A 28-day subacute oral toxicity study of Apis cerana (Fabricius) honey in Wistar rats

The use of honey as food and medicine is widespread, but insufficient data support that it is safe, especially when consumed in high doses. As a result, the present work aimed to investigate the potential toxicity using a repeated dose oral toxicity study. In the toxicity study, Wistar rats were divided into five groups, and orally administered with distilled water (control), 3, 6, 12, and 24 g/kg body weight (BW)/day of honey for 28 days in a row. Body weight, food consumption, clinical pathology, and histopathology were then examined. Significant suppression of body weight, food consumption, and body weight gain was observed at the dose of 24 g/kg BW in both sexes. Honey administration had no statistically significant effect on any of the haematological parameters. The clinical observations, blood coagulation and biochemical parameters, target organs, or histopathology did not reveal any additional nor other treatment-related adverse effects. Mild pathological changes in hepatic tissues were observed in the control, 12, or 24 g/kg BW dose groups, which were common spontaneous lesions unrelated to honey treatment. In the 24 g/kg BW group, one male rat showed non-specific reactions such as focal basophilic change of renal tubule cells, which were also regarded as spontaneous lesions. Based on these results, the no-observed-adverse-effect level (NOAEL) of honey in this repeat dose oral toxicity study was determined to be 12 g/kg BW in both sexes of Wistar rats.