• Toxicological Research
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• v.35 no.2
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• pp.119-129
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• 2019

As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

• Herbal Formula Science
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• v.17 no.2
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• pp.65-72
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• 2009

Objectives : Yukmijihwang-tang (YJT) is known as a tonifying formula for reinforcement of yin deficiency conditions. The present study was carried out to investigate the potential acute toxicity of YJT in ICR male and female mice. Methods : We investigated the acute toxicity about boiling water-extracted YJT. The test article was orally administered once by gavage to 20 male and 20 female mice at dose levels of 0 (control group), 1250, 2500 and 5000 mg/kg body weight. Mortalities, clinical findings, autopsy and body weight changes were monitored daily for the 14 days following the administration according to the Regulation of Korean Food and Drug Administration. Results : We observed survival rates, general toxicity, change of body weight, and autopsy. Single oral administration of YJT with different dosages, no animals died of the test drug. Autopsy of animal revealed no abnormal gross finding. Therefore, $LD_{50}$ value of YJT for ICR mice was more than 5000 mg/kg on oral route. Conclusions : These results suggest that no toxic dose level of YJT in mice is considered to be more than 5000 mg/kg. Consequently, it was concluded that YJT have no effect on acute toxicity and side effect in ICR mice.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.67-83
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• 2011

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

• Journal of Advanced Marine Engineering and Technology
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• v.38 no.8
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• pp.1010-1020
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• 2014

Ballast water effluent treated by an electrolytic method contains reactive chlorine species and disinfection by-products (DBPs). In this study, we conducted whole effluent toxicity (WET) testing and ecological risk assessment (ERA) to investigate its ecotoxicological effects on marine environment. WET testing was carried out for three marine pelagic organisms, i.e., diatom Skeletonema costatum, rotifer Brachionus plicatilis and fish Paralichthys olivaceus. The biological toxicity test revealed that S. costatum was the only organism that showed apparent toxicity to the effluent; it showed no observed effect concentration (NOEC), lowest observable effect concentration (LOEC) and effect concentration of 50% (EC50) values of 12.5%, 25.0% and 83.3%, respectively, at brackish water condition. In contrast, it showed insignificant toxicity at seawater condition. B. plicatilis and P. olivaceus also showed no toxicities to the effluent at the both salinity conditions. Meanwhile, chemical analysis revealed that the ballast water effluent contained total residual oxidants (TROs) below $0.03{\mu}g/L$ and a total of 20 DBPs including bromate, volatile halogenated organic compounds (VOCs), halogenated acetonitriles (HANs), halogenated acetic acids (HAAs) and chloropicrin. Based on ERA, the 20 DBPs were not considered to have persistency, bioaccumulation and toxicity (PBT) properties. Except monobromoacetic acid, the ratio of predicted environmental concentration (PEC) to predicted no effect concentration (PNEC) of the other 19 DBPs did not exceed 1. Thus, our results of WET testing and ERA indicated that the ballast water effluent treated by electrolysis and subsequently neutralization was considered to have no adverse impacts on marine environment.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.171-181
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• 1998

DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.

• Toxicological Research
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• v.34 no.1
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• pp.55-63
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• 2018

As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, $LD_{50}$ value for animals was 5,000 mg/kg or more.

• Toxicological Research
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• v.23 no.4
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• pp.383-389
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• 2007

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study we examined the single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to $1000{\mu}g/kg$. The lethal dose ($LD_{50}$) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and $200{\mu}g/kg$ (i. v.) of rhGM-CSF did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.

• Journal of Acupuncture Research
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• v.37 no.3
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• pp.167-172
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• 2020

Background: This study aimed to assess the toxicity of capsaicin (CP) pharmacopunture in an animal model. Methods: The toxicity of a single-muscular dose of CP (45.45 mg/mL) was evaluated in 6-week-old male and female Sprague-Dawley rats. A total of 20 rats were assigned to 2 groups which were sex and weight matched. All rats acclimatized for 1 week before receiving 1.0 mL of CP (45.45 mg/mL) or normal saline solution (control) intramuscularly. The general condition and mortality of the animals were observed. The rats were sacrificed 2 weeks after CP was administered and histopathology was performed. Results: No abnormal symptoms or deaths were observed, and there was no difference in body weights between the CP and control groups throughout the study. No significant differences in histopathology were observed between the groups. Conclusion: No toxicological changes related to the administration of CP were observed. This study indicated that the safe dose of CP in Sprague-Dawley rats was 1.0 mL of CP (45.45 mg/mL) or less. Further studies are needed to confirm the safety of CP in the human body.

• The Korea Journal of Herbology
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• v.32 no.4
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• pp.33-38
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• 2017

Objectives : Termitomyces albuminosus (Berk.) Heim is one of the famous wild edible mushrooms in the southern part of China. It is known that Termitomyces albuminosus, like Aconitum koreanum used in Korean traditional medicine, contains a kind of cerebroside, termitomycesphin, causing a pharmacologic effect on the neuron system. The pharmacologic effect of Termitomyces albuminosus can be used to possibly replace Aconitum koreanum. However, It needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was conducted to obtain acute information of the toxicity of dried-Termitomyces albuminosus powder and to secure its safety in clinical applications. Methods : In order to calculate approximate lethal dose(ALD), test substance was orally administered to male and female SD-rat at dose levels of 5,000 and 0 (vehicle control) mg/kg (body weight). Based on the result of this toxicity, also the estimation of safety classification was calculated using the HED-based (human equivalent dose) MOS (margin of safety). Results : There were no mortalities, test substances treatment-related clinical signs, no changes in the body or organ weights, and no gross or histopathological findings at 14 days after treatment with test substance. Thus, the approximate lethal dose of dried-Termitomyces albuminosus powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the limit dose, 5000 mg/kg, it was estimated that dried-Termitomyces albuminosus powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.

• Journal of Food Hygiene and Safety
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• v.12 no.3
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• pp.234-239
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• 1997

Guh Sung Y.L.S.-95 is one of the polyacidic solution of which main component is acetic acid. We investigated the subchronic toxicity of the Guh Sung Y.L.S.-95 using SPF ICR mouse for 4 weeks. The Guh Sung Y.L.S.-95 was administered by gastric intubation, 1.0, 2.5, 5.0 g/kg body weight. The results are as follows: 1. There are no adverse effects on the clinical obserbation and body weight changes. Also, there are some significant changes in organ weight, but it was meaningless because of the absence of dose-response relationships. 2. In the hematological patterns of administered mouse, there are no significant changes between the treated groups. Also, there are no serological enzymatic changes in the treated mouse. In the 1.0 g/kg treated group, ASP activity was increased significnatly compared with control group. But, this level of activity was fall under the normal physiological range of control mouse. 3. Histopathological findings of the brain, liver, heart, spleen, kidneys, stomach, lung, testis, ovary, uterus and thymus were not observed in the treated mouse. From the above results, the Guh Sung Y.L.S.-95 has no toxicity upto the 5.0 g/kg/day of oral dose for 4 weeks.