The second session of the 2nd Joint BSTP/ESTP Toxicologic Pathology Congress, Manchester, UK, September 23-26, 2025, entitled “New Approach Methodologies for Carcinogenicity Evaluation,” was dedicated to innovative strategies for assessing carcinogenic risks in various substances, particularly in drug development and agrochemicals. The two-year rodent cancer bioassay in two species (generally rats and mice) is currently the standard method for assessing the carcinogenic potential of agrochemicals for humans. However, this method has some weaknesses and is subject to ethical and scientific debate. Attempts to waive those studies have been proposed, but more relevant methods using less or preferably no animals are still being sought. The session featured five key presentations that explored cutting-edge methodologies aimed at improving the accuracy and reliability of carcinogenicity predictions. Below is a summary of each talk presented.
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2.
AtwoodSTLunnRMGarnerSCJahnkeGD.New perspectives for cancer hazard evaluation by the report on carcinogens: a case study using read-across methods in the evaluation of haloacetic acids found as water disinfection by-products. Environ Health Perspect. 2019;127(12):125003. doi:10.1289/ehp5672
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BatesSEvansKVDelsingLWongRCornishGBahjatM.Immune safety challenges facing the preclinical assessment and clinical progression of cell therapies. Drug Discov Today. 2024;29(12):104239. doi:10.1016/j.drudis.2024.104239
4.
BouwmeesterMCStreekstraEJStaalYCMvan EngelenJGMWestraJLuijtenM. New approach methodologies in next-generation risk assessment and safe-and-sustainable-by-design approaches – a multistakeholder workshop report. NAM Journal. 2026. Advance online publication. doi:10.1016/j.namjnl.2026.100104
5.
CairnsJLeonardEKhanK, et al. Optimal experimental design for efficient toxicity testing in microphysiological systems: a bone marrow application. Front Pharmacol. 2023;14:1142581. doi:10.3389/fphar.2023.1142581
6.
CortonJCMitchellCAAuerbachS, et al. A collaborative initiative to establish genomic biomarkers for assessing tumorigenic potential to reduce reliance on conventional rodent carcinogenicity studies. Toxicol Sci. 2022;188(1):4-16. doi:10.1093/toxsci/kfac041
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DavidRGeeSKhanKWilsonADohertyA.Three dimensional and microphysiological bone marrow models detect in vivo positive compounds. Sci Rep. 2021;11(1):21959. doi:10.1038/s41598-021-01400-5
8.
DoktorovaTYEllinger-ZiegelbauerHVinkenMVanhaeckeTvan DelftJKleinjansJ, et al. Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver. Arch Toxicol. 2012;86(9):1399-1411. doi:10.1007/s00204-012-0847-x
9.
Ellinger-ZiegelbauerHGmuenderHBandenburgAAhrHJ.Prediction of a carcinogenic potential of rat hepatocarcinogens using toxicogenomics analysis of short-term in vivo studies. Mutat Res. 2008;637(1-3):23-39. doi:10.1016/j.mrfmmm.2007.06.010
10.
GottmannEKramerSPfahringerBHelmaC.Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments. Environ Health Perspect. 2001;109(5):509-514. doi:10.1289/ehp.01109509
11.
HartwigAArandMEpeB, et al. Mode of action-based risk assessment of genotoxic carcinogens. Arch Toxicol. 2020;94(6):1787-1877. doi:10.1007/s00204-020
12.
HendriksenCFM. The ethics of research involving animals: a review of the Nuffield Council on Bioethics Report from a three Rs perspective. Altern Lab Anim. 2005;33(6):659-662. doi:10.1177/026119290503300604
13.
HermsAFernandez-AntoranDAlcoleaMP, et al. Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium. Nat Genet. 2024;56:2158-2173. doi:10.1038/s41588-024
14.
HeusinkveldHJBraakhuisHGommansR, et al. Towards a mechanism-based approach for the prediction of nongenotoxic carcinogenic potential of agrochemicals. Crit Rev Toxicol. 2020;50(9):725-739. doi:10.1080/10408444.2020.1841732
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JacobsMNColacciACorviR, et al. Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens. Arch Toxicol. 2020;94(8):2899-2923. doi:10.1007/s00204-020
16.
LiHHYaukCLChenR, et al. TGx-DDI, a transcriptomic biomarker for genotoxicity hazard assessment of pharmaceuticals and environmental chemicals. Front Big Data. 2019;2:36. doi:10.3389/fdata.2019.00036
17.
LuJChoiKEremeevM, et al. Large language models their applications in drug discovery development: a primer. Clin Transl Sci. 2025;18(4):e70205. doi:10.1111/cts.70205
18.
LynchAMZanoniTBSalkJJ, et al. Next Generation Sequencing Workshop at the Royal Society of Medicine (London, May 2022): how genomics is on the path to modernizing genetic toxicology. Mutagenesis. 2023;38(4):192-200. doi:10.1093/mutage/gead012
19.
MaddenJCEnochSJPainiACroninMTD. A review of In Silico tools as alternatives to animal testing: principles, resources and applications. Altern Lab Anim. 2020;48(4):146-172. doi:10.1177/0261192920965977
20.
MarchettiFCardosoRChenCL, et al. Error-corrected next generation sequencing – promises and challenges for genotoxicity and cancer risk assessment. Mutat Res. 2023;792(suppl 3):108466. doi:10.1016/j.mrrev.2023.108466
21.
MaronePAHallWCHayesAW.Reassessing the two-year rodent carcinogenicity bioassay: a review of the applicability to human risk and current perspectives. Regul Toxicol Pharmacol. 2014;68(1):108-118. doi:10.1016/j.yrtph.2013.11.011
22.
OECD. Users’ handbook supplement to the guidance document for developing and assessing adverse outcome pathways (OECD series on adverse outcome pathways No 1). OECD Publishing; 2018. doi:10.1787/5jlv1m9d1g32-en
23.
ParsonsBL.Clonal expansion of cancer driver gene mutants investigated using advanced sequencing technologies. Mutat Res. 2024;794:1085145. doi:10.1016/j.mrrev.2024.108514
24.
SchieferdeckerSVockE.Quantum Chemical Evaluation and QSAR modeling of N-nitrosamine carcinogenicity. Chem Res Toxicol. 2025;38(2):325-339. doi:101021acschemrestox4c00476
25.
TiceRRBassanAAmbergA, et al. In Silico approaches in carcinogenicity hazard assessment: current status and future needs. Comput Toxicol. 2021;20:100191. doi:10.1016/j.comtox.2021.100191
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VinkenMKnapenDVergauwenLHengstlerJGAngrishMWhelanM.Adverse outcome pathways: a concise introduction for toxicologists. Arch Toxicol. 2017;91(11):3697-3707. doi:10.1007/s00204-017
27.
ZhangSParsonsBLFitzgeraldD, et al. Transferability, reproducibility and sensitivity of mutation quantification by duplex sequencing. Environ Mol Mutagen. 2025;66(6-7):311-326. doi:10.1002/em.70020
