Exposure and risk assessment of urinary trans, trans-Muconic acid in school-age children in the vicinity of a petrochemical complex in Central Taiwan.

School-age children living near large petrochemical factories may be at high risk of exposure to benzene released during manufacturing processes. We aimed to investigate the urinary concentrations of trans, trans-muconic acid (t,t-MA) in school-age children living near a petrochemical complex and to estimate their cumulative risk of benzene exposure. We examined an established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-age children (aged 6-13 years) who lived near large petrochemical factories in central Taiwan between October 2013 and September 2014. The cohort comprised 297 children from five elementary schools, namely S.-C. Branch (n = 63, school A, ~0.9 km), F.-A. (n = 51, school B, ~2.7 km), C.-T. (n = 63, school C, ~5.5 km), M.-L. (n = 54, school D, ~6.9 km), and L.-F. (n = 66, school E, ~8.6 km). We analyzed the urinary t,t-MA levels of each participant and estimated their daily intake of benzene. We also performed multiple regression analysis to investigate potential risk factors for a high urinary t,t-MA level in the study cohort. The median urinary t,t-MA levels and median estimated benzene daily intake of the children from each school were as follows: school A, 64.07 ng/mL, 11.13 µg/kg/day; school B, 61.01 ng/mL, 15.32 µg/kg/day; school C, 59.38 ng/mL, 14.81 µg/kg/day; school D, 42.35 ng/mL, 11.67 µg/kg/day; school E, undetected, 0.14 µg/kg/day. The distance between a school and a petrochemical complex (greater distance: ß = -0.26, 95% confidence interval [CI] = -0.52 to 0.00, p = 0.053), and the age of the children (older age: ß = -3.44, 95% CI = -5.90 to -1.46, p < 0.001) were identified as potential risk factors. After confounders were adjusted for, the creatinine adjusted urinary t,t-MA levels of the school-age children tended to be lower when the distance between their school and a petrochemical complex was greater.

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.

Mediation effects of thyroid function in the associations between phthalate exposure and lipid metabolism in adults.

Phthalates are a group of industrial chemicals widely used in everyday products including cosmetics, food packaging and containers, plastics, and building materials. Previous studies have indicated that urinary phthalate metabolites are associated with metabolic effects including those on lipid metabolism, but the results are mixed. Furthermore, whether thyroid function mediates the association between phthalate exposure and lipid metabolism remains unclear. In the present study, we explored whether changes in thyroid function markers mediate the associations between phthalate exposure and lipid metabolism indicators in Taiwanese adults. The cross-sectional data were obtained from the Taiwan Environmental Survey for Toxicants conducted in 2013. Levels of 11 urinary phthalate metabolites, levels of 5 thyroid hormones, and 8 indicators of lipid metabolism were assessed in 222 Taiwanese adults. The relationships of urinary phthalate metabolite levels with serum thyroid hormone levels and lipid metabolism indicators were explored using multiple regression models. Mediation analysis was conducted to evaluate the role of thyroid function in the association between phthalate exposure and lipid metabolism. The metabolite of di(- 2-ethylhexyl) phthalate (∑DEHPm) exhibited a significant positive association with the lipid metabolite indicator of high-density lipoprotein cholesterol (HDL-C; ß = 0.059, 95% confidence interval [CI] = 0.009, 0.109) in adults, and the thyroid function indicator thyroxine (T4) had a significant negative association with the metabolite ∑DEHPm (ß = - 0.059, 95% CI = - 0.101, - 0.016) and a significant negative association with HDL-C (ß = - 0.284, 95% CI = - 0.440, - 0.128). The T4 indirect effect was 0.015 (95% CI = - 0.0087, 0.05), and the mediation effect was 32.2%. Our results support the assumption that exposure to phthalates influences the homeostasis of lipid metabolism by interfering with thyroid function.

Are Phthalate Exposure Related to Oxidative Stress in Children and Adolescents with Asthma? A Cumulative Risk Assessment Approach.

Childhood asthma has become one of the most common chronic diseases in children and adolescents. However, few case-control studies investigating the relationship between phthalate exposure and asthma in children and adolescents have been conducted, especially in Asia. Therefore, we assessed the potential associations between phthalate exposure and asthma among children and adolescents in Taiwan. Because various demographic and environmental variables may influence the incidence and prognosis of asthma, we performed a case-control study with propensity score matching. Out of 615 Childhood Environment and Allergic Diseases Study participants, we conditionally matched 41 children with clinically diagnosed asthma with 111 controls. We then analyzed 11 phthalate metabolites by using liquid chromatography with tandem mass spectrometry. Compared with the control group, the median urinary phthalate levels for most phthalate metabolites in the case group were slightly increased, including monomethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, monoethylhexyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, and mono-(2-carboxymethylhexyl) phthalate. Hence, our results suggest that phthalate exposure may be associated with the development of asthma. In addition, prenatal environmental factors, such as active or passive smoking during pregnancy, may increase the risk of asthma.

Associations between Oxidative/Nitrosative Stress and Thyroid Hormones in Pregnant Women-Tainan Birth Cohort Study (TBCS).

Oxidative and nitrosative stress have been linked to thyroid function in both animal and human studies. In the present study, the associations between oxidative and nitrosative stress and thyroid hormones were investigated. Measurements were obtained from 97 Taiwanese pregnant women at the first, second, and third trimesters. Levels of five oxidative and nitrosative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-nitroguanine [8-NO2Gua], 4-hydroxy-2-nonenal-mercapturic acid [HNE-MA], 8-isoprostaglandin F2α [8-isoPGF2α], and malondialdehyde [MDA]) were measured using urine samples, and levels of five thyroid hormones (triiodothyronine [T3], thyroxine [T4], free T4, thyroid-stimulating hormone [TSH], and T4-binding globulin [TBG]) were measured in blood samples. Multiple linear regressions and linear mixed-model regressions were conducted to determine the associations between oxidative or nitrosative stress biomarkers and thyroid hormones in pregnant women. We found that TSH was negatively and significantly associated with 8-NO2Gua (-14%, 95% CI [-26.9% to -1.1%]) and HNE-MA (-23%, 95% CI [-35.9% to -10.0%]) levels. However, T4 (3%, 95% CI [0.2%-5.8%]) and free T4 (4.3%, 95% CI [0.8%-7.8%]) levels were positively and significantly associated with 8-NO2Gua. The T4 to TBG and free T4 to TBG ratios were positively and significantly associated with 8-NO2Gua level (T4/TBG: 3.6%, 95% CI [0.5%-6.7%]; free T4/TBG: 5.6%, 95% CI [0.2%-11.1%]). However, the TSH to T4 ratio was negatively and significantly associated with 8-NO2Gua level (-17.3%, 95% CI [-30.4% to -4.3%]). The T3 to TSH ratio was positively and significantly associated with HNE-MA level (25.2%, 95% CI [11.2%-39.2%]). However, the TSH to T4 and TSH to free T4 ratios were negatively and significantly associated with HNE-MA level (TSH/T4: -21.2%, 95% CI [-34.5% to -7.8%] and TSH/free T4: -24.0%, 95% CI [-38.3% to -9.6%]). Our findings suggest that an imbalance of oxidative and nitrosative stress may alter thyroid hormone homeostasis during pregnancy. Disruption of the maternal thyroid homeostasis during pregnancy would affect embryonic and fetal development.