Developing a modern approach to assess ecological risk from pesticides without unnecessary vertebrate animal testing
David A. Dreier
A * , Christian Picard B , Kent Kabler A , Natalia Ryan A , Haitian Lu A , Odette Alexander-Watkins A , John Abbott A , Richard A. Currie C , Douglas C. Wolf A and Tharacad Ramanarayanan A
A
B
C
Abstract
Pesticides are critical to agriculture and food production but require ecological risk assessments. Although most risk assessments require data from vertebrate animal testing, we have developed an approach to assess risk to fish, birds and mammals using other means. This approach could help to ensure protection of the environment while minimising animal testing.
Recent directives to reduce animal testing have implications for ecological risk assessment, as several vertebrate tests are used to support these assessments. Therefore, a modern approach was devised to address these key knowledge needs without the use of chemical-specific vertebrate testing.
An ecological risk assessment for a novel acetyl-coenzyme A carboxylase (ACCase) inhibitor herbicide was conducted using alternative lines of evidence. For fish, chemical toxicity distributions were constructed to quantify the probability of effects, and these distributions were compared with exposure estimates for a representative use in soybeans. The effect distributions were further refined based on invertebrate toxicity and partitioning behaviour. For birds and mammals, a joint probability curve was constructed by integrating chemical toxicity distributions and Kenaga exposure distributions.
The lines of evidence presented in this predictive risk assessment suggest the intended use of a new ACCase inhibitor is unlikely to affect fish, birds, or mammals. Exposure was unlikely to exceed effect estimates, regardless of whether they were derived based on chemical-read across, invertebrate toxicity, or partitioning behaviour.
Key knowledge needs for ecological risk assessment can be informed by lines of evidence that do not require animal testing. The present study demonstrates such an approach by comparing predicted exposure and effects, which are expected to be protective. This predictive approach can be extended to other active ingredients and chemical classes, as well as other taxonomic groups of interest. Future research should aim to integrate new approach methods in a predictive risk assessment framework.
Keywords: animal alternatives, chemical toxicity distributions, ecological risk assessment, ecotoxicology, joint probability distributions, modern approaches for testing and evaluation, new approach methodologies, probabilistic risk assessment, read-across.
References
Barron MG, Otter RR, Connors KA, Kienzler A, Embry MR (2021) Ecological thresholds of toxicological concern: a review. Frontiers in Toxicology 3, 640183.
| Crossref | Google Scholar | PubMed |
Belanger SE, Rawlings JM, Carr GJ (2013) Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals. Environmental Toxicology and Chemistry 32, 1768-1783.
| Crossref | Google Scholar | PubMed |
Belanger SE, Sanderson H, Embry MR, Coady K, DeZwart D, Farr BA, Gutsell S, Halder M, Sternberg R, Wilson P (2015) It is time to develop ecological thresholds of toxicological concern to assist environmental hazard assessment. Environmental Toxicology and Chemistry 34, 2864-2869.
| Crossref | Google Scholar | PubMed |
Berninger JP, Brooks BW (2010) Leveraging mammalian pharmaceutical toxicology and pharmacology data to predict chronic fish responses to pharmaceuticals. Toxicology Letters 193, 69-78.
| Crossref | Google Scholar | PubMed |
Berninger JP, Williams ES, Brooks BW (2011) An initial probabilistic hazard assessment of oil dispersants approved by the United States National Contingency Plan. Environmental Toxicology and Chemistry 30, 1704-1708.
| Crossref | Google Scholar | PubMed |
Bone AJ, Brewer L, Habig C, Levine SL, Moore DRJ, Plautz S (2022) Utility of the avian sub-acute dietary toxicity test in ecological risk assessment and a path forward to reduce animal use. Integrated Environmental Assessment and Management 18, 1629-1638.
| Crossref | Google Scholar | PubMed |
Brain R, Perkins D, Ghebremichael L, White M, Goodwin G, Aerts M (2023) The shrinking land challenge. ACS Agricultural Science & Technology 3, 152-157.
