Cytochrome P450 Isoforms and the Metabolism of Volatile Hydrocarbons of Low Relative Molecular Mass: Tamie NAKAJIMA. Department of Hygiene, Shinshu University School of Medicine—Cytochrome P450 isoforms responsible for the metabolism of volatile hydrocarbons of low relative molecular mass are reviewed. Rat CYP2E1 catalyse the metabolism of all hydrocarbons with a low Km, whereas CYP1A1/2, CYP2B1/2 and CYP2C11/6 catalyse the metabolism of many hydrocarbons with a high Km although the contribution of the first two is minimal. The metabolism of hydrocarbons is affected by physiological and environmental factors, changes in the expression of P450 isoforms and the affinity of the chemicals for the isoforms. Human CYP2E1 also catalysed all of the hydrocarbons investigated, with the same kinetics as that of rat CYP2E1. Human CYP2B6 and CYP2C8 catalyse the metabolism of some hydrocarbons, but with slighty different catalytic properties for the formation of o- and p- cresol from toluene. Although CYP2B1/2 is poorly expressed in liver microsomes from control rats, CYP2B6 is found immunochemically to be constitutive in human liver microsomes. Human CYP1A2 also catalyses the metabolism of some organic solvents, with varying kinetic and catalytic features. The contribution of human CYP3A3, CYP3A4 and CYP3A5 to metabolism is very low. In conclusion, CYP2E1 is an essential isoform for the metabolism of hydrocarbons in both rodents and humans, especially at low concentrations. (J Occup Health 1997; 39: 83-91)

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Epidemiological Study of Periodontal Disease and White Blood Cell Count among Employees in a Company: Yukie YOSHIDA, et al. Osaka Prefectural College of Health Science—The purpose of this study was to investigate the relationship between the white blood cell (WBC) count and periodontal disease as classified by the Community Periodontal Index of Treatment Needs (CPITN) in 1, 241 male Japanese factory workers by determining their WBC count and the extent of their periodontal disease. The results obtained were as follows: in both smoker and non-smoker, the results of a two-way ANOVA indicated that the CPITN score 3 and 4 groups had a significantly higher WBC count than the CPITN score 0, 1 and 2 groups. The results of multiple regression analysis indicated that the WBC counts were significantly associated with age, smoking and the CPITN score. It appeared that there was a significant relationship between the WBC count and the prevalence of periodontal disease among employees in a company. (J Occup Health 1997; 39: 92-94)

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Diver's Lung Function: Influence of Smoking Habit: Shinya SUZUKI. Japan Maritime Self-Defense Force Undersea Medical Center—To assess the influence of smoking habit on divers' lung function, we measured static lung volumes, dynamic lung volumes and flows and diffusing capacity for carbon monoxide (DLco) on 71 healthy, male, JMSDF active-duty uniformed divers (46 smokers and 25 nonsmokers). All measurements were conducted with an automated system (CHESTAC-25V model; Chest Ltd., Tokyo, Japan). Comparison of lung functions between smokers and nonsmokers was assessed using a Mann-Whitney ranksum test. Vital capacity in smokers was 120.4 ± 11.3 (mean ± SD)% of the predicted value for age and height, and in nonsmokers was 119.9 ± 15.1 %. In the static lung volumes there were no differences between smokers and nonsmokers. Although the forced vital capacity (FVC), the forced expired volume in the 1st second (FEV_1.0), and the forced expiratory flow rate at 75% of FVC expired (V₇₅) showed no difference between two groups, the peak expiratory flow rate (PEFR) in smokers was lower than that in nonsmokers (p<0.005). The forced expiratory flow rate at 25% of FVC expired (V₂₅) showed no difference, while the DLco in smokers was worse than in nonsmokers (p<0.01). Lung Volumes of the divers in JMSDF were larger than predicted values in the general population. Judging from the ratio of the residual volume to total lung capacity, emphysematous change with aging was negative. PEFR, FEV_1.0 and V₇₅ depend on the ventilatory muscle strength and diameter of the large respiratory tract. To investigate the reason why only PEFR was lower in smokers than nonsmokers in this population, more data should be collected. The finding of no difference in V₂₅ between the two groups could not indicate that smokers had emphysematous change compared to nonsmokers. The decrease in DLco with age in smokers compared to nonsmokers, however, suggested the possibility of emphysema. Considering that emphysema is a contraindication for diving, a diver should not smoke. (J Occup Health 1997; 39: 95-99)

