Tomoko Takigawa

Effects of Glutaraldehyde Exposure on Human Health

Effects of Glutaraldehyde Exposure on Human Health: Tomoko Takigawa, et al. Department of Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences—Glutaraldehyde (GA) is widely used in the industrial, scientific and biomedical fields. Many adverse health effects on humans have been reported in association with biomedical uses of GA, with 2–3.5% aqueous GA solution generally used for cold sterilization and GA exposure ranges of 0.001 to 2.6 ppm for this type of use. GA is metabolized extensively to CO2, but urinary excretion of it is low. Sensory irritant effects, sensitization of skin and respiratory organs and other symptoms have been reported among endoscopy nurses and medical radiation technologists. The prevalence of chronic bronchitis and nasal symptoms in humans is significantly correlated with peak concentrations of GA exposure. The extent of primary skin irritation depends on the duration and site of contact, and the severity of symptoms is dose‐related. Chronic inhalation affects the nose and respiratory tract, and lesions become severe with prolonged duration of exposure. Increases in neither mortality nor tumor incidence have been found in workers with less than 0.2 ppm GA exposure, no evidence of carcinogenic activity has been obtained in experimental animal studies. There has been no clear evidence of genetic toxicity of GA in either in vitro or in vivo studies, and neither developmental nor reproductive toxicity has been found in humans or animals. To prevent hazards from GA exposure, use of closed‐system, fully automated washing machines is recommended, since numerous symptoms have been found in individuals with less than 0.05 ppm GA exposure, the recommended peak exposure limit in many countries.

Oxidative stress biomarkers and lifestyles in Japanese healthy people

The urinary concentrations of 8-isoprostane and 8-hydroxy-2’-deoxyguanosine (8-OHdG), which are biomarkers of oxidative stress, were measured in 677 Japanese people without any diseases, and their correlations with lifestyle facotrs, lifestyle-related blood biochemical parameters, and dietary intake of antioxidative vitamins were investigated. The mean urinary concentration of 8-isoprostane and 8-OHdG was 0.58 ng/mg creatinine and 8.43 ng/mg creatinine, respectively. Mean urinary 8-isoprostane was significantly different in terms of age, gender, smoking and alcohol consumption but not different in terms of body mass index (BMI) and exercise. By multiple regression analysis, urinary 8-isoprostane was significantly influenced by smoking and age. On the other hand, mean urinary 8-OHdG showed differences only by age group. Multiple regression analysis revealed that urinary 8-OHdG was significantly influenced by age, smoking, body weight, levels of high-sensitivity C-reactive protein (Hs-CRP) and low density lipoprotein-cholesterol in females, although it was significantly influenced by body weight in males. The present study shows that urinary 8-isoprostane is associated with lipid peroxidation related-lifestyles such as smoking, and urinary 8-OHdG is associated with arteriosclerosis related-factors such as Hs-CRP. Our findings suggest that 8-isoprostane and 8-OHdG appear to be prospective biomarkers for early prediction of lifestyle related-disease risk at the population level.

Relationship between selected indoor volatile organic compounds, so-called microbial VOC, and the prevalence of mucous membrane symptoms in single family homes

Microorganisms 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 microg/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.

Relationship between indoor chemical concentrations and subjective symptoms associated with sick building syndrome in newly built houses in Japan

ObjectivesThis study explored possible associations between chemical substances and sick building syndrome (SBS)-type symptoms of residents living in new houses in Japan.MethodsWe randomly sampled 5,709 newly built conventional homes. In the end, 1,479 residents in 425 households completed a questionnaire survey and agreed to environmental monitoring for indoor aldehydes and volatile organic compounds (VOCs) to be conducted in their homes. If the residents had complained about at least one SBS-related symptom, they were classified as suffering from SBS. Multiple logistic regression analysis was used to select predictive chemical factors of SBS symptoms.ResultsAbout 14% of the subjects suffered from SBS. Many aldehydes and VOCs were associated factors of optical, nasal, and gular symptoms in univariate analysis. After adjustment for other possible risk factors, formaldehyde dose-dependently showed to be a significant risk factor for SBS. Several chemicals had tendency to be associated with SBS symptoms.ConclusionsChemicals detected in Japanese newly built houses tend to increase the risk of subjective symptoms in residents suffering from SBS.

Exposure to house dust phthalates in relation to asthma and allergies in both children and adults.

Although an association between exposure to phthalates in house dust and childhood asthma or allergies has been reported in recent years, there have been no reports of these associations focusing on both adults and children. We aimed to investigate the relationships between phthalate levels in Japanese dwellings and the prevalence of asthma and allergies in both children and adult inhabitants in a cross-sectional study. The levels of seven phthalates in floor dust and multi-surface dust in 156 single-family homes were measured. According to a self-reported questionnaire, the prevalence of bronchial asthma, allergic rhinitis, allergic conjunctivitis, and atopic dermatitis in the 2 years preceding the study was 4.7%, 18.6%, 7.6%, and 10.3%, respectively. After evaluating the interaction effects of age and exposure categories with generalized liner mixed models, interaction effects were obtained for DiNP and bronchial asthma in adults (Pinteraction=0.028) and for DMP and allergic rhinitis in children (Pinteraction=0.015). Although not statistically significant, children had higher ORs of allergic rhinitis for DiNP, allergic conjunctivitis for DEHP, and atopic dermatitis for DiBP and BBzP than adults, and liner associations were observed (Ptrend<0.05). On the other hand, adults had a higher OR for atopic dermatitis and DEHP compared to children. No significant associations were found in phthalates levels collected from multi-surfaces. This study suggests that the levels of DMP, DEHP, DiBP, and BBzP in floor dust were associated with the prevalence of allergic rhinitis, conjunctivitis, and atopic dermatitis in children, and children are more vulnerable to phthalate exposure via household floor dust than are adults. The results from this study were shown by cross-sectional nature of the analyses and elaborate assessments for metabolism of phthalates were not considered. Further studies are needed to advance our understanding of phthalate toxicity.

