IntechOpen

Home > Books > Environmental Toxicology - Understanding, Impact, and Mitigation Strategies for a Sustainable Future

Open access peer-reviewed chapter

Histopathological Perspectives on Toxic Environmental Pollutants: Cellular Damage Pathways and Strategic Interventions in Mammalian Systems

Written By

Akinpelu Moronkeji, Temidayo Daniel Adeniyi, Samuel Ayobami Fasogbon, Joshua Olayinka Ajala, Emmanuel Tolulope Adegoke, Comfort E. Williams, Abiodun Oyeleke, Charles Egede Ugwu, Olubunmi Esan, Bob-Manuel Chinonso Osuji and Puritan Umeboro

Reviewed: 25 July 2025 Published: 10 September 2025

DOI: 10.5772/intechopen.1012228

Environmental Toxicology IntechOpen
Environmental Toxicology Understanding, Impact, and Mitigation Strateg... Edited by Suna Sabuncuoğlu and Onur Kenan Ulutaş

From the Edited Volume

Environmental Toxicology - Understanding, Impact, and Mitigation Strategies for a Sustainable Future

Suna Sabuncuoğlu and Onur Kenan Ulutaş

Book Details Order Print

Chapter metrics overview

175 Chapter Downloads

View Full Metrics
Advertisement

Abstract

Environmental toxicants (ETs) are pervasive and often exert synergistic effects that pose significant health risks to mammalian systems. Major pollutants such as airborne particulate matter (PM2.5/PM1.0), heavy metals, and various classes of agricultural pesticides continue to contribute to environmental degradation and disease burden. These toxicants originate from diverse sources, including battery manufacturing, metal plating, phosphate fertilisers, plastic stabilisers, plumbing systems, fossil fuel combustion, and intensive agricultural practices. A systematic evaluation of their public health implications is critical for informing policy and intervention. This chapter explores the mechanisms of toxicity of these environmental pollutants, highlighting their cellular and histopathological effects on mammalian tissues while proposing intervention strategies to safeguard human health and the ecosystem.

Keywords

  • environmental pollution
  • histopathology
  • mammalian system
  • oxidative stress
  • public health

1. Introduction

1.1 Overview of major environmental pollutants

Environmental toxicants (ETs) are widespread contaminants that can adversely affect mammalian health as toxicants bioaccumulate in organs, inducing oxidative stress and disrupting enzymatic functions, which can lead to DNA damage, thus predisposing to cancer and various types of metabolic diseases [1]. The exposure to ETs, like pesticides, organic pollutants, and heavy metals, can lead to multi- and transgenerational effects on fertility [2]. Reports have highlighted the integral role of the NLRP3 inflammasome in mediating the inflammatory responses triggered by ETs, contributing to organ damage and autoimmune diseases [3].

1.1.1 Airborne particulate matter (PM2.5, PM1.0)

Particulate matter (PM) is a complex mixture of solid particles and liquid droplets of varying sizes and content suspended in air. Sources include natural phenomena like volcanic eruptions and anthropogenic activities like industrial processes and vehicular emissions [4]. Indoor PM concentrations can exceed outside levels originating from activities such as cooking and smoking [5]. Fine (PM2.5) and ultrafine particulate (UFP) matter (PM1.0) represent considerable health concerns, particularly to the respiratory system and infant development.

They can penetrate deeply into the lungs, causing respiratory disorders as well as systemic effects [6]. Exposure to PM2.5 causes pro-inflammatory cytokine release, DNA damage, and the buildup of cancer metabolites [7]. PM2.5 exposure triggers pro-inflammatory cytokine release, DNA damage, and cancer metabolite accumulation [7]. PM exposure in the developing brain promotes oxidative stress, inflammation, and blood-brain barrier disruption, potentially leading to neurodevelopmental problems such as attention deficit disorders and autism spectrum disorders [8].

1.1.2 Heavy metals

Heavy metals are elements that naturally occur and have atomic weights and densities that are at least five times greater than those of water [9]. Although elements like copper are considered essential trace nutrients for biological functions, other heavy metals such as lead (Pb), cadmium (Cd), and mercury (Hg) are known for their high toxicity and tendency to bioaccumulate. These metals can infiltrate the environment through air, water, soil, and food chains, posing serious threats to human and ecological health by contributing to both acute and long-term health complications [10, 11, 12]. Anthropogenic activities associated with industrial, agricultural, and technological applications have significantly elevated the widespread presence of pollutants in the environment [13, 14]. Reports have documented the deleterious impact of heavy metal exposure, including toxicity associated with multiple organ damage, and they are classified as human carcinogens as they accumulate in environmental matrices and can enter the food chain, leading to bioaccumulation in humans and causing various diseases, including cancer [9, 15]. Lead interferes with enzymatic systems and calcium signalling, particularly affecting children’s developing nervous systems, while cadmium accumulates in the kidneys and liver, causing nephrotoxicity and increasing the risk of cancer [16, 17]. This mechanism of exerting toxicity is by strongly coordinating with biological molecules, replacing essential metals in proteins and enzymes, and inducing oxidative stress. Treatment strategies for metal poisoning often involve chelation therapy, especially in acute cases [18, 19].

1.1.3 Pesticides (pyrethroids, organophosphates, carbamates, organochlorines)

Both synthetic and natural pesticides are widely employed in agriculture and public health for pest control, but their extensive application has led to environmental contamination and potential toxic effects on various organisms [20, 21, 22]. Conventional pesticides can persist in the environment for decades, harming non-target species and ecosystems. These chemicals accumulate in the food chain, affecting human health by damaging organs, causing diseases, and potentially leading to death [23]. Biopesticides, derived from natural sources, offer a safer alternative with reduced environmental impact and lower toxicity to humans and beneficial organisms [24]. Pyrethroids, synthetic analogues of natural pyrethrins, exert neurotoxic effects by targeting sodium channels in nerve cells. Their exposure has been linked to oxidative stress, inflammation, and mitochondrial dysfunction, which could contribute to neurodegenerative diseases like Parkinson’s [25]. Pyrethroids also reduce antioxidant levels, induce kidney toxicity, alter immune responses, and disrupt carbohydrate and lipid metabolism, increasing the risk of obesity [26, 27]. Pyrethroids are classified based on their chemical structure and symptomology, with Type I and Type II compounds exhibiting different effects on sodium channel currents and neuronal excitability [28]. Organophosphates (OPs) are highly toxic compounds widely used as pesticides and in other applications. Their principal mechanism of toxicity is the inhibition of acetylcholinesterase, leading to acetylcholine accumulation in cholinergic synapses [29]. This can cause cholinergic crisis, characterised by muscle twitching, respiratory distress, and potentially death. Acute exposure can trigger status epilepticus, resulting in long-term brain damage if uncontrolled [30]. Clinical manifestations include cholinergic excess, nicotinic effects, cardiac complications, and respiratory failure, with management involving resuscitation, atropine administration, and oxime therapy [31]. Organochlorines, particularly dichlorodiphenyltrichloroethane (DDT) and its metabolites, are considered persistent organic pollutants (POPs) due to their environmental persistence, bioaccumulative potential, and toxicity [32, 33]. Furthermore, beyond reproductive toxicity, these compounds have also been implicated in the disruption of the central nervous system (CNS), immune function, and metabolic processes [34].

1.2 Sources and pathways of exposure

1.2.1 Industrial emissions

Industrial activities are significant sources of environmental contaminants, particularly heavy metals and chemical pollutants. Heavy metals like mercury, lead, and cadmium, released from industries such as battery manufacturing, can contaminate air, soil, and water. These pollutants can enter the human body via inhalation, ingestion, or dermal absorption, leading to a range of health problems such as cancer, cardiovascular disorders, and neurological impairments [35]. Likewise, the combustion of fossil fuels in industrial settings releases polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), and other airborne contaminants, which are associated with respiratory illnesses, central nervous system dysfunction, and additional adverse health effects [36].

1.2.2 Agricultural runoff and pesticide usage

Modern agricultural practices heavily rely on chemical fertilisers and pesticides, which can contaminate water resources through runoff and seepage [37]. Organophosphate pesticides, in particular, are widely used and can inhibit acetylcholinesterase, leading to neurological disorders [38]. These agrochemicals remain persistent in the environment, accumulate in aquatic organisms, and subsequently enter the food chain, ultimately posing health risks to humans. Pesticide exposure can occur via several channels, including contaminated food, water, and direct contact, resulting in developmental defects, skin disorders, and potential carcinogenic effects [23, 39]. The presence of these chemicals in the aquatic ecosystem has caused population declines in fish and other species, disrupting food webs [40].

