Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects / 生物医学与环境科学（英文）

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 is 0.002 mg/m 3. This value will provide a benchmark for determining possible OELs.

Association between urinary polycyclic aromatic hydrocarbons metabolites and high-normal blood pressure in coke oven workers / 中国职业医学

@#Objective （ ） To investigate the association between urinary polycyclic aromatic hydrocarbons PAHs metabolites - Methods and high normal blood pressure in coke oven workers. A total of 433 coke oven workers were selected as the study - subjects using convenient sampling method. They were divided into normal blood pressure group and high normal blood pressure group according to their blood pressure level. The levels of ten kinds of urinary hydroxylated PAHs metabolites were measured by - Results - high performance liquid chromatography mass spectrometry. Among the subjects,57.5% had high normal blood - ， - ， - pressure. The levels of 1 hydroxynathalene 2 hydroxyphenanthrene 1 hydroxyphenanthrene and the metabolite of total PAHs - （ P ） in the high normal blood pressure group were higher than those in the normal blood pressure group all <0.05 . The results of - ， - ， - ， the multivariate logistic regression analysis showed that urinary 1 hydroxynathalene 2 hydroxyfluorene 3 hydroxychrysene - （ P ）， and metabolite of total PAHs were all risk factors for high normal blood pressure in coke oven workers all <0.05 after ， ， ， ， ， adjusting for confounding factors such as gender length of service body mass index smoking index alcohol consumption tea ， ， ， Conclusion consumption night shift exercise frequency and other PAHs metabolites. Exposure to PAHs in coke oven plants may increase the risk of elevated blood pressure within the normal range among coke oven workers.

Influencing factors of urinary hydroxyl metabolites of polycyclic aromatic hydrocarbons in coke oven workers / 中国职业医学

OBJECTIVE: To observe the levels of four hydroxylated metabolites of polycyclic aromatic hydrocarbons(PAHs)in the urine of coke workers and its influencing factors.To explore the feasibility of using PAHs as biomarkers for exposure of coke oven emissions(COEs).METHODS: A cross-sectional survey was used to compare 261 coke oven workers in a coke oven plant as exposure group with 111 workers without COEs exposure in an oxygen making plant as control group.Ultra high liquid chromatography-mass spectrometry was used to detect four hydroxylated metabolites of PAHs,including1-hydroxypyrene(OHP),1-hydroxynaphthalene(OHN),2-OHN and 3-hydroxyphenanthrene,in urine of these two groups.RESULTS: The levels of four hydroxylated metabolites of PAHs in urine in exposure group were higher than that of the control group(P<0.01).The levels of urinary 1-OHP,1-OHN,2-OHN were followed by the sequence of bottomoven,side-oven,and top-oven subgroups among the exposure group(P<0.05).The multiple linear regression results indicated that the levels of urinary 1-OHP,1-OHN,2-OHN were correlated with COEs exposure(P<0.05),after adjusting the confounding factors of gender,age,length of service,smoking status and alcohol drinking status.The levels of urinary 1-OHP,1-OHN,2-OHN of the exposure group increased with the increase of COEs exposure levels showing a dose-effect relationship(P<0.01).The levels of 1-OHN and 2-OHN were associated with smoking apart from COEs exposure(P<0.01).CONCLUSION: The urinary 1-OHP can be used as a reliable biomarker for the evaluation of internal exposure to COEs.The 1-OHN and 2-OHN can be used as adjuvant biomarkers.

