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An Overview of Subchronic and Chronic Toxicology

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Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays

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Abstract

This chapter will explore the regulatory requirement for subchronic and chronic toxicology studies, their design and purpose. The various routes of administration and volumes as well as dose level selection will be touched upon. The importance of species and strain selection will also be discussed with a particular focus on small molecule programs that will require a carcinogenicity study as part of the package. The requirement for subchronic and chronic juvenile studies and endpoints for some programs will also be highlighted.

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References and Further Reading

  • Adamou A, Copeman C (2016) Comparison of Selected Clinical Pathology Parameters in Two Strains of Rats in Different Cage Environments Used in Toxicology Studies. Presented at the Society of Toxicology (SOT) 55th Annual Meeting, New Orleans, Louisiana, USA

    Google Scholar 

  • Adamou A, Copeman C, Brochu C (2020) Comparison of Historical Control Data in CD-1 Mice When Single vs Group-Housed and Considerations for Successful Group-Housing of Male Mice. Presented at the Society of Toxicology (SOT) 59th Annual Meeting, Anaheim, California, USA

    Google Scholar 

  • Addendum to the Guideline on Testing for Carcinogenicity of Pharmaceuticals. ICH S1B(R1). ICH Consensus Guideline

    Google Scholar 

  • American Association for Laboratory Animal Science. Training Manual (1992). Series, Vol. II Laboratory Animal Technician, p 22

    Google Scholar 

  • Bolon B, Garman RH, Pardo ID, Jensen K, Sills RC, Roulois A, Radovsky A, Bradley A, Andrews-Jones L, Butt M, Gumprecht L (2013) STP position paper: recommended practices for sampling and processing the nervous system (brain, spinal cord, nerve, and eye) during nonclinical general toxicity studies. Toxicol Pathol 41(7):1028–1048. https://doi.org/10.1177/0192623312474865. Epub 2013 Mar 7. PMID: 23475559

    Article  PubMed  Google Scholar 

  • Committee for Medicinal Products for Human Use (CHMP). Note for Guidance on Repeated Dose Toxicity. CPMP/SWP/1042/99corr

    Google Scholar 

  • Emmera KM, Russarta KLG, Walker WH II, Nelsonc RJ, DeVriesd AC (2018) Effects of light at night on laboratory animals and research outcomes. Behav Neurosci 132(4):302–314. https://doi.org/10.1037/bne0000252

    Article  Google Scholar 

  • FDA Guidance for Industry (2006) Nonclinical Safety Evaluation of Pediatric Drug Products. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Rockville

    Google Scholar 

  • Foster JR, Frost D (2018) The history of the rat. In: Suttie AW, Leininger AR, Bradley A (eds) Boorman’s pathology of the rat, reference and atlas, 2nd edn. Academic Press, Elsevier Inc., pp 7–12

    Chapter  Google Scholar 

  • Gauvin DV, Dalton JA, Harter ML, Holdsworth D, May J, Tapp R, Zimmermann ZJ, Kilgus Q, Baird TJ (2019) Relative equivalence of CNS safety (FOB) assessment outcomes in male and female Wistar-Han and Sprague-Dawley rats. J Pharmacol Toxicol Methods 95:2–11

    Article  CAS  PubMed  Google Scholar 

  • Gendron RM, Parente C, Smith SY, Copeman C (2010) Methods for Successful Conduct of Chronic Toxicology Intravenous Tail Vein Injection Studies in Rats. Presented at the Society of Toxicology (SOT) 49th Annual Meeting, Salt Lake City, Utah, USA

    Google Scholar 

  • Guidance for industry: Statistical aspects of the design, analysis, and interpretation of chronic rodent carcinogenicity studies of pharmaceuticals (May 2001) Draft guidelines. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Rockville

    Google Scholar 

  • Hayakawa K, Mimura Y, Tachibana S, Furuya M, Kodama T, Aoki T et al (2013) A study for collecting background data on Wistar Hannover [Crl:WI(Han)] rats in general toxicity studies -comparative data to Sprague Dawley rats. J Toxicol Sci 38(6):855–873

    Article  PubMed  Google Scholar 

  • ICH Harmonised Tripartite Guideline M3 (R2). Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals and Marketing Authorization for Pharmaceuticals

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S1a. Guideline on the need for carcinogenicity studies of pharmaceuticals

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S1b. Testing for carcinogenicity of pharmaceuticals

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S1c. Dose selection for carcinogenicity of pharmaceuticals

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S3a. Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S4. Duration of Chronic Toxicity Testing in Animals (Rodent and Non Rodent Toxicity Testing)

