Butyl Benzyl Phthalate Research Articles

Benzyl butyl phthalate (BBP) induces lung injury and fibrosis through neutrophil extracellular traps

Benzyl butyl phthalate (BBP) is an extensively used plasticizer that has aroused widespread concern about its potential toxicity. Previous evidences demonstrate that BBP exposure is associated with asthma and impaired lung function. Accumulating data indicates that neutrophil extracellular traps (NETs), a particular manner of neutrophil death, play a vital role in the pathogenesis of respiratory diseases. However, the immunotoxicity effects of BBP in lung injury are unclear. Here, we aimed to investigate the potential impacts of BBP-induced NETs on lung injury and fibrosis. Mice treated with BBP exhibited significant lung injury, with alveolar hemorrhage, lung edema and increased neutrophil infiltration. Meanwhile, BBP promoted extensive neutrophil infiltration in bronchoalveolar lavage fluid and NETs deposition in lung tissues. Moreover, BBP clearly triggered NETs formation in vitro, which was confirmed by net-like structures decorated with myeloperoxidase and citrullinated histone H3. Furthermore, BBP fueled glucose uptake and ROS burst of neutrophils playing essential roles during NETs formation. Additionally, we proved that NETs could promote fibrogenesis in murine lung epithelial cells and observed lung fibrosis remarkably after BBP-induced injury. Taken together, our findings indicated that exposure to BBP could increase the risk for lung injury and fibrosis by disturbing innate immunity via NETs formation.

Exposure to phthalate esters in Japanese females in Kyoto, Japan from 1993 to 2016: Temporal trends and associated health risks.

Phthalates are used as plasticizers in many products used in daily life worldwide. Due to industrial and economic developments, exposure among general population to phthalates may vary geographically and temporally. However, studies are lacking for investigating temporal changes in phthalate exposure in the Japanese population. In the present study, the temporal trends in exposure to various phthalates were assessed among a group of Japanese adult female population over 1993-2016 and derived associated risks. For this purpose, urine samples of healthy Japanese females in Kyoto, Japan (N=132) collected in 1993, 2000, 2003, 2009, 2011, and 2016, were employed and measured for the concentrations of 18 phthalate metabolites. Over this period, the detection rates of mono(3-carboxypropyl) phthalate (MCPP) and monoisobutyl phthalate (MiBP) decreased, and the geometric means of the urinary concentrations of mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) showed a significant decreasing trend. Cumulative risk due to exposure to dibutyl phthalate (DBP), diisobutyl phthalate (DiBP), butyl benzyl phthalate (BBP), and di-2-ethylhexyl phthalate (DEHP) showed a dramatic decrease only between 1993 and 2000. The maximum hazard quotient (HQM) was attributed to DEHP in most subjects regardless of sampling year. This study showed the temporal trend of the exposure of Japanese females to several phthalate esters over two decades. As of the late 2010's, DEHP was still the predominant component of phthalate ester exposure in the population. The HI value, however, indicates that direct risk due to phthalate exposure was unlikely among the studied population.

Relationships among phthalate exposure, oxidative stress, and insulin resistance in young military soldiers: A cumulative risk assessment and mediation approach.

Epidemiological studies concerning whether oxidative stress mediates phthalate exposure-insulin resistance (IR) associations in young adults are limited. Therefore, we investigated this potential mediation by using a cumulative risk approach involving daily intake (DI) and a hazard index (HIRfD). The participants were 391 Taiwanese military personnel. This study measured their IR (as homeostatic model assessment of estimated IR [HOMA-IR]), levels of oxidative stress biomarkers (8-hydroxy-2-deoxyguanosine, 8-nitroguanine, 8-iso-prostaglandin F2α, and N-acetyl-S-[tetrahydro-5-hydroxy-2-pentyl-3-furanyl]-L-cysteine [HNE-MA]), the sum of these four biomarkers (ΣOS), and urinary phthalate metabolite concentrations. The HIRfD was estimated on the basis of urinary levels of phthalate metabolite, and the DI of five phthalates was determined: dimethyl phthalate, benzyl butyl phthalate (BBzP), diethyl phthalate, dibutyl phthalate (DBP), and di (2-ethylhexyl) phthalate (DEHP). Logistic regression models were employed to explore associations among DI, HIRfD, oxidative stress biomarkers, and HOMA-IR values. The role played by oxidative stress in the phthalate exposure-HOMA-IR association was determined using mediation analysis. We discovered positive associations between high DI of DBP, BBzP, and DEHP; high HIRfD; and high ΣOS. High ΣOS and HNE-MA were associated with a higher likelihood of a high HOMA-IR value. Mediation analysis indicated that high ΣOS and HNE-MA were significant mediators of the associations between phthalates and IR. Oxidative stress may partially mediate the phthalate-IR relationship in young adults.

