Hui-Yi Liao

Six-month follow-up study of health markers of nanomaterials among workers handling engineered nanomaterials

Abstract The aim of this study was to identify the health hazards and possible exposure surveillance markers of workers exposed to nanoparticles during manufacturing and application in comparison to a group of unexposed workers. For this longitudinal study, we recruited 158 nanomaterial-handling workers and 104 non-exposed workers from 14 manufacturing plants in Taiwan (baseline). Among them, 124 nanomaterial-handling workers and 77 unexposed workers were monitored 6 months later. We investigated pulmonary and cardiovascular disease markers, inflammation and oxidative stress markers, antioxidant enzymes and genotoxicity markers. Antioxidant enzymes (superoxide dismutase, glutathione peroxidase) and cardiovascular markers (vascular cell adhesion molecule, paraoxonase) were significantly associated with nanomaterial-handling during the 6-month follow-up period. In addition, the small airway damage marker (Clara cell protein 16) and lung function test parameters were also significantly associated with handling nanomaterials. The study markers and lung function tests are possible markers that could be useful for surveillance of nanomaterial-handling workers.

Effect of Nanoparticles Exposure on Fractional Exhaled Nitric Oxide (FENO) in Workers Exposed to Nanomaterials

Fractional exhaled nitric oxide (FENO) measurement is a useful diagnostic test of airway inflammation. However, there have been few studies of FENO in workers exposed to nanomaterials. The purpose of this study was to examine the effect of nanoparticle (NP) exposure on FENO and to assess whether the FENO is increased in workers exposed to nanomaterials (NM). In this study, both exposed workers and non-exposed controls were recruited from NM handling plants in Taiwan. A total of 437 subjects (exposed group = 241, non-exposed group = 196) completed the FENO and spirometric measurements from 2009–2011. The authors used a control-banding (CB) matrix to categorize the risk level of each participant. In a multivariate linear regression analysis, this study found a significant association between risk level 2 of NP exposure and FENO. Furthermore, asthma, allergic rhinitis, peak expiratory flow rate (PEFR), and NF-κB were also significantly associated with FENO. When the multivariate logistic regression model was adjusted for confounders, nano-TiO2 in all of the NM exposed categories had a significantly increased risk in FENO > 35 ppb. This study found associations between the risk level of NP exposure and FENO (particularly noteworthy for Nano-TiO2). Monitoring FENO in the lung could open up a window into the role nitric oxide (NO) may play in pathogenesis.

Sneezing and Allergic Dermatitis were Increased in Engineered Nanomaterial Handling Workers

The aim of this study was to survey the work-relatedness of symptoms and diseases among engineered nanomaterials handling workers by questionnaire. A total of 258 exposed workers and 200 comparison workers were recruited from 14 nanomaterials handling factories in Taiwan. In addition to current disease status (prevalence), we classified the diseases worsened by employment (worsened by work). The control banding nanotool risk level matrix was adopted to categorize the severity and probability of nanomaterial exposure. The work-relatedness of symptoms was also self-reported in the questionnaire. The only symptom identified as significantly work-related was sneezing (5.88% in risk level 2 and 7.91% in risk level 1 vs. 2.00% in controls, p=0.04). The prevalences of work-related dry cough (p=0.06) and productive cough (p=0.09) in nanomaterials handling workers were also higher than those in controls. The only disease significantly worsened by work was allergic dermatitis (4.20% in risk level 2, 0% in risk level 1 vs. 0.50% in control, p=0.01). The incidence of angina in nanoworkers was also higher than in controls (p=0.06). In addition to allergic diseases, cardiopulmonary symptoms such as cough and angina may be used as screening tools for medical surveillance of people handling engineered nanomaterials.

Global DNA methylation and oxidative stress biomarkers in workers exposed to metal oxide nanoparticles

This is the first study to assess global methylation, oxidative DNA damage, and lipid peroxidation in workers with occupational exposure to metal oxide nanomaterials (NMs). Urinary and white blood cell (WBC) 8-hydroxydeoxyguanosine (8-OHdG), and exhaled breath condensate (EBC) 8-isoprostane were measured as oxidative stress biomarkers. WBC global methylation was measured as an epigenetic alteration. Exposure to TiO2, SiO2, and indium tin oxide (ITO) resulted in significantly higher oxidative biomarkers such as urinary 8-OHdG and EBC 8-isoprostane. However, significantly higher WBC 8-OHdG and lower global methylation were only observed in ITO handling workers. Significant positive correlations were noted between WBC and urinary 8-OHdG (Spearman correlation r=0.256, p=0.003). Furthermore, a significant negative correlation was found between WBC 8-OHdG and global methylation (r=-0.272, p=0.002). These results suggest that exposure to metal oxide NMs may lead to global methylation, DNA oxidative damage, and lipid peroxidation.

Increased levels of oxidative stress biomarkers in metal oxides nanomaterial-handling workers.

