Register      Login
Environmental Chemistry Environmental Chemistry Society
Environmental problems - Chemical approaches
RESEARCH ARTICLE

Robust calculus for biotransformation in wastewater generalised across thousands of chemicals and conditions

Tom M. Nolte https://orcid.org/0000-0001-8083-0749 A * , Willie J. G. M. Peijnenburg B C and Peter L. A. van Vlaardingen https://orcid.org/0009-0007-7258-338X B
+ Author Affiliations
- Author Affiliations

A Department of Environmental Science, Institute for Water and Wetland Research, Radboud University Nijmegen, 6500 GL Nijmegen, Netherlands.

B National Institute for Public Health and the Environment (RIVM), Centre for Substances and Integrated Risk Assessment (SIR), 3720 BA Bilthoven, Netherlands.

C Institute of Environmental Sciences (CML), Leiden University, PO Box 9518, 2300 RA, Leiden, Netherlands.

* Correspondence to: tom.m.nolte@gmail.com

Handling Editor: Graeme Batley

Environmental Chemistry 20(6) 249-267 https://doi.org/10.1071/EN23033
Submitted: 3 April 2023  Accepted: 1 November 2023  Published: 12 December 2023

© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing.

Abstract

Environmental context

Decades of research tried to understand the inherent complexity of biodegradation of contaminants. We describe calculus of biodegradation driven by bioavailability, redox, geometry and acclimation (adaptation) of microbiota. We tested predictions for thousands of contaminants across wastewater treatment plants, explaining up to 70% of the variance in observations. This competes with more intensive methods, and enables more efficient monitoring, experimentation and data interpretation.

Rationale

Release of harmful contaminants of emerging concern (CECs) in the environment prompts possible adverse toxicological effects. Increasing population, water use and process wastewater generation require more efficient removal of contaminants that allows for effluent discharge within environmental regulatory limits. Wastewater treatment plants (WWTPs) can remove hazardous contaminants, limiting unwanted release. Fine-tuning WWTP settings to fit the location, time, season, wastewater type, etc. may enhance removals to reduce CEC concentrations and toxic pressures.

Methodology

For this purpose, we need robust tools to calculate removal efficiencies. We studied influences of operational settings and CEC properties on their removal in WWTPs. For this purpose, we parameterised thermochemical properties of CECs: for their (1) speciation and acidification, (2) (re/im)mobilisation due to (de)sorption into solid/water, (3) redox-mediated biotransformation and (4) acclimation of biomass so to utilise metabolic pathways for biotransformation. By combining these parameters, we developed an energy-based framework for calculating biotransformation rates.

Results

We evaluated our calculus using removal efficiency (%) data for 373 measurements of 60 CECs in 14 different Dutch WWTPs and an additional 667 CECs in 49 WWTPs across the world. Our prediction precision, R2 ≈ 0.65 (P < 10−5), captures influences of wastewater characteristics (multiple measurements for each WWTP). It is higher than R2-values of modelling approaches currently available. Our model explains CEC removal with appreciative certainty. We identified outliers during evaluation. These outliers were attributed mostly to back-transformation and uncertainty in long-term background concentrations of contaminants, causing consequent acclimation of microbial consortia.

Discussion

Biodegradability and CEC-degrading biomass can be estimated from concentration and environmental residence time. Our framework and underlying parametrisations have a mechanistic basis, utilising simple WWTP operational information (CEC concentration, temperature, suspended solids concentration, oxygen demand, etc.). Thereby, our work has wide potential for implementation. Our approach can supplement current fate assessment for CECs for improved environmental risk assessments. We conclude by discussing the potential for removal enhancement.

Keywords: activated sludge, biodegradation, biotransformation, energy-based calculus, removal, surface water, wastewater.

References

ACWWA (2006) Environment Canada. Atlantic Canada Wastewater Guidelines Manual for Collection, Treatment, and Disposal.

Allen HE, Hall RH, Brisbin TD (1980) Metal speciation. Effects on aquatic toxicity. Environmental Science and Technology 14, 441-443.
| Crossref | Google Scholar | PubMed |

Arvaniti OS, Andersen HR, Thomaidis NS, Stasinakis AS (2014) Sorption of Perfluorinated Compounds onto different types of sewage sludge and assessment of its importance during wastewater treatment. Chemosphere 111, 405-411.
| Crossref | Google Scholar | PubMed |

Babel S, del Mundo Dacera D (2006) Heavy metal removal from contaminated sludge for land application: a review. Waste Management 26, 988-1004.
| Crossref | Google Scholar | PubMed |

Badu M (2011) Effect of algal biofilm and operational conditions on nitrogen removal in wastewater stabilization ponds. PhD Thesis, TU Delft, Netherlands.