Occurrence, seasonal distribution, and ecological risk assessment of microplastics and phthalate esters in leachates of a landfill site located near the marine environment: Bushehr port, Iran as a case

Plastic wastes are produced in a large amount everywhere, and are commonly disposed in landfills. So landfill leachate seems an obvious source of microplastics (MPs) and phthalate esters (PAEs) due to a huge usage as plastic additives and plasticizers. But this issue still lacks attention and the present study provides the first information on the levels of MPs and PAEs in the fresh landfill leachate of Bushehr port during different seasons. The mean levels of MPs and PAEs in the fresh leachate in all seasons were 79.16 items/L and 3.27 mg/L, respectively. Also, the mean levels of PAEs in MPs were 48.33 μg/g. A statistically significant difference was detected in the levels of MPs and PAEs among different seasons with the highest values in summer and fall. MPs with a size of >1000 μm had the highest abundance in all seasons. The most prominent shape, color, and type of MPs in the leachate were fibers black, and nylon, respectively. Dibutyl phthalate (DBP) and Di(2-ethylhexyl) phthalate (DEHP) were the most dominant PAEs present in the leachate samples. The results of this study revealed high hazard index (HI) and pollution load index (PLI) of MPs in all seasons. Dioctyl phthalate (DOP), DEHP, DBP, diisobutyl phthalate (DiBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP) represented a high risk to the sensitive organisms. The results of this study showed that significant levels of MPs and PAEs may release into the surrounding environment from the landfill sites without sufficient protection. This issue is more critical when the landfill sites in particular are located near the marine environments like the Bushehr landfill that is located near the Persian Gulf, which can lead to serious environmental problems. Thus permanent control and monitor of landfills, especially in the coastal areas are highly needed to prevent further pollution.

Curcumin-loaded magnetic chitosan-based solid-phase extraction-gas chromatography of migrated phthalate esters from pacifiers and plastic toys into baby saliva

The aim of this study was to investigate the presence of phthalate esters in the saliva of babies who use pacifiers or plastic toys mouthed by them. For this purpose, magnetic micro solid-phase extraction coupled with gas chromatography equipped with a flame ionization detector (GC–FID) was developed. The solid sorbent, curcumin loaded magnetic chitosan (CUR-MCH), successfully synthesized and characterized by FT-IR, FESEM, TEM and VSM. Parameters affecting the extraction efficiency are monitored and optimized through the univariate analysis and experimental design. Under optimum conditions, method presented good linearity [in the range 0.001–5 µg mL−1 for dimethyl phthalate (DMP), din-butyl phthalate (DBP), benzyl butyl phthalate (BBP) and di(2-ethylhexyl) (DEHP)] with coefficient of determination (R2) from 0.9823 to 0.9935 and enrichment factors from 38 to 50. The applicability of the method was examined using real samples from baby's saliva. Saliva samples are collected, extraction procedure performed on them, resultant of extraction injected to GC for separation and quantification of phthalate esters. The results of this study showed that baby accessories made of soft PVC emit phthalate species and contaminate baby's saliva. Among the phthalate species studied, DBP and DEHP are released from polymers more than other species and enter saliva and then the baby's body. Probably more of these two species have been used in the production of these products. Of course, the child's age and ability to chew plastic also play a role.

