Next Article in Journal
Co-Application of Silicate and Low-Arsenic-Accumulating Rice Cultivars Efficiently Reduces Human Exposure to Arsenic—A Case Study from West Bengal, India
Previous Article in Journal
Intrauterine and Neonatal Exposure to Opioids: Toxicological, Clinical, and Medico-Legal Issues
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Toxics
Volume 11
Issue 1
10.3390/toxics11010063
toxics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Assessment of Xenoestrogens in Jordanian Water System: Activity and Identification

by
Yazan Akkam
1,*,
Derar Omari
2,
Hassan Alhmoud
2,3,
Mohammad Alajmi
4,
Nosaibah Akkam
5 and
Islam Aljarrah
1
1
Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan
2
Department of Pharmaceutical Technology and Pharmaceutics, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan
3
Faculty of Pharmacy, Jerash University, Irbid 26110, Jordan
4
Department of Law and Science Department, Kuwait International Law School, Doha 93151, Kuwait
5
Department of Anatomy and Cell Biology, Faculty of Medicine, Universität des Saarlandes, 66424 Hamburg, Germany
*
Author to whom correspondence should be addressed.
Toxics 2023, 11(1), 63; https://doi.org/10.3390/toxics11010063
Submission received: 26 December 2022 / Accepted: 4 January 2023 / Published: 9 January 2023
(This article belongs to the Section Ecotoxicology)
Browse Figures
Versions Notes

Abstract

:
Sex hormone disruptors (xenoestrogens) are a global concern due to their potential toxicity. However, to date, there has been no study to investigate the presence of xenoestrogen pollutants in the Jordanian water system. Samples in triplicates were collected from six locations in Jordan, including dams, surface water, tap or faucet water, and filtered water (drinking water—local company). Xenoestrogens were then extracted and evaluated with a yeast estrogen screen utilizing Saccharomyces cerevisiae. Later, possible pollutants were mined using ultrahigh-performance liquid chromatography (UPLC) coupled with a Bruker impact II Q-TOF-MS. Possible hits were identified using MetaboScape software (4000 compounds), which includes pesticide, pharmaceutical pollutant, veterinary drug, and toxic compound databases and a special library of 75 possible xenoestrogens. The presence of xenoestrogens in vegetable samples collected from two different locations was also investigated. The total estrogen equivalents according to the YES system were 2.9 ± 1.2, 9.5 ± 5, 2.5 ± 1.5, 1.4 ± 0.9 ng/L for King Talal Dam, As-Samra Wastewater Treatment Plant, King Abdullah Canal, and tap water, respectively. In Almujeb Dam and drinking water, the estrogenic activity was below the detection limit. Numbers of identified xenoestrogens were: As-Samra Wastewater Treatment Plant 27 pollutants, King Talal Dam 20 pollutants, Almujeb Dam 10 pollutants, King Abdullah Canal 16 pollutants, Irbid tap water 32 pollutants, Amman tap water 30 pollutants, drinking water 3 pollutants, and vegetables 7 pollutants. However, a large number of compounds remained unknown. Xenoestrogen pollutants were detected in all tested samples, but the total estrogenic capacities were within the acceptable range. The major source of xenoestrogen pollutants was agricultural resources. Risk evaluations for low xenoestrogen activity should be taken into account, and thorough pesticide monitoring systems and regular inspections should also be established.

1. Introduction

Water treatment and pollution are major concerns worldwide, i.e., heavy metals and (recently appearing) estrogen and xenoestrogen pollutants. Xenoestrogens are estrogen mimics [1]. Many xenoestrogens found in the waterways, both natural and synthetic, can mimic or disrupt the natural estrogens found in humans and animals [2,3,4]. Estrogenic chemicals of varying potency and persistence originate from agriculture, industry, humans, household products, and pharmaceuticals [5].
Xenoestrogens as well as estrogen pollutants are not completely removed during the process of sewage treatment and are carried over into the general aquatic environment. After ground passage, they can eventually be found in drinking water [6,7,8,9]. Although the concentration of these compounds is very low in the water, it has been identified as the main cause of hormonal disruption in wildlife [7,10,11].
Xenoestrogens are widely diffused in the environment, water, and in food, and thus a large portion of the human population is exposed to them worldwide [12]. Xenoestrogens have been linked to several human diseases, such as testicular dysgenesis syndrome [13], hypospadias [14], testicular cancer [15,16], breast cancer [17], endometriosis [18], birth defects [19], decreased sperm counts [20], and others [21,22,23,24].
The scarcity of water is the greatest challenge that Jordan faces. On a per capita basis, Jordan has one of the lowest levels of water resources in the world. In addition, the situation has been exacerbated by periodic massive influxes of refugees, worsening the imbalance between population and water. Despite the presence of some surface water supplies, collectible rain is the main source of water in Jordan via dams, rivers, lakes, and groundwater [25]. To collect rain, the water should run off across long-distance interactions and be exposed to various xenoestrogens.
The pollution of estrogen and xenoestrogen in Jordan should be taken seriously, especially after it has been detected and determined in several places around Jordan, including Mediterranean coastal water [26], Jordan Valley soil [27,28], and the Jordan River [28]. In one study, estrogen was detected in 85% of the samples along the Jordan River at risk concentrations [28]. However, to date, there has been no research to test the presence of sex hormone disruptors (xenoestrogen and xenoandrogen) pollutants in the Jordanian water system.

2. Materials and Methods

2.1. Chemicals

Chemicals were purchased from Sigma-Aldrich, and 17-β-estradiol stock solutions were prepared in methanol (1 µg/µL) and stored at −20°C.

2.2. Sample Locations

The water system in Jordan is complex and composed of surface water (rivers, streams, dams) and groundwater basins (Figure 1). The Jordanian water system was discussed in detail previously [29,30,31,32]. Due to the government constraints that restrict access to water resources, the Ministry of Water and Irrigation determined the quantity and location of collected samples. Samples were collected in triplicate according to the following Table 1 and map (Figure 2).

2.3. Sample Collection

Water sample collection was conducted as described previously [34]. All glassware was washed twice with methanol, then distilled water, and baked at 180 °C for 4 h. Samples were collected in 2 L precleaned amber glass bottles containing 0.5 g of copper (II) nitrate and 6 mL of 3.6 M hydrochloric acid solution before being stored at 4 °C in the dark. To enhance the solubility of the lipophilic pollutants, 5% methanol was added to the samples. All samples were collected from the edge of the canal or dam from a deep point of around 1 m. Two other samples were also studied: tap water and drinking water. Tap water was collected from Irbid and Amman. The term “drinking water” refers to water sold at purifying stations that began with tap water. The vegetables were purchased from the local market in Irbid.

2.4. Sample Preparation

2.4.1. Water

Samples were filtered through glass fiber or glass wool (pore sizes of 0.3–1.2 µm) before solid-phase extraction was carried out. The filtered samples were loaded with a flow rate of 5.5–6 mL/min into reactivated reversed-phase C-18 cartridges (8 mL methanol, and then 8 mL of water:methanol solution (95:5). Later, the cartridges were washed with 10 mL of methanol in water (1:1), followed by 10 mL of acetone in water (1:2).
There were two methods: one for the analysis using yeast estrogen assay (YES) and the other for liquid chromatography–mass spectrometry (LC-MS) analysis.
Samples for YES: 100 µL DMSO was added, and the acetone and methanol were evaporated under a gentle stream of nitrogen.
Samples for LC-MS screening: samples were dried under nitrogen gas (99.99%), reconstituted in 100 μL methanol, completed to 50 mL by acetonitrile, and then centrifuged at 4000 rpm for 2.0 min. Finally, 1.0 mL of the sample was transferred to the autosampler.

2.4.2. Vegetables

The sample preparation was conducted via salting-out assisted liquid–liquid extraction (SALLE) as described previously [35]. Five milliliters of the sample solution was spiked with a standard solution containing the target analytes and transferred to a 15 mL screw-capped test tube. The pH of the solution was adjusted to 7.4 by adding 0.1 M NaOH, followed by 2.40 mL acetonitrile and 1.6 g NaCl. Following that, the solution was gently shaken for 2 min before being centrifuged at 4000 rpm for 5 min to cause phase separation. The upper organic phase was then carefully withdrawn with a 1 mL microsyringe. This volume was approximately 100 ± 25 µL, which was poured into a vial to avoid an anomalous peak in the HPLC chromatogram. A nitrogen stream was blown at this stage to dry it at room temperature. The final residue was reconstituted to a volume of 100 µL using a mobile phase, shaken for 2 min, and filtered through a 0.2 µm nylon filter before being injected into the HPLC system.

2.5. Yeast Screening Assays

Assays were conducted as described previously [36,37,38,39] using yeast-based microplate assay (XenoScreen YES/YAS, Xenometrix, Switzerland). Briefly, minimal medium and medium components were prepared according to the manual. Cells were incubated with serially diluted substances and positive control (17-β estradiol for YES assay) for 48 h at 32 °C in the presence of a substrate for β-galactosidase synthesis. All tested samples and the color change and growth of yeast were quantitatively measured using a BioTek Synergy HTX microplate reader at 570 and 690 nm wavelength, respectively. The results were evaluated in terms of the agonistic and antagonistic effects of estrogen. In addition, the cytotoxic effect was evaluated for the test compound by testing the optical density of each well (λ = 690 nm). Assessment of estrogen–androgen activity was performed for the samples at eight dilution levels. Each assay was repeated three times.

2.6. Data Analysis

Data analysis was conducted as described previously [40]. Dose–response curves were graphed, and then EC50 and IC50 values were calculated for those compounds that exhibited a complete dose–response curve. The agonistic endocrine activity was considered if the tested sample had an induction of at least 10% of the difference between the maximum E2 response and solvent control in agonist assay. The E2 equivalents corresponding to the measured concentrations were calculated as follows: 5 ng/L of E2 is equal to 1 relative activity in the YES assay. One-way ANOVA was performed for the analysis of the variance first, followed by Dunn’s test (if a significant difference was found). Statistical analysis was conducted using GraphPad Prism 5.00 (GraphPad Software, San Diego, CA, USA.

2.7. LC-MS/MS Analysis

All samples were analyzed using LC-MS/MS. Assays were conducted as described previously [36]. For analysis, Elute UHPLC coupled with a Bruker impact II QTOFMS (Bremen, Germany) was used. Chromatographic separation was performed using Bruker solo 2.0C-18 UHPLC column (100 mm × 2.1 mm × 2.0 μm) at a flow rate of 0.5 mL/min and a column temperature of 40 C. The solvents were (A) water with 0.05% formic acid and (B) acetonitrile. A linear gradient from 5% to 80% B over 27 min, followed by two min 95% B. The total analysis time was 35 min in positive and 35 min in negative mode and the injection volume was 3 µL.
The instrument was operated using the Ion Source Apollo II Ion Funnel electrospray source. The capillary voltage was 2500 V, the nebulizer gas was 2.0 bar, the dry gas (nitrogen) flow was 8 L/min and the dry temperature was 200 °C. The mass accuracy was ˂1 ppm, the mass resolution was 50,000 FSR (full-sensitivity resolution) and the TOF repetition rate was up to 20 kHz.
Standards for identification of ms/z with high-resolution Bruker TOF MS and the exact retention time of each analyst after chromatographic separation was used. Later, all possible hits were identified using MetaboScape software (more than 4000 compounds) which includes a list of potential pharmaceutical pollutants, a list of potential veterinary drug pollutants, a list of potential insecticides, pesticides, and herbicides pollutants, and an additional special library (constructed from chemicals reported in the literature) of possible xenoestrogens. All pollutants are listed in Supplementary Material S1–S4. The detection of xenoestrogens in tap water were used as a model for the LC-MS experiment.

