Chemical intolerance: involvement of brain function and networks after exposure to extrinsic stimuli perceived as hazardous.

BACKGROUND: Chemical intolerance (CI) is a chronic condition characterized by recurring and severe symptoms triggered by exposure to low levels of odorous or pungent substances. The etiology of CI has been a controversial subject for a long time. The aim of this review is to summarize findings on the neurological processing of sensory information during and after exposure to low levels of odorous or pungent substances in individuals with CI, focusing on the brain function and networks. METHODS: Scientific studies on CI published between 2000 and 2019 in academic peer-reviewed journals were systematically searched using medical and scientific literature databases. Only peer-reviewed articles reporting original research from experimental human studies directly associated with CI, and involving related neurological responses or brain imaging after exposure to odorous or pungent substances (i.e., in chemical provocation tests), were considered. RESULTS: Forty-seven studies were found to be eligible for a full-text review. Twenty-three studies met the selection criteria and were included in this review. Evidence indicated that differences between subjects with CI and healthy controls were observed by brain imaging during and after exposure to odorous or pungent substances. Differences in brain imaging were also observed between initial exposure and after exposure to these substances. Neurological processing of sensory information after exposure to extrinsic stimuli in the limbic system and related cortices were altered in subjects with CI. A previous documentable exposure event was likely to be involved in this alteration. CONCLUSIONS: This review documents consistent evidence for the altered neurological processing of sensory information in individuals with CI. Further neurophysiological research exploring the processing of extrinsic stimuli and cognition of sensation through the limbic system and related cortices in CI, and the appearance of symptoms in individuals with CI, are required.

Assessment of inhalation exposure to indoor air pollutants: Screening for health risks of multiple pollutants in Japanese dwellings.

Over the past few decades, multiple low level indoor pollutants have been found in domestic dwellings. The types and concentrations of these indoor pollutants have not been consistent over time and have changed with alterations in lifestyle, the development of novel products used in housing, and the development of new measurement technologies. To clarify the highest risk pollutants for which health risks should be reduced, we conducted a health risk assessment of 49 indoor air pollutants measured in 602 houses during winter and summer from 2012 to 2014. Inhalation reference concentrations were determined, and the margins of exposure were estimated for each indoor pollutant from measured indoor air concentrations. Health risks due to ammonia and acidic gases, including formic acid, acetic acid, and hydrogen chloride, were also assessed. Overall, during both winter and summer, the highest risk pollutants were acrolein, nitrogen dioxide, benzene, formic acid, and hydrogen chloride. The health risks of propanal, acetaldehyde, and 1,4-dichlorobenzene were also high. Principal component analysis (PCA) suggested an independent principal component for 1,4-dichlorobenzene. The primary source of exposure to 1,4-dichlorobenzene in Japan is an indoor household insect repellent. The improvement of individual lifestyle and housing may be appropriate targets for reducing the risk associated with this compound. The provision of further information on the risk to consumers and promotion of changes in consumer consciousness are needed. PCA suggested that the health risks of indoor air pollutants are amalgamated into similar chemical families, such as aldehydes, aliphatic hydrocarbons, aromatic hydrocarbons, or acetic esters. Our results suggest that health-based guidelines or source control measures, based on these chemical families and similar health endpoints, are appropriate for reducing total health risk due to multiple low level indoor pollutants.

Assessment of cerebral blood flow in patients with multiple chemical sensitivity using near-infrared spectroscopy--recovery after olfactory stimulation: a case-control study.

OBJECTIVES: Multiple chemical sensitivity (MCS) is a chronic acquired disorder characterized by non-specific symptoms in multiple organ systems associated with exposure to odorous chemicals. We previously observed significant activations in the prefrontal cortex (PFC) during olfactory stimulation using several different odorants in patients with MCS by near-infrared spectroscopy (NIRS) imaging. We also observed that the patients with MCS did not adequately distinguish non-odorant in the late stage of the repeated olfactory stimulation test. The sensory recovery of the olfactory system in the patients with MCS may process odors differently from healthy subjects after olfactory stimulation. METHODS: We examined the recovery process of regional cerebral blood flow (rCBF) after olfactory stimulation in patients with MCS. NIRS imaging was performed in 6 patients with MCS and in 6 controls. The olfactory stimulation test was continuously repeated 10 times. The study also included a subjective assessment of the physical and psychological status and of the perception of irritating and hedonic odors. RESULTS: After olfactory stimulation, significant activations were observed in the PFC of patients with MCS on both the right and left sides compared with controls. The activations were specifically strong in the orbitofrontal cortex (OFC). Compared with controls, autonomic perception and feelings identification were poorer in patients with MCS. OFC is associated with stimuli response and the representation of preferences. CONCLUSIONS: These results suggest that a past strong exposure to hazardous chemicals activates the PFC during olfactory stimuli in patients with MCS, and a strong activation in the OFC remains after the stimuli.

