Environmental photochemistry of dienogest: phototransformation to estrogenic products and increased environmental persistence via reversible photohydration.

Potent trienone and dienone steroid hormones undergo a coupled photohydration (in light)-thermal dehydration (in dark) cycle that ultimately increases their environmental persistence. Here, we studied the photolysis of dienogest, a dienone progestin prescribed as a next-generation oral contraceptive, and used high resolution mass spectrometry and both 1D and 2D nuclear magnetic resonance spectroscopy to identify its phototransformation products. Dienogest undergoes rapid direct photolysis (t1/2 ∼ 1-10 min), forming complex photoproduct mixtures across the pH range examined (pH 2 to 7). Identified products include three photohydrates that account for ∼80% of the converted mass at pH 7 and revert back to parent dienogest in the absence of light. Notably, we also identified two estrogenic compounds produced via the A-ring aromatization of dienogest, evidence for a photochemically-induced increase in estrogenic activity in product mixtures. These results imply that dienogest will undergo complete and facile photolytic transformation in sunlit surface water, yet exhibit greater environmental persistence than might be anticipated by inspection of kinetic rates. Photoproduct mixtures also include transformation products with different nuclear receptor binding capabilities than the parent compound dienogest. These outcomes reveal a dynamic fate and biological risk profile for dienogest that must also take into account the composition and endocrine activity of its transformation products. Collectively, this study further illustrates the need for more holistic regulatory, risk assessment, and monitoring approaches for high potency synthetic pharmaceuticals and their bioactive transformation products.

Photocatalytic decomposition of selected estrogens and their estrogenic activity by UV-LED irradiated TiO2 immobilized on porous titanium sheets via thermal-chemical oxidation.

The removal of endocrine disrupting compounds (EDCs) remains a big challenge in water treatment. Risks associated with these compounds are not clearly defined and it is important that the water industry has additional options to increase the resiliency of water treatment systems. Titanium dioxide (TiO2) has potential applications for the removal of EDCs from water. TiO2 has been immobilized on supports using a variety of synthesis methods to increase its feasibility for water treatment. In this study, we immobilized TiO2 through the thermal-chemical oxidation of porous titania sheets. The efficiency of the material to degrade target EDCs under UV-LED irradiation was examined under a wide range of pH conditions. A yeast-estrogen screen assay was used to complement chemical analysis in assessing removal efficiency. All compounds but 17ß-estradiol were degraded and followed a pseudo first-order kinetics at all pH conditions tested, with pH 4 and pH 11 showing the most and the least efficient treatments respectively. In addition, the total estrogenic activity was substantially reduced even with the inefficient degradation of 17ß-estradiol. Additional studies will be required to optimize different treatment conditions, UV-LED configurations, and membrane fouling mitigation measures to make this technology a more viable option for water treatment.

Evaluation of toxicity and estrogenicity of the landfill-concentrated leachate during advanced oxidation treatment: chemical analyses and bioanalytical tools.

Landfill-concentrated leachate from membrane separation processes is a potential pollution source for the surroundings. In this study, the toxicity and estrogenicity potentials of concentrated leachate prior to and during UV-Fenton and Fenton treatments were assessed by a combination of chemical (di (2-ethylhexyl) phthalate and dibutyl phthalate were chosen as targets) and biological (Daphnia magna, Chlorella vulgaris, and E-screen assay) analyses. Removal efficiencies of measured di (2-ethylhexyl) phthalate and dibutyl phthalate were more than 97 % after treatment with the two methods. Biological tests showed acute toxicity effects on D. magna tests in untreated concentrated leachate samples, whereas acute toxicity on C. vulgaris tests was not observed. Both treatment methods were found to be efficient in reducing acute toxicity effects on D. magna tests. The E-screen test showed concentrated leachate had significant estrogenicity, UV-Fenton and Fenton treatment, especially the former, were effective methods for reducing estrogenicity of concentrated leachate. The EEQchem (estradiol equivalent concentration) of all samples could only explain 0.218-5.31 % range of the EEQbio. These results showed that UV-Fenton reagent could be considered as a suitable method for treatment of concentrated leachate, and the importance of the application of an integrated (biological + chemical) analytical approach for a comprehensive evaluation of treatment suitability.