3. Results and Discussion

3.1. Study Area

Due to the governmental restriction from the Ministry of Water and Irrigation, the research was restricted to designated sites: two dams (King Talal Dam and Almujeb Dam), one wastewater treatment plant (As-Samra), and one canal (King Abdullah canal). King Talal Dam’s (the largest dam in Jordan) main purpose is to retain winter rainfall and treated wastewater processed at the As-Samra Wastewater Treatment Plant and is used for domestic, agricultural, and industrial uses and to control floods, improve drainage, and collect water from rivers and streams [41,42], while Almujeb Dam only collects rainwater and is used for domestic, industrial supply and irrigation [43]. As-Samra Wastewater Treatment Plant was built to improve the quality of water in Jordan. It treats wastewater released from the Zarqa River Basin. Moreover, the facility treats an average flow of 267,000 m3 of wastewater, serving a population of 2.2 million living in the Amman and Zarqa areas [44]. King Abdullah Canal is Jordan’s most important source of drinking and agricultural water. The canal is approximately 110 km long, with a head discharge capacity of 20 m3/s and a tail discharge capacity of 6 m3/s. [45]. Dair Alla Station is responsible for pumping water from the canal to Amman [45].

3.2. Estrogenicity in Water Samples

The estrogenic activity via yeast screening assay of each water sample measured as 17β-estradiol relative estrogenicity is summarized in Table 2. The relative estrogenic activities of all samples were comparable to those of other yeast assays [28,46,47,48].

3.2.1. Tap Samples

Jordan’s primary sources of tap water are surface water and groundwater wells [49]. For example, 45% of tap water in Amman comes from the Disi aquifer, 29% from the Zay treatment plant, which uses water from the King Abdullah Canal, 16% from the Zara treatment plant, which uses water from the Almoujib Dam, and 10% from a network of subterranean wells [50].
The relative estrogenicity of tap water (1.4 ± 0.9 ng/L) is lower than that reported in other countries [51,52,53,54]. According to reports, such concentrations do not constitute an immediate, acute health risk to the community [51,55]. However, the potential long-term impact of xenoestrogens on human health and the environment at low concentrations is yet to be elucidated [56]. Hence, xenoestrogens have been categorized as an “unquantified risk” [55]. The World Health Organization (WHO) has reported that xenoestrogens in such low concentrations are potentially less harmful to human health, but emphasized the necessity to limit the existence of such compounds in the water [56,57].
In the LC-MS experiment, a high-resolution database included exact mass data for parent ions, adducts, fragment ions as well as isotopic pattern and retention time. Figure S1 represents the base peak chromatogram (all MS and bbCID) for samples from both Irbid and Amman. The complete spectrum list of (Dissect and bbCID) for both Amman and Irbid are shown in Tables S1 and S2, respectively. However, only 34 compounds were identified as potential xenoestrogen or estrogen disturbances (Table 3). It is worth mentioning that around 100 compounds are still unknown in each sample.
The potential source of each xenoestrogen (as shown in Table 3) was classified into three main categories: agricultural, industrial, and pharmaceutical. In tap water, agricultural sources accounted for the majority of xenoestrogens (>70%), which include pesticides and fungicides, as shown in Figure 3. Between Amman and Irbid, minor variations were spotted, mostly in the pharmaceutical sector (such as sunscreens). According to the chemical structures of identified xenoestrogens, 94% of them were either aromatic or polycyclic with low water solubility, with only prochloraz and pregabalin exceptions. Moreover, only three of the identified xenoestrogens contained steroid rings (betamethasone, hydrocortisone, and protopanaxadiol).
The presence of xenoestrogens might result from either direct contact with water at the source, pipeline, or reservoir, or from by-products of water treatment. Jordan’s water supply network is plagued by issues such as seepage inside distribution pipe systems and intrusions (illegal use). In both circumstances, an interaction between xenoestrogens and tap water is feasible [31]. It appears that the majority of the purposeful sabotage of the water network occurred in agricultural areas, which may explain the prevalence of pesticides and fungicides. Furthermore, water losses in the Jordanian system were estimated at 50% [31].
In Jordan, water is disinfected using various disinfectants (such as chlorine), which may cause interactions with organic matter to produce disinfection by-products (halocarbon compounds) [92]. Natural organic matter (NOM) is an enormously complicated mixture of organic molecules with widely varying physical and chemical properties. NOM is both a natural occurrence in the environment and a by-product of human activity. NOM is present in particle, colloidal, and dissolved states in all ground and surface waters, including rainwater [93]. Furthermore, the infrequent usage of pipelines facilitates such reactions, particularly at the periphery networks (6 h per week). Seven halocarbon xenoestrogens were identified in the tap water samples (Table 3).

3.2.2. Surface Water

The data show that open-source water has estrogenic activity of 2.5–9.5 ng/L and is not far from most countries in the world, including bordered countries [28,46,47,48]. It has been reported that the estrogenic activity of surface water typically should be below 25 ng/L, including the effluent of the water treatment plant [94,95].
Raw wastewater has different characteristics in Jordan from most other countries. According to reports, Jordan’s wastewater is very strong, highly salinized, contains heavy metals, and contains toxic organic compounds. Furthermore, Jordan’s raw wastewater contains large organic contents resulting from low home water consumption and industrial waste [96].
The estrogenic activity of the effluent of As-Samra treatment plant was 9.5 ± 5 ng/L. This value is not far from recorded around the world. For instance, the estrogenic activity was 0.4–6.6 ng/L in England, 5–10.6 ng/L in the USA, 5.6–11 ng/L in Germany, 2.9–7.5 ng/L in Italy, 17.9 ng/L in Switzerland and 29–65 ng/L in Brazil [95,97,98]. According to reports, estrogenic activity in treatment plant effluent is deemed high enough to cause issues with public health if it exceeds 15 ng/L [99]. Hence, there are no xenoestrogen threats from the water treatment plant. However, it has been reported that As-Samra treatment plant needs further improvements [100]. More about the concentration of estrogenic activity in the surface water is found in a review [101].
The distribution of detected xenoestrogens sources in the open-source water is shown in Figure 3. Still, agricultural resources are the main source of xenoestrogens with 58%. The potential xenoestrogens in each site are summarized in Table 4; nonetheless, more than 100 compounds remained unidentified in each sample. The number of detected xenoestrogens was 12, 18, 23, and 30 for Almujeb, King Abdullah Canal, King Talal Dam, and As-Samra treatment plant, respectively. According to the chemical structures of xenoestrogens, 97% of them are aromatic with low water solubility. Only pregabalin is the exception. Moreover, no xenoestrogens containing steroid rings were detected in the samples, which implies there is no direct pollution from pharmaceutical drugs.
It is clear that Almujeb water has the least detected compounds and that may be explained by the location, where the dam and collected water are far from human pollution, such as heavy traffic and industrial areas [102]. Therefore, the estrogenic activity was below the detection limit.
On the other hand, King Talal Dam has easy access to people and is located in a crowded place surrounded by farms and agricultural areas. Furthermore, the dam retained the treated wastewater processed in the As-Samra Wastewater Treatment Plant. Hence, the pollutants from residents around the dam, the farms, and the treated wastewater augment the pollution in King Talal Dam. This may explain the presence of herbicides, pharmaceutical compounds, and natural products.
It has previously been claimed that some chemicals, such as phenolic compounds, may be released from the pharmaceutical sector or other companies engaged and located in King Talal Dam’s catchment area [103]. Moreover, it has been reported that more than 100 organic compounds were detected using GC-MS at various concentrations in King Talal Dam. The reported compounds fit well with our findings [103]. Furthermore, it has been reported that King Talal Dam has alarming biological pollution [103].
In case of King Abdullah Canal, residents toss waste and trash into and around it, and the presence of intermittent gatherings of migrant workers who live in the neighborhood exacerbates the problem. The continuous dumping of waste and its accumulation may explain the presence of such pollutants in the canal. Moreover, previous incidents of contamination have been reported [29]. It has been reported that the water canal is not safe for domestic use and needs further treatment, especially in the lower part of the canal [45].
A possible explanation for the low level of xenoestrogens in all samples is that the sample collections were conducted during the winter, which may dilute the xenoestrogens. In addition, degradation, evaporation, and adsorption are potential mechanisms contributing to lowering the activity of xenoestrogens [44].
Table
Table 4. Detected xenoestrogens in open surface water.
Table 4. Detected xenoestrogens in open surface water.
Expected CompoundAs-Samra King Talal DamAlmujeb DamKing Abdullah CanalOrigin 3Ref. 2Chemical Structure 1
3 5 6-Trichloro-2-pyridinol (TCPy) YesYesYesYesPesticide[104]Toxics 11 00063 i035
Isoferulic acidYes---Natural products[105]Toxics 11 00063 i036
AcacetinYesYesYes-Natural products[106]Toxics 11 00063 i037
5-Hydroxy MebendazoleYes---Pharmaceutical[107]Toxics 11 00063 i038
Acetamiprid---YesPesticide[108]Toxics 11 00063 i039
Alpha-zearalenolYesYesYesYesNatural product[109]Toxics 11 00063 i040
Bisphenol A YesYes-YesPolycarbonate plastic[65]Toxics 11 00063 i041
Caffeic Acid Yes-Yes-Natural products[110]Toxics 11 00063 i042
carbamazepine YesYes-YesPharmaceutical[111]Toxics 11 00063 i043
CarbendazimYes---Fungicide[67]Toxics 11 00063 i044
CotinineYes---Metabolite[112]Toxics 11 00063 i045
Diazinon-Yes--Pesticide[113]Toxics 11 00063 i046
DibutylphthalateYesYesYesYesPlasticizer[114]Toxics 11 00063 i047
DicofolYesYes--Pesticide[115]Toxics 11 00063 i048
FenamiphosYesYes-YesPesticide[116]Toxics 11 00063 i049
FerimzoneYesYesYesYesPesticide[117]Toxics 11 00063 i050
FerutinineYesYesYesYesNatural product[75]Toxics 11 00063 i051
HalofenozideYesYes-YesPesticide[118]Toxics 11 00063 i052
HexazinoneYesYesYesYesPesticide[119]Toxics 11 00063 i053
IsobavachinYesYesYesYesNatural product[120]Toxics 11 00063 i054
IsosakuranetinYesYes-YesNatural product[121]Toxics 11 00063 i055
LevamisoleYes---Pharmaceutical[122]Toxics 11 00063 i056
LidocaineYes---Pharmaceutical[123]Toxics 11 00063 i057
NitenpyramYes---Pesticide[124]Toxics 11 00063 i058
Phthalic acidYesYes-YesPlasticizer[125]Toxics 11 00063 i059
Phthalic Acid Bis(2 Ethylhexyl) EsterYesYes-YesPlastic-softening agent[126]Toxics 11 00063 i060
PregabalinYesYes--Pharmaceutical[85]Toxics 11 00063 i061
Salicylic acidYesYes--Pharmaceutical[127]Toxics 11 00063 i062
TebuconazoleYesYesYesYesPesticide[128]Toxics 11 00063 i063
1 Marvin Sketch was used to draw the chemical structures. 2 Citation describing the estrogenic activity of the identified xenoestrogen. 3 Potential source of the xenoestrogen.

