1 Introduction

Polycyclic aromatic hydrocarbons (PAHs) are a diverse group of organic compounds formed through incomplete combustion of organic materials [1]. They are ubiquitously present in the environment and are generated through various anthropogenic activities, such as industrial processes, vehicular emissions, and tobacco smoke [2]. PAHs have garnered significant attention due to their toxicological properties and adverse effects on human health [3, 4].

Over the past decades, extensive research has been conducted to elucidate the impact of PAHs on human physiology [3, 4]. It has become evident that these compounds have far-reaching consequences on various physiological systems in the human body. From the respiratory system to the endocrine system, PAHs exert their influence through diverse mechanisms, including direct interactions with cellular components, modulation of gene expression [5], and disruption of endocrine signaling pathways [6].

The respiratory system represents a prominent target for PAH-induced toxicity. Inhalation exposure to PAHs can lead to respiratory ailments such as asthma, bronchitis, and impaired lung function. Moreover, the carcinogenic potential of certain PAHs has been extensively studied, linking their exposure to an increased risk of lung cancer [7, 8]. Beyond the respiratory system, PAHs have also been implicated in disrupting cardiovascular function. These compounds can induce oxidative stress, inflammation, and endothelial dysfunction, contributing to the development of cardiovascular diseases, including atherosclerosis and hypertension [9, 10]. Furthermore, the endocrine-disrupting properties of PAHs have raised concerns about their impact on reproductive health and developmental outcomes. PAH exposure has been associated with alterations in hormone levels, impaired fertility, adverse birth outcomes, developmental abnormalities [11], and nephrotoxicity [9, 12].

While strides have been made in understanding the diverse physiological impacts of PAHs, a notable research gap persists in the comprehensive synthesis of this knowledge. Existing studies have elucidated the associations between PAH exposure and various health ailments, ranging from respiratory disorders to cardiovascular diseases and reproductive health issues. However, a holistic overview that systematically connects the dots from the sources of PAHs to the manifestation of these health concerns is notably lacking. This review aims to bridge this critical gap by offering a nuanced exploration of the entire trajectory – from the sources and ubiquity of PAHs in the environment to the intricate mechanisms through which they exert their effects on human health. By synthesizing existing findings, we endeavor to provide a cohesive narrative that not only consolidates the current state of knowledge but also illuminates avenues for future research. This comprehensive perspective is essential for guiding future investigations and interventions, ultimately contributing to a more profound understanding of the complex interplay between PAH exposure and human health.

2 Materials and methods

To conduct a comprehensive review, a systematic and rigorous approach was employed. The following materials and methods were utilized to gather relevant information and critically analyse the literature:

2.1 Literature search

A thorough search was conducted across various scientific databases, including PubMed, Google Scholar, and Web of Science. The search terms used included “polycyclic aromatic hydrocarbons,” “PAHs,” “human physiology,” “health effects,” and related keywords. Relevant articles published in peer-reviewed journals were included, with publication dates of 2012–2023.

2.2 Selection criteria

The retrieved articles were screened based on their titles and abstracts for relevance to the topic of interest. Studies focusing on the physiological effects of PAHs in humans were included, while those focusing solely on environmental aspects or nonhuman models were excluded. Review articles, original research papers, and meta-analyses were considered for inclusion.

2.3 Data extraction and analysis

Data relevant to the physiological effects of PAHs on different systems in the human body were extracted from the selected articles. Essential information was recorded, such as study design, sample size, exposure assessment, physiological endpoints measured, and main findings. The total number of downloaded articles was 310. Among them, 50 articles were excluded due to their duplication and the need for more helpful information. Therefore, the total number of articles included in this study was 260. The extracted data were organized and synthesized to identify common themes and patterns across the literature.

2.4 Critical evaluation and synthesis

The findings from the included studies were critically evaluated, considering the study designs, strengths, and limitations. The synthesis of information involved identifying consistent trends, discrepancies, and knowledge gaps in the literature. Emphasis was placed on drawing evidence-based conclusions and providing a balanced overview of the current understanding of PAH-induced physiological effects.

2.5 Brief overview of PAHs

PAHs are organic pollutants that are naturally present in the environment, persisting and posing hazards. These pollutants can be found in surface water, soil, and sediments [13]. The occurrence and concentration of PAHs in the environment are influenced by human activities, such as industrialization and urbanization, and natural events, such as forest fires and volcanic emissions [14].

PAHs exhibit various colours, ranging from colourless to pale yellow solids. They comprise two or more fused aromatic rings, which can be arranged linearly, angularly, or in cluster formations [15]. PAHs are categorized based on the number of aromatic rings they possess. Compounds with 2–3 aromatic rings are considered light, while those with 4–6 are classified as heavy [16].

These compounds have high boiling and melting points and low vapour pressure, making their degradation and metabolism challenging in the natural environment [17]. Low-molecular-weight PAHs are highly toxic and have acute effects, whereas high-molecular-weight PAHs are associated with carcinogenic, teratogenic, and mutagenic effects on living organisms [18].

