Subchronic toxicity of benzyl selenocyanate and 1,4-phenylenebis(methylene)selenocyanate in F344 rats.
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 centrilobular 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.
Conaway
C C
CC
American Health Foundation, Valhalla, New York 10595.
Upadhyaya
P
P
Meschter
C L
CL
Kurtzke
C
C
Marcus
L A
LA
el-Bayoumy
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003485:Cyanates / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D016566:Organoselenium Compounds / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D003485:Cyanates; D016566:Organoselenium Compounds; C054108:benzyl selenocyanate; C074153:1,4-phenylenebis(methylene)selenocyanate