Probabilistic risk assessment for determining nonessential metals in commercial infant formula products in Taiwan.

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.

The occurrence and probabilistic risk of exposure to parabens from bottled and hand-shaken teas in the general adult population of Taiwan.

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.

Plant-based polyphenol rich protein supplementation attenuated skeletal muscle loss and lowered the LDL level via gut microbiota remodeling in Taiwan's community-dwelling elderly.

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_UCG_013, Lactobacillus_murinus, Algibacter, Bacillus, Gordonibacter, Porphyromonas, and Prevotella_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.

Effects of preterm birth and postnatal exposure to metal mixtures on neurodevelopment in children at 24 months of age.

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 (ß = -0.63, 95% confidence interval (CI): -1.17 to -0.08) and receptive language function (ß = -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.

Human biomonitoring reference values, exposure distribution, and characteristics of metals in the general population of Taiwan: Taiwan environmental survey for Toxicants (TESTs), 2013-2016.

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. RV95 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 RV95 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.

Quantitation of α-Dicarbonyls, Lysine- and Arginine-Derived Advanced Glycation End Products, in Commercial Canned Meat and Seafood Products.

Commercial sterilization is a thermal processing method commonly used in low-acid canned food products. Meanwhile, heat treatment can significantly promote advanced glycation end product (AGE) formation in foodstuffs. In this research, the validated analytical methods have been developed to quantitate both lysine- and arginine-derived AGEs and their precursors, α-dicarbonyls, in various types of commercial canned meat and seafood products. Methylglyoxal-hydroimidazolone 1 was the most abundant AGEs found in the canned food products, followed by Nε-(carboxyethyl)lysine, Nε-(carboxymethyl)lysine, and glyoxal-hydroimidazolone 1. Correlation analysis revealed that methylglyoxal and glyoxal were only positively associated with the corresponding arginine-derived AGEs, while their correlations with the corresponding lysine-derived AGEs were not significant. Importantly, we demonstrated for the first time that total sugar and carbohydrate contents might serve as the potential markers for the prediction of total AGEs in canned meats and seafoods. Altogether, this study provided a more complete view of AGEs' occurrence in commercial canned food products.

Monitoring and evaluating the dietary risk of trace elements content in bottled and hand-shaken tea in Taiwan.

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.

Predictive Model for Oral Status in Elderly People in a Taiwanese Nursing Home Using a High-Protein Black Soybean Koji Food.

With increased age, the appetite, chewing, swallowing, and digestive ability gradually decrease. Previous studies have shown that poor oral health is associated with an inadequate intake of macro and micronutrients and malnutrition. Therefore, improving the diet of elderly people and promoting nutrient absorption will help to improve the quality of life for elderly people. However, few studies have predicted their oral ability based on different food textures and other factors. The purpose of this study was to explore the correlation between oral assessment and texture parameters of high-protein black soybean koji products in elderly people in a nursing home. We used cross-sectional study design for seventy-nine residents aged 65 years and older were recruited. Three different texture of cookies, including normal cookie hardness (1.4 × 105 N/m2), minced cookie hardness (4.4 × 104 N/m2), and pureed cookie hardness (1.4 × 104 N/m2) were provided to participants to test the oral status. An oral assessment scale was used by a dentist to evaluate the oral status of the elderly participants. Different cookie textures showed a significant positive correlation with pronunciation (r = 0.237, p < 0.05), face (r = 0.371, p < 0.01), tongue (r = 0.362, p < 0.01), pharynx (r = 0.256, p < 0.05), swallowing (r = 0.272, p < 0.05), breathing (r = 0.315, p < 0.01), and the total oral score (r = 0.339, p < 0.01). We also used the high-protein black soybean koji products combined with elderly people's comprehensions in a predictive model that had a moderately high correlation to predict the oral status in the elderly group (r = 0.612). We concluded that the high-protein black soybean koji product was associated with the oral ability of elderly people in a nursing home in Taiwan. Our findings indicated that elderly people could immediately understand the correct food texture.

Sex-specific differences in early renal impairment associated with arsenic, lead, and cadmium exposure among young adults in Taiwan.

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), ß2-microglobulin (ß2MG), 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 (ß = 0.523, 95% CI: 0.147-0.899) and ß2MG (ß = 1.502, 95% CI: 0.635-2.370) in males. However, the urinary Cd level was significantly positively associated with only urinary NAG (ß = 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.

Associations among prenatal and postnatal arsenic, lead, and cadmium exposures and motor development in 3-year-old children: a longitudinal birth cohort study in Taiwan.

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 (ß = - 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.

Associating acrylamide internal exposure with dietary pattern and health risk in the general population of Taiwan.

