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During the early months of life, infant formula plays a crucial role as a primary source of both food and essential nutrients for infants, serving as a replacement for or supplement to breast milk. However, nonessential metals in infant formulas are a concern because infants are highly vulnerable to chemical exposure. The aim of this study was to investigate infant exposure to nonessential metals in infant formula products in Taiwan and assess the associated health risks. In this study, concentrations of arsenic (As), barium (Ba), cadmium (Cd), manganese (Mn), lead (Pb), and vanadium (V) in 45 formula products for 0–1‐year‐old infants were determined by inductively coupled plasma mass spectrometry. The mean As, Ba, Cd, Mn, Pb, and V concentrations were 6.42, 280, 3.72, 1425, 20.4, and 21.9 µg/kg, respectively. According to our probabilistic simulation of the estimated daily intake of metals, the proportion of hazard quotients exceeding one was 7.69% for As and 3.29% for Mn, and that of hazard index (HI) values exceeding 1 was >17% for metals. Arsenic had the largest HI contribution (46.9%), followed by Mn (22.3%) and Pb (12.7%). The nonessential metals content in infant formula raises potential noncarcinogenic health concerns for infants in Taiwan. Therefore, regulations for nonessential metals must be imposed on related food products in Taiwan, with a particular focus on As and Mn. [ABSTRACT FROM AUTHOR]

Parabens (PBs) are esters of p-hydroxybenzoic acid, and there are growing concerns due to their potential to disrupt endocrine function and their wide use as preservatives in foodstuffs, including beverages. The consumption of bottled and hand-shaken teas is gradually replacing traditional tea consumption through brewing. However, no study has reported PB concentrations in different types of teas or packaging and their associated health risks. Our aim was to determine the concentration of PBs (methyl- (MetPB), ethyl- (EthPB), propyl- (PropPB), butyl-paraben (ButPB)) in green, black, and oolong teas in two varieties of products (bottled and hand-shaken teas), using UPLC-MS/MS. Additionally, we estimated the health risks associated with tea consumption in the general adult population of Taiwan. A Monte Carlo simulation was applied to estimate the distribution of daily PB intake through bottled (n = 79) and hand-shaken (n = 71) tea consumption. Our findings revealed geometric mean concentrations in bottled green/black/oolong teas were 714.1/631.2/532.1 ng/L for MetPB, 95.2/ 30.5/14.9 ng/L for EthPB, 77.9/28.3/non-detected (ND) ng/L for PropPB, and 69.3/26.6/ND ng/L for ButPB. Hand-shaken green/black/oolong teas exhibited concentrations of 867.5/2258/1307 ng/L for MetPB, 28.5/28.8/14.5 ng/L for EthPB, 25.4/18.3/17.8 ng/L for PropPB, and 30.3/18.0/15.5 ng/L for ButPB. The median MetPB concentrations in hand-shaken black (2333 ng/L) and oolong teas (1215 ng/L) were significantly higher than those in bottled black (595.4 ng/L) and oolong teas (489.3 ng/L). Conversely, median concentrations of EthPB, PropPB, and ButPB in bottled teas were significantly higher than those in hand-shaken teas. MetPB was the predominant PB, constituting 73.2–91.9% in bottled teas and 85–94% in hand-shaken teas. Our results showed no health risks associated with bottled or hand-shaken tea consumption based on reference doses. However, the study highlights the importance of continued vigilance given the potential chronic exposure to PBs from various sources, necessitating ongoing concern despite the absence of immediate risks from tea consumption. [ABSTRACT FROM AUTHOR]

The effects of early-life metal exposure on neurodevelopment in very low birth weight preterm (VLBMP) children (with a birth weight of <1500 g and a gestational age of <37 weeks) have not been clearly established. We aimed to investigate associations of childhood exposure to multiple metals and preterm low birth weight with neurodevelopment among children at 24 months of corrected age. VLBWP children (n = 65) and normal birth weight term (NBWT) children (n = 87) were enrolled from Mackay Memorial Hospital in Taiwan between December 2011 and April 2015. Lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg), and selenium (Se) concentrations in the hair and fingernails were analyzed as biomarkers for metal exposure. The Bayley Scale of Infant and Toddler Development, Third Edition, was used to determine neurodevelopment levels. VLBWP children had significantly lower scores in all development domains compared to NBWT children. We also investigated preliminary exposure levels of VLBWP children to metals as reference values for future epidemiological and clinical survey. Fingernails are a useful biomarker for metal exposure to evaluate the effects on neurological development. A multivariable regression analysis revealed that fingernail Cd concentrations were significantly negatively associated with cognition (β = −0.63, 95% confidence interval (CI): −1.17 to −0.08) and receptive language function (β = −0.43, 95% CI: −0.82 to −0.04) among VLBWP children. VLBWP children with a 10-μg/g increase in the As concentration in their nails had a 8.67-point lower composite score in cognitive ability and a 1.82-point lower score in gross-motor functions. Effects of preterm birth and postnatal exposure to Cd and As were associated with poorer cognitive, receptive language, and gross-motor abilities. VLBWP children are at risk for neurodevelopmental impairments when exposed to metals. Further large-scale studies are needed assess to the risk of neurodevelopmental impairments when vulnerable children are exposed to metal mixtures. [ABSTRACT FROM AUTHOR]

