Tzu-Hsuen Yuan

Cardiopulmonary toxicity of pulmonary exposure to occupationally relevant zinc oxide nanoparticles.

Abstract Exposure to zinc oxide (ZnO) metal fumes is linked to adverse human health effects; however, the hazards of ZnO nanoparticles (ZnONPs) remain unclear. To determine pulmonary exposure to occupationally relevant ZnONPs cause cardiopulmonary injury, Sprague-Dawley rats were exposed to ZnONPs via intratracheal (IT) instillation and inhalation. The relationship between intrapulmonary zinc levels and pulmonary oxidative-inflammatory responses 72 h after ZnONP instillation was determined in bronchoalveolar lavage fluid (BALF). Instilled ZnONPs altered zinc balance and increased the levels of total cells, neutrophils, lactate dehydrogenase (LDH) and total protein in BALF and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in blood after 72 h. The ZnONPs accumulated predominantly in the lungs over 24 h, and trivial amounts of zinc were determined in the heart, liver, kidneys and blood. Furthermore, the inflammatory-oxidative responses induced by occupationally relevant levels of 1.1 and 4.9 mg/m3 of ZnONP inhalation for 2 weeks were determined in BALF and blood at 1, 7 and 30 days post-exposure. Histopathological examinations of the rat lungs and hearts were performed. Inhalation of ZnONP caused an inflammatory cytological profile. The total cell, neutrophil, LDH and total protein levels were acutely increased in the BALF, and there was an inflammatory pathology in the lungs. There were subchronic levels of white blood cells, granulocytes and 8-OHdG in the blood. Cardiac inflammation and the development of fibrosis were detected 7 days after exposure. Degeneration and necrosis of the myocardium were detected 30 days after exposure. The results demonstrate that ZnONPs cause cardiopulmonary impairments. These findings highlight the occupational health effects for ZnONP-exposed workers.

Possible association between nickel and chromium and oral cancer: A case–control study in central Taiwan

Oral cancer is one of the most common cancers in Taiwan. Changhua County, in central Taiwan, has an extremely high prevalence of oral cancer, along with a high concentration of metal-related industries and soil metal contamination. The aim of this study was to clarify the possible association between metals and oral cancer within this specific area. This study recruited 101 oral cancer patients and 104 controls from the Changhua Christian Hospital. All subjects completed a questionnaire that asked about demographic information; cigarette, alcohol, and betel quid use; and environmental and occupational exposure history. Blood samples were collected and tested for metal concentrations with inductively coupled plasma mass spectrometry. A multiple logistic regression model illustrated that oral cancer was significantly associated with the blood levels of nickel and chromium (both with P<0.0001) after controlling for potential confounders. This study suggested a potential role of these two metals in the mechanism of oral cancer development.

The distance-to-source trend in vanadium and arsenic exposures for residents living near a petrochemical complex.

Biological monitoring of vanadium (V) and arsenic (As) for residents living near a big petrochemical complex has not been previously studied. This study aims to investigate distance-to-source trends in urinary levels and dispersion-estimated concentrations of V and As in areas surrounding a petrochemical complex in central Taiwan. Our study subjects were 1424 residents living in the townships up to ~40 km from the petrochemical complex, and categorized as near (Zone A), further (Zone B) and furthest (Zone C) from the complex. Urinary and ambient V and As levels were analyzed by inductively coupled plasma mass spectrometry. Two-stage dispersion model was used to estimate V and As concentrations at each study subject’s address. Multiple linear regression models were used to study the effects of distance-to-source and estimated air concentrations of V and As on the urinary V and As levels of study subjects. Area-wide levels of both V and As showed a high-to-low trend in urinary levels (μg/g-creatinine) from Zone A (V with 2.86±2.30 and As with 104.6±147.9) to Zone C (V with 0.73±0.72 and As with 73.8±90.8). For study subjects, urinary V and As levels were decreased by 0.09 and 1.17 μg/g-creatinine, respectively, with 1 km away from the emission source of the petrochemical complex, and urinary V levels were significantly elevated by 0.38 μg/g-creatinine with a 1 ng/m3 increase in estimated ambient V concentrations at their addresses. Our study concludes a distance-to-source gradient in V and As exposures exists for residents living near a petrochemical complex with oil refineries and coal-fired power plants and two-stage dispersion model can predict such a trend for V when inhalation is the major exposure route, but not for As that exposure may be from multiple sources and exposure routes.

