. 2022 Jun 23;19(13):7717. doi: 10.3390/ijerph19137717

Table 2.

Toxic effects of selected NSAIDs on various non-target aquatic organisms, based on [2,35,72].

Compound	Tested Organisms (Taxonomic Group)		Tested Concentration	Exposure Time	Effect (Acute and Chronic)	Reference
Plants
Ibuprofen	Desmodeus subspicatus	Chlorophyta	315.0 (mg/L)		Growth inhibition (EC₅₀).	[73]
Ibuprofen	Lemna minor	Tracheophyta	22.0 (mg/L)	7 d	Growth inhibition (EC₅₀).	[73]
Animals
Ibuprofen	Cyprinus carpio	Pisces	7.1 (mg/L)	12, 24, 48, 72, 96 h	Genotoxic effects: DNA damage (the intensity of the tail DNA relative to the head).	[74]
	Cyprinus carpio		1.5, 3.0, 4.5, 6.0, 7.5, 9.0, 11.5 (mg/L)	96 h	Teratogenic effect: higher mortality of oocytes and delay in hatching. Delay in embryo development and embryo malformations.	[75]
	Danio rerio		0.04, 0.2, 1.0, 5.0, 25.0 (mg/L)	56 h	Reproduction disruption: disruption of cardiac physiology of embryos.	[76]
	Danio rerio		0.000092 (mg/L)		Genotoxic effects: DNA fragmentation, apoptosis and genomic alterations.	[77]
	Danio rerio		10.0, 100.0, 1000.0 (mg/L)	14 d	Genotoxic effects: disruption of gonadotropin production. Increase in the transcription level of genes involved in the acceleration of gametogenesis, maturation of oocytes in females and spermatogenesis in males.	[78]
	Oryzias latipes		0.0001 (mg/L)	21 d	Genotoxic effects: influence of sex steroid hormones. Changes in the production of estradiol (E2). Endocrine-disrupting effect: significant increase in vitellogenin (VTG).	[79]
	Oryzias latipes		0.01, 0.1, 1.0, 10.0, 100.0, 1000.0 (mg/L)	132 d	Genotoxic effects: disruption of reproduction processes and early life stages. Reproduction disruption: delay in spawning.	[79]
	Crassostrea gigas	Molluscs	1.0, 100.0 (mg/L)	7 d	Gene expression disorder: differences in gene transcription in gill tissue. Significant upregulation of CYTP450 genes.	[80]
	Dreissena polymorpha		0.2, 1.0, 3.0 (mM)	1 h	Acute cytogenotoxic effect: irreversible DNA damage and decrease in LMS.	[81]
	Dreissena polymorpha		1.0, 9.0, 35.0 (nM)	96 h	Oxidative stress: increase in activity levels of SOD, CAT, GPx and GST.	[82]
	Ruditapes philippinarum		0.1, 5.0, 10.0, 50.0 (mg/L)	35 d	Acute cytogenotoxic effect: decrease in LMS in haemolymph.	[83]
	Ruditapes philippinarum		0.1, 5.0, 10.0, 50.0 (mg/L)	14 d	Oxidative stress: increase in GPx activity and LPO.	[84]
	Ampelisca brevicornis	Crustaceans	0.05, 0.5, 5.0, 50.0, 500.0 (ng/g)	10 d	Oxidative stress: significant increase in DBF, GST and GPX activity.	[85]
	Daphnia magna		2.9 (mg/L)	48, 96 h	Genotoxicity effect: DNA damage.	[86]
	Daphnia magna		20.0, 40.0, 80.0 (mg/L)	24 h	Endocrine disruption: deregulation of eicosanoid metabolism, the endocrine system and oogenesis.	[87]
	Daphnia magna		20.0, 40.0, 80.0 (mg/L)		Decrease in reproduction or complete reproduction inhibition.	[88]
	Daphnia magna		0.0005, 0.005, 0.05 (mg/L)	21 d, 6 h	Oxidative stress: the induction of antioxidant enzymes (GST, SOD and CAT). Reproduction disruption: significant decrease in the total number of broods per female, body length and intrinsic growth rate.	[89]
