• Title/Summary/Keyword: 독성평가

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Vinorelbine Monotherapy on Advanced Non-small Cell Lung Cancer (진행성 비소세포폐암 환자에서 Vinorelbine의 단독요법)

  • Kim, Myung-Hoon;Park, Hee-Sun;An, Jin-Yong;Kwon, Sun-Jung;Lee, Yun-Sun;Jeong, Sung-Su;Kim, Ju-Ock;Kim, Sung-Young
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.475-484
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    • 2002
  • Background : Unresectable non-small cell lung cancer has a poor response to chemotherapy and has an unfortunate prognosis. More effective and less toxic cytotoxic agents are needed to improve the outcome of these patients. The efficacy and safety of vinorelbine monotherapy in these advanced lung cancer patients was evaluanted. Materials and Methods : Sixteen patients with non-small cell lung cancer in stage III or IV, who received vinorelbine alone as an initial anticancer chemotherapy from June 1996 to December 2000 were enrolled in this study. Vinorelbine was given intravenously at a dose 30mg/$m^2$ every week. Results : A mong the sixteen patients, six had a partial response(38%) and the median survival was 16 weeks. The median response duration was 27 weeks (95% CI 6-47), and the time to progression was 16 weeks(95% CI 6-26). Among a total of 112 cycles, neutropenia(WHO grade 3 or 4) and anemia(grade 3) occurred in 9% and 3%, respectively. Only 1 patient required hospitalization for neutropenic fever. Non-hematologic toxicity was minor and was easily controlled. Conclusion : Vinorelbine monotherapy was well tolerated, and moderately effective in patients with advanced non-small cell lung cancer.

EFFECTS OF $INTERFERON-\gamma$ ON COLLAGEN AND FIBRONECTIN SYNTHESIS IN PRIMARY CULTURED PERIODONTAL LIGAMENT CELLS ($Interferon-\gamma$가 치주인대 세포의 Collagen 및 Fibronectin의 합성과 Alkaline Phosphatase 활성에 미치는 영향)

  • Kim, Gwang-Seok;Sung, Jae-Hyun;Choi, Je-Yong;Ryou, Hyun-Mo
    • The korean journal of orthodontics
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    • v.23 no.2 s.41
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    • pp.229-248
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    • 1993
  • [ $Interferon-\gamma$ ] has been suggested as a cytokine of connective tissue stabilizer. In addition, it has also been demonstrated that this cytokine inhibited bone remodeling activities of the bone derived cells. In order to illuminate the effects of this cytokine in orthodontic force induced bone remodeling, it was administered to primary cultured periodontal ligament cells which have been known to have some osteoblast like characteristics. $Interferon-\gamma$ slightly decreased $[^3H]thymidine$ incorporation rate without a significant change in the total cellular DNA content up to 1000 U/ml, which meant these doses were not cytotoxic to the cell. Total protein synthesis was not influenced by various concentration of interferon-y whether it was determined by the $[^3H]proline$ incorporation rate or by the Lowry smethod. The effect of $interferon-\gamma$ on the individual protein was, however, differential, ie, it increased $[^3H]proline$ incorporation into the noncollagenous protein marginally, while it decreased $[^3H]proline$ incorporation into the collagen, so that it caused dose-dependent suppression of the relative collagen synthesis. On the contrary, the fibronectin synthesis determined by the ELISA was increased by 1000 U/ml of $interferon-\gamma$. The differential effects of the interferon-y on the collagen and fibronectin synthesis exhibited not only their protein level but also the steady state mRNA level. $Interferon-\gamma$ decreased steady state level of ${\alpha}1(I)$ procollagen mRNA significantly, while showing no significant changes in the fibronectin mRNA level. In addition to this, it was also found that indomethacin did not affect on the $interferon-\gamma$ induced collagen decrease in this cell, which meant prostaglandins were not involed in the process of $interferon-\gamma$ induced collagen decrease. So it can be concluded that the incubation of periodontal ligament cells with 1000 U/ml of $interferon-\gamma$ for 24 hr showed differential effects on the type I collagen and fibronectin gene expression. The decrease in relative collagen synthesis in the protein level was related with decrease in the steady state level of mRNA, while the increase in the fibronectin synthesis in the protein level was not correlated with the mRNA level.

