論文

This article compares current values for occupational exposure criteria in Japan and the United States and briefly describes the Japanese organization. The values recommended by the committee of the Japan Society for Occupational Health (JSOH) correspond fairly closely with those of the American Conference of Governmental Industrial Hygienists (ACGIH®) threshold limit value (TLV®) and biological exposure index (BEI(TM)) committees, perhaps because much of the information is drawn from the same database. For only six substances do the limits differ by more than a factor of 10, while for 121 substances the limits differ by less than a factor of 2. For 28 substances the TLV exceeds the JSOH occupational exposure limit (OEL) by a factor of between 2 and 10, while for 18 the TLV is correspondingly less than the JSOH OEL. Provisional values are given, or changes proposed, for 29 substances. The principal biological limits for mercury are identical, while those for lead and hexane differ by less than a factor of 2. Classification of carcinogens differs slightly, but the numbers of proven human carcinogens are similar, as are the total numbers considered suspect.

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 neurobehavioral 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.

Using male ICR mice, the LC50 and acute and subacute inhalation toxicity of dichlorosilane (SiH2Cl2, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron in diameter. The CL50 of DCS at 4-h exposure was 144 ppm (nominal concentration). In the acute inhalation study, ten mice in each group were exposed to 64 ppm (nominal concentration) DCS for 1, 2, 4 or 8 h. Body weight loss, wheezing and piloerection were observed in mice exposed for 2 h or more. Histopathologically, injury to the nasal mucosa and trachea were observed in all exposed mice. Mice exposed to 32 ppm (nominal concentration) DCS for 2 or 4 weeks also exhibited depression of body weight gain, wheezing and piloerection. Squamous metaplasia of the nasal mucosa and tracheal epithelium was observed in both 2- and 4-week exposure groups. Exposure to DCS was irritant or corrosive to the respiratory tract with both acute and subacute inhalation. Apart from silane (SiH4), toxic effects of DCS seem to be characterized by chloride compounds derived from DCS. © 1996 Springer-Verlag.

In order to clarify the acute and subacute toxicity of diborane (B2H6, CAS: 19287-45-7) at low concentrations, male ICR mice were exposed to diborane for 1, 2, 4 or 8 h at concentrations of 1 or 5 ppm (phase I study), and for 6 h/day, 5 days/wk, over 2 or 4 wk at concentrations of 0.2 or 0.7 ppm (phase II study). Hematological and biochemical tests, and histopathological examinations of the cornea, nasal mucosa, respiratory tract and lung were carried out. All mice in both studies survived until they were sacrificed. In the phase I study, lung weight increased significantly in mice exposed to 5 ppm of diborane for 8 h. Histopathologically diffuse panbronchiolitis-like lesion was observed in mice exposed to 5 ppm of diborane for 2, 4 or 8 h. In the phase II study, slight infiltration of polymorphous neutrophil was observed mainly in the peribronchiolar region in mice exposed to 0.2 ppm or 0.7 ppm of diborane for 2 or 4 wk. In both studies, hematological and biochemical examinations failed to reveal any exposure-related changes. These results suggest that no-observed-effect level of diborane inhalation on the respiratory organs were 1 ppm in acute exposure, but 0.2 ppm of diborane inhalation for 2 or 4 wk seems to be unsafe.

To determine safe exposure levels of tetraethoxysilane (TEOS) in the kidney, groups of male ICR mice (SPF grade) containing 10 animals each were exposed to TEOS, 100 ppm or 50 ppm, for 6 hours/day, 5 days/week, for 2 or 4 weeks. Tubulointerstitial nephritis developed in mice exposed to 100 ppm for 2 and 4 weeks, but no kidney lesions or renal function changes were observed in mice exposed to 50 ppm. However, histopathological changes were detected in the nasal mucosa of mice exposed to 50 ppm TEOS. These results indicate that the occupational exposure level for TEOS should be strictly maintained below the current recommended exposure limit, 10 ppm, set by many countries and academic associations, and that renal tubular function of TEOS-exposed workers should be assessed and monitored for a long period.

