Risk Evaluation of Environmental Carcinogens: Shigeaki SATO. Department of Hygiene, Kobe University School of Medicine-Quantitative risk evaluation of environmental carcinogens is required not only for their regulation but also for primary cancer prevention. Risk evaluation of carcinogens is carried out through identification of carcinogenicity, exposure assessment, dose-response assessment, and risk characterization. Exposure assessment is made by measuring the amounts of carcinogens in the environment and their human intake is estimated. Dose-response assessment is based upon whole-life carcinogenesis experiments in animals with multiple doses of carcinogens. By downward extrapolation of the dose-response curve obtained, a virtually safe dose (VSD), i.e., a dose which yields a cancer incidence of 10^-6, is calculated and this value is compared with the actual human intake of the carcinogen concerned. When the human intake is around or less than the VSD, that environmental carcinogen is regarded safe to humans because humans as well as experimental animals develop cancer in almost 100% of cases during their whole life and the contribution of a chemical to the occurrence of cancer at an incidence of less than one out of one million is regarded as meaningless. These procedures for risk evaluation of carcinogenic food additives such as butylated hydroxyanisole and saccharin sodium showed that their human intake is one hundredth or much less than the respective VSD values, and this may be the case with most environmental carcinogens except some carcinogenic medical drugs. Human cancer development seems much more influenced by life-style factors, such as a high-fat diet or cigarette smoking, and recognition of this fact is crucial for primary cancer prevention. (J Occup Health 1996; 38: 149-154)

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Abstract: Carbon Disulfide Poisoning in Korea with Social and Historical Background: Eunil LEE, et al. Department of Preventive Medicine and Institute for Environmental Health, College of Medicine, Korea University-In Korea, carbon disulfide was used mostly in a viscose rayon factory which was established in 1962 and was closed in 1993. About 550 workers were diagnosed and compensated for CS₂ poisoning from 1987, to June 1995, and more workers will be diagnosed and compensated. There was no pertinent environmental monitoring or periodic medical examination for the workers exposed to CS₂ until 1986. The first cases of CS₂ poisoning reported in May, 1987 were 4 retired workers who were very sick. It became possible for them to be diagnosed and compensated because a democratic movements pervaded all the country after the end of military rule in Korea. After they were compensated, many other retired workers also requested to be diagnosed and compensated for CS₂ poisoning. Many radicals and radical doctors joined them against the government and company. The government promised that retired workers could be diagnosed by Compensation Insurance organization for Worker's Injury managed by the Ministry of Labor. The rayon company also promised reparation for retired workers who had CS₂ poisoning. The diagnosis of CS₂ poisoning for retired workers was carried out by the commitee of doctors half of whom were appointed by the company and the remaining half by the workers. There were conflicts between conservative doctors and radical doctors in the diagnosis of CS₂ poisoning even after the establishment of legal diagnostic criteria for CS₂ poisoning. Workers pressured doctors and the goverment to bring about a change in the diagnostic criteria, and they succeeded. The important findings of CS₂ poisoning among Korean workers were as follows: retinal microaneurysm, polyneuropathy, cerebrovascular infarction and intercapillary glomerulosclerosis. (J Occup Health 1996; 38: 155-161)

