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Environmental Science and Pollution Research (2021) 28:49507–49528

https://doi.org/10.1007/s11356-021-15861-8

REVIEW ARTICLE

A review of environmental occurrence, analysis,


bioaccumulation, and toxicity of organophosphate esters
Tadiyose Girma Bekele 1,2 & Hongxia Zhao 1 & Jun Yang 3 & Ruth Gebretsadik Chegen 4 & Jingwen Chen 1 &
Seblework Mekonen 5 & Abdul Qadeer 6

Received: 30 March 2021 / Accepted: 3 August 2021 / Published online: 10 August 2021
# The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

Abstract
The ban and restriction of polychlorinated biphenyls (PCBs) and major brominated flame retardants (BFRs), including
hexabromocyclododecane (HBCD) and polybrominated diphenyl ethers (PBDEs), due to their confirmed detrimental effects
on wildlife and humans have paved the way for the wide application of organophosphate esters (OPEs). OPEs have been
extensively used as alternative flame retardants, plasticizer, and antifoaming agents in various industrial and consumer products,
which leads to an increase in production, usage, and discharge in the environment. We compile recent information on the
production/usage and physicochemical properties of OPEs and discussed and compared the available sample treatment and
analysis techniques of OPEs, including extraction, clean-up, and instrumental analysis. The occurrence of OPEs in sediment,
aquatic biota, surface, and drinking water is documented. Toxicity, human exposure, and ecological risks of OPEs were sum-
marized; toxicological data of several OPEs shows different adverse health effects on aquatic organisms and humans. Much
attention was given to document evidence regarding the bioaccumulation and biomagnification potential of OPEs in aquatic
organisms. Finally, identified research gaps and avenues for future studies are forwarded.

Keywords Organophosphate esters . Environmental occurrence . Bioaccumulation . Biomagnification . Toxicity . Human


exposure

Introduction materials (van der Veen and de Boer 2012). Brominated


flame retardants (BFRs) have been extensively used for
To decrease the flammability/combustibility of consumer decades to maintain the fire safety of products. The ban
and industrial products, researchers focused on the syn- and restriction of polychlorinated biphenyls (PCBs) and
thesis and development of flame retardants (FRs). FRs some major BFRs, e.g., polybrominated diphenyl ethers
have different compositions. They may have phosphorus, (PBDEs) congeners, particularly Penta-BDE and Octa-
chlorine, bromine, metals, nitrogen, molybdenum, borax, BDE formulations were added to persistent organic pol-
etc., and they are important to enhance the fire safety of lutants (POPs) list of the Stockholm Convention since

Responsible editor: Hongwen Sun

* Hongxia Zhao 3
Department of Neurology, The First Hospital of China Medical
hxzhao@dlut.edu.cn University, Shenyang 110001, China
* Jun Yang 4
yangjun0224@sina.com Department of Marine Engineering, Dalian Maritime University,
No.1 Linghai Road, High-tech Zone District, Dalian 116026, China
1
Key Laboratory of Industrial Ecology and Environmental 5
Department of Environmental Health Sciences and Technology,
Engineering (MOE), School of Environmental Science and Jimma University, 378 Jimma, Ethiopia
Technology, Dalian University of Technology, Dalian 116024,
China 6
National Engineering Laboratory for Lake Pollution Control and
2
Department of Natural Resource Management, Arba Minch Ecological Restoration, Chinese Research Academy of
University, 21 Arba Minch, Ethiopia Environmental Sciences, Beijing 100012, China
49508 Environ Sci Pollut Res (2021) 28:49507–49528

2009, due to their confirmed persistence, long-range at- important to review and highlight the properties, produc-
mospheric transport (LRAT), bioaccumulation, and/or tion/usage, environmental levels, toxicity, and human ex-
toxicity in the environment, wildlife, and humans (van posure risks of OPEs.
der Veen and de Boer 2012; Stasinska et al. 2014; Several reviews about OPEs have been conducted to
Abbasi et al. 2016; UNEP 2019), have paved the way provide information mainly on the environmental occur-
for the use of organophosphate esters (OPEs). As a result, rence (van der Veen and de Boer 2012; Wei et al.
in the past decades, the production and consumption of 2015; Yang et al. 2019; Wang et al. 2020c), human
OPEs has increased and covered 30% of global FRs usage exposure (Wei et al. 2015; Hou et al. 2016), and ana-
in 2013 (Wang et al. 2015a, b, c; Wei et al. 2015). In lytical methods (Pantelaki and Voutsa 2019; Wang et al.
addition to being used extensively as FRs, OPEs have 2020b). These studies mainly addressed limited analysis
also been widely used as plasticizers and antifoaming and environmental compartments, and latest results are
agents in several industrial and consumer products still not reviewed. Besides, a comprehensive review of
(Marklund et al. 2003; van der Veen and de Boer 2012; studies focusing on different environmental compart-
Wei et al. 2015; Wang et al. 2017b). Therefore, the pro- ments, detailed analytical methods, toxicity, and human
duction and usage of OPEs could be more extensive than exposure is still lacking; thus, more information is re-
PBDEs, which are simply used as flame retardants. It quired. Given this, we made a comprehensive review
should be noted that terms like “emerging,” “new,” and and compiled recent information in the literature and
“alternate” have been commonly used when referring to gave more emphasis on production/usage, biological
organophosphate ester flame retardants and plasticizers. sample treatment and analysis, environmental occur-
Several thousand industrial and consumer products are rences, toxicity, human exposure, ecological risks, and
currently listed to contain OPEs, as the use and produc- the bioaccumulation potential of OPEs (the basic
tion of these synthetic chemicals increases, so will their information of selected OPEs is given in Table 1 and
discharge into different environmental compartments, es- Table S1, and chemical structures of selected OPEs can
pecially into freshwater and marine environments over be found in Supporting Information Figure S1). In ad-
their entire lifecycle, including production, usage, trans- dition, identified knowledge gaps and avenues for future
portation, recycling, and disposal processes (van der Veen studies are forwarded.
and de Boer 2012; Wei et al. 2015; Wolschke et al. 2015).
As a result, OPEs have been detected in various environ-
mental matrices worldwide such as dust (Cristale et al.
2016; Velázquez-Gómez et al. 2019; De la Torre et al. Methodology
2020; Zhao et al. 2020; Ali et al. 2021), water (Bekele
et al. 2019; He et al. 2019; Lai et al. 2019; Sutton et al. In this review paper, the most common online database, Web of
2019), air (Salamova et al. 2013; Wolschke et al. 2016; Science, was used to search for scientific literatures published up to
He et al. 2019; Zhang et al. 2020), biota (Greaves et al. 2021 using the following keywords (and their combinations): “or-
2016; Bekele et al. 2019, 2021; He et al. 2019; Liu et al. ganophosphate esters,” “organophosphate flame retardants,”
2019a, 2019b), sediment, and soil (Yadav et al. 2018; “OPEs,” “OPFRs,” “occurrence,” “bioaccumulation,”
Zeng et al. 2018; Zha et al. 2018; Cristale et al. 2019; “biomagnification,” “toxicity,” “human exposure,” “risk assess-
Fabiańska et al. 2019; Mo et al. 2019; Wang et al. ment,” “biota,” “surface water,” “drinking water,” and “sediment.”
2020a). Besides, OPEs have been determined in different Searching was carried out by two authors, following that further
foodstuffs and drinking water (Kim and Kannan 2018; Li inspection was done and duplicates were excluded from the col-
et al. 2019a). The ubiquity of OPEs in food, drinking lection by screening titles and abstracts of researches. The follow-
water, and human environments and their diverse toxic- ing major inclusion criteria were used: (1) the studies must be in
ities render them a potential threat to human health English and published in a scientific journal, (2) those studies
through diverse exposure routes, including the dietary in- reported the environmental occurrence and or bioaccumulation
take, dermal contact, dust ingestion, and inhalation of air or toxicity of OPEs, and (3) studies reported the detailed sample
(Xu et al. 2016; Poma et al. 2017, 2018; Zhu et al. 2020; treatment and analysis of OPEs. Using the selection criteria, further
Hou et al. 2021). Several studies have already reported screening was conducted by the authors, and the final references
OPEs in human breast milk, serum, hair, urine, nails, were critically reviewed. Overall, this review article mainly pre-
and placenta (Cequier et al. 2015; Ding et al. 2016; sented recent studies comprehensively and concisely; however,
Qiao et al. 2016; He et al. 2018a, b; Gao et al. 2019; attention should be given in comparing different concentration data
Xu et al. 2019a; Hou et al. 2020a; Li et al. 2020; Percy mainly lipid weight (lw), dry weight (dw), and wet weight (ww),
et al. 2020). Thus, they become an emerging concern to and special caution should be made when comparing ∑OPE data
the environment and human health. Therefore, it is as the number of OPE congeners varies among studies.
Table 1. Physicochemical properties of organophosphate esters (at 25 °C)

Full names of OPEs Acronym logKOW logKOC Water solubility Boiling Melting point (°C) Vapor pressure Henry’s Law
(mg/L) point (°C) (mm Hg) constant (atm/m3/mol)

Trimethyl phosphate TMP −0.65 1.1 3 × 105 197 −10 5.6 × 10−3 2.5 × 10−7
Triethyl phosphate TEP 0.8 1.68 5 × 105 216 −56 3.9 × 10−1 3.5 × 10−6
Environ Sci Pollut Res (2021) 28:49507–49528

