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A case-control study of lung cancer with special reference to the effect of air pollution in Poland.

STUDY OBJECTIVE: The aim of the study was to assess the affect of inhaled pollutants on lung cancer risk. DESIGN: The study was a retrospective case-control survey of lung cancer deaths over a six year period (1980-1985). Information on occupation, smoking habits, and residency was collected from next of kin. Classification of exposure to community air pollution was based on measured levels of total suspended particular matter and sulphur dioxide. SETTING: Cases and controls had been resident in the city of Cracow, Poland. PARTICIPANTS: Cases were male (n = 901, questionnaire response rate 70.7%) and female (n = 198, response rate 65.1%) lung cancer deaths; controls were deaths from other causes, excluding other respiratory diseases, and frequency matched by age and sex (males n = 875, response rate 73.5%; females n = 198, response rate 64.0%). MAIN RESULTS: Lung cancer risk was found to depend strongly on total cigarette consumption, on age at starting to smoke, and on time since stopping smoking. Relative risk estimates for occupational exposure in iron and steel foundries or in other industries were significantly increased in males. Relative risk in men for highest air pollution level was 1.48 (95% confidence interval 1.08-2.01), while in women the increase was not significant. The joint action of the risk facts of smoking, occupational exposure, and air pollution was found to fit almost perfectly into a multiplicative model. CONCLUSIONS: Under conditions found in Cracow, air pollution may increase lung cancer risk, acting multiplicatively with known risk factors such as smoking and industrial exposure.

Adolescent↗

The effects of severe mixed environmental pollution on human chromosomes.

Cytogenetic studies were conducted on healthy young mothers, shortly after child birth, in two residential areas each with an approximate population of 20,000, situated about 25 km from Athens, Greece. One of the areas, Elefsis, is subject to severe mixed industrial pollution, and the other, Koropi, is relatively free of pollution. Chromosomal aberrations were investigated in 16 women from each area in 72 hour lymphocyte cultures treated with gentian violet to enhance any chromosomal instability induced by the pollution. The women were of a comparable socioeconomic level, aged between 20 and 31 years, and with no history of factors associated with mutagenesis. Venous blood samples were taken from the two groups and processed concurrently. The slides were coded and examined independently by two observers, who were unaware of the source of the samples. A total of 100 cells was examined on each sample. The two observers obtained highly comparable results. Women from Elefsis had an average of 0.42 anomalies per cell and those from Koropi had 0.39. The absence of a statistically significant difference between the two groups clearly shows that the severe mixed environmental pollution of Elefsis has no significant visible effect on human chromosomes in most residents. However, two Elefsis women had abnormal results and could be at risk. Their presence is not sufficient to raise significantly their group's average, but the induction by pollution of an increased rate of chromosomal anomalies in only a few people at risk could account for the known association between urban residence and cancer mortality.

Adult↗

Impact of ambient air pollution on birth weight in Sydney, Australia.

BACKGROUND: Studies in Asia, Europe, and the Americas have provided evidence that ambient air pollution may have an adverse effect on birth weight, although results are not consistent. METHODS: Average exposure during pregnancy to five common air pollutants was estimated for births in metropolitan Sydney between 1998 and 2000. The effects of pollutant exposure in the first, second, and third trimesters of pregnancy on risk of "small for gestational age" (SGA), and of pollutant exposure during pregnancy on birth weight were examined. RESULTS: There were 138,056 singleton births in Sydney between 1998 and 2000; 9.7% of babies (13,402) were classified as SGA. Air pollution levels in Sydney were found to be quite low. In linear regression models carbon monoxide and nitrogen dioxide concentrations in the second and third trimesters had a statistically significant adverse effect on birth weight. For a 1 part per million increase in mean carbon monoxide levels a reduction of 7 (95% CI -5 to 19) to 29 (95% CI 7 to 51) grams in birth weight was estimated. For a 1 part per billion increase in mean nitrogen dioxide levels a reduction of 1 (95% CI 0 to 2) to 34 (95% CI 24 to 43) grams in birth weight was estimated. Particulate matter (diameter less than ten microns) in the second trimester had a small statistically significant adverse effect on birth weight. For a 1 microgram per cubic metre increase in mean particulate matter levels a reduction of 4 grams (95% CI 3 to 6) in birth weight was estimated. CONCLUSION: These findings of an association between carbon monoxide, nitrogen dioxide, and particulate matter, and reduction in birth weight should be corroborated by further study.

