• Toxicological Research
• /
• v.18 no.1
• /
• pp.65-71
• /
• 2002

A benchmark dose (BMD) approach has been evaluated us a replacement for the traditional NOAEL methodology currently being wed to assess the noncancer effects of toxicants. The endocrine disrupt-ing effect of endosulfan which showed decrement of sperm count and testicular testosterone level in animals, was currently reported. The amount of endosulfan used as pesticide in the country has been continuously increased. The aim of this study was to suggest the permissible intake level (PIL), corresponding to Accept-able Daily Intake (ADI), based on endocrine disrupting effect wing BMD. Various animal data were collected by consideration of critical effect showing endocrine disruption and an animal data for reproductive toxicity was selected. The Power model from BMD software for induction of $BMD_10$ having meaning which is the dose at the 95% lower confidence limit on a 10% response was used due to that the form of selected dose-response animal data was continuous data. The $BMD_10$ was estimated to be 0.393 mg/kg/day based on reproductive toxicity showing decrement of sperm count. The permissible intake level (PIL) was calculated by dividing the $BMD_10$ by the uncertainty factors of 100 with consideration of from animal to human and human variability. The PIL as 0.004 mg/kg/day was compared with traditional ADI as 0.006 mg/kg/day based on the incidence of marked progressive glomerulonephrosis and blood vessel aneurysm in males.

• The Korean Journal of Applied Statistics
• /
• v.26 no.3
• /
• pp.453-470
• /
• 2013

In this paper, we consider a Bayesian analysis of the dose-effect relationship of cadmium to evaluate a benchmark dose(BMD). For this purpose, two dose-response curves commonly used in the toxicity study are fitted based on Bayesian methods to the data collected from the scientific literature on cadmium toxicity. Specifically, Bayesian meta-analysis and hierarchical modeling build an overall dose-effect relationship that use a piecewise linear model and Hill model, where the inter-study heterogeneity and inter-individual variability of dose and effect such as gender, age and ethnicity are accounted. Estimation of the unknown parameters is made by using a Markov chain Monte Carlo algorithm based user-friendly software WinBUGS. Benchmark dose estimates are evaluated for various cut-offs and compared with different tested subpopulations with with gender, age and ethnicity based on these two Bayesian hierarchical models.

• Toxicological Research
• /
• v.34 no.4
• /
• pp.303-310
• /
• 2018

The methods of applied genetic toxicology are changing from qualitative hazard identification to quantitative risk assessment. Recently, quantitative analysis with point of departure (PoD) metrics and benchmark dose (BMD) modeling have been applied to in vitro genotoxicity data. Two software packages are commonly used for BMD analysis. In previous studies, we performed quantitative dose-response analysis by using the PROAST software to quantitatively evaluate the mutagenicity of four piperidine nitroxides with various substituent groups on the 4-position of the piperidine ring and six cigarette whole smoke solutions (WSSs) prepared by bubbling machine-generated whole smoke. In the present study, we reanalyzed the obtained genotoxicity data by using the EPA's BMD software (BMDS) to evaluate the inter-platform quantitative agreement of the estimates of genotoxic potency. We calculated the BMDs for 10%, 50%, and 100% (i.e., a two-fold increase), and 200% increases over the concurrent vehicle controls to achieve better discrimination of the dose-responses, along with their BMDLs (the lower 95% confidence interval of the BMD) and BMDUs (the upper 95% confidence interval of the BMD). The BMD values and rankings estimated in this study by using the EPA's BMDS were reasonably similar to those calculated in our previous studies by using PROAST. These results indicated that both software packages were suitable for dose-response analysis using the mouse lymphoma assay and that the BMD modeling results from these software packages produced comparable rank orders of the mutagenic potency.

• Journal of the Korean Data and Information Science Society
• /
• v.25 no.5
• /
• pp.987-998
• /
• 2014

The primary purpose of this paper is to derive a benchmark dose lower limit (BMDL) of lead for the attention deficit/hyperactive disorder (ADHD) based on a longitudinal cohort data set which is referred to as CHEER data set. The CHEER data were recently recruited from the Ministry of Environment of S. Korea to investigate the effect of environment on children's health We first confirm the correlation of ADHD with the blood lead level using a linear mixed effect model. We report from the longitudinal characteristic of CHEER data that ADHD scores tend to have "regression to the mean". A dose-response curve of blood lead level with ADHD being the end point is derived and from this dose-response curve a few BMDLs are derived based on corresponding assumptions on the benchmark region.

• Communications for Statistical Applications and Methods
• /
• v.29 no.2
• /
• pp.239-250
• /
• 2022

In many applications, we frequently encounter correlated multiple outcomes measured on the same subject. Joint modeling of such multiple outcomes can improve efficiency of inference compared to independent modeling. For instance, in developmental toxicity studies, fetal weight and number of malformed pups are measured on the pregnant dams exposed to different levels of a toxic substance, in which the association between such outcomes should be taken into account in the model. The number of malformations may possibly have many zeros, which should be analyzed via zero-inflated count models. Motivated by applications in developmental toxicity studies, we propose a Bayesian joint modeling framework for continuous and count outcomes with excess zeros. In our model, zero-inflated Poisson (ZIP) regression model would be used to describe count data, and a subject-specific random effects would account for the correlation across the two outcomes. We implement a Bayesian approach using MCMC procedure with data augmentation method and adaptive rejection sampling. We apply our proposed model to dose-response analysis in a developmental toxicity study to estimate the benchmark dose in a risk assessment.