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Treatment of Contaminated Sediment for Water Quality Improvement of Small-scale Reservoir (소하천형 호수의 수질개선을 위한 퇴적저니 처리방안 연구)

  • 배우근;이창수;정진욱;최동호
    • Journal of Soil and Groundwater Environment
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    • v.7 no.4
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    • pp.31-39
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    • 2002
  • Pollutants from industry, mining, agriculture, and other sources have contaminated sediments in many surface water bodies. Sediment contamination poses a severe threat to human health and environment because many toxic contaminants that are barely detectable in the water column can accumulate in sediments at much higher levels. The purpose of this study was to make optimal treatment and disposal plan o( sediment for water quality improvement in small-scale resevoir based on an evaluation of degree of contamination. The degree of contamination were investigated for 23 samples of 9 site at different depth of sediment in small-scale J river. Results for analysis of contaminated sediments were observed that copper concentration of 4 samples were higher than the regulation of hazardous waste (3 mg/L) and that of all samples were exceeded soil pollution warning levels for agricultural areas. Lead and mercury concentration of all samples were detected below both regulations. Necessary of sediment dredge was evaluated for organic matter and nutrient through standard levels of Paldang lake and the lower Han river in Korea and Tokyo bay and Yokohama bay in Japan. The degree of contamination for organic matter and nutrient was not serious. Compared standard levels of Japan, America, and Canada for heavy metal, contaminated sediment was concluded as lowest effect level or limit of tolerance level because standard levels of America and Canada was established worst effect of benthic organisms. The optimal treatment method of sediment contained heavy metal was cement-based solidification/stabilization to prevent heavy metal leaching.

Design of Ultrasonic Nebulizer for Inhalation Toxicology Study of Cadmium with Application of Engineering Methodology and Performance Evaluation with Light-Scattering Photometer (공학적 기법을 응용한 카드뮴의 흡입독성 연구를 위한 초음파 네뷸라이져의 설계 그리고 광산란 광도계를 이용한 성능평가)

  • Jeung Jae Yeal;Milton Donald K.;Kim Tae Hyeung;Lee Jong Young;Chong Myoung Soo;Ko Kwang Jae;Kim Sang Duck;Kang Sung Ho;Song Young Sun;Lee Ki Nam
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.3
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    • pp.464-471
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    • 2002
  • Author applied several engineering methodologies to classical ultrasonic nebulizer to cope with it's demerits. After several trials and errors, we got the several meaningful results. To evaluate the modified ultrasonic nebulizer for inhalation toxicology of cadmium, author used light-scattering photometer. This paper is the one part of inhalation exposure systems for inhalation toxicology study of cadmium. According to the testing conditions, source temperature 50℃ and inlet-duct band temperature 150℃, aerosol generation results for sodium chloride and cadmium chloride were as followings: Coefficients of variation(CV) of sodium chloride and cadmium chloride for repeated trials were 3.38 and 4.77 for 10g, 2.47 and 5.02 for 5g, and 4.70 and 2.98 for 2.5g. All the CVs were within 10% of acceptance variability. Count Per Minute(CPM) changes of NaCl and CdCl₂ for 5 repeated trials were similar. CPM ratios of CdCl₂/NaCl were 1.13 for 10g, 0.76 for 5g, and 1.06 for 2.5g. Relative aerosol generation of cadmium chloride to sodium chloride was the highest in 10g. Efficiency increases of 24.50% for 5g NaCl, 14.91 % for 2.5g NaCl, and 16.48% for 2.5g CdCl₂ with respect to theoretical efficiency were observed but 0.04% efficiency decrease was observed in 5g CdC₂. According to the modifications of source temperature(20, 50, 70℃) and inlet-duct band temperature(20, 50, 100, 150, 200℃), aerosol generation results for NaCl and CdCl₂ were as followings: CPM trends for each quantity excepting 10g NaCl in inlet-duct band temperature 200℃ were similar, and the highest CPM was observed in source temperature 70℃ to each inlet-duct band temperature. The highest CPMs to 10, 5, and 2.5g NaCl were observed in source temperature 70℃ and inlet-duct band temperature 20℃. Aerosol generation of cadmium chloride was increased with the higher source temperature, excepting inlet-duct band temperature 200℃. The highest CPMs for 10, 5, and 2.5g CdCl₂ were observed in source temperature 70℃ and inlet-duct band temperature 20℃, and this trend was similar to NaCl aerosol generation The highest CPMs for 10, 5, and 2.5g CdCl₂ were observed in source temperature 70℃ and inlet-duct band temperature 20℃, and this result was similar to NaCl aerosol generation. Observed efficiencies of 5 and 2.5g NaCl were similar to ifs theoretical efficiency but -3.08% efficiency decrease of 5g CdCl₂, 17.47% efficiency increase of 2.5g CdCl₂ were observed. CPM ratio of CdCl₂/NaCl of 10g was different to 5 and 2.5g, and 2.5g ratio was higher than 5g ratio. In conclusion, to get maximum aerosol generation for NaCl and CdCl₂ will be the conditions that set the appropriate inlet-duct band temperature for each materials and increase the source temperature. Sodium chloride can be used to evaluate the performance and predict the concentration for cadmium aerosol in aerosol generator and inhalation exposure system.

