were found in the lungs after acute exposure, and the lavage polymorphonuclear cell proportion was the most sensitive end point. Four types of evidence are presented to demonstrate that the main risk factor that initiates innate inflammation is the free endotoxin. (1) Small molecules (<10 kDa) cannot induce inflammation. (2) The endotoxin levels of 11 water samples from five different plants showed positive correlations with inflammatory responses. (3) Actual water samples showed similar activities with free endotoxins other than bacterially bound endotoxins. (4) Specific removal of endotoxins with polymyxin B affinity chromatography further confirmed the role of free endotoxins. It is noteworthy that 62.9% of the investigated tertiary-treated water had endotoxin levels higher than the allowable acute threshold (120 endotoxin units/mL) under the hypothesized car wash condition, which strongly suggests the need to carefully consider the water treatment steps required to produce safe water for various reclaimed water end uses.

  1. INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE (LA) AND AMOSITE ASBESTOS

    EPA Science Inventory

    Inhalation toxicology studies are being conducted to inform the risk assessment ofLibby amphibole. The overall purpose of these studies is to compare the toxicity of inhaled Libby amphibole fibers to a positive control fiber sample (UICC amosite). A 2-week study was conducted to ...

  2. INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE (LA) AND AMOSITE ASBESTOS

    EPA Science Inventory

    Inhalation toxicology studies are being conducted to inform the risk assessment ofLibby amphibole. The overall purpose of these studies is to compare the toxicity of inhaled Libby amphibole fibers to a positive control fiber sample (UICC amosite). A 2-week study was conducted to ...

  3. Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats

    PubMed Central

    Boyes, William K.; Bercegeay, Mark; Degn, Laura; Beasley, Tracey E.; Evansky, Paul A.; Mwanza, Jean Claude; Geller, Andrew M.; Pinckney, Charles; Nork, T. Michael; Bushnell, Philip J.

    2016-01-01

    Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000 ppm toluene by inhalation (6 hr/d, 5 d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m2) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000 ppm toluene for 4 weeks were tested approximately 1 year after the completion of exposure. No statistically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No

  4. Toluene inhalation exposure for 13 weeks causes persistent changes in electroretinograms of Long-Evans rats.

    PubMed

    Boyes, William K; Bercegeay, Mark; Degn, Laura; Beasley, Tracey E; Evansky, Paul A; Mwanza, Jean Claude; Geller, Andrew M; Pinckney, Charles; Nork, T Michael; Bushnell, Philip J

    2016-03-01

    Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000ppm toluene by inhalation (6hr/d, 5d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m(2)) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000ppm toluene for 4 weeks were tested approximately 1year after the completion of exposure. No statistically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No

  5. Job categories and their effect on exposure to fungal alpha-amylase and inhalable dust in the U.K. baking industry.

    PubMed

    Elms, Joanne; Beckett, Paul; Griffin, Peter; Evans, Paul; Sams, Craig; Roff, Martin; Curran, Andrew D

    2003-01-01

    Enzymes in flour improver, in particular fungal alpha-amylase, are known to be a significant cause of respiratory allergy in the baking industry. This study measured total inhalable dust and fungal alpha-amylase exposures in U.K. bakeries, mills, and a flour improver production and packing facility and determined whether assignment of job description could identify individuals with the highest exposures to fungal alpha-amylase and inhalable dust. A total of 117 personal samples were taken for workers in 19 bakeries, 2 mills, and a flour improver production and packing facility and were analyzed using a monoclonal based immunoassay. Occupational hygiene surveys were undertaken for each site to assign job description and identify individuals who worked directly with flour improvers. Analysis of exposure data identified that mixers and weighers from large bakeries had the highest exposures to both inhalable dust and fungal alpha-amylase among the different categories of bakery workers (p<.01). Currently, the maximum exposure limit for flour dust in the United Kingdom is 10 mg/m(3) (8-hour time-weighted average reference period). In this study 25% of the total dust results for bakers exceeded 10 mg/m(3), and interestingly, 63% of the individuals with exposure levels exceeding 10 mg/m(3) were weighers and mixers. Individuals who worked directly with flour improvers were exposed to higher levels of both inhalable dust and fungal alpha-amylase (p<.01) than those who were not directly handling these products. Before sensitive immunoassays were utilized for the detection of specific inhalable allergens, gravimetric analysis was often used as a surrogate. There was a weak relationship between inhalable dust and fungal alpha-amylase exposures; however, inhalable dust levels could not be used to predict amylase exposures, which highlights the importance of measuring both inhalable dust and fungal alpha-amylase exposures.

  6. Assessment of inhalation exposures and potential health risks to the general population that resulted from the collapse of the World Trade Center towers.

    PubMed

    Lorber, Matthew; Gibb, Herman; Grant, Lester; Pinto, Joseph; Pleil, Joachim; Cleverly, David

    2007-10-01

    In the days following the collapse of the World Trade Center (WTC) towers on September 11, 2001 (9/11), the U.S. Environmental Protection Agency (EPA) initiated numerous air monitoring activities to better understand the ongoing impact of emissions from that disaster. Using these data, EPA conducted an inhalation exposure and human health risk assessment to the general population. This assessment does not address exposures and potential impacts that could have occurred to rescue workers, firefighters, and other site workers, nor does it address exposures that could have occurred in the indoor environment. Contaminants evaluated include particulate matter (PM), metals, polychlorinated biphenyls, dioxins, asbestos, volatile organic compounds, particle-bound polycyclic aromatic hydrocarbons, silica, and synthetic vitreous fibers (SVFs). This evaluation yielded three principal findings. (1) Persons exposed to extremely high levels of ambient PM and its components, SVFs, and other contaminants during the collapse of the WTC towers, and for several hours afterward, were likely to be at risk for acute and potentially chronic respiratory effects. (2) Available data suggest that contaminant concentrations within and near ground zero (GZ) remained significantly elevated above background levels for a few days after 9/11. Because only limited data on these critical few days were available, exposures and potential health impacts could not be evaluated with certainty for this time period. (3) Except for inhalation exposures that may have occurred on 9/11 and a few days afterward, the ambient air concentration data suggest that persons in the general population were unlikely to suffer short-term or long-term adverse health effects caused by inhalation exposures. While this analysis by EPA evaluated the potential for health impacts based on measured air concentrations, epidemiological studies conducted by organizations other than EPA have attempted to identify actual impacts. Such

  7. Consumer inhalation exposure to formaldehyde from the use of personal care products/cosmetics.

    PubMed

    Lefebvre, Marc-André; Meuling, Wim J A; Engel, Roel; Coroama, Manuela C; Renner, Gerald; Pape, Wolfgang; Nohynek, Gerhard J

    2012-06-01

    We measured consumer exposure to formaldehyde (FA) from personal care products (PCP) containing FA-releasing preservatives. Six study subjects applied facial moisturiser, foundation, shower gel, shampoo, deodorant, hair conditioner, hair styling gel or body lotion at the 90th percentile amount of EU PCP consumer use. FA air concentrations were measured in the empty room, in the presence of study subjects prior to PCP use, and for one hour (breathing zone, area monitoring) after PCP use. The mean FA air concentration in the empty bathroom was 1.32 ± 0.67 μg/m³, in the presence of subjects it was 2.33 ± 0.86 μg/m³). Except for body lotion and hair conditioner (6.2 ± 0.1.9 or 4.5 ± 0.1.5 μg/m³, respectively), mean 1-h FA air concentrations after PCP use were similar to background. Peak FA air concentrations, ranging from baseline values (2.2 μg/m³; shower gel) to 11.5 μg/m³ (body lotion), occurred during 0-5 to 5-10 min after PCP use. Despite of exaggerated exposure conditions, FA air levels were a fraction of those considered to be safe (120 μg/m³), occurring in indoor air (22-124 μg/m³) or expired human breath (1.4-87 μg/m³). Overall, our data yielded evidence that inhalation of FA from the use of PCP containing FA-releasers poses no risk to human health. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. A two-generation inhalation reproductive toxicity study upon the exposure to manganese chloride.

    PubMed

    McGough, Doreen; Jardine, Lynne

    2017-01-01

    A number of published studies have suggested that high levels of exposure to manganese, especially those found in occupational settings, can adversely affect the reproductive system. The objective of this study was therefore to investigate if these findings can be replicated using the Sprague Dawley rat and, if so, to identify those parts of the reproductive system are more susceptible. Male and female rats were exposed to manganese dichloride (MnCl2) via inhalation at concentrations of 0 (air-control); 5, 10 and 20μg/L air over 10 weeks (F0) and over 11 weeks (F1) prior to mating, and then throughout mating, gestation and lactation until termination after the F1 and F2 generation had reached Day 21 of lactation respectively. Animals were monitored for clinical signs of toxicity and for effects on body weight, food consumption, effects on the entire reproductive system including maternal care. The offspring were monitored for survival and growth up to weaning. Blood samples were taken from all adult animals for bioanalytical of manganese analysis prior to dosing, prior to mating and prior to weaning/necropsy. There were no deaths related to treatment, though respiratory tract effects were observed in F0 animals in the mid and high dose animals. Body weight and food consumption were affected at high dose in both generation. There were no treatment-related effects on the oestrous cycles, mating performance, sexual maturity, fertility or duration of gestation or litter size, the sperm motility, count of morphology (sperm) or the ovary follicle scoring in either generation. The No Observed Effect Level (NOEL) for reproductive performance was considered to be the target dose level of 20μg/L. Based on these findings, manganese chloride could not be considered a reprotoxicant under these conditions of exposure. Therefore, soluble and insoluble forms of inorganic manganese compounds by extrapolation cannot be considered as reprotoxicants.

  9. Effects of subchronic inhalation exposure to ethyl tertiary butyl ether on splenocytes in mice.

    PubMed

    Li, Q; Kobayashi, M; Inagaki, H; Hirata, Y; Hirata, K; Shimizu, T; Wang, R-S; Suda, M; Kawamoto, T; Nakajima, T; Kawada, T

    2011-01-01

    Ethyl tertiary-butyl ether (ETBE) is a motor fuel oxygenate used in reformulated gasoline. The current use of ETBE in gasoline or petrol is modest but increasing. To investigate the effects of ETBE on splenocytes, mice were exposed to 0 (control), 500 ppm, 1750 ppm, or 5000 ppm of ETBE by inhalation for 6 h/day for 5 days/wk over a 6- or 13-week period. Splenocytes were harvested from the control and exposed mice, and the following cell phenotypes were quantified by flow cytometry: (1) B cells (PerCP-Cy5.5-CD45R/B220), (2) T cells (PerCP-Cy5-CD3e), (3) T cell subsets (FITC-CD4 and PE-CD8a), (4) natural killer (NK) cells (PE-NK1.1), and (5) macrophages (FITC-CD11b). Body weight and the weight of the spleen were also examined. ETBE-exposure did not affect the weight of the spleen or body weight, while it transiently increased the number of RBC and the Hb concentration. The numbers of splenic CD3+, CD4+, and CD8+ T cells, the percentage of CD4+ T cells and the CD4+/CD8+ T cell ratio in the ETBE-exposed groups were significantly decreased in a dose-dependent manner. However, ETBE exposure did not affect the numbers of splenic NK cells, B cells, or macrophages or the total number of splenocytes. The above findings indicate that ETBE selectively affects the number of splenic T cells in mice.

  10. Analysis of Intervention Strategies for Inhalation Exposure to Polycyclic Aromatic Hydrocarbons and Associated Lung Cancer Risk Based on a Monte Carlo Population Exposure Assessment Model

    PubMed Central

    Zhou, Bin; Zhao, Bin

    2014-01-01

    It is difficult to evaluate and compare interventions for reducing exposure to air pollutants, including polycyclic aromatic hydrocarbons (PAHs), a widely found air pollutant in both indoor and outdoor air. This study presents the first application of the Monte Carlo population exposure assessment model to quantify the effects of different intervention strategies on inhalation exposure to PAHs and the associated lung cancer risk. The method was applied to the population in Beijing, China, in the year 2006. Several intervention strategies were designed and studied, including atmospheric cleaning, smoking prohibition indoors, use of clean fuel for cooking, enhancing ventilation while cooking and use of indoor cleaners. Their performances were quantified by population attributable fraction (PAF) and potential impact fraction (PIF) of lung cancer risk, and the changes in indoor PAH concentrations and annual inhalation doses were also calculated and compared. The results showed that atmospheric cleaning and use of indoor cleaners were the two most effective interventions. The sensitivity analysis showed that several input parameters had major influence on the modeled PAH inhalation exposure and the rankings of different interventions. The ranking was reasonably robust for the remaining majority of parameters. The method itself can be extended to other pollutants and in different places. It enables the quantitative comparison of different intervention strategies and would benefit intervention design and relevant policy making. PMID:24416436

  11. Determination of potential dermal and inhalation operator exposure to malathion in greenhouses with the whole body dosimetry method.

    PubMed

    Machera, K; Goumenou, M; Kapetanakis, E; Kalamarakis, A; Glass, C R

    2003-01-01

    One of the steps during the authorization process of plant protection products (PPP) in the European Union is to evaluate the safety of the operator. For this purpose, information on the probable levels of operator exposure during the proposed uses of the PPP is required. These levels can be estimated by using existing mathematical models or from field study data. However, the existing models have several shortcomings, including the lack of data for operator exposure levels during spray applications by hand lance, especially in greenhouses. The present study monitored the potential dermal and inhalation operator exposure from hand-held lance applications of malathion on greenhouse tomatoes at low and high spraying pressures. The methodology for monitoring potential exposure was based on the whole body dosimetry method. Inhalation exposure was monitored using personal air pumps and XAD-2 sampling tubes. For the monitoring of hand exposure, cotton gloves were used in two trials and rubber gloves in another three. The total volumes of spray solution contaminating the body of the operator were 25.37 and 35.83 ml/h, corresponding to 0.05 and 0.07% of the applied spray solution, respectively, in the case of low pressure knapsack applications and from 160.76 to 283.45 ml/h, corresponding to 0.09-0.19% of the spray solution applied, in the case of hand lance applications with tractor-generated high pressure. Counts on gloves depended on the absorbance/repellency of the glove material. The potential inhalation exposures were estimated at 0.07 and 0.09 ml/h in the case of low pressure knapsack applications, based on a ventilation rate of 25 l/min. Both potential dermal operator exposure (excluding hands) and potential inhalation exposure were increased by a factor of approximately 7 when the application pressure was increased from 3 to 18 bar in greenhouse trials with a tractor-assisted hand lance, the rest of the application conditions being very similar.

  12. Inhalation toxicity study of methanol, toluene, and methanol/toluene mixtures in rats: effects of 28-day exposure.

    PubMed

    Poon, R; Chu, I; Bjarnason, S; Potvin, M; Vincent, R; Miller, R B; Valli, V E

    1994-01-01

    The inhalation toxicity of methanol and toluene was investigated in rats. Young Sprague Dawley rats of both sexes were exposed to vapors of methanol (300 ppm, 3000 ppm), toluene (30 ppm, 300 ppm) or methanol/toluene (300/30 ppm, 300/300 ppm, 3000/30 ppm, and 3000/300 ppm) six hrs per day, five days/week for four weeks. Control animals inhaled air only. Increased serum alkaline phosphatase activity was observed in males exposed to high-dose toluene, and decreased creatinine was noted in the group exposed to high-dose methanol/toluene. The thyroid gland in females appeared to be a target organ for inhaled methanol, toluene, and methanol/toluene, although the changes were confined to a mild, and occasionally moderate, reduction in follicle size. Histopathological changes of the nasal passages, consisting of subepithelial nonsuppurative inflammation, occurred in higher incidences in rats exposed to methanol/toluene than in those exposed to the individual vapors. Inhalation of methanol, toluene, or methanol/toluene produced no changes in liver weights, hepatic mixed-function oxidases, or serum aspartate transaminase activities, and onlly minimal changes in liver histopathology. The only liver changes were decreased liver weight and increased cytoplasmic density of the periportal areas in females exposed to high-dose methanol/toluene. These data indicated that exposure to methanol, toluene, or a mixture of both produced mild biochemical effects and histological changes in the thyroid and nasal passage. No apparent interactive effects were observed.

  13. Delayed effects of acute oral and chronic inhalational exposure to methylparathion on learning and memory in rats.

    PubMed

    George, J; Andrade, C; Joseph, T

    1992-09-01

    Impairment of acquisition phase of the learning process was observed in rats even at 3 weeks after single oral exposure to the near-lethal dose of commercial grade methylparathion (MP) followed by atropine resuscitation. Though there was a trend towards memory impairment in this group of animals, memory retention was not significantly affected. Chronic inhalational exposure to MP (one exposure/day for 3 weeks) did not significantly alter learning or memory. No significant alteration in red blood cell or brain acetylcholinesterase levels were observed in either of the two groups. It appears that behavioural effects can persist even 3 weeks after exposure to acute near-lethal doses of the pesticide, as occurs in the clinical situation of suicidal attempts; while repeated exposure to no-observed-effect-level doses as occurs in farm and factory workers, may not be associated with behavioural changes.

  14. Retrospective exposure assessment for respirable and inhalable dust, crystalline silica and arsenic in the former German uranium mines of SAG/SDAG Wismut.

    PubMed

    Dahmann, D; Bauer, H-D; Stoyke, G

    2008-08-01

    Starting shortly after the reunification of Germany and lasting up to the end of the 1990s, an extensive series of retrospective exposure investigations for the East German uranium mining industry was performed in order to provide information about the exposure situation of the miners towards respirable dust, inhalable dust, crystalline silica and heavy metals. It should provide the necessary information for legal compensation of miners with potential industrial diseases as well as for epidemiological research. Extensive side-by-side measurements using original historic equipments as well as comprehensive evaluation of the time increments of specific jobs with respect to exposure relevant tasks were performed. After attributing average exposures to the tasks, shift exposures for the jobs could be calculated. By the end a comprehensive job exposure matrix for all underground jobs of the German uranium mining industry was developed for the components mentioned, including arsenic where relevant. In the early days of SAG/SDAG Wismut dust and silica exposures were extremely high with respirable dust up to 20 mg/m(3) and respirable crystalline silica well above 2 mg/m(3) as shift averages. Beginning from about the early 1960s dust control measures started to improve conditions dramatically. It is absolutely necessary to invest sufficient effort for the estimation of exposure situations of past technological environments. Especially, the situation of early mechanised mining, characterised by low ventilation, dry drilling techniques and generally lacking dust control measures was characterized by extreme shift exposures. It is important to keep these in mind when metal mining exposure in different environments is considered.

  15. Health worker exposure risk during inhalation sedation with sevoflurane using the (AnaConDa®) anaesthetic conserving device.

    PubMed

    González-Rodríguez, R; Muñoz Martínez, A; Galan Serrano, J; Moral García, M V

    2014-03-01

    Occupational exposure to sevoflurane should not exceed 2 ppm. During inhalation sedation with sevoflurane using the anaesthetic conserving device (AnaConDa(®)) in the post-anaesthesia care unit, waste gases can be reduced by gas extraction systems or scavenging devices such as CONTRAfluran™. However, the efficacy of these methods has not been clearly established. To determine the safest scenario for healthcare workers during inhalation sedation with sevoflurane in the post-surgical intensive care unit. An experimental study on occupational exposure was conducted in a post-cardiothoracic care unit during March-August 2009. The measurements were performed in four post-cardiac surgery sedated adults in post-surgical intensive care unit and four nurses at the bedside, and at four points: scenario A, inhalation sedation without gas extraction system or contrafluran as a reference scenario; scenario B, applying a gas extraction system to the ventilator; scenario C, using contrafluran; and scenario 0, performing intravenous isolation sedation. Sevoflurane concentrations were measured in the nurses' breathing area during patient care, and at 1.5 and 8 m from the ventilator using diffusive passive monitor badges. All badges corresponding to the nurses' breathing area were below 2 ppm. Levels of sevoflurane detected using prevention systems were lower than that in the control situation. Only one determination over 2 ppm was found, corresponding to the monitor placed nearest the gas outlet of the ventilator in scenario A. Trace concentrations of sevoflurane were found in scenario 0 during intravenous sedation. Administration of sevoflurane through the AnaConDa(®) system during inhalation sedation in post-surgical intensive care units is safe for healthcare workers, but gas extraction systems or scavenging systems, such as CONTRAfluran™ should be used to reduce occupational exposure as much as possible. Copyright © 2013 Sociedad Española de Anestesiología, Reanimaci

  16. Emission testing and inhalational exposure-based risk assessment for candles having Pb metal wick cores.

    PubMed

    van Alphen, M

    1999-12-15

    Segments of seven candles with wicks having a Pb metal core have been tested in a purpose-built combustion chamber to assess air Pb emissions. Emissions were collected on glass fibre filters that have been digested in concentrated HNO3 and analysed by flame atomic absorption spectroscopy (FAAS). Despite an indication of a bimodal distribution in Pb emission rates, and a range from 450 to 1130 micrograms Pb/h, the mean rate from the seven candles was 770 micrograms Pb/h. The 38-cm long candles are, on average, capable of emitting 104,000 micrograms of Pb into the air over approximately 127 h. A mean value of 20% of the Pb metal in the wick consumed by the candle is emitted into the air, the remainder appears to accumulate at the base of a molten wax-pool adjacent to the wick. Individual Pb-bearing particles from the combustion of candles were observed in a field emission scanning electron microscope (FESEM) to have a diameter of 1 micron or less. The emission from the candles has been analysed by X-ray diffraction (XRD) and identified as Sodium Lead Carbonate Hydroxide [NaPb2(CO3)2OH]. This compound, being a Pb carbonate, is likely to be easily absorbed in the lungs and gastrointestinal tract. Risks associated with inhalational exposure have been assessed after determining indoor lead in air (PbA) concentrations. Given a lack of information on the duration of use of candles, a range of scenarios from worst possible case to daily and weekly burning regimes are evaluated. Detailed evaluations of PbA are based on the emission from a single candle at rates of 500 and 1000 micrograms Pb/h, room volumes of 25 and 50 m3, durations of emission of 1.5, 3 and 6 h and air infiltration rates of 0, 0.25, 0.5, 0.75 and 1.0 air volume changes per hour (ACH). A candle burnt for 3 h at 1000 micrograms/h in a 50 m3 room having poor ventilation at 0.25 ACH is estimated to yield a 24-h average lead in air concentration of 9.9 micrograms/m3 with a peak PbA value of 42.1 micrograms/m3

  17. Children's inhalation exposure to methamidophos from sprayed potato fields in Washington State: exploring the use of probabilistic modeling of meteorological data in exposure assessment.

    PubMed

    Ramaprasad, Jaya; Tsai, Min G-Yi; Fenske, Richard A; Faustman, Elaine M; Griffith, William C; Felsot, Allan S; Elgethun, Kai; Weppner, Sarah; Yost, Michael G

    2009-09-01

    We examined the significance of meteorology and postspray volatilization of methamidophos (an organophosphorus insecticide) in assessing potential inhalation risk to children in an agricultural community. We combined fluxes from sources and dispersion modeling with a range of possible local meteorology to create output to study the variability in potential community exposure as a result of changing temperature, wind speeds and wind directions. This work is based on an aerial spray drift study where air sampling measurements of methamidophos were made before, during and after a spray event were used to examine acute inhalation risk for children living in an Eastern Washington State community in close proximity (between 15 and 200 m) to sprayed potato fields. We compared the measured average air concentrations of methamidophos in the community to a "no observed adverse effect level" for subchronic inhalation to characterize acute and subchronic inhalation risks. The baseline estimates of inhalation exposure were below Environment Protection Agency's (EPA) level of concern based on a target margin of exposure of 300. As meteorological conditions during and after spraying influence the amount of material moving into areas where children reside we used historical meteorological data to drive model simulations that predicted likely air residue concentrations under different wind and temperature conditions. We also added variability to the decay constant and initial emission fluxes to create a 2-D simulation of estimated air concentrations in the community near the fields. This work provides a methodological framework for the assessment of air concentrations of pesticides from agricultural sprays in the absence of extended measurements, although including variability from meteorological conditions. The deterministic as well as the probabilistic risk analyses in this study indicated that postspray volatilization in the specific spray situation analyzed (methamidophos

  18. Graphical Arrays of Chemical-Specific Health Effect Reference Values for Inhalation Exposures (2009 Final Report)

    EPA Science Inventory

    This document provides graphical arrays and tables of key information on the derivation of human inhalation health effect reference values for specific chemicals, allowing comparisons across durations, populations, and intended use. A number of program offices within the Agency, ...

  19. Graphical Arrays of Chemical-Specific Health Effect Reference Values for Inhalation Exposures (2009 Final Report)

    EPA Science Inventory

    This document provides graphical arrays and tables of key information on the derivation of human inhalation health effect reference values for specific chemicals, allowing comparisons across durations, populations, and intended use. A number of program offices within the Agency, ...

  20. Acrolein inhalation alters myocardial synchrony and performance at and below exposure concentrations that cause ventilatory responses

    EPA Science Inventory

    Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we ...

  1. Pathology of acute inhalation exposure to 3-methylfuran in the rat and hamster

    SciTech Connect

    Haschek, W.M.; Morse, C.C.; Boyd, M.R.; Hakkinen, P.J.; Witschi, H.P.