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S4. Duration of Chronic Toxicity Testing in Animals (Rodent and Non Rodent Toxicity Testing). Should be included for rodent studies ≥ 6 months and for non-rodent studies ≥ 9 months

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S6 (R1). Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S7A. Guideline on Safety Pharmacology Studies for Human Pharmaceuticals

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S7B. The Non-Clinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S8. Notes for Guidance on Immunotoxicity Testing of Human Pharmaceuticals

    Google Scholar 

  • ICH Harmonised Tripartite Guideline S9. Nonclinical Evaluation for Anticancer Pharmaceuticals

    Google Scholar 

  • ICH Harmonized Guideline on Nonclinical Safety Testing In Support Of Development Of Paediatric Pharmaceuticals. Adopted 14 Apr 2020

    Google Scholar 

  • Japanese Guidelines for Nonclinical Studies of Drugs Manual (1995) Guidelines for Toxicity Studies of Drugs (Chapter 3, Repeated Dose Toxicity Studies)

    Google Scholar 

  • Lewis RW, Billington R, Debryune E, Gamer A, Lang B, Carpanini F (2002) Recognition of adverse and nonadverse effects in toxicity studies. Toxicol Pathol 30:66. https://doi.org/10.1080/01926230252824725

    Article  CAS  PubMed  Google Scholar 

  • Morse MA (2022) Rationale for Use of the Charles River Wistar Han Rat as the Default Rat Strain for Safety Testing when a Carcinogenicity Study is Required

    Google Scholar 

  • Noritake K, Ikeda T, Ito K, Miwa Y, Senuma M, Takashima H, Tateishi T, Hisada S, Maki E (2013) Study for collecting background data on Wistar Hannover [Crl:WI(Han)] rats in embryo-fetal development studies – comparative data to Sprague Dawley rats. J Toxicol Sci 38(6):847–854

    Article  PubMed  Google Scholar 

  • OECD (1998) Test No. 409: Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris. https://doi.org/10.1787/9789264070721-en

  • OECD (2018a) Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris. https://doi.org/10.1787/9789264070707-en

  • OECD (2018b) Test No. 451: Carcinogenicity Studies, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris. https://doi.org/10.1787/9789264071186-en

  • Rollin BE, Kesel ML (1995) The experimental animal in biomedical research, Care, husbandry, and well-being, an overview by species, vol 2. CRC Press

    Google Scholar 

  • Svendsen, P. and Hau, J. (1994) Selection and Handling of Animals in Biomedical Research. In Handbook of Laboratory Animal Sciences, vol. 1. pp 233–253

    Google Scholar 

  • US Food and Drug Administration Study. Data Technical Conformance Guide

    Google Scholar 

  • Van Dycke KCG, Rodenburg W, van Oostrom CTM, van Kerkhof LWM, Pennings JLA, Roenneberg T, van Steeg H, van der Horst GTJ (2015) Chronically alternating light cycles increases breast cancer risk in mice. Curr Biol 25:1932–1937

    Article  PubMed  Google Scholar 

  • Weber K (2017) Differences in types and incidence of neoplasms in Wistar Han and Sprague-Dawley rats. Toxicol Pathol 45(1):64–75

    Article  PubMed  Google Scholar 

  • Weber K, Razinger T, Hardisty JF, Mann P, Martel KC, Frische EA, Blumbach K, Hillen S, Song S, Anzai T, Chevalier H (2011) Differences in rat models used in routine toxicity studies. Internat J Toxicol 30(2):162–173

    Article  Google Scholar 

  • Wilsson M, Olovson SG, Forshult E (1998) Method for long term cerebrospinal fluid collection in the conscious dog. J Invest Surg 11(3):207–214. https://doi.org/10.3109/08941939809098035

    Article  Google Scholar 

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Authors and Affiliations

  1. Charles River Laboratories, Senneville, QC, Canada

    Anna Adamou

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  1. Anna Adamou
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Correspondence to Anna Adamou .

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Editors and Affiliations

  1. FJH Safety Pharm Consulting, Dieburg, Hessen, Germany

    Franz J. Hock

  2. Cytokinetics (United States), South San Francisco, CA, USA

    Michael K. Pugsley

Section Editor information

  1. Toxicology, Cytokinetics, South San Francisco, CA, USA

    Michael K. Pugsley

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Adamou, A. (2023). An Overview of Subchronic and Chronic Toxicology. In: Hock, F.J., Pugsley, M.K. (eds) Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays. Springer, Cham. https://doi.org/10.1007/978-3-030-73317-9_118-1

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  • DOI: https://doi.org/10.1007/978-3-030-73317-9_118-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-73317-9

  • Online ISBN: 978-3-030-73317-9

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