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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]

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 (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. [ABSTRACT FROM AUTHOR]

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

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

Abstract: The objective of this study was to first evaluate the developmental abnormalities and carry out the molecular analysis of external genitalia in newborn hypospadiac male rats induced by maternal exposure to di-n-butyl phthalate (DBP). Timed-pregnant rats were given DBP by gastric intubation at dose of 750mg/kg body weight (bw)/day from gestation day (GD) 14 to GD18 to establish a hypospadiac rat model. The incidence of hypospadias was 46.67% in male offsprings. On postnatal day (PND) 7, at the newborn stage, decreased body weight and anogenital distance (AGD)/body weight ratio were observed in newborn hypospadiac male rats. The general image and transverse serial histological analysis of genitalia of newborn hypospadiac male rats confirmed the malformation. Autopsy analysis revealed development of reproductive organs (testes, genital tubercle (GT)), hollow organs (stomach, bladder), and solid organs (brain, heart, liver, spleen, lung, kidney, pancreas) in newborn hypospadiac male rats affected by DBP. Moreover, significantly decreased gene expression of important signaling molecules necessary for GT formation including sonic hedgehog signaling molecules (Shh and Ptched 1), bone morphogenetic proteins signaling molecules (Bmp4 and Bmp7), fibroblast growth factor signaling molecules (Fgf8, Fgf10 and Fgfr2), and the transforming growth factor-β superfamily signaling molecules (TGF-β1 and TGF-β receptor III) were observed, for the first time, in the GT of newborn hypospadias induced by DBP. These results showed that the reproductive system and development conditions of newborn hypospadiac rats were damaged by DBP. These disturbed signaling pathways which orchestrating genital development might play an important role in the toxic process of DBP induced hypospadias. [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]