3.2.3. Drinking Water

Regarding drinking water, private stations have more purification systems with additional filters: sand filter, carbon filter, iron removal filter, and microfilter. In addition, the stations perform sterilization using ultraviolet radiation. Hence, the potential estrogenicity was low, below the detection limit of the YES assay (1 ng/L). However, several compounds (potential xenoestrogens) were detected by LC-MS and identified by the MetaboScape database (Table 5).
Despite estrogenic activity not being detected in drinking water using YES, the existence of xenoestrogen cannot be ruled out, because its concentration was below the YES detection limit. More sensitive screening methods have recently been developed, which can detect levels as low as 14.7 pg/L of estrogen equivalents [129]. Estrogenic-disrupting substances have been found in drinking water all around the world [99], including the USA [130], Germany [131,132], India [133,134], Italy [132], Sweden [54,135], France [132] and Spain [136]. According to the Environmental Protection Agency (US-EPA), the estrogenic risk is significant when the estrogenic activity is greater than 1 ng/L [137].
Detected xenoestrogens are listed in Table 5. It is anticipated that xenoestrogens will originate from the several sources depicted in Figure 3. Agriculture was responsible for the production of 67% of all xenoestrogens.
Carvone is a monoterpene compound that is widely used as an insecticide, fungicide, antioxidant, and plant growth regulator [138]. For instance, it is currently used as a potato germination inhibitor [139]. Carvone is easily volatilized, so it is not a persistent component in soil or water. Furthermore, when exposed to light, the volatilized carvone will undergo photochemical reactions [138]. This finding may question the source of untreated water that is used in private stations.
Mercaptobenzothiazole, in addition to being utilized in pesticide manufacturing, is also employed as a sulfur vulcanization accelerator in the synthesis of rubber plumbing items such as gaskets and O-rings, which are essential parts of water networks [140]. Mercaptobenzothiazole could therefore have reached drinking water through private station pipelines during filtration or bottle packaging. Both (carvone and mercaptobenzothiazole) have been detected in drinking water around the world [80,140,141].
The existence of pregabalin, which is used to treat neuropathic pain and convulsions, remains unknown. Pregabalin was detected in all water samples; however, its half-life has been reported to be 8 to 10 days in the aerobic environment [142], implying a potential error in the detection experiment. The detection system employs four different identification methods: mass accuracy, retention duration, diagnostic ions, and isotopic pattern. Pregabalin only satisfied the retention time and mass accuracy detection requirements. DL-2-aminooctanoic acid, also known as alpha-aminocaprylic acid, has the same molecular weight (159.229) and chemical formula (C8H17NO2) as pregabalin (Figure 4). Hence, it has identical MS data. According to FooDB (www.foodb.ca, accessed on 25 October 2022.), DL-2-aminooctanoic acid has been identified in various foods, including chicken and cow milk, and has been used as a potential biomarker for the consumption of these foods. As a result, it is more likely that the pollutant came from food metabolites rather than the anticonvulsant medicine, especially as DL-2-aminooctanoic acid is not found in the MetaboScape library. Although it is unlikely to have pregabalin in drinking water as explained previously, it has been detected in several rivers around the world [143].
The identification of xenoestrogen contaminants in the water does not always imply direct estrogenic activity, because the mass spectrometry detects traces of xenoestrogens and the estrogenic activity is concentration-dependent [144]. Although more than 700 xenoestrogens have been identified in drinking water [8], only 11 xenoestrogen are regulated by the United States Environmental Protection Agency (USEPA) [8]. As such, scientists pay attention to the fact that xenoestrogens are often found in the raw water that is used to make drinking water, and calls are made for more government control and regulations [55,145].

3.2.4. Vegetables

The presence of xenoestrogens in vegetables has been previously reported [146]. Consequently, vegetable samples were utilized to investigate the potential transfer of xenoestrogens from irrigation water to vegetables. Vegetable samples were not used in the YES experiment because plants contain phytoestrogens, which are known to interact with estrogen receptors [147]. Detected xenoestrogen in vegetables (tomato and cucumber) is summarized in Table 6, which was also detected in open surface water. The majority of vegetables are cultivated in the Jordan Valley, and farmers use the King Abdullah Canal and King Talal Dam water for irrigation, so either the xenoestrogen in the canal water contaminated the crops or the pesticides used by farmers contaminated both the crops and the King Abdullah Canal. Agricultural resources are responsible for 67% of the xenoestrogens in vegetables, as illustrated in Figure 3. The other 23% may come from industrial pollution during cultivation and shipping processes, as dibutyl phthalate was identified in the samples. All detected xenoestrogens in vegetables samples were aromatic with low water solubility Table 6.
The Ferula genus (Umbelliferae) contains the phytoestrogen ferutinin, which has a modest estrogenic activity [148] and is native to Jordan [149]. Therefore, it was probably the surrounding plants that allowed it to reach the crops. Moreover, ferutinin was detected in all water samples (except drinking water).
Butylparaben—a preservative used in cosmetic products—is not prone to photodegradation and is highly stable against sunlight; however, it is suitable for biodegradation and sorption [150]. The expected source is direct contamination from the surrounding area, not from water, as it was not detected in any water samples. Moreover, butylparaben has weak estrogenic activity [150].
Dibutyl phthalate (DBP) is a plasticizer used to improve the flexibility of plastic products, specifically polyvinyl chloride, which is used in the synthesis of packaging/greenhouse films, wires, pipes, and all flooring materials [151]. Moreover, phthalate plasticizers are not chemically bound to the polymer structure and have a high probability of being released into the environment [152]. Hence, DBP may contaminate the crops directly during farming (plastic greenhouse), cultivation (plastic pipelines), and shipping (plastic packaging). In addition, there is another possible source that DBP came from water, as DBP was detected in all surface samples from water used for irrigation. Dibutyl phthalate has moderate estrogenic activity [153].
Alpha-zearalenol (α-ZEA) is a metabolite of mycotoxin zearalenone that is widespread, particularly in pathogens (Fusarium species) of small grain cereals and corn, and might be developed under poor storage conditions [154]. Furthermore, zearalenone is thermostable and is not degraded by processing, such as milling, extrusion, storage, or heating [155]. Alpha-zearalenol is mainly formed in the liver and the small intestines of humans and animals. Therefore, it has been detected in animal body fluids such as milk and urine [155], and has also been identified in foods worldwide, such as cow’s milk-based infant formula [156], chicken heart [157], and fish meat [158]. Hence, the source of α-ZEA in vegetables mainly came from animals such as cows and chickens. This theory is supported by the fact that α-ZEA was detected in all open surface water samples. Alpha-zearalenol possesses 60 times the estrogenic activity of zearalenone [159].
Ferimzone is a systemic pyrimidine fungicide and it has been detected in surface water [160] and groundwater [161] worldwide, so the presence of ferimzone in samples was due to the direct use on the vegetables. Ferimzone has weak estrogenic activity [117], and it was detected in all surface waters.
Tebuconazole is an azole fungicide used in vegetables, citrus, and field crops [162]. Moreover, it has high photochemical stability, very slow photodegradation, and slow microbial-mediated degradation in soil [163,164]. Tebuconazole was detected in drinking water and groundwater [162,165]. Tebuconazole exhibits moderate estrogenic activity [166]. Direct application on the plant may the source of contamination in vegetables rather than the irrigation water.
3,5,6-Trichloro-2-pyridinol (TCP) is a metabolite of chlorpyrifos [104], which is an organophosphate insecticide. It has been reported that TCP can reach groundwater and surface water, and its half-life in the soil can reach 120 days [167]. Therefore, the direct application of TCP might be the source of contamination [142,143,144,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167]. Moreover, it has weak estrogenic activity, being 2500 times less estrogenic than 17β-estradiol [104].
The source of xenoestrogens in the vegetable samples was predominantly from direct interaction throughout the farming process (cultivation, irrigation, packing), and the source of xenoestrogens discovered in water was most likely from agricultural resources rather than the other way around. Traces of pesticides have previously been detected in Jordanian fruit and vegetables [169,170]. Furthermore, some of these pesticides were also found in water and soil. As a result, the necessity for proper training and enforcement of good agricultural practices in the region was advised. Comprehensive pesticide monitoring systems and frequent inspections were also highlighted [170].

4. Conclusions

Xenoestrogens are persistent, prevalent substances in the environment that accumulate and may even be further activated by biotransformation, making them hazardous to animal and human health. Xenoestrogens were detected in all water and vegetable samples, including drinking water. However, the estrogenic activity was low and does not constitute an immediate, acute health risk to the community, though there is a necessity to limit the existence of such compounds in the water. The main source of xenoestrogens was agricultural resources (pesticides, insecticides, fungicides). Therefore, proper training and implementation of good agricultural practices should be established, and comprehensive pesticide monitoring systems and frequent inspections should also be enforced. This research may serve as a whistleblower on the estrogenic contamination in the Jordanian water system.

5. Limitations and Future Work

Six locations are insufficient to provide adequate data regarding xenoestrogen pollution in the Jordanian water system. The Ministry of Water and Irrigation restricted access to water resources and barred the collection of samples freely. As a result, the number of samples from each location was limited and restricted to certain sites. Furthermore, surface water samples were collected and prepared at the ministry labs, and the samples were subsequently analyzed in the university labs.
Future studies must be more comprehensive and include more samples from various locations at each site. Even though there were more than 4000 compounds in the MetaboScape database, still there were many unidentified compounds in the samples. Hence, future work might focus on specific families of xenoestrogens, where the xenoestrogens could be quantified.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/toxics11010063/s1. Figure S1: The base peak chromatogram for tap water samples from Irbid and Amman; Table S1: The complete spectrum list of (Dissect and bbCID) for Irbid’s tap water sample; Table S2: The complete spectrum list of (Dissect and bbCID) for Amman’s tap water. Supplementary Material S1: List of potential pharmaceutical pollutants (including psychoactive substances) and their metabolites—a total of 1659 compounds. The list includes the name and CAS number of each compound. Supplementary Material S2: List of potential veterinary drug pollutants—a total of 206 compounds. The list includes the name and CAS number of each compound. Supplementary Material S3: List of potential insecticides, pesticides, and herbicides pollutants—a total of 1060 compounds. The list includes the name and CAS number of each compound. Supplementary Material S4: List of potential xenoestrogens according to the literature—a total of 75 compounds. The list includes the name, chemical formula, molecular weight, and CAS number of each compound, as well as occurrence and use.

Author Contributions

Conceptualization, Y.A. and M.A.; data curation, Y.A., N.A and I.A.; formal analysis, Y.A. and I.A.; funding acquisition, Y.A.; investigation, Y.A., I.A and N.A.; methodology, Y.A., N.A. and I.A.; project administration, Y.A.; resources, Y.A.; supervision, Y.A.; validation, Y.A., D.O., H.A. and M.A.; visualization, Y.A.; writing—original draft, Y.A. and I.A.; writing—review and editing, Y.A., M.A., D.O. and H.A. All authors have read and agreed to the published version of the manuscript.

Funding

This work was fully funded by the Deanship of Scientific Research at Yarmouk University, Irbid, Jordan (grant #: 36/2015).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Acknowledgments

We would like to pay our gratitude and our respects to our colleague Abeer Almutairi of the Science Department, College of Basic Education, Public Authority for Applied Education and Training, Safat, Kuwait. She helped with the initiation and maturation of the research idea. We would also like to thank Sameh Gharaibeh of the Department of Earth and Environmental Sciences, Faculty of Science, Yarmouk University for his comments and guidance.

Conflicts of Interest

The authors declare that they have no competing interests.