| Crossref | Google Scholar |
Braunbeck T, Boettcher M, Hollert H, Kosmehl T, Lammer E, Leist E, Rudolf M, Seitz N (2005) Towards an alternative for the acute fish LC50 test in chemical assessment: the fish embryo toxicity test goes multi-species – an update. ALTEX 22, 87-102.
| Google Scholar | PubMed |
Browne P, Judson RS, Casey WM, Kleinstreuer NC, Thomas RS (2015) Screening chemicals for estrogen receptor bioactivity using a computational model. Environmental Science and Technology 49, 8804-8814.
| Crossref | Google Scholar | PubMed |
Burden N, Maynard SK, Weltje L, Wheeler JR (2016) The utility of QSARs in predicting acute fish toxicity of pesticide metabolites: a retrospective validation approach. Regulatory Toxicology and Pharmacology 80, 241-246.
| Crossref | Google Scholar | PubMed |
Calow P (2014) Environmental risk assessors as honest brokers or stealth advocates. Risk Analysis 34, 1972-1977.
| Crossref | Google Scholar | PubMed |
Ceger P, Garcia-Reyero Vinas N, Allen D, Arnold E, Bloom R, Brennan JC, Clarke C, Eisenreich K, Fay K, Hamm J, Henry PFP, Horak K, Hunter W, Judkins D, Klein P, Kleinstreuer N, Koehrn K, LaLone CA, Laurenson JP, Leet JK, Lowit A, Lynn SG, Norberg-King T, Perkins EJ, Petersen EJ, Rattner BA, Sprankle CS, Steeger T, Warren JE, Winfield S, Odenkirchen E (2022) Current ecotoxicity testing needs among selected US federal agencies. Regulatory Toxicology and Pharmacology 133, 105195.
| Crossref | Google Scholar | PubMed |
Chen D, Huang H, Huang Y, Yang W, Shan W, Hao G, Wu J, Song B (2023) Toxicity tests for chemical pesticide registration: requirement differences among the United States, the European Union, Japan, and China? Journal of Agricultural and Food Chemistry 71, 7192-7200.
| Crossref | Google Scholar | PubMed |
Connors KA, Beasley A, Barron MG, Belanger SE, Bonnell M, Brill JL, de Zwart D, Kienzler A, Krailler J, Otter R, Phillips JL, Embry MR (2019) Creation of a curated aquatic toxicology database: EnviroTox. Environmental Toxicology and Chemistry 38, 1062-1073.
| Crossref | Google Scholar | PubMed |
Cooper J, Dobson H (2007) The benefits of pesticides to mankind and the environment. Crop Protection 26, 1337-1348.
| Crossref | Google Scholar |
Crump D, Hickey G, Boulanger E, Masse A, Head JA, Hogan N, Maguire S, Xia J, Hecker M, Basu N (2023) Development and initial testing of EcoToxChip, a novel toxicogenomics tool for environmental management and chemical risk assessment. Environmental Toxicology and Chemistry 42, 1763-1771.
| Crossref | Google Scholar | PubMed |
Currie RA, Abbott J, Dreier DA, Lu H, Ramanarayanan T, Ryan N, Watkins OA, Wolf DC (2024) Developing prototypes of a modernized approach to assess crop protection chemical safety. ALTEX 41, 119-130.
| Crossref | Google Scholar | PubMed |
Dobbins LL, Usenko S, Brain RA, Brooks BW (2009) Probabilistic ecological hazard assessment of parabens using Daphnia magna and Pimephales promelas. Environmental Toxicology and Chemistry 28, 2744-2753.
| Crossref | Google Scholar | PubMed |
Dreier DA, Rodney SI, Moore DR, Grant SL, Chen W, Valenti Jr TW, Brain RA (2021) Integrating exposure and effect distributions with the ecotoxicity risk calculator: case studies with crop protection products. Integrated Environmental Assessment and Management 17, 321-330.
