• Title/Summary/Keyword: 독성평가

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Analysis of PAHs (polycyclic aromatic hydrocarbons) in Ground Coffee Using GC-tandem Mass Spectrometry and Estimation of Daily Dose (GC-tandem mass spectrometry를 이용한 분쇄원두커피 중 PAHs(polycyclic aromatic hydrocarbons) 분석법 연구 및 인체노출량 평가)

  • Jung, So-Young;Park, Ju-Sung;Son, Yeo-Joon;Choi, Su-Jeong;Lee, Yun-Jeong;Kim, Mi-Sun;Park, So-Hyun;Lee, Sang-Me;Chae, Young-Zoo
    • Korean Journal of Food Science and Technology
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    • v.43 no.5
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    • pp.544-552
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    • 2011
  • The purpose of this study was to develop an analytical method for determining 15 polycyclic aromatic hydrocarbons (PAHs) of EU priority using gas chromatography (GC)-tandem mass spectrometry (MS). The PAHs in ground coffee were analyzed after being extracted using methods such as saponification-liquid-liquid extraction, Soxhlet extraction, and solid-liquid extraction. The solid-liquid extraction method showed the greatest repeatability and most efficient reduction of the matrix effect. GC-tandem MS for the quantification of the 15 PAHs showed better resolution and lower limit of detections (LODs) than GC-MS-selected ion monitoring (SIM) and high performance liquid chromatography with fluorescence detector. LODs of this method for the ground coffee types were 0.002-0.1 ${\mu}g/kg$ and limit of quantifications (LOQs) were 0.006-0.2 ${\mu}g/kg$ The recoveries ranged from 52.6 to 93.3%. Forty-six commercial types of ground coffee were analyzed to determine their PAHs contamination levels. PAHs concentration ranged from ND to 5.988 ${\mu}g/kg$. This study was conducted with toxicity equivalence factors, the U.S. EPA recommendation to identify dietary risks for PAHs in different types of coffee. The estimated average daily dose of PAHs was $5.24{\times}10^{-8}$ mg/kg body weight/day.

Analysis of the Thermal and Structural Stability for the CANDU Spent Fuel Disposal Canister (CANDU 처분용기의 열적-구조적 안정성 평가)

  • Lee, Jong-Youl;Cho, Dong-Geun;Kim, Seong-Gi;Choi, Heui-Joo;Lee, Yang
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.6 no.3
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    • pp.217-224
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    • 2008
  • In deep geological disposal system, the integrity of a disposal canister having spent fuels is very important factor to assure the safety of the repository system. This disposal canister is one element of the engineered barriers to isolate and to delay the radioactivity release from human beings and the environment for a long time so that the toxicity does not affect the environment. The main requirement in designing the deep geological disposal system is to keep the buffer temperature below 100$^{\circ}C$ by the decay heat from the spent fuels in the canister in order to maintain the integrity of the buffer material. Also, the disposal canister can endure the hydraulic pressure in the depth of 500 m and the swelling pressure of the bentonite as a buffer. In this study, new concept of the disposal canister for the CANDU spent fuels which were considered to be disposed without any treatment was developed and the thermal stability and the structural integrity of the canister were analysed. The result of the thermal analysis showed that the temperature of the buffer was 88.9$^{\circ}C$ when 37 years have passed after emplacement of the canister and the spacings of the disposal tunnel and the deposition holes were 40 m and 3 m, respectively. In the case of structural analysis, the result showed that the safety factors of the normal and the extreme environment were 2.9 and 1.33, respectively. So, these results reveal that the canister meets the thermal and the structural requirements in the deep geological disposal system.