Tri-n-butyl phosphate TBP 4 3.28 280 289 −80 1.2 × 10−3 1.8 × 10−4
Tripentyl phosphate TPeP 5.29 2.9 2.2 × 10−3
Tri-n-propyl phosphate TPrP 1.87 2.83 827 254 17 2.9 × 10−2 8.2 ×10−6
Trihexyl phosphate THP 7.45 5.43 9.1 354 86 7.0 × 10−5 1.1 × 10−4
Tris(2-butoxyethyl) phosphate TBEP 3.75 3.01 1.2 × 103 414 −70 2.1 × 10−7 1.3 × 10−11
Tris(2-ethylhexyl) phosphate TEHP 9.49 6.87 0.6 220 87 2.0 × 10−6 9.6 × 10−5
Tri-iso-butyl phosphate TiBP 3.6 3.05 3.72 264 16 1.3 × 10−2 2.8 × 10−4
Tris(2-choroethyl) phosphate TCEP 1.44 2.48 7.4 × 103 351 −55 1.1 × 10−4 3.3 × 10−6
Tris(2-chloroisopropyl) phosphate TCPP 2.59 2.21 1.6 × 103 359 72 1.9 × 10−6 6.0 × 10−8
Tris(1,3-dichloro-2-propyl) phosphate TDCP 3.85 2.35 1.5 457 88 7.4 × 10−8 2.6 × 10−9
Tris(2,3-dibromopropyl) phosphate TDBPP 4.29 8 5.5 1.9 × 10−5
Cresyl diphenyl phosphate CDPP 4.51 3.95 1.9 235 −38 4.7 × 10−6 4.4 × 10−8
2-Ethylhexyl diphenyl phosphate EHDP 5.73 4.21 1.9 375 87 5 × 10−5 2.4 × 10−4
Tricresyl phosphate TCP 5.11 4.35 0.36 439 77 1.8 × 10−7 9.2 × 10−7
Triphenyl phosphate TPP 4.59 3.72 1.9 370 49 1.2 × 10−5 2 × 10−7
Triphenylphosphine oxide TPPO 2.87 2.94 62.8 463 87 2.6 × 10−8 5.3 × 10−10
Dimethyl methylphosphonate DMMP −0.61 0.59 3.2 × 105 181 −48 1.2 1.3 × 10−6
Di-n-butyl phosphate DnBP 2.29 250 4.3 × 10−9
Isopropyl phenyl phosphate IPPP 5.31 2.2 424 89 5.2 × 10−7 7.7 × 10−8

logKOW octanol−water partition coefficient, logKOC soil adsorption coefficient; the data are compiled from previous reports (Marklund et al. 2003; van der Veen and de Boer 2012; Wei et al. 2015; Li et al.
2019b; Yang et al. 2019).
49509
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Physicochemical properties 2017; Li et al. 2018; Yadav et al. 2018; Zha et al. 2018; Zhong
and production/usage of organophosphate et al. 2018; Ren et al. 2019). Thus, soil and sediment are
esters among the major sinks of OPEs in the environment.
There is also a great variation in Henry’s law constant and
Physicochemical properties of OPEs vapor pressure values of OPEs at 25 °C (Table 1). The wide
variation in Henry’s law constant values of OPEs shows that
Organophosphate esters can be divided into three main groups the distribution of OPEs over air and aquatic environment is
based on their different chemical structures and functions (es- significantly variable. In addition, those OPEs with higher
ter functional groups): (1) halogenated alkyl-OPEs: TCPP, vapor pressures, i.e., TBP, TCEP, and TEP, are volatile and
TCEP, etc.; (2) non-halogenated alkyl-OPEs: TBEP, TEHP, easily diffuse into the air and deposited in large amount on
etc.; and (3) Aryl-OPEs: TPP, TCP, etc. Owing to their differ- dust than the heavier/larger OPEs (van der Veen and de Boer
ent functional groups, OPEs have substantial differences in 2012; Cristale et al. 2013; Wei et al. 2015).
their physicochemical properties (e.g., polarity, volatility,
and solubility) (Table 1) (Reemtsma et al. 2008). For example,
the presence of halogen gives an extended lifetime of the FRs Production/usage of OPEs
in the products by reducing its mobility in the polymer mole-
cule (van der Veen and de Boer 2012). In addition to the The use and production of OPEs can be tracked back several
halogens, the presence of nitrogen (nitrogen-containing hundreds of years but has increased rapidly in the past two de-
OPEs) provides a better flame retardant efficiency than those cades, due to the restriction and ban of main BFRs. Many OPEs
OPEs without nitrogen. This is because nitrogen in nitrogen- are produced in large volumes (greater than 1000 t per year)
containing FRs is mainly used as a gas source which can dilute (Cequier et al. 2014), and their level in the applied materials
the concentration of the oxygen near the flame and form a char can reach percentage amounts by weight (Alaee et al. 2003;
layer in condensed phase, which acts as a barrier/protective Kajiwara et al. 2011). In 1992, the global consumption of
layer against the heat and flame (Nguyen et al. 2012). OPEs was only 100,000 t/year (Hou et al. 2016), while between
Due to the distinct nature of substituents, there is a consid- 1995 and 2001, OPE consumption has increased from 108,000
erable difference in the physicochemical properties of OPEs in to 186,000 t (Marklund et al. 2005; van der Veen and de Boer
the environment (Table 1 and Table S1). These properties 2012; Lee et al. 2018) and climbed to 210,000 t/year in 2004
have been frequently used in the assessment of OPE fate in (Makinen et al. 2009). Similarly, in the past 10 years, the global
various environmental matrices and their potential impacts on consumption volume of OPEs has increased rapidly from
biota, particularly in aquatic organisms (van der Veen and de 500,000 to 680,000 t from 2011 to 2015 (Hou et al. 2016), and
Boer 2012). Mainly, their water solubility, Henry’s law con- more recent figures estimate 1,050,000 t/year for 2018
stant, vapor pressure (VP), the octanol−water partition coeffi- (Figure 1a) (He et al. 2017a). Such a rise comes mainly from
cient (KOW), and bioconcentration factor (BCF) showed a increased usage of OPEs in several countries, including Japan,
considerable variation between congeners (Table 1). For ex- China, and Western Europe (Figure 1). In Western Europe,
ample, TCP had limited water solubility (0.36 mg/L) when OPEs are among the high-production volume chemicals, and
compared to TCEP (700 mg/L) (van der Veen and de Boer their use as FRs sharply increased from 58,000 in 1998 to
2012). The solubility of OPEs decreases as the molecular 83,000 t/year in 2001. It climbed from 85,000 in 2005 to
mass increases and vice versa. Like the water solubility of 91,000 t/year in 2006, which might be explained by the fact that
OPEs, the KOW of OPEs is a decisive property that determines OPEs are often used as FRs, plasticizers, anti-foaming, and re-
their bioaccumulation potential in tissues of biota. The bioac- placement of PBDEs (Figure 1b) (Reemtsma et al. 2008; Wei
cumulation potential of a substance is one of the leading con- et al. 2015). On the other hand, in Japan (Figure 1c), the total use
cerns for food safety and ecosystem health. Several findings of OPEs has increased from 22,000 to 45,000 t/year from 2001 to
suggested that chemicals with higher KOW are more lipophilic 2005, and approximately 87,500 t were consumed in 2010
than hydrophilic. The logKOW values of OPEs vary substan- (Möller et al. 2012; RSD 2010; Wei et al. 2015). The consump-
tially among congeners, ranging from −9.8 to 10.6 (van der tion of OPEs in China in 2007 was 70,000 t and increased to
Veen and de Boer 2012). However, the commonly used OPEs 100,000 t in 2011, and approximately 300,000 t were consumed
have logKOW values ranging from −0.65 for TMP to 9.49 for in 2013, and it is estimated to increase around 15% per year
TEHP (van der Veen and de Boer 2012). As shown in Table 1, (Figure 1d) (Wang et al. 2010; Zhong et al. 2017). As the eco-
most OPEs have a positive logKOW value, which indicates that nomic development and growth of China is among the leading
they are more lipophilic than hydrophilic. Meanwhile, countries, the increasing trends of OPE consumption is expected
chemicals with very higher logKOW value become less bio- even greater than 15% per year, due to the high production of
available, and they bind themselves tightly with the organic industrial and consumer products which needs the application of
matters in the soil and sediment (Cao et al. 2017; Cui et al. OPEs (Wang et al. 2010; Zhong et al. 2017).
Environ Sci Pollut Res (2021) 28:49507–49528 49511

Fig. 1 Consumptions of
organophosphate ester flame
retardants and plasticizers in
different regions. a Global, b
Western Europe, c Japan, and d
China. Data are compiled from
previous studies (Björklund et al.
2004; H. He et al. 2017a, b; Hou
et al. 2016; Lee et al. 2018;
Marklund et al. 2005; Möller et al.
2012; Reemtsma et al. 2008; RSD
2010; Wang et al. 2010; Wei et al.
2015; Zhong et al. 2017).

