• 대한한의학회지
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• 제30권5호
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• pp.102-114
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• 2009

Objectives: HMCO5 is an extract obtained from 8 different herbal mixtures. We undertook a safety evaluation of HMCO5 for a dose range finding (DRF) toxicity test in specific pathogen free (SPF) Sprague-Dawley (SD) male and female rats. Methods: The male and female rats were divided into 4 groups, respectively; G(0), treated with distilled water: G(1), treated with 222 mg/kg HMC05: G(2), treated with 667 mg/kg HMC05, and G(3), treated with 2,000 mg/kg HMC05; HMC05 was administered orally for 4 weeks. The safety evaluation examined clinical signs, mortality, body weight, food consumption, water consumption, ophthalmic findings, urinalysis, hematological values, absolute & relative organ weights, and necropsy findings during the tests. Results: There were no changes in clinical signs, mortality, body weight, food consumption, water consumption, and ophthalmic findings examined during the test periods. In serum biochemical values, triglyceride was increased in male group G(3) and Na$^+$ decreased significantly in male groups G(2), G(3) and G(4). In male group G(4), spleen weight decreased relatively and increases of absolute & relative left ovary weights were found. In addition, an adhesion of liver to diaphragm was found in male group G(2). However, we could not find any dose-interrelationships in these changes. Conclusions: These results indicate that HMC05 extract did not show any toxicity in the DRF toxicity study. Therefore, it suggests that establishment of 1,000, 333 and 111 mg/kg dosages are moderate in a repeated dose 26-week oral toxicity study of HMC05.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.172-172
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• 2002

Previously, we reported a novel polymeric micellar solubilizer, Aceporol 330, that showed relatively low toxic effects when it was compared with that of Cremophor EL which is currently being used for paclitaxel. In this study, we have developed a new micellar solubilizer, Aceporol 460, that has 3-4 times higher loding capacity for paclitaxel than Aceporol 330. The single-dose and the repeated-dose toxicity of Aceporol 460 were evaluated in ICR mice. For single dose toxicity test, male and female mice were randomly assigned to one of five study groups to receive, and injected intravenously with dosages of 0, 3, 4mL Cremophor EL/kgbody weight, and 3, 4mL Aceporol 460/kg body weight, respectively. In both male and female mice, LD50 for Aceporol 460 can not he determined even at the maximal administrable dosage, 4mL/kg due to the high viscosity of chemical and there was no significant change in body weight, hematological and serum biochemical analysis, organ weight, and histopathological examination compared with that of Cremophor EL. For the repeated dose toxicity test, male and female mice were given the dosage of 0, 1.6mL Cremophor EL/kgbody weight/day, and 1.6mL Aceporol 460/kg body weight/day for 2 weeks. Results of repeated dose toxicity tests for 2 weeks suggested that Aceporol 460 treated group show no significant toxicological findings with body weight, hematological and serum biochemical analysis, organ weight, urinalysis, and ophthalmoscopic and histopathological examination compared with that of Cremophor EL. These results indicate that Aceporol 460 have higher paclitaxeL-loading capacity than Aceporol 330 and less toxic effects than Cremophor EL in male and female mice.

• 대한한의학방제학회지
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• 제28권2호
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• pp.169-177
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• 2020

Objectives : This experiment was designed to assess the single oral toxicity of Ethanol Extract Inulae Flos (IF) ethanol extracts. IF is one of the important herbs to remove phlegmy which is the viscous turbid pathological product that can accumulate in the body, causing a variety of diseases. Nevertheless, there has been a lack of research on the pharmacology toxicity of IF. Methods : In this study, IF was orally administered to 5 weeks ICR mice as an oral dose of 2,000 or 3,000 or 5,000 mg/kg. The condition of the mice was observed for 14 days and their weights were measured every two days. Results : None of the mice died for 14 days. The abnormal clinical symptoms and anatomical signs of toxicity were not found in any treatment groups. The gain of net body weight was observed. There was also no significant difference in the organ weight. The serum biochemistry and hematological analysis showed a decrease in BUN, red blood cells, white blood cells and platelets although within the normal ranges. Conclusions : These results suggest that the 50% lethal dose of IF is more than 5,000 mg/kg. This could be thought that IF is a safe drug without acute toxicity and side effects. However, IF showed some weight loss and change in blood test, so it will need to be careful when using it for high doses.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.171-171
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• 2002

This study was carried out by an Korean GLP laboratory to assess the combined repeated dose, reproduction and developmental toxicity of benzoyl peroxide for OECD SIDS(Screening Information Data Set) program. Male and female Sprague Dawley rats were exposed to benzoyl peroxide at levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for male and for 41-51 days for female.(omitted)

• Toxicological Research
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• 제12권2호
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• pp.323-330
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• 1996

Subacute toxicity study was performed in Sprague-Dawley rats after daily oral administration of KDRD-002 0.23, 0.7, 2.1 g/kg for one month. There were no clinical signs and pathological changes compared with control group but slight decrease in spontaneous motor activities and locomotions at high dose group of KDRD-002. Body weights were not significantly changed between control and KDRD-002 treated groups. In histopathological examinations, however, two animals (1 male, 1 female) showed abnormal increases in the weights of spleen tissues at middle dose group of KDRD-002. Also, there were some hemorrhages in lung tissues at low dose group of KDRD-002, but it was not considered to be caused by KDRD-002. These results suggest that KDRD-002 does not induce any significant subacute oral toxicity in Sprague-Dawley rats.