    1983-12-01

    The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in SPF Fischer-derived and CD/CR rats, and golden Syrian hamsters by determination of the 2-week LC50, and by histologic examination of animals killed 1, 3, and 14 days following a 1-hr exposure to 148 and 322 mumole 3MF/liter for CD/CR rats and hamsters, respectively. The Fischer-derived rat was more sensitive to 3MF-induced lethality than the CD/CR rat with an LC50 in the male rat of 81 mumole/liter-1 hr as compared to 222 mumole/liter-1 hr. No sex difference was found. The hamster was relatively resistant with no lethality at 322 mumole 3MF/liter-2 hr. Pulmonary damage was present in both species. In the hamster, selective necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen at 1 day with virtually complete regeneration by 14 days whereas in the rat the bronchiolar epithelial damage was more extensive and was followed by scattered peribronchiolar fibrosis and epithelial mucous metaplasia suggestive of ''small airway disease'' of man. Relatively selective 3MF-induced necrosis of olfactory epithelium occurred in the nasal mucosa of both species. Resolution of this lesion was seen by 14 days in the hamster. In the rat, however, the necrosis was much more extensive and was followed by partially occlusive fibrosis of the nasal cavity as seen at 14 days. 3MF also induced centrilobular hepatic necrosis in both species. In the rat, lymphocyte necrosis in the thymus and spleen, and esophageal necrosis was also seen.

  2. Pathology of acute inhalation exposure to 3-methylfuran in the rat and hamster

    SciTech Connect

    Haschek, W.M.; Morse, C.C.; Boyd, M.R.; Hakkinen, P.J.; Witschi, H.P.

    1983-01-01

    The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in SPF Fischer-derived and CD/CR rats, and golden Syrian hamsters by determination of the 2-week LC/sub 50/, and by histologic examination of animals killed 1, 3, and 14 days following a 1-hr exposure to 148 and 322 ..mu..mole 3MF/liter for CD/CR rats and hamsters, respectively. The Fischer-derived rat was more sensitive to 3MF-induced lethality than the CD/CR rat with an LC/sub 50/ in the male rat of 81 ..mu..mole/liter-1 hr as compared to 222 ..mu..mole/liter-1hr. No sex difference was found. The hamster was relatively resistant with no lethality at 322 ..mu..mole 3MF/liter-2 hr. Pulmonary damage was present in both species. In the hamster, selective necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen at 1 day with virtually complete regeneration by 14 days whereas in the rat the bronchiolar epithelial damage was more extensive and was followed by scattered peribronchiolar fibrosis and epithelial mucous metaplasia suggestive of ''small airway disease'' of man. Relatively selective 3MF-induced necrosis of olfactory epithelium occurred in the nasal mucosa of both species. Resolution of this lesion was seen by 14 days in the hamster. In the rat, however, the necrosis was much more extensive and was followed by partially occlusive fibrosis of the nasal cavity as seen at 14 days. 3MF also induced centrilobular hepatic necrosis in both species. In the rat, lymphocyte necrosis in the thymus and spleen, and esophageal necrosis was also seen.

  3. Distribution of kerosene components in rats following dermal exposure.

    PubMed

    Tsujino, Y; Hieda, Y; Kimura, K; Eto, H; Yakabe, T; Takayama, K; Dekio, S

    2002-08-01

    The systemic distribution of kerosene components in blood and tissues was analysed in rats following dermal exposure. Four types of trimethylbenzenes (TMBs) and aliphatic hydrocarbons (AHCs) with carbon numbers 9-16 (C(9)-C(16)) were analysed as major kerosene components by capillary gas chromatography/mass spectrometry (GC/MS). The kerosene components were detected in blood and all tissues after a small piece of cotton soaked with kerosene was applied to the abdominal skin. The amounts of TMBs detected were higher than those of AHCs. Greater increases in TMB levels were found in adipose tissue in an exposure duration-dependent manner. The amounts of TMBs detected were only at trace levels following post-mortem dermal exposure to kerosene. These findings suggest that kerosene components were absorbed percutaneously and distributed to various organs via the blood circulation. Post-mortem or ante-mortem exposure to kerosene could be distinguished when the exposure duration was relatively long. Adipose tissue would seem to be the most useful for estimating the degree of kerosene exposure.

  4. Dominant lethal study in CD-1 mice following inhalation exposure to 1,3-butadiene: Final technical report

    SciTech Connect

    Hackett, P.L.; Mast, T.J.; Brown, M.G.; Clark, M.L.; Evanoff, J.J.; Rowe, S.E.; McClanahan, B.J.; Buschbom, R.L.; Decker, J.R.; Rommereim, R.L.; Westerberg, R.B.

    1988-04-01

    The effects of whole-body inhalation exposures to 1,3-butadiene on the reproductive system was evaluated. The results of dominant lethality in CD-1 male mice that were exposed to 1,3-butadiene are described. Subsequent to exposure, males were mated with two unexposed females. Mating was continued for 8 weeks with replacement of two females each week. Gravid uteri were removed, and the total number, position and status of implantations were determined. The mice were weighed prior to exposure and at 0, 1, 2, 3, 4, 5, 6, 7, and 8 weeks after exposure and at sacrifice. The animals were observed for mortality, morbidity and signs of toxicity throughout the study. 19 refs., 5 figs., 9 tabs.

  5. Effects of a 13-week chloropentafluorobenzene inhalation exposure of Fischer 344 rats and B6C3F1 mice.

    PubMed

    Kinkead, E R; Bunger, S K; Kimmel, E C; Flemming, C D; Wall, H G; Grabau, J H

    1991-07-01

    Chloropentafluorobenzene (CPFB) has been identified as a candidate simulant for nonpersistent chemical warfare agents. Acute toxicity studies have shown that CPFB has limited adverse effects on laboratory animals. A 21-day inhalation study of rats and mice to 2.5, 0.8, and 0.25 mg CPFB/liter resulted in reduced weight gain in male and female rats exposed at the high concentration only and identified the liver as a potential target organ. This multiconcentration inhalation study was designed to detect a no-observable-effect level associated with repeated exposure to CPFB. Male and female rats and mice were exposed to 250, 50, or 10 mg CPFB/m3 (0.25, 0.05, or 0.01 mg CPFB/liter) for 13 weeks. No treatment-related effects on body weight, clinical chemistries, mortality, absolute or relative organ weight or histopathology were noted.

  6. Pulmonary cellular effects in rats following aerosol exposures to ultrafine Kevlar aramid fibrils: evidence for biodegradability of inhaled fibrils.

    PubMed

    Warheit, D B; Kellar, K A; Hartsky, M A

    1992-10-01

    Previous chronic inhalation studies have shown that high concentrations of Kevlar fibrils produced fibrosis and cystic keratinizing tumors in rats following 2-year inhalation exposures. The current studies were undertaken to evaluate mechanisms and to assess the toxicity of inhaled Kevlar fibrils relative to other reference materials. Rats were exposed to ultrafine Kevlar fibers (fibrils) for 3 or 5 days at concentrations ranging from 600-1300 fibers/cc (gravimetric concentrations ranging from 2-13 mg/m3). A complete characterization of the fiber aerosol and dose was carried out. These measurements included gravimetric concentrations, mass median aerodynamic diameter, fiber number, and count median lengths and diameters of the aerosol. Following exposures, cells and fluids from groups of sham- and fiber-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, lactate dehydrogenase (LDH), protein, and N-acetyl glucosaminidase (NAG) values were measured in BAL fluids at several time points postexposure. Alveolar macrophages were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy. The lungs of additional exposed animals were processed for deposition, cell labeling, retained dose, and lung clearance studies, as well as fiber dimensions (from digested lung tissue), histopathology, and transmission electron microscopy. Five-day exposures to Kevlar fibrils elicited a transient granulocytic inflammatory response with concomitant increases in BAL fluid levels of alkaline phosphatase, NAG, LDH, and protein. Unlike the data from silica and asbestos exposures where inflammation persisted, biochemical parameters returned to control levels at time intervals between 1 week and 1 month postexposure. Macrophage function in Kevlar-exposed alveolar macrophages was not significantly different from sham controls at any time period. Cell labeling studies were carried out immediately after exposure, as well as 1

  7. Measurement of human CYP1A2 induction by inhalation exposure to benzo(a)pyrene based on in vivo isotope breath method.

    PubMed

    Duan, Xiaoli; Shen, Guofeng; Yang, Hongbiao; Lambert, George; Wei, Fusheng; Zhang, Junfeng Jim

    2016-01-01

    Cytochrome P450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of certain carcinogens, and inducible by toxic substrates. To date, few studies have investigated in vivo CYP1A2 induction in humans and its relationship to polycylic aromatic hydrocarbons (PAHs) like benzo(a)pyrene (BaP). Non-smoking healthy male coke-oven workers (n = 30) were recruited as 'exposure' group, and non-smoking healthy office workers in the same city (n = 10) were selected as 'control' group, to test whether high inhalation exposure to PAHs can induce CYP1A2 activity in human livers. Significantly higher inhalation exposure of PAHs were found among the exposure group compared to the control. Inhalation BaP exposure concentration in the exposure group was more than 30 times higher than the control group (p < 0.001). However, the exposure group did not exhale significant higher levels of (13)CO2/(12)CO2 in breath samples (p = 0.81), and no significant relationship was found between the inhaled BaP concentration and the (13)CO2/(12)CO2 ratio (p = 0.91). A significant association was found between the (13)CO2/(12)CO2 exhalation and dietary BaP intake level. Hepatic CYP1A2 activity/induction level was not effected by inhaled BaP but was altered by ingestion of BaP.

  8. An in vivo and in vitro toxicological characterization of realistic nanoscale CeO2 inhalation exposures

    PubMed Central

    Demokritou, Philip; Gass, Samuel; Pyrgiotakis, Georgios; Cohen, Joel M.; Goldsmith, William; McKinney, Walt; Frazer, David; Ma, Jane; Schwegler-Berry, Diane; Brain, Joseph; Castranova, Vincent

    2015-01-01

    Nanoscale CeO2 is increasingly used for industrial and commercial applications, including catalysis, UV-shielding, and as an additive in various nanocomposites. Because of its increasing potential for consumer and occupational exposures, a comprehensive toxicological characterization of this nanomaterial is needed. Preliminary results from intratracheal instillation studies in rats point to cytoxicity and inflammation, though these studies may not accurately use realistic nanoscale exposure profiles. In contrast, published in vitro cellular studies have reported limited toxicological outcomes for the case of nano-ceria. Here, we present an integrative study evaluating the toxicity of nanoscale CeO2 both in vitro, using the A549 lung epithelial cell line, and in vivo using an intact rat model. Realistic nano-ceria exposure atmospheres were generated using the Harvard Versatile Engineered Nanomaterial Generation System (VENGES), and rats were exposed via inhalation. Finally, the use of a nanothin amorphous SiO2 encapsulation coating as a means of mitigating CeO2 toxicity was assessed. Results from the inhalation experiments show lung injury and inflammation with increased PMN and LDH levels in the bronchoalveolar lavage fluid of the CeO2 exposed rats. Moreover, exposure to SiO2-coated CeO2 did not induce any pulmonary toxicity to the animals, representing clear evidence for the safe by design SiO2-encapsualtion concept. PMID:23061914

  9. Effects of single and repeated inhalation exposure of Syrian hamsters to aerosols of /sup 144/CeO/sub 2/

    SciTech Connect

    Lundgren, D.L.; Hahn, F.F.; McClellan, R.O.

    1982-05-01

    Male Syrian hamsters (84 days old at the time of the initial exposure) were repeatedly exposed by inhalation at approximately 60-day intervals for 1 year (seven exposures) to aerosols of /sup 144/CeO/sub 2/ to reestablish lung burdens of 0.4, 2.0, or 10 ..mu..Ci of /sup 144/Ce. Other hamsters were exposed once when either 84, 220, or 360 days old to achieve similar initial lung burdens. Primary lung tumors were observed in 7 of 197 hamsters repeatedly exposed to /sup 144/CeO/sub 2/ that died between 177 and 685 days after the initial inhalation exposure. The cumulative adsorbed ..beta..-radiation doses to the lungs of these hamsters were 14,000 to 50,000 rad. Primary lung tumors also were observed in 6 of 153 hamsters exposed once to /sup 144/CeO/sub 2/ when 84 or 220 days old that died between 270 and 695 days after exposure. The cumulative ..beta..-radiation doses to the lungs of these hamsters were 6000 to 21,000 rad. Lung tumors were not observed in hamsters exposed when 360 days old or in control hamsters. The incidences of primary lung tumors were more dependent on the cumulative dose to the lung than the radiation dose pattern that resulted in the cumulative dose.

  10. A probabilistic modeling approach to assess human inhalation exposure risks to airborne aflatoxin B 1 (AFB 1)

    NASA Astrophysics Data System (ADS)

    Liao, Chung-Min; Chen, Szu-Chieh

    To assess how the human lung exposure to airborne aflatoxin B 1 (AFB 1) during on-farm activities including swine feeding, storage bin cleaning, corn harvest, and grain elevator loading/unloading, we present a probabilistic risk model, appraised with empirical data. The model integrates probabilistic exposure profiles from a compartmental lung model with the reconstructed dose-response relationships based on an empirical three-parameter Hill equation model, describing AFB 1 cytotoxicity for inhibition response in human bronchial epithelial cells, to quantitatively estimate the inhalation exposure risks. The risk assessment results implicate that exposure to airborne AFB 1 may pose no significance to corn harvest and grain elevator loading/unloading activities, yet a relatively high risk for swine feeding and storage bin cleaning. Applying a joint probability function method based on exceedence profiles, we estimate that a potential high risk for the bronchial region (inhibition=56.69% with 95% confidence interval (CI): 35.05-72.87%) and bronchiolar region (inhibition=44.93% with 95% CI: 21.61 - 66.78%) is alarming during swine feeding activity. We parameterized the proposed predictive model that should encourage a risk-management framework for discussion of carcinogenic risk in occupational settings where inhalation of AFB 1-contaminated dust occurs.

  11. Chronic inhalation studies of man-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs.

    PubMed

    Hesterberg, T W; Miiller, W C; Thevenaz, P; Anderson, R

    1995-10-01

    Inhalation studies were conducted to determine the chronic biological effects in rodents of respirable fractions of different man-made vitreous fibres (MMVFs), including refractory ceramic fibre (RCF), fibrous glass, rock (stone) wool and slag wool. Animals were exposed nose-only, 6 h per day, 5 days per week, for 18 months (hamsters) or 24 months (rats). Exposure to 10 mg m-3 of crocidolite or chrysotile asbestos induced pulmonary fibrosis, lung tumours and mesothelioma in rats, thus validating the inhalation model with known human carcinogenic fibres. Exposure of rats to 30 mg m-3 of refractory ceramic fibres (RCF) also resulted in pulmonary fibrosis as well as significant increases in lung tumours and mesothelioma. In hamsters, 30 mg m-3 of RCF induced a 41% incidence of mesotheliomas. Exposure of rats to 30 mg m-3 of fibre glasses (MMVF 10 or 11) or of slag wool (MMVF 22) was associated with an inflammatory response, but no mesotheliomas or significant increase in the lung tumours were observed. Rock wool (stone wool: MMVF 21) at the same exposure level resulted in minimal lung fibrosis, but no mesotheliomas or significant increase in the lung tumours were observed. Fibre numbers (WHO fibres) and dimensions in the aerosols and lungs of exposed animals were comparable in this series of inhalation studies. Differences in lung fibre burdens and lung clearance rates could not explain the differences observed in the toxicologic effects of the MMVFs. These findings indicate that dose, dimension and durability may not be the only determinants of fibre toxicity. Chemical composition and the surface physico-chemical properties of the fibres may also play an important role.

  12. Passive exposure of Earth radiation budget experiment components (A0147)

    NASA Technical Reports Server (NTRS)

    Hickey, J. R.; Griffin, F. J.

    1984-01-01

    In-flight calibration for the solr and Earth flux channels was examined. Earth Radiation on Budget (ERB) channel components were exposed to the space environment and then retrieved and resubmitted to radiometric calibration after exposure. It is suggested that corrections may be applied to ERB results and information will be obtained to aid in the selection of components for future operational solar and Earth radiation budget experiments. To assure that these high accuracy devices are measuring real variations and are not responding to changes induced by the space environment, it is desirable to test such devices radiometrically after exposure to the best approximation of the orbital environment.

  13. Passive exposure of Earth radiation budget experiment components (A0147)

    NASA Astrophysics Data System (ADS)

    Hickey, J. R.; Griffin, F. J.

    1984-02-01

    In-flight calibration for the solr and Earth flux channels was examined. Earth Radiation on Budget (ERB) channel components were exposed to the space environment and then retrieved and resubmitted to radiometric calibration after exposure. It is suggested that corrections may be applied to ERB results and information will be obtained to aid in the selection of components for future operational solar and Earth radiation budget experiments. To assure that these high accuracy devices are measuring real variations and are not responding to changes induced by the space environment, it is desirable to test such devices radiometrically after exposure to the best approximation of the orbital environment.

  14. Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure.

    PubMed

    Gosens, Ilse; Cassee, Flemming R; Zanella, Michela; Manodori, Laura; Brunelli, Andrea; Costa, Anna Luisa; Bokkers, Bas G H; de Jong, Wim H; Brown, David; Hristozov, Danail; Stone, Vicki

    2016-10-01

    Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment. Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C × T protocol). The dose is expressed as 6 h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2 mg/m(3) CuO NPs, with a primary particle size of 10 9.2-14 nm and an MMAD of 1.5 μm. Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4 mg/m(3). After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2 mg/m(3). The olfactory epithelium in the nose degenerated 24 h after exposure to 6.3 and 13.2 mg/m(3), but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver. A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period.

  15. Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

    PubMed Central

    Gosens, Ilse; Cassee, Flemming R.; Zanella, Michela; Manodori, Laura; Brunelli, Andrea; Costa, Anna Luisa; Bokkers, Bas G. H.; de Jong, Wim H.; Brown, David; Hristozov, Danail; Stone, Vicki

    2016-01-01

    Abstract Introduction: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment. Methods: Rats were exposed nose-only to a single exposure concentration and by varying the exposure time, different dose levels were obtained (C × T protocol). The dose is expressed as 6 h-concentration equivalents of 0, 0.6, 2.4, 3.3, 6.3, and 13.2 mg/m3 CuO NPs, with a primary particle size of 10 9.2–14 nm and an MMAD of 1.5 μm. Results: Twenty-four hours after a 5-d exposure, dose-dependent lung inflammation and cytotoxicity were observed. Histopathological examinations indicated alveolitis, bronchiolitis, vacuolation of the respiratory epithelium, and emphysema in the lung starting at 2.4 mg/m3. After a recovery period of 22 d, limited inflammation was still observed, but only at the highest dose of 13.2 mg/m3. The olfactory epithelium in the nose degenerated 24 h after exposure to 6.3 and 13.2 mg/m3, but this was restored after 22 d. No histopathological changes were detected in the brain, olfactory bulb, spleen, kidney and liver. Conclusion: A 5-d, 6-h/day exposure equivalent to an aerosol of agglomerated CuO NPs resulted in a dose-dependent toxicity in rats, which almost completely resolved during a 3-week post-exposure period. PMID:27132941

  16. Organ weight changes in mice after long-term inhalation exposure to manganese oxides nanoparticles

    NASA Astrophysics Data System (ADS)

    Zeman, T.; Buchtová, M.; Dočekal, B.; Míšek, I.; Navrátil, J.; Mikuška, P.; Šerý, O.; Večeřa, Z.

    2015-05-01

    Recently, it has been proven that manganese from inhaled particles of manganese compounds can accumulate in the internal organs of laboratory animals. Nevertheless, there were only a few researches dealing with changes in body morphology induced by inhalation of these particles, even though results of some studies indicate existence of such changes. The aim of our research was to assess the effect of inhaled manganese oxides nanoparticles on weight of internal organs. For this purpose a long-term inhalation experiment on laboratory mice was performed, during which the mice were exposed to MnO.Mn2O3 nanoparticles in concentration 2 × 106 particles/cm3 for 17 weeks, 24 hours a day, 7 days a week. Manganese oxides nanoparticles were synthesized continuously via aerosol route in a hot wall tube flow reactor using thermal decomposition of metal organic precursor manganese(II)acetylacetonate in the flow tube reactor at temperature 750 °C in the presence of 30 vol% of oxygen. It was proven that inhaled nanoparticles can influence the weight of internal organs of mice. Moreover, it was discovered that the resulting change in weight of selected organs is disproportional. The mice from the experimental group had statistically significantly lighter kidneys, liver and spleen and heavier pancreas compared to the mice from the control group.

  17. Population inhalation exposure to polycyclic aromatic hydrocarbons and associated lung cancer risk in Beijing region: Contributions of indoor and outdoor sources and exposures

    NASA Astrophysics Data System (ADS)

    Zhou, Bin; Zhao, Bin

    2012-12-01

    Polycyclic aromatic hydrocarbons (PAHs) are among the most toxic air pollutants in China. Efforts in assessing population inhalation exposure to PAHs, and its contribution to lung cancer risk for Chinese residents, have been limited due to insufficient data on measured indoor concentrations. A mass-balance model to predict indoor PAH concentrations was developed, along with estimated exposures and attributable lung cancer risks for residents in the Beijing region in 2006, with a 2-stage Monte Carlo simulation framework. The exposures and risks were split into three parts, based on the sources and places of exposure, to estimate the contributions of indoor and outdoor PAH sources and exposures, in order to better understand the source and place pattern of PAH exposure. PAHs bring considerable lung cancer risk to the population of Beijing region. The population attributable fraction (PAF) of lung cancer for Beijing's overall population is 2.99% [95% confidence interval (CI): 1.71%-4.26%]. Median contribution of indoor exposure to outdoor-originated PAHs (OUT-in) is 78% (CI: 73%-81%) in the overall population, for 97% (CI: 94%-99%) of whom OUT-in is the largest contributor. Rural residents are facing considerable exposure to indoor-originated PAHs (IN-in), which dominates the total exposure in 12% (CI: 2%-24%) of the rural population. This model framework could be used in quantitative comparison of different interventions on exposure to PAHs as well as other airborne pollutants.

  18. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    SciTech Connect

    Finch, G.L.; Nikula, K.J.; Barr, E.B.

    1995-12-01

    Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

  19. Neutral endopeptidase (NEP) and its role in pathological pulmonary change with inhalation exposure to JP-8 jet fuel.

    PubMed

    Pfaff, J K; Tollinger, B J; Lantz, R C; Chen, H; Hays, A M; Witten, M L

    1996-01-01

    Through a simulated flightline exposure protocol, Fischer 344 rats (F344) were subjected to an aerosol/vapor mix of the military jet fuel, JP-8. Previous studies with this model of lung injury have revealed significant increases in pulmonary resistance, increased alveolar clearance of 99mTcDTPA, and a decrease in bronchoalveolar lavage fluid (BALF) concentration of the neuropeptide substance P (SP). Exposures to JP-8 were nose-only and for one hour daily. Six groups of Fischer 344 rats were exposed for 7, 28, or 56 days at two JP-8 concentrations (low dose = 469-520 mg/m3/hr, high dose = 814-1263 mg/m3/hr). Exposed groups were matched with longitudinal controls. In response to JP-8 inhalation, exposure animals demonstrated a dose-dependent as well as duration-determined reduction in BALF SP concentration. Both JP-8 concentrations caused significant pathological changes in lower pulmonary structures.

  20. Increased Nonconducted P-Wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

    PubMed Central

    Farraj, Aimen K.; Haykal-Coates, Najwa; Winsett, Darrell W.; Hazari, Mehdi S.; Carll, Alex P.; Rowan, William H.; Ledbetter, Allen D.; Cascio, Wayne E.; Costa, Daniel L.

    2009-01-01

    Background Exposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that are reflected in the electrocardiogram (ECG), including altered cardiac rhythm, myocardial ischemia, and reduced heart rate variability (HRV). The sensitivity and reliability of ECG-derived parameters as indicators of the cardiovascular toxicity of PM in rats are unclear. Objective We hypothesized that spontaneously hypertensive (SH) rats are more susceptible to the development of PM-induced arrhythmia, altered ECG morphology, and reduced HRV than are Wistar Kyoto (WKY) rats, a related strain with normal blood pressure. Methods We exposed rats once by nose-only inhalation for 4 hr to residual oil fly ash (ROFA), an emission source particle rich in transition metals, or to air and then sacrificed them 1 or 48 hr later. Results ROFA-exposed SH rats developed nonconducted P-wave arrhythmias but no changes in ECG morphology or HRV. We found no ECG effects in ROFA-exposed WKY rats. ROFA-exposed SH rats also had greater pulmonary injury, neutrophil infiltration, and serum C-reactive protein than did ROFA-exposed WKY rats. Conclusions These results suggest that cardiac arrhythmias may be an early sensitive indicator of the propensity for PM inhalation to modify cardiovascular function. PMID:19479011

  1. Inflammatory Cytokines and White Blood Cell Counts Response to Environmental Levels of Diesel Exhaust and Ozone Inhalation Exposures

    PubMed Central

    Stiegel, Matthew A.; Pleil, Joachim D.; Sobus, Jon R.; Madden, Michael C.

