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PubMed1987

Particulate-matter content of 11 cephalosporin injections: conformance with USP limits.

The particulate-matter content of 11 dry-powder cephalosporin injections was determined using a modified version of the official United States Pharmacopeial Convention (USP) method for particulate matter in small-volume injections (SVIs). Ten vials of each cephalosporin product were each constituted with 10 mL of Water for Injections BP that had been filtered through a 0.22-micron membrane. The pooled contents of the 10 vials for each product were allowed to stand under reduced pressure to ensure removal of gas bubbles. Particulate-matter content was determined using a HIAC/Royco particle counter on six 10-mL samples obtained from the pooled solutions for each product. All solution preparation and particle counting was performed in a horizontal-laminar-airflow hood. Modifications of the USP method used in this study included the use of six rather than two samples from each pooled solution, the addition of diluent to the injections through the rubber closure with a needle instead of into the open container, and changes in the degassing method. Particle counts for all products examined were lower than USP limits for SVIs. All but two products contained less than 15% of USP limits for particles greater than or equal to 10 microns in effective diameter and particles greater than or equal to 25 microns in effective diameter. The standard USP method for degassing (standing for two minutes) was inadequate. Application of reduced pressure for up to 10 minutes was necessary for thorough degassing of products.(ABSTRACT TRUNCATED AT 250 WORDS)

Cephalosporins↗

PubMed2006

Genotoxicity of organic extracts of urban airborne particulate matter: an assessment within a personal exposure study.

Airborne particulate matter, PM(10) and PM(2.5), are associated with a range of health effects including lung cancer. Their complex organic fraction contains genotoxic and carcinogenic compounds such as polycyclic aromatic hydrocarbons (PAHs) and their derivatives. This study evaluates the genotoxicity of the PM(10) and PM(2.5) organic extracts that were sampled in the framework of a personal exposure study in three French metropolitan areas (Paris, Rouen and Strasbourg), using the comet assay, performed on HeLa S3 cells. In each city, 60-90 non-smoking volunteers composed of two groups of equal size (adults and children) carried the personal Harvard Chempass multi-pollutant sampler during 48h along two different seasons ('hot' and 'cold'). Volunteers were selected so as to live (home and work/school) in 3 different urban sectors contrasted in terms of air pollution within each city (one highly exposed to traffic emissions, one influenced by local industrial sources, and a background urban environment). Genotoxic effects are stronger for PM(2.5) extracts than for PM(10), and greater in winter than in summer. Fine particles collected by subjects living within the traffic proximity sector present the strongest genotoxic responses, especially in the Paris metropolitan area. This work confirms the genotoxic potency of particulate matter (PM(10) and PM(2.5)) organic extracts to which urban populations are exposed.

Adult↗

PubMed2004

Sensitivity to ozone, diesel exhaust particles, and standardized ambient particulate matter in rats with a listeria monocytogenes-induced respiratory infection.

Ambient particulate matter may increase respiratory allergic skewing of the T-cell-mediated immune response toward a T-helper-2 (Th2) response, with the consequence that the Th1 response develops less well. Successful clearing of a respiratory bacterial infection depends on an adequate Th1 immune response; therefore, the subject would not control the infection as well if exposed to particulate matter. To substantiate this hypothesis, we examined the effect of exposure to diesel exhaust particles (DEP) and urban particulate matter (EHC-93, Ottawa dust) on rats with a Listeria monocytogenes respiratory infection. Since this hypothesis has been confirmed for ozone, we used it as a positive control. Wistar rats were exposed to ozone (2 mg/m3 for 24 h/day for 7 days) and to DEP or to EHC-93 (50 microg/rat intranasally daily for 7 consecutive days). Twenty-four hours after the last exposure, the rats were infected intratracheally with 1 x 10(6) L. monocytogenes bacteria. The number of L. monocytogenes was determined after 3, 4 and 5 days. Statistically significant increases of the number of L. monocytogenes in rats exposed to ozone were observed in the lungs and spleen at all three times. However, we found no significant differences in the numbers of bacteria that were found in rats exposed to DEP or EHC-93 compared to the saline-treated group at any of the three times. In conclusion, the results of this study do not support the hypothesis that exposure to DEP or EHC-93 reduces subsequent resistance to a respiratory infection in rats.

