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This study aimed to evaluate personal exposures of 27 workers to indium compounds as “total” dust and its “respirable” fraction in their breathing zones at 3 Japanese indium plants. Eight-hour time-weighted average (TWA) indium concentrations of personal exposure to dust collected in sampling periods of 6 h or longer were determined by ICP-MS. The arithmetic means of exposure concentrations were 0.095 mg indium (In)/m3, when sampled as total dust, and 0.059 mg In/m3, as respirable fraction. ACGIH’s TLV-TWA of 0.1 mg In/m3 for total particulate matter and Acceptable Exposure Concentration Limit (AECL) of 3×10−4 mg In/m3 for the respirable fraction notified by the Japanese Ministry of Health, Labour and Welfare were used to evaluate the exposure concentrations. Twenty-five out of 27 workers were exposed to indium concentrations lower than TLV-TWA, while all of the workers were exposed to the indium concentrations higher than AECL. We noted that there was a large discrepancy between the two occupational exposure limits referred to in this report, and these differences were attributed to the sampling strategies and health effects used as the prevention targets. Carcinogenicity of the respirable fraction of indium-containing particulates was considered in setting AECL, whereas it was not in ACGIH’s TLV.

Objectives This study aimed to assess workers' exposure to indium and its compounds in 55 indium-handling operations among 13 Japanese plants. The surveyed plants were selected from indium-manufacturing plants whose annual indium production exceeded 500 kg. Methods The Control of Substances Hazardous to Health (COSHH) Essentials control banding toolkit, which contains simple scales for hazard levels, quantities in daily use, and "dustiness" characteristics, was used to assess generic risks of indium-handling operations. The operations were then classified into one of four Control Approaches (CAs). Results There were 35 indium-handling operations classified into CA4 (requires expert advice) and 16 grouped into CA3 (requires containment). There were three operations classified into CA2 (requires engineering controls) and only one into CA1 (requires good general ventilation (GV) and working practices). Of the 51 operations classified as CA4 and CA3, 36 were found to be improperly equipped with local exhaust ventilation, and the remaining 15 operations solely relied on GV practices. Respiratory protective equipment (RPE) used in the 13 indium plants was examined with reference to the recommendations of the COSHH Essentials and Japan's Technical Guidelines. Conclusions Our findings suggest that stringent engineering control measures and respiratory protection from indium dust are needed to improve indium-handling operations. Our results show that the most common control approach for Japanese indium-handling operations is to require expert advice, including worker health checks for respiratory diseases and exposure measurement by air sampling.

Objectives: The purpose of this research was to develop a method for monitoring personal exposure to benzyl violet 4B (BV) and direct blue 15 (DB) in workplace air for risk assessment. Methods: We evaluated the utility of the proposed method by examining the following: recovery; method limit of quantification; reproducibility; and storage stability of the samples. Results: An air sampling cassette containing a glass fiber filter was chosen as the sampler. BV and DB were extracted from the sampler filters with a solution of water and methanol (7:3, v/v) and then analyzed by a high-performance liquid chromatograph equipped with a photo-diode array detector. The overall recoveries from spiked samplers were 94-102% and 94-99% for BV and DB, respectively. The recovery after seven days of storage at 4°C exceeded 95%. The method limits of quantification were 0.250 and 1.25 μg/sample for BV and DB, respectively. The relative standard deviations, which represent the overall reproducibility defined as precision, were 0.6-4.1% and 0.8-2.9% for BV and DB, respectively. Conclusions: The proposed method enables 4 h personal exposure monitoring of BV and DB at concentrations of 1-2,000 μg/m3 for BV and 5-2,000 μg/m3 for DB, with a 240 l sampling. Thus, the proposed method is useful for estimating worker exposure to BV and DB.

For the appropriate hygienic management of workplaces where workers handled nano-TiO2 products, the status of the personal exposure of workers to respirable dust (PM4) and nanoparticles (PM0.1) was investigated. Using a cyclone sampler for PM4 and a personal sampler for PM0.1, PM4 and PM0.1 exposure levels were evaluated to discuss them in relation to worker’s duties. The number of particles of 0.01–10 µm was also monitored online in order to examine the short-term fluctuation in the concentration and size distribution of particles. The 8h-time-weighted average (TWA) and 95% upper limit for respirable dust exposure were below the occupational exposure limit specified by the Japan Society for Occupational Health and the recommended exposure limits for TWA by NIOSH. The action level was exceeded during the filling of a flexible container bag. More than 70% of particles in the breathing zone was coarse agglomerates of > 1 µm, while it may be influenced by powder properties and the handling process as well as the management of local ventilation. The maximum PM0.1 concentration (31.3 µg m–3) occurred in a powder filling booth without air ventilation. The operation of a gasoline powered forklift temporarily increased the concentration of ultrafine particles. Most of TiO2 powder was suspended as micron-order agglomerates in the breathing zone. However, since PM0.1 exposure was much larger than those in outdoor environment particularly under insufficient cares to aerosolized powder and air ventilation, PM0.1 exposure should also be monitored.

