Abstract
Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds generated during the incomplete combustion of organic materials, such as coal, oil, and biomass. PAHs are highly persistent in the environment and pose significant health risks due to their genotoxic, mutagenic, and carcinogenic properties. This review provides an overview of PAH formation, environmental accumulation, and the main human exposure pathways, including inhalation, ingestion, and dermal contact. It highlights the toxicological effects of PAHs on various systems of the human body, such as the nervous, respiratory, reproductive, immune, and cardiovascular systems. Acute exposure to PAHs can cause symptoms such as eye irritation, nausea, vomiting, and diarrhea, while chronic exposure is associated with cancer, cardiovascular diseases, respiratory issues, and reproductive dysfunction. Although most research relies on animal studies, the findings suggest that PAHs may cause severe harm to humans through mechanisms like DNA damage. Due to the limitations of extrapolating animal-based studies to human health, future researches should more thoroughly explore the specific mechanisms by which PAHs affect human health to address the challenges posed by PAH pollution.
Overview of Polycyclic Aromatic Hydrocarbons (PAHs)
Introduction to PAHs
PAHs are a class of organic compounds consisting of two or more fused aromatic rings. 1 These compounds are primarily produced during the incomplete combustion of organic materials such as coal, oil, gas, wood, and tobacco. 2 PAHs exhibit a wide range of physical properties that depend on their molecular weight and structure. 3 As the molecular weight increases, their volatility decreases, and their water solubility decreases with the number of rings. At room temperature, PAHs typically exist as colored crystalline solids. Due to their lipophilic nature, they are highly persistent in the environment, are thermally stable, and often exhibit properties such as electrical conductivity, emissivity, and corrosion resistance. Many PAHs possess photosensitive and fluorescent characteristics, emitting light at specific wavelengths when excited. Their unique ultraviolet (UV) absorption spectra also allow for the identification of various PAH isomers through UV absorption spectroscopy. 4
Formation and Deposition of PAHs
PAHs are generated through both natural and anthropogenic combustion processes. Common sources include industrial activities (eg, steel production, petroleum refining), residential heating, vehicle exhaust, forest fires, and tobacco smoke. PAHs can be released into the atmosphere in both gaseous and particulate forms during incomplete combustion. 5
Once released, PAHs can be transported over long distances before being deposited onto soil, vegetation, and water bodies via wet or dry deposition. The atmospheric behavior of PAHs is influenced by complex physical and chemical reactions, including interactions with other pollutants (eg, ozone, nitrogen oxides, sulfur dioxide) and photochemical transformations. These processes can lead to the formation of more toxic derivatives, such as nitro-PAHs and dinitro-PAHs. In colder environments, PAHs often condense onto fine particulate matter (PM2.5 and PM10), which allows them to travel further. 6 Over time, PAHs accumulate in ecosystems, leading to widespread environmental contamination.
Environmental Accumulation and Bioavailability
PAHs are highly persistent in the environment due to their stable chemical structure, and they accumulate in soil, sediments, and water bodies, often binding to organic matter. In aquatic ecosystems, PAHs tend to attach to sediments, where they can persist for extended periods. Their lipophilic nature facilitates bioaccumulation in aquatic organisms, particularly in benthic species that reside in contaminated sediments. Bioaccumulation occurs when organisms absorb PAHs faster than they can metabolize or excrete them, and this process can lead to biomagnification, resulting in higher concentrations in top predators like fish, birds, and marine mammals.
This accumulation poses significant risks to wildlife, as prolonged exposure to high levels of PAHs can result in developmental, reproductive, and immunological impairments. Due to their persistence and toxicity, PAHs are recognized as major environmental and food contaminants.