Administration, Inhalation↗

PubMed2026

Exposure to size-specific particulate matter accelerates DNA methylation aging in people with HIV.

BACKGROUND: People with HIV (PWH) face accelerated aging and increased health risks, with DNA methylation age (DNAmAge) as a critical senescence biomarker. Particulate matter is linked to DNAmAge acceleration (DNAmAA) in general population, but its impact in PWH remains unstudied. METHODS: Thirty-two PWH from Wuhan, China, were enrolled in a prospective panel study with follow-up, and each participant underwent at least two repeated measurements during the study period. Portable air quality monitor measured PM 1 , PM 2.5 , and PM 10 exposures 72 h preblood sampling. We analyzed genome-wide DNA methylation in peripheral blood and calculated six AA metrics. Linear mixed-effects and weighted quantile sum regression models evaluated associations between particulate matter exposure and DNAmAA. RESULTS: Significant associations between particulate matter exposure and DNAmAA were observed at various lag windows. For every 10 μg/m 3 increase in 24-h average PM 2.5 , Hannum DNAmAA, Pheno DNAmAA, Grim DNAmAA, SkinBlood DNAmAA, and Elastic DNAmAA increased by 0.266 years [95% confidence interval (CI): 0.035-0.480], 0.421 years (95% CI: 0.032-0.701), 0.336 years (95% CI: 0.073-0.546), 0.295 years (95% CI: 0.021-0.495), and 0.254 years (95% CI: 0.034-0.445), respectively. PM 10 contributed most substantially to the cumulative PM effect on epigenetic AA in the lag0-24 h window. CONCLUSION: Short-term particulate matter exposure, particularly PM 10 , significantly accelerates epigenetic aging in PWH, highlighting the need to integrate air quality management into healthy aging strategies for this vulnerable population.

China↗

PubMed2003

Exposure to ambient fine particulate matter and primary cardiac arrest among persons with and without clinically recognized heart disease.

The authors studied the association between incidence of primary cardiac arrest and daily measures of fine particulate matter (</=2.5 micro m) using a case-crossover study of 1,206 Washington State out-of-hospital cardiac arrests (1985-1994) among persons with (n = 774) and without (n = 432) clinically recognized heart disease. The authors compared particulate matter levels on the day of the cardiac event and the 2 days preceding the event with levels from matched reference days. The estimated relative risk for a 13.8- micro g/m(3) increase in fine particulate matter (nephelometry: 0.54 x 10(-1) km(-1 )bsp) on the day prior to cardiac arrest was 0.94 (95% confidence interval: 0.88, 1.02). Pollutant levels measured on the same day as the event and on the 2 days preceding the event demonstrated similar results. No increased risk was found among all cases with preexisting cardiac disease (odds ratio = 0.97, 95% confidence interval: 0.89, 1.07); however, an unexpected association appeared between current smokers with preexisting heart disease and increased particulate matter levels 2 days prior to the event (odds ratio = 1.29, 95% confidence interval: 1.06, 1.55). This association was not present in the 0- or 1-day lag analyses or in persons with other diseases. There was no consistent association between increased levels of fine particulate matter and risk of primary cardiac arrest.

Aged↗

PubMed2005

Coarse particulate matter and hospitalization for respiratory infections in children younger than 15 years in Toronto: a case-crossover analysis.

