• 대한약침학회지
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• 제26권4호
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• pp.348-356
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• 2023

Objectives: Neuralgia-pharmacopuncture (NP) was recently developed as a water-soluble type of pharmacopuncture inspired by CS (care special pain)-pharmacopuncture. I aimed to evaluate the toxic response and approximate lethal dose of when NP when administered intramuscularly to Sprague Dawley rats. Methods: The experimental group was divided into the NP test substance group and the saline control group and administered at a dose of 1.0 mL/animal to the posterior thigh muscles on both sides using a 1 mL syringe; each group consisted of five males and five females. Each rat was monitored for clinical signs and changes in body weight for 14 days after a single intramuscular injection. After completing observation, necropsy findings and localized tolerance at the injection site were assessed via gross necropsy and histopathological examination. Results: No deaths occurred in the NP or control group, regardless of sex. During the observation period, no changes (such as general symptoms, weight change, or visual observation results at the time of autopsy) were judged to be due to the test substance. Histopathological examination showed no changes at the administration site judged to be caused by the test substance in either the male or female test substance administration groups. In addition, mononuclear cell infiltration of the outer membrane of the femoris muscle at the administration site was observed at the same frequency and extent in the control and NP groups, and was judged to be caused by physical stimulation by the injection needle; therefore, it had no toxicological significance. Conclusion: Based on the above results, the approximate lethal dose for a single intramuscular administration of the test substance NP in Sprague-Dawley rats was judged to be > 1.0 mL/animal, and there were no findings that were judged to be due to the test substance at the administration site.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.310-313
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• 1996

Acute oral toxicity studies of KDRD-002 (Coriolus versicolor polysaccharide :DDB= 19.2:1) were carried out in Sprague-Dawley rats of both sexes. In this study, we daily examined number of deaths, clinical signs, body weights and pathological examinations for 7 days after single oral administration of KDRD-002 with different dose levels. KDRD-002 did not show any toxic effect in rats and oral LD$_{50}$ value was over 3.25 g/kg in rats.s.

• Toxicological Research
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• 제29권2호
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• pp.91-98
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• 2013

Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as it contains hydrogen cyanide and amygdalin, especially in its endocarp. Therefore, prebrewed AS that is devoid of endocarp has been traditionally used. In the present study, amygdalin content of the prebrewed AS was significantly lower ($2.73{\pm}0.32{\mu}g/ml$; p<0.01) than the content in the extract that contained the endocarps ($28.50{\pm}6.71{\mu}g/ml$); amygdalin content corresponded to 10% of the extract in the present study. Because of single oral dose toxicity of prebrewed AS according to the recommendation of Korea Food and Drug Administration Guidelines (2009-116, 2009), which was based on single oral dose toxicity study of prebrewed AS, mortality due to toxic principles was significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of 1 female rat and 1 male rat at the end of 2 hr of administration. Based on these results, the 50% lethal dose in both male and female rats was determined to be 9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart rate were observed as prebrewed AS treatment-related toxicological signs; these signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated rats. In addition, no changes were observed in body weight, organ weight, gross features, and histopathological parameters with 2,000 mg/kg of AS in both male and female rats. These findings serve as direct evidence that amygdalin in AS is the toxic principle, which can be reduced by the traditional prebrewing method involving the exclusion of endocarp.

• 대한약침학회지
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• 제17권1호
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• pp.27-34
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• 2014

Objectives: This experiment was conducted to examine the toxicity of Water soluble Carthmi-Flos herbal acupuncture (WCF) by administering a single intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and to find the lethality dose for WCF. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices under a request by the Korean Pharmacopuncture Institute. This experiment was performed based on the testing standards of "Toxicity Test Standards for Drugs" by the Ministry of Food and Drug Safety. Subjects were divided into 4 groups: 1 control group in which normal saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was administered; a single intramuscular dose was injected into 5 males and 5 females in each group. General symptoms and body weights were observed/measured for 14 days after injection. At the end of the observation period, hematological and clinical chemistry tests were performed, followed by necropsy and histopathological examinations of the injected sections. Results: No mortalities were observed in any group. Also, symptoms, body weight, hematology, clinical chemistry and necropsy were not affected. However, histopathological examination of the injected part in one female in the 1.0-mL group showed infiltration of mononuclear cells and a multi-nucleated giant cell around eosinophilic material. Conclusion: Administration of single intramuscular doses of WCF in 3 groups of rats showed that the approximate lethal dose of WCF for all rats was in excess of 1.0 mL, as no mortalities were observed for injections up to and including 1.0 mL.

