This study evaluated the safety of a water extract prepared from the roots of Asparagus officinalis L. (asparagus root extract, ARE) for its potential use as a food or functional material. Acute oral toxicity and a standard genotoxicity battery were conducted according to internationally accepted guidelines. In the acute oral toxicity study, female Sprague-Dawley rats received a single oral dose of ARE at 300 or 2,000 mg/kg body weight. No treatment-related mortality, clinical signs, suppression of body weight gain, or gross pathological findings were observed. In the bacterial reverse mutation assay, ARE did not induce any biologically relevant increase in revertant colonies in histidine-requiring Salmonella typhimurium tester strains (TA98, TA100, TA1535, and TA1537) or in Escherichia coli WP2uvrA, up to 5,000 μg/plate, with or without metabolic activation. In addition, ARE did not increase the number of structural or numerical chromosomal aberrations in Chinese hamster lung (CHL/IU) cells or the frequency of micronucleated polychromatic erythrocytes in male Institute of Cancer Research (ICR) mice, and no bone marrow toxicity was observed. These findings suggest that ARE showed low toxicity under the tested conditions and was not associated with acute oral toxicity or genotoxicity under the present experimental conditions.

This study evaluated the sub-chronic oral toxicity of freeze-dried deer velvet antler (DVA) extract in ICR mice over a 90-day period. The extract was administered orally to male and female mice at doses of 1,000, 2,000, and 5,000 mg/kg body weight daily; the control group (0 mg/kg body weight) received vehicle only. No clinical signs of toxicity or mortality were observed. Body weight gain, food consumption, and general behavior remained normal across all groups. Hematological analysis revealed no dose-dependent alterations in hemoglobin levels, platelet characteristics, or red or white blood cell counts. Males administered 2,000 mg/kg DVA exhibited a slight increase in reticulocyte count, whereas females exhibited reduced count at 5,000 mg/kg; however, neither finding was doseresponsive or toxicologically significant. Serum biochemistry including liver and kidney function markers (ALT, AST, -GT, BUN, and creatinine) remained within normal range, and no evidence of organ damage was observed. Notably, male mice exhibited a significant reduction in serum triglycerides compared with those in the control group, suggesting potential lipid-modulating effects of DVA; however, this finding requires further investigation. Based on these findings, the no-observed-adverse-effect level (NOAEL) of DVA extract was determined to be greater than 5,000 mg/kg/day in both sexes. These results support the safety profile of DVA extract at the tested doses, and its potential metabolic benefits.

인삼양영탕은 한국·중국·일본의 전통의약권에서 허약 개 선에 복용되는 14종 한약재로 구성된 의약품이다. 먼저 고 성능 액체 크로마토그래피(HPLC)를 적용하여 인삼양영탕 주요 물질을 규명하였다. 식품의약품안전처 단회투여독성 시험기준에 따라 Sprague-Dawley 랫드 암수 각 5마리에게 0, 1,000, 2,000, 5,000 mg/kg 용량으로 단회 경구 투여하 였다. 시험 결과 사망한 랫드는 없었으며 일반 증상 및 부 검소견에서도 어떠한 이상 반응도 관찰되지 않아, 랫드에 서 인삼양영탕 반수 치사량(LD50)은 5,000 mg/kg 이상으로 판단되었다. 문헌조사를 통해 조사된 인삼양영탕 일반독 성시험 5건(일본 2건, 중국 2건, 한국 1건)에 따르면 개략 치사량(ALD)은 160,000 mg/kg 초과, LD50는 10,000 mg/kg 초과, 최대내성용량(MTD)은 160,000 mg/kg 초과한다고 보 고하였다. 랫드 무독성량 5,000 mg/kg을 기준으로 인체 등 가 용량 변환하면 인삼양영탕 최대안전권장복용량(MRSD) 은 4.1 g 또는 4.8 g이며, 한의서 기준 인삼양영탕 성인 1 일 복용량 28.3 g을 랫드 독성시험 투여 용량으로 변환하 면 34,750 mg/kg 또는 29,100 mg/kg이다. 인삼양영탕 안전 성 평가를 위하여 동물과 인체 종간 등가 용량을 계산하 여 보니, 동물 독성시험 투여 용량과 실제 환자 복용 용 량 간에 유의미한 상관관계가 없음을 시사한다. 학계에서 는 전통적으로 확립된 한약처방 복용량에 대한 동물 독성 시험 평가시에 ICH 및 OECD 기준이외에 다각적인 투여 용량 검토가 필요하다고 사료된다.

