Contaminants of emerging concern and aquatic organisms: the need to consider hormetic responses in effect evaluations

Abstract

Contaminants of emerging concern are widespread in the world’s waters, raising concerns regarding their effects on living organisms. To evaluate the effects of and predict risks associated with such chemicals, dose-response studies are needed, while the nature of the dose-response relationship is critical for the outcomes of such evaluations. Here, we summarize the literature reporting hormetic responses of aquatic organisms to contaminants of emerging concern. Hormesis is a biphasic dose response encompassing stimulatory responses to low doses and inhibitory responses to high doses. We demonstrate that it occurs widely in numerous aquatic organisms exposed to a wide array of contaminants, including nano/microplastics, suggesting potential effects at doses/concentrations that are considerably lower than the traditional toxicological threshold, which cannot be identified or predicted unless hormesis is considered in the study design. To tackle the effects and associated risks of nano/microplastics and other contaminants on aquatic organisms, hormesis should therefore be taken into account early in the design of studies as well as in relevant risk assessments.

Keywords

Dose-response relationship / ecological effects / ecotoxicological testing / environmental pollution / environmental management / hormesis / regulatory risk assessment / water contaminants

References

[1] Jéquier E.Water as an essential nutrient: the physiological basis of hydration.Eur J Clin Nutr2010;64:115-23

[2] Westall F.The Importance of water for life.Space Sci Rev2018;214 PMCID:PMC6900748

[3] Frappart F.Water and life.Nature Geosci2013;6:17-17

[4] UN Environment. Global chemicals outlook II from legacies to innovative solutions: implementing the 2030 agenda for sustainable development. United Nations Environment Programme; 2019.

[5] Kümmerer K,Olsson O.A path to clean water.Science2018;361:222-4

[6] Yang H,Gundry SW.Water accessibility: boost water safety in rural China.Nature2012;484:318

[7] Calabrese EJ.Ethical failings: the problematic history of cancer risk assessment.Environ Res2021;193:110582

[8] Calabrese EJ.LNT and cancer risk assessment: Its flawed foundations part 2: how unsound LNT science became accepted.Environ Res2021;197:111041

[9] Calabrese EJ.The linear No-Threshold (LNT) dose response model: a comprehensive assessment of its historical and scientific foundations.Chem Biol Interact2019;301:6-25

[10] Calabrese EJ,Kozumbo WJ.Thresholds for carcinogens.Chem Biol Interact2021;341:109464

[11] Tsatsakis A.Toxicological risk assessment and multi-system health impacts from exposure. Elsevier; 2021.

[12] Tsatsakis AM,Kovatsi L.The dose response principle from philosophy to modern toxicology: the impact of ancient philosophy and medicine in modern toxicology science.Toxicol Rep2018;5:1107-13 PMCID:PMC6226566

[13] Agathokleous E.Hormesis: the dose response for the 21st century: the future has arrived.Toxicology2019;425:152249

[14] Leak RK,Kozumbo WJ.Enhancing and extending biological performance and resilience.Dose Response2018;16:1559325818784501 PMCID:PMC6096685

[15] Erofeeva EA.Environmental hormesis of non-specific and specific adaptive mechanisms in plants.Sci Total Environ2022;804:150059

[16] Erofeeva EA.Plant hormesis and Shelford’s tolerance law curve.J For Res2021;32:1789-802

[17] Carvalho MEA,Azevedo RA.Hormesis in plants under Cd exposure: from toxic to beneficial element?.J Hazard Mater2020;384:121434

[18] Shahid M,Rinklebe J,Dumat C.Trace elements-induced phytohormesis: a critical review and mechanistic interpretation.Crit Rev Environ Sci Technol2020;50:1984-2015

[19] Agathokleous E.A global environmental health perspective and optimisation of stress.Sci Total Environ2020;704:135263

[20] Agathokleous E.Hormesis can enhance agricultural sustainability in a changing world.Glob Food Secur2019;20:150-5

[21] Costantini D,Monaghan P.Ecological processes in a hormetic framework.Ecol Lett2010;13:1435-47

[22] Costantini D,Metcalfe NB.Prior hormetic priming is costly under environmental mismatch.Biol Lett2014;10:20131010 PMCID:PMC3949371