| Crossref | Google Scholar | PubMed |
Embry MR, Belanger SE, Braunbeck TA, Galay-Burgos M, Halder M, Hinton DE, Léonard MA, Lillicrap A, Norberg-King T, Whale G (2010) The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research. Aquatic Toxicology 97, 79-87.
| Crossref | Google Scholar | PubMed |
Embry MR, Bachman AN, Bell DR, Boobis AR, Cohen SM, Dellarco M, Dewhurst IC, Doerrer NG, Hines RN, Moretto A, Pastoor TP, Phillips RD, Rowlands JC, Tanir JY, Wolf DC, Doe JE (2014) Risk assessment in the 21st Century: roadmap and matrix. Critical Reviews in Toxicology 44(Suppl 3), 6-16.
| Crossref | Google Scholar | PubMed |
European Parliament and the Council of the European Union (2010) Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union – Legislation 276, 33-79 https://eur-lex.europa.eu/eli/dir/2010/63/oj.
| Google Scholar |
Fischer M, Belanger SE, Berckmans P, Bernhard MJ, Bláha L, Coman Schmid DE, Dyer SD, Haupt T, Hermens JLM, Hultman MT, Laue H, Lillicrap A, Mlnaříková M, Natsch A, Novák J, Sinnige TL, Tollefsen KE, von Niederhäusern V, Witters H, Županič A, Schirmer K (2019) Repeatability and reproducibility of the RTgill-W1 cell line assay for predicting fish acute toxicity. Toxicological Sciences 169, 353-364.
| Crossref | Google Scholar | PubMed |
Fletcher JS, Nellessen JE, Pfleeger TG (1994) Literature review and evaluation of the EPA food‐chain (Kenaga) nomogram, an instrument for estimating pesticide residues on plants. Environmental Toxicology and Chemistry 13, 1383-1391.
| Crossref | Google Scholar |
Haggard DE, Karmaus AL, Martin MT, Judson RS, Setzer RW, Paul Friedman K (2018) High-throughput H295R steroidogenesis assay: utility as an alternative and a statistical approach to characterize effects on steroidogenesis. Toxicological Sciences 162, 509-534.
| Crossref | Google Scholar | PubMed |
Haggard DE, Setzer RW, Judson RS, Paul Friedman K (2019) Development of a prioritization method for chemical-mediated effects on steroidogenesis using an integrated statistical analysis of high-throughput H295R data. Regulatory Toxicology and Pharmacology 109, 104510.
| Crossref | Google Scholar | PubMed |
Haigis A-C, Vergauwen L, LaLone CA, Villeneuve DL, O’Brien JM, Knapen D (2023) Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption. Toxicological Sciences 195, 1-27.
| Crossref | Google Scholar | PubMed |
Hilton GM, Odenkirchen E, Panger M, Waleko G, Lowit A, Clippinger AJ (2019) Evaluation of the avian acute oral and sub-acute dietary toxicity test for pesticide registration. Regulatory Toxicology and Pharmacology 105, 30-35.
| Crossref | Google Scholar | PubMed |
Hoerger F, Kenaga EE (1972) Pesticide residues on plants: Correlation of representative data as a basis for estimation of their magnitude in the environment. In ‘Environmental Quality and Safety: Chemistry, Toxicology, and Technology’. (Eds F Coulston, F Korte) pp. 9–28. (Georg Thieme Publishers: Stuttgart, West Germany)
Judson RS, Magpantay FM, Chickarmane V, Haskell C, Tania N, Taylor J, Xia M, Huang R, Rotroff DM, Filer DL, Houck KA, Martin MT, Sipes N, Richard AM, Mansouri K, Setzer RW, Knudsen TB, Crofton KM, Thomas RS (2015) Integrated model of chemical perturbations of a biological pathway using 18 in vitro high-throughput screening assays for the estrogen receptor. Toxicological Sciences 148, 137-154.
