Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays

Toxicol Pathol. 2016 Aug;44(6):892-903. doi: 10.1177/0192623316650050. Epub 2016 May 26.

Abstract

Retinal degeneration due to chronic ambient light exposure is a common spontaneous age-related finding in albino rats, but it can also be related to exposures associated with environmental chemicals and drugs. Typically, light-induced retinal degeneration has a central/hemispherical localization whereas chemical-induced retinal degeneration has a diffuse localization. This study was conducted to identify and characterize treatment-related retinal degeneration in National Toxicology Program rodent bioassays. A total of 3 chronic bioassays in F344/N rats (but not in B6C3F1/N mice) were identified that had treatment-related increases in retinal degeneration (kava kava extract, acrylamide, and leucomalachite green). A retrospective light microscopic evaluation of the retinas from rats in these 3 studies showed a dose-related increase in the frequencies of retinal degeneration, beginning with the loss of photoreceptor cells, followed by the inner nuclear layer cells. These dose-related increased frequencies of degenerative retinal lesions localized within the central/hemispherical region are suggestive of exacerbation of light-induced retinal degeneration.

Keywords: F344/N rat; NTP database survey; carcinogenicity bioassay; light-induced exacerbation; ocular phototoxicity; retinal atrophy; retinal degeneration.

MeSH terms

  • Acrylamide / toxicity
  • Animals
  • Disease Models, Animal
  • Kava / toxicity
  • Light / adverse effects*
  • Rats
  • Rats, Inbred F344
  • Retinal Degeneration / etiology*
  • Retinal Degeneration / pathology*
  • Rosaniline Dyes / toxicity

Substances

  • Rosaniline Dyes
  • Acrylamide
  • leucomalachite green