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JKM > Volume 44(3); 2023 > Article
Shin, Jeon, Seo, and Lee: Acute toxicity study of 77 herbal formulas according to GLP guidelines in rats

Abstract

Objectives

This study aimed to investigate the acute oral toxicity of 77 herbal formulas and performed in male and female Sprague-Dawley (SD) rats as per the guidelines mentioned in Ministry of Food and Drug Safety.

Methods

Each sex of SD rat were administered a single dose (2000 or 5000 mg/kg) of 77 herbal formulas via oral gavage; the control group received vehicle only. After administration, the mortality, clinical signs, gross findings, and body weight were followed up for 15 days.

Results

After administration of 77 herbal formulas, mortality, clinical signs, body weight changes, and gross findings related to the test substances were not observed in both male and female groups.

Conclusion

Our results demonstrate the single-dose oral administration of 77 herbal formulas produced no mortality indicating the approximate lethal dose is greater than 2000 or 5000 mg/kg body weight.

Table 1
Acute Oral Toxicity of 28 Kinds of Herbal Formula in Health Insurance
Herbal formula Reference Herbal formula Extract code (KE) Single-serving size (g) Yield of extract (%) GLP organizations Human equivalent dose for rats (mg/kg) ALD (mg/kg)
Gamisoyo-san B 57 31.870 26.80 KIT 882.6 > 5,000
Galgeun-tang U 02 44.000 12.60 KIT 572.9 > 2,000
Gumiganghwal-tang22) B 16 37.500 22.76 KIT 882.0 > 2,000
Gungha-tang B 58 21.270 20.14 KIT 442.7 > 5,000
Naeso-san B 52 41.250 11.98 KIT 510.6 > 5,000
Daesiho-tang B 61 50.640 25.62 KIT 1340.6 > 5,000
Daehwajung-eum B 62 37.520 21.38 KIT 828.9 > 5,000
Banhabaekchulcheonma-tang B 11 43.750 17.60 KIT 795.7 > 5,000
Banhasasim-tang23) D 38 37.500 14.99 KIT 580.9 > 5,000
Banhahubag-tang B 72 26.500 11.66 NIKOM 319.3 > 5,000
Bojungikgi-tang B 12 22.875 25.40 KIT 600.4 > 2,000
Bulhwangeumjeonggi-san D 55 33.750 12.48 KIT 435.2 > 5,000
Samso-eum D 28 41.250 18.60 KIT 792.8 > 2,000
Samchulgeonbi-tang D 06 43.500 24.50 KIT 1101.3 > 2,000
Saengmaek-san B 40 15.000 26.58 KIT 412.0 > 5,000
Sosiho-tang B 26 35.625 22.94 KIT 844.5 > 2,000
Socheongryong-tang24) B 13 37.500 21.70 KIT 840.9 > 2,000
Yeongyopaedog-san D 59 35.690 23.00 KIT 848.2 > 5,000
Ojeog-san B 04 56.250 21.00 KIT 1220.6 > 2,000
Ijung-tang25) B 19 26.250 24.80 KIT 672.7 > 2,000
Ijin-tang26) B 08 20.625 18.50 KIT 394.3 > 2,000
Insampaedok-san D 14 45.000 24.30 KIT 1130.0 > 5,000
Jaeumganghwa-tang B 01 43.125 20.80 KIT 926.9 > 5,000
Palmul-tang27) B 05 36.000 25.90 KIT 963.5 > 5,000
Pyeongwi-san28) D 18 26.250 23.40 KIT 634.7 > 2,000
Hyangsapyeongwi-san B 51 33.750 18.75 KIT 653.9 > 5,000
Hyeonggaeyeongyo-tang B 60 33.440 25.93 KIT 896.0 > 5,000
Hwangryeonhaedok-tang B 20 18.000 17.10 KIT 318.1 > 2,000

ALD (approximate lethal dose), B (Bang-Yak-Hap-Pyun), BW (body weight), D (Dong-Ui-Bo-Gam), GLP (good laboratory practice), KE (KIOM (Korea Institute of Oriental Medicine) evidence-based medicine), KIT (Korea Institute of Toxicology), NIKOM (National Institute for Korean Medicine Development), U (Ui-Hak-Ip-Mun)

