Risk of bladder cancer in male Japanese workers exposed to ortho-toluidine and other aromatic amines.

PURPOSE: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). METHODS: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. RESULTS: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7-104.3) and apparent dose-response relationships were revealed between the SIR and the surrogate exposure level in the 0-10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose-response relationships were observed. CONCLUSIONS: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.

Indium Lung: Discovery, Pathophysiology and Prevention.

Indium is mainly used as indium-tin oxide (ITO), which has a unique character of transparency, and is a requisite in making liquid crystal displays. Pulmonary toxicity of indium compounds in humans were not recognized until the last 2 decades. Several initial human cases of indium-related lung disease, named indium lung, were reported in Japan, with their main pathologic findings being interstitial pneumonia, emphysema and cholesterol crystals-containing granulomas. In 2010, three cases with alveolar proteinosis were reported from the United States and China. As of March 2019, more than 10 cases of interstitial pneumonia-dominant indium lung have been reported. Cross-sectional studies in indium workers indicate that the serum indium concentration (sIn) is closely related to the exposure period, the extent of interstitial as well as emphysematous changes of the lung on high-resolution computed tomography (HRCT) and serum biomarkers of interstitial pneumonia, including KL-6 and surfactant protein-D (SP-D). Longitudinal studies have shown it is possible to reduce the sIn as well as the interstitial shadows on HRCT; however, emphysematous lesions increased progressively in heavily exposed workers, even after cessation of exposure. Early detection is required to prevent irreversible changes. The first case of lung cancer associated with indium lung developed in a nonsmoking ex-worker. He had been diagnosed with indium lung and stopped working in indium processing 17 years before. This suggested there is a need for appropriate screening to detect for complications of lung cancer at early stages for those with indium lung.

Microorganism levels in spray from warm-water bidet toilet seats: factors affecting total viable and heterotrophic plate counts, and examination of the fluctuations and origins of Pseudomonas aeruginosa.

The objectives of this study were to conduct an appropriate microbial evaluation of warm-water bidet toilet seats. Health-related advantages and disadvantages have been associated with using warm-water bidet toilet seats, which are classified according to the tank type, including tanks equipped with reservoir water heaters and on-demand tankless systems equipped with an instantaneous water heater. However, related bacterial research is sparse. Here, we performed a long-term survey of the behavior of microorganisms (i.e., the total viable count (TVC), heterotrophic plate counts (HPCs), and Pseudomonas aeruginosa count) in a university campus. We also examined the differences between the tank and on-demand types, and the origins of P. aeruginosa. A low TVC (≤1/mL) in the spray waters from both on-demand and tank-type warm-water bidet toilet seats showed low bacterial contamination, although there was an increase in HPC, i.e., growth of biofilms, inside in the warm-water bidet toilet seats. When P. aeruginosa was detected in spray water over an extended duration, the P. aeruginosa origin was considered as either from feces or tap water. Collectively our findings demonstrate that hygienic safety of warm-water bidet toilet seats is being maintained overall.

[Study on the Establishment of a Specific Similar Exposure Group (SEG) in Personal Exposure Monitoring: A Case Report of Indium Tin Oxide Target Surface Grinding Process].

Surface grinding workers of Indium Tin Oxide target material are exposed to an indium compound with high toxicity. We divided individual exposure workers into similar exposure groups (SEG) and examined the effectiveness of the classification of SEG. Sampling was carried out twice a day for a total of 10 times, in 9 of which a work environment measurement in unit work area was performed at the same time. The classification examined two methods. One method was to set all the workers in the work place as one group (SEG1), and the other was to classify them depending on whether the workers handled the target material contained indium or not (SEG2). The group handled indium-contained material was SEG2(+) n=9, and the other was SEG2(-) n=9. Only the arithmetic mean value (AM) of four groups 2.8-27.4 µg/m3 in the SEG2(+) was lower than the measurement B value of the work environment measurement, but the AM of all the groups in SEG2(+) 2.8-276.8 µg/m3 was higher than the geometric mean value of measurement A 0.4-12.3 µg/m3. The concentration range of 100 µg/m3 or more of SEG2(+) AM was 20% of the total. This range was not recognized in the other items, and the variation of SEG2(+) was small. Even though the evaluation of SEG1 is control class 2, if revaluated on SEG2(+), 50% of the SEG2(+) were evaluated as control class 3. It is possible to efficiently manage chemical substances by establishing specific SEG properly stratified.