• 한국식품영양과학회지
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• 제36권8호
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• pp.960-964
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• 2007

천연생리활성물질 소재로서 파고지 추출물의 안전성을 검증하기 위하여 렛트에 대한 단회 경구투여 독성 평가와 복귀돌연변이평가를 실시하였다. 파고지 에탄올 추출분말 2 g/kg, 5 mL를 암${\cdot}$수 각각 5마리씩 경구 투여한 후 14일 동안의 일반증상, 체중변화 및 부검시의 육안적 소견을 관찰한 결과, 사망례, 일반증상 및 체중변화는 관찰되지 않았고 부검결과에서도 특이할 만한 육안적 이상소견은 관찰되지 않아, 파고지 추출물은 $LD_{50}$값이 렛트 체중 kg당 2g 이상이며 단회 경구 투여에 대한 독성을 가지는 않는 것으로 평가되었다. 파고지 추출분말의 복귀돌연변이 유발성 여부는, 히스티딘 요구성 Salmonella Typhimurium TA98, TA100, TA1535, TA1537 균주 및 트립토판 요구성 Escherichia coli WP2uvrA(pKM101) 균주를 이용하여 S9 mix 첨가 여부에 따라 실험하였다. 용량설정시험 결과, S9 mix 첨가 여부에 관계없이 사용한 모든 시험균주에서 생육저해가 관찰되었다. 시험물질의 석출은 S9 mix 첨가 여부와 상관없이 사용한 모든 시험균주의 1,250, 2,500 및 5,000 ${\mu}g/plate$에서 관찰되었지만 콜로니 계수에는 영향이 없었다. 따라서, 본 시험의　용량은 S9 mix 미첨가 TA100, TA1537 균주 및 S9 mix 첨가 RA1535 균주의 경우에는 생육저해가 관찰된 625 ${\mu}g/plate$를, S9 mix 첨가 여부에 관계없이 TA98 균주 및 S9 mix 첨가TA100, TA1537, WP2uvrA(pKM101) 균주의 경우에는 생육저해가 관찰된 1,250 ${\mu}g/plate$를, S9 mix 미첨가의 TA1535 및 WP2uvrA(pKM101) 균주의 경우에는 2,500 ${\mu}g/plate$를 최고용량으로 하였고, 그 이하 공비 2로 최고용량을 포함한 5용량의 시험물질군과 음성대조군 및 양성대조군으로 하여 실험을 실시하였다. 그 결과, 모든 시험균주에서 시험물질에 의한 복귀변이 콜로니수는 S9 mix의 첨가 여부에 관계없이 용량의존적으로 증가되지 않았으며, 음성대조군과 비교하여 2배 이상의 증가를 보이지 않았다. 시험물질에 의한 균주의 생육저해는 S9 mix첨가 여부에 관계없이 사용한 모든 시험균주의 최고용량에서 관찰되었다. 시험물질의 석출은 S9 mix 첨가 여부에 관계없이 1,250 및 2,500 ${\mu}g/plate$에서 관찰되었지만 콜로니 계수에는 영향이 없는 것으로 나타났다.

• 대한약침학회지
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• 제16권4호
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• pp.22-29
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• 2013

Objectives: This study was performed to analyze the toxicity of the test substance, anti-inflammatory pharmacopuncture (AIP), when used as a single intramuscular-dose in 6-week-old, male and female Sprague-Dawley rats and to find the lethal dose. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices. Twenty (20) female and 20 male Spague-Dawley rats were divided into 4 groups of five 5 female and 5 male animals per group. The rats in the three experimental groups received single intramuscular injections with 0.1-$m{\ell}$, 0.5-$m{\ell}$ and 1.0-$m{\ell}$/animal doses of AIP, Groups 2, 3, and 4, respectively, and the control group, Group 1, received a single intramuscular injection with a 1.0-$m{\ell}$ dose of normal saline. Clinical signs were observed and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematology, clinical chemistry, histopathological tests and necropsy were performed on the injected parts. Results: No deaths occurred in any of the groups. Also, histopathological tests showed that AIP had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusions: As a result of single intramuscular-dose tests of the test substance AIP in 4 groups of rats, the lethal dose for both males and females exceeded $1.0m{\ell}$/animal. Therefore, AIP is a relatively safe pharmacopuncture that can be used for treatment, but further studies should be performed.