Bard A, Faulkner L (2001) ‘Electrochemical Methods. Fundamentals and Applications’, 2nd edn. (John Wiley & Sons: Hoboken, NJ, USA)

Beal J (2015) Biochemical Complexity Drives Log-Normal Variation in Genetic Expression. Engineering Biology 1, 55-60.
| Crossref | Google Scholar |

Bersinger T, Le Hécho I, Bareille G, Pigot T (2015) Assessment of erosion and sedimentation dynamic in a combined sewer network using online turbidity monitoring. Water Science & Technology 72(8), 1375-1382.
| Crossref | Google Scholar | PubMed |

Boleda MR, Galceran MT, Ventura F (2013) Validation and uncertainty estimation of a multiresidue method for pharmaceuticals in surface and treated waters by liquid chromatography-tandem mass spectrometry. Journal of Chromatography A 1286, 146-158.
| Crossref | Google Scholar | PubMed |

Brown DM, Camenzuli L, Redman AD, Hughes C, Wang N, Vaiopoulou E, Saunders D, Villalobos A, Linington S (2020) Is the Arrhenius-correction of biodegradation rates, as recommended through REACH guidance, fit for environmentally relevant conditions? An example from petroleum biodegradation in environmental systems. Science of the Total Environment 732, 139293.
| Crossref | Google Scholar | PubMed |

Burgis C (2012) Predicting Biological Removal of Contaminants in Wastewater Treatment: QSBR Modeling. MSc Thesis, University of Virginia, Charlottesville, VA, USA.

Carvalhais N, Forkel M, Khomik M, Bellarby J, Jung M, Migliavacca M, Mu M, Saatchi S, Santoro M, Thurner M, Weber U, Ahrens B, Beer C, Cescatti A, Randerson JT, Reichstein M (2014) Global covariation of carbon turnover times with climate in terrestrial ecosystems. Nature 514, 213-217.
| Crossref | Google Scholar | PubMed |

Chae YJ, Kim MS, Chung SJ, Lee MK, Lee KR, Maeng HJ (2021) Pharmacokinetic Estimation Models-based Approach to Predict Clinical Implications for CYP Induction by Calcitriol in Human Cryopreserved Hepatocytes and HepaRG Cells. Pharmaceutics 13, 181.
| Crossref | Google Scholar | PubMed |

Chefetz B, Xing B (2009) Relative Role of Aliphatic and Aromatic Moieties as Sorption Domains for Organic Compounds: A Review. Environmental Science and Technology 43, 1680-1688.
| Crossref | Google Scholar | PubMed |

Chando TJ, Everett DW, Kahle AD, Starrett AM, Vachharajani N, Shyu WC, Kripalani KJ, Barbhaiya RH (1998) Biotransformation of irbesartan in man. Drug Metabolism and Disposition 26, 408-417.
| Google Scholar | PubMed |

Cheng WP, Chi FH (2002) A study of coagulation mechanisms of polyferric sulfate reacting with humic acid using a fluorescence-quenching method. Water Research 36, 4583-4591.
| Crossref | Google Scholar | PubMed |

Clark B, Henry GL, Mackay D (1995) Fugacity analysis and model of organic chemical fate in a sewage treatment plant. Environmental Science and Technology 29, 1488-1494.
| Crossref | Google Scholar | PubMed |

CMP (2021) ‘Wastewater Monitoring Program’. (Environment and Climate Change Canada, Government of Canada)

Coll C, Bier R, Li Z, Langenheder S, Gorokhova E, Sobek A (2020) Association between Aquatic Micropollutant Dissipation and River Sediment Bacterial Communities. Environmental Science and Technology 54, 14380-14392.
| Crossref | Google Scholar | PubMed |

Comber S, Gardner M, Sörme P, Ellor B (2019) The removal of pharmaceuticals during wastewater treatment: can it be predicted accurately? Science of the Total Environment 676, 222-230.
| Crossref | Google Scholar | PubMed |

Delle Site A (2001) Factors affecting sorption of organic compounds in natural sorbent/water systems and sorption coefficients for selected pollutants. A review. Journal of Physical and Chemical Reference Data 30, 187-439.
| Crossref | Google Scholar |

Dimitrov S, Pavlov T, Dimitrova N, Georgieva D, Nedelcheva D, Kesova A, Vasilev R, Mekenyan O (2011) Simulation of chemical metabolism for fate and hazard assessment. II CATALOGIC simulation of abiotic and microbial degradation. SAR and QSAR in Environmental Research 22, 719-755.
| Crossref | Google Scholar | PubMed |

Dong X, Milholland B, Vijg J (2016) Evidence for a limit to human lifespan. Nature 538, 257-259.
| Crossref | Google Scholar | PubMed |

Dosta J, Fernández I, Vázquez-Padín JR, Mosquera-Corral A, Campos JL, Mata-Alvarez J, Méndez R (2008) Short- and long-term effects of temperature on the Anammox process. Journal of Hazardous Materials 154, 688-693.
| Crossref | Google Scholar | PubMed |

Douziech M, Conesa IR, Benítez-López A, Franco A, Huijbregts M, Van Zelm R (2018) Quantifying variability in removal efficiencies of chemicals in activated sludge wastewater treatment plants - a meta-analytical approach. Environmental Science: Processes & Impacts 20, 171-182.
| Crossref | Google Scholar | PubMed |

Dowler D, Boren Z (2020) Revealed: salmonella, toxic chemicals and plastic found in sewage spread on farmland. Greenpeace quoting an Environment Agency Paper. (Unearthed: UK) [accessed 11 October 2021]

ECHA (2010) European Union System for the Evaluation of Substances (EUSES). Ver. 2.1 background report. III: Model calculations.