| Crossref | Google Scholar | PubMed |
Juraske R, Antón A, Castells F (2008) Estimating half-lives of pesticides in/on vegetation for use in multimedia fate and exposure models. Chemosphere 70, 1748-1755.
| Crossref | Google Scholar | PubMed |
Kienzler A, Halder M, Worth A (2017) Waiving chronic fish tests: possible use of acute-to-chronic relationships and interspecies correlations. Toxicological & Environmental Chemistry 99, 1129-1151.
| Crossref | Google Scholar |
Kleinstreuer NC, Ceger P, Watt ED, Martin M, Houck K, Browne P, Thomas RS, Casey WM, Dix DJ, Allen D, Sakamuru S, Xia M, Huang R, Judson R (2017) Development and validation of a computational model for androgen receptor activity. Chemical Research in Toxicology 30, 946-964.
| Crossref | Google Scholar | PubMed |
Knapen D, Stinckens E, Cavallin JE, Ankley GT, Holbech H, Villeneuve DL, Vergauwen L (2020) Toward an AOP network-based tiered testing strategy for the assessment of thyroid hormone disruption. Environmental Science and Technology 54, 8491-8499.
| Crossref | Google Scholar | PubMed |
Krebs A, van Vugt-Lussenburg BMA, Waldmann T, Albrecht W, Boei J, ter Braak B, Brajnik M, Braunbeck T, Brecklinghaus T, Busquet F, Dinnyes A, Dokler J, Dolde X, Exner TE, Fisher C, Fluri D, Forsby A, Hengstler JG, Holzer A-K, Janstova Z, Jennings P, Kisitu J, Kobolak J, Kumar M, Limonciel A, Lundqvist J, Mihalik B, Moritz W, Pallocca G, Ulloa APC, Pastor M, Rovida C, Sarkans U, Schimming JP, Schmidt BZ, Stöber R, Strassfeld T, van de Water B, Wilmes A, van der Burg B, Verfaillie CM, von Hellfeld R, Vrieling H, Vrijenhoek NG, Leist M (2020) The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods. Archives of Toxicology 94, 2435-2461.
| Crossref | Google Scholar | PubMed |
LaLone CA, Villeneuve DL, Lyons D, Helgen HW, Robinson SL, Swintek JA, Saari TW, Ankley GT (2016) Editor’s highlight: sequence alignment to predict across species susceptibility (SeqAPASS): a web-based tool for addressing the challenges of cross-species extrapolation of chemical toxicity. Toxicological Sciences 153, 228-245.
| Crossref | Google Scholar | PubMed |
Lambert FN, Vivian DN, Raimondo S, Tebes-Stevens CT, Barron MG (2022) Relationships Between Aquatic Toxicity, Chemical Hydrophobicity, and Mode of Action: Log Kow Revisited. Archives of Environmental Contamination and Toxicology 83, 326-338.
| Crossref | Google Scholar | PubMed |
Lammer E, Carr GJ, Wendler K, Rawlings JM, Belanger SE, Braunbeck T (2009) Is the fish embryo toxicity test (FET) with the zebrafish (Danio rerio) a potential alternative for the fish acute toxicity test? Comparative Biochemistry and Physiology. Toxicology & Pharmacology 149, 196-209.
| Crossref | Google Scholar | PubMed |
Langan LM, Paparella M, Burden N, Constantine L, Margiotta-Casaluci L, Miller TH, Moe SJ, Owen SF, Schaffert A, Sikanen T (2024) Big question to developing solutions: a decade of progress in the development of aquatic new approach methodologies from 2012 to 2022. Environmental Toxicology and Chemistry 43, 559-574.
