Emerging and Persistent Food Contaminants: A Decade Review of Their Health Risks and Mitigation Strategies

1. Introduction

Food safety is increasingly threatened by industrialization, environmental degradation, climate change, and global population growth.[1] Both persistent contaminants—such as heavy metals, mycotoxins, and pesticides—and emerging contaminants, including microplastics, PFAS, and pharmaceutical residues, now pervade food systems, posing serious risks to health and security.[2] Persistent contaminants are known for their bioaccumulation and links to cancer, neurotoxicity, and endocrine disruption, while emerging pollutants often evade detection and regulation due to their novel properties and low-dose complexity.[3,4]

Contamination pathways include polluted environments, agrochemical use, poor post-harvest practices, and industrial processing.[5] Climate change exacerbates these risks by altering contaminant behavior and increasing foodborne toxin production. The health impacts extend beyond acute illness to chronic diseases—mediated through oxidative stress, immune disruption, mitochondrial dysfunction, and epigenetic changes—especially in vulnerable populations lacking regulatory and nutritional safeguards. [6,7] Despite progress in detection tools and food safety policies, major gaps remain in surveillance, exposure assessment, and risk mitigation. A coordinated, multidisciplinary approach is needed to address the growing complexity of food contamination.[8] This review synthesizes the sources, mechanisms, health effects, and mitigation strategies of both persistent and emerging contaminants.

2. Methodology

This narrative review aimed to synthesize current evidence on emerging and persistent food contaminants, their health risks, and mitigation strategies. A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar was conducted for English-language publications dated between September 2014 and September 2024. The search utilized Boolean logic with targeted keywords, including “food contaminants,” “toxicology,” “emerging pollutants,” “pesticides,” “mycotoxins,” “microplastics,” “pharmaceutical residues,” “endocrine disruptors,” and “mitigation strategies.” Selection criteria focused on studies addressing contaminant sources, toxicity pathways, health outcomes, and control interventions relevant to food safety. Eligible sources included peer-reviewed original research, reviews, and gray literature or institutional reports with a focus on human or food-related environmental health. Articles lacking methodological rigor or relevance to food toxicology were excluded. Screening involved a two-step process: initial review of titles and abstracts followed by full-text evaluation. Key data were extracted into a structured matrix capturing contaminant type, route of entry into the food chain, toxicological mechanisms, associated health effects, and mitigation approaches. Due to the heterogeneity of data, findings were synthesized qualitatively and categorized thematically under major contaminant classes, health risks, and control strategies.

Although this was not a systematic review or meta-analysis, the process adhered to rigorous screening and appraisal standards, guided by the Scale for the Assessment of Narrative Review Articles (SANRA). This tool evaluates justification of topic relevance, clarity of objectives, search strategy, referencing, scientific reasoning, and data presentation. Each of the six SANRA criteria was rated from 0 (low quality) to 2 (high quality), with a maximum score of 12 [9]. This review achieved a score of 11, indicating high methodological quality and consistency (Figure 1).

3. Classification of Food Contaminants Based on Environmental Persistence and Detection Recency

Food contaminants can be broadly classified by their persistence, sources, and potential for human exposure. A widely accepted framework distinguishes between Persistent Contaminants and Emerging Contaminants, each with distinct characteristics in environmental behavior, bioaccumulation, and regulatory focus.[3,7] This classification is endorsed by major organizations, including the World Health Organization (WHO), Food and Agriculture Organization (FAO), Codex Alimentarius Commission, European Food Safety Authority (EFSA), and the United States Environmental Protection Agency (US EPA) (Table 1 & Figure 2).

Persistent Contaminants

Persistent food contaminants refer to long-established chemical hazards, known for their resistance to degradation, environmental stability, and capacity to bioaccumulate in the food chain [4]. These include heavy metals, organochlorine pesticides, and legacy industrial pollutants

Heavy metals such as lead, cadmium, mercury, and arsenic are among the most critical persistent contaminants due to their non-degradable nature and widespread occurrence stemming from both natural sources and anthropogenic activities.[10] These elements accumulate in the environment—soil, water, and biological tissues—over time. Lead contamination, largely from past industrial emissions and lead-based products, persists in the environment and is frequently found in food and water sources. It is notably neurotoxic, particularly in children, impairing cognitive and neurological development.[11] Cadmium, introduced through phosphate fertilizers and industrial waste, accumulates in leafy vegetables, cereals, and seafood, posing risks of kidney damage and bone demineralization.[12] Mercury, especially in its methylated form, bioaccumulates in aquatic organisms and threatens neurodevelopment in fetuses and young children. Arsenic, often leached from natural mineral deposits or used groundwater, is associated with carcinogenic and cardiovascular effects.[13] Other metals like chromium, nickel, and copper may become harmful at elevated levels, despite their roles as essential micronutrients.[14]

Pesticides are synthetic chemicals used to protect crops, yet many persist in the environment and remain as residues in food.[15] Organochlorine pesticides (OCPs) like DDT and aldrin, though banned in several countries, continue to contaminate agricultural products due to their chemical stability.[16] These compounds accumulate in adipose tissues and are linked to endocrine disruption, cancer, and neurotoxicity. Organophosphates (OPs) and carbamates, though less persistent, pose acute neurotoxic risks via cholinesterase inhibition, and are commonly found on fruits, vegetables, and grains.[17] Neonicotinoids, newer systemic insecticides, are moderately persistent and raise concerns regarding their potential neurotoxicity in humans and harm to pollinators. [18,19] Additionally, herbicides such as glyphosate and various fungicides contribute to ongoing residue contamination.[20]

Mycotoxins are naturally occurring toxins produced by certain fungi, especially in warm and humid climates, affecting crops both pre- and post-harvest.[21] These stable secondary metabolites often survive food processing, remaining in the final product. Aflatoxins, produced by Aspergillus species, are potent carcinogens and have been associated with liver cancer, acute toxicity, immune suppression, and impaired child growth.[21] Ochratoxin A, commonly found in cereals, coffee, and dried fruits, is nephrotoxic and possibly carcinogenic.[23] Fumonisins, mainly contaminating maize, have been linked to esophageal cancer and neural tube defects.[24] Other toxins like zearalenone and deoxynivalenol (DON) show estrogenic and immunotoxic effects. Mycotoxin prevalence is influenced by climatic conditions, crop variety, agricultural methods, and storage hygiene.[25]

Industrial pollutants contribute a diverse set of persistent contaminants in food systems. Polychlorinated biphenyls (PCBs), once used in electrical equipment, persist in sediments and accumulate in fish and animal fats, with links to endocrine disruption and cancer.[26,27] Dioxins and furans, generated during combustion and industrial processing, contaminate animal-based foods and are associated with reproductive, immune, and developmental toxicity.[28] Per- and polyfluoroalkyl substances (PFAS)—used in non-stick cookware, packaging, and industrial coatings—have recently gained concern for their bioaccumulative nature and links to immune dysfunction, metabolic disorders, and cancer.[29,30] Polycyclic aromatic hydrocarbons (PAHs), created during grilling and smoking of foods, are recognized for their mutagenic and carcinogenic properties.[31,32]

3.2. Emerging Contaminants

Emerging food contaminants are newly recognized or increasingly detected substances whose health implications and exposure pathways remain insufficiently characterized. Examples include micro- and nanoplastics, per- and polyfluoroalkyl substances (PFAS), pharmaceutical residues, and engineered nanomaterials [21].