Bidet toilet seats with warm-water tanks: residual chlorine, microbial community, and structural analyses.

Despite the reported health-related advantages of the use of warm water in bidets, there are health-related disadvantages associated with the use of these toilet seats, and the bacterial research is sparse. We conducted a survey on the hygienic conditions of 127 warm-water bidet toilet seats in restrooms on a university campus. The spray water from the toilet seats had less residual chlorine than their tap water sources. However, the total viable microbial count was below the water-quality standard for tap water. In addition, the heat of the toilet seats' warm-water tanks caused heterotrophic bacteria in the source tap water to proliferate inside the nozzle pipes and the warm-water tanks. Escherichia coli was detected on the spray nozzles of about 5% of the toilet seats, indicating that the self-cleaning mechanism of the spray nozzles was largely functioning properly. However, Pseudomonas aeruginosa was detected on about 2% of the toilet seats. P. aeruginosa was found to remain for long durations in biofilms that formed inside warm-water tanks. Infection-prevention measures aimed at P. aeruginosa should receive full consideration when managing warm-water bidet toilet seats in hospitals in order to prevent opportunistic infections in intensive care units, hematology wards, and other hospital locations.

High levels of indium exposure relate to progressive emphysematous changes: a 9-year longitudinal surveillance of indium workers.

BACKGROUND: During the last decade it has been clarified that the inhalation of indium compounds can evoke alveolar proteinosis, cholesterol granuloma, pulmonary fibrosis and emphysema. In this study, we aimed to elucidate the characteristics and time course of pulmonary disorders among indium workers using comprehensive pulmonary examinations at an indium-processing factory. METHODS: Data for 84 male workers who underwent the examinations for nine consecutive years from 2002 to 2010 were analysed regarding their symptoms, serum indium concentration (sIn), serum markers of interstitial pneumonia, pulmonary function test parameters and high-resolution CT (HRCT) findings of the lungs. RESULTS: In association with improvements in the work environment and work practice, the sIn levels decreased with significant reductions in the KL-6 and surfactant protein D (SP-D) levels. Regarding the HRCT findings, the interstitial lesions regressed partially, whereas emphysematous lesions increased progressively in the workers with high sIn values. FEV1/FVC decreased with the years and the rate of decrease was significantly greater in those with high sIn. The biological half-life of sIn was estimated to be 8.09 years. CONCLUSIONS: The present findings suggest that the sIn, SP-D, KL-6 levels and radiological interstitial changes can be reduced in indium workers by alleviating exposure to indium, whereas emphysematous lesions can progress among those with a history of heavy exposure.

Effects of sulfur dioxide on the respiratory system of Miyakejima child residents 6 years after returning to the island.

