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The objective of the study is to establish exposure-excretion relationship between dichlorometane (DCM) in air (DCM-A) and in urine (DCM-U) in workplace to confirm a previous report. Male workers in a screen-printing plant participated in the study. Time-weighted average DCM-A was measured by diffusive sampling followed by gas-chromatography (GC), and DCM in end-of-shift urine samples was by head-space GC. The data were subjected to regression and other statistical analyses. In practice, 30 sets of DCM-A and DCM-U values were available. The geometric mean DCM-A was 8.4 ppm and that of DCM-U (as observed) was 41.1 µg/l. The correlation coefficients (0.70-0.85) were statistically significant across the correction for urine density. Thus, the analysis for un-metabolized DCM in end-of-shift urine samples is applicable for biological monitoring of occupational exposure to DCM, in support of and in agreement with the previous report. In conclusion, biological monitoring of occupational DCM exposure is possible by use of analysis for un-metabolized DCM in end-of-shift urine.

This study aimed to evaluate personal exposures of 27 workers to indium compounds as “total” dust and its “respirable” fraction in their breathing zones at 3 Japanese indium plants. Eight-hour time-weighted average (TWA) indium concentrations of personal exposure to dust collected in sampling periods of 6 h or longer were determined by ICP-MS. The arithmetic means of exposure concentrations were 0.095 mg indium (In)/m3, when sampled as total dust, and 0.059 mg In/m3, as respirable fraction. ACGIH’s TLV-TWA of 0.1 mg In/m3 for total particulate matter and Acceptable Exposure Concentration Limit (AECL) of 3×10−4 mg In/m3 for the respirable fraction notified by the Japanese Ministry of Health, Labour and Welfare were used to evaluate the exposure concentrations. Twenty-five out of 27 workers were exposed to indium concentrations lower than TLV-TWA, while all of the workers were exposed to the indium concentrations higher than AECL. We noted that there was a large discrepancy between the two occupational exposure limits referred to in this report, and these differences were attributed to the sampling strategies and health effects used as the prevention targets. Carcinogenicity of the respirable fraction of indium-containing particulates was considered in setting AECL, whereas it was not in ACGIH’s TLV.

This study aimed to examine quantitative relation between ethylbenzene (EB) in air (EB-A) and un-metabolized EB in urine (EB-U) for biological monitoring of occupational EB exposure by urinalysis for EB. In total, 49 men in furniture production factories participated in the study. Time-weighted average EB-A was monitored by diffusive sampling. Urinalysis for EB was conducted by head-space gas-chromatography with end-of-shift samples. Data were subjected to regression analysis for statistical evaluation. A geometric mean (GM) and the maximum (Max) EB-A levels were 2.1 and 45.5 ppm, respectively. A GM and the Max for EB-U (observed values) were 4.6 and 38.7 µg/l. A significant linear correlation was observed. The regression equation was Y=3.1+0.73X where X is EB-A (ppm) and Y is EB-U (μg/l) (r=0.91, p

Objectives To test the reliability of the procedures (described in a previous article) for estimation of biological occupational exposure limits (BOELs). Methods Data on four organic solvents (styrene, ethyl benzene, isopropyl alcohol and tetrachloroethylene) were obtained from recent publications and added to previously cited data for 10 organic solvents. Regression analysis was used for statistical evaluation. Results and discussion The previously reported results obtained using 10 solvents were reproduced by the analysis with 14 solvents. Repeated randomized division of the 14 sets into two subgroups of equal size followed by statistical comparisons did not show a significant difference between two regression lines. This reproducibility suggests that the procedures used to estimate BOELs may be applicable across many solvents, and this may be of particular benefit for protecting the health of workers who work with skin-penetrating solvents.

Objectives This study aimed to assess workers' exposure to indium and its compounds in 55 indium-handling operations among 13 Japanese plants. The surveyed plants were selected from indium-manufacturing plants whose annual indium production exceeded 500 kg. Methods The Control of Substances Hazardous to Health (COSHH) Essentials control banding toolkit, which contains simple scales for hazard levels, quantities in daily use, and "dustiness" characteristics, was used to assess generic risks of indium-handling operations. The operations were then classified into one of four Control Approaches (CAs). Results There were 35 indium-handling operations classified into CA4 (requires expert advice) and 16 grouped into CA3 (requires containment). There were three operations classified into CA2 (requires engineering controls) and only one into CA1 (requires good general ventilation (GV) and working practices). Of the 51 operations classified as CA4 and CA3, 36 were found to be improperly equipped with local exhaust ventilation, and the remaining 15 operations solely relied on GV practices. Respiratory protective equipment (RPE) used in the 13 indium plants was examined with reference to the recommendations of the COSHH Essentials and Japan's Technical Guidelines. Conclusions Our findings suggest that stringent engineering control measures and respiratory protection from indium dust are needed to improve indium-handling operations. Our results show that the most common control approach for Japanese indium-handling operations is to require expert advice, including worker health checks for respiratory diseases and exposure measurement by air sampling.

OBJECTIVES We conducted a 6-year cohort study to evaluate the relationship between carbon disulfide (CS2) exposure and reductions in the motor and sensory nerve conduction velocity (MCV and SCV) of the median nerve. METHODS Study subjects at baseline included 432 exposed workers and 402 unexposed workers. Among the exposed workers, 145 workers terminated CS2 exposure during the follow-up period (ex-exposed workers). MCV and SCV were measured at baseline and followed up. CS2 personal exposure concentration was measured two times a year during a 6-year follow-up period and mean (range) CS2 exposure concentrations (ppm) were 5.96 (0.8-16.0) and 3.93 (0.6-9.9) in the exposed and ex-exposed workers, respectively. RESULTS Reductions in MCV during the follow-up period did not differ among the exposed, ex-exposed, and unexposed workers. Reduction in SCV (m/s) of the exposed workers (-4.47±3.94) was significantly larger than that of the unexposed (-3.38±3.97) and ex-exposed workers (-3.26±3.79). For SCV reduction, a partial multiple regression coefficient of (ex-exposed workers) / (unexposed workers) was significantly positive (+0.915, p < 0.01) after adjustment for confounding variables. CONCLUSIONS This cohort study showed that 6-year CS2 exposure around a mean level of 6 ppm did not affect MCV reduction but induced significant SCV reduction beyond the influence of aging. The effect of CS2 on SCV around a mean exposure level of 4 ppm may be reversible, since it disappeared in the ex-exposed workers after CS2 exposure cessation for a mean period of 4.1 years.

