Vector-amplified toxicity of microplastics and heavy metals in aquatic invertebrates: mechanistic insights and implications for sustainable aquaculture

1 Introduction

Aquatic ecosystems are increasingly threatened by the co-occurrence of emerging contaminants, particularly microplastics (MPs) and heavy metals (HMs). These pollutants are not only persistent and pervasive but also capable of interacting in complex ways that amplify their ecological and toxicological effects. Microplastics, plastic fragments smaller than 5 mm, are ubiquitous in both freshwater and marine systems due to the degradation of plastic waste, wastewater effluents, and diffuse runoff from urban and agricultural landscapes (Liu et al., 2021). Meanwhile, heavy metals such as cadmium (Cd), lead (Pb), copper (Cu), and mercury (Hg) accumulate in aquatic environments through industrial discharge, mining effluents, atmospheric deposition, and non-point sources, including road runoff, tire wear, and urban stormwater. These diffuse inputs, often underestimated in conventional monitoring, make coastal and estuarine zones major sinks for metal pollution and hotspots of microplastic accumulation.

In aquaculture systems, these contaminants are of particular concern due to multiple entry pathways and system-specific exposure dynamics. Microplastics and associated heavy metals can originate from contaminated feeds, plastic-based materials such as pond liners, nets, cages, and other aquaculture gear, as well as runoff from surrounding agricultural and urban areas (Boyd et al., 2020; Lusher et al., 2017). Across production systems, including earthen ponds, cage culture, and recirculating aquaculture systems (RAS), these contaminants accumulate in water and sediments, increasing exposure risks for cultured species. Feeding behavior and sediment interaction further enhance uptake, particularly in benthic and detritivorous organisms, thereby reinforcing aquaculture environments as critical interfaces for MP–HM co-contamination.

Mounting evidence indicates that MPs can adsorb, concentrate, and redistribute heavy metals because of their large surface area, hydrophobicity, and physicochemical reactivity enhanced by environmental aging (Adeleye et al., 2024; Wijesekara et al., 2020). Weathering and oxidative processes such as UV irradiation, thermal degradation, physical abrasion, and biodegradation gradually fragment plastics, increasing their surface roughness and generating oxygen-containing functional groups (–OH, –COOH, –C=O) that promote metal binding (Luo et al., 2021; Wang et al., 2025). Simultaneously, biofilm colonization modifies the surface chemistry of aged MPs, as extracellular polymeric substances (EPS) secreted by microbial communities can either chelate or release metals depending on environmental pH and salinity (Wu et al., 2024). These processes transform MPs from inert debris into reactive carriers that dynamically regulate metal partitioning, mobility, and environmental fate.

Among aquatic invertebrates, crustaceans, particularly decapods such as Litopenaeus vannamei and Scylla serrata, serve as sensitive biological indicators of aquatic contamination due to their benthic lifestyle and trophic importance. Their feeding habits result in sustained exposure to sediment-associated MPs and metals, leading to oxidative stress, immunosuppression, neurotoxicity, and reproductive impairment (Zhang et al., 2023; D'Costa, 2022). Co-exposure studies frequently report enhanced metal uptake and toxicity associated with MPs through electrostatic attraction, van der Waals forces, and hydrophobic interactions (Liu et al., 2021; Adeleye et al., 2024). These outcomes suggest that MP–HM interactions are frequently synergistic, although antagonistic and neutral responses have also been reported under specific exposure conditions.

Accordingly, this review primarily focuses on aquatic invertebrates, particularly crustaceans and mollusks, because of their ecological relevance, benthic exposure pathways, and importance in aquaculture systems. Although finfish are briefly discussed where relevant, the synthesis emphasizes invertebrate-based mechanistic evidence due to the greater availability of experimental co-exposure studies within these taxa.

Beyond ecological effects, MP–HM interactions have direct implications for aquaculture sustainability, economic performance, and food security. The accumulation of these contaminants in cultured organisms can reduce growth efficiency, compromise health, and increase mortality, ultimately affecting production outputs and profitability. Furthermore, the transfer of contaminants through aquatic food webs raises concerns regarding seafood safety and human health (Huang et al., 2020; Habumugisha et al., 2024). These issues highlight the need to integrate MP–HM dynamics into sustainable aquaculture management and policy frameworks.

Despite extensive documentation of MP–HM co-occurrence, current risk assessment paradigms continue to treat these stressors as conventional mixtures, implicitly assuming independent or weakly interacting toxicological pathways. This approach fails to account for the ability of MPs to actively reprogram metal fate, exposure routes, bioavailability, and internal distribution within organisms. Rather than behaving as passive sorbents, MPs function as toxicokinetic modifiers that alter metal uptake efficiency, tissue targeting, and downstream cellular responses. As a result, MP–HM systems generate emergent toxicological behaviors that cannot be predicted from dissolved-metal or single-contaminant frameworks alone.

This review aims to (i) synthesize mechanistic evidence of MP–HM interactions, (ii) evaluate their implications for aquaculture systems and sustainability, and (iii) identify mitigation strategies aligned with sustainable aquaculture practices and biosecurity frameworks.