Urinary concentration of endocrine-disrupting phthalates and breast cancer risk in Indian women: A case-control study with a focus on mutations in phthalate-responsive genes

BackgroundPhthalates are known endocrine-disrupting chemicals used indiscriminately as constituents in consumer products including food processing, and packaging, cosmetics, personal care and household items. Although, few studies have assessed the risk of breast cancer on exposure to phthalates, their association with breast cancer risk in Indian women have not yet been evaluated. MethodsWe conducted a case-control study involving 171 participants. Urinary concentrations of six phthalate dieters; DMP (Dimethyl phthalate), DEP (Diethyl phthalate), DBP (Dibutyl phthalate), BBP (benzyl butyl phthalate), DEHP (Di-2-ethyl-hexyl phthalate), DINOP (Di-n-octyl phthalate) were estimated by GC-MS and geometric means were calculated. Univariate and multivariable logistic regression was performed to assess breast cancer risk on exposure to phthalates. Genes responsive to phthalates were identified through literature search and matched with NGS data, and gene-enrichment analysis was performed. ResultsSignificant associations were observed between urinary phthalate concentrations and increased risk of breast cancer for di-butyl phthalate (OR=1.5, 95% CI; 1.06, 2.11, p = 0.002) and di-2-ethyl-hexyl phthalate (>median vs ≤ median; OR=2.97, 95% CI; 1.18, 7.47, p = 0.005) in multivariable analyses. We also found several phthalate-responsive gene mutations in paired breast tumor tissues, which include PTPRD (76.19%), AR (42.86%), CYP1A1 (42.86%), CYP19A1 (23.81%), AHRR (19.05%), PIK3CA (19.05%), CYP1B1 (9.52%), RB1 (9.52%) and MMP9 (9.52%). Gene-enrichment analysis revealed that these genes form a major part of ER/PR, PPAR and HIF-1α-TGF-β signaling cascades involved in breast cancer ConclusionAlthough the sample size is small, in this first case-control study from India, DBP and DEHP were found to be associated with increased risk of invasive breast cancer and tumor tissues revealed mutations in several phthalate-responsive genes. It is, therefore suggested that human biomonitoring in India and larger studies evaluating the early life genetic and epigenetic alterations on phthalates exposure are required to establish their role in breast carcinogenesis.

Cumulative risk assessment of dietary exposure to phthalates in pregnant women in Beijing, China.

Diet is an important exposure route for phthalates, such as di-iso-butyl phthalate (DiBP), dibutyl phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), and benzyl butyl phthalate (BBP). In this study, we aimed to estimate phthalate exposure in the diet of pregnant women and assess the health risk. A total of 517 pregnant women in the first trimester were recruited, and food frequency questionnaires were collected. A simple distribution assessment method was used to estimate daily exposure, and the hazard index (HI) method was used to assess cumulative risk. The maximum daily dietary exposure to DEHP, DBP, DiBP, and BBP was 5.25, 3.17, 2.59, and 0.58μg/kg bw/day, respectively, and did not exceed the safety limit values. Cereals and vegetables were the main sources of the estimated daily intake (EDI) of phthalates in the diet. The cumulative risk assessment, based on the European Food Safety Authority tolerable daily intake (TDI) and the US Environmental Protection Agency reference dose (RfD), did not exceed the threshold of 1. DiBP, DBP, and DEHP had higher hazard quotient (HQ) values for cumulative health risk than BBP. In conclusion, a low health risk was posed by the cumulative dietary exposure to phthalates for pregnant women in Beijing.