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Monitoring of Accidents and Risk Events in Industrial Plants: Krzysztof SWAT. Nofer Institute of Occupational Medicine—The aim of our 3-year study begun in 1994 is to develop an organizationally useful method of recording risk events in plant to help in finding causes of accidents and preventing them. In the first stage, four plants in different industrial branches were selected for the study: foundry, machinery, meat processing and furniture. The four plants employed a total of 2, 964 workers. Eighty-three accidents which happened in 1993 were analyzed from the view point of frequency, severity and their direct and indirect causes. Plants had different frequency rates for different types of accidents. At least 45.8% of the accidents studied involved violation of the fundamental principles of housekeeping. An additional study on accidents and minor injuries carried out in 1994 in the meat processing plant revealed that 95% of all incidents are not reported. The conclusions of the study are as follows: 1. Accidents should be recorded according to the circumstances in which they occur and especially to their types whereby information is provided on the type of relevant safety management problem; 2. One should note minor injuries in plant, especially those requiring first aid. There is a suprising repeatability of these events, their sources and effects; 3. Poor housekeeping constitutes a frequent source of accidents and housekeeping control should be incorporated into the safety monitoring system. (J Occup Health 1997; 39: 100-104)

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Prevention of a Malaria Outbreak among Non-Immune Japanese Workers Engaged in the Construction of a Thermal Power Plant in Sonebhadra, India: Hironobu KATSUYAMA, et al. Department of Health, Mitsubishi Heavy Industries—Continuous consumption of anti-malarial drugs is not always recognized as the first choice for prevention of malaria among workers residing in malarious areas for long periods. In Japan, personal protective measures have been primarily recommended. However, a high incidence of malaria was observed among workers engaged in construction of a thermal power plant in the Sonebhadra district, Uttar Pradesh, India, during the period from February to August, 1991. On-site inspection revealed the difficulties of preventing mosquito bites among personnel who had lived in industrialized countries and were not immune to malaria. Repeated education regarding the danger of malaria and rigorous precautions from mosquito bites dramatically reduced the incidence of malaria among such personnel. Not only proper usage of personal protection measures such as long sleeved shirts, mosquito repellents, mosquito nets etc., but also an effort to reduce the number of mosquitoes in living and working areas by such means as insecticides, spraying operations, etc. should be emphasized. On the other hand, chemoprophylaxis still seemed to be the most effective protective measure for workers compelled to remain outdoors until late at night. The utility and availability of protective divices may depend on the working status and circumstances, so that on-site inspection helps to ensure occupational health, and also affords an opportunity to instruct the workers on malaria prevention. (J Occup Health 1997; 39; 105-112)

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Separate Determination by Gas-Chromatography of Dimethylformamide, Dimethylacetamide, Monomethylformamide and Monomethylacetamide in Urine for Biological Monitoring: Toshio KAwAI, et al. Osaka Occupational Health Service Center—A gaschromatographic method is developed, which allows simultaneous determination of N, N-dimethylformamide (DMF) and N, Ndimethylacetamide (DMA), as well as their metabolites of N-monomethylformamide (MMF) and N-monomethylacetamide (MMA), respectively. Quantitative heat decomposition of N-hydroxymethyl-Nmethylacetamide to N-monomethylacetamide required an injection port temperature of 225%deg;C or above, similar tc the case of conversion from N-hydroxymethyl-Nmethylformamide to N-monomethylformamide. Analysis of urine samples from workers simultaneously exposed to DMF and DMA showed that the separation of small peaks for unidentified materials (which were detected in some urine samples) from that of DMF and DMA was achieved only on a 60 m-long DB-1071 column (and not on a 30 m-long one). The analysis of urine samples from 27 exposed workers showed that both DMF and DMA, in addition to MMF and MMA, were excreted in urine al measurable concentrations. There was a significant correlation between MMF and DMF, and between MMA and DMA; the ratio was about 0.02 to 0.03 for both DMF/MMF and DMA/MMA. (J Occup Health 1997; 39: 113-118)

