• Toxicological Research
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• v.12 no.2
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• pp.143-154
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• 1996

This paper reviews the toxicological role of median lethal dose ($LD_50$) based on animal and human data. Animal oral $LD_50$ values of eighty seven chemicals were collected and comparatively evaluated with human minimum toxic dose ($TD_50$). In general, animal $LD_50$ values were much higher than human $TD_50$. The ratios between $LD_50$ and TDlo were ranged from 0.01 and over 1000, suggesting safety factor of up to 1000 between humans and animals in the case of acute toxicity data. However, about 40% of chemicals investigated were within the ratio of 10. Although the cases (N=20) were small, $LD_50$ values of guinea pig were closer to human TDlo than those of other animal species. In interanimal species (rat, mouse, rabbit, dog), the ratios of $LD_50$ values were between 0.1 and 5 (up to 50-fold difference). When the data are analyzed by chemical strut-ares, human $TD_50$ values were very close to rat oral $LD_50$ values. These data suggest that rat oral $LD_50$ value might be a useful parameter predicting human TDlo and one animal species could be sufficient for acute toxicity test.

• Journal of the Korea Institute of Military Science and Technology
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• v.24 no.1
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• pp.144-150
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• 2021

This study was designed to evaluate the prophylactic efficacy of a combinational patch system containing physostigmine and procyclidine against sarin and soman using guinea pig. The median lethal dose values of two nerve agents were calculated by a probit analysis of deaths occurring within 24 h. In this study, the values of median lethal dose of sarin and soman were determined to be 33.0 and 26.7 ㎍/kg in guinea-pigs, respectively. The guinea pigs treated with a prophylactic patch(4×5 ㎠) for 24 h were 100 % protected against a challenge of 1.5 LD50. The combinational KMARK-1(atropine and 2-PAM) and prophylactic patch were more effective than a single KMARK-1, a combination of pyridostigmine and KMARK-1 significantly. Epileptiform seizures in the guinea pigs treated with the combinational antidotes led to neuropathological changes, in comparison with intact feature of brain of the animal treated with the patch.

• Journal of the Korea Institute of Military Science and Technology
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• v.24 no.3
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• pp.348-355
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• 2021

Hantaan virus(HTNV) causes hemorrhagic fever with renal syndrome(HFRS) with a case fatality rate ranging from <1 to 15 % in human. Hantavax^Ⓡ is a vaccine against the Hantavirus, which has been conditionally approved by the Ministry of Food and Drug Safety(MFDS). However, only 50 % of volunteers had neutralizing antibodies 1 year following the boost. Effective antiviral treatments against HTNV infection are limited. Hantaviruses generally cause asymptomatic infection in adult mice. On the other hand, infection of suckling and newborn mice with hantaviruses causes lethal neurological diesease or persistant infection, which is different from the disease in humans. The development of vaccines and antiviral strategies for HTNV has been partly hampered by the lack of an efficient lethal mouse model to evaluate the efficacy of the candidate vaccines or antivirals. In this report, we established a lethal mouse model for HTNV, which may facilitate in vivo studies on the evaluation of candidate drugs against HTNV. The median lethal dose value of HTNV was calculated by probit analysis of deaths occurring within two weeks. Five groups of ten ICR mice were injected intracranially with serial 2-fold dilutions (from 50 to 3.125 PFU/head) of HTNV. Mice injected with HTNV began to die at 8 days post-infection. The lethal dose required to kill 50 % of the mice (LD₅₀) was calculated to be 2.365 PFU/head.

• 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.

• 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.

• Korean Journal of Plant Resources
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• v.29 no.1
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• pp.128-135
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• 2016

This study examined radiation damage and the optimal gamma-ray dose for mutation breeding in oat (Avena sativa L. cv. Samhan). The seed germination rate decreased as the dose increased over 500 Gy. The median lethal dose (LD₅₀) was approximately 392 Gy. The median reduction dose (RD₅₀) for plant height, tiller number, root length, and flash weight was 411, 403, 394, and 411 Gy, respectively. The optimal dose of gamma irradiation for inducing oat mutation appears to be in the range 300-400 Gy. We performed the comet assay to observe nuclear DNA damage induced by gamma-ray irradiation. This assay showed a clear difference with gamma-ray treatments. DNA damage increased temporarily 7 days after treatment depending on the dose, while no significant difference was identified in response to 300 Gy 30 days after the gamma-ray treatments. The growth characteristics of the M₂ generation decreased as the dose increased over 400 Gy.

