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1.
PLoS One ; 18(4): e0284837, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37083639

RESUMO

Eight workers involved in packing cross-linked water-soluble acrylic acid polymer, an organic substance, developed pulmonary fibrosis, and the upper lobe was the most affected. The dust concentration in the polymer packing workstation was measured. Chest computed tomography (CT) was obtained for 82 individuals, including the 8 workers mentioned above. Three workers were histopathologically examined. In six of these eight workers, central pulmonary fibrosis and secondary bulla formation caused pneumothorax. Histopathologically, multiple centrilobular fibrotic foci were observed. Chest CT revealed centrilobular nodular opacity and interlobular septal thickening, suggesting early lesions in the workers because the dust concentration was remarkably high. Although the pathogenesis of the disease is unclear, we reported the occurrence of pulmonary fibrosis caused by the exposure to cross-linked water-soluble acrylic acid polymers in humans as it has not been reported earlier.


Assuntos
Fibrose Pulmonar , Transtornos Respiratórios , Doenças Respiratórias , Humanos , Fibrose Pulmonar/patologia , Polímeros , Pulmão/patologia , Doenças Respiratórias/patologia , Transtornos Respiratórios/patologia , Poeira
2.
Toxicology ; 488: 153483, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870411

RESUMO

Occupational exposure to aromatic amines is one of the most important risk factors for urinary bladder cancer. When considering the carcinogenesis of aromatic amines, metabolism of aromatic amines in the liver is an important factor. In the present study, we administered ortho-toluidine (OTD) in the diet to mice for 4 weeks. We used NOG-TKm30 mice (control) and humanized-liver mice, established via human hepatocyte transplantation, to compare differences in OTD-induced expression of metabolic enzymes in human and mouse liver cells. We also investigated OTD-urinary metabolites and proliferative effects on the urinary bladder epithelium. RNA and immunohistochemical analyses revealed that expression of N-acetyltransferases mRNA in the liver tended to be lower than that of the P450 enzymes, and that OTD administration had little effect on N-acetyltransferase mRNA expression levels. However, expression of CYP3A4 was increased in the livers of humanized-liver mice, and expression of Cyp2c29 (human CYP2C9/19) was increased in the livers of NOG-TKm30 mice. OTD metabolites in the urine and cell proliferation activities in the bladder urothelium of NOG-TKm30 and humanized-liver mice were similar. However, the concentration of OTD in the urine of NOG-TKm30 mice was markedly higher than in the urine of humanized-liver mice. These data demonstrate differences in hepatic metabolic enzyme expression induced by OTD in human and mouse liver cells, and consequent differences in the metabolism of OTD by human and mouse liver cells. This type of difference could have a profound impact on the carcinogenicity of compounds that are metabolized by the liver, and consequently, would be important in the extrapolation of data from animals to humans.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Camundongos , Humanos , Animais , Toluidinas/toxicidade , Fígado , Neoplasias da Bexiga Urinária/induzido quimicamente
3.
Sangyo Eiseigaku Zasshi ; 65(3): 125-133, 2023 May 25.
Artigo em Japonês | MEDLINE | ID: mdl-35831134

RESUMO

OBJECTIVES: Crystalline silica, which is a causative agent of silicosis (an occupational disease), is manufactured in a variety of products (particles) with different particle characteristics, such as size and surface properties. In Japan, the products are currently uniformly controlled as crystalline silica, which is a substance subject to labeling and notification requirements. However, since the toxicity of silica particles reportedly varies depending on its characteristics, businesses are encouraged to conduct appropriate risk assessments for each product to prevent silicosis. Recently, silica particles have been reported to induce lysosomal membrane damage, leading to the activation of proinflammatory factors. An indirect method to evaluate lysosomal membrane damage known as the erythrocyte hemolysis assay, in which the erythrocyte membrane is assumed to be the lysosomal membrane, was performed. This study aimed to examine the possibility of constructing a screening system for proinflammatory potential prediction of silica particles based on their erythrocyte hemolytic activity. METHODS: Hemolysis assays were performed on the silica particles with different sizes, crystallinity, and surface functional groups using the erythrocytes from a healthy volunteer. Additionally, the hemolytic activity of other element particles was compared with that of the silica particles, and 27 types of commercially available crystalline silica particle products underwent screening trials. RESULTS: The hemolytic activity of silica particles was higher in crystalline than that in amorphous and increased with the decreasing size. The hemolytic reaction was particular to silica particles and rarely occurred in particles of other elements. Moreover, the hemolytic activity was significantly suppressed if the silica particles surface was modified with metal ions (Fe3+, Al3+). The hemolytic activities of the crystalline silica products used industrially significantly differed. CONCLUSIONS: This study revealed that particle properties, such as size, crystallinity, and surface functional groups, affect the hemolytic activity of silica particles. Particularly, the surface functional groups (silanol groups) that are unique to silica particles were considered to be strongly involved in hemolytic activities. Since grading the commercially available crystalline silica particle products based on the hemolytic rate was possible, hemolytic activity was suggested to be an evaluation index for predicting the proinflammatory potential of silica particles.


