Benzene-Associated Leukemia and its Risk Assessment: Takashi KANEKO, et al. Department of Environmental Health, Medical University of Yamanashi—There is sufficient epidemiological evidence indicating that benzene is a human carcinogen. Although some reports suggest an association of benzene with multiple myeloma, malignant lymphoma and lymphatic leukemia, the closest association is found with the development of acute myeloleukemia. In contrast to epidemiological findings, benzene has induced a variety of tumors in tissues other than bone marrow in experimental animals. Attempts to induce acute myeloleukemia in rodents by benzene have not been fully successful until recently. While relatively low doses of benzene have been confirmed to induce chromosomal aberrations, sister chromatid exchanges and micronuclei in rats and mice, it has not been proven that similar changes occur in humans. For evaluation of the dose-response relation of benzene-induced leukemia, the epidemiological studies with a Pliofilm (rubber hydrochloride) cohort are considered most reliable and useful. According to recent re-examinations of the Pliofilm cohort, it is highly possible that the past epidemiological studies with this cohort underestimated the benzene exposure level, and thus overestimated the risk of benzene toward leukemia. Many extrapolation models including a linear model, a linearized multistage model, a conditioned loglogistic model, a quadratic model and a proportional hazards model have been used in the calculation of benzene risk. The risk values calculated so far with the Pliofilm cohort greatly differ according to the extrapolation models employed, and thus it cannot be determined which model is superior. While benzene exposure in the workplace is decreasing, petroleum containing a few percent of benzene has become an important source of benzene exposure for both industrial workers and the general population. Some reports suggest a positive association between gasoline exposure and the development of acute myeloleukemia.
A Review on Toxicity of 2-Bromopropane: Mainly on its Reproductive Toxicity: Yasuhiro TAKEUCHI, et al. Department of Hygiene, Nagoya University School of Medicine—2-Bromopropane has been used mostly as an intermediate for medicines, pesticides and other chemicals in closed systems. Recently it has come to be used as an alternative solvent in open systems instead of ozone layer depleting chlorofluorocarbons. An outbreak of reproductive and hematopoietic disorders occurred in workers exposed to solvents containing 2-bromopropane in a Korean factory in 1995. After that some animal experiments revealed that 2-bromopropane has a severe toxic effect on the female and male reproductive organs and hematopoietic organs. We reviewed the toxicity of 2-bromopropane based on the recent data obtained in epidemiological surveys and animal experiments. Toxicities of structurally related bromopropanes were compared with that of 2-bromopropane and its risk assessment was discussed. The conclusions are as follows: 1. 2-Bromopropane has a specific reproductive and hematopoietic toxicity in both sexes in humans and experimental animals. 2. It could impair the testes, especially spermatogonia in males. 3. It could impair the ovarian function, resulting in a disturbed estrous cycle and loss of oocytes in females. 4. It could impair the bone marrow, resulting in pancytopenia. 5. It has a weak potent mutagenicity in bacterial mutation assays. 6. A risk assessment suggests that around 0.3-10 ppm might be recommended as an occupational exposure limit for 2-bromopropane.
Estimates of Occupational Cancer in Korea: Soo-Hun CHO, et al. Department of Preventive Medicine, Seoul National University College of Medicine—An accurate estimation of the contribution of occupational exposure to cancer is very difficult. In order to evaluate the magnitude of the problem of occupational cancer in Korea, the numbers of these cancers were estimated. A panel of physicians was asked to complete a questionnaire survey asking about potentially important occupational cancers. The numbers of occupation-related cancers in Korea were estimated, based on the numbers of employees exposed to selected occupational carcinogens, the relative risks of affected cancers among exposed employees, and the incidence of those cancers among the general population. More than 90% of physicians who participated in the survey indicated their belief that many occupational cancers have occurred previously without being detected. Preventive medicine specialists reported a greater contribution (5-30%) than clinical oncologists and cancer surgeons (1-10%) of occupational exposure to cancer. Participant physicians indicated that lung, bladder, hematopoietic and skin cancer will in the future be major occupational cancers in Korea. The reported chemicals and industries in which occupational cancer will be important included asbestos, petrochemicals, benzene, dyes, radiation, coke oven emissions, polycyclic aromatic hydrocarbons, plating work, and chrome. The estimated annual total of occupational cancer cases in Korea was 5-28 after subtracting the number of cases in the general population from the number among employees exposed to occupational carcinogens. Although this study has several limitations, it was the first attempt to estimate the number of cases of occupational cancer in Korea. Future studies to accurately estimate the number of employees exposed to occupational carcinogens and to link the existing database on cancer occurrence (e.g. cancer registry, medical insurance data, etc.) with exposure data are needed.