Microplastics—plastic fragments under 5 mm—and their nanoscale counterparts (<100 nm) have become ubiquitous in the global food chain. As noted by EFSA, they originate from the degradation of larger plastics or are purposefully produced for use in packaging, cosmetics, and industrial applications.[33] These particles are now commonly detected in seafood, bottled water, honey, table salt, and even fruits and vegetables, entering the food chain through marine pollution, soil contamination, and atmospheric deposition.[34] Beyond their physical presence, they can adsorb hazardous compounds such as heavy metals and persistent organic pollutants, acting as carriers that heighten chemical exposure.[35] Research suggests micro- and nanoplastics induce oxidative stress, inflammation, cytotoxicity, and gut microbiome disruption in biological systems.[36] Nanoplastics, in particular, raise concern due to their ability to cross biological membranes and interact with cellular processes.[37] However, data from human studies remain sparse, and standardized analytical tools are still under development, leaving significant gaps in exposure assessment and risk evaluation.[38]

Residues of pharmaceuticals and personal care products—including antibiotics, hormones, analgesics, and antiseptics—are emerging as contaminants in food systems, primarily through wastewater discharge, agricultural runoff, and improper drug disposal.[39] These substances have been detected in meat, dairy, fish, and crops irrigated with contaminated water. Antibiotic residues are particularly concerning due to their role in promoting antimicrobial resistance, a recognized global health crisis.[40] Hormonal compounds from PPCPs may act as endocrine disruptors, with evidence linking chronic exposure to immune dysfunction, allergic reactions, and microbiome disturbances.[41]

EDCs encompass a wide array of chemicals that disrupt hormonal function, including bisphenol A (BPA), phthalates, DDT, PBDEs, and alkylphenols.[42] These compounds enter the food system through pesticide residues, migration from plastic packaging, and environmental accumulation in animal products.[43] Their health effects range from infertility and developmental disorders to obesity, diabetes, thyroid dysfunction, and neurodevelopmental delay.[44] Some EDCs, such as BPA, are also implicated in hormone-sensitive cancers like breast and prostate cancer.[45] Their low-dose and non-linear biological activity complicates risk assessment, especially in real-world scenarios involving exposure to multiple EDCs simultaneously.[46]

PFAS are a group of highly stable, synthetic compounds used in non-stick cookware, waterproof textiles, firefighting foams, and food packaging.[47] Their extreme environmental persistence and bioaccumulation in aquatic and agricultural systems have earned them the label “forever chemicals.” Exposure occurs through contaminated water, fish, and food-contact materials like fast-food wrappers.[48] Health effects include immune suppression, reduced vaccine response, thyroid disruption, increased cholesterol, and cancers of the kidney and testis.[49] Regulatory efforts are complicated by the vast number of PFAS compounds, many of which lack toxicological data.[50] Although some long-chain PFAS have been phased out, their short-chain alternatives may pose similar risks. [29]

Additional emerging threats include engineered nanomaterials (e.g., nanosilver, titanium dioxide), which are used in food additives and packaging and may interact with cells at the molecular level despite limited toxicological data. [51,52] Cyanotoxins, produced by harmful algal blooms intensified by climate change, contaminate water and seafood with potent neuro- and hepatotoxins. [53,54].

4. Chemical Structure, Persistence, and Physicochemical Properties

The environmental behavior, biological uptake, and toxicological impact of food contaminants are fundamentally governed by their chemical structure and physicochemical characteristics [55]. Persistent contaminants, in particular, are defined by their strong covalent bonds, low volatility, and high lipophilicity, which render them resistant to degradation and prone to accumulation in ecological and biological systems [56]. These features facilitate their persistence across environmental compartments and promote biomagnification through the food web. Heavy metals such as lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) exemplify elemental or inorganic contaminants that are chemically stable and biologically non-degradable. Their persistence in soil and water systems is strongly influenced by speciation, which dictates solubility, adsorption behavior, and subsequent uptake by crops and livestock [57]. For instance, lead can accumulate in neural tissues and bone, while cadmium preferentially targets renal and skeletal systems. Arsenic, frequently present in groundwater used for irrigation, is notably associated with cardiovascular toxicity and carcinogenesis.

Similarly, organochlorine pesticides (OCPs) such as dichlorodiphenyltrichloroethane (DDT) and its metabolites contain halogenated aromatic rings that confer high chemical and photolytic stability [58]. These structures persist for decades after application has ceased and are often detected in fatty tissues of animals and humans. Although organophosphate pesticides degrade more readily due to the presence of labile phosphate ester bonds, their acute neurotoxicity—primarily via inhibition of acetylcholinesterase—remains a major health concern. Emerging contaminants, including per- and polyfluoroalkyl substances (PFAS), present novel challenges due to their distinctive fluorinated carbon chains. These structures impart exceptional chemical and thermal stability, as well as amphiphobic properties, enabling PFAS to resist hydrolysis, oxidation, and microbial degradation in environmental and biological matrices [59]. Their widespread use in food packaging and processing materials contributes to dietary exposure, while their bioaccumulative and endocrine-disrupting effects are increasingly documented.

Microplastics and nanoplastics, consisting of synthetic polymers such as polyethylene and polypropylene, demonstrate physical persistence and capacity for contaminant adsorption. These particles are increasingly detected in marine organisms, processed foods, and drinking water, raising concerns about their role as vectors for secondary contaminants including persistent organic pollutants and heavy metals [60]. Fundamental physicochemical parameters—including water solubility, vapor pressure, molecular size, and octanol-water partition coefficient (Kₒw)—further influence contaminant fate and toxicity [61]. Lipophilic compounds with high Kₒw values are particularly prone to bioaccumulate in adipose tissues, posing long-term exposure risks, especially for apex predators and human populations consuming animal-derived products.

5. Toxicokinetic and Bioaccumulation

Toxicokinetic encompasses the processes of absorption, distribution, metabolism, and excretion (ADME) of contaminants within biological systems, critically influencing their internal dose and potential toxicity [62]. The toxicokinetic profiles of food contaminants vary considerably, shaped by factors such as molecular size, polarity, metabolic pathways, and species-specific physiology. Typically, absorption occurs primarily through the gastrointestinal tract following ingestion of contaminated food [63]. Lipophilic compounds, including organochlorine pesticides (OCPs) and per- and polyfluoroalkyl substances (PFAS), are efficiently absorbed, subsequently entering systemic circulation and preferentially accumulating in adipose tissue, liver, and kidneys. In contrast, hydrophilic contaminants may demonstrate lower absorption rates but can localize in compartments such as blood plasma. Metabolic biotransformation plays a central role in modulating toxicity: Phase I reactions—oxidation, reduction, and hydrolysis—can either detoxify xenobiotics or bioactivate them into reactive intermediates, as seen with certain mycotoxins and pesticide metabolites [64]. Phase II conjugation typically enhances water solubility, facilitating elimination via renal or biliary routes. However, some persistent contaminants resist metabolic breakdown, resulting in extended biological half-lives [65].

Bioaccumulation describes the net accumulation of contaminants within organisms from all exposure pathways, governed by the balance between uptake and elimination rates [66]. Biomagnification, the process by which contaminant concentrations increase at successive trophic levels, is particularly pronounced for lipophilic and persistent compounds [67]. For instance, methylmercury formed in aquatic environments bioaccumulates in fish, thereby posing substantial health risks to human consumers. The toxicokinetic of emerging contaminants such as microplastics and nanoplastics remain less characterized but present unique challenges owing to their particulate nature, ability to translocate across biological barriers, and interactions with co-contaminants [68]. Similarly, PFAS display complex distribution and elimination dynamics, marked by prolonged biological half-lives in humans.

Table 1. Classification and Characteristics of Persistent and Emerging Food Contaminants.

