title: Re-evaluation of the kidney tumors and renal histopathology occurring in a 2-year rat carcinogenicity bioassay of quercetin.
abstract: Renal histopathology in the most recent 2-year carcinogenicity bioassay of quercetin, in Fischer 344 rats, was re-evaluated in an attempt to determine a mode of action underlying a small increase in renal tubule tumors reported in the males (). The re-evaluation confirmed the reported increase in renal tumors in mid- and high-dose males, including a single carcinoma in a high-dose male, as well as an exacerbation of spontaneous, chronic progressive nephropathy (CPN) in male rats only. The re-evaluation also showed that there were no cellular alterations in the kidney indicative of chemical toxicity at 6 months, 15 months, or 2 years. The evidence linked the occurrence of the predominant basophilic adenomas and foci of atypical tubule hyperplasia (ATH) with the exacerbation of CPN to advanced grades of severity, supporting a mode of action involving quercetin interaction with CPN. This mode of action represents a secondary mechanism for renal tumor development, with no relevance for extrapolation to humans. In addition, the single carcinoma present in the high-dose males, along with 4 other lesions ranging from ATH to adenoma in male and female groups, were considered to have a unique phenotype associated previously with neoplasms of spontaneous and familial origin.
authors.affiliation: Private Consultant, 203 Paku Drive, Tairua 3508, New Zealand. gordonhard@mns.com
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Hard
authors.forename: John Curtis
authors.initials: JC
authors.lastname: Seely
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Betz
authors.forename: Shim-Mo
authors.initials: SM
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D005260:Female; D006965:Hyperplasia; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D011794:Quercetin / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D011794:Quercetin