The effects of selenium on fetal growth and development in CD-1 mice exposed with mercury for the gestation period (임신 중 수은을 섭취한 CD-1 마우스 태아의 성장발육과 기형발생에 미친 셀레늄의 효과)

  • Kim, Jin-suk;Lee, Sang-mok;Choi, Seok-wha;Lee, Won-chang
    • Korean Journal of Veterinary Research
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    • v.34 no.2
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    • pp.361-368
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    • 1994
  • Teratogenic and embryotoxic effects of mercury have been reported, however, there is little information about possible antidotes against mercury exposure during gestation. In order to evaluate therapeutic effects of selenium as an antidote against mercury poisoning, pregnant CD-1 mice were exposed to methylmercury chloride(20ppm) through the drinking water with treatment of sodium selenite (1.0mg, 2.0mg or 3.0mg/kg b.w., subcutaneously) or BAL(5.0mg/kg b.w., subcutaneously) under the single or combination base as the therapeutic agents from day 6 to 15 of gestation. Fetal growth parameters such as body weight and crown-rump length in the mice exposed to mercury, were reduced as was placental weight compared to those in the control. Treatment of selenium(alone, combination with BAL) reduced the harmful effects induced by mercury on the fetal growth parameters even though no specific relationship between dose and therapeutic effect. The incidence of dead fetuses/resorptions and malformed fetuses(especially cleft palate) was also increased in the mercury only treated group. Selenium treatment demonostrated reduced the incidence of abnormal fetuses under the exposure of mercury. Relative maternal organ weights(liver, kidney, spleen) were increased significantly but relative brain weight was decreased as evidenced by decreased in the mercury treated mice compared to that in the control. A subtle indication of maternal mercury toxicity evidenced by changes of relative maternal organ weights, decreased water and feed consumption were also prevented efficiently by selenium treatment. The present study suggests that methylmercuric chloride is embrytoxic and teratogenic in CD-1 mice when exposured during organogenesis and that selenium administration may have therapeutic application for the treatment of mercury poisoning although more applicable study in human should be performed with caution in the future.

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Genotoxicity of Therapeutic Dose of $^{131}I$ Analyzed by Micronuclei Test in the Mouse Bone Marrow (생쥐골수세포 미소핵검사에 의한 치료용량 방사성옥소($^{131}I$)의 유전독성 평가)

  • Bom, Hee-Seung;Kim, Ji-Yeul
    • The Korean Journal of Nuclear Medicine
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    • v.27 no.1
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    • pp.112-117
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    • 1993
  • Background Radioiodine ($^{131}I$), a major component of nuclear fallout and a valuable therapeutic agent for thyrotoxicosis and thyroid cancer, has been regarded as a mutagen or a carcinogen without any convincing evidence. To evaluate the genotoxicity of radioiodine ($^{131}I$) we performed a micronuclei test in mice bone marrow. Materials and methods : Mice (ICR strain, $25{\sim}30 g$) were divided to 4 groups: control, group 1 (0.17 mCi/kg, usual therapeutic dose for thyrotoxicosis), group 2 (1.67 mCi/kg, usual therapeutic dose for thyroid cancer), and group 3 (16.67 mCi/kg, usual accumulated dose causing bone marrow suppression). $^{131}I$ was administered intraperitoneally. Ten mice of each group were sacrificed at days 1 and 3. Bone marrow were smeared and stained with May-Grunwald Giemsa method. One thou-sand polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were counted under the light microscope, and the number of micronucleated PCEs were recorded. Results : The frequency of micronuclei in PCE (and NCE in parenthesis) in the control group was $0.25{\pm}0.07$ ($0.23{\pm}0.07$)% in day 1 and $0.24{\pm}0.07$ ($0.21{\pm}0.07$)% in day 3. Those in group 1 was $0.27{\pm}0.1$ ($0.23{\pm}0.09$)% in day 1 and $0.28{\pm}0.07$ ($0.25{\pm}0.06$)% in day 3. Micronuclei was noted in $0.29{\pm}0.08$ ($0.26{\pm}0.09$)% in day 1 and $0.31{\pm}0.05$ ($0.29{\pm}0.06$)% in day 3 in group 2, and in $0.32{\pm}0.06$ ($0.25{\pm}0.09$)% in day 1 and $0.33{\pm}0.08$ ($0.3{\pm}0.06$)% in day 3 in group 3. There was no difference in the frequency of micronuclei between each groups (p> 0.05). Conclusion : Radioiodine ($^{131}I$) did not cause any genotoxicity in mice bone marrow even at the large dose (16.67 mCi/kg).

