Exposure to Phthalate Esters and the Risk of Endometriosis.

Endometriosis is a common gynecologic disease, worldwide, whose true prevalence is uncertain because it is a difficult disease to diagnose. Endometriosis is a common cause of chronic pelvic pain, dysmenorrhea, and infertility, and is also associated with ovarian cancer. Although the risk factors for endometriosis are unclear, there is increasing evidence that exposure to environmental contaminants, especially phthalates, could affect the pathogenesis of endometriosis. Phthalates are industrial chemicals, used to make flexible plastics, and are present in numerous common plastic products, including medical devices and materials. Several in vitro studies have suggested a positive association between exposure to phthalate, or phthalate metabolites, and the risk of endometriosis. Since the 2000s, studies based on human plasma and urinary concentrations of various phthalate metabolites have been published, but there are still limitations to our understanding of the pathophysiology of phthalates and endometriosis. This report aims to review the current state of knowledge about a possible role of phthalates in the pathogenesis of endometriosis based on cell culture, animal models, and human data.

Kim JH ，Kim SH 《-》

Possible Role of Phthalate in the Pathogenesis of Endometriosis: In Vitro, Animal, and Human Data.

Kim SH ，Cho S ，Ihm HJ ，Oh YS ，Heo SH ，Chun S ，Im H ，Chae HD ，Kim CH ，Kang BM ... -  《-》

Study of possible association between endometriosis and phthalate and bisphenol A by biomarkers analysis.

Endocrine disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) are substances that may interfere with the actions of endogenous hormones and may be associated with estrogen-related diseases such as endometriosis. This paper describes a case-control study to evaluate the relationship between endometriosis and phthalates and BPA exposure, through biomarkers analysis in urine. The biomarkers of exposure analyzed were metabolites mono-methyl phthalate, mono-isobutyl phthalate (MiBP), mono-butyl phthalate, mono-cyclohexyl phthalate, mono-(ethylhexyl) phthalate, mono-isononyl phthalate, mono-octyl phthalate (MOP), mono-benzyl phthalate and BPA. Urine samples were collected from women aged 18-45 years old. The Study group (n = 30) and Control group (n = 22) were composed of women using as criteria confirmation of endometriosis by videolaparoscopy surgery with histological diagnosis and the absence of the disease, respectively. The analytical method used liquid phase microextraction with determination by gas chromatography coupled to mass spectrometry. The concentrations of biomarkers were adjusted by the creatinine concentration in urine samples of the two groups. The values obtained for the Study Group were compared with the values obtained for the Control Group. The chi-square test and Odds Ratio were used to compare dichotomized phthalate metabolites and BPA metabolite by endometriosis. All nine metabolites were found in different concentrations in the urine samples in both groups The phthalate metabolites that had the highest concentrations, were MOP and MiBP, in which the values of 670 μg g-1 and 560 μg g-1, respectively. The relationship between endometriosis and the all grouped metabolites was evaluated, but was not statistically significant with a 95% CI [X2 (df = 1) = 1.471; p = 0.225]. However, odds ratio (95% confidence interval - CI) for MiBP, which was found at relatively high concentrations in the samples, by endometriosis was 1.929 (0.507-7.332). The food habits and gynecologic history were evaluated and no difference was found between groups. Although no evidences of causal link was found, this study contributes to show that other analysis must be done for evaluating the association between endometriosis and compounds suspected of being EDC.

Moreira Fernandez MA ，Cardeal ZL ，Carneiro MM ，André LC ... -  《-》

Changes in urinary excretion of phthalates, phthalate substitutes, bisphenols and other polychlorinated and phenolic substances in young Danish men; 2009-2017.

