This is a joint FSA and FSS publication.
1. Introduction
FSA and FSS have undertaken safety assessments for CBD isolate under the novel foods legislation, assimilated Regulation (EU) 2015/2283. To support the safety assessment, the ACNFP provided the advice outlined in this opinion to the FSA and FSS.
The evaluation by the ACNFP assessed the food safety risks of the novel food and its production, in line with Article 7 of assimilated Commission Implementing Regulation (EU) 2017/2469. The regulatory framework and the technical guidance put in place by the European Food Safety Agency (EFSA) for full novel food applications is used as the basis and structure for the assessment (EFSA NDA Panel, 2021).
An application was submitted to the Food Standards Agency (FSA) and Food Standards Scotland (FSS) in February 2021 from Bridge Farm Group (“the applicant”) for the authorisation of cannabidiol (CBD) isolate as a novel food. The novel food is a ≥98% pure form CBD isolate which is intended to be used as a food ingredient in food supplements for adult (excluding pregnant and lactating women, and other specifically identified vulnerable groups including those taking medication and the immunosuppressed).
The final advice from the ACNFP was agreed at the 169th meeting, allowing the FSA and FSS to complete the risk assessment.
This document outlines the conclusions of the FSA and FSS on the safety of a ≥98% pure form CBD isolate (as detailed in application RP354) as a novel food.
2. Assessment
2.1. Identity of the Novel Food
The novel food is a cannabidiol (CBD) isolate in the form of a white to off-white crystalline powder of purity equal to or greater than 98.0%. Information to support this characterisation was provided for five batches of the novel food.
CBD is characterised by the chemical formula: C21H30O2; molecular mass: 314.46 g/mol; CAS number: 13956-29-1; IUPAC name: 2-[(1R,6R)-6-Isopropenyl-3-methylcyclohex-2-en-1-yl]-5- pentylbenzene-1,3-diol
Confirmation of its identity and purity was provided by quantitative nuclear magnetic resonance spectroscopy (q-NMR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
2.2. Production Process
The CBD isolate is manufactured using a multi-step process under controlled conditions.
Certificates of analysis for raw starting materials used in the extraction process were provided to demonstrate the effectiveness of the controls at this point in the process. The details of the commercially sensitive extraction process were shared and reviewed by the ACNFP.
Plants are grown under conditions of good horticultural practice until the flowers have matured. Biomass is harvested, dried and treated to convert cannabidiolic acid (CBDA) to cannabidiol (CBD). CBD is extracted from the treated biomass using subcritical liquid carbon dioxide as the solvent. The CBD is further purified by absorbing it onto an appropriate matrix and preferentially eluting it using subcritical liquid carbon dioxide. The purified CBD is recovered by allowing the carbon dioxide to evaporate.
The FSA and FSS considered whether the use of solvents as processing aids resulted in residues that require highlighting to risk managers. To assess the safety of the solvent residues that remain in the novel food, comparison was made to residue limits for other consumed products as detailed in Table 1.
The evidence presented (see Table 2 below) on composition indicates compliance with the specification for residues of solvents. When considered at the level of consumption the evidence suggests the levels of solvent residues in the novel food are below those which would represent a safety concern.
A HACCP statement was provided along with further details of the process and how it operates. Further information on how the production process is effectively managed was requested; the applicant provided reassurance on this by evidencing the control procedures in place. The FSA and FSS concluded the production process has characterised the potential hazards and detailed the corresponding control measures sufficiently.
2.3. Compositional Information
Results from five independent batches of the novel food demonstrated that the CBD content is produced consistently. The data is presented in Tables 2 to 6 below.
The data presented in Table 2 indicates CBD content is consistently above 98% purity with negligible amounts of starting materials detected across the five representative batches.
It is recognised that the detection and characterisation of cannabinoids in a range of food matrices is an evolving area and there are yet to be internationally recognised methods. The limitations of available analytical methodology have been subject to discussion in the Joint ACNFP and COT CBD Subgroup and remain a source of uncertainty in this assessment.
Analytical data concerning the microbiological content from five independent batches of the novel food were reported (Table 3). The process in manufacturing this novel food uses subcritical liquid carbon dioxide as an extraction solvent, high temperature steps, and drying, which may mitigate the proliferation of microbes within the final product. The microbiological data presented confirm that the novel food does not raise a safety concern and consistently meets the proposed microbial specification levels.
Results from the mycotoxin analysis for five independent representative batches of isolated CBD are presented in Table 4. The data show that the isolated CBD consistently complies with the specifications set for mycotoxins within the final product.
