Environmental Pollution 281 (2021) 116950

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Environmental Pollution
journal homepage: www.elsevier.com/locate/envpol

Review

Occurrence, influencing factors, toxicity, regulations, and abatement

approaches for disinfection by-products in chlorinated drinking
water: A comprehensive review
Sundas Kali a, Marina Khan a, Muhammad Sheraz Ghaffar a, Sajida Rasheed b,
Amir Waseem c, Muhammad Mazhar Iqbal d, e, Muhammad Bilal khan Niazi f,
Mazhar Iqbal Zafar a, *
a
Department of Environmental Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan
b
Department of Biotechnology, Faculty of Sciences, University of Kotli, Azad Jamu Kashmir, Pakistan
c
Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan
d
Laboratory of Analytical Chemistry and Applied Eco-chemistry, Department of Applied Analytical and Physical Chemistry, Ghent University, Ghent,
Belgium
e
Soil and Water Testing Laboratory, Department of Agriculture, Chiniot, Government of Punjab, Pakistan
f
Department of Chemical Engineering, National University of Sciences and Technology, Islamabad, Pakistan

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

Article history: Disinfection is considered as a vital step to ensure the supply of clean and safe drinking water. Various
Received 24 December 2020 approaches are adopted for this purpose; however, chlorination is highly preferred all over the world.
Received in revised form This method is opted owing to its several advantages. However, it leads to the formation of certain by-
9 March 2021
products. These chlorination disinfection by-products (DBPs) are genotoxic, carcinogenic and mutagenic.
Accepted 12 March 2021
Still chlorination is being practiced worldwide. Present review gives insights into the occurrence, toxicity
Available online 17 March 2021
and factors affecting the formation of regulated (THMs, HAAs) and emerging DBPs (N-DBPs, HKs, HAs and
aromatic DBPs) found in drinking water. Furthermore, remediation techniques used to control DBPs have
Keywords:
Chlorination
also been summarized here. Key findings are: (i) concentration of regulated DBPs surpassed the
Drinking water permissible limit in most of the regions, (ii) high chlorine dose, high NOM, more reaction time (up to 3 h)
Disinfection by-products and high temperature (up to 30
C) enhance the formation of THMs and HAAs, (iii) high pH favors the
Occurrence formation of THMs while low pH is suitable of the formation of HAAs, (iv) high NOM, low temperature,
Influencing factors low chlorine dose and moderate pH favors the formation of unstable DBPs (N-DBPs, HKs and HAs), (v)
Toxicity DBPs are toxic not only for humans but for aquatic fauna as well, (vi) membrane technologies, enhanced
Abatement approaches coagulation and AOPs remove NOM, (vii) adsorption, air stripping and other physical and chemical
methods are post-formation approaches (viii) step-wise chlorination is assumed to be an efficient
method to reduce DBPs formation without any treatment. Toxicity data revealed that N-DBPs are found
to be more toxic than C-DBPs and aromatic DBPs than aliphatic DBPs. In majority of the studies, merely
THMs and HAAs have been studied and USEPA has regulated just these two groups. Future studies should
focus on emerging DBPs and provide information regarding their regulation.
© 2021 Elsevier Ltd. All rights reserved.

1. Introduction

Disinfection is a crucial step for the treatment of water for public

supply (How et al., 2017). Several factors like population explosion,
* Corresponding author. climate change, industrialization and agriculture have posed
E-mail addresses: sundaschoudhary93@gmail.com (S. Kali), considerable stress on water resources (Du et al., 2017; Sun et al.,
marinakhanktk1996@gmail.com (M. Khan), sherazkhan5505@gmail.com
2016). Such activities have increased the demand of fresh water
(M.S. Ghaffar), rsajida142@gmail.com (S. Rasheed), amir@qau.edu.pk
(A. Waseem), mazhar1621@gmail.com (M.M. Iqbal), M.b.k.niazi@scme.nust.edu.pk and discharge of wastewater into the environment hence polluting
(M. Bilal khan Niazi), mzafar@qau.edu.pk (M.I. Zafar). the clean water resources (Da Costa et al., 2014; Sun et al., 2016).

