• Bulletin of the Korean Chemical Society
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• 제19권12호
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• pp.1306-1309
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• 1998

• 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.

• Mass Spectrometry Letters
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• 제4권4호
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• pp.59-66
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• 2013

A metabolomics study was conducted to identify urinary biomarkers for breast cancer, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), analyzed by principal components analysis (PCA) as well as a partial least squares-discriminant analysis (PLS-DA) for a metabolic pattern analysis. To find potential biomarkers, urine samples were collected from before- and after-mastectomy of breast cancer patients and healthy controls. Androgens, corticoids, estrogens, nucleosides, and polyols were quantitatively measured and urinary metabolic profiles were constructed through PCA and PLS-DA. The possible biomarkers were discriminated from quantified targeted metabolites with a metabolic pattern analysis and subsequent screening. We identified two biomarkers for breast cancer in urine, ${\beta}$-cortol and 5-methyl-2-deoxycytidine, which were categorized at significant levels in a student t-test (p-value < 0.05). The concentrations of these metabolites in breast cancer patients significantly increased relative to those of controls and patients after mastectomy. Biomarkers identified in this study were highly related to metabolites causing oxidative DNA damage in the endogenous metabolism. These biomarkers are not only useful for diagnostics and patient stratification but can be mapped on a biochemical chart to identify the corresponding enzyme for target identification via metabolomics.

• Animal Bioscience
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• 제36권7호
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• pp.1130-1142
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• 2023

Objective: Cow urine possesses several bioactive properties but the responsible components behind these bioactivities are still far from identified. In our study, we tried to identify the possible components behind the antimicrobial activity of cow urine by exploring the peptidome and metabolome. Methods: We extracted peptides from the urine of Sahiwal cows belonging to three different physiological states viz heifer, lactation, and pregnant, each group consisting of 10 different animals. The peptides were extracted using the solid phase extraction technique followed by further extraction using ethyl acetate. The antimicrobial activity of the aqueous extract was evaluated against different pathogenic strains like Staphylococcus aureus, Escherichia coli, and Streptococcus agalactiae. The safety of urinary aqueous extract was evaluated by hemolysis and cytotoxicity assay on the BuMEC cell line. The urinary peptides were further fractionated using high-performance liquid chromatography (HPLC) to identify the fraction(s) containing the antimicrobial activity. The HPLC fractions and ethyl acetate extract were analyzed using nLC-MS/MS for the identification of the peptides and metabolites. Results: A total of three fractions were identified with antimicrobial activity, and nLC-MS/MS analysis of fractions resulted in the identification of 511 sequences. While 46 compounds were identified in the metabolite profiling of organic extract. The urinary aqueous extract showed significant activity against E. coli as compared to S. aureus and S. agalactiae and was relatively safe against mammalian cells. Conclusion: The antimicrobial activity of cow urine is a consequence of the feeding habit. The metabolites of plant origin with several bioactivities are eliminated through urine and are responsible for their antimicrobial nature. Secondly, the plethora of peptides generated from the activity of endogenous proteases on protein shed from different parts of tissues also find their way to urine. Some of these sequences possess antimicrobial activity due to their amino acid composition.

• 한국산업보건학회지
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• 제11권2호
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• pp.135-144
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• 2001

