Retrospective identification of ricin in animal tissues following administration by pulmonary and oral routes
A previously characterised amplified ELISA for ricin (sensitivity limit approximately 200 pg mL −1) has been employed to quantify ricin following a novel recovery method from selected tissues. Tissue samples from rats dosed by pulmonary instillation or orally with ricin were homogenised and treated...
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Veröffentlicht in: | Toxicology (Amsterdam) 2006-06, Vol.223 (1), p.61-70 |
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creator | Cook, David Leslie David, Jonathan Griffiths, Gareth David |
description | A previously characterised amplified ELISA for ricin (sensitivity limit approximately 200
pg
mL
−1) has been employed to quantify ricin following a novel recovery method from selected tissues. Tissue samples from rats dosed by pulmonary instillation or orally with ricin were homogenised and treated with an elution buffer to extract ricin. This is the first time that ex vivo recovery of ricin post exposure following pulmonary or oral challenge has been achieved using clinically acceptable sampling methods, with promise in terms of diagnosis for the timely implementation of therapy.
The toxin was detected and quantified using the ELISA in conjunction with pure ricin standards. Extracts from tissues sampled, including lung, blood, liver and spleen tested positive for ricin with maximum yield in lung associated fractions for pulmonary dosing and liver tissue for oral administration. This indicates the potential of lavage and blood sampling for timely diagnosis of ricin poisoning by pulmonary and oral routes, respectively.
Time course analysis at 24 and 48
h also indicated the progression of ricin from surfaces of the lung into the lung tissue. Inter-subject variation was observed in the case of oral dosing, with data for ricin-treated and vehicle control tissues not statistically different in all samples. In addition the oral toxicity of the crude ricin administered was found to be higher than expected in the rat, based upon published information and an unpublished in house murine study. |
doi_str_mv | 10.1016/j.tox.2006.03.010 |
format | Article |
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pg
mL
−1) has been employed to quantify ricin following a novel recovery method from selected tissues. Tissue samples from rats dosed by pulmonary instillation or orally with ricin were homogenised and treated with an elution buffer to extract ricin. This is the first time that ex vivo recovery of ricin post exposure following pulmonary or oral challenge has been achieved using clinically acceptable sampling methods, with promise in terms of diagnosis for the timely implementation of therapy.
The toxin was detected and quantified using the ELISA in conjunction with pure ricin standards. Extracts from tissues sampled, including lung, blood, liver and spleen tested positive for ricin with maximum yield in lung associated fractions for pulmonary dosing and liver tissue for oral administration. This indicates the potential of lavage and blood sampling for timely diagnosis of ricin poisoning by pulmonary and oral routes, respectively.
Time course analysis at 24 and 48
h also indicated the progression of ricin from surfaces of the lung into the lung tissue. Inter-subject variation was observed in the case of oral dosing, with data for ricin-treated and vehicle control tissues not statistically different in all samples. In addition the oral toxicity of the crude ricin administered was found to be higher than expected in the rat, based upon published information and an unpublished in house murine study.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/j.tox.2006.03.010</identifier><identifier>PMID: 16650517</identifier><identifier>CODEN: TXICDD</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Administration, Oral ; Animals ; Biological and medical sciences ; Chemical Warfare Agents - analysis ; Chemical Warfare Agents - pharmacokinetics ; Chemical Warfare Agents - poisoning ; Crude ricin ; Electrophoresis, Polyacrylamide Gel ; ELISA ; Inhalation Exposure ; Instillation ; Lethal Dose 50 ; Liver - metabolism ; Lung - metabolism ; Male ; Medical sciences ; Oral route ; Organ Specificity ; Poisoning - blood ; Poisoning - diagnosis ; Pulmonary route ; Quantification ; Rats ; Rats, Sprague-Dawley ; Retrospective identification ; Ricin - analysis ; Ricin - blood ; Ricin - pharmacokinetics ; Ricin - poisoning ; Sensitivity and Specificity ; Spleen - metabolism ; Time Factors ; Tissue Distribution ; Toxicology</subject><ispartof>Toxicology (Amsterdam), 2006-06, Vol.223 (1), p.61-70</ispartof><rights>2006</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-f999595cb548c4fed0bd1c0a74af1d6f604ac8420f85c7ab9af86c4c5f4fecb43</citedby><cites>FETCH-LOGICAL-c478t-f999595cb548c4fed0bd1c0a74af1d6f604ac8420f85c7ab9af86c4c5f4fecb43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tox.2006.03.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17800266$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16650517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cook, David Leslie</creatorcontrib><creatorcontrib>David, Jonathan</creatorcontrib><creatorcontrib>Griffiths, Gareth David</creatorcontrib><title>Retrospective identification of ricin in animal tissues following administration by pulmonary and oral routes</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>A previously characterised amplified ELISA for ricin (sensitivity limit approximately 200
pg
mL
−1) has been employed to quantify ricin following a novel recovery method from selected tissues. Tissue samples from rats dosed by pulmonary instillation or orally with ricin were homogenised and treated with an elution buffer to extract ricin. This is the first time that ex vivo recovery of ricin post exposure following pulmonary or oral challenge has been achieved using clinically acceptable sampling methods, with promise in terms of diagnosis for the timely implementation of therapy.