• Communications for Statistical Applications and Methods
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• 제29권2호
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• pp.239-250
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• 2022

In many applications, we frequently encounter correlated multiple outcomes measured on the same subject. Joint modeling of such multiple outcomes can improve efficiency of inference compared to independent modeling. For instance, in developmental toxicity studies, fetal weight and number of malformed pups are measured on the pregnant dams exposed to different levels of a toxic substance, in which the association between such outcomes should be taken into account in the model. The number of malformations may possibly have many zeros, which should be analyzed via zero-inflated count models. Motivated by applications in developmental toxicity studies, we propose a Bayesian joint modeling framework for continuous and count outcomes with excess zeros. In our model, zero-inflated Poisson (ZIP) regression model would be used to describe count data, and a subject-specific random effects would account for the correlation across the two outcomes. We implement a Bayesian approach using MCMC procedure with data augmentation method and adaptive rejection sampling. We apply our proposed model to dose-response analysis in a developmental toxicity study to estimate the benchmark dose in a risk assessment.

• 대한본초학회지
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• 제25권3호
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• pp.43-51
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• 2010

Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 mg/kg/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

• 대한한방내과학회지
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• 제26권2호
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• pp.369-378
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• 2005

An herbal water extract of Bojungikkeehapdaechilkitang(BDT) was prepared to test it for single-dose and repeated-dose toxicity, genotoxicity and reproductive toxicity, and to obtain a 50% lethal dose$(LD_{50})$, approximated lethal dose(ALD), and approximated target organs for BDT. The extract was tested on female and male ICR mice according to KFDA Guideline 1999-61 at doasge level of 2000, 1000, 500, 250 and 125mg/kg/10mL In this study, clinical signs, mortalities and gross findings of principal organs were observed for 14 days of single dosing, and afterwards in some cases. The ALD and $LD_{50}$ of BDT extract obtained in this study was>2000mg/kg for both male and female ICR mice. Also, any possible digestive toxicity of BDT extract was found to be above 1000mg/kg in both male and female ICR mice. The results of this study strongly suggest that BDT extract has no toxic effect at dosage level below 500mg/kg.

• Toxicological Research
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• 제34권2호
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• pp.85-95
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• 2018

The term Butterfly tea refers to decoction of Mariposa christia vespertilionis leaves which is widely consumed by cancer patients throughout Malaysia and has gained a huge popularity among Malaysians, not only cancer patients but also researchers to discover the real potential of this plant. Herein, the study is aimed at evaluating the possible toxicity in 28-day subacute oral toxicity of ethanolic extract M. christia vespertilionis in male Sprague Dawley rats. The 28-day subacute toxicity study was conducted to detect the no-observed adverse effect level (NOAEL). In this study, a total of 30 rats were divided into the control, 5% DMSO (vehicle), low dose (75 mg/kg), medium dose (125 mg/kg) and high dose (250 mg/kg) groups. The extract was administered daily from day 1 until day 28. At the end of the study, the animals were humanely sacrificed and assessed for the effect extract of Mariposa christia vespertilionis leaves on body weight and relative organ weights and haematological, biochemical and histopathological parameters. The haematological and serum biochemical parameters for the assessment of kidney and liver injuries were carried out. Results of haematological and serum biochemistry results showed no changes in the control and treated groups. In the histopathology, evaluation of kidney tissues in all treated groups showed no significant (p > 0.05) lesions. In contrast to kidney, liver tissues showed significant differences (p < 0.05) in lesions observed in low dose (430 mg), medium dose (700 mg) and high dose (1480 mg) groups with very mild, mild and mild to moderate lesion of hepatic necrosis, in the respective groups, and very mild hepatic degeneration and hepatitis were scored in all three groups.

• Toxicological Research
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• 제24권4호
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• pp.315-320
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• 2008

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) is a glycoprotein and hematopoietic growth factors that regulates the proliferation of myeloid precursor cells and activates mature granulocytes and macrophages. In a 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 repeated dose toxicity of rhGM-CSF in SD rats. The repeated dose toxicity study was performed at each dose of 50 and 200 ${\mu}g/kg$ subcutaneous administration of rhGM-CSF everyday for 28-days period. The results 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 tested groups. The hematological and blood biochemical parameters were statistically not different in all groups. These results suggest that rhGM-CSF may show no repeated dose toxicity in SD rats under the conditions.