Assessment of toxicological effects of blood microsampling in the vehicle dosed adult rat

•Historically, satellite groups are used for rodent TK profiling.•Vehicle dosed Wistar rats were un-sampled, conventional blood volume, or μ-sampled.•Terminal clinical pathology parameters were within the historical background range.•Statistically significant haematological changes in conventionally...

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Veröffentlicht in:Regulatory toxicology and pharmacology 2014-04, Vol.68 (3), p.325-331
Hauptverfasser: Powles-Glover, Nicola, Kirk, Sarah, Wilkinson, Catherine, Robinson, Sally, Stewart, Jane
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container_title Regulatory toxicology and pharmacology
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creator Powles-Glover, Nicola
Kirk, Sarah
Wilkinson, Catherine
Robinson, Sally
Stewart, Jane
description •Historically, satellite groups are used for rodent TK profiling.•Vehicle dosed Wistar rats were un-sampled, conventional blood volume, or μ-sampled.•Terminal clinical pathology parameters were within the historical background range.•Statistically significant haematological changes in conventionally sampled rats.•μ-Sampling of adult rats is possible without adverse toxicological consequences. Historically, satellite groups are often used for rodent toxicokinetic profiling because of the haematological consequences of blood sampling. If microsampling is shown to be toxicologically benign, its adoption in rat studies would enable comparison of exposure and toxicity in individual animals (as happens in non-rodent studies) as well as obviating need for satellite groups. Groups of 10 male (200–300g) and female (150–250g) rats aged 10weeks were vehicle dosed and either left unsampled, conventional blood volume sampled (6×200μL) or microsampled (6×32μL) on Days 1 and 14. At termination on Day 15, clinical pathology plus liver and spleen weights and histopathology were obtained. All clinical pathology parameters were within background range. However, compared to unsampled controls, conventional volume sampled rats showed a statistically significant (p
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Historically, satellite groups are often used for rodent toxicokinetic profiling because of the haematological consequences of blood sampling. If microsampling is shown to be toxicologically benign, its adoption in rat studies would enable comparison of exposure and toxicity in individual animals (as happens in non-rodent studies) as well as obviating need for satellite groups. Groups of 10 male (200–300g) and female (150–250g) rats aged 10weeks were vehicle dosed and either left unsampled, conventional blood volume sampled (6×200μL) or microsampled (6×32μL) on Days 1 and 14. At termination on Day 15, clinical pathology plus liver and spleen weights and histopathology were obtained. All clinical pathology parameters were within background range. However, compared to unsampled controls, conventional volume sampled rats showed a statistically significant (p&lt;0.001) decrease in haemaglobin, haematocrit and red blood cell count, an increase in reticulocytes (at least p&lt;0.01), increased AST and GLDH and, in males only, an increase in monocytes and neutrophils. In contrast, microsampled animals showed no changes except for a slight, toxicologically insignificant decrease in haemoglobin concentration (15.0g/dL compared to the unsampled group mean of 14.4g/dL) in females (p&lt;0.05) and a small increase in monocytes (p&lt;0.05) in males. Microsampling of adult rats is possible without adverse toxicological consequences.</description><identifier>ISSN: 0273-2300</identifier><identifier>EISSN: 1096-0295</identifier><identifier>DOI: 10.1016/j.yrtph.2014.01.001</identifier><identifier>PMID: 24434616</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Animals ; Blood ; Blood Specimen Collection - methods ; Body Temperature ; Clinical chemistry parameters ; Drug Evaluation, Preclinical - methods ; Female ; Haematology ; Hematologic Tests ; Liver - anatomy &amp; histology ; Male ; Microsampling ; Pharmacokinetics ; Rats ; Rats, Wistar ; Restraint, Physical ; Rodent ; Spleen - anatomy &amp; histology ; Toxicity Tests - methods ; Toxicokinetic</subject><ispartof>Regulatory toxicology and pharmacology, 2014-04, Vol.68 (3), p.325-331</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-942ec404010aa0dda03dfed239d39c5a6d81527ef1b0f16dec5412e5572e49c53</citedby><cites>FETCH-LOGICAL-c458t-942ec404010aa0dda03dfed239d39c5a6d81527ef1b0f16dec5412e5572e49c53</cites><orcidid>0000-0002-1794-5145</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.yrtph.2014.01.