ReviewUrinary excretion rates of natural estrogens and androgens from humans, and their occurrence and fate in the environment: A review
Introduction
Endocrine disrupting compounds (EDCs) are chemicals with the potential to elicit negative effects on the endocrine systems of humans and wildlife. Research of EDCs in the past few decades has grown rapidly. With progress of research on EDCs, the definition has been widened to include a broad class of chemicals from natural estrogens, natural androgens, phytoestrogens, synthetic estrogens and androgens, to industrial chemicals (Liu et al., 2009). Among these, natural estrogens i.e., Estrone (E1), 17β-estradiol (E2) and Estriol (E3) are the core EDCs, which are the most commonly studied and monitored.
Health concerns over the effect of EDCs on the health of humans and wildlife accelerated the research of the estrogenic (androgenic) potencies of target chemicals evaluated by in vitro bioassay. Currently, there are several bioassays available such as Yeast based recombinant estrogen receptor reporter assay (YES, Routledge and Sumpter, 1996), MCF-7 cell proliferation (E-Screen, Soto et al., 1995), Estrogen receptor-mediated chemical activated luciferase gene expression assay (ER-CALUX, Legler et al., 1999), Estrogen receptor (ER) competitive ligand binding assay (ER-Binding, Bolger et al., 1998), Yeast based recombinant androgen receptor–reporter assay (YAS, Sohoni and Sumpter, 1998), Androgen receptor (AR) competitive ligand binding assay (AR-Binding, Fang et al., 2003), and so on. Among these bioassays, YES (YAS) is the most widely applied assay in environmental samples, but research has discovered that YES (YAS) would be influenced by anti-estrogens (anti-androgens) in complex environmental samples (Liu, Liu, 2004, Conroy et al., 2007, Urbatzka et al., 2007). This effect results in the findings of great different estrogenic activities between the wastewater samples and the total of their fractionations evaluated by YES/YAS (Nakada et al., 2004, Urbatzka et al., 2007, Salste et al., 2007). Although bioassays mentioned above were all applied by researchers in real wastewater samples, no bioassay was universally accepted as a standard method like the Chemical Oxygen Demand (COD). To prove the feasibility and validity of in vitro bioassays applied to wastewater samples, the relationship of sample estrogenic activity between chemical analysis and bioassay has become one of the topics of interest. In Nakada et al. (2004), the estrogenic activities of three wastewater effluent samples derived from chemical analysis were about 151.6–916.7% of those from YES assay; in Vermeirssen et al. (2005), the estrogenic activities of several river samples (sampled by Polar Organic Chemical Integrative Sampler, POCIS (pesticides)) calculated from chemical analysis were 51–353% of those from YES, in which only E1, E2 and 17α-ethynylestradiol (EE2) were monitored by LC-MS/MS. The same tendency was also observed by Salste et al. (2007), where the chemically derived estrogenic activities of two wastewater effluent samples were about 116.1–139.6% of those from another YES assay. Tan (2006) compared both influent and effluent results of five wastewater treatment plants (WWTPs) using GC-MS analysis and E-Screen, and chemical derived values ranged from about 0.1–1340% of those from E-Screen. Liu et al. (in press) monitored as much as 15 target EDCs of two WWTPs using GC-MS and LC-MS/MS, and the chemical-derived estrogenic activities were about 1.2–83.8% of those from the ER-Binding assay, and the corresponding chemical-derived androgenic activities were all less than 3% of those from the AR-Binding assay. These results above cannot adequately support the feasibility of bioassays applied for complex environmental samples. On the contrary, in a mini-review (Schlenk, 2008), the feasibility of in vitro assay (YES) for environmental samples was questioned, in which some of the water samples were detected with no estrogenic activities by YES assay, while they were proven to have in vivo response.
With the progress of chemical analysis on EDCs for environmental samples, more and more target estrogenic chemicals were monitored. As many as 30 EDCs were monitored by GC-HRMS in five Canadian wastewater samples (Fernandez et al., 2007), and the measurement of 13 androgenic chemicals was also constructed using ultra-performance liquid chromatography electrospray tandem mass spectrometry (UPLC-MS/MS) (Chang et al., 2008). These foundations enhanced the platform of EDCs on the estrogenic (androgenic) comparison of wastewater between chemical analysis and bioassay. It is difficult, time-consuming work to monitor target chemicals in complex wastewater samples. If the source of EDCs can be roughly estimated, it will be helpful for monitoring of EDCs in environmental water samples. To date, it is well known that NEAs are one of the strongest potent EDCs evaluated by in vitro assays, and their representative E2 and testosterone (Te) were often used as the standard chemicals in bioassays. For wastewater of municipal WWTPs, it is considerable that the estrogenic (androgenic) activity is mainly derived from urine or feces of humans. Although there are many reports about the concentrations of NEAs excreted in human urine or feces, few conclusions have been made.