The U.S. Environmental Protection Agency (EPA) has identified 16 priority PAHs for regulation (Table 1), including naphthalene (Nap), acenaphthylene (Acy), acenaphthene (Ace), fluorene (Flu), phenanthrene (Phe), anthracene (Ant), fluoranthene (Flt), pyrene (Pyr), benz[a]anthracene (BaA), chrysene (Chry), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), indeno[1,2,3-cd]pyrene (IcdP), dibenz[a,h]anthracene (DahA), and benzo[g,h,i]perylene (BghiP). The International Agency for Research on Cancer (IARC) has categorized these 16 PAHs into four carcinogenicity groups: Group 1 (carcinogenic to humans), Group 2A (probably carcinogenic), Group 2B (possibly carcinogenic), and Group 3 (not classifiable). 7
Information of US EPA 16 PAHs.
Given the persistence and potential health risks of PAHs in the environment, understanding their toxicological impacts and mechanisms of action is crucial. This paper reviews recent progress in evaluating the health effects of PAHs on humans, with a focus on toxicological mechanisms and risk assessment.
Routes of Exposure to Humans
Humans are exposed to PAHs through several pathways, including inhalation, ingestion, and dermal contact. 8
Inhalation
Airborne PAHs, particularly those attached to fine particulate matter, are inhaled in environments with high levels of combustion products, such as urban areas, industrial zones, and traffic-heavy regions. 9 Individuals living near industrial plants, smokers, and those exposed to second-hand smoke are at higher risk.10–12 In the atmosphere, PAHs often combine with particulate matter, which then deposits onto the terrestrial biosphere, becoming a major route for entering other environmental compartments.
Ingestion
PAHs enter the human food chain through the consumption of contaminated food and water. Cooking processes, especially high-temperature methods like grilling, baking, frying, and charring, can produce significant amounts of PAHs. Foods that are processed, dried, or smoked also contribute to PAH exposure. 13 Additionally, some crops, such as wheat, rye, and lentils, can synthesize or absorb PAHs from contaminated water, air, or soil, leading to human intake through plant consumption. Seafood and other food products from contaminated environments are also common sources of ingestion-based PAH exposure.
Dermal Contact
Skin exposure to PAHs occurs when individuals come into contact with contaminated surfaces, such as soil or water. This is particularly relevant for workers in industries involving fossil fuels, asphalt, or coal tar, who may be at increased risk of dermal exposure to PAHs. The high lipophilicity of PAHs enables their absorption into the skin, contributing to overall exposure. 14
Given their widespread environmental presence and multiple exposure pathways, it is important to understand and mitigate the risks associated with PAH exposure to protect human health.
Health Impacts of PAH Exposure
PAHs are known to cause toxicity through mechanisms such as genotoxicity, mutagenicity, and oxidative stress. 15 Inside the body, PAHs are metabolized by cytochrome P450 enzymes, leading to the formation of reactive oxygen species (ROS) and electrophilic metabolites that bind to DNA, creating DNA adducts. This process can result in mutations, initiating cancer, particularly in organs exposed to high PAH levels, such as the lungs. PAH exposure has also been associated with cardiovascular diseases, respiratory disorders like asthma, and reproductive toxicity.
Prolonged exposure to PAHs, especially in occupational settings or urban populations, has been linked to a higher risk of lung cancer. Furthermore, recent research shows that prenatal PAH exposure can negatively impact child development, causing cognitive and behavioral impairments.
