Abstract:Micro-organisms are known to produce a range of volatile organic compounds, so-called microbial VOC (MVOC). Chamber studies where humans were exposed to MVOC addressed the acute effects of objective and/or subjective signs of mucosal irritation. However, the effect of MVOC on inhabitants due to household exposure is still unclear. The purpose of this epidemiological study was to measure indoor MVOC levels in single family homes and to evaluate the relationship between exposure to them and sick building syndrome (SBS). All inhabitants of the dwellings were given a self-administered questionnaire with standardized questions to assess their symptoms.Air samples were collected and the concentrations of eight selected compounds in indoor air were analyzed by gas chromatography/mass spectrometry -selective ion monitoring mode (GC/MS-SIM). The most frequently detected MVOC was 1-pentanol at a detection rate of 78.6% and geometric mean of 0.60 μg/m 3 . Among 620 participants, 120 (19.4%) reported one or more mucous symptoms; irritation of the eyes, nose, airway, or coughing every week (weekly symptoms), and 30 (4.8%) reported that the symptoms were home-related (home-related symptoms). Weekly symptoms were not associated with any of MVOC, whereas significant associations between home-related mucous symptoms and 1-octen-3-ol (per log 10 -unit: odds ratio (OR) 5.6, 95% confidence interval (CI): 2.1 to 14.8) and 2-pentanol (per log 10 -unit: OR 2.3, 95%CI: 1.0 to 4.9) were obtained after adjustment for gender, age, and smoking.Associations between home-related symptoms and 1-octen-3-ol remained after mutual adjustment. However, concentrations of the selected compounds in indoors were lower than the estimated safety level in animal studies. Thus, the statistically significant association between 1-octen-3-ol may be due to a direct effect of the compounds or the associations may be being associated with other offending compounds. Additional studies are needed to evaluate these possibilities.
Inhalation Carcinogenicity and ChronicToxicity of Indium-tin Oxide in Rats and Mice: Kasuke NagaNo, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health Association-Objectives: Carcinogenicity and chronic toxicity of indium-tin oxide (ITO) were examined by inhalation exposure of rats and mice to ITO aerosol. Methods: Fifty mice of both sexes were exposed to ITO at 0 (control), 0.01, 0.03 or 0.1 mg/m 3 for 6 h/day, 5 day/wk for 104 wk, and 50 rats of both sexes were exposed to 0, 0.01 or 0.03 mg/m 3 ITO for the same time period. The repeated exposure of 50 rats of both sexes to 0.1 mg/m 3 ITO was discontinued at the 26th wk, followed by clean air exposure for the remaining 78 wk. Results: In rats, incidences of bronchiolo-alveolar adenomas and carcinomas, bronchiolo-alveolar hyperplasia, alveolar wall fibrosis and thickened pleural wall, alveolar proteinosis and infiltrations of alveolar macrophages and inflammatory cells were significantly increased. Combined incidences of malignant lung tumors in male rats and total lung tumors in male and female rats were significantly increased at exposure to 0.01 mg/m 3 ITO. In mice, no carcinogenic response occurred, but thickened pleural wall, alveolar proteinosis and alveolar macrophage infiltration were induced. Mice were less susceptible to ITO than rats. The lung content of indium was the greatest, followed by the spleen, kidney and liver. Blood indium levels increased dosedependently. Conclusions: There was clear evidence of carcinogenicity of inhaled ITO in male and female rats but not clear evidence in mice, together with occurrence of the chronic pulmonary lesions in both rats and mice. (J Occup Health 2011; 53: 175-187)
Two-and 13-week Inhalation Toxicities of Indium-tin Oxide and Indium Oxide in Rats: Kasuke NagaNo, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health AssociationObjectives: Two-and 13-week inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) were characterized for risk assessments of workers exposed to ITO. Methods: F344 rats of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m 3 or 13 wk at 0, 0.1or 1 mg/m 3 . An aerosol generator and inhalation exposure system was constructed. Results: Blood and lung contents of indium were elevated in a dose-related manner in the ITO-and IO-exposed rats. ITO and IO particles were deposited in the lung, mediastinal lymph node and nasal-associated lymphoid tissue. Exposures to ITO and IO