Application of a Mathematical Model to Describe the Effects of Chlorpyrifos on Caenorhabditis elegans Development
Background: The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measur...
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| description | Background: The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF) and extinction (EXT)) of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing. Methodology/Principal Findings: L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0–75 µM) and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT) and log(TOF) growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points) were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF) and log(EXT), growth rates, and time to reach change points) showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration. Conclusions: Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C. elegans development in a concentration dependent manner. The most noticeable effect on growth occurred during early larval stages: L2 and L3. This study supports the utility of the C. elegans growth assay and mathematical modeling in determining the effects of potentially toxic substances in an alternative model organism using high-throughput technologies. |
| doi_str_mv | 10.1371/journal.pone.0007024 |
| format | Article |
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As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF) and extinction (EXT)) of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing. Methodology/Principal Findings: L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0–75 µM) and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT) and log(TOF) growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points) were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF) and log(EXT), growth rates, and time to reach change points) showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration. Conclusions: Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C. elegans development in a concentration dependent manner. The most noticeable effect on growth occurred during early larval stages: L2 and L3. This study supports the utility of the C. elegans growth assay and mathematical modeling in determining the effects of potentially toxic substances in an alternative model organism using high-throughput technologies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0007024</identifier><identifier>PMID: 19753116</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adults ; Agrochemicals ; animal development ; animal growth ; Animals ; Automation ; bioassays ; Biocompatibility ; Biosort flow sorting technology ; Biotechnology ; Caenorhabditis elegans ; Caenorhabditis elegans - drug effects ; chemical concentration ; Chlorpyrifos ; Chlorpyrifos - pharmacology ; Chlorpyrifos - toxicity ; Data processing ; Dose-Response Relationship, Drug ; Environmental health ; Environmental protection ; Enzyme inhibitors ; Gene Expression Regulation, Developmental - drug effects ; Growth models ; Health sciences ; In vivo methods and tests ; Insecticides - pharmacology ; Insecticides - toxicity ; Laboratories ; laboratory techniques ; larvae ; larval development ; Markov Chains ; Mathematical analysis ; Mathematical models ; Mathematics/Statistics ; Medical screening ; Models, Statistical ; Models, Theoretical ; Nematodes ; Optical measurement ; Pesticides ; Public Health and Epidemiology/Environmental Health ; Regression Analysis ; Roundworms ; Statistical analysis ; Statistical methods ; Statistical tests ; Time Factors ; Toxic substances ; toxicity ; Toxicity testing ; Toxicology ; Worms</subject><ispartof>PloS one, 2009-09, Vol.4 (9), p.e7024</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c687t-39aa608c0a0af750bd106a83245dc0eff919f53345c6fa8fc68e6824cedbbd9f3</citedby><cites>FETCH-LOGICAL-c687t-39aa608c0a0af750bd106a83245dc0eff919f53345c6fa8fc68e6824cedbbd9f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737145/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737145/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19753116$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hart, Anne C.</contributor><creatorcontrib>Boyd, Windy A</creatorcontrib><creatorcontrib>Smith, Marjolein V</creatorcontrib><creatorcontrib>Kissling, Grace E</creatorcontrib><creatorcontrib>Rice, Julie R</creatorcontrib><creatorcontrib>Snyder, Daniel W</creatorcontrib><creatorcontrib>Portier, Christopher J</creatorcontrib><creatorcontrib>Freedman, Jonathan H</creatorcontrib><title>Application of a Mathematical Model to Describe the Effects of Chlorpyrifos on Caenorhabditis elegans Development</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Background: The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF) and extinction (EXT)) of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing. Methodology/Principal Findings: L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0–75 µM) and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT) and log(TOF) growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points) were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF) and log(EXT), growth rates, and time to reach change points) showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration. Conclusions: Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C. elegans development in a concentration dependent manner. The most noticeable effect on growth occurred during early larval stages: L2 and L3. This study supports the utility of the C. elegans growth assay and mathematical modeling in determining the effects of potentially toxic substances in an alternative model organism using high-throughput technologies.</description><subject>Adults</subject><subject>Agrochemicals</subject><subject>animal development</subject><subject>animal growth</subject><subject>Animals</subject><subject>Automation</subject><subject>bioassays</subject><subject>Biocompatibility</subject><subject>Biosort flow sorting technology</subject><subject>Biotechnology</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - drug effects</subject><subject>chemical concentration</subject><subject>Chlorpyrifos</subject><subject>Chlorpyrifos - pharmacology</subject><subject>Chlorpyrifos - toxicity</subject><subject>Data processing</subject><subject>Dose-Response Relationship, Drug</subject><subject>Environmental health</subject><subject>Environmental protection</subject><subject>Enzyme inhibitors</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Growth models</subject><subject>Health sciences</subject><subject>In vivo methods and tests</subject><subject>Insecticides - pharmacology</subject><subject>Insecticides - toxicity</subject><subject>Laboratories</subject><subject>laboratory techniques</subject><subject>larvae</subject><subject>larval development</subject><subject>Markov Chains</subject><subject>Mathematical analysis</subject><subject>Mathematical models</subject><subject>Mathematics/Statistics</subject><subject>Medical screening</subject><subject>Models, Statistical</subject><subject>Models, Theoretical</subject><subject>Nematodes</subject><subject>Optical