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Introduction: Prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).Objectives: Our aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.Methods: A total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).Results: Associations of maternal DEHP exposure (median 4.54μg/kg_bw/day) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) μg/kg_bw/dayfor an integrated CBCL score.Conclusions: The current TDI (RfD) of 50 (20) μg/kg_bw/day for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed. [ABSTRACT FROM AUTHOR]

Abstract Summer days with extremely hot temperatures in Taiwan have been increasing for the past few decades, and this continuing trend is expected to worsen heat-related mortality. To mitigate the corresponding health impacts, in this study, we developed a statistical state-space model to predict the number of extremely hot days in June–September for the next year. Based on historical data from 1951 to 2017, we estimated the climate change trend after adjusting for the nonlinear lagged effect of the Niño 3.4 index. We then developed a predictive state-space model using these two primary factors and adjusting for residual autocorrelations. Validation results comparing the extremely hot days observed over 2015–2017 with predictions showed that 86% of the average prediction errors were within 4 days of the observations. To assess the health impacts, we applied the model to the projection of heat-attributable mortality (AM) in 2018 by adopting a comparative risk assessment (CRA) approach with the reference period of 2001–2010. The results showed that the Taipei metropolitan area in northern Taiwan is the most affected region with AM of 1501 deaths from all-causes, followed by Taichung in central Taiwan with 490 deaths. The prediction model and the CRA projection provide both a tool and guidance for public health administrators to address the imminent threat posed by climate change. Graphical abstract Unlabelled Image Highlights • Nonlinear lagged association between ENSO and extremely hot days in summer • Flexible estimate of nonlinear climate change trend • Short-term prediction model for extremely hot days with high precision • Risk map of county-specific heat-attributable mortality • Provide a tool and guidance for health policy for imminent threat of climate change [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate associations between cardiovascular effects and urban ambient particle constituents using an in vivo crossover experimental design. Ambient particles were introduced to an exposure chamber for whole-body exposure of WKY rats, where the particulate matter with an aerodynamic diameter of <2.5 μm (PM 2.5 ) mass concentration, particle number concentration, and black carbon (BC) were monitored. Organic carbon (OC), elemental carbon (EC), and soluble ions of PM 2.5 were determined. In a crossover design, rats were exposed to ambient particles or high-efficiency particle arrestance (HEPA)-filtered control air for 7 days following a 7-day washout interval. The crossover exposure between particles and HEPA-filtered air was repeated 4 times. Radiotelemetric data on blood pressure (BP) [systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP)], heart rate (HR), and heart rate viability (HRV) were subsequently obtained during the entire study. Exposure to the PM 2.5 mass concentration was associated with decreases in the SBP, DBP, MAP, and HR ( p < 0.05), whereas no significant changes in the BP or HR occurred with the particle number or black carbon. For HRV, the ln 5-min standard deviation of the normal-to-normal (NN) interval (LnSDNN) and the ln root mean square of successive differences in adjacent NN intervals (LnRMSSD) were positively associated with the PM 2.5 mass concentration ( p < 0.05). There were no significant effects of the particle number concentration or BC on HRV. Alterations in the HR were associated with OC, EC, Na + , Cl − , and NO 3 − . Cl − was associated with the DBP, MAP, HR, SDNN, and RMSSD. NO 3 − was correlated with the SBP, MAP, HR, SDNN, and RMSSD. In conclusion, we observed cardiovascular responses to ambient particles in vivo using a crossover design which can reduce animal use in future environmental studies. [ABSTRACT FROM AUTHOR]

