Study of No Observed Adverse Effect Level of Nickel and Its Preliminary Evaluation Biocompatibility / 中国医疗器械杂志

The purpose of this study was to investigate the NOAEL of the nickel ion and provide with basic data for the biological evaluation of those medical devices containing nickel. Five groups SD rats were repeatedly exposed during 14 d respectively to nickel at first stage doses of 4.9, 3.7, 2.5 mg/(kg.d), and the second stage doses of 1.2, 0.25 mg/(kg.d) by the intravenous route. The results showed that the NOAEL of nickel ion is 0.25 mg/(kg.d) for SD rats, and the result was verified by subchronic systemic toxicity test of nickel alloy. The threshold of toxicological concern (TTC) of nickel is 150 μg/d (based on application of 100-fold uncertainty factor and a body weight of 60 kg)deduced by these data.

Edulcorantes no nutritivos: consumo de los niños y adolescentes, y alimentos que los aportan / Non-nutritive sweeteners: children and adolescent consumption and food sources

La disponibilidad de alimentos y bebidas con edulcorantes no nutritivos (ENN) aumentó en años recientes. Objetivos: Estimar el consumo de ENN en niños y adolescentes de la Ciudad de Buenos Aires, la prevalencia de ingesta superior a la admisible y los principales alimentos y bebidas aportadores. Material y Métodos: Estudio descriptivo de información recolectada en la Primera Encuesta Alimentaria y Nutricional de la ciudad de Buenos Aires realizada en 2011 que incluyó 2664 niños y adolescentes de 2 a 18 años. El consumo se evaluó mediante recordatorio de 24 horas. El contenido de ENN en alimentos y bebidas se obtuvo del rotulado nutricional. Se calculó la ingesta total de cada ENN y la adecuación a la ingesta diaria admisible (IDA) establecida por FAO/OMS. Resultados: El 44% de los preescolares, 53% de escolares y 51% de los adolescentes consumieron alimentos con ENN. Ningún niño presentó un consumo superior a la IDA de aspartamo, acesulfame-K y sucralosa. El 0,3% de los preescolares superó la IDA de sacarina, el 1% de preescolares, 0,9% de escolares y el 0,1% de los adolescentes superaron la IDA de ciclamato, debido al consumo de jugos concentrados para diluir. Las bebidas aportaron el 67% del ciclamato, el 91% del acesulfame-K y el 96% del aspartamo. Los edulcorantes de mesa aportaron el 30% del ciclamato y el 32% de la sacarina. Conclusión: El consumo de alimentos con ENN es usual en la población infanto juvenil, principalmente a partir de bebidas. Menos del 1% de los niños supera la IDA de ciclamato y sacarina.

The availability of food and beverages with non-nutritive sweeteners (NNSs) has increased in recent years. Objectives: To estimate NNSs consumption among children and adolescents in the Autonomous City of Buenos Aires, the prevalence of a daily intake higher than acceptable, and the main food and beverages contributing to it. Material and methods: Descriptive study about the information collected in the First Food and Nutritional/Nutrition Survey of Buenos Aires City, which was conducted in 2011 and included 2664 children and adolescents aged 2-18 years. Consumption was assessed by means of a 24-hour recall. NNSs content in food and beverages was obtained from nutrition facts labels. The total dietary intake for each NNSs and the adequacy to the acceptable daily intake (ADI) established by the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO). Results: Forty four percent of preschoolers, 53% of school children, and 51% of adolescents have had food with NNSs. No child was exposed to a consumption of aspartame, acesulfameK, and sucralose higher than the ADI. Saccharin consumption was higher than the ADI in 0.3% of preschoolers while cyclamate consumption was higher than the ADI in 0.9% of school children and 0.1% of adolescents, due to the consumption of concentrated juice, to be diluted with water. Beverages provided 67% of cyclamate, 91% of acesulfameK, and 96% of aspartame. Table-top sweeteners provided 30% of cyclamate and 32% of saccharin. Conclusion: Consumption of food and beverages with NNSs is usual among children and adolescents, mainly from beverages. Less than 1% of children are exposed to a consumption of cyclamate and saccharin higher than the ADI.