Category	Contaminant Class	Examples	Primary Sources	Toxicological Effects	Persistence/Bioaccumulation
Persistent contaminants	Heavy Metals [10,11,14]	Lead (Pb), Cadmium (Cd), Mercury (Hg), Arsenic (As), Chromium, Nickel, Copper	Industrial emissions, fertilizers, mining, water contamination	Neurotoxicity, nephrotoxicity, carcinogenicity, developmental toxicity	Highly persistent, bioaccumulate in soils and food chains
	Pesticides [16,18,19]	Organochlorines (DDT), Organophosphates, Carbamates, Neonicotinoids, Glyphosate	Agricultural application, residual soil contamination	Endocrine disruption, neurotoxicity, reproductive and developmental toxicity	Varies by type; OCPs highly persistent; OPs less persistent but acutely toxic
	Mycotoxins [22,24]	Aflatoxins, Ochratoxin A, Fumonisins, Zearalenone, Deoxynivalenol	Mold growth in cereals, nuts, stored grains	Hepatotoxicity, nephrotoxicity, immunosuppression, carcinogenicity	Stable during processing; bio accumulative in some cases
	Industrial Pollutants [29,30]	PCBs, Dioxins, Furans, PAHs, PFAS	Electrical waste, combustion, packaging, industrial effluents	Cancer, immune dysfunction, endocrine and reproductive toxicity	High environmental and biological persistence
Emerging contaminants	Microplastics & Nano plastics [33,35,36]	Polyethylene, Polypropylene, Polystyrene	Breakdown of plastic waste, packaging, textiles	Inflammation, oxidative stress, gut microbiota disruption	Physically persistent, adsorb other pollutants, bio accumulative
	Pharmaceutical & Personal Care Products (PPCPs) [40,41]	Antibiotics, Hormones, Analgesics, Antiseptics	Wastewater, veterinary use, improper disposal	Antimicrobial resistance, hormonal effects, allergic reactions	Low degradation in water; accumulation in livestock and crops
	Endocrine-Disrupting Chemicals (EDCs) [43,44,46]	Bisphenol A (BPA), Phthalates, DDT, PBDEs, Alkylphenols	Plastics, pesticides, cosmetics, detergents	Reproductive disorders, thyroid dysfunction, metabolic and neurodevelopmental effects	Lipophilic and persistent; low-dose potency
	PFAS [48,50]	PFOA, PFOS, Short-chain PFAS	Food packaging, cookware, water, firefighting foam	Immunotoxicity, cancer, endocrine disruption, developmental toxicity	“Forever chemicals”; bioaccumulate and resist degradation
	Other Emerging Contaminants	Engineered nanomaterials, Cyanotoxins, Masked mycotoxins	Additives, algal blooms, food processing	Cellular damage, hepatotoxicity, neurotoxicity	Incomplete toxicokinetic profiles; unknown persistence

Table 1. Classification and Characteristics of Persistent and Emerging Food Contaminants.

Category	Contaminant Class	Examples	Primary Sources	Toxicological Effects	Persistence/Bioaccumulation
Persistent contaminants	Heavy Metals [10,11,14]	Lead (Pb), Cadmium (Cd), Mercury (Hg), Arsenic (As), Chromium, Nickel, Copper	Industrial emissions, fertilizers, mining, water contamination	Neurotoxicity, nephrotoxicity, carcinogenicity, developmental toxicity	Highly persistent, bioaccumulate in soils and food chains
	Pesticides [16,18,19]	Organochlorines (DDT), Organophosphates, Carbamates, Neonicotinoids, Glyphosate	Agricultural application, residual soil contamination	Endocrine disruption, neurotoxicity, reproductive and developmental toxicity	Varies by type; OCPs highly persistent; OPs less persistent but acutely toxic
	Mycotoxins [22,24]	Aflatoxins, Ochratoxin A, Fumonisins, Zearalenone, Deoxynivalenol	Mold growth in cereals, nuts, stored grains	Hepatotoxicity, nephrotoxicity, immunosuppression, carcinogenicity	Stable during processing; bio accumulative in some cases
	Industrial Pollutants [29,30]	PCBs, Dioxins, Furans, PAHs, PFAS	Electrical waste, combustion, packaging, industrial effluents	Cancer, immune dysfunction, endocrine and reproductive toxicity	High environmental and biological persistence
Emerging contaminants	Microplastics & Nano plastics [33,35,36]	Polyethylene, Polypropylene, Polystyrene	Breakdown of plastic waste, packaging, textiles	Inflammation, oxidative stress, gut microbiota disruption	Physically persistent, adsorb other pollutants, bio accumulative
	Pharmaceutical & Personal Care Products (PPCPs) [40,41]	Antibiotics, Hormones, Analgesics, Antiseptics	Wastewater, veterinary use, improper disposal	Antimicrobial resistance, hormonal effects, allergic reactions	Low degradation in water; accumulation in livestock and crops
	Endocrine-Disrupting Chemicals (EDCs) [43,44,46]	Bisphenol A (BPA), Phthalates, DDT, PBDEs, Alkylphenols	Plastics, pesticides, cosmetics, detergents	Reproductive disorders, thyroid dysfunction, metabolic and neurodevelopmental effects	Lipophilic and persistent; low-dose potency
	PFAS [48,50]	PFOA, PFOS, Short-chain PFAS	Food packaging, cookware, water, firefighting foam	Immunotoxicity, cancer, endocrine disruption, developmental toxicity	“Forever chemicals”; bioaccumulate and resist degradation
	Other Emerging Contaminants	Engineered nanomaterials, Cyanotoxins, Masked mycotoxins	Additives, algal blooms, food processing	Cellular damage, hepatotoxicity, neurotoxicity	Incomplete toxicokinetic profiles; unknown persistence

6. Sources and Pathways of Exposure

The contamination of food arises from multiple interconnected pathways, reflecting the complexity of today’s global food systems. Identifying these sources and understanding their routes of entry is essential for mitigating exposure and safeguarding public health [69] (Table 2 and Figure 3).

6.1. Agricultural Practices

Agriculture remains fundamental to food production but is a major source of chemical contamination. Extensive use of pesticides and herbicides to protect crops introduces residues that persist in soil and plant tissues, often reaching concentrations that pose chronic health risks [70]. Many pesticides are chemically stable to maintain effectiveness, contributing to environmental accumulation and bioaccumulation within food chains [36]. Legacy organochlorine pesticides such as DDT persist long after bans, while newer compounds, including neonicotinoids, raise ecological concerns [71]. Fertilizers—both synthetic and organic (e.g., sewage sludge and manure)—may introduce heavy metals such as cadmium, lead, and arsenic into soils, which are subsequently taken up by crops. Livestock farming introduces further complexity, as veterinary drugs including antibiotics and hormones may leave residues in meat, milk, and eggs if improperly managed, raising toxicity and antimicrobial resistance concerns [72]. Contaminated irrigation water—frequently sourced from rivers polluted by industrial effluents or untreated sewage—adds chemical and microbial hazards to crops. Postharvest handling and storage conditions also contribute through fungal contamination and mycotoxin production (notably aflatoxins and ochratoxin A), potent carcinogens and immunosuppressants [73]. Collectively, agricultural inputs and practices are critical contributors to chemical contamination in the food supply.

6.2. Industrial Discharges and Environmental Pollution

Industrialization has intensified environmental pollution, contaminating soil, water, and air, which serve as vectors for contaminants entering the food chain. Heavy metals such as mercury, lead, cadmium, and arsenic are released from mining, metal finishing, chemical manufacturing, and energy production, contaminating agricultural lands and aquatic ecosystems [74]. These metals are persistent, bioaccumulative, and neurotoxic, and increase cancer risk. Persistent organic pollutants (POPs), including polychlorinated biphenyls and dioxins, arise from industrial processes and waste incineration, entering food chains via contaminated soil and sediments [75]. Pharmaceutical residues and personal care products, emerging contaminants discharged from pharmaceutical manufacturing, hospitals, and urban wastewater systems, bioaccumulate in aquatic organisms, raising concerns about endocrine disruption and the propagation of antibiotic resistance genes [76]. Microplastics and nanoplastics—degraded plastic debris contaminating soils and waters—adsorb toxic chemicals and microbes, increasing risks when ingested through seafood and irrigated crops [77]. Atmospheric deposition disperses airborne pollutants across wide areas, contaminating lands and waters remote from pollution sources. Urban runoff and landfill leachate contribute hydrocarbons, heavy metals, and other toxicants, compounding exposure risks [78]. Industrial activities thus contribute a complex mixture of legacy and emerging contaminants to the food supply [79].

