Exposure characteristics and cumulative risk assessment of bisphenol A and its substitutes: the Taiwan environmental survey for toxicants 2013.

Introduction: Ever since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute's exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure. Methods: Urine samples (N = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography-tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated. Results: Our study found that the median level of BPA was significantly higher in adults (9.63 µg/g creatinine) than in minors (6.63 µg/g creatinine) (p < 0.001). The DI of BPS was higher in female (0.69 ng/kg/day) than in male (0.49 ng/kg/day); however, the DIs of BPF and BPS were higher in boys (1.15 and 0.26 ng/kg/day, respectively) than in girls (0.57 and 0.20 ng/kg/day, respectively). Most HI values exceeded 1 (99% of the participants) after EFSA re-establish the TDI of BPA. Discussion: Our study revealed that the exposure profiles and risk of BPA and its substitute in Taiwanese varied by age and sex. Additionally, the exposure risk of BPA was deemed unacceptable in Taiwan according to new EFSA regulations, and food contamination could be the possible source of exposure. We suggest that the risk of exposure to BPA and its substitutes in most human biomonitoring studies should be reassessed based on new scientific evidence.

Associations between paraben exposure, thyroid capacity, homeostasis and pituitary thyrotropic function in the general Taiwanese: Taiwan Environmental Survey for Toxicants (TEST) 2013.

Several studies have suggested that some endocrine disruptors such as synthetic phenols, parabens and phthalates may disrupt thyroid hormone signaling and associated negative feed-backs with the central hypothalamic-pituitary-thyroid (HPT) axis. Therefore, we investigated urinary paraben and blood thyroid hormone levels in the Taiwanese population. Our sample comprised 264 adults (aged 18-97 years) and 75 minors (aged 7-17 years) from Taiwan Environmental Survey for Toxicants 2013. Urinary levels of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were assessed. Hormones of particular interest include: thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). We sought integrated parameters to describe the transfer of thyroid hormones in homeostatic models. The geometric mean urinary paraben levels of the adults were higher than those of the minors (adults vs. minors; MeP: 383 vs. 62.4 ng/mL; PrP: 109 vs. 8.00 ng/mL; EtP: 39.5 vs. 2.38 ng/mL, and BuP: 6.36 vs. 2.13 ng/mL). In the male adults, we discovered that 0.253% (p = 0.032), 0.256% (p = 0.041) and 0.257% (p = 0.037) decreases in the TSH, TSH/T4 and TSH/FreeT4 ratio was associated with 1% EtP increases, respectively. In the female minors, 0.093% (p = 0.044), 0.072% (p = 0.047) and 0.156 (p = 0.004) increases in the TSH ratios were associated with a 1% MeP, EtP and BuP increase, respectively. Moreover, 0.151% (p = 0.008) and 0.177% (p = 0.001) increases in TSH/T4 and TSH/free T4 ratios were associated with a BuP 1% increase, respectively. Finally, EtP was positively associated with SPINA-GT (ß: 15.66, p = 0.036) in the male adults. By contrast, EtP were positively associated with Jostel's TSH index and sTSHI (ß: 0.072, p = 0.049; ß: 0.107, p = 0.049) in the female minors. The Taiwanese population is commonly exposed to parabens, which can potentially lead to alteration of thyroid hormone homeostasis.

Assessment of heavy metals among auto workers in metropolitan city: a case study.

