Pollution Characteristics, Toxicological Properties, and Health Risk Assessment of Phthalic Acid Esters in Water, Soil, and Atmosphere

Abstract

Phthalic acid esters (PAEs) are a class of common environmental endocrine disruptors (EEDs), capable of causing considerable pollution to water, soil, and air and producing a range of adverse health impacts in humans. Although various studies have investigated the pollution characteristics and health hazards of PAEs in different media, a systematic review of PAEs in the broader environmental context is still lacking. In order to comprehensively explore current issues and suggest prospects, the current status, detection technology, toxicity, and health hazards of PAEs were investigated. The results suggest that PAE pollution is a widespread and complex global phenomenon, transported over long distances. The traditional techniques used for determination include high-performance liquid chromatography–mass spectrometry (HPLC-MS), gas chromatography–mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC). Various detection techniques offer distinct advantages and disadvantages. Moreover, PAEs can cause differing extents of harm to the nervous and reproductive systems of mammals. In the future, it is imperative to improve the detection of PAEs, establish rapid identification approaches, refine toxicological research methods, and investigate more comprehensive health risk assessment methods. These efforts will provide scientific support for the prevention and management of the resulting contaminants.

1. Introduction

Environmental endocrine disruptors (EEDs) are an emerging contaminant, comprising exogenous chemical substances frequently encountered in the environment. These substances can impact the endocrine, reproductive, neurological, and other physiological systems of humans through several entry points into the body. Moreover, they may cause immune–metabolic disorders [1,2,3,4]. Most of the current research on EEDs is centered around their health impacts. Research reveals that EEDs impact human reproductive and nervous systems by disrupting hormone synthesis, secretion, transport, binding, response, and metabolism. Presently, computer simulations can predict the activity and toxicity of EEDs [3,4,5]. Phthalic acid esters (PAEs) are a significant class of EEDs, primarily employed as plasticizers in different products like plastics, construction materials, and agricultural products [5,6]. In May 2022, the General Office of the State Council of China released the Action Program for the Control of Emerging Pollutants. This program identifies PAEs as high-production volume chemicals, alongside categories like benzothiazoles and organic phosphoric acid esters. As a result, PAEs have garnered significant attention from multiple countries [7].

PAEs are largely human-made contaminants present across a variety of environmental settings, such as indoor dust, airborne particles, surface water, sediment, soil, wastewater, and urban stormwater runoff, where they are found at varying concentrations [7]. PAEs have been found to potentially harm the nervous and reproductive systems, as well as organ function. Moreover, they are implicated as possible causes of respiratory and skin diseases [8,9,10]. Multinational agencies have established a tolerable daily intake for PAEs related to reproductive and developmental toxicity at 0.05 mg·kg⁻¹·bw·d [11]. Dimethyl phthalate (DMP), diethyl phthalate (DEHP), butyl phthalate (BBP), and diethyl phthalate (DEP) have been recognized as priority contaminants by the US Environmental Protection Agency (EPA). DEHP and BBP have been classified as possible human carcinogens. The EPA and the World Health Organization (WHO) have set the allowable limits for DEHP concentrations in drinking water at 6 and 8 μg·L⁻¹, respectively [12]. In 2018, the EU introduced new regulations to limit the use of PAEs. Under the regulation on the registration, evaluation, authorization, and restriction of chemicals (REACH) regulations, DEHP, DBP, BBP, and dibutyl phthalate (DiBP) are prohibited from being used as substances or mixtures in toys or childcare articles, with the concentration of any single PAE or a combination of four PAEs not exceeding 0.1% [13]. To date, research has been carried out on detecting the substance, evaluating its potential toxic impacts on humans and animals, and evaluating the associated risks. However, current research continues to encounter several challenges, i.e., various types of PAEs and potential substances exist that have not been adequately investigated. Most atmospheric PAE studies focus on specific regions, such as provinces, cities, or districts. At present, there is a lack of more extensive and identical national-scale measurements to assess the overall situation of atmospheric PAE in the country. Certain mechanisms of action remain unclear, and there is a lack of clarity in the methodology for evaluating the health impacts of PAEs. Thus, enhancing our understanding of PAE pollution characteristics in the environment and associated health hazards is essential.

This paper selects the China National Knowledge Infrastructure (CNKI) database as the core data source. In CNKI, phthalic acid ester, soil, atmosphere, and water were used as keywords to search. A total of 98 articles were selected after manually removing duplicate articles and articles that did not meet the subject conditions. Through an extensive literature review and detailed analysis of available data, this study elucidates the pollution characteristics of PAEs across three environmental media: water, soil, and atmosphere. This study explores the similarities and differences among key technologies employed to detect PAEs, demonstrates the potential hazards linked with PAEs in various environmental compartments, discusses efforts related to pollution prevention and control, and outlines future research, development, and prevention measures. The goal is to furnish data and scientific backing for the management of emerging contaminants and evaluate their health risk implications.

2. Sources and Pollution Status

PAEs primarily originate from everyday consumer goods and solid waste combustion. The interaction between PAEs and polymers in plastics is modest, facilitating the migration of PAEs from plastic products into the environment [4]. PAE contamination is a widespread global issue, demonstrating changing degrees of presence across different regions. Figure 1 and Table S1 display the PAE pollution in the atmosphere, soil, and water.