The hydrophobic nature (water-insolubility) and lipophilic properties (solubility in lipids) are common characteristics of PAHs. As Kronenberg et al. [19] emphasized an increase in molecular weight and the number of fused aromatic rings in PAHs leads to an escalation in their hydrophobicity, subsequently hindering their biodegradation.

PAHs originate from three primary sources: petrogenic, pyrogenic, and biological. Pyrogenic PAHs are formed during the anaerobic combustion of organic compounds at high temperatures (ranging from 350 °C to over 1200 °C). Processes such as coal conversion, combustion of motor/truck fuels, and forest fires contribute to the production of pyrogenic PAHs. Petrogenic PAHs arise from transporting and storing crude oil and its derivatives, oil spills in oceanic and freshwater environments, and leakage from large storage tanks [20]. Biological PAHs are either generated during the degradation of vegetative matter or synthesized by specific plants and bacteria [21].

The United States Environmental Protection Agency (USEPA) has classified 16 primary PAHs, including acenaphthene, benzo[ghi]perylene, chrysene, acenaphthylene, benz[a]anthracene, benzo[b]fluoranthene, anthracene, benzo[k]fluoranthene, benzo[a]pyrene, fluoranthene, indeno[1,2,3-cd]pyrene, naphthalene, phenanthrene, dibenz[a,h]anthracene, fluorene, and pyrene, as reported by Mojiri et al. [22]. Additionally, the International Agency for Research on Cancer has identified seven of these PAHs as carcinogenic, namely, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, indenol[1,2,2-cd]pyrene, and dibenzo[a,h]anthracene [23]. Among all PAHs, benzo(a)pyrene (BaP) is regarded as the most toxic due to its genotoxic activity.

2.6 Sources of PAHs

2.6.1 PAHs in air

In Pakistan, various types of PAHs, including Nap, Ace, Acy, Flu, Phe, Ant, Flt, Pyr, BaA, Chr, BbF, BkF, BaP, IcdP, Daha, and BghiP, have been identified in both indoor and outdoor air samples. The concentrations of these PAHs differ, with outdoor air recording a concentration of 2.132 ng/m3 and indoor air showing a slightly higher concentration of 2.390 ng/m3. Similarly, in Spain, the PM2.5 fraction of air has been analysed for Nap, Phe, Ant, Flt, Pyr, BaA, Chr, BbF, BkF, BaP, and IcdP, with a mean concentration of 0.79 ng/m3. The Basque Country in Spain exhibited a minimum concentration of 0.79 ng/m3 of PAHs bound with PM2.5, whereas China reported a maximum concentration of 4796.6 ng/m3 of PAHs associated with household air pollution. Table 1 provides a comprehensive overview of the identified PAHs in air samples worldwide.

Table 1 Concentration distribution and name of various PAHs in the air in different countries
Full size table

2.6.2 PAHs in soil

In China, various types of PAHs, including Nap, Ace, Flu, Phe, Ant, Flt, Pyr, Chr, BbF, BkF, BaP, IcdP, Daha, and BghiP, have been identified in agricultural soil. The mean concentration of these PAHs in the soil was recorded at 388 ng/g. Similarly, in the southeastern region of Romania, topsoil samples revealed the presence of Nap, Ace, Flu, Phe, Ant, Flt, Pyr, BaA, Chr, BbF, BkF, BaP, IcdP, Daha, and BghiP, with a mean concentration of 214 ng/g. Forest soil in the rural areas of the Pearl River Delta in southern China exhibited the minimum concentration of PAHs at 35.86 ng/g. In contrast, urban soil in Indianapolis City, USA, displayed a maximum concentration of 36,500 ng/g. Table 2 presents a comprehensive compilation of the identified PAHs in soil samples worldwide.

Table 2 Concentration distribution and name of various PAHs in different soil samples in different countries
Full size table

2.6.3 PAHs in water

In the Pearl River Delta of China, various types of PAHs, including Nap, Ace, Acy, Flu, Phe, Ant, Flt, Pyr, BaA, Chr, BbF, BkF, BaP, IcdP, Daha, and BghiP, have been detected in surface water. During the summer, their concentrations were recorded at 25.63 ng/L; in spring, the concentrations were slightly lower at 25.15 ng/L. Similarly, in Japan, seawater samples have shown the presence of Nap, Ace, Acy, Flu, Phe, Ant, Flt, Pyr, BaA, Chr, BbF, BkF, BaP, IcdP, Daha, and BghiP, with an average concentration of 0.03 ng/L. In Nigeria's Anambra River, the minimum concentration of PAHs was observed at 0.017283 ng/L, whereas South Africa's Mvudi River exhibited the highest concentration at 16,585,000 ng/L. Table 3 provides a comprehensive overview of the identified PAHs in different water samples worldwide.