Subchronic Oral Toxicity Evaluation of Lanthanum: A 90-day, Repeated Dose Study in Rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level (NOAEL), which is a critical factor in the establishment of an acceptable dietary intake (ADI).</p><p><b>METHODS</b>In accordance with the Organization for Economic Co-operation and Development (OECD) testing guidelines, lanthanum nitrate was administered once daily by gavage to Sprague-Dawley (SD) rats at dose levels of 0, 1.5, 6.0, 24.0, and 144.0 mg/kg body weight (BW) per day for 90 days, followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups. Outcome parameters were mortality, clinical symptoms, body and organ weights, serum chemistry, and food consumption, as well as ophthalmic, urinary, hematologic, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.</p><p><b>RESULTS</b>Significant decreases were found in the 144.0 mg/kg BW group in the growth index, including body weight, organ weights, and food consumption. This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day. Importantly, the 95% lower confidence value of the benchmark dose (BMDL) was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.</p><p><b>CONCLUSION</b>The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements (REEs).</p>

The Big Vitamin D Mistake / 예방의학회지

Since 2006, type 1 diabetes in Finland has plateaued and then decreased after the authorities' decision to fortify dietary milk products with cholecalciferol. The role of vitamin D in innate and adaptive immunity is critical. A statistical error in the estimation of the recommended dietary allowance (RDA) for vitamin D was recently discovered; in a correct analysis of the data used by the Institute of Medicine, it was found that 8895 IU/d was needed for 97.5% of individuals to achieve values ≥50 nmol/L. Another study confirmed that 6201 IU/d was needed to achieve 75 nmol/L and 9122 IU/d was needed to reach 100 nmol/L. The largest meta-analysis ever conducted of studies published between 1966 and 2013 showed that 25-hydroxyvitamin D levels 1 year of age, and around 8000 IU for young adults and thereafter. Actions are urgently needed to protect the global population from vitamin D deficiency.

Preclinical safety assessment of Angelica acutiloba using a 13-week repeated dose oral toxicity study in rats / 한국실험동물학회지

Angelica acutiloba (AA), a Japanese species of Danggui, has been used worldwide as a traditional herbal medicine with several bioactivities including anti-diabetic, anti-allergic, anti-inflammatory, anti-tumor, and anti-obesity. However, there is lack of toxicological data available to evaluate potential long-term toxicity and the no-observed-adverse-effect level (NOAEL) of AA extract in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In the 14-day repeat-dose toxicity study, no adverse effects on mortality, body weight change, clinical signs, and organ weights was found following repeat oral administration to rats for 14 days (125, 250, 500, 1000, and 2000 mg/kg body weight), leading that 2000 mg/kg is the highest recommended dose of AA extract for the 13-week repeat-dose oral toxicity study. In the 13-week repeat-dose oral toxicity study, the AA extract was orally administered to groups of rats for 13 weeks (125, 250, 500, 1000, and 2000 mg/kg body weight) to compare between control and AA extract groups. The administration of AA extract did not produce mortality or remarkable clinical signs during this 13-week study. And, the data revealed that there were no significant differences in food/water consumption, body weight, hematological parameters, clinical chemistry parameters, gross macroscopic findings, organ weight and histopathology in comparison to the control group. On the basis of these results, the subchronic NOAEL of the AA extract was more than 2000 mg/kg/day when tested in rats. And, the AA extract is considered safe to use orally as a traditional herbal medicine.