Assessing the risk of Legionnaires' disease: the inhalation exposure model and the estimated risk in residential bathrooms.

Legionella are widely found in the built environment. Patients with Legionnaires' disease have been increasing in Japan; however, health risks from Legionella bacteria in the environment are not appropriately assessed. We performed a quantitative health risk assessment modeled on residential bathrooms in the Adachi outbreak area and estimated risk levels. The estimated risks in the Adachi outbreak approximately corresponded to the risk levels exponentially extrapolated into lower levels on the basis of infection and mortality rates calculated from actual outbreaks, suggesting that the model of Legionnaires' disease in residential bathrooms was adequate to predict disease risk for the evaluated outbreaks. Based on this model, the infection and mortality risk levels per year in 10 CFU/100 ml (100 CFU/L) of the Japanese water quality guideline value were approximately 10(-2) and 10(-5), respectively. However, acceptable risk levels of infection and mortality from Legionnaires' disease should be adjusted to approximately 10(-4) and 10(-7), respectively, per year. Therefore, a reference value of 0.1 CFU/100 ml (1 CFU/L) as a water quality guideline for Legionella bacteria is recommended. This value is occasionally less than the actual detection limit. Legionella levels in water system should be maintained as low as reasonably achievable (<1 CFU/L).

Methodology for setting risk-based concentrations of contaminants in soil and groundwater and application to a model contaminated site.

In Japan, environmental standards for contaminants in groundwater and in leachate from soil are set with the assumption that they are used for drinking water over a human lifetime. Where there is neither a well nor groundwater used for drinking, the standard is thus too severe. Therefore, remediation based on these standards incurs excessive effort and cost. In contrast, the environmental-assessment procedure used in the United States and the Netherlands considers the site conditions (land use, existing wells, etc.); however, a risk assessment is required for each site. Therefore, this study proposes a new framework for judging contamination in Japan by considering the merits of the environmental standards used and a method for risk assessment. The framework involves setting risk-based concentrations that are attainable remediation goals for contaminants in soil and groundwater. The framework was then applied to a model contaminated site for risk management, and the results are discussed regarding the effectiveness and applicability of the new methodology.

Polychlorinated dioxins, furans, and biphenyls in blood of children and adults living in a dioxin-contaminated area in Tokyo.

The soil of a residential area in Tokyo was found to contain dioxins, namely polychlorinated dioxins, furans, and dioxin-like biphenyls, the levels of which exceeded the environmental guideline [1,000 pg toxic equivalent (TEQ)/g] by up to 6.8 times. To assess the exposure levels of people living in this area and to study the possible relationship of blood dioxin concentrations of children with breast milk and/or formula feeding, a health survey was carried out in 2006, involving a total of 138 people, including 66 children aged 3-15 years, and blood dioxin concentrations and the characteristics and lifestyles of these people were analyzed. Mean ± standard error of the mean (SEM) of blood dioxin concentrations (pg/g-lipid) of group 1 (3-6 years old), group 2 (7-15 years old), and group 3 (≥16 years old) were 13 ± 1.9, 6.6 ± 0.65, and 10 ± 0.54, respectively. The congener/isomer profile of dioxins in blood samples differed markedly from that of the contaminated soil samples. According to the feeding mode of children, blood dioxin concentrations (pg/g-lipid) were 17 ± 2.9 for breast milk only, 7.4 ± 0.82 for both breast milk and formula, and 4.7 ± 1.1 for formula only, with a significant difference from one another. We conclude that people living in the dioxin-contaminated area are less likely to be exposed to excessive amounts of dioxins, and that blood dioxin concentrations of children aged 3-15 years seem to be strongly affected by breast feeding duration.

Potential factors affecting chronic chemical intolerance associated with constitutional predisposition or lifestyle and environment during childhood: From a six-year follow-up study.