The objectives of this review are: (1) highlight estrogenic potencies of NEAs measured by different in vitro assays, which have been proven as existing in urine or feces; (2) summarize urinary excretion rates of NEAs from humans; (3) summarize occurrence and fate of NEAs in the environment, including free estrogens, free androgens and estrogen conjugates.
Section snippets
Estrogenic/androgenic potencies of NEAs by in vitro assays
In recent research, as many as 16 estrogens, and more androgens, were measured in urine or feces of humans (de la Torre et al., 2001, Xu et al., 2005, Xu et al., 2006), and several bioassays were used to measure and evaluate their estrogenic/androgenic activities. To show the relationship between chemical analysis and bioassays, the estrogenic/androgenic potencies of NEAs are included in Tables 1 and 2, in which their physicochemical properties are also given. In Table 1, estrogenic/androgenic
Urinary excretion rates of natural estrogens
There is much data on excretion of natural estrogens from human urine or feces, and some conclusions on E1, E2 and E3 are now available ( Kiuru, 2005, Tan, 2006). Johnson and Williams (2004) gave a more detailed conclusion on excretions of E1, E2 and E3 from humans, and a model to estimate their influent and effluent concentrations was also established. However, other natural estrogens in urine or feces of humans, which may also exist in wastewater, were considered negligible. With progress of
Natural estrogen conjugates in the environment
It is known that NEAs initially excreted by humans are mainly in sulfate or glucuronide conjugates, and then they are changed to free NEAs, in which glucuronide estrogens were reported easily changed to their free estrogens, while sulfate estrogens were more recalcitrant to biotransformation (Ternes et al., 1999a, Panter et al., 1999, D’Ascenzo et al., 2003). In D'Ascenzo et al. (2003), conjugated estrogens were individually spiked to one septic tank wastewater with concentration of 25 µg/L,
Conclusions
Based on numerous data, urinary excretion rates of NEAs from humans were comprehensively summarized and results on their occurrence and fate in the environment were also outlined. In this review article, some conclusions below may merit attention.
- (1)
Presently, research of natural estrogens in wastewater mainly focused on E1, E2 and E3, while other natural estrogens were considered negligible. However, based on the data of human urinary excretion rate, the contribution ratio of E1, E2, and E3 to
References (100)
- et al.
Liquid chromatography–tandem mass spectrometry analysis of estrogenic compounds in coastal surface water of the Baltic Sea
J Chromatogr A
(2005) - et al.
Analysis and occurrence of estrogenic hormones and their glucuronides in surface water and wastewater in The Netherlands
Sci Total Environ
(1999) - et al.
Rapid yeast estrogen bioassays stably expressing human estrogen receptor α and β, and green fluorescent protein: a comparison of different compounds with both receptor types
J Steroid Biochem Mol Bio
(2004) - et al.
Steroid estrogens in ocean sediments
Chemosphere
(2005) - et al.
Trace analysis of androgens and progestogens in environmental waters by ultra-performance liquid chromatography electrospray tandem mass spectrometry
J Chromatogr A
(2008) - et al.
The solids retention time — a suitable design parameter to evaluate the capacity of wastewater treatment plants to remove micropollutants
Water Res
(2005) - et al.
The preparation of pregnancy urine for an estrogen profile
Steroid
(1978) - et al.
Changes in estrogen/anti-estrogen activities in ponded secondary effluent
Sci Total Environ
(2007) - et al.
Fate of natural estrogen conjugates in municipal sewage transport and treatment facilities
Sci Total Environ
(2003) - et al.