Exposure to a single metal has been reported to damage renal function in humans. However, information regarding the association between multiple-metal exposure and markers for early renal impairment in different sexes among the young adult Taiwanese population is scarce. We assessed the association between exposure to arsenic (As), cadmium (Cd), and lead (Pb), and early renal impairment markers using urinary microalbumin (MA), β2-microglobulin (β2MG), and N-acetyl-beta-D-glucosaminidase (NAG) by analyzing 157 young adults aged 20‒29 years, in Taiwan. Inductively coupled plasma mass spectrometry was used to determine urinary As, Cd, and Pb levels. Regression models were applied to different sex groups. The results showed that after adjusting for potential confounding factors and each metal, urinary Cd levels were significantly positively associated with urinary MA (β = 0.523, 95% CI: 0.147–0.899) and β2MG (β = 1.502, 95% CI: 0.635–2.370) in males. However, the urinary Cd level was significantly positively associated with only urinary NAG (β = 0.161, 95% CI: 0.027–0.296) in females. This study thus indicates that the effect of exposure to metals (especially Cd) on early renal impairment among young adults in Taiwan is sex-specific. Our study results could contribute toward developing early intervention programs for decreasing the incidence of renal dysfunction. Further studies are warranted to confirm our findings and clarify the potential mechanisms involved. [ABSTRACT FROM AUTHOR]

Background. Using conventional esophagogastroduodenoscopy (EGD) to evaluate the infrapapillary area is not feasible. The use of sedative EGD may enable endoscopists to investigate the infrapapillary condition of the duodenum. In this study, we aimed to evaluate lesions in the infrapapillary regions by using sedative EGD. Methods. In this retrospective observational study, we used the data of patients who underwent sedative EGD examinations at a tertiary hospital in southern Taiwan. The endoscopists evaluated the esophagus, stomach, and proximal duodenum and then attempted to explore the infrapapillary portion of the duodenum as deeply as possible. We assessed the success rate for the exploration of infrapapillary areas. Furthermore, we analyzed specific clinical findings of sedative EGD examination. Results. In total, 2973 patients underwent sedative EGD between November 1, 2010, and December 31, 2011. For 2632 of these patients, it was their first sedative EGD examination. In 2511 patients (95.4%), the exploration of the infrapapillary areas was successful. In approximately 10% of the patients, specific findings were detected over the infrapapillary region, and 7 of these patients exhibited clinically significant findings (i.e., gallbladder cancer with metastasis, periampullary Vater adenoma, natural killer cell enteropathy, villous adenoma with moderate dysplasia, infrapapillary duodenal adenoma with dysplasia, duodenal perforation with tumor-like formation, and follicular lymphoma). No patient experienced minor or major adverse reactions during the sedative EGD procedure. Conclusions. The current study provided evidence that sedative EGD examination enables a safe, comfortable, and effective endoscopic examination of deeper sections of the duodenum to evaluate the papillary and infrapapillary regions. [ABSTRACT FROM AUTHOR]

Prenatal and postnatal exposures to heavy metals have been suggested to interfere with neurodevelopment, but the neurotoxicity of lead (Pb), arsenic (As), and cadmium (Cd) is still unclear. In this study, we aimed to assess the associations between the levels of As, Cd, and Pb and children's neurodevelopment. A total of 299 mother–infant pairs were recruited in this study and their meconium were collected. After three years, 53 children underwent the Bayley Scales of Infant and Toddler Development (Bayley-III) examinations and provided hair and fingernail specimens. The levels of As, Cd, and Pb in the meconium, hair, and fingernail were measured by inductively coupled plasma mass spectrometry; the median levels were the following: meconium, 42.7, 5.57, and 25.6 ng/g, respectively; hair, 0.19, 0.05, and 3.61 μg/g, respectively; and fingernail, 0.29, 0.04, and 0.84 μg/g, respectively. After adjusting for potential confounding factors, we found that the log-transformed levels of As in the hair samples was negatively associated with gross motor development (β = − 0.032; 95% confidence interval: − 0.061 to − 0.004). We conclude that postnatal exposure to As is a crucial period for gross motor development in children, while the effects of Cd and Pb on neurodevelopment are less clear. [ABSTRACT FROM AUTHOR]