1.2.3 Environmental persistence and bioaccumulation

Persistent organic pollutants (POPs) are synthetic compounds that are resistant to degradation and persist for extended periods within the environment [41]. These lipophilic substances bioaccumulate in living organisms and biomagnify through food chains, posing serious threats to human health and ecosystems [42]. POPs include pesticides, industrial chemicals, and byproducts [41]. Their ubiquitous prevalence in various environmental compartments, including water, soil, and air, facilitates long-range transport and global distribution. Table 1 shows the toxicodynamic mechanism of selected environmental toxicants affecting the mammalian system.

S/NToxicantModulatory mechanism
1.Arsenic (As)Inhibits mitochondrial enzymes such as pyruvate dehydrogenase and succinate dehydrogenase, hence disrupting cellular respiration. It causes oxidative stress, disrupts DNA repair pathways, and promotes apoptosis, making it both carcinogenic and hazardous to many organs, including the skin, liver, and kidneys [43, 44].
2.Lead (Pb)Lead interferes with several enzymatic pathways and mimics calcium. It causes long-term neurotoxicity, anaemia, and developmental abnormalities in children by interfering with the release of neurotransmitters, preventing haem synthesis by blocking enzymes such as δ-aminolevulinic acid dehydratase, and building up in bone [45, 46].
3.Mercury (Hg)Mercury exposure can lead to glutathione depletion, increased reactive oxygen species (ROS) formation, and damage to DNA and protein structures. In the nervous system, Hg alters neurotransmitter receptors, cytoskeleton, and synaptic proteins, disrupting synaptic structure and function. Methylmercury, an organic form, is particularly neurotoxic, as it can cross the blood-brain barrier and affect multiple molecular pathways, including glutamate signalling and the antioxidant [47, 48, 49].
4.Cadmium (Cd)Primarily targets the liver and kidneys, inducing oxidative stress and inflammation [50, 51]. Cadmium exposure leads to elevated ROS levels, DNA damage, and inhibition of DNA repair mechanisms. Chronic exposure can result in various cancers, osteoporosis, and respiratory issues. Exposure is also linked to mitochondrial dysfunction, epigenetic changes, and the disruption of essential metals [52, 53].
5.Benzene (C6H6)Benzene is a known haematotoxic and leukaemogenic chemical that targets haematopoietic stem cells (HSCs), causing haematological disorders and cancer. When metabolised, benzene produces toxic intermediates that accumulate in the bone marrow, generating ROS and damaging haematopoietic progenitor cells [54].
6.Particulate matter (PM2.5 and PM1.0)PM can penetrate deep into lung alveoli, entering the bloodstream, causing systemic inflammation, oxidative stress, and endothelial dysfunction by generating ROS, activating pro-inflammatory pathways, and impairing mitochondrial function, resulting in increased morbidity and mortality and contributing to cardiovascular diseases, respiratory disorders, and neurodegenerative conditions [36, 55, 56, 57, 58, 59].
7.Organophosphate pesticidesOrganophosphates (OPs) are potent neurotoxins that primarily exert their toxicity by predominantly inhibiting acetylcholinesterase (AChE), resulting in excessive accumulation of acetylcholine at synapses. This results in a cholinergic crisis, which involves continuous activation of muscles, glands, and the CNS, resulting in seizures and respiratory paralysis [30, 60, 61, 62].

Table 1.

Toxicodynamic mechanisms of some environmental contaminants on the mammalian systems.

Advertisement

2. Diagnostic relevance of histopathological evaluation in environmental toxicology

Histopathological evaluation remains integral in the diagnosis and assessment of tissue alterations induced by toxic environmental pollutants, as microscopic examination of tissue architecture provides critical insight into cellular and subcellular changes resulting from chronic or acute exposure to pollutants such as heavy metals, persistent organic pollutants (POPs), particulate matter, and volatile organic compounds [57, 63, 64]. In non-clinical toxicological evaluations, histopathology provides critical insight into organ-specific toxicity and carcinogenicity by identifying characteristic morphological alterations such as inflammation, necrosis, fibrosis, hyperplasia, and neoplasia, which serve as definitive evidence of pollutant-induced tissue damage [65]. Furthermore, while this diagnostic approach not only buttresses the link between exposure and disease manifestation, it also aids in determining the severity, reversibility, and pathogenesis of toxic insults on the mammalian system. Within environmental toxicology, histopathological analysis serves as an indispensable tool for validating experimental findings, guiding regulatory decisions, and advancing public health risk assessments [66]. For cancer detection, histopathology provides accurate identification of malignancies, guides tumour grading and staging, and detects biomarkers that influence treatment decisions [67].

2.1 Role of histopathology in detecting early and chronic tissue damage

Environmental toxicological studies often require the use of selected histopathological techniques for detecting early-stage cellular changes, inflammatory responses, degenerative alterations, and precancerous lesions [68, 69]. These methods enable detailed examination of tissue architecture and cellular morphology, allowing for accurate diagnosis and treatment planning in various conditions, including cervical cancer [70, 71]. While conventional bright-field microscopy has limitations, advanced imaging techniques can offer high-resolution 3D volumetric imaging of tissue structures at the nanometre scale, enhancing cancer pathobiology research [72]. Furthermore, machine learning approaches, including both classical and deep learning techniques, are increasingly being applied to histopathological image analysis, improving diagnostic accuracy and efficiency [73]. Despite significant progress, challenges remain in standardising techniques and scoring patterns to ensure reliability across different contexts. For instance, histopathological examination remains the gold standard for diagnosing and staging liver diseases, particularly non-alcoholic steatohepatitis (NASH). It allows for accurate assessment of disease severity, including steatosis, inflammation, and fibrosis, which are crucial for determining prognosis and guiding treatment. While non-invasive methods are advancing, they cannot yet match the detailed information provided by liver histology [74]. However, the integration of digital pathology and artificial intelligence (AI) is revolutionising histopathological analysis, as AI-based technologies can automate slide evaluation, eliminate observer subjectivity, and extract hidden patterns relevant to disease progression, further offering potential improvements in disease grading and prognostication across various organ systems [75].

2.2 Relevance in toxicological screening and health surveillance

Histopathology is particularly significant in toxicological investigations, providing vital insights into the effects of chemicals and drugs on biological tissues. It is essential for identifying target organ toxicity, evaluating dose-response relationships, and characterising mechanisms of action at the cellular level. Histopathological examination is particularly important in non-clinical toxicological evaluations, offering data on organ-specific toxicity and carcinogenicity. Recent advancements in digital pathology and deep learning have created opportunities to improve workflow efficiency and provide more objective assessments in toxicologic histopathology [76]. Mechanistic toxicology, which studies molecular, biochemical, and cellular interactions leading to toxicological effects, relies heavily on histopathology to evaluate health risks and safety in pharmacological and environmental toxicology. This approach has led to the discovery of biomarkers for monitoring potential toxicity progression following exposure to various substances [5]. In occupational health, histologic evaluation of dust burden in lung tissues can reveal environmental/occupational aetiologies that may otherwise be misclassified as idiopathic pulmonary fibrosis. Minimal criteria for dust characterisation in lung biopsies have been proposed to improve diagnosis accuracy [77].

2.3 Histopathological alterations in mammalian organs

2.3.1 Respiratory system

Globally, air pollution significantly affects human health, particularly the respiratory system. Exposure to fine PM is linked to reduced lung function, lower quality of life, and increased risks of acute respiratory infections, asthma, COPD, and lung cancer [78, 79]. Approximately 30% of respiratory diseases have been linked to personal exposure to high concentrations of ambient particulate matter (PM), which consists of tiny solid particles or liquid droplets suspended in the air [6]. These particles, originating from both human activities and natural sources, represent a heterogeneous mixture of various sizes and chemical compositions. Common constituents include sulphur dioxide, nitrogen dioxide, salts, carbonaceous materials, VOCs, polycyclic aromatic hydrocarbons (PAHs), and endotoxin [80, 81]. Exposure to PM can induce significant lung injury through multiple mechanisms. Generally, PM fractions of larger sizes (> PM2.5) deposit in the upper airways through impaction, while lesser fractions (< PM2.5) seep deeper into the lower airways and alveoli, depending on flow rates and diffusion, and could be transported to other regions through the bloodstream after inhalation [82]. Furthermore, pulmonary fibrosis is promoted by PM2.5 via the induction of mitochondrial dysfunction and epithelial-mesenchymal transition in alveolar type II cells [83]. Short-term exposure triggers inflammatory responses, particularly involving macrophages and neutrophils, but the lung can initiate repair mechanisms [84]. Exposure to PM2.5 also leads to oxidative stress, downregulation of antioxidant pathways, and damage to alveolar type II cells [85]. The NLRP3 inflammasome in macrophages plays a crucial role in PM2.5-induced lung injury by mediating pyroptosis and exacerbating inflammation, oxidative stress, and apoptosis [86]. PM2.5 causes oxidative stress in human lung tissue and BEAS-2B cells by activating enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH), quinine oxidoreductase (NQO), haem oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC). These enzymes stimulate Nrf2 via transmitting signals from phosphatidylinositol-4,5-biphosphate 3-kinase, which are linked to Nrf2 signalling, while also downregulating Nrf2-related transcription factors and increasing IL-8 gene expression [87, 88]. Additionally, PM2.5 activates the oxidative stress-related IL-6/AKT/STAT3/NF-κB signalling pathway, which upregulates intercellular adhesion molecule-1 (ICAM-1) expression in vascular endothelial cells. This cascade contributes to oxidative stress, DNA damage, and eventual death of pulmonary epithelial cells [89].