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Therapeutic Efficacy of a Few Diesters of Meso 2, 3-Dimercaptosuccinic Acid during Sub-Chronic Arsenic Intoxication in Rats: S.J.S. FLORA, et al. Division of Pharmacology and Toxicology, Defence Research and Development Establishment—The therapeutic efficacy of four diesters derivatives of meso 2, 3-dimercaptosuccinic acid (DMSA) was investigated in subchronic arsenic intoxication in rats. Dimethyl DMSA (DMDMSA), diethyl DMSA (DEDMSA), diisopropyl DMSA (DiPDMSA) and diisoamyl DMSA (DiADMSA) were the diesters of DMSA with methyl, ethyl, isopropyl and isoamyl alcohols and were administered for two 5 day courses of treatment in male rats pre-exposed to 100 ppm arsenic (III) for 8 weeks. The results show that treatment with these diesters was effective in decreasing blood and soft tissue arsenic contents but was only moderately effective in recovering biochemical indicators. The results suggest that these diesters could be effective arsenic chelators but may be inferior to DMSA in recovering biochemical/clinical indicators following sub-chronic arsenic exposure. (J Occup Health 1997; 39: 119-123)

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Relations between Exposure to o-Dichlorobenzene and Concentrations of Urinary Metabolites: Shinji KuMAGAI, et al. Department of Occupational Health, Osaka Prefectural Institute of Public Health—The present study aimed to examine the relation between exposure to airborne o-dichlorobenzene (o-DCB) and concentrations of four urinary metabolites, i.e., 3, 4-dichlorocatechol (3, 4-DCC), 4, 5-dichlorocatechol (4, 5-DCC), 2, 3-dichlorophenol (2, 3-DCP) and 3, 4-dichlorophenol (3, 4-DCP). Subjects were ten male workers exposed to o-DCB in synthesizing intermediate products for dyes. Individual exposure to o/-DCB was monitored with a passive dosimeter. Urine samples were collected during the workshift and at the end of the workshift. The concentrations of urinary 3, 4-DCC, 4, 5-DCC, 2, 3-DCP and 3, 4-DCP were determined with a high performance liquid chromatograph. The mean recovery rates for urinary metabolites obtained by our analytical method were 93.2 to 102% with coefficients of variance of 2.7 to 7.5%. The concentrations of 3, 4-DCC, 4, 5-DCC, 2, 3-DCP and 3, 4-DCP in urine collected at the end of the workshift and those during the last four hours of the workshift were shown to be well correlated to the 8-hr time weighted average (8-hr TWA) value for the exposure concentration of o-DCB. The mean ratios (as moles) of 3, 4-DCC to 4, 5-DCC, that of 2, 3-DCP and that of 3, 4-DCP at the end of the workshift were 0.78, 0.42 and 0.37, respectively. The time series of the concentrations of the four metabolites showed that these concentrations varied with time in a similar pattern. (J Occup Health 1997; 39: 124-129)