This study quantitatively assessed personal exposure of 86 workers to indium compounds as total dust at 11 Japanese indium plants. The personal exposures to indium concentrations in the breathing zone during an 8 h work-shift were determined by ICP-MS. The arithmetic mean indium concentration of all the workers was 0.098 mg Indium (In)/m3, with individual values ranging from 0.0001 to 1.421 mg In/m3. There were 11 workers whose exposure to indium concentrations exceeded the American Conference of Governmental Industrial Hygienists' Threshold Limit Value-Time Weighted Average (TLV-TWA) of 0.1 mg In/m3. Based on the condition TLV-TWA

The present study was designed to examine genotoxicity induced by 10–40 nm zinc oxide (ZnO) nanoparticles using the in vitro system. The frequency of micronuclei was significantly increased in a dose-dependent manner when cultured Chinese hamster lung (CHL/IU) cells were exposed to ZnO nanoparticles for 24, 48 and 72 h in the continuous treatment method. The maximal frequency of micronuclei was observed in exposure of CHL/IU cells to ZnO nanoparticles at a concentration of 125 μM. The frequency of micronuclei was profoundly enhanced when CHL/IU cells were exposed to ZnO nanoparticles in the presence vs. absence of S9 mixture including metabolic enzymes in the short-term treatment method, demonstrating an increase in the formation of micronuclei by S9 mixture. The maximal frequency of micronuclei was seen in exposure of CHL/IU cells to ZnO nanoparticles at a concentration of 140 μM. Similar results were obtained in chromosome aberrations, particularly structural aberrations. Surprisingly, administration of the superoxide radical scavenger, tempol, completely abolished an increase in the frequency of micronuclei in the presence or absence of S9 mixture, indicating a central role of superoxide radical in the formation of micronuclei. Indeed, reactive oxygen species (ROS) generation was elevated by simultaneous incubation of S9 mixture and ZnO nanoparticles and by exposure of CHL/IU cells to ZnO nanoparticles in the presence or absence of S9 mixture. An electron microscopic examination revealed mitochondrial damage in CHL/IU cells exposed to ZnO nanoparticles, indicating the participation of mitochondrial dysfunction in ROS generation in this setting. These observations suggest that ZnO nanoparticles evoke genotoxicity through superoxide radical-induced oxidative stress derived from mitochondrial damage in CHL/IU cells. S9 mixture appears to contribute to a further increase in genotoxicity through the generation of superoxide radical by metabolic activation of ZnO nanoparticles.

Objectives The aim of this survey was to clarify the current status of the use of respirators among dust workers in outdoor working environments. Methods The participants were 38 male workers exposed to dust, who were engaged in arc welding or quarrying in outdoor working environments. We interviewed participants about wearing and storage of respirators on site. The participants were asked 9 questions about the selection, use, fitness, maintenance, storage, and instruction in the use of respirators. Results The results of this study show that all participants wore the approved dust respirators, even though it is not legally necessary to wear a respirator in outdoor working environments. Instruction about the use of respirators was found to be effective regarding inspection of the valve and headband, the fitness between the facepiece and face, the time of wearing, and storage place. However, the interviews revealed that there was insufficient knowledge about the reasons for and frequency of filter replacement. Compared to our preliminary study, the use of a knitcover decreased from 73% to 21%. Conclusions These findings suggest that workers should be given better information on the selection, use, maintenance, and storage place of respirators to protect workers against dust exposure.

Epidemiological studies suggest that exposure to environmental and occupational electromagnetic fields (EMFs) contributes to the induction of brain tumors, leukemia, and other neoplasms. The aim of this study was to investigate the genotoxic effects of co-exposure to mitomycin C (MMC), a mutagen, and 50-Herz (Hz) EMFs, using an in vivo-ex vivo newborn rat astrocyte micronucleus assay. Three-day-old male Sprague-Dawley rats were co-exposed to 50-Hz EMFs and either 2.0 or 4.0 mg/kg of MMC. Brain cells were dissociated into single cells, cultured for 96 h, and stained with acridine orange and an antibody against glial fibrillary acidic protein. The frequency of micronucleated astrocytes was determined by fluorescence microscopy. The frequency of micronuclei was not increased in rat astrocytes exposed to EMFs alone. However, the frequencies of micronuclei significantly decreased in the rats exposed to 2.0 or 4.0 mg/kg MMC and a 7.5 or 10 mili Tesla (mT) EMF, in comparison to those in the rats exposed to 2.0 or 4.0 mg/kg MMC alone (sham-exposure, 0 mT EMF) for 72 h (p