The relationship between exposure to microbial volatile organic compound and allergy prevalence in single-family homes.

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 preceding 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, tobacco, wall-to-wall carpeting, 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 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.

A longitudinal study of environmental risk factors for subjective symptoms associated with sick building syndrome in new dwellings.

This study was performed to explore possible environmental risk factors, including indoor chemicals, mold, and dust mite allergens, which could cause sick building syndrome (SBS)-type symptoms in new houses. The study was conducted in 2004 and 2005 and the final study population consisted of 86 men and 84 women residing in Okayama, Japan. The indoor concentrations of indoor aldehydes, volatile organic compounds, airborne fungi, and dust mite allergens in their living rooms were measured and the longitudinal changes in two consecutive years were calculated. A standardized questionnaire was used concomitantly to gather information on frequency of SBS-type symptoms and lifestyle habits. About 10% of the subjects suffered from SBS in the both years. Crude analyses indicated tendencies for aldehyde levels to increase frequently and markedly in the newly diseased and ongoing SBS groups. Among the chemical factors and molds examined, increases in benzene and in Aspergillus contributed to the occurrence of SBS in the logistic regression model. Indoor chemicals were the main contributors to subjective symptoms associated with SBS. A preventive strategy designed to lower exposure to indoor chemicals may be able to counter the occurrence of SBS.

A longitudinal study of aldehydes and volatile organic compounds associated with subjective symptoms related to sick building syndrome in new dwellings in Japan

To determine whether indoor chemicals act as possible environmental risk factors responsible for sick building syndrome (SBS)-related symptoms in new houses (<6 years old) in Japan, we studied 871 people living in 260 single-family houses in 2004 and 2005. We measured the indoor concentrations of aldehydes and volatile organic compounds and longitudinal changes in the living rooms over two consecutive years. Participants answered standardized questionnaires on SBS symptoms and lifestyle habits. Approximately 14% and 12% of subjects were identified as having SBS in the first and second year, respectively. According to analysis adjusted for sex, age, smoking, and allergic diseases, increases in aldehydes and aliphatic hydrocarbons contributed to the occurrence of SBS. Elevated levels of indoor aldehydes and aliphatic hydrocarbons increased the possible risk of SBS in residents living in new houses, indicating that source controls against indoor chemicals are needed to counter SBS.

Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model

The expression of arginase I has been a focus of research into the pathogenesis of experimental asthma, because arginase deprives nitric oxide synthase (NOS) of arginine and therefore participates in the attenuation of bronchodilators such as nitric oxide (NO). The present study used an intranasal mite-induced NC/Nga mouse model of asthma to investigate the contribution of arginase to the asthma pathogenesis, using an arginase inhibitor, N(omega)-hydroxy-nor-l-arginine (nor-NOHA). The treatment with nor-NOHA inhibited the increase in airway hyperresponsiveness (AHR) and the number of eosinophils in bronchoalveolar lavage fluid. NOx levels in the lung were elevated despite suppressed NOS2 mRNA expression. Accompanied by the attenuated activity of arginase, the expression of arginase I at both the mRNA and protein level was downregulated. The levels of mRNA for T helper 2 cytokines such as IL-4, IL-5, and IL-13, and for chemotactants such as eotaxin-1 and eotaxin-2, were reduced. Moreover, the accumulation of inflammatory cells and the ratio of goblet cells in the bronchiole were decreased. The study concluded that the depletion of NO caused by arginase contributes to AHR and inflammation, and direct administration of an arginase inhibitor to the airway may be beneficial and could be of use in treating asthma due to its anti-inflammatory and airway-relaxing effects, although it is not clear whether the anti-inflammatory effect is direct or indirect.

Effect of sports activity on bone mineral density in wheelchair athletes

The present study carried out a measurement of body composition and a nutrition survey, targeting 28 male wheelchair athletes and comparing them with 25 male physically able healthy athletes as the controls. The DXA method was used to measure bone mineral density (BMD), percentage of body fat (% body fat), and lean body mass (LBM). Possible factors affecting the BMD of the wheelchair athletes with spinal injuries were analyzed including age, body part, type of sport, area of injury, length of injury, and the length of time it took before restarting sports activity after injury. BMD in the arms, body trunk, legs, and entire body was measured. There were no significant differences in the BMD of the wheelchair athletes by age group (from 20 to 29, from 30 to 39, and 40 years and older), by sports (basketball, track and field, and tennis), and by area of injury (high and low paraplegia). BMD in the legs (r = −0.549, P < 0.01), body trunk (r = −0.414, P < 0.05), and entire body (r = −0.452, P < 0.05) of the wheelchair athletes was negatively correlated with the period since injury; however, no such a relationship was observed in the arms. In addition, the multiple regression analysis for BMD of each body region showed that the earlier the wheelchair athletes restarted sports after injury, the higher values the BMD of legs (r = −0.467, P < 0.05), body trunk (r = −0.469, P < 0.05), and entire body (r = −0.488, P < 0.05), independent of age and sports. The leg BMD of the wheelchair athletes was lower than that of the physically able athletes, with a BMD 76.5% of the controls. The present study suggests that restarting sports activity in a timely manner after treatment and rehabilitation for the injury is useful in preventing loss of BMD in wheelchair athletes and ultimately improving their quality of life.