Adsorption Isotherms of Dimethyl Phthalate (DMP), DiEthyl Phthalate (DEP), Dibutyl Phthlate (DBP) and Benzyl Butyl Phthalate (BBP) Compounds in Synthetic and Sembrong River Sediment

Concentrations of Dimethyl Phthalate (DMP), Diethyl Phthalate (DEP), Dibutyl Phthlate (DBP), and Benzyl Butyl Phthalate (BBP) analysis proved present in Sembrong river sediment. These findings occurred during a certain extent of time depending on the properties of sediment and phthalates esters compound. Therefore, adsorption isotherm conducted using optimization method using manipulating variables of initial concentrations and contact times. The results analysis showed higher percentage adsorption recorded in DMP, DEP, DBP and BBP compounds by synthetic sediment which is 88.3%,89.6%,89.0% and 94.8% whereas river sediment is 87.4%,88.4%, 87.1% and 93.4%. The contributing factors aided in the adsorption of PAEs onto synthetic sediment are higher organic content (OC), smaller particle size having larger surface area and higher molecular weight of PAEs. Competitive adsorption occurred between DMP, DEP and DBP as they are low molecular weight compounds. Adsorption isotherms models by Langmuir and Freundlich isotherms models showed separation factor, RL values are favourable from 0.11 to 0.69. Good statistical fit R2 ranged from 0.97 to 0.99 of a good fit. Therefore, in conclusion, Sembrong river sediment is an adsorbent sediment storage of PAEs compounds.

The selected epigenetic effects of phthalates: DBP, BBP and their metabolites: MBP, MBzP on human peripheral blood mononuclear cells (In Vitro)

Phthalates are classified as non-genotoxic carcinogens. These compounds do not cause direct DNA damage but may induce indirect DNA lesions leading to cancer development. In the presented paper we have studied the effect of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), and their metabolites, such as mono-n-butyl phthalate (MBP) and monobenzyl phthalate (MBzP) on selected epigenetic parameters in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with tested phthalates at 0.001, 0.01 and 0.1 μg/mL for 24 h. Next, global DNA methylation, methylation in the promoter regions of tumor suppressor genes (P16, TP53) and proto-oncogenes (BCL2, CCND1) were assessed as well as the expression profile of the indicated genes was analysed. The obtained results have revealed significant reduction of global DNA methylation level in PBMCs exposed to BBP, MBP and MBzP. Phthalates changed methylation pattern of the tested genes, decreased expression of P16 and TP53 genes and increased the expression of BCL2 and CCND1. In conclusion, our results have shown that the examined phthalates disturbed the processes of methylation and expression of tumor suppressor genes (P16, TP53) and protooncogenes (BCL2, CCND1) in human PBMCs.

Quantitative Analysis of Indoor Gaseous Semi-Volatile Organic Compounds Using Solid-Phase Microextraction: Active Sampling and Calibration

Semi-volatile organic compounds (SVOCs) are important pollutants in indoor environments. Quantification of gaseous SVOC concentrations is essential to assess the pollution levels. Solid-phase microextraction (SPME) is considered to be an attractive sampling technique with merits, including simplicity of use, rapid sampling, and solvent free. However, the applications of SPME for sampling gaseous SVOCs are often limited by the fluctuating velocity of indoor air (leading to an unstable sampling rate) and the uncertainties associated with the traditional calibration of SPME. Therefore, we established an SPME-based active sampler to ensure the stable sampling of SVOCs in fluctuating air and developed a two-step calibration method based on the sampling principle of SPME. The presented method and a traditional method (sorbent tubes packed with Tenax TA) were simultaneously used to measure SVOC concentrations in an airstream generated in experiments. Three typical indoor SVOCs, diisobutyl phthalate (DiBP), tris (1-chloro-2-propyl) phosphate (TCPP), and benzyl butyl phthalate (BBzP) were chosen as the analytes. Mean concentrations measured by SPME agreed well with the sorbent tubes (relative deviations <12%), supporting the feasibility of the presented method. Further studies are expected to facilitate the application of the presented method (especially the problem associated with the sampling-tube loss of low volatile SVOCs).