| Crossref | Google Scholar | PubMed |
LaRocca J, Costa E, Sriram S, Hannas BR, Johnson KJ (2020) Short-term toxicogenomics as an alternative approach to chronic in vivo studies for derivation of points of departure: a case study in the rat with a triazole fungicide. Regulatory Toxicology and Pharmacology 113, 104655.
| Crossref | Google Scholar | PubMed |
Lehman AJ, Laug EP, Woodard G, Draize JH, Fitzhugh OG, Nelson AA (1949) Procedures for the appraisal of the toxicity of chemicals in foods. Food, Drug, Cosmetic Law Quarterly 4, 412-434.
| Google Scholar | PubMed |
Lehman AJ, Patterson WI, Davidow B, Hagan EC, Woodard G, Laug EP, Frawley JP, Fitzhugh OG, Bourke AR, Draize JH, Nelson AA, Vos BJ (1955) Procedures for the appraisal of the toxicity of chemicals in foods, drugs and cosmetics. Food, Drug, Cosmetic Law Journal 10, 679-748.
| Google Scholar |
Lillicrap A, Belanger S, Burden N, Pasquier DD, Embry MR, Halder M, Lampi MA, Lee L, Norberg-King T, Rattner BA, Schirmer K, Thomas P (2016) Alternative approaches to vertebrate ecotoxicity tests in the 21st Century: a review of developments over the last 2 decades and current status. Environmental Toxicology and Chemistry 35, 2637-2646.
| Crossref | Google Scholar | PubMed |
Lillicrap A, Moe SJ, Wolf R, Connors KA, Rawlings JM, Landis WG, Madsen A, Belanger SE (2020) Evaluation of a Bayesian network for strengthening the weight of evidence to predict acute fish toxicity from fish embryo toxicity data. Integrated Environmental Assessment and Management 16, 452-460.
| Crossref | Google Scholar | PubMed |
Mansouri K, Abdelaziz A, Rybacka A, Roncaglioni A, Tropsha A, Varnek A, Zakharov A, Worth A, Richard AM, Grulke CM, Trisciuzzi D, Fourches D, Horvath D, Benfenati E, Muratov E, Wedebye EB, Grisoni F, Mangiatordi GF, Incisivo GM, Hong H, Ng HW, Tetko IV, Balabin I, Kancherla J, Shen J, Burton J, Nicklaus M, Cassotti M, Nikolov NG, Nicolotti O, Andersson PL, Zang Q, Politi R, Beger RD, Todeschini R, Huang R, Farag S, Rosenberg SA, Slavov S, Hu X, Judson RS (2016) CERAPP: collaborative estrogen receptor activity prediction project. Environmental Health Perspectives 124, 1023-1033.
| Crossref | Google Scholar | PubMed |
Mansouri K, Kleinstreuer N, Abdelaziz AM, Alberga D, Alves VM, Andersson PL, Andrade CH, Bai F, Balabin I, Ballabio D, Benfenati E, Bhhatarai B, Boyer S, Chen J, Consonni V, Farag S, Fourches D, García-Sosa AT, Gramatica P, Grisoni F, Grulke CM, Hong H, Horvath D, Hu X, Huang R, Jeliazkova N, Li J, Li X, Liu H, Manganelli S, Mangiatordi GF, Maran U, Marcou G, Martin T, Muratov E, Nguyen DT, Nicolotti O, Nikolov NG, Norinder U, Papa E, Petitjean M, Piir G, Pogodin P, Poroikov V, Qiao X, Richard AM, Roncaglioni A, Ruiz P, Rupakheti C, Sakkiah S, Sangion A, Schramm KW, Selvaraj C, Shah I, Sild S, Sun L, Taboureau O, Tang Y, Tetko IV, Todeschini R, Tong W, Trisciuzzi D, Tropsha A, Van Den Driessche G, Varnek A, Wang Z, Wedebye EB, Williams AJ, Xie H, Zakharov AV, Zheng Z, Judson RS (2020) CoMPARA: collaborative modeling project for androgen receptor activity. Environmental Health Perspectives 128, 027002.
