Air quality health index (AQHI) based on multiple air pollutants and mortality risks in Taiwan: Construction and validation.

The currently used air quality index (AQI) is not able to capture the additive effects of air pollution on health risks and reflect non-threshold concentration-response relationships, which has been criticized. We proposed the air quality health index (AQHI) based on daily air pollution-mortality associations, and compared its validity in predicting daily mortality and morbidity risks with the existing AQI. We examined the excess risk (ER) of daily elderly (≥65-year-old) mortality associated with 6 air pollutants (PM2.5, PM10, SO2, CO, NO2, and O3) in 72 townships across Taiwan from 2006 to 2014 by performing a time-series analysis using a Poisson regression model. Random effect meta-analysis was used to pool the township-specified ER for each air pollutant in the overall and seasonal scenarios. The integrated ERs for mortality were calculated and used to construct the AQHI. The association of the AQHI with daily mortality and morbidity were compared by calculating the percentage change per interquartile range (IQR) increase in the indices. The magnitude of the ER on the concentration-response curve was used to evaluate the performance of the AQHI and AQI, regarding specific health outcomes. Sensitivity analysis was conducted using coefficients from the single- and two-pollutant models. The coefficients of PM2.5, NO2, SO2, and O3 associated with mortality were included to form the overall and season-specific AQHI. An IQR increase in the overall AQHI at lag 0 was associated with 1.90%, 2.96%, and 2.68% increases in mortality, asthma, and respiratory outpatient visits, respectively. The AQHI had higher ERs for mortality and morbidity on the validity examinations than the current AQI. The AQHI, which captures the combined effects of air pollution, can serve as a health risk communication tool to the public.

Exposure Characteristics and Cumulative Risk Assessment for Phthalates in Children Living near a Petrochemical Complex.

BACKGROUND: School-aged children living near plastics-producing factories may have higher risk of exposure to phthalates released during the manufacturing processes. OBJECTIVES: We aimed to investigate the urinary concentrations of phthalate metabolites in school-aged children living near a petrochemical complex and estimate the cumulative risk of phthalate exposure. METHODS: We used a well-established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-aged children (6-13 years old) living near polyvinyl chloride (PVC) and vinyl chloride monomer (VCM) factories in central Taiwan from October 2013 to September 2014. A total of 257 children were included from five elementary schools: Syu-Cuo Branch (n = 58, school A, ~0.9 km), Feng-An (n = 40, school B, ~2.7 km), Ciao-Tou (n = 58, school C, ~5.5 km), Mai-Liao (n = 37, school D, ~6.9 km), and Lung-Feng (n = 57, school E, ~8.6 km). We analyzed 11 metabolites of seven phthalates (including di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP)) in urine. Daily intakes (DIs) were compared with acceptable intake levels to calculate the hazard quotient (HQ) for individual phthalates, and the cumulative risk for each child was assessed using a hazard index (HI), which was the sum of the the individual HQs. RESULTS: The geometric mean and proportion of participants with HIs exceeding one for hepatic (HIhep) and reproductive (HIrep) effects were 0.33 (13.2%) and 0.24 (7.8%), respectively. The major contributors to phthalate exposure risk were DEHP, di-iso-butyl phthalate (DiBP) and DnBP in all children. Moreover, we observed a U shaped distribution of DEHP exposure by school distance from the PVC and VCM factories (school A: 7.48 µg/kg/day and school E: 80.44 µg/kg/day). This may be due to emissions (closest) and and being located downwind of PVC scrap incineration (farthest). CONCLUSIONS: Our findings suggest that children living near a petrochemical complex were at a greater risk of phthalate exposure than normal school-aged children and that phthalate exposure was mainly attributed to DEHP, DiBP and DnBP. In addition, inhalation may have been a risk factor for people living near to PVC and VCM factories.

Vinculin phosphorylation impairs vascular endothelial junctions promoting atherosclerosis.