6.3. Food Packaging and Processing

Food processing and packaging further introduce contamination risks that affect food safety and quality. Plastic packaging materials contain additives such as phthalates, bisphenol A, and per- and polyfluoroalkyl substances (PFAS), which can migrate into food under heat, prolonged storage, or mechanical stress [80]. These compounds are persistent and exhibit endocrine-disrupting properties. Processing equipment constructed from metals may leach nickel, chromium, or lead, particularly with inadequate maintenance or hygiene [29]. Food additives and preservatives, while essential for shelf-life extension and safety, can generate harmful byproducts or interact with other contaminants to exacerbate toxicity. Cross-contamination during processing, especially in multi-product facilities, can introduce allergens or chemical residues into unintended foods, posing particular risks for sensitized individuals [81]. Thermal processing methods such as frying, smoking, and grilling reduce microbial loads but may produce carcinogens such as acrylamide and polycyclic aromatic hydrocarbons (PAHs) [82].

6.4. Climate Change and Ecological Disruption

Climate change is an increasingly important factor influencing food contamination by altering ecosystems, agricultural productivity, and contaminant dynamics [83]. Rising temperatures and changing humidity foster fungal proliferation and increased mycotoxin production in crops, elevating exposure to aflatoxins and related toxins with serious human health effects [84]. Altered pest distributions lead to increased pesticide application, potentially raising residue levels in foods. Water scarcity and reduced water quality due to droughts, floods, and contamination events compel use of suboptimal irrigation sources, facilitating contaminant transfer to crops [85]. Extreme weather events mobilize soil-bound pollutants, industrial wastes, and agrochemicals into agricultural fields and water bodies, increasing contamination risks [86]. Ecological disruptions and biodiversity loss impair natural pollutant degradation pathways and may modify bioaccumulation and biomagnification within food webs [87]. These changes jeopardize the safety of fish, wildlife, and plant-based food resources consumed by humans. Consequently, climate change acts as a multiplier of existing contamination challenges.

7. Human Exposure Routes

Humans are exposed to food contaminants through three primary routes—ingestion, inhalation, and dermal contact—each varying in relevance depending on the contaminant type and exposure context. These exposures often occur as a result of environmental contact with contaminated soil, water, air, or surfaces. Ingestion remains the most significant and direct route of exposure. Contaminated foodstuffs, whether plant-based or animal-derived, serve as the principal vehicles for introducing toxic substances into the gastrointestinal tract [88]. Chronic ingestion of low-dose contaminants, including heavy metals, pesticide residues, mycotoxins, and endocrine-disrupting chemicals, can lead to bioaccumulation and systemic toxicity. Infants and young children are particularly vulnerable due to their lower body weight, developing metabolic systems, and higher intake relative to body mass [89]. Drinking water contaminated with arsenic, lead, or fluoride further contributes to oral exposure, especially in low-resource settings [90].

Though less direct, inhalation constitutes a meaningful exposure pathway, particularly in occupational environments such as agriculture and food processing. Aerosols containing pesticide residues, microplastics, and airborne heavy metal particles may be inhaled during activities such as spraying, milling, or packaging [91]. Additionally, microplastics released from food packaging during heating or originating from environmental sources can become suspended in indoor air, leading to chronic inhalation exposures. Inhalation of contaminated dust is particularly relevant in regions with inadequate industrial emission controls or in households that use biomass fuel for cooking, where volatilization of food contaminants may occur (Figure 4) [92].

Dermal exposure arises when contaminants come into contact with the skin during food handling, agricultural work, or pesticide application. Although the skin generally functions as a barrier, certain lipophilic compounds—such as organophosphate pesticides and phthalates—can penetrate and be absorbed into systemic circulation [93]. Dermal absorption may also occur via transfer of contaminants present in personal care products (e.g., triclosan, parabens) during food preparation. While cumulative dermal exposures are generally lower than those from ingestion, repeated or occupational contact can still pose health risks [94].

7.1. Vulnerable Populations and Differential Exposure and Cumulative Exposure and Biomagnification

Certain populations experience heightened exposure or increased sensitivity to food contaminants due to physiological, behavioral, or socioeconomic factors. Children and infants show greater susceptibility to toxicants such as mycotoxins, lead, and bisphenol A (BPA) owing to their developmental sensitivity. Pregnant women face elevated risks from contaminants capable of disrupting endocrine function or crossing the placental barrier, including mercury and phthalates [95]. Occupational groups—farmers, factory workers, fishermen—may encounter elevated contaminant burdens through inhalation and dermal exposure routes [96]. Low-income populations often rely on food from contaminated sources and may have limited regulatory protections, compounding exposure risks [97].

Chronic exposure to multiple low-dose contaminants via diverse routes results in cumulative toxic effects [98]. Biomagnification, especially pronounced in aquatic food chains, leads to higher contaminant concentrations in predatory fish consumed by humans. Persistent organic pollutants and lipophilic toxins accumulate in adipose tissue and organs, prolonging toxicological effects [99].

7.2. Integrated Exposure Perspective

Combined or simultaneous exposure through multiple routes is common, particularly in urban settings where individuals may inhale polluted air, ingest contaminated food, and experience dermal contact with food packaging—all potentially occurring within a single meal context [100]. These exposure pathways may act additively or synergistically, underscoring the need for integrated multi-route risk assessment models and biomonitoring for accurate exposure evaluation. Complex interactions among routes—for example, inhaled contaminants cleared by mucociliary action and subsequently swallowed—further complicate exposure dynamics [101].

Beyond primary sources, several other pathways and contextual factors influence food contamination exposure. Globalized food supply chains facilitate the translocation of contaminated products across regions and countries, potentially transferring contaminants from areas with less stringent regulations to consumers worldwide [102]. This complexity complicates traceability and control efforts. Household and consumer behaviors, including food preparation methods such as washing, peeling, cooking, and storage, can substantially modify contaminant levels; for instance, peeling root vegetables may reduce pesticide residues, while certain cooking processes may generate or degrade contaminants. Occupational exposure in agriculture and food processing affects not only worker health but may also contribute to secondary contamination of food products [103].

Table 2. Sources and Pathways of Exposure to Food Contaminants.

Category	Source / Subcategory	Contaminant Types	Pathways	Health Implications
Agricultural Practices [70,71,72,73]	Pesticides and herbicides	Organochlorines, Organophosphates, Neonicotinoids	Crop residues, soil uptake	Neurotoxicity, endocrine disruption, carcinogenicity
	Fertilizers and soil amendments	Cadmium, Lead, Arsenic	Soil → plant uptake → food	Renal damage, developmental toxicity
	Livestock inputs	Antibiotics, Hormones	Meat, milk, eggs	Antimicrobial resistance, hormonal imbalance
	Contaminated irrigation	Industrial effluents, sewage	Crops and vegetables	Multi-pathway toxicity
	Improper storage	Mycotoxins (Aflatoxins, Ochratoxin A)	Grains, nuts, cereals	Hepatotoxicity, immunosuppression, carcinogenesis
Industrial Pollution [74,75,76,77,78,79]	Mining, smelting, waste incineration	Lead, Mercury, Cadmium, Arsenic	Soil, water, air → crops, aquatic organisms	Neurological, carcinogenic effects
	POPs and industrial byproducts	PCBs, Dioxins, PAHs	Soil → food crops, fish	Endocrine disruption, immunotoxicity
	PPCPs from urban waste	Antibiotics, Hormones, Triclosan	Aquatic food, crops via irrigation	Antibiotic resistance, endocrine disruption
	Plastic pollution	Microplastics, Nano plastics	Water, seafood, airborne particles	Inflammation, oxidative stress
Food Processing & Packaging [80,81,82]	Food contact materials	Phthalates, BPA, PFAS	Migration into food during storage or heating	Endocrine disruption, immune effects
	Processing byproducts	Acrylamide, PAHs, Heavy metals	Frying, grilling, metal equipment	Carcinogenicity, neurotoxicity
	Additives and preservatives	Nitrates, Sulfites, Benzoates	Chemical interactions in processed food	Allergies, potential genotoxicity
	Cross-contamination	Allergens, chemical residues	Multi-product processing lines	Anaphylaxis, chronic illness
Climate & Ecology [83,84,85,86,87]	Fungal proliferation	Mycotoxins	Contaminated crops	Liver cancer, stunted growth
	Increased pesticide use	Modern agrochemicals	Crop residues	Bioaccumulation, ecological toxicity
	Contaminated irrigation	Floods, droughts, poor water quality	Crops and food animals	Gastrointestinal and systemic effects
	Biodiversity loss	Altered pollutant degradation	Food webs, aquatic systems	Elevated biomagnification
Human Exposure Routes [88,89,90,91,92,93,94]	Ingestion	Food, water	Heavy metals, pesticides, EDCs, mycotoxins	Systemic toxicity, chronic illness
	Inhalation	Dust, aerosols, indoor air	Microplastics, pesticides, heavy metals	Respiratory damage, mucosal uptake
	Dermal contact	Skin handling, contaminated surfaces	Organophosphates, phthalates	Local or systemic absorption
Vulnerable Populations [95,96,97]	Infants and children	BPA, Lead, Mycotoxins	Diet, environment	Neurological damage, immune dysfunction
	Pregnant women	Mercury, Phthalates	Fish, packaging	Fetal toxicity, endocrine effects
	Occupational groups	Farmers, food workers	Multiple (via air, skin)	Cumulative toxicity
	Low-income populations	Poor-quality foods	Multiple	Increased exposure, limited care access
Additional Considerations [102,103]	Globalized trade	Imported products	Variable regulation	Transboundary contamination
	Household behaviors	Cooking methods, storage	Acrylamide, PAHs, degradation products	Formation or reduction of contaminants
	Dietary choices	Fish, organic, processed foods	Metals, POPs, additives	Differential exposure