To synthesize these interacting processes, this review presents a Vector–Cascade Framework as an integrative conceptual model linking physicochemical adsorption, vector-mediated transport, organismal uptake, oxidative stress, and downstream physiological responses under aquaculture-relevant exposure conditions (Figure 1). Rather than proposing new toxicological mechanisms, the framework synthesizes established pathways while integrating aquaculture-specific exposure routes, including feed contamination, sediment ingestion, and system-specific dynamics across ponds, cages, and recirculating aquaculture systems (RAS).

2 Methodology

The review systematically synthesizes mechanistic and quantitative evidence on the toxicity of microplastic–heavy metal (MP–HM) co-exposure in aquatic invertebrates. Literature identification and screening followed a structured approach aligned with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) principles to improve transparency in study selection and eligibility assessment.

Literature searches were conducted using Scopus, Web of Science, PubMed, and Google Scholar between January and March 2025 using combinations of the following keywords: (“microplastics” OR “nanoplastics”) AND (“heavy metals” OR cadmium OR lead OR copper OR mercury) AND (“aquaculture” OR crustaceans OR mollusks OR fish) AND (“toxicity” OR bioaccumulation OR oxidative stress). After duplicate removal and title–abstract screening, full-text evaluation was performed using predefined inclusion criteria. A total of 85 experimental studies were retained for final synthesis, as summarized in the PRISMA flow diagram (Figure 2).

Studies were included if they: (1) experimentally evaluated MPs and HMs singly or in combination; (2) reported quantitative physicochemical, biological, or toxicological endpoints, including adsorption coefficients (Kd), bioaccumulation/bioconcentration factors (BAF/BCF), oxidative or enzymatic biomarkers, growth, reproduction, or behavioral responses; and (3) involved aquatic organisms or aquaculture-relevant systems, particularly crustaceans and mollusks. Review articles, modeling-only studies, and studies lacking primary experimental data were excluded. The literature search included studies published through July 2025 to capture recent advances in nanoplastic research, omics-based endpoints, and environmental modifiers such as temperature, salinity, and pH.

Screening decisions were resolved through iterative consensus evaluation among the authors to ensure consistency in study inclusion and data extraction. Included studies were qualitatively evaluated based on replication adequacy, exposure realism, particle characterization, environmental parameter reporting, and endpoint clarity. Due to substantial heterogeneity in polymer type, particle size, aging status, heavy metal species, exposure duration, taxa, and measured endpoints, a formal quantitative risk-of-bias framework and meta-analysis were not applied. Instead, the review employed structured mechanistic and semi-quantitative synthesis approaches to identify consistent patterns, mechanistic trends, and context-dependent variability across the literature.

Quantitative synthesis focused on reported means, fold changes, percentage deviations from controls, adsorption coefficients, and bioaccumulation metrics to facilitate cross-study comparison. Non-environmentally realistic exposure concentrations were retained where relevant for mechanistic interpretation but were critically contextualized with respect to ecological realism and aquaculture relevance. Potential sources of bias include variability in experimental design, inconsistent particle characterization, and limited standardization across exposure protocols.

The review primarily focuses on aquatic invertebrates, including crustaceans, mollusks, and benthic taxa, selected because of their ecological relevance, aquaculture importance, and comparable exposure pathways. This integrative approach emphasizes adsorption dynamics, toxicological mechanisms, and organismal responses while linking MP–HM interactions to aquaculture sustainability and food-safety considerations.

3 Adsorption, desorption, and environmental modifiers

The combined toxicity of microplastics (MPs) and heavy metals (HMs) originates from their physicochemical interactions in aquatic environments. MPs can adsorb heavy metals due to their surface properties, including functional group formation during aging and biofilm development (Godoy et al., 2019; Khalid et al., 2021). Experimental studies have demonstrated increased adsorption capacity in aged polystyrene and polyethylene particles. Adsorption occurs through electrostatic attraction, surface complexation, hydrophobic forces, hydrogen bonding, and π–π interactions and is commonly quantified using the distribution coefficient (Kd, L kg⁻¹), which reflects the partitioning of metals between solid and aqueous phases.

In aquaculture systems, these adsorption processes are further influenced by pond-specific environmental conditions, particularly sediment dynamics and feed inputs. Pond sediments act as major sinks for both MPs and HMs, where fluctuating redox conditions, organic matter accumulation, and microbial activity can enhance adsorption during deposition but promote desorption under acidic or disturbed conditions. These sediment-mediated processes increase the likelihood of remobilization and ingestion by benthic organisms, thereby amplifying exposure in aquaculture environments.

3.1 Adsorption and desorption dynamics

Experimental studies demonstrate that ultraviolet aging and oxidative weathering substantially enhance metal sorption capacity on microplastics by generating oxygen-containing functional groups such as –OH and –COOH. For example, aged polystyrene particles exhibited Cd adsorption coefficients approaching ~2.9 × 10⁴ L kg⁻¹, exceeding pristine particles by more than one order of magnitude under controlled laboratory conditions (Godoy et al., 2019). Similarly, Wang et al., 2021 reported increased Cu²⁺ adsorption on UV-aged polyethylene relative to pristine particles, consistent with enhanced surface polarity following photooxidation. Biofilm formation further increases sorption through extracellular polymeric substances (EPS) capable of chelating or binding metals (Khalid et al., 2021). Conversely, acidic environments, such as sediments and digestive fluids, facilitate desorption, resulting in elevated metal uptake following ingestion (Oz, 2019). Representative adsorption and desorption data under varying environmental conditions are summarized in Table 1.