Objectives To simplify the procedures to estimate biological occupational exposure limits (BOELs) by use of the ratio of geometric mean (GM) concentration of un‐metabolized organic solvent in urine (U‐GM) over GM organic solvent concentration in air (A‐GM) (the [U‐GM/A‐GM] ratio). Methods Occupational Exposure Limits (OELs) and BOELs were cited from publications from the Japan Society of Occupational Health (JSOH) and the American Conference of Governmental Industrial Hygienists (ACGIH). Data on [U‐GM/A‐GM] and the SLOPE of exposure‐excretion regression line were collected from published articles (men and women were treated separately). Correlation analysis and paired t test were employed as the method to examine statistical significances. Results Significant linear correlation was established between the SLOPE and the [U‐GM/A‐GM]. Thus, it was considered to be possible to calculate the SLOPE value from the [U‐GM/A‐GM]. Previously established equation of BOEL = SLOPE × OEL allowed to estimate BOEL values in 22 cases of data sets. The comparison of the estimated BOELs with the existing BOELs (JSOH's BOELs and ACGIH's BEIs) in terms of the ratio of [(estimated BOEL)/(existing BOEL)] showed that the ratios for the 22 cases probably distributed log‐normally with a GM of 0.85, and the maximum was 5. Therefore, the estimated BOEL may be generally applicable in occupational health when BOEL remains yet to be established. In the worst case, the estimated BOEL may be five times greater than it should be. The recommended procedures for application of estimated BOEL values were described. Conclusion Simplified procedures for estimation of BOEL values are proposed.

This study quantitatively assessed personal exposure of 86 workers to indium compounds as total dust at 11 Japanese indium plants. The personal exposures to indium concentrations in the breathing zone during an 8 h work-shift were determined by ICP-MS. The arithmetic mean indium concentration of all the workers was 0.098 mg Indium (In)/m3, with individual values ranging from 0.0001 to 1.421 mg In/m3. There were 11 workers whose exposure to indium concentrations exceeded the American Conference of Governmental Industrial Hygienists' Threshold Limit Value-Time Weighted Average (TLV-TWA) of 0.1 mg In/m3. Based on the condition TLV-TWA

OBJECTIVE This study determined the applicability of Japanese working environment measurements to assessment of personal exposure concentrations of chemicals by comparing both levels of concentrations. METHODS The chemicals measured in this study comprised eight kinds of vaporous chemicals as well as two kinds of chemicals in dust. Personal exposure measurements, Japanese working environment measurements and spot sampling measurements were undertaken in 70 companies. RESULTS Personal exposure concentrations and the arithmetic mean value (EA2) of the working environment measurement concentrations obtained according to the Japanese working environment control system had statistically positive correlations (r=0.732-0.893, p

The Industrial Safety and Health Law enacted in 1972 has contributed much to the progress of occupational safety and health (OSH) activities. Many indicators including death and illness statistics show continued improvement up to date. The establishment of OSH organization within enterprises and 5-yr administrative programs formulated by the Ministry of Health, Labour, and Welfare (MHLW) were important factors for satisfactory management. The past programs indicate that the weight of self regulation in comparison to legal control gradually increased since late 1990s. In spite of the past achievement, many hazards such as overwork, mental stress, chemical agents and others still remain to be prevented. The systematic risk assessment of unregulated chemicals by the MHLW proved to be an effective scheme for risk-based management and to deserve continued implementation. The size of human resources for OSH was estimated at 1.5 million. In view of the adverse effect on OSH by economic, social and political environment in the future, the importance of the efficiency of OSH management was indicated. Since the efficiency depends on the competence of OSH personnel and the level of scientific basis, it was concluded that the fundamental policy for the future should give high priority to education and research.

To investigate if it is appropriate to apply urine density correction when a urine sample is dense or dilute. Data on hippuric acid (HA-U), toluene (Tol-U), creatinine (CR) and specific gravity (SG) in end-of-shift urine samples and exposure to air-borne toluene were cited from previous publications. In practice, 837 cases were available, and they were classified into dense, intermediate and dilute groups taking 0.3 and 3.0 g/l of CR and 1.010 and 1.030 of SG as cut-off points. Lines of regression of HA-U and Tol-U (as observed, CR-corrected or SG-corrected) with air-borne toluene were calculated for each density groups, and correlation coefficients (CCs) were compared. The dense groups gave CCs similar to those of the intermediate groups. Dilute versus intermediate group comparison also gave promising results. These conclusions were however based primarily on the findings with observed values, because the numbers of cases in the dilute or dense group were limited when CR- or SG-correction was applied. Literature survey showed that urine density correction does not always improve the correlation between solvents in air and exposure makers in urine. It was concluded that no correction for urine density may be necessary in evaluating HA-U and Tol-U in dense (and probably also dilute) urine samples as markers of occupational toluene exposure. Just in case when correction for urine density is desired for any reason, SG-correction may be recommended.

Phenylglyoxylic acid (PhGA) and mandelic acid (MA) are two popular urinary markers of occupational exposure to styrene, but PhGA has been considered to be relatively unstable when urine samples are stored. This study was initiated to examine the stability of PhGA in urine under two storage conditions, i.e., at room temperature (at 25 degrees C) and in refrigeration (at 4 degrees C) for up to 14 days. The experiments showed that no substantial decrease was observed in either PhGA or MA even at room temperature within one day, but, depending on urine samples, a gradual decrease in PhGA took place both at 4 degrees C and more markedly at 25 degrees C when kept for a week. Further reduction was observed in two weeks even at 4 degrees C. No reduction was observed in MA up to two weeks both at 4 degrees C and at 25 degrees C. The observation on stability of MA and limited stability of PhGA (i.e., no significant decrease for 4 days when stored as refrigerated) was confirmed by a repeated experiment. Further analyses disclosed that PhGA when stored at 4 degrees C tended to be more unstable when urine samples were alkaline (e.g., at pH 8) rather than acidic (e.g., at pH 6 or below), but the trend varied subject to individual samples. Thus, the practical recommendation is that urine samples should be analyzed on the day of collection if all possible, or kept at 4 degrees C, or more preferably at -20 degrees C. Refrigeration will allow storage of up to 4 days without substantial decrease in either PhGA or MA.