Mechanism of coke oven emissions-induced acute toxicity in HL-60 cells / 中国职业医学

OBJECTIVE: To establish the cell model using human leukemia cell line HL-60 for exposure of coke oven emissions( COE) in vitro and to explore the mechanism of COE-induced acute toxicity in HL-60 cells. METHODS: HL-60 cells were collected in their logarithmic growth phase and cultured in medium that had final concentrations of COE in 2. 5,5. 0,10. 0 and 20. 0 mg / L for 24 hours. Cell survival rate was examined by CCK-8 assay. The cytotoxicity was evaluated using lactate dehydrogenase release assay. Reactive oxygen species( ROS) production was determined by the 2',7'-dichlorofluorescein diacetate and nitroblue tetrazolium method. The activation of nuclear factor-κB( NF-κB) pathway was evaluated by western blot. RESULTS: With the increasing exposure concentrations of COE,the cytotoxicity of HL-60 cells increased( P < 0. 01),the cell survival rate decreased( P < 0. 01),intracellular ROS decreased( P < 0. 01),whereas extracellular ROS increased( P < 0. 01). These changes had a dose-effect relationship. The levels of phospho-nuclear factor-kappa B p65 and phospho-inhibitor of kappa Bα were higher in all the COE-treated cells compared with untreated cells( P < 0. 05),with no dose-effect relationship. CONCLUSION: COE could cause acute toxicity in HL-60 cells in a doseeffect relationship. The mechanism may be related to the COE-induced in-balanced ROS release and removal,leading to the activation of NF-κB pathway. HL-60 cells can be used as a common cell line for COE hematotoxicity analysis.

Effects of smoking on concentration of urinary 8-hydroxydeoxyguanosine in coke oven workers / 中华劳动卫生职业病杂志

Objective@#To explore the influence of smoking and polycyclic aromatic hydrocarbons (PAHs) on urinary 8-hydroxydeoxyguanosine (8-OHdG) in coke oven workers and investigate their dose-dependent relationships.@*Methods@#A total of 436 workers exposed to coke oven emissions (COEs) and 132 controls were recruited in this study. Questionnaires were completed in a personal interview. Then their urine samples were also collected and the concentrations of urinary four OH-PAHs and 8-OHdG were determined by high performance liquid chromatography (HPLC) which was used to evaluate the levels of occupational PAHs internal exposure among workers and the DNA damage.@*Results@#The differences of concentrations of urinary 2-NAP (2-hydroxynathalene) , 2-FLU (2-hydroxyfluorene) , 9-PHE (9-hydroxyphenanthrene) , 1-OHP (1-hydroxypyrene) between exposure group and control group were statistically significant (P<0.05) . In exposure group and control group, the level of 8-OHdG in heavy smoking workers were significantly higher than that in other groups (P<0.05) . Multivariate logistic regression analysis revealed high levels of urinary 8-OHdG were associated with a significantly increased risk of having higher urinary1-hydroxypyrene levels[OR=1.43 (95%CI: 1.06-1.94) , P<0.01] and heavy smoking [OR=1.44 (95%CI: 1.08-1.91) , P<0.01], respectively. Trend test showed that linear dose response relationship between smoking, 1-OHP in urine and higher concentrations of 8-OHdG (P<0.05) . Smoking could significant modify the effects of urinary 1-hydroxypyrene, while co-exposure to both heavy smoking and high urinary 1-hydroxypyrene levels[OR=5.64 (95%CI: 2.15-14.80) , P<0.05].@*Conclusion@#Urinary 1-hydroxypyrene is a useful biomarker for evaluating total PAHs exposure, coke oven workers with heavy smoking present more serious DNA oxditive damage.

Research on reducing safrole and aristolochic acid A in Asari Radix et Rhizoma based on different processing techniques / 中草药

Objective: To study the effect of processing techniques on reducing the contents of safrole and aristolochic acid A in Asari Radix et Rhizoma. Methods: The contents of safrole and aristolochic acid A between raw herb and processed products were determined by HPLC, and the differences in the contents of toxic components between raw herb and processed products were used to evaluate the detoxification efficiency. Results: The linear ranges of safrole and aristolochic acid A were 169.2-846.0 μg (r = 0.9996) and 11.6-58.0 ng (r = 0.9996), respectively. And the average recovery rates were 99.83% (RSD = 1.67%) and 101.43% (RSD = 1.25%). The removal rate of safrole in order was as follows: salt system > fried coke > rice water system > alkali > liquorice > vinegar > ginger > wine > alkali-vinegar > honey and the removal rate of aristolochic acid A was in ordor as: fried coke > alkali-vinegar > salt system > alkali > vinegar > rice water system > liquorice > wine > honey > ginger. The removal rate of aristolochic acid A in Asari Radix et Rhizoma by fried coke was over 60%. Conclusion: The contents of safrole and aristolochic acid A in Asari Radix et Rhizoma could be decreased to different extent by processing techniques. Among the processing methods, processing by fried coke is the best method.

