Kamimura H, Koga N, Oguri K, Yoshimura H, Inoue H, Sato K, Ohkubo M
Fukuoka Igaku Zasshi. 1989 May;80(5):269-80.
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.
在之前的论文中，我们利用大鼠证明，角鲨烷（2,6,10,15,19,23 - 六甲基二十四烷）能够刺激2,3,4,7,8 - 五氯二苯并呋喃的粪便排泄，在导致油症的米糠油中发现的多氯联苯和多氯二苯并呋喃同系物中，该物质被视为油症最重要的病因。我们还报告称，在大鼠中，角鲨烷基本不会从胃肠道吸收，并且在为期3个月的治疗期间未显示出任何明显的副作用。在本论文中，我们研究了角鲨烷在比格犬体内的分布、排泄及亚急性毒性。以1200mg/kg的单次口服剂量给予雄性犬后，给药后的最初2天内，角鲨烷的粪便排泄量约占给药剂量的83%。在第3天，吸收的角鲨烷大多分布到毛发和皮肤，这些组织中的浓度在第6天下降。这些结果表明，口服的角鲨烷大部分未从胃肠道吸收，但有一部分被吸收并通过毛发排泄。此外，发现分布到肝脏中的角鲨烷消除得相当缓慢。对雄性和雌性犬以400mg/kg/天或1200mg/kg/天的剂量长期（13周）口服角鲨烷，也导致角鲨烷在肝脏中蓄积，蓄积水平约为日剂量的3%（400mg/kg）或约6%（1200mg/kg）。在所有组织中，角鲨烷在肝脏中的蓄积量最高。然而，在角鲨烷组的血清生化检测和肝功能检测中未观察到明显的毒性迹象。因此，蓄积在肝脏中的角鲨烷似乎并未干扰肝脏的生理功能。长期治疗还表明，皮肤和毛发在角鲨烷的消除中起最重要作用。总之，目前的亚急性毒性试验研究表明，角鲨烷对犬和大鼠均未产生任何显著的毒性作用。