Mutagenicity and Carcinogenicity of PAHs
The carcinogenic potential of PAHs is well-established. PAHs act as complete carcinogens, participating in various stages of carcinogenesis, including the formation of DNA adducts, which lead to mutations in critical genes, such as the tumor suppressor gene p53. PAHs with four to six rings are particularly mutagenic, and their activation by cytochrome P450 enzymes produces carcinogenic metabolites, such as epoxides and dihydrodiols, that bind to NNA. This process increases the risk of cancers such as lung, esophageal, breast, and skin cancers. 16 PAH exposure has also been associated with increased risks of cancers in occupational settings and populations exposed to environmental pollution, such as aluminum refining workers and smokers. 17
Additionally, PAHs are linked to non-respiratory cancers, including esophageal and breast cancers, where epigenetic modifications like DNA methylation and miRNA changes contribute to cancer development. 18 Studies have found that benzo[a]pyrene can enhance HPV-mediated carcinogenesis in cervical cancer and may accelerate tumor growth in skin cancers when combined with UV radiation. 19
Genetic Toxicity of PAHs
PAHs exhibit genetic toxicity by damaging DNA, 20 with benzo[a]pyrene being the most well-studied. Animal experiments have confirmed that PAHs can be embryotoxic, and prenatal exposure has been associated with developmental issues such as reduced IQ, behavioral problems, and childhood asthma. Prenatal exposure to PAHs affects not only maternal health but also the fetus, as PAHs can cross the placenta, accumulate in fetal tissues, and even penetrate the blood-brain barrier.21,22 Studies have shown that DNA adduct levels in umbilical cord blood are often higher than in maternal blood, indicating significant risks for fetal development. Furthermore, PAHs can interfere with placental and umbilical cord growth, leading to adverse birth outcomes. Advances in molecular epidemiology have highlighted the risks associated with prenatal PAH exposure, showing links to developmental delays and systemic inflammation. Future research is necessary to explore the combined effects of PAHs and other environmental pollutants and to understand genetic susceptibilities that increase health risks. Continuous monitoring of PAH concentrations, along with public health interventions to reduce exposure, will be essential to minimize their long-term impacts on human health.
Effects of PAHs on Various Systems of the Human Body
Exposure to PAHs can negatively impact multiple systems of the human body, including the nervous, respiratory, endocrine, reproductive, immune, and circulatory systems.
Impact of PAHs on the Nervous System
PAHs exhibit neurotoxic properties. Animal studies reveal that PAH exposure can lead to a reduction in monoamine neurotransmitter levels, damage to dopaminergic neurons, increased amyloid-beta protein accumulation, and cellular apoptosis. Adults chronically exposed to PAHs may experience neurodegenerative conditions, likely due to the activation of systemic inflammation, which triggers neuroinflammation and subsequent neuronal damage. Workers exposed to PAHs for extended periods often show elevated levels of plasma cytokines, inducing oxidative stress and lipid peroxidation. 23
Prenatal exposure to PAHs is strongly associated with neurodevelopmental disorders, such as ADHD. The lipophilic nature of PAHs allows them to cross the blood-brain barrier, causing synaptic dysfunction, neuronal death, 24 and impaired neurobehavioral development in children. 25 Mechanisms of neurotoxicity include PAH interaction with aromatic hydrocarbon receptors (AHR), disrupting N-methyl-D-aspartate (NMDA) receptor gene expression, thus affecting synaptic plasticity, learning, and memory. 26 Additionally, PAHs induce oxidative stress and microglial activation, both of which lead to neuroinflammation and neuronal degeneration. This oxidative stress impacts the brain globally, and PAHs can further impair cognitive function by inhibiting acetylcholinesterase, leading to cholinergic system dysfunction. 27
Effects of PAHs on the Respiratory System
PAHs inhaled from polluted air accumulate in the lungs, where they cause oxidative damage and inflammation. 28 This is largely due to PAH's lipophilic nature, which allows them to build up in lung tissues. The activation of the cytochrome P450 enzyme family by PAHs increases the production of reactive oxygen species (ROS), damaging lung epithelial cells. PAH-induced inflammation, characterized by elevated levels of cytokines such as tumor necrosis factor-alpha (TNF- alpha), interleukin-4 (IL-4), and IL-6, leads to airway hyperresponsiveness and structural remodeling, contributing to decreased lung function.
Reduced levels of protective proteins, such asCC16, further exacerbate lung damage, increasing the risk of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). 29 Asthma exacerbation is linked to immune responses initiated by macrophage-derived cytokines, which promote allergic airway inflammation, airway remodeling, and ROS-induced immune dysfunction. Furthermore, exposure to PAHs from diesel exhaust has been shown to induce apoptosis and necrosis of bronchial epithelial cells, worsening respiratory health. 30
Impact of PAHs on the Endocrine and Reproductive Systems
PAHs exhibit both estrogenic and anti-estrogenic properties, affecting reproductive health through interactions with aryl hydrocarbon receptor (AHR) and estrogen receptors (ER). They can disrupt endogenous steroid secretion, leading to alterations in estrogen synthesis and metabolism.31,32 PAHs, such as benzo[a]pyrene (BaP), can reduce sperm quality, increase the risk of male infertility, and impair male reproductive health by accumulating in testicular tissue, causing mutations in spermatogonia stem cells.
