• Toxicological Research
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• v.17
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• pp.127-133
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• 2001

Together with cytochrome P450 (CYP), flavin-containing monooxygenase (FMO) present in liver microsomes oxidizes various endogenous and exogenous chemicals. In an effort to determine the human FMO activity, we have developed two non-invasive urine analysis methods using caffeine (CA) and ranitidine (RA) as the probe compounds. As the production of theobromine (TB) and ranitidine N-oxide (RANO) from CA and RA is catalyzed primarily by the hepatic FMO, we have assigned the urinary molar ratios of TB/CA and RA/RANO as the in vivo FMO activity. In 200 age-matched Korean volunteers, the obtained TB/CA ratio ranged from 0.4 to 15.2 (38-fold difference) and the RA/RANO ratio from 5.7 to 27.2 (4.8-fold). The FMO activity of 20's, determined by caffeine metabolism, was the highest (2.5$\pm$l.9) and those of 30's, 40's, 50's, 60's and 70's were 40%, 50%, 24%, 39% and 36% of the 20's, respectively. Intake of grapefruit juice, known to contain flavonoids, inhibited the in vivo FMO (TB/CA) activity by 79%. Addition of the flavonoids like naringin, quercitrin and kaempferol, present in grapefruit juice, to the in vitro microso-mal FMO assay, thiobenzamide S-oxidation, produced 75%, 70% and 60% inhibition, respectively. Obtained Ki values of quercitrin, kaempferol and naringin on the in vitro FMO activity were 6.2, 12.0 and 13.9 $\mu\textrm{M}$, respectively. This suggested that the dose of drug should need to be adjusted to suit the individual FMO activities when the drugs metabolized by FMO are given to patients. As the intake of grapefruit juice has been identified to inhibit the FMO as well as CYP3A4 and lA2 activities, patients taking drugs metabolized by these enzymes should not drink grapefruit juice as the carrier.

• Toxicological Research
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• v.31 no.3
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• pp.279-288
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• 2015

N-nitrosamines, which are classified as carcinogens by IARC and US EPA, can be easily found in various foods. They are reaction products between nitrogen oxide and secondary amines, but can also be generated during fermentation. Ever since the 1960s, when nitrite, used as a preservative in processed meats, was suspected to generate N-nitrosamines, the usage of the food additive has been debated. However, the benefit of nitrite in food supply could not be ignored and the risk-benefit analysis has become a key issue in the use of the additive. For a risk analysis, an accurate estimation of the hazardous material is necessary; therefore, analytical methods for nitrosamines have continuously evolved from the 1950s. Solid supported liquid-liquid extraction and solid phase extractions have replaced the distillation for the clean-up steps, and tandem mass spectrometry is employed for higher selectivity and sensitivity. In the present study, for a better estimation of N-nitrosamine intake, the total diet study samples were prepared for the N-nitrosamines analysis. In order to obtain the most sensitive results, a partial preparation procedure was developed and modified for different food matrices. Among seven N-nitrosamines (N-nitrosodimethylamine, N-nitrosomethylethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitrosomorpholine) analyzed in the present study, N-nitrosodiethylamine has shown the highest detection rate in agricultural foods, while N-nitrosodimethylamine has appeared most frequently in livestock and fishery food products. The concentration of N-nitrosodimethylamine was the highest in seasoning.

• Journal of The Korean Society of Grassland and Forage Science
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• v.38 no.3
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• pp.156-164
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• 2018

Pesticide application in agriculture provides significant benefits such as protection from disease, prevention of harmful insects, and increased crop yields. However, accurate toxicological tests and risk assessments are necessary because of many related adverse effects associated with pesticide use. In this review, we discuss and analyze residual pesticides contained in livestock feed in Korea. A pesticide residue tolerance standard for livestock feed has not been precisely established; so, risk assessments are required to ensure safety. Standards and approaches for animal criteria and appropriate methods for evaluating residual pesticides are discussed and analyzed based on technology related to animal product safety in Korea. The safety of livestock feed containing pesticides is assessed to establish maximum residue limits relative to pesticides. Analysis of residual pesticides in milk, muscle, brain, and fat was performed with a livestock residue test and safety evaluation of the detected pesticide was performed. Efficacy of organic solvent extraction and clean-up of feed was verified, and suitability of the instrument was examined to establish if they are effective, rapid, and safe. This review discussed extensively how pesticide residue tolerance in livestock feed and hazard evaluation may be applied in future studies.

