Title: Three Month Oral (GAVAGE) Toxicity Study of Halofantrine Hydrochloride in Mice
Abstract: Abstract : This study evaluated the toxicity of halofantrine hydrochloride in B6C3F1 mice following thirteen weeks of daily oral (gavage) administration. Halofantrine HCl1 is being developed by WRAIR as an oral antimalarial treatment. Dose levels studied were 0 (vehicle control), 1, 5 and 25 mg/kg/day, and were based on a four week dose range-finding test in which mortality occurred at 100 mg/kg/day with anemia present at 20 and to a minimal extent at 4 mg/kg/day. The drug or vehicle was administered to 10 mice/sex/group. The animals were = 8 weeks old and weighed 23.0 - 25.8 g (males) and 17.7 - 21.7 g (females) at treatment initiation. No clinical signs of toxicity were observed and body weight gains and food consumption were not affected by test article treatment. Treatment-related ophthalmic changes were also not observed. The primary treatment-related effects of halofantrine were microcytic anemia and marginal changes in the liver. An increased severity and/or incidence of hepatic glycogen depletion was observed in high dose animals compared to control mice. In addition, individual cell necrosis was seen in two high dose females but not males. These marginal liver changes were accompanied by statistically insignificant increased serum ALT levels and decreased total protein and albumin levels in high dose males. Marginal treatment-related anemia, including decreases in hemoglobin, hematocrit, mean corpuscular volume (MCV) and/or mean corpuscular hemoglobin (MCH), in the absence of a reduction in RBC count, was observed in high dose animals. These microcytic anemic changes without corresponding compensatory responses or histopathologic changes in bone marrow are suggestive of an iron-deficiency anemia. Very slight but statistically significant microcytosis was also seen in mid dose males, but was not considered biologically significant.
Publication Year: 1995
Publication Date: 1995-05-19
Language: en
Type: article
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot