Han-Bin Huang

Traffic-related air pollution and DNA damage: a longitudinal study in Taiwanese traffic conductors.

Background There is accumulating epidemiologic evidence that exposure to traffic-related air pollutants, including particulate matter (PM) and polyaromatic hydro carbons (PAHs), plays a role in etiology and prognosis of a large scale of illnesses, although the role of specific causal agents and underlying mechanisms for different health outcomes remains unknown. Objective Our general objective was to assess the relations between personal exposure to traffic exhausts, in particular ambient PM2.5 and PAHs, and the occurrence of DNA strand breaks by applying personal monitoring of PM and biomarkers of exposure (urinary 1-hydroxypyrene-glucuronide, 1-OHPG) and effect (urinary 8-hydroxydeoxyguanosine, 8-OHdG and DNA strand breaks). Methods We recruited 91 traffic conductors and 53 indoor office workers between May 2009 and June 2011 in Taipei City, Taiwan. We used PM2.5 personal samplers to collect breathing-zone particulate PAHs samples. Spot urine and blood samples after work shift of 2 consecutive days were analyzed for 1-OHPG, 8-OHdG and DNA strand breaks, respectively. Statistical methods included linear regression and mixed models. Results Urinary 8-OHdG levels and the occurrence of DNA strand breaks in traffic conductors significantly exceeded those in indoor office workers in mixed models. Particulate PAHs levels showed a positive association with urinary 1-OHPG in the regression model (β = 0.056, p = 0.01). Urinary 1-OHPG levels were significantly associated with urinary 8-OHdG levels in the mixed model (β = 0.101, p = 0.023). Our results provide evidence that exposure to fine particulates causes DNA damage. Further, particulate PAHs could be biologically active constituents of PM2.5 with reference to the induction of oxidative DNA damages.

Exposure to Heavy Metals and Polycyclic Aromatic Hydrocarbons and DNA Damage in Taiwanese Traffic Conductors

Background: Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAH) and heavy metals, has been associated with the etiology and prognosis of many illnesses. However, the specific causal agents and underlying mechanisms for different health outcomes remain unclear. The aims of this study were to assess the relations between urinary biomarkers of exposure to PAHs (1-hydroxypyrene-glucuronide, 1-OHPG) and heavy metals (cadmium, Cd; nickel, Ni; arsenic, As; lead, Pb; and copper, Cu) and the effect of their interaction on DNA damage (8-oxo-7,8-dihydro-guanine, 8-oxodG). Methods: We recruited 91 traffic conductors and 53 indoor office workers between May 2009 and June 2011 in Taipei, Taiwan. Postshift urine samples from 2 consecutive days were analyzed for 1-OHPG, Cd, Ni, As, Pb, Cu, and 8-oxodG. To estimate the effects from PAHs and metals on DNA damage, we constructed a linear mixed model adjusted for confounding variables. Results: We found that urinary 1-OHPG and Cd levels were independent predictors of urinary 8-oxodG levels (β = 0.112; P = 0.015 for 1-OHPG; β = 0.138; P = 0.031 for urinary Cd). The joint effect of urinary 1-OHPG and Cd levels was associated with urinary 8-oxodG levels (P = 0.001). Conclusions: Co-exposure to environmental PAHs and Cd could cause oxidative DNA damage. Impact: These findings suggest that the additive interaction between exposure to environmental PAHs and Cd could enhance the burden of oxidative stress. Cancer Epidemiol Biomarkers Prev; 22(1); 102–8. ©2012 AACR.

Fetal and Childhood Exposure to Phthalate Diesters and Cognitive Function in Children Up to 12 Years of Age: Taiwanese Maternal and Infant Cohort Study