OBJECTIVE: The Japanese chemical intolerance (JCI) study was conducted in January 2012 with a cohort of 7245 adults from population-based sampling. This study aimed to investigate the childhood constitutional and environmental factors involved in the development of chronic CI from the prospective cohort study. METHODS: In the cohort, 4683 persons were identified after six years. Self-reported questionnaires were administered to the subjects to obtain information on CI status; medical history; constitution, lifestyle, and housing environment during childhood; and recent psychosomatic states. We assessed the differences between individuals with persisting CI status during the follow-up (defined as chronic CI) and controls not having CI status during the follow-up. RESULTS: A total of 2500 individuals responded. Multiple logistic regression analyses revealed significant associations between chronic CI and motion sickness to car or bus and allergic conjunctivitis during childhood. Significant associations between a possible increased risk of CI and the existence of high-voltage power lines close to housing, the use of vinyl covering in wall material, the use of strong perfume by a family member, and the experience of stinky odor of paint or wax at elementary school were observed. However, the use of carpet in floor material and plaster coating in wall material was associated with a possible decreased risk of CI. CONCLUSIONS: Some potential constitutional predisposition from childhood, including inherent susceptibility in the autonomic nervous system may be involved in the development of CI.

[Nine-month observation of effects of SO2 on the respiratory system in child Miyakejima citizens].

BACKGROUND: Mt. Oyama on Miyakejima Island erupted in June 2000 and all Miyake village citizens were forced to evacuate the island in the September, due to continuous eruptions and emission of unsafe amounts of volcanic gas, mainly sulfur dioxide (SO2). Beginning in February 2005, residents returned to live on the island despite the fact that volcanic gas was still being emitted. OBJECTIVE: To examine changes in the respiratory systems of included children from February 2006 to November 2006. METHODS: The study population was 141 children who participated in health checkups in November 2006, including 33 SO2 hypersusceptible children who had a current or past history of asthma, obstructive lung function, current symptoms of whistling and wheezing, and/or deterioration of respiratory symptoms. Respiratory effects were evaluated by a questionnaire for respiratory symptoms and by spirometry. SO2 was monitored at 7 sampling points within inhabited areas, and the mean SO2 concentration from February 2005 to November 2006 was 0.031 ppm. The area was categorized into four areas by average SO2 concentration, namely, areas L, H-1, H-2, and H-3, where the average SO2 levels were 0.019, 0.026, 0.032, and 0.045 ppm, respectively. RESULTS: Compared to children in area L, the frequencies of "phlegm" and "irritation of the nose" were significantly greater in the children in areas H-2 and H-3. %FVC and %FEV1 in hypersusceptible children were significantly reduced in November 2006 as compared to February 2006 (P = 0.047, 0.027), though no reduction observed in normosusceptible children. CONCLUSION: Respiratory functions in hypersusceptible Miyakejima children may be affected by SO2 exposure, and further follow-up observation is necessary.

[Toxicity of formaldehyde exposure and the details of its control measures].

The indoor air quality guideline (0.08 ppm) for formaldehyde was set in 1997. Afterwards, the occupational indoor air quality guideline for workplace where formaldehyde was manufactured or treated (the specific workplace handling formaldehyde) was set at the value of 0.25 ppm. In addition, the Labor Standards Bureau of the Ministry of Health, Labor and Welfare, has done a risk-based evaluation by using risk assessment analysis, in order to prevent the adverse effect of certain chemical materials on workers' health. In the case of formaldehyde, the primary evaluation value was assumed to be 0.033 ppm that corresponded in carcinogenic risk level 10(-4) with adjusted level for workers. The secondary evaluation value was assumed to be 0.3 ppm which was the Threshold Limit Value-Ceiling (TLV-C) recommended by the American Conference of Governmental Industrial Hygienists. Working environment measurement ("A" measurement methods) and/or individual exposure monitoring of formaldehyde at 22 workshops, where workers were potentially exposed to formaldehyde, were performed. The working environmental level in 3 workshops and the individual exposure level of 14 workers exceeded the secondary evaluation value (0.3 ppm). The rule for preventing the impairment of workers' health caused by the specified chemical substances was then revised so that formaldehyde was controlled more strictly and was reclassified from the third group to the second group of specified chemical substances. In addition, the administrative level of formaldehyde was set to 0.1 ppm, because of around a half of TLV-C value. Medical students have exposed to about 0.55 ppm in average formaldehyde during anatomy practice in the investigation of Japanese Association of Anatomists, though the gross anatomy practice room does not receive the restriction of the administrative level of formaldehyde. It is preferable that the exposure concentration of formaldehyde to the medical students is 0.1 ppm or less because formaldehyde is an irritant gas and a sensitizing potential, and is also a human carcinogen.

