Chizuru Ishizuka

Cross sectional observation of the effects of carbon disulphide on the nervous system, endocrine system, and subjective symptoms in rayon manufacturing workers

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.

Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing 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 Roses 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.

Effects of intratracheally administered indium phosphide on male fischer 344 rats

Effects of Intratracheally Administered Indium Phosphide on Male Fischer 344 Rats: Takamoto Uemura, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—Objective—To examine the effects of intratracheally administered indium phosphide (InP) and distribution of indium on male Fischer 344 rats. Materials and methods—Rats were intratracheally given 0, 1, 10 or 100 mg/kg of InP with a mean diameter of 0.8pm and observed for 1 and 7 days. The bronchoalveolar lavage fluid (BALF) was examined biochemically and cytologically. Serum biochemical, hematological and histopathological examinations were done, and the indium concentration in organs and serum was determined. Findings—The number of neutrophils in BALF remarkably increased in a dose‐effect manner 1 and 7 days after administration and InP particles were phagocytized in the macrophages. Total protein (TP), lactate dehydrogenase (LDH), total phospholipid (TPL) and total cholesterol (T‐Cho) in BALF showed a clear dose‐effect relationship 7 days after administration. Indium was detected in the liver and spleen and increased in a dose‐related manner on the next day and 7 days after administration. Serum indium was detected in the group given more than 10 mg/kg but did not reveal a dose relationship. Histopathological examination of the lungs showed phagocytized InP particles in the macrophages and the migration of neutrophiles in the alveoli. InP particles remained in the bronchioles and alveoli until 7 days after. No histopathological changes were detected in the liver or spleen. A hematological study did not reveal significant findings, interpretation—Intratracheally administered InP particles cause pulmonary inflammation and those particles remain in the lower airways for at least 7 days. Phagocytosis of macrophages may contribute to their disposal and distribution to the liver and spleen. Further study is required with particles with a lower toxic activity than InP and with the same particle size as the InP used in this study, to clarify their specific toxicity. Simultaneously longer observation is needed to assess toxicity in the other organs after distribution.

In Vitro Solubility and In Vivo Toxicity of Indium Phosphide.

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 lym‐ phokinetics, 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.

Toxicity of Silicon Compounds in Semiconductor Industries

Toxicity of Silicon Compounds in Semiconductor Industries: Hiroshi Nakashima, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—The toxicities of silane (SiH4), tetraethoxysilane (Si(OC2H5)4, TEOS) and dichlorosilane (SiH2CI2, DCS) were reviewed in order to compare the toxicological properties of silicon compounds used in the semi‐conductor industry. Silane and TEOS showed similar toxicities, characterized by nephrotoxicity. Mice subjected to silane (2500, 5000 and 10000 ppm) or TEOS (1000 ppm) acute exposure developed acute tubular necrosis. Tubulo‐interstitial nephritis was seen in mice which were subjected to an acute inhalation study and survived 2 wk of the observation period or those subjected to subacute inhalation studies of TEOS (100 and 200 ppm for 2 or 4 wk). Silane and TEOS, however, differed in the concentration at which they showed signs of toxicity. This may be due to their solubility in water and other metabolic factors, but their metabolic pathways have not yet been elucidated. TEOS injured nasal mucosa (1000 ppm for 2 h or more and 50, 100 and 200 ppm for 2 or 4 wk). It was observed at a lower concentration than nephrotoxicity in the 50 and 100 ppm subacute inhalation study. On the other hand, silane caused nasal mucosal lesions only at 5000 or 10000 ppm for acute inhalation, and those of subacute inhalation were mild (1000 ppm for 2 or 4 wk). DCS showed another type of adverse effect. It was an irritant and/or a corrosive agent to the respiratory tract in the acute (64 ppm for 1, 2, 4 or 8 h) and subacute (32 ppm for 2 or 4 wk) inhalation study. The fate of DCS in air was also studied and it was shown to form small particles including silicon and chlorine (Cl) atoms. Cl seems to play an important role in the toxicity of DCS.

Acute and subacute inhalation toxicity of dichlorosilane in male ICR mice

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.

Acute and Subacute Inhalation Toxicity of Highly Purified Phosphine (PH3) in Male ICR Mice.

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 his‐ topathological, 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.

Toxicity of Fire Decomposition Products of New Fire Extinguishing Agent, 1,1,1,2,3,3,3,-Heptafluoropropane.

Received June 27, 1997; Accepted Aug 11, 1997 Correspondence to: K. Omae, Department of Preventive Medicir and Public Health, School of Medicine, Keio Universitj 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan