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Abbreviation (ISO4): Prog Chem      Editor in chief: Jincai ZHAO

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Progress in Chemistry >

2024 , Vol. 36 >Issue 9: 1363 - 1379

DOI: https://doi.org/10.7536/PC240127

Review

Research Progress of Ecotoxicology of PPCP Pollutants

  • Chuanzi Gao ,
  • Haolin Liao ,
  • Yibo Wang ,
  • Yi Zheng ,
  • Chunmiao Zheng ,
  • Wenhui Qiu , *
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  • Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China
*e-mail:

Received date: 2024-01-30

  Revised date: 2024-04-04

  Online published: 2024-04-16

Supported by

National Natural Science Foundation of China(42322707)

National Natural Science Foundation of China(42077223)

National Natural Science Foundation of China(42277266)

GuangDong Basic and Applied Basic Research Foundation(2023A1515140118)

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Abstract

Pharmaceuticals and personal care products(PPCPs)are a large category of emerging pollutants that have been highly concern in recent years.the huge production and rapid consumption demand of PPCPs make them widely enter and highly exist in various environmental mediums.Due to migration,transformation and bioaccumulation,PPCPs enter the ecological environment,causing different degrees of negative impact on organisms and human bodies,thus bringing serious threats to the ecological environment and human health.in this review,we summarize the exposure sources,pathways and characteristics of current PPCPs in the environment,conclude the degradation method and pathway of PPCPs in the environment,review the main biotoxicity of PPCPs,overview the exposure concentrations and the health influences on the human body,and finally have some outlooks on the research field of ecotoxicity of PPCPs。

Contents

1 Introduction

2 Environmental exposure of PPCPs

2.1 Environment sources and migration and transform pathway of PPCPs

2.2 Environment concentration and distribution of PPCPs

3 Degradation method and mechanism of PPCPs

4 Biotoxicity of PPCPs

4.1 Acute toxicity

4.2 Neurotoxicity

4.3 Reproductive and developmental toxicity

4.4 Endocrine disruption

4.5 Immunotoxicity

4.6 Cardiovascular toxicity

4.7 Other toxicities

5 Human health risk of PPCPs

5.1 Human exposure to PPCPs

5.2 Human health risk/assessment

6 Conclusion and outlook

Key words： pharmaceuticals and personal care products (PPCPs); degradation; biotoxicity; ecotoxicity; human health risk

Cite this article

Chuanzi Gao , Haolin Liao , Yibo Wang , Yi Zheng , Chunmiao Zheng , Wenhui Qiu . Research Progress of Ecotoxicology of PPCP Pollutants[J]. Progress in Chemistry, 2024 , 36(9) : 1363 -1379 . DOI: 10.7536/PC240127

1 Introduction

Pharmaceutical and personal care products(PPCPs)is an emerging pollutant,mainly including drugs and personal care products.One is drugs,including more than 3000 kinds of analgesic and anti-inflammatory drugs,antibiotics,antibacterial drugs,beta-blockers,hormones,steroids,anticancer drugs,sedatives,antiepileptic drugs,diuretics,X-ray contrast agents,lipid regulators,caffeine,etc;The other is personal care products,such as perfume,cosmetics,sunscreen,hair dye,hair gel,soap,shampoo,sunscreen,insect repellent,preservatives and so on[1⇓⇓~4]。 Therefore,PPCPs are composed of thousands of chemicals with different chemical structures and have The potential to cause toxic effects on non-target organisms.the main classification and representative substances are shown in Figure 1[5]。 With the rapid development of the pharmaceutical and washing industry,the production and use of PPCPs In the world are growing rapidly.Taking China as an example,according to statistics,in 2012,China's drug production accounted for more than 20.0%of the total global drug production.in 2007 alone,more than 6,900 pharmaceutical companies were registered and produced more than 1,500 active drug ingredients[6]; At the same time,the rate of drug consumption in China is also quite alarming,especially the abuse of antibiotics[7]。 with the mass production and wide use of PPCPs,PPCPs and their metabolites continue to enter the environment and are widely detected in the atmosphere,dust,surface water,groundwater,drinking water,soil,sludge and other major environmental media.Usually at the nanogram and microgram levels,some of them have reached the milligram level,which has become an emerging pollutant With potential ecological risks and toxicity in the natural environment[4,8⇓~10]。 Many PPCPs exist in the environment in trace concentrations,and their components have strong biological activity,optical activity and polarity[11⇓~13]。 Since Daughton et al reported and proposed this concept in 1999,PPCPs have been regarded as a large class of environmental pollutants,and their environmental pollution status,migration and transformation,analytical treatment technology and ecotoxicological effects have been widely concerned[2]。
图1 PPCPs 的主要分类及代表物质[1⇓⇓-4]

Fig. 1 Classification of PPCPs[1⇓⇓~4]

As an important group of organic pollutants that have been closely studied in recent years,PPCPs have been reported to be ubiquitous in the global aquatic environment.PPCPs have been detected in surface water,sediment and drinking water at different concentrations in Korea,Australia,the United States,Japan,Indonesia,India,Vietnam,Brazil,Canada,Spain,China and other countries[14][15][16][17,18][19][20][20][20][21][18,22][23][24,25]。 in the face of such extensive and universal environmental exposure,extensive research has been carried out at home and abroad on the environmental pollution status,migration and transformation process,analysis and detection technology,treatment and degradation means,human exposure,risk assessment and ecotoxicological effects of PPCPs.In this paper,the exposure pathways and pollution status,degradation technologies and mechanisms,ecotoxicity and human health risks of PPCPs In the environment at home and abroad were summarized。

2 Environmental Exposure to PPCPs

the ubiquity of PPCPs in environmental media has led to close attention and research on their ecological and environmental toxicity effects and their impact on human health.It is very important to clarify the environmental sources and human exposure pathways of PPCPs,and to explore their pollution concentrations and distribution characteristics in the environment for the study of their ecological and environmental toxicity effects and human health impacts。