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Stabilization of As (arsenic(V) or roxarsone) Contaminated Soils using Zerovalent Iron and Basic Oxygen Furnace Slag (영가철(Zerovalent Iron)과 제강슬래그를 이용한 비소(V) 및 록살슨(Roxarsone) 오염토양의 비소 안정화 효율 평가)

  • Lim, Jung-Eun;Kim, Kwon-Rae;Lee, Sang-Soo;Kwon, Oh-Kyung;Yang, Jae-E;Ok, Yong-Sik
    • Journal of Korean Society of Environmental Engineers
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    • v.32 no.6
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    • pp.631-638
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    • 2010
  • The objective of this study was to evaluate the efficiency of zerovalent iron and basic oxygen furnace slag on arsenic stabilization in soils. For this, arsenic (V) contaminated soil and roxarsone contaminated soil were incubated after incorporation with zerovalent iron (ZVI) or basic oxygen furnace slage (BOFS) at four different levels (0%, 1%, 3%, and 5%) for 30 days and then the residual concentrations of arsenic were analysed following extraction with aqua reqia, 1N HCl and 0.01 M $CaCl_2$. The total concentration of arsenic was 2,285 mg/kg in the As(V) contaminated soil and 6.5 mg/kg in the roxarsone contaminated soil. 1 N HCl extractable arsenic concentration in the As(V) contaminated soil was initially 1,351 mg/kg and this was significantly declined by 713~1,034 mg/kg following incubation with ZVI while BOFS treatment showed no effect on the stabilization of inorganic arsenate except 5% treatment which showed around 100 mg/kg reduction in 1N HCl extractable arsenic. Similarly, in the roxarsone contaminated soil 1N HCl extractable concentration of arsenic was reduced from 3.13 mg/kg to 0.69 mg/kg with ZVI treatment increased from 1% to 5% while BOFS treatment did not lead to any statistically significant reduction. Available (0.01M $CaCl_2$ extractable) arsenic was initially 0.85 mg/kg in the As(V) contaminated soil and this declined by 0.79 mg/kg following incorporation with 5% ZVI, which accounted for more than 90% of the available As in the control. When As(V)-contaminated soil was treated with BOFS, the available arsenic was increased due to competing effect of the phosphate originated from BOFS with arsenate for the adsorption sites. For the roxarsone contaminated soil, the greater the treatment of ZVI or BOFS, the lower the available arsenic concentration although it was still higher than that of the control.

Therapeutic Effect of Different Doses of Recombinant Human Granulocyte Colony-Stimulating Factor(rhG-CSF) on Neonatal Sepsis Complicated by Neutropenia (호중구 감소증이 합병된 신생아 패혈증에서 Recombinant Human Granulocyte Colony-Stimulating Factor(rhG-CSF)의 투여 용량에 따른 치료 효과)

  • Choi, Moon Young;Jung, Yeon Sook;Son, Dong Woo;Ahn, Hyo Seop
    • Clinical and Experimental Pediatrics
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    • v.45 no.4
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    • pp.439-448
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    • 2002
  • Purpose : The aim of this study is to determine and compare the effects of adjunctive therapy with different doses of recombinant human granulocyte-colony stimulating factor(rhG-CSF) on reversing sepsis-associated neonatal neutropenia, and their survival rate in a group I/II-type trial. Methods : RhG-CSF was injected subcutaneously to 10 septic-neutropenic neonates with doses of $10{\mu}g/kg$ from Oct. 1995 to Sep. 1996, and was administered to another 12 septic-neutropenic neonates with doses of $5{\mu}g/kg$ from Oct. 1996 to Sep. 1997. Neutrophilic responses and the outcomes of both groups were compared. Results : In the rhG-CSF $10{\mu}g/kg$ treated group and in the $5{\mu}g/kg$ treated group, the absolute neutrophil count(ANC) was $1,065{\pm}89$($mean{\pm}SEM$) and $1,053{\pm}131$, respectively. The only difference between the two groups was the peak ANC at 48 hours. Eight patients from the remaining nine of rhG-CSF $10{\mu}g/kg$ treated group(88.9%) and ten in $5{\mu}g/kg$ treated group(83.3%) survived the sepsis and were discharged without any problems. Conclusions : RhG-CSF can increase the neutrophil count in critically ill septic neutropenic neonats. The survival rate of both groups were up to 90%. This finding suggests that both doses of rhG-CSF may be effective in a therapeutically useful time frame to treat septic neonates with neonatal neutropenia attributable to bone marrow supression or neutrophil consumption.

