Safety of Elixinol Hemp Extract: In Vitro Genetic Toxicity and Subchronic Toxicity in Rats.

IF 3.4 Q2 TOXICOLOGY
Journal of Toxicology Pub Date : 2023-12-11 eCollection Date: 2023-01-01 DOI:10.1155/2023/5982883
Margitta Dziwenka, Laurie C Dolan, Mithila Rao
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引用次数: 0

Abstract

The results of safety studies performed with Elixinol Hemp Extract, a blend of hemp extract, cannabidiol (CBD) isolate, and copaiba containing approximately 65% total CBD, are described in this paper. In a 15-day range-finding study in rats, there were no effects of treatment with up to 101.4 mg/kg bw/day of the extract by gavage on any safety parameter measured in the study, with the exception that centrilobular hepatocellular hypertrophy occurred in all treatment groups, which correlated with increases in absolute liver weight in high-dose females and liver to terminal body weight ratio in mid-dose and high-dose females. A GLP-compliant 90-day OECD Guideline 408 study in rats that included a behavioral battery and a 28-day recovery phase was also conducted with Elixinol Hemp Extract administered by gavage. The doses used in the 90-day study were 0 (vehicle), 28.94, 50.64, and 86.81 mg/kg bw/day. The findings were similar to those observed in the range-finding study. There were no effects of the test material on any test parameter in the 90-day study other than findings related to the liver (increased liver weight in high-dose main study males and mid-dose and high-dose main study females and low incidences of hepatocellular hypertrophy and vacuolation in main study high-dose males). Similar findings were not observed in the recovery animals, and there were no alterations in the clinical chemistry suggestive of liver toxicity in any of the main study or recovery animals. Therefore, the liver outcomes observed in the main study were not considered adverse. The test material also tested negative for mutagenicity in bacterial reverse mutation assays (plate incorporation and preincubation) in the absence and presence of metabolic activation. The results indicate that the oral 90-day no observed adverse effect level (NOAEL) of Elixinol Hemp Extract in rats is 86.81 mg/kg bw/day (highest dose administered), and that the extract is not mutagenic.

Elixinol 大麻提取物的安全性:大鼠的体外遗传毒性和亚慢性毒性。
本文介绍了 Elixinol 大麻提取物的安全性研究结果,该提取物是大麻提取物、大麻二酚(CBD)分离物和椰子叶的混合物,CBD 总含量约为 65%。在对大鼠进行的一项为期 15 天的范围测定研究中,通过灌胃每天服用 101.4 毫克/千克体重的提取物不会对研究中测量的任何安全性参数产生影响,但所有治疗组都出现了中心叶肝细胞肥大,这与高剂量雌性大鼠肝脏绝对重量的增加以及中剂量和高剂量雌性大鼠肝脏与终末体重比的增加有关。此外,还对大鼠进行了一项符合 GLP 标准的 90 天 OECD 准则 408 研究,其中包括行为测试和 28 天的恢复阶段。这项为期 90 天的研究使用的剂量分别为 0 毫克/千克体重/天(载体)、28.94 毫克/千克体重/天、50.64 毫克/千克体重/天和 86.81 毫克/千克体重/天。研究结果与测距研究中观察到的结果相似。在 90 天的研究中,除了与肝脏有关的结果(高剂量主要研究雄性动物和中剂量及高剂量主要研究雌性动物的肝脏重量增加,以及高剂量主要研究雄性动物肝细胞肥大和空泡化发生率较低)外,受试物质对任何测试参数都没有影响。在恢复期动物中未观察到类似的结果,而且任何主要研究或恢复期动物的临床化学指标均未出现提示肝脏毒性的变化。因此,在主要研究中观察到的肝脏结果不属于不良反应。在没有新陈代谢活化和有新陈代谢活化的情况下,在细菌反向突变试验(平板结合和预孵育)中,测试材料的诱变性也呈阴性。结果表明,大鼠口服 90 天艾利西诺大麻提取物的无观测不良效应水平(NOAEL)为 86.81 毫克/千克体重/天(最高给药剂量),且该提取物无致突变性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Toxicology
Journal of Toxicology TOXICOLOGY-
CiteScore
5.50
自引率
3.40%
发文量
0
审稿时长
10 weeks
期刊介绍: Journal of Toxicology is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of toxicological sciences. The journal will consider articles looking at the structure, function, and mechanism of agents that are toxic to humans and/or animals, as well as toxicological medicine, risk assessment, safety evaluation, and environmental health.
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