Chronic Toxicity Studies of the Potential Cancer Preventive 2-(Difluoromethyl)-DL-Ornithine

January 1994 in “ Toxicological Sciences ”

James A. Crowell, Edwin I. Goldenthal, Gary J. Kelloff, WINFRED F. MALONE, CHARLES W. BOONE

2-(difluoromethyl)-dl-ornithine alopecia hyperkeratosis skin issues

TLDR Lower dosages of 2-(difluoromethyl)-dl-ornithine might reduce side effects, supporting further research.

The study investigated the chronic toxicity of 2-(difluoromethyl)-dl-ornithine, a potential cancer preventive agent, in rats and dogs. In rats, high dosages (400, 800, and 1600 mg/kg) over 52 weeks caused weight loss, increased platelets, alopecia, skin issues, liver necrosis, and gastric inflammation, with 400 mg/kg being the no-effect dose. In dogs, dosages of 50, 100, and 200 mg/kg led to conjunctivitis, hyperkeratosis, alopecia, and cystic intestinal crypts, but a no-effect dose was not identified. Despite these toxicities, the study suggested that lower dosages might minimize adverse effects, supporting further clinical development of the compound.

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