Comparison of Paraquat Actions on Oxygen Radical Generation and Lipid Peroxidation between Submitochondrial Particle and Microsome of Mouse Liver (Paraquat에 의한 산소 Radical 생성 및 지질과산화 작용의 Mouse 간 Submitochondria Particle과 Microsome에서의 비교)

  • Choi, Jung-Hwan;Kim, Yong-Sik;Park, Jong-Hwan;Chung, Myung-Hee;Yunn, Chong-Ku
    • The Korean Journal of Pharmacology
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    • v.27 no.2
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    • pp.155-166
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    • 1991
  • In order to evaluate a potential role of mitochondria in the mediation of toxicity of paraquat (PQ), submitochondrial particle and microsome of mouse liver were compared by oxygen radical generation and lipid peroxidation. With NADH in submitochondrial particle and NADPH in microsome as electron donors, PQ stimulated production of superoxide anion and $H_2O_2$ in both fractions. Under the same conditions, PQ enhanced the generation of ethylene from methional suggestiong stimulation of OH production by PQ. But these effects by PQ were somewhat lower in submitochondrial particle than in microsome. In addition, lipid peroxidation(measured as MDA production) was stimulated by PQ in both fractions. The stimulation of lipid peroxidation in both fractions seemed to occur by the same mechanism probably through perferryl ion. This was supported by the following findings: i) The lipid peroxidation in both fractions was partially inhibited by SOD and completely inhibited by DETAPAC(an iron chelator) but not by catalase or OH scavenger. ii) Addition of $ADP-Fe^{3+}$ further increased PQ-induced lipid peroxidation but decreased ethylene production from methional suggesting no correlation between OH production and lipid peroxidation. The redox-cycling of PQ in mitochondria appeared to be linked to NADH dehydrogenase, not to CoQ since all of the observed stimulations by PQ in submitochondrial particle were inhibited by p-hydroxymercuribenzoate(a NADH dehydrogenase inhibitor) but not affected by other respiratory chain blockers. The above results demonstrate that redox-cycling properties of PQ leading to oxygen radical generation and lipid peroxidation can also occur in mitochondria in the same manner as in microsome. Therefore, the observed actions of PQ in mitochondria suggest that mitochondria may also contribute to toxicity of this drug in vivo.

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Cellular Protective Effect and Liposome Formulation for Enhanced Transdermal Delivery of Persicaria hydropiper L. Extract (여뀌 추출물의 세포 보호 작용과 피부 흡수 증진을 위한 리포좀 제형 연구)

  • Kim, Jung-Eun;Lee, Hye-Jin;Lim, Myoung-Sun;Park, Min-A;Park, Soo-Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.38 no.1
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    • pp.15-31
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    • 2012
  • In our previous studies, the antioxidant, anti-aging, and antibacterial activities of Persicaria hydropipier L. extract, and the moisturizing effect of cream containing P. hydropipier extract were investigated. In this study, the cellular protective effects of P. hydropipier extract and isoquercitrin, main component from P. hydropipier in $^1O_2$-induced photohemolysis of human erythrocytes and ultraviolet B (UVB)-exposed HaCaT cells were investigated. Liposomes such as ethosome and elastic liposome for enhanced transdermal delivery were prepared. Size, loading efficiency, stability, and cumulative permeated amounts of ethosomes and elastic liposomes were evaluated. P. hydropipier extract and isoquercitrin showed more prominent cellular protective effect than (+)-${\alpha}$-tocopherol, known as lipid antioxidant at $5{\mu}g/mL$. P. hydropipier extract didn't show any characteristics of cytotoxicity at $50{\mu}g/mL$. When HaCaT cells were exposed to a single large dose ($400mJ/cm^2$) of UVB, the extract protected the cells against UVB radiation in a concentration dependent manner ($12.5{\sim}50{\mu}g/mL$). Cell viability of HaCaT cells exposed to UVB $400mJ/cm^2$ was increased by treatment with P. hydropipier extract or isoquercitrin from 36 % (cell viability of positve control groups) to 90 % (cell viability of P. hydropipier extract or isoquercitrin- treated groups). The size of 0.04 % P. hydropiper extract loaded ethosomes was 173.0 nm and the loading efficiency was 55.58 %. 0.04 % P. hydropiper extract loaded ethosomes were stable with as monodisperse particles for 1 week. The ethosome exhibited more skin permeability than general liposome and ethanol solution. The optimal ratio of lipid to surfactant ($Tego^{(R)}$ care 450) of 0.1 % P. hydropiper extract loaded elastic liposomes was observed to be 95 : 5. Vesicle size of 0.1 % P. hydropiper extract loaded elastic liposome was 176.5 nm. The deformability index of the elastic liposome was 16.4. The loading efficiency was 68.8 %. The elastic liposome containing P. hydropiper extract showed more skin permeability than liposome without surfactant ($Tego^{(R)}$ care 450).