| Crossref | Google Scholar | PubMed |
Matthiessen P, Wheeler JR, Weltje L (2018) A review of the evidence for endocrine disrupting effects of current-use chemicals on wildlife populations. Critical Reviews in Toxicology 48, 195-216.
| Crossref | Google Scholar | PubMed |
Mittal K, Ewald J, Basu N (2022) Transcriptomic points of departure calculated from rainbow trout gill, liver, and gut cell lines exposed to methylmercury and fluoxetine. Environmental Toxicology and Chemistry 41, 1982-1992.
| Crossref | Google Scholar | PubMed |
Moe SJ, Madsen AL, Connors KA, Rawlings JM, Belanger SE, Landis WG, Wolf R, Lillicrap AD (2020) Development of a hybrid Bayesian network model for predicting acute fish toxicity using multiple lines of evidence. Environmental Modelling & Software 126, 104655.
| Crossref | Google Scholar |
Moore D, McCarroll-Butler C, Avanasi R, Chen W, White M, Brain R (2021) How protective to the environment is the pesticide risk assessment and registration process in the United States? Journal of Regulatory Science 9, 1-20.
| Crossref | Google Scholar |
Noyes PD, Friedman KP, Browne P, Haselman JT, Gilbert ME, Hornung MW, Barone Jr S, Crofton KM, Laws SC, Stoker TE, Simmons SO, Tietge JE, Degitz SJ (2019) Evaluating chemicals for thyroid disruption: opportunities and challenges with in vitro testing and adverse outcome pathway approaches. Environmental Health Perspectives 127, 095001.
| Crossref | Google Scholar | PubMed |
Perkins EJ, Ashauer R, Burgoon L, Conolly R, Landesmann B, Mackay C, Murphy CA, Pollesch N, Wheeler JR, Zupanic A, Scholz S (2019) Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessment. Environmental Toxicology and Chemistry 38, 1850-1865.
| Crossref | Google Scholar | PubMed |
Pfleeger TG, Hayes R, Ratsch H, Wickliff C, Fong A (1996) Field evaluation of the EPA (kenaga) nomogram, a method for estimating wildlife exposure to pesticide residues on plants. Environmental Toxicology and Chemistry 15, 535-543.
| Crossref | Google Scholar |
Raimondo S, Montague BJ, Barron MG (2007) Determinants of variability in acute to chronic toxicity ratios for aquatic invertebrates and fish. Environmental Toxicology and Chemistry 26, 2019-2023.
| Crossref | Google Scholar | PubMed |
Rattner BA, Bean TG, Beasley VR, Berny P, Eisenreich KM, Elliott JE, Eng ML, Fuchsman PC, King MD, Mateo R, Meyer CB, O’Brien JM, Salice CJ (2023) Wildlife ecological risk assessment in the 21st Century: promising technologies to assess toxicological effects. Integrated Environmental Assessment and Management 20, 725-748.
| Crossref | Google Scholar | PubMed |
Rawlings JM, Belanger SE, Connors KA, Carr GJ (2019) Fish embryo tests and acute fish toxicity tests are interchangeable in the application of the threshold approach. Environmental Toxicology and Chemistry 38, 671-681.
| Crossref | Google Scholar | PubMed |
Scholz S, Renner P, Belanger SE, Busquet F, Davi R, Demeneix BA, Denny JS, Léonard M, McMaster ME, Villeneuve DL, Embry MR (2013) Alternatives to in vivo tests to detect endocrine disrupting chemicals (EDCs) in fish and amphibians--screening for estrogen, androgen and thyroid hormone disruption. Critical Reviews in Toxicology 43, 45-72.
| Crossref | Google Scholar | PubMed |
Sheffield TY, Judson RS (2019) Ensemble QSAR modeling to predict multispecies fish toxicity lethal concentrations and points of departure. Environmental Science and Technology 53, 12793-12802.