Table 1. Representative adsorption/desorption data for heavy metals on microplastics under varying environmental conditions.

Kd = distribution coefficient; SW = seawater. Values represent adsorption capacity ratios (metal concentration on MPs/in solution).

In aquaculture contexts, feed pellets represent an additional and often overlooked vector for MP–HM interactions. Commercial feeds may contain microplastic contaminants originating from processing, packaging, or ingredient sources, which can adsorb metals prior to ingestion. Once introduced into pond systems, uneaten feed contributes to sediment accumulation, where MPs associated with feed particles can undergo further adsorption–desorption cycles. This dual role of feed, as both a direct ingestion pathway and an indirect sediment source, enhances the transfer of MP–HM complexes to cultured species.

Typical Kd values for metal adsorption on microplastics range from approximately 10² to 10⁴ L kg⁻¹, with the upper range approaching ~3 × 10⁴ L kg⁻¹ in aged or biofouled polymers such as polystyrene under controlled laboratory conditions (Table 1). These findings indicate that surface aging and biofilm formation can substantially enhance sorption efficiency, often by one to two orders of magnitude relative to pristine particles. Adsorption generally follows the Freundlich or Langmuir isotherms and pseudo-second-order kinetics, with reported rate constants (k₂ = 0.01–0.12 g mg⁻¹ min⁻¹) indicating chemisorption dominance (Godoy et al., 2019; Oz, 2019). Thermodynamic parameters often reveal negative ΔG° values (−15 to −35 kJ mol⁻¹), signifying spontaneous adsorption, while positive ΔH° suggests endothermic processes that intensify at higher temperatures (Sen Gupta and Bhattacharyya, 2011).

3.2 Influence of polymer type, pH, salinity, and DOM

Polymer type, pH, salinity, and dissolved organic matter (DOM) collectively govern the adsorption and desorption behavior of heavy metals on microplastic surfaces, ultimately determining their environmental fate and bioavailability. Aromatic polystyrene (PS) and non-polar polypropylene (PP) exhibit strong affinities for metal ions such as Cd²⁺, Cu²⁺, and Pb²⁺, whereas polyethylene (PE) and polyvinyl chloride (PVC) display moderate sorption capacities that significantly increase following photooxidation. In contrast, polyamide (PA or nylon) forms coordination complexes with transition metals, enhancing binding stability (Adeleye et al., 2024; Barus et al., 2023). Metal sorption generally increases under alkaline conditions as proton competition decreases; for instance, Cu²⁺ adsorption on PE rises from 0.9 × 10³ to 1.2 × 10³ L kg⁻¹ between pH 6 and 8 (Wang et al., 2021). Conversely, acidic environments promote desorption, contributing to elevated metal release within digestive tracts and sediments (Oz, 2019). Salinity and DOM further modulate electrostatic interactions and aggregation behavior, high salinity may either suppress or enhance sorption depending on polymer surface charge and the molecular composition of DOM (Khalid et al., 2021).

3.3 Nano- vs micro-plastics: sorption efficiency and bioavailability

Nano-sized plastics (NPs; < 100 nm) differ markedly from MPs in surface chemistry and environmental behavior. Their smaller particle size confers a dramatically higher specific surface area, surface curvature, and number of active binding sites, enhancing sorption efficiency and facilitating stronger electrostatic and van der Waals interactions (Liu et al., 2023; Mattsson et al., 2015). Owing to their nanoscale dimensions, NPs penetrate biological membranes more readily, leading to greater bioavailability and intracellular accumulation compared to MPs (Hong and Kim, 2024). Dynamic transformations in charge, size, and aggregation state further influence their fate and reactivity in aquatic environments (Haegerbaeumer et al., 2019). Collectively, these characteristics make nanoplastics particularly potent vectors for heavy metals, exacerbating the combined toxicity observed in aquatic invertebrates and raising new challenges for risk assessment and regulation.

Putting together, adsorption–desorption dynamics, environmental modifiers, and size-dependent properties jointly dictate the behavior of MP–HM complexes. Integrating kinetic and thermodynamic modeling parameters (k₁, k₂, ΔG°, ΔH°) with polymer chemistry and nanoscale characteristics provides a stronger mechanistic foundation for understanding the fate, transport, and biological effects of these pollutants in aquatic ecosystems.

Generalized trends in MP–HM adsorption across polymer classes and environmental settings frequently associate the highest adsorption coefficients with aged or biofouled polystyrene and polyamide, followed by polypropylene, polyethylene, and polyvinyl chloride. Sorption strength is primarily modulated by surface aging, particle size (nano > micro), and environmental pH, with alkaline conditions favoring adsorption and acidic conditions promoting desorption. Under these latter conditions, particularly within sediments and digestive environments, microplastics transition from acting as temporary contaminant sinks to effective vectors, releasing previously adsorbed metals and substantially enhancing localized bioavailability. These generalized patterns support the importance of microplastic characteristics and environmental context in governing metal transport and exposure, providing a mechanistic basis for the amplified toxicity observed under MP–HM co-exposure scenarios. These trends are illustrated in Figure 3, which summarizes the key physicochemical mechanisms controlling adsorption, desorption, and vector-mediated metal release by MPs under varying environmental conditions. In aquaculture settings, the presence of fine particles and organic-rich sediments may further enhance the retention and bioavailability of nanoplastics, increasing the risk of trophic transfer and accumulation in cultured species.

