Table 3.

Studies assessing the possible synergetic/antagonistic effect of different types of emerging pollutants combined with MPs.

MP Type	MP Size	Chemical Sorbate	Exposure Concentrations	Exposure Time	Organism	Toxicological Assessment	Highlight Results	Ref.
Pesticides
HD-PE with irregular shape	mean size: 7.73 µm	Chlorpyrifos (CPF)	CPF alone [CPF] = 0, 0.1, 1, 10, 100 µg/L MPs alone [MPs]= 0, 0.1, 1, 10, 100 µg/L MPs + CPF 100 µg/L CPF-100 µg/L MPs co-exposure and incubation treatments (incubated for 2 h)	48 h	Marine copepod (Acartia tonsa)	The survival rates Fecundity, feeding and egg viability	CPF showed higher toxicity when combined with MP than alone for all tested biological responses Higher toxicity was observed with the co-exposure treatment	[137]
PE	mean size: ranging from 2–6 µm maximum particle size: 22 µm	Chlorpyrifos	CPF alone [CPF] = 0 to 4 mg/L MPs alone [MPs]= 0.5, 1, 10 and 25 mg/L MPs + CPF (co-exposure) 0–3 mg/L CPF-1 mg/L MPs co-exposure and incubation treatments (incubated for 2 h)	72 h	Microalgae (Isochrysis galbana clone T-ISO)	Microalgae daily growth rate Inhibition of microalgae growth	MPs reduced the toxicity of CPF MPs were not small enough to penetrate the microalgal cell and cause any damage	[138]
PS	0.1 mm, 0.55 mm 5 mm	Triphenyltin chloride (TPTCl)	TPTCl alone [TPTCl] = 30 μg/L MPs alone [MPs]= 0.05, 0.5, 5 mg/L MPs + TPTCl Combination of the individual concentrations tested for both pollutants	96 h	Microalgae (Chlorella pyrenoidosa)	Morphology and structural damage Grown inhibition	PS particles toxicity to the green algae was size-dependent Toxicity of the mixture was size-dependent: MPs with smaller particle size increased the toxicity of TPTCl	[139]
Pristine PE	10–27 µm	Bifenthrin	Bifenthrin alone [Bifenthrin] = 0.1 to 3.2 µg/L MPs alone [MPs]= 5 mg/L MPs+ Bifentrin (co-exposure) 0.1–3.2 µg/L CPF-5 mg/L MPs	48 h	Freshwater larvae organism (Chironomus tepperi)	Immobilization rates	The addition of MPs to synthetic water reduced the toxicity of bifenthrin The addition of MPs to river water did not mitigate bifenthrin toxicity due to the greater interaction of bifenthrin with DOM	[140]
PET/PA fibers	length: 10 µm width: 2 µm	Three different glyphosate chemical formulations	Glyphosate alone [Glyphosate] = 2.5 mg/L PE alone [MPs]= 0.01 mg/mL Fibers alone [MPs]= 0.045–0.136 µg/L MPs + glyphosate Single treatments were combined	1 week	Daphnia magna	Mortality rate	The toxicity of the mixture was more influenced by the type and size of the MPs than their abundance Toxicity of glyphosate was enhanced by the presence of MPs	[141]
PE	1–10 µm
PS	1 µm	Dimetholate Deltamethrin	Pesticides alone [Dimetholate] = 0.156,0.313, 0.625, 1.25 and 5 mg/L [Deltamethrin]: 0.016, 0.08, 0.4, 2,5,10 µg/L MPs alone [MPs]= 300,000 particles/mL MPs + glyphosate Single treatments were combined	72 h	Daphnia magna	Mortality rate Impaired mobility	The concentrations at which detrimental effects occurred were not influenced by the presence of MPs	[142]
Pharmaceuticals
PE	1–5 µm	Cefalexin	Cefalexin alone [Cefalexin]= 1.3, 2.5, 5 and 10 mg/L MPs alone [MPs]= 0.184 mg/L MPs + Cefalexin Combination of individual exposure concentrations (Exposure experiments performed at 20 and 25 °C)	96 h	Common goby juveniles (Pomatoschistus microps)	Mortality rate Post-predatory performance AChE activity LPO levels	The temperature rise increased the toxicity for both pollutants alone and in MPs mix No significant differences between cefalexin treatment alone and in MPs mix	[143]