In recent decades, heavy metals (HMs) have emerged as a global health concern. Unfortunately, in Pakistan, there is a general lack of awareness regarding the potential health risks associated with HMs pollution among automobile workers. Herein, we investigated the concentration of heavy metals such as lead (Pb), cadmium (Cd), and chromium (Cr) among automobile workers who were occupationally exposed in Mingora City, Khyber Pakhtunkhwa, Pakistan. Three different automobile groups, i.e., battery recyclers, spray painters, and mechanics were studied in detail. A total of 40 blood samples were collected from automobile workers groups while 10 blood samples were collected as control individuals from different locations in the study area. We investigated heavy metals concentration with a standard method using an atomic absorption spectrometer AAS (PerkinElmer Analyst 700, United States). Based on our findings, the battery recycling group displayed the most elevated Pb levels (5.45 ± 2.11 µg/dL), exceeding those of both the spray painters' group (5.12 ± 1.98 µg/dL) and the mechanics' group (3.79 ± 2.21 µg/dL). This can be attributed to their higher exposure to Pb pollution resulting from the deterioration, dismantling, grinding, or crushing of old batteries. In the context of chromium (Cr) exposure, a similar trend was observed among the battery recycling group, as well as the spray painters and mechanics groups. However, in the case of cadmium (Cd), the mechanics' group exhibited the highest level of exposure (4.45 ± 0.65 µg/dL), surpassing the battery recycling group (1.17 ± 0.45 µg/dL) and the spray painters' group (1.35 ± 0.69 µg/dL), which was attributed to their greater exposure to welding fumes and other activities in their workplace. We believe that our findings will encourage regulatory measures to improve the health of automobile workers. However, further work is needed to determine various health-related issues associated with heavy metal exposure among automobile workers.

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.

Cumulative risk assessment and exposure characteristics of parabens in the general Taiwanese using multiple hazard indices approaches.

Parabens, a group of endocrine disrupting chemicals (EDCs), are well known preservatives in pharmaceuticals and personal care products (PPCPs). However, studies on parabens exposure and their cumulative effects in Asian population are limited. This study aimed to identify the exposure characteristics and estimate the cumulative risk of four parabens in the general Taiwanese. We have collected urine samples including 271 adults (18-97 yrs old) and 95 minors (7-17 yrs old), from Taiwan Environmental Survey for Toxicants 2013, and analyzed for four urinary parabens including methyl (MeP)-, ethyl (EtP)-, propyl (PrP)-, and butylparaben (BuP) by using ultraperformance liquid chromatography-tandem mass spectrometry. The health-based guidance value (HBGV) and the antiandrogenic properties of parabens were used to calculate the hazard index (HI) for cumulative risk. MeP and PrP were most abundant compounds and startlingly higher than those in other countries. Adults had a higher geometric mean level of four parabens than minors (adults: MeP, 381.7; PrP, 108.6; EtP, 39.6 and BuP 6.3 ng/mL; minors: MeP, 65.7; PrP, 7.9, EtP, 2.6 and BuP 2.2 ng/mL). Participants who used a higher number of personal care products had a significantly higher risk with higher concentrations of PrP (above 75th %tile) [adjusted odds ratio (aOR): 1.79, 95 % CI: 1.01-3.15] and BuP [aOR: 1.78, 95 % CI: 1.03-3.07]. The median and 95th %tile HI (the sum of the HQs of each paraben) was as 1.10 and 4.39-fold higher than acceptable cumulative threshold (HI <1) and PrP accounted for 90 % of the HI. Our results indicate omnipresent exposure to parabens among the Taiwanese population, which might cause certain level of concerns. These significant increasing trends of HI with age dependence were observed, which mainly driven by PPCPS used. Routine survey of parabens in PPCPs and continued biomonitoring needs to be urgently addressed.

Phthalate Exposure and Oxidative/Nitrosative Stress in Childhood Asthma: A Nested Case-Control Study with Propensity Score Matching.

