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PubMedDate not supplied

Noncancer inhalation toxicology of crystalline silica: exposure-response assessment.

Silicosis from inhalation of silica has long been recognized as an occupational hazard. Concern has arisen regarding the potential risk of silicosis from ambient silica (primarily quartz dust). This presentation reviews available data regarding ambient silica levels and estimates of the risk of silicosis at low exposure levels as they relate to the current U.S. Environmental Protection Agency National Ambient Air Quality Standards (NAAQS) for particulate matter. Current data indicate that for individuals not compromised by other respiratory ailments and for ambient environments expected to sustain 10% or less silica fraction in particulate matter with a mean aerodynamic diameter of < or = 10 microns (PM10), maintenance of the 50 micrograms/m3 annual NAAQS for PM10 is adequate to protect against fibrotic effects from ambient silica exposures. Issues such as the large divergence of risk estimates within the occupational setting (particularly at high cumulative exposures) and factors to consider for extrapolating risk in an occupational setting to risk from ambient exposure are discussed.

Air Pollutants↗

PubMed1989

Influence of post-rumen supply of nutrients on rumen digesta load and voluntary intake of a roughage by sheep.

The effects of post-rumen supply of nutrients on the rumen digesta load and voluntary consumption of roughage by Border Leicester X Merino ram lambs was investigated. A chopped wheaten hay was offered to the ram lambs (n 24), whose nutrient intake was altered by infusing into the abomasum a liquid supplement, containing reconstituted cow's milk, sodium caseinate, minerals and vitamins, for a period of at least 30 d. Either two or three lambs were allocated by live weight to each of ten rates of nutrient supplementation. The lambs were slaughtered at a target live weight of 31 kg. Voluntary intake of hay was estimated over the last 7 d of feeding. The amounts of digesta and organic matter (OM) in the rumen were measured by emptying after slaughter. The particle size distribution of the digesta was measured by wet sieving and the fractional outflow rate of particulate matter by reference to the marker lignin. Growth rate of the lambs increased linearly as total energy infused increased. The linear increase in growth rate indicated that roughage was not substituted for infused nutrients on a direct energy basis. OM intake from hay declined linearly as the amount of nutrients infused increased. The decline in intake was associated with a decline in both total digesta and the amount of rumen OM. Both the fractional digestion rate of OM and the fractional outflow rate of particulate matter from the rumen were unaffected by the amount of nutrients infused. The results indicated that the rumen digesta load of young sheep fed on a single roughage is directly related to their energy deficit, that is the difference between the capacity of the animals to use energy and the energy available to them for metabolism.

Animals↗

PubMed2005

Antimony: a traffic-related element in the atmosphere of Buenos Aires, Argentina.

Vehicular traffic is one of the main sources of antimony in highly populated urban areas like Buenos Aires where an overall traffic density of 1 500 000 vehicles per day (corresponding to 7500 vehicles km(-2)) is estimated. In this context, a study was undertaken to ascertain the levels of Sb and other traffic-related elements (TRE) in the atmosphere of this city. To this end, sixty-seven samples of PM-10 particulate matter were collected during eight days in nine representative sampling sites located downtown Buenos Aires and spread over an area of about 30 km2. The collection of particulate matter was performed on ash-free glass-fibre filters using high volume samplers with PM-10 sampling heads. A combination of aqua regia and perchloric acid was used for leaching metals from filters. The resulting solutions were evaporated and then diluted with 0.1 mol l(-1) HCl. Antimony was determined by inductively coupled plasma-quadrupole mass spectrometry (ICP-QMS) at ng g(-1) levels. Concentrations of Sb varied from 12.9 +/- 0.9 to 375 +/- 23 microg g(-1)(equivalent to 0.87 +/- 0.06 to 15.3 +/- 0.8 ng m(-3)). Statistical analysis was performed on the data set including the measured PM-10 mass and Sb concentrations for the monitored period. Correlations of Sb with other TRE namely, Cu and Mo were also assessed. The highest concentrations of Sb were detected at two sites (Hospital Alemán and Casa Rapallini) located in streets with traffic consisting mostly of passenger cars and showing a "stop-and-go" pattern in peak hours. Antimony levels in the Buenos Aires PM-10 are by far below the level of 0.5 mg m(-3)(for an 8 hour workday, 40 hour work week) set by the US Occupational Safety and Health Administration (OSHA) for occupational exposure. However, monitoring of Sb and other TRE should be carried out in a systematic fashion to detect the possibility of increases in from the present levels.

Air Pollutants↗

PubMed2006

Sources and fate of butyltins in the St. Lawrence Estuary ecosystem.

