Environment International 99 (2017) 107–119

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Environment International

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Review article

Environmental impact of estrogens on human, animal and plant life: A

critical review
Muhammad Adeel a, Xiaoming Song a, Yuanyuan Wang a, Dennis Francis a, Yuesuo Yang a,b,⁎
a
Key Lab of Eco-restoration of Regional Contaminated Environment (Shenyang University), Ministry of Education, Shenyang 11044, PR China
b
Key Lab of Groundwater Resources & Environment (Jilin University), Ministry of Education, Changchun 130021, PR China

a r t i c l e i n f o a b s t r a c t

Article history: Background: Since the inception of global industrialization, steroidal estrogens have become an emerging and seri-
Received 20 September 2016 ous concern. Worldwide, steroid estrogens including estrone, estradiol and estriol, pose serious threats to soil,
Received in revised form 10 December 2016 plants, water resources and humans. Indeed, estrogens have gained notable attention in recent years, due to their
Accepted 12 December 2016 rapidly increasing concentrations in soil and water all over the world. Concern has been expressed regarding the
Available online 29 December 2016
entry of estrogens into the human food chain which in turn relates to how plants take up and metabolism estrogens.
Objectives: In this review we explore the environmental fate of estrogens highlighting their release through effluent
Keywords:
Estrogens
sources, their uptake, partitioning and physiological effects in the ecological system. We draw attention to the po-
Environmental fate tential risk of intensive modern agriculture and waste disposal systems on estrogen release and their effects on
Endocrine disrupting chemical (EDC) human health. We also highlight their uptake and metabolism in plants.
Plant uptake Methods: We use MEDLINE and other search data bases for estrogens in the environment from 2005 to the present,
Bioavailability with the majority of our sources spanning the past five years. Published acceptable daily intake of estrogens (μg/L)
Aquatic ecology and predicted no effect concentrations (μg/L) are listed from published sources and used as thresholds to discuss
Water and soil reported levels of estrogens in the aquatic and terrestrial environments. Global levels of estrogens from river sources
and from Waste Water Treatment Facilities have been mapped, together with transport pathways of estrogens in
plants.
Results: Estrogens at polluting levels have been detected at sites close to waste water treatment facilities and in
groundwater at various sites globally. Estrogens at pollutant levels have been linked with breast cancer in
women and prostate cancer in men. Estrogens also perturb fish physiology and can affect reproductive develop-
ment in both domestic and wild animals. Treatment of plants with steroid estrogen hormones or their precursors
can affect root and shoot development, flowering and germination. However, estrogens can ameliorate the effects
of other environmental stresses on the plant.
Conclusions: There is published evidence to establish a causal relationship between estrogens in the environment
and breast cancer. However, there are serious gaps in our knowledge about estrogen levels in the environment
and a call is required for a world wide effort to provide more data on many more samples sites. Of the data avail-
able, the synthetic estrogen, ethinyl estradiol, is more persistent in the environment than natural estrogens and
may be a greater cause for environmental concern. Finally, we believe that there is an urgent requirement for
inter-disciplinary studies of estrogens in order to better understand their ecological and environmental impact.
© 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
2. Source of steroidal estrogens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

Abbreviations: E1, estrone; E2, estradiol; 17β-E2, 17β-estradiol; 17α-E2, 17α-estradiol; E3, estriol; EE2, ethinyl estradiol; CAFOs, concentrated animal feeding operations; WWTPs,
waste water treatment plants; MSH, mammalian sex hormones; CAT, catalase; POX, peroxidase; MSTPs, municipal sewage treatment plants; GLU, glucuronide; SUL, sulfate; STPs,
sewage treatment plants; BW, body weight; PNEC, predicted-no-effect concentration; NOEL, no-observed-adverse-effect; JECFA, Joint Expert Committee on Food Additives; ADI,
average daily intake; ROS, reactive oxygen species; SOD, superoxide dismutase; CAT, catalase; GPX, guaiacol peroxidase; AsA-GSH, ascorbate glutathione; APX, ascorbate peroxidase;
MDHAR, mono dehydro ascorbate reductase; DHAR, dehydroascorbate reductase; GR, glutathione reductase; AsA, ascorbate; GSH, glutathione; VTG, vitellogenin; IOP, intraocular eye
pressure; HRT, hormone replacement therapy.
⁎ Corresponding author at: Key Lab of Eco-restoration of Regional Contaminated Environment (Shenyang University), Ministry of Education, Shenyang 11044, PR China.
E-mail address: yangyuesuo@jlu.edu.cn (Y. Yang).

http://dx.doi.org/10.1016/j.envint.2016.12.010
0160-4120/© 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
108 M. Adeel et al. / Environment International 99 (2017) 107–119

3. Occurrence of steroidal estrogens in the environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109

3.1. Human intake of estrogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
3.2. Estrogens on a global scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
4. Estrogen degradation and half-life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
5. Estrogen transformation cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
6. Effects of steroidal estrogens on fish, domestic animals and human health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
6.1. Aquatic wildlife . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
6.2. Domestic animals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
6.3. Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
7. Uptake and transport mechanisms in plant systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
7.1. Transport from the root to other plant parts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
8. Accumulation of estrogen in plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
8.1. Effects of estrogens on plant growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
8.2. Effects of estrogen on plant antioxidant activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
9. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Role of the funding source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117

1. Introduction (pKa = 10.3–10.8) (see Table 1). These coefficients including Kd

Estrogens are biologically active hormones that are derived from
cholesterol and released by the adrenal cortex, testes, ovary and placen-
ta in humans and animals. Estrogenic compounds have also been found
in plants (Hamid and Eskicioglu, 2012; Ying et al., 2002). Steroid estro-
gens can be classified as natural or synthetic hormones (Fig. 1) and can
act as endocrine disrupting chemicals (EDCs).
Natural steroidal estrogens (also known as the C18 steroidal group)
share the same tetracyclic molecular framework comprising four
rings, one phenolic group, two cyclohexane and one cyclo-pentane
ring (Fig. 1). Structural differences within the C18 group lie in the
configuration of the D-ring at positions C16 and C17. For example,
estrone (E1) has a carbonyl group on C17, 17β-estradiol (E2) has a
hydroxyl group on C17, whilst estriol (E3) has two alcohol groups
on C16 and C17 (Fig. 1). The C17 hydroxyl group of the E2 can either
point downward or upward on the molecular plane, forming either
the α- or β-compound. Conjugated estrogens, which are also poten-
tial environmental hazards, are formed by esterification of free estro-
gens by glucuronide and sulfate groups at the position(s) of C3 and/
or C17 (Hamid and Eskicioglu, 2012; Khanal et al., 2006).
Understanding the physiochemical properties of steroidal estrogens
compounds is crucial in order to resolve their fate in soil and water
systems. The distribution of organic pollutants between water and
other natural solids are often considered as a partitioning process be-
tween the aqueous and organic phase. The water partition coefficient
(Kow), is the ratio of the concentration of a compound in n-octanol
and water under equilibrium conditions at a particular temperature.
Compounds with a high molecular weight and a high log Kow of N 5
are easily adsorbed to sediments and can be primarily removed by
coagulation. Estrogens are expected to be absorbed onto the solid
phases due to their significant log Kow (Pal et al., 2010). Accordingly,
among the estrogens E2 has the highest hydrophobicity but all ste-
roidal estrogens are moderately hydrophobic (log Kow = 2.4–4.0),
nonvolatile (vapor pressure 9 × 10 − 13–3 × 10 − 8 Pa), weak acids
can be used to evaluate the fate of the organic compounds during ex-
periments, thus avoiding an expensive and time-consuming analy-
sis. Furthermore, they provide a calculation method to estimate the
percentage of a substance being absorbed onto solid phase, which
is finally discharged to the environment, and that which is dissolved
in the liquid phase (Carballa et al., 2008).
Generally, unconjugated estrogens or free estrogens are not very
soluble in water; EE2 is the least soluble. At pH 7, the order of aque-
ous solubility was E1 (one OH group) to E2 (two OH groups) and
then EE2 with the added ethinyl groups at 17α-position on the D
ring; solubility appeared to be the same at pH 4 and 7. However, sol-
ubility can be pH-dependent because, for example, at pH 10, relative
solubility of estrogens are higher (Shareef et al., 2006).
The world's human population of about 7 billion discharges approx-
imately 30,000 kg/yr. of natural steroidal estrogens (E1, E2, and E3) and
an additional 700 kg/yr. of synthetic estrogens (EE2) solely from birth
control pill practices. However, the possible release of estrogens to the
environment from livestock is much higher. For example, in the United
States and European Union, the annual estrogen discharge by livestock,
at 83,000 kg/yr., is more than twice the rate of human discharge. Indeed,
possible causal relationships have been established between concen-
trated animal feeding operations (CAFOs) and the detection of estro-
gens in the aquatic environment (Shrestha et al., 2012). Clearly,
natural estrogens in animal and human waste pose a serious risk to
the environment. This risk is heightened by the application of animal
manure or sludge bio-solids to agriculture lands, being an alternative
nutrient source for organic farming, a widely adopted practice in mod-
ern agriculture (Xuan et al., 2008). Indeed, application of animal manure
to agricultural land has been identified as a main source of estrogens in
the environment (Arnon et al., 2008).
Given the serious threat posed by estrogens as pollutants, our aim,
here, is to provide a comprehensive account of their environmental im-
pact for human and eco-environmental health perspectives. We have
carried out an exhaustive search of the published literature and paid

Fig. 1. Chemical structure of natural and synthetic estrogenic compounds. Key: E1, estrone; 17β-E2, 17β-estradiol; 17α-estradiol; E3, estriol; 17α-EE2, ethinyl estradiol.
 M. Adeel et al. / Environment International 99 (2017) 107–119 109

Table 1
Physicochemical properties of steroidal estrogens.

Hormone MF MP MW LogKow pKa vp(Kpa) Solubility LogKd

°C (mg/L)

Natural
Estrone C18H22O2 258–260 270.4 3.43 10.3 3 × 10−8 13 2.44–2.7
17α-estradiol C18H24O2 178–179 272.4 4.01 NDA 3 × 10−8 13.3 NDA
17β-estradiol C18H24O2 178–179 270.4 3.94 10.6 3 × 10−8 13 NDA

Synthetic
Ethinylestradiol C20H22O2 182–183 296.4 3.67 10.4 6 × 10−9 4.8 2.65–2.86

MF: molecular formula; MP: melting point; MW: molecular weight; VP: vapor pressure; NDA: no data available.

particular attention to both the source and degradation of estrogens women on Hormone Replacement Therapy (HRT) treatment on a per
(i.e., transformation cycle, alteration of chemical structure) in different person basis, but even this level is 1.7-fold higher than the average ex-
environmental and climatic conditions. We also include recent analyses cretion rate per person of world population as a whole. Somewhat more
of the occurrence and distributions of estrogens in different media and predictably, rates of excretion in non-pregnant women, males and
under different environmental conditions. Finally, we provide some young children are progressively and substantially lower (see Table 2).
consideration of the fate of steroidal estrogens and their relationship Municipal sewage treatment plants (MSTPs) are important sources
and interaction with humans, animals and plants. of pollution by steroidal estrogens released into the environment. This
is because MSTPs may not completely remove estrogens in the effluent,
2. Source of steroidal estrogens and therefore bio-solids and wastewater effluents containing significant
concentrations of estrogens may be directly discharged to the natural
The occurrence of natural estrogen hormones as minute concentra- environment (Andaluri et al., 2012; Belhaj et al., 2015; Pal et al., 2010;
tions in the environment has been examined by many scientists and is Pessoa et al., 2014). Municipal landfills are also sources of organic con-
an emerging contamination issue. Worldwide, water has been polluted taminants and may contain leachate with significant amounts of dis-
with steroid hormones with many released from sewage treatment solved organic matter partly consisting of steroid hormones and other
plants and effluent from livestock feedlots. The dairy livestock industry contaminants. The leachate is capable of infiltrating into groundwater
has long-used a variety of growth-regulating steroids to enhance cattle (Li, 2014) (Fig. 2). Hospitals have been identified as yet another major
growth rates, feed efficiency and to procure lean muscle mass. However, source of steroidal estrogen pollution. Indeed, a few investigations re-
CAFOs have risk implications for the environment. For example, CAFOs vealed that steroidal estrogens, especially high levels of estriol, were
involving both natural and synthetic steroids have a knock-on effect found in all hospital effluent samples (Avberšek et al., 2011).
as animal manure has seeped into the aquatic environment. Steroidal
estrogens used in CAFOs have been detected in faeces, liquid manure 3. Occurrence of steroidal estrogens in the environment
and solid waste collected from cattle, lagoon effluent, and in fertilizers
applied directly to agricultural land (Biswas et al., 2013). Arguably, ani- Steroidal estrogens have been detected in effluents and influent
mal manure is the largest source of estrogen hormones in the natural from a variety of apartments of the environment; in particular, soil
environment. Certainly, poultry, cow and horse manure may contain and water bodies at regions near Sewage Treatment Plants (STPs),
the greatest amount of steroidal estrogens (Andaluri et al., 2012). Wastewater Treatment Plants (WWTPs) and animal manure. They can
About 49 tons of estrogens were excreted by farm animals in the USA be found in groundwater, soil water, runoff water from agriculture
in 2002. In the UK, total excretion of estrone (E1) and estradiol (E2) sites and surface waters (Table 3).
from the farm animal populations was 1315 and 570 kg/yr., respectively The extremely high amount of the natural estrogen, E1, was obvious-
(Ray et al., 2013). ly spotted in slurry-type sites followed closely by 17α- and then 17β-E2.
Dependent on published source, and on average, pregnant women The picture is similar in slurry from dairy pits. Radioactive tracer studies
excrete anywhere between 260–790, and 280–600 μg/day of estrone in pigs and poultry reveal that 17β-estradiol excretion is primarily in the
and 17β-estradiol, respectively and a substantial 6000 to nearly faeces (58%), whilst 17α-estradiol and estrone (E3) are mostly in the
10,000 μg/day of estriol (Table 2). These levels are much higher than urine of pigs (96%) and poultry (69%) (Hanselman et al., 2003). Hence,
corresponding levels of these estrogens excreted by menopausal it is increasingly clear that these estrogens, as part of feed programmes
associated with intensive animal husbandry, find their way into excret-
ed products easily. Indeed, note the other instances of E1 in other agri-
Table 2
culturally-linked sites (Table 3). Comparatively lower amounts of E1 are
Average steroid estrogen excretion by humans (per person) μg/day. NDA, no data
available. found in deep water sites whilst there are quite variable levels of the es-
trogens in STP/effluent. Nevertheless, Kjær et al. (2007) did report
E1 17β-E2 E3 EE2 Reference
68.1 ng/L of E1 in deep groundwater (Table 3), which is sufficiently
Pregnant women 787 277 9850 0 Kostich et al., 2013 close to drinking water to cause alarm. Also, very conspicuous by their
Menopausal, with HRT 31.50 59.20 90.70 0 absence are hardly any measurements of E3 and in particular the syn-
Menstruating woman 9.32 6.14 17.40 0
Women 7.00 2.40 4.40 NDA Andaluri et al., 2012
thetic EE2. This clearly prompts a more widespread effort to provide
Menstruating females 3.50 8.00 4.80 NDA Hamid and Eskicioglu, data on these potentially harmful estrogens from as many sites as pos-
2012 sible and particularly from deep groundwater sites.
Adult male 3.50 1.83 3.21 NDA Kostich et al., 2013 According to a National Sewage Sludge Survey of the US EPA, approx-
Menopausal, no HRT 2.93 1.49 3.90 0
imately 1,014,724,000 tons of solid waste, especially animal manure,
Menopausal females 2.30 4.00 1.00 NDA Hamid and Eskicioglu,
Males 1.60 3.90 1.50 NDA 2012 contained an estimated 76 tons of estrogens. One clearly identified
Female child 0.60 2.50 0.918 0 Kostich et al., 2013 route for estrogens into the terrestrial environment is through the appli-
Male child 0.63 0.54 0 cation of manure to agricultural land as fertilizer for crops. In manures,
Average excretion per 19.00 7.70 8100. 0.41 Laurenson et al., 2014 17α-estradiol, 17β-estradiol and estrone concentrations range from 6
person
to 462 ng/g of dry solids (Andaluri et al., 2012).
110 M. Adeel et al. / Environment International 99 (2017) 107–119

Fig. 2. Schematic illustration of main sources of estrogen release to the environment.

A widespread practice is to convert manure into renewable energy
such as biogas. In biogas digestate, estrogenic steroid levels were ob-
served up to 1478 ng/g. A liquid or sold bi-product can be used as fertil-
izer (Rodriguez-Navas et al., 2013) clearly representing another
potential source of estrogen pollution. Livestock excreta are also a
source of natural estrogens in the aquatic environment. In run-off
from manure to tile drainage systems, their maximum concentration
can range from 2.5 to 68.1 ng/L (Kjær et al., 2007). In the fresh water
of the north USA, estriol was detected at 12–196 ng/L. In effluent and
fresh water sources from European sites, estrone ranged from 1–5 to
12.4 ng/L, respectively. 17β-estradiol in WWTPs and in rivers and
fresh water in North America were 1–22 ng/L and 0–4.5 ng/L, respec-
tively (Pal et al., 2010). Also, in a study based in California, USA, steroidal
estrogens were observed in 86% samples from surface water in pastures
with a maximum 44 ng/L recorded (Kolodziej and Sedlak, 2007).
been confirmed with our recent detection of steroidal estrogens in
rural groundwater in the NE China that is used partially for public
water supply (unpublished data). There are similar concerns about es-
trogen levels in natural waters and their effect on fish physiology and
other aquatic wild life. Here we list publically available data on accept-
able daily intake of estrogens in food for humans and the so-called
“Predicted-no-effect concentrations” on aquatic wild life. We shall
refer back to these figures where appropriate in relation to estrogen
concentrations reported at various sites world-wide. However, it is
worthwhile to comment on the paucity of data on the synthetic EE2
compared with the natural E1 and E2. Therefore the big question con-
cerns the impact of steroidal estrogens on humans and eco-systems.
We envisage there is a threshold level for estrogen intake posing no
harm for human health and for the ecosystem as a whole.

3.1. Human intake of estrogens 3.2. Estrogens on a global scale

Justifiable concern has been expressed in the published literature There is an interesting worldwide distribution of estrogens; the
concerning the possible presence of estrogens in drinking water and pattern of various types of estrogen may reflect sources of estrogens
their consequent effects on human health (Gee et al., 2015). This has or specific environmental characteristics of that part of the world. We

Table 3
Summary of estrogen concentrations (ng/L) in the environment, generally ranked from high-to-low concentration. NDA, no data available.

Sample type E1 17α-E2 17β-E2 E3 EE2 Reference

Slurry in swine pit 5900–150,000 4000–84,000 1800–49,000 NDA NDA Li et al., 2010
Swine farm effluent 5200–5400 650–680 1000–1500 2200–3000 NDA Franks, 2006
Slurry in dairy pit 2500–80,000 2000–5000 800–27,000 NDA NDA Li et al., 2010
Treated cattle feedlots 720 1100 1250 NDA NDA Bartelt-Hunt et al., 2012
Dairy farm waste water 370–2356 1750–3270 351–957 NDA NDA Li et al., 2010
Lagoon pond 650 NDA NDA NDA NDA Rodriguez-Navas et al., 2013
Biogas digestate 593 50 24 NDA NDA Rodriguez-Navas et al., 2013
Sow urine 416–490 NDA 85–97 127–193 NDA Zhang et al., 2014b
Grazing land water 78 31 18 NDA NDA Kolodziej and Sedlak, 2007
Swine manure 70 175 15 NDA NDA Rodriguez-Navas et al., 2013
Swine manure leachate 68.1 2.5 NDA NDA NDA Kjær et al., 2007
1 m deep groundwater 68.1 NDA 2.5 NDA NDA Kjær et al., 2007
STP/effluent 12–196 6.4–12.6 6.2–42.2 NDA 0.59–5.6 Pal et al., 2010
Sea water NDA NDA 0.83 NDA 4.67 Pal et al., 2010
 M. Adeel et al. / Environment International 99 (2017) 107–119 111

Fig. 3. Worldwide distribution of estrogens in river and surface water sites. Each pie chart, comprises the natural estrogens: E1, E2, E3 and the synthetic EE2 as percentages of total at each
site: (See Supplementary Fig. 1 and Supplementary Table 1).