Most of OPEs are recognized as FRs and plasticizers. the recovery of OPEs from biota samples; Soxhlet ex-
However, there are still various uses of these emerging traction and microwave-assisted extraction (MAE) are
chemicals, such as their use as additives to floor polishes also frequently used.
and as stabilizers for anti-foaming to floor polishes, hydraulic
fluids, lacquers, and lubricants. The halogenated OPEs are
primarily used as FRs, while the non-halogenated ones are Accelerated solvent extraction
frequently used as plasticizers (Andresen et al. 2004).
Generally, OPEs are used as additives to different materials, ASE, also referred as pressurized liquid extraction (PLE), is an
such as textiles, furniture, mattresses, automotive, electronics, automated system that uses organic solvents for extracting
rubber, polyurethane foams, polyvinyl chloride (PVC) plas- organic compounds from solid and semisolid samples at ele-
tics, building materials, antistatic agent, cotton, cellulose, vated pressures (500−3000 psi) and temperatures (50−200 °C)
glues, epoxy resins, and phenolics resins (Andresen et al. above the boiling point of the solvents. The US
2004; van der Veen and de Boer 2012). For example, TPP, Environmental Protection Agency (USEPA) has recommend-
TEHP, and TCP are largely used in PVC and unsaturated ed ASE method as a standard method (EPA-3545A in update
polyester resins for their plasticizing properties. The most III of the USEPA SW-846 methods) because of its advantages
widely used halogenated OPEs (i.e., TCPP, TCEP, and of stable recovery and savings in time for short periods (5−10
TDCP) are primarily applied in rigid and flexible polyure- min), labor, and solvent costs over traditional extraction meth-
thane foams (Marklund et al. 2003). In addition, TBP, od (Richter et al. 1996; Dionex 2011).
TBEP, and TPP are also used as antiwear agents pressure In comparison to OPE extraction methods, ASE has been
additives in lubricants, hydraulic fluids, motor oils, and trans- successfully implemented to the pretreatment of OPEs in var-
mission fluids (Regnery and Püttmann 2010; van der Veen ious biological matrices in the last few years. For instance,
and de Boer 2012). For some industrial or consumer products, Gao et al. (2014) developed an ASE-solid-phase
several OPEs are applied. In Table S2, an overview of OPEs microextraction (SPME), followed by gas chromatography-
with their applications is given. flame photometric detector (GC-FPD) method for the deter-
mination of eight OPEs in fish. The ASE was operating at 150
°C and 1500 psi, using a 9:1 (v/v) solution of water and ace-
tonitrile. The recoveries of OPEs were from 79.8 to 107.3%,
Sample treatment and analysis of OPEs and relative standard deviations (RSDs) were below 9%. The
method detection limits (MDLs) were in the range of 0.010–
Extraction of OPEs 0.208 ng/g. Chen et al. (2012) proposed a method for the
analysis of 12 OPEs in herring gull eggs based on ASE-
Only few extraction methods of OPEs from the biota samples SPE-GPC, followed-by LC-MS/MS determination. The fol-
have been developed and optimized (Table S3). lowing ASE parameters were employed: extraction solvent
Accelerated solvent extraction (ASE) and ultrasonic ex- hexane/dichloromethane (Hex:DCM 1:1, v/v); pressure:
traction are the most commonly employed methods for 1500 psi; and temperature: 100 °C. Method quantification
49512 Environ Sci Pollut Res (2021) 28:49507–49528

limits (MQLs) and instrumental detection limits (IDLs) Clean-up methods


ranged from 0.06 to 0.20 ng/g and 0.01 to 0.12 ng/mL, respec-
tively. The mean recoveries of 12 OPEs ranged from 67 to After extraction of biological samples, a clean-up step is need-
104%, and RSD was less than 16% for all congeners. Overall, ed to reduce matrix interferences and lipid contents. SPE,
ASE is becoming popular, and different solvent combinations dSPE, and GPC are popular techniques, which have been used
have been used for the extraction of OPEs from biological for the clean-up of biota samples for OPE determination
matrices, e.g., Hex/DCM (1:1, v/v) (McGoldrick et al. (Table S3). SPE is a kind of adsorbent extraction that involves
2014), Hex/DCM (4:1, v/v) (Hou et al. 2017), ethyl acetate/ bringing the sample into contact with solid phase whereby the
cyclohexane (5:2 v/v) and cyclohexane/diethyl ether (9:1 v/v) analytes are selectively adsorbed onto the surface of the solid
(Sundkvist et al. 2010), DCM/Hex (1:1, v/v) and acetone/Hex phase. SPE column usually uses aminopropyl silica gel, hy-
(1:1, v/v) (Su et al. 2014), and DCM/acetone (1:1, v/v) drophilic lipophilic equilibrium column (Oasis HLB car-
(Hallanger et al. 2015) (Table S3). tridge), octadecyl solid phase extraction column (C18), NH2
cartridge, florisil column, or a combination of different adsor-
bent (McGoldrick et al. 2014; Su et al. 2014; Hallanger et al.
Ultrasonic-assisted extraction (UAE) 2015; Santín et al. 2016; Guo et al. 2017; Choo et al. 2018; Liu
et al. 2018b; Zhao et al. 2018; He et al. 2019; Xu et al. 2019b).
UAE is a widely used technique; it is fast (10−30 min), simple For example, Chen et al. (2012) used an aminopropyl silica
(easy procedures), and feasible, which can meet the standards gel SPE column and GPC for the clean-up of herring gull egg
of most laboratories. Chu and Letcher (2015) proposed a fast samples for OPE determination. After discarding the first frac-
UAE method for extraction of 13 OPEs from the biota sam- tion of the elutes (2 mL, 1:4 DCM/Hex v/v), 8 mL of DCM/
ples (herring gull egg, pork liver, and fish tissues) and cleaned Hex 1:4 was used to elute target OPEs. After testing different
up further by dispersive solid phase extraction (d-ESP), dispersive extraction ESP sorbents, Chu and Letcher (2015)
followed by ultra-high performance LC-MS/MS determina- reported that the primary secondary amine (PSA) bonded sil-
tion. The recovery of the method ranged from 54 to 113%, ica sorbents displayed the highest recoveries for 13 commonly
and RSD was less than 17%, with MQLs ranging from 0.05 to detected OPE congeners in biota samples. In another method
0.50 ng/g wet weight for all samples. In another study, Santín development study, Santín et al. (2016) reported that a tandem
et al. (2016) established a USE-LC-QqLIT-MS (QqLIT = of basic alumina + C18 SPE showed better performance over
quadrupole-linear ion trap) for the determination of sixteen neutral alumina + C18 and florisil + C18.
OPEs in fish tissue samples. The recoveries of OPEs were
from 45 to 115%, and RSDs were below 25%. MQLs and Instrumental analysis
MDLs were ranged from 1.12 to 38.8 ng/g lipid weight (lw)
and 0.34–11.6 ng/g lw, respectively. The developed method OPEs have considerable variations in their physicochemical
was applied to the detection of OPEs in fish collected from the properties (Table 1), varying from very hydrophobic to very
Llobregat River, Spain, and 13 major OPEs were detected. polar, which is a cause of concern for the establishment of
analytical methods. A reliable, selective, sensitive, and rapid
analytical method is vital for the accurate detection and quan-
Soxhlet extraction tification of trace environmental contaminants, including
OPEs. To date, gas chromatography (GC) and liquid chroma-
Soxhlet extraction technique has been used for long time in tography (LC)-based methods have been reported, and some
analytical procedures and is known for its time consuming representative analytical methods for OPE quantification are
(i.e., needs at least 24 h of extraction) and demand for higher briefed in Table S3. Gas chromatography-mass spectrometry
volumes of solvents. Recently, Liu et al. 2018a, b) established (GC-MS), gas chromatography-tandem mass spectrometry
a Soxhlet-SPE based method combined with GC−MS/MS for (GC-MS/MS), and liquid chromatography-tandem mass spec-
the quantification of 12 OPEs in fish. The recoveries of trometry (LC-MS/MS) are powerful instruments for structural
OPEs were in the range of 56–108%, while MDLs were identifications and play vital roles in OPE analysis in biolog-
ranged from 0.004 to 0.059 ng/g. The proposed method ical and other environmental samples. In addition, both GC
was tested for the detection of OPEs in fish collected and MS, combined with selective detectors (e.g., flame pho-
from the Pearl River Delta, China; eleven OPEs were tometric detector, FPD), were also used for the determination
detected. Different solvents have been used in Soxhlet of OPE residues in environmental samples.
extraction to determine OPEs in biological samples, Gas chromatography has been used for the analysis of non-
such as methanol (Liu et al. 2018b), DCM (Liu et al. polar compounds, via non-polar stationary phases (usually 5%
2019b), and acetone/Hex (1:1, v/v) (Cao et al. 2017; He phenyl methyl-polysiloxane) mainly DB-5MS, HP-5MS, and
et al. 2019). RTX-1614 (Gao et al. 2014; Guo et al. 2017; Choo et al. 2018;
Environ Sci Pollut Res (2021) 28:49507–49528 49513

Liu et al. 2018b, 2019b). Quadrupole or triple quadrupole are and TBP are the predominant OPEs (Wei et al. 2015; Wang
mostly employed as detectors in mass spectrometer (Guo et al. et al. 2020b). For example, a study conducted along River
2017; Liu et al. 2019b). Electron impact ionization (EI) mass Aire, UK (i.e., a river affected by anthropogenic and industrial
spectrometry is important to obtain structural information of a pressures) reported the highest level of ΣOPEs, where TCPP
compound, while selected ion monitoring (SIM) is employed was the most prominent compound with the highest concen-
to improve the sensitivity and selectivity. In GC-MS, SIM trations ranging from 113 to 26,050 ng/L (mean concentra-
mode has limited confirmation and quantification due to low tion: exceeding 6,000 ng/L) (Cristale et al. 2013). A study that
m/z range in spectrum (usually affected by constituents of monitored 14 OPEs in rivers, lakes, and seawater of New
matrix). Such interferences could increase background noise York State, USA, also reported levels of ΣOPEs in the range
level and reduce instrumental sensitivity and selectivity. GC- of 37 to 510 ng/L in rivers, 8 to 1280 ng/L in lakes, and 40 to
MS/MS shows a reduction in the limitation of GC-MS by the 60 ng/L in seawater. TBEP and TCPP were the dominant
integration of selective reaction monitoring (SRM), which compounds with average concentrations of 689 ng/L and
helps in the reduction of noise level and increase selectivity 329 ng/L in lakes, respectively (Kim and Kannan 2018).
significantly (Teo et al. 2015). In addition, multiple reaction Relatively lower levels of OPEs were examined in studies that
monitoring (MRM) acquisition mode is attainable by Triple- assessed 19 OPEs in 23 rivers of Sweden, with concentrations
quadrupole (QqQ)-MS detector, which cannot be attained via of ΣOPEs ranging from 10 to 100 ng/L (Gustavsson et al.
GC-MS/MS with SRM mode or GC-MS (SIM mode) 2018). Another recent study that monitored 18 OPEs in the
(Quintana et al. 2008). Lake Shihwa of Korea reported the highest detection frequen-
LC-MS has also been used in analyzing OPEs in biota cy (DF) for TBEP, TCPP, and TDCP, with DF of 100%, 93%,
samples; especially it is suitable for OPEs which are less vol- and 81%, respectively. The concentrations of ΣOPEs were in
atile. LC or ultra-high performance liquid chromatography the range of 28.3 to 16,000 ng/L, in which mean concentration
(UHPLC) is attained in the reversed-phase mode, mostly of TCEP (255 ng/L), TCPP (211 ng/L), TEP (182 ng/L), and
using octadecyl bonded (C18) stationary phases (Waters TBEP (164 ng/L) were the most predominant congeners (Lee
Symmetry C18, Luna C18, BEH C18, and RP-18) et al. 2018). Similarly, of 14 OPEs screened for, high DF (80–
(McGoldrick et al. 2014; Hallanger et al. 2015; Santín et al. 99%) was observed for TBEP, TCEP, TCPP, TMP, and TEP
2016; Giulivo et al. 2017; He et al. 2019). Mixtures of water in water samples collected from rivers and lakes of Beijing
(acidified with formic acid) with acetonitrile or methanol in (Shi et al. 2016). The high concentration of ΣOPEs (range:
gradient elution are the most commonly used mobile phases. 3.24–10,945 ng/L; mean: 954 ng/L) were mainly due to in-
UHPLC-MS/MS or LC-MS/MS shows high sensitivity, selec- creased human impacts from the densely populated city (Shi
tivity, and reduced matrix effect in the analysis of OPEs in et al. 2016). Seawater samples obtained from East China Sea
environmental matrices, mainly if atmospheric pressure chem- and Yellow Sea near Lianyungang, Xiamen, and Qingdao
ical ionization (APCI) or electrospray ionization (ESI) mode were screened for halogenated OPEs including TCEP,
and MRM acquisition mode are applied (Quintana et al. TCPP, TDCP, and TDBPP and contained total concentrations
2008). In general, these techniques offered low LOQs and in the range of 91.9 to 1392 ng/L, and the mean levels of these
good recoveries for most OPE congeners. four congeners were 134, 84, 109, and 97 ng/L, respectively
(Hu et al. 2014). Zhong et al. (2017) also reported seven OPEs
in the seawater from Bohai Sea and Yellow Sea, the coastal
Environmental occurrence of OPEs seas of China. Relatively low levels of ΣOPEs were detected,
with total concentration ranging from 8 to 98 ng/L (Zhong
Several researches have documented the ubiquitous occur- et al. 2017). Meanwhile, Wang et al. (2018c) have reported
rence of OPEs in different environmental compartments. At the extensive occurrence of OPEs in the coastal area of Dalian
present, OPEs are reported in surface water, soil, sediment, China, with concentration varying from 48 to 681 ng/L.
biota, air, and indoor dust, demonstrating the ubiquity of Globally, only five studies have assessed OPEs in drinking
OPEs (Santín et al. 2016; Kim and Kannan 2018; Bekele water and reported the levels in purified water, tap water,
et al. 2019, 2021; Ren et al. 2019; Wang et al. 2020a). bottled water, well water, filtered drinking water, and barreled
water from China, Korea, Pakistan, and the USA (Table 2) (Li
OPEs in surface and drinking water et al. 2014; Ding et al. 2015; Khan et al. 2016; Lee et al. 2016;
Kim and Kannan 2018). Li et al. (2014) screened for nine
Depending on the industrial and anthropogenic activities in OPEs in tap water, in China. The total concentrations of
the surrounding area, a wide range of OPE levels was detected OPEs were in the range of 85 to 325 ng/L; of the screened
in the surface water worldwide (Table 2). This demonstrates OPEs, TBEP, TPP, and TCPP were the predominant
the ubiquity of OPEs, with congener concentration ranging congeners. In another study from Eastern China, Ding et al.
from ng/L to tens of μg/L, in which TCPP, TBEP, TCEP, (2015) reported the residual levels of nine OPEs in different
49514

Table 2. A summary of ΣOPEs, dominant and frequent organophosphate esters in aquatic organisms (ng/g lw), surface water (ng/L), drinking water (ng/L), and sediment (ng/g dw) as reported in the
literature.

Matrix Region Most dominant congeners Most frequent congeners ΣOPEs References

Aquatic biota Pearl River Delta, China TBEP, TCEP, TBP, TBEP, TCEP, TBP, TCPP Ma et al. (2013)
Swedish lakes and coastal areas TCPP, TPP, TBP 34−11000 Sundkvist et al. (2010)
Llobregat River, Spain TEHP, IPPP, TBEP TEHP, IPPP, TBEP 110−1900 Santín et al. (2016)
a
Nakdong River, South Korea TEP, TBP, TCEP, TBEP TBEP 4.59−5.87 Choo et al. (2018)
Freshwater, Beijing, China TBP, TCEP, TCPP, TEHP TBP, TCEP, TCPP 264−1973 Hou et al. (2017)
Western Scheldt, The Netherlands TiBP, TBEP, TCPP, TPP TBEP, TCPP, TCEP, TPP Brandsma et al. (2015)
Taihu Lake, China TiBP, TCEP and TPP TCPP, TiBP, TDCP, TEP, EHDP, TCEP Zhao et al. (2018)
Taihu Lake, China TCPP, TMP, EHDP TPP, TCEP, TDCP, TCPP 1.8−21.75a Wang et al. (2019a)
European river basins TBP, TCEP, IPPP EHDP, TCEP, TBEP 14−650 Giulivo et al. (2017)
Laizhou Bay, North China TEHP, TBP, TBEP, TPP, EHDP TCPP, TiBP, TBP, TBEP, EHDP, TEP 21−3510 Bekele et al. (2019, 2021)
Manila Bay, The Philippines TEHP, TEP, TBP, EHDP TEP, TPeP, TBP, EHDP 110−4600 Kim et al. (2011)
Surface water River Aire, UK TCPP TCEP, TCPP, TDCP, TPP 13−26050 Cristale et al. (2013)
Rivers, lakes, and seawater, USA TCPP, TBEP TCPP, TBEP, TEP 37−1280 Kim and Kannan (2018)
Swedish river water TDCP, TEHP, TCEP Gustavsson et al. (2018)
Lake Shihwa, Korea TCEP, TCPP, TEP, TBEP TBEP, TCPP, TDCP 28−16000 Lee et al. (2018)
Rivers and Lakes, Beijing TCPP, TCEP TBEP, TCEP, TCPP, TMP 3−10945 Shi et al. (2016)
Bohai and Yellow Seas, China TCPP, TCEP, TPPO TCPP, TCEP, TDCP, TPPO 8−98 Zhong et al. (2017)
Drinking water China TBEP, TPP, TCPP TCPP, TPP, TBP, TBEP 85−325 Li et al. (2014)
East China TEP, TCPP TEP, TCEP, TBP, TPP 09−339 Ding et al. (2015)
Pakistan TCPP, TCEP TCPP, TCEP, TBP MDL−71 Khan et al. (2016)
Korea TCEP, TCPP, TBEP TCEP, TCPP, TBEP MDL−1660 Lee et al. (2016)
Tape water, NY, USA TBEP, TCPP TBEP, TCPP 3−366 Kim and Kannan (2018)
Sediment North China TCPP, TCEP TCPP, TCP, TPP 340−270000 Ren et al. (2019)
Europe TCPP, TBEP TCPP, TBEP, TCP 2.5−181 Wolschke et al. (2018)
Taihu Lake, China TCPP, TCEP TCEP, TCPP, TBEP, TiBP, TDCP, TEHP 2.8−47.5 Wang et al. (2018b)
Laizhou Bay, Bohai Sea, China TBP, TCEP, TCPP 6.7−102 Wang et al. (2017c)
Pearl River Estuary, China TCPP, TCEP, TBEP TCEP, TBEP, TEHP, TBP 13−377 Hu et al. (2017)
Sediment from European river EHDP, TCPP, IPPP EHDP, TCPP, TPP, TEHP 0.31−549 Giulivo et al. (2017)

a
Wet weight (ww) concentration
Environ Sci Pollut Res (2021) 28:49507–49528
Environ Sci Pollut Res (2021) 28:49507–49528 49515