Assuntos
Dióxido de Silício , Silicose , Humanos , Dióxido de Silício/toxicidade , Dióxido de Silício/química , Hemólise , Membrana Eritrocítica , Eritrócitos , Tamanho da Partícula
4.
J Biochem Mol Toxicol ; 36(6): e23043, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35279910

RESUMO

Ortho (o)-toluidine is a widely known carcinogenic substance associated with cancers of the human bladder. A study on British chemical factory workers exposed to 2-mercaptobenzothiazole, phenyl-ß-naphthylamine, aniline, and o-toluidine demonstrated the crucial roles of o-toluidine, 2-mercaptobenzothiazole, and phenyl-ß-naphthylamine in the development of bladder cancer. As genotoxic events are crucial steps in the initiation of cancer, in the present study, we aimed to examine the genotoxic potential of the four chemicals using phosphorylated histone H2AX (γ-H2AX), which is a sensitive and reliable marker of DNA damage, in cultured human urothelial cells. Of the four chemicals, 2-mercaptobenzothiazole was a particularly potent DNA-damaging agent. Moreover, mechanistic studies revealed that γ-H2AX generation by 2-mercaptobenzothiazole was mainly associated with the generation of reactive oxygen species via cytochrome P450 2E1-mediated metabolism. The findings of this study may provide information that is important for the assessment of risks associated with chemicals as well as the interpretation of epidemiological studies investigating occupational bladder cancer.


Assuntos
Citocromo P-450 CYP2E1 , Histonas/metabolismo , Neoplasias da Bexiga Urinária , 2-Naftilamina , Benzotiazóis , Citocromo P-450 CYP2E1/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Bexiga Urinária/induzido quimicamente
5.
Sangyo Eiseigaku Zasshi ; 64(5): 244-252, 2022 Sep 25.
Artigo em Japonês | MEDLINE | ID: mdl-34866064

RESUMO

OBJECTIVES: This study examined the characteristics of occupational mental disorders among those involved in the transport and postal activities in the trucking industry. METHOD: We examined 237 out of 3,517 cases of occupational mental disorders, compensated between the fiscal years 2010 and 2017. An assessment was made for sex, "life-or-death" status at compensation, age at the onset and suicide, the diagnosis according to the International Classification of Diseases, Tenth Revision, and other factors regarding occupational compensation. The participants were divided into two groups: truck drivers and non-truck drivers. RESULTS: Men accounted for approximately 90% of the cases. Depressive episode (F32) was the most common diagnosis in drivers and non-drivers, thus constituting 65 out of 149 and 48 out of 88 cases, respectively. The next most common type of mental disorder was adjustment disorders (F43.2), with 34 out of 149 drivers and 24 out of 88 non-drivers reporting them. Furthermore, the majority of drivers that had posttraumatic stress disorder (24 out of 27 cases) reported that they "suffered a serious illness or injury" and "experienced or witnessed a terrible accident or disaster." Occupational disasters due to long working hours were 52.4% for drivers and 73.9% for non-drivers. A total of 30.8% of the drivers reported working long hours since they joined the company. CONCLUSION: Drivers' long working hours entail waiting at the origin and cargo destination site, handling cargo, and incidental tasks other than driving. Thus, the reduction in work hours regarding these tasks needs to be a fundamental goal, and measures that include mental health care for accidents and miserable experiences must be implemented. However, long working hours for non-drivers are likely linked to job expansion/increase and reassignment/relocation. These findings highlight that to prevent overwork-related mental disorders, appropriate actions should be taken considering different sources of exposure for drivers or non-drivers.


