{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:08:39Z","timestamp":1777914519856,"version":"3.51.4"},"reference-count":32,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[1994,9,1]],"date-time":"1994-09-01T00:00:00Z","timestamp":778377600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[1994,9]]},"abstract":"<jats:p>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. The following evidence demonstrates that the 4 cases of renal tubule tumor developing in young rats in the course of 90-day studies were of spontaneous origin and not compound-induced: the tumors could not be reproduced by the test compound in a repetition of the 90-day toxicity study in which 2 of the cases occurred; pertinent renal lesions, including atypical hyperplasia, were seen only in tumor-bearing rats; there was an absence of nephrotoxicity in any of the treated rats and an absence of a dose-response relationship for the observed kidney alterations; 1 case was found in an untreated rat. The striking similarity of the tumors in these 4 cases to hereditary renal tumors occurring spontaneously in Eker rats suggests that the 90-day kidney alterations described here may be compatible with a genetic defect. As an alternative explanation, the possibility of a viral etiology was also considered.<\/jats:p>","DOI":"10.1177\/019262339402200503","type":"journal-article","created":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T19:16:47Z","timestamp":1238613407000},"page":"489-496","source":"Crossref","is-referenced-by-count":18,"title":["Atypical Tubule Hyperplasia and Renal Tubule Tumors in Conventional Rats on 90-Day Toxicity Studies"],"prefix":"10.1177","volume":"22","author":[{"given":"Gordon C.","family":"Hard","sequence":"first","affiliation":[{"name":"American Health Foundation, Valhalla, New York 10595"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip H.","family":"Long","sequence":"additional","affiliation":[{"name":"The Procter & Gamble Co., Miami Valley Laboratories, Cincinnati, Ohio 45239"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Crissman","sequence":"additional","affiliation":[{"name":"The Dow Chemical Company, Midland, Michigan 48674"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey I.","family":"Everitt","sequence":"additional","affiliation":[{"name":"Chemical Industries Institute of Toxicology, Research Triangle Park, North Carolina 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry L.","family":"Yano","sequence":"additional","affiliation":[{"name":"The Dow Chemical Company, Midland, Michigan 48674"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy A.","family":"Bertram","sequence":"additional","affiliation":[{"name":"The Procter & Gamble Co., Miami Valley Laboratories, Cincinnati, Ohio 45239"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[1994,9,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-330220-5.50020-6"},{"key":"atypb2","first-page":"311","volume":"81","author":"P. 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