• 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.

• Toxicological Research
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• v.20 no.4
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• pp.321-324
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• 2004

Lethal dose 50% ($LD_{50}$) has been commonly used as a parameter for the estimation of acute toxicity not only in animal experiment, but also in human study. Several methods to estimate $LD_{50}$ had been introduced, but Spearman-Karber and Berens-Karber method have been widely used due to their relative convenience and accuracy. However, $LD_{50}$ values estimated from the two methods showed inconsistency and variation depending on the characteristics of mortality data. In this study, the two methods were comparatively investigated in terms of accuracy and stability for the estimation of $LD_{50}$.

• Toxicological Research
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• v.26 no.1
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• pp.53-59
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• 2010

This study was conducted to obtain acute information of the oral dose toxicity of DHU001, a polyherbal formula in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (vehicle control) ml/kg (body weight). The mortality and changes on body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with DHU001. We could not find any mortalities, DHU001 treatment-related clinical signs, changes on the body and organ weights, gross and histopathological findings. The results obtained in this study suggest that $LD_{50}$ and approximate LD in mice after single oral dose of DHU001 were considered over 2000 mg/kg in both female and male mice.

• Toxicological Research
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• v.24 no.1
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• pp.79-86
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• 2008

This study was conducted to obtain information of the oral dose toxicity of low molecular fucoidan (LMF) in male and female mice. In order to calculate 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) mg/kg (body wt.). The mortality and the changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after LMF treatment. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that LMF may not be toxic in mice and may be therefore safe for clinical use. The $LD_{50}$ and approximate LD in mice after single oral dose of LMF were considered over 2000 mg/kg in both female and male mice.

• Toxicological Research
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• v.25 no.3
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• pp.147-157
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• 2009

This study was conducted to obtain acute information of the oral dose toxicity of lyophilized water extract of Pinelliae Rhizoma, a dried tuber of Pinellia ternata (PR) in male and female mice. In order to calculated 50% lethal dose (LD$_{50}$) and approximate lethal dose (ALD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body weight). The mortality and changes in body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with PR extract. We could not find any mortalities, clinical signs, changes in the body and organ weights, gross and histopathological findings except for dose-dependent increases in the hepatic fatty change frequencies detected in PR extract 2000 and 1000mg/kg treated in both male and female mice. The results obtained in this study suggest that LD$_{50}$ and approximate LD in mice after single oral dose of PR extracts were considered over 2000 mg/kg in both and female male mice, but more than 1000mg/kg of PR extracts treatment could induce slight hepatotoxicity the fatty changes in mice.

• Journal of Society of Preventive Korean Medicine
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• v.17 no.3
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• pp.19-30
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• 2013

This study was aimed to develop a new formula for herbal medicine-safety classification in terms of evidence-based medicine. Recently, human equivalent dose(HED)-based therapeutic index was developed for herbal medicine-safety classification by transforming $LD_{50}$ to HED. However, the use of the $ED_{50}$ and $LD_{50}$ to derive the therapeutic index may be misleading as to safety, depending on the slope of the dose-response curves for therapeutic and lethal effects. To overcome this deficiency, HED-based MOS(Margin of Safety)was developed and suggested in this study. The HED-based MOS developed by using $LD_1$, changing to ALD(approximate lethal dose), and $ED_{99}$. The HED-based MOS seems to be more useful and safer than HED-based therapeutic index since its values for several herbal medicines are basically two times less than the values from HED-based therapeutic index. Thus, HED-based MOS can be a good example of Evidence-based approach for herbal medicine-safety classification.

• 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.

• Toxicological Research
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• v.23 no.4
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• pp.373-382
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• 2007

This study was conducted to obtain acute information of the oral dose toxicity of PGB-1, a novel polyglucosamine polymer produced from a new strain Enterobacter sp. BL-2 in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body wt.). The mortality and changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after dosing with PGB-1. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that PGB-1 may not be toxic in mice and may be therefore safe for clinical use. The $LD_{50}$ and approximate LD in mice after single oral dose of PGB-1 were considered over 2000 mg/kg in both female and male mice.

• The Journal of Internal Korean Medicine
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• v.26 no.2
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• pp.369-378
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• 2005

An herbal water extract of Bojungikkeehapdaechilkitang(BDT) was prepared to test it for single-dose and repeated-dose toxicity, genotoxicity and reproductive toxicity, and to obtain a 50% lethal dose$(LD_{50})$, approximated lethal dose(ALD), and approximated target organs for BDT. The extract was tested on female and male ICR mice according to KFDA Guideline 1999-61 at doasge level of 2000, 1000, 500, 250 and 125mg/kg/10mL In this study, clinical signs, mortalities and gross findings of principal organs were observed for 14 days of single dosing, and afterwards in some cases. The ALD and $LD_{50}$ of BDT extract obtained in this study was>2000mg/kg for both male and female ICR mice. Also, any possible digestive toxicity of BDT extract was found to be above 1000mg/kg in both male and female ICR mice. The results of this study strongly suggest that BDT extract has no toxic effect at dosage level below 500mg/kg.

• International Journal of Industrial Entomology and Biomaterials
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• v.13 no.2
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• pp.119-122
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• 2006

As the Selenium is known to be growth promoter in sheep and cattle, the efficacy of selenium has been tested in silkworm Bombyx mori L. The V instar larvae were fed with lethal and sub-lethal doses of selenium treated leaves. The larvae fed with lethal dose showed a significant decrease in growth and Cocoon commercial characters. The treatment with sub lethal dose exhibited a significant increase in the growth of the silkworm. Correspondingly, the cocoon commercial characters on exposure to the lethal dose showed significant decrease and sub lethal dose showed a significant increase. In the light of similar findings reported earlier in other cocoon crops and vertebrates, it can be inferred that selenium at lower doses acts as a growth stimulator, resulting in the higher yield of cocoon crop.