PAEs are capable of migrating and seeping into aquatic environments, thereby causing contamination of water resources. Industrial and domestic wastewater, agricultural irrigation wastewater, and waste leachate contain increased concentrations of PAEs [14]. PAEs in the global aquatic environment show a broad range of concentrations (0.1 × 10⁻³–3.2 × 10³ μg·L⁻¹) [14]. The main PAEs found in water include DMP, DEP, DEHP, BBP, di-n-butyl phthalate (DBP), and dioctyl phthalate (DOP). Alterations in water quality may lead to differences in the dominant pollutants, but most studies indicate that DEHP is typically the primary contributor [12,15,16,17,18]. Seasonal variations can lead to significant fluctuations in PAE concentrations in water, typically demonstrating lower levels during the warm season compared to the cold season. Research into surface water concentrations of PAEs in Jabalpur City, India, demonstrated considerable seasonal variations between winter and summer. Peak concentrations were recorded during winter, reaching 7553.9 μg·L⁻¹, whereas in summer, they were considerably lower at 410.48 μg·L⁻¹ [12]. During winter, the maximum value was 18 times greater than that observed in summer. Increased photolytic activity and microbial degradation of PAEs in summer may contribute to the seasonal variation in PAE concentrations in aquatic environments. Tap water and drinking water employed in daily human activities often originate from natural water bodies, which can serve as sources of PAE pollution. Research shows that employing lakes, rivers, reservoirs, and groundwater for water supply systems can introduce PAEs into water intended for everyday use directly from the source [12,19]. Moreover, the movement of PAEs between different mediums is impacted by several factors, such as the chemical composition of the carrier, the materials, the environment, and the interacting substances [20]. The survey indicated that several factors can affect the concentration of PAEs in tap water, such as the distance traveled by the water, the materials employed in the pipeline, the duration of transit, and the use of plastic packaging, which can potentially lead to pollution of drinking water [12,19]. Daily water is required to be treated due to the possibility of PAE pollution from transportation and water supply. The comparison showed that the treated drinking water’s PAE concentration had significantly decreased [12]. Water treatment methods in water plants are primarily designed to address bacteria and heavy metals in the water. However, due to their chemical stability, existing methods are often ineffective in removing PAEs from water [14,21]. Based on the previous discussion, it is clear that there is an urgent need to improve domestic water treatment to minimize human exposure to PAEs through daily water consumption. Moreover, careful consideration needs to be given to the application of PAEs in the production and manufacturing of plastic packaging.

It is significant to note that an extensive amount of PAEs can be found in soil, which is one of the natural repositories of pollutants. PAEs demonstrate high octanol–water partition coefficients, enhancing their adsorption on soil particles [21]. PAEs in the soil show a broad range of concentrations (1 × 10⁻³–820 mg·kg⁻¹) [21]. This process consequently contributes to soil contamination. Moreover, PAEs can infiltrate the soil via surface runoff and atmospheric deposition. In soil, PAEs are predominantly linked to agricultural practices, originating from diverse sources such as agricultural films, fertilizers, sludge utilized in agriculture, and wastewater irrigation [22]. Hui et al.’s research showed that sludge organic fertilizers (SOFs) contained relatively high PAE content in the currently used organic fertilizers [23]. The result of research showed that the application of SOFs increased the accumulation of PAEs in soil profiles, increasing human health risks [23]. The variability of PAEs in agricultural soils is a widely recognized phenomenon [22,24]. The amounts of six PAEs (DMP, DEP, BBP, DBP, DEHP, and di-n-octyl phthalate (DNOP)) in soils in Lanzhou, China, reached 0.21 mg·kg⁻¹, with DNOP being the primary pollutant [24]. However, studies have found that DBP and DEHP are the primary PAEs in agricultural soils [22]. It has been hypothesized that variations in main substances may be associated with different farming practices [22,25,26,27,28]. Moreover, the conception of PAEs in greenhouse soil samples was significantly higher than in other soil samples [22,28,29]. This occurrence may be attributed to the prolonged utilization of greenhouse structures with covering films and pesticides that contain PAEs. As a result, the regulation of agricultural products plays a critical role in addressing soil contamination from PAEs.

PAEs are semi-volatile organic compounds capable of direct transport from raw materials to the atmosphere. Studies have shown that the fluctuation of single PAE pollution may be affected by natural conditions, human factors, and the physical and chemical properties of substances. The increase in temperature will lead to the volatilization of PAEs (DBP, DEHP, etc.) with lower vapor pressure from various environmental media (such as plastic products, soil, and water) into the atmosphere [21]. PAEs in the atmosphere show a broad range of concentrations (4 × 10⁻³–33,851 ng·m⁻³) [21]. As a result, the atmosphere contains a considerable amount of PAEs, with DEHP being the primary contributor [7,30,31]. Liu et al. [32] and Yang et al. [31] individually determined amounts of PAEs in indoor air in Shanghai, China, at levels of 3130 and 2464 µg·g⁻¹, respectively. The noted decrease in indoor PAE levels may be linked to various personal factors, such as the use of indoor renovation materials and household products. Seasonal variations also play a role in the observed changes in atmospheric PAE levels. In cities like Paris, France, Lornea, and Mexico, notable differences in atmospheric PAE concentrations are observed between the cooler and warmer seasons [33,34]. One possible explanation for this observation is that higher temperatures accelerate the volatilization of PAEs, and the noted improvement in source emission rates is because of the reduction in the dust–gas partition coefficient (K_d). As a result, the atmospheric concentration levels of PAEs are affected [21,35,36,37]. Moreover, the widespread use of PAEs in industrial processes raises concerns about the possible atmospheric pollution of PAEs in industrial areas. It has been noted that these areas have higher levels of pollution than other areas [7,38,39]. PAEs are complex substances in the atmosphere that can attach to particulate matter and be transported over great distances. PAEs are generally adsorbed onto suspended particulate matter, dust, and other solid surfaces. They then travel great distances through the atmosphere and undergo multi-interfacial alteration to move throughout the environment.