EFSA (2008) Opinion on a Request from EFSA Related to the Default Q 10 Value Used to Describe the Temperature Effect on Transformation Rates of Pesticides in Soil. EFSA Journal 622, 1-32.
| Google Scholar |

European Comission (2022) Proposal for a revised Urban Wastewater Treatment Directive. 26 October 2022. Directorate-General for Environment. Available at https://environment.ec.europa.eu/publications/proposal-revised-urban-wastewater-treatment-directive_en

Evenblij H, Schuman E, Kuiper M (2020) Verwijderingsrendementen van medicijnresten op 18 rwzi’s. WDOD database. Water Matters, uitgave H2O 28-31 [In Dutch].
| Google Scholar |

Fani R (2012) The Origin and Evolution of Metabolic Pathways: Why and How did Primordial Cells Construct Metabolic Routes? Evolution: Education and Outreach 5, 367-381.
| Crossref | Google Scholar |

Farkas K, Marshall M, Cooper D, Mcdonald JE, Malham SK, Peters DE, Maloney JD, Jones DL (2018) Seasonal and diurnal surveillance of treated and untreated wastewater for human enteric viruses. Environmental Science and Pollution Research International 25, 33391-33401.
| Crossref | Google Scholar | PubMed |

Fateh A, Aliofkhazraei M, Rezvanian AR (2020) Review of corrosive environments for copper and its corrosion inhibitors. Arabian Journal of Chemistry 13, 481-544.
| Crossref | Google Scholar |

Fellenz MP, Gerweck LE (1988) Influence of extracellular pH on intracellular pH and cell energy status: relationship to hyperthermic sensitivity. Radiation Research 116, 305-312.
| Google Scholar | PubMed |

Flegal TM, Schroeder ED (1976) Temperature effects on BOD stoichiometry and oxygen uptake rate. Journal of the Water Pollution Control Federation 48, 2700-2707.
| Google Scholar | PubMed |

Franco A, Struijs J, Gouin T, Price OR (2013) Evolution of the Sewage Treatment Plant Model SimpleTreat: Applicability Domain and Data Requirements. Integrated Environmental Assessment and Management 9, 560-568.
| Crossref | Google Scholar | PubMed |

Fukuzumi S, Kochi JK (1981) Electrophilic Aromatic-Substitution. Charge-Transfer Excited-States and the Nature of the Activated Complex. Journal of the American Chemical Society 103, 7240-7252.
| Crossref | Google Scholar |

Gao DW, Tao Y (2011) Versatility and application of anaerobic ammonium-oxidizing bacteria. Applied Microbiology and Biotechnology 91, 887-894.
| Crossref | Google Scholar | PubMed |

Gao K, Brandt I, Goldstone JV, Jönsson ME (2011) Cytochrome P450 1A, 1B, and 1C mRNA induction patterns in three-spined stickleback exposed to a transient and a persistent inducer. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 154, 42-55.
| Crossref | Google Scholar | PubMed |

Gedalanga PB, Pornwongthong P, Mora R, Chiang SY, Baldwin B, Ogles D, Mahendra S (2014) Identification of biomarker genes to predict biodegradation of 1,4-dioxane. Applied and Environmental Microbiology 80, 3209-3218.
| Crossref | Google Scholar | PubMed |

Gibson B, Wilson DJ, Feil E, Eyre-Walker A (2018) The distribution of bacterial doubling times in the wild. Proceedings of the Royal Society B: Biological Sciences 285, 20180789.
| Crossref | Google Scholar | PubMed |

Gogulancea V, González-Cabaleiro R, Li B, Taniguchi D, Jayathilake PG, Chen J, Wilkinson D, Swailes D, Mcgough AS, Zuliani P, Ofiteru ID, Curtis TP (2019) Individual Based Model Links Thermodynamics, Chemical Speciation and Environmental Conditions to Microbial Growth. Frontiers in Microbiology 10, 1871.
| Crossref | Google Scholar | PubMed |

Golovko O, Örn S, Sörengård M, Frieberg K, Nassazzi W, Lai FY, Ahrens L (2021) Occurrence and removal of chemicals of emerging concern in wastewater treatment plants and their impact on receiving water systems. Science of the Total Environment 754, 142122.
| Crossref | Google Scholar |

González-Benítez N, García-Corral LS, Morán X, Middelburg JJ, Pizay MD, Gattuso JP (2019) Drivers of Microbial Carbon Fluxes Variability in Two Oligotrophic Mediterranean Coastal Systems. Scientific Reports 9, 17669.
| Crossref | Google Scholar | PubMed |

Gulde R, Meier U, Schymanski EL, Kohler HP, Helbling DE, Derrer S, Rentsch D, Fenner K (2016) Systematic Exploration of Biotransformation Reactions of Amine-Containing Micropollutants in Activated Sludge. Environmental Science and Technology 50, 2908-2920.
| Crossref | Google Scholar | PubMed |

Gutierrez O, Sudarjanto G, Ren G, Ganigué R, Jiang G, Yuan Z (2014) Assessment of pH shock as a method for controlling sulfide and methane formation in pressure main sewer systems. Water Research 48, 569-578.
| Crossref | Google Scholar | PubMed |

