Repeated dose 28-day oral toxicity study of moniliformin in rats

Toxicol Lett. 2015 Feb 17;233(1):38-44. doi: 10.1016/j.toxlet.2014.11.006. Epub 2014 Dec 4.

Abstract

Moniliformin is a Fusarium mycotoxin mainly produced by several species infecting grains in different climatic conditions. According to our previous studies, it is acutely toxic to rats, with an LD50 cut-off value of 25mg/kg b.w. To further assess the possible health risks of low dose exposure to moniliformin, a subacute oral toxicity study was conducted in Sprague-Dawley rats, adapting OECD guideline 407. Five dose groups and two satellite groups, each consisting of five male rats, were daily exposed to moniliformin by gavage. Two rats in the highest dose group, showed decreased activity followed by acute heart failure and death. The rats of the lower doses (<9mg/kg b.w.) showed no signs of toxicity. The daily intake of moniliformin strongly reduced the phagocytic activity of neutrophils in all dose groups. The decrease continued in the satellite group during the follow-up period, indicating a severe impact on the immune system and a LOAEL value of 3mg/kg b.w. for moniliformin. Moniliformin was rapidly excreted into urine, ranging between 20.2 and 31.5% daily and showed no signs of accumulation. The concentration of moniliformin in faeces was less than 2%, which suggests efficient absorption from the gastrointestinal tract.

Keywords: Excretion; Fusarium mycotoxins; Moniliformin; Sprague-Dawley rats; Subacute toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cyclobutanes / toxicity*
  • Cyclobutanes / urine
  • Dose-Response Relationship, Drug
  • Feces / microbiology
  • Fusarium / chemistry
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / metabolism
  • Heart Failure / chemically induced
  • Heart Failure / pathology
  • Immunity, Innate / drug effects
  • Lethal Dose 50
  • Male
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Phagocytosis / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Toxicity Tests, Subacute*

Substances

  • Cyclobutanes
  • moniliformin