• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.325-331
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• 2009

The object of this study was to evaluate the single oral dose toxicity of Low Molecular Weight Fucoidan (LMF) in male and female rats. LMF was administered to female and male SD rats as an oral dose of 2,000, 1,000 and 500 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation organ weight and histopathology of 14 principle organs were examined upon necropsy. As the results, no LMF treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2,000 mg/kg in both female and male rats except for some sporadic findings not LMF treatment related toxicological signs. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of LMF after single oral treatment in female and male rats were considered over 2,000 mg/kg - the limited dosages recommended by KFDA Guidelines [2005-60, 2005], respectively.

• Toxicological Research
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• v.27 no.4
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• pp.217-224
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• 2011

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

• The Korean Journal of Physiology
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• v.7 no.2
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• pp.67-70
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• 1973

This experiment was carried out to investigate the influence of adrenergic receptor blockade. on digitalis intoxication. The effects of adrenergic alpha and beta receptor blockade on the lethal dose of digitonin were evaluated. $LD_{50}$ and dose mortality curve of digitonin in mice pretreated with dibenzylin or propranolol hydrochloride (Inderal) were obtained. All drugs were injected subcutaneously. Digitonin toxicity was significantly decreased in mice pretreated with beta·blockade compare with alpha-blockade and control groups.

• Toxicological Research
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• v.21 no.4
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• pp.361-365
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• 2005

This study was conducted to obtain the acute information of the oral dose toxicity of Polycan - originated from Aureobasidium pullulans SM-2001 (half of the dry material is -1,3/1,6-glucans), a UV induced mutant of A. pullulans, having various pharmacological effects, in male and female mice. In order to calculate $50\%$ lethal dose $(LD_{50})$, approximate LD and target organs, test article was administered twice by oral gavage to male and female ICR mice at total 1000, 500 and 250mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing. As the results, we could not find any mortalities, clinical signs, changes in the body weight and gross findings. The results obtained in this study suggest that the Polycan is non-toxic in mice and is therefore likely to be safe for clinical use. The L050 and approximate $(LD_{50})$ in mice after single oral dose of Polycan were considered over 1000 mg/kg, respectively.

• Natural Product Sciences
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• v.9 no.1
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• pp.22-27
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• 2003

This study was designed to investigate the effects of main constituents of Nigella sativa (NS) seed on the survival and CNS responses in experimental animals. The toxicological investigations were conducted for the determination of median lethal doses $(LD_{50})$ of NS seed constituents [i.e. aqueous extract (AE), fixed oil (FO), volatile oil (VO)] and main components of its VO [i.e. thymoquinone (TQ), ${\alpha}-pinene$ (AP) and p-cymene (PC)]. A part of this study includes evaluation NS constituents in the induction of minimal neurological deficit (MND) as a parameter for neurotoxicity using chimney test. In this study, the i.p. $LD_{50}$ values of AE, FO, VO, TQ (suspended In 0.5%CMC), TQ (dissolved in corn oil), AP and PC, were 3020, 3371, 1853, 616.6, 90.3, 1726 and 1523 mg/kg, respectively. All the NS constituents can be considered moderately toxic ($LD_{50}$ ranged from 616.6 to 3371 mg/kg), except the oily solution of TQ, which was very toxic ($LD_{50}$ was 90.3 mg/kg). It appeared that the toxicity of the whole VO is mainly due to its content of TQ and to some extent PC. All the NS constituents induced different degrees of MND at certain dose levels. The median neurotoxic (or sedating) doses $(TD_{50})$ of AE, FO, VO, TQ (suspended in CMC) and AP and PC, were 950, 1403, 306, 88.1, >173 and 368 mg/kg, respectively. TQ was the most potent component in inducing MND, whereas the FO and AE were the least. Neurotoxicity induced by the VO in the chimney test may refer basically to its contents of TQ and to some extent PC and AP.

• Korean Journal of Veterinary Service
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• v.15 no.1
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• pp.58-66
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• 1992

The insecticide p-nitropheny diethyl thiophospate is alse known by the symbol E.605 and a legion of trade names including “parathion”. The insecticide is widely used in agriculture, but it is highly toxic and now clear that parathion behaves like a cholinergic drug by inhibiting the enzyme cholinesterase. In order to know acute toxicity and the changes of glucose concentrations and activity according to time lapsed in female mice given orally single with the half dose to $LD_{50}$ of parathion, glucose contents and cholinesterase activities in serum as well as cholinesterase activities in whole brain and spinal cord were investigated, otherwise median lethal dose ($LD_{50}$) of parathion given orally against female mice was determined. The results obtained were summerized as follows ; 1. $LD_{50}$ value of parathion given orally to female mice was 7.1mg/kg(95% confidence limits, 3.8-13.1mg/kg) 2. The inhibition rate of cholinesterase activities in serum of parathion-administrated mice according to time lapsed were peakly decreased to 61% after 30 minutes in comparison to control group, but activities were completely recovered after 48 hours. 3. The inhibition rate of cholinesterase activities in whole brain of parathion-administrated mice according to time lapsed were peakly decreased to 49% after 2 hours in completely recovered after 24 hours. 4. The inhibition rate of cholinesterase activities in spinal cord of parathion-administrated mice according to time lapsed were peakly decreased to 57% after 2 hours in comparison to control group, but activities were completely recovered after 48 hours. 5. The changes of glucose contents in serum of parathion-administrated mice according to time lapsed and in directly after death due to parathion poisoning were no significantly difference.