Table 2
Acute Oral Toxicity of 26 Kinds of Herbal Formula in Dispensing Instructions
Herbal formula Reference Extract code (KE) Single-serving size (g) Yield of extract (%) GLP organizations Human equivalent dose for rats (mg/kg) ALD (mg/kg)
Goakhyangjeonggi-san D 32 33.750 12.89 KIT 449.5 > 5,000
Gwibi-tang29) D 22 43.000 24.30 KIT 1079.7 > 2,000
Danggwisu-san D 33 30.375 16.91 KIT 530.8 > 5,000
Danggwijakyak-san K 75 22.000 24.13 KIT 548.6 > 5,000
Daegunjoong-tang K 65 8.000 12.13 KIT 100.3 > 5,000
Dokhwalgisaeng-tang D 74 31.800 22.27 NIKOM 731.8 > 5,000
Bangpungtongseong-san30) D 23 44.125 17.70 KIT 807.0 > 2,000
Baenongsangeup-tang K 68 18.000 26.46 KIT 492.2 > 5,000
Buhnsimgi-eum B 54 47.250 14.57 KIT 711.4 > 5,000
Sagunja-tang31) D 24 18.750 22.30 KIT 432.1 > 5,000
Samul-tang32) D 25 18.750 33.30 KIT 645.2 > 5,000
Samryeongbaekchul-san D 39 91.875 14.10 KIT 1338.6 > 5,000
Sogeonjung-tang D 63 39.800 17.74 KIT 729.6 > 5,000
Sopung-san T 71 36.000 17.44 NIKOM 648.8 > 5,000
Sibjeondaebo-tang19) D 03 45.000 22.90 KIT/KTR 1064.9 > 5,000
Ssanghwa-tang33) D 21 37.500 25.50 KIT 988.1 > 2,000
Yeonggyechulgam-tang D 48 22.500 12.73 KIT 296.0 > 5,000
Oyaksungi-san D 27 46.125 24.40 KIT 1163.0 > 2,000
Onkyeong-tang D 41 45.000 30.60 KIT 1422.9 > 5,000
Yongdamsagan-tang D 49 26.500 18.53 KIT 507.4 > 5,000
Wiryeong-tang D 50 41.250 12.50 KIT 532.8 > 5,000
Yukmijihwang-tang21) U 07 46.875 27.00 KIT 1307.8 > 2,000
Jagamcho-tang D 73 43.020 26.12 NIKOM 1161.1 > 5,000
Chokyungjongok-tang B 64 45.730 24.02 KIT 1135.0 > 5,000
Cheongsangbangpung-tang M 69 27.460 28.20 KIT 800.2 > 5,000
Chengsimyeunja-eum D 43 31.875 13.03 KIT 429.2 > 5,000

ALD (approximate lethal dose), B (Bang-Yak-Hap-Pyun), BW (body weight), D (Dong-Ui-Bo-Gam), GLP (good laboratory practice), K (Keum-Kyue-Yo-Rak), KE (KIOM (Korea Institute of Oriental Medicine) evidence-based medicine), KIT (Korea Institute of Toxicology), KTR (Korea Testing and Research Institute), M (Man-Byeong-Ye-Chun), NIKOM (National Institute for Korean Medicine Development), T (text of Herbal Formula), U (Ui-Hak-Sim-O)

Table 3
Acute Oral Toxicity of 23 Kinds of the Rest Herbal Formula
Herbal formula Reference Extract code (KE) Single-serving size (g) Yield of extract (%) GLP organizations Human equivalent dose for rats (mg/kg) ALD (mg/kg)
Gamisoyo-san D 45 35.250 19.41 KIT 707.0 > 5,000
Gamiondam-tang B 66 29.750 22.55 KIT 693.2 > 5,000
Gyejibokryeong-hwan D 31 18.750 11.82 KIT 229.0 > 5,000
Gyeji-tang D 46 30.000 9.75 KIT 302.3 > 5,000
Daeyoung-jeon B 53 80.625 27.57 KIT 2296.9 > 5,000
Mahwang-tang D 47 38.500 4.52 KIT 179.8 > 5,000
Maekmundong-tang B 37 43.125 9.26 KIT 412.6 > 5,000
Sanjoin-tang K 90 56.25 16.80 KIT 976.5 > 5,000
Sokyunghwalhyeol-tang M 79 44.500 26.54 NIKOM 1220.4 > 5,000
Siryung-tang B 89 27.54 21.43 KIT 609.9 > 5,000
Youngseonjetong-eum B 76 33.300 26.72 NIKOM 919.4 > 5,000
Oryung-san34) D 17 28.125 22.70 KIT 659.7 > 2,000
Jagyakgamcho-tang D 42 22.500 19.35 KIT 449.9 > 5,000
Jodeung-san M 78 33.000 20.13 NIKOM 686.4 > 5,000
Cheonwangbosim-dan D 34 48.750 21.30 KIT 1073.0 > 5,000
Takrisodok-eum B 70 63.750 24.67 NIKOM 1625.1 > 5,000
Palmijihwang-hwan D 35 101.250 24.79 KIT 2593.7 > 5,000
Paljung-san D 56 36.000 9.34 KIT 347.4 > 5,000
Hyangsayukgunja-tang D 36 43.125 12.95 KIT 577.1 > 5,000
Hyangso-san D 44 33.750 13.41 KIT 467.7 > 5,000
Hyulbuchukeo-tang T 77 76.000 26.72 NIKOM 2098.4 > 5,000
Gongjin-dan B 92 6.887 - NIKOM 711.7 > 5,000
Kyuongok-go B 93 23.000 - KCL 2376.7 > 5,000

ALD (approximate lethal dose), B (Bang-Yak-Hap-Pyun), BW (body weight), D (Dong-Ui-Bo-Gam), GLP (good laboratory practice), K (Keum-Kyue-Yo-Rak), KCL (Korea Conformity Laboratories), KE (KIOM (Korea Institute of Oriental Medicine) evidence-based medicine), KIT (Korea Institute of Toxicology), M (Man-Byeong-Ye-Chun), NIKOM (National Institute for Korean Medicine Development), T (text of Herbal Formula)

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