Using pollution roses to assess sulfur dioxide impacts in a township downwind of a petrochemical complex

This study used pollution roses to assess sulfur dioxide (SO2) pollution in a township downwind of a large petrochemical complex based on data collected from a single air quality monitoring station. The pollution roses summarized hourly SO2 concentrations at the Taishi air quality monitoring station, located approximately 7.8–13.0 km south of the No. 6 Naphtha Cracking Complex in Taiwan, according to 36 sectors of wind direction during the preoperational period (1995–1999) and two postoperational periods (2000–2004 and 2005–2009). The 99th percentile of hourly SO2 concentrations 350˚ downwind from the complex increased from 28.9 ppb in the preoperational period to 86.2–324.2 ppb in the two postoperational periods. Downwind SO2 concentrations were particularly high during 2005–2009 at wind speeds of 6–8 m/sec. Hourly SO2 levels exceeded the U.S. Environmental Protection Agency (EPA) health-based standard of 75 ppb only in the postoperational periods, with 65 exceedances from 0–10˚ and 330–350˚ downwind directions during 2001–2009. This study concluded that pollution roses based on a single monitoring station can be used to investigate source contributions to air pollution surrounding industrial complexes, and that it is useful to combine such directional methods with analyses of how pollution varies between different wind speeds, times of day, and periods of industrial development. Implications: The pollution roses summarize SO2 concentrations by wind direction and to investigate source contribution to air quality. Percentile statistics can catch pollution episodes occurring in a very short time at specific wind directions and speeds. The downwind areas have already exceeded regulated 1-hr SO2 standard since the operation of the complex.

Metabolic profiling of residents in the vicinity of a petrochemical complex

No previous studies have simultaneously measured the biomarkers of environmental exposure and metabolome perturbation in residents affected by industrial pollutants. This study aimed to investigate the metabolic effects of environmental pollutants such as vanadium and polycyclic aromatic hydrocarbons (PAHs) on residents in the vicinity of a petrochemical complex. The study subjects were 160 residents, including 80 high-exposure subjects exposed to high levels of vanadium and PAHs and 80 age- and gender-matched low-exposure subjects living within a 40-km radius of a petrochemical complex. The exposure biomarkers vanadium and 1-hydroxypyrene and four oxidative/nitrosative stress biomarkers were measured in these subjects. Plasma samples from the study subjects were also analyzed using (1)H NMR spectroscopy for metabolic profiling. The results showed that the urinary levels of vanadium and 1-hydroxypyrene in the high-exposure subjects were 40- and 20-fold higher, respectively, than those in the low-exposure subjects. Higher urinary levels of stress biomarkers, including 8-OHdG, HNE-MA, 8-isoPF2α, and 8-NO2Gua, were also observed among the high-exposure subjects compared with the low-exposure subjects. Partial least squares discriminant analysis of the plasma metabolome demonstrated a clear separation between the high- and low-exposure subjects; the intensities of amino acids and carbohydrate metabolites were lower in the high-exposure subjects compared with the low-exposure subjects. The exposure to vanadium and PAHs may cause a reduction in the levels of amino acids and carbohydrates by elevating PPAR and insulin signaling, as well as oxidative/nitrosative stress.

Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper

BACKGROUND/PURPOSE Heavy metal pollution in farm soils is a problem in some parts of Taiwan. Copper can be a factor associated with increased disease activities of rheumatoid arthritis (RA). Thus, the aim of this study was to investigate whether copper pollution in farm soils is associated with worsened RA. METHODS Clinical parameters from 122 RA patients were collected from a medical center in central Taiwan. Levels of heavy metals in the blood were measured using inductively coupled plasma mass spectrometry. Levels of copper in farm soils were retrieved from a national survey. These data were analyzed to find the factors related to RA disease activities. RESULTS RA patients living where farm soils contained high levels of copper had increased white blood cell counts, erythrocyte sedimentation rate, and disease activity score 28, compared with patients living where copper levels were low. Among the nine types of heavy metal measured in the study, blood levels of copper and nickel correlated with erythrocyte sedimentation rate. CONCLUSION Our cross-sectional data suggest a correlation between RA disease activity and the level of copper at township farm soils samples. Further longitudinal studies using more rigorous methodologies are warranted to examine whether this correlation is causal.