PAHs also affect male fertility by disrupting the hypothalamic-pituitary-gonadal axis, which can result in conditions such as testicular cancer, hypospadias, and cryptorchidism. Additionally, they are linked to decreased sperm motility and concentration, potentially contributing to idiopathic male infertility. 33
Impact of PAHs on the Immune System
PAHs interact with the immune system, 34 leading to immunotoxicity, including the suppression of T and B cell function, inhibition of cytokine production, and induction of lymphocyte apoptosis. Many immunotoxic effects are mediated by PAHs binding to AHR, which promotes oxidative stress and disrupts calcium ion (Ca2+) homeostasis in immune cells. 35 This immune suppression may manifest without overt cytotoxicity, particularly at lower exposure levels. PAH-induced oxidative stress can impair phagocytosis, cytokine release, and antigen presentation by macrophages, weakening the body's immune defense.36,37
The Impact of PAHs on the Circulatory System
Exposure to PAHs has been associated with vascular dysfunction, contributing to cardiovascular disease development. 38 PAHs impair endothelial function, leading to reduced nitric oxide (NO)-dependent vasodilation, 39 a key feature of vascular dysfunction. Chronic exposure to PAHs elevates blood pressure, increases left ventricular mass, and induces cardiomyopathy and arteritis. Atherosclerosis development is linked to PAH-induced oxidative stress and cytochrome P450-mediated metabolism. This process involves PAHs binding to AHR, activating CYP1A enzymes, and contributing to plaque formation and cardiovascular damage. 40
Detection Methods for PAHs
Various methods have been developed to detect and analyze PAHs in different environmental samples. Thin-layer chromatography (TLC) is one such method, suitable for detecting PAHs with 4-6 aromatic rings in sludge, drinking water, and airborne particulate matter. It can also be used for preliminary qualitative and quantitative analysis of PAHs like naphthalene, anthracene, and phenanthrene. 41
Gas chromatography (GC) is widely regarded for its superior sensitivity and low detection limits compared to other methods. It is frequently employed to measure PAH levels in plastic toys, children's products, and plastic cutting boards. 42 High-performance liquid chromatography (HPLC), an alternative to GC, does not require complex derivatization procedures. HPLC is particularly effective for detecting PAHs in plastic products, offering high sensitivity and selectivity, which makes it suitable for meeting various detection needs.
Spectrophotometric methods are also used in PAH research, including ultraviolet spectrophotometry, fluorescence spectrophotometry, and phosphorescence spectrophotometry. In addition, electrochemical techniques have been applied to determine the concentrations of specific PAHs like 1-hydroxypyrene and benzo[a]pyrene in aqueous solutions.
With advancements in analytical techniques, newer methods such as thermal lens spectrophotometry, surface-enhanced Raman spectroscopy (SERS), immunological detection techniques, nanopore technology, capillary electrophoresis, and molecular imprinting technologies have gradually been incorporated for both qualitative and quantitative analysis of PAHs. 42 These emerging techniques are expected to further enhance the accuracy and efficiency of PAH detection across various applications.
Prevention and Control of PAH Pollution
In recent years, the harmful effects of PAHs on the environment and public health have garnered increasing attention, prompting the need for effective prevention and control strategies. The following measures are crucial for addressing PAH pollution 43 :
Intensify Public Awareness and Strengthen Legislation
Public awareness campaigns on environmental protection should be expanded to engage citizens in efforts to combat air pollution. Mobilizing the public and harnessing collective action can significantly enhance the effectiveness of air quality improvement initiatives. Strengthening legislation, standardizing air pollution control procedures, and encouraging active public participation in monitoring environmental changes are essential for achieving long-term results. Furthermore, increased investment in technology, along with policy support, will facilitate the integration of new technologies and equipment for better pollution control. Accelerating the industrialization of scientific innovations will also enhance environmental protection efforts.