This study was initiated to investigate the extents of biological variations in cadmium and three common tubular dysfunction marker levels in blood and urine through repeated sampling.A 12-month survey and a 10-week survey were conducted in an area with no known cadmium pollution. In the 12-month survey, five adult women offered urine samples once every month and blood samples once in every season, respectively. In the 10-week survey, 17 adult women gave urine samples once every week. Blood and urine samples were analyzed for cadmium (Cd-B and Cd-U) by graphite-furnace atomic absorption spectrometry, and urine samples were analyzed also for alpha 1-microglobulin (alpha 1-MG-U), beta 2-microglobulin (beta 2-MG-U) and N-acetyl-beta-D-glucosaminidase (NAG-U) by conventional methods, all under strict quality control. The results were subjected to statistical analysis to examine the extents of biological variations through-out the study periods.Variations in geometric means (GMs) for Cd-B, Cd-U, alpha 1-MG-U, beta 2-MG-U, and NAG-U were all small; the ratio of the largest GM over the lowest GM was 1.1 for Cd-B, 2 for Cd-U and 2 to 3 for alpha 1-MG-U, beta 2-MG-U, and NAG-U in the 12-month survey, and 1.7 at largest for all parameters in the 10-week survey. The within-subject variations during the 12-month or 10-week periods were however large, i.e., more than 4-5-fold difference between the smallest and the largest values obtained for the same subject. Effects of the correction for urine density to reduce the variations were limited. In contrast, within-subject variation in Cd-B was small with a ratio of 1.3.Variations in GM values for Cd-U, alpha 1-MG-U, beta 2-MG-U, and NAG-U at different time of sampling are small so that single measurement would be acceptable as far as the evaluation on a group basis is the study objective. Within-subject variations are wide however, the ratio of the largest value over the smallest value being 4-5 or more, irrespective of correction for urine density. Therefore, care should be practiced when evaluation on an individual basis is intended. Very low within-subject variation in Cd-B may suggest the advantage of Cd-B over Cd-U for individual evaluation among general populations if blood sampling is accepted.

The purpose of the present study was to compare validity of various biomarkers of occupational exposure to toluene (Tol) at low levels. The focus was placed on the comparison of un-metabolized toluene in urine (Tol-U) and peripheral blood (Tol-B) with hippuric acid in urine (HA-U).Surveys were conducted in 16 workplaces on the second half of working weeks, with participation of male solvent workers. Urine and peripheral blood samples were collected at the end of the shifts. After exclusion of cases with dense or diluted urine samples, 473 valid sets of samples were obtained for statistical evaluation. Time-weighted average exposure (for about 8-h) were monitored by diffusive sampling for toluene and other four solvents. Blood samples were subjected to the analyses for Tol-B, whereas urine samples were analyzed for HA-U and Tol-U.The solvent exposures were low, i.e., a grand geometric mean (GM) Tol concentration was 1.6 ppm, and the GM for the SUM in the additiveness equation was 0.12. The correlation analyses of the biomarkers in urine and blood with Tol exposure showed that Tol-U and Tol-B were more closely [correlation coefficients (r) being 0.67 and 0.60, respectively] related than HA-U (r = 0.27). Results of receiver operator characteristic analyses were in agreement with the correlation analysis results.Taking the non-invasive nature of sampling together, Tol in the end-of-shift spot urine sample appears to be the marker of choice for biological monitoring of occupational exposure to Tol at low levels such as2 ppm as a geometric mean.

This study was initiated to make comparative evaluation of five proposed urinary markers of occupational exposure to toluene, i.e., benzyl alcohol, benzylmercapturic acid, omicron-cresol, hippuric acid and un-metabolized toluene.In practice, six plants in Japan were surveyed, and 122 Japanese workers (mostly printers; all men) together with 12 occupationally nonexposed control subjects (to be called controls; all men) agreed to participate in the study. Surveys were conducted in the second half of working weeks. Time-weighted average exposure (about 8 h) to toluene and other solvents were monitored by diffusive sampling. End-of-shift urine samples were collected and analyzed for the five markers by the methods previously described; simultaneous determination of omicron-cresol was possible by the method originally developed for benzyl alcohol analysis.The toluene concentration in the six plants was such that the grand geometric mean (GM) for the 122 cases was 10.4 ppm with the maximum of 121 ppm. Other solvents coexposed included ethyl acetate (26 ppm as GM), methyl ethyl ketone (26 ppm), butyl acetate (1 ppm) and xylenes (1 ppm). By simple regression analysis, hippuric acid correlated most closely with toluene in air (r = 0.85 for non-corrected observed values) followed by un-metabolized toluene (r = 0.83) and o-cresol (r = 0.81). In a plant where toluene in air was low (i.e., 2 ppm as GM), however, un-metabolized toluene and benzylmercapturic acid in urine showed better correlation with air-borne toluene (r = 0.79 and 0.61, respectively) than hippuric acid (r = 0.12) or o-cresol (r = 0.17). Benzyl alcohol tended to increase only when toluene exposure was intense. Correction for creatinine concentration or specific gravity of urine did not improve the correlation in any case. Multiple regression analysis showed that solvents other than toluene did not affect the levels of omicron-cresol, hippuric acid or un-metabolized toluene. Levels of benzylmercapturic acid and un-metabolized toluene were below the limits of detection [limit of detections (LODs); 0.2 and 2 microg/l, respectively] in the urine from the control subjects.In over-all evaluation, hippuric acid, followed by un-metabolized toluene and omicron-cresol, is the marker of choice for occupational toluene exposure. When toluene exposure level is low (e.g., 2 ppm), un-metabolized toluene and benzylmercapturic acid in urine may be better indicators. Detection of un-metabolized toluene or benzylmercapturic acid in urine at the levels in excess of the LODs may be taken as a positive evidence of toluene exposure, because their levels in urine from the controls are below the LODs. The value of benzyl alcohol as an exposure marker should be limited.

