Multiphasic screening of priority chemical compounds in drinking water by process control and human health risk

The residual chemical pollutants in drinking water may cause adverse effects on human health. Chemical compounds potentially affecting human health have been widely explored, while the multiphasic evaluation of chemical compounds by process control and human health risk is still rarely reported. In the present study, we used multiphasic criteria to assess the health risk including effluent concentration, accumulation index, purification index for the removal efficiency during the drinking water treatment processes, carcinogen classification based on the International Agency for Research on Cancer standards, non-carcinogenic health hazards and carcinogenic risk. Among the monitored chemicals, 47 and 44 chemical compounds were detected in raw water and treated water, respectively. The generation and removal of chemical compounds implied that the migration and transformation of chemicals during the purification processes affected the effluent concentration, posing a direct potential health risk. Of these compounds, 41 contaminants’ profiles were screened as priority chemical compounds (PCCs). The top eight PCCs with high carcinogenic risk were highlighted. Some effective steps, such as protecting the raw water sources, improving the removal performance and reducing the disinfection by-products during the purification process by introducing advanced treatment technologies, were suggested to maintain drinking water security. Collectively, our findings provided novel scientific supports for the sustainable management of drinking water to promote human health.


Background
Drinking water security (DWS) has become a critical international issue since approximately 80% of diseases result from contaminated drinking water as reported by the World Health Organization (WHO) [1,2]. The water containing chemical compounds poses serious threats to water environment sustainability, ecosystem health, and DWS [3][4][5]. The priority chemical compounds (PCCs), characterized by wide distribution and high toxicity, are refractory with long residue times [6,7]. PCCs can enter biological organisms and tissues through exposure and food chain accumulation, and then affect the normal physiological functions of the organism through biochemical or physicochemical effects, threatening human health [8][9][10].
With the advancement of monitoring technology and toxicological studies on the chemicals, emerging Open Access *Correspondence: wanghy@craes.org.cn; lidan01@craes.org.cn 1 Environmental Standard Institute, Ministry of Ecology and Environment of the People's Republic of China, Chinese Research Academy of Environmental Sciences, 100012 Beijing, China Full list of author information is available at the end of the article contaminants in the drinking water, such as heavy metals, volatile organic compounds (VOCs), polychlorinated biphenyls (PCBs), organophosphorus pesticides (OPPs), and organochlorine pesticides (OCPs), are being concerned [11,12]. Consequently, it becomes a worldwide problem for the management of the government sector in the screening of PCCs. A majority of chemical substances with relatively low concentrations in fine fresh surface water can be removed via the purification process in drinking water treatment plants (DWTPs), while some chemicals can be generated through the degradation, biosynthesis and accumulation during the water purification processes owing to the limitations of water purification technologies in the utilities of DWTPs [13]. For example, some of these chemicals can be re-released due to membrane pollution in the treatment processes [14]. In particular, the final step, which involves the disinfection procedure for protecting drinking water against external contamination and regrowth of bacteria, can generate approximately 600-700 chemical by-products [15]. Process control of purification procedures (i.e., flocculation, coagulation, sedimentation, adoption, filtration, disinfection or oxidation processes) from raw water source to treated drinking water provides technical support for the management of DWTPs [16,17]. Therefore, monitoring the concentrations of chemical compounds in source water and identifying the removal effect of drinking water purification processes (that is the dynamics of chemical compounds from raw water source to treated drinking water) are two important factors in the assessment of drinking water.
However, the above-mentioned contaminants in the drinking water generally pose a potential risk for human health for a long-term drinking exposure. Besides, few studies have been conducted to assess above-mentioned two aspects in the screening of optimal control pollutants [18][19][20]. With the growing demand for safe drinking water, it is imperative to screen multiphasic criteria characterized by process control and health risk based on the on-site investigation, which will provide a critical perspective for the screening of PCCs, strengthening the process control during the drinking water treatment and improving the sustainable management of DWS [21,22]. Such evaluation would also fill the gaps between human health and public utilities through the management of drinking water.
In the present study, 283 water samples of raw water and treated water from 146 DWTPs were collected to identify the effects of drinking water purification processes, and 76 chemical compounds were monitored to assess and screen PCCs by process control and health risk. This work aimed to (1) analyze the occurrence and concentration distribution of chemical compounds in the influent and effluent from 146 DWTPs; (2) emphasize the removal and generation processes during the purification procedure; (3) assess the health risk of chemical compounds in the influent and effluent using the hazard index (HI) and carcinogenic risk (CR); and (4) select PCCs by using the rank assignment method for the sustainable management of DWS.