measurement</subject><subject>Pesticides</subject><subject>Public Health and Epidemiology/Environmental Health</subject><subject>Regression Analysis</subject><subject>Roundworms</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Statistical tests</subject><subject>Time Factors</subject><subject>Toxic substances</subject><subject>toxicity</subject><subject>Toxicity 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of a Mathematical Model to Describe the Effects of Chlorpyrifos on Caenorhabditis elegans Development</title><author>Boyd, Windy A ; Smith, Marjolein V ; Kissling, Grace E ; Rice, Julie R ; Snyder, Daniel W ; Portier, Christopher J ; Freedman, Jonathan H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c687t-39aa608c0a0af750bd106a83245dc0eff919f53345c6fa8fc68e6824cedbbd9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adults</topic><topic>Agrochemicals</topic><topic>animal development</topic><topic>animal growth</topic><topic>Animals</topic><topic>Automation</topic><topic>bioassays</topic><topic>Biocompatibility</topic><topic>Biosort flow sorting technology</topic><topic>Biotechnology</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans - drug effects</topic><topic>chemical concentration</topic><topic>Chlorpyrifos</topic><topic>Chlorpyrifos - pharmacology</topic><topic>Chlorpyrifos - toxicity</topic><topic>Data processing</topic><topic>Dose-Response Relationship, Drug</topic><topic>Environmental health</topic><topic>Environmental protection</topic><topic>Enzyme inhibitors</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Growth models</topic><topic>Health sciences</topic><topic>In vivo methods and tests</topic><topic>Insecticides - pharmacology</topic><topic>Insecticides - toxicity</topic><topic>Laboratories</topic><topic>laboratory techniques</topic><topic>larvae</topic><topic>larval development</topic><topic>Markov Chains</topic><topic>Mathematical analysis</topic><topic>Mathematical models</topic><topic>Mathematics/Statistics</topic><topic>Medical screening</topic><topic>Models, Statistical</topic><topic>Models, Theoretical</topic><topic>Nematodes</topic><topic>Optical measurement</topic><topic>Pesticides</topic><topic>Public Health and Epidemiology/Environmental 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Effects of Chlorpyrifos on Caenorhabditis elegans Development</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-09-15</date><risdate>2009</risdate><volume>4</volume><issue>9</issue><spage>e7024</spage><pages>e7024-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Background: The nematode Caenorhabditis elegans is being assessed as an alternative model organism as part of an interagency effort to develop better means to test potentially toxic substances. As part of this effort, assays that use the COPAS Biosort flow sorting technology to record optical measurements (time of flight (TOF) and extinction (EXT)) of individual nematodes under various chemical exposure conditions are being developed. A mathematical model has been created that uses Biosort data to quantitatively and qualitatively describe C. elegans growth, and link changes in growth rates to biological events. Chlorpyrifos, an organophosphate pesticide known to cause developmental delays and malformations in mammals, was used as a model toxicant to test the applicability of the growth model for in vivo toxicological testing. Methodology/Principal Findings: L1 larval nematodes were exposed to a range of sub-lethal chlorpyrifos concentrations (0–75 µM) and measured every 12 h. In the absence of toxicant, C. elegans matured from L1s to gravid adults by 60 h. A mathematical model was used to estimate nematode size distributions at various times. Mathematical modeling of the distributions allowed the number of measured nematodes and log(EXT) and log(TOF) growth rates to be estimated. The model revealed three distinct growth phases. The points at which estimated growth rates changed (change points) were constant across the ten chlorpyrifos concentrations. Concentration response curves with respect to several model-estimated quantities (numbers of measured nematodes, mean log(TOF) and log(EXT), growth rates, and time to reach change points) showed a significant decrease in C. elegans growth with increasing chlorpyrifos concentration. Conclusions: Effects of chlorpyrifos on C. elegans growth and development were mathematically modeled. Statistical tests confirmed a significant concentration effect on several model endpoints. This confirmed that chlorpyrifos affects C. elegans development in a concentration dependent manner. The most noticeable effect on growth occurred during early larval stages: L2 and L3. This study supports the utility of the C. elegans growth assay and mathematical modeling in determining the effects of potentially toxic substances in an alternative model organism using high-throughput technologies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19753116</pmid><doi>10.1371/journal.pone.0007024</doi><tpages>e7024</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-09, Vol.4 (9), p.e7024 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1291074860 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adults Agrochemicals animal development animal growth Animals Automation bioassays Biocompatibility Biosort flow sorting technology Biotechnology Caenorhabditis elegans Caenorhabditis elegans - drug effects chemical concentration Chlorpyrifos Chlorpyrifos - pharmacology Chlorpyrifos - toxicity Data processing Dose-Response Relationship, Drug Environmental health Environmental protection Enzyme inhibitors Gene Expression Regulation, Developmental - drug effects Growth models Health sciences In vivo methods and tests Insecticides - pharmacology Insecticides - toxicity Laboratories laboratory techniques larvae larval development Markov Chains Mathematical analysis Mathematical models Mathematics/Statistics Medical screening Models, Statistical Models, Theoretical Nematodes Optical measurement Pesticides Public Health and Epidemiology/Environmental Health Regression Analysis Roundworms Statistical analysis Statistical methods Statistical tests Time Factors Toxic substances toxicity Toxicity testing Toxicology Worms |
| title | Application of a Mathematical Model to Describe the Effects of Chlorpyrifos on Caenorhabditis elegans Development |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T23%3A27%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Application%20of%20a%20Mathematical%20Model%20to%20Describe%20the%20Effects%20of%20Chlorpyrifos%20on%20Caenorhabditis%20elegans%20Development&rft.jtitle=PloS%20one&rft.au=Boyd,%20Windy%20A&rft.date=2009-09-15&rft.volume=4&rft.issue=9&rft.spage=e7024&rft.pages=e7024-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0007024&rft_dat=%3Cgale_plos_%3EA472875421%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1291074860&rft_id=info:pmid/19753116&rft_galeid=A472875421&rft_doaj_id=oai_doaj_org_article_192ef83a96db412682bed36d6e68fc24&rfr_iscdi=true |