• 농약과학회지
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• 제11권2호
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• pp.87-94
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• 2007

본 연구는 Pyrethroid계 살충제인 deltamethrin의 작업자 노출을 평가하기 위해 약제살포 환경의 공기중 농도분석과 아울러 인체내에 흡수되어 요중으로 대사되는 산물인 3-PBA의 최적 분석법을 확립하였고, deltamethrin과 3-PBA간의 상관성을 분석하였다. 3-PBA의 가수분해 최적 조건은 시료에 HCl을 첨가하여 pH1 로 조절한 후 $90^{\circ}C$에서 60분 동안 반응시켰을 때 이었다. 요 시료는 Amberlite XAD-16에 흡착시킨 후 acetone을 0.1 mL $min^{-1}$의 속도로 3mL에서 최고의 회수율을 나타내었다. 공기중 deltamethrin의 농도는 N.D. ${\sim}0.00079\;mg\;m^{-3}$이었고, 요중 3-PBA 농도는 $467.5{\pm}2.4\;{\mu}g\;g^{-1}$ creatinine이었다.

• 한국환경보건학회지
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• 제43권4호
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• pp.280-297
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• 2017

Objectives: We assessed pesticide exposure levels according to cultivation and crop type and investigated agricultural factors related to exposure. Methods: The participants, 341 male and 127 female farmers, were divided into three groups by cultivation crop type: chili greenhouse, cucumber greenhouse, and orchard. We collected questionnaires, socioeconomic characteristics and agricultural factors, and spot urine. Pesticide exposure was examined using four organophosphate and four pyrethroids urinary metabolites: dimethylphosphate, dimethylthiophosphate, diethylphosphate, diethylthiophosphate, Cis and Trans-3-(2-2dichlorovinyl)-2, 2-dimethylcyclopropane carboxylic acid, 3-phenoxybenzoic acid (3-PBA), Cis-3-(2-2dibrmovinyl)-2, and 2-dimethylcyclopropane carboxylic acid. Each metabolite was summed ${\Sigma}DAP$ and ${\Sigma}PY$ according to the chemical class. Results: Urinary metabolite detection rates and concentrations were similar between the greenhouse groups, but the orchard group was different. Similar 3-PBA detection rates were found in the three groups, but the geometric mean was very high in the orchard group compared to the two greenhouse groups. 3-PBA concentration in the orchard group was $4.11{\mu}g/g$ creatinine; the chili and cucumber greenhouse groups were 1.27 and $1.16{\mu}g/g$ creatinine, respectively. ${\Sigma}DAP$ was significantly associated with cultivation crop type and seasonal variation, but ${\Sigma}PY$ was not relevant. Conclusions: Our results suggest that cultivation and crop type may be correlated with different pesticide types and exposure levels. Furthermore, seasonal factors were related as potential factors influencing the level of organophosphate metabolites, but not for pyrethroid metabolites.

• 환경위생공학
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• 제11권3호
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• pp.1-7
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• 1996