The toxin was detected and quantified using the ELISA in conjunction with pure ricin standards. Extracts from tissues sampled, including lung, blood, liver and spleen tested positive for ricin with maximum yield in lung associated fractions for pulmonary dosing and liver tissue for oral administration. This indicates the potential of lavage and blood sampling for timely diagnosis of ricin poisoning by pulmonary and oral routes, respectively.
Time course analysis at 24 and 48
h also indicated the progression of ricin from surfaces of the lung into the lung tissue. Inter-subject variation was observed in the case of oral dosing, with data for ricin-treated and vehicle control tissues not statistically different in all samples. In addition the oral toxicity of the crude ricin administered was found to be higher than expected in the rat, based upon published information and an unpublished in house murine study.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Chemical Warfare Agents - analysis</subject><subject>Chemical Warfare Agents - pharmacokinetics</subject><subject>Chemical Warfare Agents - poisoning</subject><subject>Crude ricin</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>ELISA</subject><subject>Inhalation Exposure</subject><subject>Instillation</subject><subject>Lethal Dose 50</subject><subject>Liver - metabolism</subject><subject>Lung - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Oral route</subject><subject>Organ Specificity</subject><subject>Poisoning - blood</subject><subject>Poisoning - diagnosis</subject><subject>Pulmonary route</subject><subject>Quantification</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Retrospective identification</subject><subject>Ricin - analysis</subject><subject>Ricin - blood</subject><subject>Ricin - pharmacokinetics</subject><subject>Ricin - poisoning</subject><subject>Sensitivity and Specificity</subject><subject>Spleen - metabolism</subject><subject>Time Factors</subject><subject>Tissue Distribution</subject><subject>Toxicology</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEQhoMo7rj6A7xILu6t20p3ku7GkyyuCgvCouAtpPMhNXQnY5Jed_69WWZgb0JBXZ63qHqKkLcMWgZMfti3JT60HYBsoW-BwTOyY-MwNT0bxXOygx6g4WP_64K8ynkPAF3P5UtywaQUINiwI-udKynmgzMF7x1F60JBj0YXjIFGTxMaDLSWDrjqhRbMeXOZ-rgs8S-G31TbFQPmkk6Z-UgP27LGoNOxhiyNqcZS3IrLr8kLr5fs3pz7Jfl58_nH9dfm9vuXb9efbhvDh7E0fpomMQkzCz4a7p2F2TIDeuDaMyu9BK7NyDvwozCDniftR2m4Eb7CZub9Jbk6zT2k-KduW9SK2bhl0cHFLSs2dJzJTlSQnUBTJeTkvDqkemY6Kgbq0bHaq-pYPTpW0KvquGbenYdv8-rsU-IstQLvz4DORi8-6WAwP3HDWB8hZeU-njhXVdyjSyobdME4i6n-Q9mI_1njH7GxnXg</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>Cook, David Leslie</creator><creator>David, Jonathan</creator><creator>Griffiths, Gareth David</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><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>20060601</creationdate><title>Retrospective identification of ricin in animal tissues following administration by pulmonary and oral routes</title><author>Cook, David Leslie ; David, Jonathan ; Griffiths, Gareth David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-f999595cb548c4fed0bd1c0a74af1d6f604ac8420f85c7ab9af86c4c5f4fecb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Chemical Warfare Agents - analysis</topic><topic>Chemical Warfare Agents - pharmacokinetics</topic><topic>Chemical Warfare Agents - poisoning</topic><topic>Crude ricin</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>ELISA</topic><topic>Inhalation Exposure</topic><topic>Instillation</topic><topic>Lethal Dose 50</topic><topic>Liver - metabolism</topic><topic>Lung - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Oral route</topic><topic>Organ Specificity</topic><topic>Poisoning - blood</topic><topic>Poisoning - diagnosis</topic><topic>Pulmonary