Assuntos
Condução de Veículo , Transtornos Mentais , Doenças Profissionais , Suicídio , Condução de Veículo/psicologia , Humanos , Japão , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia
6.
Sangyo Eiseigaku Zasshi ; 64(1): 1-11, 2022 Jan 25.
Artigo em Japonês | MEDLINE | ID: mdl-33642457

RESUMO

OBJECTIVES: Karoshi problems (overwork-related deaths and disorders caused by cerebrovascular and cardiovascular diseases) still occur in Japan. Truck drivers, who are in one of the riskiest occupations, are reported to show an increased prevalence of hypertension, obesity, hyperlipidemia, and diabetes, which are characteristic of Karoshi. Their health problems also include excessive fatigue. This cross-sectional study aimed to examine the association between work-life factors and health disorders/excessive fatigue among Japanese truck drivers. METHODS: We distributed a questionnaire regarding work hours, health status, lifestyle, burden of driving, and excessive fatigue to 5,410 truck drivers and collected a total of 1,947 responses, all from males. The association between work-life factors and health outcomes was evaluated by multivariable logistic regression analysis adjusted for age, drinking, and smoking status. RESULTS: The prevalence rates of obesity, hypertension, hyperlipidemia, diabetes, cardiovascular disease, cerebrovascular disease, and excessive fatigue were 22.2%, 19.3%, 8.5%, 5.6%, 2.5%, 0.7%, and 6.0%, respectively. Significant associations were observed for long-haul trips (two days or more) with obesity (adjusted odds ratio 1.5 [95% Confidence Interval 1.1-2.1]), local and night trips with hypertension (1.5 [1.0-2.2]), early morning awakening on workdays with obesity (1.5 [1.1-2.1]), being indoor-oriented on weekends with hypertension (1.5 [1.1-2.0]); and heavy burden of driving at night with hyperlipidemia (2.0 [1.3-3.0]). The adjusted odds ratios were significant for waking after sleep onset (2.6 [1.2-5.3]) and lack of sleep satisfaction (2.7 [1.4-5.1]) on workdays, less than six hours of sleep (2.8 [1.0-7.8]) and lack of sleep satisfaction (2.8 [1.5-5.2]) on weekends, 0-3 days off per month (3.6 [1.3-10.2]), and heavy burden of driving at night (2.2 [1.0-4.8]) with excessive fatigue. CONCLUSIONS: The present findings highlight that night and early morning work, heavy burden of night driving, and the resultant decreases in the quality and quantity of sleep may represent shared risk factors for health disorders and excessive fatigue among truck drivers. Adequate measures should be taken to limit the amount of night and early morning work, reduce the burden of night driving, and ensure days off for sleep opportunities and leisure activities, with the goal of preventing Karoshi.


Assuntos
Condução de Veículo , Veículos Automotores , Estudos Transversais , Fadiga/epidemiologia , Humanos , Japão/epidemiologia , Masculino
7.
Int Arch Occup Environ Health ; 94(6): 1427-1439, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33651159

RESUMO

PURPOSE: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). METHODS: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. RESULTS: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7-104.3) and apparent dose-response relationships were revealed between the SIR and the surrogate exposure level in the 0-10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose-response relationships were observed. CONCLUSIONS: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.


Assuntos
Aminas/toxicidade , Carcinógenos/toxicidade , Exposição Ocupacional/efeitos adversos , Neoplasias da Bexiga Urinária/epidemiologia , Adulto , Cistite/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Risco , Adulto Jovem
8.
Int Arch Occup Environ Health ; 94(5): 991-1001, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33527174