BACKGROUND AND AIMS: Atherosclerosis preferentially develops in arterial branches and curvatures where vascular endothelium is exposed to disturbed flow. In this study, the effects of disturbed flow on the regulation of vascular endothelial phosphoproteins and their contribution to therapeutic application in atherogenesis were elucidated. METHODS: Porcine models, large-scale phosphoproteomics, transgenic mice, and clinical specimens were used to discover novel site-specific phosphorylation alterations induced by disturbed flow in endothelial cells (ECs). RESULTS: A large-scale phosphoproteomics analysis of native endothelium from disturbed (athero-susceptible) vs. pulsatile flow (athero-resistant) regions of porcine aortas led to the identification of a novel atherosclerosis-related phosphoprotein vinculin (VCL) with disturbed flow-induced phosphorylation at serine 721 (VCLS721p). The induction of VCLS721p was mediated by G-protein-coupled receptor kinase 2 (GRK2)S29p and resulted in an inactive form of VCL with a closed conformation, leading to the VE-cadherin/catenin complex disruption to enhance endothelial permeability and atherogenesis. The generation of novel apolipoprotein E-deficient (ApoE-/-) mice overexpressing S721-non-phosphorylatable VCL mutant in ECs confirmed the critical role of VCLS721p in promoting atherosclerosis. The administration of a GRK2 inhibitor to ApoE-/- mice suppressed plaque formation by inhibiting endothelial VCLS721p. Studies on clinical specimens from patients with coronary artery disease (CAD) revealed that endothelial VCLS721p is a critical clinicopathological biomarker for atherosclerosis progression and that serum VCLS721p level is a promising biomarker for CAD diagnosis. CONCLUSIONS: The findings of this study indicate that endothelial VCLS721p is a valuable hemodynamic-based target for clinical assessment and treatment of vascular disorders resulting from atherosclerosis.

Ethnobotanical Survey on Skin Whitening Prescriptions of Traditional Chinese Medicine in Taiwan.

The increasing interest and demand for skin whitening products globally, particularly in Asia, have necessitated rapid advances in research on skin whitening products used in traditional Chinese medicine (TCM). Herein, we investigated 74 skin whitening prescriptions sold in TCM pharmacies in Taiwan. Commonly used medicinal materials were defined as those with a relative frequency of citation (RFC) > 0.2 and their characteristics were evaluated. Correlation analysis of commonly used medicinal materials was carried out to identify the core component of the medicinal materials. Of the purchased 74 skin whitening prescriptions, 36 were oral prescriptions, 37 were external prescriptions, and one prescription could be used as an oral or external prescription. After analysis, 90 traditional Chinese medicinal materials were obtained. The Apiaceae (10%; 13%) and Leguminosae (9%; 11%) were the main sources of oral and external medicinal materials, respectively. Oral skin whitening prescriptions were found to be mostly warm (46%) and sweet (53%), while external skin whitening prescriptions included cold (43%) and bitter (29%) medicinal materials. Additionally, mainly tonifying and replenishing effects of the materials were noted. Pharmacological analysis indicated that these medicinal materials may promote wound healing, treat inflammatory skin diseases, or anti-hyperpigmentation. According to the Spearman correlation analysis on interactions among medicinal materials with an RFC > 0.2 in the oral skin whitening prescriptions, Paeonia lactiflora Pall. (white) and Atractylodes macrocephala Koidz. showed the highest correlation (confidence score = 0.93), followed by Ziziphus jujuba Mill. (red) and Astragalus propinquus Schischkin (confidence score = 0.91). Seven medicinal materials in external skin whitening prescriptions with an RFC > 0.2, were classified as Taiwan qi bái sàn (an herbal preparation), including Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav., Wolfiporia extensa (Peck) Ginns, Bletilla striata (Thunb.) Rchb. f., Atractylodes macrocephala Koidz., Ampelopsis japonica (Thunb.) Makino, Paeonia lactiflora Pall. (white), and Bombyx mori Linnaeus. Skin whitening prescriptions included multiple traditional Chinese medicinal materials. Despite the long history of use, there is a lack of studies concerning skin whitening products, possibly due to the complex composition of traditional Chinese medicine. Further studies are required to assess the efficacy and safety of these traditional Chinese medicinal materials for inclusion in effective, safe, and functional pharmacological products.

Risk of hepatitis C virus infection in injecting and noninjecting drug users receiving opioid substitution therapy.