The removal of estrogenic activity with UV/chlorine technology and identification of novel estrogenic disinfection by-products.

As a recently developed disinfection technology, ultraviolet (UV)/chlorine treatment has received much attention. Many studies have evaluated its effects on pathogen inactivation, contaminant removal, and formation of disinfection by-products (DBPs), but its potential for environmental estrogen removal and estrogenic DBP generation, which can also be a risk to both ecosystem and human health, have not been evaluated. In this study, UV/chlorine treatment resulted in a greater removal of estrogenic activity in synthetic effluent samples containing 17ß-estradiol (E2) than did UV or chlorine treatment alone regardless of the water quality. For both the UV/chlorine and chlorine treatments, there was significant interference from NH3-N, although the UV/chlorine treatment was less affected. Estrogen receptor based affinity chromatography was used to isolate the specific estrogenic DBPs, and a novel product, with high estrogenic activity compared to E2, Δ9(11)-dehydro-estradiol, was identified. It was generated by all three treatments, and might be previously mistakenly recognized as estrone (E1). This study demonstrated that UV/chlorine is a better treatment for the removal of 17ß-estradiol than chlorine and UV alone. The new identified estrogenic DBP, Δ9(11)-dehydro-estradiol, which can be isolated by affinity chromatography, could be an emerging concern in the future.

Micropollutant removal in an algal treatment system fed with source separated wastewater streams.

Micropollutant removal in an algal treatment system fed with source separated wastewater streams was studied. Batch experiments with the microalgae Chlorella sorokiniana grown on urine, anaerobically treated black water and synthetic urine were performed to assess the removal of six spiked pharmaceuticals (diclofenac, ibuprofen, paracetamol, metoprolol, carbamazepine and trimethoprim). Additionally, incorporation of these pharmaceuticals and three estrogens (estrone, 17ß-estradiol and ethinylestradiol) into algal biomass was studied. Biodegradation and photolysis led to 60-100% removal of diclofenac, ibuprofen, paracetamol and metoprolol. Removal of carbamazepine and trimethoprim was incomplete and did not exceed 30% and 60%, respectively. Sorption to algal biomass accounted for less than 20% of the micropollutant removal. Furthermore, the presence of micropollutants did not inhibit C. sorokiniana growth at applied concentrations. Algal treatment systems allow simultaneous removal of micropollutants and recovery of nutrients from source separated wastewater. Nutrient rich algal biomass can be harvested and applied as fertilizer in agriculture, as lower input of micropollutants to soil is achieved when algal biomass is applied as fertilizer instead of urine.

Simultaneous Degradation of Estrone, 17ß-Estradiol and 17α-Ethinyl Estradiol in an Aqueous UV/H2O2 System.

UV/H2O2, which is an advanced treatment technology used to reduce multiple contaminants, is effective in potable water treatment. Simultaneous degradation effects and kinetics of three types of coexisting micropollutant estrogens (steroid estrogens, SEs), including estrone (E1), 17ß-estradiol (E2) and 17α-ethinyl estradiol (EE2), in deionized water were studied. Experiments were carried out with ultraviolet-C (UVC) radiation, together with hydrogen peroxide (H2O2), in a cylinder photoreactor. The results demonstrated that the degradation processes of all of the estrogens strongly fit first-order kinetics. Single solutions of E1, E2 and EE2 showed higher degradation rates and removal efficiencies under the same reaction conditions compared with those under mixed conditions. Coexisting combinations of estrogens were put into the UV/H2O2 system to estimate their possible competitive influences on each other by examining their removal efficiencies and reaction rate constant, k, values. E1 is predominantly reduced rapidly during the competition, while the presence of other estrogens has negligible impacts on E1; however, the degradation of E2 and EE2 is affected by the competitive background, not in relation to the types but to the existing amounts. In the UV/H2O2 system, photocatalysis of the estrogens can stably produce an intermediate X, with the highest quantity coming from E1, while considerably lower quantities are obtained from E2 and EE2.

