Complex Histopathologic Response in Rat Kidney to Oral β-myrcene

Author:

Cesta Mark F.1,Hard Gordon C.2,Boyce John T.3,Ryan Michael J.4,Chan Po C.1,Sills Robert C.1

Affiliation:

1. National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

2. Private Consultant, Tairua, New Zealand

3. Beechy Ridge Toxpath, Clay, West Virginia, USA

4. Battelle Columbus, Columbus, Ohio, USA

Abstract

Oral gavage studies with β-myrcene in male F344 rats showed a complex renal pathology comprising both alpha2u-globulin (α2u-g) nephropathy, an unusual nephrosis involving the outer stripe of outer medulla (OSOM), and an increased incidence of renal tubule tumors by 2 years. In the 90-day and 2-year studies, respectively, α2u-g nephropathy and linear papillary mineralization were observed in males at the two lower doses but were absent from the high dose. Nephrosis was characterized by dilation of the S3 tubules, nuclear enlargement (including karyomegaly), and luminal pyknotic cells, all in the outermost OSOM. Nephrosis was minimal at the higher doses in the 90-day study, but progressed to a severe grade in males dosed with 1,000 mg/kg for 2 years. Renal tubule tumors developed in treated groups with incidences up to 30% in the 250 and 500 mg/kg male dose groups. Tumors at the lower doses in males may have been associated with α2u-g nephropathy, while those at higher doses in both sexes may have been due to the nephrosis. Because β-myrcene induced a complex spectrum of renal pathology, the α2u-g nephropathy mechanism cannot be the sole mechanism of carcinogenesis in these rats.

Publisher

SAGE Publications

Subject

Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine

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