2.1 Environmental Sources and Migration and Transformation Pathways of PPCPs

Previous studies on the sources of PPCPs have provided information on their environmental load,while studies on the entry of these compounds into ecosystems and their environmental fate have mostly been conducted in areas with high population density and abundant ecological resources.Individual households,production sites,domestic waste dumping,large farms and agricultural irrigation,sewage treatment plants and medical institutions are considered to be the main sources and ways of PPCPs entering different environmental systems[26]。 It is Generally believed that human or animal drugs are one of the most important sources of PPCPs.generally speaking,after biological ingestion,a large part of drugs leave the human body or animal organisms through metabolic reactions,and are brought into sewage or sludge through urine or feces,so sewage utilization,agricultural discharge,domestic sewage and medical wastewater discharge are the main ways for drugs to enter the soil and water environment[27]。 Many studies at home and abroad have shown that the main sources of PPCPs in the environment are the discharge of wastewater and sewage treatment facilities(including hospital wastewater)and agricultural irrigation applications[3,28⇓~30]。 At the same time,PPCPs production centers and human daily activities are also the direct sources of PPCPs environmental pollution.PPCPs are discharged into sewage through wastewater discharge or daily bathing,and they are removed by sewage treatment plants through municipal pipelines.Undegraded PPCPs will enter surface water or infiltrate into underground water sources[11]。 Domestic waste and pharmaceutical residue contain a large number of discarded personal care products,expired drugs and production residues,which also become an important link for PPCPs to enter the environmental system。
When PPCPs enter the environment,a series of migration and transformation behaviors occur according to the characteristics of different substances and environmental characteristics.It was found that PPCPs in the water body precipitated to the bottom of the water body after natural separation through physical and chemical processes,and had a layered distribution law[11]。 PPCPs in soil can also be absorbed by human body through the enrichment of crops[30,31]。 Chen et al.and Yu et al.Found that PPCPs with strong adsorbability,such as triclosan and octylphenol,can be adsorbed and accumulated in the soil through the surface of soil particles after entering the soil through reclaimed irrigation water or organic sludge used as fertilizer,while some PPCPs with poor absorption,volatilization or degradation in soil water will infiltrate into groundwater except for a small part absorbed by plants[32][33][32,33][34]。 At the same time,PPCPs can enter the atmosphere by spraying reclaimed water or by receiving volatilization from soil to form aerosols[35,36]。 Precipitation can also aggravate the pollution of PPCPs in the environment,and atmospheric deposition and urban surface runoff also play a certain role in the migration and transformation of PPCPs in the environment,spreading them farther and wider[37]。 To sum up,the main environmental sources and exposure pathways of PPCPs are shown in Figure 2。
图2 PPCPs的主要环境来源和迁移转化途径

Fig. 2 Main source and migration and transform path of PPCPs

2.2 Environmental Concentration and Distribution Characteristics of PPCPs

Mass production and rapid consumption demand promote the prevalence of PPCPs in various environmental media,and the detected types and concentrations of PPCPs are shown in Table 1.the detection of PPCPs in aquatic environment is the most reported,and different concentrations of PPCPs have been reported in aquatic environment all over the world[38]。 Kasprzyk-Hordern et al.Found approximately 43 personal care products in surface waters from different countries,including China,India,Japan,Australia,France,and Germany,at concentrations ranging from not detected(ND)to 1 293 000 ng/L,depending on the specific compound,with 4-tert-octylphenol(OP)and chlorodiphenol(PCMX)being the two PPCPs with the highest reported concentrations of 1 293 000 and 358 000 ng/L,respectively[8][4,8]。 Sulfamethoxazole has been reported to be detected in surface water,seawater,sewage and sediments in China,Sri Lanka,Italy,the United States,Greece,Northern Europe,Spain and other countries/regions,with concentrations ranging from ND to 934 ng/L,with the highest concentration in surface water in Sri Lanka[25,39⇓⇓⇓⇓⇓⇓⇓⇓⇓~49]。 PPCPs are also widely Detected in aquatic organisms.For example,Zhao et al.detected Parabens in seawater and aquatic organisms(fish and shellfish)in The Pearl River Estuary in southern China in 2019.It was found that the concentrations of Parabens and their metabolites in seawater ranged from ND to 1620 ng/L,and the concentrations in shellfish were higher than those in fish.the highest concentrations were found in clam,rainbow cherry clam and ivory snail,which were 81,90,7130 and 2440 ng/G,respectively[25]。
表1 Environmental exposure concentration of PPCPs