The impact of melamine exposure on kidney outcomes in type 2 diabetes mellitus (T2D) patients remains unclear. In this prospective cohort study, 561 T2D patients during October 2016 and June 2020 were enrolled and followed until December 2021. Baseline one-spot urinary corrected melamine levels were measured by LC-MS/MS. Average daily intake (ADI) of melamine represented environmental melamine exposure in daily life, and was estimated using urinary corrected melamine level by creatinine excretion (CE)-based model. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline >5 ml/min/1.73 m2/year. Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 μg/mmol and 0.3 μg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline >5 ml/min/1.73 m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥60 ml/min/1.73 m2 or glycated hemoglobin ≤7%. In conclusion, melamine exposure is significantly associated with adverse kidney outcomes in T2D patients, especially in those with male, well sugar control or good baseline kidney function. [Display omitted] • Melamine levels in urine were significantly associated with adverse kidney outcome in type 2 diabetes mellitus (T2D). • This association was pronounced in male T2D and in those with well controlled sugar. • Physicians need to consider the potential hazard of environmental melamine on kidney function deterioration in well-controlled T2D. [ABSTRACT FROM AUTHOR]

Phthalate exposure is omnipresent and known to have developmental and reproductive effects in children. The aim of this study was to determine the phthalate exposure sources and their relative contributions among children in Taiwan. During the first wave of the Risk Assessment of Phthalate Incident in Taiwan (RAPIT), in 2012, we measured 8 urinary phthalate metabolites in 226 children aged 1-11 years old and in 181 children from the same cohort for the wave 2 study in 2014. A two-stage statistical analysis approach was adopted. First, a stepwise regression model was used to screen 80 questions that explored the exposure frequency and lifestyle for potential associations. Second, the remaining questions with positive regression coefficients were grouped into the following 6 exposure categories: plastic container/packaging, food, indoor environment, personal care products, toys, and eating out. A mixed model was then applied to assess the relative contributions of these categories for each metabolite. The use of plastic container or food packaging were dominant exposure sources for mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). The indoor environment was a major exposure source of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), and mono-isobutyl phthalate (MiBP). The consumption of seafood showed a significant correlation with MEHP. The children's modified dietary behavior and improved living environment in the second study wave were associated with lower phthalate metabolite levels, showing that phthalate exposures can be effectively reduced. [ABSTRACT FROM AUTHOR]

Abstract: Short-term exposure estimation of daily air pollution levels incorporating geographic information system (GIS) into spatiotemporal modeling remains a great challenge for assessing corresponding acute adverse health effects. Due to daily meteorological effects on the dispersion of pollutants, explanatory spatial covariables and their coefficients may not be the same as in classical land-use regression (LUR) modeling for long-term exposure. In this paper, we propose a two-stage spatiotemporal model for daily fine particulate matter (PM2.5) concentration prediction: first, daily nonlinear temporal trends are estimated through a generalized additive model, and second, GIS covariates are used to predict spatial variation in the temporal trend-removed residuals. To account for spatial dependence on meteorological conditions, the dates of the study period are divided by the sill of the daily empirical variogram into approximately temporal-invariant subgroups. Within each subgroup, daily PM2.5 estimations are obtained by combining the temporal and spatial parts of the estimations from the two stages. The proposed method is applied to the modeling of spatiotemporal PM2.5 concentrations observed at 18 ambient air monitoring stations in Taipei metropolitan area during 2006–2008. The results showed that the PM2.5 concentrations decreased whereas the relative humidity and wind speed increased with the sill subgroups, which may be due to the effects of daily meteorological conditions on the dispersions of the particles. Also, the covariates and their coefficients of the LUR models varied with subgroups and had in general higher adjusted R-squares and smaller root mean square errors in prediction than those of a single overall LUR model. [Copyright &y& Elsevier]

Summary: Background & aims: Obesity-related metabolic disorders such as hypertension, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia are major risk factors for cardiovascular disease. The aim was to compare body mass index, waist circumference, and waist-to-hip ratio as predictors of these metabolic disorders. Methods: We evaluated 1625 men and 1779 women, aged 35–64y who participated in the 2001 National Health Interview Survey and 2002 Taiwan Three High Prevalence Survey. Their anthropometric measurements were analyzed as predictors of metabolic disorders using empirical receiver-operating characteristic curves and logistic regression models. Results: Overall, waist circumference performed well as a predictor of metabolic disorders. Body mass index was the best predictor for men who smoked, whereas waist circumference and waist-to-hip ratio were better alternatives for non-smoking men and women. Anthropometric measures had higher predictabilities for those aged 35–44y but relatively weak associations with diabetes mellitus for men aged 45–64y and hypercholesterolemia for men and women. Conclusions: The associations between anthropometric measures and the metabolic disorders varied with comorbidity, gender, age groups, and smoking status. Waist-to-hip ratio was the best predictor for diabetes mellitus, especially for participants aged 45–64y. The anthropometric measures did not predict hypercholesterolemia well. [Copyright &y& Elsevier]