BACKGROUND: Hepatitis C virus (HCV) is the most common viral infection among illicit drug users in the world. Although intervention of needle and syringe program and opioid substitution therapy had engaged to prevent HCV infection, the prevalence of HCV infection does not seem to decline. The aim of this study was to estimate the risk of HCV infection in injecting drug users (IDUs) and noninjecting drug users (NIDUs) receiving opioid substitution therapy. METHODS: We recruited 1179 heroin-dependent patients (age: 20-66 years) under opioid substitution therapy from 2012 to 2015 in a Psychiatric Center, Southern Taiwan. The data of HCV, hepatitis B virus and HIV infection and liver biochemical examination were obtained. We used multivariate logistic regression analysis to predict the risk of HCV infection. RESULTS: There were 93.1% of IDUs and 68.1% of NIDUs positive for HCV infection. In IDUs, HIV infection, age of heroin initiation, duration and dose of heroin use, frequency of detoxification, and number of criminal conviction were significantly associated with HCV infection. In NIDUs, snort/sniff heroin exhibited a significantly increased risk of HCV infection. Intravenous injecting (odds ratio [OR] = 23.10, 95% CI = 8.04-66.40, p < 0.001), intravenous injecting combined snort/sniff (OR = 12.95, 95% CI = 3.90-42.97, p < 0.001), and snort/sniff (OR = 4.14, 95% CI = 1.30-13.18, p = 0.016) were significantly associated with increased risk of HCV infection compared with smoking. The trend was significant (p for trend <0.001). CONCLUSION: In Taiwan, IDUs had harmful characteristics compared with NIDUs and both had extremely high prevalence of HCV infection. We provided evidence that snort/sniff is a possible way of leak in HCV infection despite needle-syringes supplement program been provided. Opioid substitution therapy program should include HCV assessment and treatment in the new direct-acting antiviral therapy era.

Ethnobotanical Survey of Natural Galactagogues Prescribed in Traditional Chinese Medicine Pharmacies in Taiwan.

Natural medicinal materials have been used to promote breast milk secretion. Here, we investigated the natural medicinal materials prescribed in traditional Chinese medicine (TCM) pharmacies across Taiwan to induce lactation. We collected medicinal materials from 87 TCM pharmacies, identified them in the prescriptions, and analyzed their drug contents. We examined their botanical origins, biological classifications, traditional usage, and modern pharmacological properties. We used the TCM Inheritance Support System to identify core medicinal materials in galactogenous prescriptions. We collected 81 medicinal materials from 90 galactogenous prescriptions. Leguminosae accounted for 12%, whereas Apiaceae accounted for 7% of all materials examined. The primary medicinal plant parts used were roots and seeds. Nineteen frequently used medicinal materials had a relative frequency of citation of greater than or equal to 0.2. According to their efficacy, 58% were warm, 54% were sweet, and 63% were tonifying; 74% of the frequently used medicinal materials have been showed efficacy against breast cancer. The primary core medicinal material was Angelica sinensis (Oliv.) Diels, whereas the secondary core medicinal materials were Tetrapanax papyrifer (Hook.) K. Koch and Hedysarum polybotrys Hand.-Mazz. Most galactogenous prescriptions consisted of multiple materials from Leguminosae and Apiaceae. The mechanisms underlying galactogenous efficacy warrant further investigations.

The effects of fine and coarse particulate matter on lung function among the elderly.

Impaired lung function is associated with morbidity and mortality in the elderly. However, there is a paucity of data regarding the long-term effects of particulate matter (PM) on lung function among the elderly. This study evaluated the exposure-response relationship between ambient PM and different lung function indices among the elderly in Taiwan. A cross-sectional survey of individuals aged ≥65 years was conducted in Taiwan from October 2015 to September 2016. Those who attended the annual health examination for the elderly in five hospitals of varying background PM concentrations were enrolled. The long-term (2015 annual mean concentration) exposure to air pollution was estimated by the Kriging method at the residence of each subject. The association between ambient PM exposure and lung function was evaluated by linear regression modeling, with adjustments for age, sex, height, weight, educational attainment, presence of asthma or chronic obstructive pulmonary disease, smoking status, season, and co-pollutants. There were 1241 subjects (mean age, 70.5 years). The mean residential PM2.5 and PM2.5-10 in 2015 was 26.02 and 18.01 µg/m3, respectively. After adjustments for confounders and co-pollutants, the FVC decrease was best associated with fine particles (PM2.5), whereas the FEV1, FEF25-75%, FEF25% and FEF50% decreases were best associated with coarse particles (PM2.5-10). An IQR (10 µg/m3) increase in PM2.5 decreased FVC by 106.38 ml (4.47%), while an IQR (7.29 µg/m3) increase in PM2.5-10 decreased FEV1 and FEF25-75% by 91.23 ml (4.85%) and 104.44 ml/s (5.58%), respectively. Among the Taiwanese elderly, long-term PM2.5 exposure mainly decreases the vital capacity of lung function. Moreover, PM2.5-10 has a stronger negative effect on the function of conductive airways than PM2.5.