Air Pollutants↗

Respiratory cancer and air pollution from iron foundries in a Scottish town: an epidemiological and environmental study.

A geographical association between respiratory cancer and air pollution from steel foundries has been shown previously in Scotland and elsewhere. In the present study the iron-founding town of Kirkintilloch was found to have standardised mortality ratios (SMRs) for respiratory cancer in 1959-63, 1964-8, and 1969-73 that were unexceptional in comparison with Scotland. Nevertheless, when SMRs were calculated for respiratory cancer for the period 1966-76 in five zones of the town arranged, a priori, according to probable exposure to fumes from two iron foundries, and in the individual enumeration districts of the 1971 census, higher SMRs were found in the residential areas most exposed to pollution from the foundries. The gradient of the zones' SMRs--high close to the foundries to low at some distance from them--persisted despite standardisation of the SMRs for social class. A survey of the concentrations of several metals in soil cores sampled at 51 sites throughout the town showed a pattern of pollution that probably illustrated the effects of prevailing winds and topography on the pollution plumes from the foundries. The value of sampling soil cores in investigations where historical sources of metallic air pollution are of epidemiological interest was emphasised by the detection of high concentrations of Ni in an area where a nickel refinery had been located many decades previously.

Aged↗

Daily time series for cardiovascular hospital admissions and previous day's air pollution in London, UK.

OBJECTIVE: To test for a significant association between air pollution and emergency hospital admissions for circulatory diseases (international classification of diseases-9 390-459) in London, England, that would be consistent with a causal effect of pollution on the previous day. METHODS: Long term concurrent trends, temperature, humidity, day of the week, influenza epidemic of 1989, and cyclical covariations with periodicity > 20 days in daily measures of pollution and admissions for 1987-94 were allowed for. RESULTS: There were 373556 admissions. No association was found between O3 and circulatory diseases. Four other pollutants were associated with acute myocardial infarction and circulatory diseases combined. P values and attributable cases (95% confidence intervals) for acute myocardial infarction were: black smoke P = 0.003, 2.5% (0.8% to 4.3%); NO2 P = 0.002, 2.7% (0.8% to 4.6%); CO P = 0.001, 2.1% (0.7% to 3.5%); and SO2 P = 0.0006, 1.7% (0.7% to 2.6%). There were also associations between black smoke and angina (P = 0.02), NO2 and arrhythmia (P = 0.04), and CO and other circulatory diseases (P = 0.004), but none with heart failure. Acute myocardial infarction was the only diagnosis for which there were significant associations with and without adjustment for cyclical terms. The associations with acute myocardial infarction were significant only in the cool season. CONCLUSION: Population data were consistent with 1 in 50 heart attacks currently presenting at London hospitals being triggered by outdoor air pollution. Further research is now needed to investigate whether background concentrations of black smoke, NO2, CO, and SO2 are a preventable cause of myocardial infarction. These results, if applied to all myocardial infarctions in the United Kingdom, indicate a potential saving of 6000 heart attacks a year.

Air Pollutants↗

Indoor air pollution in developing countries and acute lower respiratory infections in children.