drinking water, i.e., tap, direct drinking, barreled, well, and OPEs in aquatic biota
bottled waters, with the median total concentrations of 192,
59.2, 27.6, 4.5, and 3.9, respectively. Khan et al. (2016) also Relatively few studies have investigated OPEs in aquatic or-
reported the residual levels of six OPEs in potable water from ganisms, the level of ΣOPEs ranging from tens to thousands
Pakistan, in which the total concentrations ranged from below of ng/g lw (Table 2, Table S4). For example, Ma et al. (2013)
detection limit (MDL) to 71 ng/L. In Korea, 10 OPEs were reported extremely high levels of OPEs in fish from the Pearl
screened in purified and bottled water collected from major River Delta, China. TBEP (164–8,840 ng/g lw), TCEP (83
cities; the total concentrations ranged between below MDL −4,690 ng/g lw), TBP (44−2,950 ng/g lw), and TCPP (62
and 1660 ng/L. Of the screened OPEs, TCEP, TBEP, and −883 ng/g lw) were the most predominant of all OPEs.
TCPP were predominant OPEs, and elevated residual level Similarly, Sundkvist et al. (2010) found high concentrations
of TCPP was observed due to contamination occurred during of TBP (34−4,900 ng/g lw), followed by TBEP (240−1000
purification process (Lee et al. 2016). For tap water in New ng/g lw) and TCPP (170−770) in fish from Swedish lakes and
York State, USA, 14 OPEs were screened, and total concen- coastal areas where there is known potential sources of OPEs.
trations ranged from 3 to 366 ng/L; TBEP and TBP were Another study that examined 16 OPEs in fish from Llobregat
found to be the most abundant (Kim and Kannan 2018). River, Spain, reported total concentrations of OPEs up to 2423
ng/g lw. IPPP (nd-601 ng/lw), TEHP (37−326 ng/g lw), and
OPEs in sediment TBEP (6.40−296 ng/g lw) were the dominant congeners
(Santín et al. 2016). Choo et al. (2018) reported the levels of
Apart from aquatic environment, sediment is another main OPEs in crucian carp from the Nakdong River, South Korea.
environmental compartment and major reservoir of OPEs. The total levels of OPEs ranged from 31.1 to 256 ng/mL
Several studies reported the level of ΣOPEs in sediment rang- whole blood, 6.22−18.1 ng/g wet weight (ww) in liver, 3.08
ing from a few tens to hundreds of ng/g dry weight (dw) −7.70 ng/g ww in gonad, and 4.23 to 7.75 ng/g ww in muscle.
(Table 2). However, recently, Ren et al. (2019) have reported Hou et al. (2017) also reported 8 OPEs and their metabolites in
exceptionally high level of OPEs in sediment samples near an fish from freshwater around Beijing, China, with very high
OPE manufacturing plant Hengshui, North China, with total detection frequency (100%) for TBP, TCPP, and TCEP. The
concentration ranging from 340 to 270,000 ng/g dw. TCPP total OPEs were ranged from 265 to 1973 ng/g lw. Brandsma
and TCEP were main congeners in the sediment samples and et al. (2015) measured the levels of 9 OPEs in the Western
ranged from 280 to 190,000 ng/g dw and 61 to 79,000 ng/g Scheldt estuarine food web, consisting of shrimps, crabs, and
dw, respectively. Meanwhile, Giulivo et al. (2017) screened worms, of which lugworm had the highest median concentra-
10 OPEs in sediment samples collected from three European tion for TiBP (7.4 ng/g ww), TBEP (17 ng/g ww), TCPP (4.6
river basins (the Adige, the Sava, and the Evrotas) at a level ng/g ww), and TPP (2 ng/g ww). Zhao et al. (2018) have
ranging from 0.31 to 549 ng/g dw. Another study that moni- recently screened for 17 OPEs in the food web from Taihu
tored OPEs in surface sediment samples from large river basin Lake. Plankton had the highest total OPE concentration (100 ±
deltas/estuaries across Europe reported total concentrations in 23 ng/g ww), followed by invertebrates (17.1 ± 11.0 ng/g ww)
the range of 2.5 to 181 ng/g dw, where congener concentra- and fish (9.8 ± 6.2 ng/g ww). Similarly, in another study that
tions varied from below detection limit to 142 ng/g dw with investigated the biomagnification of OPEs in a food web (in-
the dominancy of TBEP and TCPP (Wolschke et al. 2018). cluding plankton, invertebrates, and fish) in the Zhushan Bay
Wang et al. (2018b) also reported eleven OPEs in sediment of Taihu Lake, China, the ∑OPEs in the biota were in the
samples from Taihu Lake, China. The total OPE concentra- range of 1.83 ng/g ww in snakehead fish to 21.8 ng/g ww in
tions were in the range of 2.8 and 47.5 ng/g dw. In sediment bivalve, where fish accumulated less OPEs than studied inver-
samples from coastal Laizhou Bay of the Bohai Sea of China, tebrates (Wang et al. 2019a). Giulivo et al. (2017) also ana-
Wang et al. (2017c) reported eight OPEs at a concentration lyzed 14 OPE congeners in 27 fish samples from three
ranging from 6.7 to 102 ng/g dw, of which TCPP and TCEP European river basins (the Adige, the Evrotas, and the Sava)
were the predominant congeners. In comparison, lower levels and detected all OPEs with the total concentration ranging
of total OPEs were detected in sediment samples collected from 14.4 to 650 ng/g lw. TBP (102 ng/g lw), EHDP (31.8
from North Pacific (Bering Sea) to the Arctic Ocean (0.2 ng/g lw), and TCEP (18.0 ng/g lw) were the most dominant
−4.7 ng/g dw) (Ma et al. 2017) and Yellow Sea and Bohai OPEs in European fish, and the levels in benthic and pelagic
Sea (0.08−4.6 ng/g dw) (Zhong et al. 2018). Hu et al. (2017) fish do not show significant difference. In contrast, benthic
found 11 OPEs dominated by TCPP, TCEP, and TBEP in fish accumulated significantly higher OPE concentration than
sediments from three mangrove wetlands (Guangzhou, pelagic fish from studies that analyzed the food web of
Zhuhai, and Shenzhen) in the Pearl River Estuary of South Laizhou Bay, North China (Bekele et al. 2019, 2021);
China. The total OPE concentrations in the mangrove sedi- Western Scheldt, The Netherlands (Hallanger et al. 2015);
ments ranged from 13.2 to 377 ng/g dw (Hu et al. 2017). Taihu Lake, China (Wang et al. 2019a); and Manila Bay, the
49516 Environ Sci Pollut Res (2021) 28:49507–49528

Philippines (Kim et al. 2011). Generally, physicochemical


properties, bioavailability, exposure levels, accumulation
mechanisms, and biotransformation rate of the OPE are
among the decisive factors that determine the level and accu-
mulation potential of this ubiquitous chemical.

OPEs in other environmental compartments

Apart from aquatic biota, sediment, surface, and drinking water,


OPEs have been reported in soil (Cui et al. 2017; He et al.
2017b; Yadav et al. 2018; Wang et al. 2019b; Han et al.
2020), groundwater (Fries and Püttmann 2001, 2003; Hou
et al. 2019), indoor dust (Abdallah and Covaci 2014; He et al.
2015; Abafe and Martincigh 2019; Cao et al. 2019; Chen et al.
2019; Guo et al. 2019; Ali et al. 2021), and air (Luo et al. 2016;
Cao et al. 2019; He et al. 2019; Han et al. 2020; Liang et al.
2020; Sun et al. 2020). For example, Yadav et al. (2018) deter-
mined the level of OPEs in soil samples from Kathmandu
Valley, Nepal. The total OPE concentrations were in the range
of 25 to 27,900 ng/g dw, while TMP was the dominant conge- Fig. 2. Major confirmed and potential effects of OPEs to humans and
ner accounting for 35−49% of total OPEs. Meanwhile, lower other organisms (daphnia, fish, rodents, birds, etc.)
total OPEs (range: 10.1 to 315 ng/g dw) were measured in soil
from Chongqing, China; TBEP was the most concentrated of More specifically, toxicological effects were reported in
all OPEs (He et al. 2017b). Hou et al. (2019) screened for 13 fish exposed to OPEs at environmentally relevant concentra-
OPEs in groundwater from Chengdu, China, with the total con- tions. For example, Du et al. (2015) showed cardiotoxicity in
centrations ranged from 12.5 to 253 ng/L. zebrafish embryos after exposure to 100 μg/L of TPP.
Neurobehavioral effects of TPP on zebrafish were also report-
ed in several studies (Jarema et al. 2015; Noyes et al. 2015;
OPE toxicity and human exposure Shi et al. 2018). Under static exposure experiment, Behl et al.
(2015) demonstrated developmental toxicity of TPP in
OPE structural similarity to neurotoxic organophosphate pes- zebrafish and Caenorhabditis elegans. Yu et al. (2017) inves-
ticides is the cause of concern. The majority of reported stud- tigated effects of TDCP on the parent generation and larvae of
ies on the toxicity/exposure of OPEs are based on their simi- first generation of zebrafish after 240-day exposure and
larity with organophosphate pesticides. Exposure of human- reported growth and transgenerational effects. Further, Wang
kind to OPEs and the health risk have increased due to the et al. (2015b) confirmed that the neurological effects of TDCP
extensive application. Endocrine disruptive effects, develop- could be transferred from the parent generation (exposed adult
mental toxicity, neurotoxicity, and reproductive toxicity are zebrafish) to larvae.
among the effects reported in recent studies. Some OPEs are being considered as potential carcinogenic
based on animal studies, for instance, TCPP and TDCP have
Toxicity been restricted from addition in child supplies in western
countries (European Commission 2014). Frederiksen et al.
Several toxicological studies reported that OPEs such as TBP, (2018) reported that TCPP can readily permeate through the
TCPP, TBEP, TPP, TCEP, TDCP, and TCP causes develop- skin. In chicken embryos, TCPP was demonstrated to induce
mental, transgenerational, reproductive, and other health ef- developmental toxicity, reduction of tarsus length, and pip-
fects on daphnia, fish, rodents, birds, and humans (Figure 2) ping delay (Farhat et al. 2013).
(van der Veen and de Boer 2012; Greaves and Letcher 2014; Similarly, TCEP was considered carcinogenic for animals
Schang et al. 2016; Yuan et al. 2018). Carcinogenicity, neu- (WHO 1998). Apart from the carcinogenic nature, longer es-
rotoxicity, kidney toxicity (Regnery and Püttmann 2010; van trous cycle length, reduced sperm density and motility,
der Veen and de Boer 2012; WHO 1998, 2000), skin irrita- and reproductive and hemolytic effects are among the
tion, decreased sperm quality (Meeker and Stapleton 2010), major biological effects reported as toxic effects of
dermatitis (Meeker and Stapleton 2010; WHO 1991), and TCEP (Chapin et al. 1997).
endocrine disruption (Heindel et al. 2017) are among the Animal experiments and epidemiological studies have
health effects on humankind linked with OPE exposure. documented the neurotoxic effect of TCP. Noyes et al.
Environ Sci Pollut Res (2021) 28:49507–49528 49517