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Screening of Biological Activities of Acanthopanax senticosus Fruits Extracts (가시오갈피 열매 추출물의 생리활성 검정)

  • Lim, Jung-Dae;Choung, Myoung-Gun
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.56 no.1
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    • pp.1-7
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    • 2011
  • In this study, we investigated the antioxidant activities, inhibition activity against ACE (angiotensin converting enzyme) and antitumor activity of extract from Acanthopanax senticosus HARMS fruits for development novel functional resources. In order to understand the factors responsible for the potent antioxidant and antihypertensive ability of fruits in A. senticosus, it has been evaluated for anti-oxidative activity using Fenton's reagent/ethyl linoleate system and for free radical scavenging activity using the l,l-diphenyl-2-picryl hydrazyl free radical generating system. The fruits extract of A. senticosus showed higher antioxidant activities than positive control, ${\alpha}$-tocopherol at all concentrations, while fruits extract of A. senticosus showed same degree of radical scavenging activity with positive control, ${\alpha}$-tocopherol. The ability of fruit extracts from A. senticosus to influence the inhibitory activity of angiotensin converting enzyme (ACE) and xanthine oxidase (XOase) has also been discussed. The activity of growth-inhibitory of fruit extracts of A. senticosus was screened by SRB (sulphorhodamine B) method on diverse cancer cells representing different types of cancers. The fruit extracts of A. senticosus showed moderate inhibition on proliferation of LNCaP and MOLT-4F cells and did not inhibit the proliferation of other cancer cells. The fruit extracts of A. senticosus inhibited the proliferation of cancer cells with $GI_{50}$ values ranging from 5 to $10{\mu}g/mL$. This result revealed that the fruit extracts of A. senticosus was expected to be good candidate for development into source of free radical scavengers, antihypertentive, and anti-tumor agent.

Changes of Nitrogen Uptake, Growth and Activities of Nitrogen Metabolizing Enzymes by Different Source of Nitrogen in Tobacco (담배에서 질소 형태에 따른 흡수 양상 및 생육과 질소대사 효소의 활성 변화)

  • 이상각;심상인;강병화;배길관
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.42 no.5
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    • pp.515-521
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    • 1997
  • Tobacco plant was grown for 40 days hydroponically in nutrient solutions composed of different forms of nitrogen, like NO$_3$$^{[-10]}$ -N, NH$_4$$^{+}$-N, and a mixed formulation of NO$_3$$^{[-10]}$ -N and NH$_4$$^{+}$-N. Uptake response, nitrate reductase, and glutamine synthetase activity at growth stage were investigated to understand the basic knowledge of nitrogen metabolism. The better growth of shoot and root was observed in the mixed nutrient solution than NO$_3$$^{[-10]}$ -N or NH$_4$$^{+}$-N, alone. The plant growth in NH$_4$$^{+}$-N nutrient solution was poor due to ammonium toxicity. The pH of nutrient solution containing NO$_3$$^{[-10]}$ -N increased up to 40 days after transplanting. But the pH of solution containing NO$_3$$^{[-10]}$ -N decreased drastically to 3.42 at 20 days after transplant. The pH in the mixed formulation dropped to pH 3.64 at 30 days after transplant and showed re-increase. It is assumed that nitrogen of NH$_4$$^{+}$-N form was taken up preferentially at early stage and NO$_3$$^{[-10]}$ -N form was taken up preferentially at middle stage in the treatment with the mixed solution. The result indicates that the relative proportion of nitrogen forms affected the uptake patterns at each growth stages. The contents of chlorophyll and soluble protein were high with the mixed solution. Total nitrogen content was the highest in NH$_4$$^{+}$-N solution and the content also increased by the application of the mixed type of nitrogen. The amount of nitrate in leaves was high in NO$_3$$^{[-10]}$ -N treatment and the amount of ammonium was high in NH$_4$$^{+}$-N treatment. The activity of nitrate reductase or glutamine synthetase was highest in the leaves grown in mixed nutrient solution than in those with any other single of nitrogen form.