BACKGROUND: A critical review was conducted of the quantitative literature linking indoor air pollution from household use of biomass fuels with acute respiratory infections in young children, which is focused on, but not confined to, acute lower respiratory infection and pneumonia in children under two years in less developed countries. Biomass in the form of wood, crop residues, and animal dung is used in more than two fifths of the world's households as the principal fuel. METHODS: Medline and other electronic databases were used, but it was also necessary to secure literature from colleagues in less developed countries where not all publications are yet internationally indexed. RESULTS: The studies of indoor air pollution from household biomass fuels are reasonably consistent and, as a group, show a strong significant increase in risk for exposed young children compared with those living in households using cleaner fuels or being otherwise less exposed. Not all studies were able to adjust for confounders, but most of those that did so found that strong and significant risks remained. CONCLUSIONS: It seems that the relative risks are likely to be significant for the exposures considered here. Since acute lower respiratory infection is the chief cause of death in children in less developed countries, and exacts a larger burden of disease than any other disease category for the world population, even small additional risks due to such a ubiquitous exposure as air pollution have important public health implications. In the case of indoor air pollution in households using biomass fuels, the risks also seem to be fairly strong, presumably because of the high daily concentrations of pollutants found in such settings and the large amount of time young children spend with their mothers doing household cooking. Given the large vulnerable populations at risk, there is an urgent need to conduct randomised trials to increase confidence in the cause-effect relationship, to quantify the risk more precisely, to determine the degree of reduction in exposure required to significantly improve health, and to establish the effectiveness of interventions.

Acute Disease↗

Effects of air pollution and weather conditions on asthma exacerbation.

BACKGROUND: Meteorological conditions and a high concentration of air pollutants have been associated with increased respiratory morbidity. However, few studies have examined the association between asthma exacerbation and air pollution. OBJECTIVES: In the present study, the possible relationship of the concentration of black smoke and SO2 in the air, the local weather conditions and emergency room visits for asthma is investigated. METHODS: The weekly total of emergency room admissions for asthmatic adults during a 1-year period was recorded together with daily metereological conditions (average temperature, humidity, rainfall, wind speed and barometric pressure) and average weekly levels of daily pollutant concentrations (black smoke and SO2). The relationship was assessed by stepwise regression linear models and analysis of variance. The analysis took into account season and metereological variables. RESULTS: Both air pollutants correlated significantly with emergency room admissions for asthma (SO2 [r = 0. 32], black smoke [r = 0.35]); however, multiple regression analysis showed that black smoke was the only significant predictor of weekly visits. There were approximately 3.5 admissions a week per SD of change (34.6 microg.m-3). There were no significant correlations between weekly emergency room visits and the weather variables. Analysis of the data stratified by season and weather conditions demonstrated that the association of black smoke with asthma exacerbation was more pronounced in autumn (r = 0.67) or when temperatures were higher than average. CONCLUSION: In our city, a high concentration of certain air pollutants is indeed associated with an increase in the number of hospital emergency room admissions for asthma.

Adolescent↗

Acute effect of air pollution on respiratory complaints, exhaled NO and biomarkers in nasal lavages of allergic children during the pollen season.

During 2 months of the pollen season, the acute and putative adjuvant effect of traffic-related air pollution on respiratory health was investigated in children sensitised to grass pollen or house dust mite (HDM). Respiratory complaints were objectified via measurement of exhaled NO and inflammatory mediators in nasal lavage (NAL). During the study children, skin prick negative (n = 31) or positive to grass pollen (n = 22), HDM (n = 34) or grass pollen + HDM (n = 32), kept a daily diary on respiratory symptoms, and NAL and exhaled air was sampled twice a week. The level of air pollutants and pollen was monitored continuously. Like children sensitised to HDM, those sensitised to pollen reported respiratory complaints (shortness of breath, itchy eyes or blocked nose) more frequently than non-sensitised children during (but not before) the pollen season; the respiratory complaints of sensitised children were independent of the pollen level. In addition, exposure to increased levels of PM(10) induces 'shortness of breath' in pollen- and HDM-sensitised children, whereas ozone induces a blocked nose in HDM-sensitised children. Combined exposure to PM(10) + pollen and O(3) + pollen induces a blocked nose in both HDM-sensitised children and children sensitised to pollen + HDM. Significant positive associations were found between eNO and the levels of NO(2), CO, PM(2.5) and pollen in both sensitised and non-sensitised children. At the start of the pollen season, the NAL concentration of eosinophils and ECP in pollen-sensitised children was increased compared to winter, but their levels were not further affected by increased exposure to pollen or air pollution. In conclusion, during the pollen season, sensitised children continuously report a high prevalence of respiratory complaints which coincides with increased levels of upper and lower airway inflammatory markers. No additional pro-inflammatory effect of air pollution was observed, which indicates that air pollution does not facilitate allergen-induced inflammatory responses.