Table 3 Concentration distribution and name of various PAHs in water in different countries
Full size table

2.6.4 PAHs in vegetables

In China, various types of PAHs, including Nap, Ace, Acy, Flu, Phe, Ant, Flt, Pyr, 2-BrFle, 1-BrPyr, 9,10-Br2Ant, 7-BrBaA, 9-BrAnt, 9-BrPhe, 9-ClFle, 9-ClPhe, 2-ClAnt, 9-ClAnt, and 9,10-Cl2Ant, have been documented in different vegetables, such as rape, chives Pakchoi, spinach, Chinese cabbage, carrot, radish, and potato. These PAHs exhibit varying concentrations, with PAHs recorded at 3.2551875 ng/g, BrPAHs at 0.296 ng/g, and ClPAHs at 0.3655 ng/g. Similarly, in Iran, PAHs such as BaA, Chr, BbF, BkF, BaP, and Daha have been identified in vegetables, with spinach (2.042 ng/g), lettuce (2.211 ng/g), cabbage (1.143 ng/g), potato (0.589 ng/g), carrot (0.564 ng/g), and radish (0.69 ng/g) displaying different concentrations. Iran exhibits the lowest concentration of PAHs in carrots at 0.564 ng/g, whereas Bangladesh records the highest concentration of 1240 ng/g PAHs in red amaranth. Table 4 presents an overview of the identified PAHs found in vegetables across various regions worldwide.

Table 4 Concentration distribution and name of various PAHs in different vegetables in different countries
Full size table

2.6.5 PAHs in milk

In Spain, a variety of PAHs, including Nap, Ace, Acy, Flu, Phe, Ant, Flt, BaA, Chr, BbF, BkF, BaP, IcdP, Daha, and BghiP, have been detected in human milk samples. The concentrations of these PAHs differ, with colostrum recording a concentration of 2.113 ng/g and mature milk showing a slightly lower concentration of 1.34 ng/g. Similarly, in Ghana, breast milk samples have revealed the presence of Nap, 2MethNaP, 1MethNap, Ace, Acy, Flu, Phe, Ant, Flt, Pyr, BaA, Chr, BbF, BkF, BaP, IcdP, Daha, and BghiP, with a mean concentration of 1105.63 ng/g (lipid weight). Milk powder samples in Sri Lanka exhibited the minimum concentration of PAHs at 0.13 ng/g (dw), while powdered milk in Egypt displayed a maximum concentration of 8200 ng/g of PAHs. Table 5 provides a comprehensive overview of the identified PAHs in milk samples from different regions worldwide.

Table 5 Concentration distribution and name of various PAHs in different milk samples in different countries
Full size table

2.6.6 PAHs in meat

In Denmark, a variety of PAHs, including Ace, Acy, Flu, Phe, Ant, Flt, Pyr, BaA, Chr, BbF, BkF, BjF, BaP, BeP, IcdP, Daha, BghiP, CPP, PER, 5MeCHR, DBalP, DBaeP, DBaiP, and DBahP, have been documented with corresponding concentrations in different meat types. The concentrations were recorded as 79.55 ng/g (beef), 220.4166 ng/g (pork), 99.95 ng/g (chicken), 8.7 ng/g (calf), 59 ng/g (lamb), 243 ng/g (lamb on a stick), 17.2 ng/g (salmon), and 13.8 ng/g (prawn). Similarly, in South Africa, PAHs such as BkF, BaP, IcdP, and BghiP have been reported with concentrations of 1.52415 ng/g (beef), 1.847475 ng/g (pork), and 1.587875 ng/g (chicken), respectively. Table 6 comprehensively summarizes the identified PAHs in meat samples across different regions worldwide.

Table 6 Concentration distribution and name of different PAHs in different meat types in different countries
Full size table

2.6.7 Chemical nature of PAHs

PAHs are lipophilic chemicals or organic compounds composed of multiple fused aromatic rings and occur naturally in coal tar, fossil fuel combustion, forest fires, and open flame-grilled meats. PAHs are found in cigarette smoke, diesel emissions, asphalt surfacing, tar roofing, and aluminum and coke plants. They are typically formed during incomplete combustion of organic matter [140]. PAHs are mostly colorless, white, or pale yellow solid molecules [69]. Due to their mutagenic and carcinogenic qualities, PAHs are among the most common chemical compounds known to cause cancer. Several of these chemicals are carcinogenic, mutagenic, teratogenic, and genotoxic. They are usually bioaccumulate in soft tissues of animals. High stability and an array of sources contribute to PAHs, which can be generically defined as diagenetic, pyrogenic, or petrogenic [141].