| Crossref | Google Scholar | PubMed |
Sobanska M, Scholz S, Nyman A-M, Cesnaitis R, Gutierrez Alonso S, Klüver N, Kühne R, Tyle H, de Knecht J, Dang Z, Lundbergh I, Carlon C, De Coen W (2018) Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the regulatory context of Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH). Environmental Toxicology and Chemistry 37, 657-670.
| Crossref | Google Scholar | PubMed |
Solomon K, Giesy J, Jones P (2000) Probabilistic risk assessment of agrochemicals in the environment. Crop Protection 19, 649-655.
| Crossref | Google Scholar |
Staveley JP, Freeman EL, McArdle ME, Ortego LS, Coady KK, Bone A, Lagadic L, Weltje L, Weyers A, Wheeler JR (2023) Current testing programs for pesticides adequately capture endocrine activity and adversity for protection of vertebrate wildlife. Integrated Environmental Assessment and Management 19, 1089-1109.
| Crossref | Google Scholar | PubMed |
Stucki AO, Barton-Maclaren TS, Bhuller Y, Henriquez JE, Henry TR, Hirn C, Miller-Holt J, Nagy EG, Perron MM, Ratzlaff DE, Stedeford TJ, Clippinger AJ (2022) Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health. Frontiers in Toxicology 4, 964553.
| Crossref | Google Scholar | PubMed |
Swaters D, van Veen A, van Meurs W, Turner JE, Ritskes-Hoitinga M (2022) A history of regulatory animal testing: what can we learn? Alternatives to Laboratory Animals 50, 322-329.
| Crossref | Google Scholar | PubMed |
Teixidó E, Leuthold D, de Crozé N, Léonard M, Scholz S (2020) Comparative assessment of the sensitivity of fish early-life stage, Daphnia, and algae tests to the chronic ecotoxicity of xenobiotics: perspectives for alternatives to animal testing. Environmental Toxicology and Chemistry 39, 30-41.
| Crossref | Google Scholar | PubMed |
Thorley J, Schwarz C (2018) ssdtools: an R package to fit species sensitivity distributions. Journal of Open Source Software 3, 1082.
| Crossref | Google Scholar |
Tinwell H, Karmaus A, Gaskell V, Gomes C, Grant C, Holmes T, Jonas A, Kellum S, Krüger K, Malley L, Melching-Kollmuss S, Mercier O, Pandya H, Placke T, Settivari R, De Waen B (2023) Evaluating H295R steroidogenesis assay data for robust interpretation. Regulatory Toxicology and Pharmacology 143, 105461.
| Crossref | Google Scholar | PubMed |
US Environmental Protection Agency (1998) Guidelines for Ecological Risk Assessment. EPA/630/R-95/002F. (US EPA: Washington, DC, USA) Available at https://www.epa.gov/sites/default/files/2014-11/documents/eco_risk_assessment1998.pdf
US Environmental Protection Agency (2019) Directive to Prioritize Efforts to Reduce Animal Testing. (US EPA: Washington, DC, USA) Available at https://www.epa.gov/sites/default/files/2019-09/documents/image2019-09-09-231249.pdf
US Environmental Protection Agency (2021) New Approach Methods Work Plan. EPA 600/X-21/209. (US EPA: Washington, DC, USA) Available at https://www.epa.gov/system/files/documents/2021-11/nams-work-plan_11_15_21_508-tagged.pdf
US Environmental Protection Agency (2023) Models for Pesticide Risk Assessment. (US EPA) Available at https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment
van der Zalm AJ, Barroso J, Browne P, Casey W, Gordon J, Henry TR, Kleinstreuer NC, Lowit AB, Perron M, Clippinger AJ (2022) A framework for establishing scientific confidence in new approach methodologies. Archives of Toxicology 96, 2865-2879.