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24434616$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Powles-Glover, Nicola</creatorcontrib><creatorcontrib>Kirk, Sarah</creatorcontrib><creatorcontrib>Wilkinson, Catherine</creatorcontrib><creatorcontrib>Robinson, Sally</creatorcontrib><creatorcontrib>Stewart, Jane</creatorcontrib><title>Assessment of toxicological effects of blood microsampling in the vehicle dosed adult rat</title><title>Regulatory toxicology and pharmacology</title><addtitle>Regul Toxicol Pharmacol</addtitle><description>•Historically, satellite groups are used for rodent TK profiling.•Vehicle dosed Wistar rats were un-sampled, conventional blood volume, or μ-sampled.•Terminal clinical pathology parameters were within the historical background range.•Statistically significant haematological changes in conventionally sampled rats.•μ-Sampling of adult rats is possible without adverse toxicological consequences. Historically, satellite groups are often used for rodent toxicokinetic profiling because of the haematological consequences of blood sampling. If microsampling is shown to be toxicologically benign, its adoption in rat studies would enable comparison of exposure and toxicity in individual animals (as happens in non-rodent studies) as well as obviating need for satellite groups. Groups of 10 male (200–300g) and female (150–250g) rats aged 10weeks were vehicle dosed and either left unsampled, conventional blood volume sampled (6×200μL) or microsampled (6×32μL) on Days 1 and 14. At termination on Day 15, clinical pathology plus liver and spleen weights and histopathology were obtained. All clinical pathology parameters were within background range. However, compared to unsampled controls, conventional volume sampled rats showed a statistically significant (p&lt;0.001) decrease in haemaglobin, haematocrit and red blood cell count, an increase in reticulocytes (at least p&lt;0.01), increased AST and GLDH and, in males only, an increase in monocytes and neutrophils. In contrast, microsampled animals showed no changes except for a slight, toxicologically insignificant decrease in haemoglobin concentration (15.0g/dL compared to the unsampled group mean of 14.4g/dL) in females (p&lt;0.05) and a small increase in monocytes (p&lt;0.05) in males. Microsampling of adult rats is possible without adverse toxicological consequences.</description><subject>Animals</subject><subject>Blood</subject><subject>Blood Specimen Collection - methods</subject><subject>Body Temperature</subject><subject>Clinical chemistry parameters</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Female</subject><subject>Haematology</subject><subject>Hematologic Tests</subject><subject>Liver - anatomy &amp; histology</subject><subject>Male</subject><subject>Microsampling</subject><subject>Pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Restraint, Physical</subject><subject>Rodent</subject><subject>Spleen - anatomy &amp; histology</subject><subject>Toxicity Tests - methods</subject><subject>Toxicokinetic</subject><issn>0273-2300</issn><issn>1096-0295</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD1PHDEQhq0IlLtAfkGkyCXNbsYf690tUiAUCBISDRRUls-evfPJuz5sH4J_n70cpEw1xTzvvJqHkG8MagZM_djWb6nsNjUHJmtgNQD7RJYMelUB75sTsgTeiooLgAX5kvMWAHjXtZ_JgksppGJqSZ4uc8acR5wKjQMt8dXbGOLaWxMoDgPakg-LVYjR0dHbFLMZd8FPa-onWjZIX3DjbUDqYkZHjduHQpMp5-R0MCHj1_d5Rh6vfz1c_a7u7m9ury7vKiubrlS95GglSGBgDDhnQLgBHRe9E71tjHIda3iLA1vBwJRD20jGsWlajnIGxBm5ON7dpfi8x1z06LPFEMyEcZ81U60SCrpGzag4oocvcsJB75IfTXrTDPTBqd7qv071wakGpmenc-r7e8F-NaL7l_mQOAM_jwDOb754TDpbj5NF59PsT7vo_1vwB51wiek</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Powles-Glover, Nicola</creator><creator>Kirk, Sarah</creator><creator>Wilkinson, Catherine</creator><creator>Robinson, Sally</creator><creator>Stewart, Jane</creator><general>Elsevier Inc</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><orcidid>https://orcid.org/0000-0002-1794-5145</orcidid></search><sort><creationdate>20140401</creationdate><title>Assessment of toxicological effects of blood microsampling in the vehicle