Toxicity of the alkylating agent bendamustin

• Published in: Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement Vol. 8; p. 504
• Main Authors: Horn, U, Härtl, A, Güttner, J, Hoffmann, H
• Format: Journal Article
• Language: English
• Published: Germany 1985
• Subjects: Alkylating Agents - toxicity; Animals; Atrophy; Bendamustine Hydrochloride; Body Weight - drug effects; Chlorambucil - toxicity; Digestive System - drug effects; Digestive System - pathology; Kidney Diseases - chemically induced; Lethal Dose 50; Lymphoid Tissue - drug effects; Lymphoid Tissue - pathology; Male; Mice; Neutropenia - chemically induced; Nitrogen Mustard Compounds - toxicity; Rats; Testis - drug effects; Testis - pathology
• ISSN: 0171-9750
• DOI: 10.1007/978-3-642-69928-3_120

In acute toxicity studies the maximum tolerated dose (MTD), the LD50 and the LD100 of Bendamustin were determined in rats and mice after i.v. and oral administration. In a subchronic study male rats were given Bendamustin for 28 days at oral dose levels of 5, 10, 20 or 40 mg/kg/day. Chlorambucil was used as a standard at dose levels of 1, 5 and 10 mg/kg/day. Bodyweight gain, food and water intake, hematology, clinical chemistry and histopathology were evaluated. With quantitative differences the main target organs for both compounds were the bone marrow, the kidney, the intestine and the lymphatic system. Additionally, Chlorambucil caused a significant atrophy of the testes and a slight atrophy of the pancreas at a dose of 5 mg/kg/day. In conclusion, the data obtained may be used as a base to evaluate the therapeutic range of Bendamustin compared to Chlorambucil for the oral route.