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Studies have suggested that phthalates may be a risk factor for microalbuminuria, whereas little is known regarding their nephrotoxic effects on adults. We enrolled 311 participants (≥18 y, N = 241; <18 y, N = 70) who provided questionnaire information as well as blood and urine samples from a nationally cross-sectional study. Urinary phthalate metabolites were analyzed through liquid chromatography-tandem mass spectrometry. From the renal function index, we measured the serum level of blood urea nitrogen (BUN), and the urinary levels of microalbumin, albumin, protein and creatinine. We used multiple logistic regressions and a cumulative risk assessment of renal effect to evaluate the relationship between phthalate exposure and renal function in our participants. We aimed to assess the relationship between phthalate exposure and renal function including serum level of BUN, and urinary levels of microalbumin, albumin, protein, and creatinine in 311 participants (≥18 y, N = 241; <18 y, N = 70) from a population-based study. The multiple logistic regression showed that the adjusted odds ratio of the highest tertile of estimated di-2-ethylhexyl phthalate (DEHP) daily intake in participants ≥18 y for early renal impairment (microalbumin >1.9 mg/dL) was 9.40 times higher (95% confidence interval = 1.67-52.84) than the lowest tertile. The cumulative hazard index of phthalate-induced nephrotoxicity (HI nephro ) was significantly positively associated with microalbumin (β: 0.98, P < 0.001), BUN (β: 0.19, P = 0.002), and urine protein (β: 0.75, P = 0.001) in participants ≥18 y without type 2 diabetes mellitus after adjusting for confounding factors, but not in those <18 y. Our findings suggest that daily exposure to DEHP and its metabolites were significantly positively associated with an increased risk of higher microalbumin in Taiwanese ≥18 y. Comprehensive or mechanistic studies are required to elucidate these associations., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

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 NAFLD NASPGHAN and NAFLD ESPGHAN were 9.6% and 11.5%, respectively. Median levels (μg/g creatinine) of urinary TDGA of children with NAFLD NASPGHAN (vs non-NAFLD NASPGHAN ) and NAFLD ESPGHAN (vs non-NAFLD ESPGHAN ) 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 (P trend  = 0.045) for NAFLD NASPGHAN 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 NAFLD ESPGHAN 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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Toxic metal contamination in food products and the environment is a public health concern. Therefore, understanding human exposure to cadmium (Cd), lead (Pb), cobalt (Co), and copper (Cu) levels in the general population of Taiwan is necessary and urgent. We aimed to establish the human biomonitoring data of urine toxic metals, exposure profile changes, and factors associated with metal levels in the general population of Taiwan. We randomly selected 1601 participants older than 7 years of age (36.9 ± 18.7 years (7-84 years)) from the Nutrition and Health Survey in Taiwan (NAHSIT) conducted during 1993-1996 (93-96) and 2005-2008 (05-08) periods and measured the levels of four metals in the participants' urine samples using inductively coupled plasma-mass spectrometry. The median (range) levels of urinary Cd, Pb, Co, and Cu in participants from the NAHSIT 93-96 (N = 821)/05-08 (N = 780) were 0.60 (ND-13.90)/0.72 (ND-7.44), 2.28 (ND-63.60)/1.09 (0.04-48.88), 0.91 (0.08-17.30)/1.05 (0.05-22.43), and 16.87 (2.62-158.28)/13.66 (1.67-189.70) μg/L, respectively. We found that the urinary median levels of Pb and Cu in our participants were significantly lower in the NAHSIT 05-08 (Pb 1.09 μg/L, Cu 13.66 μg/L) than in the NAHSIT 93-96 (Pb 2.28 μg/L, Cu 16.87 μg/L; P < 0.01), whereas those of Cd and Co were significantly higher in the NAHSIT 05-08 (Cd 0.72 μg/L, Co 1.05 μg/L; P < 0.01). Youths had higher exposure levels of Pb, Co, and Cu than adults. Participants with alcohol consumption, betel quid chewing, or cigarette smoking had significantly higher median levels of urinary Pb or Cu (P < 0.01) than those without. Principal components and cluster analysis revealed that sex had different exposure profiles of metals. We concluded that levels of urinary Cd, Pb, Co, and Cu exposure in the general Taiwanese varied by age, sex, and lifestyles.