Effects of PM2.5 on Skeletal Muscle Mass and Body Fat Mass of the Elderly in Taipei, Taiwan.

Loss of skeletal muscle mass is common with aging and can cause morbidity and mortality in the elderly. The effects of particulate air pollution on skeletal muscle mass is not known. The study aims to assess the chronic effects of ambient fine particulates (PM2.5) on the body composition of the elderly. From October 2015 to November 2016, a cross-sectional survey on 530 elderly (age > = 65 years) was conducted in the Taipei Basin, Taiwan. The body composition was measured by bioelectrical impedance analysis (InBody 120). One year exposure to air pollution was estimated using the Kriging method at the participant's residence. Multiple linear regression analysis, after adjustments for demographics and co-pollutants, was used to examine the effects of PM2.5 on body composition indices and force of handgrip. Changes in body composition for an interquartile (1.4 µm/m3) increase in PM2.5 concentration included a 0.4 kg (95% confidence interval (CI): -0.31, -0.58; p < 0.0001) decrease in skeletal muscle mass (2.0%) and a 0.7 kg (95% CI: 0.47, 0.91; p < 0.0001) increase in body fat mass (3.6%). While PM2.5 reduced fat free mass in the upper extremities and trunk, but not in the lower extremities, it increased body fat mass in the three parts. There was no significant effect of PM2.5 on handgrip force. Higher physical activity (versus lower than median) was associated with less detrimental effect of PM2.5 on skeletal muscle mass and body fat mass (p values for interaction term: 0.009 and 0.013, respectively). Long-term PM2.5 exposure is associated with decreased skeletal muscle mass and increased body fat mass in the elderly, which can be ameliorated by physical activity.

Urinary thiodiglycolic acid is associated with increased risk of non-alcoholic fatty liver disease in children living near a petrochemical complex.

BACKGROUND: Occupational and experimental studies have revealed that high vinyl chloride monomer (VCM) exposure is associated with non-alcoholic fatty liver disease (NAFLD). Epidemiological study reported that children living near a petrochemical complex have elevated exposure levels of urinary thiodiglycolic acid (TDGA), a potential VCM biomarker. However, no studies on the association of urinary TDGA exposure with NAFLD in children are available. AIM: To assess the association of pediatric NAFLD with urinary TDGA exposure in school-aged children living near a petrochemical complex. MATERIALS AND METHODS: In total, 261 school-aged children (aged 6-13 years) living near a petrochemical complex were recruited during October 2013 to September 2014. First morning spot urine was sampled for analyzing urinary TDGA through liquid chromatography-tandem mass spectrometry. Ultrasonography and serum alanine aminotransferase (ALT) were examined in each participant. NAFLD was diagnosed as recommended by the North American and European Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN). Risk for NAFLD with urinary TDGA exposure in children was evaluated using a multivariate logistic regression model. RESULTS: The percentage of children with NAFLDNASPGHAN and NAFLDESPGHAN were 9.6% and 11.5%, respectively. Median levels (µg/g creatinine) of urinary TDGA of children with NAFLDNASPGHAN (vs non-NAFLDNASPGHAN) and NAFLDESPGHAN (vs non-NAFLDESPGHAN) were 118.0 (vs 96.6) and 113.1 (vs 96.5), respectively. Participants in the highest urinary TDGA quartile (Q4: ≥160.0 µg/g creatinine) had a significantly increased risk (odds ratio [OR] = 4.95; 95% confidence interval [CI] = 1.15-21.38; P = 0.032) and dose-response trend (Ptrend = 0.045) for NAFLDNASPGHAN compared with those in the lowest urinary TDGA quartile (Q1: <35.4 µg/g creatinine) after adjustment for age, gender, BMI, triglycerides, HOMA-IR and distance of elementary schools from the petrochemical complex. Participants in the Q4 had borderline significantly increased risk (OR = 3.45; 95% CI = 0.89-13.42; P = 0.074) correlated with NAFLDESPGHAN compared with those in the Q1 after adjustment for confounders. CONCLUSION: Our findings support the hypothesis that children exposed to higher urinary TDGA levels significantly increased pediatric NAFLD risk. Serum ALT levels can be a useful predictor for screening children's NAFLD in field studies. Large and longitudinal studies are warranted to elucidate the association.

Impacts of hazardous metals and PAHs in fine and coarse particles with long-range transports in Taipei City.