https://doi.org/10.1016/j.envpol.2021.116950
0269-7491/© 2021 Elsevier Ltd. All rights reserved.
S. Kali, M. Khan, M.S. Ghaffar et al.
List of abbreviations
DBPs Disinfection by-products
THMs Trihalomethanes
HAAs Haloacetic acids
N-DBPs Nitrogenous disinfection by-products
HANs Haloacetonitriles
HKs Haloketones
HAs Haloaldehydes
C-DBPs Carbonaceous disinfection byproducts
HPANs Halophenylacetonitriles
HNPs Halonitrophenols
HPs Halophenols
HBADs Halobenzaldehyde
HBACs Halohydroxybenzoic acids
HBQs Halobenzoquinones
NOM Natural organic matter
HOCl Hypochlorus acid
OCl Hypochlorite ion
According to World Health Organization (WHO), unsafe drinking
water is responsible for nearly 80% of human diseases in developing
countries (Sulehria et al., 2013). In Pakistan, approximately 80% of
whole population has to rely on poor quality drinking water due to
the scarcity of safe drinking water resources (Daud et al., 2017).
Moreover, 30% of all diseases and 40% of all deaths in Pakistan
occurred on account of unsafe drinking water (Nabeela et al., 2014).
Literature reported that about 0.6e1.44% of country’s Gross Do-
mestic Product (GDP) loss is associated with water borne diseases
(Khwaja and Aslam, 2018; Tahir et al., 2010). Pakistan ranked 80th
from 122 countries with respect to drinking water quality (Hisam
et al., 2014) as its 70% of surface and subsurface water is unsafe
for drinking (Abbas et al., 2014; Baig et al., 2011). Therefore,
reclaimed water is a useful alternative for socio-economic benefits.
Due to the presence of pathogens, reclaimed water needs to be
disinfected before its use for drinking purpose, agriculture, ground
water recharge or discharge is water bodies (Du et al., 2017; Li et al.,
2013).
Various methods are employed for water disinfection against
various pathogens; bacteria, viruses, protozoa and fungi (Ding et al.,
2019; Da Costa et al., 2014) such as; chlorine (Scarlet et al., 2016;
Pardakhti et al., 2011), chloramine (How et al., 2017; Moradi et al.,
2017), chlorine dioxide (Van Haute et al., 2017; Scarlet et al.,
2016), peracetic acid (Da Costa et al., 2014), ozone (Ding et al.,
2019; Zheng et al., 2017) and ultra-violet (UV) radiations (Zheng
et al., 2017; Scarlet et al., 2016).
Chlorination is a traditional and highly preferred method due to
its simple operation, effective oxidizing potential, and above all,
cost effectiveness (Chowdhury et al., 2012; Pardakhti et al., 2011;
Karim et al., 2011). It is the only trusted mechanism that developing
countries can count to disinfect water (Mahmood, 2015). According
to the WHO, residual chlorine levels should be kept equal or higher
than 0.5 mg L1 after contact time of 30 min at pH below 8 and
temperature 20ᵒC (Mahmood, 2015). It is critical to maintain
appropriate dosing amount of chlorine in order to provide enough
residual chlorine during storage and utilization. Suggestions are to
dose clear water (<10 nephelometric turbidity units [NTU]) with
free chlorine at approximately 2 mg L1 and twice (4 mg L1) to
turbid water (>10 NTU). Even though these free chlorine dosages
may leash to chlorine residues that goes beyond the recommended
chlorine residual for water which is centrally dosed at the point of
delivery, 0.2_0.5 mg L1, these doses are considered appropriate for
2
Environmental Pollution 281 (2021) 116950
HOBr Hypobroumous acid
HOI Hypoiodous acid
GI Galvanized iron
SS Stainless steel
GS Galvanized steel
HDPE High density polyethylene
PVC Polyvinyl chloride
PP Polypropylene
PE Polyethylene
DI Ductile iron
CHO Chinese hamster ovary
AOPs Advanced oxidation processes
GAC Granular activated carbon
USEPA US Environmental Protection Agency
WHO World Health Organization
IARC International Agency for Research on Cancer
GDP Gross domestic production
NTU Nephelometric turbidity unit
maintaining a free chlorine residual of 0.2 mg L1 in stored
household water treatment by chlorination (WHO, 2017).
Gaseous chlorine, sodium hypochlorite and calcium hypochlo-
rite are used for chlorination purposes (see Table 1). Hydrolysis of
these disinfectants produces hypochlorous acid (HOCl) and hypo-
chlorite ion (OCl) which are defined as free chlorine (Yang et al.,
2011). In addition to these, monochloramine (NH2Cl) and dichlor-
amine (NHCl2) are also found which is called combined chlorine.
However, several factors like pH, temperature etc. affect the
dominant form of chlorine which ultimately describes the disin-
fection process (Voukkali and Zorpas, 2015). The concentrations of
hypochlorous acid and the hypochlorite ion are approximately
equal at pH 7.5 and 25
C (De la Guardia and Garrigues, 2015).
Advantage of using chlorine is that it removes almost all kinds of
pathogens, additionally, residual chlorine also prevents microbial
recontamination in water supply systems (Hassan et al., 2010).
Nevertheless, the emergence of carcinogenic, mutagenic and gen-
otoxic disinfectant by products (DBPs) along with residual chlorine
is the major drawback of this technique (How et al., 2017; Da Costa
et al., 2014). When chlorine reacts with organic matter content,
bromine and other contaminants present in water, it oxidizes them
and produces DBPs (Abbas et al., 2014). Generally, surface waters
contain elevated concentrations of DBPs than ground water
because of the greater concentrations of organic material (Abbas
et al., 2014; Nieuwenhuijsen et al., 2000). Researchers have
blown the whistle on the presence of DBPs in disinfected drinking
water. Currently, more than 700 DBPs have been reported in dis-
infected water (Plewa et al., 2017)and many of them are reported as
carcinogenic, mutagenic, teratogenic, cytotoxic, and genotoxic,
(Benson et al., 2017). Well known classes of aliphatic DBPs include;
trihalomethanes (THMs), haloacetic acids (HAAs), haloketones
(HKs), haloaldehydes (HAs), and nitrogenous DBPs (N-DBPs) such
as haloacetonitriles (HANs), halonitromethanes (HNMs) and hal-
oacetamides (HAcAms) (Benson et al., 2017; Bond et al., 2011).
However, aromatic DBPs have also become an area of interest in the
field of DBPs research which include phenolic and heterocyclic
aromatic DBPs (Fig. 1).
The objective of the present review is to analyze the outcomes of
various studies and summarize the occurrence, influencing factors,
toxicity, regulations and remediation techniques for important
halogenated aliphatic and aromatic DBPs formed by the chlorina-
tion of surface and ground water. Moreover, the concentrations of
S. Kali, M. Khan, M.S. Ghaffar et al.
Table 1
Disinfectant and their by-products formation in drinking Water (WHO, 2017).
Disinfectant DBPs
Organohalogen Products
Chlorine (Sodium hypochlorite, Calcium THMs, HAAs, HANs, HKs, HAs, N-chloramines, Chlorophenols, Chloropicrin, Chloral hydrates, Chlorate
hypochlorite) Halo furanones, Bromohydrins
Chlorine dioxide
Fig. 1. Classification of DBPs reviewed in present study (shaded area shows that few
classes of C-DBPs are regulated while rest of them are unregulated).
these DBPs in various regions of the world have also been critically
analyzed with respect to the international regulations.
2. Methodology
A comprehensive literature review was performed for infor-
mation regarding DBPs and findings have been summarized here.
Databases like Science Direct and Google Scholar were used for
literature hunting. Articles were searched using key words like
“disinfection methods”, “chlorination”, “drinking water distribu-
tion systems”, “disinfection by-products in chlorinated drinking
water”, “natural organic matter” “regulations of DBPs”, “factors
affecting the formation of DBPs”, “trihalomethanes”, “haloacetic
acids”, “haloacetonitriles”, “haloketones”, “haloaldehydes”, “hal-
onitromethanes”, “halocacetamides”, “aromatic DBPs”, “heterocy-
clic DBPs”, “phenyl DBPs”, N-DBPs”, “C-DBPs”, “remediation of
aliphatic and aromatic DBPs”, “control of DBPs”, “pipe material and
DBPs formation”, “toxicity of DBPs”, “health impacts”, “DBPs in
municipal drinking water” etc. Gathered research articles were
screened out and 86 studies which reported: (i) various disinfection
techniques, (ii) chlorination conditions, (iii) the levels of DBPs in
drinking water, (iv) toxicity of DBPs, (v) effect of NOM and other
factors on DBPs formation, and (vi) abatement technologies for
NOM and DBPs removal, were selected. Further, websites of United
States Environmental Protection Agency (US-EPA), WHO and
Council of European Union and International Agency for Research
on Cancer (IARC) were consulted for DBPs related information.
3
Environmental Pollution 281 (2021) 116950
Inorganic Non-halogenated
Products Products
Aldehydes,
Carboxylic acids,
Benzene,
Alkanoic acid,
Cyano alkanoic acid
Chlorite, Unknown
Chlorate
3. Occurrence of DBPs in drinking water
Highly volatile THMs is the major group of DBPs followed by
non-volatile halo acetic acids (HAAs), occurring generally at around
half the concentrations of THMs (Nieuwenhuijsen et al., 2000).
Both THMs and HAAs constitute about 25% of the total DBPs (Yang
et al., 2011). The chlorine atom in hypochlorous acid act as an
electrophile, that causes electrophilic substitution (i.e. halogen
substitution) for organic compounds (Jiang et al., 2020). Further,
aromatic DBPs are also formed by the reaction of disinfectant with
organic matter. They are highly unstable compounds which
degrade into THMs and HAAs (Hu et al., 2019). Similarly, N-DBPs,
HKs and HAs also decompose into relatively stable DBPs. World-
wide reported concentrations of DBPs in drinking water has been
presented in Table 2.
3.1. Aliphatic DBPs
Among aliphatic DBPs, THMs, HAAs, N-DBPs, HKs and HAs are
commonly found in chlorinated drinking water (Table 3).
3.1.1. Trihalomethanes
THMs is the most prevalent group among DBPs. They are formed
by the reaction of chloramine and chlorine with the inorganic
species and organic matter in water (Benson et al., 2017). These are
skin permeable and highly volatile compounds. THM4 includes four
compounds (i) chloroform (CF) (ii) bromoform (BF) (iii) bromodi-
chloromethane (BDCM) and (iv) dibromochloromethane (DBCM)
(see Table 3), which have been regulated by EU (100mgL1), US
(80mgL1), and some other countries (Villanueva et al., 2016; Abbas
et al., 2014). They possess different physiochemical and toxicolog-
ical properties. Among these, chloroform is highly volatile, while
rest of the brominated THMs are more lipophilic (Villanueva et al.,
2016). They are not mutagenic but have carcinogenic and other
severe toxic effects in humans (Villanueva et al., 2015; Abbas et al.,
2014). THMs are produced during the hydrolysis reaction of un-
stable DBPs (Hong et al., 2013).
3.1.2. Haloacetic acids
HAAs include monochloroacetic acid (MCAA), dichloroacetic
acid (DCAA), trichloroacetic acid (TCAA), monobromoacetic acid
(MBAA), dibromoacetic acid (DBAA), tribromoacetic acid (TBAA),
bromochloroacetic acid (BCAA), bromodichloroacetic acid (BDCAA)
and dibromochloroacetic acid (DBCAA) (Tian et al., 2017). Among
these, first five (HAA5) are more common and produced by the
chlorination of drinking water (Benson et al., 2017; Richardson and
Postigo, 2011). These compounds are known to cause bladder
S. Kali, M. Khan, M.S. Ghaffar et al. Environmental Pollution 281 (2021) 116950

Table 2
Levels of DBPs reported in drinking water of various countries.

