SIRC-CVS CYTOTOXICITY TEST : AN ALTERNATIVE FOR PREDICTING RODENT ACUTE SYSTEMIC TOXICITY
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概要
- 論文の詳細を見る
An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC_<50> and IC_<35> values (μg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD_<50> values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC_<50> or the IC_<35> values and all the LD_<50> values. Among them, a statistically significant high correlation (r=0.8102, p<0.001) required for acute systemic toxicity prediction was obtained between the IC_<50> values and the oral LD_<50> values. By using the cut-off concentrations of 2,000 mg/kg (LD_<50>) and 4,225 μg/mL (IC_<50>), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.
- 日本トキシコロジー学会の論文
- 2006-10-23
著者
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TANAKA Noriho
Hatano Res. Inst. FDSC
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Hirota Morihiko
Shiseido Research Center
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Kitagaki Masato
Shiseido Research Center
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Itagaki Hiroshi
Shiseido Research Center
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Tanaka Noriho
Laboratory Of Genetic Toxicology Hatano Research Institute Food And Drug Safety Center
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Itagaki Hiroshi
Shiseido Co. Ltd.
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WAKURI Shinobu
Hatano Research Institute, Food and Drug Safety Center
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Wakuri Shinobu
Hatano Research Institute Food And Drug Safety Center
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Hoya Masatoshi
Shiseido Research Center
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Tanaka Noriho
Laboratory Of Cell Carcinogenesis Division Of Alternative Research Food And Drug Safety Center
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