Table 1 Concentrations of PPCPs in the environment

Sample classification Medium Location Concentration of PPCPs a Ref
Aquatic environment Surface water China Sulfamethoxazole (ND b~57.76 ng/L);Sulfamethoxazole (28.34 ng/L, median);Ofloxacin (114 ng/L, median);Norfloxacin (152 ng/L, median);Erythromycin (34 ng/L, median); Erythromycin (0~722.04 ng/L);Roxithromycin (53 ng/L, median); Roxithromycin (3.63 ng/L, max); Tetracycline (113.89 ng/L, max);Tetracycline (0~9.74 ng/L) 39,40
56,57
UK 4-tert-octylphenol (ND~1 293 000 ng/L); Chloroxylenol (ND~358000 ng/L) 8
Canada Galaxolide fragrance(HHCB) (0.031 ng/m3, mean) 58
Sri Lanka Sulfamethoxazole (ND~934 ng/L) 41
Italy Sulfamethoxazole (0.7~16 ng/L) 42
USA Sulfamethoxazole (77.7 ng/L, max) 43
Underground water China Sulfamethoxazole (ND~91 ng/L); Sulfamethazine (ND~269.7 ng/L); SMX (ND~14.2 ng/L) Sulfadiazine (29.9 ng/L, mean); Ciprofloxzcin (4~9.68 ng/L); Ciprofloxzcin (0.82 ng/L, mean) Tetracycline (2.26~9.51 ng/L); Erythromycin (1.47~13.8 ng/L); Norfloxacin (4.74~52.6 ng/L) Oxytetracycline (1.1~7.24 ng/L) 44
59
60
USA Lincomycin (0.32 ng/L, max); Sulfamethoxazole (1.11 ng/L, max) 45
Spain Sulfamethoxazole (23.4 ng/L, mean); Sulfadiazine (11.62 ng/L, mean) 46
Sediment China Sulfamethoxazole (1.27~688.59 ng/L); Sulfamethoxazole (0~11.3 ng/L); Sulfadiazine (0~0.41 ng/L); Oxytetracycline (0~8.73 ng/L); Ciprofloxzcin (0~15.33 ng/L); Ofloxacin (0.9~18.27 ng/L); Erythromycin (0.15-3.96 ng/L) 39,47
Pore water China Erythromycin (29.9 ng/L, mean); Lincomycin (20.2 ng/L, mean); Oxytetracycline (47.8 ng/L, mean); Ofloxacin (33.6 ng/L, mean) 61,62
Rainwater USA Ciprofloxzcin (10.3 ng/L, max); enrofloxacin (2.97 ng/L, max) 63
Seawater China Sulfachloropyridazine (0.2 ng/L, mean); Sulfadimethoxine (1.8 ng/L, mean); Sulfamethoxazole (7.7 ng/L, mean); Trimethoprim (7.2 ng/L, mean); Azithromycin (4.8 ng/L, mean); Clarithromycin (3 ng/L, mean); Erythromycin-H2O (0.5 ng/L, mean); Roxithromycin (2.7 ng/L, mean); Enoxacin (3.3 ng/L, mean); Enrofloxacin (7.2 ng/L, mean); Norfloxacin (0.7 ng/L, mean); Ofloxacin (25.4 ng/L, mean); Chloramphenicol (2.6 ng/L, mean); Florfenicol (7.7 ng/L, mean); Thiamphenicol (3.7 ng/L, mean); Penicillin G (0.4 ng/L, mean); Bisphenol analogues (206 ng/g, median); Parabens (13 ng/g, median); paraben metabolites (686 ng/g, median) 25,64
Northern Europe Sulfamethoxazole (42 ng/L, median); Clarithromycin (14 ng/L, median) 48
Greece Sulfamethoxazole (11 ng/L, median); Clarithromycin (16 ng/L, median) 48
Italy Sulfamethoxazole (7.2 ng/L, median); Clarithromycin (8.5 ng/L, median) 48
Wastewater Canada Galaxolide fragrance(HHCB) (1000~1800 ng/L); Toxalide fragrance(AHTN) (140~270 ng/L) 58
Greece Ibuprofen (7.0~8.9 μg/L) 65
Japan Ibuprofen (816±815 μg/L, mean） 66
USA Acetaminophen (0.006 μg/L, median); Benzophenone-3 (0.2 μg/L, median); Bisphenol A (0.12 μg/L, median); Caffeine (0.053 μg/L, median); Carbamazepine (0.08 μg/L, median); Codeine (0.139 μg/L, median); Diltiazem (0.049 μg/L, median); Galaxolide fragrance(HHCB) (0.28 μg/L, median); N,N-diethyl-m-toluamide (DEET) (0.18 μg/L, median); Sulfamethoxazole (0.15 μg/L, median); Toxalide fragrance (AHTN) (1 μg/L, median); Triclosan (0.25 μg/L, median); Trimethoprim (0.038 μg/L, median); 1,4-dichlorobenzene (0.110 μg/L, median) 49
Aquatic organism China parabens and metabolites (8190 ng/g, max); parabens and metabolites (1135 ng/g, max) 25
Air Indoor air Canada Galaxolide fragrance (HHCB) (0.30~18 ng/m3); Toxalide fragrance (AHTN) (0.09-17 ng/m3) 58
Outdoor air Canada Galaxolide fragrance (HHCB) (0.99 ng/m3, median); Toxalide fragrance (AHTN) (0.22 ng/m3, median) 58
Indoor dust China Galaxolide fragrance (HHCB) (1.87~577 ng/g, median:31.4 ng/g); Musk ketone (10.4 ng/g, median); Toxalide fragrance (AHTN) (11.7 ng/g, median); Parabens (418 ng/g, GMc); siloxanes (21.5~21 000 ng/g, mean:1540±2850 ng/g) 9,50,67
Spain Musk ketone (14.4~2300 ng/g, median:111 ng/g); Musk xylene (133 ng/g, median) 68
South Korea Parabens (2320 ng/g, GM) 9
Japan Parabens (2300 ng/g, GM) 9
USA Parabens (1390 ng/g, GM) 9
Germany Galaxolide fragrance (HHCB); (700 ng/g, median); Toxalide fragrance (AHTN); (900 ng/g, median) 69
Soil Soil China Carbamazepine (1.8 μg/kg,mean); Gemfibrozil (0.9 μg/kg, mean);Tetracycline (19.9 μg/kg, mean); Triclosan (1.8 μg/kg), mean ; Bisphenol A (3.4 μg/kg, mean) ; Diethyl Phthalate (0.178 μg/kg, mean) 10,51
USA Ibuprofen (318.5 μg/kg, mean); Estriol (7.73 μg/kg, mean); Clofibric Acid (4.27 μg/kg, mean); Naproxen (23.79 μg/kg, mean); Triclosan (8.16 μg/kg, mean); Bisphenol A (31 μg/kg, mean) 52⇓~54

a,the concentration without special annotation means the range;b,ND=not detected;c,GM=geometric mean。

in addition to aquatic environments,PPCPs have been found in a variety of other media.Although PPCPs have low volatility and limited opportunities to participate in the atmospheric environment,some PPCPs can still be found in indoor dust or air.For example,siloxanes,which are widely used in personal care products and other consumer products,have been found in indoor dust samples at total concentrations ranging from 21.5 to 21 000 ng/G[50]。 Wang et al.Have also analyzed the chemical substances contained in indoor dust in the United States,China,Japan and South Korea,and the results showed that parabens with a content of up to 110800 ng/G could be detected,and the geometric mean concentrations from high to low were South Korea(2320 ng/G)>Japan(2300 ng/G)>the United States(1390 ng/G)>China(418 ng/G)[9]。 Galaxolide musk(HHCB)and Toxalid musk(AHTN)have also been found in indoor and outdoor air in Canada at concentrations ranging from 0.09~18 ng/m3.At the same time,a variety of PPCPs existed in the soils of China and the United States,with the median concentration ranging from 0.178 to 318.5μg/kg,and the highest content of ibuprofen was 318.5μg/kg[10,32,51⇓⇓~54]。 From previous studies at home and abroad,it can be seen that the detection of PPCPs in the environment is highly dependent on geographical spatial and temporal factors,regional economy,availability and consumption of PPCPs,wastewater treatment facilities and local climate conditions.Therefore,global comparisons of PPCP levels in terms of target compounds and detected concentrations will vary widely[1]。
in recent years,with the development of economy and the growth of population,China has become a big producer and consumer of PPCPs,which also leads to the widespread existence of PPCPs in various environmental media in China[55]。 According to the incomplete statistics of Katsikaros et al in 2021,Asia is the region with the highest detection of PPCPs in aquatic environment(various water bodies,sediments,biota)reported in the past 10 years,among which China is one of the Asian countries with the largest contribution,followed by India and Sri Lanka[14]。 Therefore,the environmental and biological effects caused by the extensive exposure of PPCPs in China's environment should be paid attention to。