S2O8(2-)/UV-C and H2O2/UV-C treatment of Bisphenol A: assessment of toxicity, estrogenic activity, degradation products and results in real water.

The performance of S2O8(2-)/UV-C and H2O2/UV-C treatments was investigated for the degradation and detoxification of Bisphenol A (BPA). The acute toxicity of BPA and its degradation products was examined with the Vibrio fischeri bioassay, whereas changes in estrogenic activity were followed with the Yeast Estrogen Screen (YES) assay. LC and LC-MS/MS analyses were conducted to determine degradation products evolving during photochemical treatment. In addition, BPA-spiked real freshwater samples were also subjected to S2O8(2-)/UV-C and H2O2/UV-C treatment to study the effect of a real water matrix on BPA removal and detoxification rates. BPA removal in pure water was very fast (⩽7 min) and complete via both H2O2/UV-C and S2O8(2-)/UV-C treatment, accompanied with rapid and significant mineralization rates ranging between 70% and 85%. V.fischeri bioassay results indicated that degradation products being more toxic than BPA were formed at the initial stages of H2O2/UV-C whereas a rapid and steady reduction in toxicity was observed during S2O8(2-)/UV-C treatment in pure water. UV-C treatment products exhibited a higher estrogenic activity than the original BPA solution while the estrogenicity of BPA was completely removed during H2O2/UV-C and S2O8(2-)/UV-C treatments parallel to its degradation. 3-methylbenzoic and 4-sulfobenzoic acids, as well as the ring opening products fumaric, succinic and oxalic acids could be identified as degradation products. BPA degradation required extended treatment periods (>20 min) and TOC removals were considerably retarded (by 40%) in the raw freshwater matrix most probably due to its natural organic matter content (TOC=5.1 mg L(-1)). H2O2/UV-C and S2O8(2-)/UV-C treatment in raw freshwater did not result in toxic degradation products.

Determination of estrogenic steroids and microbial and photochemical degradation of 17α-ethinylestradiol (EE2) in lake surface water, a case study.

In this study, a GC-MS technique was applied to determine 17α-ethinylestradiol (EE2), an active ingredient of oral contraceptives, and its fate in Lake Quinsigamond, Massachusetts, USA. To the knowledge of the authors, this is the first study of EE2 and its microbial and photochemical degradation in a lake ecosystem. EE2 was detected at a concentration up to 11.1 ng L(-1). At this concentration EE2 may affect the reproduction of fish and other aquatic organisms in the lake due to its high estrogenic activity. EE2 was persistent to the biodegradation by the microorganisms in the lake. Under aerobic conditions a long lag phase (42 days) was observed before the biodegradation of EE2 and a half-life of 108 days was estimated. Under anaerobic conditions, EE2 experienced even a longer acclimation stage (63 days) and a slower microbial degradation in the lake water. The photodegradation of EE2 was rapid in the lake surface water under natural sunlight, with a half-life of less than 2 days in summer sunny days. Compared to biodegradation, photodegradation may represent a predominant removal mechanism for EE2 in natural surface waters.

Effect of water composition on TiO2 photocatalytic removal of endocrine disrupting compounds (EDCs) and estrogenic activity from secondary effluent.

The effect of inorganic ions and dissolved organic matter (DOM) on the TiO(2) photocatalytic removal of estrogenic activity from secondary effluents of municipal wastewater treatment plants was investigated. The presence of HPO(4)(2-), NH(4)(+), and HCO(3)(-) resulted in a significantly negative impact on the photocatalytic removal of estrogenic activity from synthetic water due to their strong adsorption on the surface of TiO(2). However, only a weak impact was noted during photocatalytic removal of estrogenic activity from secondary effluent with these ions added, since the presence of DOM in real wastewater played a more important role in inhibiting photocatalytic removal of estrogenic activity than inorganic ions. By investigating the effect of different DOM fractions on photocatalytic removal of estrogenic activity, polar compounds (PC) were found to cause a temporary increase in estrogenic activity during TiO(2) photocatalysis. Fluorescence spectroscopy and molecular weight (MW) analysis on secondary effluent spiked with PC during TiO(2) photocatalysis suggest that large MW organic matter (>4.5kDa) in secondary effluent, such as humic/fulvic acid, not only could play an important role in inhibiting photocatalytic removal of estrogenic activity but also is responsible for the temporary increase in estrogenic activity during the same process.