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Organic Solvents and the Kidney: Antonio MUTTI. Laboratory of industrial Toxicology, University of Parma Medical School-The association between solvent exposure and chronic glomerulonephritis is still a controversial scientific issue. Almost all published case-referent studies consistently show an association between chronic glomerulonephritis and exposure to volatile hydrocarbons. Two nested prospective studies and a recent case-referent study also suggest a role of solvent exposure in the progression of renal changes towards chronic renal failure. Cross-sectional studies carried out in groups of workers exposed to relatively low concentrations of single solvents or mixtures demonstrate tubular damage frequently associated with high molecular weight proteinuria and changes in the glomerular basal membrane. In some studies, immunological disturbances (increased titer of antilaminin and/or anti-glomerular basement membrane antibodies) have been found. Whereas unequivocal evidence of solvent-induced renal disturbances is apparent on a group basis, the health significance of such changes is difficult to assess at the individual level. Although renal cancer in the male rat chronically exposed to a variety of hydrocarbons including several organic solvents is not a good model for assessing human risk, experimental studies may not be used as a proof to exclude the cancerogenic properties of all organic solvents. Indeed, epidemiological investigations suggest that a small excess mortality from renal-cell cancer may occur as a consequence of exposure to some organic solvents, including dry-cleaning products and petroleum-derived hydrocarbons. Despite consistent results indicating renal effects of solvent exposure, no specific agents appeared to be implied more frequently, neither doseeffect nor dose response relationships were found and, finally, possible risk factors accounting for an increased individual susceptibility were not identified. Early markers of renal damage are very useful to identify groups at risk, since these subtle abnormalities may represent an early stage of clinically silent but potentially progressive renal diseases. Follow-up should confirm the observed changes and assess their course and prognostic meaning. Repeatedly positive markers of renal damage also indicate the need for intervention, including job counseling and removal from exposure. (J Occup Health 1996; 38: 162-169)

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The Role of Biomarkers in Detecting Early Changes Relating to Exposure to Occupational Carcinogens: Judith SHAHAM et al. Occupational Cancer Unit, Occupational Health and Rehabilitation Institute at Loewenstein Hospital-Increasing evidence points to the role of chemical exposure in the etiology of cancer. Approximately 4% (1-10%) of all deaths due to cancer are caused by occupational carcinogens. In recent years carcinogenic mechanisms have been equated with a continuum multistage process driven by carcinogen induced genetic and epigenetic damage. This process reflects the natural history of chemically induced neoplasia and is translated into the latency period. The development and implementation of laboratory techniques to detect biomarkers that reflect these changes provide opportunities for early diagnosis of both occult and preneoplastic tumors. In order to facilitate the use of biomarkers in the assessment of health risk, they have been divided into categories that represent the continuum between different stages involved in the carcinogenic process from exposure to disease. Thus, the focus of biomarkers has been on the internal dose, biological effective dose and biological response and their use has become an integral part of molecular epidemiology. Biomarkers are useful in strengthening the causality between exposure and malignant transformation or to serve as an indicator warning of a potential carcinogen when epidemiological data concerning the exposure-disease relationship is inconclusive or unavailable. A battery of markers that reflect different stages of the carcinogenesis process can be used to provide information on the etiology of occupational cancer, to monitor exposed populations, and to identify high risk populations in order to encourage appropriate surveillance with regard to cancer prevention, although there are ethical issues regarding risk assessment. (J Occup Health 1996; 38: 170-178)

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Evidence for an Acceleration of Programmed Cell Death in Bronchiolar Epithelium after Exposure to O, O, S-Trimethyl Phosphorothioate : Akio KOIZUMI, et al. Akita University School of Medicine-Exfoliation of Clara cells is a prelude to pathological alterations after exposure to a variety of toxicants. The reported morphological features of exfoliating Clara cells share similarity with some types of programmed cell death (PCD). The purpose of the present study is to characterize morphological changes in Clara cells in the process of PCD in physiological and pathological conditions. We used O, O, S-trimethyl phosphorothioate (OOS-TMP) as a lung toxicant. Morphological changes in the lungs of control rats and rats killed at 2 to 48 hr after treatment with OOS-TMP (po. 60 mg/kg) were investigated by electron microscopy. In situ DNAfragmentation was determined by 3''-OH end labeling in these rats. Immunoelectron microscopy was conducted to examine the morphological changes in Clara cells in PCD. Exfoliation of Clara cells started at 2 hr after dosing. At 6 hr, many Clara cells were sloughed. In situ DNA-fragmentation positive cells were detected in the bronchiolar epithelium of both control and treated rats. Their relative incidences increased 13 fold by 6 hr and returned to basal levels by 48 hr. In contrast, no positive cells were detected in the alveolar cells of either group. Positive cells in the bronchiolar epithelium were identified exclusively as Clara cells. The ultrastructure of the DNAfragmentation positive cells revealed similar changes in control and treated rats. DNA-fragmentation, a hallmark of PCD, was detected in Clara cells of both control and treated rats, but not in alveolar cells. The relative increases in the DNA-fragmentationpositive cells suggest an acceleration in PCD after treatment with OOS-TMP. The results of this study indicate that different mechanisms of cellular death occur in Clara and alveolar cells in response to toxic insults. This difference most likely reflects the cellspecific mode of the action of lung toxicants. (J Occup Health 1996; 38: 179-185)