PE	10–90 µm	Triclosan	Triclosan alone [Triclosan] = 0–300 µg/L MPs alone [MPs]= 0–25,000 MPs/mL MPs+ Cefalexin Combination of individual exposure concentrations of Triclosan and 500 MPs/mL	48 h	Marine copepod (Acartia tonsa)	Mortality of marine copepods	The LC50-values of individual pollutants and mixture were significantly different (synergistic effect)	[144]
PS	1 µm 10 µm	Roxithromycin (ROX)	ROX alone [ROX] = 0.1, 1, 5, 10, 50, 100, and 150 mg/L MPs alone [MPs] = 0.005, 0.05, 0.1, 0.2, 2, 15, 20, 25, 30, 35, and 40 mg/L MPs + ROX Mix 1: 0.1 mg/L 1-μm PS + 0.01 mg/L ROX Mix 2: 0.1 mg/L 10-μm PS + 0.01 mg/L ROX.	48 h	Daphnia magna	Mortality rate MDA levels Activities of: SOD, CAT, GST and GPx	Small-size PS was more toxic to D. magna than the large-size PS Co-exposure to 1-μm PS and ROX led to the strongest biological responses in D. magna	[6]
PS	0.1 µm	Roxithromycin (ROX)	Roxithromycin alone [ROX] = 50 µg/L MPs + ROX Mix 1: 1 µg/L MPs+50 µg/L ROX Mix 2: 10 µg/L MPs + 50 µg/L ROX. Mix 3: 100 µg/L MPs + 50 µg/L ROX.	14 days	Water fish red tilapia (Oreochromis niloticus)	Histopathological analysis (liver, gills, guts and brain) AChE, EROD, BFCOD, SOD and MDA activities	The neurotoxicity caused by ROX was alleviated due to the presence of MPs The presence of MPs may affect the metabolism of ROX in tilapia Oxidative damage in situations of co-exposure to MPs and ROX was mitigated in fish livers This study suggests that the effects of MPs combined with other pollutants cannot be ignored	[109]
unknown	1–5 µm	Florfenicol	Florfenicol alone [Florfenicol] = 1.8 and 7.1 mg/L MPs alone [MPs] = 0.2 and 0.7 mg/L MPs + Florfenicol Combination of individual exposure concentrations of both pollutants	96 h	Marine bivalve (Corbicula fluminea)	Feeding inhibition Histopathological alterations (digestive system and gills) Enzymatic activities of ChE, IDH, ODH, GST, GR, GPx and CATLPO levels	Enhanced toxicity of florfenicol in combination with MPs Differences in the toxicological effects induced by mixtures containing the lowest or the highest concentrations of both substances	[48]
PVC	< 10 µm	Venlafaxine O-desmethylvenlafaxine	Venlafaxine and derivate alone [Venlafaxine] = 0–500 µg/L O-desmethylvenlafaxine alone [O-desmethylvenlafaxine] = 0–500 µg/L MPs + chemicals Combination of individual exposure concentrations of both pollutants and 50 mg/L of MPs	4 days	Loach (Misgurnus anguillicaudatus)	SOD and MDA activities	In liver subcellular structure, MPs may help to transport pollutants into subtle areas and postpone the contaminants metabolism Mixtures enhance the oxidative stress in loach Enantioselective effects were observed in high dose exposure groups MPs combined with chemicals might cause more adverse effects to organisms compared with only chemicals themselves.	[110]