Haber F (1924) Zur Geschichte des Gaskrieges. In ‘Fuenf Vortraege aus den Jahren 1920–1923’. pp. 76–92. (Springer: Berlin, Germany) [In German]

Hakkola J, Hukkanen J, Turpeinen M, Pelkonen O (2020) Inhibition and induction of CYP enzymes in humans: an update. Archives of Toxicology 94, 3671-3722.
| Crossref | Google Scholar | PubMed |

He K, Borthwick AG, Lin Y, Li Y, Fu J, Wong Y, Liu W (2020) Sale-based estimation of pharmaceutical concentrations and associated environmental risk in the Japanese wastewater system. Environment International 139, 105690.
| Crossref | Google Scholar | PubMed |

Henari F, Culligan KG (2010) The Influence of pH on Nonlinear Refractive Index of Bromophenol Blue. Physics International 1, 27-30.
| Crossref | Google Scholar |

Hendriks AJ (2016) Chapter 7. Organisms. Syllabus for Environmental and Ecological Modelling. The power of size. Modelling (substances in) geo-hydrological, biological and social systems based on cross-disciplinary (scaling) principles. (Radboud University: Nijmegen, Netherlands)

Herz RK (2014) Chemical Reaction Engineering - Part 14 - intro to CSTRs. Continuous Stirred Tank Reactors - CSTRs. Available at https://reactorlab.net/

Hoekstra M (2017) Mainstream anammox, potential & feasibility of autotrophic nitrogen removal. PhD Thesis, Technische Universiteit Delft, Netherlands.

Hoekstra M, De Weerd FA, Kleerebezem R, Van Loosdrecht M (2018) Deterioration of the anammox process at decreasing temperatures and long SRTs. Environmental Technology 39, 658-668.
| Crossref | Google Scholar | PubMed |

Hoshino S, Kubota H (1977) Wastewater treatment with rotating biological contactor. Water Purification Liquid Waste Treatment 18, 29-35.
| Google Scholar |

Hosseini B, Darzi GN, Sadeghpour M, Asadi M (2008) The effect of the sludge recycle ratio in an activated sludge system for the treatment of Amol’s industrial park wastewater. Chemical Industry & Chemical Engineering Quarterly 14, 173-180.
| Google Scholar |

Hu HY, Fujie K, Urano K (1994) Effect of Temperature on the Reaction Rate of Bacteria Inhabiting the Aerobic Microbial Film for Wastewater Treatment. Journal of Fermentation and Bioengineering 78, 100-104.
| Crossref | Google Scholar |

Huang Y, Mu X, Wang J, Wang Y, Xie J, Ying R, Su E (2022) The recent development of nanozymes for food quality and safety detection. Journal of Materials Chemistry B: Materials for Biology and Medicine 10, 1359-1368.
| Crossref | Google Scholar | PubMed |

Hyun S, Lee LS (2004) Hydrophilic and Hydrophobic Sorption of Organic Acids by Variable-Charge Soils:  Effect of Chemical Acidity and Acidic Functional Group. Environmental Science and Technology 38, 5413-5419.
| Crossref | Google Scholar | PubMed |

Inoue M, Sumii Y, Shibata N (2020) Contribution of Organofluorine Compounds to Pharmaceuticals. ACS Omega 5, 10633-10640.
| Crossref | Google Scholar | PubMed |

IUPAC (2006) ‘Compendium of Chemical Terminology’, 2nd edn. (the “Gold Book”) (1997). Online corrected version. 10.1351/goldbook.L03551.

Iwamoto DV, Kurylo CM, Schorling KM, Powell WH (2012) Induction of cytochrome P450 family 1 mRNAs and activities in a cell line from the frog Xenopus laevis. Aquatic Toxicology 114-115, 165-172.
| Crossref | Google Scholar | PubMed |

Jaeger A, Coll C, Posselt M, Mechelke J, Rutere C, Betterle A, Raza M, Mehrtens A, Meinikmann K, Portmann A, Singh T, Blaen PJ, Krause S, Horn MA, Hollender J, Benskin JP, Sobek A, Lewandowski J (2019) Using recirculating flumes and a response surface model to investigate the role of hyporheic exchange and bacterial diversity on micropollutant half-lives. Environmental Science: Processes & Impacts 21, 2093-2108.
| Crossref | Google Scholar | PubMed |

Jaeger A, Posselt M, Schaper JL, Betterle A, Rutere C, Coll C, Mechelke J, Raza M, Meinikmann K, Portmann A, Blaen PJ, Horn MA, Krause S, Lewandowski J (2021) Transformation of organic micropollutants along hyporheic flow in bedforms of river-simulating flumes. Scientific Reports 11, 13034.
| Crossref | Google Scholar | PubMed |

Joel C, Kiprop EK, Mwamburi LA (2017) Effect of Seasonal Variation on Performance of Conventional Wastewater Treatment System. Journal of Applied & Environmental Microbiology 5, 1-7.
| Google Scholar |

Johnson DR, Helbling DE, Lee TK, Park J, Fenner K, Kohler HP, Ackermann M (2015) Association of biodiversity with the rates of micropollutant biotransformations among full-scale wastewater treatment plant communities. Applied and Environmental Microbiology 81, 666-675.
| Crossref | Google Scholar | PubMed |