• G and M levels in foods were analyzed by GC–MS followed by Soxtec extraction. • The highest concentrations of G and M were found in processed fats and cookies. • 58% of palm oil-containing foods exceeded the upper limits of G or M set by the EU. • Packaged foods with palm-derived oils had significantly higher levels of G and M. • Main exposures to G and M were from cookies and instant noodles that exceeded TDIs. Glycidyl esters (GEs) and 3-monochloropropane-1,2-diol esters (3-MCPDEs) are carcinogenic contaminants found in refined oils. This study aimed to determine levels of GEs and 3-MCPDEs in packaged foodstuffs, and estimate daily exposure levels using food consumption data. The analysis involved Soxtec extraction and gas chromatography-mass spectrometry, and the recovery of spiked GEs and 3-MCPDEs was within the range of 80%∼110%. Results showed that GEs and 3-MCPDEs were almost ubiquitous in food products (95%), with the highest concentrations found in processed fats, followed by cookies and spreads. Food products containing palm-derived oils had significantly higher levels of contaminants (p < 0.05), with up to 58.1% of palm oil-containing foodstuffs exceeding the upper limits of either GEs or 3-MCPDEs set by the European Union. Cookies and instant noodles were identified as the main sources of exposure to GEs and 3-MCPDEs, with potential daily intake levels exceeding the tolerable daily intakes in children aged 0 ∼ 12 years. [ABSTRACT FROM AUTHOR]

Drug lag—delayed approval or reimbursement—is a major barrier to accessing cutting‐edge drugs. Unlike approval lag, reimbursement lag is under‐researched. We investigated the key determinants of reimbursement lag under Taiwan National Health Insurance (NHI), and compared this lag with those in the United Kingdom, Canada, Australia, Japan, and South Korea. Using retrospective data on 190 new NHI‐reimbursed drugs from 2007 to 2014, we studied reimbursement lag in Taiwan vs. other countries, and investigated associated factors using generalized linear models (GLMs). The median reimbursement lags during before ("first‐generation") and after ("second‐generation") NHI drug reimbursement scheme in Taiwan were 378 and 458 days, respectively. The "first‐generation" lag was shorter only than that in South Korea, whereas the "second‐generation" lag only exceeded those of the United Kingdom and Japan. In GLM models, higher drug expenditure and the introduction of the "second‐generation" NHI were two statistically significant parameters associated with reimbursement lag among antineoplastic and immunomodulating agents. For other drug classes, the reimbursement price proposed by pharmaceutical companies and use of price‐volume agreements were two statistically significant parameters associated with longer reimbursement lags. The current reimbursement lag in Taiwan is longer than 1 year, but only longer than those of the United Kingdom and Japan. The determinants differ between drug categories. A specific review process for antineoplastic and immunomodulating drugs may expedite reimbursement. There is a clear need for systematic data collection and analysis to ascertain factors associated with reimbursement lag and thereby inform future policy making. [ABSTRACT FROM AUTHOR]

Human biomonitoring (HBM) provides information to identify chemicals that need to be assessed regarding potential health risks to human populations. We established a population-representative sample in Taiwan, namely the Taiwan Environmental Survey for Toxicants (TESTs) in 2013–2016. In total, 1871 participants (aged 7–97 years) were recruited from throughout Taiwan. A questionnaire survey was applied to obtain individuals' demographic characteristics, and urine samples were obtained to assess metal concentrations. Inductively coupled plasma-mass spectrometry was used to determine concentrations of urinary As (total), Cd, Co, Cr, Cu, Fe, Ga, In, Mn, Ni, Pb, Se, Sr, Tl, and Zn. The purpose of this study was to establish the human urinary reference levels (RVs) for metals in the general population of Taiwan. We found that median concentrations of urinary Cu, Fe, Pb, and Zn in males were statistically significant (p < 0.05) higher than in females (Cu: 11.48 vs. 10.00 μg/L; Fe: 11.48 vs. 10.46 μg/L; Pb: 0.87 vs. 0.76 μg/L; and Zn: 448.93 vs. 348.35 μg/L). On the contrary, Cd and Co were significantly lower in males than in females (Cd: 0.61 vs. 0.64 μg/L; and Co: 0.27 vs. 0.40 μg/L). Urinary Cd levels in the ≥18-year-old group (0.69 μg/L) were significantly higher than those in the 7-17-year-old group (0.49 μg/L, p < 0.001). Among the investigated metals, most were significantly higher in the 7-17-year-old group than in the ≥18-year-old group, except for Cd, Ga, and Pb. Participants who lived in central Taiwan had higher median levels of urinary Cd, Cu, Ga, Ni, and Zn than those in other regions. Median levels of urinary As, Cd, Pb, and Se were significantly higher in participants who lived in harbor (94.12 μg/L), suburban (0.68 μg/L), industrial (0.92 μg/L), and rural (50.29 μg/L) areas, respectively, than the others who lived in other areas. RV 95 percentiles of urinary metals (ng/mL) for 7–17/≥18-year-old groups were As (346.9/370.0), Cd (1.41/2.21), Co (2.30/1.73), Cr (0.88/0.88), Cu (28.02/22.78), Fe (42.27/42.36), Ga (0.13/0.12), In (0.05/0.04), Mn (3.83/2.91), Ni (8.09/6.17), Pb (8.09/5.75), Se (122.4/101.9), Sr (556.5/451.3), Tl (0.57/0.49), and Zn (1314.6/1058.8). In this study, we have highlighted the importance of As, Cd, Pb, and Mn exposure in the general population of Taiwan. The established RV 95 of urinary metals in Taiwanese would be fundamental information to promote the reduction of metal exposure or policy intervention. We concluded that urinary levels of exposure to certain metals in the general Taiwanese population varied by sex, age, region, and urbanization level. References of metal exposure in Taiwan were established in the current study. [ABSTRACT FROM AUTHOR]