Country Source Water THMs (4) HAAs (5) HANs(4) HKs HAs HNMs HAcAms HBADs HBACs HNPs CPANs References
Name
mg L1 ng L1

Hungary Treatment plants 0.138e458 0.16e136 Srivastav et al. (2020)

South China DWTP 2.8 1e9.8 2.9 Zhang et al. (2020)
e6.1 e8.3
Croatia DWDS 0.7e32.8 LOQ e 17.2 Kurajica et al. (2020)
Iran Surface water 92.9 ± 43.7a 70.6 ± 26.5a Dobaradaran et al. (2020)
Spain WTP 15.9e55.2 N.D. e 0.98 Dominguez-Tello et al.
3.5 e1.02 (2020)
Hungary DWTPs 14.2e143 5.2e129 <1.0e17
n et al. (2019)
Stefa
China DWTPs 0.6 Zhang et al. (2019)
e155
China WTPs 3.26e69.28 3.48e82.18 0.83 0.33 Yu et al. (2019)
e26.85 e14.28
India Sea water 38.3a 9.8 Padhi et al. (2019)
River Water 18.8a 12.8
Reservior 21.5a 20.6
Thailand WDNS 584a 30b Ratpukdi et al. (2019)
China DWTPs 170 Zhang et al. (2018)
e530
China Surface water 35e228.4 188e394.5 2.98 1.03 Hao et al. (2017)
e85.5 e17.9
China Surface water 1.12e8.20 Niu et al. (2017)
Saudi Arabia Desalinated Water 0.1e33.6 Chowdhury and Chowdhury
Blended Water 2.1e52.4 (2017)
Bahrain Desalinated Water 0.27e6.4
Kuwait Desalinated Water 7.11
e104.89
Qatar Desalinated Water 4.02e83.31
UAE Desalinated Water 7.0e15.0
China Yuqiao reservoir 79.4e136.9 133.2 8.2e9.3 Zhai et al. (2017)
e250.9
Nigeria Raw water 0 Benson et al. (2017)
Primary water 21.92
e999.64
Secondary water 26.89
e960.68
China Water distribution 10e30 N.D. e N.D. e 0.1 Huang et al. (2017)
systems 6.4 5.5 e11.4
Qatar Reservoirs 0e85 Al-Otoum et al. (2016)
Desalination plant 0e84
Consumer taps 0e89
China DWTPs 100 Mao et al. (2016)
e150
Cyprus Surface water 21.23e57.3 Ioannou et al. (2016)
Surface water 8.72e86.2
a a
United Disinfected water 2.8* 0.2 1.3 Bond et al. (2015)
Kingdom Final water 2.6a 0.2a 1a
Distribution samples 2.8a 0.2a 1.4a
Pakistan Surface water 24.42 Abbas et al., 2015
e595.86
Groundwater 189.97
e431.26
a
Average value; bmaximum value
N.D. (not defined); DWTP: Drinking water treatment plant; WTP: Wastewater treatment plant.
DWDS: Drinking water distribution system; WDNS: Water distribution network system.

cancer and other adverse reproductive anomalies. Therefore, US
EPA has set the maximum contamination level of HAA5 at 60 mgL1
(Tian et al., 2017). Natural organic matter is responsible for 80% of
HAAs formation, while rest of HAAs are formed by the reaction of
intermediate DBPs with chlorine (Bougeard et al., 2010).
3.1.3. Other aliphatic DBPs
HANs, HNMs, HacAms, HKs and HAs are unstable DBPs. They are
formed in almost all chlorinated water, but for short time. They are
also known as intermediate DBPs as they get hydrolyzed at higher
pH and temperature (Hong et al., 2013; Fang et al., 2010). Details of
these compounds have been presented in Table 3. Among HANs,
4
only 4 compounds are found in drinking water which include
dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), bromo-
chloroaceontrile (BCAN) and dibromoacetonitrile (DBAN) (Hang
et al., 2016). However, little is known about the presence of HAs in
drinking water (Mao et al., 2016; Jeong et al., 2015).
These intermediate DBPs are usually present in lower amounts
than THMs and HAAs. These compounds are usually produced
instantly during water disinfection but are decomposed rapidly
during reactions with residual disinfectants or hydrolysis reactions

n et al., 2019). Presence of ammonia in water favors the for-
(Stefa
mation of N-DBPs (Ding et al., 2018). Nevertheless, HKs and HAs are
formed by the reaction of chlorine with NOM. It has been reported
S. Kali, M. Khan, M.S. Ghaffar et al. Environmental Pollution 281 (2021) 116950

Table 3
Toxicity summary of aliphatic DBPs.

Group Name Compound names *LC50 mol General Toxicity References

L1
Regulated Aliphatic DBPs
THMs (4) Chloroform 9.62  103 Carcinogenic, Cytotoxic, Genotoxic, Reproductive anomalies, Birth Ewaid et al. (2018); Stalter et al.
Chlorodibromomethane 5.36  103 defects, Kidney and liver damage, Nervous system damage (2020); Wagner and Plewa (2017)
Bromodichloromethane 1.15  102
Bromoform 3.96  103
HAA (5) Monochloroacetic Acid 8.10  104 Carcinogenic, Reproductive anomalies, Growth retardation, Genotoxic, Mompremier et al. (2019); Stalter
Dichloroacetic Acid 7.3  103 Cytotoxic, Spleen, liver and kidney damage et al. (2020); Plewa et al. (2010)
Trichloroacetic Acid 2.4  103
Monobromoacetic acid 9.60  106
Dibromoacetic acid 5.9  104
Unregulated Aliphatic DBPs
HANs Chloroacetonitrile 6.83  105 Carcinogenic, Mutagenic, Clastogenic, Liver damage Postigo et al., 2018; Zhang et al.
Dichloroacetonitrile 5.73  105 (2017); Muellner et al. (2007)
Trichloroacetonitrile 1.60  104
Bromochloracetonitrile 8.46  106
Bromoacetonitrile 3.21  106
Dibromoacetonitrile 2.85  106
Iodoacetonitrile 3.3.  106
HNMs Bromonitromethane 7.06  10⁻6 DNA damage, cytotoxic, mutagenic, oxidative stress Dominguez-Tello et al. (2020); Yin
Chloronitromethane 5.29  10⁻4 et al. (2018); Plewa et al. (2004)
Dibromochloronitromethane 6088  10⁻6
Dichloronitromethane 3.73  10⁻4
Dibromonitromethane 6.09  10⁻6
Bromochloronitromethane 4.05  10⁻5
Bromodichloronitromethane 1.32  10⁻5
Trichloronitromethane 5.36  10⁻4
Tribromonitromethane 8057  10⁻6
HAcAms Chloroacetamide 1.48  10⁻4 Cytotoxic, Genotoxic, developmental toxicity Chu et al. (2012)
Dichloroacetamide 1.92  10⁻3 Plewa et al. (2008); Ding et al. (2020)
Trichloroacetamide 2.05  10⁻3
Bromoacetamide 1.89  10⁻6
Dibromoacetamide 1.22  10⁻5
Tribromoacetamide 3.14  10⁻6
Bromochloroacetamide 1.71  10⁻6
Bromodichloroacetamide 8.68  10⁻6
Dibromochloroacetamide 4.75  10⁻6
Iodoacetamide 1.42  10⁻6
Diiodoacetamide 6.78  10⁻7
Chloroiodoacetamide 5.97  10⁻6
Bromoiodoacetamide 3.81  10⁻6
HKs 1,1-dichloro-propanone e Mutagenic, Oxidative stress Li et al. (2020); Stalter et al. (2020)
1,1,1-trichloro-propanone e
HAs Chloroacetaldehyde 3.51  10⁻6 Mutagenic, Nephrotoxic, Cytotoxic, Chaves et al. (2019); Jeong (2014)
Bromoacetaldehyde 1.728  10⁻5
Dichloroacetaldehyde 2.925  10⁻5
Bromochloroacetaldehyde 5.34  10⁻6
Dibromoacetaldehyde 4.7  10⁻6
Chloral hydrate 1.163  10⁻3
Dibromochloroacetaldehyde 5.15  10⁻6
Bromodichloroacetaldehyde 2.035  10⁻5
Iodoacetaldehyde 6  10⁻6
Tribromoacetaldehyde 3.58  10⁻6

*LC50 values included that induced a cell density of 50% as compared to the concurrent negative controls by Chinese hamster ovary cells bioassay with the exposure time of 72
hours.
THMs: trihalomethanes; HAAs: Haloacetic acids; HANs: Haloacetonitriles; HNMs:Halonitromethanes.
HAcAms: Haloacetamides; HKs:Haloketones; HAs:Haloaldehydes.