Few studies have examined the association between environmental phthalate exposure and children’s neurocognitive development. This longitudinal study examined cognitive function in relation to pre-and postnatal phthalate exposure in children 2–12 years old. We recruited 430 pregnant women in their third trimester in Taichung, Taiwan from 2001–2002. A total of 110, 79, 76, and 73 children were followed up at ages 2, 5, 8, and 11, respectively. We evaluated the children’s cognitive function at four different time points using the Bayley and Wechsler tests for assessing neurocognitive functions and intelligence (IQ). Urine samples were collected from mothers during pregnancy and from children at each follow-up visit. They were analyzed for seven metabolite concentrations of widely used phthalate esters. These esters included monomethyl phthalate, monoethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, and three metabolites of di(2-ethylhexyl) phthalate, namely, mono-2-ethylhexyl phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate. We constructed a linear mixed model to examine the relationships between the phthalate metabolite concentrations and the Bayley and IQ scores. We found significant inverse associations between the children’s levels of urinary mono(2-ethyl-5-oxohexyl) phthalate and the sum of the three metabolites of di(2-ethylhexyl) phthalate and their IQ scores (β = -1.818; 95% CI: -3.061, -0.574, p = 0.004 for mono(2-ethyl-5-oxohexyl) phthalate; β = -1.575; 95% CI: -3.037, -0.113, p = 0.035 for the sum of the three metabolites) after controlling for maternal phthalate levels and potential confounders. We did not observe significant associations between maternal phthalate exposure and the children’s IQ scores. Children’s but not prenatal phthalate exposure was associated with decreased cognitive development in the young children. Large-scale prospective cohort studies are needed to confirm these findings in the future.

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 (&bgr;=−0.028, P=0.043) and the sum of urinary di‐(2‐ethylhexyl) phthalate (DEHP) metabolite (&bgr;=−0.045, P=0.017) levels. Free T4 levels were negatively associated with urinary mono‐ethylhexyl phthalate (MEHP) (&bgr;=−0.013, P=0.042) and mono‐(2‐ethyl‐5‐oxohexyl) phthalate (&bgr;=−0.030, P=0.003) levels, but positively associated with urinary monoethyl phthalate (&bgr;=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 (&bgr;=0.033, P=0.006) were observed. Among minors, free T4 was positively associated with urinary mono benzyl phthalate levels (&bgr;=0.044, P=0.001), and IGF‐1 levels were negatively associated with the sum of urinary DEHP metabolite levels (&bgr;=−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. HighlightsWe measured urinary phthalate metabolites, thyroid, growth hormones in the general Taiwanese.Serum T4 and Free T4 levels were negatively associated with DEHP metabolites, among adults.Serum IGF‐1 levels were negatively associated with DEHP metabolites among minors.

Prenatal and Childhood Exposure to Phthalate Diesters and Thyroid Function in a 9-Year Follow-up Birth Cohort Study: Taiwan Maternal and Infant Cohort Study

Background: Phthalates are widely used in industry, personal care products, and medications. Recent studies have suggested that phthalate exposure alters thyroid hormones. However, longitudinal studies concerning the association between phthalate exposure and thyroid function in children are scant. Therefore, we examined the association between pre- and postnatal phthalate exposure and thyroid function in children born in 2000–2001. Methods: We studied 181 mother–child pairs in central Taiwan and followed-up the children from 2000 to 2009 at 2, 5, and 8 years old. We measured serum levels of thyroxine (T4), free T4, triiodothyronine (T3), and thyroid-stimulating hormone in children by using radioimmunoassay. We quantified seven phthalate metabolites, representing the five most commonly used phthalates, in maternal and child urine samples by using liquid chromatography-tandem mass spectrometry. The metabolites were monoethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) derived from di(2-ethylhexyl) phthalate (DEHP), monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and monobenzyl phthalate (MBzP). We constructed a linear mixed model to examine these associations after adjustments for covariates. Results: The T4 levels were inversely associated with maternal urinary MEHHP (&bgr; = −0.028 [95% confidence interval (CI) = −0.051, −0.006]) and MEOHP (&bgr; = −0.027 [−0.050, −0.003]), with similar T3 levels being observed in boys, even when the children exposure levels were considered spontaneously. In the girls, the free T4 levels were inversely associated with levels of maternal urinary MEP (&bgr; = −0.042), maternal urinary MBzP (&bgr; = −0.050), and children’s urinary MEHP (&bgr; = −0.027). Conclusions: Early life phthalate exposure was associated with decreased thyroid hormone levels in young children.