4 Bioavailability, bioaccumulation, and trophic transfer

4.1 Uptake pathways

Aquatic invertebrates encounter MP–HM complexes through ingestion, filtration, or cutaneous absorption (Figure 4). Ingested particles commonly accumulate in the hepatopancreas, gills, and intestine, eliciting oxidative and metabolic stress (Watts et al., 2014; D'Costa, 2022). Desorption of metals within acidic gut conditions releases bound ions that traverse epithelial barriers via passive diffusion or active transport (Rainbow, 1997), resulting in greater uptake compared with dissolved-metal exposure (Khalid et al., 2021). MPs thus serve as mobile vectors enhancing localized bioavailability and tissue metal burdens.

These uptake pathways are directly relevant to aquaculture species, including shrimp (e.g., Litopenaeus vannamei) and finfish such as tilapia (Oreochromis spp.), where ingestion of contaminated feed, suspended particles, and sediment-bound MPs represents a primary exposure route. In pond-based systems, feeding practices and benthic interactions further increase exposure frequency, reinforcing the importance of MP-mediated uptake pathways in cultured species.

4.2 Quantitative evidence

Experimental evidence demonstrates that microplastics (MPs) significantly enhance the bioaccumulation of heavy metals in aquatic invertebrates. In Daphnia magna, exposure to Cd-laden polystyrene (PS) particles (20 µm) resulted in approximately 35% higher cadmium body burden compared with exposure to dissolved Cd alone (Zhang et al., 2022). In contrast, Scylla serrata exposed to Pb–polyethylene (Pb–PE) complexes exhibited a 1.8-fold increase in hepatopancreatic Pb accumulation (Patrick and Egbuatu, 2024). In Litopenaeus vannamei, co-exposure to microplastics and copper has been associated with increased tissue metal accumulation and altered enzymatic responses, indicating enhanced bioavailability under combined exposure conditions. However, quantitative estimates of bioaccumulation vary across studies depending on polymer type, particle size, and exposure conditions.

While waterborne uptake generally dominates initial exposure, the presence of MPs alters uptake kinetics by prolonging metal retention time and promoting desorption within microenvironments such as digestive tracts, thereby enhancing bioavailability and internal metal loading (Khalid et al., 2021).

These findings have important implications for aquaculture production, as enhanced bioaccumulation in species such as shrimp and tilapia may directly affect product quality, safety, and compliance with export standards.

4.3 Water vs MP pathways: quantitative comparison

Stable-isotope tracing has provided quantitative insights into how microplastics (MPs) influence the trophic transfer of metals across aquatic food webs. Synthesizing findings from Adeleye et al. (2024) and Wang et al., 2021, reported transfer ratios (TR) range from 0.43 to 0.58, while tissue-retention factors (TRF) are generally 1.2–1.8 times higher under MP co-exposure than in metal-only treatments.

To enhance cross-study comparability, the use of standardized indices, such as the distribution coefficient (Kd = C_MP/C_water), bioaccumulation factor (BAF = C_tissue/C_water), transfer ratio (TR = C_predator/C_prey), and tissue-retention factor (TRF = C_tissue/C_reference tissue), is recommended. These parameters help disentangle direct metal uptake from MP-mediated transport pathways, strengthening the interpretation of trophic transfer dynamics.

In aquaculture food chains, these enhanced transfer processes increase the likelihood of contaminant movement from lower trophic organisms to cultured species, thereby elevating risks associated with food safety and consumer exposure.

4.4 Biomagnification and trophic magnification factors

Trophic magnification factors (TMFs) represent the slope of the regression between contaminant concentration and trophic level, providing a robust index of bioaccumulation through food webs (Borgå et al., 2012). In traditional metal-only systems, TMFs typically range from 0.7 to 1.2, indicating limited biomagnification due to efficient metal regulation. However, in MP–HM systems, TMFs often exceed these values (1.5–2.8) because MPs act as persistent carriers that prolong metal residence times and facilitate trophic transfer (Liu et al., 2021; Adeleye et al., 2024; Devi et al., 2025).

Such elevated TMFs are particularly concerning for aquaculture systems, where repeated feeding cycles and controlled production environments may amplify contaminant accumulation, potentially compromising seafood safety and export quality standards.

4.5 Species traits influencing uptake dynamics

Species-specific biological traits modulate the accumulation and transfer of MPs and metals in aquatic invertebrates. Feeding strategy, molting frequency, lipid content, and habitat preference largely determine exposure intensity and retention.

In aquaculture, both invertebrates (e.g., shrimp, oysters) and finfish such as tilapia exhibit distinct uptake patterns influenced by feeding behavior and habitat use. For example, tilapia (Oreochromis spp.), as omnivorous and often benthic-associated feeders in pond systems, are susceptible to ingesting MP-associated metals through both feed and sediment pathways, similar to detritivorous invertebrates. Representative examples are summarized in Table 2.

Table 2. Representative biological traits influencing MP–HM uptake and bioaccumulation in aquatic invertebrates.