Air Pollution↗

Bronchial hyperreactivity and arterial carboxyhemoglobin as detectors of air pollution in Milan: a study on normal subjects.

Research has been carried out in the town area of Milan on 275 subjects. For each patient the following data have been measured: ventilatory profile, aspecific bronchial reactivity, arterial concentration in CO and acid-base balance. The results obtained have been divided into four groups, according to the level of SO2 in the area of residence of the subjects, who have also been studied with reference to the habit of smoking. The data obtained have shown (1) an alteration of the ventilatory function, with decrease of oxygen tension in arterial blood in all subjects. (2) Increase of bronchial irritability and CO concentration in arterial blood have been found in these subjects, with rates higher than those established by the WHO (1.5-1.7). (3) The division of our results according to the level of SO2 pollution in the areas of residence of the patients showed the presence, in the most polluted areas of Milan (NE and SW), of higher levels of bronchial irritability and higher CO rates in arterial blood. (4) Cigarette smoking does not seem to play a major role in causing bronchial irritability. It certainly increases CO concentration: smokers have HbCO concentration higher than nonsmokers in all four areas. (5) Air pollution is more important than cigarette smoking in determining CO saturation of blood. Nonsmokers living in the most polluted areas of Milan (NE) show a higher concentration of CO in arterial blood than smokers living in the less polluted areas (SW).

Adult↗

Ozone air pollution is associated with acute myocardial infarction.

BACKGROUND: Despite the diversity of the studied health outcomes, types and levels of pollution, and various environmental settings, there is substantial evidence for a positive link between urban air pollution and cardiovascular diseases. The objective of this study was to test the associations between air pollutants and the occurrence of acute myocardial infarction (AMI). METHODS AND RESULTS: Pollutant concentrations (SO2, NO2, and O3) were measured hourly as part of the automated air quality network. Since 1985, an AMI registry (the Toulouse MONICA Project) has been collecting data in the southwest of France. All cases of AMI and sudden and probable cardiac deaths are recorded for subjects 35 to 64 years of age. We studied the short-term exposure effect of pollution on the risk of AMI (from January 1, 1997, to June 30, 1999) using a case-crossover design method. We performed a conditional logistic regression analysis to calculate relative risks (RRs) and their 95% CIs. After adjustment for temperature, relative humidity, and influenza epidemics, the RRs (for an increase of 5 microg/m3 of O3 concentration) for AMI occurrence were significant for the current-day and 1-day-lag measurements (RR, 1.05; 95% CI, 1.01 to 1.08; P=0.009; and RR, 1.05; 95% CI, 1.01 to 1.09; P=0.007, respectively). Subjects 55 to 64 years of age with no personal history of ischemic heart disease were the most susceptible to develop an AMI (RR, 1.14; 95% CI, 1.06 to 1.23). NO2 and SO2 exposures were not significantly associated with the occurrence of AMI. CONCLUSIONS: Observational data confirm that short-term O3 exposure within a period of 1 to 2 days is related to acute coronary events in middle-aged adults without heart disease, whereas NO2 and SO2 are not.

Adult↗

Summertime haze air pollution and children with asthma.