Endocrine disruptive estrogens role in electron transfer: bio-electrochemical remediation with microbial mediated electrogenesis.

Bioremediation of selected endocrine disrupting compounds (EDCs)/estrogens viz. estriol (E3) and ethynylestradiol (EE2) was evaluated in bio-electrochemical treatment (BET) system with simultaneous power generation. Estrogens supplementation along with wastewater documented enhanced electrogenic activity indicating their function in electron transfer between biocatalyst and anode as electron shuttler. EE2 addition showed more positive impact on the electrogenic activity compared to E3 supplementation. Higher estrogen concentration showed inhibitory effect on the BET performance. Poising potential during start up phase showed a marginal influence on the power output. The electrons generated during substrate degradation might have been utilized for the EDCs break down. Fuel cell behavior and anodic oxidation potential supported the observed electrogenic activity with the function of estrogens removal. Voltammetric profiles, dehydrogenase and phosphatase enzyme activities were also found to be in agreement with the power generation, electron discharge and estrogens removal.

Biomonitoring of estrogen and melatonin metabolites among women residing near radio and television broadcasting transmitters.

OBJECTIVES: Metabolites of estrogen (estrone-3-glucuronide [E1G]) and melatonin (6-hydroxymelatonin sulfate [6-OHMS]) were characterized among women living in a community with increased radiofrequency (RF) exposure from radio and television transmitters. METHODS: RF spot measurements, and personal 60-Hz magnetic field and residential parameters were collected. Overnight urine samples were assayed for E1G and 6-OHMS excretion. RESULTS: Among premenopausal women, there were no associations between RF or 60-Hz nonionizing radiation and E1G or 6-OHMS excretion. Among postmenopausal women, increased residential RF exposures, transmitter proximity and visibility, and temporally stable 60-Hz exposures were significantly associated with increased E1G excretion. This association was strongest among postmenopausal women with low overnight 6-OHMS levels. CONCLUSIONS: RF and temporally stable 60-Hz exposures were associated with increased E1G excretion among postmenopausal women. Women with reduced nocturnal 6-OHMS excretion may represent a sensitive subgroup.

Selective photocatalytic oxidation of steroid estrogens in water treatment: urea as co-pollutant.

The objective of the present research concerns the competitive photocatalytic oxidation (PCO) and adsorption of steroid estrogens (SEs) on titanium dioxide in presence of urea. The results showed the indifference of SEs towards the presence of urea in concentrations characteristic for the domestic sewage. The selective PCO of SEs appeared to be feasible in alkaline media, in which the PCO exhibited the highest efficiency. Ethanol used for hydrophobic SEs dissolution in water appeared to be interfering with the PCO.

Photodegradation of endocrine disrupting chemical nonylphenol by simulated solar UV-irradiation.

The photolysis of nonylphenol (NP) was investigated using a solar simulator in the absence/presence of dissolved organic matter (DOM), HCO3-, NO3- and Fe(III) ions. The effects of different parameters such as initial pH, initial concentration of substrate, temperature, and the effect of hydrogen peroxide concentration on photodegradation of nonylphenol in aqueous solution have been assessed. The results indicate that the oxidation rate increases in the presence of H2O2, Fe(III) and DOM with dissolved organic carbon concentrations not higher than 3 mg L(-1). Phenol, 1,4-dihydroxylbenzene and 1,4-benzoquinone were identified as intermediate products of photodegradation of nonylphenol, through an HPLC method. In addition, the disappearance of the estrogenic activity of nonylphenol during irradiation using YES test was investigated. Based upon the YES test results, there was a strong decrease of estrogenic activity of nonylphenol after 80 h irradiation in the presence of hydrogen peroxide.