OBJECTIVES: The purpose of this study was to examine the association between ambient air pollution and hospitalization for respiratory infections among children who were younger than 15 years in Toronto during a 4-year period (1998-2001). METHODS: Exposures averaged during periods that varied from 1 to 7 days were used to assess the effects of air pollutants, including thoracic particulate matter (PM10), fine (PM2.5) and coarse (PM10-2.5) particulate matter, carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3), on hospitalization for respiratory infections. A case-crossover design was used to calculate odds ratios for the hospitalization adjusted for daily weather conditions with an incremented exposure corresponding to the interquartile range in air pollution exposures. RESULTS: When particulate matter and gaseous pollutants were mutually taken into account, the effect remained pronounced for PM10-2.5 in both boys and girls. The adjusted odds ratio for 6-day average exposure to PM10-2.5 with an increment of 6.5 microg/m3 was 1.15 (95% confidence interval: 1.02-1.30) for boys and 1.18 (95% confidence interval: 1.01-1.36) for girls. The effect also remained for PM10 in boys and for NO2 in girls. PM2.5, CO, SO2, and O3 showed no significant effects on hospitalization for respiratory infection in both genders when other pollutants were taken into consideration. CONCLUSION: Our study suggested a detrimental effect of relatively low levels of ambient particulate matter and gaseous pollutants, especially coarse particulate matter and NO2, on hospitalization for respiratory infections in children.

Adolescent↗

PubMed2004

Physicochemical characteristics and biological activities of seasonal atmospheric particulate matter sampling in two locations of Paris.

Fine particulate matter present in urban areas seems to be incriminated in respiratory disorders. The aim of this study was to relate physicochemical characteristics of PM2.5 (particulate matter collected with a 50% efficiency for particles with an aerodynamic diameter of 2.5 microm) to their biological activities toward a bronchial epithelial cell line 16-HBE. Two seasonal sampling campaigns of particles were realized, respectively, in a kerbside and an urban background station in Paris. Sampled-PM2.5 mainly consist of particles with a size below 1 microm and are mainly composed of soot as assessed by analytical scanning electron microscopy. The different PM2.5 samples contrasted in their PAH content, which was the highest in the kerbside station in winter, as well as in their metal content. Kerbside station samples were characterized by the highest Fe and Cu content, which appears correlated to their hydroxyl radical generating properties measured by electron paramagnetic resonance. Particles were compared by their capacity to induce cytotoxicity, intracellular ROS production, and proinflammatory cytokine release (GM-CSF and TNF-alpha). At a concentration of 10 microg/cm2, all samples induced peroxide production and cytokine release to the similar extent in the absence of cytotoxicity. In conclusion, whereas the PM2.5 samples differ by their PAH and metal composition, they induce the same biological responses likely either due to components bioavailability and/ or interactions between PM components.

Air Pollutants↗

PubMed2001

Quinoid redox cycling as a mechanism for sustained free radical generation by inhaled airborne particulate matter.

The health effects of airborne fine particles are the subject of government regulation and scientific debate. The aerodynamics of airborne particulate matter, the deposition patterns in the human lung, and the available experimental and epidemiological data on health effects lead us to focus on airborne particulate matter with an aerodynamic mean diameter less than 2.5 microm (PM(2.5)) as the fraction of the particles with the largest impact in health. In this article we present a novel hypothesis to explain the continuous production of reactive oxygen species produced by PM(2.5) when it is deposited in the lung. We find PM(2.5) contains abundant persistent free radicals, typically 10(16) to 10(17) unpaired spins/gram, and that these radicals are stable for several months. These radicals are consistent with the stability and electron paramagnetic resonance spectral characteristics of semiquinone radicals. Catalytic redox cycling by semiquinone radicals is well documented in the literature and we had studied in detail its role on the health effects of cigarette smoke particulate matter. We believe that we have for the first time shown that the same, or similar radicals, are not confined to cigarette smoke particulate matter but are also present in PM(2.5). We hypothesize that these semiquinone radicals undergo redox cycling, thereby reducing oxygen and generating reactive oxygen species while consuming tissue-reducing equivalents, such as NAD(P)H and ascorbate. These reactive oxygen species generated by particles cause oxidative stress at sites of deposition and produce deleterious effects observed in the lung.

Air Pollutants↗

PubMed2000

The formation of reactive oxygen species catalyzed by neutral, aqueous extracts of NIST ambient particulate matter and diesel engine particles.