Butyltins (BTs) were determined in sediment, zooplankton, benthic fish and invertebrates in the St. Lawrence Estuary and its mixing zone with the Gulf of St. Lawrence (Canada) in an attempt to assess sources and fate of these compounds in a large ecosystem before the enforcement of the world-wide ban of TBT-based antifouling paints. All BTs (MBT, DBT and TBT) were found along the studied area (450 km) where the traffic of large vessels occurs around the year. Concentrations of total butyltins (BTs) in surface sediment were below 6 ng Sn g(-1) d.w. Total BTs concentrations found in zooplankton samples at the mouth of the Saguenay Fjord were the highest (793 ng Sn g(-1) d.w.), indicating the influence of the Fjord on the St. Lawrence contamination. Although a relatively low contamination level was measured in sediment, total BTs concentrations ranged from 9 to 489 ng Sn g(-1) d.w. for benthic organisms. Biota-sediment accumulation factors (BSAFs), calculated on the basis of the organic carbon content in the sediment (concentrations normalized to 1% Corg), ranged from 0.9 to 98.3, and are an indicator of an important source of BTs from the Saguenay Fjord particulate matter. This may be explained by the fact that when TBT is released in a large and deep well stratified coastal environment, it could bind to the suspended particulate matter and then be taken in charge by water column organisms and may be mostly metabolised before it reaches bottom sediment. Sediment is not considered as the main contributor to the contamination of fish and invertebrates. It is expected that any reduction of direct inputs of TBT from ship hulls in a near future should result in a rapid reduction of butyltins in the St. Lawrence ecosystem.

Animals↗

PubMed2005

Determination of atmospheric concentrations of inorganic anions by ion chromatography following ultrasonic extraction.

The capability of the suppressed conductometric detection ion chromatography (IC) was investigated for the separation and determination of inorganic anions (F-, Cl-, NO3- and SO4(2-)) in standard reference materials SRM-1648 urban particulate matter following ultrasonic extraction. The effects of the cationic surfactant (SDS) and the anionic surfactant (CTAB) on ultrasonic extraction efficiency of inorganic anions from complex matrix of airborne particulate matter were investigated. The results showed that surfactant can enhance the extraction efficiency. Finally, the concentrations of inorganic anions in the atmosphere of the city of Isfahan were determined. The results showed a trend of SO4(2-) > NO3- > Cl- > F-.

Air Pollutants↗

PubMed2005

A review and critique of the EPA's rationale for a fine particle standard.

I review the rationale for the Environmental Protection Agency's 1996 fine particle standard, which was based almost entirely on the epidemiological data with neither support from Toxicology nor understanding of mechanism. While many epidemiological papers available in 1996 reported associations between ambient particles and adverse effects on human health, many others did not and the evidence fell far short of supporting a causal association between particle mass concentration and human health. The literature appearing after 1996 further complicates the picture. The large studies that have appeared after 1996, such as National Mortality Morbidity and Air Pollution Study, and the reanalyses of the American Cancer Society II study, report risks that are substantially smaller than the risks reported in the 1996 Criteria Document and Staff Paper. Moreover, concerns about confounding by weather, temporal trends and co-pollutants remain unresolved. Other issues having to do with model choice have resurfaced as a result of reanalyses of critical data to address a glitch in a widely used software package for time-series epidemiology studies of air pollution. Finally, contemporary examples show that the results of observational epidemiology studies can be seriously biased, particularly when estimated risks are small, as is the case with studies of air pollution. The Agency has largely ignored these issues. I conclude that a particle mass standard is not defensible on the basis of a causal association between ambient particle mass and adverse effects on human health. Such a standard may be justifiable on the basis of the precautionary principle, however. The Agency could argue that the Science raises concerns about current levels of air pollution, and that reduction of ambient fine particulate matter mass, if it could be achieved without an increase in the level of the ultrafines, could have positive effects on human health. If the Agency justifies a particulate matter mass standard on these grounds then the debate over the form and level of the standard will, for all practical purposes, belong strictly in the Policy arena.

Air Pollution↗

PubMed2005

Ambient air pollution and respiratory emergency department visits.

