Retrospective Study of the Incidence of Spontaneous Nonneoplastic Lesions in Wistar Rats (Mlac:WR) from 90-Day Oral Gavage Studies
Keywords:
Wistar rat, Spontaneous lesions, Nonneoplastic, 90-day oral toxicity studiesAbstract
Historical control data (HCD) of background lesions provide useful information on the range and incidence of spontaneous lesions in a specific animal model. The microscopic examination data were collected from 84 male and 86 female Wistar rats (Mlac:WR) used in 90-day oral gavage studies conducted at the National Laboratory Animal Center, Mahidol University (NLAC-MU), from 2023 to 2025. We retrospectively evaluated spontaneous nonneoplastic findings in the vital organs for toxicity assessment. This study reported the organ weights, numbers, incidence, and severity of the spontaneous nonneoplastic findings in the Wistar rat, aiming to establish a contemporaneous three-year database on the incidence of background lesions, as part of microscopic alterations, and to aid in the future evaluation of 90-day oral toxicity studies. The most common spontaneous findings observed in both sexes were minimal to moderate multifocal hemorrhage in the thymus (32.14% males, 22.09% females), minimal to moderate hemorrhage in bronchus-associated lymphoid tissue (BALT) (23.81% males, 17.44% females), ectopic adrenocortical tissue in the adrenal cortex (21.43% males, 19.77% females), and minimal to moderate dilation of gastric glands in the stomach (23.81% males, 12.79% females). We also reported sex-related spontaneous lesions, including hyaline casts in the renal cortex (23.81% males, 1.16% females), tubular basophilia in the renal cortex (9.52% males, 1.16% females), and ectopic thymus tissue in the thyroid gland (9.52% males, 0% females). In summary, HCD of background lesions in Wistar rats from 90-day oral gavage studies is essential for accurate histopathological interpretation in 90-day oral toxicity studies.
References
Ajayi AF, Akhigbe RE. Staging of the estrous cycle and induction of estrus in experimental rodents: an update. Fertil Res Pract. 2020;6:5.
Berridge BR, Mowat V, Nagai H, Nyska A, Okazaki Y, Clements PJ, et al. Non-proliferative and proliferative lesions of the cardiovascular system of the rat and mouse. J Toxicol Pathol. 2016;29(3 Suppl):1S-47S.
Bevin Z. Peritoneum, retroperitoneum, mesentery, and abdominal cavity. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 71-7.
Black HE, Moch RW, Frantz JD. Preparation of the pathology report for a toxicity study. In: Haschek WM, Rousseaux CG, Wallig MA, editors. Haschek and Rousseaux’s Handbook of Toxicologic Pathology. 3rd ed. London: Academic Press; 2013. p. 843-51.
Bockenstedt M, Kumar A, Laast V, Sharma A. Historical control background incidence of spontaneous nonneoplastic lesions of Sprague Dawley rats used in 104-week toxicity studies. Poster session presented at: Toxicologic pathology of the hematopoietic system. STP 41st annual symposium. Austin, TX; 2022.
Bockenstedt M, Kumar A, Laast V, Sharma A. Historical control background incidence of spontaneous nonneoplastic lesions of Sprague Dawley rats in 104-week carcinogenicity studies. Toxicol Pathol. 2025;53(2):173-86.
Boonmayaphan M, Butrat P. Postmortem macroscopic changes in rats under rat house conditions. J Appl Anim Sci. 2022;15(1):9-22.
Brändli-Baiocco A, Balme E, Bruder M, Chandra S, Hellmann J, Hoenerhoff MJ, et al. Nonproliferative and proliferative lesions of the rat and mouse endocrine system. J Toxicol Pathol. 2018;31(3 Suppl):1S-95S.
Creasy D, Bube A, de Rijk E, Kandori H, Kuwahara M, Masson R, et al. Proliferative and nonproliferative lesions of the rat and mouse male reproductive system. Toxicol Pathol. 2012;40(6 Suppl):40S-121S.
Dixon D, Alison R, Bach U, Colman K, Foley GL, Harleman JH, et al. Nonproliferative and proliferative lesions of the rat and mouse female reproductive system. J Toxicol Pathol. 2014;27(3-4 Suppl):1S-107S.
Foster JR. Liver. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 81-105.
Frazier KS, Seely JC, Hard GC, Betton G, Burnett R, Nakatsuji S, et al. Proliferative and nonproliferative lesions of the rat and mouse urinary system. Toxicol Pathol. 2012;40(4 Suppl):14S-86S.
Frith CH, Ward JM, Chandra M, Losco PE. Non-proliferative lesions of the hematopoietic system in rats. In: Guides for Toxicologic Pathology. Washington DC: STP/ARP/AFIP; 2000. p. 1-21.
Herbert RA, Janardhan KS, Pandiri AR, Cesta MF, Chen V, Miller RA. Lung, pleura, mediastinum. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 437-66.
