[Studies on distribution, excretion and subacute toxicity of squalane in dogs].
In the previous papers, we demonstrated, by using rats, that squalane (2,6,10,15,19,23-hexamethyltetracosane) could stimulate the fecal excretion of 2,3,4,7,8-pentachlorodibenzofuran, which was regarded as the most important etiologic agent of yusho among PCB and PCDF congeners found in the causal rice oil. We also reported that, in rats, squalane was not essentially absorbed from the gastrointestinal tract, and did not show any appreciable side effects during the 3-month treatment. In the present paper, we have investigated the distribution, excretion and subacute toxicity of squalane in beagle dogs. The fecal excretion of squalane accounted for about 83% of dose during the initial 2 days after administration at a single oral dose of 1,200 mg/kg to male dogs. On day 3, absorbed squalane was mostly distributed to the hair and the skin, and the concentrations in these tissues were decreased on day 6. These results suggested that most of squalane administered orally was not absorbed from the gastrointestinal tract, but a part was absorbed and excreted through the hair. In addition, squalane distributed into the liver was found to be eliminated rather slowly. A long-term (13-week) treatments with squalane orally at doses of 400 mg/kg/day or 1,200 mg/kg/day in male and female dogs, resulted also in accumulation of squalane in the liver at a level of about 3% (400 mg/kg) or about 6% (1,200 mg/kg) of the daily dose. This accumulation of squalane in the liver was highest among all the tissues. Nevertheless, no appreciable toxic signs were observed in the serum biochemical tests and the hepatic functional test for squalane groups. Therefore, squalane accumulating in the liver, did not seem to disturb the hepatic physiological functions. It was suggested also in a long-term treatment that the skin and the hair played the most important role in the elimination of squalane. In conclusion, the present studies on subacute toxicity tests suggested that squalane did not give any significant toxic effects on dogs as well as rats.
Kamimura
H
H
Koga
N
N
Oguri
K
K
Yoshimura
H
H
Inoue
H
H
Sato
K
K
Ohkubo
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004435:Eating / Q000187:drug effects; D005260:Female; D006403:Hematologic Tests; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008297:Male; D013185:Squalene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
D013185:Squalene; C019556:squalane