    2016-01-01

    Epidemiological observations of urban inhalation exposures to diesel exhaust (DE) and ozone (O3) have shown pre-clinical cardiopulmonary responses in humans. Identifying the key biological mechanisms that initiate these health bioindicators is difficult due to variability in environmental exposure in time and from person to person. Previously, environmentally controlled human exposure chambers have been used to study DE and O3 dose-response patterns separately, but investigation of co-exposures has not been performed under controlled conditions. Because a mixture is a more realistic exposure scenario for the general public, in this study we investigate the relationships of urban levels of urban-level DE exposure (300 μg/m3), O3 (0.3 ppm), DE + O3 co-exposure, and innate immune system responses. Fifteen healthy human volunteers were studied for changes in ten inflammatory cytokines (interleukins 1β, 2, 4, 5, 8, 10, 12p70 and 13, IFN-γ, and TNF-α) and counts of three white blood cell types (lymphocytes, monocytes, and neutrophils) following controlled exposures to DE, O3, and DE+O3. The results show subtle cytokines responses to the diesel-only and ozone-only exposures, and that a more complex (possibly synergistic) relationship exists in the combination of these two exposures with suppression of IL-5, IL-12p70, IFN-γ, and TNF-α that persists up to 22-hours for IFN-γ and TNF-α. The white blood cell differential counts showed significant monocyte and lymphocyte decreases and neutrophil increases following the DE + O3 exposure; lymphocytes and neutrophils changes also persist for at least 22-hours. Because human studies must be conducted under strict safety protocols at environmental levels, these effects are subtle and are generally only seen with detailed statistical analysis. This study indicates that the observed associations between environmental exposures and cardiopulmonary effects are possibly mediated by inflammatory response mechanisms. PMID:27058360

  2. Airborne exposure to inhalable hexavalent chromium in welders and other occupations: Estimates from the German MEGA database.

    PubMed

    Pesch, Beate; Kendzia, Benjamin; Hauptmann, Kristin; Van Gelder, Rainer; Stamm, Roger; Hahn, Jens-Uwe; Zschiesche, Wolfgang; Behrens, Thomas; Weiss, Tobias; Siemiatycki, Jack; Lavoué, Jerome; Jöckel, Karl-Heinz; Brüning, Thomas

    2015-07-01

    This study aimed to estimate occupational exposure to inhalable hexavalent chromium (Cr(VI)) using the exposure database MEGA. The database has been compiling Cr(VI) concentrations and ancillary data about measurements at German workplaces. We analysed 3659 personal measurements of inhalable Cr(VI) collected between 1994 and 2009. Cr(VI) was determined spectrophotometrically at 540 nm after reaction with diphenylcarbazide. We assigned the measurements to pre-defined at-risk occupations using the information provided about the workplaces. Two-thirds of the measurements were below the limit of quantification (LOQ) and multiply imputed according to the distribution above LOQ. The 75th percentile value was 5.2 μg/m(3) and the 95th percentile was 57.2 μg/m(3). We predicted the geometric mean for 2h sampling in the year 2000, and the time trend of Cr(VI) exposure in these settings with and without adjustment for the duration of measurements. The largest dataset was available for welding (N = 1898), which could be further detailed according to technique. The geometric means were above 5 μg/m(3) in the following situations: spray painting, shielded metal arc welding, and flux-cored arc welding if applied to stainless steel. The geometric means were between 1 μg/m(3) and 5 μg/m(3) for gas metal arc welding of stainless steel, cutting, hard-chromium plating, metal spraying and in the chemical chromium industry. The exposure profiles described here are useful for epidemiologic and industrial health purposes. Exposure to Cr(VI) varies not only between occupations, but also within occupations as shown for welders. In epidemiologic studies, it would be desirable to collect exposure-specific information in addition to the job title. Copyright © 2015 Elsevier GmbH. All rights reserved.

  3. Extremely low-level microwaves attenuate immune imbalance induced by inhalation exposure to low-level toluene in mice.

    PubMed

    Novoselova, Elena G; Glushkova, Olga V; Khrenov, Maxim O; Novoselova, Tatyana V; Lunin, Sergey M; Fesenko, Eugeny E

    2017-05-01

    To clarify whether extremely low-level microwaves (MW) alone or in combination with p38 inhibitor affect immune cell responses to inhalation exposure of mice to low-level toluene. The cytokine profile, heat shock proteins expression, and the activity of several signal cascades, namely, NF-κB, SAPK/JNK, IRF-3, p38 MAPK, and TLR4 were measured in spleen lymphocytes of mice treated to air-delivered toluene (0.6 mg/m(3)) or extremely low-level microwaves (8.15-18 GHz, 1μW/cm(2), 1 Hz swinging frequency) or combined action of these two factors. A single exposure to air-delivered low-level toluene induced activation of NF-κB, SAPK/JNK, IFR-3, p38 MAPK and TLR4 pathways. Furthermore, air toluene induced the expression of Hsp72 and enhanced IL-1, IL-6, and TNF-α in blood plasma, which is indicative of a pro-inflammatory response. Exposure to MW alone also resulted in the enhancement of the plasma cytokine values (e.g. IL-6, TNF-α, and IFN-γ) and activation of the NF-κB, MAPK p38, and especially the TLR4 pathways in splenic lymphocytes. Paradoxically, pre-exposure to MW partially recovered or normalized the lymphocyte parameters in the toluene-exposed mice, while the p38 inhibitor XI additionally increased protective activity of microwaves by down regulating MAPKs (JNK and p38), IKK, as well as expression of TLR4 and Hsp90-α. The results suggest that exposure to low-intensity MW at specific conditions may recover immune parameters in mice undergoing inhalation exposure to low-level toluene via mechanisms involving cellular signaling.

  4. Inhalation route effects on exposure to 2. 0 parts per million sulfur dioxide in normal subjects

    SciTech Connect

    Bedi, J.F.; Horvath, S.M. )

    1989-11-01

    To investigate possible changes in nasal resistance due to sulfur dioxide (SO{sub 2}) exposure, 14 subjects, healthy non-smokers, between the ages of 20 and 46 years, were exposed for 30 minutes to filtered air while free breathing and to 2.0 ppm SO{sub 2} with either free breathing, forced oral or forced nasal breathing with continuous exercise at a workload 300 kg{center dot}m/min below the workload which initiated cross-over from nasal to oral/nasal breathing in a preliminary incremental workload test. An incremental work test under the ambient conditions was performed immediately following the 30-minute exercise to ascertain any change in the cross-over ventilation. Pre- and post-measures of pulmonary functions were obtained to ascertain any changes in these parameters due to the exposure. There was a significant difference in the workload at which cross-over occurred following forced oral breathing in 2.0 ppm sulfur dioxide. The nasal ventilation prior to cross-over and the nasal component of ventilation were significantly smaller for this exposure condition, indicating a possible change in nasal dynamics following the 30 minutes of forced oral breathing in 2.0 ppm SO{sub 2}. Lack of concomitant changes in pulmonary function tests including airway resistance suggests that breathing 2.0 ppm SO{sub 2} does not affect normal subjects whether administration is by free, forced oral or forced nasal breathing.

  5. Modeling of occupational exposure to accidentally released manufactured nanomaterials in a production facility and calculation of internal doses by inhalation

    PubMed Central

    Vaquero-Moralejo, Celina; Jaén, María; Lopez De Ipiña Peña, Jesús; Neofytou, Panagiotis

    2016-01-01

    Background Occupational exposure to manufactured nanomaterials (MNMs) and its potential health impacts are of scientific and practical interest, as previous epidemiological studies associate exposure to nanoparticles with health effects, including increased morbidity of the respiratory and the circulatory system. Objectives To estimate the occupational exposure and effective internal doses in a real production facility of TiO2 MNMs during hypothetical scenarios of accidental release. Methods Commercial software for geometry and mesh generation, as well as fluid flow and particle dispersion calculation, were used to estimate occupational exposure to MNMs. The results were introduced to in-house software to calculate internal doses in the human respiratory tract by inhalation. Results Depending on the accidental scenario, different areas of the production facility were affected by the released MNMs, with a higher dose exposure among individuals closer to the particles source. Conclusions Granted that the study of the accidental release of particles can only be performed by chance, this numerical approach provides valuable information regarding occupational exposure and contributes to better protection of personnel. The methodology can be used to identify occupational settings where the exposure to MNMs would be high during accidents, providing insight to health and safety officials. PMID:27670588

  6. Inhalation Exposures to Particulate Matter and Carbon Monoxide during Ethiopian Coffee Ceremonies in Addis Ababa: A Pilot Study

    PubMed Central

    Keil, Chris; Kassa, Hailu; Brown, Alexander; Kumie, Abera; Tefera, Worku

    2010-01-01

    The unique Ethiopian cultural tradition of the coffee ceremony increases inhalation exposures to combustion byproducts. This pilot study evaluated exposures to particulate matter and carbon monoxide in ten Addis Ababa homes during coffee ceremonies. For coffee preparers the geometric mean (57 μg/m3) and median (72 μg/m3) contributions to an increase in a 24-hour time-weighted average exposure were above World Health Organization (WHO) guidelines. At 40% of the study sites the contribution to the 24-hour average exposure was greater than twice the WHO guideline. Similar exposure increases existed for ceremony participants. Particulate matter concentrations may be related to the use of incense during the ceremony. In nearly all homes the WHO guideline for a 60-minute exposure to carbon monoxide was exceeded. Finding control measures to reduce these exposures will be challenging due to the deeply engrained nature of this cultural practice and the lack of availability of alternative fuels. PMID:20886061

  7. Potential harmful health effects of inhaling nicotine-free shisha-pen vapor: a chemical risk assessment of the main components propylene glycol and glycerol.

    PubMed

    Kienhuis, Anne S; Soeteman-Hernandez, Lya G; Bos, Peter Mj; Cremers, Hans Wjm; Klerx, Walther N; Talhout, Reinskje

    2015-01-01

    A shisha-pen is an electronic cigarette variant that is advertised to mimic the taste of a water pipe, or shisha. The aim of this study was to assess the potential harmful health effects caused by inhaling the vapor of a nicotine-free shisha-pen. Gas chromatography analysis was performed to determine the major components in shisha-pen vapor. Risk assessment was performed using puff volumes of e-cigarettes and "normal" cigarettes and a 1-puff scenario (one-time exposure). The concentrations that reached the airways and lungs after using a shisha-pen were calculated and compared to data from published toxicity studies. The main components in shisha-pen vapor are propylene glycol and glycerol (54%/46%). One puff (50 to 70 mL) results in exposure of propylene glycol and glycerol of 430 to 603 mg/m(3) and 348 to 495 mg/m(3), respectively. These exposure concentrations were higher than the points of departure for airway irritation based on a human study (propylene glycol, mean concentration of 309 mg/m(3)) and a rat study (glycerol, no-observed adverse effect level of 165 mg/m(3)). Already after one puff of the shisha-pen, the concentrations of propylene glycol and glycerol are sufficiently high to potentially cause irritation of the airways. New products such as the shisha-pen should be detected and risks should be assessed to inform regulatory actions aimed at limiting potential harm that may be caused to consumers and protecting young people to take up smoking.

  8. INTRODUCTION: INHALATION EXPOSURE AND SYSTEMIC IMMUNOTOXICITY: MECHANISMS LINKING THE LUNG AND IMMUNE SYSTEM

    EPA Science Inventory


    Concerns regarding inhaled compounds, immune suppression and increased risk of disease have focused primarily on suppression of local immune responses in the lung and susceptibility to respiratory infections. However, a number of studies have shown that both gaseous (O3, NO2)...

  9. INTRODUCTION: INHALATION EXPOSURE AND SYSTEMIC IMMUNOTOXICITY: MECHANISMS LINKING THE LUNG AND IMMUNE SYSTEM

    EPA Science Inventory


    Concerns regarding inhaled compounds, immune suppression and increased risk of disease have focused primarily on suppression of local immune responses in the lung and susceptibility to respiratory infections. However, a number of studies have shown that both gaseous (O3, NO2)...

  10. Evaluation of the TRA ECETOC model for inhalation workplace exposure to different organic solvents for selected process categories.

    PubMed

    Kupczewska-Dobecka, Małgorzata; Czerczak, Sławomir; Jakubowski, Marek

    2011-06-01

    The aim of this work is to describe the operation principle of the TRA ECETOC model developed using the descriptor system, and the utilization of that model for assessment of inhalation exposures to different organic solvents for selected process categories identifying a given application. Measurement results were available for toluene, ethyl acetate and acetone in workplace atmosphere in Poland. The following process categories have been postulated: (1) Paints and lacquers factory: use in closed, continuous process with occasional controlled exposure; (2) Shoe factory: roller or brush application of glues; (3) Refinery: use in closed process, no likelihood of exposure. The next step was to calculate the workplace concentration at chosen process categories by applying the TRA ECETOC model. The selected categories do not precisely describe the studied applications. Very high concentration values of acetone were measured in the shoe factory, mean 443 ppm. The concentration obtained with the aid of the model is underestimated, ranging from 25.47 to 254.7 ppm, for the case with and without activation of the local exhaust ventilation (LEV), respectively. Estimated concentration at a level corresponding to that of the measured concentration would be possible if the process category involving spraying, e.g., PROC 7 was considered. For toluene and ethyl acetate, the measured concentrations are within the predicted ranges determined with the use of the model when we assume the concentration predicted with active ventilation for the beginning, and the concentration predicted with inactive ventilation for the end of the range. Model TRA ECETOC can be easily used to assess inhalation exposure at workplace. It has numerous advantages, its structure is clear, requires few data, is available free of charge. Selection of appropriate process categories related to the uses identified is guarantee of successful exposure assessment.

  11. Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure

    SciTech Connect

    Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu Kejian

    2009-12-15

    In these studies the immunotoxicity of arsenic trioxide (ATO, As{sub 2}O{sub 3}) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 mug/m{sup 3} and 1 mg/m{sup 3}. A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 mug/g tissue following the 1 mg/m{sup 3} exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 mug/m{sup 3} and 1 mg/m{sup 3} exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents.

  12. IMMUNOTOXICITY AND BIODISTRIBUTION ANALYSIS OF ARSENIC TRIOXIDE IN C57Bl/6 MICE FOLLOWING A TWO-WEEK INHALATION EXPOSURE

    PubMed Central

    Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun, Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu, Ke Jian

    2010-01-01

    In these studies the immunotoxicity of arsenic trioxide (ATO, As2O3) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 hrs per day) at concentrations of 50 μg/m3 and 1 mg/m3. A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 μg/mg tissue following the 1 mg/m3 exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 μg/m3 and 1 mg/m3 exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents. PMID:19800901

  13. Lung Cancer in Chinese Women: Evidence for an Interaction between Tobacco Smoking and Exposure to Inhalants in the Indoor Environment

    PubMed Central

    Tang, Li; Lim, Wei-Yen; Eng, Philip; Leong, Swan Swan; Lim, Tow Keang; Ng, Alan W.K.; Tee, Augustine; Seow, Adeline

    2010-01-01

    Background Epidemiologic data suggest that Chinese women have a high incidence of lung cancer in relation to their smoking prevalence. In addition to active tobacco smoke exposure, other sources of fumes and airborne particles in the indoor environment, such as cooking and burning of incense and mosquito coils, have been considered potential risk factors for lung cancer. Objectives We used a case–control study to explore effects of inhalants from combustion sources common in the domestic environment on lung cancer and their modification by active tobacco smoking. Methods We analyzed 703 primary lung cancer cases and 1,578 controls. Data on demographic background and relevant exposures were obtained by face-to-face interviews in the hospital. Results We observed a positive relationship with daily exposure to incense or mosquito coils and to cooking fumes only among smokers, and no association among lifetime nonsmokers. Interactions between smoking and frequency of cooking, or exposure to incense or mosquito coils were statistically significant and consistent with synergistic effects on lung cancer. The odds ratio (OR) comparing smokers without daily incense or mosquito coil exposure with nonsmokers without daily exposure was 2.80 [95% confidence interval (CI), 1.86–4.21], whereas the OR comparing smokers with daily exposure to the same referent group was 4.61 (95% CI, 3.41–6.24). In contrast, daily exposure to incense or mosquito coils was not associated with lung cancer among nonsmokers (OR = 0.91; 95% CI, 0.72–1.16). We observed the same pattern of associations for smokers without (OR = 2.31; 95% CI, 1.52–3.51) and with (OR = 4.50; 95% CI, 3.21–6.30) daily cooking exposure compared with nonsmokers, with no evidence of an association with daily cooking exposure among nonsmokers. Conclusion Our results suggest that active tobacco smoking not only is an important risk factor for development of lung cancer, but also may cause smokers to be more susceptible

  14. Effects of combined exposure of F344 rats to inhaled Plutonium-239 dioxide and a chemical carcinogen (NNK)

    SciTech Connect

    Lundgren, D.L.; Carlton, W.W.; Griffith, W.C.

    1995-12-01

    Workers in nuclear weapons facilities have a significant potential for exposure to chemical carcinogens and to radiation from external sources or from internally deposited radionuclides such as {sup 239}Pu. Although the carcinogenic effects of inhaled {sup 239}Pu and many chemicals have been studied individually, very little information is available on their combined effects. One chemical carcinogen that workers could be exposed to via tobacco smoke is the tobacco-specific nitrosamine 4-(N-methyl-n-nitrosamino)-1-(3-pyridyl)-1(3-pyridyl)-1-butanone (NNK), a product of tobacco curing and the pyrolysis of nicotine in tobacco. NNK causes lung tumors in rats, regardless of the route of administration and to a lesser extent liver, nasal, and pancreatic tumors. From the results presented, it can be concluded that exposure to a chemical carcinogen (NNK) in combination with {alpha}-particle radiation from inhaled {sup 239}PuO{sub 2} acts in, at best, an additive manner in inducing lung cancer in rats.

  15. Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats

    SciTech Connect

    Antonini, James M. Stone, Sam; Roberts, Jenny R.; Chen, Bean; Schwegler-Berry, Diane; Afshari, Aliakbar A.; Frazer, David G.

    2007-09-15

    Many welders have experienced bronchitis, metal fume fever, lung function changes, and an increase in the incidence of lung infection. Questions remain regarding the possible mechanisms associated with the potential pulmonary effects of welding fume exposure. The objective was to assess the early effects of stainless steel (SS) welding fume inhalation on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to gas metal arc-SS welding fume at a concentration of 15 or 40 mg/m{sup 3} x 3 h/day for 1, 3, or 10 days. The control group was exposed to filtered air. To assess lung defense responses, some animals were intratracheally inoculated with 5 x 10{sup 4}Listeria monocytogenes 1 day after the last exposure. Welding particles were collected during exposure, and elemental composition and particle size were determined. At 1, 4, 6, 11, 14, and 30 days after the final exposure, parameters of lung injury (lactate dehydrogenase and albumin) and inflammation (PMN influx) were measured in the bronchoalveolar lavage fluid. In addition, particle-induced effects on pulmonary clearance of bacteria and macrophage function were assessed. SS particles were composed of Fe, Cr, Mn, and Ni. Particle size distribution analysis indicated the mass median aerodynamic diameter of the generated fume to be 0.255 {mu}m. Parameters of lung injury were significantly elevated at all time points post-exposure compared to controls except for 30 days. Interestingly, no significant difference in lung PMNs was observed between the SS and control groups at 1, 4, and 6 days post-exposure. After 6 days post-exposure, a dramatic increase in lung PMNs was observed in the SS group compared to air controls. Lung bacteria clearance and macrophage function were reduced and immune and inflammatory cytokines were altered in the SS group. In summary, short-term exposure of rats to SS welding fume caused significant lung damage and suppressed lung defense responses to bacterial

  16. Disposition of Phenolic and Sulfated Metabolites after Inhalation Exposure to 4-Chlorobiphenyl (PCB3) in Female Rats

    PubMed Central

    2015-01-01

    PCBs, such as PCB3, are air contaminants in buildings and outdoors. Metabolites of PCB3 are potential endocrine disrupting chemicals and genotoxic agents. We studied the disposition of phenolic and sulfated metabolites after acute nose-only inhalation exposure to airborne PCB3 for 2 h in female rats. Inhalation exposure was carried out in three groups. In the first group, rats exposed to an estimated dose of 26 μg/rat were euthanized at 0, 1, 2, and 4 h after exposure. Highest concentrations of phenols and sulfates were observed at 0 h, and the values were 7 ± 1 and 560 ± 60 ng/mL in serum, 213 ± 120 and 842 ± 80 ng/g in liver, 31 ± 27 and 22 ± 7 ng/g in lung, and 27 ± 6 and 3 ± 0 ng/g in brain, respectively. First-order serum clearance half-lives of 0.5 h for phenols and 1 h for sulfates were estimated. In the second group, rats exposed to an estimated dose of 35 μg/rat were transferred to metabolism cages immediately after exposure for the collection of urine and feces over 24 h. Approximately 45 ± 5% of the dose was recovered from urine and consisted mostly of sulfates; the 18 ± 5% of the dose recovered from feces was exclusively phenols. Unchanged PCB3 was detected in both urine and feces but accounted for only 5 ± 3% of the dose. Peak excretion of metabolites in both urine and feces occurred within 18 h postexposure. In the third group, three bile-cannulated rats exposed to an estimated dose of 277 μg/rat were used for bile collection. Bile was collected for 4 h immediately after 2 h exposure. Biliary metabolites consisted mostly of sulfates, some glucuronides, and lower amounts of the free phenols. Control rats in each group were exposed to clean air. Clinical serum chemistry values, serum T4 level, and urinary 8-hydroxy-2′-deoxyguanosine were similar in treated and control rats. These data show that PCB3 is rapidly metabolized to phenols and conjugated to sulfates after inhalation and that both of these metabolites are distributed to liver

  17. A 26-Week Toxicity Assessment of AIR001 (Sodium Nitrite) by Inhalation Exposure in Rats and by Intravenous Administration in Dogs.

    PubMed

    Tepper, Jeffrey; Ochoa, Ricardo; Rix, Peter; Elliott, Gary; Hoglen, Niel; Poulin, Dominic; Parsley, Ed; Masamune, Hiroko

    2014-05-01

    Historically, nitrogen oxides (NOx) in food, drinking water, as well as in the atmosphere have been believed to be associated with adverse health consequences. More recently, NOx have been implicated in normal homeostatic regulation, and exogenous administration has been associated with health benefits. One such potential health benefit is the prospect that inhaled nitrite will lower pulmonary blood pressure (BP) in patients with pulmonary arterial hypertension (PAH), a disease with poor prognosis due to the lack of effective treatment. To characterize potential chronic toxicity associated with inhaled AIR001 (sodium nitrite) for use in the treatment of PAH, 26-week exposures to AIR001 were carried out by inhalation administration in rats and by intravenous infusion in dogs. The studies revealed that methemoglobinemia was the primary adverse effect in both species. Methemoglobin levels less than 40% were well tolerated in both species, while levels greater than 50% methemoglobin caused death in some rats. Additionally, a decrease in systemic BP was also observed with inhaled AIR001 exposure in dogs. These acute secondary and exaggerated pharmacological effects occurred daily throughout the 26-week treatment period. Chronic exposure did not alter the magnitude of either methemoglobinemia or hypotension or result in additional toxicity or compensatory responses. Based on the exposure levels that produced these pharmacodynamic responses in animals, relative to those measured in early clinical studies, it appears that an adequate margin of safety exists to support the continued clinical development of inhaled AIR001. © The Author(s) 2014.

  18. Dietary and inhalation exposure to polycyclic aromatic hydrocarbons and urinary excretion of monohydroxy metabolites – a controlled case study in Beijing, China

    PubMed Central

    Zhang, Yanyan; Ding, Junnan; Shen, Guofeng; Zhong, Junjun; Wang, Chen; Wei, Siye; Chen, Chaoqi; Chen, Yuanchen; Lu, Yan; Shen, Huizhong; Li, Wei; Huang, Ye; Chen, Han; Su, Shu; Lin, Nan; Wang, Xilong; Liu, Wenxin; Tao, Shu

    2015-01-01

    Daily dietary and inhalation exposures to 16 parent polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 13 monohydroxy metabolites (OHPAHs) were monitored for 12 non-smoking university students in Beijing, China, during a controlled feeding experiment. The relationship between the urinary excretion of OHPAHs and the uptake of PAHs was investigated. The results suggest severe exposure of the subjects to PAHs via both dietary and inhalation pathways. Large increase of most urinary OHPAHs occurred after the ingestion of lamb kabob. Higher concentrations of OHPAHs were observed for female subjects, with the intakes of parent PAHs lower than those by males, likely due to the gender differences in metabolism. It appears that besides 1-PYR, metabolites of PHE could also be used as biomarkers to indicate the short-term dietary exposure to PAHs and urinary 3-BaA may serve as the biomarker for inhalation intake of high molecular weight PAHs. PMID:24177434

  19. A pilot study of personal exposure to respirable and inhalable dust during the sanding and sawing of medium density fibreboard (MDF) and soft wood.