Mandelic acid is the major metabolite and phenylglyoxylic acid is the minor metabolite of styrene in human. This study was conducted to investigate the correlation between exposure concentrations of styrene and concentration of the metabolites in urine The concentrations of metabolites in urine and exposure concentrations were measured in 60 workers who were occupationally exposed to styrene in FRP industry as well as paint industry and musical instrument manufacturing industry and the concentrations of metabolites in urine ware measured in 90 workers not occupationally exposed to styrene for review the background level in the unexposed population. The results obtained were as follows; 1. The mean exposure concentration is 16.6 $\pm $12.2 ppm (range 0.4-49.9ppm) in the styrene exposed workers. 2. The concentration of mandelic acid in urine collected at the end of shift from worker exposed 8 hours to 50ppm of styrene, based on extrapolation from correlation equations was 578.5 mg/g creatinine and 176.8 mg/g creatinine for next morning urine, the concentration of phenylglyoxylic acid in urine collected at the end of shift was 291.1 mg/g creatinine, 177.9 mg/g creatinine in next morning urine. In the sum of mandelic acid and phenylglyoxylic acid in the urine 870.2 mg/g creatinine in urine sampled at the end of shift corresponds to an exposure of 50ppm of styrene and 366.0 mg/g creatinine for next morning sample corresponds to 50ppm. 3. The correlation of the degree of exposed with sum concentration of mandeliacid and phenylglyoxylic acid in the urine was better(r=0.079 for end of shift, r=0.78 for next morning) than the correlation with single determinant measurement in urine(r=0.75 for mandelic acid at end of shift, r=0.73 for mandelic acid at next morning, r=0.69 for phenylglyoxylic acid at end of shift, r=0.62 for phenylglyoxylic acid at next morning). The monitoring of sum concentration of mandelic acid and phenylglyoxylic acid in urine is a valuable indicator of time weighted average daily exposure ti styrene. And the exposure standard of urinary metabolites produced by styrene should be set, in distinction urine at the end of shift from urine at next morning.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.303-311
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• 2002

This study evaluated the concentrations of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) in industrial waste incineration workers. The effect of genetic polymorphisms of xenobiotic metabolism enzymes on urinary concentration of PAH metabolites was assessed. And, aromatic DNA adduct levels were also determined in total white blood cells. Fifty employees were recruited from a company handling industrial wastes located in Ansan, Korea: non-exposed group (n=21), exposed group (n=29). Sixteen ambient PAHs were determined by GC/MSD (NIOSH method) from personal breathing zone samples of nine subjects near incinerators. Urinary 1-hydroxypyrene glucuronide (1-OHPG), a major pyrene metabolite, was assayed by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11 (SFS/IAC). Multiplex PCR was used for genotyping for GSTMI/TI and PCR-RFLP for genotyping of CYP1A1 (MspI and Ile/Val). PAH-DNA adducts in peripheral blood WBC were measured by the nuclease P1-enhanced postlabeling assay. Smoking habit, demographic and occupational information were collected by self-administered questionnaire. The range of total ambient PAH levels were 0.00-7.00 mg/㎥ (mean 3.31). Urinary 1-OHPG levels were significantly higher in workers handling industrial wastes than in those with presumed lower exposure to PAHs (p=0.006, by Kruskal-Wallis test). There was a statistically significant dose-response increase in 1-OHPG levels with the number of cigarettes consumed per day (Pearson correlation coefficient=0.686, p<0.001). Urinary 1-OHPG levels in occupationally exposed smoking workers were highest compared with non-occupationally exposed smokers (p=0.053, by Kruskal-Wallis test). Smoking and GSTMI genotype were significant predictors for log-transformed 1-OHPG by multiple regression analysis (overall model R²=0.565, p<0.001), whereas smoking was the only significant predictor for log-transformed aromatic DNA adducts (overall model R²=0.249, p=0.201). Aromatic DNA adducts was also a significantly correlation between log transferred urinary 1-OHPG levels (pearson's correlation coefficient=0.307, p=0.04). However, the partial correlation coefficient adjusting for Age, Sex, and cigarette consumption was not significant (r=0.154, p=0.169). The significant association exists only in individuals with the GSTMI null genotype (pearsons correlation coefficient=0.516, p=0.010; partial correlation coefficient adjusting for age, sex, and cigarette consumption, r=0.363, p=0.038). Our results suggest that the significant increase in urinary 1-OHPG in the exposed workers is due to higher prevalence of smokers among them, and that the association between urinary PAH metabolites and aromatic DNA adducts in workers of industrial waste handling may be modulated by GSTMI genotype. There results remain to be confirmed in future larger studies.