induced alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and alveolar epithelial hyperplasia in addition to increased lung weight. ITO affected the lung more severely than IO did. Fibrosis of alveolar wall developed and some of these lesions worsened at the end of the 26-week post-exposure period. Conclusions: Persistent pulmonary lesions including alveolar proteinosis and macrophage infiltration occurred after 2-and 13-week inhalation exposures of rats to ITO and IO. Fibrosis of alveolar wall developed later. These lesions occurred after ITO exposure at the same concentration as the current occupational exposure limit in the USA and at blood indium levels below the biological exposure index in Japan for indium. (J Occup Health 2011; 53: 51-63)
Microbial volatile organic compounds (MVOCs) are a type of VOCs produced by microorganisms. Exposure to 1-octen-3-ol, one of the known MVOCs, has been reported to reduce nasal patency and increase nasal lavage myeloperoxidase, eosinophil cationic proteins, and lysozymes in both experimental and field studies. We reported in a previous paper that 1-octen-3-ol exposure at home is associated with mucosal symptoms. In this study, our aim was to investigate the relationship between asthma and allergies and MVOC exposure in single-family homes. The subjects were 624 inhabitants of 182 detached houses in six regions of Japan. Air samples were collected using diffusive samplers, and the concentrations of eight selected MVOCs were analyzed using gas chromatography/mass spectrometry in selected-ion-monitoring mode. Each inhabitant of each of the dwellings was given a self-administered questionnaire. Among the 609 subjects who answered all of the questions about allergies, history of the medical treatment for asthma, atopic dermatitis, allergic rhinitis, and allergic conjunctivitis within the past two years was 4.8%, 9.9%, 18.2%, and 7.1 %, respectively. A significant association between 1-octen-3-ol (per log 10 unit) and allergic rhinitis odds ratio (OR): 4.10, 95% confidence interval (CI): 1.71 to 9.80 and conjunctivitis (OR: 3.54, CI: 1.17 to 10.7) was found after adjusting for age, sex, environmental-tobacco-smoke exposure, wall-to-wall carpeting in the home, signs of dampness, history of treatment for hay fever, and other potentially relevant environmental factors. No relationships were found between any MVOCs and asthma or atopic dermatitis after the adjustment. The levels of MVOCs and airborne fungi were only weakly correlated. These results are consistent with previous studies that have associated higher levels of 1-octen-3-ol exposure with increased irritation of nasal 4 and ocular mucosae. Although the indoor-air concentrations of 1-octen-3-ol found in this study were relatively low, we conclude that exposure to MVOC may be related to rhinitis and conjunctivitis.
Pulmonary Toxicity in Mice by 2-and 13-week Inhalation Exposures to Indium-tin Oxide and Indium Oxide Aerosols: Kasuke NagaNo, et al., Japan Bioassay Research Center, Japan Industrial Safety and Health Association-Objectives: Inhalation toxicities of indium-tin oxide (ITO) and indium oxide (IO) in mice were characterized in comparison with those previously reported in rats. Methods: B6C3F 1 mice of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m 3 or 13 wk at 0, 0.1or 1 mg/m 3 . Results: ITO and IO particles were deposited in the lung, mediastinal lymph node (MLN) and nasalassociated lymphoid tissue. Alveolar proteinosis, infiltrations of alveolar macrophages and inflammatory cells and increased lung weight were induced by 2-and 13-week exposures to ITO and IO, while alveolar epithelial hyperplasia occurred only in the 2-week exposures. Thickened pleural wall, hyperplastic MLN, extramedullary hematopoiesis in the spleen and increased levels of erythrocyte parameters were induced by 13-week exposure to ITO. The ITO-and IO-induced pulmonary lesions were milder in mice than those previously reported in rats, and the fibrotic lesions were different between these two species. Indium levels in the lung and pooled blood were analyzed in the mice exposed to ITO and IO for 13 wk. In the 13-week inhalation exposure of mice to ITO, alveolar proteinosis and significantly increased lung weight were induced at the same exposure concentration as the current threshold limit value for indium and its compounds. (J Occup Health 2011; 53: 234-239)
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