• Toxicological Research
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• 제31권1호
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• pp.77-88
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• 2015

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

• 한국동물생명공학회지
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• 제36권1호
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• pp.17-24
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• 2021

In this study, the potential toxicity of isoprocarb was demonstrated using zebrafish embryos. We treated isoprocarb (0, 29, and 58 mg/L) to the zebrafish embryos for 72 h then, we estimated morphological changes and apoptotic cell numbers. The increasing extent of apoptosis from the anterior to posterior region of developing zebrafish larvae was correlated with toxicity in the overall development process, including growth and normal organ formation. The appearance of abnormalities in the isoprocarb-treated groups in comparison to normal developing zebrafish larvae was verified using quantitative image analysis based on ImageJ software program. The vascular system comprising a complex interconnection of blood vessels was visualized in vessel-fluorescent transgenic zebrafish (fli1:eGFP). The main vasculature was malformed on isoprocarb treatment, and this was also related to cardiac defects. Taken together, normal embryonic development in zebrafish was interrupted owing to the acute toxicity of isoprocarb.

• Journal of Preventive Medicine and Public Health
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• 제19권2호
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• pp.184-192
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• 1986

Since the wide spread application of hyperbaric oxygenation in clinical setting, the problems of oxygen toxicity have been attracting a deep interest from the researchers on hyperbaric medicine as a practical issue. Among extensive research trials, the study on the protective agents against oxygen toxicity occupied one of the most challenging field. As the mechanisms of oxygen toxicity, the role of the oxygen free radicals produced by peroxidation process are strongly accepted by the leading researchers on oxygen toxicity, the probable protective effects of antioxidant against oxygen toxicity are sustaining a sufficient rationale. In this study, the author attempted to evaluate the effect of vitamin E as a protective agent against oxygen toxicity through the observation of death rate, convulsion rate, time to convulsion, and macroscopic and microscopic pathological changes of experimental rats exposed to 100% oxygen at 5 ATA for 120 minutes. The findings observed are as follows: 1) The death rate, convulsion rate, time to convulsion, organ/body weight ratio and microscopic pathological findings were identified as reliable objective and quantitative indices for oxygen toxicity. 2) Vitamin E showed excellent protective effects against CNS and pulmonary oxygen toxicity as a strong antioxidant. The most effective dose seemed to be around 400 mg/kg 3) The results of this study are supporting the oxygen free radical hypothesis on oxygen toxicity.

• Toxicological Research
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• 제17권1호
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• pp.27-32
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• 2001

Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that consumption of EO treated foods might cause harmful effects in human. In Korea, the use EO gas for food treatment was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to evaluate the safety of irradiated ginseng on embryo and fetal developmental toxicity effects in rats. Either EO gas fumigated or $\gamma$-irradiated ginseng was administered to pregnant Wistar rats by oral gavage from gestational day 7 to 17. The amount of irradiation used in this study was 5, 10 and 30 kGy, respectively. There were no treatment related changes of dams in deaths, clinical signs, food consumption and body/organ weight. No treatment related changes in implantation ratio, litter size, sex ratio and body/organ weight of fetuses were observed. Also, no F1fetuses with external, visceral, head and skeletal mal-formation were observed. The results of this study showed that $\gamma$-irradiated ginseng, up to 30 kGy, has no adverse effects on fetal development of rats.

• Toxicological Research
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• 제22권2호
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• pp.135-144
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• 2006

This study was performed to evaluate repeated-dose toxicities of STB-HO-BM in Sprague-Dawley rats. STB-HO-BM was administered orally to rats at dose levels of 0, 100, 300 and 1,000 mg/kg/day for 13 weeks. In recent study, there were no dose related changes in mortality, clinical signs, body weight changes, food and water consumption, opthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with STB-HO-BM. Gross and histopathological findings revealed no evidence of specific toxicity related to STB-HO-BM. These results suggest that the oral no observed adverse effect level (NOAEL) of STB-HO-BM may be over 1,000 mg/kg in rats.

• Journal of Ginseng Research
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• 제39권2호
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• pp.89-93
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• 2015

Ginseng has long been used as a functional food or therapeutic supplement and it is empirically known to be safe and nontoxic. During recent decades, a number of in vitro and in vivo experiments, as well as human studies have been conducted to prove the safety of various types of ginseng samples and their components. Clinical trials, case reports, and in vitro and in vivo research articles addressing the safety, toxicity, and other adverse events of ginseng application were selected and reviewed. Patient risks associated with ginseng abuse and misuse such as affective disorder, allergy, cardiovascular and renal toxicity, genital organ bleeding, gynecomastia, hepatotoxicity, hypertension, reproductive toxicity, and anticoagulant-ginseng interaction were reviewed and summarized. There are some cases of patient risk associated with ginseng abuse and misuse depending on patients' conditions although further investigation in more cases is required to clarify these issues.