Whether low-dose phthalate exposure triggers asthma among children, and its underlying mechanisms, remain debatable. Here, we evaluated the individual and mixed effects of low-dose phthalate exposure on children with asthma and five (oxidative/nitrosative stress/lipid peroxidation) mechanistic biomarkers-8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-isoprostaglandin F2α (8-isoPF2α), and malondialdehyde (MDA)-using a propensity score-matched case-control study (case vs. control = 41 vs. 111). The median monobenzyl phthalate (MBzP) concentrations in the case group were significantly higher than those in the control group (3.94 vs. 2.52 ng/mL, p = 0.02), indicating that dust could be an important source. After adjustment for confounders, the associations of high monomethyl phthalate (MMP) (75th percentile) with 8-NO2Gua (adjusted odds ratio (aOR): 2.66, 95% confidence interval (CI): 1.03-6.92) and 8-isoPF2α (aOR: 4.04, 95% CI: 1.51-10.8) and the associations of mono-iso-butyl phthalate (MiBP) with 8-isoPF2α (aOR: 2.96, 95% CI: 1.13-7.79) were observed. Weighted quantile sum regression revealed that MBzP contributed more than half of the association (56.8%), followed by MiBP (26.6%) and mono-iso-nonyl phthalate (MiNP) (8.77%). Our findings supported the adjuvant effect of phthalates in enhancing the immune system response.

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.

Cumulative Dietary Risk Assessment of Benzophenone-Type Photoinitiators from Packaged Foodstuffs.

Photoinitiators used in ultraviolet-cured ink may migrate from food packaging materials into food products. Therefore, we conducted a dietary risk assessment of exposure to benzophenone (BP)-type photoinitiators by quantifying and reducing uncertainties associated with the risk characterization. A total of 362 food packaging samples including 180 cereals, 136 fruit and vegetable juices, and 46 milk samples were subjected to fast pesticides extraction to determine photoinitiator residues. The average daily dose (ADD) of BP was the highest in the age group of zero to three years, with a P97.5 ADD of 2.56 × 10-4 mg/kg bw/day. The ADD of 2-hydroxybenzophenone (2-OHBP) was the highest in the age group of three to six years, with a P97.5 UB ADD of 3.52 × 10-5 mg/kg bw/day. The estimated UB P97.5 ADD for each age group was below the toxicological concern threshold of 0.0015 mg/kg bw/day. The cumulative toxicity of all BPs, evaluated using the MOET value, was at an acceptable level. Although the MOET value of BPs was above the safety limit in the foodstuffs studied herein, this result may be different if Taiwan were to follow regulation guidelines for BP-type photoinitiators based on the specific migration limit for the unmeasured BP residues in other foodstuffs.

Determination of Parabens, Bisphenol A and Its Analogs, Triclosan, and Benzophenone-3 Levels in Human Urine by Isotope-Dilution-UPLC-MS/MS Method Followed by Supported Liquid Extraction.

The development of a rapid analytical approach for determining levels of antibacterial agents, plasticizers, and ultraviolet filters in biosamples is crucial for individual exposure assessment. We developed an analytical method to determine the levels of four parabens-bisphenols A (BPA) and its analogs, triclosan (TCS), triclocarban, and benzophenone-3 (BP-3)-in human urine. We further measured the levels of these chemicals in children and adolescents. We used a supported liquid extraction (SLE) technique coupled with an isotope-dilution ultraperformance liquid chromatography-tandem mass spectrometry (ID-UPLC-MS/MS) method to assess the detection performance for these chemicals. Forty-one urine samples from 13 children and 28 adolescents were assessed to demonstrate the capability and feasibility of our method. An acceptable recovery (75.6-102.4%) and matrix effect (precision < 14.2%) in the three-level spiked artificial urine samples were achieved, and good performance of the validated ID-UPLC-MS/MS method regarding linearity, limits of detection, and quantitation was achieved. The within-run and between-run accuracy and precision also demonstrated the sensitivity and stability of this analytical method, applied after SLE. We concluded that the ID-UPLC-MS/MS method with SLE pretreatment is a valuable analytical method for the investigation of urinary antibacterial agents, plasticizers, and ultraviolet filters in humans, useful for human biomonitoring.

Exposure to ZnO/TiO2 Nanoparticles Affects Health Outcomes in Cosmetics Salesclerks.