Background Arsenic exposure is a global health concern. Several studies have focused on chronic arsenic exposure in adults; however, limited data are available regarding the potential adverse effects of prenatal exposure on fetuses and neonates. Objectives To assess which time point maternal arsenic exposure may influence the fetus during pregnancy and birth outcomes. Methods In this study, total arsenic concentrations were analyzed in urine samples collected from 130 women with singleton pregnancies (22–45 years old) in Taiwan from March to December of 2010. All fetal biometric measurements in each trimester period and birth outcomes at delivery were obtained. We applied a generalized estimating equation model and multivariate regression models to evaluate the associations between maternal urinary total arsenic (UtAs) exposure during pregnancy, fetal biometric measurements, and neonatal birth outcomes. Results We observed statistically significant correlations between maternal UtAs levels and the fetal biparietal diameter over all three trimesters (β = − 1.046 mm, p < 0.05). Multiple regression analyses showed a negative association between maternal UtAs levels and chest circumference in the first trimester (β = − 0.721 cm, p < 0.05), and second-trimester UtAs exposure was associated with decreases in birth weight (β = − 173.26 g, p < 0.01), head circumference (β = − 0.611 cm, p < 0.05), and chest circumference (β = − 0.654 cm, p < 0.05). Dose-response relationships were also observed for maternal UtAs exposure and birth outcomes. Conclusions We identified a negative relationship between maternal UtAs levels during pregnancy, fetal development, and neonatal birth outcomes. These findings should be confirmed in future studies with large sample sizes. [ABSTRACT FROM AUTHOR]

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]

Background: Nonylphenol (NP) has been proven as an endocrine disrupter and had the ability to interfere with the endocrine system. Though the health effects of NP on pregnant women and their fetuses are sustained, these negative associations related to the mechanisms of regulation for estrogen during pregnancy need to be further clarified. The objective of this study is to explore the association between maternal NP and hormonal levels, such as estradiol, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and progesterone. Methods: A pregnant women cohort was established in North Taiwan between March and December 2010. Maternal urine and blood samples from the first, second, and third trimesters of gestation were collected. Urinary NP concentration was measured by high-performance liquid chromatography coupled with fluorescent detection. A mixed-effects model using a generalised estimating equation (GEE) was applied to assess the associations between maternal NP concentration and plasma hormones throughout the three trimesters. Results: In total, 162 singleton pregnant women completed this study through delivery. The geometric mean of creatinine-adjusted urinary NP concentrations were 4.27, 4.21, and 4.10 µg/g cre. in the first, second, and third trimesters respectively. A natural log-transformation of urinary NP concentrations were significantly associated with LH in the GEE model (β = −0.23 mIU/ml, p<0.01). Conclusion: This perspective cohort study demonstrates that negative association occurs between maternal NP exposure and plasma LH levels. The estrogen-mimic effect of NP might influence the negative feedback on LH during pregnancy. [ABSTRACT FROM AUTHOR]

• AA exposure and health risk assessment were studied in the general population of Taiwan. • Urinary AAMA levels positively correlated sweetened beverages and oily snacks consumption in the 6–18-year-old group. • Monte Carlo simulation showed that 1.75-19.48% among all age groups exceeded the reference dose of 2 μg/kg-body weight/day. We determined the urinary levels of acrylamide (AA) metabolites of the general Taiwanese population, explore the association between AA internal exposure and dietary intake frequency, and assess the health risk. Urine samples and dietary questionnaires were collected from the subjects of the Nutrition and Health Survey in Taiwan. AA metabolite [ N -acetyl-S-(propionamide)-cysteine (AAMA)] concentrations were analyzed by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-ToF-MS). Multiple regression was used to examine associations between AA metabolite levels and dietary patterns. A total of 706 subjects were studied. We found that per increase in weekly frequency of sweetened beverages in the 6–11-years group (β = 0.322, p = 0.018) and oily snacks intakes in the 12–18-years group (β = 0.335, p = 0.012) will increase 10 β of urinary AAMA concentrations. Assuming that 50% of the AA intake is excreted as urinary AAMA, the Monte Carlo simulation showed that 1.75–19.48% among all age groups have exceeded the reference dose of 2 μg/kg-body weight/day. [ABSTRACT FROM AUTHOR]