(2015) studied the effect of TCP on the embryonic and larval median lethal concentration (i.e., LC50) of OPEs to aquatic
zebrafish exposed statically, and hyperactivity was observed organisms varied greatly and generally in the order of mg/L.
for both developmental stages. In another experimental The LC50 values of OPEs were reported in the range of 0.42
exposure study, Jarema et al. (2015) reported developmental for TDCP to 1250 mg/L for TEP in zebrafish.
toxicity effects of TCP on zebrafish embryos and Daphnia magna, ecologically representative zooplankton,
Caenorhabditis elegans. is widely used in ecological and ecotoxicological studies. The
50% effect concentration (i.e., EC50) of OPEs documented for
Human exposure and ecological risk assessment daphnia (48 h) ranged from 0.31 for TCP to 381 mg/L
for TCEP (Table S1). Overall, most OPE congeners are
Considering the ubiquitous occurrence of OPEs in the air, considered to be toxic to humans and aquatic biota and
dust, sediment, and water and their bioaccumulation in biota hazardous for environment.
samples, humans are frequently exposed to these chemicals As a result, different regulatory bodies are taking restrictive
through air inhalation, dust ingestion, dermal absorption, and measures to address this issue with a chemical class and/or
diet. Contaminated environmental matrixes, mainly sediment, chemical-by-chemical approaches (see Table S6 for detailed
dust, and water, are the main routes for dermal exposure. For information). More restrictions have been placed on those
instance, a study from Nepal showed that dermal absorption products commonly used by infants and toddlers because of
overwhelmingly contributed to OPE exposure than inhalation their higher vulnerability to OPEs. For example, in 2010,
and dust ingestion (Yadav et al. 2017). The estimated daily Canada Consumer Product Safety Act bans foam-padded chil-
intake of ∑OPEs via dermal absorption (adults: 16.8 ng/kg dren’s products with TCEP (Government of Canada 2010).
bw/d and children: 45.22 ng/kg bw/d) were higher than via Similarly, TCEP was banned for use in children’s products by
inhalation (adults: 0.98 ng/kg bw/d and children: 3.73 ng/kg Maryland General Assembly (MD 2013), and in 2015,
bw/d) and dust ingestion (adults: 0.98 ng/kg bw/d and chil- European Commission (EU) generally prohibits the use of
dren: 3.73 ng/kg bw/d) (Yadav et al. 2017). Another study TCEP (REACH 2015). In addition, in 2017, the US
revealed that exposure pathways are different from one con- Consumer Product Safety Commission (CPSC) warned man-
gener to the other. For instance, Xu et al. (2016) assessed three ufacturers and consumers to prohibit all halogenated OPEs in
exposure pathways (dust ingestion, air inhalation, and dermal electronics, mattresses, furniture, and children’s products
absorption) and reported that air inhalation and dust (CPSC 2017).
ingestion were the most important pathways for volatile
(TCPP and TCEP) and less volatile (TCP, TBEP, and
TPP) OPEs, respectively. Bioaccumulation and biomagnification
Furthermore, several studies have revealed that foodstuff potentials of OPEs
ingestion is one of the major exposure pathways. Poma et al.
(2017) indicated that dietary intake contributed more because After Rachel Carson described the consequences of extensive
of its larger consumption rate (100,000-fold higher) than those use of chemicals in Silent Spring (Carson 1962), several coun-
of dust ingestion, air inhalation, and dermal absorption for tries, organizations, and scientists became cautious about the
humans. Different food matrices were screened, mainly meat, danger of chemicals released to the environment, and present-
vegetables, dairy product, fish, cereals, beverages, fruit, etc. ly they are evaluating the environmental behavior of thou-
(Zhang et al. 2016; Poma et al. 2017, 2018; Ding et al. 2018; sands of chemicals. In 2001, the Stockholm Convention on
Wang and Kannan 2018). From screened foodstuffs, rice in- POPs (POPs Convention) was adopted in Stockholm,
gestion was the dominant pathway for human exposure to Sweden, to identify chemical that biomagnifies, toxic, and
OPEs, and the mean daily intake of ∑OPEs was 601 and harmful and protect human beings and the environment from
539 ng/kg bw/day for females and males, respectively. the hazards of persistent organic pollutants (POPs). In addition
Additionally, Liu et al. (2019b) determined the dietary risks to the POPs Convention, EU’s REACH (Registration,
of OPEs from fish consumption, and the value ranged from 17 Evaluation, and Authorization of Chemicals) is playing a
to 98 ng/kg bw/day, indicating that fish ingestion is also the key role in identifying/restricting PBT substances. BCF/
other main pathway of human exposure to OPEs. In general, bioaccumulation factor (BAF) assessments are widely used
the reported estimated daily intake values of OPEs are two to in regulatory criteria, and they are important endpoint to spec-
five orders of magnitude lower than the available correspond- ify the adverse effects of PBT substance and help to identify
ing reference dose (RfD) values (13,000−125,000 ng/kg bw/ those chemicals that should be reduced from large-scale pro-
d) (USEPA 2014). duction (Table 3). Bioaccumulation regulations in the USA,
Several researches have reported ecotoxicological effects European Union, Canada, and Japan set specific criteria to
of OPEs. An overview of toxicological profiles of OPEs in evaluate bioaccumulative chemicals (Table 3). These regula-
fish, Daphnia, and algae is given in Table S5. The acute tions categorize bioaccumulative chemicals based on the
49518 Environ Sci Pollut Res (2021) 28:49507–49528

Table 3. Regulatory bioaccumulation assessment endpoint, criteria, and category (adopted from Arnot and Gobas (2006) and Gobas et al. (2009)

Regulatory body Bioaccumulation endpoint Criteria Category Program

Environment Canada KOW ≥100000 - CEPA 1999a


Environment Canada BCF ≥5000 - CEPA 1999a
Environment Canada BAF ≥5000 - CEPA 1999a
European Union BCF ≥2000 “Bioaccumulative” REACHb
European Union BCF ≥5000 “Very bioaccumulative” REACHb
USA BCF 1000-5000 “Bioaccumulative” TSCA, TRIc
USA BCF ≥5000 “Very bioaccumulative” TSCA, TRIc
UNEPd KOW ≥100000 - Stockholm Convention
UNEPd BCF ≥5000 - Stockholm Convention
a
CEPA Canadian Environmental Protection Act
b
REACH Registration, Evaluation, and Authorisation of Chemicals
c
TSCA Toxic Substances Control Act, TRI Toxic Release Inventory
d
United Nations Environment Program

BCF, BAF, and KOW values. These criteria are often applied rerio) for 19 days and 3 days under a semi-static aqueous
to aquatic biota, mainly fish (Arnot and Gobas 2006; Gobas exposure test. At steady state, the BCF values of OPEs were
et al. 2009). in the range of 0.50–335 L/kg ww, and all congeners showed
Meanwhile, several controlled laboratory-based studies higher accumulation potential at low exposure concentrations.
have assessed bioaccumulation potentials of OPEs in different Among the OPEs, higher BCF were observed for TCP and
fish species and showed that OPEs have the potential to accu- TPP, indicating that these congeners have higher potential to
mulate in aquatic organisms (Table 4). For instance, Wang accumulate in tissues of zebrafish. Arukwe et al. (2018) stud-
et al. (2017b) conducted a bioconcentration study to investi- ied accumulation, toxicological responses, and metabolite for-
gate accumulation and depuration of seven OPEs (TCP, TPrP, mation in juvenile salmon exposed to TCEP and TBEP for 7
TDCP, TCEP, TBEP, TPP, and TBP) in zebrafish (Danio days under exposure concentration ranging from 0.04 to 1 mg/