References

  1. Kidd, K.A.; Blanchfield, P.J.; Mills, K.H.; Palace, V.P.; Evans, R.E.; Lazorchak, J.M.; Flick, R.W. Collapse of a fish population after exposure to a synthetic estrogen. Proc. Natl. Acad. Sci. USA 2007, 104, 8897–8901. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Velicu, M.; Suri, R. Presence of steroid hormones and antibiotics in surface water of agricultural, suburban and mixed-use areas. Environ. Monit. Assess. 2009, 154, 349–359. [Google Scholar] [CrossRef] [PubMed]
  3. Zhang, H.; Shi, J.; Liu, X.; Zhan, X.; Dang, J.; Bo, T. Occurrence of free estrogens, conjugated estrogens, and bisphenol A in fresh livestock excreta and their removal by composting in North China. Environ. Sci. Pollut. Res. Int. 2014, 21, 9939–9947. [Google Scholar] [CrossRef] [PubMed]
  4. Byrns, G. The fate of xenobiotic organic compounds in wastewater treatment plants. Water Res. 2001, 35, 2523–2533. [Google Scholar] [CrossRef] [PubMed]
  5. Stevens, J.L.; Northcott, G.L.; Stern, G.A.; Tomy, G.T.; Jones, K.C. PAHs, PCBs, PCNs, organochlorine pesticides, synthetic musks, and polychlorinated n-alkanes in U.K. sewage sludge: Survey results and implications. Environ. Sci. Technol. 2003, 37, 462–467. [Google Scholar] [CrossRef]
  6. Kuch, H.M.; Ballschmiter, K. Determination of endocrine-disrupting phenolic compounds and estrogens in surface and drinking water by HRGC-(NCI)-MS in the picogram per liter range. Environ. Sci. Technol. 2001, 35, 3201–3206. [Google Scholar] [CrossRef]
  7. Majima, K.; Fukui, T.; Yuan, J.; Wang, G.; Matsumoto, K. Quantitative measurement of 17 beta-estradiol and estriol in river water by time-resolved fluoroimmunoassay. Anal. Sci. 2002, 18, 869–874. [Google Scholar]
  8. Gonsioroski, A.; Mourikes, V.; Flaws, J. Endocrine Disruptors in Water and Their Effects on the Reproductive System. Int. J. Mol. Sci. 2020, 21, 1929. [Google Scholar] [CrossRef] [Green Version]
  9. Wee, S.Y.; Aris, A.Z.; Yusoff, F.M.; Praveena, S.M. Occurrence of multiclass endocrine disrupting compounds in a drinking water supply system and associated risks. Sci. Rep. 2020, 10, 17755. [Google Scholar] [CrossRef]
  10. Routledge, E.J.; Sheahan, D.; Desbrow, C.; Brighty, G.C.; Waldock, M.; Sumpter, J.P. Identification of Estrogenic Chemicals in STW Effluent. 2. In Vivo Responses in Trout and Roach. Environ. Sci. Technol. 1998, 11, 1559–1565. [Google Scholar] [CrossRef]
  11. Adeel, M.; Song, X.; Wang, Y.; Francis, D.; Yang, Y.. Environmental impact of estrogens on human, animal and plant life: A critical review. Environ. Int. 2017, 99, 107–119. [Google Scholar] [CrossRef] [PubMed]
  12. Paterni, I.; Granchi, C.; Minutolo, F. Risks and benefits related to alimentary exposure to xenoestrogens. Crit. Rev. Food Sci. Nutr. 2017, 57, 3384–3404. [Google Scholar] [CrossRef] [PubMed]
  13. Khalil, N.; Chen, A.; Lee, M. Endocrine disruptive compounds and cardio-metabolic risk factors in children. Curr. Opin. Pharmacol. 2014, 19, 120–124. [Google Scholar] [CrossRef] [PubMed]
  14. Bianca, S.; Ingegnosi, C.; Ettore, G. Maternal and Paternal Risk Factors for Hypospadias. Environ. Health Perspect. 2005, 5, A296. [Google Scholar] [CrossRef]
  15. Ferlin, A.; Foresta, C. Testis Cancer: Genes, Environment, Hormones. Front. Endocrinol. 2014, 5, 172. [Google Scholar] [CrossRef] [Green Version]
  16. Hardell, L.; Malmqvist, N.; Ohlson, C.G.; Westberg, H.; Eriksson, M. Testicular cancer and occupational exposure to polyvinyl chloride plastics: A case-control study. Int. J. Cancer 2004, 109, 425–429. [Google Scholar] [CrossRef]
  17. St-Hilaire, S.; Mandal, R.; Commendador, A.; Mannel, S.; Derryberry, D. Estrogen receptor positive breast cancers and their association with environmental factors. Int. J. Health Geogr. 2011, 10, 32. [Google Scholar] [CrossRef]
  18. Porpora, M.G.; Resta, S.; Fuggetta, E.; Storelli, P.; Megiorni, F.; Manganaro, L.; De Felip, E. Role of environmental organochlorinated pollutants in the development of endometriosis. Clin. Exp. Obstet. Gynecol. 2013, 40, 565–567. [Google Scholar]
  19. Diamanti-Kandarakis, E.; Bourguignon, J.P.; Giudice, L.C.; Hauser, R.; Prins, G.S.; Soto, A.M.; Zoeller, R.T.; Gore, A.C. Endocrine-disrupting chemicals: An Endocrine Society scientific statement. Endocr. Rev. 2009, 30, 293–342. [Google Scholar] [CrossRef]
  20. Owen, R.; Jobling, S. Environmental science: The hidden costs of flexible fertility. Nature 2012, 485, 441. [Google Scholar] [CrossRef]
  21. Wise, A.; O’Brien, K.; Woodruff, T. Are oral contraceptives a significant contributor to the estrogenicity of drinking water? Environ. Sci. Technol. 2011, 45, 51–60. [Google Scholar] [CrossRef] [PubMed]
  22. Skakkebaek, N.E.; Rajpert-De Meyts, E.; Main, K.M. Testicular dysgenesis syndrome: An increasingly common developmental disorder with environmental aspects. Hum. Reprod. 2001, 16, 972–978. [Google Scholar] [CrossRef] [PubMed]
  23. Harris, H.A.; Albert, L.M.; Leathurby, Y.; Malamas, M.S.; Mewshaw, R.E.; Miller, C.P.; Kharode, Y.P.; Marzolf, J.; Komm, B.S.; Winneker, R.C.; et al. Evaluation of an estrogen receptor-beta agonist in animal models of human disease. Endocrinology 2003, 144, 4241–4249. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Holme, J.A.; Dybing, E. Are environmental chemicals with hormone-like properties a health problem? Tidsskr. Nor. Laegeforen. 1997, 117, 70–73. [Google Scholar]
  25. Mohsen, M.S. Water strategies and potential of desalination in Jordan. Desalination Strateg. South Mediterr. Ctries. 2007, 203, 27–46. [Google Scholar] [CrossRef]
  26. Zoller, U.; Hushan, M. The nonionic surfactant pollution profile of Israel Mediterranean Sea coastal water. Water Sci. Technol. 2001, 43, 245–250. [Google Scholar] [CrossRef] [PubMed]
  27. Shore, L.S.; Reichmann, O.; Shemesh, M.; Wenzel, A.; Litaor, M.I. Washout of accumulated testosterone in a watershed. Sci. Total Environ. 2004, 332, 193–202. [Google Scholar] [CrossRef]
  28. Barel-Cohen, K.; Shore, L.S.; Shemesh, M.; Wenzel, A.; Mueller, J.; Kronfeld-Schor, N. Monitoring of natural and synthetic hormones in a polluted river. J. Environ. Manag. 2006, 78, 16–23. [Google Scholar] [CrossRef]
  29. Alkhoury, W.; Ziegmann, M.; Frimmel, F.H.; Abbt-Braun, G.; Salameh, E. Water quality of the King Abdullah Canal/Jordan–impact on eutrophication and water disinfection. Toxicol. Environ. Chem. 2010, 92, 855–877. [Google Scholar] [CrossRef] [Green Version]
  30. Jamrah, A.; Ayyash, S. Greywater generation and characterization in major cities in Jordan. Jordan J. Civ. Eng. 2008, 2, 376–390. [Google Scholar]
  31. Al-Ansari, N.; Alibrahiem, N.; Alsaman, M.; Knutsson, S. Water supply network losses in Jordan. J. Water Resour. Prot. 2014, 6, 83–96. [Google Scholar] [CrossRef] [Green Version]
  32. Al-Kharabsheh, A. Challenges to Sustainable Water Management in Jordan. Jordan J. Earth Environ. Sci. 2020, 11, 38. [Google Scholar]
  33. Closas, A.; Molle, F. Groundwater Governance in the Arab World–Taking Stock and Addressing the Challenges; USAID/IWMI, 2016. [Google Scholar]
  34. Le, T.A.H. The YES Assay as a Tool to Analyse Endocrine Disruptors in Different Matrices in Vietnam. Doctoral Dissertation, Universitäts-und Landesbibliothek Bonn, Bonn, Germany, 2012. [Google Scholar]
  35. Hassannejad, M.; Alizadeh, K.; Nemati, M. Determination of 17-β-Estradiol in Water Samples Using Salting-out Assisted Liquid-liquid Extraction Followed by HPLC and Experimental Design for Optimization. Anal. Bioanal. Chem. Res. 2019, 6, 353–363. [Google Scholar]
  36. Beresford, N.; Baynes, A.; Kanda, R.; Mills, M.R.; Arias-Salazar, K.; Collins, T.J.; Jobling, S. Use of a Battery of Chemical and Ecotoxicological Methods for the Assessment of the Efficacy of Wastewater Treatment Processes to Remove Estrogenic Potency. J. Vis. Exp. 2016, 11, e54243. [Google Scholar] [CrossRef] [Green Version]
  37. Bistan, M.; Podgorelec, M.; Logar, R.M.; Tišler, T. Yeast Estrogen Screen Assay as a Tool for Detecting Estrogenic Activity in Water Bodies. Food Technol. Biotechnol. 2012, 50, 7. [Google Scholar]
  38. Soto, A.M.; Calabro, J.M.; Prechtl, N.V.; Yau, A.Y.; Orlando, E.F.; Daxenberger, A.; Kolok, A.S.; Guillette, L.J.; le Bizec, B.; Lange, I.G.; et al. Androgenic and estrogenic activity in water bodies receiving cattle feedlot effluent in Eastern Nebraska, USA. Environ. Health Perspect. 2004, 112, 346–352. [Google Scholar] [CrossRef] [Green Version]
  39. Lopez-Herguedas, N.; González-Gaya, B.; Cano, A.; Alvarez-Mora, I.; Mijangos, L.; Etxebarria, N.; Zuloaga, O.; Olivares, M.; Prieto, A. Effect-directed analysis of a hospital effluent sample using A-YES for the identification of endocrine disrupting compounds. Sci. Total Environ. 2022, 850, 157985. [Google Scholar] [CrossRef]
  40. Czernych, R.; Chraniuk, M.; Zagozdzon, P.; Wolska, L. Characterization of estrogenic and androgenic activity of phthalates by the XenoScreen YES/YAS in vitro assay. Environ. Toxicol. Pharmacol. 2017, 53, 95–104. [Google Scholar] [CrossRef]
  41. Maisa’a, W.S.; Abualhaija, M.M. An Analysis of Long Term Yearly Water Flow Trend and Its Impact on Sediment Yield in King Talal Dam. Int. J. Eng. Res. Technol. 2019, 12, 3041–3049. [Google Scholar]
  42. Hilal, A.H.A.; Alhaija, M.M.A. Nutrients in Water and Sediments of King Talal Dam-Jordan. Jordan J. Biol. Sci. 2010, 3, 87–100. [Google Scholar]
  43. Al-Mashakbeh, H.M. The influence of lithostratigraphy on the type and quality of stored water in mujib reservoir-Jordan. J. Environ. Prot. 2017, 8, 568. [Google Scholar] [CrossRef] [Green Version]
  44. Shigei, M.; Assayed, A.; Hazaymeh, A.; Dalahmeh, S.S. Pharmaceutical and antibiotic pollutant levels in wastewater and the waters of the Zarqa river, Jordan. Appl. Sci. 2021, 11, 8638. [Google Scholar] [CrossRef]
