• Applied Biological Chemistry
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• 제18권2호
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• pp.71-97
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• 1975

To improve the food qualities in Korea, two hundred and fourtynine kinds of food additives have been allowed in food processing, of which one hundred and nineteen kinds could be used under the limitted conditions. Hence, in practical uses in food processing, many kinds of them are mixed at random within the permitted amounts for their special purposes. For last several years, many kinds of the food additives were prohibited because they have been proved to be toxic even with the single dose. Until recently a few studies on the toxicity in the mixture of food additives were reported, however, they were shown to be no severe additional effect on the animal. This study was performed to see if any elevation of chronic or subacute toxicity of food additives occur especially when they are mixed with each other, using three kinds of food additives (DHA, AF-2, BHT) most widely used as food preservatives, antiseptics and antioxidants. One hundred and fifty young male rats were taken and divided into ten feeding groups, one first control group (food additives blank), three second control groups (DHA 0.1%, AF-2 0.1%, BHT 0.5%), three mixture groups of low level (mixture of each 60% of two second control level) and three mixture groups of high level (mixture of each 90% of two second control level). As the methods of biological and clinical tests, the change of body weight (growth rate), daily intake of diets, organ to body weight ratio, histopathological findings of organs, hematological observation, liver and kidney function tests were checked three times during the periods of 24 weeks. The following results were obtained. 1. The low level group of DHA, AF-2 mixture and DHA, BHT mixture revealed a little retardation in growth rate than the first control group, however, they were similar to the second controls, while all the mixture groups of high level showed a more remarkable retardation than the first and second controls. 2. Average daily intake of the diets was the same in each group, showing a similar decreasing tendency (70-100g/kg of body weight) in accordance with the growth rate. It was observed that there are no differences in the taste and appetite in each group of rats. 3. Abnormal enlargements of kidney and lung were not seen in all the mixture groups compared with the controls, while a slight hepatomegaly was observed in all mixture groups of low level as in the second controls. Significant differences (almost 1% level) were observed between the high level groups and the first control group. 4. Histopathological effects of the food additives on lung, kidney and liver tissues were found in all mixture group of high level. The less frequencies of the same effects were also seen in the low level groups. 5. The esterified cholesterol to total cholesterol ratio in the mixture groups of high level showed a little lower values, and the activities of serum glutamate oxaloacetate transaminase and alkaline phosphatase decreased almost with significance of 5% level compared with the first control group. The serum A/G ratio in the mixture groups also decreased. The results demonstrated that the liver function was decreased in the mixture groups compared with the controls. 6. In all groups throughout the test period, kidney functions (concentration of protein and creatinine excreated per hour in urine and renal filtration rate) were shown almost as normal as the first control. 7. Average values of hematocrit, erythrocytes and leucocytes in the mixture groups were in the normal ranges as in the controls, which denotes that the production of blood cells in bone marrow were also normal in all groups. With the above results, it is concluded that when the food additives (DHA, AF-2, BHT) were given together to the rats in several combinations even in less amount, they showed more toxic signs than the single doses.

• Journal of Ginseng Research
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• 제23권4호
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• pp.222-229
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• 1999

본 연구는 웅성 기니픽에 있어 2,3,7,8-tetrachlorod-ibenzolp-dioxin(TCDD)-유도 급성독성에 대한 홍삼의 방어효과를 병리조직학적 관찰을 통하여 밝히고저 수행되었다. 40마리의 기니픽($200{\pm}20g$)은 목적에 따라 4군으로 나누었다. 즉, 시험군 1에 대하여는 TCDD의 운반체(미량의 DMSO와 소량의 아세톤을 함유한 대두유)와 생리식염수를, 시험군 2에 대하여는 TCDD와 생리식염수를 복강 주사하였다. 시험군 3(TCDD투여 7일전부터 14일간 투여)과 4(동시투여군, 7일간)에 대하여는 홍삼 물추출물(KRG-WE)을 200mg/kg b.w./day 용량으로 복강주사 하였다. 한편, TCDD($5{\mu}g/kg$ b.w.)는 1회 복강주사 함으로서 급성독성을 유도하였다. 시험군 2에서는 장기의 무게가 현저히 감소하였으며, 특히 간(p<0.05)과 고환(p<0.05), 신장, 비장 및 폐의 무게는 시험군 1 비하여 유의하게 낮았다. 흥선은 심하게 위축되어 있어 지방조직과 구별하기 어려웠다. 폐조직에 있어서는 간질의 미만성화와 섬유아세포의 출현, 간세포의 펭윤, 비장세포에 있어서는 헤모시더린에 침착된 대식세포의 수적 증가, 고환의 정세관에서는 정자 생성 저하 및 세포의 변성이 관찰되었으며, 신장조직에 있어서도 심한 병변이 관찰되었다. 반면, 홍삼 물추출물의 전 혹은 동시 투여군에 있어서는 TCDD-단독 투여군에서 관찰되었던 병리조직학적 소견이 현저히 개선되었다. 특히, TCDD-투여로 야기되는 고환의 위축은 유의하게 억제된다는 사실을 알았다(p<0.01). 이상의 결과는 홍삼 물추출물이 TCDD투여로 야기되는 장기의 조직 손상을 현저히 방어한다는 사실을 시사한다 하겠다.

