Ontario Medical Association position paper on health effects of ground-level ozone, acid aerosols and particulate matter

This review of the evidence of the health effects of air pollutants focuses on research conducted in Ontario. Seven key Ontario studies are cited. These findings are highly significant for people living in the Great Lakes basin (and particularly the Windsor-Quebec corridor), where high levels of certain air pollutants (eg, ground-level ozone and ultra-fine particles) occur more frequently than in other parts of Canada. The issue is a serious one, requiring an integrated and comprehensive approach by many stakeholders, including the active involvement of organized medicine. It is important that the health effects of these air pollutants are understood. Governments must act to reduce emission levels through statue and regulation bolstered by noncompliance penalties. The findings of research have included the following: in a Toronto study, a 2% to 4% excess of respiratory deaths were attributable to pollutant levels; children living in rural Ontario communities with the highest levels of airborne acids were significantly more likely to report at least one episode of bronchitis, as well as to show decreases in lung function; and have been linked to increases in pollutants, emergency room visits and hospitalizations in Ontario. Every Ontarian is affected by air pollutants, although he or she may be unaware of the asymptomatic effects such as lung and bronchial inflammation. This health problem is preventable; while physicians know of the adverse health impacts of air pollution and they are concerned, individually they now focus on the treatment of symptoms. The major recommendations of the report are as follows: Enactment of more stringent sulphur and nitrogen oxide emission limits, including a provincewide sulphur dioxide reduction of 75% from current cap levels, and the maximum allowable nitrogen oxides emission limits of 6000 tonnes annually from Ontario Hydro. New transportation sector emission limits that should include California-level standards for light and heavy duty vehicles, reductions from off-road engines, an expanded vehicle inspection and maintenance program, and tougher standards for sulphur-in-fuel content. Petitioning the United States Environmental Protection Agency administrator under Section 115 of the United States Clear Air Act to require reductions in the American emission of sulphur dioxide and nitrogen oxides, which damage the health of Canadian residents and their environment. Physician advice to patients about the risks of smog exposure, physician support for more health effects research on air pollution, and physician promotion of the development of air pollution-related health education materials. The recommendations discussed in this paper will, if acted upon, lead to a significant reduction in the overall burden of illness from air pollutants, especially in children and the elderly. These recommendations have been selected from a review of recommendations made by various authorities, and are those that the OMA feels a particular responsibility to support.     

Acute effects of inhaled urban particles and ozone: lung morphology, macrophage activity, and plasma endothelin-1

We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air appear related to paracrine/endocrine disruption mechanisms.     

Genotoxicity of coke-oven and urban air particulate matter in in vitro acellular assays coupled with 32P-postlabeling and HPLC analysis of DNA adducts

This study is an in vitro part of the ongoing biomarker studies with population from a polluted region of Northern Bohemia and coke-oven workers from Czech and Slovak Republics. The aim of this study is to compare DNA adduct forming ability of chemical compound classes from both the urban and coke-oven extractable organic mass (EOM) of airborne particles. The crude extracts were fractionated into seven fractions by acid-base partitioning and silica gel column chromatography. In in vitro acellular assays we used calf thymus DNA (CT DNA) with oxidative (+S9) and reductive activation mediated by xanthine oxidase (+XO) under anaerobic conditions. Both the butanol and nuclease P1 versions of 32P-postlabeling for detection of bulky aromatic and/or hydrophobic adducts were used. The results showed that the spectra of major DNA adducts resulting from both the in vitro assays are within the fractions similar for both the urban and coke-oven samples. The highest DNA adduct levels with S9-activation were detected for the neutral aromatic fraction, followed by slightly polar and acidic fractions for both samples. With XO-mediated metabolism, the highest DNA adduct levels were detected for both the acidic fractions. Assuming additivity of compound activities, then the acidic fraction, which in the urban sample comprises a major portion of EOM mass (28%), may contain the greatest activity in both in vitro assays (39 and 69%, +S9 and +XO, respectively). In contrast, the aromatic fraction constituting only 8% of total urban EOM mass may account for comparable activity (34%) with organic acids. The highest DNA adduct forming activity of the coke-oven sample accounts for the aromatic fraction (82 and 63%, +S9 and +XO, respectively) that also contains the greatest portion of the total EOM (48%). To characterize some of the specific DNA adducts formed, we coupled TLC on 20x20 cm plates with HPLC analysis of 32P-postlabeled adducts. In both S9-treated samples of the aromatic fraction, we tentatively identified DNA adducts presumably diolepoxide-derived from: 9-hydroxy-benzo[a]pyrene (9-OH-B[a]P), benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide[+/-] (anti-BPDE), benzo[b,j,k]fluoranthenes (B[b]F, B[j]F, B[k]F), chrysene (CHRY), benz[a]-anthracene (B[a]A) and indeno[cd]pyrene (I[cd]P). These DNA adducts accounted for about 57% of total DNA adducts detected in both S9-treated samples of the aromatic fraction. DNA adducts of XO-treated samples were sensitive to nuclease P1 and HPLC profiles of the major adducts were markedly different from the major adducts of S9-treated samples. However, the combination of TLC and HPLC did not confirm the presence of DNA adducts derived from 1-nitropyrene (1 NP), 9-nitroanthracene (9 NA) and 3-nitrofluoranthene (3 NF) that were detected by GC-MS in the slightly polar fraction. We concluded that the chemical fractionation procedure facilitates the assessing of DNA adduct forming ability of different chemical compound classes. However, based on the results obtained with the whole extracts, it does not fulfil a task of the actual contribution of individual fractions within the activity of the whole extracts. Our results are the first in detecting of DNA adducts derived from urban air and coke-oven particulate matter.     