We conducted a collaborative validation study, under the auspices of the Japanese Ministry of Labour, on the in vitro micronucleus test to see if it could be used as an alternative to the in vitro chromosome aberration test for evaluation of chemical safety. We used the Chinese hamster lung cell line (CHL/IU), which is the most widely used system for the latter test in Japan, and evaluated 66 chemicals, including clastogens and polyploidy inducers. The cytochalasin B cytokinesis blocking method, which is commonly used in human lymphocyte culture, was applied to the established cell line, but did not improve the detection of chemically-induced micronuclei in continuously growing cells. The highest micronucleus frequencies were obtained at 48 or 72 h continuous treatments. In short treatments (6 h), a 42 h recovery time yielded the best responses. Concordance between the results of the micronucleus test and the chromosomal aberration test was satisfactorily high (88.7%), and we concluded that the in vitro micronucleus test could be used in place of the chromosomal aberration test as a simple and rapid method for detecting clastogens and aneugens in vitro. We also propose a protocol for the test.

It was recently reported that p-aminophenol (p-AP) induces DNA cleavage in mouse lymphoma cells, CHO cells and human lymphoblastoid cells. The mutagenicity of p-AP has not, however, been detected by reverse mutation assays. The purpose of this study was to assess the mutagenicity of p-AP by reverse mutation assay using Escherichia coli WP2uvrA/pKM101, which has a spectrum for detecting mutations different from those of other strains in the family with an AT base pair at the mutation site and has higher sensitivity to certain oxidative mutagens as compared to other strains. We found that p-AP was mutagenic to E. coli WP2uvrA/pKM101. The mutagenic activity of this compound was suppressed with the addition of dimethylsulfoxide or catalase, suggesting the involvement of active oxygen species in the mutagenic process induced by p-AP. To further elucidate the underlying mechanism, we used isolated DNA for the following experiments. It was revealed, by gel electrophoretic analysis, that p-AP induced DNA cleavage in the presence of Fe(III). However, p-AP alone did not induce this cleavage. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by p-AP in calf thymus DNA was also detected in the presence of Fe(III) by HPLC with an electrochemical detector. ESR-spin trapping experiments using DMPO detected the production of hydroxyl radical (.OH) in the solution of p-AP with Fe(III). Both p-AP mediated DNA damages and .OH production by p-AP in the presence of Fe(III) were completely inhibited by .OH scavengers (ethanol, mannitol, sodium formate, dimethylsulfoxide) and catalase. These results suggest that .OH derived from the reaction between H2O2 and Fe(III) (Fenton reaction) participates in the oxidative DNA damage. Accordingly, the same mechanism might be working in E. coli WP2uvrA/pKM101 during induction of the mutation by p-AP.

The inductions of aberrant crypt foci (ACF) by two carcinogenic heterocyclic amines (HCAs), 2-amino-9H-pyrido[2,3-b]indole (A alphaC) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), were studied in the large intestine of C57BL/6N mice. Seven-week-old mice were fed a diet supplemented with 500 or 800 ppm of A alphaC, or 400 or 600 ppm of MeIQx for 7 weeks, followed by a basal diet for another 7 weeks. A alphaC at 800 ppm induced 8.0 +/- 1.9 and 7.8 +/- 2.5 ACF in female and male mice, respectively. MeIQx at 600 ppm induced 2.8 +/- 1.8 and 1.6 +/- 0.8 ACF in females and males, respectively. At lower concentrations of A alphaC and MeIQx, many fewer ACF were induced. No ACF were induced in the control group. The size of ACF (number of aberrant crypts/ACF) in all experimental groups was between 1.0 and 1.5. More than half the A alphaC-induced ACF were located in the region about 20-40% of the distance from the ileocecal portion to the anus. Although both of these HCAs were reported to induce tumors in the liver and other organs, but not in the large intestine, of CDF1 mice, these findings suggest that both these HCAs, and especially A alphaC, induce large intestinal tumors in C57BL/6N mice.