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 (ß = 0.322, p = 0.018) and oily snacks intakes in the 12-18-years group (ß = 0.335, p = 0.012) will increase 10ß 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.

Effects of soil lead exposure and land use characteristics on neurodevelopment among children under 3 years of age in northern Taiwan.

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.

Human biomonitoring reference values and characteristics of Phthalate exposure in the general population of Taiwan: Taiwan Environmental Survey for Toxicants 2013-2016.

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.

Cumulative risk assessment of phthalates exposure for recurrent pregnancy loss in reproductive-aged women population using multiple hazard indices approaches.

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 DEHPTEQ for the antiandrogenic effect and adverse effects of the female reproductive system and the ERα 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.

Characterization of phthalate exposure in relation to serum thyroid and growth hormones, and estimated daily intake levels in children exposed to phthalate-tainted products: A longitudinal cohort study.

BACKGROUND: 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. METHODS: 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 [T3], thyroxine [T4], and free T4) 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. RESULTS: 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 T3 (ß = -0.013, p = 0.047), T4 (ß = -0.016, p = 0.006), free T4 (ß = -0.012, p = 0.002), and IGF-BP3 (ß = -0.025, p = 0.003). Urinary mono-ethyl phthalate (MEP) was negatively associated with IGF-1 (ß = -0.027, p = 0.029) and IGF-BP3 (ß = -0.016, p = 0.018). In addition, serum free T4 was positively associated with urinary mono-2-ethyl-5-hydroxy hexyl phthalate (MEHHP) (ß = 0.016, p = 0.043), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 0.015, p = 0.024), and ΣDEHPm (ß = 0.019, p = 0.020). CONCLUSIONS: Our findings support the hypothesis that specific phthalates disturb the hemostasis of thyroid and growth hormone levels in children exposed to phthalate-tainted products.

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.

Urinary thiodiglycolic acid is associated with increased risk of non-alcoholic fatty liver disease in children living near a petrochemical complex.

BACKGROUND: Occupational and experimental studies have revealed that high vinyl chloride monomer (VCM) exposure is associated with non-alcoholic fatty liver disease (NAFLD). Epidemiological study reported that children living near a petrochemical complex have elevated exposure levels of urinary thiodiglycolic acid (TDGA), a potential VCM biomarker. However, no studies on the association of urinary TDGA exposure with NAFLD in children are available. AIM: To assess the association of pediatric NAFLD with urinary TDGA exposure in school-aged children living near a petrochemical complex. MATERIALS AND METHODS: In total, 261 school-aged children (aged 6-13 years) living near a petrochemical complex were recruited during October 2013 to September 2014. First morning spot urine was sampled for analyzing urinary TDGA through liquid chromatography-tandem mass spectrometry. Ultrasonography and serum alanine aminotransferase (ALT) were examined in each participant. NAFLD was diagnosed as recommended by the North American and European Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN and ESPGHAN). Risk for NAFLD with urinary TDGA exposure in children was evaluated using a multivariate logistic regression model. RESULTS: The percentage of children with NAFLDNASPGHAN and NAFLDESPGHAN were 9.6% and 11.5%, respectively. Median levels (µg/g creatinine) of urinary TDGA of children with NAFLDNASPGHAN (vs non-NAFLDNASPGHAN) and NAFLDESPGHAN (vs non-NAFLDESPGHAN) were 118.0 (vs 96.6) and 113.1 (vs 96.5), respectively. Participants in the highest urinary TDGA quartile (Q4: ≥160.0 µg/g creatinine) had a significantly increased risk (odds ratio [OR] = 4.95; 95% confidence interval [CI] = 1.15-21.38; P = 0.032) and dose-response trend (Ptrend = 0.045) for NAFLDNASPGHAN compared with those in the lowest urinary TDGA quartile (Q1: <35.4 µg/g creatinine) after adjustment for age, gender, BMI, triglycerides, HOMA-IR and distance of elementary schools from the petrochemical complex. Participants in the Q4 had borderline significantly increased risk (OR = 3.45; 95% CI = 0.89-13.42; P = 0.074) correlated with NAFLDESPGHAN compared with those in the Q1 after adjustment for confounders. CONCLUSION: Our findings support the hypothesis that children exposed to higher urinary TDGA levels significantly increased pediatric NAFLD risk. Serum ALT levels can be a useful predictor for screening children's NAFLD in field studies. Large and longitudinal studies are warranted to elucidate the association.

Levels and temporal variations of urinary lead, cadmium, cobalt, and copper exposure in the general population of Taiwan.

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.

Association between urinary thiodiglycolic acid level and hepatic function or fibrosis index in school-aged children living near a petrochemical complex.

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 (Q4) 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.

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.