3 Degradation Technology and Mechanism of PPCPs

the extensive use of PPCPs leads to their continuous input into the environment,resulting in the phenomenon of"pseudo-persistence",so it is necessary to study their degradation technology and mechanism.Previous studies on PPCPs degradation technologies have focused on aquatic environments.At present,hydrolysis,photolysis,biodegradation(plant absorption degradation and microbial degradation)and other chemical degradation are the common degradation methods in the environment,and the degradation process is also affected by pH,temperature,coexisting ions,etc.,and the products generated in various degradation processes are also different[70,71]。 Among them,antibiotics are mainly photodegraded In water environment;Ibuprofen,iopromide and caffeine are more susceptible to biodegradation;However,the probability of hydrolysis of PPCPs in nature is low,and esters,sulfonamides and amides are the most common functional groups that are easily hydrolyzed.in addition,tetracyclines are also hydrolyzed because they are adsorbed into sediments[70,72]。 There are many degradation mechanisms of PPCPs,including hydroxylation,formylation,desulfonation,cyclization,deamination,dehalogenation,decarboxylation,redox,etc[70]。
Hydrolysis is an important way for the elimination or concentration reduction of PPCPs in aqueous environment,which is essentially a nucleophilic substitution reaction,that is,the nucleophilic group(hydroxide ion or water molecule)attacks the electrophilic group in the compound and replaces the strong electron-withdrawing group with a negative tendency[71]。 For example,Gao Xuequan found that penicillin G and amoxicillin were degraded by water through intramolecular nucleophilic attack of side chains onβ-lactam carbonyl,C-N bond cleavage and ring opening,while the main hydrolysis products of sulfonamide antibiotics were sulfanilic acid,aniline and sulfanilamide(Fig.3)[73]。 Huang et al.Found that the hydrolysis of tetracycline is an important transformation mode[74]。 Previous studies have shown that pH can affect the hydrolysis rate and hydrolysis products,because different pH values can produce different chemical reactions with the target PPCPs[75⇓~77]。 For example,sulfonamide and macrolide antibiotics have low activity and slow hydrolysis rate at pH=7,whileβ-lactone antibiotics degrade rapidly at almost any pH,while chlortetracycline has a significantly higher hydrolysis rate at alkaline and neutral conditions than at acidic conditions[76,77][78]; tylosin A can be hydrolyzed into tylosin B under acidic conditions,while tylosin-A-butyraldehyde and some polar decomposition products can be produced under neutral and alkaline conditions[72,75]。 at the same time,temperature is also an important factor affecting the hydrolysis of PPCPs.Studies have shown that the hydrolysis rate of chlortetracycline at high temperature(70℃)is much higher than that at low temperature(20℃).the highest hydrolysis rate of sulfonamides can reach 41%at 70℃,while the hydrolysis rate at 20℃is greatly reduced[78][79]。
图3 磺胺甲噁唑的降解途径及产物[73,80]

Fig. 3 Degradation pathway and products of sulfamethoxazole[73,80]

Photodegradation is also one of the main degradation pathways of PPCPs in the environment,and its mechanism is mainly due to the absorption of light energy by molecules into excited States,which triggers various reactions[81]。 photodegradation can be divided into direct photolysis and indirect photolysis.PPCPs with light-absorbing groups can absorb light energy to degrade directly;PPCPs compounds without light-absorbing groups need to obtain energy by receiving light energy absorbed by other substances in the environment,so that indirect Photodegradation reactions occur.For example,when acyclovir is added to the catalyst to absorb light energy,it undergoes electron transition to generate electron-hole pairs,thus oxidizing surface pollutants,or oxidizing adsorbed hydroxyl radicals to generate strong oxidizing hydroxyl radicals[82]。 After the addition of Fe-ZnS@TiO2/nickel foam photocatalytic system,sulfamethoxazole can be degraded into a variety of intermediate or final products through S—C bond or S—N bond cleavage,hydroxylation and oxidation(Fig.3);Diclofenac undergoes cyclization,decarboxylation,dechlorination,and direct hydroxylation to yield a variety of intermediate and final products(Figure 4 )[80]。
图4 双氯芬酸的降解途径及产物[80,83⇓~85]

Fig. 4 Degradation pathway and products of diclofenac[80,83⇓~85]

Biodegradation of PPCPs is a common degradation mode,which can include plant uptake degradation and microbial degradation.plant uptake and degradation generally refers to the reduction of PPCPs in the environment through the process of plant uptake,enrichment and transformation.A number of studies have shown that PPCPs can be adsorbed by roots,driven by transpiration,across the bilayer of the cell membrane into the cell tissue fluid,and then transported to other tissues and organs and accumulated in different tissues and organs,and ultimately achieve the removal of PPCPs[86,87]。 Zhang et al.Also found that Scirpus tabernaemontani could absorb caffeine and clofibric acid through roots and transport them to buds and other tissues for further absorption[88]; the planting of cattail can increase the removal rate of ibuprofen by 33%and the removal rate of naproxen by nearly 2 times in the constructed wetland[89]。 In addition,microbial degradation means that microorganisms change the chemical structure of PPCPs through a series of biochemical reactions under aerobic or anoxic conditions,and finally achieve the purpose of degradation and removal[71]。 For example,the biodegradation of ketoprofen is partially mineralized under aerobic conditions,along the pathway of biphenyl and diphenyl ether[90]; The biodegradation of caffeine is mainly carried out by demethylation[91]。 the efficiency of microbial degradation is largely affected by the active substance,and the degradation results brought by single strain and mixed strains are different.For example,Pseudomonas species from contaminated areas degrade carbamazepine into a variety of different products through enzymatic(cytochrome)decomposition(Figure 5),with a degradation rate of 47%;However,denitrifying bacteria PR1 successfully degraded sulfamethoxypyridine,sulfamethoxazine,sulfathiazole,sulfasalazine,sulfamoxazine and sulfapyridine to 98%,100%,47%,98%,48%and 100%within 56 H of remediation,respectively[92]。 It has also been found that diclofenac can be degraded to a variety of different products by single or mixed strains(Figure 4)[83⇓~85]。
图5 卡马西平的降解途径及产物[92]

Fig. 5 Degradation pathway and products of carbamazepine[92]

4 Biological Toxicity Effects of PPCPs

After entering the environment,PPCPs can persist in the aquatic environment due to their physical and chemical properties,while traditional water treatment methods can not effectively remove these compounds,which can bring a certain degree of biological toxicity to aquatic organisms and humans through migration,transformation and bioaccumulation.PPCPs can produce toxic effects on organisms through a variety of toxic pathways in organisms.For example,PPCPs can promote the production of excessive peroxy ROS to damage biomolecular components such as RNA,DNA and protein,induce lipid peroxidation,form oxidative stress,and then cause overall damage to the body[93,94]; Second,PPCPs are associated with ER stress,inhibiting cytochrome P450s(CYPs)present in the ER and mitochondria,which contain numerous enzymes critical for drug biotransformation,thereby disrupting the entire biotransformation system[4]。 Overall,the typical toxicities of PPCPs can be summarized as acute toxicity,chronic toxicity,neurotoxicity,reproductive and developmental toxicity,endocrine disruption,immunotoxicity,cardiovascular toxicity and other toxicities(Figure 6),while different compounds have different types and degrees of biological toxicity(Table 2)。
图6 PPCPs的主要毒性路径及分类

