Atypical tubule hyperplasia and renal tubule tumors in conventional rats on 90-day toxicity studies.
Bilateral, multicentric renal tubule tumors were found in 4 rats at the termination of 3 separate 90-day toxicity studies during the safety evaluation of 3 unrelated chemicals. The 3 studies were conducted at 2 separate locations, but the rats used were obtained from the same commercial source. The rat strains were Fischer-344 (1 male and 1 female case) and Sprague-Dawley (2 female cases). Three of the renal tumor cases were from either the high-dose or mid-dose treatment groups, and 1 case was an untreated control. The tumors were accompanied by multiple foci of atypical tubule hyperplasia but only in the tumor-bearing rats. There were no lesions associated with renal tumor pathogenesis in any of the remaining treated or untreated animals in the 3 studies. In addition, there was no indication of nephrotoxicity in the treated or untreated animals. Tumor morphology was characterized by a generally vacuolated appearance, eosinophilia, cytoplasmic and nuclear pleomorphism, and conspicuously hypertrophied nucleoli. The renal tubule tumors in these 90-day studies were compared to hereditary renal tubule tumors occurring in the Eker rat, a Long-Evans derivative with a genetic predisposition to this tumor type. The multiplicity of renal tubule tumors, early age of onset, and tumor morphology described in the cases from the 90-day studies were very similar to those characterizing the hereditary renal tumor model.(ABSTRACT TRUNCATED AT 250 WORDS)
Hard
G C
GC
American Health Foundation, Valhalla, New York 10595.
Long
P H
PH
Crissman
J W
JW
Everitt
J I
JI
Yano
B L
BL
Bertram
T A
TA
D000236:Adenoma / Q000662:veterinary; D000818:Animals; D015197:Carcinogenicity Tests; D002277:Carcinoma / Q000662:veterinary; D005260:Female; D006965:Hyperplasia / Q000662:veterinary; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000662:veterinary*; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D051381:Rats; D012376:Rodent Diseases / Q000473:pathology*; D018675:Toxicity Tests