The purpose of this study, when predicting acute oral toxicity using QSAR software, the reliability of the predicted values was studied according to a single functional group or multiple functional groups within a single chemical. Acute oral toxicity is predicted using EPA T.E.S.T S/W for chemicals registered in ChemIDplus. The effect of a combination of specific functional periods on the degree of consistency of predicted values was studied. When some specific functional groups (combinations) exist, it was confirmed that the experimental and predicted values were high and low. It was confirmed that the prediction accuracy was high when the Anion group and the Halogen group were together, and the perdiction accuracy was significantly low when the Nitrile group was present. As a result of accumulating such data and showing reliability in predicting acute oral toxicity with EPA T.E.S.T S/W for 10 SVHC substances without experimental values, the matching rate was derived from at least 0% to 73.33%. It was confirmed that there was some tendency of the QSAR prediction value according to the combination of specific complex functional groups. When 10 SVHC substances without experimental data were predicted to be toxic through T.E.S.T S/W by quantitatively databaseizing the above tendency, 0~73.33% of the results were derived as a result of showing the realiability of the program prediction

Traditional medicine and herbal remedies are gaining popularity worldwide, comprising a significant portion of healthcare research, advancements, and market demand. Growing scientific evidence supports their substantial efficacy as pharmaceutical ingredients and dietary supplements in preventive healthcare. When developing pharmaceuticals, it is crucial to ensure that ingredients are free from side effects and toxicity in order to prioritize safety. Geckos, known as shou gong, are a diverse group of lizards that are widely utilized for treating various diseases in Korean Medicine. This study was conducted to assess the potential acute toxicity of a water extract Gekko gecko by a single oral dose in Sprague-Dawley rats. Twenty rats of each sex were randomly assigned to four groups (5 rats each). Test articles were administrated once by oral gavage to rats at dose levels of 0, 500, 1,000, or 2,000 mg/kg body weight. Mortality, changes of body weight, and clinical signs of gross observation were monitored for 14 days after dosing. At the end of a 14-day observation period, all animals were sacrificed and complete macroscopic and hematological examinations were performed. There was no dead animal or test article-related effect on clinical signs, body weight, or gross finding. Other specific changes were not found between control and treated groups in hematology. Results showed no adverse effect at a dose of 500, 1,000, or 2,000 mg/kg in rats. The minimal lethal dose was considered to be over 2,000 mg/kg body weight in rats.

GN01 is a new antiviral medicine acting against Korean Sacbrood virus (KSBV) of honeybees. It contains 5 mg/mL of active ingredient, double stranded RNAs(dsRNA), that homologous to KSBV ribonucleic acid coding coat protein (VP1) of virus and inducing RNA interference (RNAi). RNA medicine is generally recognized as safe for rapid breakage by intrinsic ribonuclease and limited absorption from gastrointestinal tract. However, there were no data of repeat-dose toxicity in laboratory animals for dsRNA targeting SBV. This study was performed to investigate toxicity of GN01 in SD rats after weekly oral dosing for 28 days and to determine its no-observed-adverse-effect-level (NOAEL). Male and female SD rats were orally administered with GN01 at 0, 25, 50 and 100 mg/kg bw/day of dsRNA once per week for 28 days (total 5 administrations). The highest dose 100 mg/kg bw/day was determined based on the maximum volume injectable (20 mL/kg bw) via gavage. During treatment period, clinical signs, functional and sensory responses, body weights, food and water consumption, ophthalmological findings and urinalysis were investigated. After treatment period, hematological and clinical biochemistry tests and examination of necropsy findings, organ weights and histopathological lesions were performed. There were no significant differences between all test groups and vehicle control group in all measured parameters. Therefore, the NOAEL of GN01 was determined 100 mg/kg bw/day, the highest dose administered. In conclusion, repeated oral administration of GN01, a dsRNA medicinal product, is safe even at the maximum available dose in rats.