Increased cancers among residents living in the neighborhood of a petrochemical complex: A 12-year retrospective cohort study

This study investigates whether cancers are increased for residents living in the vicinity of a petrochemical complex with coal power plants and refineries. We recruited a residential cohort of 2388 long-term residents aged above 35 years in 2009-2012 who lived within a 40 km radius of the complex. We measured their internal exposure biomarkers of urinary carcinogenic metals and retrospectively compared cancer incidences between those who lived fewer than 10 km from the complex (high exposure, HE) and those who lived more than 10 km from the complex (low exposure, LE). Residents had lived in their respective areas for 12 years, since the complex began operating in mid-1999. This included two periods of operation: 0-9 years and 10-12 years. Crude cumulative incident rates (CIRs) of all cancers were calculated for new cancer cases (ICD-9: 140-165, 170-176, 179-208) recorded in the Taiwan Health Insurance Database over total person-years at risk in each study period. Poisson regression was applied to estimate relative risks for the CIRs of all cancers between HE and LE areas during the 10-12 years since the beginning of the complexs operation, adjusting for age, gender, body mass index, smoking, hepatitis C, and occupational exposure. We found that our study subjects in HE areas had higher urinary carcinogenic metal levels, including As, Cd, Hg, Pb, and V, and higher prevalence rates of hepatitis C than those in LE areas. After the complex had been operating for 10-12 years, SIRs per 1000 person-years for all cancers in HE and LE areas were 4.44 vs. 2.48 for all subjects, 15.2 vs. 4.86 for elder subjects aged above 60 years, and 2.94 vs. 2.71 for female subjects. Correspondingly, the adjusted relative risks of CIRs for all cancers between HE and LE areas were 1.29 (95% CI: 0.99-1.68) for all subjects, 1.52 (1.04-2.22) for elder subjects, 1.41 (1.00-1.97) for female subjects, and 1.91 (1.15-3.19) for female elderly subjects. We conclude that elder and female residents living within 10 km of a petrochemical complex had higher carcinogenic exposure and cancers than those living farther away from the complex after the complex had been operating for 10 years.

Increased cancer incidence of Changhua residents living in Taisi Village north to the No. 6 Naphtha Cracking Complex

BACKGROUND/PURPOSE Cancer risks of residents living north to the No. 6 Naphtha Cracking Complex has not been studied before. METHODS Our study subjects were recruited in 2014-16 from three zones north to the No. 6 Naphtha Cracking Complex, which included 229 participants from the Taisi Village (average 5.5 km from the complex), 1333 participants from the other 14 villages in Dacheng Township (9.2 km), and 372 participants from the Zhutang Township (19.9 km). Their occurrence of cancer in years-post-complex-operation (YPO) was defined by having a new cancer recorded (ICD-9: 140-208) in National Health Insurance Research Database since 1999. Poisson regression was conducted to compare incidence rate ratio among three zones in 10-16 YPO. RESULTS We found that all-cause cancer incidence of 10-16 YPO (per 1,000 person-years) in Taisi Village (8.44) was higher than that in Dacheng (3.42) and Zhutang (2.72). Taisi residents had significantly higher concentrations of V, Cr, Mn, Ni, Cu, As, Cd, and Tl than Dacheng and Zhutang residents. The all-cause cancer incidence rate ratio between 10-16 and 0-9 YPO was 8.44 for Taisi residents. All-cause cancer incidence rate of Taisi residents was 2.55 times higher than Dacheng residents (95% CI: 1.89-3.45) and 2.43 times higher than Zhutang residents (95% CI: 1.54-3.84) in 10-16 YPO. CONCLUSION We conclude that all-cause cancer risk was significantly increased for Taisi residents living near the No. 6 Naphtha Cracking Complex for 10-16 years after the complex began operating.