Role Perception and Expectation of Occupational Health Nursing from a Survey in North Carolina: Naoko SATO, Tokyo Women''s Medical College. School of Nursing%mdash;A descriptive study was conducted of 32 occupational health nurses working in North Carolina, 54 of their employers and 87 of their company employees. By using self-administered questionnaires, subjects were assessed as to the level of performance in 16 occupational health nursing activities to examine their current perceptions and future expectations for occupational health nursing roles. It was found that occupational health nurses currently perform numerous activities, such as direct care services, administrative tasks for the management of the occupational health department, and collaborative tasks with other health disciplines. Comparing the perceptions in the three groups, employees perceived greater needs than nurses with respect to planning and developing educational programs (p<0.05) and conducting research (p<0.01), whereas employers perceived the occupational health nursing roles similarly to nurses. Occupational health nurses, employers and employees had high expectations for the future in all activities. Among 16 activities, in particular, health policy development was reported as the priority activity by the nurses, in which they reported a significantly higher mean score for expectation than the employers (p<0.05). The results from this study indicate that occupational health nurses should have their autonomy increased in developing and managing high quality occupational health nursing. Occupational health nurses need to develop their ideal roles to meet the high expectations of employers and employees.
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 0.8μm 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.
Intraocular Pressure, Ocular Hypertension, and Glaucoma: A Comparison of White and Blue Collar Workers: Imran Ahmad QURESHI, et al. Department of Physiology, Rawalpindi Medical College—The course of glaucoma is an insidious one and most cases remains asymptomatic until the visual field has been seriously diminished. Consequently, it is a disease suited to a preventive approach. The intraocular pressure (IOP) distribution and prevalence of ocular hypertension and glaucoma have never been described in industrial workers. After controlling all IOP affecting factors, we investigated levels of intraocular pressure and its association with certain health parameters along with the prevalence of ocular hypertension and glaucoma in healthy white and blue collar workers in Karachi, the largest city in the Islamic Republic of Pakistan. In both groups, the histogram shows a skew to the right, so that the distribution was not Gaussian. This study reports that on an average, per decade, white collars have 1.1 mmHg (p<0.001) higher IOP than blue collar subjects. The average per decade increases were 0.47 mmHg and 0.33 mmHg in white and blue collar workers respectively. The age effect was statistically insignificant until the age of 40 years in both groups, after which it became quite significant. Differences in mean IOP (left minus right) were found to be 0.15 mmHg (p<0.2), and 0.12 mmHg (p<0.05) in white and blue collar subjects, respectively. In normal subjects IOP was weakly but statistically significantly correlated with the heart rate and systolic blood pressure. Heart rate, systolic and diastolic blood pressures and age were found to be risk factors for ocular hypertension. In both normotensive and ocular hypertensive subjects, weight and height were not correlated significantly. Ocular hypertensive subjects (IOP≥21 mmHg) were 2.48 times more numerous in white collar than in blue collar subjects. Most of the ocular hypertensive and several glaucoma patients were diagnosed during this survey. The results therefore strongly suggest that in routine health examination, tonometry should be included.
Prolonged Standing and Physical Exertion at Work during Pregnancy Increases the Risk of Preterm Birth for Thai Mothers: Skulrat RITSMITCHAI, et al. Epidemiology Unit, Faculty of Medicine, Prince of Songkla University—Women in Thailand are increasingly engaged in work which requires prolonged standing and physical exertion. Previous reports are inconclusive regarding the association between prolonged standing during pregnancy and preterm birth. A matched case-control study was conducted at Hat Yai Hospital, Songkhla, Thailand, between May 1 and November 30, 1993, to determine whether prolonged standing and/or physical exertion during pregnancy are associated with preterm birth. Cases were mothers with a singleton preterm infant and controls were mothers with a singleton term infant giving birth following the case and matched with the case on age (case age±5 years) and parity. Two hundred and twenty-three case-control pairs were recruited. Indicators of work activity and other potential risk factors including socioeconomic status, maternal stress, medical complications, and obstetric problems were ascertained through the medical records and by questionnairebased interviews administered to each eligible subject immediately after delivery. Conditional logistic regression was employed for multivariate analysis. After adjustment for pregnancy complications, previous preterm birth, physical exertion and physical exercise, a significant association between prolonged standing longer than 3 hr per day throughout gestation and preterm birth was demonstrated, with an odds ratio of 4.10 (95% Cl, 1.29, 13.10) when compared to no prolonged standing. Physical exertion throughout pregnancy was also an independent risk factor of preterm birth (OR=2.91, 95% Cl, 1.29, 6.58). In summary, standing longer than 3 hr per day at work throughout pregnancy, or lifting more than 10 kg weight at work, significantly increased the risk of preterm birth.