Pb = Lead; Cd = Cadmium; Hg = Mercury; As = Arsenic; PCB = Polychlorinated biphenyls; PFAS = Per- and polyfluoroalkyl substances; EDCs = Endocrine-disrupting chemicals; PPCPs = Pharmaceuticals and Personal Care Products; OCPs = Organochlorine pesticides; OPs = Organophosphates.

Table 2. Sources and Pathways of Exposure to Food Contaminants.

Category	Source / Subcategory	Contaminant Types	Pathways	Health Implications
Agricultural Practices [70,71,72,73]	Pesticides and herbicides	Organochlorines, Organophosphates, Neonicotinoids	Crop residues, soil uptake	Neurotoxicity, endocrine disruption, carcinogenicity
	Fertilizers and soil amendments	Cadmium, Lead, Arsenic	Soil → plant uptake → food	Renal damage, developmental toxicity
	Livestock inputs	Antibiotics, Hormones	Meat, milk, eggs	Antimicrobial resistance, hormonal imbalance
	Contaminated irrigation	Industrial effluents, sewage	Crops and vegetables	Multi-pathway toxicity
	Improper storage	Mycotoxins (Aflatoxins, Ochratoxin A)	Grains, nuts, cereals	Hepatotoxicity, immunosuppression, carcinogenesis
Industrial Pollution [74,75,76,77,78,79]	Mining, smelting, waste incineration	Lead, Mercury, Cadmium, Arsenic	Soil, water, air → crops, aquatic organisms	Neurological, carcinogenic effects
	POPs and industrial byproducts	PCBs, Dioxins, PAHs	Soil → food crops, fish	Endocrine disruption, immunotoxicity
	PPCPs from urban waste	Antibiotics, Hormones, Triclosan	Aquatic food, crops via irrigation	Antibiotic resistance, endocrine disruption
	Plastic pollution	Microplastics, Nano plastics	Water, seafood, airborne particles	Inflammation, oxidative stress
Food Processing & Packaging [80,81,82]	Food contact materials	Phthalates, BPA, PFAS	Migration into food during storage or heating	Endocrine disruption, immune effects
	Processing byproducts	Acrylamide, PAHs, Heavy metals	Frying, grilling, metal equipment	Carcinogenicity, neurotoxicity
	Additives and preservatives	Nitrates, Sulfites, Benzoates	Chemical interactions in processed food	Allergies, potential genotoxicity
	Cross-contamination	Allergens, chemical residues	Multi-product processing lines	Anaphylaxis, chronic illness
Climate & Ecology [83,84,85,86,87]	Fungal proliferation	Mycotoxins	Contaminated crops	Liver cancer, stunted growth
	Increased pesticide use	Modern agrochemicals	Crop residues	Bioaccumulation, ecological toxicity
	Contaminated irrigation	Floods, droughts, poor water quality	Crops and food animals	Gastrointestinal and systemic effects
	Biodiversity loss	Altered pollutant degradation	Food webs, aquatic systems	Elevated biomagnification
Human Exposure Routes [88,89,90,91,92,93,94]	Ingestion	Food, water	Heavy metals, pesticides, EDCs, mycotoxins	Systemic toxicity, chronic illness
	Inhalation	Dust, aerosols, indoor air	Microplastics, pesticides, heavy metals	Respiratory damage, mucosal uptake
	Dermal contact	Skin handling, contaminated surfaces	Organophosphates, phthalates	Local or systemic absorption
Vulnerable Populations [95,96,97]	Infants and children	BPA, Lead, Mycotoxins	Diet, environment	Neurological damage, immune dysfunction
	Pregnant women	Mercury, Phthalates	Fish, packaging	Fetal toxicity, endocrine effects
	Occupational groups	Farmers, food workers	Multiple (via air, skin)	Cumulative toxicity
	Low-income populations	Poor-quality foods	Multiple	Increased exposure, limited care access
Additional Considerations [102,103]	Globalized trade	Imported products	Variable regulation	Transboundary contamination
	Household behaviors	Cooking methods, storage	Acrylamide, PAHs, degradation products	Formation or reduction of contaminants
	Dietary choices	Fish, organic, processed foods	Metals, POPs, additives	Differential exposure

Pb = Lead; Cd = Cadmium; Hg = Mercury; As = Arsenic; PCB = Polychlorinated biphenyls; PFAS = Per- and polyfluoroalkyl substances; EDCs = Endocrine-disrupting chemicals; PPCPs = Pharmaceuticals and Personal Care Products; OCPs = Organochlorine pesticides; OPs = Organophosphates.

8. Mechanisms of Toxicity

Food contaminants, encompassing both persistent agents such as heavy metals, pesticides, and mycotoxins, and emerging threats like microplastics, pharmaceutical residues, and endocrine disruptors, induce a broad spectrum of toxic effects in humans (Table 3 and Figure 5) [104].

8.1. Oxidative Stress and Mitochondrial Damage

A primary pathway of toxicity involves oxidative stress, characterized by excessive generation of reactive oxygen species (ROS) coupled with impaired antioxidant defenses [105]. Heavy metals—including cadmium, mercury, lead, and arsenic—disturb redox balance by catalyzing free radical formation and depleting key antioxidants like glutathione [106]. Pesticides and mycotoxins similarly impair mitochondrial function, disrupting the electron transport chain and increasing superoxide and hydrogen peroxide production [106]. Mitochondrial damage hampers ATP synthesis, alters membrane potential, and triggers the release of pro-apoptotic factors such as cytochrome c and apoptosis-inducing factor, culminating in intrinsic apoptotic cell death [107]. Chronic oxidative injury to lipids, proteins, and DNA further contributes to tissue degeneration and the pathogenesis of cancer, neurodegenerative disorders, and cardiovascular diseases. Notably, microplastics and nanoplastics have recently been implicated in elevating ROS levels within gastrointestinal and hepatic tissues, highlighting oxidative stress as a common denominator among diverse contaminants [108].

8.2. Inflammatory Signaling and Immune Modulation

Inflammatory signaling represents another critical mechanism. Food contaminants activate pathways including nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), leading to the upregulation of pro-inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) [109]. Persistent inflammation fosters chronic systemic states linked to metabolic syndrome, atherosclerosis, and autoimmune diseases. Compounds like bisphenol A (BPA), phthalates, and dioxins disrupt immune homeostasis by modulating T-helper cell balance, impairing antigen presentation, and altering macrophage and dendritic cell functions, resulting in either immunosuppression or hypersensitivity reactions [110,111]. Microplastics have been shown to activate the NLRP3 inflammasome, further amplifying inflammatory responses in intestinal tissues [112]. Thus, beyond direct cellular damage, contaminants contribute to immune dysregulation that exacerbates chronic disease risks.