Figure 1. Concentration and percentage of PAEs in the water, soil, and atmospheric environments worldwide (the pie chart data come from standardized results) [7,12,19,20,22,23,24,25,26,34,40,41,42,43,44,45,46,47].

Figure 1. Concentration and percentage of PAEs in the water, soil, and atmospheric environments worldwide (the pie chart data come from standardized results) [7,12,19,20,22,23,24,25,26,34,40,41,42,43,44,45,46,47].

In conclusion, PAEs are important worldwide contaminants, with DEHP being the main one. The level of PAEs is affected by seasonal temperature variations. They can be carried and distributed over great distances by atmospheric processes, and their alteration and transportation in different media are intricate. By 2050, it is projected that 1.8 billion tons of plastic will be produced [14]. Furthermore, there are more prominent PAE contamination issues in certain areas, indicating that the environmental interaction with PAEs is becoming worse. Research on PAEs has mostly concentrated on the soil and aquatic environments in the past few years. Few research studies have been carried out regarding the issue of PAE pollution of the atmosphere, which indicates a wide knowledge gap on the subject of multi-media pollution transmission. Therefore, one of the most important steps in creating successful solutions for this problem is to intensify the investigation of PAEs in the atmosphere.

3. Determination Techniques and Strategies

PAEs are primarily ingested orally, through direct contact, and via environmental exposure. As a result, there is a pressing need to assess the media associated with these different exposure routes. Table 1 provides a summary of various approaches for detecting PAEs and their pre-treatment methods, emphasizing optimization in sample preparation and equipment utilization. The present determination methods encompass high-performance liquid chromatography–mass spectrometry (HPLC-MS), gas chromatography–mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC).

One of the main ways that people are directly exposed to PAEs is through oral intake. Ultra-performance liquid chromatography–mass spectrometry (UPLC-MS/MS) and GC-MS were used to measure the levels of PAEs in edible and medicinal mushrooms as well as agricultural products, achieving recovery rates of 79.4% and 78.2%, respectively [26,48]. PAEs in agricultural products were analyzed by GC-MS, and the detection rate of this method was 68.9% [26]. When UPLC-MS/MS was used to detect PAEs in edible fungi, the mobile phase was methanol–water, the column temperature was 35 °C, the phenyl column CSH^TM Phenyl-Hexyl was selected, the PTFE ultrafiltration membrane was selected, and the capture column Ghost-Buster HP Column was added. The detection results of 23 PAEs were optimal [48]. Testing is necessary for commonplace products that have high-frequency contact and high amounts of PAEs since direct contact is another high-frequency pathway of contact with PAEs. The appropriate wavelength and reference wavelength for the identification of six PAEs in footwear were carried out through HPLC [49]. The linear range of the method for detecting footwear products was 10~100 μg/mL, the detection limit of the method was 1.87~8.92 mg/kg, the recovery rate was 90.5~97.7%, and the relative standard deviation was 3.8~6.9%. Moreover, the appropriate mobile phase system of MeOH-H₂O and the optimal column temperature were optimized. The final limit of detection was 1.9–8.9 mg·kg⁻¹ [50]. PAEs were identified in food contact materials and plastic bags using GC-MS with ultrasonic or n-hexane extraction methods, achieving recoveries above 86% [51,52].

Further analysis of the environmental media uncovered more samples. The PAEs in soil were determined using an ultrasonic extraction–high-performance liquid chromatography technique, with the absorption wavelength set at 205 nm. The approach demonstrated a recovery rate exceeding 72% [49]. Moreover, GC-MS can be employed to detect various substances like sediments, water, dust, soil, and atmospheric particulate matter. By improving the pre-treatment and sampling filtering techniques, the identification method’s recovery rate can be enhanced. This could involve processes like glass-fiber filtration membrane filtration, liquid-phase extraction, and recirculation re-extraction. With this kind of approach, a recovery rate of more than 65% can be sustained [26,48,52,53,54,55]. Results from testing procedures that are appropriate for various inspection purposes are generally excellent.

Four factors can be considered when optimizing the pre-treatment process for PAEs: filter membrane choice, extraction liquid choice, extraction technique, and extraction durations. Comparing the previously described findings showed that, with recoveries varying from 94% to 106%, the aqueous test can be filtered through a glass fiber filter membrane with GC-MS for identifying PAEs in aquatic settings. When GC-MS was applied to the detection of PAEs in water, the detection limit was 0.006~0.01 µg·L⁻¹, and the quantitative limit was 0.018~0.045 µg·L⁻¹ [26]. A GC-MS apparatus can be used to identify and analyze soil samples after two extractions of acetone/hexane at a volume ratio of 4:1, ensuring a 78% recovery rate. A 4:1 volume ratio n-hexane/acetone mixture can be employed to extract the PAEs in the atmospheric particulate matter, and the test can be performed three times with yields varying from 76% to 130%. Furthermore, for identifying PAEs in everyday use items, liquid phase extraction with 20 mL of n-hexane and ultrasonication at 40 °C for 30 min can be employed, yielding high recoveries. All methods of identification possess distinct limits and are challenging to adjust for in real-world applications. The extraction and determination of PAEs has become more challenging due to the variety of PAEs and the complicated nature of environmental media. PAEs are challenging to separate, particularly in complex environments with lipid components. As a result, to address the continually increasing challenges with the PAE identification method, novel pretreatment techniques are required to be developed and optimized.