Psychometric Properties of Stress Check List for Self and its Relationship to Health Satisfaction and Psychological Traits (Extroversion-Introversion): Tomoyuki KAWADA, et al. Department of Public Health, Gunma University School of Medicine—This study focused on the reliability and validity of the Stress Check List for Self (SCL-S). Relationships of the SCL-S to types of work, health satisfaction, psychological traits, current medication, and stress coping were also tentatively analyzed. A self-administered questionnaire was distributed to employees of a railroad company, of whom 1, 706 men aged 18 to 55 were selected randomly and 1, 045 (61.3%) responded. The SCL-S consists of 30 items, each of which is scored 1 or 0, depending on whether or not a symptom is present. The SCL-S score is defined as the summation of each binary datum. Health satisfaction is scored as 1 (satisfied), 2 (moderately satisfied), or 3 (not satisfied). The psychological trait item is scored as 1 (extrovert) or 2 (introvert). Present medication is scored as 1 (yes) or 0 (no). We also asked the respondents whether they had experienced stress coping, hobbies and consultation with others. Each of these items was scored as 1 (yes) or 0 (no). There was a difference in the mean SCL-S value among age-groups as a whole (p<0.05). Cronbach''s alpha coefficient for the target group was 0.817. Principal factor analysis was conducted on 30 items of the SCL-S. Three factors were extracted. Factor 1 consisted of three items which related to motivation. Factor 2 consisted of six items which related to physical symptoms. Factor 3 consisted of six items which related to symptoms of autonomic imbalance. These three factors explained only 18.2% of total variation. The mean SCL-S value was quite high in the groups characterized by introversion p<0.01), having no one to consult (p<0.05), and not having a hobby (p<0.01). The higher health satisfaction score was, the lower the mean value of the SCL-S and this was significant (p< 0.01). Multiple regression analysis was conducted to predict SCL-S scores by other variables. Significant standardized partial regression coefficient items increasing the SCL-S value were introversion trait (p<0.05), not having a hobby (p<0.05), and health dissatisfaction (p<0.01). Among these three variables, health dissatisfaction contributed most to the SCL-S. The adjusted coefficient of determination was 0.185. These results raise the possibility that the SCL-S can be based on division into three different scales. Internal consistency was nearly acceptable with the adoption of an alpha value over 0.8. In addition, health satisfaction was most closely related to subjectively reported stress or stress response judged by SCL-S.
2-Bromopropane-Induced Hypoplasia of Bone Marrow in Male Rats: Tamie NAKAJIMA, et al. Department of Hygiene, Shinshu University School of Medicine—The hematotoxicity of 2 -bromo propane was investigated in thirty-six male Wistar rats. The rats were put into four groups: three groups were exposed to 0, 300, and 1, 000 ppm 2-bromopropane for 8 hr per day, for 9 weeks, respec tively, and the remaining group was exposed to 3, 000 ppm only for 9-11 days. Hematotoxicity was assessed by measuring peripheral blood cells as well as cellularity, the number of megakaryocytes and morphological findings in the bone marrow. Expo sure to 2-bromopropane decreased the numbers of erythrocytes in the peripheral blood at 300 ppm or higher, leukocytes at 1, 000 ppm, and platelets at 300 and 1, 000 ppm. Exposure to 300 ppm 2-bromo propane did not influence the indices of bone marrow toxicity. Exposure to 1, 000 ppm 2 bromopropane or a higher dose-dependently induced a hypoplastic profile with replacement of fatty spaces in the bone marrow, though the durations of exposure to 3, 000 ppm were under one sixth. These exposures also induced dose-dependent decreases in the number of megakaryocytes, with the maintained ratio of granulocytes to erythrocytes in the bone marrow. Residual progenitor cells showed some dysplastic or megaloblastic changes. These results suggest that exposure to 2-bromopropane leads to a reduction in the numbers of hematopoietic cells in the bone marrow, the result being a persistent pancytopenia in male rats.
Histopathological Changes of the Testis in Rats Caused by Subcutaneous Injection of 2-Bromopropane: Minoru OMURA, et al. Department of Hygiene, Kyushu University—Mature male rats were injected subcutaneously with 1, 355 mg/kg of 2-bromopropane five days a week for two weeks. In addition to the routine examinations concerning the effect on male reproductive system, we carried out an evaluation of change in the numbers of various types of germ cells in the seminiferous tubule at stages I, V, VII, X and XII to clarify germ cells which were affected by 2-bromopropane. 2-Bromopropane caused mild atrophy of the seminal vesicle, but did not show any adverse effects on spermatid/sperm count, sperm motility or sperm morphology. In the histopathological examination of the testis, the numbers of spermatogonia, preleptotene spermatocyte, leptotene spermatocyte, zygotene spermatocyte and pachytene spermatocyte at stages I and V decreased in the rats treated with 2-bromopropane. However, the numbers of pachytene spermatocyte at stages VII, X and XII and round spermatids in these rats were comparable with those in control rats. In two weeks, spermatocytes develop to pachytene spermatocyte at stage VII or more developed germ cells in rats. Therefore, it seemed likely that 2-bromopropane had no adverse effects on spermatocytes but affected spermatogonia, assuming that 2-bromopropane affected germ cells immediately after the injection. In conclusion, we estimated that spermatogonia were the target cells of 2-bromopropane in the testis in rats.