Exposure to phthalates in the sleeping microenvironment of university dormitories: A preliminary estimate based on skin wipe and dust sampling

Since synthetic materials that might contain phthalates are widely used to fabricate bedding and decorating materials, phthalates are typical pollutants in sleeping microenvironments. Although people spend more than 30% of time sleeping, exposure to phthalates in sleeping microenvironments has not been well characterized. In this study, we measured the occurrence of six commonly-used phthalates (dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di-2-ethylhexyl phthalate (DEHP), and di-n-octyl phthalate (DOP)) from skin wipes and settled dust in the sleeping microenvironment of university dormitories. Targeted phthalates were frequently detected (more than 80%) except for DEP (30%–58% and 70% for dermal and dust samples, respectively); and DnBP and DEHP predominated in all samples. Accumulated phthalates on skin surfaces were at similar levels on bare body parts (i.e., hands vs. forearms) during sleeping time. Phthalates in settled dust were significantly correlated with those detected from skin wipes. The estimated average daily intakes of studied phthalates (via inhalation and dermal absorption) ranged from 0.24 μg/kg/day to 1.12 μg/kg/day in the sleeping microenvironment of university dormitories (with the highest doses for DMP and DnBP). Exposure via dermal pathway contributed 38% and 64%, respectively for DMP and DEP, and over 80% for other phthalates during sleeping time. This study provides better understanding of phthalate transport, exposure, and associated control strategies in sleeping microenvironments.

Determination of phthalate acid esters (PAEs) in bottled water distributed in tehran: a health risk assessment study

ABSTRACT In this study, the levels of six PAEs [bis (2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), dimethyl phthalate (DMP) and di-n-octyl phthalate (DNOP)] were determined from four types of bottled water)non-carbonated, mineral, carbonated and carbonated flavoured) using MSPE method (magnetic solid phase extraction) and GC/MS technique (gas chromatography/mass spectrometry). The mean concentration of total PAEs was 6.11 ± 1.43 µg/L. The mean concentration of DEHP was 2.22 ± 0.76 µg/L and was lower than the United States Environmental Protection Agency (USEPA) standard level in drinking water (6 μg/L for DEHP). The highest mean level of total PAE was observed in carbonated water (7.43 ± 2.03 μg/L) and the lowest mean level of total PAE was observed in non-carbonated water (5.15 ± 0.41 μg/L). The Monte Carlo method was applied to calculate the Target Hazard Quotient (THQ), Chronic Daily Intake (CDI), and Incremental Life Cancer Risk (ILCR) indexes. In all samples, the rank order of the estimated THQ values based on the 95% percentile was DEHP (4.77E-4) > DBP (2.25E-5) > BBP (1.99E-5) > DEP (2.75E-6) and there would be unlikely non-carcinogenic risks for consumers (THQ<1). The incremental lifetime cancer risk assessment revealed that phthalate esters (DEHP) in evaluated bottled water samples did not pose a serious concern to humans.

Exposure to phthalates in early pregnancy and the risk of fetal growth restriction: a nested case–control study in a Zhuang Chinese population

Phthalates (PAEs) are common endocrine disrupting chemicals (EDCs) that disrupt fetal development. The present study aimed to evaluate the effects of single and coexposure to phthalates in early pregnancy on fetal growth restriction (FGR) by a nested case-control study based on the Guangxi Zhuang Birth Cohort (GZBC). Maternal serum concentrations of seven phthalates in 97 neonates with FGR and 291 matched controls were detected through gas chromatography-mass spectrometry (GC-MS). The associations between phthalates and FGR were analyzed using multiple logistic regression, weight quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. We found that exposures to butyl-benzyl phthalate (BBP, ORadj = 1.849, 95% CI: 1.080-3.177, Padj = 0.025, Ptrend = 0.046), di (2-ethyl-hexyl) phthalate (DEHP, ORadj = 3.893, 95% CI: 1.305-11.910, Padj = 0.015, Ptrend = 0.098) and dimethyl phthalate (DMP, ORadj = 1.722, 95% CI: 1.089-2.725, Padj = 0.020, Ptrend = 0.002) were significantly positively associated with the risk of FGR, while mono-butyl phthalate (MBP) showed a significant negative association with FGR (ORhigh = 0.192, 95% CI: 0.036-0.795, Padj = 0.033, Ptrend = 0.035) only among girls. The WQS model identified that BBP, di(2-ethyl)phthalate (DEP), DMP, DEHP, di-n-butyl phthalate (DBP), and MBP were highly weighted in the association with FGR. The BKMR model supported the positive association between joint exposure to phthalates and the risk of FGR and identified no significant interaction between the seven phthalates. Overall, maternal exposure to BBP, DEHP, and DMP may cause adverse effects on FGR, especially with combined effects.

