Renal histopathology in toxicity and carcinogenicity studies with tert-butyl alcohol administered in drinking water to F344 rats: A pathology working group review and re-evaluation

Gordon C. Hard, Richard H. Bruner, Samuel M. Cohen, John M. Pletcher, Karen S. Regan

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

An independent Pathology Working Group (PWG) re-evaluated the kidney changes in National Toxicology Program (NTP) toxicology/carcinogenicity studies of tert-butyl alcohol (TBA) in F344/N rats to determine possible mode(s) of action underlying renal tubule tumors in male rats at 2-years. In the 13-week study, the PWG confirmed that the normal pattern of round hyaline droplets in proximal convoluted tubules was replaced by angular droplet accumulation, and identified precursors of granular casts in the outer medulla, changes typical of alpha2u-globulin (α2u-g) nephropathy. In the 2-year study, the PWG confirmed the NTP observation of increased renal tubule tumors in treated male groups. Linear papillary mineralization, another hallmark of the α2u-g pathway was present only in treated male rats. Chronic progressive nephropathy (CPN) was exacerbated in high-dose males and females, with a relationship between advanced grades of CPN and renal tumor occurrence. Hyperplasia of the papilla lining was a component of CPN in both sexes, but there was no pelvic urothelial hyperplasia. High-dose females showed no TBA-related nephrotoxicity. The PWG concluded that both α2u-g nephropathy and exacerbated CPN modes of action were operative in TBA renal tumorigenicity in male rats, neither of which has relevance for human cancer risk.

Original languageEnglish (US)
Pages (from-to)430-436
Number of pages7
JournalRegulatory Toxicology and Pharmacology
Volume59
Issue number3
DOIs
StatePublished - Apr 2011

Keywords

  • Alpha2u-globulin nephropathy
  • Chronic progressive nephropathy
  • Hazard assessment
  • Renal tubule tumors

ASJC Scopus subject areas

  • Toxicology

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