Ibrahim R, Nyska A, Elmore SA, Boyle M, Ramot Y. Interpretative challenges in animal studies: review of case studies and implications for toxicologic pathology. Toxicol Pathol. 2025;53(5):440-55.
Iwaku K, Noh JY, Watanabe N, Sugino K, Ito K. Age-related reduction of the prevalence of ectopic intrathyroidal thymus in children and its size reduction with age. Thyroid Sci. 2024;1(1):2590-3000.
Keenan C, Elmore S, Francke-Carroll S, Kemp R, Kerlin R, Peddada S, et al. Best practices for use of historical control data of proliferative rodent lesions. Toxicol Pathol. 2009;37(5):679-93.
Khan KM, Hard GC, Alden CL. Kidney. In: Haschek WM, Rousseaux CG, Wallig MA, editors. Haschek and Rousseaux's Handbook of Toxicologic Pathology. 3rd ed. London: Academic Press; 2013. p. 1667-773.
Long GG, Hardisty JF. Regulatory forum opinion piece: thresholds in toxicologic pathology. Toxicol Pathol. 2012;40(7):1079-81.
McInnes EF, Scudamore CL. Review of approaches to the recording of background lesions in toxicologic pathology studies in rats. Toxicol Lett. 2014;229(1):134-43.
Mense MG, Boorman GA. Thyroid gland. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 669-86.
Nakazawa M, Tawaratani T, Uchimoto H, Kawaminami A, Ueda M, Shinoda Y, et al. Spontaneous neoplastic lesions in aged Sprague-Dawley rats. Exp Anim. 2001;50(2):99-103.
Nolte T, Brander-Weber P, Dangler C, Deschl U, Elwell MR, Greaves P, et al. Nonproliferative and proliferative lesions of the gastrointestinal tract, pancreas and salivary glands of the rat and mouse. J Toxicol Pathol. 2016;29(1 Suppl):1S-125S.
Piao Y, Liu Y, Xie X. Change trends of organ weight background data in Sprague Dawley rats at different ages. J Toxicol Pathol. 2013;26(1):29-34.
Rebelatto MC. Spleen, lymph nodes, and thymus. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 469-91.
Renne R, Brix A, Harkema J, Herbert R, Kittel B, Lewis D, et al. Proliferative and nonproliferative lesions of the rat and mouse respiratory tract. Toxicol Pathol. 2016;37(7 Suppl):5S-73S.
Schafer KA, Eighmy J, Fikes JD, Halpern WG, Hukkanen RR, Long GG, et al. Use of severity grades to characterize histopathologic changes. Toxicol Pathol. 2018;46(3):256-65.
Seely JC, Hard GC, Blankenship B. Kidney. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 125-66.
Singh S, Dwivedi R, Chaturvedi V. Influence of vehicles used for oral dosing of test molecules on the progression of Mycobacterium tuberculosis infection in mice. Antimicrob Agents Chemother. 2012;56(11):6026-8.
Srimangkornkaew P, Suwannasaroj K, Yottharat P, Sirimontaporn A. Historical control data from repeated dose 90-days oral toxicity studies of Wistar rats (Mlac:WR). Bull Dept Med Sci. 2020;63(3):595-606.
Suttie AW, Sutcliffe C. Adrenal gland. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 649-67.
Taylor I, Mowat V. Comparison of longevity and common tumor profiles between Sprague-Dawley and Han Wistar rats. J Toxicol Pathol. 2020;33(3):189-96.
Thoolen B, Maronpot RR, Harada T, Nyska A, Rousseaux C, Nolte T, et al. Proliferative and nonproliferative lesions of the rat and mouse hepatobiliary system. Toxicol Pathol. 2010;38(7 Suppl):5S-81S.
Uehara T, Elmore SA, Szabo KA. Esophagus and stomach. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 35-50.
Vidal JD, Dixon D. Ovary. In: Suttie AW, editor. Boorman's Pathology of the Rat. 2nd ed. London: Academic Press; 2018. p. 523-36.
Westwood FR. The female rat reproductive cycle: a practical histological guide to staging. Toxicol Pathol. 2008;36(3):375-84.
Willard-Mack CL, Elmore SA, Hall WC, Harleman J, Kuper CF, Losco P, et al. Nonproliferative and proliferative lesions of the rat and mouse hematolymphoid system. Toxicol Pathol. 2019;47(6):665-783.
Wolf DC, Mann PC. Confounders in interpreting pathology for safety and risk assessment. Toxicol Appl Pharmacol. 2005;202(3):302-8.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Mahidol University Faculty of Veterinary Science

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Published articles are under the copyright of the Journal of Applied Animal Science (JAAS) effective when the article is accepted for publication. The editorial boards claim no responsibility for the content or opinions expressed by the authors of individual articles in this journal. Partially or totally publication of an article elsewhere is possible only after the consent from the editors.