Duyeol Kim1, Yong-Hoon Lee1, Sun Hee Park1, Mi Ju Lee1, Myoung Jun Kim1, Ho-Song Jang1, Jung-Min Lee2, Hye-Yeong Lee1, Beom Seok Han3, Woo-Chan Son4, Ji Hyeon Seok5, Jong Kwon Lee5, Jayoung Jeong5, Jin Seok Kang6, Jong-Koo Kang7. 1. Department of Pathology, Biotoxtech Co., Ltd., 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea. 2. Department of Pathology, Biotoxtech Co., Ltd., 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea; Department of Biomedical Laboratory Science, Namseoul University, 21 Maeju-ri, Seonghwan-eup, Cheonan, Chungnam 331-707, Republic of Korea. 3. Hoseo Toxicity Research Center, Hoseo University Biomedical Laboratory Science, 79 Hoseo-ro BaeBang-Myeon, Asan, Chungnam 336-795, Republic of Korea. 4. 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. 5. Toxicological Research Divison, National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, Osong Health Technology Administration Complex, 187 Osongsaengmyeong2-ro, Osong, Cheongwon, Chungbuk 363-700, Republic of Korea. 6. Department of Biomedical Laboratory Science, Namseoul University, 21 Maeju-ri, Seonghwan-eup, Cheonan, Chungnam 331-707, Republic of Korea. Electronic address: kang@nsu.ac.kr. 7. Department of Laboratory Animal medicine, College of Veterinary medicine, Chungbuk National University, 410 Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk 361-763, Republic of Korea. Electronic address: jkkang@cbu.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Evodia, a fruit from Evodia rutaecarpa, has been used in oriental medicine, and since its various pharmaceutical actions, including anti-cancer activity, have become known, evodia has been widely used as a dietary supplement. However, information regarding its toxicity is limited. MATERIALS AND METHODS: Evodia fruit from Evodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang (0, 25, 74, 222, 667, and 2000 mg/kg) was administered orally five times per week for 13 weeks. Clinical signs, body weight, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm morphology, organ weight, and gross and histopathological findings were evaluated. RESULTS: Urinary ketone body excretion was detected in males at 667 and 2000 mg/kg and in females at 2000 mg/kg. An increase in absolute/relative liver weight was observed in both sexes at 2000 mg/kg. Although levels of serum alanine aminotransferase, glucose, total cholesterol, and triglycerides were significantly reduced in males and/or females at 200 and/or 667 and 2000 mg/kg, all values were within normal ranges and were considered non-adverse. In addition, no treatment-related differences in body weight, food consumption, hematology, vaginal cytology, sperm morphology, or gross and histopathological examination were detected. CONCLUSIONS: The subchronic no-observable-adverse-effect level for evodia fruit powder following oral administration in rats is greater than 2000 mg/kg.
ETHNOPHARMACOLOGICAL RELEVANCE: Evodia, a fruit from Evodia rutaecarpa, has been used in oriental medicine, and since its various pharmaceutical actions, including anti-cancer activity, have become known, evodia has been widely used as a dietary supplement. However, information regarding its toxicity is limited. MATERIALS AND METHODS: Evodia fruit from Evodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang (0, 25, 74, 222, 667, and 2000 mg/kg) was administered orally five times per week for 13 weeks. Clinical signs, body weight, food consumption, hematology, serum chemistry, urinalysis, vaginal cytology, sperm morphology, organ weight, and gross and histopathological findings were evaluated. RESULTS: Urinary ketone body excretion was detected in males at 667 and 2000 mg/kg and in females at 2000 mg/kg. An increase in absolute/relative liver weight was observed in both sexes at 2000 mg/kg. Although levels of serum alanine aminotransferase, glucose, total cholesterol, and triglycerides were significantly reduced in males and/or females at 200 and/or 667 and 2000 mg/kg, all values were within normal ranges and were considered non-adverse. In addition, no treatment-related differences in body weight, food consumption, hematology, vaginal cytology, sperm morphology, or gross and histopathological examination were detected. CONCLUSIONS: The subchronic no-observable-adverse-effect level for evodia fruit powder following oral administration in rats is greater than 2000 mg/kg.