Velvet antler is widely used as a traditional medicine, and numerous studies have demonstrated its tremendous nutritional and medicinal values including immunity-enhancing effects. This study aimed to investigate different deer velvet extracts (Sample 1: raw extract, Sample 2: dried extract, and Sample 3: freeze-dried extract) for proximate composition, uronic acid, sulfated glycosaminoglycan, sialic acid, collagen levels, and chemical components using ultra-performance liquid chromatography-quadrupole-time-of-light mass spectrometry. In addition, we evaluated the cytotoxic effect of the deer velvet extracts on BV2 microglia, HT22 hippocampal cells, HaCaT keratinocytes, and RAW264.7 macrophages using the cell viability MTT assay. Furthermore, we evaluated acute toxicity of the deer velvet extracts at different doses (0, 500, 1000, and 2000 mg/kg) administered orally to both male and female ICR mice for 14 d (five mice per group). After treatment, we evaluated general toxicity, survival rate, body weight changes, mortality, clinical signs, and necropsy findings in the experimental mice based on OECD guidelines. The results suggested that in vitro treatment with the evaluated extracts had no cytotoxic effect in HaCaT keratinocytes cells, whereas Sample-2 had a cytotoxic effect at 500 and 1000 μg/mL on HT22 hippocampal cells and RAW264.7 macrophages. Sample 3 was also cytotoxic at concentrations of 500 and 1000 μg/mL to RAW264.7 and BV2 microglial cells. However, the mice treated in vivo with the velvet extracts at doses of 500–2000 mg/kg BW showed no clinical signs, mortality, or necropsy findings, indicating that the LD50 is higher than this dosage. These findings indicate that there were no toxicological abnormalities connected with the deer velvet extract treatment in mice. However, further human and animal studies are needed before sufficient safety information is available to justify its use in humans.

Collagen peptides have garnered significant attention as functional foods across multiple fields due to their capacity to regulate physiological and hormonal processes, offering numerous advantages. However, despite their broad range of applications, comprehensive research on the potential toxicity of these substances remains lacking. Therefore, this study sought to assess the acute oral toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in both rats and dogs. In the rat model, CPSS was orally administered at doses of 300 and 2,000 mg/kg to Sprague-Dawley rats. An escalating single-dose oral toxicity assessment at doses of 500, 1,000, and 2,000 mg/kg was carried out in beagle dogs with 3-day intervals between doses. Throughout the 14-day post-administration assessment period, clinical signs, mortality rates, changes in body weight, and necropsy observations were closely monitored. After oral administration, no signs of toxicity associated with CPSS were observed in either rats or dogs. Therefore, the oral LD50 (approximate lethal dose for 50% mortality) for CPSS in rats was determined to exceed 5,000 mg/kg, and the maximum tolerated dose for dogs was estimated to be above 2,000 mg/kg. Consequently, this study offers safety data on the use of CPSS in functional foods and medicinal applications.

This study examined the subacute oral toxicity of Dendropanax morbiferus H.Lév leaves hot-water extracts (DMWE) using male and female Spargue-Dawley rats. Rats were orally administered the DMWE at dose levels of 0, 250, 500, 1,000, and 2,000 mg/kg body weight (BW) for four weeks. For experimental period, clinical signs and the number of deaths were examined, and feed intake and BW of all experimental animals were measured once a week for four weeks. At the end of the experiment, blood samples were collected from all rats, and all animals were euthanized and autopsies were performed to collect major organs. No dead animals were found during the experimental period. In addition, no differences were found between control and DMWE-treated groups in feed intakes, BW changes, organ weights, clinical signs, hematological parameters, and serum biochemical parameters. The results of this study provided evidence that oral administration of DMWE at the dose of 2,000 mg/kg BW is safe in rats and may not exert severe toxic effects.

In this study, the acute toxicity of Dendropanax morbiferus H.Lév leaf hot-water extracts (DMWE) was examined in male and female ICR mice. Mice were orally administered the DMWE at dose levels of 0, 250, 500, 1,000 and 2,000 mg/kg body weight (BW) for single-dose toxicity test. There were no significant differences in change of BW between control and all DMWE treated-groups. In hematological and blood biochemical analysis, none of the parameters were affected by the DMWE. Similarly, there were no significant effects on markers for liver and kidney functions in all DMWE treated-groups. Since there were no adverse effects of the DMWE in single oral toxicity tests, even at the highest doses, it was concluded that the lethal dose 50 (LD50) of DMWE is estimated at > 2,000 mg/kg BW.