Radiation damage to DNA-protein specific complexes: estrogen response element-estrogen receptor complex.

The exposure of a DNA-protein regulatory complex to ionising radiation induces damage to both partner biomolecules and thus can affect its functioning. Our study focuses on a complex formed by the estrogen response element (ERE) DNA and the recombinant human estrogen receptor alpha (ER), which mediates the signalling of female sex hormones, estrogens. The method of native polyacrylamide retardation gel electrophoresis is used to study the stability of the complex under irradiation by low LET radiation ((60)Co gamma rays) and the ability of the separately irradiated partners to form complexes. The relative probabilities of ERE DNA strand breakage and base damages as well as the probabilities of damages to the ER binding domain are calculated using the Monte Carlo method-based model RADACK.

Degradation of endocrine disrupting chemicals bisphenol A, ethinyl estradiol, and estradiol during UV photolysis and advanced oxidation processes.

The degradation of three endocrine disrupting chemicals (EDCs), bisphenol A, ethinyl estradiol, and estradiol, was investigated via ultraviolet (UV) radiation photolysis and the UV/hydrogen peroxide advanced oxidation process (AOP). These EDCs have been detected at low levels in wastewaters and surface waters in both the United States and European countries, can cause adverse effects on humans and wildlife via interactions with the endocrine system, and thus must be treated before entering the public drinking water supply. Because many EDCs can only be partially removed with conventional water treatment systems, there is a need to evaluate alternative treatment processes. For each EDC tested, direct UV photolysis quantum yields were derived for use with both monochromatic low-pressure (LP) UV lamps and polychromatic medium-pressure (MP) UV lamps and second-order hydroxyl radical rate constants were developed. These parameters were utilized to successfully model UV treatment of the EDCs in laboratory and natural waters. The polychromatic MP UV radiation source was more effective for direct photolysis degradation as compared to conventional LP UV lamps emitting monochromatic UV 254 nm radiation. However, in all cases the EDCs were more effectively degraded utilizing UV/H2O2 advanced oxidation as compared to direct UV photolysis treatment.

Rapid loss of estrogenicity of steroid estrogens by UVA photolysis and photocatalysis over an immobilised titanium dioxide catalyst.

The presence of low levels of natural and synthetic steroid estrogens in the aquatic environment, and their biological effects on aquatic organisms, are presently issues of concern. In this study, we investigated the temporal removal of estrogenic activity of several potent and environmentally relevant steroid estrogens by photocatalysis over an immobilised titanium dioxide (TiO2) catalyst. We used a recombinant yeast assay to measure estrogenic activity, which provided detection limits within the reactor of 53 ng/l for 17beta-estradiol and 17alpha-ethinylestradiol, and 100 ng/l for estrone. Pseudo-first-order kinetic data showed that photocatalysis over titanium dioxide was equally effective at removing the estrogenic activity of all three steroid substrates in aqueous solutions (initial concentrations of 10 microg/l) with a 50% reduction in estrogenicity within 10 min. In control experiments without TiO2 catalyst, the rate of UVA photolysis of the steroid substrates varied, but was most effective with 17alpha-ethinylestradiol followed by estrone, and was least effective with 17beta-estradiol (0.42, 0.2 and < 0.1 times the rate achieved with photocatalysis, respectively). The application of photocatalysis for the removal of steroid compounds within STW effluent released into the aquatic environment is discussed.

Endometrial cancer incidence in relation to electric blanket use.

Endometrial cancer is associated with endogenous and exogenous estrogen excess. Some investigators have posited that electromagnetic fields may influence cancer risk through estrogenic hormonal mechanisms; however, there have been no studies reporting on electric blanket exposure in relation to endometrial cancer. The authors examined this possible association between endometrial cancer risk and electric blanket or mattress cover use as part of a population-based, case-control study. This analysis included incident endometrial cancer cases 40-79 years of age, interviewed during 1994 (n = 148; response rate, 87%) and identified from the Wisconsin tumor registry. Female controls of similar age were randomly selected from population lists (n = 659; response rate, 85%). Information regarding electric blanket and mattress cover use and endometrial cancer risk factors was obtained through structured telephone interviews approximately 1 year after diagnosis. After adjustment for age, body mass index, and postmenopausal hormone use, the risk of endometrial cancer was similar among ever users (odds ratio = 1.04, 95% confidence interval: 0.70, 1.55) and among current users (odds ratio = 0.87, 95% confidence interval: 0.49, 1.54) as compared with never users. Despite its small size and potential misclassification of exposure, this study provides evidence against an association between electric blanket or mattress cover use and endometrial cancer.