2.3.2 Alveolar damage, bronchial inflammation, fibrosis

Particulate matter exposure adversely affects the respiratory system via oxidative stress induction and inflammation by ROS generation, further leading to the activation of immune responses involving cytokines and chemokines, creating a cycle of inflammation that can lead to apoptosis, necrosis, and widespread tissue damage, which are processes central to the pathogenesis of asthma, COPD, and other pulmonary disorders, highlighting the need for stringent protection and regulatory measures [90, 91, 92]. Histologically, PM causes alveolar wall thickening, inflammatory cell infiltration, and pulmonary fibrosis [93]. PM induces oxidative stress, triggering inflammatory responses and fibrotic changes through pathways involving TXNIP/NF-κB and TGF-β/Smad3. These mechanisms contribute to epithelial-to-mesenchymal transition, increasing fibronectin production and promoting fibrosis. Chronic PM exposure results in bronchiolitis, characterised by fibrosis and distortion of small airways, particularly the distal membranous and respiratory bronchioles. Furthermore, exposure disrupts intracellular calcium homeostasis, a key regulator of cellular processes. Elevated intracellular Ca2+ levels, triggered by ROS and lipid peroxidation, activate inflammatory pathways and further ROS production, creating a vicious cycle of cellular damage [94].

2.3.3 Hepatic system

2.3.3.1 Hepatocellular degeneration and steatosis

Non-alcoholic fatty liver disease (NAFLD), a multifactorial disorder characterised by fat accumulation in the liver, is one of the most common chronic liver conditions globally. Environmental toxicants like heavy metals and organic pollutants play a significant role in the development of metabolic dysfunction-associated steatotic liver disease [95, 96]. Acute exposure to pollutants like PM triggers low-grade inflammation in the lungs and liver, marked by elevated pro-inflammatory cytokines, as shown in Figure 1. Key molecular pathways involved include JNKs-AP1, NF-κB, and TLR4. Additionally, pollutant exposure disrupts peroxisome proliferator-activated receptor (PPAR) activity, impairing lipid and glucose metabolism [98]. Exposure to Cd, Pb, As, and Hg is associated with increased risk of non-alcoholic fatty liver disease (NAFLD) and altered liver injury markers [99]. These metals induce hepatic lipid accumulation by activating lipogenesis and inhibiting fatty acid β-oxidation through various signalling pathways [17]. Perfluorooctane sulfonate (PFOS), an organic pollutant, promotes hepatic steatosis by inhibiting AMP-activated protein kinase (AMPK) phosphorylation, leading to increased acetyl-CoA carboxylase activity and reduced fatty acid oxidation. Endocrine-disrupting chemicals (EDCs) interfere with nuclear receptors, disrupt hormonal signalling, and impair mitochondrial function, contributing to MASLD development [100]. Occupational exposure to toxicants is also implicit in MASLD progression to advanced chronic liver disease and hepatocellular carcinoma [101].

Figure 1.

Diagram of inhaled particulate matter promoting hepatic steatosis [97].

2.3.4 Renal system

Heavy metals like Pb, Cr, Cd, Hg, and As pose significant health risks because of their persistence in the environment and potential to contaminate soil and drinking water [102]. Human exposure commonly arises from industrial activities such as mining, tanning, textile dyeing (chromium), battery production (cadmium), pesticide and fertiliser use (mercury), and smelting processes (arsenic) [103]. These metals can accumulate in the body and damage vital organs. Toxicity is determined by factors such as the absorbed dose, the route of exposure, and whether the exposure was acute or chronic. Toxic effects are largely mediated by oxidative stress caused by free radical generation, resulting in cellular injury and various health disorders [104]. Kupffer cells (KCs) play an integral role in the progression of liver diseases such as alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) [95, 96]. When activated, KCs release pro-inflammatory cytokines and chemokines, contributing to liver inflammation and fibrosis [96, 105]. They interact with hepatic stellate cells, promoting their activation and subsequent fibrosis. Interestingly, KCs can also transdifferentiate into fibrocytes, directly participating in liver fibrosis. Activation of pattern recognition receptors on KCs and other liver cells causes the generation of pro-inflammatory and pro-fibrotic factors, further exacerbating liver damage [105].

2.3.4.1 Glomerular and tubular injury due to Cd and Pb exposure

Cadmium and lead are non-essential heavy metals with no physiological function in humans and are recognised for their high toxicological significance, with chronic exposure, even at low environmental levels, strongly linked to nephrotoxicity, elevated risk of chronic kidney disease (CKD), and metabolic disorders such as diabetes mellitus [106]. These metals predominantly accumulate in the proximal renal tubules, causing structural damage such as tubular atrophy, interstitial fibrosis, and glomerular injury. Chronic elevated Pb exposure can lead to irreversible kidney changes such as interstitial fibrosis, tubular atrophy, glomerular sclerosis, and, eventually, renal failure. Co-exposure to Cd and Pb has been shown to enhance nephrotoxicity, with Cd being the principal cause of renal tubular destruction and Pb amplifying Cd’s effects [106]. Pb induces oxidative stress indirectly by increasing the concentration of free Fe, which acts as a Fenton’s metal. The elevated Fe in the blood occurs due to the Pb displacement from the haemoglobin molecule (plumbemia). Pb mimics and displaces essential cations (Ca2+, Zn2+, Cu2+, and Mn2+), which are crucial cofactors of antioxidant enzymes, thus reducing their activity by elevating oxidative stress in the tissues. In addition, Cd primarily enters the body via ingestion of contaminated food, inhalation of tobacco smoke, and inhalation of polluted air. Smokers, for instance, have been found to exhibit Cd blood levels 4–5 times higher than non-smokers [107]. Once absorbed into the bloodstream, Cd binds to albumin and is transported to the liver, where it induces the synthesis of metallothionein (MT). This leads to the formation of cadmium-metallothionein (CdMT) complexes [108]. Cadmium’s long biological half-life of about 25 years leads to its progressive accumulation in renal tissue. Although only a portion of inhaled (10–50%) and ingested (5–10%) Cd is absorbed, long-term exposure poses significant health risks [109].

2.3.5 Nervous system

2.3.5.1 Neurotoxic effects of chronic pesticide exposure: Mechanisms and implications

Chronic pesticide exposure, particularly to organophosphates, pyrethroids, and fungicides, has been increasingly associated with neurological and neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). These chemicals induce oxidative stress, disrupt neurotransmission, and cause neuronal damage in brain regions such as the hippocampus, corpus striatum, cerebral cortex, and cerebellum [110, 111]. Pesticides act through multiple neurotoxic pathways. They inhibit acetylcholinesterase activity, impair mitochondrial function by disrupting the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS), and elevate ROS, resulting in oxidative damage [112]. Some pesticides, such as rotenone, DDT, and DDE, also activate NADPH oxidases, further promoting ROS accumulation and neuroinflammation [113]. Many pesticides can cross the blood-brain barrier, leading to direct neural damage and gliosis, which is directly associated with injury or neurodegeneration [114]. Pyrethroids, in particular, have been implicated in behavioural impairments, Tau hyperphosphorylation, and neurofibrillary tangle formation consistent with Alzheimer’s pathology. Fungicides at environmentally relevant doses (e.g., 0.1 μg/L in drinking water) have been shown to promote β-amyloid (Aβ1–42) fibrillogenesis, elevate BACE1 levels, reduce neprilysin activity, and increase cerebral amyloid deposition, contributing to cognitive decline and cerebral amyloid angiopathy [115, 116]. The cumulative neurotoxic effects of chronic pesticide exposure are mediated through oxidative stress, mitochondrial dysfunction, neuroinflammation, and dysregulation of Aβ and tau-related pathways, all of which compromise neuronal integrity and brain function [8, 117]. This evidence underscores the need for urgent, stricter regulatory measures and neuroprotective strategies, particularly for at-risk populations such as agricultural workers and residents in farming regions. Additionally, while certain heavy metals are well-established contributors to the development and exacerbation of various diseases, emerging pollutants have also been increasingly associated with histopathological alterations, as documented in Table 2. Figure 2 also highlights the potential neuropathological mechanisms associated with pesticide exposure.