  45. Al-Mashagbah, A.F. Assessment of surface water quality of king abdullah canal, using physico-chemical characteristics and water quality index, Jordan. J. Water Resour. Prot. 2015, 7, 339. [Google Scholar] [CrossRef] [Green Version]
  46. Fang, H.; Tong, W.; Perkins, R.; Soto, A.M.; Prechtl, N.V.; Sheehan, D.M. Quantitative comparisons of in vitro assays for estrogenic activities. Environ. Health Perspect. 2000, 108, 723–729. [Google Scholar] [CrossRef] [PubMed]
  47. Nascimento, M.T.L.d.; Santos, A.D.d.O.; Cunha, D.L.d.; Felix, L.C.; Gomes, G.; Rangel, C.M.A.; Hauser-Davis, R.A.; Fonseca, E.M.d.; Bila, D.M.; Baptista Neto, J.A. Endocrine disruptors, estrogenic activity by the YES bioassay, and acute toxicity in Southeastern Brazil metropolitan surface waters. Geochim. Bras. 2022, 36, e-22005. [Google Scholar] [CrossRef]
  48. Yusuf, A.; O’Flynn, D.; White, B.; Holland, L.; Parle-McDermott, A.; Lawler, J.; McCloughlin, T.; Harold, D.; Huerta, B.; Regan, F. Monitoring of emerging contaminants of concern in the aquatic environment: A review of studies showing the application of effect-based measures. Anal. Methods 2021, 13, 5120–5143. [Google Scholar] [CrossRef]
  49. El-Naqa, A.; Al Raei, A. Assessment of Drinking Water Quality Index (WQI) in the Greater Amman Area, Jordan. Jordan J. Earth Environ. Sci. 2021, 12, 306–314. [Google Scholar]
  50. Miyahuna Website: Our Work. 2022. Available online: https://miyahuna.com.jo/en/page/Our-Work-29 (accessed on 10 November 2022).
  51. Russo, G.; Laneri, S.; Di Lorenzo, R.; Neri, I.; Dini, I.; Ciampaglia, R.; Grumetto, L. Monitoring of Pollutants Content in Bottled and Tap Drinking Water in Italy. Molecules 2022, 27, 3990. [Google Scholar] [CrossRef]
  52. Okpara, K.E.; Phoungthong, K.; Agbozu, I.; Edwin-Isotu, E.; Techato, K. Phthalate Esters in Tap Water, Southern Thailand: Daily Exposure and Cumulative Health Risk in Infants, Lactating Mothers, Pregnant and Nonpregnant Women. Int. J. Environ. Res. Public Health 2022, 19, 2187. [Google Scholar] [CrossRef]
  53. González, A.; Kroll, K.J.; Silva-Sanchez, C.; Carriquiriborde, P.; Fernandino, J.I.; Denslow, N.D.; Somoza, G. M Steroid hormones and estrogenic activity in the wastewater outfall and receiving waters of the Chascomús chained shallow lakes system (Argentina). Sci. Total Environ. 2020, 743, 140401. [Google Scholar] [CrossRef]
  54. Johan, L.; Persson, K.M.; Agneta, O. Glass-bottled drinking water: A time capsule to study the historic presence of hazardous chemicals using effect-based methods. Environ. Sci. Eur. 2021, 33, 1–9. [Google Scholar]
  55. Yazdan, M.M.S.; Kumar, R.; Leung, S.W. The Environmental and Health Impacts of Steroids and Hormones in Wastewater Effluent, as Well as Existing Removal Technologies: A Review. Ecologies 2022, 3, 206–224. [Google Scholar] [CrossRef]
  56. Jari, Y.; Roche, N.; Necibi, M.C.; El Hajjaji, S.; Dhiba, D.; Chehbouni, A. Emerging pollutants in moroccan wastewater: Occurrence, Impact, and removal technologies. J. Chem. 2022, 2022, 9727857. [Google Scholar] [CrossRef]
  57. Chiang, Y.R.; Wei, S.T.S.; Wang, P.H.; Wu, P.H.; Yu, C.P. Microbial degradation of steroid sex hormones: Implications for environmental and ecological studies. Microb. Biotechnol. 2020, 13, 926–949. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  58. Abdelrahim, M.; Ariazi, E.; Kim, K.; Khan, S.; Barhoumi, R.; Burghardt, R.; Liu, S.; Hill, D.; Finnell, R.; Wlodarczyk, B.; et al. 3-Methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha. Cancer Res. 2006, 66, 2459–2467. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  59. Nakagawa, Y.; Tayama, K. Estrogenic potency of benzophenone and its metabolites in juvenile female rats. Arch. Toxicol. 2001, 75, 74–79. [Google Scholar] [CrossRef]
  60. Satake, K.; Yoshimoto, T.; Mukai, R.; Umeyama, K. Estrogen receptors in 7,12-dimethylbenz (a) anthracene (DMBA) induced pancreatic carcinoma in rats and in human pancreatic carcinoma. Clin. Oncol. 1982, 8, 49–54. [Google Scholar]
  61. Gellert, R.J. Kepone, mirex, dieldrin, and aldrin: Estrogenic activity and the induction of persistent vaginal estrus and anovulation in rats following neonatal treatment. Environ. Res. 1978, 16, 131–138. [Google Scholar] [CrossRef]
  62. Spencer, F.; Chi, L.; Zhu, M.X. Effect of benomyl and carbendazim on steroid and molecular mechanisms in uterine decidual growth in rats. J. Appl. Toxicol. 1996, 16, 211–214. [Google Scholar] [CrossRef]
  63. Majhi, P.D.; Sharma, A.; Roberts, A.L.; Daniele, E.; Majewski, A.R.; Chuong, L.M.; Black, A.L.; Vandenberg, L.N.; Schneider, S.S.; Dunphy, K.A.; et al. Effects of Benzophenone-3 and Propylparaben on Estrogen Receptor-Dependent R-Loops and DNA Damage in Breast Epithelial Cells and Mice. Environ. Health Perspect. 2020, 128, 17002. [Google Scholar] [CrossRef] [Green Version]
  64. Ertürk, N. Comparison of estrogen and betamethasone in the topical treatment of labial adhesions in prepubertal girls. Turk. J. Med. Sci. 2014, 44, 1103–1107. [Google Scholar] [CrossRef] [PubMed]
  65. Gao, H.; Yang, B.J.; Li, N.; Feng, L.M.; Shi, X.Y.; Zhao, W.H.; Liu, S.J. Bisphenol A and hormone-associated cancers: Current progress and perspectives. Medicine 2015, 94, e211. [Google Scholar] [CrossRef] [PubMed]
  66. Ashfaq, M.; Sun, Q.; Ma, C.; Rashid, A.; Li, Y.; Mulla, S.I.; Yu, C.-P. Occurrence, seasonal variation and risk evaluation of selected endocrine disrupting compounds and their transformation products in Jiulong river and estuary, China. Mar. Pollut. Bull. 2019, 145, 370–376. [Google Scholar] [CrossRef] [PubMed]
  67. Liu, J.; Zhang, P.; Zhao, Y.; Zhang, H. Low dose carbendazim disrupts mouse spermatogenesis might be through estrogen receptor related histone and DNA methylation. Ecotoxicol. Environ. Saf. 2019, 176, 242–249. [Google Scholar] [CrossRef]
  68. Javed, R.; Hanif, M.A.; Rehman, R.; Hanif, M.; Tung, B.T. Chapter 7—Caraway. In Medicinal Plants of South Asia; Elsevier: Amsterdam, The Netherlands, 2020; pp. 87–100. [Google Scholar]
  69. Zhao, M.; Zhang, Y.; Liu, W.; Xu, C.; Wang, L.; Gan, J. Estrogenic activity of lambda-cyhalothrin in the MCF-7 human breast carcinoma cell line. Environ. Toxicol. Chem. 2008, 27, 1194–1200. [Google Scholar] [CrossRef]
  70. Go, R.E.; Kim, C.W.; Choi, K.C. Effect of fenhexamid and cyprodinil on the expression of cell cycle- and metastasis-related genes via an estrogen receptor-dependent pathway in cellular and xenografted ovarian cancer models. Toxicol. Appl. Pharmacol. 2015, 289, 48–57. [Google Scholar] [CrossRef]
  71. Orton, F.; Rosivatz, E.; Scholze, M.; Kortenkamp, A. Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens. Environ. Health Perspect. 2011, 119, 794–800. [Google Scholar] [CrossRef] [Green Version]
  72. Petit, F.; Le Goff, P.; Cravédi, J.P.; Valotaire, Y.; Pakdel, F. Two complementary bioassays for screening the estrogenic potency of xenobiotics: Recombinant yeast for trout estrogen receptor and trout hepatocyte cultures. J. Mol. Endocrinol. 1997, 19, 321–335. [Google Scholar] [CrossRef] [Green Version]
  73. Andersen, H.R.; Bonefeld-Jørgensen, E.C.; Nielsen, F.; Jarfeldt, K.; Jayatissa, M.N.; Vinggaard, A.M. Estrogenic effects in vitro and in vivo of the fungicide fenarimol. Toxicol. Lett. 2006, 163, 142–152. [Google Scholar] [CrossRef]
  74. Sohoni, P.; Lefevre, P.A.; Ashby, J.; Sumpter, J.P. Possible androgenic/anti-androgenic activity of the insecticide fenitrothion. J. Appl. Toxicol. 2001, 21, 173–178. [Google Scholar] [CrossRef]
  75. Zavatti, M.; Guida, M.; Maraldi, T.; Beretti, F.; Bertoni, L.; La Sala, G.B.; De Pol, A. Estrogen receptor signaling in the ferutinin-induced osteoblastic differentiation of human amniotic fluid stem cells. Life Sci. 2016, 164, 15–22. [Google Scholar] [CrossRef] [PubMed]
  76. Go, R.E.; Kim, C.W.; Jeon, S.Y.; Byun, Y.S.; Jeung, E.B.; Nam, K.H.; Choi, K.C. Fludioxonil induced the cancer growth and metastasis via altering epithelial-mesenchymal transition via an estrogen receptor-dependent pathway in cellular and xenografted breast cancer models. Environ. Toxicol. 2017, 32, 1439–1454. [Google Scholar] [CrossRef] [PubMed]
  77. Stonesifer, G.L., Jr.; Lowe, R.H.; Cameron, J.L.; Ganis, F.M. Conversion of hydrocortisone to estrogen in carcinoma of the breast after oophorectomy and adrenalectomy. Ann. Surg. 1973, 178, 563–564. [Google Scholar] [CrossRef] [PubMed]
  78. Jin, C.; Zhang, R.; Fu, Z.; Jin, Y. Maternal exposure to imazalil disrupts the endocrine system in F(1) generation mice. Mol. Cell. Endocrinol. 2019, 486, 105–112. [Google Scholar] [CrossRef] [PubMed]
  79. Wang, J.; Pan, L.; Wu, S.; Lu, L.; Xu, Y.; Zhu, Y.; Guo, M.; Zhuang, S. Recent Advances on Endocrine Disrupting Effects of UV Filters. Int. J. Environ. Res. Public Health 2016, 13, 782. [Google Scholar] [CrossRef] [Green Version]
  80. Alsadik, A.; Athamneh, K.; Yousef, A.F.; Shah, I.; Ashraf, S.S. Efficient Degradation of 2-Mercaptobenzothiazole and Other Emerging Pollutants by Recombinant Bacterial Dye-Decolorizing Peroxidases. Biomolecules 2021, 11, 656. [Google Scholar] [CrossRef] [PubMed]
  81. Mathias, F.T.; Romano, R.M.; Sleiman, H.K.; de Oliveira, C.A.; Romano, M.A. Herbicide metolachlor causes changes in reproductive endocrinology of male wistar rats. ISRN Toxicol. 2012, 2012, 130846. [Google Scholar] [CrossRef] [Green Version]
  82. Matsumoto, H.; Adachi, S.; Suzuki, Y. Estrogenic activity of ultraviolet absorbers and the related compounds. Yakugaku Zasshi 2005, 125, 643–652. [Google Scholar] [CrossRef] [Green Version]