Although recent studies have shown that various stress can induce metallothionein (MT) synthesis in animal tissues, the induction of MT synthesis by exposure to static magnetic fields (SMF) has not been reported. We measured MT levels in the liver, kidney and brain of mice exposed to SMF and also evaluated the effect of SMF exposure on the induction of hepatic MT by treatment with carbon tetrachloride (CCl4). The MT content in the liver was significantly increased by exposure to 4.7 T of SMF for 6, 24, or 48 h, whereas that in the kidney or brain was not changed compared to the control. The combination of CCl4 injection and SMF exposure induced elevation of the hepatic MT content exceeding that induced by either treatment alone. These results indicate that exposure to the strong SMF induces MT synthesis in the liver in mice and enhances the hepatic MT synthesis induced by CCl4 administration.

The effects of prostaglandin E2 (PGE2), as a trigger of erythroid progenitor cells into the cell cycle, were studied on the induction of micronuclei by various mutagens; with mitomicin C (MMC) the optimal protocol was established. PGE2 itself did not induce any micronuclei in this experiment. The highest frequency of micronuclei and dose-response relationship between PGE2 doses and micronucleus frequency were observed 30 h after injection of MMC to mice administered PGE2 24 h previously. Sensitization by PGE2 pretreatment was also found for other mutagens, such as vincristine, 5-fluorouracil, benzo[a]pyrene, 1,1-dimethylhydrazine and 2-naphthylamine. These results support the hypothesis that accelerating the erythropoiesis increases the frequency of micronuclei induced by mutagens.

Objectives: The aim of this study was to investigate the genotoxic effects of indium trichloride (InCl3·4H2O; InCl3) using the in vivo bone marrow micronucleus test and the in vitro CHL/IU cell micronucleus test. Method: BALB/c mice were administered a single intraperitoneal (i.p.) injection of InCl 3 at a dose 0.625, 1.25, 2.5, 5, or 10 mg/kg b.w. The frequency of micronuclei, the ratio of polychromatic erythrocytes to normochromatic erythrocytes (P/N ratio) and body weight gain were determined 24 h after administration of the InCl3. In the in vitro micronucleus test, CHL/IU cells were treated continuously for 24, 48, or 72 h in the absence of S9mix (the continuous treatment method) and/or for 6 h with or without S9 mix followed by an 18, 42 or 66 h recovery time (the short time treatment method). The frequency of micronuclei was determined at the end of each culture period. Results: The frequency of micronuclei induced by InCl3 increased in the in vivo erythroblast-erythrocyte micronucleus test using BALB/c mice at doses of 2.5 and 5 mg/kg b.w. The P/N ratio, a marker of bone marrow toxicity, decreased significantly following the injection of InCl3. Body weight gain was also inhibited by InCl3. InCl3 induced micronuclei in the CHL/IU cell micronucleus test in both the continuous treatment method and the short time treatment method, both with and without S9mix. Conclusions: These results suggest that InCl3 has a genotoxic effect on mammalian cells both in vivo and in vitro.

The influence of essential metals, like zinc, selenium, and calcium, on the nephrotoxicity of cadmium was studied in primary cultures of rat proximal tubular cells. Damage to kidney cells was assessed by measuring the release of lactate dehydrogenase (LDH), γ-glutamyltranspeptidase (GTP), and β-N-acetylglucosaminidase (NAG) from cells into the medium and the cellular concentration of protein. Incubation with 200 μM cadmium in the presence of equivalent molar or lower concentrations of zinc and selenium showed greater release of LDH and NAG than cadmium alone, indicating an enhanced effect. However, metallothionein (MT) induced by pretreatment with a nontoxic concentration of zinc decreased significantly the release of enzyme from cells and elevated cellular protein levels in response to MT levels. MT provided partial protection against the nephrotoxicity of cadmium. Decreased calcium levels in the incubation medium also resulted in markedly increased release of LDH and NAG from cells exposed to cadmium and reduced cellular protein levels. These findings suggest that variations in zinc and calcium intake may affect the development of cadmium-induced renal dysfunction.

Biological exposure monitoring is available for detecting occupational toxic chemicals. It is possible to evaluate the exposure and adverse effects induced such the occupational toxic chemicals with biological exposure monitoring. It is used in health examination, for the recommendation of occupational exposure limits based on biological exposure monitoring, and for biological exposure indices of the American Conference of Governmental Industrial Hygienists (ACGIH).