Pollutant typeOrgan affectedHistopathological findingsReference
Polystyrene microplasticsLungCytotoxic and inflammatory[118]
Polystyrene microplasticsPlacentaOxidative stress, mitochondrial swelling, and trophoblast degeneration[119]
Polyethylene microplasticsIleumVillous atrophy, hyperplasia of goblet cells, nuclear pyknosis, and heightened immunoreactivity of p53[120]
Polystyrene microspheresLiver, kidney, brainDisruptions in amino acid metabolism, oxidative stress pathways, and pro-inflammatory cytokine expression[121]
Titanium dioxide nanoparticlesLiverFibrosis, inflammation, and hepatocellular necrosis[122]
Glyphosate agrochemicalBrainIncreased immunoreactivity[60]

Table 2.

Summary of histopathological effects of selected emerging pollutants.

Figure 2.

Diagram of potential neuropathological mechanisms of pesticides [117].

Advertisement

3. Environmental and regulatory controls

3.1 Phasing out persistent organic pollutants (POPs)

Persistent organic pollutants (POPs) are synthetic toxicants known for their environmental persistence, bioaccumulative potential, and long-range transport. Derived primarily from industrial chemicals and agricultural pesticides, these compounds pose considerable health and ecological risks due to their high toxicity and resistance to degradation [123]. Common examples include dichlorodiphenyltrichloroethane (DDT), polychlorinated biphenyls (PCBs), and dioxins. In humans, exposure mainly occurs through the intake of contaminated food, especially fatty animal-based products, where POPs accumulate in adipose tissues. Secondary exposures may occur via drinking contaminated water or dermal contact. Importantly, POPs can cross the placenta and be transferred to infants through breast milk. Despite this, global health agencies emphasise that the benefits of breastfeeding continue to outweigh the potential risks posed by POPs [124, 125].

Histopathological studies in laboratory models have demonstrated typical tissue damage from POP exposures, such as hepatocellular ballooning, renal tubular vacuolisation, and aberrant immune infiltration [125]. Additionally, zebrafish larvae exposed to realistic human-relevant POP mixtures exhibited cartilage malformations and impaired bone mineralisation, largely mediated by interference with nuclear receptor signalling pathways, including androgen, vitamin D, and retinoic acid receptors [126].

3.2 Air and water quality regulation

Air and water pollution are major global public health challenges. Airborne pollutants like PM2.5, VOCs, SO2, and NOx largely stem from fossil fuel combustion, industrial processes, and vehicle emissions, while water contaminants such as Pb, Cd, As, Hg, and pesticides are linked to activities like mining, agriculture, and improper waste disposal [127]. The variable chemical makeup of these pollutants, including trace metals, inorganic salts, and organic matter, contributes to oxidative stress, inflammation, and organ damage. PM2.5, for instance, can cause alveolar injury and fibrosis, while chronic exposure to waterborne heavy metals leads to renal and hepatic toxicity and DNA damage [128, 129]. Many developing and underdeveloped countries lack comprehensive regulatory policies on air and water quality. In contrast, developed nations like the United States have established frameworks such as the Clean Air Act and the Safe Drinking Water Act, which enable the Environmental Protection Agency (EPA) to regulate pollutants. Additionally, the World Health Organisation (WHO) offers global guidelines to protect vulnerable populations [130]. However, enforcement and implementation vary widely across regions, with significant disparities between high-income and low-resource settings [127]. Technological advancements such as satellite-based environmental monitoring, real-time air quality sensors, and community-level water testing have greatly enhanced pollution surveillance [131].

3.3 Biomedical intervention

3.3.1 Use of antioxidants and chelators

Environmental toxicants frequently induce excessive production of ROS, leading to oxidative stress that compromises mitochondrial function and causes structural damage to lipids, proteins, and DNA. This oxidative injury manifests histologically as cytoplasmic vacuolisation, necrosis, and apoptotic cell death [56, 132, 133]. Antioxidant therapies, particularly N-acetylcysteine (NAC), help restore redox balance and protect cellular structures, with evidence showing NAC’s efficacy in reversing cadmium-induced renal and mitochondrial damage [134]. Particulate matter and ultrafine particulates (UFPs), rich in trace metals and organics, further aggravate systemic oxidative stress and inflammation [135].

Chelation therapy using agents like ethylenediaminetetraacetic acid (EDTA) and dimercaptosuccinic acid (DMSA) enhances metal excretion and improves histopathological outcomes in metal-exposed individuals but must be applied carefully to prevent loss of essential minerals. Oxidative injury is often amplified by pollutants such as nitrogen dioxide, ozone, and polycyclic aromatic hydrocarbons (PAHs), which promote ROS generation through redox reactions like the Fenton reaction. These free radicals disrupt mitochondrial function, fragment DNA, and activate pro-inflammatory pathways such as NF-κB and MAPK [135]. A crucial regulator of antioxidant defence is nuclear factor erythroid 2-related factor 2 (Nrf2), which controls the expression of detoxification and cytoprotective genes [136]. Nrf2 activation mitigates oxidative damage induced by environmental pollutants, while its deficiency heightens susceptibility to cytotoxicity and inflammation [137]. This pathway is increasingly recognised as a promising therapeutic target for pollution-induced tissue injury. Recent findings by Issa et al. [138] demonstrate that chronic exposure to thiamethoxam (TMX), a widely used neonicotinoid pesticide, causes dose-dependent liver and kidney injury, marked by suppressed antioxidant activity, increased lipid peroxidation, and DNA fragmentation. Immunomodulatory drugs have shown efficacy in pollutant-induced injury. For example, corticosteroids have been used in murine models to normalise alveolar architecture and reduce lung inflammation triggered by PM via suppression of IL-1β and TNF-α [139, 140]. These interventions may reduce mucosal damage and chronic inflammation, although further clinical validation is required.

3.4 Public health strategies

3.4.1 Biomonitoring and health surveillance

Biomonitoring (BM) is a useful technique in exposure assessment since it tracks exposure to harmful contaminants and their effects in exposed subjects’ bodily fluids. This method evaluates the overall absorbed dose of xenobiotic chemicals while accounting for individual factors such as age, gender, and physiological conditions, as well as the numerous exposure sources arising from the environment and personal habits (such as diet and cigarette smoking). Using a non-invasive matrix, the measurement of chemicals in urine is a reliable method for obtaining exposure profiles at low environmental levels [141]. According to Viegas et al. [142], BM includes exposure from every source. It can be used to evaluate the efficacy of current risk-management strategies and find unintended and unforeseen exposures. Biomonitoring involves the assessment of chemicals and their metabolites within the human body, typically by analysing exhaled breath condensate, blood, urine, hair, or breast milk. It offers a combined indicator of the degree of chemical exposure from several exposure pathways.

3.4.2 Risk communication and community-based intervention

Effective risk communication remains essential for community-based interventions addressing environmental pollution, as it helps the public understand the harmful effects of chemical contamination. Success relies on delivering culturally sensitive, locally tailored messages that consider community demographics, history, and sociocultural factors [143]. Understanding community perceptions and knowledge sources enhances the relevance and impact of these strategies, further fostering trust, engagement, and more effective responses to environmental health risks [144]. In several low- and middle-income countries (LMICs), inadequate data from poor waste management and infrastructural limitations hinder accurate risk assessment, which negatively impacts effective communication that is not only crucial for guiding public health actions but also for reducing anxiety, encouraging behaviour change, fostering trust, and promoting environmental justice [145, 146, 147]. Furthermore, adequate engagement of the community further strengthens the interpretation of scientific findings, facilitates message dissemination, and ensures policies reflect public needs, which is an approach endorsed by the WHO’s Helsinki Statement [148]. Involving local stakeholders in health policy development increases its relevance and sustainability [149]. Also, multisectoral interventions spanning transport, urban planning, industry, agriculture, and personal behaviour are increasingly employed to reduce pollution exposure, often supported by legislation and public-private partnerships, while behavioural interventions remain essential for minimising personal exposure risks [150].

Advertisement

4. Conclusion

The ongoing rise in industrialisation, urban development, and global expansion continues to escalate environmental pollution, exposing mammalian systems to a wide array of toxicants such as heavy metals, pesticides, and emerging micro- and nanoplastics. These pollutants exert their harmful effects through diverse cellular and molecular mechanisms such as oxidative stress, mitochondrial dysfunction, inflammation, apoptosis, and dysregulation of signalling pathways. Histopathological assessments have proven invaluable in revealing organ-specific structural and functional damage, making them essential endpoints in environmental toxicology. While advanced technologies like digital pathology, AI-based lesion detection, and integrative omics have significantly enhanced our ability to detect and characterise toxicological impacts. However, critical research gaps remain, including the lack of chronic, low-dose exposure models, standardised detection methods for micro- and nanoplastics in tissues, and insufficient mechanistic insight into emerging toxicants. Moreover, there is a notable scarcity of human epidemiological and histopathological data, highlighting the need for dedicated biobanks and tissue repositories. To effectively mitigate the health risks associated with environmental pollutants, future efforts must adopt a holistic, interdisciplinary approach, integrating histopathology, toxicology, environmental science, and public health, with priority given to developing harmonised protocols, enhancing mechanistic studies using high-resolution molecular tools, and translating scientific findings into actionable policy through robust regulatory toxicology and stakeholder engagement.