Changes of Th17 cytokine in human bronchial epithelial cells induced by coke oven emission / 中国药理学与毒理学杂志

OBJECTIVE To find the infla mmation bio markers induced by coke oven e missions (COE),we investigated the changes of T helper 17 (Th17 )cytokines in hu man bronchial epithelial (16HBE)cells.METHODS 16HBE cells were exposed to organic extracts of COE collected fro m co-king plant at the concentrations of 5,10 and 20 mg·L -1 for 24 h or 5 d to establish short-term and long-term cell models,respectively.Cell viability was measured by MTT assay and infla mmatory da mage was assessed by lactate dehydrogenase assay (LDH).The cytokines in culture supernatant sa mples was detected by co mmercial hu man Th17 cytokine panel kit.RESULTS COE Can induce infla mmation in COE 20 mg·L -1 group and no expression on IL-17 F and IL-1 β.The concentration of IL-10 was 1 .25 ± 0.54,1 .39 ±0.13 and (1 .90 ±0.73)pg·mL -1 in COE 5,10 and 20 mg·L -1 group showing good con-centration-effect relationship (r=0.98,P <0.05 ).IL-23 expression was found only higher at 10 and 20 mg·L -1 and the concentrations were 3.38 ±3.90 and (1 .74 ±2.00 )pg·mL -1 ,respectively.In 16HBE cells treated by COE for 5 d,elevated expression of IL-17A was found in COE 5 and 10 mg·L -1 group,and there was statistically sigificant difference between COE 10 mg·L -1 and DMSO group (P<0.05).Elevated concentration of IL-17F of 10.2 ±1 1 .78 and (6.79 ±7.84)pg·mL -1 was found in COE 5 and 10 mg·L -1 group.The concentration of IL-10 was 1 .71 ±0.02,1 .49 ±0.25 and (2.82 ± 0.33)pg·mL -1 in COE 5,10 and 20 mg·L -1 group,respectively.We found increased IL-1 βexpression with concentration of 2.72 ±0.62,2.25 ±0.33 and (0.93 ±0.21 )pg·mL -1 in COE 5,10 and 20 mg·L -1 group with negative dose-response relationship.We also found more elevated TNF-αlevels in the 5 d than in the 24 h model with no COE specific relationship.CONCLUSION COE induces expression changes of Th17 cytokines profile in 16HBE cells,including IL-23 and IL-1 βfor early and long-term infla mmation,respectively.IL-10 may be a candidate marker for population study on COE induced infla mmatory injury.

Análisis termogaavimétrico en la caracterizació de carbones Colombianos empleaados en la producción de coque / Themogravimetricc analysis in the characterization f Colombian coaals used in the production of coke / Análise termogrvvimétrica na caracterização de carvões Colombiaos utilizados nna produção de coque

Cinco carbones de los departamentos de Cundinamarca, Boyacá y Norte de Santander (Colombia) se caracterizaron mediante análisis próximo, último, reológico, petrográfico, calorífico y termogravimétrico. Los parámetros analizados, especialmente aquellos que determinan las propiedades reológicas, muestran que los carbones estudiados y sus mezclas podrían producir un coque de buena calidad. Se observó la relación inversa entre el contenido de materia volátil y la reflectancia media aleatoria de la vitrinita, que se atribuye al aumento de la aromaticidad en la estructura molecular del carbón como una consecuencia del incremento en el rango. Los parámetros derivados del análisis termogravimétrico -máxima velocidad de desvolatilización y temperatura de máxima velocidad de desvolatilización- mostraron buenas correlaciones con la reflectancia media aleatoria de la vitrinita, igual que la máxima velocidad de desvolatilización con la fluidez máxima. Lo anterior indica que el análisis termogravimétrico podría ser una herramienta útil para caracterizar de manera rápida carbones usados en procesos de fabricación de coque metalúrgico.