Cyclists can be easily exposed to traffic-related pollutants due to riding on or close to the road during commuting in cities. PM 2.5 has been identified as one of the major pollutants emitted by vehicles and associated with cardiopulmonary and respiratory diseases. As routing has been suggested to reduce the exposures for cyclists, in this study, PM 2.5 was monitored with low-cost sensors during commuting periods to develop models for identifying low exposure routes in three Asian cities: Taipei, Osaka, and Seoul. The models for mapping the PM 2.5 in the cities were developed by employing the random forest algorithm in a two-stage modeling approach. The land use features to explain spatial variation of PM 2.5 were obtained from the open-source land use database, OpenStreetMap. The total length of the monitoring routes ranged from 101.36 to 148.22 km and the average PM 2.5 ranged from 13.51 to 15.40 μg/m³ among the cities. The two-stage models had the standard k-fold cross-validation (CV) R2 of 0.93, 0.74, and 0.84 in Taipei, Osaka, and Seoul, respectively. To address spatial autocorrelation, a spatial cross-validation approach applying a distance restriction of 100 m between the model training and testing data was employed. The over-optimistic estimates on the predictions were thus prevented, showing model CV-R2 of 0.91, 0.67, and 0.78 respectively in Taipei, Osaka, and Seoul. The comparisons between the shortest-distance and lowest-exposure routes showed that the largest percentage of reduced averaged PM 2.5 exposure could reach 32.1% with the distance increases by 37.8%. Given the findings in this study, routing behavior should be encouraged. With the daily commuting trips expanded, the cumulative effect may become significant on the chronic exposures over time. Therefore, a route planning tool for reducing the exposures shall be developed and promoted to the public. [Display omitted] • Cyclists' PM 2.5 exposures were monitored in Taipei, Osaka, and Seoul. • Random forest land use models are developed for mapping PM 2.5. • Spatial k-fold cross-validation is applied, showing model CV-R2 above 0.67. • Alternative routes can reduce the PM 2.5 exposure over 30% for cyclist commuters. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM 2.5) is associated with various adverse health outcomes and poses serious concerns for public health. However, ground monitoring stations for PM 2.5 measurements are mostly installed in population-dense or urban areas. Thus, satellite retrieved aerosol optical depth (AOD) data, which provide spatial and temporal surrogates of exposure, have become an important tool for PM 2.5 estimates in a study area. In this study, we used AOD estimates of surface PM 2.5 together with meteorological and land use variables to estimate monthly PM 2.5 concentrations at a spatial resolution of 3 km2 over Taiwan Island from 2015 to 2019. An ensemble two-stage estimation procedure was proposed, with a generalized additive model (GAM) for temporal-trend removal in the first stage and a random forest model used to assess residual spatiotemporal variations in the second stage. We obtained a model-fitting R2 of 0.98 with a root mean square error (RMSE) of 1.40 μ g / m 3. The leave-one-out cross-validation (LOOCV) R2 with seasonal stratification was 0.82, and the RMSE was 3.85 μ g / m 3 , whereas the R2 and RMSE obtained by using the pure random forest approach produced R2 and RMSE values of 0.74 and 4.60 μ g / m 3 , respectively. The results indicated that the ensemble modeling approach had a higher predictive ability than the pure machine learning method and could provide reliable PM 2.5 estimates over the entire island, which has complex terrain in terms of land use and topography. [Display omitted] • An improved two-stage ensemble modeling compared to random forest approach. • Leave one out cross-validation R2 0.82 and root mean squared error 3.85 μ g/ m 3. • Higher correlation between ground PM2.5 concentrations and AOD estimate of PM2.5 • Long-term PM2.5 concentrations across Taiwan substantially declined from 2015 to 2019. [ABSTRACT FROM AUTHOR]

