Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.
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 (microg/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 microg/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.
Kitagaki
Masato
M
Shiseido Research Center, Quality Assurance Center, Kanazawa, Yokohama, Japan. masato.kitagaki@to.shiseido.co.jp
Wakuri
Shinobu
S
Hirota
Morihiko
M
Tanaka
Noriho
N
Itagaki
Hiroshi
H
D000818:Animals; D002460:Cell Line; D003315:Cornea / Q000166:cytology / Q000187:drug effects*; D007928:Lethal Dose 50; D051379:Mice; D011817:Rabbits; D051381:Rats; D023382:Toxicity Tests, Acute / Q000379:methods*