Phthalates are a class of environmental endocrine disrupting chemicals which can cause reproductive system damages. However, data about reproductive toxicity spectrum of phthalate metabolites among Chinese women undergoing in vitro fertilization (IVF) treatments are scarce yet. Previous studies regarding underlying embryo toxicities focused on oxidative stress and apoptosis, while energy metabolism abnormality might be another key cause for embryo developmental disruptions. Here, we found that among the measured eight phthalate metabolites, monomethyl phthalate (MMP) had the second highest urinary concentration in women receiving IVF. Compare to the lowest exposure level group, MMP in tertile 3 was associated with fewer counts of oocyte retrieved and good-quality embryos, and MMP in tertile 2 was correlated with reduced good-quality embryo rate. The direct embryo toxicities of MMP were studied using mouse 2-cell embryos. Consistent to results found in human populations, exposure to MMP induced mouse early embryo developmental delay. Furthermore, MMP exposure led to excessive reactive oxygen species production in early embryos, and antioxidant can partially rescue the early embryo development slow down. Embryo apoptosis could also be caused by oxidative stress. To be noted, elevated apoptosis level was not found in live \"slow\" embryos but dead embryos, which suggested that apoptosis was not related to early embryo developmental delay. Additionally, MMP exposure depleted adenosine triphosphate (ATP) synthesis of early embryos, which could be reversed by antioxidant. In conclusion, MMP, as the newly found embryonic toxicant in Chinese women, resulted in early embryo development delay, apoptosis, and energy metabolism disruptions via inducing redox imbalance.

Among the possible causes of hypertension in adolescence, electrolyte imbalances and environmental pollutants are drawing increasing attention. We aimed to examine the relationship between bisphenol A (BPA), phthalate metabolites, and serum electrolytes and blood pressure.
Eighty-six participants aged 12-15 years were included in the study. Body mass index (BMI), office blood pressure and 24-h ambulatory blood pressure measurements (ABPM), and carotid intima-media thickness were determined. Blood samples were taken for hemogram, renal function tests, and serum electrolytes. Free- and total-BPA and phthalate metabolites were analyzed from urine samples.
Of the participants, 34 were evaluated as normal blood pressure profile, 33 as white-coat hypertension (WCHT), and 19 as ABPM-hypertension. Adolescents in ABPM- hypertension groups had higher BMI-standard deviation score (SDS), leucocyte, platelet count; but lower serum chloride, compared to the normal blood pressure profile group. The percentage of adolescents with detectable urinary mono-benzyl phthalate (MBzP) was higher in ABPM-hypertension (42.1%) and WCHT groups (33.3%), compared to the normal blood pressure profile group (5.9%, p = 0.004). Associations between MBzP and ABPM- hypertension and WCHT were remained after confounding factor adjustment. Adolescents with detectable MBzP levels had also higher \"albumin-corrected calcium\" and lower serum phosphate and \"albumin-corrected calcium x phosphate product\" compared to others. Adolescents with detectable urinary MBzP levels had higher blood pressure profiles in some 24-h (mean arterial pressure-SDS, systolic blood pressure-SDS), daytime (systolic blood pressure-SDS), and night-time (mean arterial pressure-SDS, systolic blood pressure-SDS, and diastolic blood pressure-SDS) measurements, compared to others. WCHT was found to be associated negatively with monomethyl phthalate and the sum of dibutyl phthalate metabolites and ABPM-HT with MCPP. There was no significant association between blood pressure profiles and free- and total-BPA status.
MBzP was associated with adverse blood pressure profiles in adolescence. Additive follow-up studies are necessary for cause-effect relations.

