Establishment of Occupational Exposure Limit for Warfarin in China

This study aims to establish the occupational exposure limit （OEL） in the air for workplace of warfarin based on the available toxicological studies and field investigations by using questionnaire and air monitoring. The clinical therapeutic dose was used as lowest observed effect level （LOEL）, and no observed effect level （NOEL） was achieved by using a safety factor. The highest concentration of warfarin monitored in the worksite of centrifuge washing, drying and packing were 0.029 mg/m3, 0.052 mg/m3 respectively, which did not exceed the OEL 0.2 mg/m3 recommended by NIOSH and ACGIH. Considering its feasibility for enforcement and protection for workers, we recommend OEL 0.2 mg/m3 of warfarin in China.

Application of Benchmark Dose (BMD) in Estimating Biological Exposure Limit (BEL) to Cadmium

Objective To estimate the biological exposure limit （BEL） using benchmark dose （BMD） based on two sets of data from occupational epidemiology. Methods Cadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium （UCd） was used as an exposure biomarker and urinary D2-microgloburin （B2M）, N-acetyl-D-D-glucosaminidase （NAG） and albumin （ALB） as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS （Version 1.3.2, EPA.U.S.A） was used to calculate BMD. Results The cut-off point （abnormal values） was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers （urinary B2M, NAG9 and ALB） and exposure biomarker （UCd）. BEL value was 5 μg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 μg/g creafinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected. Conclusion BMD can be used in estimating the biological exposure limit （BEL）. UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.

A systematic review of occupational exposure to respirable coal mine dust(RCMD)in the U.S.mining industry

Cumulative inhalation of respirable coal mine dust(RCMD)can lead to severe lung diseases,including coal worker's pneu-moconiosis(CWP),silicosis,mixed dust pneumoconiosis,dust-related diffuse fibrosis(DDF),and progressive massive fibrosis(PMF).Statistics from the number of reported cases showed a significant decrease in the progression of respiratory diseases in the 1990s.However,an unexpected increase in the number of CWP cases was reported in the late 1990s.To date,there has been no comprehensive systematic review to assess all contributing factors to the resurgence of CWP cases.This study aims to investigate the effects of various mining parameters on the prevalence of CWP in coal mines.A systematic review using the preferred reporting items for systematic reviews and meta-analysis(PRISMA)method was conducted to investigate the health effects of RCMD exposure and identify the factors that may contribute to the recent resurgence of CWP cases.The systematic review yielded a total of 401 papers,which were added to the database.The total number of 148 and 208 papers were excluded from the database in the process of screening and eligibility,respectively.Then,18 papers were considered for data selection and full-text assessment.The review revealed that factors including geographic location,mine size,mining operation type,coal-seam thickness,coal rank,changes in mining practices,technology advancement,and engi-neering dust control practices are contributing to the recent resurgence of CWP among coal workers.However,the evidence for root causes is limited owing to the methodological constraints of the studies;therefore,further detailed studies are needed.

Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects

Objective The study aimed to estimate the benchmark dose(BMD)of coke oven emissions(COEs)exposure based on mitochondrial damage with the mitochondrial DNA copy number(mtDNAcn)as a biomarker.Methods A total of 782 subjects were recruited,including 238 controls and 544 exposed workers.The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction.Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95%confidence lower limit(BMDL).Results The mtDNAcn of the exposure group was lower than that of the control group(0.60±0.29 vs.1.03±0.31;P<0.001).A dose-response relationship was shown between the mtDNAcn damage and COEs.Using the Benchmark Dose Software,the occupational exposure limits(OELs)for COEs exposure in males was 0.00190 mg/m^(3).The OELs for COEs exposure using the BBMD were 0.00170 mg/m^(3)for the total population,0.00158 mg/m^(3)for males,and 0.00174 mg/m^(3)for females.In possible risk obtained from animal studies(PROAST),the OELs of the total population,males,and females were 0.00184,0.00178,and 0.00192 mg/m^(3),respectively.Conclusion Based on our conservative estimate,the BMDL of mitochondrial damage caused by COEs is0.002 mg/m^(3).This value will provide a benchmark for determining possible OELs.

Silicosis in Automobile Foundry Workers: A 29-Year Cohort Study

Objectives The purposes were to determine the relationship between silicosis among foundry workers and their cumulative exposure to silica dust, and to establish a regression model to predict the risk for developing silicosis by a given length of employment and air concentrations of silica at worksites. Methods A 29-year cohort study was conducted, including all those employed for more than one year during January 1, 1980 to December 31, 1996 and all members of the cohort were followed-up to December 3 1, 2008. In total, 2 009 workers of an automobile foundry in Shiyan, Hubei province were recruited in the study, 1 300 at eight worksites including sand preparation, cast shakeout, and finishing, melting, moulding, core-making, overhead crane operation and pouring as exposed group, and the other 709 auxiliary workers at the same factory, such as electricians, inspectors, fitters, and so on, as control group. Person-years of observation were calculated by persons observed and years followed-up for each of them. Person-year incidence of silicosis and its relative risk （RR） or odds ratio （OR） and 95% confidence intervals （CI） among the workers were estimated, adjusted for relevant factors with logistic regression model using SPSS version 15.0 software. Results Totally, 2 009 workers were followed-up for 37 151 person-years and 48 cases of silicosis were found, with an overall incidence of 1.34 per thousand, 2.02 per thousand in exposed group, and 0.15 per thousand in control one. Risk of silicosis was significantly higher in the exposed group than that in the control one （RR=13.13, 95% CI 3.18-54.13）, higher in men than that in women （RR=13.92, 95% CI 1.92-100.93）. Risks of silicosis varied by job, highest in those exposed to cast shakeout and finishing （RR=28.14, 95% CI 6.43-123.11）, followed by those exposed to pouring （RR-22.23, 95% CI 5.01-98.55） in the foundry. Average length of employment at onset of silicosis was 25.94 years, and silicosis incidence increased with length of employment. Average age at onset of silicosis was 47.83 years old. The risk of silicosis in workers with pulmonary tuberculosis was 2.57 folds as those without it （P〈0.01）. Ten deaths were recorded in those with silicosis, with a case-fatality rate of 20.83 percent three of them died of lung cancer, three of liver cancer, two of ischemic heart disease, and two of other diseases as their immediate causes of death. Incidence of silicosis in foundry workers positively correlated with their cumulative silica exposure （OR-3.00, 95% CI 2.34-3.83）. Risks of silicosis increased by 4.38 folds with an increase of 1 mg/m^3-year of cumulative silica exposure, and by 3.79 folds with smoking, respectively, adjusted for alcohol drinking and age. Based on a logistic regression model fitted, incidence of silicosis is expected to be 44.6 per thousand for those with daily exposure to silica of 4.18 mg/m^3 in average for 30 years, and if incidence of silicosis is expected to be less than 1 per thousand, daily exposure to silica should be controlled below 0.2 mg/m^3 for those with 20 years of employment, or below 0.1 mg/m^3 for those with 30 or 40 years of silica exposure. Conclusions At present, foundry workers in China still face high risk of developing silicosis. For lowering occurrence of silicosis in exposed workers, it seems necessary that current occupational exposure limits for silica at worksites in China should be reexamined and silica dust control measures be strengthend.