An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty
This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors...
Gespeichert in:
| Veröffentlicht in: | Risk analysis 1997-08, Vol.17 (4), p.427-437 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 437 |
|---|---|
| container_issue | 4 |
| container_start_page | 427 |
| container_title | Risk analysis |
| container_volume | 17 |
| creator | Price, Paul S. Keenan, Russell E. Swartout, Jeffrey C. Gillis, Carol A. Carlson-Lynch, Heather Dourson, Michael L. |
| description | This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No‐Observed‐Adverse‐Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD |
| doi_str_mv | 10.1111/j.1539-6924.1997.tb00883.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_16092630</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>16092630</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4397-74112284254700843965999d39723e224ecb713ea02d8033eb42c1add2921b73</originalsourceid><addsrcrecordid>eNqVkM1u2zAQhImgQeq4eYQCRA-9SSGXlCj2Urj5NZImiJOiQC8EJa1ruTKpijJiv30k2PA9vCzAmZ3d_Qj5wlnM-3e-jHkidJRqkDHXWsVdzliWiXhzREYH6QMZMVAQSSHgIzkNYckYZyxRJ-RECxCZghF5mjg6aZrW22JB576lP32JdeX-0gfvCusKbOmlD0hnGBrvAgb6WnULah29WjULG6pAvaO_BmNnK9dtP5Hjua0Dnu3rmLxcX71c3Eb3jzfTi8l9VEihVaQk5wCZhESqfvn-L0201mWvgUAAiUWuuEDLoMyYEJhLKLgtS9DAcyXG5Osutt_9_xpDZ1ZVKLCurUO_DoanTEMqWG_8tjMWrQ-hxblp2mpl263hzAw4zdIMzMzAzAw4zR6n2fTNn_dT1vkKy0Prnl-vf9_pr1WN23ckm9n0eSJhuCPaJVShw80hwbb_TKqESszvhxvz5272rH7oawPiDUj4ksE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>16092630</pqid></control><display><type>article</type><title>An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Price, Paul S. ; Keenan, Russell E. ; Swartout, Jeffrey C. ; Gillis, Carol A. ; Carlson-Lynch, Heather ; Dourson, Michael L.</creator><creatorcontrib>Price, Paul S. ; Keenan, Russell E. ; Swartout, Jeffrey C. ; Gillis, Carol A. ; Carlson-Lynch, Heather ; Dourson, Michael L.</creatorcontrib><description>This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No‐Observed‐Adverse‐Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD</description><identifier>ISSN: 0272-4332</identifier><identifier>EISSN: 1539-6924</identifier><identifier>DOI: 10.1111/j.1539-6924.1997.tb00883.x</identifier><identifier>PMID: 9323872</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject><![CDATA[Acetamides - administration & dosage ; Acetamides - toxicity ; Animals ; dose response ; Dose-Response Relationship, Drug ; Drug-Related Side Effects and Adverse Reactions ; Environmental Pollutants - administration & dosage ; Environmental Pollutants - toxicity ; Hexachlorobenzene - administration & dosage ; Hexachlorobenzene - toxicity ; Humans ; Linear Models ; Mathematics ; Models, Biological ; Monte Carlo Method ; No-Observed-Adverse-Effect Level ; Noncarcinogenic ; Paraquat - administration & dosage ; Paraquat - toxicity ; Pentachlorophenol - administration & dosage ; Pentachlorophenol - toxicity ; Pharmaceutical Preparations - administration & dosage ; Pharmaceutical Preparations - standards ; probabilistic ; Probability ; reference dose ; Risk Assessment ; uncertainty]]></subject><ispartof>Risk analysis, 1997-08, Vol.17 (4), p.427-437</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4397-74112284254700843965999d39723e224ecb713ea02d8033eb42c1add2921b73</citedby><cites>FETCH-LOGICAL-c4397-74112284254700843965999d39723e224ecb713ea02d8033eb42c1add2921b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1539-6924.1997.tb00883.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1539-6924.1997.tb00883.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9323872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Price, Paul S.</creatorcontrib><creatorcontrib>Keenan, Russell E.</creatorcontrib><creatorcontrib>Swartout, Jeffrey C.</creatorcontrib><creatorcontrib>Gillis, Carol A.</creatorcontrib><creatorcontrib>Carlson-Lynch, Heather</creatorcontrib><creatorcontrib>Dourson, Michael L.</creatorcontrib><title>An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty</title><title>Risk analysis</title><addtitle>Risk Anal</addtitle><description>This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No‐Observed‐Adverse‐Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD</description><subject>Acetamides - administration & dosage</subject><subject>Acetamides - toxicity</subject><subject>Animals</subject><subject>dose response</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug-Related Side Effects and Adverse Reactions</subject><subject>Environmental Pollutants - administration & dosage</subject><subject>Environmental Pollutants - toxicity</subject><subject>Hexachlorobenzene - administration & dosage</subject><subject>Hexachlorobenzene - toxicity</subject><subject>Humans</subject><subject>Linear Models</subject><subject>Mathematics</subject><subject>Models, Biological</subject><subject>Monte Carlo Method</subject><subject>No-Observed-Adverse-Effect Level</subject><subject>Noncarcinogenic</subject><subject>Paraquat - administration & dosage</subject><subject>Paraquat - toxicity</subject><subject>Pentachlorophenol - administration & dosage</subject><subject>Pentachlorophenol - toxicity</subject><subject>Pharmaceutical Preparations - administration & dosage</subject><subject>Pharmaceutical Preparations - standards</subject><subject>probabilistic</subject><subject>Probability</subject><subject>reference dose</subject><subject>Risk Assessment</subject><subject>uncertainty</subject><issn>0272-4332</issn><issn>1539-6924</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkM1u2zAQhImgQeq4eYQCRA-9SSGXlCj2Urj5NZImiJOiQC8EJa1ruTKpijJiv30k2PA9vCzAmZ3d_Qj5wlnM-3e-jHkidJRqkDHXWsVdzliWiXhzREYH6QMZMVAQSSHgIzkNYckYZyxRJ-RECxCZghF5mjg6aZrW22JB576lP32JdeX-0gfvCusKbOmlD0hnGBrvAgb6WnULah29WjULG6pAvaO_BmNnK9dtP5Hjua0Dnu3rmLxcX71c3Eb3jzfTi8l9VEihVaQk5wCZhESqfvn-L0201mWvgUAAiUWuuEDLoMyYEJhLKLgtS9DAcyXG5Osutt_9_xpDZ1ZVKLCurUO_DoanTEMqWG_8tjMWrQ-hxblp2mpl263hzAw4zdIMzMzAzAw4zR6n2fTNn_dT1vkKy0Prnl-vf9_pr1WN23ckm9n0eSJhuCPaJVShw80hwbb_TKqESszvhxvz5272rH7oawPiDUj4ksE</recordid><startdate>199708</startdate><enddate>199708</enddate><creator>Price, Paul S.</creator><creator>Keenan, Russell E.</creator><creator>Swartout, Jeffrey C.</creator><creator>Gillis, Carol A.</creator><creator>Carlson-Lynch, Heather</creator><creator>Dourson, Michael L.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7U1</scope><scope>7U2</scope><scope>C1K</scope></search><sort><creationdate>199708</creationdate><title>An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty</title><author>Price, Paul S. ; Keenan, Russell E. ; Swartout, Jeffrey C. ; Gillis, Carol A. ; Carlson-Lynch, Heather ; Dourson, Michael L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4397-74112284254700843965999d39723e224ecb713ea02d8033eb42c1add2921b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Acetamides - administration & dosage</topic><topic>Acetamides - toxicity</topic><topic>Animals</topic><topic>dose response</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug-Related Side Effects and Adverse Reactions</topic><topic>Environmental Pollutants - administration & dosage</topic><topic>Environmental Pollutants - toxicity</topic><topic>Hexachlorobenzene - administration & dosage</topic><topic>Hexachlorobenzene - toxicity</topic><topic>Humans</topic><topic>Linear Models</topic><topic>Mathematics</topic><topic>Models, Biological</topic><topic>Monte Carlo Method</topic><topic>No-Observed-Adverse-Effect Level</topic><topic>Noncarcinogenic</topic><topic>Paraquat - administration & dosage</topic><topic>Paraquat - toxicity</topic><topic>Pentachlorophenol - administration & dosage</topic><topic>Pentachlorophenol - toxicity</topic><topic>Pharmaceutical Preparations - administration & dosage</topic><topic>Pharmaceutical Preparations - standards</topic><topic>probabilistic</topic><topic>Probability</topic><topic>reference dose</topic><topic>Risk Assessment</topic><topic>uncertainty</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Price, Paul S.</creatorcontrib><creatorcontrib>Keenan, Russell E.</creatorcontrib><creatorcontrib>Swartout, Jeffrey C.</creatorcontrib><creatorcontrib>Gillis, Carol A.</creatorcontrib><creatorcontrib>Carlson-Lynch, Heather</creatorcontrib><creatorcontrib>Dourson, Michael L.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Risk analysis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Price, Paul S.</au><au>Keenan, Russell E.</au><au>Swartout, Jeffrey C.</au><au>Gillis, Carol A.</au><au>Carlson-Lynch, Heather</au><au>Dourson, Michael L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty</atitle><jtitle>Risk analysis</jtitle><addtitle>Risk Anal</addtitle><date>1997-08</date><risdate>1997</risdate><volume>17</volume><issue>4</issue><spage>427</spage><epage>437</epage><pages>427-437</pages><issn>0272-4332</issn><eissn>1539-6924</eissn><abstract>This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No‐Observed‐Adverse‐Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>9323872</pmid><doi>10.1111/j.1539-6924.1997.tb00883.x</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0272-4332 |
| ispartof | Risk analysis, 1997-08, Vol.17 (4), p.427-437 |
| issn | 0272-4332 1539-6924 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_16092630 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Acetamides - administration & dosage Acetamides - toxicity Animals dose response Dose-Response Relationship, Drug Drug-Related Side Effects and Adverse Reactions Environmental Pollutants - administration & dosage Environmental Pollutants - toxicity Hexachlorobenzene - administration & dosage Hexachlorobenzene - toxicity Humans Linear Models Mathematics Models, Biological Monte Carlo Method No-Observed-Adverse-Effect Level Noncarcinogenic Paraquat - administration & dosage Paraquat - toxicity Pentachlorophenol - administration & dosage Pentachlorophenol - toxicity Pharmaceutical Preparations - administration & dosage Pharmaceutical Preparations - standards probabilistic Probability reference dose Risk Assessment uncertainty |
| title | An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T01%3A52%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20Approach%20for%20Modeling%20Noncancer%20Dose%20Responses%20with%20an%20Emphasis%20on%20Uncertainty&rft.jtitle=Risk%20analysis&rft.au=Price,%20Paul%20S.&rft.date=1997-08&rft.volume=17&rft.issue=4&rft.spage=427&rft.epage=437&rft.pages=427-437&rft.issn=0272-4332&rft.eissn=1539-6924&rft_id=info:doi/10.1111/j.1539-6924.1997.tb00883.x&rft_dat=%3Cproquest_cross%3E16092630%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=16092630&rft_id=info:pmid/9323872&rfr_iscdi=true |