Published papers

Aims: To clarify whether the current occupational exposure limit (OEL) for carbon disulphide (CS2) is low enough to prevent the occurrence of adverse effects on the cerebrovascular system. Methods: A total of 432 male workers exposed to CS2 and 402 male referent workers in 11 Japanese viscose rayon factories were studied at baseline; 750 of these were followed up. Brain MRI was performed at both baseline and follow up surveys. Changes in the number of hyperintense spots in T2 weighted images (HIS), which point to so-called "silent cerebral infarctions", were evaluated over six years. A total of 666 subjects (217 exposed, 125 ex-exposed, and 324 referent subjects) who twice received brain MRI were subjected to analysis. Mean duration of exposure to the end of the study was 19.6 years for the exposed workers. The geometric mean CS2 (ppm) and TTCA (mg/g creatinine) concentrations for the past six years were 4.9 and 1.6 for all exposed workers, 5.8 and 1.9 for spinning/refining workers, and 2.7 and 0.9 for other exposed workers, respectively. Results: Exposed subjects showed a significantly higher risk for an increase in the number of HIS over six years. Odds ratios adjusted for possible confounders in the exposed and ex-exposed workers were 2.27 (95% CI 1.37 to 3.76) and 1.33 (95% CI 0.70 to 2.54), respectively. No exposure-response relations were observed in a number of analyses among the exposed workers. Conclusions: Exposure to CS2 under the current Japanese OEL, 10 ppm, might increase the number of HIS in brain MRI. However, results should be interpreted with caution.

Aims: A six year prospective cohort study was conducted to clarify whether the current carbon disulphide (CS2) exposure level is low enough to prevent subclinical health impairment and/or to ameliorate health effects due to previous high exposure. This paper describes the effects on the cardiovascular systems. Methods: The study subjects were 432 male workers exposed to CS2 and 402 non-exposed workers in Japan, all of whom were examined in 1992-93. A total of 251 CS2 exposed, 140 formerly exposed, and 359 non-exposed workers participated in the follow up survey (follow up rate 89.9%) in 1998-99. Mean duration of exposure was 19.3 years at the end the study. Mean CS2 and 2-thiothiazolidine-4-carboxylic acid (TTCA) concentrations were 5.0 ppm and 1.6 mg/g creatinine. Health items examined were serum biochemical indices including lipids and coagulation-fibrinolysis factors, blood pressure, aortic stiffness, ophthalmography, and electrocardiography at rest and after Master's double 2 step test. Potential confounding factors were adjusted for. Results: Incidence of ischaemic findings, defined as Minnesota codes I, IV1-3, V 1-3 (at rest and after the load), or receiving treatment for ischaemia, was significantly higher in the exposed workers, especially for the spinning/refining workers (adjusted OR 2.1; 95% CI 1.1 to 4.0) or the highest quartile of six year mean TTCA (adjusted OR 3.9; 95% CI 1.8 to 8.7), although the observed increase in risk was diminished when rigorous ECG criteria were applied. Incidence of retinal microaneurysm was increased with marginal significance. Among cardiovascular risk factors we examined, only blood pressure values were significantly increased in the exposed workers. Conclusions: Increased risk of ischaemic electrocardiogram findings among Japanese viscose rayon workers was observed. Although its clinical significance is to be discussed, the current Japanese occupational exposure limit for CS 2, 10 ppm, would be high to prevent subclinical cardiovascular effects in this study population.

Objectives - To estimate rates of cadmium (Cd) uptake from the digestive tract and changes in Cd in biological specimens after intake of Cd mainly in rice. Methods - Twenty-five young non-smoking Japanese female volunteers (20-23 in age) were recruited and a 20-d experimental study was conducted. With polished rice containing 0.004 ppm and 0.340 ppm of Cd, Meal L and Meal H were prepared. Approximately 12% of total Cd in Meal L and 92% of total Cd in Meal H originated in rice. The volunteers ate Meal L for 11 d to achieve a stable intake-output balance of Cd. Fifteen of the 25 volunteers ate Meal H on the 12th day (Group D1), and the remaining 10 ate Meal H on the 12th, 13th and 14th day (Group D3). All 25 subjects then resumed the consumption of Meal L to the end of the study (20th day). All meals, feces and urine were collected during the study, and Cd intake from the daily meals (Cd-I), Cd in feces (Cd-F) and Cd in urine (Cd-U) were determined. For measurement of Cd in blood (Cd-B), venous blood was collected from all volunteers on the day before the study and again on the 12th and 20th day; venous blood was also collected from 4-8 volunteers at additional time points. Results - Mean Cd-I was 4.51 μg/d (range: 1.85-6.93) or 48.48 μg/d (range: 27.98-56.27) when they ate Meal L or Meal H. Cd-F and Cd-B exhibited faster responses to the change in Cd-I than did Cd-U. The Cduptake rate, defined as (1-Cd-Fexcess/Cd-Iexcess) (Fig. 1), was 47.2% (range: -9.4-83.3%) in Group D1 and 36.6% (range: -9.2-73.5%) in Group D3, and the Cdbalance rate, defined as (1-Cd-Foutput/Cd-Iintake), was 23.9% (range: -4.0-37.7%) in Group D1 and 23.7% (range: -8.2-56.9%) in Group D3. Conclusions - Cd-F and Cd-B are better biological monitoring parameters for assessing change in Cd-I than Cd-U. The Cduptake and Cdbalance rates appeared to be higher than those in previous papers when ingested Cd mainly originated in rice.