that HANs and HAs are more toxic than THMs and HAAs (Mao et al.,
2016; Jeong et al., 2015; Muellner et al., 2007). Although HAcAms
are also found in low concentration, yet their toxicity is 142, 2 and
1.4 times higher than HAAs (5), HANs and HNMs, respectively (Ding
et al., 2018).
3.2. Aromatic DBPs
Although regulated DBPs are found in higher concentration, still
their contribution towards overall toxicity of chlorinated water is
small (Ding et al., 2018). Less than 40% of total organic carbon is
responsible for the formation of well-known DBPs (Yang and
5
Zhang, 2016). Therefore, focus of the research has been diverted
to investigate the unknown classes of emerging DBPs including
aromatic DBPs. Humic fraction of NOM contains number of aro-
matic compounds which are responsible for the formation of aro-
matic DBPs (Jiang et al., 2020). Halofuranones is the very first group
of aromatic DBPs. Now, more than 100 aromatic DBPs have been
found in disinfected water (Liu et al., 2020a).
Aromatic DBPs can be classified as phenyl and heterocyclic DBPs.
Phenyl DBPs contain eight subgroups including halopeptides, hal-
ophenols (HPs), halobenzoquinones (HBQs), halophenylacetonitrile
(HPANs), halohydroxybenzaldehydes (HBADs), halonitrophenols
(HNPs), halobenzenesulfonic acids, halopyridines and
S. Kali, M. Khan, M.S. Ghaffar et al.
halohydroxybenzoic acids (HBACs). Whereas, heterocyclic DBPs
include halofuranones and halopyrroles etc. (Table 4) (Liu et al.,
2019, 2020a; Yang et al., 2019; Zhang et al., 2018; Wang et al.,
2016; Zhai et al., 2014). Heterocyclic highly DBPs are unstable and
get decompose under alkaline conditions and in the presence of
excess chlorine. Whereas, the stability of phenyl DBPs vary from
one another depending upon the presence of functional groups.
Nitrogen containing functional groups are relatively more stable,
while brominated phenyl DBPs get decompose in the presence of
chlorine (Hu et al., 2018; 2019; Nihemaiti et al., 2017). The data on
the stability of phenyl DBPs is scarce.
Aromatic DBPs are found in very low concentration i.e. ng L1 to
mg L1 (Yang et al., 2019). Due to less availability of standards and
high analysis requirements, aromatic DBPs are rarely analyzed
quantitatively (Jiang et al., 2019). Among phenyl DBPs, HPANs,
HBACs and HPs are found in higher amount due to the presence of
carboxylic group in NOM. Among heterocyclic DBPs, only halofur-
anones have been studied and found in relatively higher concen-
tration than phenyl DBPs (Liu et al., 2020a). It has been reported
that aromatic DBPs have dozen to hundred times more toxicity than
aliphatic DBPs (Liu et al., 2019). It has also been suggested that
phenyl N- DBPs are more toxic than phenyl carbonaceous (C-DBPs).
This could be associated with the hydrophilic nature of C-DBPs
(Zhang et al., 2018; 2020).
4. Factors affecting the formation of DBPs
The formation of various DBPs is dependent on number of
influential factors: (i) chorine dose (ii) temperature (iii) pH (iv)
contact time (v) organic matter content (vi) constituents of water,
and (vii) type of the pipe material (Fig. 2) (Voukkali et al., 2015;
Abbas et al., 2015). According to WHO, the residual chlorine level
must be equal or higher than 0.5 mg L1 after contact time of
30 min at pH below 8 and temperature 20ᵒC (Mahmood, 2015).
4.1. Chorine dose
High disinfectant dose leads to the formation of more hypo-
chlorous acid which react with NOM, as a result, more DBPs are
formed (Stef
an et al., 2019). An experiment was conducted by Gao
et al. (2013) in which chlorine decay was tested and concentrations
of DBPs including HAAs and THMs were measured. Results revealed
that higher the chlorine dose is responsible for higher oxidation of
organic matter in water samples. Furthermore, the concentrations
of DBPs increased with chlorine dose and reaction time (Gao et al.,
2013). The formation of THMs and HAAs generally increases with
disinfectant dose and residual chlorine (Zhang et al., 2017; Hong
et al., 2012; Mompremier et al., 2019; Gao et al., 2013). Intermediate
DBPs also increase with increasing dose, but up to a certain limit
depending upon the stability of intermediated DBPs at given dose,
pH and contact time, afterwards they react with free chlorine to
produce THMs, HAAs and other DBPs (Hong et al., 2012). For
instance, the degradation rate of DCAN is observed to be higher
than its formation at chlorine dose of 10.2 mg L1 (Fang et al., 2010).
Similarly, heterocyclic DBPs also get decompose into THMs and
HAAs in the presence of higher amount of residual chlorine (Hu
et al., 2109).
4.2. Reaction time
Reaction time impacts the formation of various categories of
DBPs in a multiple way. High contact time produces more DBPs
because of the reaction with residual chlorine. Reaction time affects
the formation of different categories of DBPs in a different way.
Hong et al. (2012) reported a significant increase in the formation of
6
Environmental Pollution 281 (2021) 116950
THMs and HAAs up to contact time of 2 h. Chlorine firstly reacts
with the active group quickly, leading to the rapid production of
DBPs in the beginning. As the chlorination continued, availability of
both reactive groups and free chlorine declined which reduced the
formation of DBPs (Hong et al., 2012). Another study reported the
increasing formation potential of HAAs in first 3-h of chlorination.
Increased contact time decreases the level of residual chlorine
which also reduces HAAs formation (Mompremier et al., 2019).
However, longer reaction time results in the formation of some
temporary DBPs (HANs, HKs and HAs) which shows increasing
followed by decreasing pattern with prolonged reaction time

n et al., 2019). They undergo hydrolysis in the existence of free
(Stefa
chlorine (Sun et al., 2013). Additionally, phenyl N-DBPs are rela-
tively stable, while rest of the aromatic DBPs get decompose. Yet,
the detailed data on stability of aromatic DBPs is limited (Liu et al.,
2020a).
4.3. Temperature
Temperature affects reaction kinetics. For chlorination, increase
in temperature leads to the formation of more THMs because
warmer environment increases the reaction rate. Additionally,
more NOM is available in summer as compared to the colder
months (Chowdhury et al., 2011). However, very high temperature
can lead to the volatilization of THMs except chloroform, which is
stable than other THMs, while temperature dependency of HAAs
formation is variable (Chowdhury et al., 2011). The yield of HAAs
firstly increases as temperature elevated from 10 to 20
C, but
declined as the temperature continuously raised up to 30
C. The
reduced production of HAAs at 30
C chiefly resulted from the
decomposition of unstable HAAs like trihaloacetic acid (THAA)
(Hong et al., 2013). Whereas, increase in temperature from 17 to
37
C also lead to the decline in HAAs formation (Mompremier
et al., 2019). This decline at temperature below 20
C could be
associated with the combined effect of various pipe materials used
in the study. Gan et al. (2013) reported the seasonal dependency of
THMs and HAAs formation which is favored by winter.
Generally, an elevation of temperature accelerates the reaction
rate. If the products are comparatively stable, their production rises
with the temperature. However, the temperature upsurge may also
improve the decomposition rate of THAAs (trihalogenated acetic
acid) as per they are thermally unstable DBPs (Chen et al., 2002;
Levesque et al., 2006). Further, high temperature also enhances the
decomposition of HANs, HK and HAs (Stef
an et al., 2019). It has been
reported that HKs production increases up to 10e20
C and then
start to decrease with further increase in temperature (Hong et al.,
2013). Therefore, the concentrations of the unstable DBPs as the
function of temperature depend on the relative quantities of their
formation and decomposition (Hong et al., 2012).
4.4. pH
High pH water produces more THMs, whereas more HAAs are
formed at low pH values (Tian et al., 2017). Moreover, hydrolysis of
HANs, HKs and HAs is also favored by higher pH values (Stef
an et al.,
2019). The effect of pH on DBPs formation is dissimilar for indi-
vidual compounds. In the study of chlorination, THMs level elevate
significantly as pH increases. This result is predictable as the alka-
line conditions can assist the hydrolysis reactions of various inter-
mediate DBPs to produce THMs (Xie, 2004). Yet for HAAs, the yields
were approximately stable as pH rose from 6 to 8 and dropped at
higher pH (Fang et al., 2010; Hong et al., 2012). Further, pH as low as
4 also increased the formation of HAAs (Fang et al., 2010). Acidic
conditions (at pH 6) favored the formation of N-DBPs (HANs), while
alkaline conditions up to pH 9 favors the formation of stable THMs
S. Kali, M. Khan, M.S. Ghaffar et al. Environmental Pollution 281 (2021) 116950

Table 4
Toxicity summary of aromatic DBPs.
a a
Group Name Compound names LC50 Compound names LC50 General Toxicity References
mol L1 mol L1