Five types of coal from the states of Cundinamarca, Boyaca and Norte de Santander (Colombia) were characterized by proximate, ultimate, rheological, petrographic, calorific and thermogravimetric analysis. The parameters used, especially the ones which determine the rheological properties show that the studied coals and its blends could produce good quality coke. It was observed the inverse relationship between the volatile matter content and the mean vitrinite reflectance, relationship which is attributed to the increase of the aromaticity in the molecular structure of the coal as a consequence of the rank increase. The parameters derived from the thermogravimetric analysis, maximum velocity of de-volatilization and the temperature of maximum velocity of de-volatilization and the media reflectance of the vitrinite showed good correlations. Also was observed an interesting correlation between the velocity ofde-volatilization and maximum fluidity. This shows that the thermogravimetric analysis can be a useful tool to characterize in a quick way coals used for metallurgical coke production.

Cinco carvões dos departamentos de Cundinamarca, Boyacá e Norte de Santander (Colômbia) foram caracterizados por análise próxima, última, reológica, petrográfica e termogravimétrica. Os parâmetros analisados, em especial aqueles que determinam as propriedades reológicas mostram que os carvões estudados e suas misturas podem produzir coque de boa qualidade. Foi observada relação inversa entre o teor de matéria volátil e refletância média vitrinite, que é atribuído ao aumento da aromaticidade da estrutura molecular do carvão como um resultado do aumento no rango. Os parâmetros derivados da análise termogravimétrica, velocidade máxima de pirólise e temperatura de máxima velocidade de pirólise mostraram boas correlações com a refletância média vitrinite, tal como a velocidade máxima de pirólise e a fluidez máxima. Isto mostra que a análise termogravimétrica pode ser uma ferramenta útil para caracterizar rapidamente carvões utilizados nos processos de fabricação de coque metalúrgico.

Nivel de níquel urinario en niños residentes en ciudades cercanas a megafuentes / Urinary nickel in children exposed to petcoke pollution

Background: Petcoke is a remmant of the oil refiningprocess that contains Ni and other heavy metáis. Undesired human exposure to these compounds may result from petcoke combustión in plants located in the vicinity ofthe cities. Aim: To compare levéis of urinary Ni in schoolchildren residing in cities exposed and not exposed to petcoke pollution. Material and methods: A cross sectional study was done in schoolchildren aged 7 to 8 years oíd in two cities in northern Chile: Mejillones (n = 59), near to a petcoke plant and Tocopilla (n = 56) as the reference city. First, morning urinary samples were collected and urinary Ni was determined by Atomic Absorption Spectrometry. Socioeconomic and environmental exposure information of families was obtained applying a questionnaire to parents. Múltiple linear regression was performed to identify other variables that may explain urinary Ni differences among the cities. Results: Median level of Ni was higher in Mejillones (4.9 fig/L) than in Tocopilla (3.9 fig/L). Residing in the exposed city was the most important explaining factor (B = 0.26; IC 0.107 - 0.428). Additionally years of residency was associated with urinary Ni (B = 0.03; IC 0.004 - 0.060). Conclusions: Urinary Ni in schoolchildren is higher in the city exposed to petcoke emissions. The difference does not imply that there are concrete hazards for the population s health. However, it warns about the existence of a higher exposure in places where petcoke is used.

Cytochrome P450 (CYP) and glutathione S-transferases (GST) polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1 and GSTT1) and urinary levels of 1-hydroxypyrene in Turkish coke oven workers