Mesothelioma risk and environmental exposure to asbestos: past and future trends in Japan.

Although asbestos has been widely distributed in the environment, health risks due to general environmental exposure to asbestos have not been estimated. Future mesothelioma risk from environmental exposure to asbestos in Japan was estimated by comparing historical exposure data and mortality attributed to environmental exposure. We developed an equation to estimate environmentally-attributable mesothelioma based on the US Environmental Protection Agency's model for occupational mesothelioma mortality. Based on our calculations, mesothelioma risks per year of exposure will reach peak levels in 2033 and range from 4.8 x 10(-6) to 1.1 x 10(-5). The number of deaths is estimated to range from 542-1276 in 2033. The cumulative number of deaths will reach around 17,000-37,000 in the years 1970-2070. Our estimation of risk approximately corresponded to observed risks. Past and predicted future disease suggest the need for social and medical support in these areas.

Noise sensitivity and subjective health: questionnaire study conducted along trunk roads in Kusatsu, Japan.

A questionnaire study was conducted in a residential area along trunk roads in Kusatsu, Japan, in order to investigate the association between noise exposure, noise sensitivity, and subjective health. Subjective health of the respondents was measured by the General Health Questionnaire (GHQ-28) which yields the total score as an index of psychiatric disorder and four subscales. Noise sensitivity was measured by the improved version of the Weinstein's noise sensitivity scale named WNS-6B. The original WNS and a single question directly asking respondents' noise sensitivity were also applied to confirm the validity of the WNS-6B for investigating the effects of road traffic noise on subjective health. Respondents were also asked about disturbances of daily life due to noise exposure to find the cause of the health effects. Three hundred and twenty three answers were entered into the analysis. Applying the WNS-6B as the noise sensitivity measurement scale, a significant correlation was found between subjective health and noise exposure in the noise-sensitive group, while no significant correlation was observed in the insensitive group. These results suggest that the adverse health effects may exist especially in the sensitive group. Application of the other two noise sensitivity measurement scales showed no significant relationship either in the sensitive group or in the insensitive group. The WNS-6B would have greater advantage for detecting adverse health effects than the other scales. Furthermore, the primary cause of the adverse health effect was investigated. The results of the analysis indicated that the adverse health effects were mainly caused by the sleep disturbance and were not caused by hearing interference.

Factors affecting self-reported chemical intolerance: A five-year follow-up study in Japan.

OBJECTIVE: Chemical intolerance (CI) has become a strong public health concern in industrialized countries. The Japanese Chemical Intolerance (JCI) study was conducted in January 2012 with a cohort of 7245 adults from population-based sampling as the baseline. The aim of the present study was to investigate the factors involved in the improvement and development of CI from the five-year follow-up study. METHODS: From the 7245 cohort, 735 persons with CI (case) were identified, and 1750 controls without CI were randomly selected to match gender and age for case and control groups. Self-reported questionnaires were administered to the subjects of the two groups to obtain information on status of CI; medical history; medical, lifestyle, or physical interventions; changes in living situation or occupation; and psychosomatic states. RESULTS: A total of 909 individuals responded during the follow-up period. After five years, improvement in CI was observed in 67.7% of the case group. Status of CI was reported in 6.7% of the control group. Multiple logistic regression analyses revealed that baseline atopic dermatitis and negative psychosomatic states including irritability, fatigue, anxiety, depressed mood, and somatic symptoms were significantly associated with development of CI in controls. Appropriate physical activity and maintaining a regular lifestyle including diet or sleep during the last three years of the follow-up period were significant factors for improvement of CI in the case group. CONCLUSIONS: Ensuring appropriate physical activity and regular lifestyle rather than improving physical environment lead to improvement of CI. Stable psychosomatic state is essential for preventing CI.

[Investigation of air pollution in a shopping center and employees' personal exposure level].

OBJECTIVES: To investigate the concentrations of chemicals found inside a shopping center (SC), we investigated the condition of air pollution in a SC and the personal exposure level of SC employees. METHODS: The survey was performed in June 2006 in Kyushu. The chemicals studied were volatile organic compounds (VOCs) and aldehydes. The chemicals were collected by a personal passive sampler. RESULT: Thirty-one VOCs and aldehydes were detected inside the SC. The results showed that the concentrations of all the chemicals detected in indoor air were less than those specified in the indoor air quality guideline of Ministry of Health, Labor and Welfare, Japan. The chemical concentrations in the SC decreased in the order of food corner > electric, clothing corner > outdoor and were clearly higher than those outdoors. Therefore, it is thought that the source of chemicals is indoors. The high indoor concentration of 2-ethyl-1-hexanol may be due to diffusion from the walls and floors. In addition, it is suggested that the personal exposure condition of the employees reflected the indoor concentration of each sales floor. The exposure level to formaldehyde was higher at nonworking time than at working time, suggesting that a larger exposure source exists in the place of residence than in the work place. CONCLUSIONS: We found that indoor air quality in SC is maintained at good levels. This might be because of the Japanese strict regulations that require administrations of large-scale buildings to provide adequate ventilation and perform regular measurement of indoor air quality.