Distributions of DWTPs
In the present study, 140 water samples from the influent (raw water) and 143 water samples from the effluent (treated water for drinking) were collected from 146 DWTPs located in 24 cities in the seven major river basins of China, including the Songhuajiang River, Liao River, Huai River, Yellow River, Hai River, Yangtze River, and Pearl River. The water supply capacity for each DWTP was more than 1000 tons/day water and the service population is more than 10,000 persons. More detailed information is provided in Additional file 1: Table S1. Figure 1 shows the geographic information for sampling sites covering 24 cities and 146 DWTPs.
All collected water samples were stored in a portable cooler with dry ice and immediately transported to the laboratory for analysis. A total of 76 chemical compounds, including heavy metals, VOCs, PCBs, OPPs, and OCPs, were monitored and analyzed.
The presence of heavy metals was determined using atomic absorption spectroscopy. Other compounds were determined via spectrophotometry, headspace gas chromatography (HS GC), solid-phase extraction gas chromatography (SPE GC), high-performance liquid chromatography (HPLC), and ultra-performance liquid chromatography (UPLC). Details on the compounds and analytic methods were provided in Additional file 1: Table S2.

Multiphasic evaluation analysis
Given the urgent requirements of environmental sustainability, safe drinking water, and human health, the concentrations of the chemical compounds, classification of carcinogens based on the International Agency for Research on Cancer (IARC) standards, accumulation index (AI), carcinogenic risks (CR), and hazard index (HI) were selected as the multiphasic evaluation variables (Fig. 2). The water treatment processes at the DWTPs were found to produce by-products, and health risk was generally a result of the exposure concentration of the treated water. Therefore, a novel and simple rank assignment method was established based on on-site investigations of concentration, technological developments and health risk.
This method was established to avoid human impacts when screening PCCs ( Table 1). The concentration rank was assigned according to the pollutants concentrations. In general, when C i was greater than the standard concentration [23], the pollutant was considered to be safe. The carcinogenic rank was assigned according to the IARC classification [24,25]. The HI and CR ranks were assigned through sequential data analysis. When  The flowchart of rank assignment system for the screening of chemical compounds HI < 1.00, the pollutant was considered to pose no significant risk of non-carcinogenic effects [26]. When CR < 10 −6 , the carcinogenic risk of the pollutant was acceptable and considered a low risk to human health, whereas the carcinogenic risk was unacceptable when CR > 10 −4 [27]. Particularly, when the SF values of pollutants could not be obtained, the rank assignment was conducted based on the IARC classification. Missing data were recorded as moderate or low, dependent on the specific characteristics of the chemical compounds (as the IARC guidelines). This multiphasic screening method also avoided significant human error caused by the selection of weight coefficients in the weight assignment method. The intuitive and simple evaluation analysis reflected the possible problems on human health risk in the processes from raw water protection to the treated drinking water, providing multiphasic management suggestions for DWS.

Data statistics
The detection rate (DR), excess rate (ER), removal efficiency (RE), AI, and purification index (PI) were calculated as follows: where n, n e , and N are the number of samples detected, the number of samples exceeding the standard concentration, and the total number of water samples collected, respectively; C i and C o are the chemical compound concentrations in the influent and effluent (mg/L), respectively; n a is the number of sample pairs where RE < 0; n p is the number of sample pairs where RE ≥ 0; and N RE is the number of sample pairs where the RE value was available.