Fig. 6 Main toxicity pathway and classification of PPCPs

表2 Chronic biological toxicity of PPCP

Table 2 Chronic biotoxicity of PPCPs

Toxicity classification Organism Species PPCPs chemicals Effective concentration Toxicity effect Ref
Neurotoxicity Mammal Mice Triclosan 1000 mg/kg, 2000 mg/kg,
4000 mg/kg		 Causes behavioral disorders in mice 140
Mice Acetaminophen 30 + 30 mg/kg, 4 h apart Decline in memory, learning ability and cognitive flexibility 94
Fish Gambusia affinis Fluoxetine 0.05~5 μg/L Sleeping time expanded 141
Gobiocypris rarus Alprazolam 10 ng/L Disturb GPC、CHOP、Met et al. neurosubstances 100
Gobiocypris rarus Lorazepam 100 ng/L Disturb the Cho、5-HT、Trp、5-HIAA et al. neurosubstances
Invertebrate Clams Caffeine 50 μg/L AChE activity declines 56% 101
Carbamazepine 0. 1 μg/L AChE activity declines 53%
Reproductive toxicity Mammal Rat 17β-Estradiol 10~50 mg/kg (E2) Centrilobular hepatocellular hypertrophy: diffuse Pituitary hyperplasia; breast hyperplasia: increased number of cystic follicles in the ovaries, endometrial and endometrial glandular hypertrophy 110
Rat 17β-Estradiol ng/kg~mg/kg (E3, E2) Uterine response: increased uterine weight due to water retention and cell proliferation 111
Fish Juvenile 17β-Estradiol 0.05~0.5 mg/kg (E2) Affects spawning 112
Oryzias latipes Diclofenac 10 mg/L Reduced egg hatchability 142
Oryzias latipes Ibuprofen 0.0001 mg/L Reduce hatchability and yolk proteins content 143
Dicentrarchus 17β-Estradiol 10 mg/kg (E2) Affect reproduction 113
Pimephales
Promelas		 Fadrozole 2 μg/L 21-day exposure Decline in reproduction rate 144
Pimephales promelas Fluoxetine 1 μg/L Impacted mating behavior, specifically nest building and defending in male fish 145
Invertebrate Daphnia magna Propranolol 0.128 mg/L Reduced fecundity and reproductive rate 146
Lumbriculus variegatus 3-benzylidene-camphor 44.2 μmol/L Substantial reduction in fertility and significant increase in mortality 114
Chironomus riparius Carbamazepine 0.625 mg/kg 28-day exposure Inhibit pupa to be formed 109
Developmental toxicity Plant Lactuca sativa Erythromycin 0.1~300 mg/kg Inhibition of bud development 147
Brassica rapa chinensis Chlortetracycline 2.5~20 mg/kg Inhibition of bud development 148
Oenanthe javanica Oxytetracycline 0.5~10 mg/kg Inhibition of plant height 149
Solanum lycopersicum Sulfadiazine 0.1~300 mg/kg Inhibition of bud development 147
Fish Danio rerio Musk xylene 33 μg/L Significant impact in early life stages 150
Danio rerio Amitriptyline 0.001~1000 μg/L Inhibition of growth and development; alteration of ACTH concentration level; oxidative stress 151
Danio rerio Muscone 33 μg/L Reduced fish mass and length of females and reduced fecundity 107
Pimephales promelas β-blocker Propranolol 3.4 mg/L Reduced body weight and egg hatchability 152
Algae Scenedesmus obliquus NSAIDs (Ibuprofen, aspirin, ketoprofen) 107.91, 103.05, and
4.03 mg/L,
respectively		 Inhibition of algal growth 153
Chlorella pyrenoidosa Diclofenac >100 mg/L Alteration of chlorophyll a, lipid accumulation, and antioxidant enzyme function, thereby affecting growth 154
amphibian species Bufo americanus. Acetaminophen 100 μg/L 28-day exposure Survival rates influenced 155
Rana pipiens Acetaminophen 1 μg/L 14-day of exposure Behavior affected
Endocrine disruption Invertebrate Mytilus spp. Gemfibrozil 1000 μg/L Endocrine disruption 121
Reptilia Trachemys scripta Estradiol 1 μg/g Induction of VTG (vitellogenin) 156
Fish Oryzias latipes Fluoxetine (100~500 μg/L) 28-day exposure Affects estradiol concentrations in fish 157
Mammal Rat Benzophenone 2（BP-2） 1000 mg/kg Causes anti-thyroid effects in the body goiter 120
Immunotoxicity Fish Danio rerio Enrofloxacin 10 μg/L, 100 μg/L Significant reductions in macrophage and neutrophil populations and biomarkers of immunosuppressive effects in zebrafish 122
Danio rerio Tetracycline 100 μg/L Neutrophil counts were significantly reduced in offspring zebrafish 123
\ \ Butylated hydroxytoluene \ Often causes skin, eye, and lung irritation and toxic to immune system 124
Invertebrate Clams Fluoxetine 1 μg/L, 5 μg/L Influenced immunological parameters and Acetylcholinesterase (AChE) decreased significantly 125
Cardiovascular
toxicity
 Mammal Human Caffeine \ Correlation with cardiovascular disease (CVD) 126
Beagle dogs Sibutramine 30 mg/kg Increasing Heart Rate and Blood Pressure 128
Invertebrate Manila Clam (Venerupis philippinarum) Caffeine, ibuprofen, carbamazepine,
novobiocin		 Caffeine =15 μg/L,
Ibuprofen =10 μg/L,
Carbamazepine =1 μg/L,
Novobiocin =1 μg/L		 Decrease the blood cell viability 158
Manila Clam caffeine 15 μg/L Decreased blood cell viability 4
Fish S.trutta f.fario Water-borne diclofenac 5~50 μg/L Affects integrity of kidney and gill 129
Gasterosteus aculeatus Naproxen 299 and 1232 μg/L Increased renal hematopoietic hyperplasia 130
Other toxicity Birds Domestic fowl Diclofenac 9.8 mg/kg Showed signs of gout with deposits of urates in the kidneys, liver, heart and spleen 131
Mammal Rat Triclosan 30~250mg/kg Liposynthesis was affected, and TG levels of serum, liver, and adipose tissue were reduced 132
Rat Propranolol and atenolol 5, 10, and 20 μg/mL Induction of reactive oxygen species and mitochondrial damage to cardiac tissue 133
Rat Mesalazine 25, 50, 100 μM Triggers overproduction of mitochondrial ROS, releases cytochrome c, and causes cardiotoxic effects 134
Invertebrate Daphnia magna Indomethacin, ibuprofen 1 mg/L Reduced feeding rate and modulated activities of key enzymes like Alkalineand acid phosphatases, lipase, peptidase, β-galactosidase, and glutathione stransferase 135
Mytilus galloprovincialis Propranolol, Acetaminophen Propranolol (11 microg/L),
Acetaminophen (23 and 403 μg/L)		 Modulates antioxidant enzyme activity and induces oxidative stress 136
Mytilus galloprovincialis Carbamazepine, ibuprofen,
fluoxetine		 0.05~500 ng/g Regulates enzyme activities indicative of oxidative stress and DNA damage 102
Mytilus galloprovincialis Ibuprofen 250 ng/L Affects the arachidonic pathway 137
Algae Chlorella vulgaris, Microcystis
aeruginosa		 Ser-HCL 25~200 μg/L Altered the composition of photosynthetic community. 138
Chlorella vulgaris, Desmodesmus armatus. Bisoprolol and Ketoprofen 100 mg/L Regulation of antioxidant enzyme activity, cell morphology, chlorophyll content 139