dosed adult rat</title><author>Powles-Glover, Nicola ; Kirk, Sarah ; Wilkinson, Catherine ; Robinson, Sally ; Stewart, Jane</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-942ec404010aa0dda03dfed239d39c5a6d81527ef1b0f16dec5412e5572e49c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Blood</topic><topic>Blood Specimen Collection - methods</topic><topic>Body Temperature</topic><topic>Clinical chemistry parameters</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Female</topic><topic>Haematology</topic><topic>Hematologic Tests</topic><topic>Liver - anatomy &amp; histology</topic><topic>Male</topic><topic>Microsampling</topic><topic>Pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Restraint, Physical</topic><topic>Rodent</topic><topic>Spleen - anatomy &amp; histology</topic><topic>Toxicity Tests - methods</topic><topic>Toxicokinetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Powles-Glover, Nicola</creatorcontrib><creatorcontrib>Kirk, Sarah</creatorcontrib><creatorcontrib>Wilkinson, Catherine</creatorcontrib><creatorcontrib>Robinson, Sally</creatorcontrib><creatorcontrib>Stewart, Jane</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>Regulatory toxicology and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Powles-Glover, Nicola</au><au>Kirk, Sarah</au><au>Wilkinson, Catherine</au><au>Robinson, Sally</au><au>Stewart, Jane</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assessment of toxicological effects of blood microsampling in the vehicle dosed adult rat</atitle><jtitle>Regulatory toxicology and pharmacology</jtitle><addtitle>Regul Toxicol Pharmacol</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>68</volume><issue>3</issue><spage>325</spage><epage>331</epage><pages>325-331</pages><issn>0273-2300</issn><eissn>1096-0295</eissn><abstract>•Historically, satellite groups are used for rodent TK profiling.•Vehicle dosed Wistar rats were un-sampled, conventional blood volume, or μ-sampled.•Terminal clinical pathology parameters were within the historical background range.•Statistically significant haematological changes in conventionally sampled rats.•μ-Sampling of adult rats is possible without adverse toxicological consequences. Historically, satellite groups are often used for rodent toxicokinetic profiling because of the haematological consequences of blood sampling. If microsampling is shown to be toxicologically benign, its adoption in rat studies would enable comparison of exposure and toxicity in individual animals (as happens in non-rodent studies) as well as obviating need for satellite groups. Groups of 10 male (200–300g) and female (150–250g) rats aged 10weeks were vehicle dosed and either left unsampled, conventional blood volume sampled (6×200μL) or microsampled (6×32μL) on Days 1 and 14. At termination on Day 15, clinical pathology plus liver and spleen weights and histopathology were obtained. All clinical pathology parameters were within background range. However, compared to unsampled controls, conventional volume sampled rats showed a statistically significant (p&lt;0.001) decrease in haemaglobin, haematocrit and red blood cell count, an increase in reticulocytes (at least p&lt;0.01), increased AST and GLDH and, in males only, an increase in monocytes and neutrophils. In contrast, microsampled animals showed no changes except for a slight, toxicologically insignificant decrease in haemoglobin concentration (15.0g/dL compared to the unsampled group mean of 14.4g/dL) in females (p&lt;0.05) and a small increase in monocytes (p&lt;0.05) in males. Microsampling of adult rats is possible without adverse toxicological consequences.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>24434616</pmid><doi>10.1016/j.yrtph.2014.01.001</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-1794-5145</orcidid></addata></record>
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subjects Animals
Blood
Blood Specimen Collection - methods
Body Temperature
Clinical chemistry parameters
Drug Evaluation, Preclinical - methods
Female
Haematology
Hematologic Tests
Liver - anatomy & histology
Male
Microsampling
Pharmacokinetics
Rats
Rats, Wistar
Restraint, Physical
Rodent
Spleen - anatomy & histology
Toxicity Tests - methods
Toxicokinetic
title Assessment of toxicological effects of blood microsampling in the vehicle dosed adult rat
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