  83. Matsumoto, H.; Adachi, S.; Suzuki, Y. Risk Assessment of Ethylhexyl Dimethyl PABA in Cosmetics. Toxicol. Res. 2019, 35, 131–136. [Google Scholar]
  84. Kim, S.S.; Lee, R.D.; Lim, K.J.; Kwack, S.J.; Rhee, G.S.; Seok, J.H.; Lee, G.S.; An, B.S.; Jeung, E.B.; Park, K.L. Potential estrogenic and antiandrogenic effects of permethrin in rats. J. Reprod. Dev. 2005, 51, 201–210. [Google Scholar] [CrossRef] [Green Version]
  85. Taha, S.H.N.; Zaghloul, H.S.; Ali, A.; Rashed, L.A.; Sabry, R.M.; Gaballah, I.F. Molecular and hormonal changes caused by long-term use of high dose pregabalin on testicular tissue: The role of p38 MAPK, oxidative stress and apoptosis. Mol. Biol. Rep. 2020, 47, 8523–8533. [Google Scholar] [CrossRef] [PubMed]
  86. Hofmeister, M.V.; Bonefeld-Jørgensen, E.C. Effects of the pesticides prochloraz and methiocarb on human estrogen receptor α and β mRNA levels analyzed by on-line RT-PCR. Toxicol. Vitr. 2004, 18, 427–433. [Google Scholar] [CrossRef] [PubMed]
  87. Bonefeld-Jorgensen, E.C.; Grünfeld, H.T.; Gjermandsen, I.M. Effect of pesticides on estrogen receptor transactivation in vitro: A comparison of stable transfected MVLN and transient transfected MCF-7 cells. Mol. Cell. Endocrinol. 2005, 244, 20–30. [Google Scholar] [CrossRef] [PubMed]
  88. Gu, C.J.; Cheng, J.; Zhang, B.; Yang, S.L.; Xie, F.; Sun, J.S.; Huang, L.Q.; Yu, J.J.; Li, M.Q. Protopanaxadiol and metformin synergistically inhibit estrogen-mediated proliferation and anti-autophagy effects in endometrial cancer cells. Am. J. Transl. Res. 2017, 9, 4071–4082. [Google Scholar]
  89. Medjakovic, S.; Zoechling, A.; Gerster, P.; Ivanova, M.M.; Teng, Y.; Klinge, C.M.; Schildberger, B.; Gartner, M.; Jungbauer, A. Effect of nonpersistent pesticides on estrogen receptor, androgen receptor, and aryl hydrocarbon receptor. Environ. Toxicol. 2014, 29, 1201–1216. [Google Scholar] [CrossRef]
  90. Kim, S.-H.; Bae, J.-W.; Kim, D.-H.; Jeong, D.-J.; Ha, J.J.; Yi, J.K.; Kwon, W.-S. Detrimental effects of temephos on male fertility: An in vitro study on a mouse model. Reprod. Toxicol. 2020, 96, 150–155. [Google Scholar] [CrossRef]
  91. Kim, S.S.; Kwack, S.J.; Lee, R.D.; Lim, K.J.; Rhee, G.S.; Seok, J.H.; Kim, B.H.; Won, Y.H.; Lee, G.S.; Jeung, E.B.; et al. Assessment of estrogenic and androgenic activities of tetramethrin in vitro and in vivo assays. J. Toxicol. Environ. Health A 2005, 68, 2277–2289. [Google Scholar]
  92. Richardson, S.D.; Postigo, C. Drinking water disinfection by-products. In Emerging Organic Contaminants and Human Health; Springer: Berlin/Heidelberg, Germany, 2011; pp. 93–137. [Google Scholar]
  93. Li, X.-F.; Mitch, W.A. Drinking Water Disinfection Byproducts (DBPs) and Human Health Effects: Multidisciplinary Challenges and Opportunities. Environ. Sci. Technol. 2018, 52, 1681–1689. [Google Scholar] [CrossRef]
  94. Tiedeken, E.J.; Tahar, A.; McHugh, B.; Rowan, N.J. Monitoring, sources, receptors, and control measures for three European Union watch list substances of emerging concern in receiving waters—A 20year systematic review. Sci. Total Environ. 2017, 574, 1140–1163. [Google Scholar] [CrossRef]
  95. Moreira, I.S.; Murgolo, S.; Mascolo, G.; Castro, P.M.L. Biodegradation and Metabolic Pathway of 17β-Estradiol by Rhodococcus sp. ED55. Int. J. Mol. Sci. 2022, 23, 6181. [Google Scholar] [CrossRef]
  96. Mrayyan, B.; Hussein, I. Integrated assessment of the control of wastewater pollution in Zarqa Governate, Jordan. Int. J. Environ. Pollut. 2004, 22, 580–596. [Google Scholar] [CrossRef]
  97. Argolo, A.d.S.; Gomes, G.; Bila, D.M. Insights into total estrogenic activity in a sewage-impacted urban stream assessed via ER transcriptional activation assay: Distribution between particulate and dissolved phases. Ecotoxicol. Environ. Saf. 2021, 208, 111574. [Google Scholar] [CrossRef] [PubMed]
  98. Simon, E.; Duffek, A.; Stahl, C.; Frey, M.; Scheurer, M.; Tuerk, J.; Gehrmann, L.; Könemann, S.; Swart, K.; Behnisch, P. Biological effect and chemical monitoring of Watch List substances in European surface waters: Steroidal estrogens and diclofenac–Effect-based methods for monitoring frameworks. Environ. Int. 2022, 159, 107033. [Google Scholar] [CrossRef] [PubMed]
  99. Raeburn, R.H.; Rockett, L.S.; Rumsby, P.C. Chapter 20—Considerations of Endocrine Disrupters in Water. In Endocrine Disruption and Human Health, 2nd ed.; Darbre, P.D., Ed.; Academic Press: Cambridge, MA, USA, 2022; pp. 415–444. [Google Scholar]
  100. Al-Omari, A.; Al-Houri, Z.; Al-Weshah, R. Impact of the As Samra wastewater treatment plant upgrade on the water quality (COD, electrical conductivity, TP, TN) of the Zarqa River. Water Sci. Technol. 2013, 67, 1455–1464. [Google Scholar] [CrossRef]
  101. Tang, Z.; Liu, Z.-h.; Wang, H.; Dang, Z.; Liu, Y. A review of 17α-ethynylestradiol (EE2) in surface water across 32 countries: Sources, concentrations, and potential estrogenic effects. J. Environ. Manag. 2021, 292, 112804. [Google Scholar] [CrossRef] [PubMed]
  102. Al Khateeb, W. Plants genotoxicity as pollution bioindicator in Jordan using comet assay. Physiol. Mol. Biol. Plants 2018, 24, 89–97. [Google Scholar] [CrossRef]
  103. Fandi, K.G.; Qudsieh, I.Y.; Muyibi, S.A.; Massadeh, M. Water pollution status assessment of King Talal Dam, Jordan. Adv. Environ. Biol. 2009, 3, 92–100. [Google Scholar]
  104. Echeverri-Jaramillo, G.; Jaramillo-Colorado, B.; Sabater-Marco, C.; Castillo-López, M. Cytotoxic and estrogenic activity of chlorpyrifos and its metabolite 3,5,6-trichloro-2-pyridinol. Study of marine yeasts as potential toxicity indicators. Ecotoxicology 2021, 30, 104–117. [Google Scholar] [CrossRef]
  105. Belkaid, A.; Čuperlović-Culf, M.; Touaibia, M.; Ouellette, R.J.; Surette, M.E. Metabolic Effect of Estrogen Receptor Agonists on Breast Cancer Cells in the Presence or Absence of Carbonic Anhydrase Inhibitors. Metabolites 2016, 6, 16. [Google Scholar] [CrossRef] [Green Version]
  106. Ta, N.; Walle, T. Aromatase inhibition by bioavailable methylated flavones. J. Steroid Biochem. Mol. Biol. 2007, 107, 127–129. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  107. Pantziarka, P.; Bouche, G.; Meheus, L.; Sukhatme, V.; Sukhatme, V.P. Repurposing Drugs in Oncology (ReDO)-mebendazole as an anti-cancer agent. Ecancermedicalscience 2014, 8, 443. [Google Scholar] [CrossRef] [PubMed]
  108. Halawa, E.; Ryad, L.; El-Shenawy, N.S.; Al-Eisa, R.A.; El-Hak, H.N.G. Evaluation of acetamiprid and azoxystrobin residues and their hormonal disrupting effects on male rats using liquid chromatography-tandem mass spectrometry. PLoS ONE 2021, 16, e0259383. [Google Scholar] [CrossRef] [PubMed]
  109. Khosrokhavar, R.; Rahimifard, N.; Shoeibi, S.; Hamedani, M.P.; Hosseini, M.J. Effects of zearalenone and alpha-Zearalenol in comparison with Raloxifene on T47D cells. Toxicol. Mech. Methods 2009, 19, 246–250. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  110. Rosendahl, A.H.; Perks, C.M.; Zeng, L.; Markkula, A.; Simonsson, M.; Rose, C.; Ingvar, C.; Holly, J.M.; Jernström, H. Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer. Clin. Cancer Res. 2015, 21, 1877–1887. [Google Scholar] [CrossRef] [Green Version]
  111. Vlasov, P.N.; Karlov, V.A.; Kushlinskiĭ, N.E. The pharmacological and hormonal effects of carbamazepine and valproic acid in the treatment of reproductive age women with epilepsy. Zhurnal Nevrol. I Psikhiatrii Im. SS Korsakova 2001, 101, 26–30. [Google Scholar]
  112. d’Adesky, N.D.; de Rivero Vaccari, J.P.; Bhattacharya, P.; Schatz, M.; Perez-Pinzon, M.A.; Bramlett, H.M.; Raval, A.P. Nicotine Alters Estrogen Receptor-Beta-Regulated Inflammasome Activity and Exacerbates Ischemic Brain Damage in Female Rats. Int. J. Mol. Sci. 2018, 19, 1330. [Google Scholar] [CrossRef] [Green Version]
  113. Medithi, S.; Kasa, Y.D.; Jee, B.; Venkaiah, K.; Jonnalagadda, P.R. Alterations in reproductive hormone levels among farm women and their children occupationally exposed to organophosphate pesticides. Women Health 2022, 62, 454–464. [Google Scholar] [CrossRef]
  114. Wójtowicz, A.K.; Szychowski, K.A.; Wnuk, A.; Kajta, M. Dibutyl Phthalate (DBP)-Induced Apoptosis and Neurotoxicity are Mediated via the Aryl Hydrocarbon Receptor (AhR) but not by Estrogen Receptor Alpha (ERα), Estrogen Receptor Beta (ERβ), or Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Mouse Cortical Neurons. Neurotox. Res. 2017, 31, 77–89. [Google Scholar]
  115. Hoekstra, P.F.; Burnison, B.K.; Garrison, A.W.; Neheli, T.; Muir, D.C. Estrogenic activity of dicofol with the human estrogen receptor: Isomer- and enantiomer-specific implications. Chemosphere 2006, 64, 174–177. [Google Scholar] [CrossRef]
  116. Yamada, K.; Terasaki, M.; Makino, M. Estrogenic Activity of Alkyl(thio)phenols and 4,4’-thiodiphenol Formed from Degradation of Commercial Insecticides. J. Health Sci. 2011, 57, 134–141. [Google Scholar] [CrossRef] [Green Version]
  117. Kojima, H.; Katsura, E.; Takeuchi, S.; Niiyama, K.; Kobayashi, K. Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells. Environ. Health Perspect. 2004, 112, 524–531. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  118. Daas, O.; Scaps, P.; Bouzerna, N.; Descamps, M. Effects of two ecdysteroid analogs (RH-0345 and RH-2485) on the total growth of eupolybothrus nudicornis (myriapoda, chilopoda). Vie Milieu/Life Environ. 2007, 57, 39–43. [Google Scholar]
  119. Vandenberg, L.N.; Colborn, T.; Hayes, T.B.; Heindel, J.J.; Jacobs, D.R., Jr.; Lee, D.H.; Shioda, T.; Soto, A.M.; vom Saal, F.S.; Welshons, W.V.; et al. Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses. Endocr. Rev. 2012, 33, 378–455. [Google Scholar] [CrossRef]
  120. Dong, X.; Fan, Y.; Yu, L.; Hu, Y. Synthesis of four natural prenylflavonoids and their estrogen-like activities. Arch. Pharm. 2007, 340, 372–376. [Google Scholar] [CrossRef] [PubMed]