Fatal G-CSF-induced pulmonary toxicity

Inherited thrombophilia has been suggested as a cause of Legg-Calvé-Perthes disease in up to 75% of patients. This prevalence seems high compared to the prevalence of inherited thrombophilia in other thrombotic disorders (average, 30%). Therefore, we investigated 44 patients with Legg-Calvé-Perthes disease for antithrombin-III, protein-C, and protein-S deficiency and activated protein C (APC) resistance. Three (6.8%) of our patients were positive for APC resistance, and one patient (2.2%) showed deficiency of protein-C activity. Our results suggest that inherited thrombophilia is not associated with avascular necrosis of the femoral head (Legg-Calvé-Perthes disease).     

Phosphatidylcholine synthesis and pulmonary oxygen toxicity

That organisms cannot remember events occurring during infancy may be the result of common forgetting processes exacerbated by the organism's increase in size during development or a unique process such as insufficient neurological development at the time of the early experience. To establish the uniqueness of infantile forgetting, size change was made irrelevant by exposing infant rats to "off-baseline" Pavlovian fear conditioning and assessing the effect of an apparatus-free conditioned stimulus upon independently established bar pressing. In Experiment 1, bar pressing by rats exposed to Pavlovian contingencies when 20-22 days old was substantially suppressed by the conditioned stimulus both 1 and 42 days after conditioning. In Experiment 2, pups conditioned when 17-19 and 20-22 days old again showed excellent retention, whereas pups conditioned when 11-13 and 14-16 days old showed total forgetting 42 days later. In Experiment 3, pups conditioned when 14-16 days old remembered well after 5 days, less well 10 days later, and not at all after 20 days. These findings suggest that size change may contribute to the forgetting of events occurring late in development, but that neurological immaturity may underly the forgetting of earlier events.     

Acute toxicity and pharmacokinetics of dibekacin mice

The LD50 values of dibekacin to mice were determined following three different methods of administration, namely, intravenous constant infusion, intravenous bolus injection, and intramuscular injection. The serum levels of dibekacin were pharmacokinetically analyzed. The differences in LD50 values between the methods of administration were discussed from the viewpoints of pharmacokinetics. 1) The LD50 value following the intravenous constant infusion was higher than that following the intravenous bolus injection and approached the level of that following the intramuscular injection, when the infusion rate of the drug was decreased by increasing the infusion period. 2) The biological half-life of dibekacin in mice was 24--45 min. 3) The volume of distribution increased as its dose increased, and a linear correlation was noted between log Vd and log (dose). 4) The difference among the maximum serum concentrations calculated with dibekacin following the administration of LD50 was small, which coincided with the results of the experiment that the serum concentrations of dibekacin at the death following the administration of LD100 were almost the same regardless of the method of administration.     