    PubMed

    Hursthouse, Andrew; Allan, Fraser; Rowley, Louise; Smith, Frank

    2004-08-01

    A pilot study of production of respirable and inhalable dusts from sawing and sanding medium density fibreboard (MDF) and softwood in a typical cabinet-making workshop produced high but variable exposure levels at the bench and operator position. Exposure levels for the total inhalable fraction (approximately <100 microm) were 6.9-91 mg m(-3) for MDF and 2.5-45 mg m(-3) for softwood. For the respirable fraction (< 10 microm) levels were 0.4-13 mg m(-3) for MDF and 0.4-2.9 mg m(-3) for softwood. These results show significant dust loading is produced in the coarser fraction and that the material used has a significant impact on levels produced. It suggests that fuller evaluation of operator influence of fine dust production is needed and may question the common application of a single inhalable exposure standard for wood dust to all wood working scenarios.

  20. Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc.

    PubMed

    Pickrell, J A; Snipes, M B; Benson, J M; Hanson, R L; Jones, R K; Carpenter, R L; Thompson, J J; Hobbs, C H; Brown, S C

    1989-08-01

    The relationship between the inhalation exposure concentration of talc and the resulting lung burdens and histologic lesions was studied using groups of 20 F344/Crl rats and 20 B6C3F mice (10 male and 10 female) exposed to one of three concentrations of asbestos-free talc for 6 hr/day, 5 days/week for 4 weeks. Controls were exposed to filtered air using the same schedule. The pulmonary retention of talc and the development of pulmonary pathology were evaluated. The mass median aerodynamic diameter (MMAD) of the talc aerosol was 3.0 microns with a geometric standard deviation (sigma g) of 1.9. The mean exposure concentrations for rats were 0, 2.3, 4.3, and 17 mg talc/m3. Lung burdens in rats averaged 0, 0.07, 0.17, and 0.72 mg talc/g lung after the 20-day inhalation exposure; thus, the amount retained in the lung per unit of exposure concentration increased with increasing concentration. Mean exposure concentrations for the mice were 0, 2.2, 5.7, and 20.4 mg of talc/m3, which resulted in lung burdens of 0, 0.10, 0.29, and 1.0 mg talc/g lung; thus, the relationship between exposure concentration and the amount retained in the lung was approximately constant. Lung burdens from this study were used to project lung burdens that would result from longer exposures of rodents and man. No clinical signs were observed in the rats or mice prior to sacrifice 24 hr after the last exposure day. Histologic alterations in lung tissue consisted of only a modest, diffuse increase of talc-containing, free macrophages within alveolar spaces in both rat and mouse groups exposed to the highest level of talc for 20 days. A model simulating chronic talc inhalation exposure of rats and mice predicted lung burdens of 2-3 mg talc/g lung (wet wt) if animals were exposed to 17 mg talc/m3 for 2 years, and deposition and clearance of talc were unchanged by continued exposure. A potential limitation in this modeling is that if clearance of talc is delayed by continued exposure, the accumulated

  1. Amphibole asbestos in tree bark--a review of findings for this inhalational exposure source in Libby, Montana.

    PubMed

    Ward, Tony J; Spear, Terry M; Hart, Julie F; Webber, James S; Elashheb, Mohamed I

    2012-01-01

    In June 2009, the U.S. Environmental Protection Agency (EPA) designated the town of Libby, Montana, a public health emergency--the first and only time the EPA has made such a determination under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). From about 1920 until 1990, the leading source of vermiculite ore for the United States and the world was from a mine near Libby. This vermiculite ore was contaminated with fibrous and asbestiform amphibole in veins throughout the deposit. Today, areas surrounding the abandoned vermiculite processing/mining facilities and much of the town of Libby are contaminated with these asbestos fibers, contributing to an outbreak of asbestos-related diseases in the Libby population. Trees in Libby and in forested areas surrounding the abandoned mine have accumulated amphibole asbestos fibers on their bark surface, providing for inhalational exposures. Several studies have been conducted to further understand this exposure pathway. To address exposures to the public, Libby amphibole (LA) was measured in personal breathing zone and Tyvek surface wipe samples collected during firewood harvesting simulations, as well as in the ash and emissions of woodstoves when amphibole-contaminated firewood was combusted. Occupational studies simulating wildland firefighting and routine U.S. Department of Agriculture (USDA) Forest Service activities have also been conducted in the forested areas surrounding the abandoned mine, demonstrating the potential for inhalational exposures during common regional workplace activities. We present a review of the findings of this emerging environmental health concern impacting not only the residents of Libby but applicable to other populations living near asbestos-contaminated areas.

  2. Design, construction, and characterization of a novel robotic welding fume generator and inhalation exposure system for laboratory animals.

    PubMed

    Antonini, James M; Afshari, Aliakbar A; Stone, Sam; Chen, Bean; Schwegler-Berry, Diane; Fletcher, W Gary; Goldsmith, W Travis; Vandestouwe, Kurt H; McKinney, Walter; Castranova, Vincent; Frazer, David G

    2006-04-01

    Respiratory effects observed in welders have included lung function changes, metal fume fever, bronchitis, and a possible increase in the incidence of lung cancer. Many questions remain unanswered regarding the causality and possible underlying mechanisms associated with the potential toxic effects of welding fume inhalation. The objective of the present study was to construct a completely automated, computer-controlled welding fume generation and inhalation exposure system to simulate real workplace exposures. The system comprised a programmable six-axis robotic welding arm, a water-cooled arc welding torch, and a wire feeder that supplied the wire to the torch at a programmed rate. For the initial studies, gas metal arc welding was performed using a stainless steel electrode. A flexible trunk was attached to the robotic arm of the welder and was used to collect and transport fume from the vicinity of the arc to the animal exposure chamber. Undiluted fume concentrations consistently ranged from 90-150 mg/m(3) in the animal chamber during welding. Temperature and humidity remained constant in the chamber during the welding operation. The welding particles were composed of (from highest to lowest concentration) iron, chromium, manganese, and nickel as measured by inductively coupled plasma atomic emission spectroscopy. Size distribution analysis indicated the mass median aerodynamic diameter of the generated particles to be approximately 0.24 microm with a geometric standard deviation (sigma(g)) of 1.39. As determined by transmission and scanning electron microscopy, the generated aerosols were mostly arranged as chain-like agglomerates of primary particles. Characterization of the laboratory-generated welding aerosol has indicated that particle morphology, size, and chemical composition are comparable to stainless steel welding fume generated in other studies. With the development of this novel system, it will be possible to establish an animal model using

  3. Personal Exposure to Inhalable Dust and the Specific Latex Aero-Allergen, Hev b6.02, in Latex Glove Manufacturing in Thailand

    PubMed Central

    Sanguanchaiyakrit, Nuthchyawach; Povey, Andrew C.; de Vocht, Frank

    2014-01-01

    Objectives: Latex product manufacturing is an important industry in south-east Asia but has the potential for considerable occupational exposure of workers to latex allergens. Although exposure to latex allergens can result in adverse health reactions, few studies to characterize this exposure have been conducted to date. This study therefore aimed to characterize current airborne inhalable dust and the specific allergen, Hev b 6.02, exposures in this industry in Thailand. Methods: Workers were recruited from three factories in the southern part of Thailand. Full-shift inhalable dust personal air sampling was conducted using IOM sampling heads equipped with polytetrafluoroethylene filters at a 2.0 l min−1 flowrate. After weighing to determine inhalable dust levels, filters were extracted and analysed for Hev b 6.02 using an enzyme immunometric assay. Results: Two hundred and seventy-five workers agreed to participate, resulting in a total of 292 measurements. Geometric mean (GM) personal exposure to inhalable dust was 0.88mg m–3, but individual exposures up to 12.34mg m–3 were measured. The pattern of exposure was similar across factories, with highest exposures in the stripping (GM 2.08–4.05mg m–3 for the 3 factories) and tumbling departments (1.11–2.17mg m–3). Within-worker (day-to-day) variability contributed 92% to total variability. The Hev b 6.02 exposure pattern was similar with time-weighted average GM exposure levels in the oldest factory ranging from 8.7mg m–3 in the laboratory to 30.2mg m–3 in the stripping department. In contrast to inhalable dust exposure, total exposure variability was primary driven by variability between workers (67%). Conclusions: Workers in these latex product factories get routinely exposed to measurable Hev b 6.02 levels, which may give rise to increased incidence of allergic symptoms and occupational asthma. Also, in this measurement campaign a 10mg m–3, but not 15mg m–3, occupational exposure limit for

  4. Personal exposure to inhalable dust and the specific latex aero-allergen, Hev b6.02, in latex glove manufacturing in Thailand.

    PubMed

    Sanguanchaiyakrit, Nuthchyawach; Povey, Andrew C; de Vocht, Frank

    2014-06-01

    Latex product manufacturing is an important industry in south-east Asia but has the potential for considerable occupational exposure of workers to latex allergens. Although exposure to latex allergens can result in adverse health reactions, few studies to characterize this exposure have been conducted to date. This study therefore aimed to characterize current airborne inhalable dust and the specific allergen, Hev b 6.02, exposures in this industry in Thailand. Workers were recruited from three factories in the southern part of Thailand. Full-shift inhalable dust personal air sampling was conducted using IOM sampling heads equipped with polytetrafluoroethylene filters at a 2.0 l min(-1) flowrate. After weighing to determine inhalable dust levels, filters were extracted and analysed for Hev b 6.02 using an enzyme immunometric assay. Two hundred and seventy-five workers agreed to participate, resulting in a total of 292 measurements. Geometric mean (GM) personal exposure to inhalable dust was 0.88 mg m(-3), but individual exposures up to 12.34 mg m(-3) were measured. The pattern of exposure was similar across factories, with highest exposures in the stripping (GM 2.08-4.05 mg m(-3) for the 3 factories) and tumbling departments (1.11-2.17 mg m(-3)). Within-worker (day-to-day) variability contributed 92% to total variability. The Hev b 6.02 exposure pattern was similar with time-weighted average GM exposure levels in the oldest factory ranging from 8.7 mg m(-3) in the laboratory to 30.2mg m(-3) in the stripping department. In contrast to inhalable dust exposure, total exposure variability was primary driven by variability between workers (67%). Workers in these latex product factories get routinely exposed to measurable Hev b 6.02 levels, which may give rise to increased incidence of allergic symptoms and occupational asthma. Also, in this measurement campaign a 10mg m(-3), but not 15 mg m(-3), occupational exposure limit for inhalable dust was occasionally exceeded

  5. Assessment of potential (inhalation and dermal) and actual exposure to acetamiprid by greenhouse applicators using liquid chromatography-tandem mass spectrometry.

    PubMed

    Marín, A; Martínez Vidal, J L; Egea Gonzalez, F J; Garrido Frenich, A; Glass, C R; Sykes, M

    2004-05-25

    New analytical methods based on liquid chromatography with electrospray tandem mass spectrometry (LC-MS/MS) have been developed and validated for assessing the exposure of greenhouse workers to acetamiprid. Both ambient (potential inhalation and dermal exposure) and internal dose (biological monitoring of urine samples) measurements were carried out. Potential inhalation exposure was assessed using Chromosorb 102 cartridges connected to air personal samplers. Potential dermal exposure was estimated by using whole body dosimetry. The measurement of actual exposure was done by analyzing the parent compound in urine samples of the applicators, after a solid-phase extraction (SPE) step. The methods showed a good accuracy (72-92%), precision (2-13%) and lower limits (few microg l(-1)). The validated approaches have been applied to assess potential and actual exposure of agricultural workers spraying acetamiprid in greenhouses. The results shown the need to wear personal protective equipment (suits) in order to reduce the absorbed dose of acetamiprid.

  6. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A(®)) Following Acute Repeated Inhalation Exposure.

    PubMed

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m(3), five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution by day 7. In summary, acute

  7. Mimicking exposures to acute and lifetime concentrations of inhaled silver nanoparticles by two different in vitro approaches

    PubMed Central

    Herzog, Fabian; Loza, Kateryna; Balog, Sandor; Clift, Martin J D; Epple, Matthias; Gehr, Peter; Petri-Fink, Alke

    2014-01-01

    Summary In the emerging market of nano-sized products, silver nanoparticles (Ag NPs) are widely used due to their antimicrobial properties. Human interaction with Ag NPs can occur through the lung, skin, gastrointestinal tract, and bloodstream. However, the inhalation of Ag NP aerosols is a primary concern. To study the possible effects of inhaled Ag NPs, an in vitro triple cell co-culture model of the human alveolar/airway barrier (A549 epithelial cells, human peripheral blood monocyte derived dendritic and macrophage cells) together with an air–liquid interface cell exposure (ALICE) system was used in order to reflect a real-life exposure scenario. Cells were exposed at the air–liquid interface (ALI) to 0.03, 0.3, and 3 µg Ag/cm2 of Ag NPs (diameter 100 nm; coated with polyvinylpyrrolidone: PVP). Ag NPs were found to be highly aggregated within ALI exposed cells with no impairment of cell morphology. Furthermore, a significant increase in release of cytotoxic (LDH), oxidative stress (SOD-1, HMOX-1) or pro-inflammatory markers (TNF-α, IL-8) was absent. As a comparison, cells were exposed to Ag NPs in submerged conditions to 10, 20, and 30 µg Ag/mL. The deposited dose per surface area was estimated by using a dosimetry model (ISDD) to directly compare submerged vs ALI exposure concentrations after 4 and 24 h. Unlike ALI exposures, the two highest concentrations under submerged conditions promoted a cytotoxic and pro-inflammatory response after 24 h. Interestingly, when cell cultures were co-incubated with lipopolysaccharide (LPS), no synergistic inflammatory effects were observed. By using two different exposure scenarios it has been shown that the ALI as well as the suspension conditions for the lower concentrations after 4 h, reflecting real-life concentrations of an acute 24 h exposure, did not induce any adverse effects in a complex 3D model mimicking the human alveolar/airway barrier. However, the highest concentrations used in the ALI setup, as well as

  8. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A®) Following Acute Repeated Inhalation Exposure

    PubMed Central

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    INTRODUCTION Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. METHODS The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m3, five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. RESULTS No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution

  9. Health Risk Assessment for Inhalation Exposure to Methyl Tertiary Butyl Ether at Petrol Stations in Southern China

    PubMed Central

    Hu, Dalin; Yang, Jianping; Liu, Yungang; Zhang, Wenjuan; Peng, Xiaowu; Wei, Qinzhi; Yuan, Jianhui; Zhu, Zhiliang

    2016-01-01

    Methyl tertiary butyl ether (MTBE), a well known gasoline additive, is used in China nationwide to enhance the octane number of gasoline and reduce harmful exhaust emissions, yet  little is known regarding the potential health risk associated with occupational exposure to MTBE in petrol stations. In this study, 97 petrol station attendants (PSAs) in southern China were recruited for an assessment of the health risk associated with inhalation exposure to MTBE. The personal exposure levels of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS, and the demographic characteristics of the PSAs were investigated. Cancer and non-cancer risks were calculated with the methods recommended by the United States Environmental Protection Agency. The results showed that the exposure levels of MTBE in operating workers were much higher than among support staff (p < 0.01) and both were lower than 50 ppm (an occupational threshold limit value). The calculated cancer risks (CRs) at the investigated petrol stations was 0.170 to 0.240 per 106 for operating workers, and 0.026 to 0.049 per 106 for support staff, which are below the typical target range for risk management of 1 × 10−6 to 1 × 10−4; The hazard quotients (HQs) for all subjects were <1. In conclusion, our study indicates that the MTBE exposure of PSAs in southern China is in a low range which does not seem to be a significant health risk. PMID:26861375

  10. Health Risk Assessment for Inhalation Exposure to Methyl Tertiary Butyl Ether at Petrol Stations in Southern China.

    PubMed

    Hu, Dalin; Yang, Jianping; Liu, Yungang; Zhang, Wenjuan; Peng, Xiaowu; Wei, Qinzhi; Yuan, Jianhui; Zhu, Zhiliang

    2016-02-06

    Methyl tertiary butyl ether (MTBE), a well known gasoline additive, is used in China nationwide to enhance the octane number of gasoline and reduce harmful exhaust emissions, yet little is known regarding the potential health risk associated with occupational exposure to MTBE in petrol stations. In this study, 97 petrol station attendants (PSAs) in southern China were recruited for an assessment of the health risk associated with inhalation exposure to MTBE. The personal exposure levels of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS, and the demographic characteristics of the PSAs were investigated. Cancer and non-cancer risks were calculated with the methods recommended by the United States Environmental Protection Agency. The results showed that the exposure levels of MTBE in operating workers were much higher than among support staff (p < 0.01) and both were lower than 50 ppm (an occupational threshold limit value). The calculated cancer risks (CRs) at the investigated petrol stations was 0.170 to 0.240 per 10⁶ for operating workers, and 0.026 to 0.049 per 10⁶ for support staff, which are below the typical target range for risk management of 1 × 10(-6) to 1 × 10(-4); The hazard quotients (HQs) for all subjects were <1. In conclusion, our study indicates that the MTBE exposure of PSAs in southern China is in a low range which does not seem to be a significant health risk.

  11. Toxicity of chemical components of fine particles inhaled by aged rats: effects of concentration.

    PubMed

    Kleinman, Michael T; Hyde, Dallas M; Bufalino, Charles; Basbaum, Carol; Bhalla, Deepak K; Mautz, William J

    2003-09-01

    This study tested the hypothesis that exposure to mixtures containing fine particles and ozone (O3) would cause pulmonary injury and decrements in functions of immunological cells in exposed rats (22-24 months old) in a dose-dependent manner. Rats were exposed to high and low concentrations of ammonium bisulfate and elemental carbon and to 0.2 ppm O3. Control groups were exposed to purified air or O3 alone. The biological end points measured included histopathological markers of lung injury, bronchoalveolar lung fluid proteins, and measures of the function of the lung's innate immunological defenses (macrophage antigen-directed phagocytosis and respiratory burst activity). Exposure to O3 alone at 0.2 ppm did not result in significant changes in any of the measured end points. Exposures to the particle mixtures plus O3 produced statistically significant changes consistent with adverse effects. The low-concentration mixture produced effects that were statistically significant compared to purified air but, with the exception of macrophage Fc receptor binding, exposure to the high-concentration mixture did not. The effects of the low- and high-concentration mixtures were not significantly different. The study supports previous work that indicated that particle + O3 mixtures were more toxic than O3 alone.

  12. The Total Human Environmental Exposure Study (THEES) to benzo(a)pyrene: comparison of the inhalation and food pathways.

    PubMed

    Lioy, P L; Waldman, J M; Greenberg, A; Harkov, R; Pietarinen, C

    1988-01-01

    The assessment of human exposure to an environmental contaminant requires the measurement of levels present in each pathway of possible contact. In this paper, the design considerations and Phase I results of a human exposure study focused on Benzo(a)pyrene (BaP) are discussed. This study site, located in Phillipsburg, New Jersey, is a city that contains a metal pipe foundry, which is a suspected major source of BaP. Three outdoor PM-10 samplers (used to collect BaP-containing particles with an aerodynamic size of less than or equal to 10 micron) were located in residential areas surrounding the foundry. Ten homes were sampled indoors for PM-10. Some homes have indoor combustion sources, e.g., cigarette smoke or a coal burning stove. The indoor and outdoor samples were 24 hr in duration. The mean outdoor concentration of BaP was 0.9 ng/m3, and the indoor concentrations ranged from 0.1-8.1 ng/m3. Food samples were acquired from family meals each day. They represented a one-third portion of each meal eaten at home. The range of BaP per gram of wet weight of food was between 0.004 and 1.2 ng/g. Of the 20 wk of exposure (10 x 2 wk), 10 had higher food exposures and the other 10 had higher inhalation exposures. Of the two groups, the higher food exposures usually had a greater number of ng of BaP/wk. The dominance of one or the other pathway appeared to depend upon personal eating habits and indoor combustion source use. In some instances, outdoor air pollution led to a major portion of indoor air BaP exposures. Water appears to be a minor source of BaP exposures in the study area.

  13. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX.

    PubMed

    Nambiar, Madhusoodana P; Gordon, Richard K; Rezk, Peter E; Katos, Alexander M; Wajda, Nikolai A; Moran, Theodore S; Steele, Keith E; Doctor, Bhupendra P; Sciuto, Alfred M

    2007-03-01

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m(3) of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

  14. Total Human Environmental Exposure Study (THEES) to benzo(a)pyrene: comparison of the inhalation and food pathways

    SciTech Connect

    Lioy, P.L.; Waldman, J.M.; Greenberg, A.; Harkov, R.; Pietarinen, C.

    1988-07-01

    The assessment of human exposure to an environmental contaminant requires the measurement of levels present in each pathway of possible contact. In this paper, the design considerations and Phase I results of a human exposure study focused on Benzo(a)pyrene (BaP) are discussed. This study site, located in Phillipsburg, New Jersey, is a city that contains a metal pipe foundry, which is a suspected major source of BaP. Three outdoor PM-10 samplers (used to collect BaP-containing particles with an aerodynamic size of less than or equal to 10 micron) were located in residential areas surrounding the foundry. Ten homes were sampled indoors for PM-10. Some homes have indoor combustion sources, e.g., cigarette smoke or a coal burning stove. The indoor and outdoor samples were 24 hr in duration. The mean outdoor concentration of BaP was 0.9 ng/m3, and the indoor concentrations ranged from 0.1-8.1 ng/m3. Food samples were acquired from family meals each day. They represented a one-third portion of each meal eaten at home. The range of BaP per gram of wet weight of food was between 0.004 and 1.2 ng/g. Of the 20 wk of exposure (10 x 2 wk), 10 had higher food exposures and the other 10 had higher inhalation exposures. Of the two groups, the higher food exposures usually had a greater number of ng of BaP/wk. The dominance of one or the other pathway appeared to depend upon personal eating habits and indoor combustion source use. In some instances, outdoor air pollution led to a major portion of indoor air BaP exposures. Water appears to be a minor source of BaP exposures in the study area.

  15. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

    SciTech Connect

    Nambiar, Madhusoodana P.; Doctor, Bhupendra P.

    2007-03-15

    To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m{sup 3} of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure did not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.

  16. Exposure to inhalable dust and its cyclohexane soluble fraction since the 1970s in the rubber manufacturing industry in the European Union.

    PubMed

    de Vocht, F; Vermeulen, R; Burstyn, I; Sobala, W; Dost, A; Taeger, D; Bergendorf, U; Straif, K; Swuste, P; Kromhout, H

    2008-06-01

    As exposures to airborne particulates in the European rubber industry might still be causing genotoxic risks, it is important to assess trends in levels of inhalable dust and its cyclohexane soluble fraction (CSF) between the 1970s and 2003. 13 380 inhalable and 816 respirable dust and 5657 CSF measurements, collected within the framework of the European Union Concerted Action EXASRUB, were analysed. Hierarchical mixed effects models were applied to assess exposure trends, taking into account between-factory, between-worker/location and day-to-day variances. Geometric mean levels of inhalable dust and CSF exposure changed by -4% (range -5.8 to +2.9%) and -3% (range -8.6 to 0%) per year, respectively. Significant reductions in inhalable dust concentrations were found in all countries for handling of crude materials and mixing and milling (-7% to -4% per year), as well as for miscellaneous workers (-11% to -5% per year), while significant CSF exposure reductions were found in curing (-8.6% per year) and maintenance and engineering departments (-5.4% per year). These analyses suggest that on average exposure levels of inhalable dust and its CSF in the European rubber manufacturing industry have steadily declined. Most likely genotoxic risks have also lessened over time since exposure levels have decreased and the most toxic chemicals have been replaced. In addition to differences in exposure reductions and levels among various stages of the production process, large differences across countries were noted. These patterns should be taken into account in retrospective assessment of exposure for epidemiological studies assessing cancer risk in the rubber industry.

  17. Instillation versus Inhalation of Multiwalled Carbon Nanotubes: Exposure-Related Health Effects, Clearance, and the Role of Particle Characteristics

    PubMed Central

    2015-01-01

    Inhaled multiwalled carbon nanotubes (MWCNTs) may cause adverse pulmonary responses due to their nanoscale, fibrous morphology and/or biopersistance. This study tested multiple factors (dose, time, physicochemical characteristics, and administration method) shown to affect MWCNT toxicity with the hypothesis that these factors will influence significantly different responses upon MWCNT exposure. The study is unique in that (1) multiple administration methods were tested using particles from the same stock; (2) bulk MWCNT formulations had few differences (metal content, surface area/functionalization); and (3) MWCNT retention was quantified using a specialized approach for measuring unlabeled MWCNTs in rodent lungs. Male Sprague–Dawley rats were exposed to original (O), purified (P), and carboxylic acid functionalized (F) MWCNTs via intratracheal instillation and inhalation. Blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected at postexposure days 1 and 21 for quantifying biological responses and MWCNTs in lung tissues by programmed thermal analysis. At day 1, MWCNT instillation produced significant BALF neutrophilia and MWCNT-positive macrophages. Instilled O- and P-MWCNTs produced significant inflammation in lung tissues, which resolved by day 21 despite MWCNT retention. MWCNT inhalation produced no BALF neutrophilia and no significant histopathology past day 1. However, on days 1 and 21 postinhalation of nebulized MWCNTs, significantly increased numbers of MWCNT-positive macrophages were observed in BALF. Results suggest (1) MWCNTs produce transient inflammation if any despite persistence in the lungs; (2) instilled O-MWCNTs cause more inflammation than P- or F-MWCNTs; and (3) MWCNT suspension media produce strikingly different effects on physicochemical particle characteristics and pulmonary responses. PMID:25144856

  18. Estimating the contribution of inhalation exposure to di-2-ethylhexyl phthalate (DEHP) for PVC production workers, using personal air sampling and urinary metabolite monitoring.