A number of epidemiological studies have suggested that exposure to environmental and occupational electromagnetic fields (EMFs) contribute to the induction of brain tumors. The aim of this study was to investigate the mutagenetic effects of co-exposure to 50-Hz, 10-mT EMFs and bleomycin (BLM) using an ex vivo newborn rat astrocyte micronucleus assay. We also investigated whether the mutagenetic effects of EMFs were related to active oxygen species by using 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (tempol), a superoxide radical scavenger. Three-day-old male Sprague-Dawley rats were co-exposed to 50-Hz EMFs and BLM (5 or 10mg/kg body weight (BW)) in each group (n=6; total 6 group), and were co-exposed to 50-Hz EMFs and 10mg/kg BW BLM with administration of 200μmol/kg BW tempol in each group (total 4 group). Brain cells were dissociated into single cells, cultured for 96h, incubated with an antibody against glial fibrillary acidic protein, and stained with acridine orange. The frequency of micronucleated astrocytes was determined using a fluorescence microscope. The frequency of micronucleated astrocytes in the 10mg/kg BW bleomycin plus EMF exposure group (Mean±SD: 19.8±5.2‰) was 1.6 times higher than that in the 10mg/kg BW bleomycin plus sham-exposure group (Mean±SD: 12.7±3.3‰) (p

The effect of estrogen on the induction of micronucleated polychromatic erythrocytes (MPCE) by mutagens was examined in male mice. In the dose-response study, a dose-related inhibition of the mitomycin C (MMC)-induced MPCE frequency by estradiol (E2) treatment was observed. In the time study, inhibitory effects of E2 on MPCE frequency by MMC were observed when MMC was administered at 0 or 1 day after injection of E2. The most effective protocol for inhibition was when E2 and MMC were used on the same day. Of mutagens other than MMC, only vincristine (VCR) showed a significant decrease in MPCE frequency when used together with E2. Benzo[a]pyrene (BaP) and 5-fluorouracil (5-FU) showed no significant decrease in MPCE frequency. The data suggest that the induction of micronuclei by mutagens is inhibited by treatment with estrogen, and this could result in a sex difference in the sensitivity of mice employed in the micronucleus test. Mechanisms of the inhibitory effects of estrogen are discussed, these might include a suppression of erythropoiesis and a possible effect on the cell membrane permeability of erythroblasts.

The aim of this study was to determine the mechanism of the rodent bone marrow micronucleus test in relation to erythropoiesis. We have previously reported that an acceleration of erythropoiesis increases the frequency of micronucleated polychromatic erythrocytes (MPCE) induced by mutagens. The blood plasma erythropoietin level increased after the injection of N6-2-O-dibutyladenosine-3',5'-cyclic monophosphate into adenosine 3',5'-cyclic monophosphate (cAMP) at a dose of 500 mg/kg. A peak of erythropoietin induction was observed 3 h after the injection of cAMP. cAMP itself did not induce any micronuclei in erythroblasts of BALB/c mice. So, the frequency of MPCE did not increase after injection of cAMP. The highest frequency of MPCE and the dose-response relationship between the cAMP doses and micronucleus frequency were observed 30 h after injection of mitomycin C (MMC) in mice which had been administered cAMP 24 h previously. The highest effect of cAMP on the increase of MPCE was observed when cAMP was given 24 h before MMC injection, thus indicating that accelerating the multiplication of erythroblasts increases the frequency of MPCE induced by mutagens. The induction of MPCE in the bone marrow by three other chemicals (carboquone, 5-fluorouracil, and vincristine) also increased after pretreatment with cAMP. Our results suggest that the increase of MPCE induced by mutagens can be amplified following the acceleration of erythropoiesis by pretreatment with cAMP.

An increase in incidence of the illegal use of tablets containing 3,4-methylenedioxymethamphetamine hydrochloride (MDMA) has recently become a widespread social problem. MDMA ingested orally reacts with nitrite in the stomach and is synthesized intoN-nitroso-3,4-methylenedioxymethamphetamine (N-MDMA). The aim of this study is to investigate the genotoxic effects of MDMA and N-MDMA on the basis of the results of an in vitro micronucleus (MN) test and an in vitro chromosomal aberration (CA) test using a Chinese hamster lung fibroblast cell line (CHL/IU). Tablets containing MDMA obtained from the Regional Bureau of the Ministry of Health, Labor and Welfare were purified, and N-MDMA was synthesized from MDMA in our laboratory. To evaluate the effects of MDMA and N-MDMA, the MN test established by our laboratory and the CA test in accordance with the guidelines for toxicity studies of drugs recommended by the Ministry of Health, Labor and Welfare were performed. In the MN test, no increased frequency of MNs was not found for MDMA. On the other hand, an apparently increased frequency of MNs was observed for N-MDMA. In the CA test, no CA was found for MDMA, but CA was observed for N-MDMA apparently. N-MDMA genotoxicity was observed in the MN and CA tests. However, no MDMA genotoxicity was observed.