To develop a proper protocol for biological exposure monitoring of acetone, we evaluated whether exposure to acetone on the previous day affects the biological monitoring value at the end of a work day. One hundred and ten male workers exposed to acetone in three acetate fiber manufacturing plants were monitored using a liquid passive sampler on two consecutive working days after 2 days without exposure. Urine samples were collected at the start of the workshift and the end of the shift on both days for each subject. For ten exposed workers urine samples were collected approximately every 2 h during and after the first working day until the following morning. Acetone concentrations in urine (Cu) at the start of the first working day were 1.3 ± 2.4 (range: ND-14.1) mg/l in nonexposed workers and 2.4 ± 5.6 (range: ND-40.3) mg/l in exposed workers. The urinary acetone concentration at the beginning of the second working day indicated that urinary levels of acetone do not decline to background level by the following morning when exposure concentration exceeds 300 ppm. However, linear regression analysis demonstrated that the relationship between environmental exposure level and urine level was similar on the 1st day and the 2nd day. Thus, although urine acetone levels did not return completely to baseline after high exposures, under the present exposure levels the exposure on the previous day did not significantly affect urinary acetone at the end of the workshift of the next day. © 1995 Springer-Verlag.

Exposure-effect and exposure-response relation between exposure to lead and δ-aminolaevulinic acid concentration in blood (ALA-B) were examined in 238 male workers exposed to lead. Concentrations of ALA-B ranged from 26 to 352 μg/l and lead concentrations in blood (Pb-B) from 7.1 to 86.0 μg/dl. Concentrations of ALA-B correlated closely with concentrations of Pb-B (r = 0.74), and increased ALA-B concentration occurred at Pb-B concentrations of around 30 μg/dl. Exposure-response curves indicated that the 50 percentile response doses were roughly 30, 40, and 50 μg/dl Pb-B when cut off points of ALA-B were set at 50, 60, and 70 μg/l respectively. The sensitivity and specificity of measurements of ALA-B concentrations for health screening were sufficiently high when the health based exposure limits of lead were set at 30-50 μg/dl. Moreover, a pronounced increase in ALA-B concentrations occurred when the inhibition rate of erythrocyte ALA dehydratase exceeded 85%. These findings suggest that ALA-B is a useful indicator for assessing the early effects of exposure to lead on haem biosynthesis.

In order to examine the toxicity of silane, male ICR mice were exposed to silane for 30 min (n=8), 1 or 4 h (n=12) at concentrations of 2500, 5000, 7500 (30-min experiment only) or 10000 ppm. In the 1- and 4-h experiments, 12 mice were divided into two sub-groups: four for 2-day observation and eight for 2-week observation. The mortality was six deaths out of eight mice exposed to 10000 ppm for 4 h. No deaths occurred in any of the other experiments. In the mice sacrificed 2 days after the exposure, acute renal tubular necrosis was observed at 10000 ppm (1-h exposure) or at 2500 ppm or more (4-h exposure). Reduction in body weight, increase in relative kidney weight and blood urea nitrogen (BUN) level, and splenic atrophy and inflammatory changes of the nasal mucosa were also seen in the 10000 ppm-4 h exposure group. In the mice sacrificed 2 weeks after the exposure, tubulo-interstitial nephritis (TIN) developed at 7500 ppm or more (30-min exposure) or at 5000 ppm or more (1- and 4-h exposure). BUN increased in a dose-dependent manner, and BUN in TIN positive mice was significantly higher than that in TIN negative mice (1- and 4-h exposure). No histopathological changes were observed in the glomeruli. These results indicate that the LC50 of silane in mice is between 5000 and 10000 ppm for 4-h exposure and is greater than 10000 ppm for 1-h or 30-min exposure. The target site of silane toxicity is the renal tubule, and the no-observed-effect levels of silane for acute inhalation exposure in mice are 1000 ppm for 4-h exposure (from the previous report of our research group), 2500 ppm for 1-h exposure and 5000 ppm for 30-min exposure. © 1993 Springer-Verlag.