Exposure to fine particulate matter causes oxidative and methylated DNA damage in young adults: A longitudinal study

An increased understanding is needed of the physiological effects and plausible biological mechanisms that link PM2.5 (particulate matter with an aerodynamic diameter below 2.5μm) exposure to mortality and morbidities such as atherosclerosis and respiratory disease. PM2.5 causes carcinogenic health effects. Biomonitoring in humans has suggested that 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-oxodG) and N7-methylguanine (N7-MeG) are correlated with oxidative and methylated DNA damage. Thus, it is meaningful to explore the mechanisms of mutagenesis and carcinogenesis associated with oxidative and methylated DNA damage by simultaneously measuring these two markers. We recruited 72 participants from 2 areas (residential and commercial as well as residential and industrial) in the greater Taipei metropolitan area at baseline. Personal samplers were used to collect 24-hour PM2.5-integrated samples. All participants completed an interview, and blood and urine samples were collected the next morning. All collection procedures were repeated twice after a two-month follow-up period. Urinary 8-oxodG and N7-MeG were assayed as biomarkers of oxidative and methylated DNA damage, respectively. Plasma superoxide dismutase (SOD) and glutathione peroxidase-1 (GPX-1) were measured as biomarkers of antioxidants. Urinary 1-hydroxypyrene (1-OHP) was used as a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs). The mean PM2.5 level was 37.3μg/m3 at baseline. PM2.5 concentrations were higher during winter than during spring and summer. After adjusting for confounds through a generalized estimating equation (GEE) analysis, N7-MeG was significantly increased by 8.1% (β=0.034, 95% CIs=0.001-0.068) per 10μg/m3 increment in PM2.5. 8-oxodG levels were positively correlated with N7-MeG according to both cross-sectional and longitudinal analyses, and 1-OHP was significantly associated with increasing 8-oxodG and N7-MeG concentrations. Exposure to PM2.5 increases methylated DNA damage. The mean level of urinary N7-MeG was 1000-fold higher than that of 8-oxodG.

Longitudinal assessment of prenatal phthalate exposure on serum and cord thyroid hormones homeostasis during pregnancy - Tainan birth cohort study (TBCS)

An increasing number of studies have revealed that phthalate exposure alters thyroid hormone homeostasis in the general population, but there is insufficient evidence of the effect of longitudinal maternal phthalate exposure on maternal and fetal thyroid hormones during pregnancy. We longitudinally assessed the effect of prenatal phthalate exposure in pregnant women on umbilical cord and maternal thyroid hormones at three trimesters during pregnancy. We recruited 98 pregnant women and collected urine and blood samples at three trimesters in an obstetrics clinic in Southern Taiwan from 2013 to 2014. We analyzed the concentrations of 11 urinary phthalate metabolites, including monoethylhexyl phthalate, mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-n-butyl phthalate, monoisobutyl phthalate (MiBP), monoethyl phthalate (MEP), using online liquid chromatography-tandem mass spectrometry. The cord and maternal serum levels of thyroxine (T4), free T4, triiodothyronine (T3), thyroid-stimulating hormone (TSH), and thyroxine-binding globulin were measured using an electrochemiluminescence immunoassay. A mixed-model analysis was utilized to assess the effect of longitudinal phthalate exposure on thyroid hormones and adjusted for significant covariates. We found that urinary MiBP (β=-0.065, 95% confidence interval (CI): -0.124, -0.005), and MEOHP (β=-0.083, 95% CI: -0.157, -0.009) were significantly negatively associated with serum TSH. Urinary MECPP was inversely related to serum T3 (β=-0.027, 95% CI: -0.047, -0.006). Urinary MEP (β=0.014, 95% CI: -0.001, 0.028) and MiBP (β=0.033, 95% CI: 0.018, 0.049) were positively related to free T4. We found that cord serum T3 (β=0.067, 95% CI: 0.003, 0.131) and free T4 (β=0.031, 95% CI: 0.001, 0.062) levels had significant positive associations with maternal ΣDBPm levels at the second trimester. We concluded that different phthalates exposure windows during gestation may alter cord and serum thyroid hormone homoeostasis.

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.