[Biodistribution of ultrafine particles of titanium dioxide by intratracheal administration to mice].

TiO2 ultrafine particles are used as photo-catalysis. When ultrafine particles are exposed to hosts, they are invaded in alveolar, transferred to organs through blood vessels and may express biological effects. We administered TiO2 ultra-fine particles (5 nm, 100 nm) intratracheally to mice, and collected whole blood and removed organs (liver, lung, kidney, spleen and brain) after 1, 4 and 24 hours. The quantity of Ti in the blood and these organs was analyzed by PIXE (Particle Induced X-Ray Emission) or ICP/MS (Inductively Coupled Plasma-Mass Spectrometry). Compared to control mice, the quantity of Ti in the exposed mice was not different. Consequently, we observed the solution of dissolved TiO2 ultrafine particles by Scanning Electron Microscope, and observed the particles which aggregated. That diameter was about 1 microm. We concluded that the particles had aggregated before administration to mice, so they didn't invade the blood vessels or organs from the pulmonary alveolus in the lung.

Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice.

In this study, we evaluated the inhalation toxicity of acetaldehyde in Aldh2 KO (Aldh -/-) mice, using pathological method. Male C57BL/6 (Aldh2 +/+) mice and Aldh -/- mice were exposed to atmospheres containing acetaldehyde at levels of 0, 125, and 500 ppm for 24 h/day during 14 days. Although the average blood acetaldehyde concentration of Aldh -/- mice was higher than that of Aldh2 +/+ mice in the acetaldehyde exposure group, observable effects by the acetaldehyde exposure on the lung and liver were not different between wild type and ALDH2 null mice. In Aldh2 -/- mice, the levels of 1) erosion of respiratory epithelium and the subepithelial hemorrhage in nose, 2) hemorrhage in nasal cavity, 3) degeneration of respiratory epithelium in larynx, pharynx and trachea, and 4) degeneration of dorsal skin were higher compared with Aldh2 +/+ mice, indicating that Aldh2 -/- mice are more acetaldehyde-sensitive than Aldh2 +/+ mice. This is the first example for studying pathological effects of Aldh2 deficiency using Aldh -/- mice exposed to a low level of acetaldehyde.

Effects of lifestyle on urinary 1-hydroxypyrene concentration.

This study aimed to clarify the variation of urinary excretion of 1-hydroxypyrene, which is a major metabolite of pyrene, in relation to lifestyle, including factors such as diet and smoking. The study subjects were 251 workers (male: 196, female: 55, mean age: 44.3) who were not occupationally exposed to PAHs. Urine specimens were collected from 8:00 a.m. to 11:00 a.m. and their 1-hydroxypyrene concentrations were determined by HPLC. A questionnaire was distributed in order to learn gross aspects of the subjects' lifestyles, i.e., smoking, alcohol consumption, coffee/black tea intake, and dietary habits. Multiple linear regression analysis revealed that cigarette consumption most strongly affected the 1-hydroxypyrene level in urine, followed by dietary balance. The urinary 1-hydroxypyrene concentrations of smokers were about 2 times higher than those of non-smokers. Subjects who ate more meat and/or fish excreted 1.5-2 times more 1-hydroxypyrene in urine than those who ate more vegetables.

[Investigation of the condition of asbestos in large-scale buildings in Kitakyushu].

Recently, asbestos-related diseases have become serious all over the world. We investigated the condition of asbestos in large-scale buildings. The survey was performed in 2006 in Kitakyushu with self-administered questionnaires which were sent to managers of 250 buildings. We received 150 answers. Eighteen buildings out of 150 used chrysotile or crocidolite, and 6 buildings out of 18 took measures to deal with the situation. The number of buildings where asbestos was used increases with the age of the buildings. The older the buildings are, the more buildings used asbestos, probably reflecting the extent of legal regulations and recognition of the harmfulness of asbestos. Twenty-one buildings out of 150 gave education on asbestos, 9 buildings out of 21 buildings used asbestos, and half the buildings didn't give education on asbestos. These results suggest that the measures against and education on asbestos are insufficient in large-scale buildings.