    PubMed

    Fong, Jer-Pei; Lee, Fang-Jin; Lu, I-Syuan; Uang, Shi-Nian; Lee, Ching-Chang

    2014-01-01

    Because of troubling reports of high urinary metabolite levels and adverse reproductive health effects in workers exposed to di(2-ethylhexyl)phthalate (DEHP) in occupational settings, concern about exposure to DEHP in occupational settings is increasing. However, the contributions of different routes of exposure to DEHP are unclear. We used personal air sampling and biomonitoring to determine the contribution of inhalation exposure to the body burden of DEHP in the workplace. Eighty-nine workers (high-exposure group: 66 raw-materials workers; low-exposure group: 23 administrative workers) were recruited from three polyvinyl chloride (PVC) factories. Urinary levels of mono(2-ethylhexyl) phthalate (MEHP), (mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were measured in pre-shift and post-shift samples. The geometric means of airborne concentrations of DEHP were 5.3 μg/m3 (low-exposure group) and 32.7 μg/m3 (high-exposure group) (P<0.01). Correlation analysis showed a consistently significant association between airborne DEHP concentration and urinary DEHP metabolite levels in the high-exposure group. Calculating daily DEHP intake based on total urinary metabolite levels showed that the geometric means of total daily urinary metabolite levels of DEHP were 9.2 μg/kg/day (low-exposure group) and 15.5 μg/kg/day (high-exposure group) (P<0.01). A quartile analysis of all workers showed a significant trend toward an association between the individual contribution of inhalation exposure to DEHP and urinary DEHP metabolite levels, for which the mean inhalation contribution was 46.7% in the highest quartile. We conclude that inhalation-absorbed airborne DEHP significantly increased the total body burden of DEHP in these occupationally exposed workers.

  19. Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice.

    PubMed

    Ganguly, Koustav; Ettehadieh, Dariusch; Upadhyay, Swapna; Takenaka, Shinji; Adler, Thure; Karg, Erwin; Krombach, Fritz; Kreyling, Wolfgang G; Schulz, Holger; Schmid, Otmar; Stoeger, Tobias

    2017-06-20

    The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardio-vascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM. Equivalent surface area CNP doses in the blood (30mm(2) per animal) were applied by IAI or inhalation (lung-deposited dose 10,000mm(2); accounting for 0.3% of lung-to-blood CNP translocation). Mice were analyzed for changes in hematology and molecular markers of endothelial/epithelial dysfunction, pro-inflammatory reactions, oxidative stress, and coagulation in lungs and extra-pulmonary organs after CNP inhalation (4 h and 24 h) and CNP infusion (4 h). For methodological reasons, we used two different CNP types (spark-discharge and Printex90), with very similar physicochemical properties [≥98 and ≥95% elemental carbon; 10 and 14 nm primary particle diameter; and 800 and 300 m(2)/g specific surface area] for inhalation and IAI respectively. Mild pulmonary inflammatory responses and significant systemic effects were observed following 4 h and 24 h CNP inhalation. Increased retention of activated leukocytes, secondary thrombocytosis, and pro-inflammatory responses in secondary organs were detected following 4 h and 24 h of CNP inhalation only. Interestingly, among the investigated extra-pulmonary tissues (i.e. aorta, heart, and liver); aorta revealed as the most susceptible extra-pulmonary target following inhalation exposure. Bypassing the lungs by IAI however did not induce any extra-pulmonary effects at 4 h as compared to inhalation. Our findings indicate that extra-pulmonary effects due to CNP

  20. Human inhalation exposures to toluene, ethylbenzene, and m-xylene and physiologically based pharmacokinetic modeling of exposure biomarkers in exhaled air, blood, and urine.

    PubMed

    Marchand, Axelle; Aranda-Rodriguez, Rocio; Tardif, Robert; Nong, Andy; Haddad, Sami

    2015-04-01

    Urinary biomarkers of exposure are used widely in biomonitoring studies. The commonly used urinary biomarkers for the aromatic solvents toluene (T), ethylbenzene (E), and m-xylene (X) are o-cresol, mandelic acid, and m-methylhippuric acid. The toxicokinetics of these biomarkers following inhalation exposure have yet to be described by physiologically based pharmacokinetic (PBPK) modeling. Five male volunteers were exposed for 6 h in an inhalation chamber to 1/8 or 1/4 of the time-weighted average exposure value (TWAEV) for each solvent: toluene, ethylbenzene, and m-xylene were quantified in blood and exhaled air and their corresponding urine biomarkers were measured in urine. Published PBPK model for parent compounds was used and simulations were compared with experimental blood and exhaled air concentration data. If discrepancies existed, Vmax and Km were optimized. Urinary excretion was modeled using parameters found in literature assuming simply stoichiometric yields from parent compound metabolism and first-order urinary excretion rate. Alternative models were also tested for (1) the possibility that CYP1A2 is the only enzyme implicated in o-cresol and (2) a 2-step model for describing serial metabolic steps for mandelic acid. Models adapted in this study for urinary excretion will be further used to interpret urinary biomarker kinetic data from mixed exposures of these solvents. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs.

    PubMed

    Rezk, Peter E; Graham, Jacob R; Moran, Theodore S; Gordon, Richard K; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2007-03-01

    Exposure to a chemical warfare nerve agent (CWNA) leads to severe respiratory distress, respiratory failure, or death if not treated. We investigated the toxic effects of nerve agent VX on the respiratory dynamics of guinea pigs following exposure to 90.4 mug/m3 of VX or saline by microinstillation inhalation technology for 10 min. Respiratory parameters were monitored by whole-body barometric plethysmography at 4, 24, and 48 h, 7 d, 18 d, and 4 wk after VX exposure. VX-exposed animals showed a significant decrease in the respiratory frequency (RF) at 24 and 48 h of recovery (p value .0329 and .0142, respectively) compared to the saline control. The tidal volume (TV) slightly increased in VX exposed animals at 24 and significantly at 48 h (p = .02) postexposure. Minute ventilation (MV) increased slightly at 4 h but was reduced at 24 h and remained unchanged at 48 h. Animals exposed to VX also showed an increase in expiratory (Te) and relaxation time (RT) at 24 and 48 h and a small reduction in inspiratory time (Ti) at 24 h. A significant increase in end expiratory pause (EEP) was observed at 48 h after VX exposure (p = .049). The pseudo lung resistance (Penh) was significantly increased at 4 h after VX exposure and remained slightly high even at 48 h. Time-course studies reveal that most of the altered respiratory dynamics returned to normal at 7 d after VX exposure except for EEP, which was high at 7 d and returned to normal at 18 d postexposure. After 1 mo, all the monitored respiratory parameters were within normal ranges. Bronchoalveolar lavage (BAL) 1 mo after exposure showed virtually no difference in protein levels, cholinesterase levels, cell number, and cell death in the exposed and control animals. These results indicate that sublethal concentrations of VX induce changes in respiratory dynamics and functions that over time return to normal levels.

  2. A COMPUTER-CONTROLLED WHOLE-BODY INHALATION EXPOSURE SYSTEM FOR THE OIL DISPERSANT COREXIT EC9500A

    PubMed Central

    Goldsmith, William Travis; McKinney, Walter; Jackson, Mark; Law, Brandon; Bledsoe, Toni; Siegel, Paul; Cumpston, Jared; Frazer, David

    2015-01-01

    An automated whole-body inhalation exposure system capable of exposing 12 individually housed rats was designed to examine the potential adverse health effects of the oil dispersant COREXIT EC9500A, used extensively during the Deepwater Horizon oil spill. A computer–controlled syringe pump injected the COREXIT EC9500A into an atomizer where droplets and vapor were formed and mixed with diluent air. The aerosolized COREXIT EC9500A was passed into a customized exposure chamber where a calibrated light-scattering instrument estimated the real-time particle mass concentration of the aerosol in the chamber. Software feedback loops controlled the chamber aerosol concentration and pressure throughout each exposure. The particle size distribution of the dispersant aerosol was measured and shown to have a count median aerodynamic diameter of 285 nm with a geometric standard deviation of 1.7. The total chamber concentration (particulate + vapor) was determined using a modification of the acidified methylene blue spectrophotometric assay for anionic surfactants. Tests were conducted to show the effectiveness of closed loop control of chamber concentration and to verify chamber concentration homogeneity. Five automated 5-h animal exposures were performed that produced controlled and consistent COREXIT EC9500A concentrations (27.1 ± 2.9 mg/m3, mean ± SD). PMID:21916743

  3. A computer-controlled whole-body inhalation exposure system for the oil dispersant COREXIT EC9500A.

    PubMed

    Goldsmith, William Travis; McKinney, Walter; Jackson, Mark; Law, Brandon; Bledsoe, Toni; Siegel, Paul; Cumpston, Jared; Frazer, David

    2011-01-01

    An automated whole-body inhalation exposure system capable of exposing 12 individually housed rats was designed to examine the potential adverse health effects of the oil dispersant COREXIT EC9500A, used extensively during the Deepwater Horizon oil spill. A computer-controlled syringe pump injected the COREXIT EC9500A into an atomizer where droplets and vapor were formed and mixed with diluent air. The aerosolized COREXIT EC9500A was passed into a customized exposure chamber where a calibrated light-scattering instrument estimated the real-time particle mass concentration of the aerosol in the chamber. Software feedback loops controlled the chamber aerosol concentration and pressure throughout each exposure. The particle size distribution of the dispersant aerosol was measured and shown to have a count median aerodynamic diameter of 285 nm with a geometric standard deviation of 1.7. The total chamber concentration (particulate + vapor) was determined using a modification of the acidified methylene blue spectrophotometric assay for anionic surfactants. Tests were conducted to show the effectiveness of closed loop control of chamber concentration and to verify chamber concentration homogeneity. Five automated 5-h animal exposures were performed that produced controlled and consistent COREXIT EC9500A concentrations (27.1 ± 2.9 mg/m(3), mean ± SD).

  4. Hardwood smoke alters murine splenic T cell responses to mitogens following a 6-month whole body inhalation exposure

    SciTech Connect

    Burchiel, Scott W. . E-mail: Sburchiel@salud.unm.edu; Lauer, Fredine T.; Dunaway, Sandy L.; Zawadzki, Jerome; McDonald, Jacob D.; Reed, Matthew D.

    2005-02-01

    The purpose of these studies was to assess the effects of hardwood smoke (HWS) inhalation (30-1000 {mu}g/m{sup 3}) on the systemic immune responses of A/J mice evaluated after 6 months of daily exposures. Spleen cells obtained from mice were assessed for changes in cell number, cell surface marker expression [B, T, macrophage, and natural killer (NK) cells], and responses to B cell (LPS, endotoxin) and T cell (Con A) mitogens. Results showed that HWS smoke increased T cell proliferation in the 100 {mu}g/m{sup 3} exposure group and produced a concentration-dependent suppression of T cell proliferation at concentrations >300 {mu}g/m{sup 3}. There were no effects on B cell proliferation or in spleen cell surface marker expression. Analyses of the exposure atmospheres revealed the presence of significant levels of naphthalene and methylated napthalenes, fluorene, phenanthrene, and anthracene in the exposure chambers, as well as low concentrations of several metals (K, Ca, and Fe). Our results demonstrate that environmentally relevant concentrations of HWS may be immunosuppressive to the immune system of mice exposed during a 6-month period.

  5. RECONSTRUCTING POPULATION EXPOSURES FROM DOSE BIOMARKERS: INHALATION OF TRICHLOROETHYLENE (TCE) AS A CASE STUDY

    EPA Science Inventory

    Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through bi...

  6. RECONSTRUCTING POPULATION EXPOSURES FROM DOSE BIOMARKERS: INHALATION OF TRICHLOROETHYLENE (TCE) AS A CASE STUDY

    EPA Science Inventory

    Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through bi...

  7. Ecstasy exposure & gender: examining components of verbal memory functioning.

    PubMed

    Price, Jenessa S; Shear, Paula; Lisdahl, Krista M

    2014-01-01

    Studies have demonstrated verbal memory deficits associated with past year ecstasy use, although specific underlying components of these deficits are less understood. Further, prior research suggests potential gender differences in ecstasy-induced serotonergic changes. Therefore, the current study investigated whether gender moderated the relationship between ecstasy exposure and components of verbal memory after controlling for polydrug use and confounding variables. Data were collected from 65 polydrug users with a wide range of ecstasy exposure (ages 18-35; 48 ecstasy and 17 marijuana users; 0-2310 ecstasy tablets). Participants completed a verbal learning and memory task, psychological questionnaires, and a drug use interview. Increased past year ecstasy exposure predicted poorer short and long delayed free and cued recalls, retention, and recall discrimination. Male ecstasy users were more susceptible to dose-dependent deficits in retention than female users. Past year ecstasy consumption was associated with verbal memory retrieval, retention, and discrimination deficits in a dose-dependent manner in a sample of healthy young adult polydrug users. Male ecstasy users were at particular risk for deficits in retention following a long delay. Gender difference may be reflective of different patterns of polydrug use as well as increased hippocampal sensitivity. Future research examining neuronal correlates of verbal memory deficits in ecstasy users are needed.

  8. Ecstasy Exposure & Gender: Examining Components of Verbal Memory Functioning

    PubMed Central

    Price, Jenessa S.; Shear, Paula; Lisdahl, Krista M.

    2014-01-01

    Objective Studies have demonstrated verbal memory deficits associated with past year ecstasy use, although specific underlying components of these deficits are less understood. Further, prior research suggests potential gender differences in ecstasy-induced serotonergic changes. Therefore, the current study investigated whether gender moderated the relationship between ecstasy exposure and components of verbal memory after controlling for polydrug use and confounding variables. Method Data were collected from 65 polydrug users with a wide range of ecstasy exposure (ages 18–35; 48 ecstasy and 17 marijuana users; 0–2310 ecstasy tablets). Participants completed a verbal learning and memory task, psychological questionnaires, and a drug use interview. Results Increased past year ecstasy exposure predicted poorer short and long delayed free and cued recalls, retention, and recall discrimination. Male ecstasy users were more susceptible to dose-dependent deficits in retention than female users. Conclusion Past year ecstasy consumption was associated with verbal memory retrieval, retention, and discrimination deficits in a dose-dependent manner in a sample of healthy young adult polydrug users. Male ecstasy users were at particular risk for deficits in retention following a long delay. Gender difference may be reflective of different patterns of polydrug use as well as increased hippocampal sensitivity. Future research examining neuronal correlates of verbal memory deficits in ecstasy users are needed. PMID:25545890

  9. Pulmonary Endpoints (Lung Carcinomas and Asbestosis) Following Inhalation Exposure to Asbestos

    PubMed Central

    Mossman, Brooke T.; Lippmann, Morton; Hesterberg, Thomas W.; Kelsey, Karl T.; Barchowsky, Aaron; Bonner, James C.

    2011-01-01

    Lung carcinomas and pulmonary fibrosis (asbestosis) occur in asbestos workers. Understanding the pathogenesis of these diseases is complicated because of potential confounding factors, such as smoking, which is not a risk factor in mesothelioma. The modes of action (MOA) of various types of asbestos in the development of lung cancers, asbestosis, and mesotheliomas appear to be different. Moreover, asbestos fibers may act differentially at various stages of these diseases, and have different potencies as compared to other naturally occurring and synthetic fibers. This literature review describes patterns of deposition and retention of various types of asbestos and other fibers after inhalation, methods of translocation within the lung, and dissolution of various fiber types in lung compartments and cells in vitro. Comprehensive dose-response studies at fiber concentrations inhaled by humans as well as bivariate size distributions (lengths and widths), types, and sources of fibers are rarely defined in published studies and are needed. Species-specific responses may occur. Mechanistic studies have some of these limitations, but have suggested that changes in gene expression (either fiber-catalyzed directly or by cell elaboration of oxidants), epigenetic changes, and receptor-mediated or other intracellular signaling cascades may play roles in various stages of the development of lung cancers or asbestosis. PMID:21534086

  10. Inhalation exposure of rats to asphalt fumes generated at paving temperatures alters pulmonary xenobiotic metabolism pathways without lung injury.

    PubMed Central

    Ma, Jane Y C; Rengasamy, Apavoo; Frazer, Dave; Barger, Mark W; Hubbs, Ann F; Battelli, Lori; Tomblyn, Seith; Stone, Samuel; Castranova, Vince

    2003-01-01

    Asphalt fumes are complex mixtures of various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). PAHs require bioactivation by the cytochrome P-450 monooxygenase system to exert toxic/carcinogenic effects. The present study was carried out to characterize the acute pulmonary inflammatory responses and the alterations of pulmonary xenobiotic pathways in rats exposed to asphalt fumes by inhalation. Rats were exposed at various doses and time periods to air or to asphalt fumes generated at paving temperatures. To assess the acute damage and inflammatory responses, differential cell counts, acellular lactate dehydrogenase (LDH) activity, and protein content of bronchoalveolar lavage fluid were determined. Alveolar macrophage (AM) function was assessed by monitoring generation of chemiluminescence and production of tumor necrosis factor-alpha and interleukin-1. Alteration of pulmonary xenobiotic pathways was determined by monitoring the protein levels and activities of P-450 isozymes (CYP1A1 and CYP2B1), glutathioneS-transferase (GST), and NADPH:quinone oxidoreductase (QR). The results show that acute asphalt fume exposure did not cause neutrophil infiltration, alter LDH activity or protein content, or affect AM function, suggesting that short-term asphalt fume exposure did not induce acute lung damage or inflammation. However, acute asphalt fume exposure significantly increased the activity and protein level of CYP1A1 whereas it markedly reduced the activity and protein level of CYP2B1 in the lung. The induction of CYP1A1 was localized in nonciliated bronchiolar epithelial (Clara) cells, alveolar septa, and endothelial cells by immunofluorescence microscopy. Cytosolic QR activity was significantly elevated after asphalt fume exposure, whereas GST activity was not affected by the exposure. This induction of CYP1A1 and QR with the concomitant down-regulation of CYP2B1 after asphalt fume exposure could alter PAH metabolism and may lead to potential

  11. Modeling potential occupational inhalation exposures and associated risks of toxic organics from chemical storage tanks used in hydraulic fracturing using AERMOD.

    PubMed

    Chen, Huan; Carter, Kimberly E

    2017-05-01

    Various toxic chemicals used in hydraulic fracturing fluids may influence the inherent health risks associated with these operations. This study investigated the possible occupational inhalation exposures and potential risks related to the volatile organic compounds (VOCs) from chemical storage tanks and flowback pits used in hydraulic fracturing. Potential risks were evaluated based on radial distances between 5 m and 180 m from the wells for 23 contaminants with known inhalation reference concentration (RfC) or inhalation unit risks (IUR). Results show that chemicals used in 12.4% of the wells posed a potential acute non-cancer risks for exposure and 0.11% of the wells with may provide chronic non-cancer risks for exposure. Chemicals used in 7.5% of the wells were associated with potential acute cancer risks for exposure. Those chemicals used in 5.8% of the wells may be linked to chronic cancer risks for exposure. While eight organic compounds were associated with acute non-cancer risks for exposure (>1), methanol the major compound in the chemical storage tanks (1.00-45.49) in 7,282 hydraulic fracturing wells. Wells with chemicals additives containing formaldehyde exhibited both acute and chronic cancer risks for exposure with IUR greater than 10(-6), suggesting formaldehyde was the dominant contributor to both types of risks for exposure in hydraulic fracturing. This study also found that due to other existing on-site emission sources of VOCs and the geographically compounded air concentrations from other surrounding wells, chemical emissions data from storage tanks and flowback pits used in this study were lower than reported concentrations from field measurements where higher occupational inhalation risks for exposure may be expected.

  12. Inhalation Study of Mycobacteriophage D29 Aerosol for Mice by Endotracheal Route and Nose-Only Exposure.

    PubMed

    Liu, Ke-Yang; Yang, Wen-Hui; Dong, Xiao-Kai; Cong, Li-Ming; Li, Na; Li, Yun; Wen, Zhan-Bo; Yin, Zhe; Lan, Zhi-Jie; Li, Wei-Peng; Li, Jin-Song

    2016-10-01

    Lytic mycobacteriophage D29 has the potential for tuberculosis treatment including multidrug-resistant strains. The aims of this study are to investigate deposition and distribution of aerosolized phage D29 particles in naive Balb/C mice, together with pharmacokinetics and evaluation of acute lung injury. Pharmacokinetics and BALF (bronchoalveolar lavage fluids) were analyzed after administration of phage D29 aerosols by endotracheal route using Penn-century aerosolizer; Collison 6-jet and Spinning top aerosol nebulizers (STAG) were used to generate phage aerosols with different particle size distributions in nose-only inhalation experiments. After exposure, deposited amounts of phage D29 particles in respiratory tracts were measured, and deposition efficiencies were calculated. A typical path deposition model for mice was developed, and then comparisons were made between predictions and experimentally measured results. Approximately 10% of aerosolized phages D29 reached lung of mouse for pulmonary delivery, and were completely eliminated until 72 h after administration. In contrast, about 0.1% of intraperitoneal injected phages reached the lung, and were almost eliminated at 12 h time point. The inflammation was hardly observed in lung according to the results of BALF analysis. The CMADs (count median aerodynamic diameters) of generated aerosol by Collison and STAG nebulizer were 0.8 μm and 1.5 μm, respectively. After nose-only exposure, measured deposition efficiencies in whole respiratory tract for 0.8 and 1.5 μm phage particles were below 1% and 10%, respectively. Predictions of the computer deposition model compared fairly well with experimentally measured results. This is the first systematic study of phage D29 aerosol respiratory challenge in laboratory animals. It provides evidence that aerosol delivery of phage D29 is an effective way for treating pulmonary infections caused by Mycobacterium tuberculosis. This research will also provide

  13. Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles.

    PubMed

    Liao, Chung-Min; Chiang, Yu-Hui; Chio, Chia-Pin

    2008-12-15

    This paper proposed a model-based approach to assess inhalation risk levels to manufacturing workers in titanium dioxide (TiO2) production factories. The risk level-based analytical schemes were present for investigations of job-related airborne nano/fine TiO2 dust exposures. A Hill model was used to reconstruct dose-response function based on data from rats exposed by chronic inhalation to poorly soluble fine and nanosized particles. A physiologically based lung model was used to predict surface area-based TiO2 burdens in alveolar surface and interstitial granuloma, respectively. The exposure effect was characterized by polymorphonuclear leukocytes (PMN) elevation effect on lung surface and lung tumor proportion on interstitium. Combining laboratory, field, and modeling results, two major findings were proposed to the current epidemiological studies: (i) the estimated median effective surface area-based TiO2 lung burden (EC50) for PMN elevation effect is 0.11 m2 g(-1) lung (95% CI: 0.04-0.2) and EC50 for lung tumor proportion is 1.15 m2 g(-1) lung (95% CI: 0.65-1.89) and (ii) the estimates of risk curves are the pivotal results for public policy. The results demonstrate that packers in US factories have approximately 85.77 fold (95% CI: 63.84-94.33) of standard PMN counts of 10(6), whereas 86.97 fold (95% CI: 66.72-94.54) for surface treatment workers in EU factories at risk of 0.5. The lung had approximately 45% (95% CI: 15%-54%) tumor proportion for packers in US factories, whereas 48.19% (95% CI: 20-53.79%) for surface treatment workers in EU factories at risk of 0.5. The findings point out that dry/wet treatment and ore handlers in US and maintenance mechanics in EU factories were unlikely to pose substantial lung cancer risks.

  14. Circulating factors induce coronary endothelial cell activation following exposure to inhaled diesel exhaust and nitrogen dioxide in humans: Evidence from a novel translational in vitro model**

    EPA Science Inventory

    The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

  15. Inhalation Cancer Risk Associated with Exposure to Complex Polycyclic Aromatic Hydrocarbon Mixtures in an Electronic Waste and Urban Area in South China

    PubMed Central

    Wang, Jing; Chen, Shejun; Tian, Mi; Zheng, Xiaobo; Gonzales, Leah; Ohura, Takeshi; Mai, Bixian; Simonich, Staci L. Massey

    2012-01-01

    Atmospheric particulate matter samples were collected from May 2010 to April 2011 in a rural e-waste area and in Guangzhou, South China, to estimate the lifetime inhalation cancer risk from exposure to parent polycyclic aromatic hydrocarbons (PAHs), high molecular weight PAHs (MW 302 PAHs), and halogenated PAHs (HPAHs). Seasonal variations in the PAH concentrations and profile within and between the e-waste and urban areas indicated different PAH sources in the two areas. Benzo[b]fluoranthene, BaP, dibenz[ah]anthracene, and dibenzo[al]pyrene made the most significant contribution to the inhalation cancer risk. MW 302 PAHs accounting for 18.0% of the total cancer risk in the e-waste area and 13.6% in the urban area, while HPAHs made a minor contribution (< 0.1%) in both the areas. The number of lifetime excess lung cancers due to exposure to parent PAHs, MW 302 PAHs, and HPAHs ranged from 15.1 to 1198 per million people in the e-waste area and from 9.3 to 737 per million people in Guangzhou. PAH exposure accounted for 0.02 to 1.94% of the total lung cancer cases in Guangzhou. On average, the inhalation cancer risk in the e-waste area was 1.6 times higher than in the urban area. The e-waste dismantling activities in South China led to higher inhalation cancer risk due to PAH exposure than the urban area. PMID:22913732

  16. Circulating factors induce coronary endothelial cell activation following exposure to inhaled diesel exhaust and nitrogen dioxide in humans: Evidence from a novel translational in vitro model**

    EPA Science Inventory

    The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

  17. Effects of subchronic inhalation exposure of rats to emissions from a diesel engine burning soybean oil-derived biodiesel fuel.