Table 1. Common detection methods for PAEs.

Detection Settings	Pre-Treatment or Instrument Optimization	Detection Media	Advantage	Disadvantage	Recovery Rate (%)	Detection Limit	Quantification Limit	Linear Range	References
GC-MS	Accelerated solvent extraction and cycle extraction (two times)	Soil and atmospheric particulate matter	Fast extraction speed, small amount of organic solvent, and high automation degree	False positives, poor reproducibility, and stability are possible and costly	65.7~108	-	-	-	[26,48,51,52,53,54,55]
	Ultrasonic extraction	Food contact material	-		86.0~108.0	-	-	0.02~2.0 µg·mL−1
	20 mL n-hexane extraction. Ultrasonic extraction was performed at 40 °C for 30 min	Express plastic bag	Simple pretreatment, good recovery rate, and precision		85.0~107.2	2.0~10.0 mg·kg−1	-	0.05~1.0 µg·mL−1
	Acetone/n-hexane (1:1) was extracted twice; extraction for 10 min	Soil/agricultural products	-		78.2	1.04~14.24 µg·L−1	0.24~0.45 µg·L−1
	N-hexane/acetone (4:1), repeated three times	Dust	-		76.0~130.0	-	10 µg·kg−1	-
	Determination of DOC, WEOC, and TOC in water by catalytic oxidation at high-temperature glass fiber membrane filtration	Water	-		94.0~106.0	0.006~0.01 µg·L−1	0.018~0.045 µg·L−1	-
		Sediments	-		77.0~113.0	0.003~0.008 mg·kg−1	0.009~0.024 µg·kg−1	-
UPLC-MS/MS	35 °C column temperature and methanol–water mobile phase	Edible and medicinal fungi	The method is simple to operate and has high accuracy	-	79.4~104.3	-	0.2~8.0 µg·kg−1	0.2~500 µg·mL−1	[48]
Liquid chromatography	226 nm test wavelength, 325 nm reference wave, and methanol–water mobile phase	Shoes	Short analysis time and good repeatability	Susceptible to interference from other chromatographic peaks	90.5~97.7	1.9~8.9 mg·kg−1	-	10~100 µg·mL−1	[50,56]
HPLC	Ultrasonic extraction has a maximum UV absorption wavelength of 205 nm	Soil	A wide linear range	-	72.59~91.89	0.005~0.03 mg·kg−1	-	0.1~100 µg·mL−1	[49]

Table 1. Common detection methods for PAEs.

Detection Settings	Pre-Treatment or Instrument Optimization	Detection Media	Advantage	Disadvantage	Recovery Rate (%)	Detection Limit	Quantification Limit	Linear Range	References
GC-MS	Accelerated solvent extraction and cycle extraction (two times)	Soil and atmospheric particulate matter	Fast extraction speed, small amount of organic solvent, and high automation degree	False positives, poor reproducibility, and stability are possible and costly	65.7~108	-	-	-	[26,48,51,52,53,54,55]
	Ultrasonic extraction	Food contact material	-		86.0~108.0	-	-	0.02~2.0 µg·mL−1
	20 mL n-hexane extraction. Ultrasonic extraction was performed at 40 °C for 30 min	Express plastic bag	Simple pretreatment, good recovery rate, and precision		85.0~107.2	2.0~10.0 mg·kg−1	-	0.05~1.0 µg·mL−1
	Acetone/n-hexane (1:1) was extracted twice; extraction for 10 min	Soil/agricultural products	-		78.2	1.04~14.24 µg·L−1	0.24~0.45 µg·L−1
	N-hexane/acetone (4:1), repeated three times	Dust	-		76.0~130.0	-	10 µg·kg−1	-
	Determination of DOC, WEOC, and TOC in water by catalytic oxidation at high-temperature glass fiber membrane filtration	Water	-		94.0~106.0	0.006~0.01 µg·L−1	0.018~0.045 µg·L−1	-
		Sediments	-		77.0~113.0	0.003~0.008 mg·kg−1	0.009~0.024 µg·kg−1	-
UPLC-MS/MS	35 °C column temperature and methanol–water mobile phase	Edible and medicinal fungi	The method is simple to operate and has high accuracy	-	79.4~104.3	-	0.2~8.0 µg·kg−1	0.2~500 µg·mL−1	[48]
Liquid chromatography	226 nm test wavelength, 325 nm reference wave, and methanol–water mobile phase	Shoes	Short analysis time and good repeatability	Susceptible to interference from other chromatographic peaks	90.5~97.7	1.9~8.9 mg·kg−1	-	10~100 µg·mL−1	[50,56]
HPLC	Ultrasonic extraction has a maximum UV absorption wavelength of 205 nm	Soil	A wide linear range	-	72.59~91.89	0.005~0.03 mg·kg−1	-	0.1~100 µg·mL−1	[49]