Benzyl alcohol (BeOH) is a urinary metabolite of toluene, which has been seldom evaluated for biological monitoring of exposure to this popular solvent. The present study was initiated to develop a practical method for determination of BeOH in urine and to examine if this metabolite can be applied as a marker of occupational exposure to toluene. A practical gas-liquid chromatographic method was successfully developed in the present study with sensitivity low enough for the application (the limit of detection; 5 microg BeOH /l urine with CV=2.7%). Linearity was confirmed up to 10 mg BeOH/l, the highest concentration tested, and the reproducibility was also satisfactory with a coefficient of variation of 2.7% (n=10). A tentative application of the method in a small scale study with 45 male workers [exposed to toluene up to 130 ppm as an 8-h time-weighted average (8-h TWA)] showed that BeOH in the end-of-shift urine samples was proportional to the intensity of exposure to toluene. The calculated regression equation was Y=50+1.7X (r=0.80, p

Objectives This study was initiated to examine if exposure to cadmium (Cd) was high also outside of the previously identified Itai-itai disease endemic region in the Jinzu River basin in Toyama prefecture in Japan. Methods Morning spot urine samples were collected in June–August 2004 from 651 adult women (including 535 never-smokers) in various regions in Toyama prefecture, and subjected to urinalyses for cadmium (Cd), α 1 -microglobulin (α 1 -MG), β 2 -microglobulin (β 2 -MG), N -acetyl-β- d -glucosaminidase (NAG), specific gravity (SG or sg) and creatinine (CR or cr). Three months later, the second urine samples were collected from those with elevated Cd in urine (e.g., ≧ 4 μg/g cr), together with answers to questionnaires on shellfish consumption. Results The geometric mean (GM) Cd, α 1 -MG, β 2 -MG and NAG (after correction for CR) for the total participants were 2.0 μg/g cr, 2.4 mg/g cr, 104 μg/g cr and 2.8 units/g cr, respectively; further analysis with never-smoking cases only did not induce significant changes in these parameters. Analyses of the second urine samples from the high Cd subjects showed that there was substantial decrease (to about a half) in Cd in the 3-month period, and that the decrease was accompanied by reduction in α 1 -MG and NAG (β 2 -MG did not show elevation even in the first samples). The urinalysis results in combination with the results of the questionnaire survey suggest that the high urinary Cd was temporary and might be induced by intake of shellfish that is edible whole. Conclusions The overall findings appear to suggest that Cd exposure in Toyama populations (outside of the Itai-itai disease endemic region) was at the levels commonly observed on the coast of the Sea of Japan, and that the Cd level in urine might be modified by the intake of some types of seafood. Further studies are necessary to elucidate the relation of urinary Cd with seafood intake.

The critical Cd exposure level to induce tubular dysfunctions is a focus of public concern among general populations in Japan. To answer this question, one group each (about 1000 adult women/area) in nonpolluted areas with high (Area H) and low Cd exposure (Area L) was obtained, and 742 strictly age-matched pairs of never-smoking adult women were selected for comparison. Cd, alpha1-MG (microglobulin) and beta2- MG in urine were taken as markers of exposure and tubular dysfunction, respectively. Geometric mean Cd levels as corrected for creatinine (Cdcr) was greater than three times higher in Area H (2.8 microg/g cr) than in Area L (0.8 microg/g cr). Nevertheless, beta2-MGcr did not differ between the two areas (125 microg/g cr for Area H vs 118 microg/g cr for Area L). alpha1-MGcr was only marginally higher in Area H (2.8 mg/g cr) than in Area L (2.1 mg/g cr), with no biomedical significance. Results were essentially the same when analyses were conducted with noncorrected observed values or values corrected for a specific gravity. Thus, the effects of Cd exposure in Area H on renal tubular function should be essentially nil.

Objectives: The objectives of the present analyses were to examine if Cd and tubular dysfunction marker levels in urine show age-dependent changes among women who lived in areas with no known cadmium (Cd) pollution in Japan, and if the trends would be further modified by correction of analyte concentration in terms of urinary creatinine (CR or cr) or urine specific gravity (SG or sg). Methods: The results of urinalysis for Cd, α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), and N-acetyl-β-D-glucosaminidase (NAG) concentrations together with CR and SG were cited from previously established databases. A majority of urine samples were collected in 2000–2002 from adult women (mostly at 40–60 years of age) in various areas in Japan, and the collection was supplemented by cases of ≧60-year-old women in 2003. In total, 11,090 never-smoking cases were subjected to statistical analysis. The values as observed (e.g., Cdob), together with after correction for CR (e.g., Cdcr) or SG (e.g., Cdsg), were examined by linear regression analysis after logarithmic conversion. Results: The geometric mean (GM) values for Cd were 1.10 μg/l (as observed) or 1.32 μg/g cr (after correction for creatinine concentration). No increases were found in the levels of α1-MG, β2-MG or NAG on a group basis, in agreement with the conditions that there was no known environmental pollution with Cd in the sampling areas. There were almost linear increases in logarithm of Cd, α1-MG, β2-MG and NAG concentrations as age advanced. As CR, and to a lesser extent SG, also decreases steadily throughout life (Ikeda et al. 2005; Moriguchi et al. 2005), the correction of the analyte concentrations for urine density induced substantial increases in the analyte values; i.e., the correction by CR and SG induced amplification of the increases by two- and 1.4-times, respectively, compared with the increase in non-corrected observed values. Conclusions: There were age-related increases in Cd and tubular dysfunction markers in urine among women in areas with no known Cd pollution. The increase was amplified two- or 1.4-times when CR or SG correction was applied, respectively. The observation suggests that care should be practiced in applying CR or SG correction, especially when evaluation of Cd exposure and resulting health effects is made among elderly populations.

Cadmium (Cd) is a toxic element ubiquitous in the environment, and general populations have been exposed to this element primarily via foods. Thus, the critical level of non-occupational Cd exposure to cause any health effects among general populations is of public health as well as toxicological concern. The objectives of the present study were to examine the quantitative relationship between cadmium (Cd-U) and beta2-microglobulin in urine (beta2-MG-U) as a marker of exposure to Cd and as a marker of renal tubular dysfunction, respectively, and to identify a threshold Cd-U, if present, in causing a substantial increase in beta2-MG-U. Thus, paired data on geometric mean (GM) Cd-Ucr (i.e., Cd-U as corrected for creatinine [cr] concentration) and GM beta2-MG-Ucr (beta2-MG-U as corrected for cr) of residents in polluted as well as nonpolluted areas in Japan were retrieved in international and domestic sources. In practice, 245 cases of the data pairs were obtained in 51 articles published since 1975. Statistical analysis on ordinary scales disclosed that beta2-MG-Ucr increased markedly when Cd-Ucr exceeded a certain level. The relation between the two parameters after double-logarithmic conversion was in a shape of the letter J or a stick for ice hockey. Analysis for Cd-Ucr at the flexion point gave Cd-Ucr of 4 (on double logarithmic scales) or 7 microg/g cr (on ordinary scales). Cd-Ucr levels that correspond to a beta2-MG-Ucr of 1,000 microg/g cr were estimated to be 8-9 microg/g cr, by ordinary and logarithmic assumption as well as by the 3rd degree regression analysis. Thus, it is concluded that there is a threshold Cd-Ucr level that leads to a substantial increase in beta2-MG-Ucr, and that the threshold level is greater than 4 microg/g cr.

