General toxicity and genotoxicity of altertoxin I: A novel 28-day multiendpoint assessment in male Sprague-Dawley rats

J Appl Toxicol. 2022 Aug;42(8):1310-1322. doi: 10.1002/jat.4297. Epub 2022 Feb 13.

Abstract

The mycotoxin altertoxin I (ATX-I) is one of secondary metabolites produced by Alternaria fungi and is frequently detected as food and feed contaminants. Little is known about the genotoxicity of the ATX-I. In order to evaluate potential genotoxicity and general toxicity of ATX-I, the novel 28-day multiendpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity platform was applied. Male Sprague-Dawley (SD) rats were randomized to five groups (six rats per group), that is, a positive control group (N-ethyl-N-nitrosourea [ENU], 40 mg/kg.bw/d), two solvent control groups (PBS and corn oil), and two ATX-I-treated groups (low-dose group [1.10 μg/kg.bw/d] and high-dose group [5.51 μg/kg.bw/d]). Treatments were administered by oral gavage to male SD rats for 28 consecutive days. Histopathological damages in the liver, kidney, and spleen were observed, but without significant changes in hematological and serum biochemical parameters. Genotoxic endpoints indicated that ATX-I could cause DNA damage. To summarize, in a relatively low-dose range, ATX-I may not have direct genotoxicity in vivo but could induce liver, kidney, and spleen damage.

Keywords: Pig-a assay; altertoxin I; comet assay; genotoxicity; micronucleus.

Publication types

  • Randomized Controlled Trial, Veterinary
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Comet Assay
  • DNA Damage
  • Male
  • Micronucleus Tests
  • Mycotoxins*
  • Perylene* / analogs & derivatives
  • Perylene* / toxicity
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Mycotoxins
  • altertoxin I
  • Perylene