  121. Galluzzo, P.; Ascenzi, P.; Bulzomi, P.; Marino, M. The nutritional flavanone naringenin triggers antiestrogenic effects by regulating estrogen receptor alpha-palmitoylation. Endocrinology 2008, 149, 2567–2575. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  122. Liu, L.L.; Liu, L.; Liu, H.H.; Ren, S.S.; Dou, C.Y.; Cheng, P.P.; Wang, C.L.; Wang, L.N.; Chen, X.L.; Zhang, H.; et al. Levamisole suppresses adipogenesis of aplastic anaemia-derived bone marrow mesenchymal stem cells through ZFP36L1-PPARGC1B axis. J. Cell. Mol. Med. 2018, 22, 4496–4506. [Google Scholar] [CrossRef] [PubMed]
  123. Zhou, D.; Wang, L.; Cui, Q.; Iftikhar, R.; Xia, Y.; Xu, P. Repositioning Lidocaine as an Anticancer Drug: The Role beyond Anesthesia. Front. Cell Dev. Biol. 2020, 8, 565. [Google Scholar] [CrossRef]
  124. Mesnage, R.; Biserni, M.; Genkova, D.; Wesolowski, L.; Antoniou, M.N. Evaluation of neonicotinoid insecticides for oestrogenic, thyroidogenic and adipogenic activity reveals imidacloprid causes lipid accumulation. J. Appl. Toxicol. 2018, 38, 1483–1491. [Google Scholar] [CrossRef]
  125. Pavan, B.; Biondi, C.; Ferretti, M.E.; Lunghi, L.; Paganetto, G. Phthalic acid mimics 17beta-estradiol actions in WISH cells. Toxicol. Lett. 2001, 118, 157–164. [Google Scholar] [CrossRef]
  126. Cheon, Y.P. Di-(2-ethylhexyl) Phthalate (DEHP) and Uterine Histological Characteristics. Dev. Reprod. 2020, 24, 1–17. [Google Scholar] [CrossRef]
  127. Dündar, Y.; Özatik, Y.; Özatik, O.; Ergin, V.; Önkol, T.; Menevşe, A.; Erol, K.; Sahin, M.F. Synthesis and biological evaluation of the salicylamide and salicylic acid derivatives as anti-estrogen agents. Med. Chem. 2012, 8, 481–490. [Google Scholar] [CrossRef]
  128. Li, S.; Sun, Q.; Wu, Q.; Gui, W.; Zhu, G.; Schlenk, D. Endocrine disrupting effects of tebuconazole on different life stages of zebrafish (Danio rerio). Environ. Pollut. 2019, 249, 1049–1059. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  129. Ren, Y.; Zheng, J.; Wang, H. Transiently gene-modulated cell reporter for ultrasensitive detection of estrogen-like compounds in tap water. Chemosphere 2022, 289, 133161. [Google Scholar] [CrossRef] [PubMed]
  130. Jones, R.R.; Stavreva, D.A.; Weyer, P.J.; Varticovski, L.; Inoue-Choi, M.; Medgyesi, D.N.; Chavis, N.; Graubard, B.I.; Cain, T.; Wichman, M. Pilot study of global endocrine disrupting activity in Iowa public drinking water utilities using cell-based assays. Sci. Total Environ. 2020, 714, 136317. [Google Scholar] [CrossRef] [PubMed]
  131. Wagner, M.; Oehlmann, J. Endocrine disruptors in bottled mineral water: Estrogenic activity in the E-Screen. J. Steroid Biochem. Mol. Biol. 2011, 127, 128–135. [Google Scholar] [CrossRef] [Green Version]
  132. Pironti, C.; Ricciardi, M.; Proto, A.; Bianco, P.M.; Montano, L.; Motta, O. Endocrine-disrupting compounds: An overview on their occurrence in the aquatic environment and human exposure. Water 2021, 13, 1347. [Google Scholar] [CrossRef]
  133. Kumawat, M.; Sharma, P.; Pal, N.; James, M.M.; Verma, V.; Tiwari, R.R.; Shubham, S.; Sarma, D.K.; Kumar, M. Occurrence and seasonal disparity of emerging endocrine disrupting chemicals in a drinking water supply system and associated health risk. Sci. Rep. 2022, 12, 9252. [Google Scholar] [CrossRef]
  134. Tue, N.M.; Matsukami, H.; Tuyen, L.H.; Suzuki, G.; Viet, P.H.; Sudaryanto, A.; Subramanian, A.; Tanabe, S.; Kunisue, T. Estrogenic, androgenic, and glucocorticoid activities and major causative compounds in river waters from three Asian countries. Environ. Sci. Pollut. Res. 2022, 1–10. [Google Scholar] [CrossRef]
  135. Yu, M.; Lavonen, E.; Oskarsson, A.; Lundqvist, J. Removal of oxidative stress and genotoxic activities during drinking water production by ozonation and granular activated carbon filtration. Environ. Sci. Eur. 2021, 33, 124. [Google Scholar] [CrossRef]
  136. Fekadu, S.; Alemayehu, E.; Dewil, R.; Van der Bruggen, B. Pharmaceuticals in freshwater aquatic environments: A comparison of the African and European challenge. Sci. Total Environ. 2019, 654, 324–337. [Google Scholar] [CrossRef]
  137. Ronderos-Lara, J.G.; Saldarriaga-Noreña, H.; Murillo-Tovar, M.A.; Alvarez, L.; Vergara-Sánchez, J.; Barba, V.; Guerrero-Alvarez, J.A. Distribution and Estrogenic Risk of Alkylphenolic Compounds, Hormones and Drugs Contained in Water and Natural Surface Sediments, Morelos, Mexico. Separations 2022, 9, 19. [Google Scholar] [CrossRef]
  138. Huang, C.; Zhou, W.; Bian, C.; Wang, L.; Li, Y.; Li, B. Degradation and Pathways of Carvone in Soil and Water. Molecules 2022, 27, 2415. [Google Scholar] [CrossRef] [PubMed]
  139. Hartmans, K.J.; Diepenhorst, P.; Bakker, W.; Gorris, L.G.M. The use of carvone in agriculture: Sprout suppression of potatoes and antifungal activity against potato tuber and other plant diseases. Ind. Crops Prod. 1995, 4, 3–13. [Google Scholar] [CrossRef]
  140. Whittaker, M.H.; Gebhart, A.M.; Miller, T.C.; Hammer, F. Human health risk assessment of 2-mercaptobenzothiazole in drinking water. Toxicol. Ind. Health 2004, 20, 149–163. [Google Scholar] [CrossRef] [PubMed]
  141. EFSA Scientific Committee. Scientific Opinion on the safety assessment of carvone, considering all sources of exposure. EFSA J. 2014, 12, 3806. [Google Scholar] [CrossRef]
  142. Toth, C. Pregabalin: Latest safety evidence and clinical implications for the management of neuropathic pain. Ther. Adv. Drug Saf. 2014, 5, 38–56. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  143. Wilkinson, J.L.; Boxall, A.B.A.; Kolpin, D.W.; Leung, K.M.Y.; Lai, R.W.S.; Galbán-Malagón, C.; Adell, A.D.; Mondon, J.; Metian, M.; Marchant, R.A. Pharmaceutical pollution of the world’s rivers. Proc. Natl. Acad. Sci. USA 2022, 119, e2113947119. [Google Scholar] [CrossRef] [PubMed]
  144. King, A.C.F.; Giorio, C.; Wolff, E.; Thomas, E.; Roverso, M.; Schwikowski, M.; Tapparo, A.; Bogialli, S.; Kalberer, M. Direct Injection Liquid Chromatography High-Resolution Mass Spectrometry for Determination of Primary and Secondary Terrestrial and Marine Biomarkers in Ice Cores. Anal. Chem. 2019, 91, 5051–5057. [Google Scholar] [CrossRef]
  145. Datel, J.V.; Hrabankova, A. Pharmaceuticals load in the svihov water reservoir (Czech Republic) and impacts on quality of treated drinking water. Water 2020, 12, 1387. [Google Scholar] [CrossRef]
  146. Lu, J.; Wu, J.; Stoffella, P.J.; Wilson, P.C. Analysis of bisphenol A, nonylphenol, and natural estrogens in vegetables and fruits using gas chromatography–tandem mass spectrometry. J. Agric. Food Chem. 2013, 61, 84–89. [Google Scholar] [CrossRef]
  147. Lecomte, S.; Demay, F.; Ferrière, F.; Pakdel, F. Phytochemicals Targeting Estrogen Receptors: Beneficial Rather Than Adverse Effects? Int. J. Mol. Sci. 2017, 18, 1381. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  148. Ikeda, K.; Arao, Y.; Otsuka, H.; Nomoto, S.; Horiguchi, H.; Kato, S.; Kayama, F. Terpenoids Found in the Umbelliferae Family Act as Agonists/Antagonists for ERα and ERβ: Differential Transcription Activity between Ferutinine-Liganded ERα and ERβ. Biochem. Biophys. Res. Commun. 2002, 291, 354–360. [Google Scholar] [CrossRef] [PubMed]
  149. Aloshoush, A. Medicinal Plants used in Traditional Herbal Medicine in the Fifa Village/Southern Jordan. Int. J. Med. Plants Nat. Prod. (IJMPNP) 2020, 6, 5–8. [Google Scholar]
  150. Yamamoto, H.; Watanabe, M.; Katsuki, S.; Nakamura, Y.; Moriguchi, S.; Sekizawa, J. Preliminary ecological risk assessment of butylparaben and benzylparaben -2. Fate and partitioning in aquatic environments. Environ. Sci. 2007, 14, 97–105. [Google Scholar] [PubMed]
  151. Markit, I.H.S. Plasticizers. Chemical Economics Handbook; HIS Markit Ltd.: London, UK, 2018. [Google Scholar]
  152. Yan, Y.; Zhu, F.; Zhu, C.; Chen, Z.; Liu, S.; Wang, C.; Gu, C. Dibutyl phthalate release from polyvinyl chloride microplastics: Influence of plastic properties and environmental factors. Water Res. 2021, 204, 117597. [Google Scholar] [CrossRef]
  153. Sedha, S.; Lee, H.; Singh, S.; Kumar, S.; Jain, S.; Ahmad, A.; Bin Jardan, Y.A.; Sonwal, S.; Shukla, S.; Simal-Gandara, J.; et al. Reproductive toxic potential of phthalate compounds—State of art review. Pharmacol. Res. 2021, 167, 105536. [Google Scholar] [CrossRef]
  154. Torres Acosta, J.A.; Michlmayr, H.; Shams, M.; Schweiger, W.; Wiesenberger, G.; Mitterbauer, R.; Werner, U.; Merz, D.; Hauser, M.-T.; Hametner, C. Zearalenone and ß-zearalenol but not their glucosides inhibit heat shock protein 90 ATPase activity. Front. Pharmacol. 2019, 10, 1160. [Google Scholar] [CrossRef] [Green Version]
  155. Falkauskas, R.; Bakutis, B.; Jovaišienė, J.; Vaičiulienė, G.; Gerulis, G.; Kerzienė, S.; Jacevičienė, I.; Jacevičius, E.; Baliukonienė, V. Zearalenone and Its Metabolites in Blood Serum, Urine, and Milk of Dairy Cows. Animals 2022, 12, 1651. [Google Scholar] [CrossRef]
  156. Meucci, V.; Soldani, G.; Razzuoli, E.; Saggese, G.; Massart, F. Mycoestrogen pollution of Italian infant food. J. Pediatr. 2011, 159, 278–283. [Google Scholar] [CrossRef]
  157. Wang, L.; Zhang, Q.; Yan, Z.; Tan, Y.; Zhu, R.; Yu, D.; Yang, H.; Wu, A. Occurrence and quantitative risk assessment of twelve mycotoxins in eggs and chicken tissues in China. Toxins 2018, 10, 477. [Google Scholar] [CrossRef]
  158. Mwihia, E.W.; Lyche, J.L.; Mbuthia, P.G.; Ivanova, L.; Uhlig, S.; Gathumbi, J.K.; Maina, J.G.; Eshitera, E.E.; Eriksen, G.S. Co-Occurrence and levels of mycotoxins in fish feeds in Kenya. Toxins 2020, 12, 627. [Google Scholar] [CrossRef] [PubMed]