Advertisement

Conflict of interest

The authors declare no conflict of interest.

Advertisement

Abbreviations

AI

artificial intelligence

CdMT

cadmium-metallothionein

CKD

chronic kidney disease

DDT

dichlorodiphenyltrichloroethane

ETs

environmental toxicants

GCLC

glutamate-cysteine ligase catalytic subunit

HO-1

haem oxygenase-1

ICAM-1

intercellular adhesion molecule-1

KCs

Kupffer cells

MT

metallothionein

NADPH

nicotinamide adenine dinucleotide phosphate

NAFLD

non-alcoholic fatty liver disease

NASH

non-alcoholic steatohepatitis

NQO

quinine oxidoreductase

PAHs

polycyclic aromatic hydrocarbons

PM

particulate matter

POPs

persistent organic pollutants

PPAR

peroxisome proliferator-activated receptor

ROS

reactive oxygen species

UFPs

ultrafine particulates

VOCs

volatile organic compounds

References

  1. 1. Ibadi EA, Awad HK, Hussain LI. Environmental toxins and their organ-specific effects: A comprehensive review of human exposure and accumulation. Journal of Agricultural, Environmental and Veterinary Sciences (JAEVS). 2024;8(2):10-24
  2. 2. Rebuzzini P, Fabozzi G, Cimadomo D, et al. Multi- and transgenerational effects of environmental toxicants on mammalian reproduction. Cells. 2022;11:1-24
  3. 3. Moloudizargari M, Moradkhani F, Asghari N, et al. NLRP inflammasome as a key role player in the pathogenesis of environmental toxicants. Life Sciences. 2019;231:116585
  4. 4. Matei E, Râpă M, Mateș IM, et al. Heavy metals in particulate matter—Trends and impacts on environment. Molecules. 2025;30:1-29
  5. 5. Singh GK, Rai S, Jadon N. Major ambient air pollutants and toxicity exposure on human health and their respiratory system: A review. Journal of Environmental Management and Tourism. 2021;12:1774-1788
  6. 6. Mack SM, Madl AK, Pinkerton KE. Respiratory health effects of exposure to ambient particulate matter and bioaerosols. Comprehensive Physiology. 2020;10:1-20
  7. 7. Kaura S, Ding Y. Particulate matter with a diameter of 2.5 μm causes multiple pathological dysfunctions as presented by various biomarkers. Environmental Disease. 2019;4:57
  8. 8. Shang M, Tang M, Xue Y. Neurodevelopmental toxicity induced by airborne particulate matter. Journal of Applied Toxicology. 2023;43:167-185
  9. 9. Mitra S, Chakraborty AJ, Tareq AM, et al. Impact of heavy metals on the environment and human health: Novel therapeutic insights to counter the toxicity. Journal of King Saud University - Science. 2022;34:101865
  10. 10. Adeniyi TD, Achukwu PU, Abubakar AA, et al. Heavy metals obtained from waterways induced neurodegeneration in the prefrontal cortex of Wistar rats. European Journal of Anatomy. 2019;23:65-76
  11. 11. Phaenark C, Phankamolsil Y, Sawangproh W. Ecological and health implications of heavy metal bioaccumulation in Thai Fauna: A systematic review. Ecotoxicology and Environmental Safety. 2024;285:117086
  12. 12. Jomova K, Alomar SY, Nepovimova E, et al. Heavy Metals: Toxicity and Human Health Effects. Berlin Heidelberg: Springer; 2025. DOI: 10.1007/s00204-024-03903-2
  13. 13. Briffa J, Sinagra E, Blundell R. Heavy metal pollution in the environment and their toxicological effects on humans. Heliyon. 2020;6:e04691
  14. 14. Angon PB, Islam MS, Shreejana KC, Das A, Anjum N, Poudel A, et al. Sources, effects and present perspectives of heavy metals contamination: Soil, plants and human food chain. Heliyon. 2024;10(7):e28357
  15. 15. Das S, Sultana KW, Ndhlala AR, Mondal M, Chandra I. Heavy metal pollution in the environment and its impact on health: Exploring green Technology for Remediation. Environmental Health Insights. 2023;17:11786302231201259. DOI: 10.1177/11786302231201259
  16. 16. Abubakar US. Copper and lead as environmental pollutant and their elemental toxicity – A review. Scientific World Journal. 2024;19:342-346
  17. 17. Zhu H, Tang X, Gu C, et al. Assessment of human exposure to cadmium and its nephrotoxicity in the Chinese population. Science of The Total Environment. 2024;918:170488
  18. 18. Balali-Mood M, Naseri K, Tahergorabi Z, et al. Toxic mechanisms of five heavy metals: Mercury, lead, chromium, cadmium, and arsenic. Frontiers in Pharmacology. 2021;12:1-19
  19. 19. Peana M, Pelucelli A, Medici S, et al. Metal toxicity and speciation: A review. Current Medicinal Chemistry. 2021;28:7190-7208
  20. 20. Ahmad MF, Ahmad FA, Alsayegh AA, et al. Pesticides impacts on human health and the environment with their mechanisms of action and possible countermeasures. Heliyon. 2024;10:e29128
  21. 21. Kaur R, Choudhary D, Bali S, et al. Pesticides: An alarming detrimental to health and environment. Science of The Total Environment. 2024;915:170113
  22. 22. Zhou W, Li M, Achal V. A comprehensive review on environmental and human health impacts of chemical pesticide usage. Emerging Contaminants. 2025;11:100410
  23. 23. Ray S, Shaju ST. Bioaccumulation of pesticides in fish resulting toxicities in humans through food chain and forensic aspects. Environmental Analysis, Health and Toxicology. 2023;38(2):e2023017. DOI: 10.5620/eaht.2023017
  24. 24. Daraban GM, Hlihor RM, Suteu D. Pesticides vs. biopesticides: From pest management to toxicity and impacts on the environment and human health. Toxics. 2023;11(12):983. DOI: 10.3390/toxics11120983
  25. 25. Mohammadi H, Ghassemi-Barghi N, Malakshah O, et al. Pyrethroid exposure and neurotoxicity: A mechanistic approach. Arhiv za Higijenu Rada i Toksikologiju. 2019;70:74-89
  26. 26. Atere AD, Ajani OF, Moronkeji A, et al. Immunomodulatory response and serum level of neutrophil gelatinase associated lipocalin (NGAL) as a marker of acute kidney injury in Wistar rats exposed to pyrethroids. Journal of Cellular Biotechnology. 2021;7:99-109
  27. 27. Atere AD, Moronkeji A, Moronkeji AI, et al. Serum levels of inflammatory biomarkers, glycaemic control indices and leptin receptors expression in adult male Wistar rats exposed to pyrethroids. Journal of Cellular Biotechnology. 2021;7:41-55
  28. 28. Du Y, Nomura Y, Luo N, et al. Molecular determinants on the insect sodium channel for the specific action of type II pyrethroid insecticides. Toxicology and Applied Pharmacology. 2009;234:266-272
  29. 29. Tsai YH, Lein PJ. Mechanisms of organophosphate neurotoxicity. Current Opinion in Toxicology. 2021;26:49-60
  30. 30. Aroniadou-Anderjaska V, Figueiredo TH, de Araujo Furtado M, Pidoplichko VI, Braga MFM. Mechanisms of organophosphate toxicity and the role of acetylcholinesterase inhibition. Toxics. 2023;11(10):866. DOI: 10.3390/toxics11100866
  31. 31. Ramírez-Mendoza AA, Mendoza-Magaña ML, Ramírez-Herrera MA, Hernández-Nazara ZH, Domínguez-Rosales JA. Nitrooxidative stress and neuroinflammation caused by air pollutants are associated with the biological markers of neurodegenerative diseases. Antioxidants (Basel). 7 Mar 2024;13(3):326. DOI: 10.3390/antiox13030326
  32. 32. Giesy JP, Solomon KR, Mackay D, et al. Evaluation of evidence that the organophosphorus insecticide chlorpyrifos is a potential persistent organic pollutant (POP) or persistent, bioaccumulative, and toxic (PBT). Environmental Sciences Europe. 2014;26:1-20
  33. 33. Tasselli S, Marziali L, Roscioli C, Guzzella L. Legacy dichlorodiphenyltrichloroethane (DDT) pollution in a river ecosystem: Sediment contamination and bioaccumulation in benthic invertebrates. Sustainability. 2023;15(8):6493. DOI: 10.3390/su15086493
  34. 34. Martyniuk CJ, Mehinto AC, Denslow ND. Organochlorine pesticides: Agrochemicals with potent endocrine-disrupting properties in fish. Molecular and Cellular Endocrinology. 2020;507:110764
  35. 35. Soni D, Dass A, Yadav N, et al. Unveiling the invisible threat: A review of heavy metal exposure and its devastating health consequences. International Journal of Engineering Technology and Management Sciences. 2024;8:315-323
