Abstract
Senna (Tinnevelly senna fruits), a known laxative derived from plants, was administered by gavage to Sprague-Dawley (Crl:CD® (SD) BR) rats once daily at dose levels of 0, 25, 100 and 300 mg/kg/day for up to 104 consecutive weeks. Based upon clinical signs related to the laxation effect of senna, the highest dose (300 mg/kg/day) was considered to be a maximum tolerated dose. Sixty animals per sex were assigned to the control and dose groups. Assessments included clinical chemistry, hematology, full histology (control and high-dose groups; in addition, low and mid dose: intestinal tract, adrenals, liver, kidneys, brain and gross lesions) and toxicokinetics. The primary treatment-related clinical observation was mucoid feces seen at 300 mg/kg/day. When compared to controls, animals administered 300 mg/kg/day had slightly reduced body weights, increased water consumption and notable changes in electrolytes in serum (increases in potassium and chloride) and urine (decreases in sodium, potassium and chloride). The changes in electrolytes are most likely physiologic adaptations to the laxative effect of senna. At necropsy, dark discoloration of the kidneys was observed in animals in all treated groups. Histological changes were seen in the kidneys of animals from all treated groups and included slight to moderate tubular basophilia and tubular pigment deposits. In addition, for all treated groups, minimal to slight hyperplasia was evident in the colon and cecum. These histological changes, together with the changes seen in the evaluation of clinical chemistry and urine parameters, have been shown to be reversible in a previous 13-week rat study of senna. No treatment-related neoplastic changes were observed in any of the examined organs. Based upon these data, it is concluded that senna is not carcinogenic even after daily administration for 2 years at dosages of up to 300 mg/kg/day in Sprague-Dawley rats.
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Acknowledgements
The authors wish to thank the technical staff of CTBR and MADAUS AG for their support. This study was conducted at CTBR Bio-Research Inc. (CTBR), Senneville, Quebec, Canada, H9X 3R3. All procedures were in compliance with the Good Laboratory Practice Regulations of the United States Food and Drug Administration (21 CFR Part 58). The study was also performed in accordance with the Animal Health regulations, on the harmonization of laws, regulations or administrative provisions relating to the protection of animals used for experimental and other scientific purposes, and in accordance with the guidelines of the USA National research Council and the Canadian Council on Animal care (CCAC).
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Mitchell, J.M., Mengs, U., McPherson, S. et al. An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat. Arch Toxicol 80, 34–44 (2006). https://doi.org/10.1007/s00204-005-0021-9
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DOI: https://doi.org/10.1007/s00204-005-0021-9