Phenyl DBPs
HPs 2,4-dichlorophenol 2-chloro-6-iodo-4- Cytotoxic, developmental Zhang et al. (2020); Liu et al. (2019);
methyl-phenol anomalies, endocrine Yang et al. (2019); Liberatore et al.
2-bromophenol 2,6-dibromo-4- 1.33  10⁻4 disruptive and growth (2017); Wagner and Plewa (2017)
chlorophenol inhibition
4-bromophenol 2,6-dichloro-4-iodophenol
2,4,6-trichlorophenol 2.44  10⁻4 2,4,6-tribromophenol 9.99  10⁻5
2-iodophenol 6.01  10⁻4 2,4,6-tribromoresorcinol
4-iodophenol 2.16  10⁻4 2,4-diiodophenol
4-iodo-2-methylphenol 1.63  104 2,6-diiodophenol
2-iodo-24-methylphenol 4,6-diiodo-2,3-
dimethyphenol
2,6-dichloro-4 1.75  10⁻4 2-chloro-4,6-diiodophenol
bromophenol
2-iodo-4,5-dimethylphenol 2,4,6-triiodophenol 7.01  10⁻5
4-iodo-2,5-dimethylphenol 2,4,6-triiodo-1,3,5-
benzenetriol
4-hydroxy-3-iodophenyl 4.08  104 4-hydroxy-3,5- 3.32  105
diiodophenyl
4-iodo-2,6-dimethylphenol 2,4-dibromophenol
HBQs 2,5-dibromohydroquinone 2,3,6-trichloro-1,4- Developmental Yang et al. (2019); Wang et al.
benzoquinone malformations, cytotoxic
zka
(2018); Sun et al. (2019); Procha
2,6-dichloro-p- 1.2  105 2,6-Dibromo-p- 1.7  105 et al. (2015)
benzoquinone benzoquinone
2,6-dichloro-3-methyl-1,4- 2,6-dibromo-1,4-
benzoquinone benzoquinone
HBACs 5-chlorosalicylic acid 3,5-dibromo-4- 1.96  103 Growth inhibition, Zhang et al. (2020); Wagner and
hydroxybenzoic acid cytotoxic Plewa (2017); Zhai and Zhang
3,5-dichlorosalicylic acid 4.77  104 3,5-dibromosalicylic acid 2.21  104 (2011)
3,5-dichloro-4- 2.16  103 4-hydroxy-5-iodo-1,3-
hydroxybenzoic acid benzenedicarboxylic acid
5-bromosalicylic acid 2,6-dichloro-4-iodo-3,5-
dihydroxy-benzoic acid
5-bromo-3-methyl- 4-hydroxy-3,5- 2.88  104
salicylic acid diiodobenzoic acid
3-bromo-5-chloro-4- 3,5-diiodosalicylic acid
hydroxybenzoic acid
3-bromo-5-chlorosalicylic 3.35  104 3,5-diiodosalicylic acid
acid
3-iodo-4-hydroxybenzoic 1.5  105 5,6-diiodo-3-ethyl-
acid salicylic acid
3-iodo-4-hydroxy-5-
methylbenzoic acid
HBADs 3,5-dichloro-4-hydroxy- 3.20  104 3,5-dibromo-4- 1.30  104 Cytotoxic, developmental Zhang et al. (2020); Yang et al.
benzaldehyde hydroxybenzaldehyde effects (2019); Zhai and Zhang (2011)
3-bromo-5-chloro-4- 2.04  104 4-hydroxy-3,5-
hydroxy-benzaldehyde diiodobenzaldehyde
4-hydroxy-3- 2-hydroxy-3,5-
iodobenzaldehyde diiodobenzaldehyde
2,6-dibromo-4-
hydroxybenzaldehyde
HNPs 2,6-dichloro-4-nitrophenol 6.73  105 2,4-dibromo-6- Cytotoxic, developmental Zhang et al. (2020); Selvam et al.
nitrobenzenediol defects (2018); Wagner and Plewa (2017);
2-bromo-4-nitrophenol 2,4-diiodo-6-nitrophenol Zhai et al. (2014)
5
2-bromo-6-chloro-4- 8.01  10 2,6-diiodo-4-nitrophenol 3.35  105
nitrophenol
2,6-dibromo-4-nitro- 5.07  105
phenol
HPANs Phenylacetonitrile 2,5- Cytotoxic, developmental Liu et al. (2020a); Zhang et al.
dichlorophenylacetonitrile effects (2018)
4
2-chlorophenylacetonitrile 1.48  10 2,6-
dichlorophenylacetonitrile
3-chlorophenylacetonitrile 2,5-
dichlorophenylacetonitrile
4-chlorophenylacetonitrile 3,4- 8.3  105
dichlorophenylacetonitrile
2,4-
dichlorophenylacetonitrile
Halodipeptidesb NeCl-Phe-Gly NeBreNeCl-Tyr-Ala Tian et al. (2020); Huang et al.
NeCl-Tyr-Gly 3-I-Tyr-Gly (2019)
NeCl-Tyr-Ala 3-I-Tyr-Ala 5.0  103
N,N-di-Cl-Phe-Gly N,N-di-Br-Tyr-Gly
(continued on next page)

7
S. Kali, M. Khan, M.S. Ghaffar et al. Environmental Pollution 281 (2021) 116950

Table 4 (continued )
a a
Group Name Compound names LC50 Compound names LC50 General Toxicity References
mol L1 mol L1

N,N-di-Cl-Tyr-Gly N,N-di-Br-Tyr-Ala
NeBr-Tyr-Gly NeBr-3-I-Tyr-Gly
N,N-di-Cl-Tyr-Ala NeBr-3-I-Tyr-Ala
NeBr-Tyr-Ala 3,5-di-Cl-Tyr 4.2  103
NeBreNeCl-Tyr-Gly 3,5-di-Br-Tyr 1.9  103
3-Cl-Tyr 1.15  102 3,5-di-I-Tyr 5.5  104
3-Br-Tyr 1.16  102 3,5-di-I-Tyr-Gly
3-I-Tyr 1.06  103 3,5-di-I-Tyr-Ala 7.8  104
Halobenzenesulfonic 2-iodo-3,4,5-trihydroxy- 2,6-dichloro-3,5- Liu et al. (2020a)
acids benzenesulfonic acid dihydroxy-4-
dodecylbenzenesulfonic
acid
2-chloro-6-iodo-3,4,5- 2,6-diiodo-3,4,5-
trihydroxybenzenesulfonic trihydroxy-
acid benzenesulfonic acid
3,5-dichloro-4- 2,6-dibromo-3,5-
dodecylbenzenesulfonic dihydroxy-4-
acid dodecylbenzenesulfonic
acid
2-bromo-6-iodo-3,4,5-
trihydroxy-
benzenesulfonic
Acid
Other phenyls DBPs 4-bromo-2-methoxy-5- 4-hydroxy-3-iodo-5- Liu et al. (2020a)
methylphenol nitro-benzaldehyde
2,6-dibromo-4- 2-hydroxy-3,5-diiodo-4-
methoxyphenol formyl-benzoic acid
3-formyl-4-hydroxy-5- 2,4,6-triiodo-5-methoxy-
iodo-benzoic acid 1,3-benzenediol
Heterocyclic DBPs
Halopyrroles 3-chloro-2,5-furandione 2,3,5-tribromopyrrole 6.1  105 Developmental toxicity Liu et al. (2020a)
2,3,4,5-tetrabromopyrrol 2,3,4-tribromo-5-
chloropyrrol
2-hydroxy-3,5,6- 2,3,4-tribromo-5-
trichloropyridine iodopyrrol
Halofuranones chloro-4-methyl-5- trichloro-4-methyl-5- 2.75  104 Carcinogenic, genotoxic,
s and
Diana et al. (2019); Corte
hydroxy-2(5H)-furanones hydroxy-2(5H)-furanones mutagenic developmental Marcos (2018); Wang et al. (2013)
chloro-5-methyl-5- trichloro-5-methyl-5- malformations
hydroxy-2-furanones hydroxy-2-furanones
dichloro-4-methyl-5- tertchloro-5-methyl-5-
hydroxy-2(5H)-furanones hydroxy-2-furanones
trichloro-5-methyl-5- tertchloro-5-methyl-5-
hydroxy-2-furanones hydroxy-2-furanones
a
LC50 values obtained by Chinese hamster ovary cells bioassay with the exposure time of 72 hours. b48 hours exposure duration.
HP: Halophenols; HBQs: Halobenzoquinone; HBACs: Halohydroxybenzoic acids; HBADs: Halohydroxybenzaldehydes; HNPs: Halonitrophenols; HPANs: (Halo)
phenylacetonitriles