  36. 36. Manisalidis I, Stavropoulou E, Stavropoulos A, et al. Environmental and health impacts of air pollution: A review. Frontiers in Public Health. 2020;8:1-13
  37. 37. Ssedyabane F, Niyonzima N, Ngonzi J, Tusubira D, Ocan M, Akena D, et al. The diagnostic accuracy of serum microRNAs in detection of cervical cancer: A systematic review protocol. Diagnostic and Prognostic Research. 2023;7(1):4. DOI: 10.1186/s41512-023-00142-4
  38. 38. Kaushal J, Khatri M, Arya SK. A treatise on organophosphate pesticide pollution: Current strategies and advancements in their environmental degradation and elimination. Ecotoxicology and Environmental Safety. 2021;207:111483
  39. 39. Saha R, Dutta SM. Pesticides’ mode of action on aquatic life. Toxicol Reports. 2024;13:101780
  40. 40. Ram MA. Route of exposure and impact of pesticides pollution on human health and aquatic ecosystem. International Journal of Zoological Investigations. 2022;08:85-99
  41. 41. Thakur M, Pathania D. Chapter 12 - Environmental fate of organic pollutants and effect on human health. In: Singh P, Kumar A, Borthakur A, editors. Abatement of Environmental Pollutants. Elsevier; 2020. pp. 245-262. DOI: 10.1016/B978-0-12-818095-2.00012-6
  42. 42. Adeniyi T, Moronkeji A, Fikayomi A. Histological and biochemical evaluation of the protective potential of ascorbate and alpha-tocopherol against cypermethrin-induced toxicity. The Journal of Experimental Life Sciences. 2024;14:33-39
  43. 43. Vergara-Gerónimo CA, León Del Río A, Rodríguez-Dorantes M, et al. Arsenic-protein interactions as a mechanism of arsenic toxicity. Toxicology and Applied Pharmacology. 2021;431:115738
  44. 44. Speer RM, Zhou X, Volk LB, et al. Arsenic and cancer: Evidence and mechanisms. Advances in Pharmacology. 2023;96:151-202
  45. 45. Debnath T, Ghosh M, Lee YM, et al. Identification of phenolic constituents and antioxidant activity of Aloe barbadensis flower extracts. Food and Agricultural Immunology. 2018;29:27-38
  46. 46. Chlubek M, Baranowska-Bosiacka I. Selected biochemical mechanisms of lead neurotoxicity. Pomeranian Journal of Life Sciences. 2023;69:33-39
  47. 47. Zulaikhah ST, Wahyuwibowo J, Pratama AA. Mercury and its effect on human health: A review of the literature. International Journal of Public Health Science (IJPHS). 2020;9:103-114
  48. 48. Azevedo LF, Karpova N, Rocha BA, Barbosa Junior F, Gobe GC, Hornos Carneiro MF. Evidence on neurotoxicity after intrauterine and childhood exposure to organomercurials. International Journal of Environmental Research and Public Health. 2023;20(2):1070. DOI: 10.3390/ijerph20021070
  49. 49. Adeniyi T, Moronkeji A, Oluwatunase G, et al. Mercury-induced oxidative stress and neuropathologic changes in the prefrontal cortex of Wistar rats. Nigerian Journal of Neuroscience. 2024;15:97-104
  50. 50. Moronkeji A, Adeniyi T, Olubunmi E, et al. Modulatory effects of Aframomum melegueta and Rauvolfia vomitoria in cadmium-induced renal toxicity in adult rats. Journal of Cellular Biotechnology. 2025;11(1):3-13. DOI: 10.1177/23523689251329719
  51. 51. Moronkeji A, Temidayo A, Benita A, et al. Methanolic leaf extract of Vernonia amygdalina mitigates cadmium-induced oxidative stress in the liver and kidney of adult male Wistar rats. Egyptian Journal of Basic and Applied Sciences. 2024;11:469-478
  52. 52. Zhang H, Reynolds M. Cadmium exposure in living organisms: A short review. Science of The Total Environment. 2019;678:761-767
  53. 53. Genchi G, Sinicropi MS, Lauria G, Carocci A, Catalano A. The effects of cadmium toxicity. International Journal of Environmental Research and Public Health. 2020;17(11):3782. DOI: 10.3390/ijerph17113782
  54. 54. Dewi R, Hamid ZA, Rajab NF, et al. Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche. Human & Experimental Toxicology. 2020;39:577-595
  55. 55. Møller P, Folkmann JK, Forchhammer L, et al. Air pollution, oxidative damage to DNA, and carcinogenesis. Cancer Letters. 2008;266:84-97
  56. 56. Moronkeji A, Akinbo FO. Genotoxic response and histological alterations in rat lungs exposed to gasoline generator exhaust. Sultan Qaboos University Journal for Science [SQUJS]. 2024;29:15-27
  57. 57. Moronkeji A, Adeniyi TD, Atere AD. Oxidative stress response to gasoline generator exhaust emission in adult male Wistar rats. Environmental Analysis, Health and Toxicology. 2024;39:2-11
  58. 58. Marchini T, Wolf D, Michel NA, et al. Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages. Basic Research in Cardiology. 2016;111:1-14
  59. 59. Jaiswal C, Singh AK. Particulate matter exposure and its consequences on hippocampal neurogenesis and cognitive function in experimental models. Environmental Pollution. 2024;363:125275
  60. 60. Duque-Díaz E, Hurtado Giraldo H, Rocha-Muñoz LP, Coveñas R. Glyphosate, AMPA and glyphosate-based herbicide exposure leads to GFAP, PCNA and caspase-3 increased immunoreactive area on male offspring rat hypothalamus. European Journal of Histochemistry. 2022;66(4):3428. DOI: 10.4081/ejh.2022.3428
  61. 61. Dowd FJ. Chapter 6—Cholinergic agonists and muscarinic receptor antagonists. In: Dowd FJ, Johnson BS, Mariotti AJBT-P, editors. Pharmacology and Therapeutics for Dentistry. 7th ed. Elsevier; 2017. pp. 82-97. DOI: 10.1016/B978-0-323-39307-2.00006-0
  62. 62. Dzwilewski KLC, Schantz SL. Prenatal chemical exposures and child language development. Journal of Communication Disorders. 2015;57:41-65
  63. 63. Banaee M. Perspective chapter: Exploring the toxicity effect of heavy metals on aquatic organisms – A comprehensive analysis. In: Heavy Metals in the Environment - Contamination, Risk, and Remediation. London, UK: IntechOpen; 2024. DOI: 10.5772/intechopen.1006890
  64. 64. Bibi S, Naz S, Saeed S, et al. A review on histopathological alterations induced by heavy metals (Cd, Ni, Cr, Hg) in different fish species. Punjab University Journal of Zoology. 2021;36:81-89
  65. 65. Jerrett M, Finkelstein MM, Brook JR, et al. A cohort study of traffic-related air pollution and mortality in Toronto, Ontario, Canada. Environmental Health Perspectives. 2009;117:772-777
  66. 66. Knoblaugh SE, Hohl TM, La Perle KMD. Pathology principles and practices for analysis of animal models. ILAR Journal. 2018;59:40-50
  67. 67. Aljehani Mohammad R, Alamri Fouad H, Elyas MEK, et al. The importance of histopathological evaluation in cancer diagnosis and treatment. International Journal of Health Sciences (Qassim). 2023;7:3614-3623
  68. 68. Basaad A, Basurra S, Vakaj E, et al. A BERT-GNN approach for metastatic breast cancer prediction using histopathology reports. Diagnostics. 2024;14:1-20
  69. 69. Oboma YI, Ekpenyong BO, Umar MS, et al. Histopathological, cytological and radiological correlations in allergy and public health concerns: A comprehensive review. Journal of Asthma and Allergy. 2024;17:1333-1354
  70. 70. Gamde MS, Adeleye TM, Adisa JO. Review on histopathological techniques in cervical cancer screening. Asian Pacific Journal of Cancer Care. 2024;9:785-791
  71. 71. Moronkeji A, Adeniyi T, Samuel A, Eze G, Akinbo F, Temidayo O, et al. Cervical lesion evaluation in females of reproductive age in Ondo town, Nigeria. Nigerian Medical Journal. 2025;66:407-419
  72. 72. Liu Y, Xu J. High-resolution microscopy for imaging cancer pathobiology. Current Pathobiology Reports. 2019;7:85-96
  73. 73. McGenity C, Clarke EL, Jennings C, et al. Artificial intelligence in digital pathology: A systematic review and meta-analysis of diagnostic test accuracy. npj Digital Medicine. 2024;7:6-9
  74. 74. Neuberger J, Patel J, Caldwell H, et al. Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of pathology. Gut. 2020;69:1382-1403
  75. 75. Wu B, Moeckel G. Application of digital pathology and machine learning in the liver, kidney and lung diseases. Journal of Pathology Informatics. 2023;14:100184