4. Toxicity and Potential Hazards

4.1. Non-Reproductive Toxicity

PAEs represent a major neurological risk factor that impacts neurobehavior, learning and memory capabilities, and neurodevelopment. The impacts on children’s intelligence are gender-specific, with boys being more affected than girls [57]. In animal experiments, DEHP has a neurotoxic effect on the brain tissue of mice. Single exposure to DEHP can lead to learning and memory impairment in mice and reduce the spatial exploration ability of mice [58]. The study of Vahid Farzanehfar et al. [8] showed that oral intake of DBP for 14 days can cause neurobehavioral adverse reactions in mice, damage the memory function of mice, and induce anxiety. Moreover, among other consequences, PAEs have been shown to harm the body’s organs and cause liver tissue to change in a way that increases the risk of cancer [11,59,60]. For example, in animal experiments, it was found that rats exposed to DEHP showed signs of intoxication such as hyperactivity, fluffy coats, and local hair removal, accompanied by weight loss, increased liver weight, and decreased spleen, kidney, brain, testis, and epididymis weight [11]. In one study, eight PAE metabolites were examined in the urine of 202 kids, indicating that kids who are confronted with PAEs run the risk of developing liver injury [61]. Human symptoms, including eczema, rhinitis, and asthma, may potentially be linked to indoor dust containing specific concentrations of PAEs [9]. In immunology, asthma is classified as an I-type hypersensitivity reaction. Exposure to allergens along with adjuvant factors amplifies the severity of asthma attacks, with PAEs being a common adjuvant among them [10]. Moreover, long-chain PAEs (such as DEHP and diisononyl phthalate (DiNP)) are more prone to triggering asthma compared to short-chain PAEs [9].

There might be a connection between PAEs and obesity. PAEs can impact adipocyte differentiation and contribute to disorders in lipid metabolism [62]. Studies have demonstrated a positive correlation between the concentration of DEHP metabolites in urine and obesity in adult women. Furthermore, high-molecular-weight DEHP metabolites are linked to obesity in men aged 60 and above [63]. At the same time, various metabolites are stored in various sites, suggesting that PAEs display chemical and sex-specific characteristics in the human body [64]. Metabolites of PAEs affect metabolic pathways associated with obesity in school-age children by stimulating the body’s metabolism of aromatic compounds, thereby influencing the development of childhood obesity [65]. However, some reports have demonstrated that there is no statistically significant association between PAE exposure and human obesity [66]. The complex mechanism by which PAEs contribute to weight gain remains debated, predominantly based on animal experiments with sparse human research. To more thoroughly comprehend the pathogenic principle of PAEs, mechanism investigations are imperative to be reinforced in the future.

4.2. Reproductive Toxicity

PAEs primarily cause reproductive toxicity by disrupting the hypothalamic–pituitary–gonadal axis [67]. The size and molecular structure of PAEs are similar to those of human hormones. Upon entering the human body, PAEs can bind with hormone receptors, leading to impacts that mimic those of human hormones. This disrupts the normal stabilization of hormones in the human bloodstream, affecting reproductive development and leading to disorders induced by impairment to the reproductive system. Simultaneously, it irreversibly impairs the later development of offspring [53].

PAEs can cause fluctuations in androgen levels, thereby impacting the body’s endocrine system. This can lead to alterations in the structure and function of germ cells, potentially resulting in pathological variations in the tissues of reproductive organs. Moreover, it may lead to a decrease in germ cell parameters, adversely affecting the quantity and quality of sperm [10,68]. PAEs have been found to disrupt ovarian function in females by preventing the growth of primordial follicles and injuring ovarian tissue [69]. PAEs from the mother can traverse the placental barrier and impair the normal development of testicular mesenchymal and supporting cell functions in male fetuses, potentially resulting in reproductive system abnormalities in the offspring [68]. Furthermore, metabolites of PAEs have been demonstrated to impact levels of reproductive hormones in children. For instance, in one study, urinary levels of the PAE metabolite monophthalate were considerably associated with serum luteinizing hormone levels in 6-year-old children, particularly among girls. Furthermore, levels of monobutyl phthalate in children were notably linked to serum levels of follicle-stimulating hormone [70]. In the animal model experiment, the experimental animals showed symptoms such as hypospadias, cryptorchidism, shortened anogenital distance, infertility, and testicular cancer, which were consistent with the clinical symptoms of testicular hypoplasia, known as phthalate syndrome [71]. Previous evidence has shown that phthalate syndrome, or testicular dysplasia syndrome, is one of the main negative characteristics of PAE exposure toxicity [72].

Animal studies have shown that specific PAEs can affect the male reproductive system and germ cells at the molecular level by impacting DNA. For example, Ma et al. [73] and Chi et al. [74] found that contact with PAEs induced DNA methylation in the gonads of male zebrafish and caused structural alterations in the DNA of herring spermatozoa, leading to harm in their reproductive systems. Studies involving humans have indicated that PAEs can influence DNA at a molecular level, potentially enhancing the risk of adverse reproductive, cardiometabolic, and other outcomes [75,76]. In recent scientific developments, the problem of the binding interaction between PAEs and DNA has also been explored [77]. However, contemporary DNA-related research has been scarce, and additional evidence is required to demonstrate the correlation between PAEs and genes and any possible health hazards related to them.

Various experimental studies have revealed that PAEs have a relatively strong reproductive toxicity impact, causing varying degrees of reproductive problems in both men and women. According to a female-centric perspective, it has been observed that the reproductive health effects of PAEs may extend across generations, showing a cross-generational influence. In the future, it is imperative to conduct further investigations and studies to delineate the specific mechanisms and effects of PAE-related harm to the human body. This endeavor is important for determining suitable treatments and solutions to reduce the deleterious influences of PAEs.