• Herbal Formula Science
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• v.8 no.1
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• pp.191-211
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• 2000

Objectives: In order to evaluate the effect of jungcheonwhadamgangki-tang on Balb/c mouse of allergy-sensitive to bronchial asthma induced by ovalbumin. Methods: The changes of diameter lumen of trachea which was upper respiratory organ, weight and gross appearance of lung, histology of lung and trachea, numbers of inflammatory cells in the bronchoalveolar lavage fluld(BALF) were observed. Results : The results are obtained as follows. 1. The diameters of trachea lumen were significantly increased in Jungcheonwhadam gangki-tang treated group as compared with control group. 2. Inflammatory cells including neutrophil and eosinophil in BALF were significantly. in Jungcheonwhadamgangki-tang treated group as compared with control group. 3. Weight of lung and black spots, which resulted from infiltration of inflammatory were significantly decreased in Jungcheonwhadamgangki-tang treated group as compared with control group.4. Hypertrophy of mucous membrane of trachea and bronchus and bronchioles in the lung, peritracheal, peribronchus and peribronchiolar inflammatory cell infiltration, and mucoid exudate deposit in the lumen were significantly decreased in Jungcheonwhadamgangki-tang treated group as compared with control group. Conclusions : It is considered that Jungcheonwhadamgangki-tang has somewhat favorable effect on the bronchial asthma because the bronchial asthma specific series of abnormalities in respiratory system were decreased after oral administration of Jungcheonwhadamgangki-tang in this study. In future, it is needed that the toxicological and dosage specific study of Jungcheonwhadamgangki-tang to use against bronchial asthma with safe.

• Journal of Pharmacopuncture
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• v.18 no.4
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• pp.38-44
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• 2015

Objectives: Radix Ginseng has been used for thousands of years to treat a wide variety of diseases. Radix ginseng has also been used as a traditional medicine for boosting Qi energy and tonifying the spleen and lungs. Traditionally, its effect could be obtained orally. Nowadays, a new method, the injection of herbal medicine, is being used. This study was performed to investigate the single-dose intravenous toxicity of water-soluble ginseng pharmacopuncture (WSGP) in Sprague-Dawley (SD) rats. Methods: All experiments were carried out at Biotoxtech, an institute authorized to perform non-clinical studies under the regulation of Good Laboratory Practice (GLP). At the age of six weeks, 40 SD rats, 20 male rats and 20 female rats, were allocated into one of 4 groups according to the dosages they would receive. The WSGP was prepared in the Korean Pharmacopuncture Institute under the regulation of Korea-Good Manufacturing Practice (K-GMP). Dosages of WSGP were 0.1, 0.5 and 1.0 mL/animal for the experimental groups, and normal saline was administered to the control group. The rat's general conditions and body weights, the results of their hematological and biochemistry tests, and their necropsy and histopathological findings were investigated to identify the toxicological effect of WSGP injected intravenously. The effect was examined for 14 days after the WSGP injection. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech. Results: No deaths were found in this single-dose toxicity test on the intravenous injection of WSGP, and no significant changes in the rat's general conditions and body weights, the results on their hematological and biochemistry test, and their necropsy findings were observed during the test. The local area of the injection site showed minial change. The lethal dose was assumed to be over 1.0 mL/animal in both sexes. Conclusion: These results indicate that WSGP is safe at dosages up to 1 mL/animal.

• Journal of The Korean Society of Clinical Toxicology
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• v.9 no.2
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• pp.49-55
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• 2011

Purpose: Acetanilide has been in widespread use as an amide herbicide compound. However, available data regarding acute human poisoning is scarce. The aim of this study was to analyze the clinical characteristics of acetanilide poisoning in order to identify the risk factors associated with severity. Methods: We conducted a retrospective observational study encompassing the period January 2005 to December 2010, including adult ED patients suffering from acetanilide intoxication. Toxicological history, symptoms observed, clinical signs of toxicity, and laboratory test results were collected for each patient. The patients were classified into two groups for analysis, according their poisoning severity score (PSS). Resulting clinical data and prognostic variables were compared between mild-to-moderate poisoning (PSS 1/2 grades), and severe poisonings and fatalities (PSS 3/4 grades). Results: There were a total of 37 patients, including 26 alachlor, 6 s-metolachlor, 4 mefenacet, and 1 butachlor cases. The majority of patients (81.1%) were assigned PSS 1/2 grades. Changes in mental status and observation of adverse neurologic symptoms were more common in the PSS 3/4 group. The median ingested volume of amide herbicide compound was 250 ml (IQR 200-300 ml) in the PSS 3/4 group, and 80 ml (IQR 50-138 ml) in the PSS 1/2 group. Also, the median GCS observed in the PSS 3/4 group was 13 (IQR 10-14), which was markedly low as compared to a median GCS of 15 in the PSS 1/2 group. Overall mortality rate was 5.4%, and profound cardiogenic shock was observed prior to death in all fatalities. Conclusion: When compared to previous reports, acute acetanilide poisoning resulted in relatively moderate severity. The presence of neurologic manifestations, hypotension, lower GCS score, and larger ingested volumes was associated with more serious effects and mortalities.

