Subchronic toxicity study of Coptidis rhizoma in rats.
BACKGROUND
Coptidis Rhizoma (CR) is a medical herb from the family Ranunculacease that has been used to treat gastroenteritis, dysentery, diabetes mellitus, and severe skin diseases.


OBJECTIVE
To evaluate the no-observed-adverse-effect level (NOAEL) and the toxicity of CR, following repeat oral administration to rats for 13 weeks.


METHODS
CR was administered by oral gavage to groups of rats (n=10/group, each sex) at dose levels of 0 (control), 25, 74, 222, 667 or 2000 mg/kg/day 5 times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology and sperm morphology, organ weights, gross and histopathological findings were compared between control and CR groups.


RESULTS
Urinalysis showed a significant increase in N-acety1-β-glucosaminidase in males in the 2000 mg/kg/day group (P<0.01). However, no mortality or remarkable clinical signs were observed during this 13-week study. No adverse effects on body weight, food consumption, hematology, serum chemistry, organ weights, gross lesion, histopathology, vaginal cytology, sperm motility, or deformity were observed in the males or female rats treated with CR.


CONCLUSIONS
On the basis of these results, the NOAEL of CR is determined to be 667 mg/kg/day for males and 2000 mg/kg/day for females.
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea.
Yong-Hoon
YH
Lee
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea.
Duyeol
D
Kim
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea.
Mi Ju
MJ
Lee
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea.
Myoung Jun
MJ
Kim
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea.
Ho-Song
HS
Jang
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea.
Sun Hee
SH
Park
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea; Department of Biomedical Laboratory Science, Namseoul University, 21 Maeju-ri, Seonghwan-eup, Cheonan 331-707, Chungnam, Republic of Korea.
Jung-Min
JM
Lee
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea.
Hye-Yeong
HY
Lee
Division of Toxicopathology, Hoseo Toxicology Research Center, Hoseo University, 79 Hoseo-ro, BaeBang-Myeon, Asan 336-795, Chungnam, Republic of Korea.
Beom Seok
BS
Han
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea.
Woo-Chan
WC
Son
Toxicological Research Divison, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong Health Technology Administration Complex, 187 Osongsaengmyeong2-ro, Osong, Cheongwon 363-700, Chungbuk, Republic of Korea.
Ji Hyeon
JH
Seok
Toxicological Research Divison, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong Health Technology Administration Complex, 187 Osongsaengmyeong2-ro, Osong, Cheongwon 363-700, Chungbuk, Republic of Korea.
Jong Kwon
JK
Lee
Toxicological Research Divison, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osong Health Technology Administration Complex, 187 Osongsaengmyeong2-ro, Osong, Cheongwon 363-700, Chungbuk, Republic of Korea.
Jayoung
J
Jeong
Department of Biomedical Laboratory Science, Namseoul University, 21 Maeju-ri, Seonghwan-eup, Cheonan 331-707, Chungnam, Republic of Korea. Electronic address: kang@nsu.ac.kr.
Jin Seok
JS
Kang
Department of Pathology, Biotoxtech Co., Ltd, 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun 363-883, Chungbuk, Republic of Korea; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chungbuk National University, 410 Naesudong-ro, Heungdeok-gu, Cheongju 361-763, Chungbuk, Republic of Korea. Electronic address: jkkang@cbu.ac.kr.
Jong-Koo
JK
Kang
D000118:Acetylglucosaminidase / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000089042:Coptis chinensis; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D059550:Toxicity Tests, Subchronic
D004365:Drugs, Chinese Herbal; C107393:Coptidis rhizoma extract; D000118:Acetylglucosaminidase
Coptidis Rhizoma; Fischer 344 rat; GLP; NOAEL; Subchronic toxicity