In order to investigate associations between summertime haze air pollution and asthma at an individual level, 52, 58, and 56 children (ages 7 to 13) attending a summer "asthma camp" were followed during the last week of June in 1991, 1992, and 1993, respectively. Most of the subjects had moderate to severe asthma. Daily records were kept of the environmental conditions, as well as of subject medication use, lung function, and medical symptoms. Air pollution was found to be significantly and consistently correlated with acute asthma exacerbations, chest symptoms, and lung function decrements. The pollutant most consistently associated with adverse health consequences was ozone (O3), although associations with sulfates and hydrogen ion suggest a possible role by fine particles as well. Effects were found to be roughly monotonic as a function of O3 concentration. Regression of morning (8:00 A.M.) to afternoon (5:00 P.M.) peak flow change on O3 indicated pulmonary function reductions similar to those previously reported for more active children without asthma. Moreover, analyses also indicated an increased risk of an asthma exacerbation and of experiencing chest symptoms of approximately 40% on the highest pollution day, relative to the mean. Based on these relative risk estimates, a rise in the 1-h daily maximal O3 from 84 ppb to 160 ppb was associated in this group with an increase from 20 to 28 (+/- 2) in the expected number of unscheduled medications administered/day, and from 29 to 41 (+/- 3) in the expected total number of chest symptoms/day. Thus, air pollution can be a major contributor to the respiratory problems experienced by children with asthma during the summer months.

Adolescent↗

Long-term ambient air pollution and respiratory symptoms in adults (SAPALDIA study). The SAPALDIA Team.

The association between long-term exposure to ambient air pollution and respiratory symptoms was investigated in a cross-sectional study in random population samples of adults (aged 18 to 60 yr, n = 9,651) at eight study sites in Switzerland. Information on respiratory symptoms was obtained with an extended version of the European Community Respiratory Health Survey questionnaire. The impact of annual mean concentrations of air pollutants was analyzed separately for never-, former, and current smokers. After controlling for age, body mass index, gender, parental asthma, parental atopy, low education, and foreign citizenship, we found positive associations between annual mean concentrations of NO2, total suspended particulates, and particulates of less than 10 micrometers in aerodynamic diameter (PM10) and reported prevalences of chronic phlegm production, chronic cough or phlegm production, breathlessness at rest during the day, breathlessness during the day or at night, and dyspnea on exertion. We found no associations with wheezing without cold, current asthma, chest tightness, or chronic cough. Among never-smokers, the odds ratio (95% confidence interval) for a 10 micrograms/ m3 increase in the annual mean concentration of PM10 was 1. 35 (1.11 to 1.65) for chronic phlegm production, 1.27 (1.08 to 1.50) for chronic cough or phlegm production, 1.48 (1.23 to 1.78) for breathlessness during the day, 1.33 (1.14 to 1.55) for breathlessness during the day or at night, and 1.32 (1.18 to 1.46) for dyspnea on exertion. No associations were found with annual mean concentrations of O3. Similar associations were also found for former and current smokers, except for chronic phlegm production. The observed associations remained stable when further control was applied for environmental tobacco smoke exposure, past and current occupational exposures, atopy, and early childhood respiratory infections when restricting the analysis to long-term residents and to non- alpine areas, and when excluding subjects with physician-diagnosed asthma. The high correlation between the pollutants makes it difficult to sort out the effect of one single pollutant. This study provides further evidence that long-term exposure to air pollution of rather low levels is associated with higher prevalences of respiratory symptoms in adults.

Adolescent↗

Respiratory health and PM10 pollution. A daily time series analysis.