Acute and 13-week subchronic toxicological evaluations of turanose in mice

BACKGROUND/OBJECTIVES: Turanose, α-D-glucosyl-(1→3)-α-D-fructose, is a sucrose isomer which naturally exists in honey. To evaluate toxicity of turanose, acute and subchronic oral toxicity studies were conducted with ICR mice. MATERIALS AND METHODS: For the acute oral toxicity study, turanose was administered as a single oral dose [10 g/kg body weight (b.w.)]. In the subchronic toxicity study, ICR mice were administered 0, 1.75, 3.5, and 7 g/kg b.w. doses of turanose daily for 13 weeks. RESULTS: No signs of acute toxicity, including abnormal behavior, adverse effect, or mortality, were observed over the 14-day study period. In addition, no changes in body weight or food consumption were observed and the median lethal dose (LD₅₀) for oral intake of turanose was determined to be greater than 10 g/kg b.w. General clinical behavior, changes in body weight and food consumption, absolute and relative organ weights, and mortality were not affected in any of the treatment group for 13 weeks. These doses also did not affect the macroscopic pathology, histology, hematology, and blood biochemical analysis of the mice examined. CONCLUSION: No toxicity was observed in the acute and 13-week subchronic oral toxicology studies that were conducted with ICR mice. Furthermore, the no-observed-adverse-effect level is greater than 7 g/kg/day for both male and female ICR mice.

La subjetividad del fenómeno "Efectos adversos" alrededor de los cuidados de enfermería / Subjectivity of the "Adverse efects" Phenomenon aroud nursing care

Las posturas que identifican las causas de un efecto adverso (EA) han sido vistas únicamente desde una perspectiva cuantitativa, con fines de determinar la incidencia, evitabilidad y factores de riesgo, lo que resulta complicado por la subjetividad del fenómeno.

Risk assessment of di(2-ethylhexyl) phthalate in the workplace

OBJECTIVES: A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. METHODS: Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor (“Survey on the work environment”) and by the Ministry of Environment (“Survey on the circulation amount of chemicals”). Risk was determined according to exposure in workplaces and chemical hazard. RESULTS: In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be 0.990 mg/m³, as compared to the threshold exposure level of 5 mg/m³. The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. CONCLUSIONS: DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the occupational exposure limit. Therefore, we suggest management of working environments, with exposure levels below 5 mg/m³ and all workers utilizing local exhaust ventilation and respiratory protection when handling DEHP.

Comparative Study of First-in-Human Dose Estimation Approaches using Pharmacometrics

OBJECTIVE: First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches. METHODS: First-in-human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches. RESULTS: Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability. CONCLUSION: This study introduced and compared all methods for first-in-human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats / 한국실험동물학회지

The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.

The Efficacy and Safety of Non-Nutritive Sweeteners / 임상당뇨병

High intake of added sugars increases the risk for obesity, type 2 diabetes, and cardiovascular disease. Non-nutritive sweeteners (NNS) are widely used in many beverages and food products to reduce calories and sugar content. NNS have higher intensity of sweetness per gram than caloric sweeteners such as sucrose, corn syrup, and fruit juice concentrates. NNS approved for use have been tested and determined to be safe at levels that are within acceptable daily intake by the Joint Food Agriculture Organization/World Health Organization Expert Committee on Food Additives. The eight items of sweeteners are regulated as food additives in Korea. Dietary intake of the sweeteners was suggested as safety level by the ministry of Food and Drug Safety in 2012. If substituted for caloric sweeteners without intake of additional calories from other food sources, NNS may help consumers limit carbohydrate and energy intake as a strategy to manage blood glucose and weight. Dietitians can provide guidance on the use of NNS that give the desired results in food preparation and use at the table.

Hepatotoxicity and nephrotoxicity of gallotannin-enriched extract isolated from Galla Rhois in ICR mice / 한국실험동물학회지

To evaluate the hepatotoxicity and nephrotoxicity of Galla Rhois (GR) toward the liver and kidney of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed after oral administration of 250, 500 and 1,000 mg/kg body weight/day of gallotannin-enriched extract of GR (GEGR) for 14 days. GEGR contained 68.7+/-2.5% of gallotannin, 25.3+/-0.9% of gallic acid and 4.4+/-0.1% of methyl gallate. Also, the level of malondialdehyde (MDA), a marker of lipid peroxidation, was decreased with 19% in the serum of high dose GEGR (HGEGR)-treated mice. The body and organ weight, clinical phenotypes, urine parameters and mice mortality did not differ among GEGR-treated groups and the vehicle-treated group. Furthermore, no significant increase was observed in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the GEGR-treated group relative to the vehicle-treated group. Moreover, the specific pathological features induced by most toxic compounds such as CCl4 were not observed upon liver and kidney histological analysis. Overall, the results of the present study suggest that GEGR does not induce any specific toxicity in liver and kidney organs of ICR at doses of 1,000 mg/kg body weight/day, indicating that this is no observed adverse effect level (NOAEL).