reviewed the occurrence of various estrogen compounds mainly in river
and surface water sites.
Fig. 3 portrays potential estrogen contamination of rivers and sur-
face water on a global scale. Clearly, major occurrence of estrogens in
river water is not a universal phenomenon but largely restricted to the
American mid-west, to the eastern sea board of North America, to
Mexico, Ecuador, Brazil and Chile, and to countries bordering or close
to the Mediterranean basin of Europe, and to Asia and South Australia.
Indeed, considerable swathes of the world comprise rivers that appear
not to exhibit such levels of estrogen pollution, or, perhaps are areas
for which we simply lack data. That said major areas of intense farming
such as the mid-West of the USA and South Australia provide an imme-
diate link to the rise in estrogen levels in rivers in those areas. Also of
note is the north south divide of the Americas for the occurrence of
the synthetic EE2 in river water. In particular, in Brazil, it would seem
that EE2 may be posing a serious pollution threat. The same can be
said about the very large number of the Far East sites where high levels
of EE2 have been recorded from river locations (Fig. 3). In a fresh water
site at ARO-Volcani (Israel) estrone concentration was 0.6–1.1 ng/L
whilst in a kibbutz at Revadim (Israel) it was 1.2–1.5 ng/L with waste
water effluents rising to 2.3–3.3 ng/L (Shargil et al., 2015).
Estrogen compounds have also been detected in influent and efflu-
ent of sewage treatment plants (STPs) in several countries (Fig. 4). Av-
erage concentration of estrogenic steroids (E1, E2, E3 and EE2) in Italian
STPs was 80, 12, 3 and 52 ng/L, respectively. The concentrations of E2 in
influents of Japanese STPs ranged from 30 to 90 ng/L and 20 to 94 ng/L
in autumn and summer seasons, respectively (Ying et al., 2002). In
Beijing, one study showed that N 40% of natural estrogens and 60% of

Fig. 4. Worldwide distribution of steroidal estrogens through WWTPs. Each pie chart comprises the natural estrogens: E1, E2, E3 and the synthetic EE2 as percentages of total at each site.
(See Supplementary Fig. 2 and Supplementary Table 2.)
112 M. Adeel et al. / Environment International 99 (2017) 107–119

Table 4 17β-E2 and E1 occurred in English rivers with a half-life of 0.2 to

Acceptable daily intake for humans via food (μg/day) and Predicted-no-effect concentra- 9 days at 20 °C (Jürgens et al., 2002) (Table 5).
tion for aquatic life (PNEC) (ng/L). NDA, no data available.
In a groundwater system (aquifer sediments and groundwater fluid)
E1 17β-E2 EE2 Reference under aerobic conditions, E2 degraded rapidly within 10 days. However,
Adult/60 kg NDA 3 NDA Lu et al., 2012 over the same interval, EE2 was not degraded but its concentration de-
Child/10 kg NDA 0.5 NDA creased from 1–0.62 μg/g. Thus the synthetic estrogen was much more
Human/kg bw/day NDA 5 NDA Plotan et al., 2014 persistent in this environment than the natural one. Indeed, the half-
Mixed diet adult 0.1 0.1
life under aerobic conditions for E2 and EE2 was 2 and 81 days, respec-
Men 1 NDA NDA Shargil et al., 2015
Women 50 NDA NDA tively. Under anaerobic conditions, the two steroidal estrogens did not
Adult NDA 0.0041e 0.0028e Wenzel et al., 2003 degrade clearly indicating that the oxidative state of the source has a
Infant NDA 0.0016e 0.0011e critical bearing on half-life and rate of degradation (Ying et al., 2003).
PNEC for aquatic NDA 2a NDA Anderson et al., 2012 Half-lives also differ depending on the location of the detected estrogen.
wildlife (ng/L) NDA 5b NDA
NDA NDA 0.035c Laurenson et al., 2014
For example, in aerated soil, E2 and EE2 degraded within 15 days with a
NDA NDA 0.5c Nagpal and Meays, 2009 half-life of 3 to 4.5 days. However, in anaerobic soil, degradation was
100d 8.7d 0.1d Caldwell et al., 2012 very slow and in which E2 had an estimated 24 d half-life (Ying and
a
Long term PNEC Kookana, 2005). So not only location but also the relative REDOX state
b
Short term PNEC of the sites of study can clearly affect half-life and rate of degradation
c
PNEC of estrogens.
d
Reproductive stage, test species Oryzias latipes, NOEC E1 and E2 are biodegraded under different REDOX conditions, with
e
Via drinking water (2 L). All figures with superscripts are in unit of ng/L.
estrogens being more susceptible to biodegradation under biotic condi-
tions. For example, some bacteria present in the environment can
EE2 in waste water may be entering into receiving water. The average completely degrade estrogenic compounds into harmless products e.g.
concentrations of E1, E2, E3, and EE2 in the receiving water ranged gram-negative Rhodococcus zopfii and Rhodococcus equi in sewage
from 48 to 70 ng/L, 2 to 19 ng/L, 50 to 320 ng/L, and 6 to 7 ng/L, respec- sludge. The aforementioned bacteria have the potential to degrade E2
tively (Zhou et al., 2012b); note the acceptable limits for human within 24 h (Hamid and Eskicioglu, 2012; Khanal et al., 2006). Several
consumption of estrogens (see Table 4). In the largest wastewater treat- other factors can affect the half-life and rate of degradation of estrogens
ment plant in Beijing, the maximum concentrations of E1, E2, E3, and EE2 in the environment: hydrophobic partitioning, covalent bonding, ligand
were 74.2, 3.9, 5.1, and 4.6 ng/L, respectively (Zhou et al., 2012a). exchange and migration to microsites on soil particles. In addition, these
Here the picture for North and South America is similar to that re- processes can also be affected by the concentration of organic contami-
garding river pollution but with notably high EE2 levels in Chile where- nants that are absorbed on to soil particles and cannot be recovered by
as it is at comparatively lower concentrations in North America. extraction procedures.
However, the profile for Western Europe is different for WWTPs com- Estrogens such as E2 and EE2 in aquatic environments are also sus-
pared with rivers, with the inclusion of the UK, France, Germany and ceptible to breakdown by photocatalysis and photolysis. The extent of
Austria as countries in which estrogens are reaching pollution levels degradation by photolysis and photocatalysis depends upon an
(Fig. 4). Generally, WWTP effluent levels of estrogens are similar to estrogen's chemical structure. Photolysis, biodegradation, and sorption
river levels in Asian countries and Australia. Once again, we emphasize are the likely leading attenuation pathways controlling the fate of E2
that the distribution profiles in Fig. 4 reflect available data and may not (17β-estradiol) in surface waters (Petrie et al., 2015; Writer et al.,
necessarily be a true global picture. It may also reflect the differences in 2011). Also, EE2 degradation was studied in a lake site in the USA.
interpretation of environmental standards of the WWTP that are used Under aerobic conditions, half-life was estimated as 108 days whilst
worldwide. there wasn't any biodegradation by microbes in the lake water. Howev-
er, under natural sunlight, photo degradation accounted for a much
shorter half-life of 23 h (Zuo et al., 2013). Further investigations are re-
4. Estrogen degradation and half-life quired to determine the impact of photolysis on organic contaminants
in environmental conditions e.g. depth of river, shading from bankside
The half-life of an estrogen will depend on its rate of degradation, vegetation.
reflecting its initial quantity and that remaining after a measured period
of time. Half-life can be determined by first order decay or regression 5. Estrogen transformation cycle
curve kinetics whereas rate of degradation can be estimated directly
from decay kinetics. Clearly, the longer the half-life of a pollutant, the As mentioned previously, estrone (E1), estradiol (E2), and estriol
more persistent it will be in the environment. Steroidal estrogens that (E3) lie on interconnecting metabolic pathways (Casey et al., 2003;
are excreted by humans and animals have short half-lives. Because D'Alessio et al., 2014; Duncan et al., 2015; Goeppert et al., 2014;
they are hydrophobic, their concentrations decrease significantly in Goeppert et al., 2015). Indeed, microorganisms living in aerobic condi-
the aqueous phase. Their half-lives were calculated as 2 to 6 days in tions can convert one estrogen to another (Fig. 5). For example, some
water and sediments in a test batch (Ying et al., 2002). Degradation of microbes (e.g. nitrifying bacteria), can convert E1 to E3, and others

