Toxicity of Ultrafine Nickel Particles in Lungs after Intratracheal Instillation: Qunwei ZHANG, et al. Department of Environment Health. Fukui Medical University-To study the lung acute and subacute toxicity of ultrafine nickel particles, rats were intratracheally instilled with 0, 0.1, 0.5, 1 and 5 mg ultrafine nickel (Uf-Ni), respectively. At 3 days after injection, the body weight and wet lung weight were determined. At the same time, bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein (TP), and total cell and differential cell counts. The results showed that indicators of lung injury and inflammation in BALF were markedly raised with increased Uf-Ni from 0 to 1 mg, and there were no differences in the indices between injection of Uf-Ni at 1 mg and at 5 mg. Rats were intratracheally instilled with 1 mg Uf-Ni, and wet lung weight, and bronchoalveolar lavage fluid (BALF) profiles were analyzed 1, 3, 7, 15 and 30 days later. The effects of Uf-Ni on indices that can be presumed to reflect epithelial injury and permeability (LDH or TP) were dramatically increased from day I up to 30 days after injection. Lung histology findings generally confirmed the BALF data, showing severe lung inflammation at I day after injection of Uf-Ni, and epithelial hyperplasia and inflammation still present at 30 days after injection. Our findings suggest that Uf-Ni causes persistent inflammation following instillation of a small dose.

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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.

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Occupational Exposure to Low Concentrations of Organic Solvents in Shipyards: Hironobu KATSUYAMA, et al. Department of Public Health, Kawasaki Medical School-Because shipbuilders have to use organic solvents in very confined spaces, they have a higher risk of inhaling the solvents than workers working in an open space. The working environment at 14 workplaces with very limited space was examined and biological monitoring was performed on 18 workers who worked in such places. Out of 14 workplaces, only 4 did not exceed the assessment criterion. Although exhaust ventilation fans and chemical cartridge respirators were used to avoid exposure to solvent vapor irrespective of the concentrations of solvents, biological samples revealed inhalation of solvent vapor. Urinary excretion of hippuric acid and methylhippuric acid varied from 0.07 to 0.92 g/g Cr and 0.02 to 0.42 g/g Cr at the end of the shift, respectively. Concentration of toluene and xylene in the end-exhaled air varied from <0.1 to 5.0 ppm and <0.1 to 10.6 ppm, respectively. The concentration of metabolites in urine and the concentration of solvent in the end-exhaled air revealed a strong correlation in the case of xylene but not toluene. Because of the limitation of space, the mean concentration of solvents in the working environment is not always available in shipyards, which make it difficult to estimate the amounts inhaled by workers. Biological monitoring of the end-exhaled air provides useful information to make it possible to avoid continuous and/or unexpected exposure of workers who have to work in a very limited space.

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Liver Damage among Environmental Disinfestation Workers: Francesco TOMEI, et al. Occupational Medicine Dept., “La Sapienza” University, Rome-It has been reported that exposure to high doses of insecticides can damage the liver. It is now becoming apparent that even exposure to low doses may affect the liver and blood. Studies on the effects on the health of disinfestation workers are scant. This study investigated 37 males doing environmental disinfestation work. They all employed the same types and amounts of pesticides. They were compared with 60 controls not exposed to hepatotoxic substances. In the presence of a physician, all subjects completed a clinical-history questionnaire. They all underwent a general clinical examination and specific blood chemistry tests were done. In the exposed group we found liver test values to be higher than controls (p<0.001), including AST (p<0.025), alkaline phosphatase (p<0.001 ), and total bilirubin (p<0.001 ). We found no abnormal hematological changes. The findings indicate that the use of pesticides in environmental disinfestation alters liver function and that this screening protocol is valid for identifying subjects at risk for he atotoxicity.