It is important to characterize the chemical properties of particulate matter in order to understand how low doses, inhaled by a susceptible population, might cause human health effects. The formation of reactive oxygen species catalyzed by neutral, aqueous extracts of two ambient particulate samples, National Institute of Standards & Technology (NIST) Standard Reference Materials (SRM) 1648 and 1649, and two diesel particulate samples, NIST SRM 1650 and SRM 2975, were measured. The formation of reactive oxygen species was estimated by measuring the formation of malondialdehyde from 2-deoxyribose in the presence of ascorbic acid; H2O2 was not added to this assay. SRM 1649, ambient particulate matter collected from Washington, DC, generated the most malondialdehyde, while SRM 2975, diesel particulate matter collected from a forklift, yielded the least amount. Desferrioxamine inhibited the formation of malondialdehyde from the particulate samples providing additional data to support the observation that transition metals were involved in the generation of reactive oxygen species. Six transition metal sulfates (iron sulfate, copper sulfate, vanadyl sulfate, cobalt sulfate, nickel sulfate, and zinc sulfate) were assayed for their ability to generate reactive oxygen species under the same conditions used for the particulate samples in order to facilitate comparisons between particles and these transition metals. The concentration of transition metals was measured in aqueous extracts of these particulate samples using ion-coupled plasma mass spectrometry (ICP-MS) analysis. There was qualitative agreement between the concentrations of Fe, Cu, and V and the amount of malondialdehyde produced from extracts of these particulate samples. These data suggest that transition metals can be dissolved from particles in neutral, aqueous solutions and that these metals are capable of catalyzing the formation of reactive oxygen species.

Air Pollutants, Occupational↗

PubMed2004

Distribution of lead in relation to size of airborne particulate matter in Islamabad, Pakistan.

Airborne particulate matter (PM) collected from two sampling stations in Islamabad, Pakistan, was analyzed for lead content and size gradation. A high volume air sampler was used to trap particulates on glass fiber filters for 8-12 h on a daily basis. Lead was estimated using a nitric acid digestion based AAS method on 44 samples from station 1 and 61 samples from station 2. Particle size fractions were categorized as <2.5, 2.5-10, 10-100 and >100 microm. The correlation between lead concentration and particle size was investigated. The results from two stations indicated average airborne lead concentrations of 0.505 and 0.185 microg/m3. Enhanced levels of lead were measured at a maximum of 4.075 microg/m3 at station 1 and 4.000 microg/m3 at station 2. PM < 2.5 and PM > 100 were found to constitute the local atmosphere in comparable proportions. A comparison of the lead levels is made with the existing permissible levels of this element laid down by different international agencies.

Air Pollutants↗

PubMed2004

Modelling the size separated particulate matter (SSPM10) from vehicular exhaust at traffic intersections in Mumbai.

The study was carried out to predict the size separated particulate matter below 10 microm size (SSPM10) from vehicular exhausts at traffic intersections using modified general finite line source model (GFLSM). Two air quality control regions (AQCRs) were selected in Mumbai City for this study. One was industrial area (AQCR1) containing the busy intersection, i.e. Marol link road, with the heavy inflow of two-three wheelers. And, the other was commercial busy district area (AQCR2) containing the busy intersection, i.e. Dadar circle, with a heavy traffic flow especially cars. The model was applied at both the traffic intersections. The data were collected for modelling study for three winter months in 1995 using cascade impactor of nine size ranges. The prediction results revealed that modified GFLSM underpredicted the SSPM10 concentrations for all the size ranges. However, showed considerable correlation between observed and predicted values for the size range below 4.7 microm at both the intersections. The relative high concentrations observed in the coarser range of 10-4.7 microm are attributed to the resuspension of the roadside particulate matter. Hence, the amount of underprediction was more for this range, which was due to the characteristics of model that does not take into account the factor for resuspension of roadside particulate matter caused by traffic movements. The model was also applied to predict the total particulate matter for downwind distances from the road intersection. The statistical evaluation of model was done, which indicated that the model's performance was good for the finer range of particles (below 4.7 microm) with r-square values of 0.49 and 0.57 found at both the intersections in AQCR1 and AQCR2, respectively. However, it is not unusual that the model uncertainty is likely to exist due to data input errors and stochastic fluctuations irrespective of the models accurateness. The statistical distribution model was therefore identified using Kolmogorov-Smirnov test. At both the intersections, SSPM10 concentration data were found lognormally distributed.