These compounds are not directly carcinogenic and act like synergists. The number of aromatic rings present varies among the hundreds of PAH and similar compounds found and identified. PAH is not a single chemical but a mixture of several PAH components. They range in volatility from the pure gas phase (2-ring) through phase distributed (3,4-ring) and essentially non-volatile (5,6-ring) compounds [142] (Fig. 1). There are two types of PAHs: high-molecular-weight PAHs (HMW PAHs, having four or more aromatic rings) and light-molecular-weight PAHs (LMW PAHs, having 2 or 3 aromatic rings). Depending on their molecular weight, they are released either in the form of particles (HMW PAHs) or as gaseous phases (LMW PAHs) [143]. PAHs have a higher resistance to nucleophilic attack due to their biological persistence, which is caused by the presence of concentrated electrons on aromatic rings (Fig. 1). Higher molecular weight PAHs are more complicated when dissolved molecules because they become more lipophilic and lose their water solubility.

Fig. 1
figure 1figure 1

Different polycyclic aromatic hydrocarbons with their chemical structure [146]

Full size image

Since PAHs are produced by industrial processes, thermal breakdown of organic materials—such as biomass or fossil fuels—and landfill effluents, which have been documented to contain different quantities of PAHs in the US, Sweden, and Poland, there are numerous sources of PAHs [144]. In an aerobic environment, PAHs released into the soil quickly biodegrade; however, because they may be poisonous to microorganisms, they may remain for prolonged in anaerobic environments or at high concentrations. Some of them tend to be adsorbed on the soil surface based on their octanol-carbon coefficient (Koc), volatilize based on their vapor pressure from dry soil or wet soil based on their Henry's law coefficient, and migrate towards groundwater if they are not biodegraded in the soil. After entering groundwater, certain PAHs have the tendency to dissolve in water based on their solubility and octanol–water coefficient (Kow); others have the tendency to volatilize from water based on their solubility and Henry's law constant (H); still, others tend to remain at the top of the water or migrate to the base of the groundwater body [145].

2.6.8 Toxic natures of PAHs

PAHs exhibit significant toxicity, exerting genotoxic, mutagenic, teratogenic, immunotoxic, and carcinogenic effects on microorganisms, laboratory animals, and humans. Their lipophilic and hydrophobic nature necessitates metabolic activation to manifest these adverse effects. The intricate combination of various PAH structures within a mixture enhances their toxicity, often through synergistic interactions [147, 148].

IARC has categorized PAHs into the following four groups [149]:

Group 1: Carcinogenic to humans.

Group 2A: Most likely carcinogenic to humans.

Group 2B: Possibly carcinogenic to humans.

Group 3: Not classifiable as carcinogenic to humans.

The toxicological impacts of PAHs are influenced by various factors, including their source, exposure dose, and duration. Soil-bound PAHs, primarily from biomass burning, present the highest cancer risk to humans. These PAHs enter the bodies of organisms primarily through ingestion, followed by dermal contact and inhalation [61, 150]. The health effects associated with PAH exposure range from acute manifestations, such as eye and skin irritation, inflammation, diarrhea, and confusion, to chronic outcomes, including kidney and liver damage, reproductive system abnormalities, compromised immune function, and respiratory dysfunction. Due to their high lipophilicity, PAHs accumulate readily in organisms' internal organs and adipose tissue, particularly in humans [20].

Among the various PAHs, naphthalene and benzo(a)pyrene (B(a)P) act as direct skin irritants. Naphthalene, a prominent component found in mothballs, can induce the breakdown of red blood cells when inhaled in substantial quantities due to its hemolytic properties. B(a)P exhibits neurotoxic and carcinogenic activities within the human body [21, 151]

PAHs also exert adverse effects on the immune system, although higher concentrations are typically required to induce immunotoxicity rather than carcinogenesis. Exposure to PAHs affects the bone marrow, the central site for immune cell production, maturation, and haematopoiesis. Consequently, structural and functional changes occur in the bone marrow, leading to apoptosis of lymphoid tissue, suppression of B and T cells, tumour development, and hypersensitivity. The primary mechanism underlying these effects involves the specific binding of PAHs to aryl hydrocarbon receptors (AhRs) present in immune cells, triggering the production of immune-toxic oxidative and electrophilic metabolites [151,152,153].

2.7 Toxic effects of PAHs on human health

2.7.1 Effect on the respiratory system

PAHs are a significant class of environmental pollutants known for their adverse health impacts, particularly on the human respiratory system. These compounds, characterized by multiple fused benzene rings, are primarily generated through incomplete combustion of organic matter, including fossil fuels, biomass, and tobacco. Decades of research have underscored the toxicity of soot particles containing PAHs, but recent studies have deepened our understanding of the specific chemical constituents and their mechanisms of harm (Table 7; Fig. 2).

