Dose and time dependent ototoxicity of aspartame in rats

Acta Otolaryngol. 2017 Apr;137(4):421-425. doi: 10.1080/00016489.2016.1256498. Epub 2016 Nov 30.


Conclusion: Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased.

Objectives: While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats.

Methods: The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months.

Results: While audiological parameters deteriorated with 100 mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500 mg/kg/day and 1000 mg/kg/day applications after the 2nd month. In 2000 mg/kg/day and 4000 mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively.

Keywords: ABR; DPOAE; aspartame; ototoxicity.

MeSH terms

  • Animals
  • Aspartame / toxicity*
  • Female
  • Hearing / drug effects*
  • Rats
  • Rats, Wistar
  • Sweetening Agents / toxicity*


  • Sweetening Agents
  • Aspartame