This study assessed the impact on air quality and health risk by long-range transported (LRT) PM2.5-10- and PM2.5-bound metals and PAHs in Taipei City, Taiwan. Several methods with receptor aerosol measurements were used to quantify the effect of LRT. The hybrid single particle lagrangian integrated trajectory model (HYSPLIT) was used in conjunction with the potential source contribution function (PSCF) to distinguish the LRT aerosols. By using a general linear model (GLM) with a marginal mean and positive matrix fraction (PMF), this study also evaluated the annual increased level of LRT (AIRLRT) for each source contribution to the concentration and the resultant health risk of particle-bound metals and polycyclic aromatic hydrocarbons (PAHs). The LRT influenced fine-sized metals and PAHs rather than coarse-sized ones. We found that the level of PM2.5-bound toxic metals (Pb, Cd, and As) and PAHs (Benzo[a]pyrene and dibenzo[a,e]pyrene) could increase by 90% under the influence of LRT in 2014, while an AIRLRT value of 25% for the PM2.5 mass concentration was observed. Overall, the excess cancer risk (ECR) resulting from PM2.5-bound metal and PAH exposures was 6.40 × 10-5 in relation to coal combustions (20.7%), traffic-related emissions (59.7%) and re-suspended aerosols (19.6%). Among these contributors, LRT-related metals and PAHs in PM2.5 accounted for 51% of the total ECR.

Association between urinary thiodiglycolic acid level and hepatic function or fibrosis index in school-aged children living near a petrochemical complex.

The effect of exposure to vinyl chloride monomer (VCM) on susceptibility to hepatotoxicity in children is unknown, although experimental studies have demonstrated a significantly increased risk of hepatocellular carcinoma in rodents exposed to VCM in early life. Epidemiological studies have revealed a high prevalence of liver fibrosis and abnormal liver function in workers exposed to high VCM levels. We aimed to assess the association among urinary thiodiglycolic acid (TDGA) level, abnormal liver function, and hepatic fibrosis in school-aged children living near a petrochemical complex. A total of 303 school-aged (6-13 years) children within 10 km nearly a petrochemical complex was recruited in central Taiwan. First-morning urine and blood samples were collected from each subject, and urinary TDGA level was analyzed through liquid chromatography-tandem mass spectrometry. Liver function was determined by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Hepatic fibrosis was assessed using the AST to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). Risk of hepatotoxicity induced by TDGA exposure was estimated using multivariate logistic regression. The median (range, subclinically abnormal %) AST and ALT levels of all subjects were 26.0 (17.0-99.0, 25.7%) and 15.0 (7.0-211.0, 5.9%) IU/L, respectively. Children in the highest urinary TDGA quartile (≥160.0 µg/g creatinine) exhibited significantly elevated median AST levels compared with those in the lowest quartiles (<35.4 µg/g creatinine, p = 0.033). After adjustment for potential confounding factors, children in the highest quartiles (Q4) of TDGA level had significantly increased odds ratio (OR) of subclinically abnormal AST (OR = 3.86; 95% confidence interval: 1.54-9.67) compared with those in the lowest quartile. A dose-response trend (p = 0.004) was observed. Our findings support the hypothesis that elevated urinary TDGA level in children living near petrochemical complex is associated with susceptibility to hepatotoxicity.

Increased risk of phthalates exposure for recurrent pregnancy loss in reproductive-aged women.

Recurrent pregnancy loss (RPL) is the termination of pregnancies, usually before 20 weeks of gestation, and is defined as the loss of two or more pregnancies. In Taiwan, after 2011 di-2-ethylhexyl phthalate (DEHP) exposure episode, more reproductive-aged women still expose to high levels of DEHP and di-butyl phthalate (DBP) than have women of other age groups. Phthalates might be involved in the RPL pathogenesis. This study assessed the association of phthalate exposure with RPL risk in reproductive-aged Taiwanese women. This study recruited 103 patients diagnosed by a physician with RPL of unknown etiology and 76 controls from the Department of Obstetrics and Gynecology at a medical center in southern Taiwan between August 2013 and August 2017. Urine samples were analyzed for 11 phthalate metabolites through liquid chromatography-tandem mass spectrometry; subsequently, principal component analysis (PCA) and hierarchical clustering analysis were performed to determine the main sources of phthalate exposure. Finally, multivariate logistic regression was used to determine the RPL risk. The creatinine-unadjusted median levels of mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) in RPL/control were 9.8/5.3, 27.2/13.1, 11.4/8.1, and 12.9/9.5 ng/mL, respectively; furthermore, ΣDBPm and ΣDEHPm in RPL/control were 0.18/0.10 and 0.15/0.12 nmol/mL, respectively. PCA revealed three primary components of phthalate exposure: diethyl phthalates (DEP), DEHP, and DBP. Plastic food container use and medication were identified as the main phthalate exposure sources. After adjustment for potential confounding factors (urinary creatinine, age, age at menarche, education, and plastic food container use), we found that the urinary level of ΣDBPm was significantly associated with elevated risk for RPL (OR = 2.85, p = 0.045). Our findings supported the hypothesis that exposure to phthalates increases RPL risk. The development of a strategy to reduce phthalate exposure among reproductive-aged women should be emphasized.