This study was performed to measure airborne dimethylformamide(DMF), methyl ethyl ketone(MEK) and toluene and their urinary metabolites concentrations and to determine the relationship between airborne and urinary concentration. Airborne samples and their urinary metabolites were measured 98 male workers who work for 8 synthetic leather factories in a portion of Kyoung-In area. Urine samples were collected at end-of-shift to estimate the exposure levels. 1. The concentration of airborne DMF by process was 8.81 ppm for wet-mixing, 15.05 ppm for wet-coating, 6.03 ppm for dry-mixing, 5.58 ppm for dry-coating, 5.37 ppm for printing, and 9.03 ppm for total. There was statistically significant difference by process. Urinary NMF concentrations of wet-mixing, wet-coating, dry-mixing, dry-coating and printing were $90.55mg/{\ell}$, $79.80mg/{\ell}$, $39.86mg/{\ell}$, $25.23mg/{\ell}$, and $38.15mg/{\ell}$, respectively, and total geometric mean was $56.24mg/{\ell}$. There was significant difference by process. 2. The concentration of airborne MEK by process was 1.89 ppm for wet-mixing, 1.96 ppm for wet-coating, 10.33 ppm for dry-mixing, 29.24 ppm for dry-coating, 14.98 ppm for printing, and 4.87 ppm for total. There was statistically significant difference by process. Urinary MEK concentrations of wetmixing, wet-coating, dry-mixing, dry-coating and printing were $0.93mg/{\ell}$, $0.70mg/{\ell}$, $3.29mg/{\ell}$, $3.29mg/{\ell}$, and $1.06mg/{\ell}$, respectively, and total geometric mean was $1.25mg/{\ell}$. There was statistically significant difference by process. Urinary MEK 3. The concentration of airborne toluene by process was 0.35ppm for wet-mixing, 0.42ppm for wet-coating, 2.95ppm for dry-mixing, 11.67ppm for dry-coating, 4.88ppm for printing, 1.24ppm for total. There was statistically significant difference by process. Urinary hippuric acid concentrations of wet-mixing, wet-coating, dry-mixing, dry-coating and printing were 0.24g/g creatinine, 0.21g/g creatinine, 0.34g/g creatinine, 0.52g/g creatinine, and 0.29g/g creatinine, respctively and total geometric mean was 0.28g/g creatinine. There was statistically significant difference by process. 4. No. of exceeded KPEL was 40 workers(40.8%) for DMF(10ppm), 1 worker(1.0%) for MEK(200ppm), and no worker for toluene(100ppm). No. of exceeded KBEI was 62 workers(63.3%) for urinary NMF($40mg/{\ell}$), 29 workers(29.6%) for urinary MEK, 1 worker(1.0%) for urinary hippuric acid. 5. The regression equations were Log(NMF)=0.4094*Log(DMF)+1.3587(r=0.4516) for DMF, Log(MEKU)=0.1859*Log(MEK)-0.0324(r=0.3303) for MEK, Log(HA)=0.2106*Log(Toluene)-0.5685(r=0.4497) for toluene. Synthetic leather factory workers expose to 3 kinds of organic solvents which are DMF, MEK and toluene. Their urinary NMF and MEK levels were higher than their concentration levels through respiratory. It seems that the urinary levels were affected skin absorption for working habit and alcohol intake.

• 분석과학
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• 제20권4호
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• pp.315-322
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• 2007

본 연구는 1명의 건강한 성인남자로부터 pseudoephedrine과 dextromethorphan 복합제제 약물의 복용 후 24시간동안 배설된 소변을 채취하여 이들 혼합약물의 대사과정과 배설에 관하여 연구를 수행 하였다. 소변 중에 약물과 대사체의 검출을 위하여 가수분해 및 추출과정을 거쳐 MSTFA와 MBTFA를 사용하여 유도체 반응 후 GC-MS로 동시 분석을 수행하였다. 각 대사체는 질량스펙트럼의 해석을 통하여 구조가 규명되었으며, 시간에 따른 모 약물과 대사체의 배설율을 조사하였으며, 본 실험결과로부터 pseudoephedrine과 dextromethorphan의 체내 대사경로를 제안하였다.

• 한국환경보건학회지
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• 제39권5호
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• pp.408-417
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• 2013

Objectives: Phthalates are used as plasticizers in polyvinyl chloride (PVC) plastics. As phthalate plasticizers are not chemically bound to the PVC, they can leach, migrate or evaporate into indoor air and atmosphere, foodstuffs, other materials, etc. Therefore, humans are exposed through ingestion, inhalation, and dermal exposure over their entire lifetime, including during intrauterine development. In particular, university students have a great number of opportunities to contact products including phthalates during campus life (food packaging, body care products, cosmetic, lotions, aftershave, perfume etc.). The purpose of this study was to examine levels of phthalate exposure as undergraduate students begin to use pharmaceuticals and personal care products including phthalates. Methods: Phthalate metabolites, mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-2- ethylhexyl phthalate (MEHP), {(mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP}, and mono-(2-ethlyl-5-oxohexyl) phthalate (MEOHP} were examined. 80 urine samples collected from university students were analyzed using LC/MS/MS(API 4000, Applied Bioscience) with on-line enrichment and columnswitching techniques. This study was carried out at Y university located in Gyonggi Province from 2008 to 2011. Results: The detection limit of phthalate metabolites were 0.03 ng/mL for MEP, 0.11 ng/mL for MnBP, 0.08 ng/mL for MiBP, 0.93 ng/mL for MEHP, 0.19 ng/mL for MEOHP and 0.16ng/mL for MEHHP. MnBP showed the highest urinary levels (median: 31.6 ug/L, 24.8 ug/g creatinine (cr)). Concentrations were also high for MEHHP (median: 24.1 ug/L, 19.0 ug/g cr), followed by MEOHP (median: 22.8 ug/L, 17.9 ug/g cr). In individual cases, the maximum level reached up to 348 ug/L, and 291 ug/g cr, respectively. The urinary and creatinine adjusted levels of MEP were lower than those for DBP and DEHP metabolites, but were higher in 95th percentiles. As a result, the mean daily DEP intake value was 2.3 ${\mu}g/kg$ bw/day, 3.5 ${\mu}g/kg$ bw/day for DEHP and 4.9 ${\mu}g/kg$ bw/day for DBP. Conclusion: These students' phthalate exposure levels were below the international safe level set by the EU, but higher than the 2012 KFDA survey of the age group from 3 to 18.

