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
Hauptverfasser: Hwang, Myungsil, Yun, Eukyung, Shin, Jae-Ho, Choi, Hong Serck, Kim, Ja Young, Jang, Dong Deuk, Yoo, Tae Moo
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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
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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&lt;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. 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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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