The purpose of the present study was to evaluate the validity of alpha1-microglobulin (alpha1-MG) in comparison with popularly used beta2-microglobulin (beta2-MG). A database on 8975 cases of never-smoking adult women was revisited; the data were based on spot urine samples from the women in 10 prefectures all over Japan. The validity of alpha1-MG was examined following essentially the same protocol as beta2-MG was examined in a previous study. Comparisons were made for alpha1-MG as observed (e.g. alpha1-MG(ob)), as corrected for creatinine (CR or cr) (e.g. alpha1-MGcr) and as corrected for a specific gravity (SG or sg) of 1.016 (e.g. alpha1-MGsg). A cut-off value of 5.0 mg alpha1-MG/g cr or l was deduced from 400 microg beta2-MG/g cr taking advantage of the regression equation between alpha1-MG and beta2-MG. The prevalence of alph1-microglobulinuria as corrected for a specific gravity of 1.016 (or alpha1-MGsg-uria in short) was essentially unchanged irrespective of SG, except for in very dense or very thin urine samples. alpha1-MGcr-uria prevalence decreased at higher CR. Comparison of the present observation with previous findings on beta2-MG-uria prevalence showed that the variation in prevalence of MG-uria as a function of urine density was smaller for alpha1-MGsg whereas it was substantially larger for beta2-MGcr, and thus it appeared prudent to consider alpha1-MGsg rather than beta2-MGcr as a marker of tubular dysfunction.

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 (CS 2 ) 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 CS 2 and 402 non-exposed workers in Japan, all of whom were examined in 1992–93. A total of 251 CS 2 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 CS 2 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, IV 1–3 , 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.

Comparative evaluation was made on alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG), as a marker of renal tubular dysfunction after environmental exposure to cadmium (Cd), with special references to the effects of aging and correction for creatinine concentration. For this purpose, a previously established database of 817 never-smoking Japanese women (at the ages of 20 to 74 years) on hematological [hemoglobin, serum ferritin (FE), etc.] and urinary parameters [alpha(1)-MG, beta(2)-MG, creatinine (cr), and a specific gravity] was revisited. For the present analysis, the database was supplemented by the data on RBP and NAG in urine. The exposure of the women to Cd was such that the geometric mean Cd in urine was 1.3 microg/g cr. Among the four tubular dysfunction markers, NAG showed the closest correlation with Cd, followed by alpha(1)-MG and then beta(2)-MG, and RBP was least so although the correlations were all statistically significant. The observed values of the markers gave the best results, whereas correction for a urine specific gravity gave poorer correlation, and it was the worst when correction for creatinine concentration was applied. Age was the most influential confounding factor. The effect of age appeared to be attributable at least in part to the fact that both creatinine and, to a lesser extent, the specific gravity decreased as a function of age. Iron deficiency anemia of sub-clinical degree as observed among the women did not affect any of the four tubular dysfunction markers. In conclusion, NAG and alpha(1)-MG, rather beta(2)-MG or RBP, are more sensitive to detect Cd-induced tubular dysfunction in mass screening. The use of uncorrected observed values of the markers rather than traditional creatinine-corrected values is recommended when comparison covers people of a wide range of ages.

To examine whether environmental exposure to cadmium has been inducing kidney dysfunction among middle-aged women in the general population in Japan.This study was conducted in 2000 and 2001. Morning spot urine samples were collected from 10,753 women (mostly aged 35 to 60 years) in ten prefectures all over Japan (thus about 1,000 women per site). Urine samples were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), alpha(1)- and beta(2)-microglobulins (alpha(1)- and beta(2)-MG-U). The urinary analyte concentrations were corrected for creatinine (cr) concentration (i.e., Ucr). The data thus obtained were subjected to statistical evaluation by chi-square test, ANOVA, multiple comparison test, and simple regression analysis (SRA) as well as multiple regression analysis (MRA) including logistic regression analysis (LRA). Log-normal distribution was assumed for Cd-Ucr, alpha(1)-MG-Ucr and beta(2)-MG-Ucr, whereas normal distribution was considered for age, Ca-Ucr, Mg-Ucr and Zn-Ucr.Geometric mean values (GM) of Cd-Ucr were distributed unevenly, depending on the sampling areas, with a grand GM of 1.3 microg/g cr, the highest (3.2 microg/g cr) and lowest GM values(0.8 microg/g cr) being significantly different from GMs of other areas. Correlation matrix analysis with subjects of all ages showed that log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr correlated significantly (r=0.272 and 0.202, respectively) with log Cd-Ucr, but they correlated also with age (r=0.280 and 0.213, respectively). The same analysis with the two selected age groups (41-50 and 51-60 years), however, failed to show close correlation of alpha(1)-MG-Ucr and log beta(2)-MG-Ucr with Cd-Ucr. Both MRA and LRA indicated that age was a confounding factor in the evaluation of the effect of Cd-U on the two MG levels. Whereas the LRA with the all-age group showed a positive influence of log Cd-Ucr on log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr, such effect disappeared in parallel with the disappearance of age effects when LRA was conducted with the two selected age groups. An exceptional observation was the influence of log Cd-Ucr on log alpha(1)-MG-Ucr (but not on log beta(2)-MG-Ucr) in LRA when a cut-off value of 5.00 mg for alpha(1)-MG-U/g cr was applied. Comparison between the low and high Cd-U groups showed that both alpha(1)-MG-Ucr and beta(2)-MG-Ucr were higher in the high Cd-U groups, but prevalence of cases with alpha(1)-MG-Ucr and beta(2)-MG-Ucr in excess of the cut-off values did not differ between the two groups except when a cut-off value of 5.00 mg/g cr was employed for alpha(1)-MG-U.In over-all evaluation, no clear-cut evidence was obtained in the present study to show that environmental exposure to Cd has induced tubule dysfunction among middle-aged women in the general population in Japan. It might be the case, however, that an increase in alpha(1)-MG-U was associated with Cd exposure. In this sense, it is apparently desirable from public health viewpoints to make further efforts to reduce the intensity of the general population's exposure to environmental Cd.