Jones AW (2011) Early drug discovery and the rise of pharmaceutical chemistry. Drug Testing and Analysis 3, 337-344.
| Crossref | Google Scholar | PubMed |

Kadokami K, Ueno D (2019) Comprehensive Target Analysis for 484 Organic Micropollutants in Environmental Waters by the Combination of Tandem Solid-Phase Extraction and Quadrupole Time-of-Flight Mass Spectrometry with Sequential Window Acquisition of All Theoretical Fragment-Ion Spectra Acquisition. Analytical Chemistry 91, 7749-7755.
| Crossref | Google Scholar | PubMed |

Karthikeyan S, Anandan C, Subramanian J, Sekaran G (2013) Characterization of iron impregnated polyacrylamide catalyst and its application to the treatment of municipal wastewater. RSC Advances 3, 15044-15057.
| Crossref | Google Scholar |

Kato H (2020) Computational prediction of cytochrome P450 inhibition and induction. Drug Metabolism and Pharmacokinetics 35, 30-44.
| Crossref | Google Scholar | PubMed |

Kelly SL, Kelly DE (2013) Microbial cytochromes P450: biodiversity and biotechnology. Where do cytochromes P450 come from, what do they do and what can they do for us? Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 368, 20120476.
| Crossref | Google Scholar | PubMed |

Kim SD, Ma H, Allen HE, Cha DK (1999) Influence of dissolved organic matter on the toxicity of copper to Ceriodaphnia dubia: effect of complexation kinetics. Environmental Toxicology and Chemistry 18, 2433-2437.
| Crossref | Google Scholar |

Kolvenbach BA, Helbling DE, Kohler HP, Corvini PF (2014) Emerging chemicals and the evolution of biodegradation capacities and pathways in bacteria. Current Opinion in Biotechnology 27, 8-14.
| Crossref | Google Scholar | PubMed |

Krumschnabel G, Manzl C, Schwarzbaum PJ (2001) Regulation of intracellular pH in anoxia-tolerant and anoxia-intolerant teleost hepatocytes. Journal of Experimental Biology 204, 3943-3951.
| Crossref | Google Scholar | PubMed |

Kutsuno Y, Sumida K, Itoh T, Tukey RH, Fujiwara R (2013) Glucuronidation of drugs in humanized UDP-glucuronosyltransferase 1 mice: similarity with glucuronidation in human liver microsomes. Pharmacology Research & Perspectives 1, e00002.
| Crossref | Google Scholar | PubMed |

Landmark CJ, Johannessen SI (2008) Modifications of antiepileptic drugs for improved tolerability and efficacy. Perspectives in Medicinal Chemistry 2, 21-39.
| Google Scholar | PubMed |

Langenkamp H, Part P (2001) ‘Organic Contaminants in Sewage Sludge for Agricultural Use.’ (European Commission Joint Research Centre, Institute for Environment and Sustainability, Soil and Waste Unit: Brussels, Belgium)

Lautz LS, Struijs J, Nolte TM, Breure AM, Van Der Grinten E, Van De Meent D, Van Zelm R (2017) Evaluation of SimpleTreat 4.0: Simulations of pharmaceutical removal in wastewater treatment plant facilities. Chemosphere 168, 870-876.
| Crossref | Google Scholar | PubMed |

Leithold J, Fernandes CVS, Knapik HG, Azevedo JCR (2017) Quali-quantitative characterization of organic matter in urbanized drainage basins as a basis for the application of Water Resources Management Instruments. RBRH 22, e55.
| Crossref | Google Scholar |

Leoniak M, Balbierz P (2017) Manometric measurements of temperature influence on Anammox activity. E3S Web of Conferences 17, 00052.
| Crossref | Google Scholar |

Liljestrand HM (1985) Average rainwater pH, concepts of atmospheric acidity, and buffering in open systems. Atmospheric Environment 19, 487-499.
| Crossref | Google Scholar |

Lijklema L (1969) Factors affecting pH change in alkaline waste water treatment—I. Water Research 3, 913-930.
| Crossref | Google Scholar |

Lijklema L (1971) Factors affecting pH change in alkaline wastewater treatment—II. carbon dioxide production. Water Research 5, 123-142.
| Crossref | Google Scholar |

Lim BR, Huang X, Hu HY, Goto N, Fujie K (2001) Effects of temperature on biodegradation characteristics of organic pollutants and microbial community in a solid phase aerobic bioreactor treating high strength organic wastewater. Water Science and Technology 43, 131-137.
| Google Scholar | PubMed |

Liu Y, Li J, Wan N, Fu T, Wang L, Li C, Qie Z, Zhu A (2020) A Current Sensing Biosensor for BOD Rapid Measurement. Archaea 2020, 8894925.
| Crossref | Google Scholar | PubMed |

Loon AV, Pronk T, Raterman B, Ros S (2020) Grondwaterkwaliteit Nederland. Anorganische parameters, bestrijdingsmiddelen, farmaceutica en overige verontreinigende stoffen in de grondwatermeetnetten van de provincies. KWR. Vastgesteld door Platform Meetnetbeheerders 25/06/2020. (KWR 2020.067) [In Dutch]