It is important to assess the risk of static magnetic fields (SMFs) on human health, because epidemiological studies have indicated that SMFs play a role in the development of diseases such as leukemia and brain tumor. In our environment, we have numerous chances to be exposed to not only SMFs but also many chemicals containing mutagens. The aim of this study is to investigate the effect of SMFs on the induction of micronuclei induced by some mutagens.BALB/c mice were exposed to 4.7 tesla (T) SMF for 24 hr immediately after the injection of carboquone (alkylating agent), colcemid (spindle poison), mitomycin C (cross-linking agent), vincristine (spindle poison), sodium fluoride (a byproduct of aluminum plants under strong SMF) or 1-ethyl-1-nitrosourea (brain tumor-, gliomas- and thymic lymphoma-inducing chemical).The frequency of micronuclei induced by six mutagens increased after co-exposure to SMF.An additive/synergistic effect of SMF and chemicals was observed from the results of increased frequency of micronuclei induced by mutagens in mouse bone marrow erythrocytes.

Ketamine hydrochloride (KT) is a secondary amine that has been safely used as an injectable anesthetic and analgesic to avoid the production of nitroso compounds in the stomach. However, ketamine in the tablet form has recently become an abused, recreational drug. The aim of this study was to investigate the genotoxic effects of N-nitrosoketamine (NKT) and KT on the basis of an in vitro micronucleus (MN) test using a Chinese hamster lung fibroblast cell line (CHL/IU). NKT was synthesized from KT in our laboratory. In the MN tests, CHL/IU cells were continuously treated with either NKT or KT for 24, 48, or 72 hours without the S9 mix. The cells were also treated with NKT or KT with or without the S9 mix for 6 hours, followed by a recovery period of 18, 42, or 66 hours (short-term treatment). The results were considered to be statistically significant when the p-values of both Fisher’s exact test and the trend test were less than 0.05. After the short-term treatment with either NKT or KT with and without the S9 mix, the frequency of micronuclei significantly increased. However, the frequency of micronuclei did not significantly increase after the continuous treatment with either NKT or KT. Both NKT and KT were determined to be genotoxic in the short-term treatment with or without the S9 mix, but they were determined to be nongenotoxic in continuous treatment. Our findings suggest that NKT has a stronger genotoxic effect than KT.

We speculated that there would be more occupational stress in an apparel company than in other areas of business, because employees work long hours and under poor conditions. We investigated 66 employees of an apparel company who visited an occupational physician to consult about their mental health. There were 561 male and 387 female employees in that company. The employees who had visited an occupational physician had worked long every day under poor conditions, and they had been required to be more artistic than other employees in that company. Female employees visited occupational physicians more than males. Apparel companies, use a system of "specialty store retailer of Private-label Apparel (SPA)", and several sections make special trademark "brands". These sections compete with each other. Employees must plan, design, make patterns, and sew new dresses in a 7-day cycle. They are extremely busy and this therefore creates stress. We came to the conclusion that many apparel companies were stressful workplaces. It is important that a psychiatrist examines employees who occupational physicians have diagnosed as unhealthy. Frequent consultation with occupational physicians is as important as a psychiatrists examination. Managers must manage absence, efficiency, and written correspondence of all employees. These are useful signs of mental disorder. When employees return to work after sick leave, rehabilitation in the workplace after absence is useful. The employee should work for only two hours a day at first. Working hours are then extended gradually. The employee can then return to work easily if this rehabilitation program is followed.

Epidemiological studies have suggested that exposure to environmental and occupational electromagnetic fields (EMFs) contribute to the induction of brain tumors, leukemia, and other neoplasms. The aim of this study was to investigate the genotoxic effects of exposure to 50-Hz EMFs. and of co-exposure to cisplatin, a mutagen and carcinogen, and 50-Hz EMFs, using an in vivo newborn rat astrocyte micronucleus assay.Three day-old male Sprague-Dawley rats were co-exposed to 50-Hz EMFs and 1.25 or 2.5 mg/kg of cisplatin. Brain cells were dissociated into single cells and cultured for 96 hours, then stained with acridine orange and an antibody against glial fibrillary acidic protein. The frequency of micronucleated astrocytes was counted with a fluorescent microscope.The frequency of micronuclei was not increased in rat astrocytes exposed to EMFs alone. However, the frequencies of micronuclei in co-exposure to 2.5 mg/kg cisplatin and EMFs (7.5- and 10-mT) were significantly increased, compared with those in exposure to 2.5 mg/kg cisplatin alone (sham-exposure, 0-mT EMFs) for 72 hours (p0.01).Exposure to EMFs alone did not have a genotoxic effect but co-exposure to EMFs increased the genotoxic activity induced by cisplatin. Our findings suggest that EMFs enhance the genotoxic effects of cisplatin.

