• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.5
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• pp.612-620
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• 2012

This study was performed to investigate the 4-week repeated-dose toxicity of $Lactobacillus$ $plantarum$ AF1 ($Lb.$ $plantarum$ AF1), a lactic acid bacteria isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four groups, with 10 animals in each group. The test article was administered once daily by gavage to rats at dosage levels of 0, 0.5, 1.0, and 2.0 g/kg/day for 4-weeks. There were no test articlerelated deaths or abnormal clinical signs in either gender of rat during the observation period. Furthermore, no differences were found between the control and treatment groups in terms of body weight changes, food intake, and water consumptions. Hematological parameters, serum biochemical analysis, and any other findings also showed no significant or dose-dependent alterations. There were no alterations in organ weights upon administration of $Lb.$ $plantarum$ AF1. These results suggest that there were no adverse effects of oral application of $Lb.$ $plantarum$ AF1 up to a dosage level of 2.0 g/kg in both male and female rats.

• Toxicological Research
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• v.22 no.1
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• pp.61-67
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• 2006

Changes in hematology and serum biochemistry after treatment of recombinant human erythropoietin (rHuEPO, HM10760) were screened in 4 male cynomolgus monkeys (Macaca fascicularis). Four monkeys, composed of a treatment group of HM10760 and a positive control group of $Aranesp^(R}$, were subcutaneously administered at same dose of $100{\mu}g/kg$. Both groups did not show any change in body weights and food consumption for 4 weeks compared with those of pretreatment. Both groups did not show any change in total leukocyte count (WBC) and platelet count, while both groups showed increased platelet distribution width (PDW) percentage in HM10760 group during a period from day 5 to day 59 and in $Aranesp^(R}$ group during a period from day 9 to day 26. Both groups showed increases in red blood cells (RBC), hemoglobin (HGB), and hematocrit (HCT) approximately 10 days after treatment compared with those of pretreatment (day 0). The increased levels of RBC, HGB, and HCT were much higher in HM10760 than in $Aranesp^(R}$ by the increases of $3.2%{\sim}12.5%$ for RBC, $3.8%{\sim}17.1%$ for HCT, and $1.85%{\sim}11%$ for HGB. Both groups showed increases in red cells distribution width (RDW) and reticulocyte (RET) compared with those of pretreatment, showing the highest peak from day 9. The increased level of RET lasted up to day 14 in $Aranesp^(R}$ group, while it lasted up to day 23 in HM10760 group. The increased level of RDW lasted up to day 59, it was much higher in HM10760 by the increase of $10.1%{\sim}17.6%$ than in $Aranesp^(R}$ group. In serum biochemistry, both groups showed a decrease in chloride level compared with those of pretreatment. These findings indicated that HM10760 increased RBC, HGB, HCT, RDW, and RET compared with those of pretreatment, and the increased levels were much higher in HM10760 than in $Aranesp^(R}$.

• Food Science and Preservation
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• v.20 no.3
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• pp.394-403
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• 2013

This study was performed to investigate the four-week repeated-dose toxicity of the crude antifungal compounds produced by Lactobacillus plantarum AF1 (Lb. plantarum AF1), a lactic acid bacterium isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four groups, with 10 animals in each group. The test article was administered once daily by gavage to rats at dosage levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. There were no test-article-related deaths or abnormal clinical signs in both the male and female rats during the observation period. Furthermore, no differences in the body weight changes, food intake and water consumption levels of the control and treatment groups were found. The hematological parameters, serum biochemical analysis results, histopathological examination results and all other findings also showed no significant or dose-dependent changes. There were also no changes in the organ weights upon the administration of the crude antifungal compounds produced by Lb. plantarum AF1. These results suggest that the oral administration of the crude antifungal compounds produced by Lb. plantarum AF1 had no adverse effects up to a dosage level of 2,000 mg/kg in both male and female rats.

• Korean Journal of Food Science and Technology
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• v.50 no.6
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• pp.629-635
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• 2018

In this study, the safety aspect of Maesil-cheongs with reduced amygdalin levels was investigated in terms of toxicokinetics and repeated oral toxicity. Plasma or UVC treatment was utilized to obtain Maesil-cheongs with reduced amygdalin levels. The toxicokinetic study demonstrated that the oral absorption of amygdalin decreased remarkably after a single-dose oral administration of both plasma- and UVC-treated Maesil-cheongs. The fourteen-day repeated oral toxicity study revealed that plasma- or UVC-treated Maesil-cheongs did not cause changes in body weight, food intake, water consumption, and absolute and relative organ weights. No significant effects on hematological and serum biochemical parameters were found. Histopathological examination showed no abnormality or toxicological change. These findings suggest that plasma- and UVC-treated Maesil-cheongs have no toxicity potential, and these processes will be useful to obtain products with safe, reduced amygdalin levels.