OBJECTIVES: This study investigated the health effects of volcanic gas, mainly sulfur dioxide (SO2), exposure on the children of Miyakejima Island. METHODS: Health checkups were conducted in November from 2006 to 2011. Health effects were evaluated through a self-administered questionnaire on respiratory and irritative symptoms, and spirometry. SO2 was measured continuously from February 2005 onward at six fixed monitoring stations in inhabitable areas. Based on mean SO2 concentration during 3 months before each health checkup, inhabitable areas were classified into three categories: (1) lower (area L); (2) higher (area H-1); and (3) highest (area H-2). RESULTS: Average concentrations (ppb) of SO2 decreased year-by-year and ranged from 11.3 to 2.47 in area L, from 32.2 to 12.2 in area H-1, and from 75.1 to 12.1 in area H-2, respectively. In general, prevalence of respiratory and irritative symptoms was higher in area H-2, and the prevalence decreased year-by-year in all three areas by Cochran-Armitage test for trend. We defined a study population in area L in 2008 as a reference population because we had no unexposed population. Applying a logistic regression model, age-, sex-, and hypersusceptibility-adjusted prevalence odds ratios to the reference population showed clear exposure-dependent increases in some irritative symptoms such as "Irritation and/or pain in throat" and "in eyes," and approximately 30 ppb seemed to be the threshold concentration. Spirometry did not show any significant differences. CONCLUSIONS: Though no pulmonary functions were affected, some subjective symptoms were detected dose-dependently by SO2 exposure concentration in child residents during the 6 years after the eruption.

[Current status of measures against prevention of occupational diseases in Japan].

In Japan, measures against prevention of occupational diseases are carried out by legal regulations. The superordinate law is the Labor Standards Law, and the Industrial Safety and Health Law(ISHL) and related Ordinances were promulgated in 1972. Abiding by the ISHL and the Ordinances, the employers are required to execute health checkups, assessment of working conditions, improvement of work environment, installation of exposure protection devices/facilities, and so forth to prevent employees from the occupational diseases. Since 2005, the employers are also requested to voluntarily perform health risk assessment and management activities by themselves to avoid health risk due to hazardous conditions unregulated by the ISHL and the Ordinances.

[Indium lung disease].

"Indium lung" is a new occupational lung disease. The global demand for indium, the major material used in manufacturing flat-screen display panels, has skyrocketed since the 1990s (Japan comprises 85% of the worldwide demand). The first case was reported in Japan in 2003, followed by seven cases (interstitial pneumonia and emphysema) in Japan. Two pulmonary alveolar proteinosis (PAP) cases in the USA followed in 2011. Indium lung has been described as interstitial pneumonia, pneumothorax, emphysema, and PAP. In 2013, The Japan Ministry of Health, Labor and Welfare issued an "Ordinance on the Prevention of Hazards Due to Specified Chemical Substances" requiring employers to provide regular health checks for employees and measurements of work environment concentrations of respirable indium dust.

Beta-3-adrenergic receptor Trp64Arg polymorphism: does it modulate the relationship between exercise and percentage of body fat in young adult Japanese males?

OBJECTIVES: The Trp64Arg polymorphism of the beta-3-adrenergic receptor gene has been studied as a potential genetic factor contributing to the development of obesity. Several studies have investigated whether or not this polymorphism affects weight reduction due to exercise, but the results of these studies have not been consistent. Moreover, information on a population characterized by a wide ranges of physical activities is scarce. Thus, to further understand the impact of this polymorphism, we examined whether the polymorphism modulates the relationship between physical activity due to exercise (PAE) and percentage of body fat (%BF). METHODS: The study population was 70 Japanese male young adults with a high prevalence of habitual exercise. PAE was estimated by a questionnaire, and %BF was measured by bioelectrical impedance analysis. Genotyping was done by PCR-restriction fragment length polymorphism analysis. RESULTS: The median PAE value of the subjects was 6.9 MET-h/day with an interquartile range of 1.5-10.3 MET-h/day. PAE correlated significantly with %BF in the entire population and within the two subpopulations, namely, carriers or non-carriers of the Arg allele. Multiple regression analysis of PAE, Trp64Arg polymorphism, and the interaction term revealed that while the PAE-derived independent variable was statistically significant, the interaction term was insignificant. When the two regression lines of subjects with and without the Arg allele were considered, the difference between the two slopes did not deviate from zero, nor did the vertical distance of the two regression lines. These findings suggest that the impact of this polymorphism is limited. CONCLUSIONS: In our study population of young adult Japanese males, the impact of the Trp64Arg polymorphism on the association between exercise and body composition was weak, if it existed at all.