Through literature survey, paired data on cadmium (Cd) and beta(2)-microglobulin (beta(2)-MG) levels (as corrected for creatinine concentration) in urine (i.e., Cd-Ucr and beta(2)-MG-Ucr) among Japanese populations were available for 32 groups of men and 58 groups of women in 12 publications. Plotting of the Cd-Ucr and beta(2)-MG-Ucr data for the groups of women showed that beta(2)-MG-Ucr stayed unchanged when Cd-Ucr was at lower levels, whereas beta(2)-MG-Ucr increased sharply when Cd-Ucr was in excess of 10-20 microg/g cr. Regression analysis was made for groups of women with no elevation in beta(2)-MG-Ucr, and those with >400 or >1000 microg beta(2)-MG-U/g cr. A threshold Cd-Ucr level in relation to an increase in beta(2)-MG-Ucr was estimated as Cd-Ucr at the point of intercept of the two regression lines, one with no beta(2)-MG-Ucr elevation, and the other with >400 or >1000 microg beta(2)-MG-U/g cr. Cd-Ucr at the point of flexion thus calculated was 11-12 microg/g cr. Such observation was quantitatively reproduced by the analysis of data for men, giving 10-11 microg Cd-U/g cr at the point of flexion. This study suggests that the relationship of beta(2)-MG-Ucr with Cd-Ucr is not linear but in the shape of letter 'J', i.e., beta(2)-MG-Ucr increases sharply when Cd-Ucr is in excess of 10-12 microg/g cr.

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 12(th) day (Group D1), and the remaining 10 ate Meal H on the 12(th), 13(th) and 14(th) day (Group D3). All 25 subjects then resumed the consumption of Meal L to the end of the study (20(th) 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 12(th) and 20(th) day; venous blood was also collected from 4-8 volunteers at additional time points. RESULTS Mean Cd-I was 4.51 microg/d (range: 1.85-6.93) or 48.48 microg/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 Cd(uptake) rate, defined as (1-Cd-F(excess) /Cd-I(excess)) (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 Cd(balance) rate, defined as (1-Cd-F(output) /Cd-I(intake)), 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 Cd(uptake) and Cd(balance) rates appeared to be higher than those in previous papers when ingested Cd mainly originated in rice.

Diet and smoking are the major routes of cadmium (Cd) intake. In Japanese populations, dietary Cd intake is higher than in other countries, for example, China, Finland, Germany, Malaysia, and Sweden. In determining a tolerable daily/weekly intake of Cd from foods and beverages, the rate of absorption of Cd from the digestive organs is a crucial factor, but it remains controversial. To design a human volunteer experiment for assessing the absorption rate, a preliminary experiment was performed to clarify short-term intake-output balance of Cd and to estimate better biological monitoring parameters for Cd absorption.

Urinary Excretion of TTCA after Intake of brassica Vegetables: Yuriko KIKUCHI, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—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. Resul ts: TTCA-U reached peak concentrations 3–9 h after cabbage intake, gradually decreased, and was below the detection limit (

The aim of this study was to clarify whether phenotypic variation exists when subjects with different genotypes of cytochrome P450 2E1 (CYP2E1) are exposed to N,N-dimethylformamide (DMF). The genotypes of CYP2E1 were confirmed in 123 healthy male volunteer subjects. Of the 123 subjects, the numbers of c1 homozygotes, c2 heterozygotes, and c2 homozygotes were 77, 45, and 1, respectively. Seven of the c1 homozygotes, five of the c2 heterozygotes, and the one c2 homozygote (mean age: 22.7 years, range: 20–27 years) were exposed to DMF vapor twice, once via the skin and once via the lung, for a total of 8 h per subject at a concentration below 10 ppm, the occupational exposure limit recommended by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, at 27°C and 44% relative humidity. Exposure levels were 6.2±1.0 ppm in dermal exposure and 7.1±1.0 ppm in inhalation exposure. Urine samples were collected until 72 h after exposure. The half-lives of urinary N-methylformamide (NMF) were obtained as the phenotype. The average urinary NMF half-lives of the c1 homozygotes, the c2 heterozygotes, and the c2 homozygote were 3.86±1.90, 4.38±1.53, and 4.2 h after dermal exposure, and 1.58±0.42, 1.84±0.61, and 3.2 h after respiratory exposure. The NMF half-lives of the c1 homozygotes were not significantly different from those of the c2 heterozygotes, and there were no differences between the NMF half-lives on the subjects with and without the c2 allele. Even though the data were obtained from only one c2 homozygote, it is noteworthy that the NMF half-life of this subject was slightly less than that of the c1 homozygotes after respiratory exposure.

Objectives: We investigated the potential for the dermal absorption of N,N-dimethylacetamide (DMAC: CAS No. 127-19-5) vapor, the biological half-life of N-methylacetamide (NMAC) in urine as the biological exposure item of DMAC, and the adjustment method for urinary concentrations. Methods: Twelve healthy male volunteers (mean age 25.2 years, range 21–43 years) were exposed to DMAC for 4 h on two occasions at intervals of 96 h or above. Each volunteer sat inside a whole-body-type exposure chamber for the dermal exposure experiment or outside the chamber for the inhalation exposure experiment. The temperature and relative humidity in the chamber were controlled at approximately 26 °C and 40% in order to keep the skin (90% naked) of the volunteers dry. DMAC concentrations were 6.1 ± 1.3 ppm for dermal exposure and 6.1 ± 1.3 ppm for inhalation exposure. Urine samples were collected from 0 h through 36 h and at 48 h and 72 h after the exposure. Extrapolations from exposure concentrations for 4 h to 10 ppm for 8 h were performed. Results: Mean dermal absorption was estimated to be 40.4% of the total DMAC uptake. The biological half-lives of urinary NMAC were 9.0 ± 1.4 h and 5.6 ± 1.3 h via skin and lung, respectively. Mean NMAC in urine just after 5 consecutive workdays (8 h/day) at 10 ppm DMAC exposure was assumed to be 33.7 mg/g · Cr (18.6–70.0 mg/g · Cr). Creatinine-adjusted NMAC concentration in urine for each volunteer within 12 h after the exposure was more closely correlated with the total excretion amount of NMAC up to 36 h than with urinary-volume-adjusted or specific-gravity-adjusted NMAC concentration in both the dermal and inhalation exposure experiments. Conclusions: DMAC vapor was significantly absorbed through the skin. Estimated NMAC values indicate that 20 mg/g · Cr NMAC seems to be appropriate as the biological exposure index.

