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 vitr...
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| Veröffentlicht in: | Journal of toxicological sciences 2006, Vol.31(4), pp.371-379 |
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| creator | KITAGAKI, Masato WAKURI, Shinobu HIROTA, Morihiko TANAKA, Noriho ITAGAKI, Hiroshi |
| description | 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 |
| doi_str_mv | 10.2131/jts.31.371 |
| format | Article |
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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.</description><identifier>ISSN: 0388-1350</identifier><identifier>EISSN: 1880-3989</identifier><identifier>DOI: 10.2131/jts.31.371</identifier><identifier>PMID: 17077590</identifier><language>eng</language><publisher>Japan: The Japanese Society of Toxicology</publisher><subject>Animals ; Cell Line ; Cornea - cytology ; Cornea - drug effects ; Lethal Dose 50 ; Mice ; Rabbits ; Rats ; Toxicity Tests, Acute - methods</subject><ispartof>The Journal of Toxicological Sciences, 2006, Vol.31(4), pp.371-379</ispartof><rights>2006 The Japanese Society of Toxicology</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5391-9937ca5861e480e111f2832b82d1cc1cba0c82c1ffbd948b6722e6960737fd3c3</citedby><cites>FETCH-LOGICAL-c5391-9937ca5861e480e111f2832b82d1cc1cba0c82c1ffbd948b6722e6960737fd3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,1884,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17077590$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KITAGAKI, Masato</creatorcontrib><creatorcontrib>WAKURI, Shinobu</creatorcontrib><creatorcontrib>HIROTA, Morihiko</creatorcontrib><creatorcontrib>TANAKA, Noriho</creatorcontrib><creatorcontrib>ITAGAKI, Hiroshi</creatorcontrib><title>SIRC-CVS CYTOTOXICITY TEST: AN ALTERNATIVE FOR PREDICTING RODENT ACUTE SYSTEMIC TOXICITY</title><title>Journal of toxicological sciences</title><addtitle>J Toxicol Sci</addtitle><description>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.</description><subject>Animals</subject><subject>Cell Line</subject><subject>Cornea - cytology</subject><subject>Cornea - drug effects</subject><subject>Lethal Dose 50</subject><subject>Mice</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Toxicity Tests, Acute - methods</subject><issn>0388-1350</issn><issn>1880-3989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE9PwjAYhxujEUQvfgDTkweTYd92o60Xs5SBS5CZrRo5LVvpFMI_Vzj47Z0B8fL-Du-T5_AgdA2kS4HB_Xzrugy6jMMJaoMQxGNSyFPUJkwID1hAWujCuTkhlJPAP0ct4ITzQJI2es_iVHnqLcNqohOdvMcq1hOso0w_4HCMw5GO0nGo47cID5IUv6RRP1Y6Hg9xmvSjscahetURziaZjp5jhf8Ul-isKhbOXh22g14HkVZP3igZxioceSZgEjwpGTdFIHpgfUEsAFRUMFoKOgVjwJQFMYIaqKpyKn1R9jiltid7hDNeTZlhHXS7927q9dfOum2-nDljF4tiZdc7l4P0OWUN3kF3e9DUa-dqW-WberYs6u8cSP7bMW865s00HRv45mDdlUs7_UcP4RrgcQ_M3bb4sEegqLczs7B_Lv9wOBw_5rOoc7tiP0nyfOg</recordid><startdate>200610</startdate><enddate>200610</enddate><creator>KITAGAKI, Masato</creator><creator>WAKURI, Shinobu</creator><creator>HIROTA, Morihiko</creator><creator>TANAKA, Noriho</creator><creator>ITAGAKI, Hiroshi</creator><general>The Japanese Society of Toxicology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>200610</creationdate><title>SIRC-CVS CYTOTOXICITY TEST: AN ALTERNATIVE FOR PREDICTING RODENT ACUTE SYSTEMIC TOXICITY</title><author>KITAGAKI, Masato ; WAKURI, Shinobu ; HIROTA, Morihiko ; TANAKA, Noriho ; ITAGAKI, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5391-9937ca5861e480e111f2832b82d1cc1cba0c82c1ffbd948b6722e6960737fd3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Cell Line</topic><topic>Cornea - cytology</topic><topic>Cornea - drug effects</topic><topic>Lethal Dose 50</topic><topic>Mice</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Toxicity Tests, Acute - methods</topic><toplevel>online_resources</toplevel><creatorcontrib>KITAGAKI, Masato</creatorcontrib><creatorcontrib>WAKURI, Shinobu</creatorcontrib><creatorcontrib>HIROTA, Morihiko</creatorcontrib><creatorcontrib>TANAKA, Noriho</creatorcontrib><creatorcontrib>ITAGAKI, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Journal of toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KITAGAKI, Masato</au><au>WAKURI, Shinobu</au><au>HIROTA, Morihiko</au><au>TANAKA, Noriho</au><au>ITAGAKI, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SIRC-CVS CYTOTOXICITY TEST: AN ALTERNATIVE FOR PREDICTING RODENT ACUTE SYSTEMIC TOXICITY</atitle><jtitle>Journal of toxicological sciences</jtitle><addtitle>J Toxicol Sci</addtitle><date>2006-10</date><risdate>2006</risdate><volume>31</volume><issue>4</issue><spage>371</spage><epage>379</epage><pages>371-379</pages><issn>0388-1350</issn><eissn>1880-3989</eissn><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.</abstract><cop>Japan</cop><pub>The Japanese Society of Toxicology</pub><pmid>17077590</pmid><doi>10.2131/jts.31.371</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cell Line Cornea - cytology Cornea - drug effects Lethal Dose 50 Mice Rabbits Rats Toxicity Tests, Acute - methods |
| title | SIRC-CVS CYTOTOXICITY TEST: AN ALTERNATIVE FOR PREDICTING RODENT ACUTE SYSTEMIC TOXICITY |
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