Effect of the Cleanliness of Spray Nozzle on the Concentration of Microorganisms in the Spray Water in Warm-Water Bidet Toilet Seats.

Bidet-toilets are widely used in households and public spaces in Japan. The effect of nozzle cleanliness on spray water quality of warm-water bidet toilet seats is unknown. We conducted a long-term experimental model-based study (2015-2016) and two survey-based studies (A: 2018-2019 and B: 2020-2021) at a university campus. Survey A measured the effect of nozzle cleansing on total viable count (TVC) and heterotrophic plate counts (HPCs) in spray water. Survey B measured the total organic carbon, residual chlorine concentration, TVC, and HPC of different fractions of sprayed water. We found no upstream migration of microbes from the nozzle to water tanks. While daily cleaning of the nozzle surface could reduce bacterial count in spray water, continuous discharge of water washed away bacterial contamination. Fecal indicator bacteria were in traces in spray water, indicating proper maintenance of these toilet seats.

Indium lung--case reports and epidemiology.

PURPOSE: The present review is aimed to introduce an new occupational lung disease, Indium Lung. METHODS: We searched case reports and epidemiological studies concerning indium-related lung diseases and reviewed. RESULTS: Up to March, 2010, 7 cases of interstitial pneumonia in Japanese indium-exposed workers, two cases of pulmonary alveolar proteinosis (PAP) in US indium-exposed workers, one case of PAP in a Chinese indium-exposed worker, and 4 cross-sectional surveys in Japan had been published. All cases and epidemiological studies in Japan indicate that exposure to hardly soluble indium compounds causes interstitial as well as emphysematous lung damages, which we call "Indium Lung". Based on the epidemiological studies, the Japan Society for Occupational Health proposed 3 µg/l of indium in serum as an occupational exposure limit based on biological monitoring to prevent significant increase of KL-6. COMMENTS: Long-term follow-up of currently and formerly indium-exposed workers is essential not only to clarify the natural history of indium lung but also to trace the incidence of lung cancer. It is also necessary to elucidate the mechanism of indium lung and difference in clinical manifestations between Japanese and US cases.

[Validity of serum surfactant protein D measurements in a cross-sectional study].

BACKGROUND: In October, 2008, the method for enzyme-linked immunoassay for serum surfactant protein D (SP-D) was changed from SP-D kit (Yamasa) EIA to SP-D kit (Yamasa) EIA2 in Japan. In our follow-up survey on 144 indium-exposed workers from December, 2008 to June, 2009, SP-D showed systematically higher values compared to the first survey from March to July, 2008. Geometric means (prevalence rate) of serum SP-D of the first and follow-up study were 52.1 ng/mL (4.1%) and 72.1 ng/mL (14.6%), respectively, though serum KL-6 and SP-A were stable. Thus, we examined the validity of the old and new methods. METHOD AND RESULTS: As a result of examining about 200 subjects, the correlation between the two methods was good. However, as a reproducibility examination of about another 300 subjects between the post-measured and the pre-measured values with the same new method at Laboratory A, the differences between vales in each observation are not acceptable. Especially, examinations performed using the lot 804, 805, and 105 at laboratory A showed systematic higher values than others. CONCLUSION: Various factors might have caused the large measurement bias; in particular, the new method lacks sufficient reproducibility between lots. When observing the chronological change of SP-D, attention must be given in comparisons of serum SP-D after October, 2008 to before that because of the metrology-dependent measurement bias.

Indium concentration in serum is an excellent predictor for assessing accumulated indium concentration in the lungs.