Table 7 Different studies related to the effects of polycyclic aromatic hydrocarbons (PAHs) on the human respiratory system
Full size table
Fig. 2
figure 2

Effects of PAHs on the Human Respiratory System

Full size image

Mass spectrometry analysis has revealed that particles with medium oxidation states contain the highest abundance of oxygen-containing PAHs (OPAHs), such as 1,4-naphthoquinone, 9-fluorenone, and anthranone. These compounds are particularly harmful as they induce oxidative stress in human alveolar basal epithelial cells (A549), upregulating metabolites linked to inflammation and cell damage. Pathway analysis indicates that exposure to these OPAHs disrupts critical cellular functions, including the tricarboxylic acid cycle, cell proliferation, and transcriptional regulation, further highlighting their potential to cause respiratory diseases and cancer (Table 7).

Epidemiological studies corroborate the toxicological findings, linking PAH exposure to increased risks of lung inflammation and cancer. In Dhaka, Bangladesh, for instance, traffic emissions during winter led to significant airway deposition of PM2.5- and PM10-bound PAHs, resulting in heightened lung cancer risk. Similarly, in Benin City, Nigeria, PM2.5-bound PAHs in automobile workshops were found to exceed acceptable risk levels for adults, underlining the occupational hazards in urban environments (Table 7).

At the molecular level, PAHs have been shown to alter the expression of microRNAs (miRNAs), which regulate various physiological processes. Dysregulated miRNA expression due to PAH exposure may serve as biomarkers for respiratory conditions, providing a potential tool for early detection and intervention. Furthermore, urinary metabolites of PAHs, such as 1-hydroxynaphthalene and 2-hydroxyfluorene, have been associated with chronic obstructive pulmonary disease (COPD), emphasizing the systemic effects of these pollutants.

Interestingly, maintaining an antioxidant-rich diet and lifestyle has been shown to mitigate some of the adverse effects of PAHs on lung function. A study utilizing data from the National Health and Nutrition Examination Survey (NHANES) revealed that individuals with higher oxidative balance scores exhibited less severe lung function impairment in response to PAH exposure. This suggests that antioxidants might play a protective role against the oxidative damage induced by PAHs (Table 7).

The public health implications of PAH exposure are profound, especially in densely populated urban areas where vehicular emissions are a major source of these pollutants. The cumulative risk from combined chemical and non-chemical stressors necessitates a comprehensive approach to environmental regulation and pollution control. Bioremediation techniques using microorganisms to degrade PAHs in polluted environments offer a promising strategy to reduce their prevalence and associated health risks (Table 7).

Therefore, all these evidences highlight the multifaceted impact of PAHs on the human respiratory system, from molecular disruptions to significant public health challenges. Continued research and stringent regulatory measures are crucial to mitigate the health risks posed by these pervasive environmental contaminants. Addressing PAH pollution through improved combustion technologies, enhanced emission controls, and lifestyle interventions will be essential in safeguarding respiratory health and reducing the burden of related diseases.

2.7.2 Effect on the cardiovascular system

Exposure to PAHs is pervasive, occurring through inhalation of polluted air, ingestion of contaminated food and water, and dermal contact. Increasing evidence highlights the detrimental impact of PAHs on cardiovascular health through various mechanistic pathways, involving oxidative stress, inflammation, endothelial dysfunction, and dysregulation of lipid metabolism (Fig. 3).

Fig. 3
figure 3

Flow diagram of possible effects of PAHs on human cardiovascular systems

Full size image

Oxidative stress is a primary mechanism by which PAHs exert cardiovascular toxicity. PAHs undergo metabolic activation via cytochrome P450 enzymes to form reactive oxygen species (ROS) and PAH-DNA adducts. These ROS initiate a cascade of oxidative damage to cellular lipids, proteins, and nucleic acids, leading to cellular dysfunction. Inflammatory responses are subsequently triggered as immune cells, such as macrophages, release pro-inflammatory cytokines like IL-6, IL-8, and TNF-α. Chronic inflammation induced by PAHs contributes to the progression of atherosclerosis, a key underlying cause of cardiovascular diseases (CVDs) (Table 8).

Table 8 Different studies regarding the effects of polycyclic aromatic hydrocarbons (PAHs) on the human cardiovascular system
Full size table

Endothelial cells lining the blood vessels play a critical role in maintaining vascular homeostasis. PAH exposure disrupts endothelial function by decreasing nitric oxide (NO) bioavailability, a potent vasodilator and anti-inflammatory molecule. The reduction in NO is partly due to increased ROS, which scavenge NO, and the induction of endothelial nitric oxide synthase (eNOS) uncoupling. This dysfunction is characterized by impaired vasodilation, increased vascular permeability, and a pro-thrombotic state, all of which facilitate the development of atherosclerotic plaques (Table 8).

PAHs also influence lipid metabolism, contributing to cardiovascular risk. Studies have shown that PAH exposure is associated with elevated levels of total cholesterol, low-density lipoprotein (LDL), and triglycerides. This dyslipidemia promotes lipid accumulation within arterial walls, fostering plaque formation. Additionally, PAHs enhance the expression of scavenger receptors on macrophages, increasing the uptake of oxidized LDL and forming foam cells, which are hallmark features of atherosclerosis (Table 8).