Löscher W, Schmidt D (2006) Experimental and Clinical Evidence for Loss of Effect (Tolerance) during Prolonged Treatment with Antiepileptic Drugs. Epilepsia 47, 1253-1284.
| Crossref | Google Scholar | PubMed |

Lotti T, Kleerebezem R, van Loosdrecht MC (2015) Effect of temperature change on anammox activity. Biotechnology and Bioengineering 112, 98-103.
| Crossref | Google Scholar | PubMed |

Ma Y, Modrzynski JJ, Yang Y, Aamand J, Zheng Y (2021) Redox-dependent biotransformation of sulfonamide antibiotics exceeds sorption and mineralization: evidence from incubation of sediments from a reclaimed water-affected river. Water Research 205, 117616.
| Crossref | Google Scholar | PubMed |

Maktabifard M, Zaborowska E, Makinia J (2018) Achieving energy neutrality in wastewater treatment plants through energy savings and enhancing renewable energy production. Reviews in Environmental Science and Bio/Technology 17, 655-689.
| Crossref | Google Scholar |

Martinez GM, Olabisi J, Ruekert L, Hasan S (2019) A Call for Caution in Prescribing Gabapentin to Individuals With Concurrent Polysubstance Abuse: A Case Report. Journal of psychiatric practice 25, 308-312.
| Crossref | Google Scholar | PubMed |

Maruya KA, Mehinto AC, Lao W, Sutton R, Jabusch T, Sun J, Lin D, Davis J, Fadness R (2018) Pilot Monitoring of Constituents of Emerging Concern (CECs) in the Russian River Watershed (Region 1). Final Report. Southern California Coastal Water Research Project. SCCWRP Technical Report 1020. SWAMP-MR-RB1-2018-0002. (California Water Boards: Sacramento, CA, USA)

Michener JK, Camargo Neves AA, Vuilleumier S, Bringel F, Marx CJ (2014) Effective use of a horizontally-transferred pathway for dichloromethane catabolism requires post-transfer refinement. eLife 3, e04279.
| Crossref | Google Scholar | PubMed |

Milo R, Phillips R (2016) ‘Cell Biology by the numbers.’ (Garland Science: New York, USA)

Mines RO, Lackey LW, Behrend GH (2007) The Impact of Rainfall on Flows and Loadings at Georgia’s Wastewater Treatment Plants. Water, Air, and Soil Pollution 179, 135-157.
| Crossref | Google Scholar |

Molinspiration (1986). Molinspiration Cheminformatics [Online]. Nova ulica, SK-900 26 Slovensky Grob, Slovak Republic. Available at http://www.molinspiration.com/ [accessed 11 October 2021]

Mooij D (2019) Modelling Biodegradation of Micropollutants in Urban Wastewater Treatment Plants Based on Quantitative Structure Properties. MSc Thesis, Radboud University, Nijmegen, Netherlands.

MOTE (1997) ‘Chapter 5. Environmental Quality Standards for Waters. Standards Related to Conversation of Living Environment’. pp. 43–54. (Ministry of the Environment, Government of Japan)

Nelson DR (2018) Cytochrome P450 diversity in the tree of life. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1866, 141-154.
| Crossref | Google Scholar | PubMed |

Newman J, Thomas-Alyea KE (2004) ‘Electrochemical Systems’, 3rd edn. (John Wiley & Sons, Inc.: Hoboken, NJ, USA)

Nolte TM, Ragas AMJ (2017) A review of quantitative structure-property relationships for the fate of ionizable organic chemicals in water matrices and identification of knowledge gaps. Environmental Science-Processes & Impacts 19, 221-246.
| Crossref | Google Scholar | PubMed |

Nolte TM, Pinto-Gil K, Hendriks AJ, Ragas AMJ, Pastor M (2018) Quantitative structure-activity relationships for primary aerobic biodegradation of organic chemicals in pristine surface waters: starting points for predicting biodegradation under acclimatization. Environmental Science-Processes & Impacts 20, 157-170.
| Crossref | Google Scholar | PubMed |

Nolte TM, Chen GC, Van Schayk CS, Pinto-Gil K, Hendriks AJ, Peijnenburg WJGM, Ragas AMJ (2020a) Disentanglement of the chemical, physical, and biological processes aids the development of quantitative structure-biodegradation relationships for aerobic wastewater treatment. Science of the Total Environment 708, 133863.
| Crossref | Google Scholar |

Nolte TM, Peijnenburg WJGM, Van Bergen TJHM, Hendriks AJ (2020b) Transition-state rate theory sheds light on ‘black-box’ biodegradation algorithms. Green Chemistry 22, 3558-3571.
| Crossref | Google Scholar |

Nolte TM, Hendriks AJ, Novák LA, Peijnenburg WJGM (2021) A universal free energy relationship for both hard and soft radical addition in water. Journal of Phyical Organic Chemistry 35, e4317.
| Crossref | Google Scholar |

Nolte TM, Peijnenburg WJGM, Rios-Miguel AB, Zhang YN, Hendriks AJ (2022a) Stoichiometric ratios for biotics and xenobiotics capture effective metabolic coupling to re(de)fine biodegradation. Water Research 217, 118333.
| Crossref | Google Scholar | PubMed |