[23] Costantini D.The linear no-threshold model is less realistic than threshold or hormesis-based models: an evolutionary perspective.Chem Biol Interact2019;301:26-33

[24] Costantini D.Hormesis promotes evolutionary change.Dose Response2019;17:1559325819843376 PMCID:PMC6484245

[25] Calabrese EJ.The hormetic dose-response mechanism: Nrf2 activation.Pharmacol Res2021;167:105526

[26] Kozumbo WJ.Two decades (1998-2018) of research Progress on Hormesis: advancing biological understanding and enabling novel applications.J Cell Commun Signal2019;13:273-5 PMCID:PMC6732134

[27] Calabrese EJ.Hormesis commonly observed in the assessment of aneuploidy in yeast.Environ Pollut2017;225:713-28

[28] Cedergreen N,Kudsk P,Duke SO.The occurrence of hormesis in plants and algae.Dose Response2006;5:150-62 PMCID:PMC2477694

[29] Moore MN,Pascoe C,Viarengo A.Anti-oxidative hormetic effects of cellular autophagy induced by nutrient deprivation in a molluscan animal model.Mar Environ Res2020;156:104903

[30] Laughlin RB Jr,Guard HE.Hormesis: a response to low environmental concentrations of petroleum hydrocarbons.Science1981;211:705-7

[31] Stebbing ARD.The effects of low metal levels on a clonal hydroid.J Mar Biol Ass1976;56:977-94

[32] Stebbing A.Hormesis—stimulation of colony growth in Campanularia flexuosa (hydrozoa) by copper, cadmium and other toxicants.Aqua Toxicol1981;1:227-38

[33] Stebbing A.Hormesis — the stimulation of growth by low levels of inhibitors.Sci Total Environ1982;22:213-34

[34] Agathokleous E,Iavicoli I.The two faces of nanomaterials: a quantification of hormesis in algae and plants.Environ Int2019;131:105044

[35] Agathokleous E,Barceló D.Micro/nanoplastics effects on organisms: a review focusing on 'dose'.J Hazard Mater2021;417:126084

[36] Sun T,Li F,Wu H.Evidence-based meta-analysis of the genotoxicity induced by microplastics in aquatic organisms at environmentally relevant concentrations.Sci Total Environ2021;783:147076

[37] Sun T,Li F,Wu H.Effect of microplastics on aquatic biota: a hormetic perspective.Environ Pollut2021;285:117206

[38] Li J,Min Z,Han J.Physiological, biochemical and transcription effects of roxithromycin before and after phototransformation in Chlorella pyrenoidosa.Aquat Toxicol2021;238:105911

[39] Mao Y,Ma Z.Azithromycin induces dual effects on microalgae: Roles of photosynthetic damage and oxidative stress.Ecotoxicol Environ Saf2021;222:112496

[40] Pikula K,Vakhniuk I.Aquatic toxicity of particulate matter emitted by five electroplating processes in two marine microalgae species.Toxicol Rep2021;8:880-7 PMCID:PMC8085665

[41] Cantalupi A,Pretali L.Glucocorticoids in freshwaters: degradation by solar light and environmental toxicity of the photoproducts.Int J Environ Res Public Health2020;17:8717 PMCID:PMC7727706

[42] Zhang M,Xue Q,Xu Y.Effects of erythromycin and sulfamethoxazole on Microcystis aeruginosa: Cytotoxic endpoints, production and release of microcystin-LR.J Hazard Mater2020;399:123021

[43] Qu H,Barrett H.How microplastics affect chiral illicit drug methamphetamine in aquatic food chain? From green alga (Chlorella pyrenoidosa) to freshwater snail (Cipangopaludian cathayensis).Environ Int2020;136:105480

[44] Song C,Wang C,Kitamura Y.Different interaction performance between microplastics and microalgae: the bio-elimination potential of Chlorella sp. L38 and Phaeodactylum tricornutum MASCC-0025.Sci Total Environ2020;723:138146

[45] Guo J,Peng J.Transcriptomic analysis of Raphidocelis subcapitata exposed to erythromycin: the role of DNA replication in hormesis and growth inhibition.J Hazard Mater2021;402:123512

[46] Cai H,Ning XA,Li Y.Algal toxicity induced by effluents from textile-dyeing wastewater treatment plants.J Environ Sci (China)2020;91:199-208