• 대한예방의학회:학술대회논문집
• /
• 1994.02a
• /
• pp.412-415
• /
• 1994

The fundamental assumption that thresholds exist for noncarcinogenic toxic effects of chemicals is reviewed; this assumption forms the basis for the no-observed-effect level/ safety-factor (NOEL/SF) approach to risk assessment for such effects. The origin and evolution of the NOEL/SF approach are traced, and its limitations are discussed. The recently proposed use of dose-response modeling to estimate a benchmark dose as a replacement for the NOEL is explained. The possibility of expanding dose-response modeling of non carcinogenic effects to include the estimation of assumed thresholds is discussed. A new method for conversion of quantitative toxic responses to a probability scale for risk assessment via dose-response modeling is outlined.

• The Korean Journal of Applied Statistics
• /
• v.25 no.3
• /
• pp.389-401
• /
• 2012

This paper derives a benchmark dose(BMD) and its 95% lower confidence limit(BMDL) using a semi-parametric regression model for small lead based changes in attention-deficit hyperactivity disorder(ADHD) scores in the first wave of the Children's Health and Environment Research(CHEER) survey data, which have been regularly collected in South Korea since 2005. Ha et al. (2009) showed that the appearance of ADHD symptoms had a borderline trend of increasing with the blood lead concentration. Butdz-J${\o}$rgensen (EFSA, 2010a) derived the BMDL of lead corresponding to a benchmark region of 1 full intelligent quotient (IQ) score using the raw data in Lanphear et al. (2005, EHP). European Food Safety Authority (EFSA, 2010b) determined the BMDL of $1.2{\mu}g/dl$ as a reference point for the characterization of lead when assessing the risk of the intellectual deficit measured by IQ scores. Kim et al. (2011) indicated that an even lower BMDL could be obtained based on the ADHD score; however, the BMDLs depended heavily upon the model assumptions. We show in this paper that a semi-parametric approach resolves the model dependence of BMDLs.

• Progress in Medical Physics
• /
• v.13 no.3
• /
• pp.149-155
• /
• 2002

Recent advances in radiation transport algorithms, computer hardware performance, and parallel computing make the clinical use of Monte Carlo based dose calculations possible. To compare the speed and accuracies of dose calculations between different developed codes, a benchmark tests were proposed at the XIIth ICCR (International Conference on the use of Computers in Radiation Therapy, Heidelberg, Germany 2000). A Monte Carlo treatment planning comprised of 28 various Intel Pentium CPUs was implemented for routine clinical use. The purpose of this study was to evaluate the performance of our system using the above benchmark tests. The benchmark procedures are comprised of three parts. a) speed of photon beams dose calculation inside a given phantom of 30.5 cm$\times$39.5 cm $\times$ 30 cm deep and filled with 5 ㎣ voxels within 2% statistical uncertainty. b) speed of electron beams dose calculation inside the same phantom as that of the photon beams. c) accuracy of photon and electron beam calculation inside heterogeneous slab phantom compared with the reference results of EGS4/PRESTA calculation. As results of the speed benchmark tests, it took 5.5 minutes to achieve less than 2% statistical uncertainty for 18 MV photon beams. Though the net calculation for electron beams was an order of faster than the photon beam, the overall calculation time was similar to that of photon beam case due to the overhead time to maintain parallel processing. Since our Monte Carlo code is EGSnrc, which is an improved version of EGS4, the accuracy tests of our system showed, as expected, very good agreement with the reference data. In conclusion, our Monte Carlo treatment planning system shows clinically meaningful results. Though other more efficient codes are developed such like MCDOSE and VMC＋＋, BEAMnrc based on EGSnrc code system may be used for routine clinical Monte Carlo treatment planning in conjunction with clustering technique.

• Proceedings of the Korean Nuclear Society Conference
• /
• 1998.05b
• /
• pp.618-623
• /
• 1998

A shielding analysis was performed for the end shield of CANDU 6 reactor. The one-dimensional discrete ordinate code ANISN with a 38-group neutron-gamma library, extracted from DLC-37D library, was used to estimate the dose rate for the natural uranium CANDU reactor. For comparison MCNP-4B calculation was performed for the same system using continuous, discrete and multi-group libraries. The comparison has shown that the total dose rate of the ANISN calculation agrees well with that of the MCNP calculation. However, the individual dose rate (neutron and gamma) has shown opposite trends between AMISN and MCNP estimates, which may require a consistent library generation for both codes.

• Progress in Medical Physics
• /
• v.19 no.1
• /
• pp.21-34
• /
• 2008

The parallel Monte Carlo electron and photon transport (PMCEPT) code [Kum and Lee, J. Korean Phys. Soc. 47, 716 (2006)] for calculating electron and photon beam doses has been developed based on the three dimensional geometry defined by computed tomography (CT) images and implemented on the Beowulf PC cluster. Understanding the limitations of Monte Carlo codes is useful in order to avoid systematic errors in simulations and to suggest further improvement of the codes. We evaluated the PMCEPT code by comparing its normalized depth doses for electron and photon beams with those of MCNP5, EGS4, DPM, and GEANT4 codes, and with measurements. The PMCEPT results agreed well with others in homogeneous and heterogeneous media within an error of $1{\sim}3%$ of the dose maximum. The computing time benchmark has also been performed for two cases, showing that the PMCEPT code was approximately twenty times faster than the MCNP5 for 20-MeV electron beams irradiated on the water phantom. For the 18-MV photon beams irradiated on the water phantom, the PMCEPT was three times faster than the GEANT4. Thus, the results suggest that the PMCEPT code is indeed appropriate for both fast and accurate simulations.