Novel food products must comply with the legal requirements for heavy metal contaminants in food. Analytical data, presented for five independent batches of the novel food, demonstrated that heavy metals were present in low quantities and below established EU limits where applicable (applicable for arsenic, cadmium, mercury and lead) (Table 5).
Results from the residual solvent analysis and pesticide analysis for five independent representative batches of isolated CBD are presented in Table 6. The data show that the isolated CBD is able to consistently comply with the specifications set for residual solvents and pesticides within the final product.
THC as a Potential Contaminant in the Novel Food
The extraction process may result in other cannabinoids remaining as contaminants. In particular, delta-9-tetrahydrocannabinol (Δ9-THC) and its precursor acid delta-9-tetrahydrocannabinolic acid (Δ9-THCA) were analysed due to the potential for toxic effects resulting from their consumption and the status of Δ9-THC as a controlled drug within the UK (Table 2). Along with Δ9-THC, other minor cannabinoids which occur at contaminant levels have the potential to play a role in the toxicity of CBD novel food products; as such, they require due consideration and monitoring to ensure the novel foods remain safe. As a result, the robustness, accuracy, and precision of the methods have been considered in interpreting the data on Δ9-THC and were considered appropriate in this case.
A literature review was undertaken as part of the assessment of CBD as a novel food, to understand the impact on the safety of foods with trace levels of contamination with Δ9-THC. The Joint ACNFP and COT Subgroup reviewed the information from literature and identified a point of departure from the European Food Safety Authority (EFSA) opinion on Δ9-THC as a contaminant in milk and meat (EFSA, 2015).
Evidence from an EFSA review by the CONTAM panel suggested a point of departure from a LOAEL (lowest observed adverse effect level) of 0.036 mg/kg/bw/day, which is drawn from the most sensitive individuals and at the lowest dose tested in the clinical studies that were reviewed (EFSA, 2015). Uncertainty factors were then applied to identify a safe upper intake level. These included a factor of 3 to extrapolate from a LOAEL to a NOAEL (no observed adverse effect level), which was considered appropriate as the effects are mild to moderate in severity. A further factor of 10 was applied for person-to-person variation, resulting in total of an applied uncertainty factor of 30. This resulted in a safe upper intake level of 1 µg/kg bw/day for Δ9-THC consumed as a contaminant in food. This was identified an acute reference dose (ARfD) (EFSA, 2015).
The Subgroup agreed the acute reference dose (ARfD) to be sufficiently protective to apply to the UK population. It was noted that in applying the acute reference dose, EFSA has assumed that the effects seen would be the same if humans were exposed to multiple doses of THC at very low levels (EFSA, 2015). The Subgroup commented that there were no data to verify this assumption, but if setting limits the dataset is the best available.
The analysis for delta-9-tetrahydrocannabidiol as a potential contaminant in the novel food was declared as 42 – 185 mg/kg in the five batches tested, (Table 2), with a reporting limit of 2.5 mg/kg.
The levels of Δ9-THC, where detected in the novel food, once adjusted to reflect the proposed use of 10 mg of CBD being consumed a day, were below the ARfD identified by EFSA of 1 µg/kg bw/day or 70 µg/day for a healthy adult. This level does not present a concern in terms of consumer safety for the novel food under the proposed conditions of use.
To ensure Δ9-THC levels remain consistently low in the production of CBD, THC and its precursor acid combined should be a standard substance included in the specification as relevant to all batches produced.
The data presented did not indicate any additional hazards for inclusion in the specification.
2.4. Stability
The stability of the novel food was assessed in real-time under the recommended storage conditions (4°C) in five batches for 6 months. Results showed that the novel food meets the specification criteria for CBD and other cannabinoid content over this time period.
Stability results for the CBD isolate preparation using a model system based on a 1% solution of CBD in different vegetable oils was reviewed. The accelerated shelf-life study was performed at 60°C for 24 days in clear glass packaging in full light conditions. The results of this study were interpreted and demonstrated the CBD isolate is stable for 12 months in hemp oil.
The data provided supports the stability of CBD isolate for a period of at least 12 months.
2.5. Specification
The applicant’s specification parameters reported in Table 7 were assessed using internationally recognised methods or determined using internally developed and validated methods. The results of the analysis are detailed in Table 2 to 6 and indicate the novel food can be produced consistently to the specification.
The information provided is sufficient for the specification of CBD and appropriately characterises the novel food seeking authorisation.
