title: Chronic progressive nephropathy in male F344 rats in 90-day toxicity studies: its occurrence and association with renal tubule tumors in subsequent 2-year bioassays.
abstract: The occurrence and severity of spontaneous chronic progressive nephropathy (CPN) in control male F344 rats as well as the frequency of treatment-related CPN exacerbation were histopathologically reevaluated. A series of 43 National Toxicology Program (NTP) 90-day toxicity studies comparing the influence of NIH-07 or NTP-2000 diets was examined. Relationships between the histopathologic findings at 90 days and renal tubule proliferative lesions recorded in subsequent 2-year bioassays for 24 chemicals were statistically analyzed. CPN lesions were observed in 100% of the control male rats regardless of diet, but CPN was more severe in control rats fed NIH-07. Approximately one-third of the 90-day studies demonstrated a treatment-related exacerbation of CPN severity, which was independent of diet. For chemicals that proceeded to 2-year bioassays, all studies with a statistically significant increase in renal tubule tumors (RTT) at 2 years had treatment-related exacerbation of CPN in the 90-day and 2-year studies. These findings indicate that CPN occurs ubiquitously in young male F344 rats and that treatment-related exacerbation of CPN in 90-day studies is a relatively common occurrence, having the potential to be predictive of an increased incidence of RTT in subsequent 2-year bioassays.
authors.affiliation: National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, USA. travlos@niehs.nih.gov
authors.forename: Greg S
authors.initials: GS
authors.lastname: Travlos
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Hard
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Betz
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
mesh_terms: D000171:Acrolein / Q000633:toxicity; D000821:Animal Feed; D000818:Animals; D001577:Benzophenones / Q000633:toxicity; D001681:Biological Assay; D004032:Diet / Q000009:adverse effects* / Q000592:standards; D007204:Indium / Q000633:toxicity; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D023421:Models, Animal; D010720:Phosphines / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D018675:Toxicity Tests; D014520:Urethane / Q000633:toxicity
chemical_list: D001577:Benzophenones; D010720:Phosphines; D007204:Indium; D014520:Urethane; C047723:benzophenone; D000171:Acrolein; C090882:indium phosphide