• Toxicological Research
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• v.35 no.3
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• pp.225-232
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• 2019

Thymus vulgaris L. is widely used as an ingredient in cooking and in herbal medicine. However, there is little information about its toxicity. The present study was performed to evaluate the acute and repeated 28-day oral dose toxicity of thyme essential oil in rats. For the acute toxicity test, two groups of three rats were used. The rats received a single dose of essential oil: 300 or 2,000 mg/kg of body weight (bw). The rats were observed individually during the first four hours, and then daily until day 14. For the toxicity test with repeated doses, four groups of 10 rats were used. Doses of 100, 250, and 500 mg/kg/day were tested for 28 days. At the end of the experiment, blood was collected and the animals were sacrificed. Histopathological examination showed that in the lungs of rats given the 2,000 mg/kg bw dose, polymorph nuclear infiltrates, hemosiderin macrophages, and interstitial space thickening were present. In the repeated dose study, all rats survived the 28-day treatment period and apparently showed no signs of toxicity. The hematological and biochemical parameters were not altered. The histopathological study of the organs showed severe changes in the lung, with the dose of 500 mg/kg/day; in the other organs, no alterations were observed or the changes were slight. The body weight was only altered in male rats given the 500 mg/kg dose. The relative weight of the organs did not show any significant changes. Our studies revealed that the essential oil of Thymus vulgaris has moderate oral toxicity according to the results of the acute test, whereas the results of the 28-day oral toxicity test suggest that the no-observed-adverse effect level (NOAEL) is greater than 250 mg/kg/day.

• Korean Journal of Medicinal Crop Science
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• v.23 no.3
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• pp.185-189
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• 2015

In this study, the clinical safety and toxicology of oral ingestion of supplement capsules containing ginseng radix was investigated in healthy young volunteers. This study was a pilot randomized, double blinded, placebo controlled trial. The healthy volunteers were divided into 6 groups of 20 each (10 males and 10 females). They took the ginseng powder for 35 days (3g/day) for safety evaluation. There were measured general healthy levels such as hematological, biochemical and electrocardiographic parameters. After the first week, besides Korean white ginseng the other treatments led to an significant increase of white blood cells. Korean red ginseng increased UREA (blood urea nitrogen) in healthy volunteers, but it didn't exceed the range of normal values, and in the subsequent process of treatment there is no effect of elevating UREA. After the three weeks, Korean white ginseng showed relatively low the content of blood glucose and low-density lipoprotein cholesterol. After the five weeks, compared with the other treatments, Korean red ginseng increased white blood cells, platelet distribution width and average volume of platelet. Korean white ginseng decreased low-density lipoprotein cholesterol. American ginseng decreased blood creatinine in healthy volunteers. In conclusion, through test the blood routine, urine routine, liver function, renal function, blood glucose, blood lipid and electrocardiogram, the healthy volunteers continuous taking ginseng for 35 days (3 g/day) is safe and reliable, and have no obvious adverse reactions and side effects.

• Journal of Dairy Science and Biotechnology
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• v.34 no.2
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• pp.99-116
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• 2016

We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.10
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• pp.1406-1413
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• 2016

This study was carried out to evaluate the toxicity of ethanolic extracts of Morus alba L. branch (ME). In the reverse mutation test, Salmonella Typhimurium TA98, TA100, TA1535, TA1357, and Escherichia coli WP2uvrA were used to estimate the mutagenic potential of ME. Sprague-Dawley rats were orally administered ME at levels of 1,250, 2,500, and 5,000 mg/kg for the single-dose toxicity test and 500, 1,000, and 2,000 mg/kg/d for the repeated-dose toxicity test for 28 consecutive days. As expected, reverse mutation was not detected at any concentration of ME, regardless of application of the metabolic activation system with or without S9 mix. In the single-dose toxicity test, ME caused neither significant visible signs of toxicity nor mortality in rats, and $LD_{50}$ was estimated to be over 5,000 mg/kg. In the repeated-dose toxicity test, ME administration at 500, 1,000, and 2,000 mg/kg for 28 days to male or female rats did not result in mortality. Similarly, no toxicologically significant treatment-related changes in body weight, food intake, or organ weights were noted. Several hematological and biochemical parameters in both genders showed significant differences, but these were within normal ranges. These results support the safe use of ME.