The paradox of human equivalent dose formula: A canonical case study of abrus precatorius aqueous leaf extract in monogastric animals

摘要

There is abundant literature on the toxicity of A. precatorius seeds. However there is a need to define the toxicity limit of the Abrus precatorius leaf in monogastric animals. Human Equivalent Dose (HED) which is equal to animal dose multiplied by animal km (metabolism constant) divided by human km was used to project the LD50 of fifteen monogastric animals , where human km factor is body weight (kg) divided by body surface area (m2). Human Equivalent No-observable Adverse Effect Doses were determined by multiplying the animal no-observable adverse effect dose by animal weight (Wa) divided by human weight (Wh). The LD50 of the aqueous leaf extract of Abrus precatorius in mice was estimated to be between 2559.5 and 3123.3 mg/kg body weight. The LD50 extrapolated from mouse to rat (1349.3-1646.6 mg/kg), hamster (1855.3-2264.1 mg/kg), guinea pig (1279.5-1561.4 mg/kg), rabbit (618.4-754.7 mg/kg), monkey (593.7-724.5 mg/kg), cat (392.7-479.2 mg/kg), dog and baboon (371.1-452.8 mg/kg), child (297-362 mg/kg) and adult human (197.8-241.5 mg/kg) body weight respectively could be a reality. The therapeutic safe dose range for the animals was 1-12.5 mg/kg body weight for a period of 7 days, but at a dose (≤ 200 mg/kg body weight) the leaf extract showed haematinic effect. However, at a higher dose ( 200 mg/kg), the extract showed haemolytic activity in rats, whereas at a dose (≥25.0 mg/kg), the leaf extract might be organotoxic in hamster, guinea pig, rabbit, monkey, cat, dog, baboon, child and adult human if administered orally for a period of 7 days.