OBJECTIVE: To clarify whether indium in serum (In-S) is an appropriate parameter for assessing accumulated indium concentration in the lungs (In-L). METHODS: During our approximately 15-year Japanese cohort follow-up, five male indium-tin oxide (ITO) or/and indium trioxide-exposed workers underwent lung surgical procedures to treat lung diseases or to confirm a diagnosis of lung impairments. We measured In-L of these Cases 1-5 and were able to assess the relationship between In-L and the most recent In-S. Another 1 Japanese case (Case 6) exposed to indium trioxide and indium hydroxide was referred from an article. RESULTS: Cases 1 and 3 had lung cancer, Case 2 suffered from recurrent pneumothorax, and Case 4 had interstitial pneumonia with mild emphysema. Case 5 had severe emphysema with pulmonary hypertension and underwent bilateral lung transplantation. In Cases 1-5, In-L and In-S ranged from 3.4 to 161.2 µg/g wet weight and 0.7 to 60.4 ng/mL, respectively, and In-L/In-S ratios ranged from 2484 to 4857. The slope of the single regression equation with zero intercept was 2767 and the correlation coefficient was 0.995. In contrast, Case 6 was extraordinarily outlying, but the reason is unclear. CONCLUSIONS: In-S is an excellent predictor for assessing indium load in the lungs in ITO or/and indium trioxide-exposed workers. However, number of cases was only five and not enough to authorize definite conclusion. It is desirable to add more cases to confirm our conclusion.

[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.

Indium kinetics in an indium exposed worker before and after bilateral lung transplantation.

BACKGROUND: A male worker with indium-tin oxide (ITO)-induced pneumoconiosis underwent bilateral lung transplantation (LT). METHODS: Post-LT histopathological investigations of the isolated lungs and hilar lymph nodes were performed and indium concentration in serum (In-S) and serum Krebs von den Lungen-6 (KL-6) were tracked for 122 weeks. RESULTS: He has attained the ultimate treatment goal of > 2-year survival. The main histopathological characteristics were pan-lobular emphysematous change, interstitial fibrosis, and lymphocytic infiltration in the peribronchiolar/perivascular portions, and numerous cholesterol clefts and giant cells containing brown particles. These findings support the conclusion that the lung injury was caused by the inhalation of ITO. Metal element mapping and indium in the isolated lungs revealed that inhaled ITO particles in humans migrate to the lymph nodes. In-S remained at remarkably high levels (≥30 ng/mL) and showed wide fluctuation with bimodality until 46 weeks after LT, but KL-6 remained in the normal range for almost the entire period. The indium concentration in the donor's resection lung at 10 weeks after LT was 143.5 ng/g wet-weight, which was only one one-thousandth of the recipient's lung (161 µg/g wet-weight). After 48 weeks of LT, the recipient's In-S had gradually decreased; the biological half-life was 1.2 years. These results clearly suggest that indium remaining in the recipient's tissues did not adversely influence the transplant donor's lungs. CONCLUSIONS: The transplanted donor's lungs were not influenced by indium in the recipient's organs. Bilateral LT is thus an effective treatment option in severe indium lung disease cases.

Possibility of lung cancer risk in indium-exposed workers: An 11-year multicenter cohort study.

BACKGROUND: We established a causal relationship between indium exposure and lung interstitial and emphysematous effects. Lung cancer has been clearly demonstrated in rats and mice exposed to indium phosphide and in rats exposed to indium tin oxide. However, no information is available on human indium-related lung cancer. METHODS: The baseline studies were conducted on 381 indium-exposed and 150 referent workers in 11 factories from 2003 to 2006. Items examined included indium concentration in serum (In-S), occupational history, Krebs von den Lungen-6 (KL-6), chest high-resolution computed tomography (HRCT), medical history, smoking habits, and subjective symptoms. Subjects received follow-up health checkups, and a total of 220 indium-exposed and 26 nonexposed workers were examined at least once with chest HRCT from 2013 to 2018. RESULTS: Four lung cancer cases were identified only in indium-exposed workers. Two were prevalent cases and two were incident cases. The averages (range) of age (years), exposure duration (years), In-S (µg/L), and KL-6 (U/mL) at the baseline survey were 58 (50-74), 1.7 (0.3-4.8), 3.1 (0.3-9.7), and 663 (414-942). The mean (range) latency from initial indium exposure was 5.3 (0.4-11) years. The HRCT findings in two incident cases were mild interstitial/emphysematous change and mild interstitial change. The standardized incidence ratio (SIR) of the incident cases was 1.89 (95%CI 0.52-6.88). CONCLUSIONS: Although the SIR was not statistically significant, there was an undeniable possibility of indium-related lung cancer due to the short follow-up duration being insufficient to disclose lung cancer and the small number of lung cancer cases. Further follow-up is necessary.