• 대한약침학회지
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• 제18권1호
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• pp.56-62
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• 2015

Objectives: The purpose of the study is to assess both the approximate lethal dose and the single dose intramuscular injection toxicity of Danggui (Angelica gigantis radix) pharmacopuncture (DGP) in Sprague-Dawley (SD) rats. Methods: The experiments were conducted at the good laboratory practice (GLP) laboratory, Biotoxtech Co., which is a laboratory approved by the ministry of food and drug safety (MFDS). The study was performed according to the GLP regulation and the toxicity test guidelines of the MFDS (2009) after approval of the institutional animal care and use committee of Biotoxtech. Single doses of DGP were injected intramuscularly into the rats in three test groups of 6 week old SD rats (5 male and 5 female rats per groups) in the amounts of 0.1, 0.5, and 1.0 mL/animal for groups 2, 3, and 4, respectively, and normal saline solution in the amount of 1.0 mL/animal was injected intramuscularly into the rats (5 male and 5 female rats) in the control group. Observations of the general symptoms and weight measurements were performed during the 14 day observation period after the injection. Hematologic and serum biochemical examination, necropsy, and a local tolerance test at the injection site were done after the observation period. Results: No death was observed in three test groups (0.1, 0.5 and 1.0 mL/animal group). In addition, the injection of DGP had no effect on general symptoms, weights, hematologic and serum biochemical examination, and necropsy. The results from the local tolerance tests at injection site showed no treatment related effects in the SD rats. Conclusion: The results of single dose intramuscular injection of DGP suggest that the approximate lethal dose is above 1.0 mL/animal for both male and female SD rats and that intramuscular injection of DGP may be safe.

• 한국식품영양과학회지
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• 제36권5호
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• pp.527-533
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• 2007

건강효능이 우수한 고품질 유색미 과피의 안전성 규명을 목적으로 ICR계 마우스 암수 각각 10마리를 이용하여 적진주벼, 흑진주벼 및 흑향벼 과피를 80% EtOH로 추출한 농축물을 1회 경구투여 후 14일 동안 실시한 급성독성 평가 결과는 다음과 같다. 시험물질을 1회 경구투여한 경우, 총 14일의 실험기간 동안 모든 시료투여군의 암수 동물에서 정상적인 체중증가가 관찰되었으며, 체중증가는 유의적인 차이를 나타나지 않았으며, 시료투여군의 경우 용량의존적인 체중변화도 관찰되지 않았다. 시험물질 투여 14일 후 부검결과, 암수 모든 실험군의 간장, 신장(좌, 우), 비장, 심장, 폐 및 뇌에서 시험물질 투여에 따른 어떤 육안적 이상 소견도 발견되지 않았다. 치사시킨 동물의 혈액 생화학적 검사 결과, 모든 시료 투여군의 ALT와 AST 활성도가 정상 수치를 나타냈으며, 본 실험의 최고 용량인 10.0 g/kg투여에도 정상치를 나타내는 것으로 보아, 유색미 과피 추출물을 10.0 g/kg 이하 섭취할 경우에는 어떠한 간독성도 나타내지 않음을 확인할 수 있었다. 이상의 실험결과를 통해 고품질 유색미인 적진주벼, 흑진주벼 및 혹향벼 과피 추출물의 단회 경구투여에 의한 독성시험 시, 시험물질 투여에 의한 표적 장기가 관찰되지 않았으며, 어떠한 독성학적인 변화도 관찰되지 않는 것으로 보아, 무해 용량은 암수 모두 10.0 g/kg을 상회할 것으로 추정할 수 있었다.

• 한국식품과학회지
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• 제46권2호
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• pp.249-255
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• 2014

본 연구에서는 사용된 가시오가피 영지버섯 발효물과 가시오가피 상황버섯 발효물에 대한 열수추출물을 최고 2 g/kg의 농도로 단회 투여한 SD-rats에 체중 변화, 임상증상 등에서 어떠한 독성도 관찰할 수 없었으며, 1 g/kg 이하의 농도로 4주간 반복 투여한 SD-rats에서도 체중변화, 임상증상, 장기 무게, 혈액학적 성상, 혈액생화학적 성상 등에서 어떠한 독성과 비정상적인 소견을 관찰할 수 없었다. 따라서, 본 연구의 결과로 볼 때 가시오가피 영지버섯 발효물 열수추출물(FM-5111)과 가시오가피 상황버섯 발효물 열수추출물(FM-5131)은 본 연구에서 사용한 농도 내에서의 안전성을 확인할 수 있었다. 황 함유 아미노산의 결핍은 여러 가지 간질환 등의 증상을 야기한다(27). 또한, Choi와 Ahn(28)은 오가피 부위별 50% (v/v) 메탄올 추출액의 전자공여능은 줄기 추출물에서 90.21%, 뿌리 추출물에서 85.71%로 높은 활성을 보고하여 오가피의 항산화능을 규명하였다. 따라서, 본 연구에 사용된 시료 또한 항산화능과 같은 기능성을 가질것으로 사료되며, 추가 연구로 아미노산 분석을 통해 황 함유 아미노산의 함량 변화를 분석하고 간 기능 개선 효능을 평가하여 안전성이 확보된 기능성 식품소재 개발 연구를 진행할 계획이다.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
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• pp.37-40
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• 2004