Air Pollutants↗

PubMedDate not supplied

Particulate matter determination in LVPs produced in Dutch hospital pharmacies. Part 2: Overview of the results.

The Laboratory of Dutch Pharmacists determines LVP particulate matter contamination of LVPs produced in Dutch hospital pharmacies. The investigated LVPs must conform to the NVZA/LNA criteria, which prescribes eight samples and sets limits for particles > or = 2 microns, > or = 5 microns, > or = 10 microns, and > or = 25 microns for both mean and mean + 2x standard deviation. LVPs produced in 500 mL glass containers or plastic containers mostly met the NVZA/LNA criteria, but LVPs produced in 100 mL glass containers showed higher levels of particulate matter contamination. The composition of the LVP significantly affected the extent of particulate matter contamination, but the effect was relatively small when compared to the influence of the type of container. LVPs produced in Dutch hospital pharmacies and LVPs obtained from pharmaceutical industries showed comparable amounts of particulate matter contamination.

Drug Contamination↗

PubMed1995

Induction of rat hepatic P4501A1 by organic extracts from airborne particulate matter in Santiago, Chile.

1. Organic extracts from particulate matter collected in downtown Santiago, Chile, in 1990 were administered to female Wistar rats. 2. Extracts shifted the maximal absorption wavelength P450 spectra of the reduced-CO complex of hepatic microsomal P450 from 450 to 448 nm, and enhanced the total content of P450. In addition, substantial increases in aryl hydrocarbon hydroxylase, ethoxyresorufin O-deethylase and ethoxycoumarin O-deethylase activities were observed, whereas aminopyrine N-demethylase activity was not affected by treatment. 3. Western blotting using polyclonal antibodies against P4501A isozymes showed the appearance of a distinct and intense P4501A1 band in microsomes from rat pretreated with air particle extracts, and was not observed in microsomes from control rat. On the other hand, the intensity of the P4501A2 isoenzyme was apparently not affected. 4. These findings suggest that the organic extracts from airborne particulate matter modify the composition of rat liver P450 isozymes by inducing those isoforms responsible for the activation of precarcinogenic to carcinogenic agents.

Air Pollutants↗

PubMed1984

Determination of polycyclic aromatic hydrocarbons in diesel exhaust particulate matter and diesel fuel oil.

Clean-up procedures were developed for a method for determining the amount of polycyclic aromatic hydrocarbons (PAHs) in diesel exhaust particulate matter and in diesel fuel oils using reversed-phase high-performance liquid chromatography (HPLC). They were based mainly on the elimination of insoluble matter and aliphatic compounds that affect the performance of HPLC, from the dichloromethane extracts of particulate matter or from oils, with the aid of a disposable preparation column containing reversed-phase packings (Sep-Pak C18). Using these procedures, it is possible to detect 1 ng of benzo(a)pyrene in 30 mg of particulate matter with more than a 97% recovery or 0.5 ng in 50 microliters of oil with 91% recovery. Examples of analyses are given for particulate matter emitted from a diesel test engine and for diesel fuel oils, such as gas oil, residual oil and coal-liquefied oil.

Chromatography, High Pressure Liquid↗

PubMed2003

Risk assessment dosimetry model for inhaled particulate matter: I. Human subjects.

Pollutant particulate matter (PM) is a serious global problem, presenting a threat to the health and well being of human subjects. Inhalation exposures tests with surrogate animals can be performed to estimate the threat. However, it is difficult to extrapolate the findings of animal tests to human conditions. In this two-part series, interspecies dosimetry models especially designed for implementation with risk assessment protocols are presented. In Part I, the mathematical integrity of the source model per se was tested with data from human subjects, and theoretical predictions agreed well with experimental measurements. In Part II, for surrogate (rat) simulations, appropriate algorithms for morphologies and ventilatory parameters were used as subroutines in the validated model. We conducted a comprehensive series of computer simulations describing the behavior of a representative air pollutant, secondary cigarette smoke. For risk assessment interests, a range of states from rest to exercise was considered. PM hygroscopicity had a pronounced effect on deposition in a complex but systematic manner, in humans and rats: deposition was increased for particles larger than about 1 microm, but was decreased for particles smaller than about 0.1 microm. The results clearly indicate that dosimetry models can be effectively used to a priori determine the laboratory conditions necessary for animals tests to accurately mimic human conditions. Moreover, the use of interspecies models is very cost effective. We propose, therefore, that mathematical models be used in a complementary manner with inhalation exposure experiments and be actively integrated into PM risk assessment protocols.

