US EPA

5343805 

Journal Article 

Histopathology re-examination of the NTP toxicity/carcinogenicity studies of tert-butyl alcohol to identify renal tumor and toxicity modes of action 

Hard, GC; Cohen, SM; Ma, J; Yu, F; Arnold, LL; Banton, MI 

2019 

1 

Regulatory Toxicology and Pharmacology
ISSN: 0273-2300
EISSN: 1096-0295 

102 

65-73 

English 

30590081 

10.1016/j.yrtph.2018.12.011 

WOS:000463848300009 

Tert-butyl alcohol (TBA) targets the rat kidney following repeated exposures, including renal tubule tumors. The mode of action (MOA) of these tumors, concluded by a pathology working group, involves both alpha2u-globulin nephropathy (α2u-gN) and exacerbated chronic progressive nephropathy (CPN), but has been disputed and an undefined MOA proposed. This study further reviews the histology slides of male and female rat kidneys from the NTP drinking water 13-week toxicity and 2-year carcinogenicity studies, including the 15-month interim sacrifice group. The papillary epithelial lining alteration formerly referred to as "transitional cell hyperplasia" develops as part of advanced CPN and does not represent a separate toxicity. No changes were observed in the kidney pelvis urothelium. The only alterations in subchronic male rats involved α2u-gN and CPN, without test article-related alterations in females. Focused examination of areas of parenchyma unaffected by CPN in TBA-treated male and female rats of the chronic studies revealed no renal tubule abnormalities other than from the effects of α2u-gN and CPN. Unrelated to toxicity were spontaneous amphophilic or vacuolar tubule proliferative lesions. All observed TBA-associated non-neoplastic and neoplastic histopathological changes in the kidney can be explained by α2u-gN or enhanced CPN, neither of which are relevant to humans. 

ten-Butyl alcohol; alpha2u-globulin nephropathy; Chronic progressive nephropathy; Renal tubule tumors; Modes-of-action