Changes in androgenic steroid profile duo to urine contamination by microorganisms: a prospective study in the context of doping control
Anal Biochem
(2001)
An assessment of estrogenic organic contaminants in Canadian wastewaters
Sci Total Environ
Quantitation of estrogens in ground water and swine lagoon samples using solid-phase extraction, pentafluorobenzyl/trimethylsiyl derivatizations and gas chromatography-negative ion chemical ionization tandem mass spectrometry
J Chromatogr A
The multicomponent analysis of estrogens in urine by ion exchange chromatography and GC-MS-II. Fraction and quantitation of the main groups of estrogen conjugates
J Steroid Biochem
The multicomponent analysis of estrogens in urine by ion exchange chromatography and GC-MS-I. Quantitation of estrogens after initial hydrolysis of conjugates
J Steroid Biochem
An improved method for the simultaneous analysis of phenolic and steroidal estrogens in water and sediment
Talanta
Monitoring of selected estrogenic hormones and industrial chemicals in groundwaters and surface waters in Austria
Sci Total Environ
Determination of estrogens and their conjugates in water using solid-phase extraction followed by liquid chromatography–tandem mass spectrometry
J. Chromatogr A
Horizontal distribution of steroid estrogens in surface sediments in Tokyo bay
Environ Pollut
Occurrence and treatment trials of endocrine disrupting chemicals (EDCs) in wastewaters
Chemosphere
Estimating steroid oestrogen inputs into activated sludge treatment works and observations on their removal from the effluent
Sci Total Environ
Occurrence and biological effect of exogenous steroids in the Elkhorn river, Nebraska, USA
Sci Total Environ
Analysis of estrogens in river sediments by liquid chromatography–electrospray ionisation mass spectrometry comparison of tandem mass spectrometry and time-of-flight mass spectrometry
J Chromatogr A
Analytical methodologies for determining the occurrence of endocrine disrupting chemicals in sewage treatment plants and natural waters
Anal Chim Acta
Bioassay-derived androgenic and estrogenic activity in municipal sewage in Australia and New Zealand
Ecotoxicol Environ Safe
Removal mechanisms for endocrine disrupting compounds (EDCs) in wastewater-physical means, biodegradation, and chemical advanced oxidation: a review
Sci Total Environ
Combined isolation and purification procedures prior to the high-performance liquid chromatographic-ion-trap tandem mass spectrometric determination of estrogens and their conjugates in river sediments
J Chromatogr A
Studies on testosterone metabolism. VI. Precursors of urinary androstanediols
Steroids
Transformation of a non-oestrogenic steroid metabolite to an oestrogenically active substance by minimal bacterial activity
Chemosphere
Monitoring of estrogens, pesticides and bisphenol A in natural waters and drinking water treatment plants by solid-phase extraction–liquid chromatography mass spectrometry
J Chromatogr A
Determination of estrogens and estrogenic activity in wastewater effluent by chemical analysis and the bioluminescent yeas assay
Sci Total Environ
Are steroids really the cause for fish feminization? A mini-review of in vitro and in vivo guided TIEs
Mar Pollut Bull
Distribution of estrogens, 17β-estradiol and estrone, in Canadian municipal wastewater treatment plants
Sci Total Environ
Toxicological profile of pollutants in surface water from an area in Taihu lake, Yangtze Delta
Toxicology
Washout of accumulated testosterone in a watershed
Sci Total Environ
Behaviour and occurrence of estrogens in municipal sewage treatment plants-II. Aerobic batch experiments with activated sludge
Sci Total Environ
Behavior and occurrence of estrogens in municipal sewage treatment plants-I. Investigations in Germany, Canada and Brazil
Sci Total Environ
Androgenic and antiandrogenic activities in water and sediment samples from the river Lambro, Italy, detected by yeast androgen screen and chemical analyses
Chemosphere
Analysis of estrogens in river water and effluents using solid-phase extraction and gas chromatography-negative chemical ionization mass spectrometry of the pentafluorobenzoyl derivatives
J Chromatogr A
Oestrogen in human pregnancy faeces
ACTA Endocrinologica
Monitoring natural and synthetic estrogens at activated sludge sewage treatment plants and in a receiving river water
Environ Sci Technol
Characterization of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor
APMIS
Rapid screening of environmental chemicals for estrogen receptor binding capacity
Environ Health Environ
Occurrence of natural and synthetic glucocorticoids in sewage treatment plants and receiving river waters
Environ Sci Technol
An assessment of endocrine disrupting activity changes during wastewater treatment through the use of bioassays and chemical measurements
Water Environ Res
Identification of metabolites of trenbolone acetate in androgenic runoff from a beef feedlot
Environ Health Perspect
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor
Chem Res Toxicol
Chemistry and structural biology of androgen receptor
Chem Rev
Analysis of free estrogens and their conjugates in sewage and river waters by solid phase extraction then liquid chromatography–electrospray–tandem mass spectrometry
Chromatographia
Urine steroid hormone analysis in cytochrome P450 oxidoreductase deficiency:implication for the backdoor pathway to dihydrotestosterone
J Clin Endocrin Metab
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