RESUMO

PURPOSE: We aimed to cross-sectionally investigate how work and sleep conditions could be associated with excessive fatigue symptoms as an early sign of Karoshi (overwork-related cerebrovascular and cardiovascular diseases; CCVDs). METHODS: We distributed a questionnaire regarding work, sleep, and excessive fatigue symptoms to 5410 truck drivers, as the riskiest occupation for overwork-related CCVDs, and collected 1992 total samples (response rate: 36.8%). The research team collected 1564 investigation reports required for compensation for Karoshi. Of them, 190 reports listed the prodromes of Karoshi, which were used to develop the new excessive fatigue symptoms inventory. RESULTS: One-way analyses of variance showed that the excessive fatigue symptoms differed significantly by monthly overtime hours (p < 0.001), daily working time (p < 0.001), work schedule (p = 0.025), waiting time on-site (p = 0.049), number of night shifts (p = 0.011), and sleep duration on workdays (p < 0.001). Multivariate mixed-model regression analyses revealed shorter sleep duration as the most effective parameter for predicting excessive fatigue symptoms. Multiple logistic regression analysis confirmed that the occurrences of CCVDs were significantly higher in the middle [adjusted ORs = 3.56 (1.28-9.94)] and high-score groups [3.55 (1.24-10.21)] than in the low-score group. CONCLUSION: The findings suggested that shorter sleep duration was associated more closely with a marked increase in fatigue, as compared with the other work and sleep factors. Hence, ensuring sleep opportunities could be targeted for reducing the potential risks of Karoshi among truck drivers.


Assuntos
Doenças Cardiovasculares/epidemiologia , Fadiga/epidemiologia , Doenças Profissionais/epidemiologia , Sono , Carga de Trabalho , Adulto , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Veículos Automotores , Ocupações , Fatores de Risco , Indenização aos Trabalhadores
9.
Sangyo Eiseigaku Zasshi ; 63(2): 31-42, 2021 Mar 25.
Artigo em Japonês | MEDLINE | ID: mdl-32788509

RESUMO

OBJECTIVES: Beryllium is primarily used in its metallic form, in alloys, or in beryllium oxide ceramics. Its physical and mechanical properties make it useful for many applications across a range of industries. Because beryllium is recognized as a sensitizing and carcinogenic agent, the management of occupational health for workers who may be occupationally exposed to beryllium has long been an important issue in the world. Under these circumstances, the U.S. Occupational Safety and Health Administration (OSHA) had published a rule in January 2017, to prevent the development of chronic beryllium disease and lung cancer. This rule strengthens the regulations governing the use of beryllium and its compounds. With the announcement of the OSHA rule in January 2017, the purpose of this study is to gain insight into the health problems and industrial hygiene associated with the use of beryllium and share the issues related to the management of occupational health for persons working with beryllium in Japan. METHODS: We collected information regarding the beryllium industry, beryllium exposure, beryllium-induced health disorders, OSHA rule of January 2017, and regulations for beryllium use in Japan. After reviewing them, we discussed the issues concerning occupational health management of workers exposed to beryllium in Japan. RESULTS: It has been reconfirmed that in recent years, the most serious health problem due to beryllium exposure is chronic beryllium disease caused by beryllium sensitization. Management of occupational health that emphasizes reduction of beryllium sensitization and early detection of beryllium-sensitized workers is important. CONCLUSIONS: It was suggested that the following should be considered as the issues of management of occupational health of workers exposed to beryllium in Japan: (1) Collect epidemiologic data on health hazards from beryllium exposure in Japan. (2) Review the diagnostic items of special medical check-ups. (3) Review the definition of beryllium and its compounds in the Ordinance on Prevention of Hazards due to Specified Chemical Substances.


Assuntos
Beriliose/etiologia , Beriliose/prevenção & controle , Berílio/efeitos adversos , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Local de Trabalho , Beriliose/diagnóstico , Beriliose/epidemiologia , Berílio/análise , Doença Crônica , Feminino , Humanos , Japão , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/prevenção & controle , Masculino , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Exposição Ocupacional/análise , Saúde Ocupacional/tendências
10.
Toxicol In Vitro ; 66: 104880, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32387221