Phthalates bioconcentration in the soft corals: Inter- and intra- species differences and ecological aspects

The bioconcentration of dimethyl phthalate (DMP) diethyl phthalate (DEP) dibutyl phthalate (DBP) butyl benzyl phthalate (BBzP), di-(2-ethy hexyl) phthalates (DEHP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-(2-ethy hexyl) phthalate (MEHP) in the soft corals Coelogorgia palmosa, Sinularia sp., Sarcophyton glaucum, and Lobophytum sp. was investigated. Specimens were cultured in a microcosm environment built-up at the Genova Aquarium and analyses were carried out by in vivo SPME-LC-MS/MS. The distributions of the phthalates among the four surveyed species resulted significantly different. Calculated bioconcentration factors (BCFs) showed values spanning over two orders of magnitude, from a minimum of log10 BCFDEP = 1.0 in Sarcophyton glaucum to a maximum of log10 BCFDBP = 3,9 calculated for Coelogorgia palmosa. Moreover, the calculated BCFs of the long chain phthalates resulted up to three orders of magnitude lower than theoretically predicted (from logKow), whereas BCF of short chain phthalates resulted higher. This, together with the detection of phthalic acid monoesters, suggests the presence of species-specific different metabolic transformation among the surveyed soft coral species that involve DEHP.

Non-covalent binding interaction between phthalic acid esters and DNA.

The interaction of phthalic acid esters (PAEs) with DNA is known to be responsible for the disruption of endocrine functions and the teratogenic and carcinogenic effects. However, the binding strength and mechanism of this important process has often been neglected. Here, we confirmed the binding interaction between PAEs and DNA via fluorescence titration quenching experiment. The linear fitting curve proved that PAEs could bind to DNA, and the binding constants (KA) were 4.11×105, 1.04×105, 7.60×104, 1.99×104, and 1.42×103 L/mol for diethyl phthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), dimethyl phthalate (DMP), and benzyl butyl phthalate (BBP), respectively. DNA melting point, UV-vis spectra and Fourier transform infrared spectroscopy (FTIR) analyses revealed that PAEs interact predominantly with thymines in the DNA minor groove. Quantum chemical calculations showed that hydrogen bonding and van der Waals force formation between PAEs and DNA bases dominated the binding interaction. However, PAEs-DNA binding did not induce any DNA conformation change since the circular dichroism and FTIR spectra of B-DNA were not change. The electrostatic surface potential (ESP) might act an important role in PAEs-DNA binding interaction. This work will broaden our understanding of the interaction between PAEs and genetic materials.

Association of childhood rhinitis with phthalate acid esters in household dust in Shanghai residences.

Phthalate acid esters (PAEs) have been identified to be associated with children's health. Present study was conducted to assess associations between PAEs in household dust and childhood rhinitis. Based on phase II of CCHH study (China, Children, Home, Health) conducted in Shanghai, China, 266 indoor dust samples were collected from participants' families. Concentrations of PAEs in dust samples were measured by chemical treatment and gas chromatograph-mass spectrometer. Information about individuals and residences was surveyed by questionnaires. Logistic regression models were applied to obtain the associations between PAEs and childhood rhinitis. Higher concentrations of benzyl butyl phthalate (BBP) were found in those families with children who had diagnosed rhinitis. Significantly higher concentrations of bis(2-ethylhexyl) phthalate (DEHP) and PAEs with high molecular weight (HMW-PAEs) were found in the positive group of lifetime rhinitis. Using the multiple and ordinal logistic regression models adjusted by covariates, dibutyl phthalate (DBP), DEHP, and HMW-PAEs were found to be significantly associated with diagnosed rhinitis. Boys who exposure to higher concentrations of DBP, DEHP, HMW-PAEs, and total PAEs have significant associations with diagnosed rhinitis compared with girls who exposure to lower concentration of PAEs. Present observational study indicated that exposure to high concentrations of DBP, DEHP, and HMW-PAEs in house settled dust was a risk factor for rhinitis for children, especially for boys.