Association between environmental noise and subjective symptoms related to cardiovascular diseases among elderly individuals in Japan.

Noise in housing environments may increase the risk of cardiovascular diseases (CVDs); however, the most significant sources of noise among elderly individuals remain poorly understood. A nationwide cross-sectional study comprised of 6,181 elderly people (age ≥ 65 years) was conducted using a web-based self-reported questionnaire in 2014. Questions pertaining to CVD-related subjective symptoms within the past year addressed symptoms of chest pain, disturbances in pulse, acute impaired tongue movement, limb paralysis, and foot pain or numbness during walking. Questions concerning noise included awakening during the night due to noise, automobile, neighborhood, construction, railway, and aircraft noise. The multivariable analyses revealed that all symptoms were significantly associated with awakening during the night due to noise. Automobile, construction, railway, and aircraft noise were significantly associated with more CVD-related symptoms at nighttime than at daytime. Our results suggest that noise at nighttime is an important risk factor for CVDs. Although several different sources of environmental noise, including automobile, neighborhood, construction, railway, and aircraft noise were found to be significantly associated with CVD-related symptoms, the strongest association was observed for construction noise, followed by neighborhood and automobile noise. The adjusted odds ratios (95% confidence intervals) for construction noise at nighttime were 1.12 (1.06-1.19) with disturbances in pulse, 1.21 (1.08-1.35) in acute impaired tongue movement, 1.25 (1.15-1.36) in limb paralysis, and 1.19 (1.12-1.28) in foot pain or numbness during walking. The associations with railway and aircraft noise were found to be weaker than those with automobile, neighborhood, and construction noise. Our study suggests that CVD-related symptoms may exhibit a greater association with construction, neighborhood, and automobile noise than with railway and aircraft noise.

Urinary 8-hydoxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels in Aldh2 knock-out mice under acetaldehyde exposure.

To clarify the carcinogenicity of acetaldehyde when associated with ALDH (aldehyde dehydrogenase) 2 polymorphism, Aldh2 knock-out (Aldh2-/-) mice and their wild type (Aldh2+/+) mice were exposed to two different concentrations of acetaldehyde (125 ppm and 500 ppm) for two weeks. Aldh2-/- mice, which have the same genetic background as C57BL/6J (wild mice) except for the Aldh2 gene, were used as models of humans who lack ALDH2 activity. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. At 125 ppm acetaldehyde exposure for 12 d, urinary 8-OHdG levels in Aldh2+/+ mice did not increase. However, urinary 8-OHdG levels in Aldh2-/- mice were slightly increased by the end of the exposure. On the other hand, plasma MDA levels did not increase in either Aldh2-/- orAldh2+/+ mice. At 500 ppm, urinary 8-OHdG levels in both Aldh2-/- and Aldh2+/+ mice significantly increased after 6 and 12 d, but there was no genetic difference. On the other hand, plasma MDA levels in Aldh2+/+ and Aldh2-/- mice did not increase at either 125 ppm or 500 ppm after two weeks of exposure. In conclusion, it is suspected that DNA was damaged by acetaldehyde inhalation, and that susceptibility to acetaldehyde varies according to Aldh2 genotype.

Salivary chromogranin A as a measure of stress response to noise.

Effects of noise on the secretion of salivary chromogranin A (CgA), which is considered to be a substitute measure of catecholamines, were investigated in a laboratory experiment. This study included 20 male subjects with normal hearing; their ages ranged from 21 to 24 years. Prior to the experiment, the subjects were asked to answer a questionnaire containing the 28-item General Health Questionnaire (GHQ-28) and Weinstein's noise sensitivity scale. White noise at 90 dB was presented to the subjects for 15 min with 15-minute-rest periods before and after noise exposure. It was shown that salivary CgA levels increased significantly during noise exposure and decreased immediately after it (Friedman's test, p = 0.001, two tailed). This result suggests that salivary CgA can be used to measure the stress response to noise. Furthermore, individual differences in the change in salivary CgA levels were discussed in relation to the subjective responses of the participants to the questionnaire. Some subjects showed prolonged elevation in the salivary CgA levels and the others showed immediate recovery or no effects. These individual differences correlated with the score on the somatic symptoms in GHQ-28; this implies that the score on the somatic symptoms in GHQ-28 could be a measure of physiological sensitivity to noise.