| Crossref | Google Scholar | PubMed |
Viljanen M, Minnema J, Wassenaar PNH, Rorije E, Peijnenburg W (2023) What is the ecotoxicity of a given chemical for a given aquatic species? Predicting interactions between species and chemicals using recommender system techniques. SAR and QSAR in Environmental Research 34, 765-788.
| Crossref | Google Scholar |
Villeneuve DL, Blackwell BR, Blanksma CA, Cavallin JE, Cheng W-Y, Conolly RB, Conrow K, Feifarek DJ, Heinis LJ, Jensen KM, Kahl MD, Milsk RY, Poole ST, Randolph EC, Saari TW, Watanabe KH, Ankley GT (2023) Case study in 21st-Century ecotoxicology: using in vitro aromatase inhibition data to predict reproductive outcomes in fish in vivo. Environmental Toxicology and Chemistry 42, 100-116.
| Crossref | Google Scholar | PubMed |
Vliet S, Markey KJ, Lynn SG, Adetona A, Fallacara D, Ceger P, Choksi N, Karmaus AL, Watson A, Ewans A, Daniel AB, Hamm J, Vitense K, Wolf KA, Thomas A, LaLone CA (2023) Weight of evidence for cross-species conservation of androgen receptor-based biological activity. Toxicological Sciences 193, 131-145.
| Crossref | Google Scholar | PubMed |
Wang Z, Dinh D, Scott WC, Williams ES, Ciarlo M, DeLeo P, Brooks BW (2019) Critical review and probabilistic health hazard assessment of cleaning product ingredients in all-purpose cleaners, dish care products, and laundry care products. Environment International 125, 399-417.
| Crossref | Google Scholar | PubMed |
Wang Z, Berninger JP, You J, Brooks BW (2020) One uncertainty factor does not fit all: identifying mode of action and species specific acute to chronic ratios for aquatic life. Environmental Pollution 262, 114262.
| Crossref | Google Scholar | PubMed |
Weltje L, Simpson P, Gross M, Crane M, Wheeler JR (2013) Comparative acute and chronic sensitivity of fish and amphibians: a critical review of data. Environmental Toxicology and Chemistry 32, 984-994.
| Crossref | Google Scholar | PubMed |
Wheeler JR, Maynard SK, Crane M (2014) An evaluation of fish early life stage tests for predicting reproductive and longer-term toxicity from plant protection product active substances. Environmental Toxicology and Chemistry 33, 1874-1878.
| Crossref | Google Scholar | PubMed |
Williams ES, Berninger JP, Brooks BW (2011) Application of chemical toxicity distributions to ecotoxicology data requirements under REACH. Environmental Toxicology and Chemistry 30, 1943-1954.
| Crossref | Google Scholar | PubMed |
Williams AJ, Grulke CM, Edwards J, McEachran AD, Mansouri K, Baker NC, Patlewicz G, Shah I, Wambaugh JF, Judson RS, Richard AM (2017) The CompTox Chemistry Dashboard: a community data resource for environmental chemistry. Journal of Cheminformatics 9, 61.
| Crossref | Google Scholar |
Wolf DC, Bhuller Y, Cope R, Corvaro M, Currie RA, Doe J, Doi A, Hilton G, Mehta J, Saltmiras D, Sewell F, Trainer M, Déglin SE (2022) Transforming the evaluation of agrochemicals. Pest Management Science 78, 5049-5056.
| Crossref | Google Scholar | PubMed |
Wu J, D’Ambrosi S, Ammann L, Stadnicka-Michalak J, Schirmer K, Baity-Jesi M (2022) Predicting chemical hazard across taxa through machine learning. Environment International 163, 107184.
| Crossref | Google Scholar | PubMed |
Zubrod JP, Galic N, Vaugeois M, Dreier DA (2023) Physiological variables in machine learning QSARs allow for both cross-chemical and cross-species predictions. Ecotoxicology and Environmental Safety 263, 115250.
| Crossref | Google Scholar | PubMed |