• Journal of Pharmaceutical Investigation
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• 제23권3호spc1호
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• pp.9-18
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• 1993

Sugar spheres loaded with melatonin (MT) were coated with $Aquacoat^{\circledR}$ to control the release rate of MT over 8 hours. A zero-order release pattern over 8 hours was obtained with 20% coating on 8-10 mesh beads in USP basket dissolution studies. MT in 20% coated beads was quite stable at room temperature with less than 5% MT degraded during 6 months' storage. Dissolution profiles were also unchanged after 6 months. An oral preparation containing MT-loaded uncoated beads for immediate release and 20% coated beads with $Aquacoat^{\circledR}$ for controlled release over 8 hours was evaluated in six human subjects. When total 0.5 mg MT as low dose (immediate release portion of MT, 0.1 mg) was administered to four subjects, average peak plasma MT concentration was reached at about 600 pg/ml and maintained at about 10 pg/ml over 8 hours. Plasma MT concentration-time profiles were similar in shape to computer-simulated profiles. However, maximal plasma MT concentrations were three times greater compared to computer simulated curve. These results suggest that MT dose, ratio of immediate and controlled release MT, and pharmacokinetic parameters selected are adjusted to mimic endogenous MT concentration-time curve. In another study, 0.2 mg MT having 10% of immediate release portion and 80% controlled release portion produced plasma MT concentration-time curve which is more similar to endogenous profiles. A low bioavailability (<20%) may result from extensive first pass metabolism and remaining amounts of MT from controlled beads. A good correlation between plasma MT concentration and urinary excretion rate of 6-sulphatoxymelatonin (6-STMT), a major metabolite of MT was observed. As plasma MT concentration increased, urinary excretion rate of 6-STMT increased concomitantly. The linear relation between plasma MT and urinary excretion rate of 6-STMT was statistically significant. This result suggests that urinary 6-STMT may be used as an index of circadian rhythms of MT in humans.

• Nutrition Research and Practice
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• 제1권4호
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• pp.305-312
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• 2007

A group of 101 women, aged 40-65 years consisted of 48 premenopausal subjects and 53 postmenopausal ones living in Daegu and Gyeongbuk area in Korea were evaluated with their general characteristics, lifestyle factors, nutrient and phytoestrogen intakes, blood and urinary indices concerning antioxidant status and bone metabolism. Body mass index (BMI), waist hip ratio (WHR) and systolic blood pressure (SBP) of the postmenopausal women were significantly higher (23.8, 0.86, and 126.9 mmHg, respectively) than those of the premenopausal women (22.6, 0.82, and 115.9 mmHg; respectively). Nutrient intakes of the postmenopausal and premenopausal groups were not different except lower fat intake and higher dietary fiber and iron intakes in the postmenopausal group. Daily total phytoestrogen intake was significantly higher in the postmenopausal group (48.54 mg) than the premenopausal (31.41 mg) and was resulted mostly from higher intakes of daidzein and genistein from soy and soy products (45.42 mg vs 28.91 mg). Serum genistein level and excretion of enterolactone, major lignan metabolite, were not very different between the two groups. Serum retinal and ${\alpha}$- tocopherol levels were higher in the postmenopausal group but TBARS levels were not different between the two groups. Serum osteocalcin (7.18 ng/mL) and urinary deoxypyridinoline (7.15 nmol/mmol creatinine), in the postmenopausal group were significantly higher than those in the premenopausal group (4.80 ng/mL, 5.95 nmol/mmol creatinine). Urinary excretion of enterolactone was positively correlated with serum osetocalcin in premenopausal women and serum genistein negatively correlated with the urinary DPD in postmenopausal women. Dietary phytoestrogen intake was negatively correlated with serum level of TBARS in all subjects. It is concluded that the effect of total phytoestrogen intake is beneficial on body antioxidant status in all middle-aged women regardless of menopause but the effect on bone metabolism appears different by the type of the phytoestrogen and the menopausal state.