Aim: Recent studies have made it clear that brassica vegetables contain 2-thiothiazolidine-4-carboxylic acid (TTCA), which is the most widely used biological monitoring index of exposure to carbon disulfide (CS2). This study aimed to assess the time-course of TTCA excretion in urine (TTCA-U) after eating brassica vegetables. Methods: After a 1-d break from eating brassica vegetables, ten volunteers (6 males and 4 females) ingested 100 grams of chopped raw cabbage containing 4.3 mg/kg of TTCA, and the TTCA concentration in urine samples was determined over 24 h. TTCA concentrations in brassica vegetables purchased from a local supermarket were also measured. Results: TTCA-U reached peak concentrations 3-9 h after cabbage intake, gradually decreased, and was below the detection limit (<0.1 mg/l) in 8 of 10 volunteers in the last urine samples. The total amount of TTCA excreted in 24 h ranged from 0.19 to 0.42 mg, and half of the total TTCA was excreted within 6.5 h on average (range: 4.5-10.1). The excretion profiles of young and middle-aged volunteers seemed to differ, but not those of young males and young females. TTCA was detected in both raw and boiled cabbage, Japanese radish, turnip, and broccoli, but was not detected in Chinese cabbage or chingentsuai. Conclusion: TTCA-U may be overestimated as an index of CS2 exposure when brassica vegetables are ingested within approximately 24 h before collection of the urine sample.

An important challenge to occupational health services in Japan is the necessary shift from regulation-based occupational health program to health risk-based program. The Occupational Safety and Health Management System (OSHMS) is an effective tool for introducing risk-based activities. To date, the Five Management system has been used to manage occupational health activities. This classification, however, does not show the interactions among the listed activities. Nor is it clear how this system contributes to the PDCA (Plan/Do/Check/Act) cycle for continual improvement. The category in the Five Management system called "Roles of the Occupational Physician" covers most of the occupational health services required in Japan. The items listed in the Five Management system were compared to the guidelines of OSHMS from the International Labour Office and issues that should be solved for occupational health activities with OSHMS were clarified. Seven issues are discussed in this paper; (1) occupational safety and health policy and audit that can drive the PDCA cycle effectively, (2) reclassification of occupational health activities with several different objectives, (3) set up of targets, (4) risk assessment methods that can prioritize health risks compared to safety risks, (5) exposure assessment methods for risk assessment, (6) flexibility of laws and regulations, and (7) development of talented professionals for risk-based occupational health activities.

Human asthma is characterized by three critical phenotypic traits: intermittent reversible airway obstruction, airway hyperresponsiveness and airway inflammation. In animal models of asthma, airway hyperresponsiveness is an important feature. This trait is characterized by an exaggerated bronchoconstrictor response that would have little physiological consequence in an otherwise unaffected or normal individual. In this article we explore two distinct facets of airway responsiveness. The first is the genetic basis for variations in airway responsiveness that occur in mice in the absence of any specific environmental manipulation. We demonstrate that standard genetic approaches can be successfully applied to the identification of regions of the mouse genome linked to the expression of airway hyperresponsiveness. The second topic addressed in this review is the change in airway responsiveness induced in rats by repeated exposure to sulphur dioxide gas. With daily exposure to high concentrations of sulphur dioxide gas, there is chronic injury and repair of epithelial cells. Over time, rats develop mucous hypersecretion, airway inflammation, increased airway resistance and airway hyperresponsiveness. This model has provided useful information on the mechanisms underlying the pathophysiological events that typify the chronic bronchitis in humans.