Concerns about the effects of nanoparticles (NPs) on human health are being raised by researchers because the risks of nanocosmetics like sunscreen are unknown. We explored the association between urinary oxidative stress markers and exposure of cosmetics salesclerks to 20 cosmetics that might contain titanium dioxide (TiO2)/zinc oxide (ZnO) NPs. We then recruited 40 cosmetics salesclerks and 24 clothing salesclerks and categorized them based on their exposure to ZnO and TiO2 NPs. Nineteen and 15 samples met the EU definition for TiO2 and ZnO nanomaterials, respectively. Participants with a higher co-exposure index of ZnO and TiO2 NPs had a significantly higher base level of urinary 8-hydroxy-2'-deoxyguanosin (8-OHdG) concentrations than the lower co-exposure group (5.82 vs. 2.85 ng/mL, p < 0.001). After potential confounding factors had been adjusted for, the TiO2 and ZnO NP co-exposure index was significantly positively associated with the urinary 8-OHdG base concentration (ß = 0.308, 95% CI = 0.106 to 0.510) and the creatinine-adjusted concentration (ß = 0.486, 95% CI = 0.017 to 0.954). Current evidence suggests that the likelihood of harm from using sunscreens containing nanoparticles might result in higher urinary 8-OHdG. However, our limited number and types of sample cosmetics might underestimate the risk.

Spatiotemporal patterns of polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin-like polychlorinated biphenyls in foodstuffs in air quality regions in Taiwan.

High-fat food intake is the main source of dioxin-like compounds for humans, such as consumption of meat, dairy and eggs, and seafood products. Fruits, vegetables, and cereals have relatively low levels of dioxin-like compounds, but because of high consumption they also contribute to the food-borne intake. It is necessary to clarify dietary dioxin exposure affected by different food contamination levels and dietary habits among different geographic areas. We aimed to evaluate chronic dietary PCDD/Fs and DL-PCBs exposure in 725 individual foods in 14 categories in 6 Taiwan air quality regions (AQRs) and a total of 2441 foods from 2004 to 2018. We estimated daily PCDD/Fs + DL-PCBs intake on the basis of sex- and age-specific foodstuff ingestion rate and PCDD/Fs+ DL-PCBs concentrations using a probabilistic approach. PCDD/F+ DL-PCB levels among the different sampling periods exhibited a decreasing trend in fish and aquatic products (from 0.384 ± 0.764 to 0.206±0.223pgWHO05-TEQg-1 w.w.) (p for trend=0.043), livestock products (from 0.133±0.298 to 0.035±0.043 pgWHO05-TEQ g-1 w.w.), eggs (from 0.221 ± 0.373 to 0.056 ± 0.048 pgWHO05-TEQ g-1 w.w.) (p for trend = 0.002), and dairy samples (from 0.066 ± 0.075 to 0.024 ± 0.026 pgWHO05-TEQ g-1 w.w.) (p for trend= 0.001). All lifetime average daily doses (LADD) were below provisional tolerable monthly intake (PTMI) but higher than the TWI for PCDD/Fs and DL-PCBs in food. The percentages of the contribution of each food group to the total dietary intake of TEQPCDD/F+PCB in different ambient air dispersion areas and age groups. The total daily intake of PCDD/Fs and DL-PCBs by Taiwanese differed between AQRs (0.188-0.397 pgWHO05-TEQ kg-1 b.w. day-1). The observed geographical variations were likely due to differences in food habits, cuisines, culture and levels of environmental contamination among various regions in Taiwan. By sensitivity analysis, we have identified the major contribution to LADD, which was the dioxin levels in marine fish, fresh water fish and fish related products, and followed by dioxin levels in duck eggs. In addition, marine and freshwater fish consumption rate accounts more than 10.2%. These major exposure variables was also consistent with the findings of total daily intake in different AQRs.

Reduced adiponectin:leptin ratio associated with inhalation exposure to vinyl chloride monomer.