BACKGROUND: A number of emergency department studies have corroborated findings from mortality and hospital admission studies regarding an association of ambient air pollution and respiratory outcomes. More refined assessment has been limited by study size and available air quality data. METHODS: Measurements of 5 pollutants (particulate matter [PM10], ozone, nitrogen dioxide [NO2], carbon monoxide [CO], and sulfur dioxide [SO2]) were available for the entire study period (1 January 1993 to 31 August 2000); detailed measurements of particulate matter were available for 25 months. We obtained data on 4 million emergency department visits from 31 hospitals in Atlanta. Visits for asthma, chronic obstructive pulmonary disease, upper respiratory infection, and pneumonia were assessed in relation to air pollutants using Poisson generalized estimating equations. RESULTS: In single-pollutant models examining 3-day moving averages of pollutants (lags 0, 1, and 2): standard deviation increases of ozone, NO2, CO, and PM10 were associated with 1-3% increases in URI visits; a 2 microg/m increase of PM2.5 organic carbon was associated with a 3% increase in pneumonia visits; and standard deviation increases of NO2 and CO were associated with 2-3% increases in chronic obstructive pulmonary disease visits. Positive associations persisted beyond 3 days for several of the outcomes, and over a week for asthma. CONCLUSIONS: The results of this study contribute to the evidence of an association of several correlated gaseous and particulate pollutants, including ozone, NO2, CO, PM, and organic carbon, with specific respiratory conditions.

Adolescent↗

PubMed2005

Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.

CONTEXT: Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.

Air Pollutants↗

PubMed1998

Micronucleus induction in V79 cells after direct exposure to whole cigarette smoke.

Previous investigations on the effects of cigarette smoke on cultured cells have used mainly smoke condensate dissolved in culture medium. A system has been designed which allows direct exposure of cells to fresh cigarette smoke, without an intervening layer of growth medium between the cells and the smoke. Preliminary results have been obtained which demonstrate the viability of the system. V79 cells were cultured on porous membranes (Transwell; Costar). During smoke exposure only the lower surface of each Transwell is supplied with culture medium from the bottom of the culture chambers. In this way the cells had direct contact with the atmosphere at the upper surface and could be exposed directly to the test compound. The constructed exposure system consists of a smoke generator and an exposure unit containing six Transwells, the latter contained in an incubator. Cigarette smoke was generated using a standard 2 s, 35 ml puff once per min. The puff is diluted with conditioned air from the incubator and injected into the exposure unit. Following exposure of the cells to air only for 3 h there was no effect upon V79 cell viability. However, after exposure to smoke containing between 88 and 224 mg/m3 particulate matter, an inhibition of cell proliferation and induction of micronuclei was measured. When a Cambridge filter pad was placed between the cigarette and the cell exposure system to remove particulate matter cell proliferation was also reduced and an increased frequency of micronuclei above the control value was measured.

Aerosols↗

PubMed2004

Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association.

Air pollution is a heterogeneous, complex mixture of gases, liquids, and particulate matter. Epidemiological studies have demonstrated a consistent increased risk for cardiovascular events in relation to both short- and long-term exposure to present-day concentrations of ambient particulate matter. Several plausible mechanistic pathways have been described, including enhanced coagulation/thrombosis, a propensity for arrhythmias, acute arterial vasoconstriction, systemic inflammatory responses, and the chronic promotion of atherosclerosis. The purpose of this statement is to provide healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease. In addition, the implications of these findings in relation to public health and regulatory policies are addressed. Practical recommendations for healthcare providers and their patients are outlined. In the final section, suggestions for future research are made to address a number of remaining scientific questions.

Air Pollutants↗

PubMed2002

Cigarette smoke-induced airway hyperresponsiveness is not dependent on elevated immunoglobulin and eosinophilic inflammation in a mouse model of allergic airway disease.

Epidemiologic studies suggest that children raised in homes of cigarette smokers have a higher incidence of asthma than children who are raised in homes of nonsmokers. We sought to develop an experimental model to understand the mechanisms involved. Female BALB/c mice were paired with male DO11.10 ovalbumin (OVA)-T cell receptor hemizygous (+/-) mice such that the offspring were either transgene positive (+/-) or negative (-/-). Mice were exposed to either air or mainstream cigarette smoke (100 mg/m(3) total particulate matter, 6 hours/day, 7 days/week) during pregnancy. Immediately after birth, newborn mice were exposed for 4 weeks to either air or sidestream cigarette smoke (SS; 5 mg/m(3) total particulate matter, 6 hours/day, 5 days/week) and then exposed for the following 6 weeks to either air, SS, OVA (5 mg/m(3), 6 hours/day, 5 days/week) or a combination of OVA-SS. DO11.10 +/- offspring exposed to OVA had increased airway hyperresponsiveness (AHR) to methacholine challenge, total IgE, OVA-specific IgE and IgG(1), lymphocytes, and neutrophils in bronchoalveolar lavage and perivascular and peribronchiolar inflammation. Exposure to SS alone caused a significant increase in AHR in both +/- and -/- mice. Transgene -/- mice did not exhibit AHR after OVA exposure unless it was delivered in combination with SS. When compared with OVA-only exposure, OVA-SS exposure decreased total IgE, OVA-specific IgE, and IgG(1) amounts in +/- mice. These results indicate that exposure to SS after birth enhanced AHR in offspring that are both predisposed (+/-) and nonpredisposed (-/-) to develop an allergic response to OVA, but this AHR was not associated with elevated lung eosinophilia or OVA-specific Ig amounts.