Ambient VOCs in residential areas near a large-scale petrochemical complex: Spatiotemporal variation, source apportionment and health risk.

This study investigated ambient volatile organic compounds (VOCs) and assessed excess health risks for child, adult and elderly populations in a residential area near a large-scale petrochemical complex in central Taiwan. A total of 155 daily VOC samples were collected in canisters from nine sites in spring, summer and winter during 2013-2014. We used a positive matrix factorization (PMF) model incorporating a conditional probability function (CPF) to quantify the potential sources of VOCs with the influences of local source directions. We then evaluated the non-cancer and cancer risks of specific VOCs with probabilistic distributions by performing a Monte-Carlo simulation for the child, adult, and elderly populations. Most of the VOCs were higher in summer than in winter or spring for the sampling sites. The presence of vinyl acetate, chloroethene, and 1,2-dichloroethane were significantly high within a 5-km radius of the petrochemical complex. Four potential sources of ambient VOCs, industrial emission (49.2%-63.6%), traffic-related emission (13.9%-19.1%), fuel evaporation (12.3%-16.9%), and aged emission (10.2%-14.8%), were identified. The cancer risk of ambient VOC exposure was mainly attributed to the industrial source in the study area, while the non-cancer risk was of less concern. Benzene associated with fuel evaporation resulted in the highest cancer risk (4.1 × 10-5-5.5 × 10-5) as compared to that of the other toxic VOCs.

Lifetime exposure to particulate air pollutants is negatively associated with lung function in non-asthmatic children.

BACKGROUND: Pulmonary function is known to be affected by acute and subacute exposure to ambient air pollution. However, the impacts of lifetime exposure to air pollution on the pulmonary function of children have been inconsistent. The present study investigated the impact of lifetime residential exposure to intermediate levels of air pollution on the pulmonary function of schoolchildren. METHODS: In 2011, a survey of children aged 6-15 years was conducted in 44 schools in Taiwan. Atopic history, residential history, and environmental factors were recorded. Spirograms were obtained from a random sample of children without asthma. A total of 535 girls and 481 boys without a history of asthma were enrolled. Lifetime residential exposure to air pollutants, including particulate matter with an aerodynamic diameter less than 10 µm (PM10), ozone (O3), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO), was estimated using the kriging method, based on monitored data from the Taiwan Environmental Protection Administration. Multiple linear regression was used to analyze the association between lifetime air pollution exposure and pulmonary function, after adjustment for potential confounders and recent exposure. RESULTS: After adjustment for 7-day average air pollutant levels, a 10 µg/m3 increase in PM10 was related to reductions in the forced expiratory volume in 1 s (-2.00%; 95% confidence interval [CI] -3.09% to -0.90%), forced vital capacity (-1.86%; CI: -2.96% to -0.75%), and maximal midexpiratory flow (-2.28%; CI: -4.04% to -0.51%). These associations were independent of the other pollutants. CONCLUSION: Lifetime exposure to 25-85 µg/m3 of PM10 has negative impacts on the pulmonary function of children.