Lead (Pb) exposure increases the risks of neurodevelopmental disorders in children. Child-specific activities and land use scenarios may lead to elevated opportunities for Pb exposure through the soil. Therefore, we investigated hair and fingernail Pb concentrations among young children in northern Taiwan, in relation to soil Pb pollution and land use characteristics. We also explored the effect of the Pb exposure burden and land use scenarios on neurobehavioral development. In total, 139 healthy children under 3 years of age were recruited in October 2011 to April 2014. Pb levels in hair and fingernail samples were determined using an inductively coupled plasma/mass spectrometer. Pb concentrations in soils and land use types surrounding the children's homes were accessed by a geographic information system to identify any associations with hair Pb levels. The Bayley Scales of Infant and Toddler Development (Bayley-III) were used to evaluate the cognitive, language, and motor development of the children. A multivariable regression model was performed to assess the effects of soil Pb levels and land-use status on Pb exposure in children, as well as associations of Pb exposure and land-use scenarios with neurodevelopmental abilities. Geometric mean Pb concentrations in hair, fingernails, and soil were 2.9 ± 4.8 μg/g, 0.8 ± 5.1 μg/g, and 20.8 ± 4.3 mg/kg, respectively. The multivariable analysis indicated that soil Pb concentrations and green areas around residences had potential links with Pb exposure among children in northern Taiwan. Hair Pb concentrations were negatively associated with expressive language scores. Soil Pb exposure was positively associated with hair Pb concentrations. Land use types around the children's homes in northern Taiwan were associated with their neurodevelopment. Increased green areas were negatively associated with hair Pb concentrations. Living near a highway may have had negative impacts on gross motor scores. A healthy residence can avoid potential health risks for children during their early life. [Display omitted] • Soil Pb levels were positively associated with hair Pb concentrations. • Soil Pb and green areas surrounding homes had potential links with Pb exposure. • Hair Pb concentrations were negatively associated with expressive language scores. • Living near a highway had a negative impact on gross motor scores. • Healthy residences can avoid potential health risks for children in early life. [ABSTRACT FROM AUTHOR]

Since a 2011 incident involving phthalate-tainted food, Taiwanese people have become concerned with food quality, and they are still being exposed to certain levels of phthalates. However, no nationwide human biomonitoring survey had been conducted to gather information on levels or reference values (RVs) of phthalates in the Taiwanese population. We aimed to establish the urinary levels and RVs of phthalate metabolites and identify exposure characteristics among Taiwan's population. We enrolled 1857 participants 7 years of age and older from the Taiwan Environmental Survey for Toxicants (TESTs) conducted during 2013-2016. Levels of 11 phthalate metabolites in each participant's urine samples were determined using liquid chromatography-tandem mass spectrometry. For all phthalate metabolites except for mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), and mono-ethylhexyl phthalate (MEHP), urinary median levels were significantly higher in the 7-17-year old group than in the ≧18-year-old group. For most phthalate metabolites and in the general population, the geometric mean decreased with increasing age. Median levels of MEP (19.55 μg/L), mono-benzyl phthalate (MBzP) (2.11 μg/L), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (22.82 μg/L), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEOHP) (16.08 μg/L), ΣDibutyl phthalate metabolites (ΣDBPm) (0.17 nmol/mL), Σdi-(2-ethylhexyl) phthalate metabolites (ΣDEHPm) (0.29 nmol/mL) were higher in participants from central Taiwan than those from other areas. The median level of DBP (ΣDBPm: 0.20 nmol/mL) was significantly higher in participants from harbor areas than those from other urbanization groups. The RV of the 95 percentile (P95) for phthalate metabolites in the 7-17/≧18-year-old groups were 185.95/208.19 μg/L for MMP, 198.46/265.81 μg/L for MEP, 119.85/69.99 μg/L for mono-isononyl phthalate (MiBP), 165.19/204.32 μg/L for Mono-n-butyl phthalate (MnBP), 15.61/11.73 μg/L for MBzP, 62.09/59.23 μg/L for MEHP, 149.70/69.66 μg/L for MEHHP, 112.06/35.07 μg/L for MEOHP, 195.20/93.83 μg/L for mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), 45.66/27.69 μg/L for mono-(2-carboxymethylhexyl) phthalate (MCMHP), and 9.09/12.13 μg/L for mono-iso-nonyl phthalate (MiNP). We concluded that phthalate exposure of the general population in Taiwan varies by sex, age, region, and urbanization level. Exposure by the 7-17-year-old group to DMP, DBP, and DEHP in Taiwan remains higher than that of youth from other countries. RV of phthalate metabolites in Taiwan were established in the current study. [ABSTRACT FROM AUTHOR]