Risk assessment for clinical external application of calomel / 中国中药杂志

Calomel is a common traditional Chinese medicine (TCM) containing mercury in clinical external application. Although the toxicity of calomel has attracted concern, there is no unified standard yet in clinical external application. Risk assessment is used for evaluating the potential health effects of hazardous substances. The purpose of this article was to evaluate the health risk of calomel in clinical external application on the basis of toxicity data, to ensure safe and rational application of TCM containing calomel. The toxicity data of transdermal administration of calomel or mercurous chloride were collected by searching the literature. The daily maximum exposure dosage of calomel in clinical external application was estimated by following the four procedures of risk assessment, and Margin of Safety (MOS) as an evaluation indicator was then calculated to evaluate the safety of calomel on clinical application. It has been reported that the adult in single transdermal administration of calomel at 1. 5 g was lethal. Based on the LOAEL of calomel for long-term transdermal exposure (1 month) in rats was 0.096 g · kg(-1) · d(-1), the NOAEL of calomel for patients (about 60 kg) by external application within 2 weeks was estimated to be 1.46 mg · kg(-1) · d(-1). When MOS value equals to 1, the daily maximum exposure of calomel in clinical external application within 2 weeks was calculated to be 1.1 g. The results suggest that daily single dose of calomel in clinical external application should be lower than 1.5 g for adults, and more attention should be paid to changes in hepatic and renal function of patients when repeated dose more than 1.1 g within 2 weeks. The approach of risk assessment could be helpful in rational application of TCM containing mercury.

Efficacy of Zinc Supplementation as an Adjunct to Anti Tubercular Drug Therapy.

Zinc being a stronger electron acceptor than iron might replace iron from the critical thiol groups. So, Zinc supplementation in Tubercular Subjects might help the decompartmentalised state of iron in the body to revert back to normal compartmentalized state of iron. Again, Zinc inhibits the formation of superoxide radicals. Thus, Zinc supplementation might decrease the excess superoxide with simultaneous decrease in the formation of soluble oxygen made by dismutation reaction by the iron cofactored superoxide dismutase secreted extracellularly by the pathogenic M. tuberculosis. The study shows early and effective recovery with Zinc supplementation (50mgm. of elemental zinc orally / day for one month) along with anti - Tubercular drug therapy. This gets support by the significant changes in the serum level of three enzymes – Glutamine Synthetase, Superoxide Dismutase and Cholienesterase. Again, the dose of zinc supplementation instituted with a great benefit and without any toxic symptoms and signs, is below the Lowest Observed Adverse Effect Level (LOAEL) based on the superoxide dismutase activity in erythrocytes with zinc intake.

13-week subchronic toxicity study of a novel ginsenoside composition from ginseng leaves in rats / 한국실험동물학회지

UG0712 is a new ginsenoside extract processed from ginseng leaves. A subchronic toxicity study of UG0712 was conducted in male and female SD rats. Rats were treated with UG0712 at doses of 100, 400 and 1,600 mg/kg/day for 13 weeks, and observed followed by 4-week recovery period at a highest dose. No-treatment-related effects were observed regarding the mortality, ophthalmic examination, urinalysis and histopathology. Although the changes in clinical sign, body weight, organ weight, hematology, and serum biochemistry were observed, they were temporal and pharmacological effects. Based on the present experiment conditions, the no observed adverse effect level was considered to be more than 1,600 mg/kg/day in both sexes of rats.