Genetic polymorphisms of xenobiotic metabolizing enzymes have been associated with cancer risk. We evaluated the influences of genetic polymorphisms of polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes on urinary 1-hydroxypyrene (1-OHP) excretion in Turkish coke oven workers. Urinary 1-OHP was analyzed by HPLC after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping of cytochrome P450 (CYP) polymorphisms (CYP1A1 and CYP1B1) and glutathione S-transferases (GST) polymorphisms (GSTM1, GSTT1 and GSTP1). The mean urinary 1-OHP levels of coke oven workers were significantly higher than that of controls. No significant difference was detected in the mean urinary 1-OHP levels of smokers and non-smokers either for coke oven workers or controls. Genetic polymorphisms of the CYPs and GSTs studied had no significant influence on 1-OHP excretion in coke oven workers, but in the control group the urinary 1-OHP levels of individuals carrying the GSTT1- genotype were significantly higher than those of individuals carrying GSTT1+ genotype. The duration of occupational exposure and metabolic genotype for GSTT1 were the significant predictors of urinary 1-OHP levels. The control individuals carrying combined GSTM1-/GSTT1- genotypes also had significantly higher levels of urinary 1-OHP than those of individuals carrying GSTM1+/GSTTI+, GSTM1-/GSTT1+, and GSTM1+/GSTT1- genotypes. These results indicate that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that genetic polymorphism of GSTT1 may also to some extent reflect the interindividual variation in susceptibility to PAHs only at low PAH exposure.

Lung Cancer Occurring in a Worker Exposed to Coke Oven Emissions / 대한산업의학회지

OBJECTIVES: We report a case of lung cancer (small cell carcinoma) occurring in a worker exposed to coke oven emissions. METHODS: We examined the chest CT and pathologic findings of the patient. We reviewed previous environmental measurements for coke oven emissions at the workers place of employment. Also we measured the airborne concentrations for coke oven emissions and total polycyclic aromatic hydrocarbons in the work area. Finally, we analyzed the 1-hydroxypyrene and 2-naphthol concentrations in the subjects urine and compared this with student controls. RESULTS: This case was a 56-year-old male who had worked in a coke oven plant within a steel manufacturing factory for 21 years (1977-1998). The airborne concentrations of coke oven emissions at the worksite were above the permissible exposure level (0.2 mg/m3) in 45 cases (33.1%) among 136 workers. The concentrations of 1-hydroxypyrene and 2-naphthol in the subjects urine were statistically significantly elevated as compared with those of controls (P<0.01). CONCLUSIONS: We confirmed that the lung cancer occurring in this patient was as an occupational disease due to exposure to coke oven emissions. To prevent occupational cancer in coke oven plant workers, we must remodel the engineering procedure, begin comprehensive medical surveillance, educate workers on risks and the benefits of smoking cessation, and increase awareness of safety regulations in the workplace.

Effects of occupation, life style and genetic polymorphism of CYP1A1, GSTM1, and GSTT1 on urinary 1-hydroxypyrene and 2-naphthol concentration / 대한산업의학회지

OBJECTIVES: This study was performed to describe the distribution patterns of urinary 1-hydroxypyrene (1-OHP) and 2naphthol concentration in coke oven workers and workers not occupationally exposed to polycyclic aromatic hydrocarbons (PAH), and to determine the effects of occupation life style, and genetic polymorphism of cytochrome P450 1A1 (CYP1A1), glutathione Stransferase mu 1 (GSTM1) and theta 1 (GSTT1) on urinary 1- OHP and 2-naphthol concentration. METHODS: The study subjects were 19 coke oven workers and 156 shipyard workers. A questionnaire was used to obtain data about detailed smoking and food intake history. Urinary 1OHP and 2naphthol concentration and genetic polymorphism of CYPIA1, GSTM1, and GSTT1 were analyzed. RESULTS: The urinary 1-OHP and 2-naphthol concentration was higher in the coke oven workers and in smokers. Urinary 1-OHP concentration was significantly correlated with time after last intake of roasted meat in non-smoking coke oven workers, whereas urinary 2-naphthol concentration was with amount of cigarette smoking at the sampling day in smoking shipyard workers. Urinary 1-OHP, but not 2-naphthol, concentration of the shipyard workers with Ile/Ile type of CYP1A1 vas significantly lower than that of the shipyard workers with other CYP1A1 genotype. CONCLUSIONS: Urinary 1-OHP would be a better marker for occupational exposure to PAH in coke oven workers, and urinary 2naphthol might be better for non-occupational inhalation exposure to PAH. CYP1A1 would not play an important role in the metabolism of naphthalene but in the metabolism of pyrene.