• The lower bound of benchmark dose (benchmark response 0.1) ranged from 0.74 to 2.03 μ g / k g _ b w / d a y. • A threshold one to two orders lower than the WHO and US FDA recommended levels. • Consistent associations with kidney outcomes over a median follow-up of 7.0 years. • Early-stage CKD patients is more susceptible to melamine than urolithiasis patients. Environmental melamine exposure has been associated with deteriorating kidney function in early-stage chronic kidney disease patients. In this study, a benchmark dose (BMD) approach was used to establish melamine exposure threshold in 293 patients with eGFR ≥ 30 ml/min per 1.73 m2. The patients were enrolled 2006–2010 and followed-up for a median of 7.0 years to monitor kidney outcomes. Average daily intakes (AvDI) of melamine were estimated using one-spot urine samples collected at enrollment. BMDs and corresponding one-sided 95% lower bound (BMDLs) were derived using established dose–response models relating estimated AvDIs and dichotomous kidney outcomes: doubling of serum creatine levels, eGFR decreased > 3 ml/min per 1.73 m2 per year, and >30% decline in eGFR during the first 2 years. In addition, survival time to doubling of serum creatinine and eGFR decline over time were assessed as continuous endpoints. Given a benchmark response of 0.10, BMDLs ranged from 0.74 to 2.03 μ g / k g _ b w / d a y after Bayesian model averaging, a range one to two orders lower than the current WHO recommended tolerable daily intake of 200 μ g / k g _ b w / d a y and the US FDA's 63 μ g / k g _ b w / d a y. Our results suggest that early-stage CKD patients should strictly refrain from using melamine tableware and related melamine-made products. [ABSTRACT FROM AUTHOR]

Extreme temperature events have been observed to appear more frequently and with greater intensity in Taiwan in recent decades due to climate change, following the global trend. Projections of temperature extremes across different climate zones and their impacts on related mortality and adaptation have not been well studied. We projected site-specific future temperature extremes by statistical downscaling of 8 global climate models followed by Bayesian model averaging from 2021 to 2060 across Taiwan under the representative concentration pathway (RCP) scenarios RCP2.6, RCP4.5, and RCP8.5. We then calculated the attributable mortality (AM) in 6 municipalities and in the eastern area by multiplying the city/county- and degree-specific relative risk of mortality according to the future population projections. We estimated the degree of adaptation to heat by slope reduction of the projected AM to be comparable with that in 2018. The annual number of hot days with mean temperatures over 30 °C was predicted to have a substantial 2- to 5-fold increase throughout the residential areas of Taiwan by the end of 2060 under RCP8.5, whereas the decrease in cold days was less substantial. The decrease in cold-related mortality below 15 °C was projected to outweigh heat-related mortality for the next two decades, and then heat-related mortality was predicted to drastically increase and cross over cold-related mortality, surpassing it from 2045 to 2055. Adjusting for future population size, the percentage increase in heat-related deaths per 100,000 people could increase by more than 10-fold under the worst scenario (RCP8.5), especially for those over 65 years old. The heat-related impacts will be most severe in southern Taiwan, which has a tropical climate. There is a very high demand for heat-adaptation prior to 2050 under all RCP scenarios. Spatiotemporal variations in AM in cities in different climate zones are projected in Taiwan and are expected to have a net negative effect in the near future before shifting to a net positive effect from 2045 to 2055. However, there is an overall positive and increasing trend of net effect for elderly individuals under all the emission scenarios. Active adaptation plans need to be well developed to face future challenges due to climate change, especially for the elderly population in central and southern Taiwan. Unlabelled Image • Spatiotemporal differences across areas of sub-tropical and tropical climate zones. • A substantial 2- to 5-fold increase in hot days over 30 °C under RCP8.5 by 2060. • Cold-related mortality outweigh that of heat prior to 2045. • A crossover of heat-related mortality surpasses that of cold in 2045–2055. • Southern Taiwan of tropic climate has the most severe health impacts in mortality. [ABSTRACT FROM AUTHOR]

