Developmental toxicity of flucytosine following administration to pregnant rats at a specific time point of organogenesis

Congenit Anom (Kyoto). 2019 Mar;59(2):39-42. doi: 10.1111/cga.12282. Epub 2018 May 2.

Abstract

To investigate the abnormalities that are specific to administration of flucytosine at one time point during embryonic organogenesis, flucytosine was administered orally to pregnant Sprague Dawley (SD) rats in a single dose on day 11 of pregnancy at 25 or 35 mg/kg. Fetuses on day 20 of pregnancy were externally, viscerally, and skeletally examined. Maternal body weight gain and food consumption were suppressed the day after administration of a 35 mg/kg. Fetal examinations revealed various alterations in both dose groups: externally preaxial polydactyly in the hind limb; skeletally fused lumbar centrum, absent sacral centrum, supernumerary sacral vertebra, and absent ribs. Our findings indicated that specific types of external and skeletal anomalies were induced following flucytosine administration on day 11 of pregnancy.

Keywords: 5-fluorocytosine; developmental toxicity; fetal morphological alteration; flucytosine; rats.

MeSH terms

  • Abnormalities, Drug-Induced / etiology
  • Abnormalities, Drug-Induced / pathology*
  • Administration, Oral
  • Animals
  • Drug Administration Schedule
  • Eating / drug effects
  • Ectromelia / chemically induced
  • Ectromelia / pathology*
  • Female
  • Fetal Development / drug effects*
  • Fetus
  • Flucytosine / toxicity*
  • Hindlimb / abnormalities
  • Hindlimb / drug effects
  • Lumbosacral Region / abnormalities
  • Male
  • Maternal Exposure / adverse effects
  • Organogenesis / drug effects
  • Polydactyly / chemically induced
  • Polydactyly / pathology*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Ribs / abnormalities
  • Ribs / drug effects
  • Teratogens / toxicity*
  • Weight Gain / drug effects

Substances

  • Teratogens
  • Flucytosine