Standardized green tea extract was evaluated for exposure and toxicity in Beagle dogs following oral dosing by capsules. The main component (-)-epigallocatechin gallate (EGCG) accounted for 56-72% of the material. A 9-month chronic study (0, 200, 500, and 1000 mg/kg/day) was done in fasted dogs to take advantage of the reported improved catechin bioavailability with fasting. Extensive morbidity, mortality, and pathology of many major organs led to its early termination at 6.5 months and prevented identification of the toxicity mechanisms. A follow-up 13-week study examined the exposure to and toxicity of the extract. In general, toxicities were less severe than in the chronic study during the same interval. Dosing in a fed state resulted in considerably lower and less variable exposure than found under fasted conditions. Toxicity was less frequent and of lesser severity with lower exposure but limited sample size and large variability prevented reaching that definitive conclusion. Differences in mortality and morbidity between the preliminary terminated chronic and follow-up subchronic studies with the same dose of the same drug lot and similar exposure were not fully resolved as there may be other as yet unclear confounding factors.

中文翻译：

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禁食和非禁食狗中绿茶多酚的暴露和毒性。


在比格犬口服胶囊后，评估了标准化绿茶提取物的暴露和毒性。主要成分(-)-表没食子儿茶素没食子酸酯(EGCG)占该物质的56-72%。一项为期 9 个月的慢性研究（0、200、500 和 1000 毫克/公斤/天）在禁食的狗中进行，以利用已报道的禁食提高儿茶素生物利用度的优势。广泛的发病率、死亡率和许多主要器官的病理学导致其在 6.5 个月时提前终止，并阻碍了毒性机制的识别。一项为期 13 周的后续研究检查了提取物的暴露程度和毒性。一般来说，毒性不如同一时间段的长期研究严重。与禁食条件下相比，在进食状态下给药导致的暴露量显着降低且变化较小。由于暴露程度较低，中毒发生的频率较低，严重程度也较低，但样本量有限且变异性较大，无法得出明确的结论。由于可能存在其他尚不清楚的混杂因素，初步终止的慢性研究和后续亚慢性研究之间的死亡率和发病率差异尚未完全解决，这些研究使用相同剂量的相同药物批次和相似的暴露。