Biological monitoring of o-toluidine in urine pretreated by an enzymatic deconjugation method.

OBJECTIVES: To establish an enzymatic deconjugation method to separately quantify urinary o-toluidine (OT), its six metabolites, another six chemicals present in an OT-processing plant, and one metabolite of p-toluidine, and to propose optimal urinary biological monitoring items of OT exposure. METHODS: Thirty-six urine samples of an OT-processing plant's workers were obtained and pretreated by an enzymatic deconjugation method employing ß-glucuronidase/arylsulfatase for 3 hours at 37°C and measured by liquid chromatograph-mass spectrometry (LC-MS). An alkaline hydrolytic pretreatment and 1-chlorobutane extraction procedure was also examined as a widely used urinary OT measurement method. RESULTS: The 14 chemicals were separated by LC-MS condition set by us and 13 chemicals other than 2-chloroaniline showed satisfiable linearity and limits of determination. Standard substances of six OT metabolites decomposed after the alkaline heating. In the 36 urine samples, OT, N-(4-hydroxy-2-methylphenyl) acetamide (NHM), and 4-amino-m-cresol (ACR) accounted for approx. 90% of the total OT and OT metabolites, but inter-individual variation of the three substance excretion seemed to be wide. Time course of urinary excretion revealed that concentration of the three substances was higher 24 hours after the work shift's end rather than just after the work shift. CONCLUSIONS: OT and its six metabolites can each be determined with LC-MS. The alkaline method is not so optimal for exact biological monitoring. Rather, the sum of urinary OT, NHM, and ACR measured by the enzymatic method is a better index, and "end of the workweek" is a good urine-sampling time for the biological monitoring of OT exposure.

Job strain and arteriosclerosis in three different types of arteries among male Japanese factory workers.

OBJECTIVES: This study evaluated the association between job strain and subclinical indicators of arteriosclerosis simultaneously in the cerebral artery, the aorta, and the carotid artery. METHODS: The participants in this cross-sectional study consisted of 352 male factory workers between the ages of 24.9 to 55.8 (mean 41.7) years who had not been exposed to any hazardous chemicals in Japan. Job strain was measured using a Japanese version of the Job Content Questionnaire developed by Karasek. The following subclinical indicators of arteriosclerosis were examined by noninvasive procedures: hyperintense spots in T2-weighted images in brain magnetic resonance imaging (MRI), pulse wave velocity of the aorta, and the stiffness parameter of the carotid artery using ultrasound and systolic and diastolic blood pressure. RESULTS: After control for potential confounders, high job strain was associated with an increased prevalence of hyperintense spots (adjusted odds ratio 2.53, 95% confidence interval 1.14-5.63), and elevated pulse-wave velocity (adjusted increase in percent 3.5, 95% confidence interval 0.0-6.9). The stiffness parameter tended to be elevated in the high job-strain group although this trend was not statistically significant. Job strain showed no relation to blood pressure. CONCLUSIONS: In this study, job strain was associated with subclinical indicators of arteriosclerosis in different arteries although the association was not statistically significant for the carotid artery. New information is offered by brain MRI for arteriosclerosis in the cerebral artery. An increase in hyperintense spots may explain the link between job strain and cerebrovascular disease.