This study evaluated changes in respiratory health associated with daily changes in fine particulate pollution (PM10). Participants included a relatively healthy school-based sample of fourth and fifth grade elementary students, and a sample of patients with asthma 8 to 72 yr of age. Elevated PM10 pollution levels of 150 micrograms/m3 were associated with an approximately 3 to 6% decline in lung function as measured by peak expiratory flow (PEF). Current day and daily lagged associations between PM10 levels and PEF were observed. Elevated levels of PM10 pollution also were associated with increases in reported symptoms of respiratory disease and use of asthma medication. Associations between compromised respiratory health and elevated PM10 pollution were observed even when PM10 levels were well below the 24-h national ambient air quality standard of 150 micrograms/m3. Associations between elevated PM10 levels, reductions in PEF, and increases in symptoms of respiratory disease and asthma medication use remained statistically significant even when the only pollution episode that exceeded the standard was excluded. Concurrent measurements indicated that little or no strong particle acidity was present.

Adolescent↗

Effect of ambient winter air pollution on respiratory health of children with chronic respiratory symptoms.

The acute respiratory effects of ambient air pollution were studied in a panel of 73 children with chronic respiratory symptoms in the winter of 1990 to 1991. The participating children were selected from all children aged 6 to 12 yr in Wageningen and Bennekom, two small, nonindustrial towns in the east of the Netherlands. Peak flow was measured twice daily with MiniWright meters. A diary was used to register the occurrence of acute respiratory symptoms and medication use by the children. Exposure to air pollution was characterized by the ambient concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), black smoke (BS), and particulate matter less than 10 microns (PM10). Associations between air pollution concentrations and health outcomes were analyzed using time series analysis. During the study period an air pollution episode occurred, with moderately elevated concentrations of PM10 and SO2. There were 6 days with 24-h average PM10 concentrations in excess of the WHO suggested lowest observed effect level of 110 micrograms/m3. After adjustment for ambient temperature, there were small but statistically significant negative associations of PM10, BS, and SO2 with both morning and evening PEF. There was a consistent positive association between PM10, BS, and SO2 with the prevalence of wheeze and bronchodilator use. Overall, the observed associations suggest a mild to moderate response to these moderately elevated levels of air pollution in a group of potentially sensitive children.

Air Pollution↗

Air pollution from traffic and the development of respiratory infections and asthmatic and allergic symptoms in children.

Despite the important contribution of traffic sources to urban air quality, relatively few studies have evaluated the effects of traffic-related air pollution on health, such as its influence on the development of asthma and other childhood respiratory diseases. We examined the relationship between traffic-related air pollution and the development of asthmatic/allergic symptoms and respiratory infections in a birth cohort (n approximately 4,000) study in The Netherlands. A validated model was used to assign outdoor concentrations of traffic-related air pollutants (nitrogen dioxide, particulate matter less than 2.5 micro m in aerodynamic diameter, and "soot") at the home of each subject of the cohort. Questionnaire-derived data on wheezing, dry nighttime cough, ear, nose, and throat infections, skin rash, and physician-diagnosed asthma, bronchitis, influenza, and eczema at 2 years of age were analyzed in relation to air pollutants. Adjusted odds ratios for wheezing, physician-diagnosed asthma, ear/nose/throat infections, and flu/serious colds indicated positive associations with air pollutants, some of which reached borderline statistical significance. No associations were observed for the other health outcomes analyzed. Sensitivity analyses generally supported these results and suggested somewhat stronger associations with traffic, for asthma that was diagnosed before 1 year of age. These findings are subject to confirmation at older ages, when asthma can be more readily diagnosed.

Air Pollutants↗

Ambient air pollution and oxygen saturation.