Air Pollutants↗

PubMed1991

32P-postlabelling analysis and micronuclei induction in primary Chinese hamster lung cells exposed to tobacco particulate matter.

The genotoxicity of tobacco particulate matter (TPM) derived from a low-tar, low-nicotine cigarette has been examined by measuring micronucleus induction in a primary pulmonary cell line, both in the absence and presence of an exogenous source of metabolic activation. In an attempt to correlate the cytogenetic damage observed with DNA adduct formation, DNA extracted from TPM-treated cells has been analysed with two different modifications of the 32P-postlabelling assay. The results from the 32P-postlabelling analysis taken together with the pattern of micronucleus induction provide strong evidence that bioreactivated aromatic carcinogens, such as benzo[a]pyrene, are unlikely to be responsible for the TPM-induced cytogenetic damage observed in cultured mammalian cells.

Animals↗

PubMed2005

Omega-3 fatty acid prevents heart rate variability reductions associated with particulate matter.

CONTEXT: Environmental exposure to particulate matter of 2.5 microm or less (PM2.5) has been associated with changes in heart rate variability (HRV). OBJECTIVE: To evaluate the effect of supplementation with omega-3 polyunsaturated fatty acids on the reduction of HRV associated with PM2.5 exposure. DESIGN: Randomized double-blind trial. SETTING: Mexico City, Mexico. PARTICIPANTS: 50 nursing home residents older than 60 yr. INTERVENTION: Randomization to either 2 g/d of fish oil versus 2 g/d of soy oil as the control, with 6 mo follow-up (1-mo presupplementation and 5-mo supplementation) or repeated HRV measurements. PM2.5 was monitored indoors and outdoors. MAIN OUTCOME MEASURE: The association between HRV and 1 SD change in PM2.5 (8 microg/m3). RESULTS: In the group receiving fish oil, the reduction in HRV-high-frequency log(10)-transformed associated with a 1-SD change in PM2.5 was -54% (95% confidence interval, -72, -24) in the presupplementation phase, and only -7% (95% confidence interval, -20,+7) in the supplementation phase (p < 0.01 for the effect of supplementation), with changes in other HRV parameters also being significantly less pronounced during supplementation. Small decreases in PM2.5-associated reductions in HRV parameters also occurred in the group receiving soy oil, but these were not significant. Fish oil supplementation was significantly better in preventing the reduction in percentage of successive normal RR intervals differing by more than 50 ms (p = 0.03) and the root square of the mean of the sum of the squares of differences between adjacent intervals (p = 0.05) than soy oil supplementation. INTERPRETATION: Supplementation with 2 g/d of fish oil prevented HRV decline related to PM2.5 exposure in the study population.

Aged↗

PubMed2003

Particulate matter in ambient air and mortality: toxicologic perspectives.

U.S. regulations that set standards for acceptable concentrations of respirable particulate matter (PM) in outdoor air, particularly total fine particulate matter (PM(2.5)), are based largely on the belief that current concentrations cause death and illness, and that reducing these concentrations will save lives. Because the mortality risk estimates from important observational epidemiologic studies are extremely weak, derived from studies unable to control for relevant confounding causes, and inconsistent by location, toxicologic and clinical information is necessary to judge the likelihood and degree to which such findings are causal. Toxicologic data on typical forms of pollution-derived PM strongly suggest that current ambient concentrations in the U.S. are too small to cause significant disease or death. We review here the results of inhalation studies using concentrated ambient particles, diesel engine exhaust particulate matter, and sulfate and nitrate salts, and find no evidence that moderate concentrations are lethal. The expectation that lives will be saved by reducing ambient PM(2.5) in the U.S. is not supported by the weight of scientific evidence, although other bases for regulating PM may be justifiable.

Air Pollutants↗