This study evaluated whether exposure to fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) is associated with cardiovascular effects by examining a panel of 89 healthy subjects in Taipei, Taiwan. The subjects received two health examinations approximately 8 months apart in 2013. Brachial–ankle pulse wave velocity (baPWV), a physiological indicator of arterial stiffness, and high-sensitivity C-reactive protein (hsCRP), a biomarker of vascular inflammations, were measured during each examination. Two exposure assessment methods were used for estimating the subjects' exposure to PM 2.5 and NO 2 . The first method involved constructing daily land use regression (LUR) models according to measurements collected at ambient air quality monitoring stations. The second method required combining the LUR estimates with indoor monitoring data at the workplace of the subjects. Linear mixed models were used to examine the association between the exposure estimates and health outcomes. The results showed that a 10-μg/m 3 increase in PM 2.5 concentration at a 1-day lag was associated with 2.1% (95% confidence interval: 0.7%–3.6%) and 2.4% (0.8%–4.0%) increases in baPWV based on the two exposure assessment methods, whereas no significant association was observed for NO 2 . The significant effects of PM 2.5 remained in the two-pollutant models. By contrast, NO 2 , but not PM 2.5 , was significantly associated with increased hsCRP levels (16.0%–37.3% in single-pollutant models and 26.4%–44.6% in two-pollutant models, per 10-ppb increase in NO 2 ). In conclusion, arterial stiffness might be more sensitive to short-term PM 2.5 exposure than is inflammation. [ABSTRACT FROM AUTHOR]

Ambient mass spectrometry thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) can rapidly identify chemicals without pretreatment of biological samples. This study used a rapid semi-quantitative TD-ESI/MS screening technique for the probe skin sampling of melamine workers occupationally exposed to different ambient melamine concentrations to create avatar-like body images, which were then used to study temporal and dynamic changes in nephrotoxic melamine exposure. We enrolled four voluntary melamine workers from one factory, each from one of four worksites. Melamine exposure was highest in manufacturing and molding, followed by grinding and polishing, packing, and administration, the lowest. Skin samples were collected Friday (end-of-shift) and Monday (pre-shift). Early morning one-spot urine samples were also collected right after skin sampling. 2198 probe skin samples were collected and subjected to semi-quantitative TD-ESI/MS analyses of melamine chemical within 40 h. After normalization, converted body image scores revealed exposure to be highest in the manufacturing worker on Friday and lowest in the administrative worker on Monday. The absolute differences (Friday minus Monday) of normalized body image scores were all significantly positive in each individual worker and across all four workers (permutation test, all p-values < 0.002). The slope estimates of the linear regression line between body image scores and urinary melamine levels were 0.81 (p-value = 0.008). We concluded that this fast and non-invasive technique can potentially be used to study temporal and dynamic changes in exposure to occupational hazards. A future study of developing an automatic and reproducible TD-ESI/MS sampling platform is needed. [Display omitted] • TD-ESI/MS can rapidly identify chemicals without pretreating biological samples. • Melamine workers were exposed to a wide range of ambient melamine concentrations. • TD-ESI/MS was used to analyze 2198 skin samples from four melamine workers <40 h. • Body image scores of melamine on skin were correlated with urinary melamine levels. • This fast and non-invasive technique can be applied to other hazards on human skin. [ABSTRACT FROM AUTHOR]

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/kg bw/day) and tolerable daily intake (TDI-50 μg/kg bw/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. [ABSTRACT FROM AUTHOR]