RESUMO

Recently, it was reported that ten cases of bladder cancer occurred among employees, who handled several kinds of aromatic amines, at a Japanese chemical plant. The common aromatic amines were identified as ortho-toluidine, para-toluidine, aniline, ortho-chloroaniline, ortho-anisidine, and 2,4-dimethylaniline. All of these aromatic amines, except ortho-chloroaniline, have been found to be carcinogenic in animals and/or humans. Genotoxic events are known to be crucial steps in the initiation of cancer; information on the genotoxicity of these aromatic amines is insufficient and consistent results have not been obtained. In this study, we examined the genotoxicity of the six different aromatic amines associated with bladder cancer by assessing phosphorylated histone H2AX (γ-H2AX) in a cultured human urothelial cell line, 1T1. We showed that all six aromatic amines generated γ-H2AX. In addition, the γ-H2AX-inducing potential of these six aromatic amines was distinctly different; ortho-chloroaniline and 2,4-dimethylaniline showed particularly high potential, followed by ortho-toluidine, ortho-anisidine, para-toluidine ≒ aniline. The findings of this study may provide important information for the risk assessment of chemicals and for interpreting epidemiological studies on occupational bladder cancer.


Assuntos
Compostos de Anilina/toxicidade , Dano ao DNA , Histonas/metabolismo , Mutagênicos/toxicidade , Urotélio/citologia , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos
11.
Arch Toxicol ; 93(12): 3617-3631, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31673724

RESUMO

Recent epidemiological studies have indicated that occupational exposure to the aromatic amine acetoaceto-o-toluidide (AAOT) was associated with a marked increase in urinary bladder cancers in Japan. However, little is known about the carcinogenicity of AAOT. To evaluate the urinary bladder carcinogenicity of AAOT, male and female F344 rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks followed by dietary administration of 0, 0.167, 0.5, or 1.5% AAOT for 31 weeks. The incidences and multiplicities of bladder tumors were significantly increased in the 0.5 and 1.5% groups of male and female rats in a dose-response manner. AAOT and seven downstream metabolites were detected in the urine of the male and female rats administered AAOT with levels increasing in a dose-dependent manner. The most abundant urinary metabolite of AAOT was the human bladder carcinogen o-toluidine (OTD), which was at least one order of magnitude higher than AAOT and the other AAOT metabolites. In a second experiment, male F344 rats were administered 0, 0.167, or 1.5% AAOT for 4 weeks. Gene expression analyses revealed that the expression of JUN and its downstream target genes was increased in the urothelium of male rats treated with 1.5% AAOT. These results demonstrate that AAOT promotes BBN-induced urinary bladder carcinogenesis in rats and suggest that overexpressed of JUN and its downstream target genes may be involved the bladder carcinogenicity of AAOT. In conclusion, AAOT, like other carcinogenic aromatic amines, is likely to be a carcinogen to the urinary bladder, and OTD metabolized from AAOT is the ultimate carcinogen.


Assuntos
Butilidroxibutilnitrosamina/toxicidade , Carcinógenos/toxicidade , Toluidinas/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Animais , Testes de Carcinogenicidade , Carcinógenos/administração & dosagem , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas c-jun/metabolismo , Ratos Endogâmicos F344 , Reação em Cadeia da Polimerase em Tempo Real , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
13.
J Occup Health ; 61(5): 339-348, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31004382

RESUMO

OBJECTIVES: The incidence of occupational low back pain (LBP) is high among caregivers. The use of care equipment and training about care methods could prevent LBP among caregivers. However, in care facilities in Japan, these measures are not adequately employed. Moreover, the care facilities have faced issues regarding poor staffing in recent years. The present study investigated the relationship between LBP and occupational safety and health activities (OSHAs) for preventing LBP among caregivers and aimed to validate the priority approaches of OSHA. METHODS: This cross-sectional study was conducted in care facilities for the elderly in Japan. Questionnaires for administrators and caregivers were distributed to 1,000 facilities and 5,000 caregivers, respectively. Questionnaires completed by 612 facilities and 2,712 caregivers were analyzed. RESULTS: No direct association was observed between severe LBP and OSHA, but indirect association was done. A significant relationship was noted between severe LBP and the care methods. Direct factors causing severe LBP were lifting a resident using human power and taking an unsuitable posture. These care methods were associated with the following OSHAs: promoting the use of care equipment, training about care methods, and consultation regarding the use of care equipment and employing an appropriate care method with the person in charge. CONCLUSIONS: These OSHAs decreased lifting a resident using human power and taking an unsuitable posture, which are the primary risk factors of LBP. Therefore, these OSHAs should be implemented as priority approaches to prevent LBP among caregivers in care facilities for the elderly.