Heart rate variability (HRV), a measure of autonomic nervous system function, is adversely affected by PAH exposure. Research involving coke oven workers indicated that higher PAH levels correlate with reduced HRV, reflecting autonomic imbalance and increased cardiovascular risk. Furthermore, PAHs are linked to elevated blood pressure through mechanisms involving sympathetic nervous system activation and direct vascular effects. Elevated blood pressure and reduced HRV are both significant predictors of cardiovascular morbidity and mortality (Table 8).

Recent findings suggest that red blood cell distribution width (RDW) may mediate the effects of PAHs on cardiovascular outcomes, such as ischemic heart disease (IHD). Higher RDW, indicative of red cell size variability, is associated with inflammation and oxidative stress. Mediation analysis reveals that RDW accounts for a small yet significant portion of the total effect of PAH exposure on IHD, highlighting its potential role in PAH-induced cardiovascular pathology (Table 8).

Mitigating the cardiovascular effects of PAHs involves both reducing exposure and enhancing resilience through lifestyle interventions. Studies have demonstrated that adopting a healthy lifestyle, including regular physical activity; can attenuate PAH-induced cardiovascular damage. Exercise has been shown to reduce oxidative stress, inflammation, and endothelial dysfunction, thereby offering protective effects against PAH toxicity. Additionally, maintaining adequate levels of essential metals like chromium may counteract the negative impact of PAHs on HRV and other cardiovascular parameters (Table 8).

2.7.3 Effect on the endocrine system

Hormones play a crucial role in maintaining the normal functioning of the endocrine system, acting as chemical messengers secreted by various glands in the body. Once released, hormones travel through the bloodstream, either conjugated or bound to carrier proteins, to reach their target cells. Through genomic and nongenomic mechanisms, hormones specifically bind to receptors on target cells, initiating signalling pathways.

In the genomic mechanism, a hormone binds to its receptor and dissociates chaperone proteins associated with it, allowing receptor dimerization. The dimerized receptor then binds to specific "response elements" on DNA, leading to alterations in gene expression. On the other hand, the nongenomic mechanism involves hormone binding to cell surface receptors, initiating intracellular signaling pathways.

However, certain chemicals, such as PAHs or endocrine-disrupting chemicals (EDCs), can disrupt the normal functioning of hormones and adversely impact living organisms. PAHs interfere with hormone synthesis, transport, metabolism, and the binding of hormones to target cell receptors, often mimicking hormone actions inappropriately. They can act as agonists or antagonists of estrogen, primarily disrupting the actions of steroid hormones such as estrogens and androgens. This disruption is attributed to the structural similarity of PAHs to the benzene rings found in steroid and thyroid hormones (TSH, T3, and T4).

EDCs, including PAHs, can cross the placenta, leading to potential health consequences for developing fetuses and infants that may manifest later in adulthood. These consequences include reproductive abnormalities, metabolic programming, an impaired immune system, alterations in adrenocortical function, obesity, diabetes, and cardiovascular diseases [87, 172, 173].

2.7.4 Effect on the thyroid gland

Recent research has revealed a special connection between urinary metabolites of PAHs and thyroid hormone (TSH) levels in children and adolescents. In females, elevated levels of PAH urinary metabolites (1-OH Nap, 2-OH Phe, and 1-OH Pyr) demonstrated a positive correlation with increased levels of T3, as depicted in Fig. 4. Conversely, among males, urinary metabolites (1-OH Phe, 2-OH Phe, and 9-OH Pyr) were associated with decreased levels of free T4 [174, 175].

Fig. 4
figure 4

Effect of PAHs on the human endocrine system

Full size image

2.7.5 Effect on the pancreas

Pancreatic β cells express two types of receptors: estrogen receptors (ERs) and androgen receptors (ARs). The ERs consist of two subtypes, ERα and ERβ, which play a critical role in the survival, maturation, protection against apoptosis, and transcription of the insulin gene in β cells. Conversely, AR increases the β cell mass, as depicted in Fig. 4. However, exposure to PAHs leads to a downregulation of pancreatic ER expression and decreased AR activity. Consequently, there is a reduction in β-cell mass and impaired insulin secretion [176,177,178].

2.7.6 Effect on the adrenal gland

The adrenal gland plays a crucial role in functioning the hypothalamic‒pituitary‒adrenal (HPA) axis, which is essential for maintaining human well-being. However, as endocrine disruptors, PAHs interfere with the proper functioning of the HPA axis, as depicted in Fig. 4. This disruption can be attributed to the structural and chemical characteristics of PAHs, including increased blood supply, lipophilicity resulting from an abundance of polyunsaturated fatty acids in the plasma membrane, and the presence of CYP450 enzymes that produce toxic metabolites and free radicals. The adrenal gland cortex produces steroid hormones, such as glucocorticoids, mineralocorticoids, and androgens. One essential glucocorticoid hormone is cortisol. Excessive production of cortisol hormone can lead to Cushing's syndrome (hypercortisolism), while insufficient production can result in Addison's disease. These hormonal imbalances significantly impact human health [179, 180].

