[Analytical methods for urinary biomarkers of human exposure to phthalates]. Huang Chaonan,Li Yun,Peng Junyu,Chen Jiping Se pu = Chinese journal of chromatography Phthalates (PAEs) are a class of endocrine-disrupting chemicals. In recent years, the harmful effects of PAEs on human health, in particular their toxicity toward the reproductive system and development, have received significant attention because of their increasing production and usage. PAEs are ubiquitous in the environment and food products, resulting in unavoidable and long-term exposure in humans. Therefore, exposure and risk assessments of PAEs in humans are necessary. Screening and quantification of phthalate metabolites in urine is an important method for evaluating PAEs exposure, and establishing accurate analytical methods for this purpose has become a high priority. Phthalate monoesters and secondary metabolites are the most commonly targeted biomarkers of exposure to short-and long-chain PAEs, respectively. The combination of off-line or on-line solid phase extraction (SPE) with high performance liquid chromatography-tandem mass spectrometry has become the preferred method for the determination of phthalate metabolites. This paper reviews the analytical methods available for the detection of urinary phthalate metabolites and discusses the advantages, limitations, and challenges presented by each method in practical applications. 10.3724/SP.J.1123.2019.03029
    GC-MS determination of phthalate esters in human urine: A potential biomarker for phthalate bio-monitoring. Babu-Rajendran Ramaswamy,Preethi Gopalakrishnan,Poopal Rama Krishnan,Nikhil Nishikant Patil,Vimalkumar Krishnamoorthi,Subramanian Annamalai,Krishna-Kumar Selvaraj Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Six phthalic acid esters (PAEs) in human urine sampled randomly from three districts (Erode, Thanjavur, and Perambalur) in Tamil Nadu State and a Union Territory (Pondicherry) in India were quantified. We determined gender-wise, age-wise and location-wise distribution of PAEs and measured estrogenic activity of urine by molecular docking. Bis(2‑ethylhexyl) phthalate (DEHP) was the predominant phthalic acid ester found and had a recovery of 104.5% (ultrasonic extraction at 15 min). Gender-wise (pregnant women: 185 ng/mL, children: 156 ng/mL, female: 151 ng/mL, and male: 138 ng/mL), age-wise (1-20 y: 157 ng/mL, 21-40 y: 156 ng/mL, and >40 y: 146 ng/mL), location-wise (urban: 154 ng/mL, and rural: 151 ng/mL), and region-wise (Erode district: 185 ng/mL, Thanjavur district: 155 ng/mL, Perambalur district: 117 ng/mL, and Pondicherry: 135 ng/mL) differences with total mean of Σ PAEs were found. The molecular docking study showed a high negative binding energy of PAEs with microbial receptors. Based on the results we conclude that urine could be used as an ideal biomarker to understand PAEs exposure in humans. 10.1016/j.jchromb.2018.01.039
    Feasibility of ultra-high performance liquid and gas chromatography coupled to mass spectrometry for accurate determination of primary and secondary phthalate metabolites in urine samples. Herrero Laura,Calvarro Sagrario,Fernández Mario A,Quintanilla-López Jesús Eduardo,González María José,Gómara Belén Analytica chimica acta Phthalates (PAEs) are ubiquitous toxic chemical compounds. During the last few years, some phthalate metabolites (MPAEs) have been proposed as appropriate biomarkers in human urine samples to determine PAE human intake and exposure. So, it is necessary to have fast, easy, robust and validated analytical methods to determine selected MPAEs in urine human samples. Two different instrumental methods based on gas (GC) and ultra-high performance liquid (UHPLC) chromatography coupled to mass spectrometry (MS) have been optimized, characterized and validated for the simultaneous determination of nine primary and secondary phthalate metabolites in urine samples. Both instrumental methods have similar sensitivity (detection limits ranged from 0.03 to 8.89 pg μL(-1) and from 0.06 to 0.49 pg μL(-1) in GC-MS and UHPLC-MS(2), respectively), precision (repeatability, expressed as relative standard deviation, which was lower than 8.4% in both systems, except for 5OH-MEHP in the case of GC-MS) and accuracy. But some advantages of the UHPLC-MS(2) method, such as more selectivity and lower time in the chromatographic runs (6.8 min vs. 28.5 min), have caused the UHPLC-MS(2) method to be chosen to analyze the twenty one human urine samples from the general Spanish population. Regarding these samples, MEP showed the highest median concentration (68.6 μg L(-1)), followed by MiBP (23.3 μg L(-1)), 5cx-MEPP (22.5 μg L(-1)) and MBP (19.3μgL(-1)). MMP (6.99 μg L(-1)), 5oxo-MEHP (6.15 μg L(-1)), 5OH-MEHP (5.30 μg L(-1)) and MEHP (4.40 μg L(-1)) showed intermediate levels. Finally, the lowest levels were found for MBzP (2.55 μg L(-1)). These data are within the same order of magnitude as those found in other similar populations. 10.1016/j.aca.2014.09.043