Development of an in Vitro-Based Risk Assessment Framework for Predicting Ambient Particulate Matter-Bound Polycyclic Aromatic Hydrocarbon-Activated Toxicity Pathways.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed throughout the atmosphere as mixtures attached to ambient particulate matter (PM). PAHs usually elicit similar toxicological pathways but do so with varying levels of efficacy. In this study, we utilized high-throughput screening (HTS) in vitro data of PAHs to predict health risks associated with coarse and fine PM. PM samples with 22 PAH compounds obtained from residential areas close to industrial parks in central Taiwan were analyzed. On the basis of the PM-bound PAH concentrations and their activities reported in HTS assays, we developed a probabilistic model for estimating cumulative exposure of humans to PAHs. Activity-to-exposure ratio (AER) values were calculated to compare relative risks of activating the aryl hydrocarbon receptor (AhR), nuclear factor erythroid 2-related factor 2 (Nrf2), and tumor suppressor gene (p53) when children or adults were exposed to fine or coarse PM in different seasons. On the basis of AER values, the risk of fine PM exposure was relatively higher than the risk of exposure to coarse PM in pathway activation. Children as a susceptible population had a risk of the activating AhR pathway greater than that of adults. Particularly higher risks were observed in winter than in summer. Among three pathways, AhR was the most sensitive one activated by exposure to PAHs. In addition, the activation of the AhR, Nrf2, and p53 pathways was compared by in vitro reporter assays with and without the pre-extraction of PAHs from PM. Our proposed novel approach accounts for mixture toxicities in characterizing in vitro pathway-based risks via inhalation exposure to ambient PAHs.

Ambient PM2.5 in the residential area near industrial complexes: Spatiotemporal variation, source apportionment, and health impact.

This study systemically investigated the ambient PM2.5 (n=108) with comprehensive analyses of the chemical composition, identification of the potential contributors, and estimation of the resultant respiratory physician visits in the residential regions near energy-consuming and high-polluting industries in central Taiwan. The positive matrix fraction (PMF) model with chemical profiles of trace metals, water-soluble ions, and organic/elemental carbons (OC/EC) was applied to quantify the potential sources of PM2.5. The influences of local sources were also explored using the conditional probability function (CPF). Associations between the daily PM2.5 concentration and the risk of respiratory physician visits for the elderly (≥65years of age) were estimated using time-series analysis. A seasonal variation, with higher concentrations of PM2.5, metals (As, Cd, Sb, and Pb), OC/EC and ions (i.e., NO3-, SO42- and NH4+) in the winter than in the spring and summer, was observed. Overall, an increase of 10µgm-3 in the same-day PM2.5 was associated with an ~2% (95% CI: 1.5%-2.5%) increase in respiratory physician visits. Considering the health benefits of an effective reduction, we suggest that the emission from coal combustion (23.5%), iron ore and steel industry (17.1%), and non-ferrous metallurgy (14.4%), accounting for ~70% of the primary PM2.5 in the winter are prioritized to control.

Estimated Daily Intake and Cumulative Risk Assessment of Phthalates in the General Taiwanese after the 2011 DEHP Food Scandal.

A food scandal occurred in Taiwan in 2011 because the DEHP (di-2-ethylhexyl phthalate) had been intentionally used in food products. We assessed the daily intakes (DIs) and cumulative risk of phthalates in Taiwan's general population after the scandal. The DIs of 6 phthalates, including di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), and DEHP, were evaluated using urinary phthalate metabolites. Hazard quotients of phthalates classified as affecting the reproductive (HQrep) and hepatic (HQhep) systems were assessed using cumulative approach. The creatinine-based model showed that the highest DI values in children 7-to 12- years-old were for DEHP (males: median: 4.79 µg/kg bw/d; females: median: 2.62 µg/kg bw/d). The 95th percentile (P95) of HQrep values were all >1 in the 7- to 12-year-old and 18- to 40-year-old male groups. The P95 of HQhep values were all >1 in the 7- to 18- year-old male groups. Most of the HQrep was attributable to the HQs of DnBP and DiBP (53.9-84.7%), and DEHP contributed most to HQhep (83.1-98.6%), which reveals that DnBP, DiBP and DEHP were the main risk of phthalate exposure for Taiwanese. Taiwan's general population is widely exposed to DnBP, DiBP and DEHP, especially for young children.

Does exposure to phthalates influence thyroid function and growth hormone homeostasis? The Taiwan Environmental Survey for Toxicants (TEST) 2013.

