P12: Benchmark dose for 3-monochloro-propane-1,2-diol (3-MCPD) in rat 2-year study
Chronic exposure guideline levels for the public are generally based on doses that produce no effects, following a NOAEL/LOAEL approach. Benchmark dose (BMD) approach devised by Crump (1982) may use to determine critical effect dose that are more or less conservative than the NOAEL/LOAEL approach. I...
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Veröffentlicht in: | Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2009-05, Vol.61 (3), p.287-287 |
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container_title | Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie |
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creator | Hwang, Myungsil Yun, Eukyung Shin, Jae-Ho Choi, Hong Serck Kim, Ja Young Jang, Dong Deuk Yoo, Tae Moo |
description | Chronic exposure guideline levels for the public are generally based on doses that produce no effects, following a NOAEL/LOAEL approach. Benchmark dose (BMD) approach devised by Crump (1982) may use to determine critical effect dose that are more or less conservative than the NOAEL/LOAEL approach. In this study, the use of the BMD as an alternative to a NOAEL approach was investigated as a mean to improve current risk assessment values of 3-monochloro-propane-1,2-diol (3-MCPD). We reviewed for the critical toxicological endpoints of 3-MCPD, namely nephropathy, tubular hyperplasia and tubule adenoma identified from the two available critical studies. Using the USEPA BMD software, considering available dichotomous models, we calculated BMDs of 3-MCPD, and their lower confidence limits (BMDLs) at response levels of 10%. The BMDs and BMDLs for the three end points were estimated using the Weibull, Probit, Linear, and Log-logistic models for each end point. All models passed the
x
2 test statistics (
p |
doi_str_mv | 10.1016/j.etp.2009.02.049 |
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x
2 test statistics (
p<0.1) for all the toxicity endpoints tested. The Log-logistic model provided a reasonable fit to all of the data sets. A Benchmark response (BMR) of 10% extra risk was chosen and the Akaike's information criterion (AIC) was used in selecting the appropriate model. Based on the Log-logistic model, the BMDL estimates derived were found to be slightly higher than NOAEL for same endpoint but never exceed the LOAEL, indicating a reasonable association of the BMDL10 with the NOAEL. The BMD and BMDL for tubular hyperplasia, the most critical effect associated with 3-MCPD exposure, were 0.94 and 0.68
mg/kg/day, respectively. This value will be used in the eventual determination of Tolerable Daily Dose (TDI) for 3-MCPD. This study has provided evidence that the BMD approach is a useful tool in reducing uncertainty in determination of an experimental threshold for adverse effects and improving the risk assessment for contaminants in food. This is an abstract of a proposed presentation and doses not reflect Korea Food and Drug Administration (KFDA) policy. Further studies are necessary to confirm whether proposed BMDL should be suggested in determination of the limit guidance level in KFDA.</description><identifier>ISSN: 0940-2993</identifier><identifier>EISSN: 1618-1433</identifier><identifier>DOI: 10.1016/j.etp.2009.02.049</identifier><language>eng</language><publisher>Elsevier GmbH</publisher><ispartof>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie, 2009-05, Vol.61 (3), p.287-287</ispartof><rights>2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.etp.2009.02.049$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids></links><search><creatorcontrib>Hwang, Myungsil</creatorcontrib><creatorcontrib>Yun, Eukyung</creatorcontrib><creatorcontrib>Shin, Jae-Ho</creatorcontrib><creatorcontrib>Choi, Hong Serck</creatorcontrib><creatorcontrib>Kim, Ja Young</creatorcontrib><creatorcontrib>Jang, Dong Deuk</creatorcontrib><creatorcontrib>Yoo, Tae Moo</creatorcontrib><title>P12: Benchmark dose for 3-monochloro-propane-1,2-diol (3-MCPD) in rat 2-year study</title><title>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie</title><description>Chronic exposure guideline levels for the public are generally based on doses that produce no effects, following a NOAEL/LOAEL approach. Benchmark dose (BMD) approach devised by Crump (1982) may use to determine critical effect dose that are more or less conservative than the NOAEL/LOAEL approach. In this study, the use of the BMD as an alternative to a NOAEL approach was investigated as a mean to improve current risk assessment values of 3-monochloro-propane-1,2-diol (3-MCPD). We reviewed for the critical toxicological endpoints of 3-MCPD, namely nephropathy, tubular hyperplasia and tubule adenoma identified from the two available critical studies. Using the USEPA BMD software, considering available dichotomous models, we calculated BMDs of 3-MCPD, and their lower confidence limits (BMDLs) at response levels of 10%. The BMDs and BMDLs for the three end points were estimated using the Weibull, Probit, Linear, and Log-logistic models for each end point. All models passed the
x
2 test statistics (
p<0.1) for all the toxicity endpoints tested. The Log-logistic model provided a reasonable fit to all of the data sets. A Benchmark response (BMR) of 10% extra risk was chosen and the Akaike's information criterion (AIC) was used in selecting the appropriate model. Based on the Log-logistic model, the BMDL estimates derived were found to be slightly higher than NOAEL for same endpoint but never exceed the LOAEL, indicating a reasonable association of the BMDL10 with the NOAEL. The BMD and BMDL for tubular hyperplasia, the most critical effect associated with 3-MCPD exposure, were 0.94 and 0.68
