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
Hard, GC; Bruner, RH; Cohen, SM; Pletcher, JM; Regan, KS
HERO ID
699314
Reference Type
Journal Article
Year
2011
Language
English
PMID
| HERO ID | 699314 |
|---|---|
| In Press | No |
| Year | 2011 |
| Title | 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 |
| Authors | Hard, GC; Bruner, RH; Cohen, SM; Pletcher, JM; Regan, KS |
| Journal | Regulatory Toxicology and Pharmacology |
| Volume | 59 |
| Issue | 3 |
| Page Numbers | 430-436 |
| 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 alpha(2u)-globulin (α(2u)-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 α(2u)-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 α(2u)-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. |
| Doi | 10.1016/j.yrtph.2011.01.007 |
| Pmid | 21296119 |
| Wosid | WOS:000288981500009 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000288981500009 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Renal tubule tumors; Alpha(2u)-globulin nephropathy; Chronic progressive nephropathy; Hazard assessment |
| Is Qa | No |