Health risk assessment
The health risk of drinking water is directly related to oral ingestion. The method developed by the USEPA was used in this study to assess the health risk associated with the ingestion of various chemical compounds [13,28]. The chronic daily intake (CDI, mg/kg day) via the ingestion of pollutants in drinking water is typically used for health risk assessment, which was calculated as follows: where C o is the pollutant concentration in the effluent (mg/L), DIR is the daily ingestion rate of drinking water (L/day), which typically has a value of 2 L/day, EF is the exposure frequency (day/year), which is typically equal to 365 days/year, ED is the exposure duration (year), which is set as 30 years for non-carcinogens and 70 years for carcinogens, BW is the body weight (kg), with a standard value of 70.0 kg, and AT is the average exposure period (days), with typical values of 30 × 365 days for non-carcinogens and 70 × 365 days for carcinogens. The CR and HI of the pollutants were calculated as follows: where RfD is the reference dose for toxic pollutants (mg/ kg day) and SF is the pollutant slope factor (kg day/mg). Both the RfD and SF were collected from the websites of the US Integrated Risk Information System (IRIS) and USEPA.
The concentrations of chemical compounds in the influent differed from those in the effluent (Fig. 3). The concentration of eight chemical compounds (Sb, B, Ni, Ba, acrylamide, dibutyl phthalate, microcystin-LR, and formaldehyde) in the influent exceeded the standard values [17], while the concentrations of seven chemicals (Sb, Ni, Ba, acrylamide, dibutyl phthalate, trichloroacetaldehyde and trichloromethane) in the effluent were higher compared with the standard values.
DWTPs with exceedingly high concentrations of Ba were located at Binzhou City, Dongying City, and Zibo City in the Yellow River basin owing to the high background values of the compounds in the local soil [32]. DWTPs, where the Ni concentrations exceeded the standard value, were located in the Hai River basin, owing to the high background values of Ni compounds in the local soil as well as the excessive compound discharge from local chemical enterprises [33]. Liang et al. [34] have shown that the maximum concentrations of Sb, Ni and Ba in the Jiulongjiang River in Southeast China are 9.67 µg/L, 10.05 ug/L and 231.42 µg/L, respectively, while Wu et al. [35] have shown that the maximum concentration of Sb, Ni and Ba from rural areas of China are 0.653 µg/L, 15.2 µg/L and 384 µg/L, respectively. All of these values are lower compared with our results (12.5 µg/L, 212 µg/L and 1060.7 µg/L, respectively). These differences resulted from various factors, such as different compound background values, local variations of discharge, and removal performance of different treatment processes, as well as the degradation rate of chemical compounds during the water plant treatment processes [18,[36][37][38]. Additional file 1: Table S5 provided more detailed information. High concentrations of dibutyl phthalate and acrylamide appeared in the Yangtze River basin, which was mainly attributed to the accumulation of chemical compounds during the water treatment processes in DWTPs [39][40][41]. Microplastics act as vectors for contaminants including dibutyl phthalate and acrylamide, which are difficult to remove in the DWTPs [42]. The same result has been reported by Koelmans et al. [43] that higher concentrations in the effluent probably reflect the retention of microplastics. High concentrations of trichloroacetaldehyde and trichloromethane in the effluent were generally caused by the chlorine disinfection procedure, with the excess rates of 3.50% and 2.10%, respectively. The above-mentioned chemicals indicated that the treatment processes affected the concentrations of chemical compounds in the effluent, posing a direct risk to human health for long-term drinking exposure [44].