4.1 Acute toxicity

in the acute toxicity study of PPCPs In aquatic organisms,among the compounds studied,dextropropoxybenzene,sertraline,thionazine and diphenhydramine were considered to have relatively greater acute toxicity to the algae,invertebrates and fish populations studied[95]。 It was also found that bacteria,fish and amphibians were relatively insensitive to the acute toxicity of analgesic drugs,while phytoplankton and invertebrates were the most sensitive[95,96]。 triclocarban,triclosan and their metabolites are often detected in algae,which have the highest abundance of plant biomass in aquatic environments.Acute toxicity studies on invertebrates,fish,amphibians,algae and plants have shown that triclosan and its derivatives are more toxic than Triclocarban[38,97]。 However,the vast majority of acute toxicity studies are based on exposure to high concentrations of reagents,which are far from the actual environmental concentrations.In general,antiarrhythmic,antidepressant,antidiabetic,antiandrogen,and synthetic estrogens do not pose a risk of acute toxicity at expected environmental concentrations[3,94]。 it is important to note that PPCPs are always present as a mixture in the environment,so even if a particular substance does not pose a risk of acute toxicity,It may become significantly toxic when combined with one or more toxic or non-toxic compounds.For example,a mixture of diclofenac,ibuprofen,naproxen,and aspirin has considerable acute toxicity to the same species,whereas none of them is toxic when used alone[98,99]。

4.2 Neurotoxicity

the concentration of PPCPs in the natural environment is very low,mostly at the trace level,which is usually not easy to cause acute toxicity,but it exists in the environment For a long time and will cause chronic toxicity to organisms through bioaccumulation(Table 2).A variety of PPCPs have been found to have neurotoxic effects.for example,exposure to the psychoactive substances alprazolam,lorazepam,codeine,and morphine is able to interfere with the neurochemicals of different neurotransmission systems of rare minnow,thereby affecting its behavior,showing neurotoxic effects[100]。 Acetaminophen at 30 mg/kg caused a decrease in both memory and learning ability in mice[94]。 Caffeine(50μg/L)and carbamazepine(0.1μg/L)had neurotoxic effects on clams,the lowest concentration had a significant induction of acetylcholinesterase(AChE)(p<0.05),and the higher concentration had a significant reduction of AChE activity[101]。 In addition,ethinylestradiol（EE2）w as widely used for contraception and is considered to be a neuroendocrine disruptor in invertebrates,and studies have found that sea worms exposed to EE2（only environmental concentrations),propranolol,ibuprofen,and fluoxetine can induce neurotoxicity[102]。

4.3 Reproductive and developmental toxicity

Many antibiotics,hormones,fragrances,sunscreen products,painkillers,and antidepressants have been found to have significant reproductive and developmental toxicity.Artificial musks are the most investigated personal care products due to their strong bioaccumulation tendency in aquatic organisms[55,97,103,104]。 Of these,polycyclic musks are the most dangerous because they accumulate not only in fish and mussels,but also in human breast milk[105,106]。 Through 8 weeks of exposure to zebrafish,it was found that muscone could reduce the body weight and body length of female zebrafish,and weaken the reproductive capacity,and the lowest toxic effect concentration was 33μg/L[107]。 Long-term exposure to antibiotics can have potential reproductive effects on pregnant female zebrafish.Qiu et al.Conducted exposure experiments on female zebrafish to 15 common antibiotics,and found that the mixed toxicity of the studied antibiotics caused significant growth disorders in the offspring of zebrafish[108]。 Aguirre-Mart Martínez et al.Found that ibuprofen,carbamazepine and neobiotin caused DNA damage and genotoxic effects on cuttlefish(p<0.05),and that carbamazepine inhibited pupal formation at 0.625 mg/kg for 28 days[101][109]。 17β-estradiol has also been found to be reproductively toxic to both rats and fish,affecting spawning,uterine reactions,and uterine injury,while sunscreen products reduce reproductive rates and increase mortality in benthic invertebrates after prolonged exposure[110⇓⇓~113][114]。

4.4 Endocrine disruption

some PPCPs have the characteristics of endocrine disruption,such as hormones,medicinal progesterone,Some antibiotics and cosmetics,which can lead to hormone disorders in the body[3,55,115]。 Many aquatic species exhibit sexual inhibition at levels of detected environmental estrogen concentrations[116,117]。 Some PPCPs have also been reported to bioaccumulate in fish,leading to feminization effects,the study noted[115]。 Sunscreen products have a tendency to bioaccumulate in aquatic organisms and have estrogenic activity due to their highly lipophilic（log Kow=3~7）and environmental stability.Some in vitro and in vivo rat-based studies have found that when ingested at high doses,some of the sunscreen components can mimic estrogen function and cause antithyroid effects of goiter in vivo[118,119][120]。 In addition,gemfibrozil,a lipid regulator,can cause significant endocrine disruption effects on mussels at 1000μg/L[121]。

4.5 Immunotoxicity

the immunotoxicity of PPCPs has been highly concerned recently.Although there is little information about its immunotoxicity or immunogenetics,the research on immunotoxicity is increasing.Many compounds have shown a certain degree of immunotoxic effects in the study.Qiu et al.Found that enrofloxacin could induce intestinal microbiota-mediated immunosuppression in zebrafish,and antibiotic tetracycline could cause transgenerational immunosuppression through NF-κB pathway[122][123]。 Butylated hydroxytoluene,which is often used as a food additive,antioxidant and flavoring,often causes skin,eye and lung irritation and is toxic to the immune system[124]。 Fluoxetine has also been found to significantly affect immune parameters and acetylcholinesterase activity in clams[125]。