Concurrent Chemoradiotherapy with Biweekly Gemcitabine and Cisplatin in Patients with Locally Advanced Non-small Cell Lung Cancer (진행성 비소세포폐암 환자에서 Gemcitabine/Cisplatin을 이용한 동시 화학 방사선 요법)

  • Oak, Chul-Ho;Kim, Ja-Kyung;Jang, Lee-La;Moon, Dae-Sung;Jang, Tae-Won;Jung, Maan-Hong;Cho, Sung-Whan;Jeung, Tae-Sig
    • Radiation Oncology Journal
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    • v.26 no.3
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    • pp.160-165
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    • 2008
  • Purpose: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy(CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine ($1,200\;mg/m^2$, $1^{st}$ and 8th day) and cisplatin ($60\;mg/m^2$) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range $3{\sim}39$ months) and the median survival time was 16 months (95% CI; $2.4{\sim}39.2$ months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.

Antioxidant and Anti-Adipogenic Effects of Ethanolic Extracts from Tartary and Common Buckwheats (쓴메밀 및 단메밀 에탄올 추출물의 항산화 및 지방세포 분화억제 효과)

  • Yoon, Bo-Ra;Cho, Bong-Jae;Lee, Hyo-Ku;Kim, Dae-Jung;Rhee, Seong-Kap;Hong, Hee-Do;Kim, Kyung-Tack;Cho, Chang-Won;Choi, Hyeon-Son;Lee, Boo-Yong;Lee, Ok-Hwan
    • Food Science and Preservation
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    • v.19 no.1
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    • pp.123-130
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    • 2012
  • In this study, 80% ethanolic extracts of tartary and common buckwheats were assessed for their total phenol content, total flavonoids content, antioxidant activity (DPPH, ABTS radical scavenging activity and reducing power), and anti-adipogenic effects. Our results show that total phenol contents of 80% ethanolic extract from tartary and common buckwheats were $17.35{\pm}0.41$ and $8.20{\pm}0.28\;{\mu}g$ GAE/g, respectively. Antioxidant activities of 80% ethanolic extract from tartary buckwheat were significantly higher than that of common buckwheat extract (p<0.05). During adipocyte differentiation, 80% ethanolic extracts of tartary and common buckwheat significantly inhibited lipid accumulation compared to control cells. We further evaluated the effect of buckwheat extracts on the changes of key gene expression associated with 3T3-L1 adipogenesis and ROS production. Tartary buckwheat extract was more suppressed the mRNA expressions ($PPAR{\gamma}$ and aP2) than that of common buckwheat extract. Moreover, tartary buckwheat inhibited the mRNA expression of both NOX4 (NADPH oxidase 4) and G6PDH (glucose-6-phosphate dehydrogenase). These results indicate that anti-adipogenesis effect of tartary buckwheat can be attributed to phenolic compound that may potentially inhibit ROS production.