We investigated the association between fine particulate air pollution and oxygen saturation as measured with a peripheral oxygen saturation monitor during a 12-week repeated-measures study of 28 older Boston residents. Oxygen saturation and air pollution particulates with a mean diameter less than or equal to 2.5 microm were measured continuously during a protocol of rest, standing, exercise, postexercise rest, and 20 cycles of slow, paced breathing. In fixed-effect models, mean pollution concentration was associated with reduced oxygen saturation during the baseline rest period (6 hours: mean, -0.173%; 95% confidence interval [CI], -0.345 to -0.001), postexercise (6 hours: mean, -0.173%; 95% CI, -0.332 to -0.014), with a trend toward decrease during postexercise paced breathing (6 hours: mean, -0.142%; 95% CI, -0.292 to 0.007) but not during exercise. Participants taking beta-blockers had a greater pollution-related decrease in oxygen saturation at rest (6 hours: mean, -0.769%; 95% CI, -1.210 to -0.327) (interaction for particulates with a mean diameter less than or equal to 2.5 microm by beta-blocker, p < 0.0005) than did those not taking beta-blockers (p > 0.25). The reduction in oxygen saturation associated with air pollution may result from subtle particulate-related pulmonary vascular and/or inflammatory changes. Further investigation may contribute to our understanding of the mechanisms through which particulates may increase respiratory and cardiac morbidity among vulnerable populations.

Adrenergic beta-Antagonists↗

Air pollution and child respiratory health: a case-crossover study in Australia and New Zealand.

RATIONALE: The strength of the association between outdoor air pollution and hospital admissions in children has not yet been well defined. OBJECTIVES: To estimate the impact of outdoor air pollution on respiratory morbidity in children after controlling for the confounding effects of weather, season, and other pollutants. METHODS: The study used data on respiratory hospital admissions in children (three age groups: < 1, 1-4, and 5-14 years) for five cities in Australia and two in New Zealand. Time series of daily numbers of hospital admissions were analyzed using the case-crossover method; the results from cities were combined using a random-effects meta-analysis. MEASUREMENTS AND MAIN RESULTS: Significant increases across the cities were observed for hospital admissions in children for pneumonia and acute bronchitis (0, 1-4 years), respiratory disease (0, 1-4, 5-14 years), and asthma (5-14 years). These increases were found for particulate matter with a diameter less than 2.5 microm (PM2.5) and less than 10 microm (PM10), nephelometry, NO2, and SO2. The largest association found was a 6.0% increase in asthma admissions (5-14 years) in relation to a 5.1-ppb increase in 24-hour NO2. CONCLUSIONS: This study found strong and consistent associations between outdoor air pollution and short-term increases in childhood hospital admissions. A number of different pollutants showed significant associations, and these were distinct from any temperature (warm or cool) effects.

Adolescent↗

Toxic interactions in the rat nose: pollutants from soiled bedding and methyl bromide.

Interactions between test chemicals and pollutants can confound toxicology studies. To test the sensitivity of the regenerating olfactory epithelium to additional challenge with the olfactory epithelial toxicant methyl bromide (MeBr), Fischer 344 (F344) rats received 2 6-hr inhalation exposures (separated by a 28-day recovery period) to either 0 or 175 ppm MeBr. The regenerating epithelium was resistant to the second MeBr exposure. In addition, histopathologic examination revealed squamous epithelial hyperplasia in the vestibule; inflammation, epithelial necrosis, mucosal erosions, and squamous metaplasia of the respiratory epithelium in the anterior nose; and olfactory sensory cell loss in the dorsal medial meatus. These changes could not be attributed to MeBr, but they were correlated with housing in filter-capped cages between MeBr exposures and were presumably caused by volatile pollutants from soiled bedding. Moreover, olfactory sensory cell loss in the dorsal medial meatus was associated with local resistance to MeBr-induced damage in rats with pollutant-induced changes. Analysis of cage air revealed a progressive increase in ammonia levels between bedding changes (up to 50 ppm), but exposure to 300 ppm ammonia in an additional experiment reproduced only the anterior nasal lesions and not olfactory sensory cell loss. This study demonstrates that 1) regenerating olfactory epithelium is refractory to further MeBr toxicity; 2) pollutants from soiled bedding (in addition to ammonia) produce nasal lesions; and 3) pollutant-induced changes modify the nasal response to inhaled MeBr.

Administration, Inhalation↗