Impact of Storage on Levels of Phthalates in Sachet and Bottled Water Brands in Enugu State, Nigeria

ABSTRACT The determination of phthalate ester concentrations in stored packaged water brands produced in Enugu State was carried out and the health risks evaluated. Packaged water samples were obtained in four batches from six sachet water and six bottled water factories, and stored outdoor for 1 month before analysis, while control samples were obtained and analysed immediately after purchase. Solvent extraction was carried out using dichloromethane, and phthalates concentrations were determined using Gas Chromatography-Mass Spectrometry. The range of limit of detection, recovery analysis and limit of quantitation were 0.001-0.002 mg/L, 81.26–91.47% and 0.003-0.006 mg/L respectively. The concentrations (µg/L) of DMP, BBP, MEHP, DBP and PADHE were<0.002–0.13, 0.41–1.84, <0.002–19.66, 0.76–4.22 and <0.002–0.81 in the bottled water and 0.11–0.36, <0.002–0.43, 0.21–5.75, 0.87–3.28 and <0.002–0.57 in the sachet water. Dimethyl phthalate (DMP) concentrations in the exposed and stored sachet water were significantly higher (P˂0.05) than that obtained from bottled water. There were also significantly higher (P<0.05) concentrations of Diethyl phthalate (DEP), Butyl benzyl phthalate (BBP), Di-butyl phthalate (DBP) and phthalic acid decyl hept-2-yl ester (PADHE), and pH in exposed sachet water than the control. Non-carcinogenic hazard quotient for phthalate esters in the packaged water samples was ˂1, which indicates no carcinogenic health risk. The contribution of individual phthalates to drinking water for Mono-2-ethylhexyl phthalate in both adults and toddlers exceeded the 0.5% TDI in some of the packaged water brands. Results suggest that increased concentrations of phthalate esters in the exposed packaged water samples were as a result of storage temperature, while the presence of phthalate esters in few of the control samples was probably from the packaging process. Although the levels of phthalates were low, regular consumption of packaged water could be detrimental to health of the general populace.

Estrogenic activity and ecological risk of steroids, bisphenol A and phthalates after secondary and tertiary sewage treatment processes

Effluents of sewage treatment plants (STPs) are an important source of estrogenic substances to the receiving water bodies affecting their ecological safety. In this study, steroids, bisphenol A (BPA) and phthalates were assessed in the secondary (SE) and tertiary effluent (TE) of three typical urban STPs in Beijing (China). In addition, the overall estrogenic activity in these effluents was assessed by an in-vitro bioassay (ERE-CALUX). Results showed that the concentrations and activities of estrogenic compounds in TE were lower than those in SE. The residual concentration of 17β-estradiol (E2) was the highest among the detected steroids, accounting for 51.6 ± 5.1% in SE and 57.5 ± 24.8% in TE. The residual level (25.2–41.6 ng/L) of BPA in effluents was significantly higher than that of steroids (0.2–28.8 ng/L). The residual concentration of diethyl phthalate was the highest among the detected phthalates accounting for 47.1 ± 5.1% in SE and 37.6 ± 11.5% in TE. Steroids and BPA had a higher removal rate (83.5% and 96.7%) in secondary and tertiary treatment than phthalates (68.8% and 83.1%). The hydrophobic characteristics of these estrogenic compounds determined the removal mechanism. The removal of steroids, BPA, dimethyl phthalate and diethyl phthalate (LogKow= 1.61–4.15) mainly occurred through biodegradation in the water phase, while the removal of dibutyl phthalate, butylbenzyl phthalate and di(2-ethylhexyl) phthalate (LogKow= 4.27–7.50) mainly occurred in the solid phase after adsorption on and sedimentation of the suspended particulate matter. According to ERE-CALUX, the estrogenic activity in the final STP effluents was 3.2–45.6 ng E2-equivalents/L, which is higher than reported levels in the effluents of European STPs. Calculation of estrogenic equivalents by using substance specific chemical analysis indicated that the dominant contributor was E2 (56.4–88.4%), followed by 17α-ethinylestradiol (EE2) (4.1–34.8%), both also exerting a moderate risk to the aquatic ecosystem. While the upgrade of treatment processes in STPs has efficiently reduced the emission of estrogenic substances, their ecological risk was not yet phased out.