  159. Keller, L.; Abrunhosa, L.; Keller, K.; Rosa, C.A.; Cavaglieri, L.; Venâncio, A. Zearalenone and Its Derivatives α-Zearalenol and β-Zearalenol Decontamination by Saccharomyces cerevisiae Strains Isolated from Bovine Forage. Toxins 2015, 7, 3297–3308. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  160. Ito, H.C.; Shiraishi, H.; Nakagawa, M.; Takamura, N. Combined impact of pesticides and other environmental stressors on animal diversity in irrigation ponds. PloS ONE 2020, 15, e0229052. [Google Scholar] [CrossRef] [PubMed]
  161. Viegas, S.; Assunção, R.; Martins, C.; Caetano, L.A.; Viegas, C. Portuguese Groundwater Contamination with Fungicides: The Need for Action. 2021. Available online: https://repositorio.ipl.pt/handle/10400.21/13622 (accessed on 4 November 2022).
  162. Del Puerto, O.; Gonçalves, N.P.F.; Medana, C.; Prevot, A.B.; Roslev, P. Attenuation of toxicity and occurrence of degradation products of the fungicide tebuconazole after combined vacuum UV and UVC treatment of drinking water. Environ. Sci. Pollut. Res. 2022, 29, 58312–58325. [Google Scholar] [CrossRef]
  163. Albers, C.N.; Bollmann, U.E.; Badawi, N.; Johnsen, A.R. Leaching of 1, 2, 4-triazole from commercial barley seeds coated with tebuconazole and prothioconazole. Chemosphere 2022, 286, 131819. [Google Scholar] [CrossRef]
  164. Bending, G.D.; Rodríguez-Cruz, M.S.; Lincoln, S.D. Fungicide impacts on microbial communities in soils with contrasting management histories. Chemosphere 2007, 69, 82–88. [Google Scholar] [CrossRef]
  165. Da Silva, J.P.; Da Silva, A.M.; Khmelinskii, I.V.; Martinho, J.M.G.; Ferreira, L.F.V. Photophysics and photochemistry of azole fungicides: Triadimefon and triadimenol. J. Photochem. Photobiol. A Chem. 2001, 142, 31–37. [Google Scholar] [CrossRef]
  166. Wang, Y.; Ning, X.; Li, G.; Sang, N. New insights into potential estrogen agonistic activity of triazole fungicides and coupled metabolic disturbance. J. Hazard. Mater. 2022, 424, 127479. [Google Scholar] [CrossRef]
  167. Lu, P.; Li, Q.; Liu, H.; Feng, Z.; Yan, X.; Hong, Q.; Li, S. Biodegradation of chlorpyrifos and 3, 5, 6-trichloro-2-pyridinol by Cupriavidus sp. DT-1. Bioresour. Technol. 2013, 127, 337–342. [Google Scholar] [CrossRef]
  168. Wang, L.; Wu, Y.; Zhang, W.; Kannan, K. Characteristic Profiles of Urinary p-Hydroxybenzoic Acid and its Esters (Parabens) in Children and Adults from the United States and China. Environ. Sci. Technol. 2013, 47, 2069–2076. [Google Scholar] [CrossRef]
  169. Alawi, I.N.T.M.A.; Abu, R.H.S.R.M. Pesticide Residues in Commonly Consumed Fruits and Vegetables in Jordan and Their Associated Health Risk Assessments. Jordan J. Chem. (JJC) 2019, 14, 69–80. [Google Scholar]
  170. Al-Nasir, F.M.; Jiries, A.G.; Al-Rabadi, G.J.; Alu’datt, M.H.; Tranchant, C.C.; Al-Dalain, S.A.; Alrabadi, N.; Madanat, O.Y.; Al-Dmour, R.S. Determination of pesticide residues in selected citrus fruits and vegetables cultivated in the Jordan Valley. LWT 2020, 123, 109005. [Google Scholar] [CrossRef]
Toxics 11 00063 g001 550
Figure 1. Summary of the Jordanian water system. (A) Surface water including dams, rivers, and streams. (B) Groundwater basins and their annual safe yield in millions of cubic meters [33].
Figure 1. Summary of the Jordanian water system. (A) Surface water including dams, rivers, and streams. (B) Groundwater basins and their annual safe yield in millions of cubic meters [33].
Toxics 11 00063 g001
Toxics 11 00063 g002 550
Figure 2. The distribution of sample collection sites.
Figure 2. The distribution of sample collection sites.
Toxics 11 00063 g002
Toxics 11 00063 g003 550
Figure 3. The distribution of potential sources of detected xenoestrogens in: (A) tap water, (B) open surface water, (C) drinking water, and (D) vegetables. The percentage in each sector represents the ratio of the overall number of xenoestrogens in a particular sector to the total number of xenoestrogens across all sectors.
Figure 3. The distribution of potential sources of detected xenoestrogens in: (A) tap water, (B) open surface water, (C) drinking water, and (D) vegetables. The percentage in each sector represents the ratio of the overall number of xenoestrogens in a particular sector to the total number of xenoestrogens across all sectors.
Toxics 11 00063 g003
Toxics 11 00063 g004 550
Figure 4. Elemental analysis of pregabalin (left) and DL-2-aminooctanoic acid (right), generated using Marvin Sketch.
Figure 4. Elemental analysis of pregabalin (left) and DL-2-aminooctanoic acid (right), generated using Marvin Sketch.
Toxics 11 00063 g004
Table
Table 1. Sample collection sites.
Table 1. Sample collection sites.
NameSamples Collection by
King Talal DamMWI 1
Almujeb DamMWI
As-Samra Wastewater Treatment PlantMWI
King Abdullah Canal: Dair AllaMWI
Tap water Researchers
Drinking water Researchers
1 MWI: Ministry of Water and Irrigation.
Table
Table 2. The estrogenic activity using the YES assay.
Table 2. The estrogenic activity using the YES assay.
NameTotal 17β-Estradiol Equivalents (ng/L)
King Talal Dam2.9 ± 1.2
Almujeb DamND
As-Samra Wastewater Treatment Plant9.5 ± 5
King Abdullah Canal: Dair Alla2.5 ±1.5
Tap water 1.4 ± 0.9
Drinking water ND
Table
Table 3. Detected xenoestrogens in tap water.
Table 3. Detected xenoestrogens in tap water.
Expected CompoundIrbidAmmanOrigin 3Ref. 2Chemical Structure 1
3-MethylcholanthreneYesYesPesticide/fungicide[58]Toxics 11 00063 i001
4-HydroxybenzophenoneYesYesIntermediate of clomiphene[59]Toxics 11 00063 i002
7,12-Dimethyl-benz(a)anthraceneYesYesIncomplete combustion of gasoline and coal[60]Toxics 11 00063 i003
AldrinYesYesBanned insecticide [61]Toxics 11 00063 i004
BenomylYesYesFungicide[62]Toxics 11 00063 i005
Benzophenone-3-YesSunscreen agent [63]Toxics 11 00063 i006
Betamethasone valerateYesYesCorticosteroid[64]Toxics 11 00063 i007
Bisphenol AYesYesManufacturing of various plastics[65]Toxics 11 00063 i008
CarbanilideYesYesPesticide[66]Toxics 11 00063 i009
CarbendazimYesYesFungicide[67]Toxics 11 00063 i010
CarvoneYesYesInsect repellent[68]Toxics 11 00063 i011
CyhalothrinYesYesPesticide[69]Toxics 11 00063 i012
CyprodinilYesYesFungicide[70]Toxics 11 00063 i013
DimethomorphYes-Fungicide[71]Toxics 11 00063 i014
Dodemorph IIYesYesPesticide [72]Toxics 11 00063 i015
FenarimolYesYesFungicide[73]Toxics 11 00063 i016
FenitrothionYesYesPesticide[74]Toxics 11 00063 i017
Ferutinin-YesNatural product[75]Toxics 11 00063 i018
FludioxonilYesYesFungicide[76]Toxics 11 00063 i019
HydrocortisoneYesYesHormone cortisol[77]Toxics 11 00063 i020
ImazalilYes-Pesticide[78]Toxics 11 00063 i021
Isopentyl-4-methoxycinnamate-YesSunscreen product[79]Toxics 11 00063 i022
2-Mercaptobenzothiazole-YesPesticide[80]Toxics 11 00063 i023
MetolachlorYesYesHerbicide[81]Toxics 11 00063 i024
Octocrylene-YesSunscreen product[82]Toxics 11 00063 i025
Para amino-benzoic acid-YesSunscreen product[83]Toxics 11 00063 i026
PermethrinYesYesInsecticide[84]Toxics 11 00063 i027
PregabalinYesYesPharmaceuticals[85]Toxics 11 00063 i028
ProchlorazYesYesFungicide[86]Toxics 11 00063 i029
PropamocarbYesYesFungicide[87]Toxics 11 00063 i030
ProtopanaxadiolYesYesNatural product [88]Toxics 11 00063 i031
PyrimethanilYesYesFungicide [89]Toxics 11 00063 i032
TemephosYesYesOrganophosphate larvicide [90]Toxics 11 00063 i033
TetramethrinYesYesInsecticide [91]Toxics 11 00063 i034
1 Marvin Sketch was used to draw the chemical structures. 2 Citation describing the estrogenic activity of the identified xenoestrogen. 3 Potential source of the xenoestrogen.
Table
Table 5. Detected xenoestrogens in drinking water.
Table 5. Detected xenoestrogens in drinking water.
Expected CompoundOrigin 3Ref. 2Chemical Structure 1
CarvoneInsect repellent[68]Toxics 11 00063 i064
2-MercaptobenzothiazolePesticide [80]Toxics 11 00063 i065
PregabalinPharmaceutical[85]Toxics 11 00063 i066
1 Marvin Sketch was used to draw the chemical structures. 2 Citation describing the estrogenic activity of the identified xenoestrogen. 3 Potential source of the xenoestrogen.
Table
Table 6. Detected xenoestrogens in vegetables.
Table 6. Detected xenoestrogens in vegetables.
Expected CompoundOrigin 3Ref. 2Chemical Structure 1
FerutininNatural product [75]Toxics 11 00063 i067
ButylparabenSunscreens [168]Toxics 11 00063 i068
DibutylphthalatePlasticizer [114]Toxics 11 00063 i069
Alpha-zearalenolNatural product [109]Toxics 11 00063 i070
FerimzoneFungicide[117]Toxics 11 00063 i071
TebuconazoleFungicide [128]Toxics 11 00063 i072
3 5 6-Trichloro-2-pyridinol Pesticide [104]Toxics 11 00063 i073
1 Marvin Sketch was used to draw the chemical structures. 2 Citation describing the estrogenic activity of the identified xenoestrogen. 3 Potential source of the xenoestrogen.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Akkam, Y.; Omari, D.; Alhmoud, H.; Alajmi, M.; Akkam, N.; Aljarrah, I. Assessment of Xenoestrogens in Jordanian Water System: Activity and Identification. Toxics 2023, 11, 63. https://doi.org/10.3390/toxics11010063

AMA Style

Akkam Y, Omari D, Alhmoud H, Alajmi M, Akkam N, Aljarrah I. Assessment of Xenoestrogens in Jordanian Water System: Activity and Identification. Toxics. 2023; 11(1):63. https://doi.org/10.3390/toxics11010063

Chicago/Turabian Style

Akkam, Yazan, Derar Omari, Hassan Alhmoud, Mohammad Alajmi, Nosaibah Akkam, and Islam Aljarrah. 2023. "Assessment of Xenoestrogens in Jordanian Water System: Activity and Identification" Toxics 11, no. 1: 63. https://doi.org/10.3390/toxics11010063

APA Style

Akkam, Y., Omari, D., Alhmoud, H., Alajmi, M., Akkam, N., & Aljarrah, I. (2023). Assessment of Xenoestrogens in Jordanian Water System: Activity and Identification. Toxics, 11(1), 63. https://doi.org/10.3390/toxics11010063

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop