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In 2012, a social issue arose concerning a high incidence of cholangiocarcinoma (bile duct cancer) among printing workers. The cause was prolonged exposure to high concentrations of 1,2-dichloropropane that was included in the ink cleaning agent. Until then, it was not known that this substance could cause cancer in humans. The author was involved in this incident from the beginning. This article describes the course from the start of the investigation to the recognition of cholangiocarcinoma as an occupational disease. Furthermore, the article presents the pathological characteristics of occupational cholangiocarcinoma, as well as epidemiological analysis results.

Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N -methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense technology. In this paper, we describe the synthesis of GuNA[Me] phosphoramidites bearing other typical nucleobases including adenine (A), guanine (G), and 5-methylcytosine ( m C). The phosphoramidites were successfully incorporated into oligonucleotides following the method previously developed for the GuNA[Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or - m C toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides.

BackgroundRabeprazole at 10 or 20 mg twice daily (b.i.d.) has been reported to be highly effective in the treatment of proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) that is refractory to the standard once-daily PPI regimen. We evaluated the efficacy and safety of rabeprazole maintenance therapy at 10 mg once daily (q.d.) or b.i.d. for longer than 8 weeks.MethodsPatients with RE refractory to standard PPI regimens for at least 8 weeks were enrolled. They were treated with rabeprazole at 10 or 20 mg b.i.d. for 8 weeks during the open-label treatment period. After endoscopic examination, those with confirmed healing entered the subsequent double-blind maintenance therapy. During this period, the subjects were randomized to receive rabeprazole 10 mg q.d. (control) or 10 mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at Week 52.ResultsIn total, 517 subjects entered the treatment, and 359 subjects continued on maintenance therapy. The full analysis set for central assessment included 343 subjects. The no-recurrence rate at Week 52 was significantly higher in the b.i.d. group (73.9%; p < 0.001, χ2 test) than in the q.d. group (44.8%). In particular, the b.i.d. regimen was more effective in all subgroups with Los Angeles Classification Grade B to D at treatment entry.ConclusionsIn the maintenance treatment of PPI-resistant RE, rabeprazole at 10 mg b.i.d. exerted a stronger recurrence-preventing effect than 10 mg q.d. over 52 weeks. No particular safety issues were noted during long-term administration.ClinicalTrials.gov number: NCT02135107.

Abstract Rationale Little is known about neighborhood exposure to asbestos and mesothelioma risk among residents around an industrial source of asbestos. Objectives To investigate the magnitude of the risk among residents by asbestos exposure levels and to determine the range of the area affected by asbestos. Methods We calculated standardized mortality ratios of mesothelioma from 1995 to 2006 among the estimated population at risk that lived around a former large asbestos cement pipe plant in Amagasaki City, Japan, between 1957 and 1975, the time when the plant had used crocidolite and chrysotile. The distance between the plant and homes and relative asbestos concentrations obtained by diffusion equations involving meteorological conditions were used to determine asbestos exposure levels among residents. Measurements and Main Results We identified 73 mesothelioma deaths of 35 men and 38 women who had no occupational exposure to asbestos. Among persons who had lived within a 300-m radius of the plant, the standardized mortality ratio of mesothelioma was 13.9 (95% confidence interval, 5.6–28.7) for men and 41.1 (95% confidence interval, 15.2–90.1) for women. When the study area was divided into five regions by relative asbestos concentration, standardized mortality ratios of mesothelioma declined, for both sexes, in a linear dose-dependent manner with concentration. The regions with a significantly elevated standardized mortality ratio reached 2,200 m from the plant in the same direction in which the wind predominantly blew. Conclusions Neighborhood exposure to asbestos can pose a serious risk to residents across a wide area.

A causal relationship between mesothelioma and occupational asbestos exposure is well known, while some studies have shown a relationship to non‐occupational exposures. The aim of this study was to quantify the risk of mesothelioma death associated with neighborhood asbestos exposure due to a large‐scale asbestos‐cement (AC) plant in Amagasaki, Japan, adjusting properly risk factors including occupational exposures. We conducted a nested case‐control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with the neighborhood exposure were estimated by a conditional logistic‐regression model. For quantitative assessments for neighborhood exposure, we adopted cumulative indices for individuals' residential histories at each residence‐specific asbestos concentration multiplied by the duration during the potential exposure period of 1957–1975 (crocidolite). We observed an increasing, dose‐dependent risk of mesothelioma death associated with neighborhood exposure, demonstrating that ORs in the highest quintile category were 21.4 (95% confidence interval [CI] 5.8–79.2) for all, 23.7 (95% CI 3.8–147.2) for males, and 26.0 (95% CI 2.8–237.5) for females compared to the lowest quintile, respectively. A quantitative assessment for risk of mesothelioma deaths, adjusting for occupational and non‐occupational exposures separately, showed a dose‐dependent association with neighborhood exposure and no substantial gender differences in magnitude. We adopted cumulative indices that considered residence‐specific asbestos (crocidolite) concentrations and durations exposed during the period 1957–1975 for evaluation of neighborhood exposure. By adjusting properly for occupational and other considerable exposures, we demonstrated quantitative risk assessments of mesothelioma deaths dose‐dependently associated with neighborhood exposure due to a large‐scale asbestos cement plant in Amagasaki City, Japan. Our findings also showed there was no substantial gender difference in the magnitude of the risk in relation to neighborhood asbestos exposure.