• Korean Journal of Acupuncture
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• v.34 no.4
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• pp.241-250
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• 2017

Objectives : This study was performed to examine the toxicity of Aconitum ciliare Decaisne pharmacopuncture(ADP). Methods : The toxicity was evaluated for lethal dose for 50 percent kill(LD50), single dose and repeated dose for 4 weeks. Toxic symptoms, weight measurement, hematological test, blood biochemical test, visual examination and weight measurement of major organs and histopathological test were observed for 4 weeks. Dose of 300, 600, 1,200, 2,400, 3,600, 4,800, 6,000, 7,200 mg/kg in the LD50 experiment, 300, 600, 1,200 mg/kg/day in the single experiment, 150, 300, 600 mg/kg/day in 4 weeks experiments were injected into BALB/c mice. The ADP was injected into ST36 of the right leg. Normal saline solution of same volume was used for control group. In 24 hours after the last treatment, blood samples were taken after anesthesia by inhalation of ethyl ether. After that, the BALB/c mice were euthanized. Their heart, lungs, kidneys, liver and reproductive organs were removed and weighed. Histopathological evaluation was also performed. Results : ADP's LD50 was measured at 6,000 mg/kg. In both single and repeated dose toxicity test, no BALB/c mouse died during the experiments. ADP treatment for 4 weeks did not show any significant changes in toxic symptoms, weight measurement, hematological test, blood biochemical test, visual examination and weight measurement of major organs and histopathological test. Conclusions : As a result, ADP's LD50 was 6,000 mg/kg and repeated dose at a concentration of 600 mg/kg or less is considered to be not harmful for clinical treatment.

• The Journal of Korean Medicine
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• v.35 no.1
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• pp.114-123
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• 2014

Objectives: Evidence-based medicine(EBM) advocates the use of up-to-date "best" scientific evidence from health care research as the basis for making medical decisions. EBM also has been applied to traditional Korean medicine(TKM), especially in the field of safety. Recently, the standard prescription for TKM by Korea Institute of Oriental Medicine was published based on toxic index from various toxicity tests. However, there are some limitations when the results from the study based on EBM are applied in clinics. To overcome these imitations, the term "evidence-based practical medicine" was developed and defined as clinically applicable results from the study based on EBM. And safety classification for TKM was suggested as an example of evidence-based practical medicine. Methods: For safety classification for TKM, the data for $LD_{50}$(50% lethal dose), which was transformed to theoretical $LD_1$(1% lethal dose), was analyzed as one of tools for EMB study and divided by maximum dose used in clinics. Results and Conclusions: As a result, human equivalent dose(HED)-based MOS(margin of safety) for korean traditional medicine was calculated and used for safety classification with 5 categories. These categories would be helpful for oriental medicine clinicians to decide the increase and decrease of dosage according to various factors such as patient's sensitivity, potential toxicity of herbal medicines, clinician's experience for better cure. Thus, this safety classification provides some evidences enough that evidence-based practical medicine should be not the same with EBM and defined differently from EBM.

• Journal of Oral Medicine and Pain
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• v.44 no.1
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• pp.11-15
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• 2019

Purpose: The aim of this study was to compare the potency-stabilizing effects of two different diluents of botulinum toxin A (10% dextrose solution and 0.9% saline). Methods: A mouse lethality bioassay was undertaken. Ninety mice were divided into experimental and control groups which received varying dosages in subgroups of 10. The experimental group was injected with botulinum toxin A diluted with 10% dextrose solution and the control group was injected with botulinum toxin A diluted with 0.9% saline. A 72 hours after intraperitoneal injection, the number of dead mice was counted to confirm median lethal dose ($LD_{50}$) of each group. Results: The value of $LD_{50}$ in the experimental group was approximately 0.131 mL (1.31 U) and the value of $LD_{50}$ in the control group was approximately 0.107 mL (1.07 U). The potency preservation rate of the experimental group was estimated to be 93.5% and that of the control group was estimated to be 76.3%. Conclusions: Dilution with 10% dextrose solution displayed less potency loss than 0.9% saline.

• The Journal of Internal Korean Medicine
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• v.33 no.2
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• pp.145-159
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• 2012

Objectives : The object of this study was to obtain acute toxicity information (single oral dose toxicity) of Armeniacae Semen (AS), a medicinal herb used for treating constipation and various respiratory diseases, in rats. Methods : In order to observe the $LD_{50}$ (50% lethal dose), approximate lethal dosage (ALD) and target organs, AS aqueous extracts were orally administered once to female and male Sprague Dawley rats at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight). The mortality, changes in the body weight, clinical signs and gross observation were monitored for 14 days after single oral treatment of AS extracts, and the organ weights and histopathological findings of principle organs were observed after sacrifice. Results : After single oral treatment of AS 2,000 and 1,000 mg/kg, all (5/5; 100%) female and male rats died within 30 minutes after treatment, while no mortalities were observed in the female and male rats treated with 500 mg/kg of AS extract. Therefore, $LD_{50}$ in female and male rats was calculated as 741.95 mg/kg. Seizure, loss of locomotion, salivation, increases of respiration and heart-beat were observed after AS extract treatment, which were observed in all rats including the lowest dosage group, 500 mg/kg in the present study. In addition, lung congestion was visible in all mortal rats with AS 2,000 and 1,000 mg/kg, respectively. Conclusions : The results obtained in this study suggest that AS extract ranges in Class III, because the $LD_{50}$ and ALD in both female and male rats were calculated as 741.95 mg/kg and 500~1,000 mg/kg, respectively. However, AS extract should be carefully treated at clinical applications, because salivation, increase of respiration and heart-beat were also observed in the lowest dosage group, 500 mg/kg in the present study.