Removal and generation of chemical compounds
The treatment processes play a pivotal role in water purification since they influence the chemical compounds composition via chemical removal and generation. Removal and generation of various chemicals via different processes were characterized by AI and PI values (Fig. 4). The AI values were closely linked to the generation and accumulation of chemicals, and the PI values were associated with the removal characteristics of chemicals in the purification treatment process.
The results showed that metal compounds (Ba, Sb, Be, Ti, and V) were easily removed in the DWTPs. Ion exchange technology and adsorption are commonly used for the intensive purification of drinking water, thus cationic metal compounds are easily removed during the treatment processes [26]. Certain organic compounds, including acrolein, atrazine, benzene, formaldehyde, microcystin-LR, polychlorinated biphenyls, toluene, xylene, and 2,4,6-trinitrophenol are also easily removed in the purification processes. These substances are easily transformed, degraded, or removed by different processes, including adsorption, microbial action, disinfection, and the use of ozone and associated oxidation processes [19,20,45,46].
Nevertheless, certain volatile halohydrocarbons, including 1,2-dichloroethane, carbon tetrachloride, trichloromethane, and some benzenecontaining compounds including 1,2-dichlorobenzene, 2,4-dinitrotoluene, nitrobenzene, trichlorobenzene, dibutyl phthalate, and dioctyl phthalate were difficult to remove via the treatment processes. Especially, chlorinecontaining compounds may be generated or produced due to chlorine disinfection during the treatment process [47][48][49]. Benzene-containing compounds usually present good stability with refractory biological properties. Certain nitro-containing compounds are also difficult to be removed with adsorption or oxidation processes via the purification process [50,51]. Trichloroacetaldehyde, (di(2-ethylhexyl)adipate), Ni, B, acrylamide, and acrylonitrile were also accumulated in the effluent. Free radical substitution reactions easily occur during chlorine or ozone disinfection, which can explain the higher concentrations of trichloroacetaldehyde, trichloromethane, and acrylamide in the effluent [52,53]. Acrylamide hurts human reproductive organs and neurological systems and it is classified as a 2A carcinogen by the IARC [39,54]. Acrylamide was concentrated in the effluent because (1) the coagulation flocculant (polyacrylamide) commonly used in the treatment process contained acrylamide and acrylonitrile; and (2) acrylamide could also be produced from acrylonitrile with oxidation processes. Compared with the other compounds, dibutyl phthalate, dioctyl phthalate, and di(2-ethylhexyl)adipate are stable and less polar, which render the removal of those pollutants. The DBPs, usually associated with cancer, pose a serious threat to human health through long-term drinking exposure [55,56]. The results illustrated that the concentration changes of chemical compounds in the effluent were linked with their occurrence in the influent. These chemical by-products could be generated through synthesis, transformation, and degradation owing to biochemical or chemical reactions that occurred during the purification and disinfection processes [57,58].