	Hediste diversicolor	Polychaeta	5.0, 500.0 (ng/g)		Genotoxic effect: DNA damage.	[90]
Plants
Diclofenac	Desmodeus subspicatus	Chlorophyta	72.0 (mg/L)		Growth inhibition (EC₅₀).	[73]
	Dunaliella tertiolecta		185.7 (mg/L)	96 h	Growth inhibition (EC₅₀).	[55]
	Pseudokirchneriella subcapitata		20.0 (mg/L)	96 h	Growth retardation.	[65]
	Scenedesmus vacuolatus		23.0 (mg/L)		Inhibition of reproduction.	[91]
	Lemna minor	Tracheophyta	7.5 (mg/L)	7 d	Growth inhibition (EC₅₀).	[73]
	Polystichum setiferum	Tracheophyta	0.0003 (mg/L)	48 h	Hormetic effects in mitochondrial activity in spores.	[92]
Animals
Diclofenac	Cirrhinus mrigala	Pisces	0.001 (mg/L)	96 h	Oxidative stress: induction of enzymatic activity.	[93]
	Cyprinus carpio		0.001 (mg/L)	96 h	Alterations in hematological and biochemical activities.	[94]
	Cyprinus carpio		17.6 (mg/L)	12, 24, 48, 72, 96 h	Genotoxic effects: DNA damage (the intensity of the tail DNA relative to the head).	[74]
	Cyprinus carpio		1.25, 2.5 and 5.0 (mg/L)	21 d	Deformations: histopathological changes in gills, liver and kidney. Lesions included necrosis of epithelial cells.	[95]
	Danio rerio embryos		12.5 (mg/L)	48 h	Oxidative stress: deregulation of kinase activities. Metabolic disorders: deregulation of gluconeogenesis and lipid metabolism.	[96]
	Hoplias malabaricus		0.2, 2.0, 20.0 (mg/kg)		Metabolic disorders: interferences with metabolic pathways. Oxidative stress: increase in the activity of SOD, GPx and GSH.	[97]
	Oncorhynchus mykiss		0.005 (mg/L)	28 d	Deformations: renal lesions and alterations in the gills.	[98]
	Oryzias latipes		7.1, 37.0,78.0 (mg/L)	14 d	Morphological abnormalities.	[99]
	Rhamdia quelen		25.0 (mg/L)		Behavioral changes: respiratory disorders and loss of balance.	[100]
	Rhamdia quelen		0.2, 2.0, 20.0 (mg/L)	21 d	Oxidative stress: significant reduction in SOD activity, increase in activity of GSH and GST. Disruption of antioxidant defense systems in the liver.	[101]
	Brachionus calyciflorus	Rotatoria	25.0 (mg/L)	48 h	Reproduction retardation.	[65]
	Dreissena polymorpha	Molluscs	0.2, 0.5, 0.8 (mM)	1 h	Acute cytogenotoxic effect: significant DNA damage.	[81]
	Dreissena polymorpha		1000.0 (mg/L)	96 h	Oxidative stress: increase in GST activity, LPO expression and methallothioneins (MTs) alterations.	[102]
	Dreissena polymorpha		0.001 (mg/L)	96 h	Oxidative stress: high lipid peroxidation levels. Significant reduction in haemocyte viability.	[81,103]
	Perna perna		20.0, 200.0, 2000.0 (ng/L)	48, 96 h	Genotoxic effects: DNA damage. Significant decrease in LMS. Gene expression upregulation. COX inhibition in gill tissue.	[104]
	Atyaephyra desmarestii	Crustaceans	13.3, 70.6 (mg/L)	96 h	Metabolism disorder: decrease in respiration under reduced oxygen content.	[105]
	Carcinus maenas		0.00001, 0.0001 (mg/L)		Osmoregulation disturbances. Effect on haemolymph osmolality and osmolality capacity.	[106]