Table 5
Half-life (in days) of steroidal estrogens from different aquatic sources.

Medium Oxygen status E1 17β-E2 E3 EE2 Reference

Natural soil Aerobic 2.8–4.9 0.8–1.1 0.7–1.7 NDA Biswas et al., 2013
Aire river water Aerobic 2.4 2.3 NDA NDA Jürgens et al., 2002
Calder river water Aerobic 2.2 2.7 NDA NDA
Thames river water Aerobic 3.1 4.1 NDA NDA
River water NDA 2–3 2–3 NDA 4–6 Ying et al., 2002
Sandy-loam Anaerobic NDA NDA NDA NDA Ying and Kookana, 2005
Aquifer materials Aerobic NDA NDA NDA 81 Ying et al., 2003
Natural water Aerobic NDA NDA NDA 1.5 Zheng et al., 2011
 M. Adeel et al. / Environment International 99 (2017) 107–119
Fig. 5. Interconversion pathways of natural and synthetic estrogens.
degrade E1, E2 and EE2 (e.g Novosphingobium sp. in activated sludge)
(Ma et al., 2016). Furthermore, the synthetic EE2 can be converted to
E1 by Sphingobacterium sp. (Haiyan et al., 2007). Also, there is a diverse
array of anaerobic bacteria that can transform one estrogen to another.
For example, in lake water and sediment under anaerobic conditions, E2
was chemically transformed to E1 under methanogenic, sulfate, iron,
and nitrate-reducing conditions but in contrast, EE2 degradation was
not reported on (Czajka and Londry, 2006).
Many studies indicate that E1 (estrone) is the main degradation
product of E2. For example, in a silt loam soil, E1 was a major product
of E2 degradation under abiotic conditions (Xuan et al., 2008). However,
note a racemization reaction between 17α-estradiol and 17β-estradiol
via estrone occurred in waste water under anaerobic conditions
(Zheng et al., 2012). Interestingly, in lake water and sediment, a racemi-
zation reaction can occur between E1 and 17α-estradiol. Moreover, EE2
transforms to E1 under all but nitrate-reducing conditions (Czajka and
Londry, 2006).
Under artificial rainfall, a concentration decrease of 17α-estradiol
was accompanied by an equivalent increase in estrone and 17β-
estradiol in superficial soil obtained from steer feedlots (Mansell et
al., 2011) indicating the activity of microbial enzymes catalyzing these
conversions. Similarly, rapid conversion of 17β-E2 to E1 occurs in the
presence of swine manure colloids (Prater, 2012) and 17α-E2 to E1 in
dairy waste disposal systems (Zheng et al., 2007). Prater et al. (2015)
also noted reversible reactions between E1 and E2. Within 24 h, a re-
versible conversion from E2 to E1, and then back to E2 occurred in a
swine manure colloidal suspension closed to the atmosphere (Prater
et al., 2015). However, degradation of E2 to E1 does not always require
biological interaction (Goeppert et al., 2014).
The rate of 17β-E2 degradation in soil increases steadily as soil mois-
ture is increased so that in dry conditions estrogens may persist at
higher levels. However, the estrogen concentrations also remained con-
stant upon moistening of the soil by simulated rainfall (Mansell et al.,
2011; Xuan et al., 2008). Stability of EE2 in the soil environment has
113
been further examined. Rapid dissipation of EE2 occurred in aerated
soil, whilst in a separate study, bacterial assemblages were present ca-
pable of rapid degradation of EE2 under both aerobic and anaerobic con-
ditions (Carr et al., 2011; Lorenzen et al., 2006; Sarmah and Northcott,
2008). Cajthaml et al. (2009) concluded that EE2 was decomposed
slowly by anaerobic bacteria. The dissipation period could exceed
1000 days and the degradation was achieved under sulfate-, nitrate-,
as well as iron reducing-conditions (Cajthaml et al., 2009).
6. Effects of steroidal estrogens on fish, domestic animals and
human health
6.1. Aquatic wildlife
There is significant accumulated evidence that fish exhibit perturbed
development in waters which receive the effluent from STPs (Hotchkiss
et al., 2008). However, it is important to note threshold concentrations
of toxicity by estrogens on fish life. In the U.S. watersheds, human de-
rived estrogens have a short term predicted-no-effect concentration
(PNEC) of 5 ng/L and a long term PNEC of 2 ng/L on fish (Anderson et
al., 2012). Seemingly, EE2 is the most potent hormone with a PNEC of
0.1 ng/L for aquatic chronic toxicity (Laurenson et al., 2014).
More specifically, several studies demonstrated that elevated con-
centrations of natural and synthetic estrogens feminize male fish e.g. re-
duce testes size (Arnold et al., 2014; Tetreault et al., 2011), affect
reproductive fitness (Rose et al., 2013), lower sperm count, induce the
production of vitellogenin (VTG) (Kidd et al., 2007) and alter other re-
productive characteristics (Van Donk et al., 2016). Additionally, EE2
caused a considerable reduction in fish biomass and interrupted the
aquatic food chain (Hallgren et al., 2014). However a seven year micro-
satellite field study revealed that, remarkably, fish can overcome the ef-
fects of EE2 as evidenced by latent increases in fish population levels
(Blanchfield et al., 2015). On the other hand, EE2 does have severe del-
eterious effects on other forms of aquatic life. For example, in a recent
114 M. Adeel et al. / Environment International 99 (2017) 107–119
study, EE2 at 10 ng/L directly affected the heart function of bullfrog tad-
poles (Salla et al., 2016).
6.2. Domestic animals
Phytoestrogens (isoflavones, which are structurally and functionally
similar to 17β-E2) cause developmental abnormalities in domestic
animals. These effects are manifest morphologically with cows
exhibiting changes in teat length and color of the vulva (Burton
and Wells, 2002). Some plants also contain sufficient concentrations
of estrogens to cause reproductive alterations in domestic animals.
For example, sheep grazed on the clover plant, which contains po-
tent levels of phytoestrogens, develop permanent infertility, so
called “clover disease” (Hotchkiss et al., 2008). The effect of estro-
gens can also impair vision. Intraocular eye pressure (IOP) varies
from species to species in domestic animals but progesterone can in-
crease the IOP in lions, and estrogen similarly in cats (Shemesh and
Shore, 2012).
6.3. Humans
Estrogen hormones are crucial for human biology and physiology.
They help regulate reproduction, cardiovascular function, bone
strength, cognitive behavior, successful pregnancy and gastrointesti-
nal systems. Arguably, the most widely discussed issue concerning
estrogens and human health is HRT. This is where menopausal
women can be administered estrogens to replace endogenous hor-
mones that are no longer produced in adequate quantities to main-
tain normal health. The Joint FAO/WHO Expert Committee on Food
Additives, evaluated 17β-E2 in relation to the HRT treatment in men-