4.6 Semi-quantitative synergy classification

To synthesize empirical patterns without a formal meta-analysis, MP–HM interactions can be classified into three semi-quantitative synergy regimes: (1) Low synergy: Large MPs, pristine surfaces, neutral pH- minimal enhancement of metal bioavailability; (2) Moderate synergy: Aged MPs and moderate environmental variability- intermediate amplification; (3) High synergy: Nano-sized MPs and acidic environments- maximal bioavailability and trophic transfer.

5 Cellular and organismal mechanisms of synergistic toxicity

Synergistic MP–HM toxicity arises from cumulative disturbances to oxidative balance, neural signaling, endocrine regulation, immune defense, and genomic stability (Adeleye et al., 2024; Liu et al., 2022). These interacting stress pathways produce greater physiological damage than either contaminant alone. Representative organismal endpoints under MP–HM co-exposure are summarized in Table 3.

Table 3. Representative organismal endpoints under MP–HM co-exposure.

Several exposure concentrations summarized in this table represent mechanistic laboratory conditions and may exceed currently reported environmental concentrations in aquaculture systems.

Many experimental studies summarized in this review employ MP concentrations exceeding 1–50 mg L⁻¹ and HM concentrations above environmentally typical ranges observed in aquaculture systems. While such exposure levels are useful for resolving mechanistic pathways under controlled laboratory conditions, they may overestimate ecological risk relative to chronic field exposures, which are generally lower, spatially variable, and influenced by multiple interacting physicochemical stressors.

5.1 Oxidative stress

Oxidative stress represents a central mechanistic response under MP–HM co-exposure. In Crassostrea gigas, co-exposure to polystyrene microplastics and Cd increased malondialdehyde (MDA) levels by approximately 2.4-fold while reducing superoxide dismutase (SOD) activity by 45%, indicating substantial oxidative imbalance (Liu et al., 2022). Similarly, Procambarus clarkii exposed to polyethylene microplastics and Pb exhibited elevated ROS production and catalase suppression relative to single-contaminant treatments (Zhou et al., 2021). These findings support the role of reactive oxygen species as upstream mediators linking MP-mediated metal transport to downstream cellular toxicity. These oxidative imbalances activate Nrf2/Keap1 and NF-κB pathways, triggering transcriptional changes in antioxidant and stress-response genes (sod, cat, gst, HSPs, MTs) and linking environmental exposure to a cascade of downstream physiological damage.

5.2 Neurotoxicity

Neurotoxic responses under MP–HM co-exposure have been documented in several aquatic invertebrates. In Litopenaeus vannamei, combined exposure to polyethylene microplastics and Cu reduced acetylcholinesterase (AChE) activity by approximately 30% and impaired swimming behavior relative to controls (Chen et al., 2024). In Daphnia magna, Cd-associated polystyrene particles reduced phototactic responses by 42%, suggesting disruption of neural signaling pathways (Zhang et al., 2022). Mechanisms involve AChE inhibition, calcium dysregulation, and apoptosis gene activation (Caspase-3, Bax). Smaller-bodied species show faster impairment due to higher MP uptake, emphasizing the role of particle-mediated exposure in the cascade.

5.3 Endocrine disruption and reproduction

Oxidative stress cascades also impair hormonal balance. Scylla serrata exposed to PS + Cd showed a 28% decrease in gonadosomatic index (GSI) and reduced E₂/T ratio to 0.65 (Rodríguez, 2024), while Penaeus monodon exhibited a 35% reduction in egg-clutch size (Zou, 2005; Knigge et al., 2021). Leached plastic additives can further amplify endocrine disruption. These outcomes are positioned downstream of oxidative stress, forming part of the integrated toxicity cascade.

5.4 Immune and genotoxic effects

MP–HM co-exposure suppresses immune function and causes DNA damage. Carcinus maenas showed 40% hemocyte reduction under PVC + Zn exposure (Adeleye et al., 2024), while Mytilus edulis had a 75% increase in DNA damage (Liu et al., 2021). Oxidative stress underlies both immunotoxicity and genotoxicity, linking upstream ROS generation to downstream cellular dysfunction.

5.5 Epigenetic and transcriptional regulation

Transcriptomic studies reveal dysregulation of antioxidant, apoptosis, and metal-sequestration genes (sod, cat, gst, bcl-2, caspase-3, HSPs, MTs), with DNA methylation changes potentially driving transgenerational sensitivity (Lee et al., 2025; Putri et al., 2025). This further supports the central role of oxidative stress as the initiating event that propagates molecular disruptions.

5.6 Integrative mechanistic cascade

Oxidative stress functions as the upstream convergence node, initiating a cascade that leads to neurotoxicity, endocrine disruption, immune impairment, and genotoxicity. MPs amplify this cascade by extending metal residence time and promoting sustained ROS generation, increasing downstream physiological impacts. This section explicitly integrates multiple pathways into a coherent mechanistic framework, emphasizing causal linkages rather than isolated endpoints.

5.7 Behavioral impacts

Behavioral endpoints reflect the integrated cascade. Daphnia magna exhibited 42% phototaxis reduction (Zhang et al., 2022), and L. vannamei showed reduced swimming corresponding to 30% AChE inhibition (Chen et al., 2024). These impairments represent emergent outcomes of oxidative, neural, and endocrine dysregulation within the mechanistic cascade illustrated in Figure 5.