Iron deficiency is known to be a common nutritional disorder in many countries, especially among children, women of childbearing age and pregnant women. SUNACTIVE Fe-P80 is a new type of iron supplement that applies nanotechnlateology for the purpose of overcoming the disadvantages of food supplements. This study was conducted to investigate the potential adverse effects of a 28-day repeated oral dose of SUNACTIVE Fe-P80 in rats. SUNACTIVE Fe-P80 was administered once daily by gavage to Sprague-Dawley rats for 28 days at doses of 0, 500, 1,000, and 2,000 mg/kg/day. Additional recovery groups from the control and highdose groups were observed for a 14-day recovery period. At the scheduled termination, the animals were sacrificed, their organs weighed, and blood samples collected. There were no treatment-related effects in the context of clinical signs, body weight, food intake, ophthalmoscopy, urinalysis, necropsy findings, organ weights, and hematologic, serum biochemical and histopathological parameters at any dose tested. Under the present experimental conditions, the no-observed-adverse-effect level of SUNACTIVE Fe-P80 was ≥ 2,000 mg/kg/day in both the sexes, and no target organs were identified. Thus, the results suggest that SUNACTIVE Fe-P80 is relatively safe, as no treatment-related adverse effects were observed following a 28-day repeated oral dose experiment.

Artemisia annua (AA) is a well-known as a source of antimalarial drug (artemisinin), which also has been traditionally used as an antipyretic and hemostatic agent in Korea and China. In preclinical effective study, a water extract of Artemisia annua (WEAA) ameliorated weight gain and hepatic lipid accumulation in high-fat diet-fed mice. The plasma levels of triglyceride, AST, and ALT were reduced in the WEAA-treated group. Based on these results, the safety of WEAA as a functional ingredient for liver health was evaluated in this repeated dose oral toxicity study before the clinical trial. Sprague- Dawley (SD) rats were treated by gavage with 20 times (1,000 mg/kg) more than the effective dose for 13 weeks. All rats had survived at the end of the study, and there were no changes indicating obviously abnormal clinical sign and behavior. The treatment of WEAA were also observed no obvious toxicities in the body weights, urine, hematological, serum biochemical, ophthalmic and histopathological examinations. Based on the results of this study, the NOAEL (no-observed-adverse-effect level) of WEAA in SD rats was estimated to be 1,000 mg/kg. In conclusion, WEAA could be used as a safe functional ingredient for the improvement of liver health in individuals with hepatic diseases including nonalcoholic steatohepatitis.

This study was carried out to investigate the acute oral toxicity of Chamaecyparis obtusa (C. obtusa) essential oil (CBE) in New Zealand white male and female rabbits. Acute oral treatment with the CBE did not reveal any sign of toxicity or mortality in treated rabbits. The body weight of the rabbits was not affected after a single oral administration of the CBE during the 14-day observation period. In both the hematological and blood biochemical analysis, all parameters of the treated group with 2,000 mg/kg body weight of the CBE were not significantly different than those of the control group. Therefore, the lethal dose 50 of the CBE was estimated to be greater than 2,000 mg/kg body weight in rabbits, which indicated that the CBE is non-toxic. In conclusion, this study suggests that oral administration of the CBE is safe on rabbits.

The present study was carried out to investigate the acute oral toxicity of Chamaecyparis obtusa (C. obtusa) essential oil in ICR male and female mice. Acute oral treatment with C. obtusa essential oil did not reveal any sign of toxicity or mortality in treated mice. Mouse body weights were not affected after single oral administration of C. obtusa essential oil during the 14-day observation period. In the hematological and blood biochemical analysis, all parameters of the treated group with 2,000 mg/kg body weight of the essential oil were not significantly different those of the control group. Therefore, the lethal dose 50 of the essential oil was estimated to be greater than 2,000 mg/ kg body weight in mice, which indicated that the essential oil is non-toxic. In conclusion, this study suggests that C. obtusa essential oil orally safe ICR mice.