    PubMed

    Finch, G L; Hobbs, C H; Blair, L F; Barr, E B; Hahn, F F; Jaramillo, R J; Kubatko, J E; March, T H; White, R K; Krone, J R; Ménache, M G; Nikula, K J; Mauderly, J L; Van Gerpen, J; Merceica, M D; Zielinska, B; Stankowski, L; Burling, K; Howell, S

    2002-10-01

    There is increasing interest in diesel fuels derived from plant oils or animal fats ("biodiesel"), but little information on the toxicity of biodiesel emissions other than bacterial mutagenicity. F344 rats were exposed by inhalation 6 h/day, 5 days/wk for 13 wk to 1 of 3 dilutions of emissions from a diesel engine burning 100% soybean oil-derived fuel, or to clean air as controls. Whole emissions were diluted to nominal NO(x) concentrations of 5, 25, or 50 ppm, corresponding to approximately 0.04, 0.2, and 0.5 mg particles/m(3), respectively. Biologically significant, exposure-related effects were limited to the lung, were greater in females than in males, and were observed primarily at the highest exposure level. There was a dose-related increase in the numbers of alveolar macrophages and the numbers of particles in the macrophages, as expected from repeated exposure, but no neutrophil response even at the highest exposure level. The macrophage response was reduced 28 days after cessation of the exposure. Among the high-level females, the group mean lung weight/body weight ratio was increased, and minimal, multifocal bronchiolar metaplasia of alveolar ducts was observed in 4 of 30 rats. Lung weights were not significantly increased, and metaplasia of the alveolar ducts was not observed in males. An increase in particle-laden macrophages was the only exposure-related finding in lungs at the intermediate and low levels, with fewer macrophages and fewer particles per macrophage at the low level. Alveolar histiocytosis was observed in a few rats in both exposed and control groups. There were statistically significant, but minor and not consistently exposure-related, differences in body weight, nonpulmonary organ weights, serum chemistry, and glial fibrillary acidic protein in the brain. There were no significant exposure-related effects on survival, clinical signs, feed consumption, ocular toxicity, hematology, neurohistology, micronuclei in bone marrow, sister

  18. Pulmonary response after exposure to inhaled nickel hydroxide nanoparticles: short and long-term studies in mice

    PubMed Central

    Gillespie, Patricia A.; Kang, Gi Soo; Elder, Alison; Gelein, Robert; Chen, Lu; Moreira, Andre L.; Koberstein, Jeffrey; Tchou-Wong, Kam-Meng; Gordon, Terry; Chen, Lung Chi

    2010-01-01

    Short and long-term pulmonary response to inhaled nickel hydroxide nanoparticles (nano-Ni(OH)2, CMD = 40 nm) in C57BL/6 mice was assessed using a whole body exposure system. For short-term studies mice were exposed for 4 h to nominal concentrations of 100, 500, and 1000 mg/m3. For long-term studies mice were exposed for 5 h/d, 5 d/w, for up to 5 months (m) to a nominal concentration of 100 mg/m3. Particle morphology, size distribution, chemical composition, solubility, and intrinsic oxidative capacity were determined. Markers of lung injury and inflammation in bronchoalveolar lavage fluid (BALF); histopathology; and lung tissue elemental nickel content and mRNA changes in macrophage inflammatory protein-2 (Mip-2), chemokine ligand 2 (Ccl2), interleukin 1-alpha (Il-1α), and tumor necrosis factor-alpha (Tnf-α) were assessed. Dose-related changes in BALF analyses were observed 24 h after short-term studies while significant changes were noted after 3 m and/or 5 m of exposure (24 h). Nickel content was detected in lung tissue, Ccl2 was most pronouncedly expressed, and histological changes were noted after 5 m of exposure. Collectively, data illustrates nano-Ni(OH)2 can induce inflammatory responses in C57BL/6 mice. PMID:20730025

  19. Differences in aerosolization of Rift Valley fever virus resulting from choice of inhalation exposure chamber: implications for animal challenge studies

    PubMed Central

    Bethel, Laura M.; Powell, Diana S.; Caroline, Amy L.; Hartman, Amy L.

    2014-01-01

    Abstract The aerosol characteristics of Rift Valley fever virus (RVFV) were evaluated to achieve reproducible infection of experimental animals with aerosolized RVFV suitable for animal efficacy studies. Spray factor (SF), the ratio between the concentrations of the aerosolized agent to the agent in the aerosol generator, is used to compare performance differences between aerosol exposures. SF indicates the efficiency of the aerosolization process; a higher SF means a lower nebulizer concentration is needed to achieve a desired inhaled dose. Relative humidity levels as well as the duration of the exposure and choice of exposure chamber all impacted RVFV SF. Differences were also noted between actual and predicted minute volumes for different species of nonhuman primates. While NHP from Old World species (Macaca fascicularis, M. mulatta, Chlorocebus aethiops) generally had a lower actual minute volume than predicted, the actual minute volume for marmosets (Callithrix jacchus) was higher than predicted (150% for marmosets compared with an average of 35% for all other species examined). All of these factors (relative humidity, chamber, duration, and minute volume) impact the ability to reliably and reproducibly deliver a specific dose of aerosolized RVFV. The implications of these findings for future pivotal efficacy studies are discussed. PMID:24532259

  20. Sensitisation of guinea pigs by inhalation exposure to low molecular weight chemicals.

    PubMed

    Botham, P A; Hext, P M; Rattray, N J; Walsh, S T; Woodcock, D R

    1988-05-01

    Guinea pigs could be immunologically sensitised (as shown by the development of antigen-specific homocytotropic antibodies) to toluene diisocyanate by exposing them for 3 h a day for 5 consecutive days to atmospheres containing free chemical. Pulmonary reactions could be elicited in many of the sensitised animals by challenging them with atmospheres containing protein conjugates of the chemical and then measuring changes in respiratory rate. Successful elicitation of pulmonary reactions appeared to depend upon a number of factors, including the quality of the protein conjugate used for the challenge, but possibly also the development of IgE as well as IgG1 antibodies. Antigen-specific homocytotropic antibodies were detected in guinea pigs similarly exposed by inhalation to two non-isocyanate respiratory allergens, trimellitic anhydride and a reactive dye. Although the animals were immunologically sensitised to the chemicals, challenge with atmospheres containing appropriate chemical-protein conjugates failed to stimulate changes in respiratory rate.

  1. Toxicity evaluation of exposure to an atmospheric mixture of polychlorinated biphenyls by nose-only and whole-body inhalation regimens

    PubMed Central

    Hu, Xin; Adamcakova-Dodd, Andrea; Lehmler, Hans-Joachim; Thorne, Peter S.

    2016-01-01

    The health risk of inhalation exposure to polychlorinated biphenyls (PCB) cannot be assessed due to the lack of rigorous inhalation studies providing a low dose effect level. One large uncertainty rests on the exposure regimen. Whole-body exposure systems allow oral PCB intake that confounds the exposure. Thus, we sought to compare the whole-body and nose-only exposure methods by conducting contemporaneous PCB inhalation exposures. Vapor-phase PCBs were generated from the Chicago Air Mixture supplemented with PCB 11 (CAM+). Female Sprague-Dawley rats were exposed concurrently to a PCB concentration of 533 ± 93 µg/m3, 4 h/day, 6 days/week, for 4 weeks. Congener-specific analysis using gas chromatography– mass spectrometry (GC/MS) showed higher total PCB concentration in the lungs of nose-only exposed animals than the whole-body exposed, resulting in a higher dose level for nose-only group. Congener profiles were consistent among exposure groups and tissue types and were dominated by PCB 28/31 and higher-chlorinated congeners reflecting rapid metabolism of other lower-chlorinated PCBs. No significant change was seen regarding metabolic enzyme expression, glutathione, or histopathology. However, diminished weight gain and reduced plasma total thyroxine levels were found in both groups compared with controls, with stronger response in the nose-only group. Lipid peroxidation was also elevated in the liver of nose-only exposed animals. We conclude that nose-only exposure was the preferred regimen for 4-wk PCB inhalation studies and thyroid hormone dysregulation was observed at an estimated dose of 1320 µg/kg b.w., providing information on a preliminary lowest-observed-adverse-effect-level (LOAEL). PMID:26348937

  2. Occupational exposure to nitrous oxide during procedural pain control in children: a comparison of different inhalation techniques and scavenging systems.

    PubMed

    Messeri, Andrea; Amore, Elena; Dugheri, Stefano; Bonari, Alessandro; Pompilio, Ilenia; Arcangeli, Giulio; Rizzo, Giuliana

    2016-09-01

    Nitrous oxide (N2 O 50% in oxygen) is commonly used for painful procedures in children. Potential negative health effects associated with chronic workplace exposure limit its use. Safe occupational N2 O exposure concentrations are below 25 ppm environmental concentration as a time-weighted average (TWA) and below 200 ppm as a short-time exposure level (STEL) of 15 min. The aim was to assess occupational exposure of staff during nitrous oxide administration to children using different inhalation delivery devices and scavenging systems. Staff nitrous oxide exposure during use of a double face mask (DFM) with or without a demand valve (DV) was compared with a conventional single face mask (FM). We also compared exposure using the hospital central scavenging system with a portable evacuation system. N2 O concentrations, representing exposure values, were monitored within proximity to staff. Urine N2 O concentration was measured in staff administering the N2 O at the end of the procedural session. The mean and median values of TWA and STEL within the working area were lower than recommended values in the DFM (10.8, 11.6 ppm for TWA; 13.9, 11.0 ppm for STEL) and DFM-DV groups (2.3, 2.8 ppm for TWA; 4.4, 3.5 ppm for STEL) using the portable evacuation system. The N2 O urine exposure in DFM-DV group was lower than DFM group: a mean difference of 9.56 ppm (95% CI 2.65-16.46). Staff N2 O urinary concentrations were within safe biological limits in both the DFM and DFM-DV groups. High exposure concentrations to N2 O were recorded in all FM and FM-DV environmental and biological samples. The DFM system, with or without a DV, connected to a portable evacuation system during N2 O administration to children for painful procedures kept N2 O levels within the local environment below recommended limits. © 2016 John Wiley & Sons Ltd.

  3. Changes in distortion product otoacoustic emission components after music exposure.

    PubMed

    Torre, Peter; Grace, Jennifer

    2014-10-01

    Young adults experience some type of recreational noise exposure on a daily basis; this includes using personal music (PM) systems with earphones. In most cases, this exposure is intermittent and the short-term effects of this exposure on the auditory system are becoming better understood. The purpose of this study was to examine the effects of one hour of music exposure using a PM system on distortion product otoacoustic emission (DPOAE) absolute levels and generator and characteristic frequency (CF) component levels. Young adults (n = 101) between 18-30 years with normal hearing participated listened to one hour of music through earphones. A second group of young adults (n = 21) served as controls and did not listen to music, but sat in the sound-treated room for one hour. Otoscopy, tympanometry, and a hearing screening (≤20 dB HL at 0.5, 1, 2, and 4 kHz) were completed in a randomly determined test ear. Preferred listening level, in dBA, was obtained and DPOAEs (2f1-f2) were measured between 1 and 6 kHz with stimulus levels fixed at L1,L2 = 55,40 dB SPL. Absolute DPOAE levels, along with generator and CF components levels were measured before and after each participant listened to one hour of music at their preferred level in a quiet setting. For data analyses, absolute DPOAE and generator and CF component levels were collapsed into 1/3rd octave bands centered around 1, 1.5, 2, 3, 4, and 6 kHz. Mean preferred listening level was 57.8 dBA, with males having a higher mean level of 61.1 dBA compared with females who had a mean level of 55.7 dBA. Females and males had negligible mean changes in absolute DPOAE levels at 1, 1.5, and 2 kHz, but males had 0.4-1 dB mean decreases after music at 3, 4, and 6 kHz compared to females, although not statistically significant. For DPOAE generator component data, females had small mean decreases for the two lower frequencies whereas males had mean decreases of 0.4-0.8 dB at 3, 4, and 6 kHz. Because of missing data, analyses of

  4. DEVELOPMENT OF EXPOSURE-RESPONSE MODELS FOR THE ACUTE RESPIRATORY EFFECTS OF INHALED IRRITANTS IN HUMANS

    EPA Science Inventory

    In order to conduct quantitative risk assessment with minimal uncertainty for short-term exposure to ozone and other respiratory irritants, one must identify exposure-response (E-R) models which accurately predict the distribution of the magnitudes of response (or the proportion ...

  5. DEVELOPMENT OF EXPOSURE-RESPONSE MODELS FOR THE ACUTE RESPIRATORY EFFECTS OF INHALED IRRITANTS IN HUMANS

    EPA Science Inventory

    In order to conduct quantitative risk assessment with minimal uncertainty for short-term exposure to ozone and other respiratory irritants, one must identify exposure-response (E-R) models which accurately predict the distribution of the magnitudes of response (or the proportion ...

  6. Inhalation exposure to isocyanates of car body repair shop workers and industrial spray painters.

    PubMed

    Pronk, Anjoeka; Tielemans, Erik; Skarping, Gunnar; Bobeldijk, Ivana; VAN Hemmen, Joop; Heederik, Dick; Preller, Liesbeth

    2006-01-01

    As part of a large-scale epidemiological study, occupational isocyanate exposure was assessed in spray-painting environments. The aim was to assess which compounds contribute to isocyanate exposure in car body repair shops and industrial painting companies, and to identify tasks with high risk of isocyanate exposure. Mainly personal task-based samples (n = 566) were collected from 24 car body repair shops and five industrial painting companies using impingers with DBA in toluene. Samples were analysed by LC-MS for isocyanate monomers, oligomers and products of thermal degradation. From the 23 analysed compounds, 20 were detected. Exploratory factor analysis resulted in a HDI, TDI and MDI factor with the thermal degradation products divided over the TDI and MDI factors. The HDI factor mainly consisted of HDI oligomers and was dominant in frequency and exposure levels in both industries. Spray painting of PU lacquers resulted in the highest exposures for the HDI factor (Exposure variability during PU spray painting was large with a variability over time of (ww)S(2) = 9.1 compared with between-worker variability of (bw)S(2) = 1.6. Lower level exposure to the HDI factor was found during other painting-related tasks and even tasks without direct exposure to paint. Exposure to the TDI factor was found more regularly in car body repair shops than in industrial painting companies. Exposure levels were low (Exposure to the MDI factor was found incidentally during spraying and welding in car body repair shops (exposure in both industries with highest exposures during PU spraying. However, since respiratory protection is less extensively used during other

  7. Inhalation of chlorine gas.

    PubMed Central

    Williams, J. G.

    1997-01-01

    The clinical features of acute chlorine gas inhalation, and its management are reviewed. Current medical views on the chronic effects of an acute overwhelming exposure on lung function (reactive airways dysfunction syndrome), and the more controversial field of lung disease secondary to repeated inhalations of lower concentrations of chlorine gas are discussed. Images Figure PMID:9519180

  8. Characterization of the phase dependent pulmonary response following irritant inhalation exposure to nitrogen dioxide gas

    SciTech Connect

    Siegel, P.D.

    1988-01-01

    The present study utilized NO{sub 2} to fingerprint the biochemical reaction of the pulmonary compartment to oxidative damage and to correlate this with histopathology following acute and subacute exposures to NO{sub 2}. Acute exposure to NO{sub 2} produced dose-dependent immediate increases in the nonenzymatic parameters of pulmonary protein content, protease inhibitor activity and lung weight. The enzymatic activities of lactate dehydrogenase (LDH), choline kinase and beta-glucuronidase were elevated by two days following acute exposure. All of the above parameters were elevated following subacute exposure, however, nonenzymatic manifestations were attenuated with respect to enzymatic alterations. Hydroxyurea-induced granulocytopenia attenuated the increases in activities of LDH and beta-glucuronidase following acute, but not subacute exposures. Cycloheximide-induced protein synthesis inhibition decrease the LDH and beta-glucuronidase response to NO{sub 2} without altering the increases in protein content or protease inhibitor activity.

  9. Dermal, inhalation, and internal exposure to 1,6-HDI and its oligomers in car body repair shop workers and industrial spray painters.

    PubMed

    Pronk, A; Yu, F; Vlaanderen, J; Tielemans, E; Preller, L; Bobeldijk, I; Deddens, J A; Latza, U; Baur, X; Heederik, D

    2006-09-01

    To study inhalation and dermal exposure to hexamethylene diisocyanate (HDI) and its oligomers as well as personal protection equipment (PPE) use during task performance in conjunction with urinary hexamethylene diamine (HDA) in car body repair shop workers and industrial spray painters. Personal task based inhalation samples (n = 95) were collected from six car body repair shops and five industrial painting companies using impingers with di-n-butylamine (DBA) in toluene. In parallel, dermal exposure was assessed using nitril rubber gloves. Gloves were submerged into DBA in toluene after sampling. Analysis for HDI and its oligomers was performed by LC-MS/MS. Urine samples were collected from 55 workers (n = 291) and analysed for HDA by GC-MS. Inhalation exposure was strongly associated with tasks during which aerosolisation occurs. Dermal exposure occurred during tasks that involve direct handling of paint. In car body repair shops associations were found between detectable dermal exposure and glove use (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.09 to 0.57) and inhalation exposure level (OR 1.34, 95% CI 0.97 to 1.84 for a 10-fold increase). HDA in urine could be demonstrated in 36% and 10% of car body repair shop workers and industrial painting company workers respectively. In car body repair shops, the frequency of detectable HDA was significantly elevated at the end of the working day (OR 2.13, 95% CI 1.07 to 4.22 for 3-6 pm v 0-8 am). In both branches HDA was detected in urine of approximately 25% of the spray painters. In addition HDA was detected in urine of a large proportion of non-spray painters in car body repair shops. Although (spray) painting with lacquers containing isocyanate hardeners results in the highest external exposures to HDI and oligomers, workers that do not perform paint related tasks may also receive a considerable internal dose.

  10. A Method for Quantifying the Acute Health Impacts of Residential Non-Biological Exposure Via Inhalation

    SciTech Connect

    Logue, Jennifer M.; Sherman, Max H.; Singer, Bret C.

    2014-08-01

    The inability to monetize the health costs of acute exposures in homes and the benefits of various control options is a barrier to justifying policies and approaches that can reduce exposure and improve health.We synthesized relationships between short-term outdoor concentration changes and health outcomes to estimate the health impacts of short-term in-home exposures. Damage and cost impacts of specific health outcomes were taken from the literature. We assessed the impact of vented and non-vented residential natural gas cooking burners on Southern California occupants for two pollutants (NO2 and CO).

  11. Estimating safe human exposure levels for lunar dust using benchmark dose modeling of data from inhalation studies in rats.

    PubMed

    Scully, Robert R; Lam, Chiu-Wing; James, John T

    2013-12-01

    The pulmonary toxicity of airborne lunar dust was assessed in rats exposed by nose-only inhalation to 0, 2.1, 6.8, 20.8 and 60.6 mg/m3 of respirable size lunar dust. Rats were exposed for 6 h/d, 5 d/week, for 4 weeks (120 h). Biomarkers of toxicity were assessed in bronchial alveolar lavage fluid (BALF) collected at 1 d, 1 week, 4 weeks or 13 weeks post-exposure for a total of 76 endpoints. Benchmark dose (BMD) analysis was conducted on endpoints that appeared to be sensitive to dose. The number of endpoints that met criteria for modeling was 30. This number was composed of 13 endpoints that produced data suitable for parametric analysis and 17 that produced non-normal data. Mean BMD values determined from models generated from non-normal data were lower but not significantly different from the mean BMD of models derived from normally distributed data. Thus BMDs ranged from a minimum of 10.4 (using the average BMD from all 30 modeled endpoints) to a maximum of 16.6 (using the average BMD from the most restricted set of models). This range of BMDs yields safe exposure estimate (SEE) values of 0.6 and 0.9 mg/m3, respectively, when BMDs are extrapolated to humans, using a species factor of 3 and extrapolated from a 1-month exposure to an anticipated 6-month lunar surface exposure. This estimate is very similar to a no-observable-adverse-effect-level (NOAEL) determined from the same studies (0.4 mg/m3) and a SEE derived from a study of rats that were intratracheally instilled with lunar dusts (0.5-1.0 mg/m3).

  12. Inhalation exposure to sulfur mustard in the guinea pig model: Clinical, biochemical and histopathological characterization of respiratory injuries

    SciTech Connect

    Allon, Nahum; Amir, Adina; Manisterski, Eliau; Rabinovitz, Ishay; Dachir, Shlomit; Kadar, Tamar

    2009-12-01

    Guinea pigs (GP) were exposed (head only) in individual plethysmographs to various concentrations of sulfur mustard vapor, determined online, using FTIR attached to flow chamber. The LCt{sub 50} and the inhaled LD{sub 50} were calculated at different time points post exposure. Surviving animals were monitored for clinical symptoms, respiratory parameters and body weight changes for up to 30 days. Clinical symptoms were noted at 3 h post exposure, characterized by erythematic and swelling nose with extensive mucous secretion (with or without bleeding). At 6 h post exposure most of the guinea pigs had breathing difficulties, rhonchi and dyspnea and few deaths were noted. These symptoms peaked at 48 h and were noted up to 8 days, associated with few additional deaths. Thereafter, a spontaneous healing was noted, characterized by recovery of respiratory parameters and normal weight gain with almost complete apparent healing within 2 weeks. Histopathological evaluation of lungs and trachea in the surviving GPs at 4 weeks post exposure revealed a dose-dependent residual injury in both lung and trachea expressed by abnormal recovery of the tracheal epithelium concomitant with a dose-dependent increase in cellular volume in the lungs. These abnormal epithelial regeneration and lung remodeling were accompanied with significant changes in protein, LDH, differential cell count and glutathione levels in the bronchoalveolar lavage (BAL). It is suggested that the abnormal epithelial growth and cellular infiltration into the lung as well as the continuous lung inflammation could cause recurrent lung injury similar to that reported for HD exposed human casualties.

  13. Changes in HPBMC markers of immmune function following controlled short-term inhalation exposures of humans to hardwood smoke.

    PubMed

    Burchiel, Scott W; Lauer, Fredine T; MacKenzie, Debra; McClain, Shea; Kuehl, Philip J; McDonald, Jacob D; Harrod, Kevin S

    2016-01-01

    Previous studies have shown that complex mixtures containing particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) produce systemic immunotoxicity in animal models following inhalation exposures. While we and others have shown that emissions associated with hardwood smoke (HWS), cigarette smoke and diesel exhaust can suppress the immune systems of animals in vitro and in vivo, there have been few immune function studies on human peripheral blood mononuclear cells (HPBMC) following exposure of humans to HWS. Our work shows that T cells are an important targets of PM and PAH immunotoxicity. These studies were conducted on HPBMC from 14 human volunteers receiving four 2 h nightly exposures to clean air or HWS at a concentration of 500 ug/m(3). We measured anti-CD3/anti-CD28 stimulated T-cell proliferation and HPBMC cytokine production in cell supernatants, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), TH1 cytokines γIFN and IL-2, TH2 cytokine IL-4, Th17 cytokine interleukin 17A (IL-17A) and interleukin 10 (IL-10). We analyzed results using analysis of variance (ANOVA), t-tests and Pearson correlation. Results showed that there was significant variation in the amount of T-cell proliferation observed following polyclonal activation with anti-CD3/anti-CD28 antibodies in both the air and HWS-exposed groups. There was not a significant effect of HWS on T-cell proliferation. However, we did find a strong relationship between the presence of proinflammatory cytokines (IL-1β, TNF-α, IL-6, but not IL-8) and the amount of T-cell proliferation seen in individual donors, demonstrating that brief exposures of humans to HWS can produce changes in systemic immunity that is associated with proinflammatory cytokines.

  14. ESTIMATED RATE OF FATAL AUTOMOBILE ACCIDENTS ATTRIBUTABLE TO ACUTE SOLVENT EXPOSURE AT LOW INHALED CONCENTRATIONS

    EPA Science Inventory

    Acute solvent exposures may contribute to automobile accidents because they increase reaction time and decrease attention, in addition to impairing other behaviors. These effects resemble those of ethanol consumption, both with respect to behavioral effects and neurological mecha...

  15. ESTIMATED RATE OF FATAL AUTOMOBILE ACCIDENTS ATTRIBUTABLE TO ACUTE SOLVENT EXPOSURE AT LOW INHALED CONCENTRATIONS

    EPA Science Inventory

    Acute solvent exposures may contribute to automobile accidents because they increase reaction time and decrease attention, in addition to impairing other behaviors. These effects resemble those of ethanol consumption, both with respect to behavioral effects and neurological mecha...

  16. Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung injury following inhalation exposure to nerve agent VX.