During the past two decades human exposure to bisphenol A (BPA) and phthalates such as di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP) and di-(2-ethyl-hexyl) phthalate (DEHP) has received substantial interest due to widespread population exposures and potential endocrine disrupting effects. Therefore, these chemicals have gradually been restricted and phased out through legislation. However, humans are still exposed to a wide range of other less studied phthalates, phthalate substitutes and BPA analogues as well as other polychlorinated and phenolic substances. In this study, we investigated human exposure to these chemicals over the past decade. Three hundred urine samples collected in 2009, 2013 and 2017 (100 samples each year) from young Danish men of the general population, participating in a large on-going cross-sectional study, were selected for the present time trend study. The urinary concentration of metabolites of 15 phthalates, di-2-ethylhexyl terephthalate (DEHTP) and di-iso-nonyl-cyclohexane-1,2-dicarboxylate (DINCH), seven bisphenols including BPA, bisphenol S (BPS) and bisphenol F (BPF), as well as triclosan, triclocarban, benzophenone-3, three chlorophenols and two phenylphenols were analyzed by two new sensitive LC-MS/MS methods developed and validated for the present study. A significant decrease in urinary concentrations over time was observed for the majority of the chemicals. Median concentrations of BPA and the metabolites of DiBP, DnBP, BBzP and DEHP were more than halved from 2009 to 2017. Similar decreases were observed for triclosan and the chloro- and phenylphenols. In contrast, metabolites of the two phthalate substitutes DEHTP and DINCH increased more than 20 and 2 times, respectively. The potential BPA substitutes; BPS and BPF also increased, but only slightly. Despite these new exposure patterns, the exposure to the old well-known chemicals, such as DiBP, DnBP, BBzP, DEHP and BPA was still higher in 2017 compared to the exposure level of the new substitutes such as DEHTP, DINCH, BPS and BPF. A significant decrease in internal exposure to most of the common phthalates and BPA over the past decade was observed, reflecting market changes and regulatory measures implemented in EU. Despite increasing exposures to some of the known phthalate substitutes and BPA analogues, the total amount of each measured chemical group (original and substitute analytes combined) was lower in the more recently collected samples. This indicates only partial direct substitution or substitution by chemicals not covered in this approach, or a general decline in the exposure to these chemical/product groups over the last decade.

Frederiksen H ，Nielsen O ，Koch HM ，Skakkebaek NE ，Juul A ，Jørgensen N ，Andersson AM ... -  《-》

Considerable exposure to the endocrine disrupting chemicals phthalates and bisphenol-A in intensive care unit (ICU) patients.

Critical care medicine has largely benefited from plastic-containing medical devices. However, bisphenol-A (BPA) and phthalates present in the plastics can leach from such devices. We hypothesized that intensive care unit (ICU) patients are exposed to BPA and phthalates through (plastic) medical devices. Serum (n = 118) and urine (n= 102) samples of adult ICU patients (n = 35) were analyzed for total BPA and phthalate metabolites (PMs). Our results showed that adult ICU patients are continuously exposed to phthalates, such as di(2-ethylhexyl)phthalate (DEHP), as well as to BPA, albeit to a lesser extent. This exposure resulted in detectable high serum and urinary levels in almost every patient and at every studied time point. Moreover, these levels were significantly higher than in controls or compared to referenced literature. The chronology of exposure was demonstrated: pre-operative urinary and serum levels of the DEHP metabolites were often below the detection limit. Plastic-containing medical devices were the main source of DEHP exposure: post-operative patients on hemofiltration, extracorporeal membrane oxygenation or both showed serum levels 100-or 1000-fold higher than the levels in the general population reported in the literature. The serum and some of the urinary levels of the DEHP metabolites are the highest ever reported in humans; some at biologically highly relevant concentrations of ≥ 10-50 μM. Despite the continuously tightening regulations, BPA and DEHP appear to be still present in (some) medical devices. Because patient safety is a concern in the ICU, further research into the (possibly toxic and clinical) effects of these chemicals released from medical devices is imperiously necessary.

Huygh J ，Clotman K ，Malarvannan G ，Covaci A ，Schepens T ，Verbrugghe W ，Dirinck E ，Van Gaal L ，Jorens PG ... -  《-》