• Radiation Oncology Journal
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• 제25권2호
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• pp.101-108
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• 2007

목 적: 70세 이상 고령의 비소세포성폐암 환자에서 단독방사선치료 및 화학방사선병행요법에 대한 독성과 생존율을 비교하였다. 대상 및 방법: 1998년에서 2002년까지 만 70세 이상의 III기 비소세포성폐암으로 방사선치료를 시행한 57명에 대해 후향적 분석을 시행하였다. 중앙추적조사기간은 9개월($1{\sim}53.4$개월)이었다. 단독방사선치료(갑군)를 시행한 환자가 33명, 동시화학방사선치료(을군)를 시행한 환자가 16명, 화학요법 후 방사선치료(병군)를 시행한 환자가 8명이었다. 남자, 여자가 각각 51, 6명, 중앙연령은 74 ($70{\sim}85$)세였다. IIIa와 IIIb기가 각각 23, 34명이었다. 갑군과 을군의 비교 시 종양의 크기가 갑군이 더 큰 것 외에는 의미 있는 분포의 차이는 없었다. 방사선치료의 분할선량은 동시화학방사선치료 시에는 1.8 Gy로, 그 외의 경우는 방사선치료범위를 고려하여 $1.8{\sim}3\;Gy$로 하였고 분할선량에 따라 $51{\sim}63\;Gy$를 조사하고자 하였다. 계획된 방사선량을 모두 조사받은 경우를 완전종결로 하였고 그렇지 못한 경우를 불완전종결로 하였다. 결 과: 57명 중 52명의 환자가 추적조사기간 중 사망하였다. 갑, 을, 병군에서 완전종결 환자는 28, 10, 7명이었고 중앙방사선치료기간은 각각 35, 60.5, 35일이었다. 전체 환자의 중앙생존기간은 10.1개월이었고 1년, 2년 생존율은 39.8, 17.6%였다. 갑, 을, 병군의 중앙생존기간은 각각 8.9, 8.2, 11.7개월이었고 1년 생존율은 38.4, 37.5, 50%였다. 방사선치료가 불완전 종결된 갑, 을, 병군은 각각 5, 6, 1명으로 N병기(N3)(p=0.081), 치료방법의 차이(p=0.079)가 불완전 종결에 영향을 줄 가능성이 높았다. 을군에서 병용 화학요법제를 시행한 8명 중 4명은 부작용으로 치료를 중단하였다. 예후인자의 평가에서 T병기(T3 이상), 종양의 크기(5 cm 이상), KPS (70 이하), 불완전 종결이 단일변량분석과 다변량분석에서 유의하였다. 결 론: 고령의 비소세포성폐암 환자에서 단독방사선치료는 타 치료와 비교 시 대등한 생존기간을 나타냈으며 동시 화학방사선치료에 비해 부작용으로 치료를 중단하는 경우가 적어 대체로 고령의 환자가 치료에 잘 견디는 치료였다. 고령의 환자에서 동시화학방사선치료를 고려할 시에는 치료의 견딤 정도를 고려하여 환자의 선택 및 약제의 선택에 주의하여야 할 것이다.