    Toxicological characterization of phthalic Acid. Bang Du Yeon,Lee In Kyung,Lee Byung-Mu Toxicological research There has been growing concern about the toxicity of phthalate esters. Phthalate esters are being used widely for the production of perfume, nail varnish, hairsprays and other personal/cosmetic uses. Recently, exposure to phthalates has been assessed by analyzing urine for their metabolites. The parent phthalate is rapidly metabolized to its monoester (the active metabolite) and also glucuronidated, then excreted. The objective of this study is to evaluate the toxicity of phthalic acid (PA), which is the final common metabolic form of phthalic acid esters (PAEs). The individual PA isomers are extensively employed in the synthesis of synthetic agents, for example isophthalic acid (IPA), and terephthalic acid (TPA), which have very broad applications in the preparation of phthalate ester plasticizers and components of polyester fiber, film and fabricated items. There is a broad potential for exposure by industrial workers during the manufacturing process and by the general public (via vehicle exhausts, consumer products, etc). This review suggests that PA shows in vitro and in vivo toxicity (mutagenicity, developmental toxicity, reproductive toxicity, etc.). In addition, PA seems to be a useful biomarker for multiple exposure to PAEs in humans. 10.5487/TR.2011.27.4.191
    Bisphenol A and phthalates exhibit similar toxicogenomics and health effects. Singh Sher,Li Steven Shoei-Lung Gene Plastics are widely used in modern life, and their unbound chemicals bisphenol A and phthalates can leach out into the surrounding environment. BPA and PAEs have recently attracted the special attention of the scientific community, regulatory agencies and the general public because of their high production volume, widespread use of plastics, and endocrine-disrupting effects. In The Comparative Toxicogenomics Database, BPA and five most frequently curated PAEs (DEHP/MEHP and DBP/BBP/MBP) were found to have 1932 and 484 interactions with genes/proteins, respectively. Five of their top ten toxicity networks were found to be involved in inflammation, and their top ten diseases included genital, prostatic, endomentrial, ovarian and breast diseases. BPA and PAEs were found to exhibit similar toxicogenomics and adverse effects on human health owning to their 89 common interacting genes/proteins. These 89 genes/proteins may serve as biomarkers to assay the toxicities of different chemicals leached out from the widely used plastics. 10.1016/j.gene.2011.11.035
    Co-exposure to polycyclic aromatic hydrocarbons and phthalates and their associations with oxidative stress damage in school children from South China. Yu Yingxin,Peng Mengmeng,Liu Yanlin,Ma Jinjing,Wang Ning,Ma Shengtao,Feng Nannan,Lu Shaoyou Journal of hazardous materials Monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), phthalate metabolites (mPAEs), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine of school children aged 8-11 years from Shenzhen, China were measured in order to investigate oxidative stress damage from co-exposure to PAHs and PAEs. The concentrations of OH-PAHs and mPAEs in urine were 0.36-36.5 (median: 3.86) and 9.48-1609 (median: 240) ng/mL respectively. Gender and age did not influence urinary concentrations of ΣOH-PAHs and ΣmPAEs, but geographical variations (i.e., urban versus suburban) were observed. Levels of 8-OHdG were positively correlated with urinary OH-PAHs and mPAEs, with correlation coefficients (r) varying between 0.160 and 0.365 (p < 0.05). OH-PAHs made a greater contribution to oxidative DNA damage than mPAEs when these two types of pollutants were present at the same concentrations. Human health risks were assessed using the hazard quotient and the hazard index for the cumulative risk of a complex of chemicals. The results demonstrated that risks from PAHs could be neglected, but that 29.5 % of school children may be subject to obvious health risks from PAEs, especially diethylhexyl phthalate. 10.1016/j.jhazmat.2020.123390
