PREDNISOLONE FARNESYLATE (PNF)ゲルのラットを用いた経皮投与による52週間反復投与毒性試験および8週間回復試験 A 52-WEEK DERMAL TOXICITY STUDY OF PREDNISOLONE FARNESYLATE (PNF) GEL IN RATS WITH A RECOVERY PERIOD OF 8 WEEKS

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合成糖質コルチコイド製剤, PNFゲルの0.125, 0.5および2.0mg/kg/dayをCrj: CD(SD)系雌雄ラットに52週間経皮投与し, 反復投与毒性を検討するとともに, 8週間休薬による回復性について検討した。1. PNFゲル2.0mg/kg投与群では, 投与部皮膚の非薄化, 体重増加抑制傾向, 白血球数の減少, GOTおよびGPT活性の上昇, 遊離脂肪酸の増加, α_1-グロブリン分画比率の低下, 胸腺, 脾臓および副腎重量の減少と肉眼的な投与部皮膚の非薄化がみられた。病理組織学的には, 胸腺の萎縮, 副腎束状帯の萎縮, 投与部での皮膚付属器の萎縮を伴う皮膚の非薄化と肝臓小葉周辺帯で核肥大を伴う肝細胞の肥大がみられた。2. PNFゲル0.5mg/kg投与群では, 投与部皮膚の非薄化と, α_1-グロブリン分画比率の低下がみられた。また, 組織学的には投与部位で皮膚付属器の萎縮を伴う皮膚の非薄化がみられた。3. PNFゲルの0.125mg/kg投与群では被験物質投与に起因する変化はみられなかった。4. 8週間の休薬により, 投与部皮膚における変化が2.0mg/kg投与群にみられたが, 投与終了時と比較して軽減化を示し, その他の変化は消失しておたことからいずれも可逆性の変化と判断された。 5. 以上の結果から, 本試験におけるPNFゲルの確実中毒量は0.5mg/kg/dayであり, 無影響量は0.125mg/kg/dayと判断された。

The toxicity of Prednisolone farnesylate (PNF) gel, a synthetic glucocorticoid, was investigated in the Sprague-Dawley rat. PNF gel was administered dermally to the rats at doses of 0.125, 0.5 and 2.0 mg/kg/day for 52 weeks, then the drug was withdrawn for 8 weeks to evaluate the reversibility. The results are summarized as follows: 1. In the PNF gel 2.0 mg/kg/day group, thinning of the skin at the application site, slightly retarded body weight gains, a tendency toward a decrease in the white blood cell count, an elevation of serum GOT and GPT activity, free fatty acid level, and a decrease in α_l-globulin fraction were observed. In the pathological examinations, decreased organ weights of the thymus, spleen and adrenal glands, and thinning of the skin were observed. Histopathological examination revealed atrophy of the thymus and zona fasciculata of the adrenal glands, thinning of the skin with atrophied skin appendages, and hepatocellular hypertrophy with hypertrophied uncleus in the perilobular zone. 2. In the PNF gel 0.5 mg/kg/day group, thinning of the skin at the application site and a decrease in α_l-globulin fraction were observed. Histopathologically, thinning of the skin with atrophied skin appendages was observed. 3. In the PNF gel 0.125 mg/kg/day group, there were no toxic signs induced by the drug. 4. After the 8-week recovery period, the changes in the skin were observed in the 2.0 mg/kg/day group, but the severity was lowered. The other changes disappeared and so it was demonstrated that the changes were reversible. 5. Based on these results, it was concluded that the overt toxic does of PNF gel was 0.5 mg/kg/day and the non-toxic does was 0.125 mg/kg/day in the present study.

収録刊行物

  • The Journal of Toxicological Sciences

    The Journal of Toxicological Sciences 17(Supplement III), 91-122, 1992-11-30

    日本毒性学会

被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    110001805165
  • NII書誌ID(NCID)
    AN00002808
  • 本文言語コード
    JPN
  • 資料種別
    雑誌論文
  • ISSN
    03881350
  • データ提供元
    CJP引用  NII-ELS  J-STAGE 
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