(chloroform) (Ding et al., 2018). Further, when pH reaches 7.6, hy-
pochlorite become dominant species which has less disinfectant
potential, therefore, less DBPs are formed (Sun et al., 2013; Tian
et al., 2017).
Alkaline pH (>8) leads to the hydrolysis of N-DBPs and HKs
(Stef

an et al., 2019). The yields of HKs at pH 6 and 7 are reported to
be higher than pH 8. As HKs and HAs are unstable, they can easily
decompose under the higher pH conditions and convert into more
stable DBPs i.e., THMs and HAAs (Hong et al., 2013). Moreover,
alkaline conditions also lead to the decomposition of halofuranones
(Nihemaiti et al., 2017).
4.5. Organic matter content
DBPs are formed by the reaction of disinfectants with NOM or
the other constituents of water. Therefore, NOM plays vital role in
the formation of DBPs. NOM is usually higher in surface water as
compared to the ground water, therefore, more DBPs are formed in
surface water as compared to the groundwater (Benson et al., 2017;
Abbas et al., 2015). The complex nature of NOM makes it difficult to
8
understand the proper mechanism and impact of various ions and
metals on DBPs formation (Zhao et al., 2016). Molecular weight,
structure and hydrophobicity of NOM also affect the formation of
DBPs. The hydrophobic organic matter usually consists of high
molecular weight organic materials like humic substances,
whereas, hydrophilic organic matter is composed of low molecular
weight organic contents i.e. amino acids, carboxylic acids, carbo-
hydrates etc. (Korotta-Gamage and Sathasivan, 2017). Literature
reported that low molecular weight NOM promote the formation of
brominated DBPs (e.g. DBCM and BDCM) (Kristiana et al., 2017;
Gough et al., 2012). During chlorination, bromide and iodide gets
oxidized into HOBr and HOI. Hydrophilic/low MW organic fractions
are more reactive towards HOBr and HOI and form brominated and
iodinated DBPs. Besides, hydrophobic/high molecular weight NOM
fractions enhance the formation of THMs and HANs (Li et al., 2017;
Lin et al., 2014). It has been observed that hydrophobic NOM has
two times higher THMs formation potential than hydrophilic frac-
tions because THMs formation occur due to the reaction of HOCl/
OCl with the humic like substances (Korotta-Gamage and
Sathasivan, 2017). However, no effect of hydrophobicity or
S. Kali, M. Khan, M.S. Ghaffar et al.
Fig. 2. Factors affecting the formation of DBPs.
hydrophilicity has been observed on other classes like HKs and HAs


(Li et al., 2017; Swietlik and Sikorska, 2004). Hydrophobic and
HMW NOM contains more phenolic groups, hence, increase the
formation of aromatic DBPs (Diemert et al., 2013).
4.6. Constituents of water
In drinking water treatment facilities, the high reactivity of
bromine with phenol-like organic structures led to the production
of brominated DBPs during chlorination (Dong et al., 2017). A study
exhibited that the existence of Br and I boost the production of
halogenated DBPs, however the impact of Br is dominants and
forms more toxic DBPs (Dong et al., 2017). In bromine containing
water, Br gets oxidized by HOCl to HOBr which is a strong
oxidizing agent and incorporate bromine in DBPs (Chowdhury,
2013). High concentration of brominated furanones and bromi-
nated benzoquinones have been reported in bromine rich water
(Pan and Zhang, 2013). Similarly, presence of iodine produces HOI/
OI which also reacts with NOM producing I-DBPs (Pantelaki and
Voutsa, 2018). Nevertheless, both processes are pH dependent.
Literature reported that bromine has more reactivity for THMs and
HAAs formation as compared to chlorine. Bond et al. (2012) re-
ported that only 5e10% hypochlorous acid became incorporated
into THMs, however, 50% bromine gets incorporated in THMs for-
mation. Generally, chlorinated HAAs are dominant but the presence
of Br favors the formation of brominated HAAs, hence, making
them dominant specie (Hong et al., 2012). Other anions, SO 
4 , NO3