The hepatic toxicity of vinyl chloride monomer (VCM) has often been reported, but few studies have assessed insulin resistance or adipose tissue dysfunction. We analyzed the chronic health effects of moderate exposure to VCM on factory workers in Taiwan. Data were collected from personal air samples, urine samples, and immunohistochemical (IHC) examinations of 122 recruited voluntary participants. Air samples were analyzed to assess personal levels of exposure to VCM and ethylene dichloride (EDC). Urine samples were collected from each worker before they started and after they finished their daily shift. Urinary thiodiglycolic acid (TDGA) levels were analyzed using high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). IHC examinations included liver function and serum adipokine level tests for insulin resistance. Consequently, the participants included for the final analysis were 113. After confounders had been adjusted for, the airborne VCM concentration significantly (P = 0.043) correlated with pre-shift urinary TDGA levels (ß = 0.194). A multivariate analysis showed a significant (P = 0.013) inverse correlation between the adiponectin:leptin ratio and the airborne VCM concentration (ß = -0.283), which means that exposure to VCM might increase the risk of insulin resistance and adiponectin abnormalities. We hypothesized that pre-shift urinary TDGA levels can be used as exposure biomarkers for the exposure of workers to VCM.

Phthalate exposure increased the risk of early renal impairment in Taiwanese without type 2 diabetes mellitus.

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 (HInephro) was significantly positively associated with microalbumin (ß: 0.98, P < 0.001), BUN (ß: 0.19, P = 0.002), and urine protein (ß: 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.

Efficiency and performance tests of the sorptive building materials that reduce indoor formaldehyde concentrations.

The adsorption of volatile organic compounds by building materials reduces the pollutant concentrations in indoor air. We collected three interior building materials with adsorption potentials-latex paint, micro-carbonized plywood, and moisture-buffering siding-used the sorptive building materials test (SBMT) to determine how much they reduced indoor formaldehyde (HCHO) concentrations, and then assessed the consequent reduction in human cancer risk from HCHO inhalation. Adsorption of HCHO by building materials significantly improved the effective ventilation efficiency. For example, the equivalent ventilation rate for Celite siding-used for humidity control-was 1.44 m3/(m2·h) at 25°C, 50% relative humidity (RH); the loading factor (L) was 0.4 m2/m3, and the HCHO concentration was 0.2 ppm; this effect is equivalent to a higher ventilation rate of approximately 0.6 air changes per hour in a typical Taiwanese dwelling. There was also a substantial reduction of risk in Case MCP-2 (Cin,te: 245 µg/m3, 30°C, 50% RH): males: down 5.73 × 10-4; females: down 4.84 × 10-4). The selection of adsorptive building materials for interior surfaces, therefore, significantly reduces human inhalation of HCHO. Our findings should encourage developing and using innovative building materials that help improve indoor air quality and thus provide building occupants with healthier working and living environments.

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.

Crystal structure of the central and the C-terminal RNase domains of colicin D implicated its translocation pathway through inner membrane of target cell.

Colicins are protein toxins produced by and toxic to Escherichia coli strains. Colicin D consists of an N-terminal domain (NTD), central domain (CD) and C-terminal RNase domain (CRD). The cognate immunity protein, ImmD, is co-synthesized in producer cells to block the toxic tRNase activity of the CRD. Previous studies have reported the crystal structure of CRD/ImmD complex. Colicin D hijacks the surface receptor FepA and the energy transducer TonB system using the NTD for translocation across the outer membrane of the target cells. The CD is required for endoproteolytic processing and the translocation of CRD across the inner membrane, and the membrane-associated protease FtsH and the signal peptidase LepB are exploited in this process. Although several regions of the CD have been identified in interactions with the hijacked inner membrane system or immunity protein, the structural basis of the CD is unknown. In this study, we determined the crystal structure of colicin D, containing both the CD and CRD. The full-length colicin D/ImmD heterodimer structure was built by superimposing the CD-CRD structure with the previously determined partial structures. The overall translocation process of colicin D, including the interaction between CD and LepB, is discussed.