    Human exposure to phthalate esters associated with e-waste dismantling: Exposure levels, sources, and risk assessment. Zhang Bo,Zhang Tao,Duan Yishuang,Zhao Zhen,Huang Xiongfei,Bai Xueyuan,Xie Lei,He Yuan,Ouyang Jiping,Yang Yanduo,Wu Yili,Sun Hongwen Environment international Phthalate esters (PAEs) can be released into the environment during the dismantling of electronic waste (e-waste), but urinary levels of PAE metabolites (mPAEs) in humans living in e-waste sites have not been documented. In this study, 11 mPAEs were determined in urine samples collected from participants living in e-waste dismantling sites and a reference area in Southern China. The total urinary concentrations of the 11 mPAEs (∑mPAEs) in the e-waste sites (range: 11.1 ng/mL to 3380 ng/mL) were dominated by mono-(2-isobutyl) phthalate and mono-n-butyl phthalate. Participants living in the e-waste sites had significantly higher (p < 0.05) urinary concentrations of ∑mPAEs (and 5 individual mPAEs) than those in the reference area. Hence, e-waste dismantling activities contributed to human exposure to PAEs. The exposure doses of di-n-butyl phthalate, di(2-ethylhexyl)phthalate, di-iso-butyl phthalate, dimethyl phthalate, and diethyl phthalate were 3.41, 3.04, 1.37, 0.25, and 0.20 μg/kg bw/day, respectively. Furthermore, the health risk assessment in terms of hazard quotient and hazard index showed that approximately 22% of the participants living in the e-waste sites had HI values exceeding 1; importantly, 68% of them were non-adults (i.e., 0-18 years old). In the e-waste sites, 8 of the 11 mPAEs in urine samples had significantly positively associations (r = 0.185-0.358, p < 0.05) with the urinary concentration of 8-hydroxy-2'-deoxyguanosine, a marker of DNA oxidative stress. Therefore, people living in e-waste dismantling areas may have a potential health risk caused by PAE exposure. To the best of our knowledge, this study is the first to measure urinary mPAE levels in people living in e-waste dismantling areas. 10.1016/j.envint.2018.12.035
    Association between phthalate exposure and glycosylated hemoglobin, fasting glucose, and type 2 diabetes mellitus: A case-control study in China. Duan Yishuang,Sun Hongwen,Han Liping,Chen Liming The Science of the total environment Epidemiological studies have shown that exposure to phthalates (PAEs) is associated with type 2 diabetes mellitus (T2DM) and related markers, but limited evidence has been found in Chinese people. Given that China has the highest number of people with DM and Chinese people show relatively higher exposure levels of PAEs, a case-control study was conducted in China to explore the associations of PAE exposure with T2DM and two glycemic indicators, including fasting glucose and glycosylated hemoglobin (HbA1c). Two hundred fifty people with T2DM and 250 controls were recruited in this study. Multivariable logistic regression analyses showed significant positive associations between urinary concentrations of most studied PAE metabolites (mPAEs) and T2DM, with odd ratios comparing extreme mPAEs quartiles ranging from 2.09 to 40.53, whereas two secondary metabolites, mono (2-ethyl-5-carboxypentyl) phthalate and mono [(2-carboxymethyl) hexyl] phthalate showed significant inverse relationships with T2DM. In addition, multivariable linear regression analyses showed that urinary concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate were positively associated with HbA1c levels in controls (β = 0.013; 95% CI: 0.003, 0.023). A significant positive association was also observed for urinary mono (2-ethylhexyl) phthalate and fasting glucose (β = 0.009; 95% CI: 0.002, 0.016). In the stratified analyses, the significant associations of mPAEs with T2DM were more likely to be observed in the younger people, compared to the older people. The significant positive associations between urinary mPAEs and HbA1c levels were more likely to be found in the lower body mass index (BMI) subgroup. Additionally, urinary specific mPAEs were found to be significantly positively related to fasting glucose in males and the older people. The findings suggest that exposure to PAEs is associated with T2DM, fasting glucose, and HbA1c levels in Chinese people and the associations of exposure to PAEs with T2DM, fasting glucose, and HbA1c may differ between sexes, BMIs, or ages. 10.1016/j.scitotenv.2019.03.192