mg/kg/day, respectively. This value will be used in the eventual determination of Tolerable Daily Dose (TDI) for 3-MCPD. This study has provided evidence that the BMD approach is a useful tool in reducing uncertainty in determination of an experimental threshold for adverse effects and improving the risk assessment for contaminants in food. This is an abstract of a proposed presentation and doses not reflect Korea Food and Drug Administration (KFDA) policy. Further studies are necessary to confirm whether proposed BMDL should be suggested in determination of the limit guidance level in KFDA.</description><issn>0940-2993</issn><issn>1618-1433</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNp9kEtPwzAQhC0EEqXwA7j5hEDCYf3Iw3CC8pSKqBCcrcTZqClpXOwUqf8eV-XMafcwM5r5CDnlkHDg2dUiwWGVCACdgEhA6T0y4hkvGFdS7pMRaAVMaC0PyVEICwABOuUj8j7j4preYW_ny9J_0doFpI3zVLKl652dd847tvJuVfbI-KVgdes6ei7Z62R2f0HbnvpyoIJtsPQ0DOt6c0wOmrILePJ3x-Tz8eFj8symb08vk9sps1ykKhYrCiwyrCoFqZWiQZAVV01uUVohcy15JUUaf1S5TkvkecohyypbVqgwlWNytsuN7b7XGAazbIPFrotN3ToYAWmmCqWikO-E1rsQPDZm5du4dmM4mC09szCRntnSMyBMpBc9NzsPxgU_LXoTbBspYd16tIOpXfuP-xdtbHRJ</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Hwang, Myungsil</creator><creator>Yun, Eukyung</creator><creator>Shin, Jae-Ho</creator><creator>Choi, Hong Serck</creator><creator>Kim, Ja Young</creator><creator>Jang, Dong Deuk</creator><creator>Yoo, Tae Moo</creator><general>Elsevier GmbH</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20090501</creationdate><title>P12: Benchmark dose for 3-monochloro-propane-1,2-diol (3-MCPD) in rat 2-year study</title><author>Hwang, Myungsil ; Yun, Eukyung ; Shin, Jae-Ho ; Choi, Hong Serck ; Kim, Ja Young ; Jang, Dong Deuk ; Yoo, Tae Moo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1254-1488e86ebb405c32fe03b14f7ce3c237931b3253c2e4795ae1751066bcabe4e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hwang, Myungsil</creatorcontrib><creatorcontrib>Yun, Eukyung</creatorcontrib><creatorcontrib>Shin, Jae-Ho</creatorcontrib><creatorcontrib>Choi, Hong Serck</creatorcontrib><creatorcontrib>Kim, Ja Young</creatorcontrib><creatorcontrib>Jang, Dong Deuk</creatorcontrib><creatorcontrib>Yoo, Tae Moo</creatorcontrib><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hwang, Myungsil</au><au>Yun, Eukyung</au><au>Shin, Jae-Ho</au><au>Choi, Hong Serck</au><au>Kim, Ja Young</au><au>Jang, Dong Deuk</au><au>Yoo, Tae Moo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>P12: Benchmark dose for 3-monochloro-propane-1,2-diol (3-MCPD) in rat 2-year study</atitle><jtitle>Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie</jtitle><date>2009-05-01</date><risdate>2009</risdate><volume>61</volume><issue>3</issue><spage>287</spage><epage>287</epage><pages>287-287</pages><issn>0940-2993</issn><eissn>1618-1433</eissn><abstract>Chronic exposure guideline levels for the public are generally based on doses that produce no effects, following a NOAEL/LOAEL approach. Benchmark dose (BMD) approach devised by Crump (1982) may use to determine critical effect dose that are more or less conservative than the NOAEL/LOAEL approach. In this study, the use of the BMD as an alternative to a NOAEL approach was investigated as a mean to improve current risk assessment values of 3-monochloro-propane-1,2-diol (3-MCPD). We reviewed for the critical toxicological endpoints of 3-MCPD, namely nephropathy, tubular hyperplasia and tubule adenoma identified from the two available critical studies. Using the USEPA BMD software, considering available dichotomous models, we calculated BMDs of 3-MCPD, and their lower confidence limits (BMDLs) at response levels of 10%. The BMDs and BMDLs for the three end points were estimated using the Weibull, Probit, Linear, and Log-logistic models for each end point. All models passed the
x
2 test statistics (
p<0.1) for all the toxicity endpoints tested. The Log-logistic model provided a reasonable fit to all of the data sets. A Benchmark response (BMR) of 10% extra risk was chosen and the Akaike's information criterion (AIC) was used in selecting the appropriate model. Based on the Log-logistic model, the BMDL estimates derived were found to be slightly higher than NOAEL for same endpoint but never exceed the LOAEL, indicating a reasonable association of the BMDL10 with the NOAEL. The BMD and BMDL for tubular hyperplasia, the most critical effect associated with 3-MCPD exposure, were 0.94 and 0.68
mg/kg/day, respectively. This value will be used in the eventual determination of Tolerable Daily Dose (TDI) for 3-MCPD. This study has provided evidence that the BMD approach is a useful tool in reducing uncertainty in determination of an experimental threshold for adverse effects and improving the risk assessment for contaminants in food. This is an abstract of a proposed presentation and doses not reflect Korea Food and Drug Administration (KFDA) policy. Further studies are necessary to confirm whether proposed BMDL should be suggested in determination of the limit guidance level in KFDA.</abstract><pub>Elsevier GmbH</pub><doi>10.1016/j.etp.2009.02.049</doi><tpages>1</tpages></addata></record> |
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title | P12: Benchmark dose for 3-monochloro-propane-1,2-diol (3-MCPD) in rat 2-year study |
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