In 2012, a social issue arose concerning a high incidence of cholangiocarcinoma (bile duct cancer) among printing workers. The cause was prolonged exposure to high concentrations of 1,2-dichloropropane that was included in the ink cleaning agent. Until then, it was not known that this substance could cause cancer in humans. The author was involved in this incident from the beginning. This article describes the course from the start of the investigation to the recognition of cholangiocarcinoma as an occupational disease. Furthermore, the article presents the pathological characteristics of occupational cholangiocarcinoma, as well as epidemiological analysis results.

Abstract: This Document, \"Guidelines for personal exposure monitoring of chemicals\" (\"this Guideline\"), has been prepared by \"The Committee for Personal Exposure Monitoring\"(\"the Committee\") of the Expert Division of Occupational Hygiene & Ergonomics, Japan Society for Occupational Health. Considering the background of the growing importance of personal exposure monitoring in risk assessment and the need to prepare for the introduction of monitoring using personal samplers from an administrative perspective in recent years, the Committee was organized in November 2012. The Committee has prepared this Guideline as a \"practical guideline\" for personal exposure monitoring, so as to offer proposals and recommendations to the members of the Japan Society for Occupational Health and to society in general. The scope of this Guideline covers all chemical substances and all related workplaces regarded as targets for general assessment and the management of risk. It thus is not to be considered to comment on legal regulations and methodology. The main text provides the basic methods and concepts of personal exposure monitoring, while 31 \"Appendices\" are provided in this Guideline throughout the series; technical descriptions, statistical bases, and actual workplace examples are provided in these appendices, to assist better understanding. The personal exposure monitoring described as per this Guideline is equivalent to an \"expert-centered basic method to reasonably proceed with the assessment and management of risk at workplaces.\" It is considered that practicing and expanding on this method will significantly contribute in reforming the overall framework of occupational hygiene management in Japan.

[Abstract] : This Document, \"Guidelines for personal exposure monitoring of chemicals\" (\"this Guideline\"), has been prepared by \"The Committee for Personal Exposure Monitoring\" (\"the Committee\") of the Expert Division of Occupational Hygiene & Ergonomics, Japan Society for Occupational Health. Considering the background of the growing importance of personal exposure monitoring in risk assessment and the need to prepare for the introduction of monitoring using personal samplers from an administrative perspective in recent years, the Committee was organized in November 2012. The Committee has prepared this Guideline as a \"practical guideline\" for personal exposure monitoring, so as to offer proposals and recommendations to the members of the Japan Society for Occupational Health and to society in general. The scope of this Guideline covers all chemical substances and all related workplaces regarded as targets for general assessment and the management of risk. It thus is not to be considered to comment on legal regulations and methodology. The main text provides the basic methods and concepts of personal exposure monitoring, while 31 \"Appendices\" are provided later in this Guideline throughout the series ; technical descriptions, statistical bases, and actual workplace examples are provided in these appendices, to assist better understanding. The personal exposure monitoring described as per this Guideline is equivalent to an \"expert-centered basic method to reasonably proceed with the assessment and management of risk at workplaces.\" It is considered that practicing and expanding on this method will significantly contribute in reforming the overall framework of occupational hygiene management in Japan.

ObjectivesThis study aimed to evaluate the relationship between cumulative exposure to 1,2-dichloropropane (1,2-DCP) and incidence risk of cholangiocarcinoma among workers in the offset proof-printing section of a small printing company in Osaka, Japan.MethodsWe identified 95 workers of a printing company (78 men and 17 women) who had been exposed to 1,2-DCP between 1987 and 2006, and calculated the standardised incidence ratio (SIR) of cholangiocarcinoma from 1987 to 2012. We estimated cumulative exposure to 1,2-DCP and calculated SIRs in four exposure categories. We also calculated incidence rate ratios (RRs) adjusted by sex, age, calendar year and dichloromethane (DCM) exposure for three exposure categories using Poisson regression analysis.ResultsCumulative exposures to 1,2-DCP ranged from 32 to 3433 ppm-years (mean, 851 ppm-years) and the SIR was 1171 (95% CI 682 to 1875). In the analysis of the four exposure categories, SIRs increased significantly in the three highest exposure categories, but not in the lowest category. Adjusted RRs in the middle and high exposure categories were 14.9 (95% CI 4.1 to 54.3) and 17.1 (95% CI 3.8 to 76.2), respectively, in the analysis without lag time, and were 11.4 (95% CI 3.3 to 39.6) and 32.4 (95% CI 6.4 to 163.9), respectively, in the analysis with a 5-year lag. The trend analysis revealed a significant increase in RR in association with increasing cumulative exposure to 1,2-DCP. DCM exposure was not significantly associated with the development of cholangiocarcinoma.ConclusionsThe present study demonstrated an exposure–response relationship between exposure to 1,2-DCP and the development of cholangiocarcinoma.

Issue Title: Contamination related to anthropic activities. Characterization and remediation