Assuntos
Cuidadores/estatística & dados numéricos , Remoção/efeitos adversos , Dor Lombar/prevenção & controle , Doenças Profissionais/epidemiologia , Doenças Profissionais/prevenção & controle , Saúde Ocupacional/normas , Adulto , Estudos Transversais , Equipamentos Médicos Duráveis , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
14.
Arch Toxicol ; 92(10): 3093-3101, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30132044

RESUMO

The Japanese Ministry of Health, Labour, and Welfare recently reported an outbreak of bladder cancer among workers who handled aromatic amines in Japan. 2,4-dimethylaniline (2,4-DMA) is one of the chemicals that workers are considered to have the most opportunities to be exposed. Genotoxic events are known to be crucial steps in the initiation of cancer. However, studies on the genotoxicity of 2,4-DMA are limited, particularly studies investigating the mechanism behind the genotoxicity by 2,4-DMA are completely lacking. We examined genotoxic properties of 2,4-DMA using phosphorylated histone H2AX (γ-H2AX), a sensitive and reliable marker of DNA damage, in cultured human urothelial and hepatic cells. Our results clearly showed that 2,4-DMA at a concentration range of 1-10 mM generates γ-H2AX in both cell lines, indicating that 2,4-DMA is genotoxic. During mechanistic investigation, we found that 2,4-DMA boosts intracellular reactive oxygen species, an effect clearly attenuated by disulfiram, a strong inhibitor of cytochrome P450 2E1 (CYP2E1). In addition, CYP2E1 inhibitors and the antioxidant, N-acetylcysteine, also attenuated γ-H2AX generation following exposure to 2,4-DMA. Collectively, these results suggest that γ-H2AX is formed following exposure to 2,4-DMA via reactive oxygen species produced by CYP2E1-mediated metabolism. Continuous exposure to genotoxic aromatic amines such as 2,4-DMA over a long period of time may have contributed to the development of bladder cancer. Our results provide important insights into the carcinogenicity risk of 2,4-DMA in occupational bladder cancer outbreaks at chemical plants in Japan.


Assuntos
Compostos de Anilina/toxicidade , Família 2 do Citocromo P450/metabolismo , Hepatócitos/efeitos dos fármacos , Histonas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Inibidores do Citocromo P-450 CYP2E1/farmacologia , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Ureter/citologia
15.
Ind Health ; 56(5): 419-426, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29910229

RESUMO

Many care workers at elderly care facilities in Japan suffer occupational low back pain (LBP) despite the utilization of welfare equipment. When introducing welfare equipment such as hoists and sliding boards, education on appropriate care methods using welfare equipment is usually conducted, but the effect of education diminishes with time. This intervention study aimed to examine the effect of re-education on appropriate care methods using welfare equipment on the prevention of care workers' LBP at an elderly care facility. At the intervention facility, 49 care workers were enrolled in ergonomic education program for 1.5 yr in order to improve care methods using welfare equipment. At the non-intervention facility, 33 care workers were not enrolled in the program. Rates of severe LBP were not significantly different between the facilities. However, during the study period, the rate of severe LBP among care workers did not increase at the intervention facility, while it doubled among care workers at the non-intervention facility. The care workers at the intervention facility showed improvement in care methods using welfare equipment during the study period. Hence, we think that re-education regarding appropriate care methods using welfare equipment has the potential to prevent exacerbation of LBP.


Assuntos
Desenho de Equipamento , Pessoal de Saúde/educação , Dor Lombar/prevenção & controle , Movimentação e Reposicionamento de Pacientes/métodos , Doenças Profissionais/prevenção & controle , Adulto , Ergonomia , Feminino , Seguimentos , Instituição de Longa Permanência para Idosos/organização & administração , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Casas de Saúde/organização & administração , Saúde Ocupacional
16.
J Occup Health ; 60(4): 307-311, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29743389