Administration, Inhalation↗

PubMed1978

The cytochemical localization of adenylate cyclase: fact or artifact?

In a study of the location of adenylate cyclase activity in rat pancreas with the method of Reik et al. (Science 168:382, 1970), as modified by Howell and Whitfield (J Histochem Cytochem 20:873, 1972) it was found that (a) unspecific staining occurs in rat pancreatic tissue fragments incubated in the Reik-Howell medium in the absence of substrate; (b) addition of adenylyl-imidodiphosphate (AMP-PNP) as substrate, either alone or together with stimulants of rat pancreas adenylate cyclase (secretin. NaF), does not result in increased precipitation; (c) cytochemical incubation of isolated rat pancreatic acinar cells and of rat liver and kidney fragments does not lead to substrate-specific precipitation. In subsequent chemical studies we have found that cyclic adenosine monophosphate (AMP) formation from [alpha32P]AMP-PNP in the presence of rat pancreatic particulate matter is very low in the Reik-Howell medium without lead ions, but is stimulated by addition of lead nitrate (4 mM). Whereas heat-treatment of the particulate matter abolishes all cyclic AMP formation in the absence of lead ions, it actually increases cyclic AMP production in the presence of 4 mM lead nitrate. This indicates that the cyclic AMP formation in the complet Reik-Howell medium occurs by a nonenzymatic mechanism. In addition, this medium shows a tendency to become turbid, particularly when calcium ions are added to the medium, suggesting a possible explanation for the apparently specific cytochemical detection observed by other authors. A revised cytochemical medium, with barium replacing lead and with a pH of 8.9 (optimal for adenylate cyclase with AMP-PNP substrate), leaves rat pancreatic adenylate cyclase activity intact and hormone sensitive, while it is still able to precipitate imidodiphosphate. However, cytochemical incubation of isolated rat pancreatic acinar cells in this revised medium in the presence of AMP-PNP and secretin does not yield an electron-dense precipitate, showing that the enzyme activity is to low to produce sufficient imidodiphosphate. These findings throw further doubt on the validity of the cytochemical detection of adenylate cyclase, reported by other investigators, notwithstanding the alleged positive results.

Adenylyl Cyclases↗

PubMedDate not supplied

USP perspectives on particle contamination of injectable products.

It is widely recognized that the level of particulate matter in an injectable product is one measure of quality, directly reflecting the success with which the manufacturer applies good quality control. The current USP XXII 1990 limits for particulate matter derived from knowledge that goes back to the 1970s but does not reflect the quality of the product available today. This presentation will discuss the purpose and background of proposed new limits intended to be adopted in the USP 23 revision cycle. The limits tests are structured in two stages for both Large-Volume and Small-Volume Injections, effectively employing an improved light obscuration method as a screening procedure. Product which fails this stage is then evaluated by a second stage, filtration and microscopic examination using a considerably improved procedure in which all of the container contents are sampled (or pooled to 25 mL) and the filter examined episcopically.

Drug Contamination↗

PubMed1984

Synovial response to laser induced carbon ash residue.

Most surgical applications of CO2 laser energy permit carbonized and devitalized tissue to slough and become exteriorized through some natural orifice. The use of laser energy in joints with no external communication, however, must rely on synovial response to clear the carbon ash residue. Sixteen New Zealand white rabbits underwent arthrotomy and subtotal laser meniscectomy with no effort to cleanse the carbon residue. The animals were sacrificed at regular intervals up to 8 weeks, and the menisci and synovium were harvested for microscopic inspection. The initial synovial response was characterized by hypertrophic changes with a moderate increase in cell population and subsynovial interstitial fluid. Particulate matter was invested by the synovium, and provoked an influx of acute inflammatory cells. By 6 weeks, only rare particles of carbonaceous material were found in the synovium and no particulate matter could be located by 8 weeks. Laser induced carbon ash residue appears relatively innocuous to the joint in vivo and is readily cleared by an adequate and short-lived synovial response.