The influence of the "shukko" (temporary transfer) work system on health was examined. "Shukko" is a Japanese individual work system. The life-time employment system was general in Japan. "Shukko" work system was devised to reduce the number of personnel in Japan. "Shukko" personnel belong to their present company but they must do the work of another company. Generally, the disadvantages of "shukko". Personnel are greater than in former "shukko" The subjects are 483 office workers in a certain industrial company. 143 workers work in a subsidiary of this company (Age: 42.2 +/- 5.5) (strategic shukko group), 30 workers work in the other company, having resigned their administrative post in the head office (55.6 +/- 2.1) (Demotion by the manager shukko group), and 310 workers work in the head office of this company (41.8 +/- 5.2) (head office working group). The medical examination results (degree of obesity, systolic blood pressure (SBP), GPT, GGTP, total cholesterol, triglyceride (TG), fasting blood sugar (FBS), uric acid (UA), electrocardiography (ECG), and gastrography were compared by mean of multiple regression analysis. In the "Demotion by the manager shukko" group, the average age and SBP were higher than in the other groups. (p < 0.0001). The "strategic shukko" group was compared with the "head office working" group. There is no significant difference in average age. The average SBP (p < 0.001) and FBS (p < 0.0001) of the "head office working" group was significantly higher than those of the "strategic shukko" group. ECG findings were more serious in the "Demotion by the manager shukko" group than in the other groups (p < 0.0001). There is a significant correlation between SBP and "degree of obesity, FBS and UA" (p < 0.0001). There is significant correlation between FBS and "GGTP, SBP, UA, GPT and TG" (p < 0.0001). And there is significant correlation between ECG findings and "working form and SBP" (p < 0.05). The prevention and early diagnosis of geriatric diseases is important for the "Demotion by the manager shukko" group, and their average age is older than that of the other groups. A problem with the head office working group is obesity. In this group it is important to take into consideration life related diseases. The workers complaint a lot in the "strategic shukko" group, but there are no abnormal findings. We think that their complaints are due to their mental stress. In this group measuring mental stress is important.

The aim of this experiment was to investigate whether static magnetic fields (SMFs) have cytogenetic effects in mouse bone marrow cells. The frequency of micronuclei was significantly increased by exposure of mice to 3.0 T for 48 and 72 h and 4.7 T for 24, 48 and 72 h. The increase in micronucleus frequency was dose dependent at all times. Micronucleus frequency at 4.7 T was higher than at 3.0 T. We consider that the increased numbers of micronuclei may be attributable to a stress reaction caused by SMFs or a direct clastogenic/spindle disturbance effect of SMFs.

Possible mutagenic and co-mutagenic effects of strong static magnetic fields were estimated using bacterial mutagenicity test. Mutagenic potential of static magnetic fields up to 5T (T:1T=10,000 G) was not detected by the bacterial mutagenicity test using four strains of Salmonella typhimurium (TA98, TA100, TA1535 and TA1537) and Escherichia coli WP2 uvrA either in the pre-incubation method or in the plate incorporation method. In the co-mutagenicity test, E. coli WP2 uvrA cells were treated with various chemical mutagens and were simultaneously exposed to a 2T or a 5T static magnetic field. Mutation rate in the exposed group was significantly higher than that in the non-exposed group when cells were treated with N -ethyl- N ′-nitro- N -nitrosoguanidine (ENNG), N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG), ethylmethanesulfonate (EMS), 4-nitroquinoline- N -oxide (4-NQO), 2-amino-3-methyl-3 H -imidazo[4,5-f]quinoline (IQ) or 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (AF-2). The mutagenicity of 2-aminoanthracene (2-AA), 9-aminoacridine (9-AA), N 4 -aminocytidine and 2-acetoamidofluorene (2-AAF) was not affected by the magnetic field exposure. Possible mechanisms of the co-mutagenicity of magnetic fields are discussed.

Since several epidemiological studies have indicated an elevated risk for certain types of cancer in both living and working environments where exposure to an extremely low-frequency electromagnetic field (ELF) occurs, public concern about ELF has been increasing because it is impossible to imagine life today without electricity. We reviewed studies on biological effects of ELF with respect to their cytological and biochemical effects, including mutagenicity, clastogenicity and carcinogenicity. The studies can be summarized as follow: 1) There is evidence that outer surface of the cell membrane is the primary locus for ELF-induced cellular alterations. 2) ELF modulate the proliferation of normal as well as transformed cells in vivo and in vitro. The magnitude of the proliferative effects depends on ELF intensity, exposure duration and other cellular factors. 3) No studies clearly demonstrate deleterious effects of ELF exposure on mammalian reproduction and development, but several suggest such effects. 4) Reported evidence does not demonstrate that the ELF acts as a cancer initiator. However, it might act as a promoter or affect tumor progression. Further observations and epidemiological studies of ELF must be accompanied by laboratory experiments to evaluate biological and health effects.