    PubMed

    Graham, Jacob R; Wright, Benjamin S; Rezk, Peter E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2006-06-01

    Respiratory disturbances play a central role in chemical warfare nerve agent (CWNA) induced toxicity; they are the starting point of mass casualty and the major cause of death. We developed a microinstillation technique of inhalation exposure to nerve agent VX and assessed lung injury by biochemical analysis of the bronchoalveolar lavage fluid (BALF). Here we demonstrate that normal guinea pig BALF has a significant amount of cholinesterase activity. Treatment with Huperzine A, a specific inhibitor of acetylcholinesterase (AChE), showed that a minor fraction of BALF cholinesterase is AChE. Furthermore, treatment with tetraisopropyl pyrophosphoramide (iso-OMPA), a specific inhibitor of butyrylcholinesterase (BChE), inhibited more than 90% of BChE activity, indicating the predominance of BChE in BALF. A predominance of BChE expression in the lung lavage was seen in both genders. Substrate specific inhibition indicated that nearly 30% of the cholinesterase in lung tissue homogenate is AChE. BALF and lung tissue AChE and BChE activities were strongly inhibited in guinea pigs exposed for 5 min to 70.4 and 90.4 microg/m3 VX and allowed to recover for 15 min. In contrast, BALF AChE activity was increased 63% and 128% and BChE activity was increased 77% and 88% after 24 h of recovery following 5 min inhalation exposure to 70.4 microg/m3 and 90.4 mg/m3 VX, respectively. The increase in BALF AChE and BChE activity was dose dependent. Since BChE is synthesized in the liver and present in the plasma, an increase in BALF indicates endothelial barrier injury and leakage of plasma into lung interstitium. Therefore, a measure of increased levels of AChE and BChE in the lung lavage can be used to determine the chronology of barrier damage as well as the extent of lung injury following exposure to chemical warfare nerve agents.

  17. Gene expression profiling of kidneys from Sprague-Dawley rats following 12-week inhalation exposure to silver nanoparticles.

    PubMed

    Dong, Mi Sook; Choi, Ji-Yoon; Sung, Jae Hyuck; Kim, Jin Sik; Song, Kyung Seuk; Ryu, Hyun Ryol; Lee, Ji Hyun; Bang, In Seok; An, Kangho; Park, Hyun Min; Song, Nam Woong; Yu, Il Je

    2013-07-01

    The specific properties of silver nanoparticles (AgNPs), such as antimicrobial activity and electrical conductivity, allow them to be used in many fields. However, their expanding application is also raising health, environmental and safety concerns. Previous in vivo AgNP toxicity studies have indicated a gender-different accumulation of silver in the kidneys, with 2-3 times more silver in female kidneys compared to male kidneys. However, no other studies have further addressed this gender difference. Accordingly, the current study investigated the gender-dependent effect of AgNPs on the kidney gene level based on toxicogenomic studies of kidneys obtained from rats exposed to AgNPs via inhalation for 12 weeks. When compared with the fresh air control, the silver nanoparticle-exposed kidneys included 104 genes with a more than 1.3-fold expression increase. For the male rat kidneys exposed to a low or high dose of silver nanoparticles, 96 genes exhibited expression changes, where six genes changed with both the low and high dose; four increased and two decreased. Meanwhile, for the female rat kidneys exposed to a low or high dose of silver nanoparticles, 66 genes exhibited expression changes, where 11 genes changed with both the low and high dose; nine increased and two decreased. Gender-dependent gene expression changes of more than 2-fold were linked to 163 genes, with 79 genes in the male kidneys and 84 genes in the female kidneys, plus gender-dependent gene expression changes of more than 5-fold were linked to 21 genes. However, no genes involved in apoptosis or the cell cycle were activated by the 12-week silver nanoparticle inhalation exposure. Overall, the male rat kidneys showed a higher expression of genes involved in xenobiotic metabolism, while the female rat kidneys showed a higher expression of genes involved in extracellular signaling.

  18. Occurrence of benzophenone-3 in indoor air from Albany, New York, USA, and its implications for inhalation exposure.

    PubMed

    Wan, Yanjian; Xue, Jingchuan; Kannan, Kurunthachalam

    2015-12-15

    Benzophenone-3 (BP-3) is a widespread environmental contaminant and an estrogenic compound. Very little is known with regard to the occurrence in indoor air and the inhalation exposure of humans to BP-3. In this study, 81 indoor air samples were collected from various locations in Albany, New York, USA, in 2014 and analyzed for BP-3 by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). BP-3 was found in all indoor air samples and the overall concentrations in bulk air (vapor plus particulate phases) were in the range of 0.19-72.0 ng/m(3) (geometric mean: 2.67 ng/m(3)). The highest concentrations (geometric mean: 10.7 ng/m(3)) were found in cars, followed by barber shops (6.57) ˃ public places (5.75)>homes (3.27) ˃ offices (1.96) ˃ garages (1.04) ˃ laboratories (0.47). The estimated geometric mean daily intake (EDI) of BP-3 for infants, toddlers, children, teenagers, and adults through indoor air inhalation from homes was 1.83, 1.74, 1.18, 0.69, and 0.51 ng/kg-bw/day, respectively. Although high concentrations of BP-3 were measured in some microenvironments, the estimated contribution of indoor air to total BP-3 intake was <5% of the total BP-3 intake in humans. This is the first survey on the occurrence of BP-3 in indoor air. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. [Occupational exposure of operating room staff to anesthetic gases during inhaled induction--a comparison with intravenous anesthesia induction].

    PubMed

    Hasei, Mari; Hirata, Takahiko; Nishihara, Hidenobu; Tanigami, Hironobu; Takashina, Masaki; Mori, Takahiko

    2003-04-01

    The risk of occupational exposure to waste anesthetic gases still remains during inhaled induction. In this study we investigated how much we were occupationally exposed to anesthetic gases during induction period. Twenty-six adult patients were induced with sevoflurane 5% using a face mask for three minutes and maintained with sevoflurane 1% after end-tracheal intubations (IH-Group). Twenty-two adult patients were induced with intravenous anesthetics and maintained with sevoflurane 1% after end-tracheal intubations(IV-Group). The concentration of sevoflurane was measured by Multi-gas Monitor 1302 (Bruel & Kjaer: Denmark) every 70 seconds. Sample gas was suctioned from breathing zone of anesthesiologists. All of our operating rooms are equipped with waste gas scavenging system. The peak concentration of sevoflurane is significantly higher in IH-Group (15.91 +/- 22.64 ppm) compared with IV-group (0.36 +/- 0.25 ppm). The period when sevoflurane concentration exceeded 0.5 ppm is significantly longer IH-Group (18.55 +/- 10.51 min.) compared to IV-Group (1.92 +/- 4.56 min.). The induction with intravenous anesthetics is a better method in order to reduce occupational exposure of anesthesiologists to anesthetic gases.

  20. Atmospheric thorium pollution and inhalation exposure in the largest rare earth mining and smelting area in China.

    PubMed

    Wang, Lingqing; Zhong, Buqing; Liang, Tao; Xing, Baoshan; Zhu, Yifang

    2016-12-01

    Exposure to radionuclide thorium (Th) has generated widespread public concerns, mainly because of its radiological effects on human health. Activity levels of airborne (232)Th in total suspended particulate (TSP) were measured in the vicinity of the largest rare earth mine in China in August 2012 and March 2013. The mean activity concentrations of (232)Th in TSP ranged from 820μBqm(-3) in a mining area in August 2012 to 39,720μBqm(-3) in a smelting area in March 2013, much higher than the world reference of 0.5μBqm(-3). Multistatistical analysis and Kohonen's self-organizing maps suggested that (232)Th in TSP was mainly derived from rare earth mining and smelting practices. In addition, personal inhalation exposures to (232)Th associated with respirable particulate (PM10) were also measured among local dwellers via personal monitoring. The mean dose values for different age groups in the smelting and mining areas ranged from 97.86 to 417μSvyear(-)(1) and from 101.03 to 430.83μSvyear(-1), respectively. These results indicate that people living in the study areas are exposed to high levels of widespread (232)Th.

  1. Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.

    PubMed

    Graczyk, Halshka; Lewinski, Nastassja; Zhao, Jiayuan; Sauvain, Jean-Jacques; Suarez, Guillaume; Wild, Pascal; Danuser, Brigitta; Riediker, Michael

    2016-06-10

    Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is

  2. Post-Exposure Antioxidant Treatment in Rats Decreases Airway Hyperplasia and Hyperreactivity Due to Chlorine Inhalation

    PubMed Central

    Bracher, Andreas; Doran, Stephen F.; Squadrito, Giuseppe L.; Fernandez, Solana; Postlethwait, Edward M.; Bowen, Larry; Matalon, Sadis

    2012-01-01

    We assessed the safety and efficacy of combined intravenous and aerosolized antioxidant administration to attenuate chlorine gas–induced airway alterations when administered after exposure. Adult male Sprague-Dawley rats were exposed to air or 400 parts per million (ppm) chlorine (a concentration likely to be encountered in the vicinity of industrial accidents) in environmental chambers for 30 minutes, and returned to room air, and they then received a single intravenous injection of ascorbic acid and deferoxamine or saline. At 1 hour and 15 hours after chlorine exposure, the rats were treated with aerosolized ascorbate and deferoxamine or vehicle. Lung antioxidant profiles, plasma ascorbate concentrations, airway morphology, and airway reactivity were evaluated at 24 hours and 7 days after chlorine exposure. At 24 hours after exposure, chlorine-exposed rats had significantly lower pulmonary ascorbate and reduced glutathione concentrations. Treatment with antioxidants restored depleted ascorbate in lungs and plasma. At 7 days after exposure, in chlorine-exposed, vehicle-treated rats, the thickness of the proximal airways was 60% greater than in control rats, with twice the amount of mucosubstances. Airway resistance in response to methacholine challenge was also significantly elevated. Combined treatment with intravenous and aerosolized antioxidants restored airway morphology, the amount of airway mucosubstances, and airway reactivity to control levels by 7 days after chlorine exposure. Our results demonstrate for the first time, to the best of our knowledge, that severe injury to major airways in rats exposed to chlorine, as characterized by epithelial hyperplasia, mucus accumulation, and airway hyperreactivity, can be reversed in a safe and efficacious manner by the post-exposure administration of ascorbate and deferoxamine. PMID:22162906

  3. Chronic inhalation exposure of hamsters to nickel-enriched fly ash

    SciTech Connect

    Wehner, A.P.; Dagle, G.E.; Milliman, E.M.

    1981-10-01

    Hamsters were chronically exposed to approx.70 ..mu..g/liter respirable nickel-enriched fly ash (NEFA) aerosol, approx.17 ..mu..g/liter NEFA, or approx.70 ..mu..g/liter fly ash (FA) for up to 20 months. A control group received sham exposures. The NEFA particles of respirable size contained approximately 6% nickel, compared to about 0.3% for FA. Five hamsters/group were sacrificed after 4, 8, 12, or 16 months of exposure. An additional five hamsters/group were withdrawn from exposure at the same intervals for lifelong observations. Exposures to NEFA had no significant effect on body weight and life span of the animals although heavy deposits of NEFA in the lungs were demonstrated. However, lung weights of the high NEFA- and of the FA-exposed animals were significantly higher than those of the low-NEFA group and the controls, and mean lung volumes were significantly larger for the high-NEFA grop and the FA group than for the low-NEFA group and the controls. Dust was deposited (anthracosis) in the lungs of all exposed hamsters. Incidence and severity of interstitial reaction and bronchiolization were significantly higher in the dust-exposed groups than in the sham-exposed controls. The severity of anthracosis, interstitial reaction, and bronchiolization was significantly lower in the low-NEFA group than in the high-NEFA and FA groups. While two malignant primary thorax tumors were found in two hamsters of the high-NEFA group, no statistically significant carcinogenesis was observed. Of the exposure-related changes, only anthracosis decreased after withdrawal from exposure. Pulmonary nickel burdens after 20 months of exposure suggest that the pulmonary clearance rate was slower in the high-NEFA group than in the low-NEFA group.

  4. Short-term inhalation exposure to mild steel welding fume had no effect on lung inflammation and injury but did alter defense responses to bacteria in rats.

    PubMed

    Antonini, James M; Roberts, Jenny R; Stone, Sam; Chen, Bean T; Schwegler-Berry, Diane; Frazer, David G

    2009-02-01

    Many workers worldwide are continually exposed to complex aerosols generated from welding processes. The objective was to assess the effect of inhalation exposure to mild steel (MS) welding fume on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to MS fume at a concentration of 40 mg/m(3) x 3 h/day x 3 or 10 days using a robotic welding fume generator. Controls were exposed to filtered air. To assess lung defense responses, a group of animals were intratracheally inoculated with 5 x 10(4) Listeria monocytogenes 1 day after the last daily exposure. Welding particles were collected during exposure, and chemical composition and particle size were determined. After exposure, lung injury, inflammation, and host defense (bacterial clearance) were measured. The particles were composed of iron (80.6 %) and manganese (14.7 %) with a mass median aerodynamic diameter of 0.31 microm. No significant difference was observed in lung injury or inflammation after MS fume inhalation at 1, 4, and 11 days after the last exposure. However, there were significantly more bacteria at 3 days after infection in the lungs of the animals exposed to MS fume compared to air controls. Acute exposure of rats to MS fume had no effect on injury and inflammation, but suppressed lung defense responses after infection. More chronic inhalation studies are needed to further examine the immune effects and to elucidate the possible mechanisms of the suppressed lung defense response to infection associated with the inhalation of MS welding fume.

  5. Comparative occupational exposures to formaldehyde released from inhaled wood product dusts versus that in vapor form.

    PubMed

    Gosselin, Nathalie H; Brunet, Robert C; Carrier, Gaétan

    2003-05-01

    Particle boards and other wood boards are usually made with formaldehyde-based resins. Woodworkers are thus exposed to formaldehyde in vapor form as well as from airborne dust once it enters their respiratory tract. These workers remain exposed to formaldehyde released from the dust still present in their upper respiratory tract, even after their work shift. In assessing the risk associated with formaldehyde exposure, one needs to consider the relative importance of these two sources of exposure. This study proposes two kinetic models to estimate and compare the exposures. For various exposure scenarios, one model predicts the amount of formaldehyde absorbed from the ambient vapor form and the other predicts the amount absorbed by the respiratory tract upon its release from wood product dust. Model parameters are determined using data from published studies. Based on a daily work shift of 8 hr, with a dust concentration in air of 5 mg/m(3) and a formaldehyde concentration bound to dust of 9 microg/mg, model simulations predict that the amount of absorbed formaldehyde released from wood dust is approximately 1/100 of the amount absorbed from the ambient vapor form at a concentration level of 0.38 mg/m(3) (0.3 ppm). Since the formaldehyde concentration in wood dust used above is much higher than usually observed while the dust and vapor form formaldehyde concentrations are of the order of acceptable upper values, these results indicate that the formaldehyde exposure from wood dust is comparatively negligible.

  6. Developmental effects after inhalation exposure of gravid rabbits and rats to ethylene glycol monoethyl ether.

    PubMed Central

    Andrew, F D; Hardin, B D

    1984-01-01

    The effects of ethylene glycol monoethyl ether (EGEE) were determined on development in utero. Pregnant New Zealand White rabbits were exposed to air or 160 or 617 ppm EGEE for 7 hr/day from 1 to 18 days of gestation (dg). Virgin Wistar rats were exposed to 150 or 649 ppm EGEE or air 5 days/week for the 3 weeks immediately preceding their breeding. Sperm-positive rats were subsequently exposed to air or 202 or 767 ppm EGEE for 7 hr/day from 1 to 19 dg. Group sizes were 29 to 38 per concentration for both species. Pregestational exposure of rats had no effect on mating success, and there was no effect of EGEE exposure on establishment of pregnancy in either species. Rabbits exposed to the both concentrations had decreased food intake and depressed weight gain. Exposure-related mortality occurred in the 617 ppm EGEE group of rabbits. The only toxic sign seen in rats was reduced weight gain after exposure to 767 ppm EGEE. Exposure induced high embryomortality at maternal toxic concentrations in rats and rabbits, while lower levels induced fetal growth retardation in rats but not in rabbits. Gestational exposure increased the incidence of anomalies and variations; these were primarily of soft tissues in rabbits and of skeleton in rats. Thus, significant evidence of terata, fetal growth retardation and embryomortality were induced in rabbits and rats at levels that were below or similar to those that induced maternal manifestation of toxicity. These data implicate EGEE as a teratogen. PMID:6499796

  7. Intra-oral formication induced by occupational exposure mimicking inhalation abuse.

    PubMed

    Thomas, Erin; Johnson, Cleverick

    2012-01-01

    Multiple cases of nail salon workers with occupational exposure to acetone, toluene, and acrylic monomers, namely methyl methacrylate and cyanoacrylates, presented separately to our clinic with similar complaints of factitious gingival stomatitis and formication--an abnormal sensation like ants crawling on or inside the skin. Recognizing oral manifestations resulting from possible toxic chemical exposure is not generally thought to be within the realm of most dental practices, yet to assure appropriate care, dentists must be vigilant and include thorough patient interviews in the diagnostic equation.

  8. Inhalation toxicology models of endotoxin- and bioaerosol-induced inflammation.

    PubMed

    Thorne, P S

    2000-11-02

    Inhalation toxicology studies in rodents have proven their usefulness for furthering our understanding of the causal agents, mechanisms, and pathology associated with exposures to environmental endotoxins and bioaerosols. Inhalation animal models are used to determine which components of a mixture are the most important toxicants for inducing the observed adverse outcome. They are used to obtain exposure-response relationships for allergens and pro-inflammatory agents to help elucidate disease mechanisms and contribute quantitative data to the risk assessment process. Inhalation models serve as important adjuncts to epidemiology studies and human exposure studies. They are also useful for establishing phenotype in studies of genetic polymorphisms and disease susceptibility and are widely applied for evaluation of safety and efficacy for potential therapeutic agents. In order to produce reliable data, rigorous exposure chamber design, aerosol generation systems, exposure quantitation and experimental protocols must be utilized.

  9. Demonstrating the Protective Efficacy of the Novel Fluoroquinolone Finafloxacin against an Inhalational Exposure to Burkholderia pseudomallei

    PubMed Central

    Hamblin, Karleigh A.; Richards, Mark I.; Laws, Thomas R.; Vente, Andreas; Atkins, Helen S.; Harding, Sarah V.

    2017-01-01

    ABSTRACT Burkholderia pseudomallei is the causative agent of melioidosis, a serious disease endemic in Southeast Asia and Northern Australia. Antibiotic treatment is lengthy and relapse often occurs. Finafloxacin is a novel fluoroquinolone with increased antibacterial activity in acidic conditions in contrast to other fluoroquinolones which demonstrate reduced activity at a lower pH. Therefore, finafloxacin may have improved efficacy against B. pseudomallei, which can survive within host cells where the local pH is acidic. In vitro analysis was performed using MICs, minimal bactericidal concentrations (MBCs), time-kill assays, persister cell assays, and macrophage assays. Finafloxacin showed increased bactericidal activity at pH 5 in comparison to pH 7 and ciprofloxacin at pH 5. In vivo studies in BALB/c mice included pharmacokinetic studies to inform an appropriate dosing regimen. Finafloxacin efficacy was evaluated in an inhalational murine model of melioidosis where antibiotic treatment was initiated at 6 or 24 h postchallenge and continued for 14 days, and mice were observed for 63 days. The survival of infected mice following 14 days of treatment was 80%, 60% or 0% for treatments initiated at 6 h and 60%, 30% or 0% for treatments initiated at 24 h for finafloxacin, co-trimoxazole, or ciprofloxacin, respectively. In summary, finafloxacin has increased bactericidal activity for B. pseudomallei under acidic conditions in vitro and improves survival in a murine model of melioidosis compared with those for ciprofloxacin. Furthermore, finafloxacin improves bacteriological clearance compared with that of co-trimoxazole, suggesting it may offer an effective postexposure prophylaxis against B. pseudomallei. PMID:28438936

  10. Assessing Inhalation Exposures Associated with Contamination Events inWater Distribution Systems

    EPA Pesticide Factsheets

    EPANET network models (inp files) used in paper. The file ??cdf2003-12singles.txt?? developed using ATUS data, that contains tab-separated values for the starting times and cumulative probabilities plotted in Fig. 2 in supporting design report. There are 101 rows in the file. The first entry in each row is the cumulative probability (0 to 1.0) and the second entry is the corresponding starting time (0.0 to 24.0 hours). The second file (??two events 2003-12.txt??) was developed that contains data for all 36,652 ATUS respondents who reported two grooming events in 2003 to 2012. Results in this file are used in TEVA-SPOT to generate random starting time for individuals who take two showers per day. The file has 36,652 rows and five tab-separated columns. The first column contains the year the data were collected and the second column contains the ATUS identifiers used for the respondents. The third column contains the starting times in hours local time for the first event and the fourth column contains the starting time in hours local time for the second event. The fifth column provides the ATUS weights for the respondents. Weights are needed to compensate for the manner in which sampling and data collection were carried out in ATUS. The Report (EPA/600/R-15/271) documents the design for incorporating the capability for estimating inhalation doses in TEVA-SPOT.This dataset is associated with the following publication:Janke , R., M. Davis, and T. Taxon. Assessing In

  11. Effects of repeat exposure to inhalation anesthetics on liver and renal function

    PubMed Central

    Nishiyama, Tomoki

    2013-01-01

    Background: Cross hypersensitivity to inhalation anesthetics has not been studied. The aim of this study was to investigate it by comparing liver and renal function after repeated anesthesia with sevoflurane and isoflurane retrospectively. Materials and Methods: The adult patients who received general anesthesia twice within the interval of 14 days to 1 year were retrospectively analyzed. Those who received sevoflurane anesthesia twice (SS group, 53 cases), isoflurane anesthesia twice (II group, 31 cases), sevoflurane followed by isoflurane anesthesia (SI group, 29 cases), isoflurane followed by sevoflurane anesthesia (IS group, 35 cases), and propofol–fentanyl anesthesia twice (PP group, 58 cases) were enrolled. Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (Bil), gamma-glutamyl transpeptidase (γ-GTP), blood urea nitrogen (BUN), and creatinine (Cr) measured 1-3, 5-8, and 12-16 days after surgery were investigated. Results: In the IS group, the number of the patients with abnormal values of ALT and γ-GTP 5–8 days after surgery were significantly smaller at second anesthesia compared to the first anesthesia. The number of the patients with abnormal values of AST, ALT, and γ-GTP were significantly larger in the II group than the SS and PP groups. The number of patients who had higher values in each parameter at second anesthesia compared to the first anesthesia was not different among the groups. Conclusions: Sevoflurane and isoflurane might have no cross hypersensitivity. Both anesthetics might not have any additional risks to increase liver and renal damage by second anesthesia. PMID:23493664

  12. Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques

    PubMed Central

    Comer, Jason E.; Stark, Gregory V.; Ray, Bryan D.; Tordoff, Kevin P.; Knostman, Katherine A. B.; Meister, Gabriel T.

    2012-01-01

    Appropriate animal models are required to test medical countermeasures to bioterrorist threats. To that end, we characterized a nonhuman primate (NHP) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the U.S. Food and Drug Administration Animal Rule. A clinical profile was recorded for each NHP exposed to a lethal dose of Bacillus anthracis Ames spores. Specific diagnostic parameters were detected relatively early in disease progression, i.e., by blood culture (∼37 h postchallenge) and the presence of circulating protective antigen (PA) detected by electrochemiluminescence (ECL) ∼38 h postchallenge, whereas nonspecific clinical signs of disease, i.e., changes in body temperature, hematologic parameters (ca. 52 to 66 h), and clinical observations, were delayed. To determine whether the presentation of antigenemia (PA in the blood) was an appropriate trigger for therapeutic intervention, a monoclonal antibody specific for PA was administered to 12 additional animals after the circulating levels of PA were detected by ECL. Seventy-five percent of the monoclonal antibody-treated animals survived compared to 17% of the untreated controls, suggesting that intervention at the onset of antigenemia is an appropriate treatment trigger for this model. Moreover, the onset of antigenemia correlated with bacteremia, and NHPs were treated in a therapeutic manner. Interestingly, brain lesions were observed by histopathology in the treated nonsurviving animals, whereas this observation was absent from 90% of the nonsurviving untreated animals. Our results support the use of the cynomolgus macaque as an appropriate therapeutic animal model for assessing the efficacy of medical countermeasures developed against anthrax when administered after a confirmation of infection. PMID:22956657

  13. Cellulosic building insulation versus mineral wool, fiberglass or perlite: installer's exposure by inhalation of fibers, dust, endotoxin and fire-retardant additives.

