衛生福利部國家中醫藥研究所(中醫藥所)委託財團法人食品工業發展研究所(食工所)進行臺灣清冠中藥 (包含臺灣清冠一號(NRICM101)及臺灣清冠二號(NRICM102)臨床水煎劑) 之安全性及基因毒性試驗。其依據中華實驗動物學會『實驗動物管理與使用指南』及食工所實驗動物照護及使用委員會(IACUC)所制定『實驗動物照護及使用指引』之規範，進行評估試驗，試驗內容包括：重複劑量毒性試驗 (亞急性毒性試驗)、單一劑量口服急毒性試驗，及基因毒性試驗 (微生物、體外哺乳類細胞、及動物體內)，試驗結果可提供臺灣清冠中藥作為生體使用安全性劑量之參考依據。

  實驗結果顯示，臺灣清冠一號及二號在連續經口管餵30天之低劑量組 (1.6 g/kg bw/day)、中劑量組 (3.2 g/kg bw/day)及高劑量組 (4.8 g/kg bw/day)皆未觀察大鼠有任何異常生理現象，且於試驗期間均未有死亡紀錄，其攝食量及體重也未有明顯差異；血液、尿液、生化檢驗及臟器相對重量與對照組也未有明顯差異。其各臟器之病理組織檢查經國立中興大學動物醫學研究中心切片判讀，其結果顯示，高劑量組與對照組比較，高劑量組之腎上腺、腦、心臟、腎臟、肝臟、肺臟、脾臟、胸腺、睪丸及副睪 (雄鼠) 或卵巢及輸卵管 (雌鼠) 等臟器均無明顯與試驗物質有關之組織病理變化。因此，根據綜合病理檢查結果證實，管餵低、中及高劑量連續1個月後，對雌雄SD大鼠各重要臟器並未造成毒性。單一劑量口服急毒性試驗，也試驗結果顯示，ICR小鼠及SD大鼠分別餵食5 g/kg bw之臺灣清冠中藥14天後，未產生死亡的現象且臟器外觀正常，無誘發動物活體體產生單一劑量口服急毒性之生理現象。另外在基因毒性試驗結果顯示，清冠中藥之沙門氏菌回復突變試驗檢測結果為非致變異性；體外鼷鼠淋巴瘤tk分析在含有代謝活化系統S9混合物之測試條件下，不具致變異性；進行動物體內基因毒性測試之週邊血液微核試驗，評估受測物是否會造成遺傳基因的損害中顯示，結果顯示網狀紅血球之「微核生成比例」及紅血球中之「網狀紅血球生成比例」，與陰性對照組間均無顯著性差異。

Safety Assessment of Taiwan NRICM101 and NRICM102

The National Research Institute of Chinese Medicine (NRICM), under the Ministry of Health and Welfare, commissioned the Food Industry Research and Development Institute (FIRDI) to conduct safety and genotoxicity tests on Taiwan Chingguan Traditional Chinese Medicine (TCM), including Taiwan Chingguan No. 1 (NRICM101) and Taiwan Chingguan No. 2 (NRICM102) clinical decoctions. These tests were conducted in accordance with the Guidelines for the Management and Use of Laboratory Animals by the Chinese Association for Laboratory Animal Science and the Guidelines for the Care and Use of Laboratory Animals established by FIRDI's Institutional Animal Care and Use Committee (IACUC). The evaluations included repeated-dose toxicity tests (subacute toxicity tests), single-dose oral acute toxicity tests, and genotoxicity tests (microbial, in vitro mammalian cell, and in vivo animal tests). The results of these tests provide reference dosages for the safe use of Taiwan Chingguan TCM in humans.

The experimental results showed that in both low (1.6 g/kg bw/day), medium (3.2 g/kg bw/day), and high (4.8 g/kg bw/day) dose groups administered orally for 30 consecutive days, no abnormal physiological phenomena were observed in rats. There were no recorded deaths during the trial, and no significant differences in food intake or body weight were noted. Blood, urine, biochemical examinations, and relative organ weights showed no significant differences compared to the control group. Histopathological examinations of various organs (adrenal glands, brain, heart, kidneys, liver, lungs, spleen, thymus, testes and epididymis in males, or ovaries and oviducts in females) performed by the Animal Disease Diagnostic Center at National Chung Hsing University revealed no significant treatment-related changes in the high-dose group compared to the control group. Comprehensive pathological examination results confirmed that continuous oral administration of low, medium, and high doses for one month did not cause toxicity to the major organs of male and female SD rats. 

Additionally, the single-dose oral acute toxicity tests showed that ICR mice and SD rats administered a single dose of 5 g/kg bw of Taiwan Chingguan TCM exhibited no deaths over a 14-day period, and their organ appearances remained normal, indicating no acute toxic physiological phenomena. Genotoxicity test results indicated that Taiwan Chingguan TCM was non-mutagenic in the Salmonella reverse mutation test. The in vitro mouse lymphoma tk assay, under conditions including the S9 metabolic activation system, also showed no mutagenic effects. The in vivo peripheral blood micronucleus test revealed no significant differences in the frequency of micronuclei in reticulocytes or in the proportion of reticulocytes among total red blood cells compared to the negative control group, indicating no genotoxic effects.

Thus, these findings suggest that Taiwan NRICM101 and NRICM102 are safe for use at the tested dosages, with no observed toxicity or genotoxicity in the studied animal models.