  76. 76. Mehrvar S, Himmel LE, Babburi P, et al. Deep learning approaches and applications in toxicologic histopathology: Current status and future perspectives. Journal of Pathology Informatics. 2021;12:42
  77. 77. Sanyal S, Crawford JA, Abraham JL. Overlooked role of histopathology in evaluations for occupational/environmental exposures. American Journal of Respiratory and Critical Care Medicine. 2020;201:1581
  78. 78. Park SY, An KS, Lee B, et al. Establishment of particulate matter-induced lung injury model in mouse. Laboratory Animal Research. 2021;37:1-12
  79. 79. Wang J, Li Y, Zhao P, et al. Exposure to air pollution exacerbates inflammation in rats with preexisting COPD. Mediators of Inflammation. 2020;2020(1):4260204. DOI: 10.1155/2020/4260204
  80. 80. Van Pinxteren D, Brüggemann E, Gnauk T, Iinuma Y, Müller K, Nowak A, et al. Size‐and time‐resolved chemical particle characterization during CAREBeijing‐2006: Different pollution regimes and diurnal profiles. Journal of Geophysical Research: Atmospheres. 2009;114(D2):D00G09. DOI: 10.1029/2008JD010890
  81. 81. Srivastava D, Vu TV, Tong S, et al. Formation of secondary organic aerosols from anthropogenic precursors in laboratory studies. npj Climate and Atmospheric Science. 2022;5:22. DOI: 10.1038/s41612-022-00238-6
  82. 82. Singh K, Tripathi D. Particulate matter and human health. In: Environmental Health. London, UK: IntechOpen; 2021. DOI: 10.5772/intechopen.100550
  83. 83. Chang EM, Chao CC, Wang MT, et al. PM2.5 promotes pulmonary fibrosis by mitochondrial dysfunction. Environmental Toxicology. 2023;38:1905-1913
  84. 84. Li Y, Lin B, Hao D, et al. Short-term PM2.5 exposure induces transient lung injury and repair. Journal of Hazardous Materials. 2023;459:132227
  85. 85. Niu R, Cheng J, Sun J, Li F, Fang H, Lei R, et al. Alveolar type II cell damage and Nrf2-SOD1 pathway downregulation are involved in PM2. 5-induced lung injury in rats. International Journal of Environmental Research and Public Health. 2022;19(19):12893. DOI: 10.3390/ijerph191912893
  86. 86. Xiong R, Jiang W, Li N, et al. PM2.5-induced lung injury is attenuated in macrophage-specific NLRP3 deficient mice. Ecotoxicology and Environmental Safety. 2021;221:112433
  87. 87. Deng X, Rui W, Zhang F, et al. PM2.5 induces Nrf2-mediated defense mechanisms against oxidative stress by activating PIK3/AKT signaling pathway in human lung alveolar epithelial A549 cells. Cell Biology and Toxicology. 2013;29:143-157
  88. 88. Shih C-H, Chen J-K, Kuo L-W, et al. Chronic pulmonary exposure to traffic-related fine particulate matter causes brain impairment in adult rats. Particle and Fibre Toxicology. 2018;15:1-17
  89. 89. Gangwar RS, Bevan GH, Palanivel R, et al. Oxidative stress pathways of air pollution mediated toxicity: Recent insights. Redox Biology. 2020;34:101545
  90. 90. Li R, Peng X, Wu Y, et al. Exposure to PM2.5 during pregnancy causes lung inflammation in the offspring: Mechanism of action of mogrosides. Ecotoxicology and Environmental Safety. 2021;228:112955
  91. 91. Huang F, Wang P, Pan X, Wang Y, Ren S. Effects of short-term exposure to particulate matters on heart rate variability: A systematic review and meta-analysis based on controlled animal studies. Environmental Pollution. 2020;256:113306. DOI: 10.1016/j.envpol.2019.113306
  92. 92. Ma N, Wei W, Fan X, Ci X. Farrerol attenuates cisplatin-induced nephrotoxicity by inhibiting the reactive oxygen species-mediated oxidation, inflammation, and apoptotic signaling pathways. Frontiers in Physiology. 2019;10:1419. DOI: 10.3389/fphys.2019.01419
  93. 93. Ha JH, Lee BW, Yi DH, et al. Particulate matter-mediated oxidative stress induces airway inflammation and pulmonary dysfunction through TXNIP/NF-κB and modulation of the SIRT1-mediated p53 and TGF-β/Smad3 pathways in mice. Food and Chemical Toxicology. 2024;183:114201
  94. 94. Kim YK, Jung JS, Lee SH, et al. Effects of antioxidants and Ca2+ in cisplatin-induced cell injury in rabbit renal cortical slices. Toxicology and Applied Pharmacology. 1997;146:261-269
  95. 95. Slevin E, Baiocchi L, Wu N, et al. Kupffer cells: Inflammation pathways and cell-cell interactions in alcohol-associated liver disease. The American Journal of Pathology. 2020;190:2185-2193
  96. 96. Xu GX, Wei S, Yu C, et al. Activation of Kupffer cells in NAFLD and NASH: Mechanisms and therapeutic interventions. Frontiers in Cell and Development Biology. 2023;11:1-13
  97. 97. Arciello M, Gori M, Maggio R, et al. Environmental pollution: A tangible risk for NAFLD pathogenesis. International Journal of Molecular Sciences. 2013;14:22052-22066
  98. 98. Zheng Z, Xu X, Zhang X, et al. Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model. Journal of Hepatology. 2013;58:148-154
  99. 99. Tinkov AA, Aschner M, Santamaria A, et al. Dissecting the role of cadmium, lead, arsenic, and mercury in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Environmental Research. 2023;238:117134
  100. 100. Mentsiou Nikolaou E, Kalafati IP, Dedoussis GV. The interplay between endocrine-disrupting chemicals and the epigenome towards metabolic dysfunction-associated steatotic liver disease: A comprehensive review. Nutrients. 2024;16(8):1124. DOI: 10.3390/nu16081124
  101. 101. Tovoli F, Stefanini B, Mandrioli D, et al. Exploring occupational toxicant exposures in patients with metabolic dysfunction-associated steatotic liver disease: A prospective pilot study. Digestive and Liver Disease. 2024;56:S53
  102. 102. Jannetto PJ, Cowl CT. Elementary overview of heavy metals. Clinical Chemistry. 2023;69:336-349
  103. 103. Rahman Z, Singh VP. The relative impact of toxic heavy metals (THMs) (arsenic (As), cadmium (Cd), chromium (Cr)(VI), mercury (Hg), and lead (Pb)) on the total environment: An overview. Environmental Monitoring Assessment. 2019;191(7):419. DOI: 10.1007/s10661-019-7528-7
  104. 104. Jaishankar M, Tseten T, Anbalagan N, et al. Toxicity, mechanism and health effects of some heavy metals. Interdisciplinary Toxicology. 2014;7:60-72
  105. 105. Katsarou A, Moustakas II, Pyrina I, et al. Metabolic inflammation as an instigator of fibrosis during nonalcoholic fatty liver disease. World Journal of Gastroenterology. 2020;26:1993-2011
  106. 106. Satarug S, Vesey DA, Gobe GC. Current health risk assessment practice for dietary cadmium: Data from different countries. Food and Chemical Toxicology. 2017;106:430-445
  107. 107. Rafati Rahimzadeh M, Rafati Rahimzadeh M, Kazemi SMA. Cadmium toxicity and treatment: An update. Caspian Journal of Internal Medicine. 2017;2017(8):135-145
  108. 108. Klaassen CD, Liu J, Diwan BA. Metallothionein protection of cadmium toxicity. Toxicology and Applied Pharmacology. 2009;238:215-220
  109. 109. Lin H-C, Hao W-M, Chu P-H. Cadmium and cardiovascular disease: An overview of pathophysiology, epidemiology, therapy, and predictive value. Revista Portuguesa de Cardiologia (English Edition). 2021;40:611-617
  110. 110. Arab A, Mostafalou S. Neurotoxicity of pesticides in the context of CNS chronic diseases. International Journal of Environmental Health Research. 2022;32:2718-2755
  111. 111. Elmorsy E, Al-Ghafari A, Al Doghaither H, Salama M, Carter WG. An investigation of the neurotoxic effects of Malathion, Chlorpyrifos, and Paraquat to different brain regions. Brain Sciences. 2022;12(8):975. DOI: 10.3390/brainsci12080975
  112. 112. Naughton SX, Terry AV. Neurotoxicity in acute and repeated organophosphate exposure. Toxicology. 2018;408:101-112
  113. 113. Tarafdar A, Pula G. The role of NADPH oxidases and oxidative stress in neurodegenerative disorders. International Journal of Molecular Sciences. 2018;19(12):3824. DOI: 10.3390/ijms19123824