8.3. DNA Interaction and Genotoxicity

Genotoxicity is a hallmark of many foodborne toxicants. Some, like aflatoxin B1, undergo metabolic activation to reactive intermediates (e.g., AFB1-8,9-epoxide) that covalently bind DNA, causing mutations notably in tumor suppressor genes such as TP53 [113]. Heavy metals induce oxidative DNA damage, including strand breaks and cross-links, through ROS-mediated mechanisms [114]. Additionally, certain contaminants inhibit DNA repair enzymes, compounding genotoxic stress. Emerging contaminants such as pharmaceutical residues and per- and polyfluoroalkyl substances (PFAS) induce epigenetic DNA alterations, including aberrant methylation patterns that can activate oncogenes or silence tumor suppressors [115].

8.4. Hormonal Interference and Endocrine Disruption

Endocrine disruption is a further key mechanism, with endocrine-disrupting chemicals (EDCs) interfering at multiple points in hormonal signaling [116]. EDCs may mimic hormones, antagonize receptors, or alter hormone synthesis and metabolism. BPA acts as a xenoestrogen engaging estrogen receptors, while phthalates impair testosterone biosynthesis by inhibiting steroidogenic enzymes. PFAS affect thyroid hormone transport proteins, disrupting thyroxine signaling [117]. These perturbations are especially consequential during sensitive developmental windows—prenatal life, puberty, and pregnancy—and are linked to reproductive abnormalities, infertility, developmental delays, and hormone-dependent cancers [118,119].

8.5. Disruption of Gut Microbiota (Gut Dysbiosis)

An emerging area of concern is the disruption of gut microbiota, or gut dysbiosis, resulting from contaminant exposure. The gut microbiome regulates immunity, metabolism, and neurochemistry, but antibiotics, heavy metals, microplastics, and additives can reduce beneficial bacterial populations and promote pathogens [120,121]. Dysbiosis compromises the intestinal barrier, increasing permeability to microbial products like lipopolysaccharides (LPS), which trigger systemic inflammation implicated in metabolic, neurological, and immune disorders via the gut-brain axis [122,123]. Altered microbiota also affect xenobiotic metabolism, potentially modulating contaminant toxicity.

8.6. Epigenetic Modifications

Epigenetic modifications constitute a vital, non-genotoxic pathway through which food contaminants exert long-lasting and heritable effects. These include changes in DNA methylation, histone modifications, and regulation by non-coding RNAs such as microRNAs [124]. Contaminants such as BPA, phthalates, and arsenic induce aberrant methylation patterns, affecting genes critical for development and disease suppression [125]. Histone modifications influenced by organophosphate pesticides alter chromatin structure and gene expression, exacerbating toxic outcomes [126]. Dysregulation of microRNAs involved in inflammation, cell survival, and tumorigenesis has also been documented following contaminant exposure [129]. Crucially, epigenetic alterations may persist transgenerationally, with maternal exposure during gestation linked to offspring developmental delays, immune dysfunction, and increased chronic disease risk [130,131].

8.7. Disruption of Cell Signaling and Apoptosis

Several food contaminants interfere with intracellular signaling pathways that regulate cell proliferation, differentiation, and programmed cell death (apoptosis) [132]. Persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dioxins activate the aryl hydrocarbon receptor (AhR), modulating the transcription of detoxification enzymes while dysregulating pathways involved in cell growth and immune responses [133]. Pesticides and mycotoxins like deoxynivalenol (DON) activate stress kinases including c-Jun N-terminal kinase (JNK) and p38 MAPK, leading to increased expression of pro-apoptotic proteins such as Bax and reduced levels of the anti-apoptotic protein Bcl-2 [134]. This imbalance promotes caspase-dependent apoptosis in hepatocytes, neurons, and other target cells. Dysregulated apoptosis, especially when combined with impaired DNA repair and chronic inflammation, contributes to tissue damage, fibrosis, and tumorigenesis [135].

8.8. Bioaccumulation and Chronic Low-Dose Toxicity

Many persistent food contaminants exhibit bioaccumulative properties due to their lipophilicity, chemical stability, and resistance to metabolic breakdown. Compounds such as methylmercury, PCBs, and per- and polyfluoroalkyl substances (PFAS) accumulate in adipose tissue, liver, kidneys, and the nervous system, with long biological half-lives [136]. Chronic exposure—even at low environmental levels—can result in cumulative tissue burdens surpassing toxicity thresholds over time. Furthermore, emerging evidence shows that several contaminants display non-monotonic dose-response relationships, where low-dose effects are not predictable from high-dose exposures [137]. Vulnerable groups including pregnant women, infants, elderly individuals, and those with preexisting health conditions are particularly at risk. The extended latency between exposure and disease manifestation complicates causal inference, underscoring the need for improved epidemiological methods and biomonitoring strategies [138]. The bioaccumulative nature of contaminants stresses the importance of preventive measures aimed at reducing exposure before toxic effects arise [139].

8.9. Synergistic and Additive Effects of Contaminant Mixtures

Exposure to mixtures of food contaminants often results in synergistic or additive toxic effects that exceed those of individual substances [140]. For example, combined exposure to heavy metals and pesticides increases oxidative stress and tissue damage more than single agents alone [141]. Mycotoxins and endocrine disruptors together amplify genotoxicity and suppress detoxification enzymes [142]. Microplastics can carry other toxicants, enhancing their bioavailability and toxicity [143]. These interactions are often non-linear and dose-dependent, complicating risk assessments. Advanced tools and regulatory focus on mixture toxicity are essential to address cumulative risks, especially for vulnerable populations [144].

Table 3. The Mechanism of Food Contaminants Toxicity.

Toxicological Mechanism	Key Food Contaminants	Biological Effects	Health Implications	Supporting Evidence
Oxidative Stress & Mitochondrial Damage [105,106,107,108]	Heavy metals (Cd, Hg, Pb, As), pesticides, mycotoxins, microplastics	ROS overproduction, mitochondrial dysfunction, ATP depletion, cytochrome c release	Neurodegeneration, carcinogenesis, cardiovascular diseases	Mitochondrial ETC inhibition, lipid peroxidation, apoptosis induction
Inflammatory Signaling & Immune Modulation [109,110,111,112]	BPA, phthalates, dioxins, microplastics	NF-κB and MAPK activation, cytokine upregulation, inflammasome activation	Chronic inflammation, autoimmune disease, infection susceptibility	IL-6, TNF-α, IL-1β elevation; NLRP3 inflammasome activation in intestines
DNA Interaction & Genotoxicity [113,114,115]	Aflatoxin B1, arsenic, chromium, PFAS, pharmaceutical residues	DNA adducts, strand breaks, oxidative lesions, impaired DNA repair	Mutagenesis, carcinogenesis	TP53 mutations; inhibition of BER/NER pathways; promoter methylation changes
Endocrine Disruption [116,117,118,119]	BPA, phthalates, PFAS, dioxins	Hormone mimicry/antagonism, disrupted synthesis and signaling	Reproductive disorders, hormonal cancers, developmental delays	Xenoestrogen activity; steroidogenesis inhibition; altered thyroid function
Gut Microbiota Disruption (Dysbiosis) [120,121,122,123]	Antibiotics, heavy metals, microplastics, additives	Microbial imbalance, barrier dysfunction, endotoxin leakage	Metabolic syndrome, inflammation, neurobehavioral disorders	Leaky gut; LPS-induced systemic inflammation; altered xenobiotic metabolism
Epigenetic Modifications [124,125,126,127]	BPA, phthalates, arsenic, cadmium, lead, mycotoxins	DNA methylation changes, histone modification, miRNA dysregulation	Cancer, neurodevelopmental and metabolic disorders, transgenerational effects	p16/p53 hypermethylation; miR-21 overexpression; heritable epigenetic reprogramming
Cell Signaling Disruption & Apoptosis [132,133,134,135]	PCBs, dioxins, pesticides, mycotoxins, microplastics	AhR activation, MAPK/JNK signaling, altered Bcl-2/Bax ratio	Fibrosis, organ damage, tumorigenesis	Apoptotic gene dysregulation; necroptosis induction in GI tissues
Bioaccumulation & Chronic Low-Dose Toxicity [136,137,138,139]	Methylmercury, PCBs, PFAS	Lipid accumulation, prolonged half-life, systemic burden	Delayed toxicity, vulnerable population risks	Non-monotonic dose-response; toxic threshold accumulation
Synergistic & Additive Mixture Effects [140,141,142,143,144]	Heavy metals + pesticides, mycotoxins + PAHs, microplastics + POPs	Amplified toxicity, detoxification impairment, "Trojan horse" effects	Multi-organ damage, cumulative risk, low-dose potentiation	Co-exposure amplifies oxidative stress, inflammation, neurotoxicity