DNA damages with Fpg/Endo Ⅲ FLARE Assay in cynomolgus monkeys exposed to stainless steel welding fume (용접흄 흡입노출 영장류에서 Fpg/Endo Ⅲ FLARE Assay를 이용한 DNA 손상 및 회복)

  • Rim, Kyung Taek;Kim, Soo Jin;Chung, Yong Hyun;Kim, Hyeon Yeong;Maeng, Seung Hee;Yu, Il Je
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.17 no.4
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    • pp.272-281
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    • 2007
  • 선박제조업을 비롯한 운송업 및 건축업 등의 다양한 분야에서 용접기술이 이용되어 옴에 따라 용접근로자들에 대한 산업보건학적 관심이 높아지고 있다. 노출정도가 다양하기는 하지만 용접흄은 6가 크롬을 비롯한 금속화합물과 유해가스, 화학물질 등을 복합적으로 포함하고 있는 스테인레스 스틸 용접흄에 대한 유전독성영향을 평가하기 위하여 흡입챔버를 이용, 실험동물인 영장류에 스테인레스 스틸 용접흄을 노출시키고 혈액 내 lymphocytes에 생성된 용접흄 노출농도 및 시간별 DNA 손상정도 및 그 회복효소를 측정함으로써, 유해성이 완전하게 확인되지 않은 용접흄에 노출되어 나타날 수 있는 암을 비롯한 심각한 건강영향을 예방하기 위한 각 지표들을 찾아 그 유용성을 비교하고자 하였다. 영장류를 노출시키기 위해 robotic arm을 장치한 영장류 흡입노출 시스템을 개발하였으며, 이 노출 시스템을 이용하여 수컷 영장류 6마리에 대해 용접흄 노출시험을 실시하였는데 실험군은 대조군 2, 저농도 ($31mg/m^3$) 노출군 2, 고농도 ($63mg/m^3$) 노출군 2마리로 구성하였고, 1일 2시간씩 일주일에 5일 동안 용접흄에 노출시켰다. 노출 농도는 지속적으로 모니터링 하였고, 노출과정 중에 영장류의 혈액을 채취하여 lymphocytes를 분리, 단세포 DNA 손상을 선별하기 위해 DNA 손상회복 효소인 E. coli formamidopyrimidine-DNA glycosylase (Fpg)와 endonuclease Ⅲ (Thymine Glycol-DNA glycosylase) 투여와 Comet asaay (single cell gel electrophoresis, 단세포겔전기영동기법)를 결합시켜 이용하는 Fpg/Endo III FLARE 분석법을 사용하였다. Fpg enzyme에 의한 olive tail moment값의 변화는 16주 노출군부터 노출부검(34주)군 까지 노출농도가 높아짐에 따른 olive tail moment 기하평균 값의 양 반응관계를 보기는 어렵지만, 고농도군의 경우 27주 노출군에서 가장 높은 olive tail moment 값을 보이고 이후 차츰 감소하였다. 한편 16주에서 22주까지의 노출기간에서는 대조군에 비해 노출군에서 DNA손상정도(olive tail moment값)는 모두 유의하게 높았으나, 6, 12, 18, 25, 31, 33, 35주간 노출하였을 때는 다른 결과를 보였다. 각 실험군의 Fpg enzyme에 의한 tail length값의 분포를 살펴볼 때, 저농도군 및 고농도군에서 27주간 노출하였을 때 가장 높은 tail length 값을 보이고 이후 차츰 감소하는 경향을 보였다. 또한 16, 22주간 노출하였을 때 대조군에 비해 노출군에서 tail length 값이 유의하게 높았으나, 20주간에서만 양 반응관계가 관찰되었고, 다른 주간에서는 양 반응 및 기간 반응관계를 나타내지는 않았다. Endo III enzyme에 의한 olive tail moment값의 변화는 기간별 노출군에서 대조군에 비해 높은 DNA손상정도(olive tail moment값)를 나타내는 결과들이 있었지만, 10, 12, 16, 22, 25, 31주간 노출하였을 때 등 상당수 노출기간에서 반응관계를 나타내지는 않았다. 각 실험군의 Endo III enzyme에 의한 tail length값의 분포를 살펴볼 때, 18, 20, 27, 33주간 노출하였을 때 대조군에 비해 노출군에서 tail length 값이 조금 높았지만, 양 반응 및 기간 반응관계를 보이지 않았고 수치의 크기가 불규칙하게 변화하였다. 즉, DNA에 있어 산화된 pyrimidine을 형성하여 손상된 부위의 염기를 제거함으로써 AP site (abasic site)를 만들고 이들이 Comet assay를 통해 break로 전환된 것을 포함한 DNA손상을 측정하기 위하여 endonuclease III (Endo III)를 첨가시킨 Endo III FLARE 분석법을 실시한 결과, 본 연구에서 나타난 결과는 용접흄 노출 영장류에서 Olive tail moment 및 tail length 공히 노출량 및 노출기간 반응관계를 볼 수 없었다. Endo III FLARE 분석법을 통한 산화적 DNA 손상지표는 영장류에 적용하기에는 적응반응현상으로 대조군과 유의한 차이도 관찰할 수 없었고 더욱이 역으로 대조군에서의 자연발생적 수치가 더 높아질 수 있어 용접흄 노출 영장류의 모니터링 지표로 사용하기에는 제한점이 있었다.