A national survey of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) in emission gases from the municipal waste incinerators in 1997 revealed that the Nose Bika Center was heavily contaminated by PCDF. Ninety-four workers underwent a physical examination, and blood biochemistry, lymphocyte marker, and NK activity studies were carried out, along with blood dioxin measurements. Information on working history, life-style, and dietary habits was obtained by questionnaire and interview. The blood dioxin levels were as follows. The median TEQ of dioxins was 39.7 pg I-TEQ/g lipid, and the range was 13.3 to 805.8. The median 2,3,7,8-TCDD concentration was 3.9 pg TEQ/g lipid, and the range was

Cardiogenic shock developed in a 72-year-old Japanese woman during combination therapy with verapamil and atenolol for recurrent supraventricular arrhythmia. She had coronary atherosclerosis, liver cirrhosis and brady-cardia-tachycardia syndrome. Despite of the high-dose catecholamines and counterpulsation, she progressively deteriorated. Bolus administration of intravenous calcium chloride (CaCl2) immediately resolved her hemodynamic collapse.

The occupational exposure limit for acrylonitrile (AN) has been set by many organizations on the basis of its carcinogenicity. However, recent epidemiological studies do not afford evidence supporting the hypothesis that AN is carcinogenic to humans. Review of the 18 published cohort studies revealed that, although there is not adequate evidence in humans for carcinogenicity of AN, the possibility of a causal association between high exposure to AN and lung cancer in humans cannot be excluded. It was pointed out that carcinogenic potential of AN may be weak, if any, to humans, and the current occupational exposure limit (OEL) for AN of 2 ppm was evaluated as appropriate in view of AN exposure levels reported by epidemiological studies. Based also on review of the literature on health effects other than carcinogenicity, it was concluded that the current OEL for AN is a reasonable value and there is no need for a revision at present.

OBJECTIVES: A prospective cohort study was initiated to clarify whether the current level of exposure to carbon disulphide (CS2) is low enough to prevent occurrence of subclinical health impairments or to ameliorate health effects due to past high exposure. This paper describes the effects of exposure to CS2 on the nervous and endocrine systems, and the subjective symptoms in a baseline observation. METHODS: The effects were evaluated of CS2 on the median nerve conduction velocity, neurobehavioural and psychological tests, and subjective symptoms related to solvents in 432 male workers exposed to CS2 and 402 reference workers from 11 rayon factories in Japan. Adjustment was made for potential confounding factors such as age or alcohol drinking. Exposure to CS2 was either dichotomised or categorised into three groups by job type. RESULTS: Reductions were observed in motor (-1.9 m/s) and sensory (-0.91 m/s for orthodromic and -1.1 m/s for antidromic) nerve conduction velocities in the workers exposed to CS2 at the spinning and refining processes. Small but significant increases were found in self rated depression scale score and decrease in digit span (backward) in the workers exposed to CS2. Of 54 subjective symptoms many were increased--namely, heavy feeling in the head, light headedness, fainting after suddenly standing up, tremor, dullness, and increased sensitivity of skin in the extremities, reduced grasping power, reduced sexual desire, and increased rough skin. The endocrinological indicator--the concentration of glycosylated haemoglobin--was also increased in the workers exposed to CS2. CONCLUSIONS: Subclinical effects on the nervous system and on glucose metabolism were found in the workers exposed to CS2. One interpretation is that relatively higher exposure to CS2 in the past may induce these, but the effects are still not entirely ameliorated under the current exposure to CS2. Another possibility is that the current exposure to CS2 may cause these positive findings. A follow up observation is necessary to clarify these questions.

A Cross-Sectional Observation of the Effects of Hydrazine Hydrate on Workers' Health: Tetsuo NOMIYAMA, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University-Objective: To clarify the current and cumulative effects of hydrazine hydrate (HH) (N2H4 • H2O: CAS No. 7803-57-8) on workers' health. Methods: A cross-sectional survey was carried out on 172 male HH-exposed workers (age 18-60, mean 39.6; exposure duration 0.50-34.17) and 125 male referent workers (age 19-58, mean 40.9) at 5 factories making HH or hydrazine derivatives in Japan. Current exposure concentrations were assessed by determining hydrazine in the breathing zones and urinary hydrazine + acetylhydrazine. The cumulative exposure level was assessed by multiplying the individuais' working durations at the job sites and the estimated past environmental levels at the job sites. Clinical examinations were performed with particular focus on hepatic and renal function tests. N-acetyltransferase (NAT2) phenotypes were assessed. Acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. Results: No hydrazine was detected in either the breathing zones or the urine of the referent workers. The mean hydrazine concentration in the breathing zones, hydrazine + acetylhydrazine in urine, and cumulative exposure level were 0.0109 ppm (N.D.-0.2003), 0.8660μmol/g • Cr (N.D.-14.20), and 2.80 ppm-years (0.003-19) respectively. There was no difference and no dosedependent change in either the means or the prevalence of abnormal findings in health examination items between the HH-exposed and the referent workers after adjusting confounding factors and by means of the differences of NAT2 phenotypes. Among 90 subjective symptoms, complaint of “nightmares” was significantly related to HH exposure. Conclusion: In this study, no health effect regarding current and cumulative HH exposure was observed in the HH-exposed workers when compared to the referent workers.

OBJECTIVE: A prospective cohort study was designed to clarify the relations between occupational exposure to carbon disulphide (CS2) and its effects on arteriosclerosis in workers in 11 Japanese rayon manufacturing factories. This report is a cross sectional baseline observation in the first study year. METHODS: Study subjects were 432 male rayon workers (mean (range) age 35.5 (19.1-47.8); duration of exposure 13.4 (0.3-29.0)) and 402 male referent workers (age 35.8 (18.9- 49.8)). Exposure to CS2 was assessed by determining the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Mean (SD) TTCA was 3.42 (2.73) mg/g creatinine (Cr) (n = 422). About a quarter of the urine samples were > 5 mg/g Cr, a biological exposure index recommended by the American Conference of Governmental Industrial Hygienists. Health effects on arteriosclerosis were evaluated by measuring blood pressure, serum lipids, pulse wave velocity of the aorta, stiffness and blood flow of the carotid artery, and blood coagulation and fibrinolysis indices, and by use of brain magnetic resonance imaging, electrocardiogram (at rest and after exercise), ophthalmograph, and Rose's questionnaire. Information on potential confounding factors was collected by self administered questionnaire. RESULTS: Prevalence of microaneurysm of the retinal artery was significantly higher in workers exposed to CS2 (8.1%) than in referent workers (3.4%), and increased with age. Other examinations did not show any differences between the two groups even after allowance for confounding factors. CONCLUSIONS: Significant effects of CS2 on arteriosclerosis were not found in current rayon manufacturing workers, with the exception of induction of microaneurysm of the retinal artery.