• 대한의생명과학회지
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• 제12권4호
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• pp.361-370
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• 2006

To evaluate an effect of pathological liver damage on the conjugation of cyclohexane metabolites, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1 ml/100 g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function, the animals pretreated with $CCl_4$ 10 times were identified as acutely liver damaged ones and the animals pretreated with $CCl_4$ 17 times were identified as severly liver damaged ones. To these liver damaged animals, cyclohexane (a single dose of 1.56 g/kg body weight, i.p.) was administered at 48 hr after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hr after injection of cyclohexane. The cyclohexane metabolites, cyclohexanol (CH-ol), cyclohexane-1,2-diol (CH-1,2-diol), cyclohexane-1,4-diol (CH-1,4-diol), and their glucuronyl conjugates and cyclohexanone were detected in the urine of cyclohexane treated rats. The urinary concentration of cyclohexane metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. And liver damaged.ats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to CH-ol analogues compared with normal group. Futhermore, CH-1,2 and 1,4-diol were all conjugated with glucuronic acid in $CCl_4$ 17 times injected animals. On the other hand, the increasing rate of activities of hepatic cytochrome P450 dependent aniline hydroxylase, alcohol dehydrogenase and urine diphosphate glucuronyl transferase was higher in 17 times $CCl_4$-treated rats compared with normal and $CCl_4$ 10 times injected animals. Taken all together, it is assumed that an increased urinary excretion amount of cyclohexane metabolites in liver damaged rats might be caused by an increase in the activities of cyclohexane metabolizing enzymes. And enhanced conjugating ability of CH-ol in liver damaged animals and novel finding of conjugating form of CH-1,2 and 1,4-diol might be caused by increase in the activity of hepatic diphosphouridine glucuronyltransferase.

• 한국산업보건학회지
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• 제9권2호
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• pp.100-109
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• 1999

This study evaluates the pretreatment for analysis of benzidine metabolites in urine by measuring the recovery rates according to the temperature and periods of storage of the urine. By the solid phas e extraction, the recovery rates of basic hydrolysis are benzidine 67.4 %, monoacetylbenzidine 105.1 %, and diacetylbenzidine 115.8 %, respectively. By the liquid extraction, the recovery rates of back-extraction into 0.1 M perchloric acid are benzidine 105.7%, monoacetylbenzidine 94.2 %, diacetylbenzidine 72.8 %, respectively. The difference of the recovery rates between the back-extraction into 0.1 M HCl and 0.1 M perchloic acid after basic hydrolysis are 101 % and 98.8 %, respectively. When the recovery rates of the urinary s amples of pH 3, pH 7, pH 12 at $25^{\circ}C$ and $-76^{\circ}C$ are compared for four weeks, there are no differences according to the temperature and the periods of storage. The above results show that the solid phase extraction and back-extraction by 0.1 M perchloric acid after basic hydrolys is are suitable for the analysis of benzidine metabolites. There are no difference of the recovery rates of the urinary samples stored at $25^{\circ}C$ and $-76^{\circ}C$ at pH 3, pH 7, pH 12, respectively for 28 days.

• Journal of Preventive Medicine and Public Health
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• 제31권4호
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• pp.680-691
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• 1998

본 연구는 흰쥐와 마우스에서 TCE 경구투여 후 주대사산물인 TCE-OH와 TCA의 요중 배설량과 시간에 따른 배설량의 변화와 이에 대한 ethanol의 영향 및 종간의 차이를 조사하여 다음과 같은 결과를 얻었다. 1. TCE 경구 투여 후 요중 TTC 배설양상은 실험동물의 종간에 현저한 차이가 있었으며, 흰쥐에서는 TTC 배설량이 투여량에 따라 증가하다가 체중 kg당 1,000 mg 용량 이상에서 포화되는 양상을 나타내었으나, 마우스에서는 2,000 mg까지 거의 선형적으로 증가하였다. 투여용량에 따른 TTC 배설 량은 흰쥐보다 마우스에서 유의하게 높았다(p<0.01). 2. TCE 투여 후 경과시간에 따른 대사산물 배설양상은 종이나 투여용량에 관계없이 비슷한 양상을 나타내었다. TCE-OH는 12시간에서 거의 대부분$(82.8\sim87.6%)$이 배설되었으며, TCA는 12 시간 $(39.2\sim41.6%)$과 24시간$(33.4\sim36.6%)$에 최고치를 보였고 그 후 서서히 배설되었다. 3. Ethanol 전처치시 횐쥐에서는 TTC와 TCE-OH 배설량이 유의하게 증가하였으나(p<0.01), TCA 배설량은 증가하지 않았다. 마우스에서는 TTC, TCE-OH 및 TCA 배설량 모두 ethanol 군과 대조군 사이에 유의한 차이가 없었다.