Nolte TM, Rios-Miguel A, Hendriks AJ, Kuiper M (2022b) ‘Biologische afbreekbaarheid van organische microverontreinigingen in waterzuiveringsinstallaties.’ (H2O: Netherlands) [In Dutch]

Nopens I, Capalozza C, Vanrolleghem PA (2001) Technical Report: Stability analysis of a synthetic municipal wastewater. Coupure Links 653, B-9000 Gent. (Universiteit Gent, Department of Applied Mathematics, Biometrics and Process Control: Belgium)

OECD (1992) ‘OECD guidelines for the testing of chemicals. Guideline No. 301, Ready Biodegradability.’ (Organisation for Economic Cooperation and Development)

Patel M, Kumar R, Kishor K, Mlsna T, Pittman Jr CU, Mohan D (2019) Pharmaceuticals of Emerging Concern in Aquatic Systems: Chemistry, Occurrence, Effects, and Removal Methods. Chemical Reviews 119, 3510-3673.
| Crossref | Google Scholar | PubMed |

Patoczka J (2014) ‘Wet Weather Design and Operation in Water Resource Recovery Facilities. Chapter 12: Primary Treatment, Water Environment Federation.’ (WEF Special Publication: Alexandria, VA, USA) Available at http://www.wef.org

Pérez-Pantoja D, Nikel PI, Chavarría M, De Lorenzo V (2021) Transcriptional control of 2,4-dinitrotoluene degradation in Burkholderia sp. R34 bears a regulatory patch that eases pathway evolution. Environmental Microbiology 23, 2522-2531.
| Crossref | Google Scholar | PubMed |

Plósz BG, Langford KH, Thomas KV (2012) An activated sludge modeling framework for xenobiotic trace chemicals (ASM-X): assessment of diclofenac and carbamazepine. Biotechnology and Bioengineering 109, 2757-2769.
| Crossref | Google Scholar | PubMed |

Poursat BAJ, van Spanning RJM, De Voogt P, Parsons JR (2019a) Implications of microbial adaptation for the assessment of environmental persistence of chemicals. Critical Reviews in Environmental Science and Technology 49, 2220-2255.
| Crossref | Google Scholar |

Posthuma L, Van Gils J, Zijp MC, Van De Meent D, De Zwart D (2019) Species sensitivity distributions for use in environmental protection,assessment, and management of aquatic ecosystems for 12 386 chemicals. Environmental Toxicology and Chemistry 38, 905-917.
| Crossref | Google Scholar | PubMed |

Price PB, Sowers T (2004) Temperature dependence of metabolic rates for microbial growth, maintenance, and survival. Proceedings of the National Academy of Sciences of the United States of America 101, 4631-4636.
| Crossref | Google Scholar | PubMed |

Riffat R, Husnain T (2022) ‘Fundamentals of wastewater treatment and engineering.’ (CRC Press: London, UK)

Rios Miguel AB (2022) Microbial Removal of Organic Micropollutants Under WastewaterTreatment Conditions. PhD Thesis, Radboud University, Nijmegen, Netherlands.

Rios Miguel AB, Jetten MSM, Welte CU (2020) The role of mobile genetic elements in organic micropollutant degradation during biological wastewater treatment. Water Research X 9, 100065.
| Crossref | Google Scholar | PubMed |

Rose C, Parker A, Jefferson B, Cartmell E (2015) The Characterization of Feces and Urine: A Review of the Literature to Inform Advanced Treatment Technology. Critical Reviews in Environmental Science and Technology 45, 1827-1879.
| Crossref | Google Scholar | PubMed |

Rubin J (1983) Transport of reacting solutes in porous-media: relation between mathematical nature of problem formulation and chemical nature of reactions. Water Resources Research 19, 1231-1252.
| Crossref | Google Scholar |

Salonen LM, Ellermann M, Diederich F (2011) Aromatic rings in chemical and biological recognition: energetics and structures. Angewandte Chemie International Edition 50, 4808-4842.
| Crossref | Google Scholar | PubMed |

Schumacher G, Sekoulov I (2002) Polishing of secondary effluent by an algal biofilm process. Water Science and Technology 46, 83-90.
| Google Scholar | PubMed |

Shahzad M, Khan SJ, Paul P (2015) Influence of Temperature on the Performance of a Full-Scale Activated Sludge Process Operated at Varying Solids Retention Times Whilst Treating Municipal Sewage. Water 7, 855-867.
| Crossref | Google Scholar |

Slade AH, Thorn GJS, Dennis MA (2011) The relationship between BOD:N ratio and wastewater treatability in a nitrogen-fixing wastewater treatment system. Water Science & Technology 63, 627-632.
| Crossref | Google Scholar | PubMed |

Song CW, Griffin R, Park HJ (2006) Influence of Tumor pH on Therapeutic Response. In ‘Cancer Drug Resistance’ (Ed. BA Teicher) pp. 21–42. (Humana Press: Totowa, NJ, USA)

Stephen FD, Drahushuk AT, Olson JR (1997) Cytochrome P450 1A1 induction in rat lymphoid tissues following in vivo and in vitro exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin requires protein kinase C. Toxicology 124, 39-51.
| Crossref | Google Scholar | PubMed |

Strous M, Kuenen JG, Jetten MS (1999) Key physiology of anaerobic ammonium oxidation. Applied and Environmental Microbiology 65, 3248-3250.
| Crossref | Google Scholar | PubMed |