2.6. History of Use
Hemp has been widely consumed in the UK and EU as a seed oil, in tea and as an alternative to hops in beer. Extracts of hemp including CBD and synthetic CBD have not been widely consumed and are considered novel foods. While CBD products are widely available on the UK high street, indicating some consumption of CBD as a food, at the time of publication, no previous applications for CBD have yet received authorisation as a novel food.
As detailed in the COT review of the literature there has been use of both hemp-derived and synthetic forms of CBD for medicinal purposes. These provide an indication of the toxicological effects that should be explored in the testing regime – primarily effects on liver and thyroid, and potential impacts on reproductive organs. Also reported are behavioural effects such as somnolence (sleepiness) (COT, 2020).
As reported in the COT review of the publicly available data on CBD and summary data on a medicinal product, signs of adverse effects on the liver were observed at doses of CBD as low as 5 mg/kg bw/day in patients and healthy human volunteers; this dose is equivalent to 350 mg in a 70 kg adult. The data in the literature also suggested that humans might be more sensitive to the adverse effects of CBD in the liver than laboratory animals.
Somnolence effects were noted at doses ≤10 mg/kg bw/day in human studies. Inhibitory drug-drug interactions have also been observed with some medications when CBD is co-administered at doses of 1 mg/kg bw/day (equivalent to 70 mg in a 70 kg adult); the likelihood of effects at lower doses has not been determined (COT, 2020). Based on the COT assessment, therefore, the FSA concluded in February 2020 that 1 mg/kg bw/day, or 70 mg in a 70 kg adult, of CBD represented a pragmatic upper level of intake above which there would be clear concerns about safety, until further data are available.
It is noted that the doses used for medicinal purposes are higher than those proposed for food use. The purpose of an assessment for medicines authorisation is different to that for food and this is reflected in the data requirements. Unlike medicines, there is no risk-benefit context in foods with the requirement instead being that the products are safe. This means that outcomes that are considered an adverse event for food might not be considered as such in a medicinal study.
Within the literature, further human studies utilising chemically derived CBD provides further evidence of a history of synthetic CBD use (Izegelov et al., 2020; Klotz et al., 2019; Stero Biotechs Ltd., 2020; Wheless et al., 2019). A review by Huestis et al., 2019 of Cannabidiol Adverse effects and Toxicity notes that, while CBD is not risk-free, severe adverse events occur at doses higher than those recommended for human pharmacotherapies which are prescribed to treat forms of epilepsy.
The data on previous consumption of CBD suggest areas for careful consideration in the toxicological review to understand potential effects at the lower doses used in foods.
2.7. Proposed Use and Anticipated Intake
The proposed use for the novel food is food supplements as defined by The Food Supplements (England, Scotland and Wales) Regulations 2003 as capsules, liquid or drops in dose form.
The applicant initially proposed a use level of 40 mg/day CBD for the novel food in adults (excluding pregnant and lactating women, and other specifically identified vulnerable groups including those taking medication and the immunosuppressed). As a result of consultation with the applicant the proposed uses have been updated to reflect the provisional acceptable daily intake (ADI) for the use of ≥98% pure form CBD established at 10 mg per day (ACNFP and COT, 2023). The proposed maximum use levels for the novel food are outlined in Table 8.
It is noted that consumers may be exposed to CBD from a range of food categories. The standard methodology for calculating exposure for a novel food would explore intake from a range of sources and ensure that exposure via the proposed uses would not exceed any safety level identified when consumption of the food category was analysed. It is noted that for CBD that there are already many products available. As such, the assessment has been made on the basis of identification of a maximum level of CBD that can be consumed per day. As such proposed uses will only be considered safe within the assessment when at a maximum consumption of 10 mg of CBD per day from all sources (as concluded in section 2.10 of this assessment).
Concerns were raised by the Committee regarding the potential for foreseeable misuse of CBD if consumed in multiple formats on a single day. This is because of the increased risk of consuming CBD above the provisional acceptable daily intake (ADI). The scope of the assessment is restricted to the uses proposed and any further uses or additional food categories would be subject to the change in conditions of use process. Risk managers must consider whether consumers would benefit from information on the CBD content of foods in order to ensure their consumption does not exceed the maximum intake of 10 mg per day for a healthy adult.