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No Evidence for a Diuretic Effect of Benzisothiazolinone (BIT) in an Experimental Animal Model Employing Anaesthetised Rats: Björn HELLMAN, et al. Department of Occupational and Environmental Medicine, University Hospital, Uppsala-The diuretic effects of benzisothiazolinone (BIT), vapours from a water-based paint, and the reference compound furosemide, were investigated in an experimental model employing anaesthetised rats. BIT (90 mg/kg body weight) was given orally 2 or 12 hr before the rats were anaesthetised. The paint vapours and furosemide were administered during anaesthesia. Urinary flow, osmolality, urinary concentrations of sodium and potassium, and blood pressure were measured as indicators of renal function. Whereas all these parameters were significantly affected after an injection with furosemide, neither BIT nor the vapours from the paint were found to induce any biologically significant effects. Provided that the experimental model with anaesthetised rats is relevant when studying the mechanisms for diuresis in man, the results of the present study suggest that previously reported problems with frequent urination among painters working with water-based paints are symptoms not related to a direct diuretic effect of BIT or the vapours from these paints.

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Plasma Free Amino Aoids in Workers Working under Different Stress Conditions: Tang-Chun Wu et al. Institute of Occupational Medicine, Tongji Medical University-Many harmful occupational factors induce the stress response and result in both the induction of heat stress proteins and the inhibition of the synthesis of other cellular proteins. Since amino acid levels are intimately linked to protein synthesis, we examined the free amino acid levels in the plasma of workers subjected to prolonged exposure to heat, carbon monoxide (CO) or both. The results showed that the levels of most amino acids tended to increase in the plasma of workers in stressful environments, and that free methionine and tryptophan increased significantly (p<0.05) in the heat, CO, and heat+CO groups when compared to a control group. The largest increase was seen in the heat+CO group, followed by the heat group, and finally the CO group. The changes in plasma free amino acid levels in the stress-exposed workers correlate to the induction of heat stress proteins. These findings suggest that the regulation of plasma amino acids levels, by preventing amino acid accumulation possibly resulting from a decrease in the rate of protein synthesis following exposure to stressors, may help to protect workers from these extreme conditions.

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A Cross-Sectional Observation on The Association of Menopause with Coronary Risk Factors in Japanese Female Workers: Yuka NOBORISAKA, et al. Department of Hygiene, Kanazawa Medical University-Biological risk factors for coronary heart disease (CHD), i.e., blood pressure, serum lipids and uric acid (UA), blood glucose and hemoglobin A1c, together with serum hepatic enzymes, were measured in 260 female workers consisting of 118 40-year-olds, 102 50-y.o. and 40 60-y.o., and the age-related differences were compared with male workers of the same age. The association of menopause with the risk factors and serum hepatic enzymes was also evaluated. Serum total cholesterol (Tch), triglycerides (TG), UA, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels were higher in the females in higher age groups, much more noticeably than in the males. Serum Tch was lower in the females aged 40 y than in the males, but higher in the females aged 50 and 60 y. Other parameters remained better in the females in all three age groups. A significant association of menopause was found with a higher serum Tch level and was suggested with higher serum ALT and GGT levels. Tch was highest in women ≤5 years from menopause while ALT and GGT were highest in women 5 to 9 years from menopause, suggesting a quick change in serum Tch and gradual changes in serum hepatic enzymes after menopause. These adverse changes in serum lipids and hepatic enzymes after menopause should be taken into consideration in industrial health care for middleaged women.

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Effects of breathing resistance while inhaling 30% carbon dioxide during steady-state exercise: Masayoshi TAKAHASHI, et al. National Institute for Resources and Environment-The purpose of the study was to determine the effects of breathing resistance on the human body while inhaling 3% Carbon dioxide and to evaluate the appropriateness of self-contained self-rescuer (SCBA) criteria in the Japan Industrial Standard (JIS). Eight male subjects volunteered for the study and breathed both normal air and 3% carbon dioxide with both low and high breathing resistance during moderate steady-state exercise. The high breathing resistance produced a pressure level that was almost the same as the upper permitted limit for SCBA in the JIS. Increasing the breathing resistance did not cause any significant effect on the human body while breathing normal air but, in the case of 3% carbon dioxide, the high resistance increased end-tidal carbon dioxide significantly and caused strong distress in the test subjects. Based on these results, it is recommended that carbon dioxide levels be kept low to improve human performance while wearin SCBAs.