6 Environmental modulators of MPs–HMs synergy

The combined toxicity of microplastics (MPs) and heavy metals (HMs) in aquatic ecosystems is strongly governed by abiotic modulators such as temperature, salinity, pH, dissolved organic matter (DOM), and climate-related stressors including ocean warming and acidification. These parameters influence the physicochemical dynamics of adsorption–desorption and, consequently, metal bioavailability and organismal stress responses (Adeleye et al., 2024; Khalid et al., 2021). Ignoring these modulators in conventional risk assessments can substantially underestimate ecological and human-health hazards, particularly in estuarine and aquaculture systems where environmental gradients are pronounced.

In aquaculture systems, these modulators are further shaped by pond-specific variability, including fluctuations in organic loading, feeding intensity, water exchange, and sediment disturbance. Such variability alters local pH, redox conditions, and DOM composition, thereby influencing MP–HM adsorption–desorption dynamics and exposure intensity. Understanding these system-specific variations is essential for improving predictive ecotoxicological modeling and risk assessment in aquaculture environments.

Representative abiotic and biotic modulators affecting MP–HM adsorption, bioavailability, and toxicity are summarized in Table 4. Quantitative evidence indicates that variations in these parameters can alter adsorption coefficients (Kd) by ±25–40%, producing corresponding shifts in oxidative-stress intensity and bioaccumulation levels in crustaceans and mollusks.

Table 4. Abiotic and biotic modulators influencing MP–HM interactions and toxicity in aquatic invertebrates.

6.1 Temperature and climate warming

Temperature accelerates both microplastic weathering and organismal metabolic rates. Elevated temperatures increase oxidative aging and surface polarity of MPs, enhancing their affinity for cationic metals (Adeleye et al., 2024). Cd adsorption on aged PS, for instance, rises by ~30% when the temperature increases from 20 °C to 30 °C (Wang et al., 2021). Thermal stress in Litopenaeus vannamei under MP–HM co-exposure causes a 1.6× increase in lipid peroxidation and ROS production compared with 25 °C conditions (Bal et al., 2021).

In pond-based shrimp systems, fluctuating pH and sediment redox conditions may periodically shift MPs from temporary contaminant sinks to active vectors of metal release, increasing chronic exposure potential in benthic organisms.

6.2 Salinity and pH interactions

Salinity and pH jointly regulate ionic competition, electrostatic charge, and desorption equilibria. Higher salinity reduces Cu²⁺ adsorption on PE by ~25% (Khalid et al., 2021), while low-pH conditions (pH 6.0) increase Cd desorption from PS by ~40%, simulating gut environments of crustaceans (Oz, 2019).

In aquaculture ponds and coastal farming systems, salinity and pH fluctuations are often driven by rainfall events, evaporation, feeding inputs, and water exchange practices, creating dynamic conditions that may enhance episodic desorption and localized toxicity. These gradients determine whether MPs act as pollutant sinks or active vectors, complicating predictions of MP–HM behavior.

6.3 Dissolved organic matter and biofilm formation

DOM modifies sorption behavior through complex interactions: humic substances can compete with MPs for free metals or introduce new binding sites. Humic-acid-coated MPs showed a 1.3× higher Cd sorption capacity compared with pristine MPs (Godoy et al., 2019; Cao et al., 2021). Similarly, biofilm colonization increases Kd from 10² to 10⁴ L kg⁻¹ by introducing chelating ligands and polar groups that enhance metal retention (Adeleye et al., 2024).

In aquaculture systems, elevated organic loading from feeds and waste accumulation enhances DOM availability and biofilm formation, further increasing the retention and vector potential of MPs. Neglecting these system-specific conditions may underestimate bioavailability and oxidative stress potential in cultured organisms.

6.4 Combined climate stressors: ocean warming, acidification, and hypoxia

Future climate projections indicate that ocean warming, acidification, and hypoxia will act synergistically with MP–HM co-contamination, amplifying toxicity (Krishna et al., 2025; Jin et al., 2021). Ocean acidification lowers seawater pH, enhancing the desorption of metals from MPs. Simultaneously, hypoxic conditions weaken antioxidant defenses and disrupt energy metabolism in crustaceans, compounding oxidative damage.

In aquaculture systems, these climate-related stressors are further intensified by management practices and environmental variability, particularly in intensive pond systems where oxygen depletion, temperature spikes, and pH fluctuations are common. Failure to incorporate these modulators can lead to inaccurate risk predictions in aquaculture environments. Meta-analyses show that interactions between acidification and heavy metals yield predominantly additive (67%) but also substantial synergistic (25%) effects (Jin et al., 2021). Integrating climate stressors into predictive models is essential for realistic aquaculture risk assessments.

6.5 Towards species sensitivity distribution modeling

The complexity of MP–HM co-toxicity under variable environments necessitates advanced modeling tools for ecological risk prediction. The Species Sensitivity Distribution (SSD) approach provides a probabilistic framework for deriving predicted no-effect concentrations (PNECs) based on interspecies response variability (Ciffroy, 2007). Recent work demonstrates SSD applicability to microplastics, identifying critical thresholds for food dilution (~0.5–35 particles L⁻¹) and tissue translocation (~60–4100 particles L⁻¹) (Mehinto et al., 2022).