5. Exposure Levels and Health Risk Assessment

Prolonged exposure of the human body to PAE-enriched environments leads to significant health impairments. Particularly, DMP, DEHP, BBP, and DEP are classified as priority pollutants, with DEHP and BBP identified as potential carcinogens. Currently, the non-carcinogenic risk (NCR) and carcinogenic risk (CR) assessments are widely employed to determine the risks associated with human inhalation of PAEs. An NCR value less than 1 denotes a low or negligible non-carcinogenic risk, whereas a value greater than 1 shows a significant non-carcinogenic risk. A CR value below 10⁻⁶–10⁻⁴ shows a low or negligible risk of cancer, while a CR value exceeding 10⁻⁴ suggests a high risk of cancer. The calculation formula is as follows:

$$NCR={\displaystyle \frac{ADD}{RfD}}$$

(1)

$$CR=LADD\times CSF$$

(2)

where ADD denotes the average daily dose of non-carcinogens, mg·kg⁻¹·d⁻¹; RfD signifies the reference dose of a single substance, mg·kg⁻¹·d⁻¹. The common PAEs included DMP, DEP, BBP, DiBP, DBP, and DEHP, with RfD of 10 mg·kg⁻¹·d⁻¹, 0.8 mg·kg⁻¹·d⁻¹, 0.2 mg·kg⁻¹·d⁻¹, 0.1 mg·kg⁻¹·d⁻¹, 0.1 mg·kg⁻¹·d⁻¹, 0.02 mg·kg⁻¹·d⁻¹, and 0.05 mg·kg⁻¹·d⁻¹, respectively [78]. CFS represents cancer slope factor, while LADD denotes the lifetime average daily dose of inhaled carcinogens, mg·kg⁻¹·d⁻¹. The ADD and LADD can be calculated by Equations (3) and (4) [79,80]:

$$ADD=C\times {\displaystyle \frac{InhR\times EF\times ED}{BW\times AT}}\times cf$$

(3)

$$LADD=C\times {\displaystyle \frac{EF}{AT}}({\displaystyle \frac{{InhR}_{children}\times {ED}_{children}}{{BW}_{children}}}+{\displaystyle \frac{{InhR}_{adults}\times {ED}_{adults}}{{BW}_{adults}}})\times cf$$

(4)

where C signifies the concentration of pollutant, ng·m⁻³; InhR denotes the inhalation rate, m³·d⁻¹; EF represents exposure frequency, d; ED denotes the exposure time; BW signifies the average weight, kg; AT represents the average time, d; and cf represents the conversion coefficient.

Similarly, PAE exposure levels are determined by daily intake (EDI) [78]:

$$EDI={\displaystyle \frac{C\times IR}{BW}}$$

(5)

where C denotes the concentration of pollutant, ng·m⁻³; IR signifies the uptake rate or inhalation rate, m³·d⁻¹; and BW represents the average weight, kg.

Furthermore, the assessment of exposure levels and health risks associated with PAEs can involve the calculation of the hazard quotient (HQ) and hazard index (HI), which are determined through the following equations [81,82].

$$HQ={\displaystyle \frac{EDI}{Rfd}}$$

(6)

$$HI=\sum {HQ}_i$$

(7)

Table 2 displays the risk assessment findings for PAEs across various media. Currently, only the carcinogenic risk resulting from DEHP is more significant than the overall low carcinogenic and non-carcinogenic risks of PAEs. It is important to note that while the majority of health risk assessment findings fall below the standard threshold, studies indicate that the health risk assessment results for adult males approach the maximum threshold (10⁻⁴) [83]. Therefore, vigilance is required regarding the exposure hazards posed by PAEs. Furthermore, there is limited comprehensive assessment and analysis of all PAEs health hazards in the national environment, and the majority of current research on PAEs health risks mainly focuses on certain regions or compounds.

Table 2. Risk assessment results of PAEs in different media.

Evaluation Media	Pollutant	Evaluation Object	Risk	References
Drinking water	DEHP	Adults, children	Health risks	[12]
Surface water	ΣPAEs	Adults, children	Non-carcinogenic risks are negligible	[15]
Surface water	ΣPAEs	Adults, children	Potential carcinogenic risk	[15]
Domestic tap water	DEP, DBP	Adults, children	Non-carcinogenic risks are negligible	[20]
Domestic tap water	DEHP	Adults, children	Potential carcinogenic risk	[20]
Urban soil	ΣPAEs	Adults, children	Carcinogenic/non-carcinogenic risks are negligible	[20]
Drinking water	ΣPAEs	Adult male	health risks	[84]
Petrochemical atmosphere	ΣPAEs	Adults, children	Low health risks	[46]
University dormitory dust	ΣPAEs	Adults	Low non-carcinogenic risk	[35]
University dormitory dust	DEHP, BBP	Adults	Low carcinogenic risk	[35]
Industrial area atmosphere	ΣPAEs	Adults, children	Carcinogenic/non-carcinogenic risks are negligible	[38]
Industrial area atmosphere	ΣPAEs	Adults, children	Carcinogenic/non-carcinogenic risks are negligible	[7]
Plastic lunch box	ΣPAEs	Adults, children	Carcinogenic/non-carcinogenic risks are negligible	[84]
Surface water	DEHP	Adults, children	Low health risks	[85]
Menstrual pad	ΣPAEs	Adults, children	Non-carcinogenic risks are negligible	[85]
Menstrual pad	DEHP	Adults, children	Potential carcinogenic risk	[85]

Table 2. Risk assessment results of PAEs in different media.