• Toxicological Research
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• 제33권3호
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• pp.239-253
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• 2017

Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide ($Nd_2O_3$) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized $Nd_2O_3-containing$ aerosols via a nose-only inhalation system at doses of $0mg/m^3$, $0.5mg/m^3$, $2.5mg/m^3$, and $10mg/m^3$ for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the $2.5mg/m^3$ and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the $0.5mg/m^3$ treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the $0.5mg/m^3$ group, but were exacerbated in the $10mg/m^3$ group. The lowest-observed-adverse-effect concentration of nano-sized $Nd_2O_3$ was determined to be $0.5mg/m^3$, and the target organ was determined to be the lung, under the present experimental conditions in male rats.

• 대한한의학방제학회지
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• 제16권1호
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• pp.147-168
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• 2008

HYTE (Hyeonggaeyeongyotang Extract), a polyherbal formula has been used as folk medicine, 28days repeat oral dose toxicity was tested in SD rats according to KFDA Guideline[2005-60]. Methods : In this study, mortality, clinical signs, body weight and gains, food and water consumption, ophthalmologic observation, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathological observations were conducted during 28days of dosing periods. Results: 1. No HYTE treatment-related mortalities and clinical signs were detected in all dosing levels tested in male and female rats during the whole experimental periods. 2. No HYTE treatment-related changes on body weight, gains and food consumption were detected in all dosing levels tested in male and female rats during the whole experimental periods except for 2000mg/kg-dosing female groups in which significantly increase of body weight, gains, food and water consumption were detected compared to that of vehicle control in some points. 3. No HYTE treatment-related changes on ophthalmologic examination were detected in all dosing levels tested in male and female rats. 4. No HYTE treatment-related changes on urinalysis were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing female groups in which, significantly increase of urine volume and related decrease on the urine specific gravity were detected as secondary effects of increase on the water consumptions not HYTE treatment-related toxicological signs. 5. No HYTE treatment-related changes on hematology were detected in all dosing levels tested in male and female rats except for increases in the total WBC count and lymphocytes of 2000mg/kg-dosing male and female groups with decrease of large unstained cells as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. 6. No HYTE treatment-related changes on serum biochemistry were detected in all dosing levels tested in male and female rats. 7. No HYTE treatment-related changes on gross findings, organ weight and histopathology were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing male and female groups in which, spleen and thymus organ weights, hypertrophy at gross observation and hyperpalsia of lymphoid cells and follicles at histopathological observation in spleen and thymus were detected as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. Conclusions : Based on these results, the NOAEL and MTD of HYTE in SD rats were considered as over 2000mg/kg, respectively at 28days repeat oral dose toxicity test because most of these findings were considered as results of pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs or secondary effects.

• 한국가스학회지
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• 제19권3호
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• pp.1-8
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• 2015

본 연구는 신발, 타이어, 접착제 제조에 많이 사용되는 클로로프렌(chloroprene)에 대해 취급근로자의 건강장해 예방을 위해 유해성을 조사하고, 취급사업장에 대해 작업환경을 측정 노출농도 및 용량반응을 통해 위험성을 평가하였다. 클로로프렌은 국제암연구소(IARC)로부터 발암추정물질(2B), 표적장기 전신독성 및 생식독성물질로 국내 취급 사업장은 27개소, 연간 약 1,300톤이 사용되었으며, 노출 위험성은 노출환경에 따라 Monte-carlo simulation을 이용하여 산출하였다. 그 결과 국소배기장치가 없으며 1일 4시간 초과 작업시 발암을 일으킬 수 있는 위험성의 평균값은 26,404로, 국소배기장치가 있으며 15분 미만의 단시간 작업 경우 2,199에 비교해 매우 높은 위험성을 보였다. 그리고 표적장기 전신독성의 경우도 169.06으로 단시간 작업 경우 4.10에 비교해 표적장기 전신독성 발생 위험이 높은 것으로 평가되어 물질의 노출시간 및 환기방식에 깊은 상관관계가 있는 것으로 나타났다. 따라서 클로로프렌 노출에 의한 근로자의 건강장해 예방하기 위해 국소배기장치의 가동과 방독마스크의 착용 등 노출저감을 위한 작업환경 관리의 필요성이 있었다. 특히 클로로프렌은 발암성, 생식독성 물질로 미국 산업안전보건청(OSHA)에서는 TWA를 5 ppm($18mg/m^3$) 이하로 관리하고 있으며, 본 유해성조사 결과에서도 현행 노출기준 10 ppm이하에서 표적장기독성, 생식기 장해 등 생체에 미치는 영향이 있는 것으로 나타나 있어, 위험성이 강하게 예측되므로 현재 사용하고 있는 우리나라 작업환경 노출기준(TWA 10 ppm)도 5 ppm 수준으로 강화하여 근로자 건강장해 예방에 기여할 필요성이 있는 것으로 판단되었다.

• Toxicological Research
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• 제27권2호
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• pp.61-70
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• 2011

Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague-Dawley rats.