• 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.

• Journal of Environmental Health Sciences
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• v.43 no.4
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• pp.247-256
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• 2017

Objectives: The deaths of Korean victims exposed to the disinfectant CMIT/MIT have remained unresolved. This is mainly due to a lack of concordance between the few available toxicity tests and the abundant epidemiological data, making it difficult to establish a cause-and-effect relationship. Therefore, this study was carried out to investigate any potential associations between CMIT/MIT exposure and death. Methods: Groups of experimental and control C57BL/6 mice were instilled (in the trachea) with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot. CMIT/MIT was instilled over a period of three days and eight weeks, respectively, to achieve acute and chronic exposures. A threshold dose-response model was applied for estimating the threshold level as one line of evidence for a causal association between CMIT/MIT and death. Results: An acute exposure of 1.2 mg ai/kg/day of CMIT/MIT was estimated to reflect the threshold for death. The dose-response curve with this threshold showed a very steep slope and a narrow range of CMIT/MIT exposures. The narrow range of CMIT/MIT exposures, in particular, indicated an evident boundary between survival and death, thus implicating a strong causal association. A similar threshold dose-response relationship observed following acute exposure was also seen following chronic exposure to CMIT/MIT. Airborne disinfectant exposure was visible as minimal or mild lung damage with no fibrosis, as shown by histopathological tests. However, many observations are considered to be functional respiratory tract or lung failure due to death, as observed in necropsies of the mice that died due to CMIT/MIT exposures. Conclusions: There are two strong lines of evidence for a causal association between death and CMIT/MIT exposure: 1) The threshold dose-response curve, with a very steep slope and a narrow range of CMIT/MIT exposures showing a visible boundary between survival and death; and 2) many cases of functional respiratory or lung failure.

• Toxicological Research
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• v.25 no.3
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• pp.147-157
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• 2009

This study was conducted to obtain acute information of the oral dose toxicity of lyophilized water extract of Pinelliae Rhizoma, a dried tuber of Pinellia ternata (PR) in male and female mice. In order to calculated 50% lethal dose (LD$_{50}$) and approximate lethal dose (ALD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body weight). The mortality and changes in body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with PR extract. We could not find any mortalities, clinical signs, changes in the body and organ weights, gross and histopathological findings except for dose-dependent increases in the hepatic fatty change frequencies detected in PR extract 2000 and 1000mg/kg treated in both male and female mice. The results obtained in this study suggest that LD$_{50}$ and approximate LD in mice after single oral dose of PR extracts were considered over 2000 mg/kg in both and female male mice, but more than 1000mg/kg of PR extracts treatment could induce slight hepatotoxicity the fatty changes in mice.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.127-132
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• 2007

The object of this study was to evaluate the acute toxicity of lyophilized water extract of Radix Araliae Cordatae (RA) in male and female mice. The extract was administered to female and male ICR mice as an oral dose of 2000 mg/kg (body wt.) according to the recommendation of KFDA Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy, organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, changes in the body weight and gross findings except for increases of hypertrophy of lymph nodes in male RA extracts-dosing group. In addition, no RA extracts-treatment related abnormal changes in the organ weight and histopathology of principle organs except for some sporadic accidental findings. The results obtained in this study suggest that the RA extracts does not cause any toxicological signs. The LD$_{50}$ and approximate LD of RA extracts in both female and male mice were considered as over 2000 mg/kg.

• Journal of The Korean Society of Clinical Toxicology
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• v.18 no.1
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• pp.42-46
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• 2020

Tetramine toxicity due to sea snail ingestion is generally mild and has a good prognosis. Tetramine toxicity acts on the acetylcholine receptor, affecting the neuromuscular junction and autonomic nervous system. A 78-year-old female patient visited the emergency room with vomiting and dyspnea after eating sea snails. At the time of admission, the vital signs recorded were 140/80 mmHg-105/min-24/min-36.5℃, and 90% oxygen saturation. Arterial blood test revealed hypercapnia (pCO₂ 58.2 mmHg) and respiratory acidosis (pH 7.213, HCO₃^- 22.5 mmol/L), whereas other blood tests showed no specific findings. Due to decreased consciousness and hypoxia, endotracheal intubation and mechanical ventilation were administered to the patient. Successful weaning was accomplished after 12 hrs, and the patient was discharged without any further complications. Although tetramine toxicity rarely results in acute respiratory failure due to paralysis of the respiratory muscle, caution is required whilst treating the patient.

• Korean Journal of Pharmacognosy
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• v.14 no.4
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• pp.149-160
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• 1983

It has been known that Gentianae macrophyllae Radix is reputed to be effective in removal of 'Pungseub' and 'Heoyeol', and to be analgesic. Since ancient times, however, there have been many examples of substituting Lycoctoni Radix for Gentianae macrophyllae Radix. For that reason, this experiment was conducted to compare the diuretic, analgesic, anti-inflammatory, anti-pyretic, anti-bacterial effect, and toxicity of Lycoctoni Radix with those of Gentianae macrophyllae Radix. The results obtained in this work were summarized as follows; In the test of acute toxicity, Lycoctoni Radix was found to be toxic in comparison to Gentianae macrophyllae Radix which was found to be non-toxic. Both herbs were found to be diuretic and Gentianae macrophyllae Radix was more effective than the other and to be ineffective for the blood pressure and respiration. Lycoctoni Radix was found to be more analgesic than the other. Gentianae macrophyllae Radix was found to be more anti-inflammatory of the two and both demonstrated anti-pyretic effect. Anti-bacterial effect was detected only in Lycoctoni Radix. It is concluded that Gentianae macrophyllae Radix has mild diuretic, analgesic, anti-inflammatory and anti-pyretic effect, but Lycoctoni Radix, due to its toxicity, can not be substituted for Gentianae macrophyllae Radix.

