One-month Percutaneous Toxicity of OCT in Rats.
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Accession number;99A0490415
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| Title;One-month Percutaneous Toxicity of OCT in Rats. |
| Author;
OTABE KOJI
(Chugai Pharmaceutical Co., Ltd.)
MATSUSHITA TOMOCHIKA
(Chugai Pharmaceutical Co., Ltd.)
WATANABE KAZUTO
(Chugai Pharmaceutical Co., Ltd.)
HONMA NORIO
(Chugai Pharmaceutical Co., Ltd.)
KOMATSU HIROMICHI
(Chugai Pharmaceutical Co., Ltd.)
SUGIMOTO TETSURO
(Chugai Pharmaceutical Co., Ltd.)
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Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.27;NO.Suppl.2;PAGE.S.591-S.612(1999)
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| Figure&Table&Reference;FIG.4, TBL.7, REF.20 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;The repeated toxicity of OCT in rats(Slc: SD) was evaluated by daily percutaneous application for one month with the doses of 0(ointment base), 0.33,3.3,33.MU.g/kg/day. Each dose was consisted with 13 males and 13 females, and 3 of them were employed for the additional one-month withdrawal period to evaluate the reversibility of the observed toxicity. No animals died in any groupes. The corneal opacity was observed in 3.3.MU.g/kg group or more. In 33.MU.g/kg, although the body weight gain was not affected, the food consumption increased and the food efficiency decreased. The water consumption increased in 3.3.MU.g/kg or more. In urinalysis, the urinary calcium excretion increased in 0.33.MU.g/kg or more. The urinary pH decreased and urinary inorganic phosphorus excretion increased in 3.3.MU.g/kg or more. Furthermore, in 33.MU.g/kg, the decreased urinary chloride excretion and the increased ketone body were observed. Blood biochemistry revealed the increased serum calcium in 3.3.MU.g/kg or more. In 0.33.MU.g/kg, the increased urinary calcium excretion was observed while the serum calcium level had been remained within the physiological range. This change was judged as the homeostatic change in response to the increased calcium loading, and it was not the toxic change. In pathological examination, the autopsy revealed the corneal opacity in 3.3.MU.g/kg or more. The increased thymus weight in 3.3.MU.g/kg or more and the increased adrenal and kidney weights in 33.MU.g/kg was observed. Histopathologically, the increased incidence of the renal tubular calcification and the increased degree of the corneal calcification in 3.3.MU.g/kg or more, and the dilation of renal tubules in 33.MU.g/kg were observed. However, the histological lesions were not observed in the adrenal glands. At the application site of skin, the thickness of horny layer and the increased keratohyaline granules in 0.33.MU.g/kg or more, and the hyperplasia of keratinocytes in 3.3.MU.g/kg were observed, respectively.... (author abst.) |
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