2.7.7 Effect on the nervous system

As lipophilic compounds, PAHs possess endocrine-disrupting properties and can easily cross the placenta via passive diffusion. Consequently, they harm fertility and can enter the fetus from the mother's body. PAHs exert genotoxic effects on the developing fetus by undergoing metabolic activation through CYP450 enzymes and forming bulky PAH-DNA adducts. These adducts are associated with reduced birth weight, neural tube defects, decreased head circumference, and congenital heart defects in the developing fetus and newborn, as depicted in Fig. 5.

Fig. 5
figure 5

Effect of PAHs on the human nervous system

Full size image

Due to their lipophilic nature, PAHs can penetrate the blood‒brain barrier and induce changes in neuronal activity and synaptic plasticity within the central nervous system. Their exposure can lead to systemic inflammation. Among PAHs, benzo(a)pyrene (BaP), in conjunction with reactive oxygen species (ROS), triggers apoptosis in various brain regions by disrupting the balance of the antioxidant system. Ultimately, this neuronal cell death contributes to conditions such as attention-deficit hyperactivity disorder (ADHD), learning and memory impairment, dysregulated neurotransmitter regulation, anxiety, and depression [3, 181, 182].

Aβ42, abundant in cerebrospinal fluid, strongly interacts with PAHs, particularly BaP, leading to structural alterations. This disruption results in the deposition of Aβ42, causing neuronal damage and disturbance of electrochemical signals. Collectively, these activities contribute to the development of Alzheimer's disease [183].

2.7.8 Effect on the excretory system

PAHs primarily affect the lungs but also have implications for the liver and kidneys due to their involvement in detoxification and excretion processes. Once absorbed into the body, PAHs undergo rapid detoxification by the liver and are subsequently eliminated through the kidneys in urine, as depicted in Fig. 6. Therefore, the urinary concentrations of PAH metabolites, such as 2-hydroxyphenanthrene (2–OH Phe) and 3-hydroxyphenanthrene (3–OH Phe), serve as biomarkers of PAH exposure [184,185,186].

Fig. 6
figure 6

Effects of PAHs on the human excretory system

Full size image

The level of urinary PAH metabolite shows a positive correlation with serum uric acid levels. Uric acid primarily affects endothelial cells and promotes the production of reactive oxygen species (ROS), leading to increased oxidative stress. Consequently, elevated uric acid levels can impair kidney function and raise the risk of cardiometabolic diseases in children [184, 187].

PAHs transform the liver through three major pathways: (1) the CYP1A1/1B1 and epoxide hydrolase pathway (CYP/EH pathway), (2) the CYP peroxidase pathway, and (3) the aldo–keto reductase pathway (AKR). PAHs, including benzo(a)pyrene (BaP), primarily follow the CYP/EH pathway, leading to the formation of PAH metabolites such as B(a)P-7,8-diol-9,10-epoxides (BPDE). These metabolites can form adducts with DNA and act as carcinogens [188, 189].

Consequently, exposure to PAHs can result in nephrotoxicity and various kidney disorders, including albuminuria, chronic kidney disease (CKD), a decline in estimated glomerular filtration rate (eGFR), kidney stones, and end-stage renal diseases (ESRD) [190,191,192].

Kidney stones have become a prevalent and recurrent disease characterized by the abnormal accumulation of calcium oxalate (CaOx) crystals within the kidneys. The generation of reactive oxygen species (ROS) by PAH metabolites and PAH-DNA adducts is a significant contributing factor. ROS induce oxidative stress in mitochondria, leading to the formation of CaOx crystals, apoptosis, and damage to renal tubular epithelial cells. These apoptotic processes and structural changes in cell membranes facilitate the adhesion of CaOx crystals, initiating a cascade of kidney stone formation [193,194,195].

2.7.9 Effect on male and female reproductive systems

The hypothalamus-pituitary–gonadal (HPG) axis is critical in male and female reproductive processes. The hypothalamus releases GnRH, which stimulates the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These hormones act on the testes and ovaries, promoting the production of testosterone, estrogens, and progesterone, which are essential for reproductive functions. However, PAHs have been shown to disrupt these hormones and exhibit endocrine-disrupting properties [147, 196].

As endocrine disruptors, PAHs function as antiestrogens and antiandrogens; they bind to and activate estrogen receptors and aryl hydrocarbon receptors (AhRs). AhR and proteins such as heat shock protein 90 (Hsp90) and p23 reside in the cytoplasm. The binding of PAHs, such as benzo(a)pyrene (BaP), to AhR leads to the formation of an AhR-PAH complex in the cytoplasm, releasing Hsp90. This complex then translocates to the nucleus and binds to xenobiotic response elements (XREs) located in the promoter region of the CYP1A and CYP1B genes. Cytochrome P450 enzymes activate PAHs through monooxygenation, converting them into reactive diols and epoxides, as illustrated in Fig. 7. These reactive intermediates form adducts with DNA, inducing lipid peroxidation, generation of reactive oxygen species (ROS), DNA damage, and ultimately apoptosis.