4.6 Cardiovascular toxicity

Various PPCPs have also been shown to have some negative effects on the cardiovascular system.For example,caffeine,the most consumed stimulant in the world,is also a class of PPCPs,and according to Doepker et al.,it is associated with triggering reproductive,behavioral,and cardiovascular effects[126]。 sibutramine is an oral drug for the treatment of obesity.Illegal use of drugs containing sibutramine can cause cardiovascular toxicity.Moreover,sibutramine at 30 mg/kg can significantly increase the heart rate and blood pressure of beagles[127][128]。 It was also found that diclofenac sodium(5-50μg/L)and naproxen(1232μg/L)had negative effects on renal hematopoiesis and gill integrity in fish[129,130]。

4.7 Other toxicities

in addition to the above toxicities,PPCPs have been found to have some other toxicities.For example,diclofenac,triclosan,propranolol,atenolol,and mesalazine at certain concentrations can induce excessive production of mitochondrial reactive oxygen species,affect fat synthesis,and cause toxic damage to the heart,liver,and kidney In mice and poultry[131⇓⇓~134]。 Studies on invertebrates such as Daphnia magna,clam and mussel have found that carbamazepine,ibuprofen,acetaminophen,fluoxetine and propranolol can regulate various enzyme activities,affect arachidonic pathway,induce oxidative stress and DNA damage,and reduce the feeding rate of Daphnia magna[102,135⇓~137]。 In addition,bisoprolol,ketoprofen and diclofenac can affect and change the chlorophyll,regulate enzyme activity and cell morphology of algae,and the composition of photosynthetic community[138,139]。

5 Population health risk of PPCPs

5.1 Exposure characteristic of PPCPs in human body

Although the concentrations of PPCPs in most environments are in the range of ng~μg,low concentrations of various PPCPs still pose a serious threat to the ecological environment and human health after long-term exposure and synergistic bioaccumulation.PPCPs bioaccumulate after entering the human body through environmental exposure.A large number of studies have shown that PPCPs have been found in human milk,blood,urine,feces,nails,fat,skin and other human specimens around the world,with concentrations ranging from ng/G to ng/L(Table 3)[26,159⇓⇓~162]。 Humans are generally exposed to PPCPs through Daily use of personal care products or dietary intake.daily personal care products include toothpaste,shampoo,shower gel,soap,body lotion and cosmetics,which contain a large number of chemicals,such as common antibiotics,triclosan,artificial musk,essence and so on.Li et al.Have detected an average concentration of 3.55μg/G of triclosan in the urine of children and adults aged 3 to 24 years[160]。 in Austria,the concentrations of the polycyclic compounds of artificial musks,Galaxolide and musk xylene,were detected In adult plasma ranging from 11 to 450 ng/L[159]。 Artificial musk has also been detected in human breast milk samples from Sichuan,the United States,Denmark,Sweden and other countries,and its lipid content ranges from<1.4 to 917 ng/G[106][163][164][165]。 Long ago,Høverstad et al.Studied the antibiotic content in the excreta of patients within 6 days of normal medication,and found that erythromycin,nalidixic acid and vancomycin had high detectable concentrations in the feces[166]。 Since then,Wang et al.Detected a variety of antibiotics in the feces of the general population(children,young people,and the elderly),with maximum concentration values ranging from 16.78 to 45.4μg/kg[167]。
表3 Human exposure concentration of PPCPs

Table 3 Concentrations of PPCPs in human

Medium Location Concentration of PPCPs a Ref
Plasma China Galaxolide fragrance (HHCB) ( <8~125.9 ng/g lwb); Toxalide fragrance (AHTN) ( <8~2.7 ng/g lw); Musk xylene ( <8~69.0 ng/g lw); Musk ketone ( <8~60.6 ng/g lw); Galaxolide fragrance (HHCB ) ( <8~314.7 ng/g lw); Toxalide fragrance (AHTN) ( <8~39.5 ng/g lw); Musk xylene ( <8~39.0 ng/g lw); Musk ketone (<8~43.5 ng/g lw); 161
South Korea Galaxolide fragrance (HHCB) (170~1400 ng/g lw); Toxalide fragrance (AHTN) (<170~1400 ng/g lw); Musk xylene (170~510 ng/g lw); Musk ketone (<170 ng/g lw); Galaxolide fragrance (HHCB) (<670~2700 ng/g lw); Toxalide fragrance(AHTN) (670~2700 ng/g lw); Musk xylene (<670 ng/g lw); Musk ketone (<670 ng/g lw); 178
USA Galaxolide fragrance (HHCB) (380~1700 ng/L) 179
Austria Galaxolide fragrance (HHCB) (450 ng/L, median); Musk xylene (11 ng/L, median) 159
Italy Daphomycin (19~199 μg/mL) 180
Breast milk China Galaxolide fragrance(HHCB) (4.42~58.2 ng/g lw) 181
China Toxalide fragrance (AHTN) (3.33~29 ng/g lw); Musk ketone (<1.40~10.71 ng/g lw); Triclosan (0.41~0.77 μg/kg); Triclocarban (0.03~4.28 μg/kg); Galaxolide fragrance (HHCB) (92 ± 70 ng/g, mean）Tonalide (16 ± 12 ng/g, mean）Musk xylene (26 ± 22 ng/g, mean）Musk ketone (16 ± 14 ng/g, mean） 181⇓~183
Italy Daphomycin (0.12~0.32 μg/mL) 180
Sweden Galaxolide fragrance (HHCB) (63. 9 ng/g, median); Tonalide (10.4 ng/g, median) 165
Denmark Galaxolide fragrance (HHCB) (38~422 ng/g); Toxalide fragrance (AHTN) (5.58~37.9 ng/g lw); AHMI (nd~9.94 ng/g lw); Musk xylene (nd~46.4 ng/g lw); Musk ketone (nd~26.9 ng/g lw) 164
Japan Galaxolide fragrance (HHCB) (<50~440 ng/g lw); Toxalide fragrance (AHTN) (<50~190 ng/g lw) 184
South Korea Galaxolide fragrance (HHCB) (<5.00~1346 ng/g lw); Toxalide fragrance (AHTN) (<5.00-350 ng/g lw); Musk xylene (<2.00~73.5 ng/g lw); Musk ketone (<2.00~250 ng/g lw) 185
Czech Republic Galaxolide fragrance (HHCB) (13~720 ng/g lw); Toxalide fragrance (AHTN) (13~720 ng/g lw); Musk xylene (<10~156 ng/g lw); Musk ketone (<10~93 ng/g lw) 186
USA Galaxolide fragrance(HHCB) (<5~917 ng/g lw); Toxalide fragrance(AHTN) (<5~144 ng/g lw); Musk xylene (<2~150 ng/g lw); Musk ketone (<2~238 ng/g lw); Galaxolide fragrance(HHCB) (20.1~131.6 ng/g lw); Toxalide fragrance (AHTN) (26.4~41.4 ng/g lw) 163
Germany Musk xylene (10~1220 ng/g lw); Musk ketone (<10~240 ng/g lw); Galaxolide fragrance (HHCB) (21~1316 ng/g lw)
Toxalide fragrance (AHTN) (16~148 ng/g lw); Musk xylene (1.3~47.9 ng/g lw); Musk ketone (2.1~82.9 ng/g lw); Galaxolide fragrance (HHCB) (16~108 ng/g lw); Toxalide fragrance (AHTN) (11~58 ng/g lw); Musk xylene (10~30 ng/g lw); Musk ketone (5~15 ng/g lw)		 187⇓~189
Fatty Germany Musk xylene (20~220 ng/g lw); Musk ketone (10~220 ng/g lw) 190
Switzerland Galaxolide fragrance (HHCB) (12~171 ng/g lw); Toxalide fragrance (AHTN) (1~23 ng/g lw); Musk xylene (6,7~288 ng/g lw); Musk ketone (<1~173 ng/g lw); 191
Italy Galaxolide fragrance (HHCB) (361 ± 467 ng/g lw, mean); Toxalide fragrance (AHTN) (132 ± 264 ng/g lw, mean) 192
Urine China Triclosan (0. 36 μg/L, mean); Triclocarban (0.36 μg/L, mean); Doxycycline (4.6 ng/mL, 95th); Azithromycin (1.5 ng/ml, 95th); Trimethoprim (0.48 ng/ml, 95th); Florfenicol (0.32 ng/mL, 95th); Amoxicillin (15.70 ng/mL, 95th); Azithromycin (7.02 ng/mL, 90th); Erythromycin (78.05 ng/ml, 95th); Clarithromycin (183 ng/mL, 95th); Ofloxacin (35.1 ng/mL, 95th); Tetracycline (10.7 ng/mL, 90th); Sulfamethoxazole (0.11 ng/mL, 95th); rimethoprim (0.23 ng/mL, 90th); Azithromycin (0.03 ng/mL, 90th); Penicillin G (2.53 ng/mL, 90th); Penicillin V (1.20 ng/mL, 95th); Tetracycline (0.18 ng/mL, 90th); Doxycycline (0.19 ng/ml, 75th); Norfloxacin (0.14 ng/mL, 95th); Florfenicol (0.10 ng/ml, 95th); Bisphenol A (2.75 μg/g creatinine /3.00 μg/L, GMc); 4-Nonylphenol (15.92 μg/g creatinine/17.40 μg/L, GM); Triclosan (3.55 μg/g creatinine /3.77 μg/L, GM) 162
193⇓~195
160
Fingernail China Triclosan (5.67 μg/kg, mean/2.0~760.7 μg/kg); Triclocarban (41.50 μg/kg, mean/4.1~1926.5 μg/kg) 162
Toenail China Triclosan (13.57 μg/kg, mean); Triclocarban (84.66 μg/kg, mean) 162
Skin China Galaxolide fragrance (HHCB) (7.8 μg/(kg·d);, median); Siloxanes ( (3.69 mg/d, median); Synthetic musks (3.38 mg/d, median) 196,197
Faeces China Sulfamethoxazole (45.4 μg/kg, max); Trimethoprim (38.33 μg/kg, max); Sulfadimethoxine (16.78 μg/kg, max); Tetracycline (38.65 μg/kg, max); Erythromycin (36.79 μg/kg, max); Amoxicillin (43.72 μg/kg, max) 167