RESUMO

BACKGROUND: ortho-Toluidine (OT) was listed as a Group 1 carcinogen by the International Agency for Research on Cancer in 2012 based on epidemiological observations of workers co-exposed to OT and aromatic amines. From 2014 to 2017, several cases of bladder cancer (BCa) secondary to occupational exposure, primarily to OT, were detected in Japan. OBJECTIVE: To describe 10 cases of BCa in male Japanese workers exposed primarily to OT at two plants that produce organic dye and pigment intermediates. METHODS: Details of the 10 cases were obtained from company records and through a questionnaire and interview. The surrogate level of exposure to each aromatic amine was calculated as the total job-weight/month for each process for each job-year. RESULTS: No quantitative exposure data were available. In most cases the surrogate level of exposure to OT was higher than to other amines. All 10 cases were exposed primarily to OT and co-exposed to para-toluidine, ortho-anisidine, aniline, 2,4-xylidine or ortho-chloroaniline. The age range at diagnosis was 41-71 years (mean 56). The duration of OT exposure was 7-28 years (mean 16.5). Disease latency was 16-28 years (mean 21.9). Eight patients were smokers. The main symptom at diagnosis was hematuria (70%). CONCLUSIONS: The characteristics of BCa cases were associated with a high surrogate level of OT exposure and a disease latency of more than 20 years from the initial OT exposure. The main route of OT exposure was likely through the skin. It is necessary to continue health examinations in these target groups.


Assuntos
Carcinógenos/toxicidade , Epidemias , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Toluidinas/toxicidade , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/epidemiologia , Adulto , Idoso , Indústria Química , Hematúria/etiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Exposição Ocupacional/análise
17.
Reprod Toxicol ; 76: 78-83, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29360564

RESUMO

Adverse effects of prenatal mercury exposure on pregnancy outcomes remain a public health concern. We assessed the relationship between prenatal mercury exposure and newborn anthropometric characteristics in 334 mother-child pairs from the early stages of pregnancy to delivery in Tokyo, Japan, between December 2010 and October 2012. We found a negative correlation between blood mercury levels during the first and second trimesters of gestation and birth weight (r = -0.134 and -0.119, respectively; p < 0.05). Multiple linear regression analysis confirmed the relationship between first-trimester maternal blood mercury levels and birth weight when adjusted for independent variables (ß = -0.170, t = -2.762; p = 0.006). Mean mercury levels in umbilical cord blood were twice as high as maternal blood levels (10.15 ±â€¯7.74 and 4.97 ±â€¯3.25 µg/L, respectively; r = 0.974, p < 0.001). Our findings suggest that pregnant women and women of reproductive age should avoid mercury exposure, even at low levels, because of its potentially adverse effects on fetal development.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Mercúrio/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adulto , Antropometria , Poluentes Ambientais/sangue , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Masculino , Mercúrio/sangue , Gravidez , Trimestres da Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
18.
Sangyo Eiseigaku Zasshi ; 58(4): 130-42, 2016 07 29.
Artigo em Japonês | MEDLINE | ID: mdl-27302832

RESUMO

OBJECTIVE: The purpose of this study was to clarify the causes of low back pain among workers in care facilities for the elderly after the introduction of welfare equipment. METHODS: We conducted anonymous questionnaire surveys among administrators and care workers in eight elderly care facilities. The questionnaires were designed to investigate the status of both the care workers and facility. In reference to the care facility, the questionnaires were comprised items for investigating basic information, occupational safety, and health activities. For care workers, in addition to basic information, occupational safety, and health activities, the questionnaires also comprised items for investigating resident transfer and bathing methods, low back pain, and occupational stress. RESULTS: Completed questionnaires were returned by eight care facility administrators (response rate: 100%) and 373 care workers (response rate: 92.3%), among which 367 were used for analyses. Many care workers participated in a variety of occupational safety and health activities that were conducted in the facilities. Various types of welfare equipment were introduced into the care facilities and subsequently used by many care workers during resident transfer and bathing. As a result, 89.9% of the care workers reported having only slight or no low back pain. The remaining 10.1% reported having serious low back pain that interfered with their work. On the basis of logistic regression analysis, low back pain was associated with the following variables: failure to provide the appropriate method of care to each resident, failure of colleagues to discuss methods for improving care, lack of instructions regarding the use of welfare equipment, and inappropriate job rotation. An association was also found between low back pain and poor posture, poor resident-lifting technique, insufficient time to complete work, and a shortage of workers to assist with resident transfer or bathing. CONCLUSION: Although care workers received instructions on the health and safety activities extracted from the surveys, an association was still found between these activities and low back pain. This was thought to result from some care workers not establishing the appropriate method of care for each resident, not discussing methods for improving care with other colleagues, not using the welfare equipment, and failing to practice appropriate job rotation. These results suggest that low back pain among care workers in the facilities for the elderly that have introduced welfare equipment is caused by a failure to sufficiently conduct appropriate care methods.