Acetaminophen toxicity in an urban county hospital

BACKGROUND: The prevalence and characteristics of acetaminophen-associated liver injury in hospitalized patients are not well defined. METHODS: We identified patients hospitalized for excessive acetaminophen ingestion at an urban county hospital over a 40-month period (1992 to 1995) and reviewed their medical records to determine the incidence and clinical features of the ingestions and their outcomes. RESULTS: Of the 71 patients studied, 50 were classified as having taken acetaminophen during suicide attempts and 21 as having accidentally poisoned themselves while attempting to relieve pain. The suicidal patients had ingested almost twice as much acetaminophen as those in the accidental-overdose group (median, 20 vs. 12 g; P=0.009). Among the patients for whom data were available, 63 percent of those in the accidental-overdose group and 25 percent of those in the suicidal group had chronic alcohol abuse (P=0.009). The patients in the accidental-overdose group more often had severe liver necrosis (aminotransferase levels, >3500 IU per liter; 52 percent vs. 14 percent; P=0.002), and were more likely to have hepatic coma (33 percent vs. 6 percent, P=0.006). There were four deaths (19 percent) in the accidental-overdose group and one (2 percent) in the suicidal group (P=0.04). Five patients -- three in the accidental-overdose group and two in the suicidal group -- had ingested 4 g of acetaminophen or less. Acetaminophen ingestion accounted for 12 percent of all patients hospitalized with overdoses (71 of 589) and 40 percent of patients with acute liver failure (10 of 25) during the study period. CONCLUSIONS: In an urban county hospital, patients hospitalized with acetaminophen toxicity related to accidental misuse had higher rates of morbidity and mortality than those who attempted suicide, even though the latter had taken more acetaminophen. A higher frequency of chronic alcohol abuse among the patients with accidental overdoses may be one explanation.     

Effects of agitation on size distribution of particulate matter in large-volume parenterals

The particle-size distributions of six types of large-volume parenterals subjected to different degrees of agitation were determined using an automatic particle counter. Data acquired from each solution, which had been maintained in a stored condition, subjected to agitation by inverting 20 times, and then mechanically shaken for 30 min, produced a linear relationship between log N greater than D and log D. Both the slope (K) and the number of particles per milliliter exceeding 1 micrometer in diameter (N greater than 1) exhibited a dependence on the degree of agitation. Their combined effect indicates that agitation by 20 hand inversions removed particulate matter from the surface of the container, which increased the total number of particles in solution (greater than 1 micrometer) but did not significantly alter the relative size distribution. Agitation for 30 min, however, disintegrated agglomerates and produced a particle-size distribution with a greatly increased number of particles whose diameters were less than 1 micrometer and a corresponding decrease in the number of particles exceeding 1 micrometer in diameter. The particle-size distribution of a parenteral solution determined by this in situ instrumental method was, therefore, dependent upon the degree of agitation to which the parenteral was subjected prior to examination.     

International interlaboratory comparison of lead and cadmium determination in samples of suspended particulate matter

Equal parts of six real samples of suspended particulate matter were analysed for lead and cadmium by laboratories in three different countries. The results agreed very well. The agreement is encouraging considering queries that arise when results in international projects are compared.     

Acute mucocutaneous toxicity following high-dose hydroxyurea

Three patients with advanced acute myeloid leukemia were treated with oral high-dose hydroxyurea at a dose of 10 g daily for 8-10 days. Severe acute stomatitis developed in all three patients. In addition, two of the patients developed a peculiar acute cutaneous type of toxicity associated with soreness, violet erythema, and edema of the palms and foot soles followed by intense universal hyperpigmentation of the skin. Apparently, the pronounced acute mucocutaneous toxicity was caused by the sustained high daily dose of hydroxyurea, indicating that myelosuppression may not be the dose-limiting toxicity of this drug.     

铁矿烧结过程微细颗粒物排放行为

 采用ELPI+设备(荷电低压撞击器)对铁矿烧结过程微细颗粒物进行在线检测与采样,利用场发射扫描电子显微镜(FESEM EDS)对采集的颗粒物形貌特征进行分析,研究铁矿烧结过程中微细颗粒物的排放行为。研究结果表明,PM10大量释放集中在烧结升温段,且颗粒物质量浓度与数目浓度在粒径分布上有较大差异,其中质量浓度峰值区间为5.37～10.00 μm,数目浓度峰值区间为0.10～0.16 μm;形貌特征上,微细颗粒物呈规则的球形、方块形和片状;不同粒径物质组成差异明显,其中颗粒物中的K、Na主要以KCl和NaCl的形式存在,含量随颗粒物粒级的增大而略有降低。