Subchronic toxicity of benzyl selenocyanate and 1,4-phenylenebis(methylene)selenocyanate in F344 rats

C. Clifford Conaway, Pramod Upadhyaya, Carol L. Meschter, Christine Kurtzke, Lee Ann Marcus, Karam Et-bayoumy

23 Scopus citations

Abstract

Chemopreventive agents benzyl selenocyanate (BSC) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) were fed in NIH-07 diet to male and female F344 rats (4, 2, and 0.5 mg/kg/day for BSC and 20, 10, and 5 mg/kg/day for p-XSC) for 13 weeks. Weight gains were depressed for male and female rats fed 4 and 2 mg/kg/day BSC, females fed 0.5 mg/kg/day BSC, and male rats fed 20 and 10 mg/kg/day p-XSC. At necropsy, no clear treatment-related lesions were noted, but dose-dependent hepatomegaly was observed in both sexes of BSC and p-XSC groups. Plasma transaminases AST and ALT were elevated in the higher dose groups, while hemoglobin, HCT, and RBC were reduced in most BSC and some p-XSC treatment groups. Plasma glucose was reduced in BSC-treated males. Significant histologic findings included moderate to severe hepatic centrilobular hypertrophy with fatty change in all males and females in the 4 mg/kg/day BSC groups and in 9/15 males and 3/15 females in the 2 mg/kg/day BSC groups. Dose-dependent, mild centrilob ular hypertrophy with minimal fatty change was observed in the mid-and low-dose BSC groups and in all p-XSC groups. Mild to moderate renal tubular and interstitial nephritis occurred in the 4 mg/kg/day male BSC group. Dietary maximum tolerated dose levels for chemoprevention studies are 0.5 mg/kg/day (3.0 ppm Se) for BSC and 5 mg/kg/day (32.5 ppm Se) for p-XSC, compared to literature values of 2-3 ppm Se for Na2SeO3.

Original languageEnglish (US)
Pages (from-to)563-574
Number of pages12
JournalToxicological Sciences
Volume19
Issue number4
DOIs
Publication statusPublished - Nov 1 1992

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All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Conaway, C. Clifford ; Upadhyaya, Pramod ; Meschter, Carol L. ; Kurtzke, Christine ; Marcus, Lee Ann ; Et-bayoumy, Karam. / Subchronic toxicity of benzyl selenocyanate and 1,4-phenylenebis(methylene)selenocyanate in F344 rats. In: Toxicological Sciences. 1992 ; Vol. 19, No. 4. pp. 563-574.