Effect of repeated Paecilomyces japonica treatment on rats / 대한수의학회지

Cordyceps is a fungus used as a traditional medicine in China, Japan, and Korea. Paecilomyces (P.) japonica is a new cordyceps that was recently cultivated on silkworm pupae in Korea. The present study evaluated the toxicological effects of P. japonica in rats. Forty rats were treated with oral doses of P. japonica (0, 20, 100, or 500 mg/kg/day) for 4 weeks. Twenty additional rats were treated with 0 or 500 mg/kg/day of P. japonica for 4 weeks and then maintained for 2 weeks without treatment. Clinical signs, body weight, food and water consumption, and organ weight as well as hematology, serum biochemistry, and histopathology data were examined. Body weight gain of the group treated with 500 mg/kg/day was significantly reduced. Microscopically, karyomegaly, single cell necrosis, and mitosis were observed in the renal tubular epithelium of all treated groups. In conclusion, P. japonica caused a reduction of body weight and renal injury in rats. The no observed adverse effect level (NOAEL) of P. japonica was less than 20 mg/kg/day.

Toxicity of fermented soybean product (cheonggukjang) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on liver and kidney of ICR mice / 한국실험동물학회지

To investigate the toxic effects of cheonggukjang (CKJ) manufactured using mixed cultures of Bacillus subtilis MC31 and Lactobacillus sakei 383 on the liver and kidney of ICR mice, an alteration on the related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed after oral administration at dosage of 25, 50 and 100 mg/kg body weight/day of CKJ for 14 days. Any significant toxicity was not observed on the body and organ weight, clinical phenotypes, urine parameters and mortality in the CKJ-treated group compared with the vehicle-treated group. Also, liver toxicity analysis revealed no significant increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) or lactate dehydrogenase (LDH) in response to CKJ. Additionally, the specific pathological features induced by most toxic compounds were not observed upon liver histological analysis. Furthermore, kidney toxicological analysis revealed that blood urea nitrogen (BUN) and the serum creatinine (Cr) levels and pathological features on histological sections did not differ significantly between the vehicle- and CKJ-treated groups. Overall, these results suggest that CKJ does not induce any specific toxicity in liver and kidney organs of ICR at dose of 100 mg/kg body weight/day as no observed adverse effect level (NOAEL).

Specific nephrotoxicity and cardiotoxicity of BT-CAL(R), Sigma Anti-bonding Molecule Calcium Carbonate, in mice / 한국실험동물학회지

According to a high anti-osteoporotic efficacy of Sigma Anti-bonding Molecule Calcium Carbonate (SAC), repeated-dose toxicities of SAC were investigated to assess its feasibility as drug or functional food ingredient. Male ICR mice were given drinking water containing 0.006, 0.02 or 0.06% SAC for 4 weeks. SAC feeding decreased the body weights and feed and water consumptions of mice in a dose-dependent manner, especially, leading to severe emaciation and 70% death in 3 weeks in the high-dose (0.06%) group. Not only kidney and heart weights, but also the levels of blood urea nitrogen, creatinine, aspartate transaminase, and creatine phospokinase significantly increased after SAC administration, indicative of nephrotoxicity and cardiotoxicity. Such renal and cardiac toxicities were also confirmed by microscopic findings, exhibiting renal crystals and cardiac fibrosis, which may be due to the insoluble crystal formation and calcium overload, respectively. In conclusion, it is suggested that no observed adverse effect level of SAC is lower than 0.006% in mice, and that a long-term intake may cause serious adverse effects on renal and cardiac functions.

4-Week repeated oral dose toxicity study of 1,4-dichlorobutane in rats / 한국실험동물학회지

The present study investigated the potential subacute toxicity of 1,4-dichlorobutane by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to male rats at dose levels of 0, 100, 300, and 1,000 mg/kg/day for 4 weeks. All rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weight, hematology, serum biochemistry, gross findings, and organ weight were examined. At 1,000 mg/kg/day, an increase in the clinical signs and weights of the liver and kidneys was observed in the male rats. Serum biochemical investigations revealed an increase in alanine aminotransferase, alkaline phosphatase, total cholesterol, total bilirubin, phospholipids, blood urea nitrogen, and gamma glutamyl transferase levels. There were no treatment-related adverse effects in the low and middle-dose groups. In the present experimental conditions, the target organs were determined to be liver and kidney. The no-observed-adverse-effect level was considered to be 300 mg/kg/day in rats.

Subacute Oral Toxicity Study of Korean Red Ginseng Extract in Sprague-Dawley Rats

Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energy-giving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day.