For aquaculture systems, incorporating pond variability and climate-driven modifiers into SSD models is essential to improve predictive accuracy and ensure applicability under real production conditions. Conventional SSDs that exclude these factors may underestimate risks associated with MP–HM co-exposure. Future work should integrate environmental variability, aquaculture practices, and mechanistic biomarkers to better capture system-specific responses.

Figure 6 illustrates the key environmental modulators of MP–HM interactions and their mechanistic influence on adsorption, bioavailability, and oxidative stress, highlighting critical hotspots in both natural and aquaculture systems.

While many experimental studies employ microplastic and heavy metal concentrations exceeding environmentally observed levels (e.g., MPs >1 mg L⁻¹; metals >10 µg L⁻¹), these conditions are often necessary to resolve mechanistic pathways such as oxidative stress, enzymatic disruption, and bioaccumulation dynamics. In contrast, environmental concentrations in aquaculture systems are typically lower but may involve chronic exposure and complex mixtures. Distinguishing between mechanistic laboratory conditions and environmentally relevant scenarios is essential for accurate risk assessment and interpretation of MP–HM interactions in real-world aquaculture systems.

Many mechanistic laboratory studies summarized in this review employ MP concentrations exceeding 1 mg L⁻¹ and HM concentrations above 10 µg L⁻¹, which may exceed currently reported environmental levels in most aquaculture systems. However, such concentrations are frequently used to resolve mechanistic pathways involving oxidative stress, enzymatic disruption, and bioaccumulation dynamics under controlled conditions. In contrast, environmental exposures in aquaculture environments are generally lower, more variable, and often chronic, occurring simultaneously with multiple physicochemical stressors.

7 Mitigation strategies and future research

Addressing the synergistic toxicity of microplastics (MPs) and heavy metals (HMs) demands an integrated framework that combines pollution prevention, circular bioeconomy principles, standardized ecotoxicological testing, and scalable bioremediation. In aquaculture systems, mitigation strategies must explicitly target key exposure pathways, including feed contamination, sediment accumulation, water recirculation, and plastic-derived inputs. The following subsections outline targeted actions and research priorities to mitigate MP–HM impacts, with emphasis on sustainable aquaculture applications.

7.1 Source reduction and policy integration

The dual challenge of MP–HM contamination requires coordinated regulatory control. Current water-quality standards often address plastics and metals separately, overlooking mixture effects (Barceló and Picó, 2019).

In aquaculture, source reduction should prioritize minimizing plastic inputs and controlling external contamination pathways, including improved runoff management, filtration wetlands, and stricter feed-quality regulations. Regulatory frameworks should incorporate mixture-based indicators (e.g., Kd, BAF) and explicitly include aquaculture systems in monitoring programs.

7.2 Bioremediation and circular bioeconomy approaches

Biopolymer-based adsorbents offer dual benefits of pollution mitigation and waste valorization. Chitosan derived from crustacean shell waste has demonstrated 70–85% efficiency in removing MPs and metals from aquaculture effluents (Omoregie et al., 2023).

Integration into recirculating aquaculture systems (RAS) as filtration media represents a promising strategy for reducing contaminant loads, while aligning with circular bioeconomy principles. Advanced composites (e.g., chitosan–biochar) may further enhance removal efficiency and scalability.

7.3 Standardization of toxicity testing and regulatory implications

Variability in microplastic–heavy metal (MP–HM) exposure protocols limit cross-study comparability. Establishing standardized test designs, covering pH, salinity, temperature, particle size, and exposure duration, is essential for reliable synthesis (Patrick and Egbuatu, 2024). Harmonized biomarkers, such as SOD/CAT ratios, AChE inhibition, and gonadosomatic index (GSI), should serve as baseline indicators across laboratories. Adopting OECD-style co-exposure guidelines for invertebrate bioassays would strengthen regulatory acceptance and allow derivation of predicted no-effect concentrations (PNECs) specific to MP–HM mixtures.

Current risk assessment frameworks relying on single-contaminant PNECs inadequately capture the complexity of MP–HM interactions. Particle-mediated exposure—through adsorption–desorption equilibria, vectoring of metals, and prolonged retention—can amplify toxicity and bioavailability, particularly in benthic and estuarine systems. Studies in crustaceans, including Litopenaeus vannamei and Scylla spp., demonstrate measurable oxidative, enzymatic, and physiological responses to MP-associated metals, confirming their suitability as sentinel taxa.

Ignoring particle-mediated pathways may yield false safety conclusions. Policy adaptations should incorporate multi-stressor PNECs, particle-inclusive exposure models, and mandatory inclusion of sentinel species in monitoring programs. Aligning these approaches with OECD co-exposure guidelines and EU environmental quality standards enhances ecosystem and aquaculture protection. Integrating particle-mediated exposure into risk assessment frameworks ensures that regulatory strategies reflect real-world contaminant dynamics and effectively safeguard both ecological and human health.

For aquaculture, incorporating particle-mediated exposure pathways into regulatory testing is critical, particularly for benthic species such as shrimp that are highly exposed to sediment-associated contaminants. Ignoring these pathways may underestimate real-world risks.