In order to clarify the effects of acetone (AC) exposure on health, a cross-sectional study was carried out in 110 male AC-exposed and 67 male nonexposed shift workers. The AC workers ranged in age from 18.7 to 56.8 years (mean: 37.6 years) and in length of AC exposure from 0.5 to 34.3 years (mean: 14.9 years). The nonexposed workers ranged in age from 20.7 to 57.5 years (mean: 41.9 years). AC exposure levels assessed by personal passive monitors and biological monitoring indices measured at the end of the workshift were 19.6-1018 ppm in the breathing zone (AC-E, mean: 364 ppm), 2.5-422 ppm in alveolar air (AC-A, mean: 97.3 ppm) 4-220 mg/l in blood (AC-B, mean 66.0 ppm), and 0.75-170 mg/l in urine (AC-U, mean: 37.8 mg/l). Symptoms at the end of the workshift with good exposure-response relationships were eye irritation, tearing, and acetone odor, and symptoms within the previous 6 months with good exposure-response relationships were heavy, vague, or faint feeling in the head, nausea, loss of weight, and slow healing of an external wound. In the 30-44 year age range, simple reaction time and digit span scores in a short computerized neuro-behavioral test battery were significantly lower in AC workers, but exposure-response relationships were not clear. Manifest Anxiety Scale scores, Self-rating Depression Scale scores, R-R interval variation on the ECG, hematological examinations, serum biochemistry examinations for liver function, and phagocytic activity of peripheral neutrophils did not show any AC-related differences between the two groups. In view of the reported findings, the current occupational exposure limit of 750 ppm recommended by many governmental and academic associations seems to be too high to prevent the health effects of AC observed in this study.

Acute and Subacute Inhalation Toxicity of Highly Purified Phosphine (PH3) in Male ICR Mice: Kazuyuki OMAE, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University-The acute and subacute inhalation toxicity of highly purified phosphine (PH3, CAS No. 7803-51-2, 99.995%) in male ICR mice was investigated. LC50 for one-hour exposure was greater than 59.2 ppm and that for four-hour exposure was between 26.5 ppm and 33.4 ppm. Experiments involving acute exposure to 25 ppm PH3 for one, two, four or eight hours, and subacute exposure to 5 ppm PH3 for six hours/day, five days/week, for two or four weeks were conducted. All mice subjected to acute eight-hour exposure died but a histopathological examination failed to reveal the actual causes of death. In the nasal cavity, exposure-time related inflammatory changes were observed in the acute two-, four-, and eight-hour exposure groups, and in the subacute four-week exposure group. Other histopathological, hematological, and serum biochemical examinations did not reveal PH3-related changes. Further study is necessary to assess the actual effects of PH3 on the cause of death. (J Occup Health 1996; 38: 36-42)

In Vitro Solubility and In Vivo Toxicity of Indium Phosphide : Isamu KABE et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—This study was designed to clarify the in vitro solubility and the in vivo basic toxicity of indium phosphide (InP). InP powder was clearly soluble in synthetic gastric fluid and quite insoluble in saline or synthetic lung fluid. Male ICR mice (SPF grade) were given InP at the doses of 0, 1, 000, 3, 000, and 5, 000 mg/kg, intraperitoneally (i. p.) or orally (p. o.). During a 2-week observation, no mice died. In i. p. treated mice, the serum indium concentration showed a dose-dependent increase, and indium mainly accumulated in the lungs and liver. Dose-dependent increases in lung and spleen weight were observed. Black granules of InP were deposited in the lymph nodes, spleen, lungs, and liver. Extramedullary granulopoiesis was observed. And eosinophilic exudates and mononuclear cells were seen in the pulmonary alveoli. Considering these findings, InP particles were presumably transferred to the spleen, liver, and lungs by way of lymphokinetics, causing reticuloendothelial responses. Hematological examination showed increased proportions of stab cells and monocytes in 5000 mg/kg i. p. dosed mice. The p. o. administered mice showed no clear relationship between the dose and biological effects. (J Occup Health 1996; 38: 6-12)

テトラエトキシシラン(TEOS)は,防水,耐酸性があるためにレンガ,モルタル等を保持するために使用される他,半導体製造においては絶縁シリコン酸化膜形成に用いられる. TEOSの毒性については, 1937～51年の間に4編の動物実験の文献があり,標的臓器は肺,肝,腎と報告されている.近年,中島らは半導体製造に使用する超高純度のTEOSを使用した雄性ICRマウスの腹腔内投与実験の結果,腎が標的臓器であり,肝,肺には組織病理学的な変化を見いださなかったことを報告した.また,中島らは雄性ICRマウスを用いて1,000 ppm急性吸入曝露実験, 200 ppm亜急性吸入曝露実験をおこなった結果,鼻腔粘膜の強い炎症,腎の急性尿細管壊死(Acute Tubular Necrosis, ATN),尿細管間質性腎炎(Tubulo-Interstitial Nephritis, TIN)の発生を観察している.本研究は,亜急性吸入曝露による鼻腔および腎への無影響曝露レベルを明らかにする目的で実施した. TEOS濃度を100 ppmおよび50 ppmに調整し,雄性ICRマウスに6時間/日, 5日間/週, 2または4週間曝露した.体重の増加,臓器重量,腎機能・肝機能の血清生化学的指標,尿中NAG活性,尿中LDH活性にコントロール群と曝露群間の差はなく,肝,肺,気管,脾,膵,胸腺,甲状腺,角膜に病理組織学的変化を認めなかった.しかし腎では, 100 ppm曝露で2および4週間曝露により10匹中2匹のマウスにTINが観察され,鼻粘膜では50 ppm曝露で2および4週間曝露により10匹中10, 7匹に炎症が観察された.以上の結果より, TEOS吸入曝露おいては,腎と鼻粘膜がTEOSの標的臓器であり,腎では100 ppm,鼻粘膜では50 ppmで病理組織学的所見が陽性であることから,労働環境におけるTEOS曝露は,現行の許容濃度10 ppm以下に保たれるべきであり,不可逆的影響と考えられる腎への影響を長期にわたり観察する必要がある.