• Toxicological Research
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• 제18권1호
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• pp.65-71
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• 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.

• Toxicological Research
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• 제34권4호
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• pp.303-310
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• 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.

• 응용통계연구
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• 제26권3호
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• pp.453-470
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• 2013

본 논문에서는 카드뮴의 반응-용량 모형에 대한 베이지안 분석을 실시하고 기준용량에 대한 추정값들을 유도하고 비교한다. 이를 위하여 독성물질에 대한 용량반응곡선에서 많이 활용되는 두 가지 모형을 사용하고, 카드뮴의 독성연구에 관련한 기존의 문헌으로 수집된 자료에 대한 성별, 연령, 인종, study code 등과 같은 소집단 간의 개별적 형질을 반영할 수 있는 베이지안 메타분석 관점에서의 모형분석을 실시한다. 이러한 두 가지 모형에 대한 베이지안 분석을 위하여 WinBUGS를 이용한 마르코프 연쇄 몬테칼로(Markov chain Monte Carlo; MCMC) 방법을 통하여 모수를 추정하고 이에 따른 다양한 기준용량들을 계산하고 비교해보았다. 베이지안 모형 적합뿐만 아니라 편차정보기준을 통해서 주어진 자료를 더 잘 설명하는 모형을 선택하는 베이지안 모형 선택을 고려하였고, 이를 실제 자료에 적용해본다.

• 응용통계연구
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• 제25권3호
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• pp.389-401
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• 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.

• 한국식품위생안전성학회지
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• 제17권3호
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• pp.137-145
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• 2002

국내 6개 주요도시에서 조사된 어패류 오염도 현황을 토대로 우리나라 사람들의 어패류 섭취를 통한 유기주석화합물 인체노출량을 예측하고, 이에 따른 위해도를 추계하였다. 본 연구결과를 살펴보면 갈치의 경우, 성인이 식품수급표에서 제시하는 일일섭취량 3.02g/day를 평생 섭취한다는 노출시나리오하에 평균일일노출량은 확률분포로 나타냈을 때 그 중간값이 6.48$\times$ $10^{-7}$ mg/kg/day, 상한치 95th percentile값이 8.78$\times$$10^{-7}$ mg/kg/day로 나타났음을 알 수 있다. 본 연구에서는 비발암독성영향을 평가하기 위하여 BMD$_{10}$ 을 활용한 참고치(Reference dose)를 예측하였다. 이 때 BMD$_{10}$은 10% 비교변화를 BMR으로 하였을때 해당하는 용량의 95% 하한치이다. 본 연구에서 활용한 BMD는 digestion에 의한 근육내의 IgE titer, T.spiraris larvae와 조직학에 의한 근육내 T.spiraris larvae에 근거하여 예측된 것으로 0.03 mg/kg/day이다. 참고치는 BMD$_{10}$ 0.03 mg/kg/day에 불확실성 계수 100을 고려한 값으로 0.003 mg/kg/day이며, 이 때 활용한 불확실성계수는 실험동물에서 인체로의 외삽과정에서 고려한 계수 10과 인구집단 내 민감그룹 고려를 위한 계수 10을 적용한 것이다. 각 어패류의 위험지수(50th percentile)를 살펴보면 고등어에서 2.04$\times$ $10^{-2}$으로 가장 높게 나타났으며, 소라에서 2.70$\times$ $10^{-5}$으로 가장 낮은 값을 나타냈다.

• 한국환경성돌연변이발암원학회지
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• 제22권3호
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• pp.187-198
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• 2002

Chlorpyrifos is an organophosphate insecticide and one of the most commonly and widely used insecticide. However, a little known about the dermal risk of chlorpyrifos on human being. Therefore, this study was conducted for the dermal risk assessment after exposure to chlorpyrifos in Korean farmers. First, skin irritation by chlorpyrifos (10 mg/$\textrm{cm}^2$, 50 mg/$\textrm{cm}^2$, 100 mg/$\textrm{cm}^2$, 250 mg/$\textrm{cm}^2$ in acetone) was determined in rabbits for 5 days considering the usage of chlorpyrifos short term highly exposure. The index of skin irritation by chlorpyrifos was increased in each dose and length of exposure dependent manners. Next, using benchmark dose (BMD$_{5}$) approach, the dose-response relationship was assessed to calculate the reference dose (RfD). The value of RfD was 2.84 $\mu\textrm{g}$/kg/day from 142.16 $\mu\textrm{g}$/kg/day BMD5 value divided uncertainty factor 50. Finally, we assessed human dermal risk of chlorpyrifos with exposure level and RfD. Skin absorbed levels were assumed with several exposure scenarios encounting the circumstances of exposure that application method, protection equipment and cloth, exposure time and exposure frequency during chlorpyrifos spraying. By the comparison of skin absorbed dose with the reference dose, it was identified that risk values (risk index) to skin chlorpyrifos exposure were 0.958 from the point of above results and it was recommended that the occurrence of hazard effect (skin irritation toxicity) of chlorpyrifos would not be expected. Risk index was smaller than 1 in the case of spraying vehicle mounted application, 1hour exposure time and wearing protective cloth exposure. Whereas, risk index was above 1 in the case of hand-held application, 2hour exposure time and wearing common cloth. Comparing two kinds of application method, total risk index of the hand held application (1.67) was higher than vehicle mounted (0.27). Therefore, chlorpyrifos skin exposure was mainly affected by application equipment and applied form. The results of risk assessment on the human dermal toxicity of chlorpyrifos should be required to control in keeping safety rules, skin surface area available for contact, spraying time ,and spraying frequency.y.

• 한국환경과학회지
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• 제25권4호
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• pp.505-516
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• 2016

With the development of nanotechnology, nanomaterials are used in various fields. Therefore, the interest regarding the safety of nanomaterial use is increasing and much effort is diverted toward establishment of exposure assessment and management methods. Occupational exposure limits (OELs) are effectively used to protect the health of workers in various industrial workplaces. This study aimed to propose an OEL for domestic multi-walled carbon nanotubes (MWCNTs) based on animal inhalation toxicity test. Basic procedure for development of OELs was examined. For OEL estimation, epidemiological study and quantitative risk assessment are generally performed based on toxicity data. In addition, inhalation toxicity data-based no observed adverse effect level (NOAEL) and benchmark dose (BMD) are estimated to obtain the OEL. Three different estimation processes (NEDO in Japan, NIOSH in USA, and Baytubes in Germany) of OELs for carbon nanotubes (CNTs) were intensively reviewed. From the rat inhalation toxicity test for MWCNTs manufactured in Korea, a NOAEL of $0.98mg/m^3$ was derived. Using the simple equation for estimation of OEL suggested by NEDO, the OEL of $142{\mu}g/m^3$ was estimated for the MWCNT manufacturing workplace. Here, we used test rat and Korean human data and adopted 36 as an uncertainty factor. The OEL for MWCNT estimated in this work is higher than those ($2-80{\mu}g/m^3$) suggested by previous investigators. It may be greatly caused by different physicochemical properties of MWCNT and their dispersion method and test rat data. For setting of regulatory OELs in CNT workplaces, further epidemiological studies in addition to animal studies are needed. More advanced technical methods such as CNT dispersion in air and liquid should be also developed.