	Ceriodaphnia dubia		2.0 (mg/L)	7 d	Reproduction inhibition.	[65]
	Daphnia magna		32.0 (mg/L)	21 d	Oxidative stress.	[103]
	Daphnia magna		9.7 (mg/L)	48, 96 h	Genotoxicity effect: DNA damage.	[86]
	Arenicola marina	Polychaetes	From 0.6 to 842.0 (ng/L)		Reproduction disruption: decrease in swimming speed of sperm.	[107]
	Hediste diversicolor	Polychaetes	0.5, 1.0, 2.0 (mg/L)	28 d	Gene expression upregulation: significant effect on the activity of GST enzymes.	[108]
Plants
Naproxen	Cymbella sp.	Ochrophyta	102.8 (mg/L)	72 h	Growth inhibition (EC₅₀).	[109]
	Desmodeus subspicatus	Chlorophyta	>320.0 (mg/L)		Growth inhibition (EC₅₀).	[73]
	Raphidocelis subcapitata		0.0318 (mg/L)	72 h	Growth inhibition (EC₅₀).	[110]
	Scenedesmus quadricauda		101.5 (mg/L)	72 h	Growth inhibition (EC₅₀).	[109]
	Scenedesmus subspicatus		625.5 (mg/L)	48 h	Growth inhibition (EC₅₀).	[70]
	Lemna minor	Tracheophyta	24.2 (mg/L)	7 d	Growth inhibition (EC₅₀).	[70]
Animals
Naproxen	Danio rerio	Pisces	1.0, 100.0 (mg/L)	14 d	Gene expression: upregulation of gene expression. Metabolism disorders: upregulation of the activity of GST by affecting glutathione S-transferase P2 (GST P2) mRNA in the intestine.	[111]
	Oryzias latipes	Pisces	0.005, 0.05, 0.5, 5.0, 50.0 (mg/L)		Endocrine disruption: significant increase in the expression of VTG and E2 receptors genes. Reduction in conditions: decrease in the survival of juvenile animals.	[112]
	Daphnia magna	Crustaceans	46.7 (mg/L)	48 h	Immobilization (EC₅₀).	[112]
	Daphnia magna		2.9 (mg/L)	48, 96 h	Genotoxicity effect: DNA damage. Oxidative stress: increase in enzyme activity (SOD, CAT and GPx).	[86]
	Hyalella azteca		76.6, 339.2 (mg/kg)	48 h	Genotoxicity effect: DNA damage. Oxidative stress: increase in SOD and CAT activity and decrease in GPX activity.	[113]
	Moina macrocopa		74.1 (mg/L)	48 h	Immobilization (EC₅₀).	[112]
	Elliptio complanata	Molluscus	0.6 to 23.0 (mg/L)	24 h	Immunotoxic effects. Phagocytic activity, intracellular esterase activity, cell adherence and lipid peroxidation.	[114]
	Hydra magnipapillata	Cnidaria	LC₅₀ 52.0, 45.0, 43.0 (mg/L)	24, 48, 72 h	Morphological changes: stimulation of the contraction of the body column and tentacles. Genotoxicity effect: DNA damage or instability.	[115]
Plants
Ketoprofen	Lemna minor	Tracheophyta	0.2, 1.2, 6.0, 30.0 (mg/L)	4 d	Oxidative stress: alterations in enzyme activities (CAT, GSTs and CA).	[116]
Animals
Ketoprofen	Ceriodaphnia dubia	Crustaceans	From 1.0 to 1000.0 (mg/L)		Chronic toxicity. Effects on reproduction at the highest concentration.	[117]
	Daphnia magna	Crustaceans	0.2, 1.2, 6.0, 30.0 (mg/L)	4 d	Oxidative stress: alterations in enzyme activities (CAT, GSTs and CA).	[116]
	Mytilus galloprovincialis	Molluscus	0.0025 (mg/L)	14, 30, 60 d	Alterations in immunological parameters, genotoxic effects and modulation of lipid metabolism. Reduction in lysosomal membrane stability.	[118]
	Planorbarius corneus	Molluscus	100.0 (mg/g)	48 h	Antipyretic effect. Inhibition of symptoms of behavioral fever and influenced thermal preference.	[119]