a,the concentration without special annotation means the range;b,lw=lipid weight;c,GM=geometric mean。

5.2 Population health risk

it is clear that even if the exposure concentration of PPCPs in environmental water found at present does not cause acute toxicity to human body,it is inevitable to cause chronic toxicity once it is exposed and bioaccumulated for a long time[168]。 For example,while life-long effects of environmental concentrations of PPCPs in drinking water generally do not appear until decades later,reproductive and developmental defects,reduced testosterone levels,and the development of testicular and thyroid cancers are common in shorter exposure times[169]。 Moreover,some PPCPs have strong pathogenicity,and hormone drugs,such as nitrofurans and estrogens,have been proved to have three effects(mutagenesis,carcinogenesis and teratogenesis)[170]。 at the same time,PPCPs can also be used as endocrine disruptors,which have been proved to have endocrine disrupting effects even At concentrations far below the environmental concentration,and have potential hazards and risks to the human endocrine system[1]。 in addition,the consumption of crops,vegetables and fruits containing residual PPCPs may cause allergic reactions in children,and there is an interaction in the case of large intake in a short period of time[171][172]。 antibiotic resistance will also occur in the population after the intake of vegetables rich in Antibiotic residues[173]。
In terms of the toxic effects of PPCPs compounds on human health,studies have shown that cardiovascular and gastrointestinal drugs are the most dangerous categories based on predicted hazards,potential bioaccumulation,and frequency[174]。 For example,in a case study in Spain,Ortiz de Garc García et al.Estimated the toxicity impact scores of 49 PPCPs on ecology and human health,and showed that.Certain receptor blockers(e.g.,valsartan,irbesartan),lipid modulators(e.g.,simvastatin,atorvastatin),H2-blockers(e.g.,omeprazole)and antidepressants(e.g.,sertraline)are the drugs with the highest risk to human health in all environmental parts of the environment[175]。 In the current research context,although it is difficult to pinpoint the harmful effects of PPCPs on human health,the common health effects are nervous system damage,hormonal function changes,developmental delay,cancer,immune and endocrine system disruption,and reproductive disorders[3,176,177]。

6 Conclusion and prospect

PPCPs are a new class of pollutants that have been highly concerned in recent years.Although there have been many studies,the understanding of the ecotoxicological effects and human health risks of PPCPs is far from comprehensive.A large number of existing studies mainly focus On the detection and risk assessment of PPCPs in aquatic environment.on the basis of previous studies,future studies need to highlight the following four aspects。
(1)the group of PPCPs pollutants is expanding day by day.At present,the research on PPCPs focuses on several main compounds.In the future,it is necessary to expand the scope and study a wider range of PPCPs compounds to supplement the research blind spots。
(2)at present,most of the biological toxicity studies of PPCPs are acute and subacute toxicity studies At high test concentrations,which are inconsistent with the actual environmental exposure,and future toxicity studies should be based on concentrations close to the actual environment。
(3)the pollutants in the environment do not exist independently and are not a single toxicity,and future research should focus on the joint toxicity and environmental synergy between PPCPs and other pollutants。
(4)It is necessary to deeply understand the environmental health effects of PPCPs,and to deeply understand and study the human health effects of sensitive groups(occupational exposed persons,fetuses,infants,pregnant women,etc.)when facing common environmental exposure。

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