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Rapid Detection of Radioactive Strontium in Water Samples Using Laser-Induced Breakdown Spectroscopy (LIBS) (Laser-Induced Breakdown Spectroscopy (LIBS)를 이용한 방사성 스트론튬 오염물질에 대한 신속한 모니터링 기술)

  • Park, Jin-young;Kim, Hyun-a;Park, Kihong;Kim, Kyoung-woong
    • Economic and Environmental Geology
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    • v.50 no.5
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    • pp.341-352
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    • 2017
  • Along with Cs-137 (half-life: 30.17 years), Sr-90 (half-life: 28.8 years) is one of the most important environmental monitoring radioactive elements. Rapid and easy monitoring method for Sr-90 using Laser-Induced Breakdown Spectroscopy (LIBS) has been studied. Strontium belongs to a bivalent alkaline earth metal such as calcium and has similar electron arrangement and size. Due to these similar chemical properties, it can easily enter into the human body through the food chain via water, soil, and crops when leaked into the environment. In addition, it is immersed into the bone at the case of human influx and causes the toxicity for a long time (biological half-life: about 50 years). It is a very reductive and related with the specific reaction that makes wet analysis difficult. In particular, radioactive strontium should be monitored by nuclear power plants but it is very difficult to be analysed from high-cost problems as well as low accuracy of analysis due to complicated analysis procedures, expensive analysis equipment, and a pretreatment process of using massive chemicals. Therefore, we introduce the Laser-Induced Breakdown Spectroscopy (LIBS) analysis method that analyzes the elements in the sample using the inherent spectrum by generating plasma on the sample using pulse energy, and it can be analyzed in a few seconds without preprocessing. A variety of analytical plates for samples were developed to improve the analytical sensitivity by optimizing the laser, wavelength, and time resolution. This can be effectively applied to real-time monitoring of radioactive wastewater discharged from a nuclear power plant, and furthermore, it can be applied as an emergency monitoring means such as possible future accidents at a nuclear power plants.

Elucidation of Dishes High in N-Nitrosamines Using Total Diet Study Data (총식이조사 자료를 이용한 음식별 니트로사민 함량 분포 규명)

  • Choi, Seul Ki;Lee, Youngwon;Seo, Jung-eun;Park, Jong-eun;Lee, Jee-yeon;Kwon, Hoonjeong
    • Journal of Food Hygiene and Safety
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    • v.33 no.5
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    • pp.361-368
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    • 2018
  • N-nitrosamines are probable or possible human carcinogens, which are produced by the reaction between secondary amines and nitrogen oxide in the acidic environment or by heating. Common risk assessment procedure involves the comparison between exposures expressed in the unit, mg/kg body weight/day and the Health-Based Reference dose expressed in the same unit. This procedure is suitable for the policy decision-making and is considered as inappropriate for the consumers to get information about their dietary decision-making. Therefore, the distributions of NDMA (N-nitrosodimethylamine), NDBA (N-nitrosodibutylamine), the six N-nitrosamines (NDMA, NDBA, NDEA (N-nitrosodiethylamine), NPYR (N-nitrosopyrrolidine), NPIP (N-nitrosopiperidine), and NMOR (N-nitrosomorpholine) in the menus grouped based on the presence of main ingredients and cooking methods were analyzed to generate consumer-friendly information regarding food contaminants. Recipes and intakes were taken from 2014 to 2016 KNHANES (The Korean National Health and Nutrition Examination Survey) and only the data from ages of 7 years or older were used. The contamination data were collected from the 2014~2016 Total Diet Study and all the analysis were performed using R software. Rockfish, eel, anchovy broth and pollock were mainly exposed to N-nitrosamines. In terms of cooking methods, soups and stews appeared to contain the highest amount of N-nitrosamines. Cereals, fruits, and dairy products in the ingredient categories, and rice dishes and rice combined with others in recipe categories had the lowest level exposure to N-nitrosamines. In case of N-nitrosamines, unlike other cooking related food contaminants, boiled dishes such as soups and stews and dishes mainly consisting of fishes and shellfishes had highest level of exposure, showing a large discrepancy with the previous thought of processed meat is the main source of N-nitrosamines.