opausal women. They found that adverse hormonal effects occurred
at much lower than expected concentrations and subsequently
established an acceptable daily intake (ADI) of 0–50 ng/kg body
weight (bw) (Plotan et al., 2014). A no-observed-adverse-effect
(NOEL) for humans of 0.3 mg/day (equivalent to 5 μg/kg bw/day)
has been calculated by Plotan et al. (2014) but estrogens are capable
of affecting human health as soon as above this safe level (see also,
Table 4). However, we are surprised that these authors have used a
value of 0.3 mg/day as an acceptable daily limit. This may need fur-
ther study. In China, the estrogenic steroids, 17β-E2 and estrone,
were detected in 53 out of 62 drinking water treatment works
(DWTWs) and 31 out of 62 DWTWs from 31 major cities. The maxi-
mum detected concentrations were 1.7 ng/L and 0.1 ng/L for 17β-E2
and E1, respectively (Fan et al., 2013). To our knowledge, this is the
first study on the occurrence of estrogens in drinking water that
may represent a risk to human health.
Clearly, estrogens are essential for normal human physiology but
can have serious adverse effects if allowed to accumulate in the envi-
ronment and enter the human food chain. If consumed at levels above
the safe thresholds they can increase the risk of cancer and induce
cardiovascular diseases in humans (Wocławek-Potocka et al., 2013). In-
deed supraoptimal levels of estrogens have been linked with increased
incidences of breast cancer in females (Moore et al., 2016) and prostate
cancer in men (Nelles et al., 2011), although cause-and-effect is hotly
debated. Estrogens preferentially bind with receptor cells in breast tis-
sues leading to cell proliferation that can ultimately form tumours. As
noted by Liang and Shang (2013), the US National Toxicology Program
listed estrogens as carcinogens. The predominant intracellular estrogen
is 17β-E2. It binds with estrogen receptors (ER α and β). ER α targets
genes that promote cell proliferation or decrease apoptosis (cell
death). A key cell cycle gene, cyclin D1 is expressed rapidly in estrogen
treatments (Butt et al., 2005). In mice, ER α and β have opposing effects
on cell proliferation and apoptosis (Dupont et al., 2000). Post-surgery,
breast cancer patients are often administered tamoxifen, a drug capable
of blocking this selective binding of estrogens with the receptors or are
treated with enzyme inhibitors or other agents that block the release of
estrogen at source. Whatever the exact link is between estrogens in the
environment and breast cancer, water authorities world-wide include,
or should include routine screening of estrogen concentrations (togeth-
er with all EDCs) as part of their aim to deliver clean and wholesome
water (Gee et al., 2015).
The risk of environmental estrogens on breast cancer was examined
in 198 women at time of diagnosis. Sixteen organochloride pesticides
and total xenoestrogen levels were measured and comparisons made
with 260 unaffected women. A sub-group of leaner post-menopausal
women showed an increased risk of breast cancer (Ibarluzea et al.,
2004). More recently, exposure to environmental endocrine disrupting
compounds was also correlated with cancer susceptibility (Trevino
et al., 2015).
Steroidal estrogens in food and water can also induce premature
menopause and affect reproductive development, also causing
virilization in young women. Several studies also revealed that estro-
gens were involved in the decline of sperm counts and disorders of
the male reproductive system and feminization of men (Bolong et
al., 2009; Sumpter and Jobling, 2013). Steroidal estrogens singly or
in combination with progesterone also reduce IOP after menopause
in humans which might increase the risk of developing glaucoma
(Shemesh and Shore, 2012). Besides phytoestrogens can also affect
reproduction, the immune system and metabolism (Alexander,
2014). Accumulative evidence points clearly to serious health con-
cerns regarding estrogens making it crucial to ensure that both es-
trogens from human and animal waste and phytoestrogens are not
consumed in food and water at levels above the accepted NOELs.
7. Uptake and transport mechanisms in plant systems
The use of plants for phytoremediation of toxic environments is
well known. Phytoremediation relies on some plants' capacities to
adapt and grow in environments where few other eukaryote organ-
isms can survive. Natural populations of weeds growing on rock
faces, through cracks in paving stone and in desert conditions are
just a few illustrative examples. Some plant species have also
adapted to grow in soils contaminated with toxic metals. For exam-
ple, the grass species, Festuca rubra, has several cultivars one of
which is tolerant to toxic levels of zinc (Gómez et al., 2016) whereas
others may be zinc sensitive. Other plants show remarkable toler-
ance to a range of toxic metals. For example, the alpine pennycress,
Thlaspi caerulescens has multiple tolerance to cadmium, cobalt,
copper, molybdenum, nickel, lead and zinc. The willow-related
tree, Salix viminalis is another with tolerance to silver, selenium,
manganese and zinc. Interestingly, this tree also tolerates polluted
levels of petroleum products and organic solvents (Marmiroli and
McCutcheon, 2003; Prasad, 2005; Schmidt, 2003). In contrast, and
to our knowledge, there are fewer reports of plants capable of accu-
mulating animal or synthetic estrogens: wetland macrophytes, leafy
vegetables and algae together with poplar, maize and willow. For ex-
ample, in a lab study, Scirpus validus (emergent wetland plant) and
Populus deltoides nigra (wetland plant), could reduce the concentra-
tion of 17β-E2, E1, E3 and EE2 from the solution through transforma-
tion suggesting efficient uptake into root tissues (Bircher, 2011) (see
Table 6).
Phytoaccumulating plants share the common property of up-take of
potentially harmful molecules through transport systems that normally
process nutrients but instead sequester toxic substances in the plant
vacuole. Hence, plants have evolved a relatively unique method to
take up and place toxic substances in locations that are not harmful to
the plant's metabolism. They do this by accepting these substances
through membrane bound pumps and carriers that normally take up
nutrients that the plant requires. The extent to which uptake of organic
matter follows the same pathway(s) is less clear.
Roots are the most essential part of plant for uptake of nutrients
from soil and they also take up organic contaminants from both water
 M. Adeel et al. / Environment International 99 (2017) 107–119 115

Table 6
Phytoremediation of steroidal estrogens.