The aim of the study was carried out to investigate a single oral toxicity of a 50% ethanol extract derived from fruiting body of Poria cocus (PCE) using male and female SD rats. Groups consisted of five male and female rats were treated with a single dose of the test substance intragastrically at 0, 5, 50, 300 and 2,000 mg/kg, respectively. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. As the results, we could not find any mortality. Compared with the control group, significant weight change was not observed in the experimental group. Also there was no difference in water and food consumption or gross pathological findings at terminal sacrifice among the groups of rat treated with different doses of the test substance. The results suggested that the approximate lethal dose of ACM in both female and male rats were considered as over 5000 mg/kg.

본 연구는 Spragye-Dawely 계통의 암컷 랫드에서 종합 비타민의 반복경구투여 독성평가와 대식세포 Raw 264.7 세포의 NO 및 TNF-α assay를 통한 면역 활성을 평가하기 위해서 실시하였다. 종합비타민을 대식세포의 활성능을 측정하기 위해 Raw 264.7 세포에서 NO와 TNF-α의 생성을 측정하였다. 종합비타민을 대식세포에 24시간 처리한 결과 대조군과 비교 시 NO와 TNF-α가 유의적으로 상승하였다. 이 결과 종합비타민이 대식세포인 Raw 264.7 세포를 활성화시키는 것으로 사료된다. 또한 랫드에서 종합비타민의 독성평가를 위하여 랫드에 종합비타민을 0.24 g/ kg, 1 g/kg 그리고 2 g/kg을 4주 동안 경구투여를 하였다. 종합비타민의 안전성을 확인하기 위해 다음과 같은 관찰 및 검사를 하였다. 검사항목으로는 체중과 사료 섭취량, 임상증상, 혈청생화학적 검사를 관찰한 결과 대조군과 투여군을 비교 시 유의적인 변화가 나타나지 않았다. 따라서 종합비타민은 생리대사에 무해하며 면역증강의 효과를 나타내는 것으로 사료된다.

This study was designed to evaluate to acute oral toxicity and skin irritation of Chrysanthemum dye in Sprague-Dawley (SD) rats. SD rats were orally treated with Chrysanthemum dye at a dose of 0, 1 and 2 ml/kg body weight. After oral administration, the rats were observed for 14days. In primary skin irritation test, SD rats were dermally treated with Chrysanthemum dye and observed for 3 days. To ensure the safety of Chrysanthemum dye such as the following were observed and tested. We examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the histopathological test, the mortality and skin irritation. As a result, no significant differences were found in body weight, feed intake and histopathological test between control and Chrysanthemum dye treated group. In the result of skin irritation test, Chrysanthemum dye did not induce erythema and edema after topical application. Primary irritation index was “0” in the test. Therefore, it is suggested that Chrysanthemum dye has no effect on acute toxicity and side effect in SD rats and is non-irritant material based on the score “0” of primary irritation index.

This study was designed to evaluate a repeated oral dose toxicity and immunomodulating activity of Pulsatilla koreana and Artemisiae annuae in Sprague-Dawley rats. The female rats were treated with Pulsatilla koreana and Artemisiae annuae of control group, low group (0.5 ml/kg), medium group (1 ml/kg), high group (2 ml/ kg) for distilled water, intragastrically for 4 weeks, respectively. To ensure the safety of Pulsatilla koreana and Artemisiae annuae such as the following were observed and tested. We examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. Hematological results were the increase of neutrophils, lymphocytes and monocytes in the high dose group of Pulsatilla koreana. The increase immune cells in the high dose group of Pulsatilla koreana might immunomodulating activity. No significant differences in body weight, feed intake, serum biochemical analysis and histopathological between control and fed group were found. In conclusion, Pulsatilla koreana and Artemisiae annuae is physiologically safe and improve immunomodulating activity.

This study was carried out to investigate the toxicity of food Red No.2 in the Sprague-Dawley (SD) female rat for 4 weeks. SD rats were orally administered for 28 days, with dosage of 500, 1,000, 2,000 mg/kg/day. Animals treated with food Red No.2 did not cause any death and show any clinical signs. They did not show any significant changes of body weight, feed uptake and water consumption. There were not significantly different from the control group in urinalysis, hematological, serum biochemical value and histopathological examination. In conclusion, 4 weeks of the repetitive oral medication of food Red No.2 has resulted no alteration of toxicity according to the test materials in the group of female rats with injection of 2,000 mg/kg. Therefore, food Red No.2 was not indicated to have any toxic effect in the SD rats, when it was orally administered below the dosage 2,000 mg/kg/day for 4 weeks.