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 (ß=-0.065, 95% confidence interval (CI): -0.124, -0.005), and MEOHP (ß=-0.083, 95% CI: -0.157, -0.009) were significantly negatively associated with serum TSH. Urinary MECPP was inversely related to serum T3 (ß=-0.027, 95% CI: -0.047, -0.006). Urinary MEP (ß=0.014, 95% CI: -0.001, 0.028) and MiBP (ß=0.033, 95% CI: 0.018, 0.049) were positively related to free T4. We found that cord serum T3 (ß=0.067, 95% CI: 0.003, 0.131) and free T4 (ß=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.

Characterization of phthalates exposure and risk for cosmetics and perfume sales clerks.

High levels of phthalates in name-brand cosmetics products have raised concerns about phthalate exposure and the associated risk for cosmetics sales clerks. We assessed the exposure and risk of phthalates in 23 cosmetics, 4 perfume, and 9 clothing department store sales clerks. We collected 108 urine samples pre- and post-shift and analyzed for phthalate monoesters through liquid chromatography-electrospray ionization-tandem mass spectrometry. Phthalates in 32 air samples were collected and analyzed through gas chromatography-mass spectrometry. Demographic characteristics and information on the exposure scenarios were obtained through questionnaires. Principal component analysis, cluster and risk analysis were applied to identify the exposure profile and risk of phthalate. Median post-shift levels of urinary mono-2-ethylhexyl phthalate (MEHP) and monomethyl phthalate (MMP) were significantly higher than the corresponding pre-shift levels in cosmetics group (53.3 vs. 30.9 µg/g-c for MEHP; 34.4 vs. 22.5 µg/g-c for MMP; both P < 0.05) and the post-shift levels of urinary MMP was significantly higher than the corresponding pre-shift levels in perfume group (26.6 vs. 14.9 µg/g-c, P < 0.05). Median levels of air diethyl phthalate (DEP) in cosmetics (1.77 µg/m3) and perfume (1.75 µg/m3) groups and di-(2-ethylhexyl) phthalate (DEHP) in perfume group (6.98 µg/m3) were higher than those in clothing group (DEP: 0.89; DEHP: 2.16 µg/m3). Over half of cosmetic (70%) and perfume sale clerks had exceeded cumulative risk of phthalate exposure for anti-androgenic effect. We concluded that cosmetic and perfume workers had increased risks of reproductive or hepatic effects for DBP and DEHP exposure. We suggest that not only inhalation but dermal exposure is important route of phthalate exposure for cosmetics and perfume workers.

Association Between Dioxin and Metabolic Syndrome by Age and Sex in an Endemic Area of Exposure in Taiwan.

BACKGROUND: Some of the effects of dioxins seem to be different between men and women, and exposures starting at an early age seem to have more prominent effects. Therefore, we conducted a study in Taiwan to evaluate the associations between exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and metabolic syndrome (MetS) starting at different ages in both sexes. METHODS: We recruited participants from an area where residents were exposed to PCDD/Fs released from a factory and defined serum PCDD/Fs levels ≥20 pg WHO98-TEQDF/g lipid as high dioxin levels. MetS was defined as meeting three of the following criteria: fasting glucose ≥100 mg/dl or under treatment for diabetes, waist circumference ≥90 cm in men or ≥80 cm in women, triglycerides ≥150 mg/dl or under treatment for elevated triglycerides, high-density lipoprotein <40 mg/dl in men or <50 mg/dl in women, and blood pressures ≥130/85 mmHg or under treatment for hypertension. RESULTS: Of the 2758 participants, 785 patients with MetS were identified, and we observed positive associations between a high dioxin level and MetS. After adjusting for sex, age, and age at starting exposure, we found that a high dioxin level was an independent predictor for MetS (adjusted odds ratio =1.38; 95% confidence interval = 1.11, 1.72). When we stratified the participants by gender, we found that a high dioxin level remained an independent predictor of MetS in men, but not in women, regardless of the age at starting exposure. CONCLUSIONS: Exposure to PCDD/Fs was associated with MetS in men, independent of age and age at starting exposure.