Risk assessment of chemical compounds
The occurrence and concentration of the respective compounds reflected the environmental impact of the raw water. However, the concentrations of the chemical compounds in the raw water changed during the treatment processes, which altered the concentrations of compounds in the effluent. Figure 5 illustrates that the HI and CR values of detected 47 chemical compounds. The RFD and SF values used to calculate HI and CR values were also presented in Additional file 1: Table S6.
When HI > 1.00, non-carcinogenic effects were more likely to occur, while HI < 1.00 indicated no significant risk of non-carcinogenic effects on human health for lifetime exposure. The HI values of acrolein, microcystin-LR, antimony and titanium ranged from 5.7 × 10 -4 -2.6, 2.5 × 10 -4 -63.5, 3.6 × 10 -2 -1.6 and 0.5-4.8, respectively, suggesting that a higher HI value increased the occurrence of non-carcinogenic effects [26]. The highest HI values of microcystin-LR occurred in the source water, which illustrated that the concentration of microcystin-LR in the source water should attach much attention. As previously reported, acrolein can cause cellular gene mutation, reduce cell repairability, and harm the retina [59]. Long-time drinking exposure to microcystin-LR can impair the functions of colorectal and liver tissues [60,61]. An upper limit concentration of microcystin-LR (1 µg/L) in the drinking water is recommended by WHO [62]. In Ain Zada, the concentrations of microcystin-LR were found in the dam range from 19.6 µg/L in raw water to 6.3 µg/L in drinking water [63]. Wang et al. [64] have shown that Oliveira's survey. The preferable removal performance of microcystin-LR is obtained in the DWTPs in the Amazon River basin, which is consistent with this study. Of note, the maximum 0.011 µg/L of microcystin-LR in the treated water was found in this study. Due to great removal performance for microcystin-LR in the DWTPs, the potantial hazard was effectively controlled. Antimony is one of the most concerning global toxic metals, with a maximum concentration of 22.9 µg/L in the influent and 12.5 µg/L in the effluent. The health risk of these compounds was assessed using the IARC carcinogenicity classification. The IARC carcinogenicity classification for respective compounds was presented in Additional file 1: Table S6. Chloral, styrene, and tetrachlorobenzene have been classified in Group 2A by the IARC, indicating that they are likely carcinogenic to humans. Boron, 1,2-dichlorobenzene, xylene, toluene, and acrolein are listed in Group 3, showing that they are not carcinogenic to humans.
To explore the carcinogenicity for chemicals, the evaluation of CR values in Fig. 5 provided more information. The CR values of 16 chemical compounds were not calculated due to missing SF values. Considering the acceptable range of non-carcinogenic risk (10 -4 -10 -6 ) defined by the USEPA, the CR values of 23 chemical compounds were lower than 10 −4 in the effluent, demonstrating that the carcinogenic risk of these compounds was acceptable and the human health risk was very low over a lifetime of exposure. In contrast, eight chemical compounds exhibited high CR values, particularly Ba (2.4 × 10 -4 − 6.0 × 10 -2 ), Mo (1.9 × 10 -4 -2.4 × 10 -4 ) and Ni (2.3 × 10 -4 -7.5 × 10 -3 ). Metal compounds can easily bioaccumulate in the human body, which should be the subject of further investigations. Barium exhibited a relatively low cancer risk. However, it demonstrated one of the highest potential carcinogenic risk for human health in this study due to its high concentration, followed by Mo and Ni, beryllium, formaldehyde, trichloroethylene, vinyl chloride, benzene, and PCBs. These chemicals are classified as Group 1 carcinogens by the IARC, which are carcinogenic to human health even at low concentrations on the order of ng/L, as reported by Li et al. [66]. Although these chemical compounds were at low concentrations, high toxicity of chemical compounds can still pose risk to human health. For example, formaldehyde has been proven to be related to leukemia and is widely considered as one of the main factors affecting the human hematopoietic system. The increasing number of private cars, as well as building and decorative materials, has intensified formaldehyde discharge, which threatens the ecosystem and water resource cycle [67,68]. Therefore, the carcinogenic risk factor was affected by both the concentration and carcinogenicity of the chemical compounds. Figure 6 displayed a profile map of the chemical compounds in the influent and effluent. The screening of PCCs was first dependent on the rank of CR values, then the classification of IARC and HI values. Given the importance of carcinogenic risk on human health, the classification of IARC was secondly highlighted when the SF values of chemicals were not found. Based on the above-mentioned criterion, 41 chemical compounds, except for 1,2-dichlorobenzene, toluene, xylene, Fig. 6 Heat map of the priority chemical compounds. Green dot of "No" was no carcinogenic risk. Blank in the CR column was no valid values, which was due to the missing values of SF. The sequence of criteria in the rank assignment method was carcinogenic risk, then followed by classification of carcinogenic risk based on IARC with no SF. If the pollutant concentration was in high level, resulting in potential hazard, HI was the priority, followed by concentration level and AI heptachlor epoxide, 2,4,6-trinitrophenol, and chloroprene were considered as PCCs. The top eight chemical compounds (Sb, Ba, Mo, Ni, acrylamide, 1,2-dichloroethane, trichloromethane, and acrylonitrile) demonstrated a high carcinogenic risk connected to long-term drinking exposure. Tetrachloroethylene, 1,2-dichloroethylene, hexachlorobenzene, 1,4-dichlorobenzene, trichlorobenzene, 2,4-dinitrotoluene, benzo(a)pyrene and di (2-ethylhexyl)adipate demonstrated no carcinogenic risk in this study. The HI values of formaldehyde and acrolein were high, indicating that they were a potential health hazard and should be monitored closely. Removing 1,2-dichlorobenzene via treatment processes is challenging, and this compound can even be generated during the chlorine disinfection process through free radical reactions [13,58].

