• Applied Biological Chemistry
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• v.18 no.2
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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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• v.23 no.4
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• pp.222-229
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• 1999

Histopathological study has been carried out to elucidate the protective effect of Korean red ginseng water extract (KRG-WE) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced acute toxicity in male guinea pigs. Forty male guinea pigs ($200{\pm}20g$) were divided into 4 groups: normal controls (group 1) received vehicle and saline; group 2 (single TCDD-treated) received TCDD (5 ${\mu}g/kg$, single dose) and saline; group 3 received KRG-WE (200 mg/kg, i.p.) for 2 weeks starting 1 week before TCDD-exposure; group 4 received same dose of KRG-WE for 7 days from the day of TCDD-exposure. Weights of liver, testis, kidney, spleen and lung of the TCDD-exposed guinea pigs were significantly decreased. Thymus was severely shrunken, thereby could not be distinguished from adipose tissue in group 2 animals. Focal interstitial inflammation and fibrosis were observed from the lung parenchyma of group 2 animals. Furthermore, moderate swelling of hepatocyte, diffused aggregates of hemosiderin-laden macrophages from the Prussian blue stained spleen, marked decrease in spermatogenesis, and pyknotic and degenerative changes in the renal tubules were observed from intestinal organs of group 2 animals. On the other hand, histopathological damage was moderately to markedly alleviated in groups 3 and 4, but pretreatment of KRG-WE was more effective than the simultaneous treatment. In particular, TCDD-induced testicular atrophy was significantly attenuated by KRG-WE (p<0.01). From these results, it could be suggested that Korean red ginseng might be a useful herb that prevented TCDD-induced toxicity on liver, testis, kidney and spleen.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.101-108
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• 2007

[ $\underline{Purpose}$ ]: To compare radiation therapy alone to combined modality therapy about survival rate and tolerance of elderly patients ($70=or{\geq}$) with non-small-cell lung cancer (NSCLC). $\underline{Materials\;and\;Methods}$: Between 1998 and 2002, 57 patients given radiation therapy due to NSCLC (Stage III) were analysed retrospectively. Radiation therapy alone (RT), concurrent chemoradiation (CRT), and sequential chemoradiation (SCRT) was done to 33, 16 and 8 patients, respectively. Patients' median age was 74 (range $70{\sim}85$). Male and female are 51 patients and 6 patients, respectively. 23 patients were stage IIIa and 34 were stage IIIb. Patients' characteristic distribution of RT and CRT was not significantly different except mass size that RT has a bigger than CRT. The fraction size of radiation therapy was 1.8 Gy in CRT and $1.8{\sim}3\;Gy$ in other groups. Total radiation dose was $51{\sim}63\;Gy$ according to the fraction size. If the prescribed total radiation dose was successfully irradiated, we stated that it was completion of radiation therapy. $\underline{Results}$: 52 patients were dead. Median period of radiation therapy was as follow: RT, 35 days, CRT, 60.5 days and SCRT, 35 days. Overall median survival time (MST) was 10.1 months. The 1 yr- and 2 yr-overall survival rate was 39.8% and 17.6%, respectively. MST of RT, CRT and SCRT was 8.9, 8.2 and 11.7 months, respectively. The 1 yr survival rate of RT, CRT and SCRT was 38.4%, 37.5% and 50% (not significant). Patients given incomplete radiation therapy were 12 (RT, 5 CRT, 6 SCRT, 1). N stage (p=0.081) and the difference of treatment methods (p=0.079) were the factors affecting incompletion of radiation therapy, but it was not significant. In case of combined-agents chemotherapy, 4 of 8 ceased radiation therapy. T stage ($T{\geq}3$), mass size (${\geq}5\;cm$), Karnofsky performance scale (${\leq}70$) and completion of radiation therapy were the prognostic factors in uni- and multi-variate analysis. $\underline{Conclusion}$: In elderly patients with NSCLC, radiation therapy alone was a treatment method with similar survival period compared with other methods. Generally, patients given radiation therapy alone was tolerable to a treatment. Before planning concurrent chemoirradiation in elderly patients with NSCLC, physicians pay attention to a selection of patients and chemotherapy agents considering general condition and toxicity.

• The Journal of Korean Society for Radiation Therapy
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• v.24 no.2
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• pp.95-106
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• 2012

Purpose: The objective of this study was to investigate the usefulness of an IMRT treatment plan according to whether there was a shell-type pseudo target during radiation therapy for patients in Stage III or IV of non-small cell lung cancer (NSCLC). Materials and Methods: After setting an IMRT (Intensity-Modulated Radiation Therapy, IMRT) plan for when there was a shell-type pseudo target (SPT) and when there was none (WSPT) with 22 patients in Stage III or IV of NSCLC, the investigator analyzed dose-volume histograms (DVHs) and made assessment with dosimetric comparisons such as homogeneity index (HI) inside the tumor target, conformity index (CI) of the tumor target, spinal cord maximum dose, Esophagus $V_{50%}$, mean lung dose (MLD), and $V_{40%}$, $V_{30%}$, $V_{20%}$, $V_{10%}$, $V_{5%}$. Results: The mean CI of WSPT and SPT was $1.22{\pm}0.04$ and $1.16{\pm}0.032$ ($.000^*$), respectively, and the mean HI of WSPT and SPT was $1.06{\pm}0.015$ and $1.07{\pm}0.014$ ($.000^*$), respectively. In SPT, the mean of each CI difference decreased by $-5.16{\pm}2.54%$, while HI increased by average $0.81{\pm}0.47%$. Esophagus $V_{50%}$ recorded $14.54{\pm}12.01%$ (WSPT) and $12.14{\pm}11.09%$ ($.000^*$, SPT) with the mean of SPT differences dropping by $-26.37{\pm}25.05%$. Mean spinal cord maximum dose was $3,898.44{\pm}1,075.0$ cGy (WSPT) and $3,810.8{\pm}1,134.9$ cGy ($.004^*$, SPT) with SPT dropping by average $-3.36{\pm}5.81%$. As for lung $V_{X%}$, the mean of $V_{5%}$ and $V_{10%}$ differences was $-1.62{\pm}2.29%$ ($.006^*$) and $-1.98{\pm}5.02%$ ($.005^*$), respectively with SPT making a decrease. The mean of V20%, V30%, and V40% differences was $-3.51{\pm}3.07%$ ($.000^*$), $-4.84{\pm}6.01%$ ($.000^*$), and $-6.16{\pm}8.46%$ ($.001^*$), respectively, with SPT making a decrease with statistical significance. In MLD assessment, SPT also dropped by average $-2.83{\pm}2.41%$ ($.000^*$). Those results show that SPT allows for mean 169 cGy (Max: 547 cGy, Min: 6.4 cGy) prescription dose. Conclusion: An IMRT treatment plan with SPT during radiation therapy for patients in Stage III or IV of NSCLC will help to reduce the risk of lung toxicity and radiation-induced pneumonia by cutting down radiation doses entering the normal lung, reduce the local control failure rate during radiation therapy due to increasing prescription doses to a certain degree, and increase treatment effects.

• Korean Journal of Veterinary Service
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• v.38 no.3
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.4
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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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• v.25 no.3
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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.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.24 no.2
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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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• v.15 no.17
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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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• v.20 no.1
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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.