• 대한방사선치료학회지
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• 제24권2호
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• pp.95-106
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• 2012

목 적: 비소세포폐암(Non-Small Cell Lung Cancer, NSCLC) III, IV기 환자의 방사선 치료 시 Shell-Type Pseudo Target의 유무에 따른 IMRT 치료계획의 유용성을 알아보고자 한다. 대상 및 방법: NSCLC III, IV기 환자 22명을 대상으로 Shell-Type Pseudo Target이 있을 때와(SPT) Shell-Type Pseudo Target이 없을 때(WSPT) 각각의 세기변조방사선치료(Intensity-Modulated Radiation Therapy, IMRT)계획을 세운 후, 선량-체적 히스토그람(Dose-Volume Histogram, DVH) 분석을 통해 종양 표적 내의 균일성 지수(Homogeneity Index, HI), 종양 표적에 대한 선량조형 지수(Conformity Index, CI), 척수 최대선량(Spinal Cord Maximum Dose), 식도에 대한 $V_{50%}$, 평균 폐 선량(Mean Lung Dose, MLD), 폐에 대한 $V_{40%}$ $V_{30%}$ $V_{20%}$ $V_{10%}$ $V_{5%}$ 등의 선량학적인 비교를 통해서 평가하였다. 결 과: WSPT와 SPT에 따른 각각의 CI 값은 평균 $1.22{\pm}0.04$, $1.16{\pm}0.032$ (.000*), HI 값은 평균 $1.06{\pm}0.015$, $1.07{\pm}0.014$ (.000*)로 나타났으며, CI 값은 SPT의 경우에서 각각의 차이 값에 대한 평균은 $-5.16{\pm}2.54%$의 감소를 보였으며, HI 값은 SPT의 경우에서 평균 $0.81{\pm}0.47%$ 증가된 것으로 나타났다. 식도에 대한 $V_{50%}$에서는 각각 $14.54{\pm}12.01%$ (WSPT), $12.14{\pm}11.09%$ (.000*, SPT)로 SPT에서 차이 값에 대한 평균이 $-26.37{\pm}25.05%$ 감소되었고, 척수 최대선량에서도 평균 선량이 각각 $3,898.44{\pm}1,075.0$ cGy (WSPT), $3,810.8{\pm}1,134.9$ cGy (.004*, SPT)로 SPT의 경우 평균 $-3.36{\pm}5.81%$ 감소되었다. 폐에 대한 $V_{X%}$에서는 $V_{5%}$, $V_{10%}$의 경우 차이 값에 대한 평균이 $-1.62{\pm}2.29%$ (.006*), $-1.98{\pm}5.02%$ (.005*)로 SPT의 경우에서 감소됨을 보여 주었고, 마찬가지로 $V_{20%}$, $V_{30%}$, $V_{40%}$에서도 각각 $-3.51{\pm}3.07%$ (.000*), $-4.84{\pm}6.01%$ (.000*), $-6.16{\pm}8.46%$ (.001*)로 SPT 경우에서 통계학적으로 유의함을 보이면서 감소한 것으로 나타났다. MLD의 평가에서도 SPT의 경우에서 평균 $-2.83{\pm}2.41%$ (.000*)의 감소를 보여주었으며, 이는 평균 169 cGy (Max: 547 cGy, Min: 6.4 cGy)의 처방선량을 SPT 사용 시 올릴 수 있는 결과를 보여주었다. 결 론: NSCLC III, IV기 환자의 방사선 치료 시 SPT를 이용한 IMRT 치료계획이 정상 폐에 들어가는 방사선량을 줄임으로 인해 방사선치료로 유발되는 폐렴의 위험을 감소시킬 수 있을 거라 생각되고, 또한 얼마간의 처방선량 증가로 인한 방사선치료 국소제어실패율을 감소시키는 동시에 치료효과를 증대 시킬 수 있을 것이라 사료된다.