[47] Chae Y,An YJ.Effects of micro-sized polyethylene spheres on the marine microalga Dunaliella salina: focusing on the algal cell to plastic particle size ratio.Aquat Toxicol2019;216:105296

[48] Chamsi O,Faucon B.Effects of herbicide mixtures on freshwater microalgae with the potential effect of a safener.Ann Limnol - Int J Lim2019;55:3

[49] Zhang Y,Zhang J,Qin M.A trigger mechanism of herbicides to phytoplankton blooms: from the standpoint of hormesis involving cytochrome b₅₅₉, reactive oxygen species and nitric oxide.Water Res2020;173:115584

[50] Guo X,Zhong H.Potential of Myriophyllum aquaticum for phytoremediation of water contaminated with tetracycline antibiotics and copper.J Environ Manage2020;270:110867

[51] Guo X,Zhong H,Zhang C.Response of antibiotic and heavy metal resistance genes to tetracyclines and copper in substrate-free hydroponic microcosms with Myriophyllum aquaticum.J Hazard Mater2021;413:125444

[52] González-Doncel M,Pablos MV,López Arévalo M.The role of PFOS on triclosan toxicity to two model freshwater organisms.Environ Pollut2020;263:114604

[53] Li Y,Li M.Effects of nanoplastics on antioxidant and immune enzyme activities and related gene expression in juvenile Macrobrachium nipponense.J Hazard Mater2020;398:122990

[54] Liu Y,Tang S.Single and mixture toxicities of BDE-47, 6-OH-BDE-47 and 6-MeO-BDE-47 on the feeding activity of Daphnia magna: From behavior assessment to neurotoxicity.Chemosphere2018;195:542-50

[55] Cesar-Ribeiro C.Chemical contents of disposed light sticks affect the physiology of rocky crab Pachygrapsus transversus and gray shrimps Litopennaeus vanammei.Bull Environ Contam Toxicol2021;107:370-7

[56] Bordin ER,Panicio PP.Transgenerational effects of environmentally relevant concentrations of atrazine and glyphosate herbicides, isolated and in mixture, to freshwater microcrustacean Daphnia magna.Res Sq2021;

[57] Wang P,Zhang B.Employing multi-omics to elucidate the hormetic response against oxidative stress exerted by nC₆₀ on Daphnia pulex.Environ Pollut2019;251:22-9

[58] Xu K,Juneau P.Toxic and protective mechanisms of cyanobacterium Synechocystis sp. in response to titanium dioxide nanoparticles.Environ Pollut2021;274:116508

[59] Wu S,Li X.Mutual impacts and interactions of antibiotic resistance genes, microcystin synthetase genes, graphene oxide, and Microcystis aeruginosa in synthetic wastewater.Environ Sci Pollut Res Int2021;

[60] Wan Q,Chen Y.Comparative growth and cellular responses of toxigenic Microcystis exposed to different types of microplastics at various doses.Environ Pollut2021;290:117950

[61] Zuo S,Jiang X.Magnetic Fe₃O₄ nanoparticles enhance cyanobactericidal effect of allelopathic p-hydroxybenzoic acid on Microcystis aeruginosa by enhancing hydroxyl radical production.Sci Total Environ2021;770:145201

[62] Biswas S.Adaptive mechanisms induced by sparingly soluble mercury sulfide (HgS) in zebrafish: behavioural and proteomics analysis.Chemosphere2021;270:129438

[63] Constantine LA,Schneider SZ.Ibuprofen: fish short-term reproduction assay with Zebrafish (Danio rerio) based on an extended OECD 229 protocol.Environ Toxicol Chem2020;39:1534-45

[64] Ding J,Razanajatovo RM,Zhu W.Accumulation, tissue distribution, and biochemical effects of polystyrene microplastics in the freshwater fish red tilapia (Oreochromis niloticus).Environ Pollut2018;238:1-9

[65] Ding Y,Chen J,Wu Y.Toxic effects of ZnSe/ZnS quantum dots on the reproduction and genotoxiticy of rare minnow (Gobiocypris rarus).Comp Biochem Physiol C Toxicol Pharmacol2021;247:109065

[66] Fan X,Jia J,Wei X.Discrepant dose responses of bisphenol A on oxidative stress and DNA methylation in grass carp ovary cells.Chemosphere2020;248:126110