and Cl has no direct effect on DBPs formation (Zhang et al., 2019).
Whereas, F has indirect effect on DBPs formation with respect to
pH. F shows no interaction with NOM or disinfectant, however, it
affects pH of the solution because of same OH and F radius. As,
the active specie of disinfectant changes with pH, so it influence the
THMs speciation (Ta et al., 2020).
Among cations, Kþ has no notable influence on DBPs formation
during chlorination (Zhang et al., 2019). Hardness reduces the for-
mation of THMs. As, Ca2þ and Mg2þ bind with the functional groups
of humic acid in the form of chelates or poly dentate complexes
reducing its availability to react with disinfectant to form DBPs (Ta
et al., 2020). However, some studies reported that hardness has
catalytic effect for THMs and HAAs formation (Zhao et al., 2016;
9
Environmental Pollution 281 (2021) 116950
Navalon et al., 2009) depending upon the type of NOM (Ta et al.,
2020; Zhao et al., 2016). Similarly, NHþ 4 consumes disinfectant,
hence, reduce the formation of THMs (Ta et al., 2020; Sun et al.,
2013). It is suggested that NHþ 
4 reacts with ClO and converted into
NH2Cl. As a result, availability of disinfectant decreases which
eventually leads to the decreased THMs formation (Ta et al., 2020).
However, NHþ 4 favors the formation of N-DBPs (Zhang et al., 2019;
Voukkali and Zorpas, 2015).
Presence of multiple metal ions showed analogous but not
synergistic effect on the formation of DBPs, specifically THMs and
HAAs (Liu et al., 2012). Influence of each metal ion on DBPs for-
mation is highly dependent upon the structure and molecular
weight of the precursors (Zhao et al., 2016). Presence of As3þ re-
duces THMs formation as it consumes the disinfectant (Ta et al.,
2020). During the chlorination of tannic acid containing water in
the presence of Mg2þ, Fe2þ, Mn2þ, Cu2þ and Al3þ inhibit the for-
mation of THMs with the order of Mg2þ < Cu2þ < Fe2þ
< Mn2þ < Al3þ and promote the formation of HAAs with the order
of Mg2þ < Mn2þ < Cu2þ < Al3þ < Fe2þ (Liu et al., 2012). The reaction
mechanism of each metal is different. Fe3þ, Cu2þ, and Al3þ accel-
erates THMs formation as they make bond with humic acid and Cl
or Br present in water. An intermediate product (e.g. metald Cl
dhumic acid) is formed which weakens the original bonds of hu-
mic acid and they get easily attacked by the disinfectant (Ta et al.,
2020). The catalytic effect of iron and copper depends upon the
molecular structure and molecular weight of NOM, respectively
(Zhao et al., 2016). Presence of Mn2þ with co-existing algal blooms
in water can enhance the formation potential of HAAs (Tada et al.,
2020).
4.7. Type of the pipe material
Chlorine reacts differently with pipe material and formation of
DBPs varies with the type pipe material used in the water distri-
bution networks (Mompremier et al., 2019). Generally, pipe mate-
rials used in water supply systems include three generic types:
cementitious, plastic, and metallic. Among them, high density
polyethylene (HDPE), polypropylene (PP), polyvinyl chloride (PVC),
ductile iron pipe (DI), stainless steel pipe (SS), galvanized steel
pipes (GS) and polyethylene (PE) pipe are widely applied
(Mompremier et al., 2019; Zhang et al., 2017). In recent years,
plastic pipes have become the dominant material for various
diverse types of supply networks owing to their high flexibility high
corrosion resistance, ease of installment, jointing properties, low
cost, low weight and durability. These pipe materials have great
effect on production of DBPs (Poleneni and Innis, 2019).
Literature suggested that the formation of THMs under the three
different pipe materials followed the order as: PE > DI > SS (Zhang
et al., 2017). Relying on the analysis data of chlorine decay, most of
the chlorine decay in SS pipe is wall decay, which denotes that a
small amount of chlorine is left in bulk water to react with organic
matter to produce DBPs, therefore causing declined formation of
DBPs. However, based upon bacterial analysis, it is suggested that
DI and SS pipes are more suitable to be used in water distribution
systems as compared to PE. Because DI and SS pipes support less
complex bacterial and less abundance of potential opportunistic
pathogens than PE pipes (Zhang et al., 2017). Another study sug-
gested that HAAs concentration in the four pipe loop systems fol-
lowed the order: HDPE > PP > PVC > GS, due to the variation of
chlorine concentration within the pipe loop system. SG pipe loop
showed higher chlorine decay rate as compared to the other pipe
loop systems (Mompremier et al., 2019).
Literature reported that the concentrations of THMs and HAAs
in the different segments of the distribution systems varied
depending on other variables as well, such as age of the pipe
S. Kali, M. Khan, M.S. Ghaffar et al.
material, diameter of the pipe and presence of NOM (Zhong et al.,
2012; Mompremier et al., 2019; Zimoch et al., 2016). Zhong et al.
(2012) reported that under the conditions of the same initial
chlorine concentrations the ranking of the pipe material in different
pipe materials was PVC > SS > DI. Similarly, it has also been re-
ported that the formation of DBPs increases with increasing
diameter of the pipe (Zhong et al., 2012). The reaction time is the
most important factor determining the formation process of THMs
and depends on the distance between disinfection points and
sampling points in a distribution system. It has been observed that
THMs concentration drops with the increasing distance (Zimoch
et al., 2016).
5. Toxicity of DBPs
Chlorination cause mutation in bacterial DNA, however, its ef-
fect on mammalian cell has also been documented previously (de
Castro Medeiros et al., 2019). A study reported that THMs
(750 mg L1) are responsible for hepatotoxicity, hyperplasia in
urinary bladder and metaplasia in small intestine of male Wistar
rats at dose 16.17 mg kg1 and time duration of 1 month (Abd El-
Halim et al., 2017). Another study suggested that THMs could be
responsible for almost 700 cancer cases in Canada (Chowdhury
et al., 2011). THMs and HANs formed as a result of chlorination
are two times more genotoxic and cytotoxic than same DBPs
formed by chloramination because chlorination yields higher con-
centration of DBPs than chloramination at same disinfectant doses
(Ding et al., 2018). Chloroform and bromoform can cause cytotox-
icity in human cell (Lodhi et al., 2017). Studies showed that HAAs
are genotoxic as they inhibit glyceraldehyde-3-phosphate dehy-
drogenase (GADPH) which leads to the disruption of cellular
metabolism and energy homeostasis (Dad et al., 2018). Dad et al.
(2018) evaluated the effects of three HAAs on Chinese hamster
ovary (CHO) cells. Results revealed that mono-HAAs were the
strongest inhibitors of GAPDH and greatly reduced cellular ATP
levels. However, di- and tri-HAAs showed weak inhibition of
GAPDH and enhanced cellular ATP levels. Further, HAAs also acti-
vated pyruvate dehydrogenase complex (PDC) by inhibiting pyru-
vate dehydrogenase kinase (Dad et al., 2018). Further, brominated
HAAs are 201 times more toxic than chlorinated HAAs (Pan and
Zhang, 2013). HANs are known for causing genotoxicity and cyto-
toxicity in Chinese hamster ovary cell (Muellner et al., 2007).
Further, HANs has been reported to cause DNA damage and ROS
generation in human derived hepatoma cell line (Lu et al., 2018).
Although HANs are unregulated, yet they are more toxic than
regulated DBPs. Similarly, HAs are known to cause aneuploidy, DNA
damage and chromosomal aberrations in mammalian cells. Liter-
ature reported that HAs can cause nephrotoxicity in humans and
cytotoxicity in rats (Jeong et al., 2015). Further, HAcAms are known
to cause cytotoxicity and DNA damage in Chinese hamster ovary
(CHO) cells (Plewa et al., 2008). Toxicity data and LC50 values of
aliphatic DBPs have been summarized in Table 3.
Chlorination can exhibit high acute toxicity for aquatic biota as
well. Literature reported that chlorination of wastewater with
2.5_5 mg Cl2 L1 caused toxicity to fishes with enhanced mortality
of Daphnia magna neonates (Da Costa et al., 2014). This could be
associated with the presence of DBPs. Niu et al. (2017) reported that
ecological risk levels of THMs in freshwater are higher than sea
water. However, risk assessment of THMs in surface water was
notably low. Teixido
et al. (2015) evaluated the effects of THMs and
HAA5 on the development of zebra fish embryo at concentration
range of 20e100 mgmL1. Results revealed that THMs caused
adverse developmental effects and weak induction of DNA damage
10
Environmental Pollution 281 (2021) 116950
in addition to the reduced tail length, whereas HAA (tribromoacetic
acid and dichloroacetic acid) significantly enhanced the malfor-
mation rate (Teixido
et al., 2015). Another study reported the
biochemical changes and liver damage in Cyprinus carpio induced
by DBPs (chloroform and iodoform) (Perveen et al., 2019).
It has been reported that aromatic DBPs degraded into aliphatic
DBPs (THMs and HAAs) either through ring opening or cleavage of
the side chain. The formation of intermediate compound during
this conversion are known to be more toxic than the parent/
daughter compounds. For example, HBQs formed by the degrada-
tion of halophenols are 1000 times more cytotoxic than regulated
aliphatic DBPs (Li et al., 2015). Similarly, halofuranones have also
been reported as mutagenic and genotoxic. Aromatic DBPs are
10e100 time more toxic than aliphatic DBPs in term of develop-
mental toxicity and growth inhibition (Wang et al., 2018; Wagner
and Plewa, 2017). For instance, HBQs exposed to zebrafish em-
bryo caused oxidative stress, curved spines, heart malformation
and other developmental defects, and this toxicity potential of
HBQs was 200 times higher than aliphatic HAAs (Wang et al., 2018).
Similarly, 2,4,6-tribromophenol was 125 times more toxic than
HAAs to Tetraselmis marina and 72 times to the embryo of Platy-
nereis dumerilii (Liu and Zhang, 2014). Additionally, HPANs showed
higher cytotoxicity in CHO cells as compared to their aliphatic
counterparts (HANs) (Zhang et al., 2018). Further, selected groups of
phenyl DBPs were evaluated in term of oxidative stress in CHO cells
in vitro. Toxicity order was HNPs > HPs > HBADs > HBACs (Zhang
et al., 2020). Toxicity of aromatic DBPs and their LC50 values have
been described in Table 4.
6. International regulations
Based upon toxicity of DBPs, US EPA has regulated two groups of
DBPs: THMs and HAAs and EU has regulated THMs only (Table 5).
Canada has set different maximum permissible limit (80 mgL1 for
HAAs) and each province of Canada has different guideline values
(Chowdhury et al., 2011). Nigeria has 1 mgL1 maximum allowable
limit for THMs in drinking water (Benson et al., 2017). Similarly,
South Africa, Australia and Singapore has their own drinking water
quality standards (Yang et al., 2018).
7. Abatement approaches
The effective removal of DBPs by several treatment processes
can be achieved such as adsorption, air stripping, ozonation fol-
lowed by chlorination, enhanced coagulation, membrane tech-
niques, and advanced oxidation processes (Chaukura et al., 2020).
Granulated activated carbon (GAC) is also useful for the removal of
THMs and HAAs and other aromatic DBPs (Marais et al., 2018; Jiang
et al., 2017). High temperature and longer contact time can enhance
the removal of DBPs. However, biological activity of carbon can
effectively remove HAAs and other biodegradable DBPs from water
distribution systems (Korotta-Gamage and Sathasivan, 2017).
Physical methods: boiling, addition of sodium carbonate and
ascorbic acid can also be used for the abatement of DBPs (Liu et al.,
2021). Summary of all these possible techniques has been provided
in Table 6.
Among physical methods, boiling is one of the easiest ways to
reduce DBPs levels in drinking water. Shi et al. (2017) reported the
removal of halo-DBPs through boiling. Removal of HANs after
boiling involves both volatilization and decomposition steps (Shi
et al., 2017). In addition to boiling, incorporation of lemon in
chlorinated water has been reported as a successful method for the
abatement of halo-DBPs (Liu et al., 2021). They have also reported
S. Kali, M. Khan, M.S. Ghaffar et al. Environmental Pollution 281 (2021) 116950

Table 5
Guideline values of various DBPs.

