Chemisches und Veterinäruntersuchungsamt Karlsruhe, 76187 Karlsruhe, Germany.
Abteilung Lebensmittelchemie, Technische Universität Kaiserslautern, 67663 Kaiserslautern, Germany.
Front Biosci (Landmark Ed). 2022 Jul 25;27(8):228. doi: 10.31083/j.fbl2708228.
In the past 60 years, L. has been an object of increasing interest because of the psychotropic effects of some of its constituents. These effects mainly arise from the cannabinoid Δ-tetrahydrocannabinol (Δ-THC). species also synthesize and accumulate the non-psychotropic compound cannabidiol (CBD). Due to their therapeutic potential, both cannabinoids are an object of medical research and drug development. More recently, CBD has received increasing interest as an ingredient in electronic cigarette liquids (e-liquids). This trend may have been reinforced by health and disease-related claims, often based on clinical studies, which are used to advertise CBD. CBD liquids may be based on full-spectrum hemp extracts, CBD isolates, or synthetic CBD, all of which may contain some residual levels of Δ-THC from either natural content (in the extracts) or from possible degradation of CBD to Δ-THC, which may occur during storage. There is uncertainty about safety regarding the consumption of CBD (and Δ-THC) in e-liquids. The aim of this publication was to present an approach for a toxicological risk assessment of CBD and Δ-THC relevant to e-liquids by using the benchmark dose (BMD) approach.
Before an analysis to estimate a reference dose (RfD) for both cannabinoids, a systematic review of dose-response data was conducted. The data obtained were analyzed using the BMD approach to derive a benchmark dose lower confidence limit (BMDL). The BMDL was used as a point of departure to estimate the RfD.
No adequate human data suitable for dose-response modeling were identified. Based on animal data, the RfD values for the most sensitive endpoints were selected. For CBD, an RfD for acute exposure of 1 mg/kg body weight (bw) was estimated. For Δ-THC, an acute RfD was found to be 0.006 mg/kg bw. Additionally, the RfD for chronic exposure to CBD was estimated to be 4 mg/kg bw per day. The respective endpoints for CBD were a reduction in norepinephrine turnover and a reduction in uterus weight. The endpoint for Δ-THC was a change in blood pressure.
Because of the limited availability and quality of dose-response data, it cannot be excluded that the estimated RfD values might be afflicted with considerable uncertainties. Therefore, it is recommended to conduct further research on dose-response data, preferably from human studies.
在过去的 60 年中，由于其某些成分的致幻作用，L. 一直是人们越来越感兴趣的对象。这些作用主要来自于大麻素 Δ-四氢大麻酚（Δ-THC）。 种也合成并积累非致幻化合物大麻二酚（CBD）。由于它们具有治疗潜力，这两种大麻素都是医学研究和药物开发的对象。最近，由于与健康和疾病相关的说法，CBD 作为电子烟液（e- 液体）的成分越来越受到关注。这种趋势可能因经常基于临床研究的健康和疾病相关说法而得到加强，这些说法用于宣传 CBD。CBD 液体可能基于全谱大麻提取物、CBD 分离物或合成 CBD，所有这些都可能含有一些来自天然含量（在提取物中）或 CBD 可能降解为 Δ-THC 的残留水平，这可能发生在储存过程中。关于 CBD（和 Δ-THC）在 e- 液体中的消费安全性存在不确定性。本出版物的目的是通过使用基准剂量（BMD）方法，提出一种针对 e- 液体中 CBD 和 Δ-THC 的毒理学风险评估方法。
在分析估计这两种大麻素的参考剂量（RfD）之前，对剂量-反应数据进行了系统审查。使用 BMD 方法对获得的数据进行分析，以得出 BMD 的置信下限（BMDL）。BMDL 被用作估计 RfD 的起点。
没有确定适合剂量-反应建模的足够人类数据。基于动物数据，选择了最敏感终点的 RfD 值。对于 CBD，估计急性暴露的 RfD 值为 1 毫克/千克体重（bw）。对于 Δ-THC，发现急性 RfD 为 0.006 毫克/千克 bw。此外，还估计了 CBD 慢性暴露的 RfD 值为每天 4 毫克/千克 bw。CBD 的相应终点是去甲肾上腺素转化率降低和子宫重量降低。Δ-THC 的终点是血压变化。
由于剂量-反应数据的有限可用性和质量，不能排除所估计的 RfD 值可能存在相当大的不确定性。因此，建议对剂量-反应数据进行进一步研究，最好是来自人体研究。