Establish Comprehensive Monitoring Networks and Define Governmental Responsibilities
To ensure accurate and timely data on PAH levels, monitoring networks should be expanded and upgraded. This will allow for dynamic monitoring across various regions, enabling authorities to better understand PAH distribution patterns and respond more effectively to pollution control challenges. Governments should take responsibility for supervising and coordinating pollution control efforts, ensuring that the relevant units fulfill their roles. Improved communication and collaboration among departments will help resolve issues and increase the effectiveness of air pollution control initiatives.
Develop New Emission Standards for Pollutants
As the atmosphere's capacity to regulate pollutants is limited, controlling PAH emissions at the source is critical. New, stricter emission standards should be introduced to lower atmospheric pollutant levels. Industrial enterprises must comply with these standards by regularly testing their emissions, with environmental authorities monitoring results and implementing reward and punishment mechanisms accordingly.
Optimize Industrial Structures
A key step in reducing PAH pollution is to adjust industrial structures, modernize production technologies, and phase out outdated production capacities. This approach will limit PAH emissions at the source while promoting cleaner production processes and improving resource utilization efficiency.
Control Automobile Exhaust Pollution
Vehicle emissions are a major source of PAH pollution, particularly as the number private cars continues to rise. To mitigate this, several actions should be taken:
Promote the development and adoption of electric vehicles and solar-powered batteries, encouraging consumers to choose cleaner transportation options. Implement real-time monitoring of vehicle emissions, banning vehicles that exceed emission standard from road usage. Improve urban transportation systems and encourage the use of public transportation to reduce private car usage. Strengthen cooperation between environmental and traffic management departments to inspect and penalize vehicles that violate emission regulations. Urban greening efforts should also be prioritized, as plants can absorb PAHs, thus reducing atmospheric concentrations. Expanding green spaces will contribute to improved air quality.
Discussion
PAHs continue to be a significant environmental and public health concern due to their persistence, widespread distribution, and ability to bioaccumulate. The health risks associated with PAHs, particularly their carcinogenic and mutagenic properties, are well-documented. Prolonged exposure, whether through inhalation of polluted air, ingestion of contaminated food, or dermal contact, has been linked to serious health conditions, including cancer, respiratory diseases, and developmental issues in children. Importantly, prenatal exposure to PAHs is emerging as a critical area of concern, with potential long-term effects on neurodevelopment and respiratory health.
The complexity of PAH exposure lies not only in their environmental persistence but also in the multiplicity of their toxicological mechanisms. PAHs can induce oxidative stress, generate reactive oxygen species (ROS), and form DNA adducts, all of which contribute to genetic mutations and cellular damage. The lipophilic nature of PAHs allows them to accumulate in fat tissues and persist for long periods, further compounding their health impacts. As more research highlights the interaction between PAHs and other environmental pollutants, the need for a comprehensive approach to understanding their synergistic effects becomes paramount.
The regulatory framework around PAH management has made significant strides, with agencies like the U.S. Environmental Protection Agency (EPA) identifying priority PAHs for monitoring. However, challenges remain, particularly in addressing the industrial sources of PAH emissions and managing the cumulative exposure risks in urban and industrial settings. Efforts to reduce emissions at the source, such as improving industrial practices, transitioning to cleaner energy sources, and optimizing transportation infrastructure, are essential to reducing the global burden of PAHs. In addition, advances in detection technology, such as gas chromatography (GC) and high-performance liquid chromatography (HPLC), are improving our ability to monitor PAHs in various environments.
Further research is needed to better understand the full spectrum of PAH toxicity, particularly in vulnerable populations such as children, pregnant women, and those with preexisting health conditions. Understanding individual genetic susceptibilities to PAH exposure and the potential for interventions to mitigate adverse outcomes will be crucial in advancing public health measures. Public education campaigns, stricter regulations, and international collaboration are vital in addressing the long-term challenges posed by PAHs and reducing their harmful impacts on human health and the environment.
Footnotes
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