Table 4. Measured bioconcentration factors (BCFs) of OPEs in different fish species

OPEs Test organisms Exposure concentration (μg/L) Exposure time (days) BCF (L/kg ww) Reference

TCP Adult zebrafish (Danio rerio) 0.8–4.3 19 56–364 Wang et al. (2017b)
TEHP Rare minnow (Gobiocypris rarus) 10 30 19.4–29.3 Hou et al. (2020b)
TDCP Adult zebrafish 4–100 90 10.1–84.1 Wang et al. (2015a)
TDCP Zebrafish (Danio rerio) 0.5–7.5 240 45–66 Yu et al. (2017)
TDCP Juvenile common carp 4.3 28 4.8–35 Tang et al. (2019)
TBEP Juvenile salmon 0.04–1 mg/L 7 0.17–1.77 Arukwe et al. (2018)
TBEP Juvenile common carp 5.4 28 4.8–14.8 Tang et al. (2019)
TPP Rainbow trout (Salmo gairdneri) 50 24 573 Muir et al. (1983)
TPP Flathead minnows (Pimephales promelas) 50 24 561 Muir et al. (1983)
TPP Adult zebrafish 20 19 32–157.4 Wang et al. (2016)
TCEP Juvenile salmon 0.04–1 mg/L 7 0.16–0.34 Arukwe et al. (2018)
TCEP Juvenile common carp (Cyprinus carpio) 9.1 28 1.5–4.2 Tang et al. (2019)
TCPP Juvenile common carp 7.3 28 2.5–5.4 Tang et al. (2019)
TBP Juvenile common carp 5.9 28 1.7–31.4 Tang et al. (2019)
EHDP Juvenile common carp 5.3 28 3.5–65.3 Tang et al. (2019)

a
1 month old
Environ Sci Pollut Res (2021) 28:49507–49528 49519

L. Low BCF values for both TCEP (BCF: 0.16–0.34 L/kg which exceeds the bioaccumulation standard set by POPs con-
fresh weight) and TBEP (BCF: 0.17–1.77 L/kg fresh weight) vention. On the other hand, a study from Beiyun river system,
were reported. At high exposure concentration, the BCF value Beijing, China, reported the bioaccumulation of eight OPEs
of TCEP and TBEP were higher. Hou et al. 2020a, b) studied with average BAF value ranging from 34.5 to 1983 L/kg ww
tissue-specific accumulation and metabolism of TEHP in rare (Hou et al. 2017). The results showed that, except for TEHP,
minnows (Gobiocypris rarus) under static water exposure for the BAF values of screened OPEs were far below the bioac-
30 days. Under 10 μg/L exposure concentration, the BCF cumulation standard of POPs Convention (BAF/BCF ≥ 5000
values were in the range of 19.4–29.3 L/kg ww, in which L/kg, Table 3). Liu et al. (2019a) quantified eight OPE con-
kidney accumulated the highest TEHP. The half-life of geners in fish and invertebrates from freshwater body pond,
TEHP was in the range of 1.03 days in testis and 2.57 days South China. Their average BAF values are in the range of
in muscle. Muir et al. (1983) studied uptake and depuration of 6.6–1109 L/kg ww, which are 1–3 order of magnitude lower
TPP in rainbow trout (Salmo gairdneri) and fathead minnows than the bioaccumulation standard of POPs Convention. In
(Pimephales promelas) using short-term static exposures. The contrast, much higher BAF values (2–50119, 24–31623, 4–
BCF value of TPP was 573 L/kg ww in rainbow trout and 561 2570, and 4–1479 L/kg ww for invertebrates, planktons, ben-
L/kg ww in flathead minnows. thic fish, and pelagic fish, respectively) were found in a food
Like the controlled laboratory studies, bioaccumulation of web from Taihu Lake, China (Wang et al. 2019a), which also
OPEs has also been demonstrated in field-based studies. exceeded the bioaccumulation standard of POPs Convention.
However, the bioaccumulation factor (BAF) values of OPEs Comparatively, very few field-based studies on bioaccu-
in many field aquatic organisms are higher than those simu- mulation potential of OPEs were reported than laboratory-
lated experimental studies (Table 5). For instance, Choo et al. based studies. In most controlled laboratory studies, the expo-
(2018) reported the bioaccumulation potential of OPEs in a sure time is short, there is difficulty of reaching equilibrium,
field study on Crucian carp (Carassius auratus) from the the exposure pathway is limited (mostly consider absorption
Nakdong River, South Korea; BAFs of 2440–71000 L/kg of OPEs in gills, which ignored dietary intake), and usually,
ww, 5900–140000 L/kg ww, and 1970–59900 L/kg ww were data are obtained from the fitted BCF kinetics. In contrast, in
measured in muscle, liver, and gonad tissues, respectively, the actual aquatic environment, the above limitations (factors)

Table 5. Bioaccumulation factors (BAF) of OPEs in aquatic organisms from different regions.

Region OPEs Aquatic organisms Average BAF (L/kg ww) Reference

Nakdong River, South Korea TEP Crucian carp (Carassius auratus) 44700 Choo et al.
TBP Crucian carp 140000 (2018)
TCEPCrucian carp 14100
TCPPCrucian carp 5900
TBEPCrucian carp 21100
Beiyun river system, Beijing, TPP Topmouth gudgeon (Pseudorasbora parva), 1008 Hou et al. (2017)
China TEHP loach (Misgurnus anguillicaudatus) and Crucian carp 1983
Freshwater body pond, South TPP Oriental river prawn (Macrobrachium nipponense), 898 Liu et al. (2019a)
China TEHP crucian carp, mud carp (Cirrhinus molitorella), 1109
TCP catfish (Clarias batrachus), and snakehead (Ophiocephalus 906
argus)
Zhushan Bay of Taihu Lake, TEHP Phytoplankton, zooplankton, invertebrates, pelagic fishes, 31623a Wang et al.
China TMP benthic fishes 10471a (2019a)
EHDP 19055a
TPP 513a
Laizhou Bay, North China TPeP Invertebrates, pelagic fishes, benthic fishes 5350a Bekele et al.
THP 12358a (2019)
TPP 5097a
EHDP 5134a
TEHP 35768a
TCP 15529a
CDPP 26147a
a
Maximum measured values.
49520 Environ Sci Pollut Res (2021) 28:49507–49528

are insignificant, and the measured BAF values are thermody- mechanisms from aqueous phase to biological phase are com-
namic BAF. These differences might be the reasons for having parable with distribution between octanol and water. Thus, the
different accumulation patterns in controlled laboratory-based octanol–water partition coefficient (KOW) can be used to ex-
studies and field-based studies; hence, the accumulation plain the distribution capacity of organic pollutants between
pattern and mechanism warrant further attention. aqueous and biological phases, which is related to solubility,
Relatively very limited studies have examined OPEs in biological enrichment, and toxicity. In addition, KOW is usu-
aquatic food web and reported their trophic transfer and ally used to identify and evaluate bioaccumulative substances
biomagnification potentials. For example, Wang et al. of hydrophobic organic pollutants in aquatic organisms along
(2019a) documented bioavailability and biomagnification of with BCFs and BAFs by different regulatory authorities
OPEs in a food web (mainly composed of plankton, inverte- (Kelly et al. 2007). Different laboratory and field-based stud-
brates, and fish) in the Zhushan Bay of Taihu Lake, China, ies show that bioaccumulation and biomagnification potential
and explored their trophic transfer potentials. The highest tro- of organic pollutants in tissues of aquatic organisms have
phic magnification factor (TMF) value (TMF = 3.61) was good correlations with KOW (Fisk et al. 1998; Kelly et al.
calculated for TEHP, which was because of lower metabolic 2007; Greaves et al. 2016; Bekele et al. 2018, 2019, 2021;
potential in high trophic level (TL) fish and its relatively high Liu et al. 2018a). As a result, regulatory bodies classify
logKOW value. Another study was conducted to explore the bioaccumulative chemicals as hydrophobic, usually fat-
biomagnification potential of OPEs in a benthic food web of soluble substance having high KOW (≥100,000) (Kelly et al.
the Western Scheldt estuary, The Netherlands (Brandsma 2007). Generally, it is believed that those organic pollutants
et al. 2015). The results showed that three OPE congeners with higher KOW are strongly hydrophobic, and they are ex-
undergo trophic magnification, with TMF values of 2.2, 2.6, pected to have high BCF/BAF values, which could result in
and 3.5 for TCPP, TCEP, and TBEP, respectively. Similarly, the greater bioaccumulation/biomagnification capacity (Fisk
in a study that evaluated the bioaccumulation and et al. 1998; Kelly et al. 2007). However, some substances with
biomagnification potential of 20 OPEs in a marine food web KOW ≥100,000 have less or no bioaccumulative potential than
of the Laizhou Bay, North China, a BAF of > 5000 L/kg ww estimated, mainly because of rapid biotransformation
(benchmark value for bioaccumulative substance) were re- (Weisbrod et al. 2007).
ported for seven congeners (Bekele et al. 2019). In addition, For most hydrophobic organic pollutants, bioaccumulation
a TMF > 1 were reported for Cl alkyl-OPEs (1.17−1.84), non- is viewed as a physical-chemical partitioning process between
Cl alkyl-OPEs (1.06−2.52), and aryl-OPEs (1.75−2.03), the organism body water and body fat. In the absence of suf-
which shows the potential of OPEs to biomagnify in aquatic ficient excretion or metabolism, hydrophobic organic pollut-
food web (Bekele et al. 2019). In contrast, much lower TMF ants, once absorbed, are more easily distributed into the lipid
values of 0.39, 0.42, and 0.55 for TDCP, TMP, and TCPP, phase of the cells because of their high affinity for lipid than to
respectively, were reported in a study that detects nine OPEs water and accumulate in organism (Gobas et al. 1986). On the
from food web of Taihu Lake, China (Zhao et al. 2018). These other hand, hydrophilic chemicals are more likely to be
differences observed in TMFs among studies could be the discharged in vitro. As a result, the bioaccumulation potential
difference in ecosystem characteristics that determine the tro- of hydrophobic organic pollutants is greater than those of
phic transfer behavior of OPEs and, subsequently, the degree hydrophilic organic pollutants. OPEs have positive logKOW
of biomagnification. The difference in ecosystem characteris- (range 0.8–10.6), most of the congeners had high/extremely
tics can be explained by main distinct differences in species hydrophobic (logKOW > 4) properties, and certain compounds
composition; habitat condition, food chain length, pollution may present high bioaccumulative potential. Additionally,
level, biotransformation of OPEs in biota, and other environ- molecular weight of a compound could affect assimilation
mental factors could play a major role in the reported incon- efficiency, that is if the compounds with too large molecular
sistencies (Borga et al. 2013; Sun et al. 2015, 2017; Walters weight tend to be absorbed by the intestinal mucosa of aquatic
et al. 2016). Several studies indicated that bioaccumulation/ organisms, eventually, biological amplification may not oc-
biomagnification potential of OPEs and their trophic transfer cur. On top of that, as the compound molecular mass in-
behavior is mainly governed by physicochemical properties, creases, the solubility decreases (Mackintosh et al. 2004; van
biotransformation, and lipid content; these factors are der Veen and de Boer 2012).
discussed in detail.
Biotransformation
Physicochemical factors
Apart from physicochemical factors, metabolism is an impor-
Physicochemical properties are vital in determining the degree tant biological factor that controls the degree of
of bioaccumulation or biomagnification potentials of organic biomagnification potential of pollutants in aquatic organisms.
pollutants in aquatic organisms. Organic matter enrichment It can eliminate or reduce the expected bioaccumulation or
Environ Sci Pollut Res (2021) 28:49507–49528 49521