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 (Q 4 ) 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Despite a close interaction between cadmium (Cd) and long-chain polyunsaturated fatty acid (LC-PUFA) metabolism, the influence of Cd exposure on the endogenous synthesis of LC-PUFA has received little attention. In the present study, we hypothesized that Cd exposure would affect the synthesis of LC-PUFA in the marine fish silver pomfret (Pampus argenteus). Therefore, the molecular basis of LC-PUFA biosynthesis and regulation was investigated as the first step to understanding the mechanisms underpinning the effects of Cd exposure. Thereafter, transcriptional regulation of the genes that participate in LC-PUFA biosynthesis and regulation by Cd exposure were also explored. Our results showed that fatty acyl desaturase 2 (Fads2) and elongases of very long-chain fatty acids 5 (Elovl5), two key enzymes involved in LC-PUFA biosynthesis, enabled silver pomfret to biosynthesize 20:3n-6 and 20:4n-3 from 18:2n-6 and 18:3n-3. The results also raise the possibility that silver pomfret may have the ability to produce docosahexaenoic acid (DHA, 22:6n-3) from endogenous eicosapentaenoic acid (EPA, 20:5n-3). The expression of silver pomfret fads2 and elovl5 was transcriptionally regulated by the peroxisome proliferator activated receptor α (Pparα). The expression of fads2, elovl5 and pparα in the brain was significantly increased in response to Cd exposure. In addition, Cd exposure significantly reduced the DHA concentration and significantly increased the malondialdehyde concentration in the brain of silver pomfret. Cd exposure likely increases brain-specific DHA synthesis from EPA by transcriptionally activating fads2 and elovl5 via Pparα in silver pomfret. This regulation may be a coping mechanism for the reduction of DHA caused by Cd-oxidative stress in the brains of silver pomfret., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization reported that more than 10 % of women are severely affected by infertility, making the condition a major worldwide public health problem. Lead (Pb), cadmium (Cd), and arsenic (As) are environmental pollutants that may contribute to reproductive disorders. This cross-sectional study investigated the association between blood concentrations of Pb, Cd, and As and risk factors for infertility in women., Methods: Women who were infertile (N = 310) or pregnant (N = 57) were recruited from the gynecology and obstetrics department of a hospital. The participants were interviewed to obtain their sociodemographic, reproductive, and lifestyle information. The concentrations of Pb, Cd, and As in their blood samples were measured using inductively coupled plasma mass spectrometry., Results: Our findings suggested that the concentrations of Pb and As, but not Cd, were significantly higher in the blood of infertile women than in that of pregnant women. A higher percentage of the infertile women consumed more alcohol, used Chinese herbal medicine more frequently, and lacked physical activity compared with the pregnant women. After accounting for potentially relevant predictors, we observed that blood Pb levels might be elevated by using Chinese herbal medicine 1-6 times per week (aOR = 2.82, p = 0.05). In addition, engaging in physical activity 1-2 times per week (aOR = 0.37, p = 0.05) might assist in reducing Pb accumulation in infertile women, though the p value was borderline., Conclusions: Lack of physical activity and frequent use of Chinese herbal medicine may be associated with elevated blood Pb levels in infertile women. Chinese herbal medicine use was observed to increase the Pb body burden of both infertile and pregnant women in this study. The risk-benefit for Chinese herbal medicine intake should be evaluated by women of childbearing age.