Evaluation Media	Pollutant	Evaluation Object	Risk	References
Drinking water	DEHP	Adults, children	Health risks	[12]
Surface water	ΣPAEs	Adults, children	Non-carcinogenic risks are negligible	[15]
Surface water	ΣPAEs	Adults, children	Potential carcinogenic risk	[15]
Domestic tap water	DEP, DBP	Adults, children	Non-carcinogenic risks are negligible	[20]
Domestic tap water	DEHP	Adults, children	Potential carcinogenic risk	[20]
Urban soil	ΣPAEs	Adults, children	Carcinogenic/non-carcinogenic risks are negligible	[20]
Drinking water	ΣPAEs	Adult male	health risks	[84]
Petrochemical atmosphere	ΣPAEs	Adults, children	Low health risks	[46]
University dormitory dust	ΣPAEs	Adults	Low non-carcinogenic risk	[35]
University dormitory dust	DEHP, BBP	Adults	Low carcinogenic risk	[35]
Industrial area atmosphere	ΣPAEs	Adults, children	Carcinogenic/non-carcinogenic risks are negligible	[38]
Industrial area atmosphere	ΣPAEs	Adults, children	Carcinogenic/non-carcinogenic risks are negligible	[7]
Plastic lunch box	ΣPAEs	Adults, children	Carcinogenic/non-carcinogenic risks are negligible	[84]
Surface water	DEHP	Adults, children	Low health risks	[85]
Menstrual pad	ΣPAEs	Adults, children	Non-carcinogenic risks are negligible	[85]
Menstrual pad	DEHP	Adults, children	Potential carcinogenic risk	[85]

In summary, PAEs exposure risk assessment methods can be broadly categorized into two groups: (1) evaluation of the exposure level to individual substances and the associated carcinogenic/non-carcinogenic risks, including parameters such as ADD, LADD, NCR, and CR; and (2) assessment of cumulative risks such as HI and HQ. Figure 2 presents the difficulties, existing evaluation results, and methods for evaluating PAEs. However, as the previous discussion demonstrated, the current evaluation methods are not novel, and more thorough research is required to determine the risk and toxicity of human contact with PAEs [16], in addition to improvements to the pollution level and health assessment system of PAEs.

6. Prevention and Control of PAE Pollution

Currently, many countries have implemented specific guidelines regarding the use of PAEs in products. Some of these protocols are detailed in Table 3. Considering the enhanced risk PAEs pose to children [57,60,70], many countries and international organizations, like China, have emphasized the importance of limiting the use of PAEs in products intended for infants. In 1999, toys and childcare goods meant for children under three years old were forbidden by the European Union (EU) from containing DiNP, DEHP, DBP, DiBP, DOP, and BBP [86]. The 2009 Consumer Product Safety Improvement Act (CPSIA) regulations forbid the consumption of DEHP, DBP, and BBP in children’s toys and care products. Moreover, the concentration of all three substances is restricted to 0.1% [87]. In 2009, China introduced rules concerning six particular kinds of PAEs, such as DEHP and DBP. These guidelines required the combined concentration of DEHP, DBP, and BBP not to exceed 0.1%, while the combined concentration of DiNP, DiDP, and DnOP not to exceed 0.1% [88]. The latest update from the WHO pertains to regulating the concentration of DEHP in water, setting a limit of no more than 8 µg/L [89].

Table 3. Relevant provisions of international organizations on PAEs.

Year	Nations/Organizations	Substance	Requirement	References
1999	EU	DiNP, DEHP DBP, DiBP DOP, BBP	Prohibited in the production of toys and childcare products for children under 3 years of age.	[86]
2009	US. CPSIA	DEHP, DBP BBP	Permanent ban on the use, distribution, and import of these substances in children’s toys and childcare products. Restricted use: 0.1%.	[87]
2009	US. CPSIA	DiNP, DiDP DnOP	Can be used in children’s oral products and care products. Restricted use: 0.1%.	[87]
2009	CHINA	DEHP, DBP BBP	DEHP, DBP, and BBP sum less than or equal to 0.1%.	[88]
2009	CHINA	DiNP, DiDP DnOP	DiNP, DiDP, and DnOP sum less than or equal to 0.1%.	[88]
2011	EU	BBP	Quantity contained less than 0.1%. Migration less than 0.3 mg·kg−1.	[90]
2011	EU	DEHP	Quantity contained less than 0.1%. Migration less than 30 mg/kg.	[90]
2011	EU	DiDP	Quantity contained less than 0.1%. The sum of DiDP and DiNP is less than 9 mg·kg−1.	[90]
2011	EU	DiNP	Quantity contained less than 0.1%. The sum of DiNP and DiNP is less than	[90]
2012	US. EPA	DEHP	C water ≤ 6 µg·L−1	[90]
2018	EU. REACH	DEHP, DBP BBP, DiBP	1. Substances or mixtures that may not be used as toys or childcare products. 2. Individual or combined concentration of four PAEs less than or equal to 0.1%.	[13]
2018	EU. REACH	DEHP DBP BBP	1. Substances or mixtures that may not be used as toys or childcare products. 2. Individual or combined concentration of three PAEs less than or equal to 0.1%.	[13]
2022	WHO	DEHP	C water ≤ 8	[89]

Table 3. Relevant provisions of international organizations on PAEs.