Phthalates, a class of widely used endocrine-disrupting chemicals (EDCs), are toxic to various organ systems in animals and humans. Intrahepatic cholestasis of pregnancy (ICP) is a reversible liver dysfunction causing cholestasis in late pregnancy. Evidence on the associations between exposure to phthalates and ICP is still lacking. In the present study, we investigated the relationships between urinary concentrations of phthalate metabolites and the risk of ICP in a Chinese population-based birth cohort. Pregnant women participated in the Ma\'anshan Birth Cohort (MABC) study in China. Seven phthalate metabolites were detected in a urine sample in early pregnancy. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for urine creatinine, race, education, poverty status, smoking status, alcohol consumption, maternal age, prepregnancy body mass index (BMI), parity, twin pregnancy, and pregnancy-related liver complications. Of 3474 women recruited into the Ma\'anshan Birth Cohort, 2760 met the inclusion criteria and contributed to further analysis and biomonitoring data. Elevated odds ratios (ORs) of ICP were observed in the highest quartiles of monomethyl phthalate (MMP) exposure (OR = 1.59, 95% confidence intervals (CI) = 1.01-2.51) and monobutyl phthalate (MBP) exposure (OR = 1.82, 95% CI = 1.16-2.85) in the adjusted analyses. Our findings add to the evidence that supports the role of maternal phthalate exposure in the first trimester of gestation as a risk factor for ICP.

To understand the behavior of dimethyl phthalate (DMP) and realize the effect of DMP and its metabolite, monomethyl phthalate (MMP), on the conformation changes of bovine serum albumin (BSA), the interaction mechanisms of DMP and MMP with BSA were investigated by multispectroscopy and molecular docking. The results of the fluorescence quenching experiment showed that the fluorescence quenching of BSA by DMP and MMP was due to the formation of a complex though static quenching, which was also confirmed by time-resolved fluorescence measurements. The binding constants were 8.06 × 104 M-1 and 4.74 × 104 M-1 for DMP-BSA and MMP-BSA, respectively, and the number of binding sites were 1.20 (DMP) and 1.18 (MMP). The thermodynamic parameters showed different binding forces for DMP and MMP with BSA. The binding of DMP to BSA was driven mainly by hydrophobic interactions and hydrogen bonding, and MMP bound to BSA by van der Waals forces and hydrogen bonding, which were in accordance with the results from the molecular docking. The conformation and structural alterations of BSA upon DMP or MMP binding were studied by UV-vis spectroscopy, circular dichroism spectroscopy and synchronous fluorescence spectroscopy. The presence of metabolite did not change the quenching mechanism but decreased the binding affinity of DMP toward BSA as well as shortened the binding distance, which may be attributed to the competition between DMP and MMP for binding to BSA. This study revealed the combined effects of DMP and its metabolite on BSA at the molecular level.

Some phthalates, parabens and phenols have shown adverse endocrine disrupting effects in animal studies and are also suspected to be involved in human reproductive problems. However, knowledge about exposure sources and biomonitoring data in different subsets of populations are still scarce. Thus, in this study first morning urine samples were collected from 6 to 11 years Danish children and their mothers. The content of seven parabens, nine phenols and metabolites of eight different phthalates were analysed by LC-MS/MS. Two parabens, six phenols and metabolites from six phthalate diesters were measurable in more than 50%, 75% and 90% of the participants, respectively. Thus the children and their mothers were generally exposed simultaneously to a range of phthalates, phenols and parabens. In general, the levels were low but for several of the compounds extreme creatinine adjusted concentrations 100-500-fold higher than the median level were seen in some participants. Children were significantly higher exposed to bisphenol A (BPA) and some of the phthalates (DiBP, DnBP, BBzP, DEHP and DiNP) than their mothers, whereas mothers were higher exposed to compounds related to cosmetics and personal care products such as parabens (MeP, EtP and n-PrP), benzophenone-3, triclosan and diethyl phthalate. However, a very high correlation between mothers and their children was observed for all chemicals. A high individual exposure to one chemical was often associated with a high exposure to other of the chemicals and the possibility of combination effects of multiple simultaneous exposures cannot be excluded.

Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007-2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6-49 year old survey respondents (n=3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age×creatinine, age×sex and fasting status×creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP. The least square geometric mean (LSGM) estimates for volumetric concentration (μg/L) of the metabolites derived from respective regression models were used to assess the patterns in the metabolite concentrations among population sub-groups. The results indicate that children had significantly higher urinary concentrations of MnBP, MBzP, MEHP, MEHHP, MEOHP and MCPP than adolescents and adults. Moreover, MEP, MBzP, MnBP and MEOHP concentrations in females were significantly higher than in males. We observed that fasting status significantly affects the concentrations of MEHP, MEHHP, MEOHP, and MCPP metabolites analyzed in this study. Moreover, our results indicate that the sampling time could affect the DEHP metabolite concentrations in the general Canadian population.