biomagnification potential if the metabolic transformation rate 2011; Bekele et al. 2019, 2021). These studies documented a
is sufficiently high (Kelly et al. 2007). Recent studies have linear and significant relationship between the levels OPEs in
reported the metabolic transformation of OPEs in vitro cells or tissues of organisms and their extractable lipid content,
microsomes; only few studies have shown the metabolic indicating that lipid content is among the main factors that
transformation of OPEs in vivo. However, the whole metabol- govern accumulation of OPEs in aquatic organisms. Kim
ic transformation pathways are yet not fully developed. et al. (2011) reported a significant and positive correlation
Recently, Wang et al. (2017a) reported metabolic transforma- between lipid contents and the level of TPeP and TEP.
tion of six OPEs (TBEP, TPrP, TBP, TCEP, TDCP, and TCP) Bekele et al. (2019) also reported a linear and significant in-
in adult zebrafish in a laboratory; the major metabolites were crease in Σ17OPEs concentrations (ng/g dw) with an increase
organophosphate diester, hydroxylated organophosphate dies- in the extractable lipid content. In addition, Wang et al.
ter, hydroxylated organophosphate triesters, and glucuronic (2017b) showed significant and positive correlation between
acid conjugated metabolites after hydroxylation. BCF of OPEs (TBP, TDCP, EHDP, and TPP) and lipid con-
Van den Eede et al. (2015) reported hydroxylated metabo- tents. However, no correlation was observed between lipid
lites in liver of zebrafish, and the oxidation of organophos- contents and BCF of TCPP, and TCEP. Kim et al. (2011) also
phates occurred in the body of fish that may be catalyzed by showed similar observations, where most OPE concentration
the enzyme cytochrome P450 (CYPs). Van Den Eede et al. do not depend on lipid content. Meanwhile, Wang et al.
(2013) also showed further transformation of hydroxylated (2016) demonstrated an increase in TPP-d15 concentration in
metabolites in zebrafish to their sulfuric acid conjugates or the liver, muscle, and brain of zebrafish with the in-
glucuronic acid catalyzed by sulfotransferases (SULTs) or crease in lipid contents. Therefore, lipid (particularly
glucuronyl transferases (UGTs). In another recent experimen- phospholipids) might play a vital role in the accumula-
tal study, Hou et al. (2020) investigated the metabolites of tion of OPEs in aquatic organisms.
TEHP in rare minnow (Gobiocypris rarus); TEHP was oxi- Apart from the three factors discussed above, other biolog-
datively metabolized to di 2-ethylhexyl phosphate (DEHP) or ical factors mainly breeding season, sex, feeding habit, body
dealkylated metabolite and hydroxylated TEHP (OH-TEHP). size, body weight, developmental stage, growth rate, habitat,
Further, OH-TEHP transformed into phase II and yield glucu- selective excretion abilities, and trophic level of species are
ronic acid conjugates. Some of the transformed metabolites important factors that may affect bioaccumulation and
are similar to the metabolites reported in human liver micro- biomagnification of OPEs in aquatic organisms (Brandsma
somes via in vitro cell experiments (Arukwe et al. 2018). In et al. 2015; Hou et al. 2016; Kim et al. 2011). Due to these
general, OPEs can be metabolized through phase-I and phase- factors, the accumulation potential of OPEs is different among
II biotransformation to metabolites. Hou et al. (2016) summa- species and individuals. For example, Sundkvist et al. (2010)
rized and proposed the general metabolic pathways for each reported that total OPE concentrations in small perch were
group of OPEs (halogenated alkyl-OPEs, non-halogenated al- lower than in large perch. This indicates that larger fishes
kyl-OPEs, and aryl-OPEs). could accumulate more OPEs. In a controlled laboratory
study, Wang et al. (2015b) showed that concentration of
Lipid TDCP in male zebrafish were lower than females after expo-
sure to similar concentration and period, indicating sex-
Lipids are the major components for the accumulation of organic dependent bioaccumulation of OPEs.
pollutants in organisms. Measured chemical levels in biota sam-
ples are usually normalized to the total lipid content of the biota to
estimate the degree of bioaccumulation (Endo et al. 2011). Conclusions and perspectives
Accordingly, concentration proportion of chemicals in biota to
different environmental phases (e.g., BCF, BAF, BSAF) are fre- In this study, we made a comprehensive review on production/
quently calculated based on the concentrations in biota, which are usage, biological sample treatment and analysis, environmental
normalized to total lipid content. occurrences, toxicity, human exposure, and the bioaccumulation
Organic chemical distribution in tissues is mainly governed potential of OPEs. Consumptions of OPEs in different regions
by passive diffusion to the lipid compartment. Several studies including China, Japan, and Western Europe and global usage
reported that OPE concentration had a significant correlation have been summarized in this review; however, the production,
with lipid content. Recent controlled laboratory-based studies use, and environmental levels of OPEs in Oceania, South
showed that lipid contents played a significant role in the America, and Africa are poorly documented. These data will assist
bioaccumulation potential of OPEs (Wang et al. 2016, future studies on OPEs in this region and will provide insight into
2017b; Bekele et al. 2018). Similarly, field-based studies also the global production and consumption trends of OPEs.
indicated a significant effect of lipid contents on the degree of Meanwhile, limited extraction methods of OPEs from biological
OPE accumulation in tissues of aquatic organisms (Kim et al. samples have been developed; ASE, UAE, MAE, and Soxhlet are
49522 Environ Sci Pollut Res (2021) 28:49507–49528

the common techniques. ASE has been successfully implemented RGC: Data curation, investigation, and writing—reviewing and editing.
JC: Project administration, resources, validation, and supervision.
and expected to be increasingly used because of its high degree
SM: Writing—reviewing and editing.
automation and advantages. To reduce matrix interferences and AQ: Writing—reviewing and editing.
lipid contents of biological samples, SPE, dSPE, and GPC tech- All authors read and approved the final manuscript.
niques are preferred for the clean-up of biota samples for OPE
analysis. Mainly GC–MS, GC–MS/MS, and LC-MS/MS have Funding This work was financially supported by the Arba Minch
University, Ethiopia (GOV/AMU/TH4/COA/NaRM/01/2010), the
been used in analyzing OPEs in biota samples. LC-MS/MS-based
National Science Foundation of Liaoning Province (Grant 2019-MS-
analysis is more advantageous than GC-MS techniques in its 057), and the Petro China Innovation Foundation (2019D-5007-0502).
higher selectivity and suitability for OPEs which are less volatile;
however, the high lipid proportion and matrix interference of biota Data availability Not applicable.
samples remains challenging when analyzing OPEs. Hence, there
is a need for robust extraction and clean-up method for the quan- Declarations
tification of OPEs and their metabolites in a biological sample.
Due to their extensive uses and weak chemical bonding to the Ethics approval and consent to participate Not applicable.
substrate material, OPEs are easily released to various environ-
mental compartments during production and usage. As a result, Consent for publication Not applicable.
OPEs have been reported in various matrices and become ubiqui-
Competing interests The authors declare no competing interests.
tous. The residual levels of OPEs in surface and drinking water,
sediment, and aquatic organisms have been summarized in this
review. Relatively limited data are documented on the contamina-
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