Year	Nations/Organizations	Substance	Requirement	References
1999	EU	DiNP, DEHP DBP, DiBP DOP, BBP	Prohibited in the production of toys and childcare products for children under 3 years of age.	[86]
2009	US. CPSIA	DEHP, DBP BBP	Permanent ban on the use, distribution, and import of these substances in children’s toys and childcare products. Restricted use: 0.1%.	[87]
2009	US. CPSIA	DiNP, DiDP DnOP	Can be used in children’s oral products and care products. Restricted use: 0.1%.	[87]
2009	CHINA	DEHP, DBP BBP	DEHP, DBP, and BBP sum less than or equal to 0.1%.	[88]
2009	CHINA	DiNP, DiDP DnOP	DiNP, DiDP, and DnOP sum less than or equal to 0.1%.	[88]
2011	EU	BBP	Quantity contained less than 0.1%. Migration less than 0.3 mg·kg−1.	[90]
2011	EU	DEHP	Quantity contained less than 0.1%. Migration less than 30 mg/kg.	[90]
2011	EU	DiDP	Quantity contained less than 0.1%. The sum of DiDP and DiNP is less than 9 mg·kg−1.	[90]
2011	EU	DiNP	Quantity contained less than 0.1%. The sum of DiNP and DiNP is less than	[90]
2012	US. EPA	DEHP	C water ≤ 6 µg·L−1	[90]
2018	EU. REACH	DEHP, DBP BBP, DiBP	1. Substances or mixtures that may not be used as toys or childcare products. 2. Individual or combined concentration of four PAEs less than or equal to 0.1%.	[13]
2018	EU. REACH	DEHP DBP BBP	1. Substances or mixtures that may not be used as toys or childcare products. 2. Individual or combined concentration of three PAEs less than or equal to 0.1%.	[13]
2022	WHO	DEHP	C water ≤ 8	[89]

However, there are still a lot of issues with PAE prevention and management, which can be roughly divided into three primary areas: One primary issue is the emission of PAEs from various sources. These sources include industrial emissions, agricultural activities, and waste incineration. Therefore, addressing the sources of PAEs can begin by focusing on these three areas. Industrial areas currently display enhanced PAE emissions compared to other regions [7,38,39]. Thus, it is essential to put policies in place to lessen the release and buildup of industrial wastewater and solid waste, with an emphasis on hindering the plastics industry’s polluting discharge and lowering the movement and penetration of PAEs into the environment at their source. Although PAEs are often employed as plasticizers in the manufacturing of plastic items, their physical and chemical characteristics make it easy for them to seep into the environment [4,5,6,60], so optimizing the plastics manufacturing process, developing biodegradable alternatives to PAEs, and enhancing the bonding between polymers and PAEs in plastic products are essential steps. These measures aim to reduce the release of PAEs into the environment and support the long-term growth of the industry. PAEs may migrate into the soil environment as a result of mulching, sewage irrigation, and the use of chemical and organic fertilizers. Due to regional variations in farming practices, soil PAE pollution levels and major pollutants range [22,91,92]. Thus, to minimize the entry of PAEs into the soil environment and maintain the sustainability of agricultural output, it is essential that farming techniques be optimized and site-specific management strategies be put in place. Moreover, one of the main causes of PAEs in the atmosphere is waste incineration [4]. This emphasizes the need for more effective plastic product recycling methods rather than directly burning plastic garbage.

The problem of the composite removal technique is the second. The total removal of PAEs from wastewater treatment plants is still a difficult task, making PAE disposal difficult. The process is made more complex by the strong hydrophobicity and adsorption of suspended organic debris, which prevents PAEs from mineralizing and makes treatment more challenging [14]. However, a study carried out in the Eastern Cape city of Alice, South Africa, revealed that 98% of the PAEs in the wastewater were removed during the treatment procedure, indicating that effective PAE purification in the aquatic environment is possible [92]. However, there is insufficient research on technologies for removing PAEs from atmospheric, food, and other environments. Therefore, developing integrated removal approaches, such as physicochemical processes, biodegradation, and advanced oxidation, is essential to ensure effective, secure, and reliable PAE degradation without causing secondary pollution in the environment. Microorganisms are important in the natural breakdown of PAEs, and microbial degradation of PAEs is becoming a significant area for future research. The hydrolysis mechanism of PAEs has been largely understood, and investigations into the degradation of these compounds in water and soil environments are ongoing [14,93,94,95,96,97]. This study component could provide new information regarding methods to remove PAEs from complicated environments, such as the atmosphere, that have not yet been studied. At the same time, surroundings involving lipid components (food) also need to have effective and feasible extraction, detection, and degradation techniques established. The best ways to remove PAEs from various environments continue to be researched, and when these techniques are applied in practical contexts, they can provide reliable scientific evidence in favor of PAE management and prevention, safeguarding public health.

Thirdly, the problem of pertinent rules and guidelines. Specifications for using various PAEs have been developed by several international organizations, which limit the usage of specific products [14,17,25,95,98]. Because of the diverse types and extensive applications of PAEs, it is essential to broaden restrictions on PAEs to safeguard the health and safety of all individuals. This includes establishing differentiated standards for PAE usage across different industries, particularly in plastics manufacturing such as food packaging, medical equipment, and agricultural films. Simultaneously, enhanced regulation of the plastics industry and the development of corresponding regulatory rules are necessary to manage pollution emissions from these sectors.

7. Conclusions

The possible effects of PAEs on human health have garnered a great deal of interest. Even though research on PAEs in the environment and living organisms has advanced significantly in recent years, many areas still need development and in-depth analysis. For example, there are several issues with the technology now in use to identify PAEs. These challenges involve constraints in identification speed and complexities in applying separation technologies within complicated settings. Moreover, the variability and complexity of assessing the health impacts of PAEs require a thorough investigation into their mechanisms of action. This effort not only improves our ability to accurately gauge the potential health risks associated with PAEs but also offers a scientific basis for developing efficient preventive and control strategies. Given the points raised earlier, future research might focus on the following areas: enhancing the establishment of more sophisticated and effective PAE identification technologies to meet the need for rapid and accurate detection; conducting detailed investigations into the impact mechanisms of PAEs and constructing a comprehensive and scientifically rigorous health risk assessment system; and exploring more effective methods for mitigating PAE pollution to minimize its impact on both the environment and human health. The use of these research avenues will enable more efficient solutions to the problems presented by ecological hazards and PAE contamination, thereby safeguarding the environment and public health.