route</topic><topic>Quantification</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Retrospective identification</topic><topic>Ricin - analysis</topic><topic>Ricin - blood</topic><topic>Ricin - pharmacokinetics</topic><topic>Ricin - poisoning</topic><topic>Sensitivity and Specificity</topic><topic>Spleen - metabolism</topic><topic>Time Factors</topic><topic>Tissue Distribution</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cook, David Leslie</creatorcontrib><creatorcontrib>David, Jonathan</creatorcontrib><creatorcontrib>Griffiths, Gareth David</creatorcontrib><collection>Pascal-Francis</collection><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>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cook, David Leslie</au><au>David, Jonathan</au><au>Griffiths, Gareth David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retrospective identification of ricin in animal tissues following administration by pulmonary and oral routes</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>2006-06-01</date><risdate>2006</risdate><volume>223</volume><issue>1</issue><spage>61</spage><epage>70</epage><pages>61-70</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><coden>TXICDD</coden><abstract>A previously characterised amplified ELISA for ricin (sensitivity limit approximately 200
pg
mL
−1) has been employed to quantify ricin following a novel recovery method from selected tissues. Tissue samples from rats dosed by pulmonary instillation or orally with ricin were homogenised and treated with an elution buffer to extract ricin. This is the first time that ex vivo recovery of ricin post exposure following pulmonary or oral challenge has been achieved using clinically acceptable sampling methods, with promise in terms of diagnosis for the timely implementation of therapy.
The toxin was detected and quantified using the ELISA in conjunction with pure ricin standards. Extracts from tissues sampled, including lung, blood, liver and spleen tested positive for ricin with maximum yield in lung associated fractions for pulmonary dosing and liver tissue for oral administration. This indicates the potential of lavage and blood sampling for timely diagnosis of ricin poisoning by pulmonary and oral routes, respectively.
Time course analysis at 24 and 48
h also indicated the progression of ricin from surfaces of the lung into the lung tissue. Inter-subject variation was observed in the case of oral dosing, with data for ricin-treated and vehicle control tissues not statistically different in all samples. In addition the oral toxicity of the crude ricin administered was found to be higher than expected in the rat, based upon published information and an unpublished in house murine study.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>16650517</pmid><doi>10.1016/j.tox.2006.03.010</doi><tpages>10</tpages></addata></record> |
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subjects | Administration, Oral Animals Biological and medical sciences Chemical Warfare Agents - analysis Chemical Warfare Agents - pharmacokinetics Chemical Warfare Agents - poisoning Crude ricin Electrophoresis, Polyacrylamide Gel ELISA Inhalation Exposure Instillation Lethal Dose 50 Liver - metabolism Lung - metabolism Male Medical sciences Oral route Organ Specificity Poisoning - blood Poisoning - diagnosis Pulmonary route Quantification Rats Rats, Sprague-Dawley Retrospective identification Ricin - analysis Ricin - blood Ricin - pharmacokinetics Ricin - poisoning Sensitivity and Specificity Spleen - metabolism Time Factors Tissue Distribution Toxicology |
title | Retrospective identification of ricin in animal tissues following administration by pulmonary and oral routes |
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