• 한국동물위생학회지
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• 제38권3호
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• pp.173-180
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• 2015

Environmental pesticides used for insect control can be transferred from plants to animals even to livestock animals through food chain. Human beings also can be exposed to pesticides by consuming polluted dairy products, including meats, eggs and other milk products. Therefore, the Ministry of Food and Drug Safety (MFDS) established Standard for Pesticide Residue Limits in dairy products. The QuEChERS (quick, easy, cheap, effective, rugged and safe) methods for detecting residual pesticides are relatively well established for fruits and vegetables, however, the methods for meat have not been appropriately studied yet. In the present work, pyraclofos was used as an organophosphate pesticide to examine its tissue residue in experimental animals by QuEChERS methods. For this, pyraclofos (150 mg/kg body weight) was orally administered to male rats once a day for 2 days. After 6, 12, and 24 hr of the treatment, the tissue residues in liver and femoral muscle of the rats were determined using QuEChERS methods followed by HPLC analyses. In preliminary studies, the recovery rates of spiking samples of pyraclofos demonstrated approximately 109~110% from the tissues. In previous study, pyraclofos tissue residues were observed with significantly high levels in livers and muscles at 6 hr of oral treatment. Then, they were almost completely disappeared after 24 hr of the administration, indicating the orally exposed pyraclofos is rapidly absorbed and distributed to body organs, then quickly excreted from the body with a negligible level of tissue residue. The alterations in blood chemistry as well as the histopathology of heart, lung, liver, spleen and kidney have also been investigated in the experimental animals for assessing acute toxic effects of pyraclofos. The obtained blood chemistry indexes (ALT and AST) showed maximum peak values at 12 hr after the oral administration and decreased to the normal levels at 24 hr of the treatment. Histopathologic observation exhibited acute hepatic damages at 24 hr of the treatment. In conclusion, we suggest that QuEChERS method can be adequately optimized for the analysis of pyraclofos residues in animal tissues.

• 동의생리병리학회지
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• 제32권4호
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• pp.255-260
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• 2018

Chung-Sang (CS) is an experimental herbal remedy that is formulated to treat respiratory diseases implicated by inflammation. The herbs comprised of CS are frequently prescribed for treating various inflammatory symptoms: Menthae haplocalycis Herba, Magnoliae Flosis, Xanthii Fructus, Herba Asari, and Caryphylli Flos. Here, we prepared the extract of CS with boiling water (wCS) or with 50 % ethanol (eCS) and examined whether the two different extracts of CS exhibit a toxicity to cultured cells and mice. RAW 264.7 cells were treated with wCS or eCS, and the cytotoxicity of these extracts to RAW 264.7 cells was determined by an MTT assay. Although the production of intracellular reactive oxygen species that are detrimental to the cells was not increased by the extracts, the cytotoxicity to the cells was evident from 10 mg/ml of wCS and 100 mg/ml of eCS, suggesting that eCS is less cytotoxic. When mice (n = 10/group) received a single intratracheal wCS or eCS daily for 14 days, wCS yielded 40 % mortality, whereas eCS showed none. Both wCS and eCS did not significantly affect the weight of the body and of vital organs, except the lung. Biochemical analyses of mice blood indicated no damage to liver or kidney. However, unlike eCS, wCS significantly increased the level of IgE in serum. Collectively, our results show that eCS was less toxic than wCS, suggesting that CS prepared with 50 % ethanol is preferential over the conventional way of preparing CS.

• Toxicological Research
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• 제25권3호
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• pp.140-146
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• 2009

This study was performed to evaluate the toxicity of cadmium selenide for a period of 28 days in Sprague-Dawley rats. Each of 10 healthy male and females rats per group received daily oral administration for 28-day period at dosage levels 30, 300 and 1,000 mg/kg of body weight. Mortality and clinical signs were checked, and body weight, water intake and food consumption were also recorded weekly. There were no dose-related changes in food consumption or urine volume. All animals survived to the end of study with no clinical signs or differences in body weight gain observed when compared with the control group. At the end of study, all animals including control group, were subjected to necropsy. Blood samples were collected for hematology tests including coagulation time and biochemistry analysis. Blood coagulation time and relative organ weight were unaffected by all received doses. White Blood Cell (WBC) counts significantly increased in the 300 mg/kg administered male animal group when compared to the control. Monocyte (MO) value were also increased significantly in both 300 and 1,000 mg/kg male animal group. However, Mean Corpuscular Volume (MCV) were significantly decreased compared with the control in the 1,000 mg/kg dose groups for male and female animals. Mean Corpuscular Hemoglobin (MCH) decreased significantly for female in the 300 and 1,000 mg/kg group compared to the control. Blood biochemical values of Inorganic phosphorus (IP) were significantly increased in both the 300 and 1,000 mg/kg dose groups in male animals when compared to the control. Creatinine (CRE) levels indicated significant increase in kidney function for the female, 30 mg/kg dose group when compared with control. There was a significant decrease in thymus absolute organ weight in the female, 1,000 mg/kg dose group when compared with control. Histopathological findings revealed no evidence of injury related to cadmium selenide except for one case of focal hepatic inflammation in the high dose (1,000 mg/kg) group. One case of lung inflammation was also seen in the control group. Basis on these result, the No Observable Adverse Effect Level (NOAEL) of cadmium selenide was determined to be more than 1,000 mg/kg/day for male and female rats under conditions in this study.