• Korean Journal of Food Science and Technology
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• v.30 no.4
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• pp.775-780
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• 1998

Gamma irradiation at 5 kGy was applied to beefs for evaluation of their possible genotoxicity and acute oral toxicity. The genotoxicity of 5 kGy irradiated beef was evaluated by Salmonella typhimurium reversion assay and in vivo micronucleus assay using mouse bone marrow cells. The results were negative in the bacterial reversion assay with S. typhimurium TA98, TA100, TA1535, TA1537. Clastogenic effects were not shown in vivo mouse micronucleus assay at 5 kGy dose tested. In an acute toxicity test, 5 kGy-irradiated beef was administrated orally at a dose level of 313 to 5,000 mg/kg, and then number of deaths, clinical signs, body weights, and pathological examinations were examined daily for 14 days post-administration. The results indicate that 5 kGy irradiated beef did not show any toxic effect on mice and oral $LD_{50}$ value was over 5,000 mg/kg on ICR mice.

• YAKHAK HOEJI
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• v.40 no.5
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• pp.608-615
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• 1996

6-[(N-3,4-Difluorophenyl)amino]-7-chloro-5,8-quinolinedione(RCK4) was tested for antifungal activities, against systemic infections with Candida albicans in normal mice. The therapeutic potential of RCK4 had been assessed in comparison with ketoconazole and fluconazole. RCK4 had $ED_{50},\;0.30{\pm}0.14$ but ketoconazole and fluconazole had $ED_{50},\;8.00{\pm}0.73,\;10.00{\pm} 0.43mg/kg$ respectively. Intraperitoneally administered RCK3 at the $ED_{50}$ for 7 days and 14 days reduced Candida albicans colony count in the kidneys and liver as well as ketoconazole and fluconazole at these $ED_{50}$. And administered RCK4 at the $ED_{50}$ for 14 days improved survival rates as well as ketoconazole. Acute oral toxicity studies of RCK4 were carried out in ICR mice of both sexes. These acute oral toxicities of RCK4 were low and $LD_{50}$ values were over 2,850mg/kg in ICR mice. The genotoxicities of RCK4 had been evaluated. RCK4 was negative in Ames test with Salmonella typhimurium and chromosomal aberration test in CHL cells. The clastogenicity was tested on the RCK4 with in vivo mouse micronucleus assay. RCK4 did not show any clastogenic effect in mouse peripheral blood and was negative in mouse micronucleus assay. These results indicate that RCK4 has no genotoxic potential under these experimental conditions.

• Journal of Sasang Constitutional Medicine
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• v.9 no.2
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• pp.203-225
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• 1997

Jihwangbakhotang(地黃白虎楊) is made by Li Je Ma, the creator of the Four Constitutional Medicine. Single and 13 weeks oral repeated dose toxicity studies were conducted in Sprague Dawley rats of both sexes to elucidate the potential acute and subchronic toxicity of JBT extract and reversibility of any effects. In the single dose study, JBT extract was administered orally to rats with the dose of 2 g/kg and 8 g/kg. In the long term administration of 13 weeks, the JBT extract of 125 mg/kg/day, 500 mg/kg/day, 2000 mg/kg/day was administered to rats. The change of blood weight, urine volume, electrolyte in urine, hematological change, the change of blood chemistry, autopsy finding, and histological observation were researched, the results were as follows; 1. The lethal dose of JBT extract seems to be over 10 g/kg, the single administration of JBT extract 8 g/kg showed no toxical signs except little increase of urine volume. 2. The change of body weight had the trend of decrease in the group of, but has no significance, and also the consumption of food and water had no changes. 3. The hematological changes induced by the 13 weeks administration of JBT extract showed the significance in the item of Hb, MCH, MCV, WBC in the group of 125 mg/kg/day. 4. In the test of blood chemistry, total cholesterol showed little decrease and A/G ratio showed little increase, but the change was not clear, and the standard error was large. So the result was obtained insignificantly and the toxicity of JBT extract was not observed. 5. In the male group after recovery period, the level of cholesterol and triglyceride decreased slightly, but the result was not significant. 6. In the urine test, the little change of electrolyte was appeared, but it seemed not to be the result induced by the toxicity of JBT extract. 7. In each group of male and female rats, the weight change of organ and the serum histological changes was observed, but the result did not showed the dose dependent toxicity. So the toxicity of JBT extract was not regarded. In the conclusion, the toxicity of JBT extract was not observed in the single dose treatment and long term repetitive administration of JBT extract.

• The Korea Journal of Herbology
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• v.35 no.4
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• pp.45-50
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• 2020

Objective : This study was performed to evaluate the toxicity after a single oral administration of black raspberry extract to male and female Sprague-Dawley (SD) rats and to determine the approximate lethal dose (ALD). Methods : We previously showed that the black raspberry extract repressed the simvastatin-mediated expression of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and improved Low-Density Lipoprotein cholesterol (LDL-C) uptake by hepatocytes through the induction of the Low-Density Lipoprotein Receptor expression in hepatocytes. The groups consisted of black raspberry extract groups, as an oral dose of 2,000 mg/kg and a control group. 5 weeks SD rats were randomly assigned to 4 groups of 5 rats. Each male and female SD rats were administered orally once. For 14 days after the administration, mortality, clinical signs, changes in body weight, and necropsy findings were observed according to the "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity- Fixed Dose Procedure" of OECD Test Guideline. Results : There were no cases of mortality in the group administered with 2,000 mg/kg of male and female, and no abnormalities in body weight change and clinical signs. Also, no gross abnormalities were observed at the autopsy. Conclusions : As a result of a single oral administration of the black raspberry extract to SD rats, the ALD was determined to exceed 2,000 mg/kg for both male and female SD rats.