Publication: Repeated dose oral toxicity study of purified 5-hydroxymethylfurfural on the female reproductive system of nulliparous sprague dawley rats
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Date
2026-01
Authors
Sofian, Nur Athirah Ainaa
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Abstract
5-Hydroxymethylfurfural (HMF) is a heat‑generated contaminant commonly found in carbohydrate‑rich foods and can accumulate in over‑processed or long‑stored products. Its safety concerns have increased following evidence of systemic toxicity at high experimental doses in rodents. This study aimed to evaluate the repeated-dose oral toxicity of purified HMF on the female reproductive system in 32 female nulliparous Sprague Dawley (SD) rats (n=8/group). After confirming satisfactory baseline data during the pre-treatment periods, the rats were treated orally by gavage with HMF (1000 mg/kg and 2000 mg/kg), isotretinoin (25 mg/kg, positive control) or distilled water (vehicle control) for 28 consecutive days. A substantial number of parameters were assessed including the fate of females (survivability or death), general health and behaviour, body weight patterns and oestrous cycle length, macroscopical assessment of reproductive organs (cervix, uterus, fallopian tubes and ovaries) as well as the absolute and relative weights of reproductive organs in the female SD rats. The results obtained demonstrated that no significant differences were observed in clinical signs, behaviour, and body‑weight gain among all rats. The mean length of the oestrous cycle was not statistically altered, although inconsistent cycle irregularities occurred in most HMF- and isotretinoin-treated rats. The reproductive organ weights of cervix, uterus, fallopian tubes and ovary showed no marked treatment‑related changes across all groups. In conclusion, repeated oral exposure of purified HMF at 1000 and 2000 mg/kg/day for 28 days did not produce overt reproductive toxicity in adult female SD rats, though disturbances in oestrous cyclicity were observed. Further studies should be conducted to investigate the mechanisms underlying these subtle oestrous cycle alterations, to refine safety assessments for high‑level dietary HMF exposure thus offering insights for a better understanding of these occurrences.