Fig. 7
figure 7

Effect of PAHs on the human reproductive system

Full size image

In males, exposure to PAHs can result in a short telomere length (STL) of sperm DNA, leading to male infertility and poor semen quality. Reproductive dysfunctions such as idiopathic male infertility and cryptorchidism are among the significant consequences of endocrine disruption caused by PAH exposure [197,198,199].

In females, exposure to PAHs can cause menstrual cycle abnormalities, DNA damage in oocytes, ovarian damage, polycystic ovary syndrome, and reproductive diseases. Additionally, exposure to PAHs during pregnancy can result in adverse birth outcomes, including low IQ, birth weight, and premature delivery [151, 200].

The exposure of males to PM2.5 has deleterious effects on the hypothalamic-pituitary axis, spermatogenesis, and fertilization. PM2.5 triggers the production of reactive oxygen species (ROS) in the body, leading to oxidative stress. This oxidative stress initiates damage signals, depletion of antioxidants, and lipid peroxidation of the sperm plasma membrane, ultimately reducing membrane fluidity. These changes ultimately lead to DNA damage, apoptosis, and potential carcinogenesis, as illustrated in Fig. 7. Moreover, oxidative stress diminishes the production of endothelial NO, which plays a critical role in smooth muscle relaxation within the cavernosa. Consequently, PM2.5 impairs the ability to achieve an erection, leading to erectile dysfunction [201,202,203].

In females, exposure to Phe (phenantherene) hampers ovarian development and gives rise to various health issues in offspring. Excessive ROS in the oocyte leads to oxidative stress, disrupting calcium homeostasis and mitochondrial membrane potential. This imbalance affects mitochondrial fusion and fission due to the overexpression of Drp1 and Mfn2. Additionally, aberrant TPX2 expression disrupts spindle assembly and morphology, which is crucial for oocyte meiosis. As a result, these factors collectively impact oocyte maturation [204, 205].

3 Conclusion

In conclusion, this review article provides a comprehensive overview of the impact of PAHs on human physiology. PAHs are ubiquitous environmental pollutants that pose significant risks to human health. The extensive literature examined in this review highlights the detrimental effects of PAH exposure on various physiological systems, including the respiratory, cardiovascular, endocrine, reproductive, renal, and central nervous systems. The respiratory system is particularly vulnerable to PAHs, with evidence linking exposure to respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. PAH-induced inflammation, oxidative stress, and DNA damage contribute to the pathogenesis of these respiratory conditions.

Furthermore, PAHs disrupt cardiovascular homeostasis, leading to endothelial dysfunction, hypertension, and an increased risk of cardiovascular diseases. The mechanisms underlying these effects involve oxidative stress, inflammation, and the disruption of nitric oxide pathways. The endocrine-disrupting properties of PAHs have been extensively documented, affecting hormone synthesis, secretion, and receptor signalling. Dysregulation of the hypothalamic-pituitary–gonadal axis, thyroid function, and adrenal gland activity can lead to reproductive dysfunction, hormonal imbalances, and adverse developmental outcomes. PAH exposure has also been associated with renal toxicity, including nephrotoxicity, albuminuria, chronic kidney disease, and the formation of kidney stones. Oxidative stress and the formation of reactive oxygen species contribute to renal damage and impaired kidney function. PAHs can cross the blood‒brain barrier in the central nervous system and exert neurotoxic effects. They have been linked to neurodevelopmental disorders, cognitive impairments, altered neurotransmitter regulation, and an increased risk of neurodegenerative diseases such as Alzheimer's disease. Overall, the evidence suggests that PAHs have profound implications for human physiology, posing risks to multiple organ systems and contributing to the burden of various diseases. Understanding the mechanisms of these effects is crucial for developing effective preventive strategies and interventions. Given the ubiquity of PAHs in the environment and the potential for exposure through air pollution, occupational settings, and dietary sources, it is imperative to prioritize efforts to reduce PAH emissions, improve monitoring and risk assessment, and implement appropriate regulatory measures. Further research is needed to fill knowledge gaps, particularly regarding the long-term health effects of low-level chronic PAH exposure, the role of genetic susceptibility, and the potential for remediation strategies. Additionally, studies exploring interventions and protective measures to mitigate the adverse effects of PAHs on human physiology are warranted.

Therefore, this review underpins the importance of recognizing PAHs as significant environmental pollutants with profound implications for human health. Enhanced awareness, continued research, and targeted interventions are essential for minimizing exposure, protecting human physiology, and promoting healthier environments for current and future generations.