7.4 Aquaculture-specific mitigation strategies

Effective mitigation of microplastic–heavy metal (MP–HM) co-contamination in aquaculture systems requires integrated and system-specific interventions targeting the major exposure pathways associated with feeds, sediments, water circulation, and plastic-derived infrastructure. Feed contamination control should prioritize the screening of raw materials and processing inputs for microplastics, alongside improved storage and handling practices to minimize secondary contamination. Sediment management strategies, including periodic sediment removal, sediment treatment, and the application of biofloc systems or sediment traps, may reduce the accumulation and remobilization of MP–HM complexes in benthic production environments. In recirculating aquaculture systems (RAS) and pond systems, advanced filtration technologies such as membrane filtration, biochar-based filters, and biopolymer adsorbents can help remove suspended microplastics and associated metals prior to water recirculation. Furthermore, reducing the use of conventional plastic-based infrastructure through the adoption of biodegradable or more durable alternatives may minimize long-term microplastic release into culture systems. Collectively, these interventions directly target major MP–HM entry pathways and are essential for improving aquaculture sustainability, biosecurity, and food safety.

7.5 Molecular and “omics” approaches

Advanced “omics” techniques enable mechanistic mapping of MP–HM synergy. Studies in crustaceans demonstrate activation of oxidative and detoxification pathways under co-exposure (Bhagat et al., 2022; Razali et al., 2024). These approaches support biomarker development for early detection of contamination stress in aquaculture systems.

7.6 Integrative ecosystem and aquaculture management

Research findings on MPs–HM interactions should directly inform fisheries and aquaculture management (Figure 7; Table 5). In recirculating aquaculture systems (RAS) and coastal nurseries, minimizing suspended solids, contaminated feed inputs, and synthetic polymer materials is critical for maintaining organismal health and production efficiency. Eco-engineering interventions, such as constructed wetlands, biochar-integrated filtration systems, and sediment-trapping lagoons, can effectively intercept co-pollutants before they enter aquatic food webs (Wei et al., 2024), as summarized in the integrated mitigation framework (Figure 7) and corresponding practical recommendations (Table 5). Crustaceans, owing to their benthic habitat and high sensitivity to pollutant accumulation, should be incorporated into long-term biomonitoring programs as sentinel taxa to track cumulative contamination stress and evaluate the effectiveness of mitigation strategies.

Table 5. Practical mitigation strategies for managing MP–HM co-contamination in aquaculture systems.

7.7 Strategic research priorities

To refine mechanistic understanding and strengthen management responses, future studies should pursue the targeted research priorities summarized in Table 6.

Table 6. Strategic research priorities for advancing MPs–HMs synergy assessment.

Integrating physicochemical modifiers (e.g., salinity, pH, temperature), trophic dynamics, and cellular stress pathways into a unified MP–HM toxicity model would bridge individual-level responses with ecosystem-scale outcomes. Such synthesis could advance predictive frameworks for ecological risk assessment and aquaculture biosecurity, providing a systems-based foundation for evaluating pollutant interactions in changing environments. Framing future research through this integrative lens will help translate mechanistic insights into actionable management strategies that align with Nature-based Solutions and blue economy goals.

8 Conclusion

Microplastics (MPs) and heavy metals (HMs) constitute an emergent class of coupled contaminants that amplify ecological risk by enhancing metal bioavailability and triggering multi-pathway toxicity. Quantitative evidence across taxa shows that co-exposure can elevate oxidative stress markers by up to 2.4×, suppress antioxidant enzyme activity by 45%, and increase tissue metal burdens by 30–80% relative to single-contaminant exposures. Environmental modulators, including temperature, salinity, pH, and dissolved organic matter, govern adsorption–desorption kinetics and shape organismal responses, underscoring the dynamic complexity of MP–HM systems.

From an aquaculture perspective, these interactions represent a critical production risk, as continuous exposure through feeds, sediments, and water systems can impair growth performance, compromise health status, and reduce overall productivity of cultured species. The accumulation of MP–HM complexes in edible tissues further raises concerns for food safety, export quality, and consumer acceptance, while increasing pressure on aquaculture biosecurity frameworks to address not only pathogens but also emerging contaminant stressors.

Current risk paradigms remain incomplete, as they fail to account for particle-mediated interactions, mixture toxicity, and cross-scale ecological effects. To address these gaps, research must advance standardized experimental designs, multi-omics mechanistic models, and circular bioeconomy-inspired bioremediation strategies. Crucially, future frameworks should integrate laboratory mechanistic insights with aquaculture system dynamics and socioeconomic considerations to enable robust, evidence-based management of MP–HM mixtures.

Scientific and policy action must converge, with regulatory guidelines adopting particle-inclusive, multi-stressor assessment models and incorporating aquaculture-relevant monitoring approaches, including sentinel species and system-level indicators. Strengthening management strategies, such as feed quality control, sediment management, water filtration, and plastic reduction, will be essential to mitigate co-contaminant exposure and enhance system resilience.

Integrating mechanistic insights into aquaculture management frameworks is essential to safeguard productivity, ecosystem health, and food security in multi-pollutant environments.

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Footnotes

Edited by: Gulnihal Ozbay, Delaware State University, United States

Reviewed by: Caio Cesar-Ribeiro, Rio de Janeiro State University, Brazil

Bireshwar Bera, St Joseph’s College, Darjeeling, India