6. Margin of Exposure As discussed above, it is difficult to set maximal acceptable daily intake levels of hemp-derived products because the levels and modes of delivery in the general population vary greatly. Therefore, the margin of exposure of any product will be based on its intended use and formulation. For example, the exposure for pure CBD will likely be different from hemp extracts.
As with any dietary supplement, food, or cosmetic ingredient, FDA’s current regulatory framework is sufficient to evaluate safety concerns of hemp-derived ingredients, including CBD. For example, FDA’s GRAS procedures provide that firms must evaluate the substances dietary exposure. This includes an evaluation of any self-limiting levels of use and the history of consumption of the substance by a significant number of consumers. Similarly, NDI notifications often provide evidence that the substance was safely consumed as a food or dietary supplement. This may include information about the mean and high (e.g., 90th percentile) exposure levels and intake level of the dietary ingredient based on the intended conditions of use, or related scientific evidence on the ingredient. Furthermore, the safety assessment should describe and discuss situations in which conditions of use and composition of the new dietary ingredient differ from the documented conditions of use. Therefore, the burden of establishing margins of exposure for hemp-derived ingredients will be on the manufacturers completing the self-GRAS process, or submitting GRAS and NDI notifications to FDA.
7. General Use in Food In December 2018, the FDA issued three “no questions letters” in response to GRAS notifications for hemp seed-derived food ingredients. Therefore, companies have already used FDA’s regulatory framework to establish the safety of cannabis-derived products for use in food. In addition, cannabis has been grown in various locations around the world and has commonly been used in cooking as an herb, an additive, and also consumed as tea (Booth, 2004). In recipes, cannabis has been used in beverages and added to home-made sweets, biscuits, and cakes.
In 2018, Roundtable member CV Sciences published a study examining the genotoxicity and subchronic toxicity of hemp extract to understand its toxicological profile as part of its self-affirmed GRAS assessment. A battery of toxicological studies were conducted on the hemp extract containing about 25% cannabinoids. No evidence of genotoxicity was found and a 14-day repeated oral dose-range finding rat study at 1000, 2000, and 4000 mg/kg bw/day resulted in effects where a NOEL could not be concluded (Marx, 2018). Based on those results, a 90-day repeated dose oral toxicity study was performed in rats using doses of 100, 360, and 720 mg/kg bw/day, followed by a 28-day recovery period for two satellite groups. Significant decreases in body weight, body weight gain, and differences in various organ weights compared to controls were observed. At the end of the recovery period, many of the findings were trending toward normal; thus, the changes appeared to be reversible. The NOAEL for the hemp extract was determined to be 100 mg/kg bw/day for males and 360 mg/kg bw/day for females. The study concluded that the hemp-extract was nonmutagenic, nonclastogenic, and nongenotoxic in the current bacterial reverse mutation, in vitro mammalian chromosomal aberration, and in vivo mouse micronucleus tests, respectively.
Recently, Manitoba Harvest also announced that it completed a safety assessment and self-affirmed its Broad Spectrum Hemp Extract as GRAS. The GRAS applies to the intended use in products for the general population age 2 years and older excluding pregnant and lactating women. Its hemp extract products include 15 mg CBD plant protein powder, 10 mg CBD oil drops, 5 mg CBD oil spray, and 15 mg CBD oil soft gel formats (Manitoba, 2019). [
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