    PubMed

    Breum, N O; Schneider, T; Jørgensen, O; Valdbjørn Rasmussen, T; Skibstrup Eriksen, S

    2003-11-01

    A task-specific exposure matrix was designed for workers installing building insulation materials. A priori, a matrix element was defined by type of task (installer or helper), type of work area (attic spaces or wall cavities) and type of insulation material (slabs from mineral wool, fiberglass or flax; loose-fill cellulosic material or perlite). In the laboratory a mock-up (full scale) of a one-family house was used for simulated installation of insulation materials (four replicates per matrix element). Personal exposure to dust and fibers was measured. The dust was analyzed for content of endotoxin and some trace elements (boron and aluminum) from fire-retardant or mold-resistant additives. Fibers were characterized as WHO fibers or non-WHO fibers. In support of the exposure matrix, the dustiness of all the materials was measured in a rotating drum tester. For installers in attic spaces, risk of exposure was low for inhalation of dust and WHO fibers from slab materials of mineral wool or fiberglass. Slab materials from flax may cause high risk of exposure to endotoxin. The risk of exposure by inhalation of dust from loose-fill materials was high for installers in attic spaces and for some of the materials risk of exposure was high for boron and aluminum. Exposure by inhalation of cellulosic WHO fibers was high but little is known about the health effects and a risk assessment is not possible. For the insulation of walls, the risk of installers' exposure by inhalation of dust and fibers was low for the slab materials, while a high risk was observed for loose-fill materials. The exposure to WHO fibers was positively correlated to the dust exposure. A dust level of 6.1 mg/m3 was shown to be useful as a proxy for screening exposure to WHO fibers in excess of 10(6) fibers/m3. In the rotating drum, slabs of insulation material from mineral wool or fiberglass were tested as not dusty. Cellulosic loose-fill materials were tested as very dusty, and perlite proved to be

  14. EXHALED HUMAN BREATH MEASUREMENT OF JET FUEL CONSTITUENTS: DISTINGUISHING BETWEEN INHALATION AND DERMAL EXPOSURE ROUTES

    EPA Science Inventory

    In response to anecdotal reports, perceived health issues, and widespread complaints, the U.S. military launched an investigation into the occupational and environmental human exposure to jet fuel. The work described in the presentation assesses the correlation between two breat...

  15. EXHALED HUMAN BREATH MEASUREMENT OF JET FUEL CONSTITUENTS: DISTINGUISHING BETWEEN INHALATION AND DERMAL EXPOSURE ROUTES

    EPA Science Inventory

    In response to anecdotal reports, perceived health issues, and widespread complaints, the U.S. military launched an investigation into the occupational and environmental human exposure to jet fuel. The work described in the presentation assesses the correlation between two breat...

  16. Cerium Oxide Nanoparticle Nose-Only Inhalation Exposures Using a Low-Sample-Consumption String Generator

    EPA Science Inventory

    There is a critical need to assess the health effects associated with exposure of commercially produced NPs across the size ranges reflective of that detected in the industrial sectors that are generating, as well as incorporating, NPs into products. Generation of stable and low ...

  17. Selective Cognitive Deficits in Adult Rats after Prenatal Exposure to Inhaled Ethanol

    EPA Science Inventory

    Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by i...

  18. Selective Cognitive Deficits in Adult Rats after Prenatal Exposure to Inhaled Ethanol

    EPA Science Inventory

    Increased use of ethanol blends in gasoline suggests a need to assess the potential public health risks of exposure to these fuels. Ethanol consumed during pregnancy is a teratogen. However, little is known about the potential developmental neurotoxicity of ethanol delivered by i...

  19. Cerium Oxide Nanoparticle Nose-Only Inhalation Exposures Using a Low-Sample-Consumption String Generator

    EPA Science Inventory

    There is a critical need to assess the health effects associated with exposure of commercially produced NPs across the size ranges reflective of that detected in the industrial sectors that are generating, as well as incorporating, NPs into products. Generation of stable and low ...

  20. Systemic immunotoxicity in AJ mice following 6-month whole body inhalation exposure to diesel exhaust.

    PubMed

    Burchiel, Scott W; Lauer, Fredine T; McDonald, Jacob D; Reed, Matthew D

    2004-05-01

    The purpose of these studies was to determine the effects of subchronic diesel exposure on indicators of systemic immunity in mice. AJ mice were exposed daily for 6 months (6 h/day) to atmospheres containing one of four concentrations (30, 100, 300, and 1000 microg/m(3)) of diluted diesel exhaust (DE) in whole body exposure chambers. The effects of DE were compared to chamber exposure controls receiving fresh air. DE was assessed for effects on systemic immunity by measuring the proliferative response of spleen cells following stimulation with T cell (phytohemagglutinin, or PHA) or B cell (lipopolysaccharide, or LPS) mitogens. The results showed that DE at all exposure levels suppressed the proliferative response of T cells. B cell proliferation was increased at 30 microg/m(3) and was unaffected at the 100, 300, and 1000 microg/m(3) exposures. Polycyclic aromatic hydrocarbons (PAHs) are known to suppress spleen cell mitogenic responses, and it has been hypothesized by several groups that PAHs and perhaps benzo(a)pyrene (BaP)-quinones (BPQs) may be responsible for the effects of DE or diesel exhaust particles (DEP). Therefore, a second purpose of these studies was to determine the effects of in vitro BPQs on AJ mouse spleen cell mitogenic responses and compare to DE in preliminary studies. Unlike DE, BPQs were found to increase T cell proliferation. In addition, analysis of chamber atmospheres showed that there was little if any PAH and BPQs in DE. Therefore, these results demonstrate that because of the absence of BPQs in DE, they are likely not responsible for the immunosuppressive effect of DE on murine spleen cell responses.

  1. Perfluorooctanesulfonate (PFOS) Conversion from N-Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) in male Sprague Dawley rats after inhalation exposure.

    PubMed

    Chang, Sue; Mader, Brian T; Lindstrom, Kent R; Lange, Cleston C; Hart, Jill A; Kestner, Thomas A; Schulz, Jay F; Ehresman, David J; Butenhoff, John L

    2017-05-01

    Ethyl-N-(2-hydroxyethyl)-perfluorooctanesulfonamide (EtFOSE) was one of the key building blocks for many of the perfluorooctanesulfonyl-based chemistry and laboratory studies have shown that EtFOSE can metabolically degrade to perfluorooctanesulfonate (PFOS). Non-occupational contribution sources to PFOS are thought to occur in general population via diets, drinking water, air and dust. For workers, however, the exposure route was mostly airborne and the exposure source was predominantly to precursor compounds such as EtFOSE. We undertook this study to investigate how much EtFOSE was converted to PFOS in the serum for male rats after 6h of exposure to EtFOSE vapor (whole body) at ambient temperature, which simulated a work place exposure scenario. There were no abnormal clinical observations and all rats gained weight during study. Interim tail-vein blood samples, collected up to 21 days after exposure, were analyzed for Et-FOSE and PFOS concentrations by LC-MS/MS. Upon inhalation exposure, the biotransformation of EtFOSE to PFOS in serum in the male rats was rapid and very little EtFOSE was detected in the serum within 24h after EtFOSE exposure. The highest conversion to PFOS in serum after exposure to EtFOSE vapor appeared to occur between Day 8-14 post exposure. Considering the potential surface and fur adsorption of test compound in the whole-body exposure system, our data would support that at least 10% of the inhaled EtFOSE was biotransformed to PFOS in the serum based on the range of lower 95% CI (confidence interval) values. This information is valuable because it quantitatively translates EtFOSE exposure into serum PFOS concentration, which serves as a matrix for internal dosimetry (of PFOS exposure) that can be used as an anchor across species as well as between different exposure routes. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Air pollution impacts on avian species via inhalation exposure and associated outcomes

    NASA Astrophysics Data System (ADS)

    Sanderfoot, Olivia V.; Holloway, Tracey

    2017-08-01

    Despite the well-established links between air pollution and human health, vegetation, and aquatic ecosystems, less attention has been paid to the potential impact of reactive atmospheric gases and aerosols on avian species. In this literature review, we summarize findings published since 1950 regarding avian responses to air pollution and discuss knowledge gaps that could be addressed in future studies. We find consistent evidence for adverse health impacts on birds attributable to exposure to gas-phase and particulate air pollutants, including carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2), smoke, and heavy metals, as well as mixtures of urban and industrial emissions. Avian responses to air pollution include respiratory distress and illness, increased detoxification effort, elevated stress levels, immunosuppression, behavioral changes, and impaired reproductive success. Exposure to air pollution may furthermore reduce population density, species diversity, and species richness in bird communities.

  3. Asbestosis occurring after brief inhalational exposure: usefulness of bronchoalveolar lavage in diagnosis.

    PubMed Central

    Barbers, R G; Abraham, J L

    1989-01-01

    A case of clinically and radiologically typical asbestosis manifesting in a 55 year old man occurred 36 years after a brief exposure period of less than one year. A transbronchial lung biopsy was performed but the samples were considered non-diagnostic. The diagnosis was supported by the use of bronchoalveolar lavage to obtain alveolar samples and scanning electron microscopy-energy dispersive x ray analysis of fibres found in the bronchoalveolar lavage fluid which showed a predominance of amosite. Images PMID:2538140

  4. Asbestosis occurring after brief inhalational exposure: usefulness of bronchoalveolar lavage in diagnosis.

    PubMed

    Barbers, R G; Abraham, J L

    1989-02-01

    A case of clinically and radiologically typical asbestosis manifesting in a 55 year old man occurred 36 years after a brief exposure period of less than one year. A transbronchial lung biopsy was performed but the samples were considered non-diagnostic. The diagnosis was supported by the use of bronchoalveolar lavage to obtain alveolar samples and scanning electron microscopy-energy dispersive x ray analysis of fibres found in the bronchoalveolar lavage fluid which showed a predominance of amosite.

  5. Dust inhalation exposures from the handling of small volumes of powders.

    PubMed

    Cowherd, C; Grelinger, M A; Wong, K F

    1989-03-01

    Worker exposure to airborne particulates was stimulated in a laboratory under controlled conditions. Small volumes, 3.8 L (1 gal.), of finely divided powders were transferred at 1-min intervals to 23-L (6-gal.) containers over 30-min time intervals. A high-volume filter array in the exit vent of the specially designed exposure laboratory was used both to control the ventilation rate and to determine the emission factor of the pouring operation. The room ventilation rate, method of transfer, and drop height were varied, and the resulting particulate concentrations were monitored by personal and area samplers. The four powders studied were talc, sodium chloride, Portland cement, and Direct Yellow 4 dye. Based on this study, a model was developed to predict potential worker exposure from the pouring of small volumes of powders. The model is based on the following major conclusions. First, the space- and time-averaged concentration of suspended particulate matter at breathing height agrees well with the mean concentration of suspended particulate matter in the room air effluent. Second, material-specific suspended particulate emission factors vary approximately in direct proportion to the drop height. Third, emission factors for scooping/dumping operations agree well with factors for pouring operations for a given drop height. Fourth, emission factors compare well with dustiness indexes that were determined using a bench-scale dustiness test chamber described in a companion paper. Parameters of the exposure model include dustiness index, drop height of the pouring operation, total quantity of material poured, averaging time, and the fraction of respirable material. For the validation of the model, additional data would be necessary.

  6. Inhalation Exposure to Jet Fuel (JP8) Among U.S. Air Force Personnel

    DTIC Science & Technology

    2010-10-01

    be comparable to our high exposure group. Puhala el al.(2) reported full-shift mean naphtha levels of 1.33 ppm (10 mg/m3) for aircraft maintenance...Safety and Health (NIOSH): Naphthas : Mclh"d 1550. In NJOSII Mam",1 of An"lytic,,1 Methods (NMAM). Fourth Edition, P.c. Schlechl and J.>.F. O’Connor

  7. Effects of inhalation exposure to SRC-II heavy and middle distillates

    SciTech Connect

    Springer, D.L.; Miller, R.A.; Weimer, W.C.; Ragan, H.A.; Buschbom, R.L.; Mahlum, D.D.

    1984-11-01

    To expand the data base on potential health effects of coal liquefaction materials, we have performed studies with both solvent refined coal (SRC)-II heavy distillate (HD) and middle distillate (MD). Weight gain for exposed animals was less than that of controls and was dose-related, ranging from no significant difference for animals in the low-exposure group to failure to gain in the high-dose animals. Liver weights increased significantly over controls, and thymus weights decreased for animals sacrificed at 5 and 13 weeks. After both exposure periods, there were significant treatment-related decreases in erythrocyte parameters and in certain types of white blood cells (WBC). Bone marrow cellularity, and numbers of megakaryocytes consistently decreased, suggesting that bone marrow is a target tissue for high-boiling coal liquids. Microscopic evaluation of tissue indicated exposure-related changes is listed. In contrast to the reported mutagenic and carcinogenic effects observed for the high-boiling coal liquids, middle-boiling-range materials lacked such activity in these assays. These data demonstrate a great deal of similarity in the kinds of effects observed following exposure to middle- and high-boiling-range coal liquids. However, the significance of changes in organ weights and peripheral blood parameters are not always readily apparent following a subchronic study. Because of this, we exposed animals to HD in a manner similar to that for the subchronic experiment and have followed these animals throughout their lives for the development of adverse effects such as reduced longevity and the appearance of tumors. Results from this study will be available for mice in FY 1985 and for rats in FY 1986.

  8. Changes in collagen metabolism and proteinolysis after repeated inhalation exposure to ozone

    SciTech Connect

    Pickrell, J.A.; Hahn, F.F.; Rebar, A.H.; Horoda, R.A.; Henderson, R.F.

    1987-04-01

    To study the changes in collagen metabolism that occur in the pathogenesis of pulmonary fibrosis, female rats were exposed to 0, 0.57, and 1.1 ppm ozone for 19 hr/day for 11 days and sacrificed 12 or 60 days after initiation of exposure. The lungs of rats sacrificed at 12 days after initiation of exposure to 1.1 ppm had interstitial pneumonia characterized by a mixed inflammatory cell infiltrate, type II cell hyperplasia, and fibroplasia, a proliferation of the collagen-producing cells; increased cathepsin D and macrophage elastase activity, indicating macrophage-induced proteinolysis; a reduced percentage of the increased collagen production that was ultrafilterable, indicating a decreased rate of intracellular degradation of newly produced collagen prior to its secretion; and increased lavage fluid hydroxyproline, indicating turnover of extracellular collagenous matrix. Reduced intracellular collagen degradation correlated directly with both increased net collagen production and fibroplasia in rats exposed to 1.1 ppm ozone for 11 days. These changes preceded an increased total lung collagen and the development of modest fibroplasia and fibrosis in the alveolar duct regions by 60 days after the 1.1 ppm ozone exposure was initiated.

  9. Acute nose-only inhalation exposure of rats to di- and triphosgene relative to phosgene.

    PubMed

    Pauluhn, Jürgen

    2011-02-01

    Groups of young adult Wistar rats were acutely exposed to trichloromethyl chloroformate (diphosgene) and bis(trichloromethyl) carbonate (triphosgene) vapor atmospheres using a directed-flow nose-only mode of exposure. The exposure duration used was 240 min. The median lethal concentration (LC50) of diphosgene and triphosgene was 13.9 and 41.5 mg/m3, respectively. Based on the molar exposure concentrations, the LC50s of phosgene (previously published), diphosgene, and triphosgene were 0.07, 0.07, and 0.14 mmol/m3, respectively. Although the principal toxic mode of action of the volatile diphosgene was similar to phosgene gas, the vapor phase of triphosgene appeared to be different to that of phosgene and diphosgene based on a more persistent occurrence of signs of respiratory distress and a biphasic onset of mortality. While all substances caused mortality within 1 day postexposure, triphosgene induced a second phase of mortality 11?14 days postexposure. The vapor saturation concentration of triphosgene at ambient temperature is ?100 times its LC50. In summary, triphosgene-induced lung injury patterns are different from that of phosgene and diphosgene. More research is needed to close the substantial data gaps of triphosgene.

  10. Acetalated Dextran Microparticulate Vaccine Formulated via Coaxial Electrospray Preserves Toxin Neutralization and Enhances Murine Survival Following Inhalational Bacillus Anthracis Exposure.

    PubMed

    Gallovic, Matthew D; Schully, Kevin L; Bell, Matthew G; Elberson, Margaret A; Palmer, John R; Darko, Christian A; Bachelder, Eric M; Wyslouzil, Barbara E; Keane-Myers, Andrea M; Ainslie, Kristy M

    2016-10-01

    Subunit formulations are regarded as the safest type of vaccine, but they often contain a protein-based antigen that can result in significant challenges, such as preserving antigenicity during formulation and administration. Many studies have demonstrated that encapsulation of protein antigens in polymeric microparticles (MPs) via emulsion techniques results in total IgG antibody titers comparable to alum formulations, however, the antibodies themselves are non-neutralizing. To address this issue, a coaxial electrohydrodynamic spraying (electrospray) technique is used to formulate a microparticulate-based subunit anthrax vaccine under conditions that minimize recombinant protective antigen (rPA) exposure to harsh solvents and high shear stress. rPA and the adjuvant resiquimod are encapsulated either in separate or the same acetalated dextran MPs. Using a murine model, the electrospray formulations lead to higher IgG2a subtype titers as well as comparable total IgG antibody titers and toxin neutralization relative to the FDA-approved vaccine (BioThrax). BioThrax provides no protection against a lethal inhalational challenge of the highly virulent Ames Bacillus anthracis anthrax strain, whereas 50% of the mice vaccinated with separately encapsulated electrospray MPs survive. Overall, this study demonstrates the potential use of electrospray for encapsulating protein antigens in polymeric MPs.

  11. Single inhalation exposure to /sup 90/SrCl/sub 2/ in the beagle dog: late biological effects

    SciTech Connect

    Gillett, N.A.; Muggenburg, B.A.; Boecker, B.B.; Griffith, W.C.; Hahn, F.F.; McClellan, R.O.

    1987-08-01

    Late-occurring biologic effects were studied in beagle dogs that were given graded levels of /sup 90/SrCl/sub 2/ via single brief inhalation exposures and were subsequently observed for their life-span. Due to the soluble chemical form of the aerosol, /sup 90/Sr was rapidly translocated from lung and deposited in bone where it was subsequently retained for a long period of time. Radiation-induced lesions were confined to the bone, bone marrow, and adjacent soft tissue. Forty-five primary bone tumors occurred in 31 of 66 exposed dogs. Metastasis occurred from 21 tumors, with the lung being the most frequent site of metastasis (76%). Twenty-seven tumors were classified as different subtypes of osteosarcoma, 14 as hemangiosarcomas, 3 as fibrosarcomas, and 1 as a myxosarcoma. Four carcinomas arising from soft tissues adjacent to bone were also considered to be /sup 90/Sr induced. In contrast to bone tumors arising in beagles chronically exposed to 90Sr through ingestion, histologic lesions of radiation osteodystrophy were minimal in this study, indicating that these lesions are not a necessary precursor of osteosarcoma development. The incidences of hemangiosarcomas (31%) and telangiectatic osteosarcomas (11%) in addition to osteosarcomas suggest that the cell of origin for all of these neoplasms is a multipotent mesenchymal cell with the potential for various morphologic expressions dependent on local environmental factors.

  12. Effect of inhalation exposure to toluene on the activity of organic anion transporting polypeptide (Oatp) using pravastatin as a probe drug in rats.

    PubMed

    Mauro, Mariana; Lepera, Jose Salvador; Borsari, Bruno; Capela, Jorge Manuel Vieira; de Moraes, Natália Valadares

    2017-07-25

    1. Toluene, used as a pure substance or in solvent mixtures, is the cause of occupational exposures of large numbers of workers in the world. The organic anion transporting polypeptides (OATP: human; Oatp: rodents) are drug carriers which have been frequently associated to drug-drug interactions. The objective of this study was to evaluate the influence of inhalation exposure to toluene in Oatp in vivo activity using pravastatin as a probe drug in rats. 2. Male Wistar rats ((n = 6 per sampling time) were exposed to 85 mg/m(3) toluene by inhalation or air in a nose only exposure system for 6 h/d, 5 d/week during 4 weeks, in order to simulate the occupational exposure to toluene at level slightly above the occupational exposure limit proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). After 4 weeks of exposure, animals received a single dose of 20 mg/kg pravastatin orally. 3. Areas under concentration × time curves extrapolated to infinite (AUC(0-∞)) were calculated by Gauss Laguerre quadrature. Non-exposed animals showed AUC(0-∞) of 726.0 (261.8) ng h/mL for pravastatin and rats exposed to toluene 85 mg/m3 showed AUC(0-∞) of 681.8 (80.1) ng h/mL [data presented as mean (standard error of the mean)]. No significant difference was observed in pravastatin kinetic disposition between groups in terms of 95% confidence interval for the difference between means. 4. Toluene exposure by inhalation did not change the in vivo activity of Oatp evaluated by pravastatin kinetic disposition in rats.

  13. Method for determining the lung burden of talc in rats and mice after inhalation exposure to talc aerosols.

    PubMed

    Hanson, R L; Benson, J M; Henderson, T R; Carpenter, R L; Pickrell, J A; Brown, S C

    1985-10-01

    A method has been developed to quantitate talc lung burdens in rats and mice after inhalation exposure to talc aerosols. The method is based on acid-insoluble magnesium (Mg) determination by flame atomic absorption. Precipitating protein from homogenates of lungs of unexposed rodents with 5% perchloric acid and washing with 5% trichloroacetic acid removed the soluble and naturally occurring Mg. This resulted in residual Mg content averaging 0.43 micrograms Mg per g lung in rats and less than 0.1 microgram Mg per g lung in mice for young rodents less than 12 weeks old. Rodents 12-18 months old had residual mean (+/- SD) Mg contents of 3.4 +/- 2.0 micrograms Mg per g rat lung (n = 17) and 6.5 +/- 2.9 micrograms Mg per g mouse lung (n = 12). Thus, the background residual acid-insoluble Mg content in rodent lungs appears to increase with age. Negligible quantities of Mg were extracted directly from the talc treated by these procedures. Adding 50-2000 micrograms talc to lungs from unexposed rodents, followed by the sample treatment, gave mean (+/- SD) Mg recoveries of 89 +/- 12% (n = 19) for rat lungs and 96 +/- 26% (n = 15) for mouse lungs. The lung burden of talc in rodents exposed to talc aerosols for 6 h per day, 5 days per week for 4 weeks was determined. Mean lung burdens in rats were 77, 187, and 806 micrograms talc per g lung (n = 10) for exposures at 2.3, 4.3, and 17 mg talc m-3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Evaluation of Decision Rules in a Tiered Assessment of Inhalation Exposure to Nanomaterials.

    PubMed

    Brouwer, Derk; Boessen, Ruud; van Duuren-Stuurman, Birgit; Bard, Delphine; Moehlmann, Carsten; Bekker, Cindy; Fransman, Wouter; Klein Entink, Rinke

    2016-10-01

    Tiered or stepwise approaches to assess occupational exposure to nano-objects, and their agglomerates and aggregates have been proposed, which require decision rules (DRs) to move to a next tier, or terminate the assessment. In a desk study the performance of a number of DRs based on the evaluation of results from direct reading instruments was investigated by both statistical simulations and the application of the DRs to real workplace data sets. A statistical model that accounts for autocorrelation patterns in time-series, i.e. autoregressive integrated moving average (ARIMA), was used as 'gold' standard. The simulations showed that none of the proposed DRs covered the entire range of simulated scenarios with respect to the ARIMA model parameters, however, a combined DR showed a slightly better agreement. Application of the DRs to real workplace datasets (n = 117) revealed sensitivity up to 0.72, whereas the lowest observed specificity was 0.95. The selection of the most appropriate DR is very much dependent on the consequences of the decision, i.e. ruling in or ruling out of scenarios for further evaluation. Since a basic assessment may also comprise of other type of measurements and information, an evaluation logic was proposed which embeds the DRs, but furthermore supports decision making in view of a tiered-approach exposure assessment. © The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  15. Efficacy of post exposure administration of doxycycline in a murine model of inhalational melioidosis.

    PubMed

    Gelhaus, H Carl; Anderson, Michael S; Fisher, David A; Flavin, Michael T; Xu, Ze-Qi; Sanford, Daniel C

    2013-01-01

    Burkholderia pseudomallei is the causative agent of melioidosis. Treatment of melioidosis is suboptimal and developing improved melioidosis therapies requires animal models. In this report, we exposed male BALB/c mice to various amounts of aerosolized B. pseudomallei 1026b to determine lethality. After establishing a median lethal dose (LD(50)) of 2,772 colony forming units (cfu)/animal, we tested the ability of doxycycline administered 6 hours after exposure to a uniformly lethal dose of ~20 LD(50) to prevent death and eliminate bacteria from the lung and spleens. Tissue bacterial burdens were examined by PCR analysis. We found that 100% of mice treated with doxycycline survived and B. pseudomallei DNA was not amplified from the lungs or spleens of most surviving mice. We conclude the BALB/c mouse is a useful model of melioidosis. Furthermore, the data generated in this mouse model indicate that doxycycline is likely to be effective in post-exposure prophylaxis of melioidosis.

  16. Inhalation study of polymethyl methacrylate following radiologist exposure during percutaneous vertebroplasty.

    PubMed

    Amoretti, Nicolas; Coco, Lucia; Nouri, Yasir; Marcy, Pierre-Yves; Ianessi, Antoine; Amoretti, Marie-Eve; Hauger, Olivier

    2013-02-01

    To assess the atmospheric concentrations of methyl methacrylate (MMA) vapors during percutaneous vertebroplasty for the interventional radiologist and the other operating room staff. During percutaneous vertebroplasty, a polymethyl methacrylate (PMMA) mixture (about 20 mL) was prepared with a mixing system in a normally ventilated room. Atmospheric concentrations of MMA vapors were measured by a gas absorbent badge for individual exposure (GABIE) passive sampler attached to the surgical gowns of the interventional radiologist