title: Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays.
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.
authors.affiliation: Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA In Vivo Animal Core, Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hoenerhoff
authors.affiliation: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
authors.forename: Shyamal D
authors.initials: SD
authors.lastname: Peddada
authors.affiliation: Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Sills
authors.affiliation: Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA pandiriak@niehs.nih.gov.
authors.forename: Arun R
authors.initials: AR
authors.lastname: Pandiri
mesh_terms: D020106:Acrylamide / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D020901:Kava / Q000633:toxicity; D008027:Light / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D012162:Retinal Degeneration / Q000209:etiology* / Q000473:pathology*; D012394:Rosaniline Dyes / Q000633:toxicity
chemical_list: D012394:Rosaniline Dyes; D020106:Acrylamide; C015320:leucomalachite green
keywords: F344/N rat; NTP database survey; carcinogenicity bioassay; light-induced exacerbation; ocular phototoxicity; retinal atrophy; retinal degeneration