Multiphasic evaluation of PCCs
Comprehensive assessments, including the evaluation of treatment processes through AI values, should be accounted for the screening of prior pollutants, which can promote the drinking water supply sector to attach importance to purification technologies. Non-carcinogenic B is harmful to human health at a high concentration, even if it is only detected in trace amounts in the human body. Barium, B, and V are not included in the PCCs list of both the United States and China [69]. However, these substances were detected at relatively high carcinogenic risk or potential hazard, indicating that they should be monitored. Given the scientific management of chemical compounds and the development of environmental sustainability, we introduced the concentrations of substances to the evaluation method. Dibutyl phthalate and di(2-ethylhexyl) phthalate are two common plasticizers for microplastics that have attracted negligible attention in previous studies. These substances and their metabolites have been proven to influence the endocrine system of the human body [70][71][72]. Due to its high AI values, the safety of microplastics will become the future focus and attract much attention.

Management suggestions for PCCs
The above-mentioned results implied that the multiphasic assessment of chemicals by process control and health risk was comprehensive for the screening PCCs. The standard values of some chemical compounds should be re-modified, such as Mo and 1,2-dichloroethane. CR values suggested that even an acceptable concentration was lower than the standard values in the effluent, which still threatened human health. To meet the DWS, modifying the standard values is one of the most important measures. Effective steps were suggested to keep a safe drinking concentration of pollutants in the effluent, such as protecting the raw water from pollution, introducing new advanced treatment technologies, and strengthening the removal performance of the drinking water treatment processes. Among these motions, protecting raw water from pollution is an indicative premise of the water environment and ecosystem health. The specific measure including the division of water source protection zones, is primary for the management of DWS in the government sector.
The dynamics of PCCs with the above-mentioned treatment processes implied that processes in the treatment of drinking water could be of great significance for process control and sustainable management. Thus, reliable and effective techniques used to increase DWS could facilitate the optimization of the purification process in DWTPs. Improving the removal performance during the purification process and reducing the generation of DBPs by introducing new advanced treatment technologies are suggested to be explored in future research for intensifying DWS and the sustainability of human health.
Last but not least, emerging pollutants (i.e., antibiotics, endocrine-disrupting chemicals and microplastics) should also be taken into consideration in the screening of PCCs. Occurrence (concentration), the performance on process control, health exposure and carcinogenic risk via an exhaustive evaluation for screening the PCCs is necessary for strengthening the optimization of process control and management of DWS. Moreover, with the continuous development of monitoring technology and the requirement of public health, more attention should be paid to the emerging pollutants and synchronous evaluation systems.

Conclusions
In the present study, we developed a novel multiphasic evaluation by simple rank assignment analysis, which could be used for selecting PCCs by process control and health risk in drinking water. The effluent concentrations, removal performance, non-carcinogenic health hazard, classification of carcinogens and carcinogenic risk were selected as multi-process indicators. Among the 76 monitored chemicals, 47 and 44 chemical compounds were detected in the influent and effluent, respectively. The difference between raw and treated water implied that many chemical compounds could be removed during the treatment processes. By-products were generated during purification and disinfection processes through synthesis, transformation, and degradation due to chemical reactions or biochemical reactions. The assessment result illustrated that the top eight PCCs with high carcinogenic risk were highlighted. Among the detected chemical compounds, the profiles of 41 contaminants could be scientifically applied to select PCCs targets. However, some emerging contaminants (i.e., antibiotics, microplastics, and endocrine-disrupting chemicals) have not been evaluated in this study. More on-site investigations on the emerging pollutants should be carried out in the future for the human health and management of DWS.
Finally, some effective measures should be implemented to ensure drinking concentrations of chemical pollutants in the effluent safety, such as protecting the raw water from contamination, enhancing removal performance and reducing by-products by introducing new advanced treatment technologies during the purification process. Collectively, the multiphasic assessments of PCCs provided a novel method and scientific support of process control to strengthen the sustainable management of source water and DWS.
Additional file 1. Additional information about supplementary data were list in the tables.