Criminal cases involving stimulant abuse have increased since 1970 but have now leveled off. Some of the offenders claimed to have used the Vicks Inhaler containing a stimulant (1-methamphetamine) which is used for the treatment of nasal obstruction. The aim of this experiment was to measure the amount of 1-methamphetamine contained in the Vicks Inhaler by stimulating the human respiratory system. The results are as follows: 1) The data from the stimulation experiment showed that the inhalation level of 1-methamphetamine was estimated to be 320.4ng. From this value, the level of 1-methamphetamine absorbed per one respiration was calculated to be 21ng. 2) The data from quantitative and qualitative analysis by gas-chromatography showed that menthol interfered with the methamphetamine. 3) A qualitative test for the stimulant in urine was negative when the subject inhaled the Vicks Inhaler only once. However, this test turned positive when the subject inhaled it more than 17 times.

The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by cobalt dichloride pretreatment. Cobalt dichloride was used to induce erythropoietin, a growth factor for erythropoiesis. The increase in mutagen-induced micronucleus response following cobalt pretreatment, therefore, may have been due to a change in the rate of erythropoiesis. The greatest interaction between cobalt pretreatment and mutagen treatment for the induction of micronucleated polychromatic erythrocytes (MPCE) occurred when mice were injected with 1,1-dimethylhydrazine (DMH) 12–24 hr after pretreatment with cobalt dichloride and killed 30 hr later. Increased sensitivity of the micronucleus test was attributable to the administration of mutagen during the differentiation and multiplication of erythroblast, which is presumed to have been accelerated by pretreatment with cobalt dichloride. An increased induction of MPCE in the bone marrow by two chemicals—benzo(a)pyrene, 2-naphthylamine—was also observed following pretreatment with cobalt dichloride. © 1993 Wiley-Liss, Inc.

In spite of strict laws prohibiting it, criminal cases involving marijuana abuse are increasing, resulting in a serious social problem in Japan. The most common method of ingestion is smoking, since abusers feel that this method produces quick psychological effects controversial. Marijuana is known to induce psychological addiction, but it's genotoxic effects are still argued. Marijuana smoking tar has been extracted from seized pipes. The amounts of polycyclic aromatic hydrocarbons (PAH) in the tar were weighed and the mutagenic activity was tested. The results are as follows: 1) Five of the seven PAHs were detected in marijuana tar, although benzo(e)pyrene and perylene were not. 2) There was more pyrene than any other substance detected in the tar, with fluoranthene having the next highest concentration. 3) Mutagenic activity was observed in all samples, with relative mutagenic potency ranging from 0.03 to 1.59. 4) The type of smoking pipe and burning temperature may affect the mutagenic activity and the amount of PAH. 5) Since marijuana smoking tar contains carcinogens, promoters, and mutagens, there is a risk of developing cancer just as in the case of tobacco.

Although recent studies have shown that radiation can induce metallothionein (MT) synthesis in normal tissues, the induction of tumor MT synthesis by irradiation has not been reported. We examined the accumulation of MT in the Meth-A tumor (mouse fibrosarcoma cells) transplanted into mice exposed to whole-body X irradiation. In the present study, the MT content in the tumor cells was increased by X irradiation in a dose-dependent manner. The MT level induced in the tumor cells by X irradiation was elevated not only after a single exposure but also after repeated exposures. Several studies have shown that MT is one of the important cellular factors in resistance to various anti-cancer drugs and ionizing radiation. Thus our results suggest that the radiation-induced MT in the tumor cells may have to be taken into consideration when designing protocols for radio-and chemotherapy. 29 refs., 3 figs.

The mutagenicity of N-nitrosomethamphetamine and N-nitrosoephedrine synthesized from methamphetamine and ephedrine in our laboratory was proved to be significant by the modified method of the Ames assay using Salmonella typhimurium TA100 and TA98 and E. coli WP2 uvrA/pKM in the presence of hamster S9.The formation of N-nitrosomethamphetamine from methamphetamine and nitrite when incubated in vitro in the human urine or in human gastric juice was found. On the other hand, N-nitrosomethamphetamine was detected from the urine of methamphetamine addicts.The identification of N-nitrosomethamphetamine was carried out by GC/MS.