[67] Han Y,Yao S,Hu C.In vivo and in silico evaluations of survival and cardiac developmental toxicity of quinolone antibiotics in zebrafish embryos (Danio rerio).Environ Pollut2021;277:116779

[68] Jin M,Paudel YN.The possible hormetic effects of fluorene-9-bisphenol on regulating hypothalamic-pituitary-thyroid axis in zebrafish.Sci Total Environ2021;776:145963

[69] Pandelides Z,Lovitt KG.Developmental exposure to Δ⁹-tetrahydrocannabinol (THC) causes biphasic effects on longevity, inflammation, and reproduction in aged zebrafish (Danio rerio).Geroscience2020;42:923-36 PMCID:PMC7286997

[70] Alkimin GD,Soares AMVM.Ecotoxicological effects of the azole antifungal agent clotrimazole on the macrophyte species Lemna minor and Lemna gibba.Comp Biochem Physiol C Toxicol Pharmacol2020;237:108835

[71] Liu Y,Yang L,Wang D.Responses of Hydrocharis dubia (Bl.) Backer and Trapa bispinosa roxb. to tetracycline exposure.Ecotoxicol Environ Saf2020;202:110890

[72] Peres L,Cruz C.Hormesis effect of herbicides subdoses on submerged macrophytes in microassay conditions.Planta daninha2017;35

[73] Di Baccio D,Bertolotto P.Response of Lemna gibba L. to high and environmentally relevant concentrations of ibuprofen: Removal, metabolism and morpho-physiological traits for biomonitoring of emerging contaminants.Sci Total Environ2017;584-585:363-73

[74] Farooq N,Tanveer A.Differential hormetic response of fenoxaprop-p-Ethyl resistant and susceptible phalaris minor populations: a potential factor in resistance evolution.Planta daninha2019;37:e019187554

[75] Hu H,Li X.Phytoremediation of anaerobically digested swine wastewater contaminated by oxytetracycline via Lemna aequinoctialis: nutrient removal, growth characteristics and degradation pathways.Bioresour Technol2019;291:121853

[76] Liu F,Wu H.Dose-dependent effects induced by cadmium in polychaete Perinereis aibuhitensis.Ecotoxicol Environ Saf2019;169:714-21

[77] Zhan J,Li F,Wu H.Dose-dependent responses of metabolism and tissue injuries in clam Ruditapes philippinarum after subchronic exposure to cadmium.Sci Total Environ2021;779:146479

[78] Xu H,Sun H.Dose-dependent effects of Di-(2-Ethylhexyl) phthalate (DEHP) in mussel Mytilus galloprovincialis.Front Mar Sci2021;8:658361

[79] Vera MS.First evaluation of the periphyton recovery after glyphosate exposure.Environ Pollut2021;290:117998

[80] Mao Y,Chen Y.Phytoplankton response to polystyrene microplastics: Perspective from an entire growth period.Chemosphere2018;208:59-68

[81] Ianna ML,Howe PL.Application of a behavioural and biochemical endpoint in ecotoxicity testing with Exaiptasia pallida.Chemosphere2020;257:127240

[82] Howe PL,Clark MW.Development of a chronic, early life-stage sub-lethal toxicity test and recovery assessment for the tropical zooxanthellate sea anemone Aiptasia pulchella.Ecotoxicol Environ Saf2014;100:138-47

[83] Svigruha R,Padisak J.Progestogen-induced alterations and their ecological relevance in different embryonic and adult behaviours of an invertebrate model species, the great pond snail (Lymnaea stagnalis).Environ Sci Pollut Res Int2021;28:59391-402 PMCID:PMC8542004

[84] Nong QY,Qin LT.Toxic mechanism of three azole fungicides and their mixture to green alga Chlorella pyrenoidosa.Chemosphere2021;262:127793

[85] Agathokleous E,Calabrese EJ.US EPA: is there room to open a new window for evaluating potential sub-threshold effects and ecological risks?.Environ Pollut2021;284:117372

[86] Calabrese EJ,Kozumbo WJ,Leonard D.Estimating the range of the maximum hormetic stimulatory response.Environ Res2019;170:337-43

[87] Rohr JR,Nisbet RM.Chemical safety must extend to ecosystems.Science2017;356:917