• Journal of Pharmacopuncture
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• v.16 no.2
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• pp.28-32
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• 2013

Objective: This study was performed to analyze the single-dose toxicity of D-amino acid oxidase (DAAO) extracts. Methods: All experiments were conducted at the Korea Testing & Research Institute (KTR), an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: In all 4 groups, no deaths occurred, and the $LD_{50}$ of DAAO extracts administered by IV was over 0.3 ml/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusion: The above findings suggest that treatment with D-amino acid oxidase extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

• Journal of Pharmacopuncture
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• v.13 no.4
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• pp.43-61
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• 2010

Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 mg/kg body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 mg/kg in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.335-335
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• 1994

Possibility whether lead ingestion can cause selective toxicity to central serotonergic nervous system in rats was tested. Three groups of wistar rats; 1)Control, 2) Low dose and 3) High dose groups, were prepared. In prenatally lead-exposed rats, until parturition from dams, rat pups were intoxicated via placenta of mother rats having received drinking water containing either 0%(control ), 0.05%(low dose) or 0.2%(high dose) of lead acetate respectively, In postnatally lead-exposed rats, right after parturition from dams rat pups received drinking water containing either 0％ (control), 0.05%(low dose) or 0.2％(high dose) of lead acetate. At 2, 4, 6 and 8 weeks of age, tryptophan hydroxylase (TPH) activity and Na$\^$+//K$\^$+/-ATPase activity were measured in 4 areas of rat brain; Telencephalon, Diencephalon, Midbrain and Pons/Medulla. TPH activities were assayed by modified method of Beevers et al. (1983) using L-(5-$^3$H)-tryptophan as substrate. TPH activity was determined as a criterion of lead poisoning to central serotonergic nervous system and Na$\^$+//K$\^$+/-ATPase activity as a criterion of non specific lead poisoning to any kinds of tissues. Selective toxicity of lead poisoning to central serotonergic nervous system was evaluated by the changes of TPH activities without concomitant changes of Na$\^$+//K$\^$+/-ATPase activities. In prenatally lead-exposed rats. this selectivity was found in Telencephalon (2 weeks of age), Diencephalon/Midbrain (2 weeks of age), Midbrain (4 and 6 weeks of age), Pons/Medulla (2, 4 and 6 weeks of age) In rats exposed to low dose of lead and Pons/Medulla (2 weeks of age) to high dose of lead. In postnatal Iy lead-exposed rats, this selectivity was found in Telencephalon (8 weeks of age), Diencephalon(8 weeks of age), Pons/Medulla (6 and 8 weeks of age) in rats exposed to low dose of lead and Pons/Medulla (8 weeks of age) to high dose of lead. These results suggest that lead poisoning may exhibit selective toxicity to central serotonergic nervous system.

• Toxicological Research
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• v.22 no.2
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• pp.87-93
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• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.

• Toxicological Research
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• v.34 no.2
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• pp.111-125
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• 2018

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of $356mg/m^3$ (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions.

• Journal of Microbiology and Biotechnology
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• v.30 no.6
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• pp.920-925
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• 2020

In India, nanotechnology has been used in therapeutic applications for several millennia. One example of a traditional nanomedicine is Rajath Bhasma (also called calcined silver ash), which is used as an antimicrobial and for the treatment of various ailments and conditions such as memory loss, eye diseases, and dehydration. In this study, we aimed to characterize the physical composition and morphology of Rajath Bhasma and its suitability for use as a non-toxic antimicrobial agent. First, Rajath Bhasma was physically characterized via i) Fourier-transform infrared spectroscopy to analyze the surface functional groups, ii) scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy to observe the morphology and elemental composition, and iii) X-ray diffraction to determine the crystalline phases. Thereafter, functional characterization was performed through toxicity screening using zebrafish embryos and through antimicrobial activity assessment against gram-positive (Staphylococcus epidermidis) and gram-negative (Escherichia coli) bacteria. Rajath Bhasma was found to harbor alkene, hydroxyl, aldehyde, and amide functional groups originating from biological components on its surface. The main component of Rajath Bhasma is silver, with particle size of 170-210 nm, and existing in the form of spherical aggregates with pure crystalline silver structures. Furthermore, Rajath Bhasma did not exert toxic effects on zebrafish embryos at concentrations below 5 ㎍/ml and exhibited effective antimicrobial activity against both gram-positive and gram-negative bacteria. The present results indicate that Rajath Bhasma is a potentially effective antimicrobial agent without toxicity when used at concentrations below 5 ㎍/ml.

• 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 Korean Society of Environmental Engineers
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• v.34 no.2
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• pp.136-142
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• 2012

Various factors affecting on the bioassay were investigated. Experiments with a low mixture ratio (cell to toxicant solution) of 0.5 : 9.5 (v/v) produced observable bioluminescence intensity for assay. Both sodium lactate and potassium nitrate stimulate bioluminescence activity; 2.6~4.0 times of control. Distilled water and MSM, which gave non significant effects on the bioluminescence activity, were determined as proper diluent or extract solutions. A wide range of toxic responses of metals and organics were observed. In general, organics were much less sensitive than metals. Samples collected from eleven sites showed the bioluminescence activity ranging from 29 to 111% of the control. Significant correlation between toxicity and total metal contents was not observed, but the toxicity of two groups, sorted based on the contaminated arsenic concentration in soils, was 44% and 20%, showing considerable differences.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.41 no.5
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• pp.309-314
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• 2008

The toxicity of five species of puffer fish, Arothron firmamentum (Byeolbok), Lagocephalus gloveri (Heukmilbok), L. wheeleri (Eunmilbok), L. inermis (Minmilbok) and L. lunaris (Milbok), collected from fish markets in Korea, was determined using a mouse bioassay. In A. firmamentum, the proportion of toxic specimens containing >10 MU/g was 87.5% in the ovaries, and 10.0% in the skin; no toxicity was detected in the muscle, fin, liver, intestine and gallbladder using the mouse bioassay. The highest toxin levels were found to be 87 MU/g in the ovaries, and 13 MU/g in the skin. Toxic specimens containing >10 MU/g were not detected from samples taken from any of the organs in L. wheeleri and L. inermis. In L. gloveri, most specimens were found to be non-toxic, but toxin levels of 11-72 MU/g were detected from within the skin, fins, and intestines in one specimen. In L. lunaris, the proportion of toxic specimens was 50.0% in the ovaries, and 7.1% in the gallbladder; no toxicity was detected in the other organs by the mouse bioassay. The highest toxin levels were 75 MU/g in the ovaries, and 14 MU/g in the gallbladder. Therefore, the toxicities of edible muscle and skin in the five species of puffer fish marketed in Korea were found to be within acceptable levels for human consumption.

• Toxicological Research
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• v.30 no.2
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• pp.121-130
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• 2014

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.