[Display omitted] • A major public health issue in Taiwan in 2011 involved phthalate-tainted foods. • This cohort study followed three waves in affected children over five years. • Past daily DEHP intake from DEHP-tainted foods and time had significant effects on urinary ACR, with negative interactions. • Urinary melamine levels increased urinary ACR and oxidative stress over time. • Impact of DEHP-tainted foods on urinary ACR was highest in the first wave and diminished gradually. In 2011, phthalates, mainly di-(2-ethylhexyl) phthalate (DEHP), were found to have been added to a variety of foods in Taiwan, increasing the risk of microalbuminuria in children. Exposure to melamine perhaps modifies that risk. This prospective cohort study investigates whether renal injury resulting from exposure to DEHP-tainted foods from the 2011 Taiwan Food Scandal is reversed over time. The temporal and interactive effects of past daily DEHP intake, current daily DEHP intake, and urinary melamine levels on oxidative stress and renal injury were also examined. Two hundred possibly DEHP-affected children (aged < 18 years) were enrolled in the first survey wave (August 2012–January 2013), with 170 and 159 children in the second (July 2014–February 2015) and third waves (May 2016–October 2016), respectively. The first wave comprised questionnaires that were used to collect information about possible past daily DEHP intake from DEHP-tainted foods. One-spot first morning urine samples were collected to measure melamine levels, phthalate metabolites, and markers indicating oxidative stress (malondialdehyde and 8-oxo-2′-deoxyguanosine), and renal injury (albumin/creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase) in all three waves. Generalized estimating equation (GEE) modeling revealed that both past daily DEHP intake and time might affect urinary ACR. However, most interactions were negative and significant correlation was observed only during the second wave (P for interaction = 0.014) in the group with the highest past daily DEHP intake (>50 μg/kg/day). Urinary melamine levels were found to correlate significantly with both urinary ACR and oxidative stress markers. The highest impact associated with exposure to DEHP-tainted foods in increasing urinary ACR of children was observed during the first wave, and the effect may partially diminish over time. These results suggest that continuous monitoring of renal health and other long-term health consequences is required in individuals who were affected by the scandal in 2011. [ABSTRACT FROM AUTHOR]

The present study assessed the association between phthalate exposure and mitochondrial DNA (mtDNA) polymerase γ (POLG) methylation along with the potential effect on the characteristics of body fat in children. A total of 152 children were enrolled. The urinary concentrations of phthalate metabolites were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Genomic DNA was extracted from the buffy coat, and bisulfite-treated DNA was subjected to a pyrosequencing assay. In total, 17 CpG sites in the exon 2 region of POLG were included in the analysis. A multivariable regression model was applied to determine whether characteristics of body fat were associated with phthalate exposure and methylation of POLG. After adjustment for covariates, male children with a ten-fold increase in mono-methyl phthalate (MMP) or mono-benzyl phthalate (MBzP) concentrations had significantly higher measurements for total body fat (MMP: β = 6.47%; MBzP: β = 3.54%), and trunk fat (MMP: β = 6.67%; MBzP: β = 3.90%). Male children who had hypermethylation at the 2nd CpG site in exon 2 of POLG also had high measurements for BMI (β = 1.66 kg/m2), waist (β = 4.49 cm) and hip (β = 4.81 cm) circumference, total body fat (β = 5.48%), and trunk fat (β = 6.21%). A dose-response relationship existed between methylation at the 2nd CpG site in exon 2 of POLG and characteristics of body fat (p for trend<0.01). This study suggested that male children who are exposed to phthalic acid esters have high body weight, BMI, and body and trunk fat percentages. Methylation of the exon 2 region of POLG is a possible mechanism behind the causal effect of endocrine-disrupting substances. Unlabelled Image • Mono-methyl phthalate (MMP) exposure level was associated with hypermethylation in exon 2 of polymerase γ (POLG) in children. • The dose-response relationship existed between methylation at the 2nd CpG site in exon 2 of POLG and body fat percentage. • The association between MMP exposure or hypermethylation of POLG and body fat percentage in male children was observed. [ABSTRACT FROM AUTHOR]