No information is available on the long-term effects on thyroid and growth hormones of children exposed to phthalate-tainted products, despite the infamous 2011 Taiwan phthalate episode. We investigated estimated daily intake levels and their long-term effects on serum thyroid and growth hormone levels in children. We recruited 166 children (2–18 years old) in three visits who provided specimens and filled out a questionnaire from the Risk Assessment of Phthalate Incident in Taiwan (RAPIT) project study from 2012 to 2016. Morning spot urine samples were analyzed for nine phthalate metabolites. Serum thyroid (triiodothyronine [T 3 , thyroxine [T 4 , and free T 4) and growth hormone (insulin-like growth factor-1 [IGF-1] and its binding protein 3 [IGF-BP3]) levels were measured. A generalized estimating equation model was used to evaluate associations between phthalate metabolite levels and children's thyroid and growth hormone levels. The median metabolite levels of monomethyl phthalate (MMP), Σdibutyl phthalate (DBP), and Σdi-(2-ethylhexyl) phthalate (DEHP) at visits 1, 2, and 3 were 6.59, 10.5, and 21.0 ng/mL, 0.15, 0.24, and 0.20 nmol/mL, and 0.15, 0.17, and 0.12 nmol/mL, respectively. After adjusting for potential confounding factors, we found that levels of urinary MMP were negatively associated with T 3 (β = −0.013, p = 0.047), T 4 (β = −0.016, p = 0.006), free T 4 (β = −0.012, p = 0.002), and IGF-BP3 (β = −0.025, p = 0.003). Urinary mono-ethyl phthalate (MEP) was negatively associated with IGF-1 (β = −0.027, p = 0.029) and IGF-BP3 (β = −0.016, p = 0.018). In addition, serum free T 4 was positively associated with urinary mono-2-ethyl-5-hydroxy hexyl phthalate (MEHHP) (β = 0.016, p = 0.043), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 0.015, p = 0.024), and ΣDEHPm (β = 0.019, p = 0.020). Our findings support the hypothesis that specific phthalates disturb the hemostasis of thyroid and growth hormone levels in children exposed to phthalate-tainted products. Image 1 • A longitudinal cohort study assessed phthalate exposure and thyroid and growth hormone levels. • MMP was negatively related to T 3 , T 4 , free T 4 , and IGF-BP3. • MEP was negatively related to IGF-1 and IGF-BP3. Capsule : Urinary phthalate metabolite levels are associated with thyroid and growth hormones in children exposed to phthalate-tainted products. [ABSTRACT FROM AUTHOR]

Highlights: [•] A cohort of pregnant women was established and followed until delivery. [•] Maternal NP exposure profile throughout three trimesters was characterized. [•] For multiparas and primiparas, urinary NP levels were not significantly different during gestation. [•] Second-trimester NP level is associated with a risk of low neonatal weight, especially for primiparas. [Copyright &y& Elsevier]

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]

Abstract: Background: Nonylphenol (NP) is an environmental hormone with proven estrogenic effects. Although its adverse effects on animals are well documented, the effects of NP exposure on humans remain unclear, and those on the human foetus are completely unknown. This study explores the effects of intrauterine NP exposure on neonates. Methods: A cohort of pregnant women was established in a medical centre in northern Taiwan. Urine samples from the first, second, and third trimesters of gestation were collected. Urinary NP concentration was measured by high-performance liquid chromatography coupled with fluorescent detection. Neonatal outcomes were evaluated immediately after delivery. A mixed-effects model using a generalised estimating equation was applied to assess the association between gestational age, maternal body weight, and maternal NP concentration throughout the three trimesters. A multivariable regression model was used to determine the association between maternal NP level in urine in each trimester and neonatal outcomes. Results: In total, 162 singleton pregnant women completed this study through delivery. The geometric mean of creatinine-adjusted urinary NP concentrations were 4.27μg/g, 4.21μg/g, and 4.10μg/g in the first, second, and third trimesters, respectively. Pregnant women whose urinary NP concentrations were above the median in the second trimester had low maternal weight gain (β=−1.55kg, p=0.02) and short neonatal body length (β=−0.47cm, p=0.04). Women with an above-median urinary NP concentration had an odds ratio of having a small for gestational age (SGA) neonate of 7.81 (p<0.05). Conclusions: This study indicates that maternal high NP exposure in the second trimester is associated with SGA, decreased foetal body length at birth, and low maternal weight gain. The effects of this endocrine-disrupting substance on pregnant women and foetuses should be a concern during gestation. [Copyright &y& Elsevier]