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Leg Swelling during Continuous Standing and Sitting Work without Restricting Leg Movement: Akihiko SEO, et al. Department of Public Health, Hiroshima University School of Medicine-To clarify the dynamics of leg swelling during standing and sitting work without restricting leg movement, lower leg swelling and subjective complaints were measured during work under three working conditions: Straight standing, buttock chair sitting and ordinary chair sitting. Twelve subjects (eight males and four females) were assigned jigsaw puzzles as a task for an hour. The lower leg swelling and subjective complaints were recorded every two minutes. The lower leg swelling was measured by the bioelectrical impedance method. The results were as follows: (1) The lower leg swelling increased during the work under all working conditions. The swelling was least for straight standing and greatest for ordinary chair sitting. The mean and standard deviations for leg swelling after one hour''s work were 5.8±3.9% for straight standing, 8.2±4.7% for buttock chair sitting and 9.7±7.5% for ordinary chair sitting. (2) The subjective complaints also increased during work. Complaining of lower leg dullness was least for ordinary chair sitting and greatest for straight standing. The relation to the leg swelling was reversed. Complaining of low back pain was more common for buttock chair sitting than for other working postures. It is reasonable that prolonged standing is more likely to cause leg swelling than sitting because of high hydrostatic pressure. This theory has been supported by studies on motionless standing and sitting. Our results obtained without restricting leg movement, however, showed a reversed relation. It was considered that leg swelling factors such as low muscle activity and lymph pumps, low interstitial pressure brought on by low muscle activity, and the seat pressure during prolonged sitting may be dominant in the sitting posture although the hydrostatic pressure was low compared with the standing posture. (J Occup Health 1996; 38: 186-189)

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Effects on the Blood among Art Restorers: Francesco TOMEI, et al. Department of Occupational Medicine, University of Rome “La Sapienza”-Restoration of art works is usually assessed from an artistic viewpoint, and little attention is paid to the restorers'' health. There appear to be no specific published reports. Art restoration is a craftsman''s job, often done by students as part of their art courses, and they are exposed to low doses of a hard-to-classify range of different substances. This study employed a protocol designed for use in the workplace to check whether art restoration work had effects on the blood of the young people doing it. We studied 65 art restorer students and teachers, most of them young, who did different types of restoration work: on stone and archaeological findings, frescoes, paintings on wood and canvas, paper and parchment, plaster, fabrics, metals, wood or painted linings. Seventy-one non-exposed workers were compared as controls. We found significant reductions in RBC, Hb and Ht among exposed workers but no change in WBC. These findings suggest there may be problems in the effect on the blood of art restorers exposed to low doses of solvents. It would appear useful for these workers to undergo periodic blood screening tests, and the protocol we employed appeared suitable for identifying subjects at risk in their workplace. (J Occup Health 1996; 38: 190-195)

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A Survey of Blood Pressure in Cadmium-Exposed Workers. Guicheng ZHANG, et al. Xinxiang Occupational Institute-An investigation was performed on the prevalence of hypertension and hypotension among 362 cadmium-exposed workers in a nickel-cadmium battery factory with 526 control workers/farmers. Cadmium in urine was 1 2.5μg/l in the cadmium workers and 2.4, μg/l in the control group. Increased risk of hypertension had not been found in the workers exposed to cadmium. The prevalence of hypotension which was 3.9% in cadmium workers was lower than that in the control group. Logistic regression analysis revealed that the odds ratio of hypotension was 0.26 cadmium-exposed workers (p=0.0004). The results showed that cadmium exposure could decrease the prevalence of hypotension. (J Occup Health 1996; 38: 198-200)

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