Species Accumulation characteristics Estrogen type Reference

Chlorella vulgaris Biotransformation and bio concentration of steroidal estrogens E2, E1 Lai et al., 2002
Populus deltoids nigra, Scirpus validus Phytoremediation of natural and synthetic steroid growth promoters 17β-E2 EE2 Bircher, 2011
Lemna species Removal of natural and synthetic estrogens from wastewater 17β-E2, EE2, E1 Shi et al., 2010
algal genera: treatment system
Anabaena cylindrica,
Chlorococcus,
Spirulina platensis,
Chlorella,
Scenedesmus quadricauda
Zea mays, Uptake and transformation of natural and synthetic estrogens by 17β-E2, E1 Card et al., 2012; Card et al., 2013
Golden Cross Bantam (hybrid) maize seedlings
Portulaca oleracea Removal of phenolic endocrine disruptors 17β-E2 Imai et al., 2007
Salix exigua Phytoremediation of pharmaceutical EE2 Franks, 2006
Arabidopsis thaliana
(Lactuca sativa L.) Impact of estrogen on lettuce with biosolids and waste water E1 Shargil et al., 2015
effluent application

and soil. There are two main uptake mechanisms for plant uptake of or-
ganic contaminants: passive and active through the root system. In up-
take studies of non-ionized contaminants from a solution culture, two
steps were identified. Firstly, an equilibrium is established between
the nutrient or pollutant concentration in the aqueous phase within
the plant root and the external soil solution, and secondly, chemical
sorption onto lipophilic bodies occurs. These solids contain lipids that
attach in membranes and cell walls (Collins et al., 2006; Collins et al.,
2011; Dodgen, 2014; Trapp and Legind, 2011).
Nonionic organic contaminants have the potential to pass cell
membranes easily and thus have greater potential to be taken up
by the roots. They tend to be transported in the roots by water flow
driven by the water potential gradient and thus accumulate at a
maximum concentration in the leaves (Fig. 6, the plant background
from web) (Collins et al., 2011; Dodgen, 2014; Malchi et al., 2014).
Indeed, organic (hydrophobic) contaminants have greater potential
to partition into plant root lipids than hydrophilic contaminants.
Mostly, the octanol-water partition coefficient (Kow, see Section 1)
is used as a surrogate measure of pollutant lipophilic tendency. A
non-ionized contaminant with log Kow N 4 has a maximum potential
for retention in plant roots. Indeed, pollutants with a log Kow higher
than 3.5 are too hydrophobic to move through the vascular tissues
(Card, 2011). Other additional parameters such as the contaminant's
pKa, pH, ionic strength, biodegradation, and sorption might also af-
fect uptake (Collins et al., 2011; Malchi et al., 2014).
The uptake of organic contaminants from the soil into plants is
strongly affected by their concentration in the voids between soil and
water. The concentration of these contaminants can be affected by:
soil pH, dissolved organic carbon, and REDOX potential in the pore
water which can indirectly influence the passive uptake of the organic
contaminants. They can be attached to several components in soil in-
cluding clays, iron oxides, and other organic matter. Many other factors
are likely to be important, including: hydrogen bonding, surface com-
plexion, and cation exchange. In addition, the partitioning behavior of
the ionizable EDCs is highly susceptible to changes in soil pH, as changes
in pH may alter the ionic fraction. Empirical relationships exist between