• Exposure to DEHP increased the risk of early recurrent pregnancy loss. • Cumulative risks indices of phthalate related to early pregnancy loss. • New approaches of hazard index, relative potency and receptor effect posed for female reproduction. Phthalates, which are commonly used in flexible plastics and consumer products, have been reported to be toxic to reproductive and developmental function in mammals. Past studies have focused on the toxic effects on male reproduction, with only a few studies conducted on the risks that cumulative exposure to phthalates have on the female reproductive system. We recruited 260 patients with recurrent pregnancy loss (RPL) of unknown etiology and 203 controls from the clinics of Obstetrics and Gynecology at a medical center in southern Taiwan from 2013 to 2020. The daily intake of phthalates was estimated from urine samples using the back-calculation method, after which the cumulative risk was determined using multiple hazard indices, including a dose-addition model, a receptor effect model, and a hazard index approach. The patients with RPL had a significantly higher cumulative exposure to phthalates (p < 0.05) than did the controls with a hazard index above one. After adjusted logistic regression analysis, we found that the risk of RPL was strongly related to the higher quartiles of DEHP, the DEHP TEQ for the antiandrogenic effect and adverse effects of the female reproductive system and the ER α binding effect (p < 0.05). Our work suggests that more attentions should be paid to the adverse effects induced by phthalates on female reproduction, especially the effects caused by the cumulative exposure to phthalates in women of reproductive age. [ABSTRACT FROM AUTHOR]

Sarcopenia, characterized by muscle loss, negatively affects the elderly's physical activity and survival. Enhancing protein and polyphenol intake, possibly through the supplementation of fermented black soybean koji product (BSKP), may alleviate sarcopenia by addressing anabolic deficiencies and gut microbiota dysbiosis because of high contents of polyphenols and protein in BSKP. This study aimed to examine the effects of long-term supplementation with BSKP on mitigating sarcopenia in the elderly and the underlying mechanisms. BSKP was given to 46 participants over 65 years old with early sarcopenia daily for 10 weeks. The participants' physical condition, serum biochemistry, inflammatory cytokines, antioxidant activities, microbiota composition, and metabolites in feces were evaluated both before and after the intervention period. BSKP supplementation significantly increased the appendicular skeletal muscle mass index and decreased the low-density lipoprotein level. BSKP did not significantly alter the levels of inflammatory factors, but significantly increased the activity of antioxidant enzymes. BSKP changed the beta diversity of gut microbiota and enhanced the relative abundance of Ruminococcaceae &#95; UCG&#95;013 , Lactobacillus&#95;murinus , Algibacter , Bacillus , Gordonibacter , Porphyromonas , and Prevotella &#95; 6 . Moreover, BSKP decreased the abundance of Akkermansia and increased the fecal levels of butyric acid. Positive correlations were observed between the relative abundance of BSKP-enriched bacteria and the levels of serum antioxidant enzymes and fecal short chain fatty acids (SCFAs), and Gordonibacter correlated negatively with serum low-density lipoprotein. In summary, BSKP attenuated age-related sarcopenia by inducing antioxidant enzymes and SCFAs via gut microbiota regulation. Therefore, BSKP holds potential as a high-quality nutrient source for Taiwan's elderly, especially in conditions such as sarcopenia.