  114. 114. Cresto N, Forner-Piquer I, Baig A, et al. Pesticides at brain borders: Impact on the blood-brain barrier, neuroinflammation, and neurological risk trajectories. Chemosphere. 2023;324:138251
  115. 115. Lafon PA, Wang Y, Arango-Lievano M, et al. Fungicide residues exposure and β-amyloid aggregation in a mouse model of Alzheimer’s disease. Environmental Health Perspectives. 2020;128:1-20
  116. 116. Hersh L, Rodgers D. Neprilysin and amyloid Beta peptide degradation. Current Alzheimer Research. 2008;5:225-231
  117. 117. Tang BL. Neuropathological mechanisms associated with pesticides in Alzheimer’s disease. Toxics. 2020;8:1-16
  118. 118. Di DC, Chen CW, Chen YC, et al. Polystyrene microplastic particles: In vitro pulmonary toxicity assessment. Journal of Hazardous Materials. 2020;385:121575
  119. 119. Aghaei Z, Mercer GV, Schneider CM, et al. Maternal exposure to polystyrene microplastics alters placental metabolism in mice. Metabolomics. 2023;19:7-8
  120. 120. Saleh SMM, Abdel-Zaher S, Mohamed MS, et al. Microplastics induced ileum damage: Morphological and immunohistochemical study. Microscopy Research and Technique. 2025;88:251-269
  121. 121. Garcia MM, Romero AS, Merkley SD, Meyer-Hagen JL, Forbes C, Hayek EE, et al. In vivo tissue distribution of microplastics and systemic metabolomic alterations after gastrointestinal exposure. BioRxiv [Preprint]. 2023:2023.06.02.542598. DOI: 10.1101/2023.06.02.542598
  122. 122. Ali SA, Rizk MZ, Hamed MA, et al. Assessment of titanium dioxide nanoparticles toxicity via oral exposure in mice: Effect of dose and particle size. Biomarkers. 2019;24:492-498
  123. 123. Serrano QA, Le Garf S, Martin V, Colson SS, Chevalier N. Is physical activity an efficient strategy to control the adverse effects of persistent organic pollutants in the context of obesity? A narrative review. International Journal of Molecular Sciences. 2024;25(2):883. DOI: 10.3390/ijms25020883
  124. 124. Fu Z, Bin XH, Elm J, et al. Formation of low-volatile products and unexpected high formaldehyde yield from the atmospheric oxidation of methylsiloxanes. Environmental Science & Technology. 2020;54:7136-7145
  125. 125. World Health Organization. Ambient (outdoor) air pollution. In: Ambient (Outdoor) Air Pollution. Geneva, Switzerland: World Health Organization; 2022. Available from: https://www.who.int/news-room/fact-sheets/detail/ambient-(outdoor)-air-quality-and-health?gad_source=1&gclid=Cj0KCQjwvb-zBhCmARIsAAfUI2uht3D3H9sSC_f4cCZwKJkYFA1xGuiMGJc8xCmOuHgYhXC3yi7HDpgaAgJQEALw_wcB
  126. 126. Guerrero-Limón G, Zappia J, Muller M. A realistic mixture of ubiquitous persistent organic pollutants affects bone and cartilage development in zebrafish by interaction with nuclear receptor signaling. PLoS One. 2024;19:1-24
  127. 127. Landrigan PJ, Fuller R, Acosta NJR, et al. The lancet commission on pollution and health. Lancet. 2018;391:462-512
  128. 128. Lodovici M, Bigagli E. Oxidative stress and air pollution exposure. Journal of Toxicology. 2011;2011:487074. DOI: 10.1155/2011/487074
  129. 129. Tan W, Zhu H, Zhang N, et al. Characterization of the PM2.5 concentration in surgical smoke in different tissues during hemihepatectomy and protective measures. Environmental Toxicology and Pharmacology. 2019;72:103248
  130. 130. Abadin H, Ashizawa A, Stevens YW, Llados F, Diamond G, Sage G, et al. Toxicological Profile for Lead. Atlanta (GA): Agency for Toxic Substances and Disease Registry (US); 2007
  131. 131. Olawade DB, Wada OZ, Ige AO, et al. Artificial intelligence in environmental monitoring: Advancements, challenges, and future directions. Hygiene and Environmental Health Advances. 2024;12:100114
  132. 132. Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nature Reviews. Molecular Cell Biology. 2020;21:363-383
  133. 133. Sies H. On the history of oxidative stress: Concept and some aspects of current development. Current Opinion in Toxicology. 2018;7:122-126
  134. 134. Atkuri KR, Mantovani JJ, Herzenberg LA, et al. N-Acetylcysteine—A safe antidote for cysteine/glutathione deficiency. Current Opinion in Pharmacology. 2007;7:355-359
  135. 135. Gurgueira SA, Lawrence J, Coull B, et al. Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation. Environmental Health Perspectives. 2002;110:749-755
  136. 136. Adeniyi TD, Akinpelu M, Omokehinde Oseni Akinlami FO, Alaga MMA. Evaluation of the combined extract of Rauwolfia vomitoria and Aframomum melegueta on the kidney and liver of adult male Wistar rats. Sokoto Journal of Medical Laboratory Science. 2024;9:203-212
  137. 137. Zhang Z, Zhao L, Zhou X, et al. Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets. Frontiers in Immunology. 2023;13:1-18
  138. 138. Issa SY, Rahman SMA, Gaber YM, et al. Toxicological impact of Thiamethoxam on adult male rats: Histopathological, biochemical, and oxidative DNA damage assessment. Toxicol Reports. 2025;14:101983
  139. 139. Song J, Shen Q, Shi J, et al. Changes in microbial community structure due to chronic trace element concentrations in different sizes of soil aggregates. Environmental Pollution. 2021;268:115933
  140. 140. Zhao X, Wang S, Li X, et al. Cadmium exposure induces TNF-α-mediated necroptosis via FPR2/TGF-β/NF-κB pathway in swine myocardium. Toxicology. 2021;453:152733
  141. 141. Cattaneo A, Campo L, Iodice S, et al. Environmental and biological monitoring of personal exposure to air pollutants of adult people living in a metropolitan area. Science of The Total Environment. 2021;767:144916
  142. 142. Viegas S, Jeddi MZ, Hopf NB, et al. Biomonitoring as an underused exposure assessment tool in occupational safety and health context—Challenges and way forward. International Journal of Environmental Research and Public Health. 2020;17:1-20
  143. 143. Wireman JR, Long GC. Communicating risk in diverse communities. Toxicology and Industrial Health. 2001;17:298-301
  144. 144. Marchwińska-Wyrwał E, Teaf CM, Dziubanek G, et al. Risk assessment and risk communication in environmental health in Poland. European Journal of Public Health. 2012;22:742-744
  145. 145. Shetty SS, Deepthi D, Harshitha S, Sonkusare S, Naik PB, Kumari SN, et al. Environmental pollutants and their effects on human health. Heliyon. 2023;9(9):e19496. DOI: 10.1016/j.heliyon.2023.e19496
  146. 146. Lahr J, Kooistra L. Environmental risk mapping of pollutants: State of the art and communication aspects. Science of The Total Environment. 2010;408:3899-3907
  147. 147. Marsili D, Pasetto R, Iavarone I. Environmental public health communication to engage stakeholders and foster social capacity in poorly involved communities living in industrial contaminated sites: The case study of Porto Torres (Italy). Frontiers in Communication. 2023;8:1217427. DOI: 10.3389/fcomm.2023.1217427
  148. 148. Ward F, Lowther-Payne HJ, Halliday EC, et al. Engaging communities in addressing air quality: A scoping review. Environmental Health : A Global Access Science Source. 2022;21:1-18
  149. 149. Collman GW. Community-based approaches to environmental health research around the globe. Reviews on Environmental Health. 2014;29:125-128
  150. 150. Tan T, Junghans C, Varaden D. Empowering community health professionals for effective air pollution information communication. BMC Public Health. 2023;23:1-12

Written By

Akinpelu Moronkeji, Temidayo Daniel Adeniyi, Samuel Ayobami Fasogbon, Joshua Olayinka Ajala, Emmanuel Tolulope Adegoke, Comfort E. Williams, Abiodun Oyeleke, Charles Egede Ugwu, Olubunmi Esan, Bob-Manuel Chinonso Osuji and Puritan Umeboro

Reviewed: 25 July 2025 Published: 10 September 2025

© 2025 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Continue reading from the same book

View All

Your cart

Discounts available on purchase of multiple copies. View rates

Subtotal €0.00

Local taxes (VAT) are calculated in later steps, if applicable.

Support: orders@intechopen.com