The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Original Article
SIRC-CVS CYTOTOXICITY TEST: AN ALTERNATIVE FOR PREDICTING RODENT ACUTE SYSTEMIC TOXICITY
Masato KITAGAKIShinobu WAKURIMorihiko HIROTANoriho TANAKAHiroshi ITAGAKI
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2006 Volume 31 Issue 4 Pages 371-379

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Abstract

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 IC50 and IC35 values (μg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD50 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 IC50 or the IC35 values and all the LD50 values. Among them, a statistically significant high correlation (r=0.8102, p<0.001) required for acute systemic toxicity prediction was obtained between the IC50 values and the oral LD50 values. By using the cut-off concentrations of 2,000 mg/kg (LD50) and 4,225 μg/mL (IC50), 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.

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© 2006 The Japanese Society of Toxicology
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