Acute and repeated dose 28-day oral toxicity of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) nanoparticles in Sprague-Dawley rats

Regul Toxicol Pharmacol. 2018 Jun;95:280-288. doi: 10.1016/j.yrtph.2018.03.011. Epub 2018 Mar 19.


This study aimed to investigate the oral acute and subacute toxicity of Poly [3-hydroxybutyrate-co-4-hydroxybutyrate], P(3HB-co-4HB) in the form of nanoparticles in Sprague-Dawley rats. Acute oral administration of P(3HB-co-4HB) nanoparticles was performed as a single dose up to 2000 mg/kg in six female rats for 14 days. Subacute toxicity study via oral administration for 28 days at doses of 0 (control), 500, 1000 and 2000 mg/kg in rats (10 rats in each group, female:male = 1:1) was conducted. The estimated lethal dose (LD50) of P(3HB-co-4HB) nanoparticles was >2000 mg/kg. No mortality, unusual changes in behaviour, adverse clinical signs, abnormal changes in body weights or food consumption were observed on all animals treated with P(3HB-co-4HB) nanoparticles during 14 days of the acute toxicity study. In the subacute test, there was no mortality and toxicologically significant changes in clinical signs, body weights, food consumption, hematology, clinical biochemistry, urinalysis, macroscopic findings, organ weights as well as histopathological examination were observed.

Keywords: Acute oral toxicity; Nanoparticles; P(3HB-co-4HB); Sprague-Dawley rats; Subacute toxicological evaluation.

MeSH terms

  • Administration, Oral
  • Animals
  • Female
  • Hydroxybutyrates / toxicity*
  • Lethal Dose 50
  • Male
  • Nanoparticles / toxicity*
  • Polyesters / toxicity*
  • Rats, Sprague-Dawley
  • Toxicity Tests, Acute
  • Toxicity Tests, Subacute


  • Hydroxybutyrates
  • Polyesters
  • poly(3-hydroxybutyrate-co-4-hydroxybutyrate)