Cd: Cadmium; Hg: Mercury; Pb: Lead; As: Arsenic; BPA: Bisphenol A; PFAS: Per- and polyfluoroalkyl substances; POP: Persistent Organic Pollutant; PAH: Polycyclic Aromatic Hydrocarbon; ETC: Electron Transport Chain; LPS: Lipopolysaccharide; AhR: Aryl hydrocarbon receptor; MAPK/JNK: Mitogen-Activated Protein Kinase/c-Jun N-terminal kinase; BER/NER: Base/Nucleotide Excision Repair.

Table 3. The Mechanism of Food Contaminants Toxicity.

Toxicological Mechanism	Key Food Contaminants	Biological Effects	Health Implications	Supporting Evidence
Oxidative Stress & Mitochondrial Damage [105,106,107,108]	Heavy metals (Cd, Hg, Pb, As), pesticides, mycotoxins, microplastics	ROS overproduction, mitochondrial dysfunction, ATP depletion, cytochrome c release	Neurodegeneration, carcinogenesis, cardiovascular diseases	Mitochondrial ETC inhibition, lipid peroxidation, apoptosis induction
Inflammatory Signaling & Immune Modulation [109,110,111,112]	BPA, phthalates, dioxins, microplastics	NF-κB and MAPK activation, cytokine upregulation, inflammasome activation	Chronic inflammation, autoimmune disease, infection susceptibility	IL-6, TNF-α, IL-1β elevation; NLRP3 inflammasome activation in intestines
DNA Interaction & Genotoxicity [113,114,115]	Aflatoxin B1, arsenic, chromium, PFAS, pharmaceutical residues	DNA adducts, strand breaks, oxidative lesions, impaired DNA repair	Mutagenesis, carcinogenesis	TP53 mutations; inhibition of BER/NER pathways; promoter methylation changes
Endocrine Disruption [116,117,118,119]	BPA, phthalates, PFAS, dioxins	Hormone mimicry/antagonism, disrupted synthesis and signaling	Reproductive disorders, hormonal cancers, developmental delays	Xenoestrogen activity; steroidogenesis inhibition; altered thyroid function
Gut Microbiota Disruption (Dysbiosis) [120,121,122,123]	Antibiotics, heavy metals, microplastics, additives	Microbial imbalance, barrier dysfunction, endotoxin leakage	Metabolic syndrome, inflammation, neurobehavioral disorders	Leaky gut; LPS-induced systemic inflammation; altered xenobiotic metabolism
Epigenetic Modifications [124,125,126,127]	BPA, phthalates, arsenic, cadmium, lead, mycotoxins	DNA methylation changes, histone modification, miRNA dysregulation	Cancer, neurodevelopmental and metabolic disorders, transgenerational effects	p16/p53 hypermethylation; miR-21 overexpression; heritable epigenetic reprogramming
Cell Signaling Disruption & Apoptosis [132,133,134,135]	PCBs, dioxins, pesticides, mycotoxins, microplastics	AhR activation, MAPK/JNK signaling, altered Bcl-2/Bax ratio	Fibrosis, organ damage, tumorigenesis	Apoptotic gene dysregulation; necroptosis induction in GI tissues
Bioaccumulation & Chronic Low-Dose Toxicity [136,137,138,139]	Methylmercury, PCBs, PFAS	Lipid accumulation, prolonged half-life, systemic burden	Delayed toxicity, vulnerable population risks	Non-monotonic dose-response; toxic threshold accumulation
Synergistic & Additive Mixture Effects [140,141,142,143,144]	Heavy metals + pesticides, mycotoxins + PAHs, microplastics + POPs	Amplified toxicity, detoxification impairment, "Trojan horse" effects	Multi-organ damage, cumulative risk, low-dose potentiation	Co-exposure amplifies oxidative stress, inflammation, neurotoxicity

Cd: Cadmium; Hg: Mercury; Pb: Lead; As: Arsenic; BPA: Bisphenol A; PFAS: Per- and polyfluoroalkyl substances; POP: Persistent Organic Pollutant; PAH: Polycyclic Aromatic Hydrocarbon; ETC: Electron Transport Chain; LPS: Lipopolysaccharide; AhR: Aryl hydrocarbon receptor; MAPK/JNK: Mitogen-Activated Protein Kinase/c-Jun N-terminal kinase; BER/NER: Base/Nucleotide Excision Repair.

9. Health Risks Associated with Food Contaminants

Food contaminants—both persistent and emerging—have been strongly linked to a broad spectrum of diseases including neurodevelopmental delays, cancer, metabolic disorders, and immune dysfunction [55,123]. Their toxic effects arise through diverse mechanisms like oxidative stress, endocrine disruption, DNA damage, and immune interference, with severity influenced by exposure level, duration, life stage, bioaccumulation, genetic factors, and co-exposure (Table 4 & Figure 4). Neurotoxic effects are especially concerning, as heavy metals like lead, mercury, and arsenic impair cognition and behavior in children and promote neurodegeneration, while pesticides and EDCs disrupt neuroendocrine signaling and neurotransmission [145,146,147,148]. Carcinogens such as aflatoxins, arsenic, nitrates, and dioxins induce cancer via DNA adducts, epigenetic changes, hormone mimicry, and chronic inflammation, increasing risks for liver, breast, prostate, and gastrointestinal cancers [149,150,151,152]. Liver and kidney toxicity result from bioaccumulation of mycotoxins, metals, PFAS, and pesticides that impair detoxification and excretion, often progressing silently to fibrosis or organ failure [24,63,153]. Reproductive and developmental effects emerge from endocrine disruptors like BPA, phthalates, and dioxins, reducing fertility, altering hormone levels, and inducing fetal malformations or transgenerational epigenetic changes [154,155,156,157]. Metabolic disruptions—including obesity and diabetes—are linked to contaminants that affect PPAR signaling, glucose metabolism, and adipogenesis, particularly in early life [158,159,160,161]. Immune toxicity arises from metals, mycotoxins, POPs, and microplastics, leading to weakened defenses, hypersensitivity, and altered cytokine responses, while PFAS reduce vaccine efficacy [43,120,162,163,164]. Finally, gastrointestinal effects stem from epithelial damage and microbiota disruption caused by metals, mycotoxins, microplastics, pesticides, and EDCs, resulting in leaky gut, inflammation, reduced beneficial bacteria, and long-term systemic impacts, especially during early development [120,123,165,166].

10. Mitigation Strategies for Emerging and Persistent Food Contaminants

Mitigating the threats posed by emerging and persistent food contaminants demands more than isolated actions—it requires an integrated, multidisciplinary strategy that harmonizes regulatory frameworks, technological advancement, environmental stewardship, and collaboration across all stakeholders (Table 5). The following sections explore the most widely adopted and scientifically supported strategies currently shaping the global response to food contamination.

10.1. Regulatory Control and Policy Interventions

Regulatory control remains the cornerstone of food contaminant mitigation. Across the world, national governments and global institutions—including the Codex Alimentarius Commission, the World Health Organization (WHO), and the Food and Agriculture Organization (FAO)—have instituted comprehensive standards to protect public health [167]. Maximum residue limits (MRLs) are established and enforced for hazardous substances such as arsenic, mercury, lead, pesticide residues, and mycotoxins. These legal limits help curb the accumulation of toxic substances in the food supply. Countries have simultaneously enacted food safety laws, environmental protection acts, and structured waste management policies, aiming to minimize the entry of contaminants into agricultural systems and food chains [168]. When contamination occurs, food recall mechanisms are activated to rapidly withdraw unsafe products from the market, thus averting public health emergencies [169]. Harmonization of international standards through Codex Alimentarius also facilitates global food trade while maintaining safety. As new threats emerge—like microplastics and by-products from novel food technologies—frequent policy updates based on scientific evidence and surveillance data become essential.