• 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.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.31 no.4
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• pp.473-483
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• 2021

Objectives: The present study aimed to evaluate the potential toxicity of 2-butoxyethanol after intratracheal instillation in male rats. Methods: In order to calculate median lethal dose (LD₅₀) of 2-butoxyethanol using Probit analysis with SAS program, the 2-butoxyethanol was administered with dose levels of 0, 101.64, 203.28 and 406.56 mg/kg by once intratracheal instillation to male rats. During the test period, clinical signs, mortality, body weights, organ weights, hematology, and serum biochemistry were examined. At the end of 14 days observation period, all animals were sacrificed and gross finding and histopathological examination were performed. Results: All animals of 406.56 mg/kg group died within 2 weeks after the administration of 2-butoxyethanol. Treatment-related clinical signs, gross observation and histopathological changes (mucous cell hyperplasia, alveolar macrophage aggregation, and hemorrhage) of lung exhibited an increased in 2-butoxyethanol treated groups in a dose dependent manner. However, there were no changes in the organ weights, hematology and serum biochemistry, and histopathology of any other organ except lung. Conclusions: On the basis of the results, it was concluded that a single intratracheal instillation of 2-butoxyethanol in male Sprague-Dawley rats resulted in some adverse effects on mortality, clinical sign, and histopathology in the lung. In the experimental conditions, the LD₅₀ of 2-butoxyethanol was considered to be 287.2 mg/kg and lung was founded to be the target organ of 2-butoxyethanol.

• The Korean Journal of Mycology
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• v.14 no.4
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• pp.265-271
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• 1986

To screen biologically active components of the higher fungi of Korea, the dried carpophores of Auricularia polytricha were extracted with water. The extract was examined for acute toxicity in ICR mice. A low molecular weight toxin of this fungus was purified by a acetone precipitation followed by cellulose, silica gel and Sephadex LH-20 column chromatography. Major symptoms of this toxin were decreasing of normal motility, eye extrusion, hair erection, shivering, trembling of head, paralysis, rapid running or moving before death and depression of respiration. The median lethal doses of the total extract were 1. 28 g/kg and 4. 31 g/kg by i.p. and p.o. administrations, respectively. The amounts of one mouse lethal unit of the total extract and final fraction that killed a 20 g mouse within 30 minutes were 28.5 and 12.0 mg/mouse, respectively.

• Korean Journal of Veterinary Service
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• v.14 no.1
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• pp.71-77
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• 1991

Parathion 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 cholinesterase activity according to time lapsed in Sprague-Dawley rats injected single with half dose to LD$_{50}$ of parathion, cholinesterase activities in serum, spinal cord, whole brain and median lethal dose between sex difference were investigated. The results obtained were summerized as follows ; 1. 4LD_{50}$ values of parathion given intraperitoneally to male and female rats were 10.5mg / kg(95% confidence limits, 6.6-16.8mg/ kg) and 3.3mg/ kg(95% confidence limits, 1.9-5.6mg/ kg). 2. The inhibition rate of cholinesterase activities in serum of parathion-injected rats according to time lapsed were peakly decreased to 35.4%(male) and 32.4%(female) after 1 hour in comparison to control group, but cholinesterase activities were completely recovered after 48 hours. 3. The inhibition rate of cholinesterase activities in spinal cord of parathion-injected rats according to time lapsed were peakly decreased to 31.1% (male) and 36.3% (female) after 30 minutes in comparison to control group, but cholinesterase activities were completely recovered after 48 hours. 4. The inhibition rate of cholinesterase activities in whole brain of parathion -injected rats according to time lapsed were peakly decreased to 32.2%(male) and 42.6%(female) after 1 hour in comparison to control group, but cholinesterase activities were completely recovered after 48 hours.s.