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The Standardized Nordic Questionnaire Applied to Workers Exposed to Hand-Arm Vibration: Orawan KAEWBOONCHOO, et al. Department of Hygiene, School of Medicine, Wakayama Medical University-The standardized Nordic questionnaire (SNQ) is not yet widely used in Japan. This paper describes the possibility whether the SNQ, translated into Japanese, can be applied to workers exposed to hand-arm vibration. The musculoskeletal symptoms of 40 chain saw operators (CS) in private forests and 40 agematched bush cleaner operators (BC) in the public service sector were assessed by the SNQ and the Japanese questionnaire (JQ). Both the SNQ and the JQ showed that CS had a higher prevalence of symptoms than BC. By the SNQ, there were significant differences in the prevalence of musculoskeletal symptom in the elbows, upper back and knees. By the JQ, CS had significantly higher prevalence of pain in the shoulders and elbows than BC. These results show the SNQ also fits the musculoskeletal symptoms and clearly differentiates between the prevalences in the two groups. The SNQ enables us to identify the severity, the duration, the treatment and the disability, but does not include items related to finger numbness and finger blanching. For that reason some JQ items should be a lied to workers exposed to hand-arm vibration.

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CYP2E1 Level in Rat Liver Injured by the Interaction between Carbon Tetrachloride and Chloroform: Hisayoshi IKATSU, et al. Center for Environmental Science and Technology. Okayama University-The toxic interaction between carbon tetrachloride (CCI₄) and chloroform (CHCI₃) was investigated in rats chronically pretreated with ethanol, and in rat liver microsomes. A combined exposure to 10 ppm CCI₄ and 50 ppm CHCI₃ increased plasma alanine aminotransferase (ALT) activity to a level similar to that by a single exposure to 50 ppm CCI_4^* The single exposure decreased liver reduced glutathione (GSH) and cytochrome P450 (CYP) content, and N-nitrosodimethylamine N-demethylase (NDMAD) activity. The effects of combined exposure, however, were little or less than those of the single exposure. Immunoblot analysis with monoclonal antibody to CYP2E1 indicated that CYP2E1 was appreciably decreased after the single exposure but the enzyme remained after the combined exposure. The antibody inhibited CCI₄-induced lipid peroxidation in microsomes from ethanol-treated rats. Ethanol pretreatment increased the metabolic rate of CCI₄ and CCI₄-induced lipid peroxidation, but the coexistence of CHCI₃ and other hydrocarbons such as trichloroethylene and 1, 1, 1-trichloroethane did not increase the in vitro metabolic rate or the lipid peroxidation. The addition of GSH decreased CCI₄-induced lipid peroxidation, and the effect reached its maximum at 0.3 mM of GSH, so that the hepatotoxic interaction between CCI₄ and CHCI₃ at low dose exposure is more than additive when judged by the plasma ALT activity, but this is not true of the changes in drug-metabolizing enzyme activity and GSH de pletion.

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The Effect on Workers' Knowledge, Attitudes and Behavior of a Group Health Care Program for Small Sized Plants in Pusan, Korea: Hae-Sook SOHN, et al. Department of Preventive Medicine, Medical College, Inje University—To investigate the effect of a group health care program by observing differences in knowledge, attitudes and behavior (K, A and B) regarding occupational health services, a cross sectional survey of 201 workers served under a Group Health Care Program (GHCP) was carried out from November, 1995 to January, 1996. The K, A and B of workers were assessed by questionnaires about occupational health services. Subjects were divided to two groups according to the duration they had been served with group health care (Group I: <1 year, Group II: >= 3 years). K, A and B were compared in the two groups. All measures of K, A and B related to occupational health services, except satisfaction with the GHCP, were higher in Group II than in Group I. Group II was significantly higher in K, A and B (P<0.01) about personal protective equipment. This study confirmed that workers' K, A and B were positively influenced by the GHCP. The fact that the percentages of workers wearing personal protective equipment (PPE) and of proper use of PPE in Group II were significantly higher indicates that GHCP may be effective in the prevention of some aspects of occupation-related diseases.

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