Evaluation of occurrence, fate and removal of priority phthalate esters (PAEs) in wastewater and sewage sludge by advanced biological treatment, waste stabilization pond and constructed wetland

Phthalate Esters (PAEs), detected in high concentrations generally in treated wastewater discharged from wastewater treatment plants (WWTPs), are important pollutants that restrict the reuse of wastewater. Investigating the fate of these endocrine-disrupting chemicals in WWTPs is crucial in order to protect both receiving environments and ecosystems. For this purpose, di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP) and benzyl butyl phthalate (BBP) in the group of PAEs were monitored in simultaneously both in wastewater and sludge lines of selected two nature-based WWTPs and one advanced biological WWTP.Although it was frequently stated that phthalates were significantly removed in WWTPs in many studies found in literature, negative removal efficiencies of selected phthalates in investigated WWTPs during the sampling period were observed generally in this study. One of the reasons for this concentration increase could be releasing of phthalates from microplastics in wastewater during the treatment process or the desorption of PAEs from treatment sludge. DNOP was the compound with the highest concentration increase at almost each treatment unit of the three WWTPs. On the other hand, total PAEs load was 1997 g d−1 in advanced biological WWTP and adsorption onto sludge of PAEs were determined as 90%. The side-stream total load returned from the decanter supernatant was 0.02% of the total PAEs load coming to advanced biological WWTP from the sewer system.As a result of detailed statistical analysis, the correlation between raw wastewater and primary clarifier (PC) effluent was determined as an increasing linear relation for DEHP and DNOP. On the other hand, moderate and strong correlations were observed both between septic tank and constructed wetland (CW) processes with raw wastewater. In the waste stabilization pond (WSP), while a significant correlation was not found between the sludge line data, homogeneous variance, strong and moderate correlations were obtained in the wastewater line data. However, while mean differences for all investigated PAEs were not significant (p > 0.05) in the wastewater line, mean differences of DEHP (p < 0.05) were significant in the sludge line according to ANOVA analysis.

Effects of Pubertal Exposure to Butyl Benzyl Phthalate, Perfluorooctanoic Acid, and Zeranol on Mammary Gland Development and Tumorigenesis in Rats.

Endocrine-disrupting chemicals (EDCs)—including butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and zeranol (α-ZAL, referred to as ZAL hereafter)—can interfere with the endocrine system and produce adverse effects. It remains unclear whether pubertal exposure to low doses of BBP, PFOA, and ZAL has an impact on breast development and tumorigenesis. We exposed female Sprague Dawley rats to BBP, PFOA, or ZAL through gavage for 21 days, starting on day 21, and analyzed their endocrine organs, serum hormones, mammary glands, and transcriptomic profiles of the mammary glands at days 50 and 100. We also conducted a tumorigenesis study for rats treated with PFOA and ZAL using a 7,12-dimethylbenz[a]anthracene (DMBA) model. Our results demonstrated that pubertal exposure to BBP, PFOA, and ZAL affected endocrine organs and serum hormones, and induced phenotypic and transcriptomic changes. The exposure to PFOA + ZAL induced the most phenotypic and transcriptomic changes in the mammary gland. PFOA + ZAL downregulated the expression of genes related to development at day 50, whereas it upregulated genes associated with tumorigenesis at day 100. PFOA + ZAL exposure also decreased rat mammary tumor latency, reduced the overall survival of rats after DMBA challenge, and affected the histopathology of mammary tumors. Therefore, our study suggests that exposure to low doses of EDCs during the pubertal period could induce changes in the endocrine system and mammary gland development in rats. The inhibition of mammary gland development by PFOA + ZAL might increase the risk of developing mammary tumors through activation of signaling pathways associated with tumorigenesis.