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Estimation of Background Exposure to Toluene Using a Physiologically-Based Kinetic Model: Crispin H. PIERCE, et al. Department of Environmental Health, University of Washington—Estimation of environmental exposure to toxicants has generally been limited to concentration measurements in air, water, and foods. Measurement of background levels of toxicants in biological tissues for this purpose has been limited by analytical detection. After developing a sensitive headspace GC-MS method, we conducted 33 controlled human exposures of 50 ppm ¹H₈ toluene and 50 ppm ²H₈ toluene for 2 h, and measured concentrations in blood and breath for 100 h post-exposure. Blood and breath samples from a separate cohort of 9 men exposed to ²H₈ toluene only were also measured for background ¹H₈-toluene levels. A physiologically-based kinetic (PBK) model, previously constructed and validated in an analysis of the ²H₈ toluene data, was used to predict the level of ambient ¹H₈-toluene exposure that produced the observed breath levels. The model-derived estimate of mean background ¹H₈-toluene exposure was 47 ± 44 ppb (mean ± s.d.), which is consistent with indoor air measurements from this and previous studies of 3-27 ppb and outdoor measurements of 2-43 ppb. According to the PBK model, background exposure was expected to produce an average blood concentration of 5.9 nmol/l, which was within a measured range of 3-16 nmol/l, and a corresponding alveolar air concentration of 310 nmol/m³, within a range of 138-764 nmol/m³. This work extends the use of physiologic modeling to back-predict environmental dose, and found that significant differences in inter-individual ¹H₈ toluene background exposures exist. (J Occup Health 1997; 39: 130-137)

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An Outbreak of Hematopoietic and Reproductive Disorders Due to Solvents Containing 2-Bromopropane in an Electronic Factory, South Korea: Epidemiological Survey: Jung-Sun PARK, et al. Industrial Health Research Institute, Korea Industrial Safety Corporation (KISCO)—Objectives: This survey was conducted to identify the causative agent in the outbreak in an electronic factory in Korea. Methods: The questionnaire administered to subjects consisted of questions regarding medical and occupational history, including current work practices. Employees were also examined for liver, kidney, brain, reproductive organ and bone marrow function, etc. Detailed investigation of industrial hygiene was conducted to identify the potential source of occupational exposure. Results: Among the three subject groups, all 23 intoxication cases (6 males and 17 females) were found in the only section using a new cleaning solution, the Tactile Switch Assembly Operation (total workers: 8 males and 25 females). Abnormal findings in the cases were only hypofunctions of the reproductive organs (ovarian failure, azoospermia or oligospermia) and the bone marrow (pancytopenia). 2-bromopropane is the main component in the cleaning solution (97.4%). Until late November, 1994, workers were exposed to the cleaning solution directly without using proper protective equipment. The solvent was changed from Freon 113 to the above mixture solution in February, 1994. There has been no case among workers who quit before February, 1994. Freon 113 can therefore be excluded as a possible causative agent in the outbreak. Conclusions: The outbreak in the section of Tactile Switch Assembly Operation was caused by exposure to the new cleaning solution. The causative agent is most likely to be 2-bromopropane. (J Occup Health 1997; 39: 138-143)

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Ovarian Toxicity of 2-Bromopropane in the Non-Pregnant Female Rat: Michihiro KAMIJIMA, et al. Department of Hygiene, Nagoya University School of Medicine—A cluster of patients with amenorrhea, oligospermia and anemia were found among workers in an electronics factory in the Republic of Korea. 2-Bromopropane was suspected to cause the disorders. This study aimed to clarify its ovarian toxicity in the virgin rat. Female Wistar rats were daily exposed to 0, 100, 300, or 1, 000 ppm 2-bromopropane for eight hours a day for 9 weeks. During the experimental period, vaginal smears were taken everyday to monitor ovarian cyclicity. Tissues were histopathologically examined and plasma concentrations of luteinizing hormone (LH) and folliclestimulating hormone (FSH) were determined at the end of experiment. The vaginal smear test showed that the number of normal cycles decreased significantly both in the 300 and 1, 000 ppm groups. The histopathological examination revealed dose-dependent ovarian follicle atresia accompanied by a decreased number of normal antral and growing follicles in the 300 and 1, 000 ppm groups. Especially, in the ovaries of rats with persistent estrous smears in the 1, 000 ppm group, most of the follicles were atretic and there were no newly formed corpora lutea. There still remained normal antral follicles and corpora lutea in the ovaries of the remaining rats of the group and of the 300 ppm group with constant diestrous and occasional estrous smears. Hormonal examination revealed no statistically significant change in LH or FSH concentrations between any groups. The results showed that 2-bromopropane has ovarian toxicity in rats, indicating that the secondary amenorrhea in human cases was due to 2-bromopropane exposure. (J Occup Health 1997; 39: 144-149)

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