Experimental Studies on Lead Toxicity in Domestic II. Histopathology (고양이의 납중독에 관한 실험적 연구 2. 조직병리학적 소견)

  • Hong Soon-Ho;Han Hong Ryul
    • Journal of Veterinary Clinics
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    • v.11 no.1
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    • pp.485-505
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    • 1994
  • Lead toxicity was evaluated in forty-five cats on a balanced diet, treated with 0(control), 10, 100(low), 1, 000, 2, 000 and 4, 000(high)ppm of lead acetate orally on a body weight basis. The objectives were to describe the gross and histopathologic changes and to demonstrate what tissue lead concentrations correlate with the known dosages of lead. In subclinical lead toxicity, greater than 80% of the absorbed lead was deposited in the bone, whereas in more acute lead toxicity, 42% of absorbed lead was deposited in the bone and 36% and 20% of absorbed lead was deposited in the kidneys and in the liver, respectively. No gross lesions were found in the nervous system. Yellow-brown colored livers appear to be associated with lead toxicity. Neuronal necrosis in the cerebrum was the most predominant histopathologic finding. Astrocytic proliferation in the cerebral gray matter was observed in 1 high dose cat. Gliosis was noted in the cerebral cortex of 6 high dose cats. Two high dose cats had demyelination in the deepest layer of the cortical gray matter of the cerebrum. Extravasation of red cells and cavitation around the vessels were found in the cerebrum of 1 high dose cat. Six high dose cats had degeneration of Purkinje cells in the cerebellum. The microscopic findings in the peripheral nerves were ambiguous. In more acute toxicity, the cats had lead inclusions in the epithelial cells of proximal tubules of the kidneys of 7 cats and hepatocytes of the liver of S cats. These inclusions could be seen wlth H&E, but were more prominent with orcein staining. Two high dose cats had granulomas and connective tissue hyperplasia between tubules of the kidneys. Periportal hepatocyte vacuolization was observed in the liver of 22 cats. Vacuolization of seminiferous tubules and a reduced number of spermatogonia(indicative of reduced spermatogenesis) were found in the testis of 5 treated cats. Cystic ovaries were observed in 3 high dose cats and poor development of oogonia was found in 2 cats. The diagnosis of lead toxicity in cats can be suspected on the basis of the histopathologic lesions described, and can be of value in contributing to a diagnosis. A reliable diagnosis of lead poisoning can be helped utilizing tissue lead analysis(post molten)

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