Tea is the most frequently consumed beverage worldwide and is obtained from the leaves Camellia sinensis. The traditional way of tea consumption through brewing is gradually being replaced by the consumption of bottled and hand-shaken tea. Despite the different ways of tea consumption, trace elements accumulation and contamination of tea leaves have caused concerns. However, limited studies have reported trace element concentrations in different types of tea in bottled or hand-shaken tea and their health risks. This study aimed to determine the level of trace elements (V, Cr, Co, As, Cd, Pb, Mn, and Zn) in green tea, black tea, and Oolong tea in two varieties of products (bottled and hand-shaken tea). The health risks associated with tea consumption in various age subgroups among Taiwan's general population were also estimated. A Monte Carlo simulation was applied to estimate the distribution of daily trace elements intake through bottled and hand-shaken tea consumption. As to the non-carcinogenic risks, the Monte Carlo simulation showed that hand-shaken green tea had a higher percentage of hazard index (HI) >1 (1.08%~6.05%) among all age groups. As to carcinogenic risks, the Monte Carlo simulation showed that the risks of As exposure from bottled Oolong tea and hand-shaken black, green, and Oolong teas in the 90th percentile in >18 to ≤65 and >65-year-old groups were higher than 10 -6 . The current study findings provided some information about trace elements of both bottled and hand-shaken tea and human health risks in the general population of Taiwan., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Healthcare expenditure on pharmaceuticals, especially innovative oncology drugs, is escalating. Current knowledge on this topic is largely limited to studies conducted upon reimbursement of new drugs. We investigated how endogenous factors (e.g., changed reimbursement criteria, such as an expanded indication) and exogenous factors (e.g., competing drugs) affect the level and trends of innovative oncology drug utilization in the Taiwan National Health Insurance (NHI) system, both upon reimbursement and afterward. This retrospective longitudinal study analyzed monthly data (January 2009 to December 2014) from the NHI Research Database on the consumption (prescribing volume) of 15 innovative oncology drugs reimbursed by the NHI between 2007 and 2013. Effects of endogenous and exogenous factors on drug utilization were evaluated using interrupted time series analyses. In segmented regression analyses, changed drug prescribing volume after the indication expanded (endogenous factor) was statistically significant; however, drug volume did not change significantly after prescription restrictions changed. First-competitors and non-first-competitors (exogenous factors) were significantly associated with drug prescription levels or utilization rates. Taking sorafenib as an example, the post-reimbursement drug prescribing volume did not change significantly after its therapy line changed (endogenous factor), whereas the reimbursement of first-competitors (exogenous factor) was significantly associated with a lower level or usage rate of sorafenib. Utilization of innovative oncology drugs in Taiwan changed dramatically after NHI reimbursement, driven largely by expanded indications and new competitors. Drug utilization evaluations should investigate both endogenous and exogenous factors., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Objective: Cancers result in significant economic burdens on patients, health sectors and society. Reliable burden estimates will help guide resource allocation. This study aimed to perform a nationwide cost analysis of the direct and indirect costs of the top ten most costly cancers, and acute coronary syndrome (ACS), as a comparison, in Taiwan., Setting: A population-based cohort study., Participants: In total, 545 221 patients with newly diagnosed cancer (lung cancer, female breast cancer, colorectal cancer, liver cancer, oral cancer, leukaemia, prostate cancer, non-Hodgkin's lymphoma, gastric cancer and oesophageal cancer) and 170 879 patients with ACS between 2007 and 2014 were identified., Primary and Secondary Outcome Measures: Direct medical costs were calculated from claims recorded in the National Health Insurance Research Database . Indirect costs, comprising morbidity-associated and mortality-associated productivity losses, were estimated from public life expectancy, average wage and employment data. The costs incurred in the 3 years after diagnosis were assessed. As a comparison, the cost of ACS was also estimated using the same study frame. A cost driver analysis was conducted to identify factors impacting cancer costs., Results: The cancers with the highest mean direct medical costs and total costs were leukaemia (US$28 464) and oesophageal cancer (US$81 775), respectively. Indirect costs accounted for over 50% of the total economic burden of most cancers, except for prostate cancer and female breast cancer. The costs of ACS were lower than those of most cancers. From the cost driver analysis, older age at diagnosis significantly (p<0.05) decreased the total cost of cancer; in contrast, male, tumour metastasis, comorbidities and treatment in medical centres increased the costs., Conclusions: This study demonstrates the comprehensive economic burden of the top 10 most costly cancers in Taiwan. These results are valuable for optimising healthcare resource allocation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

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.)

Prenatal exposure and the health effects of that exposure have been intensively studied for a variety of environmental pollutants and trace elements. However, few studies have compared susceptibilities among the three trimesters of gestation. Manganese (Mn) is a naturally occurring and abundant trace element in the environment. Although the effects of Mn on animals are well documented, knowledge of the effects of Mn exposure on pregnant women and fetuses remains limited. A longitudinal study was conducted by collecting blood samples during all three trimesters, and Mn exposure was completely characterized during gestation. The aims of this study were to examine the effects of maternal Mn exposure on neonatal birth outcomes and to explore the critical stage of these effects. In total, 38, 76 and 76 samples were obtained from singleton pregnant women in their first, second and third trimesters, respectively. The cohort of pregnant women was selected at a medical center in northern Taiwan. Erythrocyte samples were collected during the first, second and third trimesters of gestation. Erythrocyte Mn concentrations were measured by inductively coupled plasma mass spectrometry. Neonatal birth outcomes were evaluated immediately after delivery. A multivariate regression model was used to determine the associations between maternal Mn levels in erythrocytes in each trimester and neonatal birth outcomes. The geometric mean concentrations of Mn were 2.93 μg/dL, 3.96 μg/dL and 4.41 μg/dL in the first, second and third trimesters, respectively. After adjusting for potential confounders, a consistently negative association was found between maternal Mn levels throughout the three trimesters and birth outcomes. Log-transformed Mn levels in maternal erythrocytes in the second trimester were significantly associated with neonatal birth weight, head and chest circumferences, respectively (β=-556.98 g, p=0.038; β=-1.87 cm, p=0.045; β=-2.74 cm, p=0.024). Despite the limited sample size in the first trimester, negative effects of maternal Mn levels on birth weight (β=-1108.95 g, p<0.01) and chest circumference (β=-4.40 cm, p=0.019) were also observed., (Copyright © 2014 Elsevier Inc. All rights reserved.)