Background: Some phthalic acid esters (PAEs) and nonylphenol (NP) are endocrine-disrupting chemicals (EDCs) that are widely used in consumer products. Consequently, the general population is exposed simultaneously to both groups of chemicals., Objective: To investigate the single- and co-exposure effects of PAEs (DMP, DEP, DnBP, DiBP, BBzP, and DEHP) and NP on obesity and pubertal maturity to compare the body sizes of general adolescents with the complainants of the phthalate-tainted foods scandal that occurred in Taiwan., Methods: This study included 270 general adolescents aged 6.5-15.0 years and 38 complainants aged 6.5-8.5 years. Nine metabolites of the five PAEs and of NP were measured in urine. We used a questionnaire to evaluate pubertal maturity, measured anthropometric indices (APs) to assess body size, and collected urine samples to measure the two groups of chemicals., Results: We found that urinary PAE metabolite concentrations (specifically, metabolites of DEP, DnBP, DiBP, and DEHP) were positively associated with the APs for abdominal obesity (including skinfold thickness, waist circumference, waist-to-height ratio, and waist-to-hip) and indicated a dose-response relationship. Mono-methyl phthalate (MMP) exposure was inversely associated with pubarche among boys. The daily intake of DEHP in general adolescents exceeded the reference doses (RfD-20 μg/kgbw/day) and tolerable daily intake (TDI-50 μg/kgbw/day) by 3.4% and 0.4%, respectively. No associations were observed between NP exposure or co-exposure and the APs or pubertal maturity. No significant differences were observed between general adolescents and the complainants with regard to weight, height, or BMI., Conclusions: The study suggests that PAE (specifically, DEP, DnBP, DiBP, and DEHP) exposure is associated with abdominal obesity in adolescents and that the APs for abdominal obesity are more sensitive than BMI for measuring obesity among adolescents. We suggest that the RfD and TDI for PAEs should be revised to provide sufficient protection., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: The World Health Organization reported that more than 10 % of women are severely affected by infertility, making the condition a major worldwide public health problem. Lead (Pb), cadmium (Cd), and arsenic (As) are environmental pollutants that may contribute to reproductive disorders. This cross-sectional study investigated the association between blood concentrations of Pb, Cd, and As and risk factors for infertility in women.Methods: Women who were infertile (N = 310) or pregnant (N = 57) were recruited from the gynecology and obstetrics department of a hospital. The participants were interviewed to obtain their sociodemographic, reproductive, and lifestyle information. The concentrations of Pb, Cd, and As in their blood samples were measured using inductively coupled plasma mass spectrometry.Results: Our findings suggested that the concentrations of Pb and As, but not Cd, were significantly higher in the blood of infertile women than in that of pregnant women. A higher percentage of the infertile women consumed more alcohol, used Chinese herbal medicine more frequently, and lacked physical activity compared with the pregnant women. After accounting for potentially relevant predictors, we observed that blood Pb levels might be elevated by using Chinese herbal medicine 1-6 times per week (aOR = 2.82, p = 0.05). In addition, engaging in physical activity 1-2 times per week (aOR = 0.37, p = 0.05) might assist in reducing Pb accumulation in infertile women, though the p value was borderline.Conclusions: Lack of physical activity and frequent use of Chinese herbal medicine may be associated with elevated blood Pb levels in infertile women. Chinese herbal medicine use was observed to increase the Pb body burden of both infertile and pregnant women in this study. The risk-benefit for Chinese herbal medicine intake should be evaluated by women of childbearing age. [ABSTRACT FROM AUTHOR]

The contamination of a clouding agent with di(2-ethylhexyl) phthalate (DEHP), a substitute emulsifier-containing compound used in a variety of foods was announced on May 23, 2011. The aims of this study were as follows (1) compare the urine phthalates (PAE) metabolites concentration and estimate the daily intake (DI) of PAEs in pregnant women before and after the tainted food scandal and (2) examine the effect of relatively high PAEs exposure on birth outcome. One-hundred twelve pregnant women in Northern Taiwan participated in this study from March to December 2010, i.e., before the tainted food scandal. After the tainted food scandal, we collected 69, 73, and 180 urine specimens (January 2013 to August 2014) from women whom were in their first, second, and third trimesters of pregnancy, respectively. We measure urinary DEHP metabolite concentrations to estimate the DI of DEHP and the hazard quotient (HQ) of subjects. This was the first study to assess the effects of DEHP-tainted food scandal exposure in pregnant women across the three trimesters of pregnancy. After the tainted food report, the concentrations of urine PAE metabolite were significantly decreased, especially those of DEHP metabolites. Based on different reference limit values, the percentages of pregnant women whose HQ DEHP value exceeded the limit ranged from 0.53% to 8.93%. Despite this low frequency, the higher ΣPAE exposure during the second trimester may significantly increase the risk of relatively low birth height compared to the lower exposure group (β = − 0.63 (− 1.20 to − 0.06)). Our results support the hypothesis that exposure to relatively high concentrations of DEHP in pregnant Taiwanese women may have an adverse effect on birth outcomes. The percentage of subjects whose exposure level exceeded the exposure limit was low; however, high PAEs exposure appears to be significantly associated with birth outcomes. Therefore, we suggest that reference dose for PAEs should be revised. [ABSTRACT FROM AUTHOR]