• 한국산업보건학회지
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• 제24권2호
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• pp.122-129
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• 2014

Objectives: Because of its properties such as resistance to heat, chemicals and corrosion; tensile strength; sound absorption; and affordable price, asbestos has been widely used as a building material, fire resistant and retardant, thermal and heat insulator, soundproofing material, and electrical insulation. Since the prolonged inhalation of asbestos can cause serious illnesses such as lung cancer, mesothelioma, and asbestosis after an incubation period of 20 to 40 years, the mineral was classified as a Group 1 carcinogen by the International Agency for Research on Cancer, an intergovernmental agency forming part of the World Health Organization. Children and infants are more at risk than are adults if they are exposed to carcinogens, due to aweaker immunity that has not yet been fully developed. Most childcare centers are operated all day and children tend to spend a great amount of time in the centers. This is why it is important for them to be systematically isolated from environments that may expose them to asbestos. Materials: In order to understand both indoor and outdoor hazards to which children may have been exposed, the study focused on actual surveys of asbestos used in childcare centers, paying special attention to slate-roofed buildings in the vicinity of the centers. Results: A survey of a total of 211 childcare centers showed that the buildings of 18.1% of the centers contained asbestos, with 60.53% of the material being found in classroom ceilings. "Tex" was the most used material for ceilings, making up 89.47% of all ceilings. An outdoor survey showed that childcare centers in Daegu Metropolitan City had an average of 143 slate-roof buildings within a distance of 1km. Conclusions: Buildings housing mainly toddlers, children, teenagers and others more vulnerable to the toxicity of asbestos are not subject to asbestos investigation by law. A legal and practical basis for asbestos control is required for such buildings. In particular, housing materials which contain asbestos in day care centers require asbestos control. GIS should be used to identify the location of buildings with slate roofing materials in the vicinity of daycare centers in order to gauge toxicity of exposure to asbestos caused by potential asbestos friability possibility in outdoor conditions.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7195-7200
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• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• Toxicological Research
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• 제20권1호
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• pp.83-88
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• 2004

The present study was carried out to investigate the potential adverse effects of CKD-602 by a 5-day repeated intravenous dose in Sprague-Dawley rats. The test article, CKD-602, was administered intravenously to male and female rats at dose levels of 0.07, 0.22, 0.67, 2.0 and 6.0 mg/kg/day for 5 days consecutively. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period after cessation of the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. There were 2 and 5 treatment related deaths in the 0.67 and 2.0 mg/kg/day dose groups of both genders, respectively. Treatment related clinical signs, including hair loss, skin paleness, decreased locomotor activity, emaciation, and changes in stool were observed in a dose-dependent manner from the third day after initiation of the injection. Decrease or suppression of body weight was also observed dose-dependently in males and females of the treated groups. Gross postmortem examinations revealed a dose-dependent increase in the incidence and severity of atrophy or hypertrophy and white membrane formation in the spleen, atrophy of the thymus, diffuse white spots and paleness of the liver, paleness of the lung, kidney and adrenal gland, and dark red discoloration and dark red contents in the alimentary tract. Based on these results, it was concluded that the 5-repeated intravenous injection of CKD-602 to male and female rats resulted in increased incidence of abnormal clinical signs and death, decreased or suppressed body weight, and increased incidence of abnormal gross findings. In the present experimental conditions, the $LD_{50}$ value was 2.07 (95% confidence limit not specified) mg/kg/day in both genders and the $LD_{10}$ value was 1.72 (95% confidence limit not specified) mg/kg/day in both genders.