• 약학회지
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• 제42권6호
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• pp.576-582
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• 1998

Fenfluramine, an anorectic agent, is widely abused as a diet pill in Korea because it is freely marketed in China without any regulation. The optical isomers of fenfluramine hav e different phamacological actions: d-form is used as an anorectic agent, while l-form as a neuroleptic agent. To investigate the metabolism when racemic fenfluramine was administered orally, the urinary excretion of fenfluramine was studied in rats. The enantiomeric separation of fenfluramine was performed on achiral column by gas chromatography using (S)-N-(trifluoroacetyl)-l-prolyl chloride (TFP) as a derivatizing agent. After administration of 15mg/kg of racemic fenfluramine to rats, d-, l-fenfluramine and its metabolites d- and l norfenfluramine in urine were determined by chromatographic separation of TFP derivatives on DB-1 at retention time of 11.2, 11.8, 8.4 and 8.6 min respectively. Urinary recoveries of d and l-fenfluramine in rat were 0.42-5.9O% and 0.18-1.20% respectively in urine specimens collected during first 24hr. The comparison in the levels of isomers showed that d- fenfluramine were higher than l-form, while d-norfenfluramine were lower than l-form. The ratios between parent compound and metabolite revealed that d-norfenfluramine to d-fenfluramine ranged from 1.0 to 4.4, while the ratio of l-norfenfluramine to l-fenfluramine was 8.2-21.1 indicating that l-fenfluramine is metabolized faster than the d-isomer.

• Toxicological Research
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• 제17권
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• pp.263-270
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• 2001

The carcinogenic potential of steviol, a metabolite of/ stevioside (a compound that is used as a sweetener for food and drink), was examined in hamsters of both sexes. Groups of 55 male and 55 female hamsters were given diets containing steviol at 0, 100 and 500 mg/kg diet for 22 months in males and 18 months in females. After 6, 12 and 22 months in males and 18 months in females. hamsters from each group were sacrificed for hematological and biochemical tests. Growth food utilization and consumption, general appearance and mortality were similar in treated and control groups. The mean life span of hamsters given steviol was not significantly different from that of the controls. No treatment-related changes were observed in hematological, urinary and biochemical values at any stage of the study. There was no significantly altered development of neoplastic or non-neoplastic lesions attributable to steviol treatment in any organ or tissue. The highest level oj steviol in the diet which still causes no effects in hamsters was 500 mg/kg diet, under the experimental conditions used.

• Safety and Health at Work
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• 제2권1호
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• pp.57-64
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• 2011

Objectives: Although phthalates like dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are commonly used as plasticizers and their metabolites are especially suspected of reproductive toxicity, little is known about occupational exposure to those phthalates. The aim of this study was to assess the utility of measuring the metabolite concentrations of DBP and DEHP in serum and urine samples as an indicator of occupational exposure to those phthalates. Methods: Phthalate metabolites were analyzed by using column-switching high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: We detected phthalate metabolites in serum and urine matrices at approximately 10-fold lower than the limit of detection of those metabolites in the same matrix by LC-MS/MS without column switching, which was sufficient to evaluate concentrations of phthalate metabolites for industrial workers and the general population. Conclusion: The accuracy and precision of the analytical method indicate that urinary metabolite determination can be a more acceptable biomarker for studying phthalate exposure and adverse health outcomes.

• Journal of Pharmaceutical Investigation
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• 제28권4호
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• pp.215-221
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• 1998

In order to elucidate the fraction of sulfoxidation in the over all in vivo metabolism of chlorpromazine (CPZ), the sulfoxidation of CPZ to chlorpromazine sulfoxide (CPZSO) was studied in rats. CPZ (10 mg/kg) and CPZSO (1 mg/kg) were injected into the rat femoral vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of CPZ and CPZSO determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the total excreted amounts of CPZ and CPZSO via urinary and biliary route were lower than 1.4% and 10.61% of the administered dose, respectively. And also, it was found that the fraction of systemic clearance of CPZ which formed CPZSO $(F_{mi})$ was 0.115. These results showed that CPZ was sulfoxized by 11.5% in rats and the residue would be metabolized via the other routes.