Assuntos
Cuidadores , Equipamentos e Provisões , Dor Lombar/etiologia , Dor Lombar/prevenção & controle , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Saúde Ocupacional , Assistência ao Paciente/instrumentação , Instituições Residenciais , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Gestão da Segurança , Inquéritos e Questionários , Tolerância ao Trabalho Programado
19.
Ann Occup Hyg ; 57(2): 251-60, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23002276

RESUMO

OBJECTIVES: To investigate the association between occupational contamination and exposure levels to antineoplastic drugs and the application of control measures in a hospital work environment. METHODS: Wipe samples of equipments were collected at a hospital in Osaka Prefecture, Japan, from 2007 to 2011. These samples were subjected to measurements of cyclophosphamide (CP), gemcitabine (GEM), platinum-containing drugs (Pt), and fluorouracil (5FU). Additionally, 24-h urine samples were collected from pharmacists who handled antineoplastic drugs, which were analyzed for CP and alpha-fluoro-beta-alanine (AFBA). The application of control measures was scored according to a checklist, which consisted of the following five items: safety equipment and maintenance, training and documentation, devices for safe handling, personal protective equipment, and emergency care. The aim was to obtain a score of 80%. RESULTS: The median CP, GEM, and 5FU concentrations of all wipe samples were significantly lower during the period when the mean score was >80% (attainment period) versus when the mean score was ≤80% (nonattainment period; all P < 0.001, Mann-Whitney's U-test). Additionally, the median urinary CP and AFBA concentrations of pharmacists during the attainment period tended to be lower than that of those during the nonattainment period (P = 0.061 and 0.061, respectively, using Mann-Whitney's U-test). CONCLUSIONS: Contamination and levels of exposure to antineoplastic drugs decreased with a score higher than 80%. The scores of the items on the checklist appeared to adequately reflect the condition of the control measures, as increases in all five items were associated with reductions in the contamination by and levels of exposure to all drugs.


Assuntos
Antineoplásicos/análise , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Equipamentos de Proteção/estatística & dados numéricos , Antineoplásicos/urina , Biomarcadores/urina , Contaminação de Equipamentos/estatística & dados numéricos , Substâncias Perigosas/análise , Substâncias Perigosas/normas , Hospitais , Humanos , Higiene , Japão , Farmácia
20.
Ind Health ; 50(2): 147-55, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22293727

RESUMO

Various applications of multiwalled carbon nanotubes (MWCNT) have been developed. One of these applications is an efficient sheet heating element that is woven from MWCNT-coated yarn. In this research, we assessed the exposure to MWCNT and/or the probability of particle release from broken MWCNT-coated yarn during the weaving process. This was accomplished using particle concentrations, microscopic observation, and carbon analysis. In the weaving process, neither an increase in the number of particles nor a difference in particle-size distribution was observed. In the scanning electron micrographic observation, nanosize MWCNT particles were not detected, but there were micron-size particles containing MWCNT as fragments of the yarn. Carbon analysis showed the concentration of micron-size particles containing MWCNT did not exceed 0.0053 mg-C/m(3) around the loom. This value was much lower than the respirable dust mass concentration. Most of micron-size particles seemed to originate from polyester yarn without MWCNT coating. It is recommended that workers use conventional (even not specialized for nanoparticles) personal protective equipment such as respirators and gloves to prevent exposure to respirable-size MWCNT-containing particles. The probability of MWCNT fall-off from the MWCNT-coated yarn was not detected by transmission electron microscopic observation of MWCNT-coated yarn before or after the weaving process.


Assuntos
Poluentes Ocupacionais do Ar/análise , Vestuário , Poeira/análise , Indústrias , Nanotubos de Carbono/análise , Exposição Ocupacional/análise , Humanos , Exposição por Inalação/análise , Japão , Medição de Risco/métodos
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