10.2. Technological Innovations in Detection and Monitoring

In today’s food safety landscape, early detection and efficient monitoring of contaminants are vital. Recent progress in analytical chemistry and biosensor technology now enables the identification of trace contaminants with extraordinary precision [170]. Tools such as gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and inductively coupled plasma mass spectrometry (ICP-MS) allow laboratories to accurately analyze complex samples for a wide array of toxicants including heavy metals, pesticide residues, and mycotoxins [171]. Beyond the lab, portable biosensors and rapid detection kits facilitate immediate field assessments, particularly in resource-constrained settings. Technological innovations have also reached the digital realm—smart packaging, blockchain technology, and sensor-based supply chain tracking are being integrated to enhance food traceability and real-time contaminant monitoring [172]. Artificial intelligence (AI) and big data analytics offer promising avenues for predicting contamination events by analyzing environmental, agricultural, and logistics data sets [173], allowing authorities and companies to act preemptively rather than reactively.

10.3. Agricultural and Pre-Harvest Interventions

Effective mitigation often begins in the field. Reducing contamination at the agricultural level is not only cost-effective but also environmentally sustainable. Good Agricultural Practices (GAP) are at the forefront of this effort, promoting clean irrigation, judicious use of fertilizers and pesticides, regular soil testing, and safe handling of agrochemicals [174]. Integrated Pest Management (IPM), which blends biological, physical, and chemical controls, reduces pesticide reliance while maintaining pest control efficacy [175]. Advances in crop genetics—including selective breeding and genetic engineering—have created plant varieties that either resist fungal contamination or limit heavy metal uptake. These traits decrease the occurrence of foodborne toxins such as aflatoxins and ochratoxin A. Additionally, soil remediation approaches like phytoremediation—using plants that absorb toxic metals—have shown promise in detoxifying contaminated agricultural lands [176]. These pre-harvest efforts lay the groundwork for a safer food supply from the very start of production.

10.4. Post-Harvest Handling, Processing, and Storage Controls

Contamination doesn’t end at harvest—processing, storage, and transportation stages are equally critical. Proper post-harvest handling can prevent fungal proliferation and bacterial growth, especially in grains and nuts where mycotoxins are common [177]. Maintaining optimal moisture, temperature, and ventilation significantly reduces mold risks. Processing methods such as washing, peeling, heat treatment, and fermentation help remove or degrade pesticide residues and chemical pollutants [178]. Meanwhile, new decontamination technologies like ultraviolet (UV) light, ozone treatment, and irradiation are being implemented to neutralize pathogens and toxins without compromising food quality. Packaging is another vital control point—modern food-grade packaging materials are now designed to be biodegradable, non-toxic, and resistant to contaminant leaching, particularly of microplastics [179]. These cumulative interventions significantly lower the likelihood of contamination persisting into consumer-ready products.

10.5. Industry Responsibility and Supply Chain Management

The responsibility for food safety doesn’t rest with regulators alone. The food industry—from farmers and processors to distributors and retailers—plays an integral role in contamination mitigation. Many companies now adopt food safety systems like Hazard Analysis and Critical Control Points (HACCP) and adhere to internationally recognized standards such as ISO 22000, Global G.A.P., and BRC Global Standards [180]. Auditing suppliers, testing raw ingredients, and enforcing traceability systems have become best practices. Blockchain and digital traceability tools empower companies to track products from origin to shelf, allowing swift responses in the event of contamination [181]. Moreover, firms are increasingly embracing environmental sustainability and ethical sourcing practices to prevent upstream contamination from agricultural and industrial sources. These collaborative efforts among industry actors, regulators, and consumers help foster a transparent, accountable, and resilient food system [182].

10.6. Environmental Protection and Waste Management

Environmental contamination is a major contributor to food contaminants, particularly for heavy metals, persistent organic pollutants, and emerging pollutants like microplastics. Effective waste management and pollution control strategies are therefore critical for long-term mitigation [183]. Industrial activities such as mining, manufacturing, and chemical production must adhere to strict environmental regulations to prevent the release of contaminants into soil, water, and air. The safe disposal and treatment of industrial and agricultural waste, including pesticides, fertilizers, and packaging materials, reduce the risk of environmental contamination [184]. Global agreements such as the Stockholm Convention on Persistent Organic Pollutants aim to eliminate or restrict the production and use of harmful chemicals that can accumulate in the food chain [185]. Furthermore, improved wastewater treatment, stormwater management, and control of agricultural runoff help protect water sources used for irrigation and aquaculture. Climate change adaptation strategies, such as promoting drought-resistant crops and improving pest control, also contribute to reducing contamination risks exacerbated by environmental stressors [186].

10.7. Research, Education, and International Collaboration

Scientific research and international collaboration are essential to develop innovative solutions and enhance global capacity to mitigate food contaminants. Research efforts focus on improving detection methods, understanding the toxicological impacts of emerging contaminants, and developing safer alternatives to hazardous chemicals used in agriculture and food processing [187]. Public and private investment in research accelerates the development of biopesticides, natural preservatives, and green technologies that reduce contaminant levels in food. Capacity building, particularly in developing countries, is critical to strengthen laboratory infrastructure, surveillance systems, and regulatory frameworks [188]. Education and awareness campaigns targeted at farmers, food handlers, industry stakeholders, and consumers promote the adoption of safe practices and empower individuals to make informed food choices [189]. Global data sharing platforms, such as those facilitated by the WHO, FAO, European Food Safety Authority (EFSA), and International Food Safety Authorities Network (INFOSAN), enable real-time exchange of information on food safety incidents and emerging risks [190]. Through coordinated efforts at national, regional, and international levels, the food safety community can effectively address the complex challenge of emerging and persistent food contaminants.

11. Strengths, Limitations, and Future Directions

This review provides a comprehensive synthesis of current knowledge on emerging and persistent food contaminants, integrating molecular toxicity mechanisms with advances in detection and mitigation strategies. Its methodological rigor, ensured through SANRA appraisal, strengthens the reliability of findings and supports evidence-based recommendations. However, limitations include potential publication bias and uneven data availability across regions, particularly from low-income countries where surveillance is limited. Additionally, rapid technological developments may outpace the literature covered, underscoring the need for continuous updates.

Future research should focus on standardizing detection methods and harmonizing regulatory policies globally to improve monitoring and control of contaminants. Greater emphasis is needed on scalable, cost-effective mitigation technologies suitable for diverse socioeconomic contexts. Interdisciplinary studies combining toxicology, environmental science, and socioeconomics can provide holistic insights into food safety challenges. Moreover, enhancing international collaboration and public engagement will be crucial in addressing knowledge gaps and fostering sustainable food safety solutions amid evolving environmental and industrial landscapes.

12. Conclusion

Emerging and persistent food contaminants pose a significant and evolving challenge to global food safety and public health. Despite advances in detection technologies and mitigation strategies, many contaminants continue to evade comprehensive monitoring and effective control, particularly in developing regions. This review highlights the multifaceted health risks associated with these contaminants, driven by complex molecular mechanisms such as oxidative stress, endocrine disruption, and genotoxicity. While innovative approaches like phytoremediation, bioadsorbents, and green processing show promise, their large-scale application remains limited by regulatory, technological, and socioeconomic barriers. Strengthening international regulatory frameworks, fostering cross-sector collaboration, and investing in research are critical to closing existing knowledge gaps. Moreover, integrating advanced detection systems with risk assessment and public awareness campaigns can enhance early identification and management of food contaminants. Future efforts must prioritize sustainable, cost-effective solutions to safeguard food systems worldwide, ensuring health protection in the face of ongoing environmental and industrial changes.