Abstract This study assessed oxidatively damaged DNA and antioxidant enzyme activity in workers occupational exposure to metal oxides nanomaterials. Exposure to TiO2, SiO2, and ITO resulted in significant lower antioxidant enzymes (glutathione peroxidase and superoxide dismutase) and higher oxidative biomarkers 8-hydroxydeoxyguanosine (8-oxodG) than comparison workers. Statistically significant correlations were noted between plasma and urine 8-oxodG, between white blood cells (WBC) and urine 8-oxodG, and between WBC and plasma 8-oxodG. In addition, there were significant negative correlations between WBC 8-oxodG and SOD and between urinary 8-oxodG and GPx levels. The results showed that urinary 8-oxodG may be considered to be better biomarker.

0061 Epidemiological study of lung inflammation and oxidative damage in indium tin oxide workers

Objectives Indium Tin Oxide (ITO) is widely used in many kinds of touch panels nowadays. Workers could expose to ITO particles from sintering granules, splashing, pulverisation, cutting, and grinding processes. This study aimed to assess the relationship between ITO exposure and lung inflammation and oxidative damage in ITO workers. Method We recruited 148 exposed workers and 38 control workers from ITO powder process, recycling and ITO target manufacturing plants in Taiwan. Indium in serum (S-In) and urine (U-In) was determined as biomarkers of exposure. Exposed group was further divided as high (S-In > 3 µg/L and low exposed groups (S-In £3 µg/L). Urinary and plasma 8-hydroxy-2-deoxyguanosine (8-OHdG), serum Clara cell protein (CC16), and fractional exhaled nitric oxide (FENO) were measured as biomarkers of oxidative damage and pulmonary inflammation, respectively. Results The geometric mean air concentrations of indium were 0.0041 ± 2.49 mg/m3 by area sampling and 0.017 ± 5.20 mg/m3 by personal sampling. The mean S-In level and U-In level in high exposed group were 8.01 ppb and 3.45 ppb, respectively. The mean levels of S-In and U-In in high exposed group were significantly higher than those of low exposed group. The mean levels of serum CC16 and urinary 8-OHdG in high exposed group were also significantly higher than those of low exposed groups. After adjusting potential confounders, dose-response gradients were found between S-In and CC16 (p = 0.020) and between S-In and urinary 8-OHdG (p = 0.027), respectively. Conclusions We concluded that indium particles exposure may induce lung inflammation and DNA oxidative damage.

Usefulness of overnight pulse oximeter as the sleep assessment tool to assess the 6-year risk of road traffic collision: evidence from the Taiwan Bus Driver Cohort Study

Background In order to support health service organizations in arranging a system for prevention of road traffic collisions (RTC), it is important to study the usefulness of sleep assessment tools. A cohort study was used to evaluate the effectiveness of subjective and objective sleep assessment tools to assess for the 6-year risk of both first RTC event only and recurrent RTC events. Methods The Taiwan Bus Driver Cohort Study (TBDCS) recruited 1650 professional drivers from a large bus company in Taiwan in 2005. The subjects were interviewed in person, completed the sleep assessment questionnaires and had an overnight pulse oximeter survey. Moreover, this cohort of drivers was linked to the National Traffic Accident Database (NTAD) and researchers found 139 new RTC events from 2005 to 2010. Primary outcomes were traffic collisions from NTAD, nocturnal oxygen desaturation index (ODI) from pulse oximeter, Pittsburg sleeping quality score, Epworth daytime sleepiness score, Snore Outcomes Survey score and working patterns from questionnaires. A Cox proportional hazards model and an extended Cox regression model for repeated events were performed to estimate the hazard ratio for RTC. Results The RTC drivers had increased ODI4 levels (5.77 ± 4.72 vs 4.99 ± 6.68 events/h; P  = 0.008) and ODI3 levels (8.68 ± 6.79 vs 7.42 ± 7.94 events/h; P  = 0.007) in comparison with non-RTC drivers. These results were consistent regardless of whether ODI was evaluated as a continuous or a categorical variable. ODI4 and ODI3 levels increased the 6-year RTC risks among professional drivers even after adjusting for age, education, history of cardiovascular disease, caffeine intake, sleeping pills used, bus driving experience and shift modes. Moreover, there was an increased trend for ODI between the stratification of the number of RTCs in comparison with the non-RTC group. In the extended Cox regression models for repeated RTC events with the Anderson and Gill intensity model and Prentice-Williams-Petersen model, measurement of ODI increased hazards of the subsequent RTC events. Conclusion This study showed that an increase in the 6-year risk of RTC was associated with objective measurement of ODI for a sign of sleep-disordered breathing (SDB), but was not associated with self-reported sleeping quality or daytime sleepiness. Therefore, the overnight pulse oximeter is an effective sleep assessment tool for assessing the risk of RTC. Further research should be conducted regarding measures to prevent against SDB among professional drivers.