DBPs Cancer group (EPA)b WHO (2008) US EPA (1998) European Union (Directive, 1998)

mg L1
THM4 80 100
Chloroform B2 300 70
Bromodichloromethane B2 60 0
Chlorodibromomethane C 100 60
Bromoform B2 100 0
HAA5 60
Dichloroacetic acid B2c 50 0
Trihloroacetic acid C 200 20
Monochloroacetic acid D 20 70
a
Monobromoacetic acid D
a
Dibromoacetic acid D
HANs
Dibromoacetonitrile C 70
Dichloroacetonitrile C 20
a
Bromochloroacetonitrile
a
Trichloroacetonitrile
HKs
a
Chloroacetones (1,1-Dichloroacetone)
HAs
Chloral hydrate (Trichloroacetaldehyde) C 10
Phenyl DBPs
a
2- Chlorophenol D
a
2,4-Dichlorophenol D
2,4,6-Trichlorophenol B2 200
a
Inadequate data in available for setting guideline values.
b
B2¼ Probable human carcinogen based upon enough data from animal studies; C¼ Possible human carcinogen; D ¼ Not classified as human carcinogenic.
c
Probable human carcinogen according to IARC (2004).

that heating of lemon containing water up to 100
C can reduce the
cytotoxicity of tap water up to 67%. Ascorbic acid (3.7 mg L1) can
quench residual chlorine which restricts the formation of DBPs (Liu
et al., 2021). Similar results has been reported by the addition of
sodium carbonate (Liu et al., 2020b).
Membrane technologies involves reverse osmosis, nano-
filtration, microfiltration, ultrafiltration and ceramic membranes.
These membranes are used for purification of treated water and
eliminates NOM and other DBPs precursors which ultimately
reduce the formation potential of DBPs. Each membrane has
different NOM elimination potential. However, accumulation of
microbes, NOM and other precursors on membranes can fill the
voids reducing the efficiency of membranes (Chaukura et al., 2020;
Xu et al., 2019; Marais et al., 2018). Fu et al. (2017) conducted a pilot
scale experiment to evaluate a biofiltration process for the removal
of DBPs precursors in order to maintain the formation potential (FP)
of 36 different DBPs. The biofiltration process included sand/
anthracite (SA) filtration coupled with a biologically-active GAC
followed by pretreatments. Results revealed that biofiltration pro-
cess reduced the FP of total DBPs (24%), more specifically; HAs
(33.62%) > HAAs (28.13%) > THMs (20.46%) > HKs (13.46%) > HANs
(8.82%). However, the precursors of HANs were recalcitrant towards
biofiltration process, hence showed negative removal. This method
proved to be more efficient for the halogenated DBPs as compared
to the other (Fu et al., 2017). So, biofiltration processes can be used
as effective method for the removal or control of DBPs formation,

Table 6
Summary of various approaches used for the abatement of DBPs.

Techniques Principle DBPs References

Boiling Decomposition and Volatilization All halo-DBPs Shi et al. (2017);

Liu et al. (2020b); 2021
Pan et al., 2014
Ascorbic Acid Quenching of residual chlorine All halo-DBPs Liu et al., 2021
Sodium Carbonate Increase pH which consequently increase the All halo-DBPs except THMs Liu et al. (2020b)
dehalogenation of DBPs
Adsorption (GAC) Concentration of DBPs on adsorbent; NOM removal THMs, HAAs, HKs, HAs, Chen et al. (2019);
aromatic DBPs Jiang et al. (2017); Chowdhury
(2013)
Air stripping Transfer of volatile compounds into air/gas THMs Valdivia-Garcia et al. (2019)
Enhanced Co-agulation NOM/DOC removal, THMs, HAAs, phenyl DBPs €a
Sillanpa € et al. (2018)
Membrane technologies Filtration/removal of NOM, microbes, TOC and other THMs, HAAs Guo et al. (2019);
DBP precursors Xu et al. (2019);
Marais et al. (2018);
Osawa et al. (2017)
Advanced oxidation processes NOM removal, mineralization and degradation of DBP THMs, HAAs, aromatic DBPs Sharma et al. (2018)
precursors
Combined approaches (Ozonation followed by Oxidation/breakdown of DBP precursors THMs, HAAs, N-DBPs, HKs, Chen et al. (2019);
chlorination) Phenyl DBPs Sillanpa€a€ et al. (2018)
Huang et al., 2018
Stepwise Chlorination Reduce chlorine dose Overall DBPs Li et al. (2017)

11
S. Kali, M. Khan, M.S. Ghaffar et al.
however, efficiency of the method depends upon the indigenous
microbial communities, used in supporting media, and their
respective efficiencies (Chen et al., 2019; Fu et al., 2017).
Advanced oxidation processes (AOPs) involves both photo-
chemical (UV technology) and non-photochemical (ozonation and
Fenton reaction) processes. Another technique, non-thermal
plasma is also used for the degradation of NOM and DBPs. This is
one of the most feasible AOP due to its low operational cost and
high efficiency (Ma et al., 2020; Aziz et al., 2019). A study reported
that ozonation process (0.7 mg of O3/mg of DOC) followed by
chlorination reduced the FP of THMs, HAAs, HANs and HKs but no
notable change was observed in the FP of HAs (Chen et al., 2019).
This process reduced the FP of overall DBPs up to 25%, however, it
enhance the bromate formation. Up-flow biological activated car-
bon (UBAC) at 15 min empty bed contact time (EBCT) followed by
chlorination reduced the formation potential of DBPs up to 35%.
Further, combined O3/UBAC process (with same condition) not only
reduce the formation potential of total DBPs up to 50% but also
reduce their toxicities (Chen et al., 2019). Combined approaches are
also used to reduce the formation potential of DBPs. For instance,
UV combined with chlorination reduces the formation of HAcAms
(Liu et al., 2020c). Details of all these methods have already been
explained elsewhere (Chaukura et al., 2020).
Several points must be considered while selecting of appro-
priate control strategies i.e. control efficiency, cost effectiveness
and potential health hazards etc. It is obvious that boiling, coagu-
lation and optimization of disinfection process are economical
techniques. However, adsorption, membrane technologies, AOPs
and combined treatments are costly, yet efficient methods for the
control of DBPs. Therefore, appropriate technique must be selected
and further methods should be explored which are cost effective
and efficient.
8. Conclusions and recommendations
This paper summarized the literature on the formation of THMs,
HAAs, HANs, HKs and HAs in drinking water. It has been concluded
that increase in chlorine dose, NOM, contact time and temperature
enhances the formation of THMs and HAAs. Whereas, high pH fa-
vors the formation of THMs but oppose HAAs. Hydrophobic NOM
favors the formation of THMs, N-DBPs and aromatic DBPs. Unstable
DBPs hydrolyzed into THMs and HAAs, however, they become
stable at low temperature, moderate pH and low residual chlorine
concentration. Similarly, constituents of water also influence DBPs
formation in various ways. Presence of Br and I promotes the
formation of brominated and iodinated DBPs, respectively, while
SO4, NO3, Cl and F have no direct effect. Besides, the presence
of multiple metal ions also showed analogous but not synergistic
effect on the formation of DBPs. Similarly, PE pipes enhance the
formation of DBPs. Toxicity data revealed that not only humans, but
aquatic biota is also at risk. Though N-DBPs and aromatic DBPs are
not regulated, they are also genotoxic and cytotoxic. Aromatic DBPs
are found in very low concentration (ng L1), yet they are more
toxic than aliphatic DBPs. Further, most of the remediation tech-
niques are post-formation and expensive. Economically feasible
technologies should be developed for the abatement of DBPs.
Stepwise chlorination approach can be applied as it reduces DBPs
formation, increase disinfection efficiency and reduce operational
cost.
12
Environmental Pollution 281 (2021) 116950
9. Future perspectives
Literature asserts that following gaps exist
 Little attention has been paid on emerging DBPs (HANs), though
some studies reported that HANs are more toxic than the
regulated DBPs.
 Future studies should focus on generating the data to regulate
emerging DBPs.
 Specific NOM with respect to water source should be evaluated.
 New methods should be developed to quantify aromatic DBPs at
such low concentrations.
 Economical feasible technologies must be improved.
 Toxicological studies are limited and human risk data is also
scarce.
 Most of the technologies deal with the post-formation removal
of DBPs, pretreatment removal of precursors should be
explored.
Authors contribution
Sundas Kali, collected the research articles, reviewed and pre-
pared first original draft, screened and analyzed the key findings.
Marina Khan, collected the research articles, reviewed and pre-
pared first original draft. Muhammad Sheraz Ghaffar, collected the
research articles, reviewed and prepared first original draft. Sajida
Rasheed, screened and analyzed the key findings. Amir Waseem,
screened the papers, constructed the database, review and editing.
Muhammad Mazhar Iqbal, refined and improved the document and
Revisions. Muhammad Bilal khan Niazi, refined and improved the
document and Revisions. Mazhar Iqbal Zafar, supervised the whole
work, Conceptualization, writing and review, and finalized the
manuscript.
Declaration of competing interest
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
Acknowledgement
This work is supported by a grant awarded by Higher Education
Commission (HEC), Pakistan and part of the project #: 9139/Fed-
eral/NRPU/HEC. Further, authors would like to pay their sincere
indebtedness to M. Phil student Zenab Azam for her help in
improving the graphical abstract and figures. and international
scientific community for providing valuable and necessary scien-
tific information for the completion of review article.
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