Animals↗

PubMed2003

PM(10) and its impacts on health - a case study in Mumbai.

Air pollution in urban areas is a major health concern. Air pollution in cities has been linked to increased rates of mortality and morbidity in developed and developing countries. There is consistent evidence that the levels of fine particulate matter in the air are associated with risk of death from all causes of cardiovascular and respiratory illness. The present study predicts the health impact due to PM(10) (respirable particulate matter) in an industrial, residential and commercial area of Mumbai city. The estimates of the impacts on health is mainly based on Ostro's approach.

Adolescent↗

PubMed1995

Quality evaluation of commercial lyophilized human growth hormone preparations.

The quality of three commercial injections (Genotropin, Humatrope and Norditropin) of lyophilized recombinant human growth hormone (r-hGH) was evaluated in tests by visual inspection, high-performance gel permeation chromatography, polyacrylamide gel electrophoresis, scanning electron microscopy and energy dispersion X-ray microanalysis. The influence of the reconstitution method on gel formation was examined as follows: rapid injection of the diluting solution into a vial against the wall, slow injection onto the surface of the content, and rapid injection onto the surface of the content. The degree of gel formation differed among reconstitution methods. Moreover, fibrous particulate matter in addition to degradation products of r-hGH were evident in all preparations. The quality of r-hGH injection differed among commercial products. Norditropin included the least particulate matter when examined immediately after reconstitution, but it was easily denatured after storage in solution. We advise medical specialists to reconstitute a preparation by the optimal method.

Drug Compounding↗

PubMed2004

Mobile resonance enhanced multiphoton ionisation-time-of-flight mass spectrometer with a novel hybrid laser desorption/molecular beam ion source for rapid detection of aromatic trace compounds from gas phase and solid samples.

A mobile, field applicable resonance enhanced multiphoton ionisation-time-of-flight mass spectrometer (REMPI-TOFMS) for direct-inlet gas-phase analysis as well as for characterisation of solid samples, has been developed. For solid-sample analysis, laser desorption (LD) with IR-laser pulses is used for volatilisation of the neutral analytes from a target in the ion source prior to REMPI-TOFMS analysis. For direct inlet gas-phase analysis, a needle gas inlet is used and the formed molecular beam is REMPI-ionised directly in the ion source. A special ion source was developed, which can be rapidly interchanged between the REMPI-TOFMS and the LD-REMPI-TOFMS modes. The system is equipped with a tuneable optical parametrical oscillator (OPO)-laser system. The analytical properties are characterised for both modes of operations. In both cases, analytical performance is similar to that achieved with instruments specifically designed for either gas-phase or solid-phase characterisation. Results from field measurements of a wood combustion flue gas of a 174 kW bio mass furnace are given. Gas-phase analysis was applied for time-resolved on-line REMPI-TOFMS of the semi-volatile aromatic flue gas constituents. The low-volatile aromatic compounds, which were precipitated with the particulate matter in the filtering unit of the sampling train, were characterised by direct LD-REMPI-TOFMS of the glass fibre filter material. By combining the gas-phase and particulate results a rather comprehensive characterisation of the aromatic species present in the flue gas (i.e. aerosol--gas phase plus particulate matter) was achieved.

Mass Spectrometry↗

PubMed2005

Natural background visibility and regional haze goals in the Southeastern United States.

The goal of the regional haze mitigation program in the United States is to attain "natural conditions" in national parks and wilderness areas by 2064. Results of research investigations on background concentrations of sea salt and biogenic organic matter, of episodic Saharan and Asian dust, and of carbon from natural fires were reviewed to provide a basis for making site-specific estimates of what the concentrations of atmospheric fine particulate matter components might be under natural conditions in the Southeastern United States. Based on this review, rough estimates were made of potential contributions of these aerosol components to natural background visibility. Natural organic particles were the dominant influence on the rate of visibility improvement required to reach natural conditions at an inland, mountainous location, and organic particles and sea salt were the dominant influences on the rate at a coastal location. African dust also had a large episodic effect, but the current regulatory approach is not designed to address episodic background variations. Insufficient data exist to quantify the contributions of wildfires with any detail, although global air pollution modeling provides insight, and their emissions can be locally dominant. Conservative regional refinements to the default natural background estimates do not greatly alter the region-wide rates of reduction of ambient particulate matter concentrations that will be needed to accomplish the first phase of the regional haze program. However, refinements at specific Class I areas may have considerable influence on defining the nature (magnitude and spatial and temporal distribution) of local emission reduction efforts there.

Air Pollution↗