Pelvic radiotherapy, sex hormones, and breast cancer.

Radiotherapy for malignant and benign gynecologic disease in middle age has been found to be associated inversely with the risk of breast cancer in several published studies. The ovaries received substantial doses of radiation from such treatments, in the tens of Gray (Gy) from radiotherapy for cervical cancer and one to 10 Gy from radiotherapy for benign gynecologic disease (BGD). The relative risk of breast cancer incidence or mortality decreased with increasing radiation dose to the ovaries between zero to six Gy but varied little with further increases in dose. Evidence of a protective effect even among women irradiated past the age of 50 suggests a mechanism other than that associated with induction of an early menopause. An inverse association with radiotherapy among women over age 50 was seen only for women with ovarian doses exceeding about four to five Gy, namely, those treated for cervical cancer or with external beam X-rays for BGD. Ovarian doses of two to three Gy from intrauterine radium (226Ra) treatments for BGD were not associated with an appreciably reduced risk of breast cancer, even though the treatments had the intended effect of inducing menopause in women in their mid-40s. The relevant target cells in the ovaries for radiologic menopause likely are those involved in estrogen production. Although the postmenopausal ovary has largely stopped producing estrogens, it continues to secrete androgens. Serum hormone measurements on a small sample of cervical cancer patients indicate that high-dose pelvic radiotherapy eliminates or greatly reduces this residual androgen-producing activity in ovaries of postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

[The mechanisms of the therapeutic action and the basis for the frequency of performing sessions of ultraviolet blood irradiation in treating acute pneumonia. 1]. / Nekotorye mekhanizmy lechebnogo deistviia i obosnovanie kratnosti provedeniia seansov ul'trafioletovogo oblucheniia krovi v lechenii ostroi pnevmonii. Soobshchenie 1.

Mechanisms of therapeutic action of UV blood irradiation and optimal irradiation scheduling were studied in the course of UV-irradiated blood transfusions capable of correcting lipid peroxidation (LPO) and antioxidant system (AOS) in acute pneumonia (AP) patients. Single and multiple measurements of LPO and AOS parameters (malonic dialdehyde, diene conjugates, red cell resistance to peroxide hemolysis, catalase, superoxide dismutase, cerulloplasmin, plasma total estrogens, progesterone and testosterone) were made in 10 young males with moderate AP and 20 healthy controls. UV blood irradiation in AP is shown to be pathogenetically validated. It works via effective stabilization of LPO as a result of early adequate stimulation of endogenic AOS. Positive changes were also induced in the system of hormonal regulation. It is suggested that hyperestrogenemia plays a compensatory role in AP pathogenesis.

Effect of low dose endometrial after-loading irradiation upon the hypophysis-ovarian axis.

Endometrial inactivation by irradiation, while simultaneously preserving the ovarian function is sometimes clinically indicated. We have found that after 1100 cGy (rad) the ovarian function remains intact, yet endometrial inactivation is unsatisfactory. Therefore, four premenopausal subjects, with clinical indications for eliminating disturbing uterine bleedings, received each an endometrial dose of 1600 cGy by using a Cathetron afterloading unit. When pre- and post-treatment cycles were compared, the circulating gonadotrophin and estrogen levels were unchanged in three subjects. Nine to 12 weeks after the treatments there were no signs of ovulation and the gonadotrophin levels were generally increased. None of the subjects had experienced any bleedings. We conclude that an endometrial dose of 1600 cGy is effective in inactivating endometrium, but may also lead to an impaired ovarian function and to a premature menopause.