• Journal of Environmental Health Sciences
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• v.40 no.2
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• pp.105-113
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• 2014

Objectives: It is necessary to apply quantitative structure activity relationship (QSAR) for the various chemicals with insufficient toxicity data that are used in the workplace, based on the precautionary principle. This study aims to find application plan of QSAR software tool for predicting health hazards such as genetic toxicity, and carcinogenicity for some chemicals used in the electronics industries. Methods: Toxicity prediction of 21 chemicals such as 5-aminotetrazole, ethyl lactate, digallium trioxide, etc. used in electronics industries was assessed by Toxicity Prediction by Komputer Assisted Technology (TOPKAT). In order to identify the suitability and reliability of carcinogenicity prediction, 25 chemicals such as 4-aminobiphenyl, ethylene oxide, etc. which are classified as Group 1 carcinogens by the International Agency for Research on Cancer (IARC) were selected. Results: Among 21 chemicals, we obtained prediction results for 5 carcinogens, 8 non-carcinogens and 8 unpredictability chemicals. On the other hand, the carcinogenic potential of 5 carcinogens was found to be low by relevant research testing data and Oncologic TM tool. Seven of the 25 carcinogens (IARC Group 1) were wrongly predicted as non-carcinogens (false negative rate: 36.8%). We confirmed that the prediction error could be improved by combining genetic toxicity information such as mutagenicity. Conclusions: Some compounds, including inorganic chemicals and polymers, were still limited for applying toxicity prediction program. Carcinogenicity prediction may be further improved by conducting cross-validation of various toxicity prediction programs, or application of the theoretical molecular descriptors.

• Journal of Acupuncture Research
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• v.37 no.2
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• pp.110-117
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• 2020

Background: The aim of this pilot study was to assess the safety and dosing of scolopendrid pharmacopuncture (SPP). Methods: A total of 40 healthy Sprague-Dawley rats (males and 20 females 20) were selected following a 7-day inspection and acclimation period. SPP was administered via intramuscular injection, over a 2-week period using 3 doses including a high-dose [0.84 mg of scolopendrid per kg of body weight (BW)], a med-dose (0.42 mg/kg BW), and a low-dose (0.21 mg/kg BW). The control group was injected with sterile water into the muscles. Unusual changes caused by administration of the test substance were observed. Weight, feed intake, organ weight, and hematological examinations were compared among the groups. Using the SPSS statistical program, Levene's test was performed to evaluate the homogeneity of variances, and a one-way ANOVA test was subsequently performed to assess the significance between each test group. Results: During the experiment no animals died. Weight change, food consumption, organ weight, hematological test, and blood biochemical tests showed no significant differences in the treatment groups compared to controls. Conclusion: No toxicological changes related to the administration of test substances were observed. Therefore, the LD₅₀ (lethal-dose that kills 50%) of scolopendrid pharmacoupuncture in rats was greater than 0.84 mg/kg.

• Herbal Formula Science
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• v.21 no.1
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• pp.186-199
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• 2013

Objectives : The objectives of this study was to obtain acute information (single oral dose toxicity) of Red-Koji (Monascus purpureus 12002) Fermented Scutellariae Radix Aqueous Extracts (fSR), has been traditionally used in Korean medicine for treating various diseases including inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, fSR powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14days after single oral treatment of fSR with organ weights and histopathological observations of 12 types of principle organs. Results : After single oral treatment of fSR, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents, on the body and organ weights, clinical signs, gross and histopathological observations, except for some accidental findings. Conclusions : The results obtained in this study suggest that the LD50 and ALD of fSR in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg and can be safety used in clinics.

• The Journal of Korean Medicine
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• v.32 no.3
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• pp.18-24
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• 2011

Objective: Leejung-tang (Rechu-to in Japanese) is a traditional Korean herbal formula used for treatment of gastrointestinal disorders such as vomiting, stomach pain, chronic gastritis and gastrointestinal ulceration. The present study was carried out to investigate the potential acute toxicity of Leejung-tang water extract (LJT) by a single oral dose in Crl:CD (SD) rats in compliance with current guidelines. Methods: In the preliminary study, there were no adverse effects such as death, clinical signs, and body weight changes at dose levels of 500, 1000, and 2000 mg/kg/day body weight. Based on the results, a dose of 2000 mg/kg was selected as the toxicological limited dose. LJT was administered once by gavage to male and female rats at dose levels of 0 and 2000 mg/kg bodyweight. During the study period, mortalities, clinical findings, and body weight changes were observed for 14 days following the administration. On day 14 after the treatment, the animals were sacrificed by carbon dioxide overdose and complete gross postmortem examinations were performed. Results: In present study, no treatment-related deaths were observed. There were no adverse effects on clinical signs and body weight changes. In addition, there were no observed gross findings in all groups except for a kidney cyst in the 2000 mg/kg/day female group. Conclusion: The results indicated that LJT did not induce toxic effects at a dose level up to 2000 mg/kg in rats and its median lethal dose ($LD_{50}$) was considered to be over 2000 mg/kg/day body weight for both genders.