Fig. 6. Uptake and transport processes of organic chemicals in the soil–plant system.
116 M. Adeel et al. / Environment International 99 (2017) 107–119
a chemical's lipophilicity and its affinity to sorption to soil organic mat-
ter (Collins et al., 2011; Dodgen, 2014).
7.1. Transport from the root to other plant parts
Plant root structure is well understood comprising the epidermis,
cortex, endodermis and vascular tissue containing xylem and phloem.
Water and solutes are moved upward from the root into other plant
parts through the xylem by mass flow due to a pressure gradient creat-
ed throughout the plant during transpiration. For contaminants taken
up by plant roots to reach the xylem, they must pass through a number
of layers: the epidermis, cortex, endodermis, and pericycle. At the endo-
dermis all solutes must cross the cell membrane, and it is the combina-
tion of their aqueous solubility and their solubility in the lipid-rich cell
membrane of the endodermis that affects their potential movement
into roots from the soil pore water and later transport to other plant
parts via the xylem (Collins et al., 2006; Collins et al., 2011). Water
and solutes transported in the xylem may also diffuse laterally into
nearby layers
Contaminant concentration might be high in plant shoots as a result
of the equilibration of the aqueous phase and partitioning into lipophilic
solids. Other influential factors include: rate of root uptake, concentra-
tion of lipophilic solids and the plant transpiration stream. There is po-
tential for sorption to stem parts as the contaminants moves up the
stem; this sorption becomes maximized with increasing lipophilicity
(Collins et al., 2006).
8. Accumulation of estrogen in plants
A series of recent papers describe estrogen uptake studies in
plants. Batch and continuous flow tests involving waste water indi-
cated that algae and duckweed play a crucial role in the removal of
estrogens (Shi et al., 2010). In maize seedlings, uptake of two natu-
ral steroidal estrogens, 17β-E2 and E3 and two synthetic estrogens
was measured. All four were detected in roots at concentrations
up to 0.19 μM but only 17β-E2 was transported to the shoot (Card
et al., 2012; Card et al., 2013). Sandbar willow and Arabidopsis
thaliana also remove estrogens actively from solution. Both plants
grown in estrogen-polluted medium eliminated 86% of the synthet-
ic estrogen, 17α-ethynyl estradiol (EE2) in 24 h (Franks, 2006). In a
hydroponic study in Osaka, Japan, one hundred different garden
plant species were tested for phenolics and EDCs; Portulaca oleracea
was the only effective phytoremediator. It removed EDCs having a
phenol group, including 17β-estradiol (E2), within 24 h (Imai et
al., 2007). In another study, steroidal estrogens were determined
in fruits and vegetables obtained from local markets in Fort Pierce,
FL, USA. Significant concentrations of estrogens were observed in
the vegetables especially in lettuce. 17β-E2 in vegetables and fruits
was 1.3 to 2.2 μg/kg. According to the Joint FAO/WHO Expert Com-
mittee on Food Additives (JECFA), the toxic level for daily intake
(ADI) of 17β-estradiol for a 60 kg adult is 3.0 μg/day and that for a
10 kg baby is 0.5 μg/day. Clearly, in this study 17β-E2 exceeded this
limit for infants (Lu et al., 2012).
8.1. Effects of estrogens on plant growth
Various studies have examined the effects of exogenous steroid hor-
mones on seed germination and plant development. For example, in po-
tato (Solanum tuberosum L. cv. ‘Iwa’) root growth and tuber size were
reduced at 0.1 to 10 mg/L of E1, 17β-E2 and E3, (Brown, 2006). On the
other hand, maize seedling growth was consistently inhibited at
10 mg/L but was stimulated by 0.1 mg/L 17β-E2 (Bowlin, 2014). In to-
mato seedlings, estrone and 17β-estradiol at 1 μM in Hoagland
solution, reduced growth as well as root number (Janeczko and
Skoczowski, 2011). However, in mung beans estrone and estradiol at
low concentrations of 0.1 μM augmented germination and vegetative
growth but were inhibitory at high concentrations (60 μM) (Guan and
Roddick, 1988). A stimulation of growth was also induced by E2 at
10− 9 M in germinating chickpea. Hence, a fairly consistent theme is
that estrogens at low concentrations could be beneficial in agriculture
overcoming dormancy problems experienced by some plant species
(Erdal and Dumlupinar, 2010).
Estrogens have other both positive and negative concentration-de-
pendent effects on plant growth. In lentil, 17β-E2 treatment enhanced
embryo growth and improved tolerance to cadmium and copper stress
during germination (Chaoui and El Ferjani, 2013). However, in
Arabidopsis thaliana, natural estrogens E1, 17β-E2 and E3 at 0.1 μM, re-
duced the number of generative plants (Janeczko et al., 2003). Also, the
estrogenic hormone, androstenedione, maximized net photosynthetic
rates. The impact of androstenedione was demonstrated during the re-
hydration of plants that had undergone a period of drought (Janeczko et
al., 2012). Conversely, a recent study in Sweden highlighted the nega-
tive effects of EE2 (at 7 μM) on growth and photosynthesis in the
green alga, Chlamydomonas reinhardtii. They concluded that the dis-
charge of EE2 in the waste water stream posed a deleterious effect not
only by removing atmospheric CO2, but also in inhibiting algal growth.
It was later suggested that further investigations are needed for the neg-
ative impacts of estrogen on plant growth (Pocock and Falk 2014).
8.2. Effects of estrogen on plant antioxidant activity
Reactive oxygen species (ROS) are generated as a normal product
associated with plant cellular metabolism. A variety of environmen-
tal stresses cause excessive ROS production leading to progressive
oxidative injury and ultimately, cell death. Detoxification associated
with excess ROS is usually accomplished by an effective antioxida-
tive system comprising non enzymic as well as enzymic antioxidants
(Genisel et al., 2013; Sharma et al., 2012).
Enzymic antioxidants include superoxide dismutase (SOD), catalase
(CAT), guaiacol peroxidase (GPX), as well as enzymes of the ascorbate
glutathione (AsA-GSH) cycle such as ascorbate peroxidase (APX),
monodehydroascorbate reductase (MDHAR), dehydroascorbate reduc-
tase (DHAR), and glutathione reductase (GR). Ascorbate (AsA), glutathi-
one (GSH), carotenoids, tocopherols, and phenolics serve as potent
nonenzymic antioxidants within the cell (Erdal, 2012). In plants, ROS
activation involves two different mechanisms (Fig. 7, adopted and
redrawn after Sharma et al., 2012). ROS is generated in different organ-
elles and cellular locations such as: chloroplasts, mitochondria, plasma
membranes, peroxisomes, the apoplast, endoplasmic reticulum, and
cell walls (Sharma et al., 2012).
Interestingly, several recent reports provide evidence that estrogens
can alleviate some of the symptoms associated with toxic metal-
induced oxidative damage. In maize and chickpea, exogenous an-
drosterone treatment reduced significantly, oxidative damage
caused from chilling stress by increasing the levels of antioxidant
enzymes, including superoxide dismutase (SOD), guaiacol peroxi-
dase (POX), catalase, ascorbate peroxidase (APX) and glutathione
reductase (Erdal, 2012; Genisel et al., 2013). Similarly, β-estradiol
has an ameliorative effect on growth of maize seeds suffering from
salt-induced oxidative damage once again by enhancing antioxi-
dant activity (Erdal and Dumlupinar, 2011a). Consequently MSH in-
cluding progesterone, β-estradiol and androsterone, significantly
improved plant growth, resulting in increased levels of soluble pro-
tein and sugar (Erdal and Dumlupinar, 2011b). Root growth, lead
content, protein content, amylase activity, and antioxidant activity
were measured in wheat seeds under lead stress in the presence
of 17β-estradiol (E2). Once again, the estrogen suppressed lead-in-
duced oxidative damage. Also there was less DNA damage in wheat
seedlings exposed to lead but treated with 17β-estradiol (Genisel et
al., 2015). Furthermore, in bean seed, EE2 induced antioxidant en-
zyme activity and significantly decreased the extent of lipid perox-
idation and lowered endogenous H202 levels (Erdal, 2009).
 M. Adeel et al. / Environment International 99 (2017) 107–119
Fig. 7. Schematic illustration of generation of reactive oxygen species (ROS) in plants.
9. Conclusions
In this review study we have examined the effects of exogenous es-
trogens on animal and human health, on pollution of aquatic systems
and on plant growth and development. We have also tried to raise crit-
ical awareness of the route of potentially harmful estrogens through the
food chain. We conclude that:
• Clarification is required about safe threshold levels of estrogens in the
terrestrial, aquatic and human environments;
• Sewage treatment plants, wastewater treatment plants and sewage
constituents used in manure constitute major potential sources of es-
trogen pollution;
• Global sites of estrogen release into rivers and from waste water
plants are highly asymmetric and more data from more locations
are required to test if this is a real effect;
• Half-lives of E1 and E2 are short and both can be biodegraded relative-
ly rapidly but EE2 is more persistent in the environment;
• E1, E2, E3 and EE2 are easily transformable into each other by aerobic
organisms but transformation rates are positively related to moisture
content of soils;
• Fish, domestic and wild animal together with human health can be
disrupted by rising levels of estrogens;
• There is a link between environmental estrogens and breast cancer
that may be restricted to sub-sets of patients on a general weight-de-
pendent basis;
• Plants synthesise phytoestrogens and take up mammalian-derived es-
trogens both actively and passively. Estrogens' hydrophobicity and li-
pophilic properties facilitates relatively easy passage through plant
membranes;
• Plants can accumulate estrogens in both roots and shoots;
• In a concentration dependent manner, estrogens can stimulate or in-
hibit plant growth and development and also they can ameliorate the
ROS-induced damage caused by other stresses such as toxic metals.
Finally, we make the following specific points regarding estrogens in
the environment, according to current literature review:
1. Estrogen should be listed as a toxic organic pollutant which is con-
firmed by several studies;
117
2. Many more data about estrogen levels in the natural environment
from many more sites world-wide are urgently required;
3. A greater data pool should enable tests that model the accumulation
of natural as opposed to synthetic estrogens in the environment and
in particular at those sites close to water treatment and sewage dis-
posal systems;
4. Estrogen pollution is becoming a vital environmental concern and
has deleterious effects on human, animal and plant growth and de-
velopment at significant levels. Attention to this issue is crucial and
demands further in-depth investigation;
5. Establishing a causal link between increased presence of environ-
mental estrogens and increased incidences of breast cancer requires
more data;
6. The role of estrogens in biological systems is also ambiguous. In addi-
tion, further studies are also required to determine tolerance, be-
cause still the impact of estrogen-toxicity in many ecosystems is
not clear.
Role of the funding source
We thank the National Natural Science Foundation of China (Grants:
41272255 and 41472237), Liaoning Innovation Team Project (no.
LT2015017) and Shenyang Sci-Tech Program (Grants F14-133-900,
F15-113-9-00).
Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.envint.2016.12.010.
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