185 Four-year follow-up study of health hazards among workers handling engineered nanomaterials

Objectives The aim of this study was to investigate the health hazards in workers exposed to nanoparticles during manufacturing and application of nanomaterials. Methods For this 4-year longitudinal study, we recruited 283 nanomaterial-handling workers and 213 non-exposed control workers from 15 manufacturing plants in Taiwan. Follow-up measurements were done at 6, 12, 24, 36, and 48 months. Among them, 206 nanomaterial-handling workers and 140 unexposed workers were followed up for more than twice. For each participant, a self-administered questionnaire was distributed to collect work history and personal habits after informed consent. Since there was a lack of equipment for personal sampling and summary index for mixed exposure, we adopted the control banding nanotool risk level matrix to categorise the risk level for each participant. Blood, urine and exhaled breath condensate (EBC) were collected to examine markers of cardiopulmonary injuries, lung and systemic inflammation, oxidative stress, and genotoxicity. Generalised Estimating Equation (GEE) model was applied to analyse these repeated measurements. Results There were 108 workers in risk level 1, and 91 workers in risk level 2, and 7 in risk level 3. Although depression of antioxidant enzymes and increase of cardiovascular markers were found in the cross-sectional and early follow-up study, no significant difference was revealed between exposed workers and controls in the changes of biomarkers in this 4-year longitudinal study. The non-significant markers included lung injuries markers, cardiovascular disease markers, heart rate variability (HRV), inflammation markers, oxidative stress and lipid peroxidation markers, comet assay, pulmonary function test, and neurobehavioral function test. Conclusions This longitudinal study suggests that there was no evidence of health hazards among nanomaterials handling workers. The preliminary survey of nanoparticle exposure level in the workplace was quite low. Such exposure level was not high enough to induce systemic health effects in nanoworkers.

0015 The significance and application of salivary biomarkers of stress, cortisol awakening response, in occupational psychology

Objectives This study aims to investigate the correlation between cortisol awakening response (CAR) and sleep quality, mental stress, fatigue, workload and health status in a period of 28 days. Materials and Methods A total of 28 subjects participated in this study. The saliva was collected by cotton-based Salivette at awakening, 30 min after awakening, and bedtime for a period of 4 weeks. The saliva cortisol was measured by LC-MS-MS. Four parameters were used to present CAR, 30 min post-awakening cortisol, CAR denoting rise from awakening to 30 min post-awakening (slope), AUC for CAR, and full AUC (= AUC for CAR + AUC for late decline). The outcomes variables included sleep quality measured by Pittsburgh sleep quality index (PSQI) questionnaire, and self-rated workload, mental stress, fatigue, and health score for each day. Results CAR were correlated with fatigue score and stress score, but not with sleep quality (PSQI), workload and health score. Regarding parameters of CAR, AUC for CAR and full AUC are better than CAR slope and 30 min post-awakening to correlate with fatigue and stress. AUC for CAR and full AUC may represent the degree of mental stress and fatigue in the previous day. Discussion We have found single day CAR and 4 week CAR were correlated with mental stress. But how to design a study to elaborate whether CAR can predict the occurrence of cardiovascular diseases (Karoshi) needs further to be solved. Solution for variation of CAR day-to-day and pick-up the day of most stressful are urgent.

0016 Association between pm 2.5 exposure and lipid peroxidation was confirm by repeated measurements longitudinal study with a proper interaction term

Objective to examine the relations between personal exposure to PM2.5 and inflammatory and oxidation markers. Methods We conducted a panel study with three sampling time points (baseline, two months follow-up, and four months follow-up) among 68 healthy non-smoking young adults from 3 different areas (Area A [residential and commercial area], Area B [industrial area] and Area C [scientific park]). Results the average PM2.5 concentrations was 37.3 µg/m3 for personal sampling and 31.6 µg/m3 for nearest air quality monitoring station. Among them, the personal PM2.5 concentrations in B zone was significant highest than A and C zone. For the longitudinal study, we used linear Mixed-model was as follows: Yit =α0 + α1Timeit + β0Zkm + β1ZkmTimeit +γXi0 + εkm + εi + εit, where Zkm used four PM2.5 counting methods: (1) personal PM2.5 concentrations; (2) average personal PM2.5 concentrations at three sampling times; (3) average personal PM2.5 concentrations with area under the curve during 120 days; (4) average personal PM2.5 concentrations during 120 days (>35 µg/m3 vs.≤35µg/m3 ). After adjustment for age, gender, smoking habits, sampling zones, height, weight, temperature, and relative humidity, we found that the Urinary N7-MeG/creatinine was significantly decreased with PM2.5 exposure concentrations, and Urinary HEL/creatinine was significantly increased with PM2.5 exposure concentrations by time, regardless of which PM2.5 exposure models were used. While we only used average personal PM2.5 concentrations at three sampling times, we found that SDNN and GPx were significantly increased with PM2.5 exposure concentrations by time.