BACKGROUND: Previous epidemiologic and toxicological studies provide some inconsistent evidence that exposure to phthalates may affect thyroid function and growth hormone homeostasis. OBJECTIVE: To assess the relations between exposure to phthalates and indicators of thyroid function and growth hormone homeostasis disturbances both among adults and minors. METHODS: We conducted a population-based cross-sectional study of 279 Taiwanese adults (≥18 years old) and 79 minors (<18 years old) in 2013. Exposure assessment was based on urinary biomarkers, 11 phthalate metabolites measured by using online liquid chromatography/tandem mass spectrometry. Indicators of thyroid function included serum levels of thyroxine (T4), free T4, triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin (TBG). Growth hormone homeostasis was measured as the serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3). We applied multivariate linear regression models to examine these associations after adjusting for covariates. RESULTS: Among adults, serum T4 levels were negatively associated with urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate (ß=-0.028, P=0.043) and the sum of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolite (ß=-0.045, P=0.017) levels. Free T4 levels were negatively associated with urinary mono-ethylhexyl phthalate (MEHP) (ß=-0.013, P=0.042) and mono-(2-ethyl-5-oxohexyl) phthalate (ß=-0.030, P=0.003) levels, but positively associated with urinary monoethyl phthalate (ß=0.014, P=0.037) after adjustment for age, BMI, gender, urinary creatinine levels, and TBG levels. Postive associations between urinary MEHP levels and IGF-1 levels (ß=0.033, P=0.006) were observed. Among minors, free T4 was positively associated with urinary mono benzyl phthalate levels (ß=0.044, P=0.001), and IGF-1 levels were negatively associated with the sum of urinary DEHP metabolite levels (ß=-0.166, P=0.041) after adjustment for significant covariance and IGFBP3. CONCLUSIONS: Our results are consistent with the hypothesis that exposure to phthalates influences thyroid function and growth hormone homeostasis.

Ambient PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) in Changhua County, central Taiwan: Seasonal variation, source apportionment and cancer risk assessment.

This study investigates PM2.5-bound PAHs for rural sites (Dacheng and Fangyuan) positioned close to heavy air-polluting industries in Changhua County, central Taiwan. A total of 113 PM2.5 samples with 22 PAHs collected from 2014 to 2015 were analyzed, and Positive Matrix Factorization (PMF) and diagnostic ratios of PAHs were applied to quantify potential PAH sources. The influences of local and regional sources were also explored using the conditional probability function (CPF) and potential source contribution function (PSCF) with PMF-modeled results, respectively. Annual mean concentrations of total PAHs were 2.91 ± 1.34 and 3.04 ± 1.40 ng/m3 for Dacheng and Fangyuan, respectively, and their corresponding BaPeq were measured at 0.534 ± 0.255 and 0.563 ± 0.273 ng/m3 in concentration. Seasonal variations with higher PAHs found for the winter than for the spring and summer were observed for both sites. The lifetime excess cancer risk (ECR) from inhalation exposure to PAHs was recorded as 4.7 × 10-5 overall. Potential sources of PM2.5-bound PAHs include unburned petroleum and traffic emissions (42%), steel industry and coal combustion (31%), and petroleum and oil burning (27%), and unburned petroleum and traffic emission could contribute the highest ECR (2.4 × 10-5). The CPF results show that directional apportionment patterns were consistent with the actual locations of local PAH sources. The PSCF results indicate that mainly northeastern regions of China have contributed elevated PM2.5-bound PAHs from long-range transports.

Schoolchildren's antioxidation genotypes are susceptible factors for reduced lung function and airway inflammation caused by air pollution.

BACKGROUND: We recently reported the relationship between exposure to ambient air pollutants and changes in lung function and nasal inflammation among schoolchildren. A study was conducted to investigate whether antioxidation genotypes influence these associations. METHODS: A follow-up study of 97 schoolchildren was conducted in New Taipei City, Taiwan. A structured respiratory health questionnaire was administered in September 2007, followed by monthly spirometry and measurement of nasal inflammation from October 2007 to November 2009. During the study period, complete daily monitoring data for air pollutants were obtained from the Environmental Protection Administration monitoring station and Aerosol Supersite. The genotypes of glutathione S-transferase (GST) subunits M1, T1, P1 and superoxide dismutases subunit 2 (SOD2) were characterized. Mixed-effects models were used, adjusting for known confounders. RESULT: GSTM1 null children had significant PM2.5-related increment in leukocyte (8.52%; 95% confidence interval (CI): 3.13-13.92%) and neutrophil (9.68%; 95% CI: 4.51-14.85%) in nasal lavage. Ozone levels were significantly and inversely associated with forced expiratory flow at 25% of forced vital capacity (FEF25%) (-0.43L/s; 95% CI: -0.58,-0.28L/s) in SOD2 Ala16 variant children. CONCLUSION: In this longitudinal study of schoolchildren. Our data provide evidence that antioxidation genotype modifies the airway inflammation caused by PM2.5. Antioxidation genotype also acts as an effect modifier, but not strong, in ozone-related small airway function response.