Struijs J (2014) ‘SimpleTreat 4.0: a model to predict the fate and emission of chemicals in wastewater treatment plants. Background report describing the equations’. RIVM Report 601353005/201. RIVM

Struijs J (2015) Application of SimpleTreat 4.0 in European substance regulations. SimpleTreat 4.0 ed.: Umweltbundesamt (UBA) Texte 13/2015, 45 p, 2015, UBA. Available at https://www.umweltbundesamt.de/publikationen/application-of-simpletreat-40-in-european-substance

Tabasso S, Berto S, Rosato R, Marinos JA, Ginepro M, Zelano V, Daniele PG, Montoneri E (2015) Chemical modeling of acid-base properties of soluble biopolymers derived from municipal waste treatment materials. International Journal of Molecular Sciences 16, 3405-3418.
| Crossref | Google Scholar | PubMed |

Tan L, Tan X, Ren X, Mei H, Wang X (2018) Influence of pH, soil humic acid, ionic strength and temperature on sorption of U(VI) onto attapulgite. Journal of Radioanalytical and Nuclear Chemistry 316, 981-991.
| Crossref | Google Scholar |

TGD (2003) Technical Guidance Document on Risk Assessment in support of Commission Directive 93/67/EEC on Risk Assessment for new notified substances. European Commission. Regulation No 1488/94 on Risk Assessment for existing substances. Part II. EUR 20418 EN/2.

Thunnissen NW, Van De Meent D, Struijs J, Hjort M, Redman AD, Smit MGD, Hendriks AJ, Van Zelm R (2021) Simulating behavior of petroleum compounds during refinery effluent treatment using the SimpleTreat model. Chemosphere 263, 128081.
| Crossref | Google Scholar |

Tian L, Nawrocki WJ, Liu X, Polukhina I, van Stokkum IHM, Croce R (2019) pH dependence, kinetics and light-harvesting regulation of nonphotochemical quenching in Chlamydomonas. Proceedings of the National Academy of Sciences of the United States of America 116, 8320-8325.
| Crossref | Google Scholar | PubMed |

Tipthara P, Thongboonkerd V (2016) Differential human urinary lipid profiles using various lipid-extraction protocols: MALDI-TOF and LIFT-TOF/TOF analyses. Scientific Reports 6, 33756.
| Crossref | Google Scholar | PubMed |

UBA (2018) Umweltbundesamt. Database “Pharmaceuticals in the environment”. Available at https://www.umweltbundesamt.de/themen/chemikalien/arzneimittel/die-uba-datenbank-arzneimittel-in-der-umwelt

USEPA (2012) Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.11. (United States Environmental Protection Agency: Washington, DC, USA)

van Bergen TJHM, Rios Miguel AB, Nolte TM, Ragas AM, Graumans M, Scheepers P, Jetten MSM, Hendriks AJ, Welte C (2020) Do initial concentration and activated sludge seasonality affect pharmaceutical biotransformation rate constants? Environmental Biotechnology 105, 6515-6527.
| Crossref | Google Scholar | PubMed |

Vanbriesen JM, Small M, Weber C, Wilson J (2010) Chapter 4 - Modelling Chemical Speciation: Thermodynamics, Kinetics and Uncertainty. In ‘Modelling of Pollutants in Complex Environmental Systems’. (Ed. G Hanrahan) pp. 134–149. (ILM Publications)

Vink JPM (2009) The origin of speciation: Trace metal kinetics over natural water/sediment interfaces and the consequences for bioaccumulation. Environmental Pollution 157, 519-527.
| Crossref | Google Scholar | PubMed |

Vanrolleghem PA (2003) Models in advanced wastewater treatment plant control. AutoAgro 2003. In ‘Colloque Automatique et Agronomie’, Montpellier, 22–24 Janury 2003. (AutoAgro: Montpellier, France)

Vink J, Verschoor A (2010) ‘Biotic Ligand Models: availability, performance and applicability for water quality assessment.’ (Deltares)

VMM (2017) Medicijnen in de waterketen. Resultaten verkennend onderzoek in de periode 2014–2016. (Vlaamse Milieumaatschappij)

von Sperling M, Verbyla ME, Oliveira SMAC (2020) ‘Assessment of Treatment Plant Performance and Water Quality Data: A Guide for Students, Researchers and Practitioners. Chapter 13: Loading rates applied to treatment units.’ (IWA Publishing)

Wang H, Zhang S, Pratush A, Ye X, Xie J, Wei H, Sun C, Hu Z (2018) Acclimation of Culturable Bacterial Communities under the Stresses of Different Organic Compounds. Frontiers in Microbiology 9, 225.
| Crossref | Google Scholar | PubMed |

Yoon SA, Park SY, Cha Y, Gopala L, Lee MH (2021) Strategies of Detecting Bacteria Using Fluorescence-Based Dyes. Frontiers in Chemistry 9, 743923.
| Crossref | Google Scholar | PubMed |

Zare Abyaneh H (2014) Evaluation of multivariate linear regression and artificial neural networks in prediction of water quality parameters. Journal of Environmental Health Science and Engineering 12, 40.
| Crossref | Google Scholar | PubMed |