unknown	1–5 µm	Procainamide Doxycycline	Procainamide alone [Procainamide] = 4, 8, 16, 32, 64, 128 and 256 mg/l Doxycycline alone [Doxicycline] = 4, 8, 16, 32, 64 and 128 mg/l MPs alone [MPs] = 0.75, 1.5, 3, 6, 12, 24 and 48 mg/l MPs + chemicals Combination of individual exposure concentrations of both chemicals and 1.5 mg/L of MPs	96 h	Marine microalga (Tetraselmis chuii)	Inhibition of average specific grow per day Chlorophyll concentration decrease	Significant toxicity enhancement of each pharmaceutical in mixture with MPs was found for procainamide (chlorophyll), and doxycycline (both parameters)	[145]
PS	30 µm 500 nm	Sertraline (Ser)	Ser. alone [Ser]=100ng/L MPs alone [MPs]= 0.29 mg/L MPs+ Ser. Combination of individual exposure concentrations of both pollutants	14 days	Bivalve mollusk (Tegillarca granosa)	ROS generation Apoptosis status MDA, ACh and GABA levels Plama cortisol content ATP content and PK activity Transcriptomic analysis	Evident synergistic immuno-toxic effect was observed between Ser. and NPs NPs could exert more toxic effects than larger MPs	[146]
Others (UV Filters, Surfactants, Plasticizers, …)
PE irregular shape	3.4 µm 9.9 µm	4-Nonylphenol (4-NP) 4- MBC	4-NP alone [4-NP] = 4, 25 and 70 µg/l 4-Nonyphenol alone [4-MBC] = 70, 150 and 350 µg/l MPs + chemicals Combination of individual exposure concentrations of both chemicals with 1 and 10 mg/L of MPs	48 h	Marine zooplanktons	Effective concentration reducing the larval size Mortality rate	The presence of MPs did not increase the toxicity of both chemicals tested	[111]
PE irregular shape	3.4 µm 9.9 µm	4-Nonylphenol (4-NP)	4-NP alone [4-NP] = 20 and 60 µg/l MPs+ 4-NP Combination of individual exposure concentrations of 4-NP with 1 and 10 mg/L of MPs	48 h	Planktonic sea-urchin larvae	Filtering rate Effective concentration reducing larval growth	The ingestion of MPs did not increase the toxicity of 4-NP	[147]
PE	50 nm	BPA	BPA alone [BPA] = 0.78 and 1 µg/l NPs alone [NPs]= 1 mg/l NPs+ BPA 1 µg/L BPA + 1 mg/L NPs	3 days	Zebrafish (Danio rerio)	Gene expression analysis AChE activity Dopamine level Protein content	The co-exposure of NPs and BPA led to increased neurotoxic effects in both CNS and dopaminergic system The reduction of the AChE activity in co-exposure treatment was alleviated in comparison to single experiments	[113]
PS	0.1 mm 0.55 mm 5 mm	Dibutyl phthalate (DBP)	DBP alone [DBP] = 0.25, 0.5, 1, 2, 4, 8 and 16 mg/l MPs alone [MPs]= 0.5, 1, 2, 4, 8, 16, 32 and 64 mg/l MPs + BPA Combination of individual exposure concentrations of both pollutants (MPs size: 0.1 mm)	96 h	Microalgae (Chlorella pyrenoidosa)	Grow inhibition rate Changes in morphology and structural damage Chlorophyll levels	The interaction between MPs and DBP was antagonistic at low concentrations of DBP Synergistic effect was found at relatively high concentrations of DBP when [MPs]< 10mg/L Antagonistic effect was found across all concentrations of MPs above 10 mg/L	[148]
Rigid PVC	4–141 µm	Diisononylphthalate (DiNP)	Rigid PVC (PVC) 4320 MP particles/100mL Flexible PVC with DiNP 4320 particles/100 mL ([DiNP] in PVC was 30% of plastic weight)	25–31 days	Daphnia magna	Mortality rate Morphology changes and body length Reproductive output	MPs containing DiNP significantly affect the number of offspring as well as the growth of D. magna The relevance of long-term chronic exposure experiments, as effects did emerge relatively late in the experiment	[149]
Flexible PVC	12–276 µm

* Shadowed cells represent environmental relevant concentrations.