As recommended in the ACNFP and COT statement on CBD of 98% purity, “The provisional ADI is recommended, subject to the existing advice to consumers that pregnant and breastfeeding women and people taking any prescription medication should avoid the consumption of CBD if possible. Consumers on regular medications should seek advice from a medical professional before using any type of CBD food product. In addition, children and prospective parents trying for a baby are advised against consumption of CBD, as are those who are immunosuppressed, due to remaining data gaps and residual uncertainties concerning the safety of CBD for these groups of consumers” (ACNFP and COT, 2023).
The ACNFP explored the potential for foreseeable misuse of the novel food. They advised that the availability of multiple formats of the novel food could create conditions where exposure estimates are exceeded. It is highlighted to risk managers that they may wish to consider whether risk management measures are needed beyond those in the food supplements regulation to ensure consumers are aware of the provisional ADI of 10 mg CBD/day for the product, a dose at which it is considered that no adverse effects would be expected.
It is also strongly recommended that risk managers consider how consumers can be supported to manage their intake appropriately within the safe limits identified and appreciate the nature of the potential risks at higher doses, for uses that are not in dosed forms.
The food supplement products are to be labelled in accordance with the labelling requirements of Food Supplements (England) Regulations 2003 and the equivalent legislation in the nations of GB. The ACNFP recommended that the applicant’s proposed warning labelling be updated to include information on not exceeding the safe limit of 10 mg/day for a 70 kg healthy adult, that the product is not suitable for use under the age of 18 or for use during pregnancy or breastfeeding. As well as information on its suitability if consumers are taking medication or have existing health conditions.
2.8. Absorption, Distribution, Metabolism and Excretion (ADME)
The Absorption, Distribution, Metabolism and Excretion (ADME) of CBD are known to be complicated by the food matrix in which the CBD is delivered and are currently still being defined by professional bodies.
The oral bioavailability of CBD is low, indicating that it is not absorbed to any notable extent following ingestion (Mechoulam et al., 2002). Published works report the bioavailability of CBD to be between 13 and 19% (Grotenhermen, 2003) or 6% (Hawksworth & McArdle, 2004). The low systemic availability was demonstrated by Martin-Santos et al., 2012 and further supported by a literature search which identified the pharmacokinetics of CBD in humans (Millar et al., 2018). The COT statement on CBD of 2020 noted that although CBD has low fasting bioavailability (<10%), consumption with food could increase CBD uptake, by for example, 5-fold if eaten with a high fat meal. As such the potential for matrix effects that impact bioavailability cannot be ruled out. The applicant has submitted additional information in the form of a pharmacokinetic study, which was reviewed by the ACNFP (Johnson et al., 2022).
Following oral consumption, CBD is extensively metabolised in the liver. This rapid first pass metabolism contributes to the low oral bioavailability reported in the literature (Taylor et al., 2018; WHO, 2018). In vitro studies indicate that CYP3A4 and CYP2C19 are the primary hepatic enzymes responsible for first-pass metabolism of CBD; however, several other hepatic cytochrome P450 isoforms (CYP1A1, CYP1A2, CYP2C9, CYP2D6, and CYP3A5) have also demonstrated a capability of metabolising CBD (Jiang et al., 2011; Zendulka et al., 2016).
The metabolism of CBD is thought to follow two separate pathways. One is P450-mediated, in which CBD is metabolised into its major metabolite 7-COOH-CBD. This is followed by further metabolic reactions which yield the minor metabolites of CBD, including 6-OH-CBD (Devinsky et al., 2018; Taylor et al., 2018). The other involves decarboxylation (Kraemer et al., 2019). The resultant metabolites are predominantly excreted in faeces and urine (Hawksworth & McArdle, 2004; WHO, 2018).
Multiple dosing with CBD is associated with a steady state concentration up to 2-fold accumulation of CBD in plasma when compared with a single dose (Taylor et al., 2018). Minimal evidence of plasma accumulation has also been reported in dosing studies over 5–9 days (Millar et al., 2018; Sellers et al., 2013; Stott et al., 2013).
The pharmacokinetics of CBD have been systematically reviewed by Millar et al. (2018) in 24 studies, most of which assessed the administration of CBD at doses of 5–20 mg/day. This correlates to a low dose application similar to this CBD novel food application. Following oral administration, single doses of 5.4 and 10 mg CBD achieved peak serum concentrations (Cmax) of 0.9 and 2.5 ng/mL. The time to maximum concentration (Tmax) was approximately 1 hour, with a half-life between 1 and 3 hours. Given the intended use of this CBD as a food supplement, with an approximate half-life of 1 to 3 hours, with a total clearance of 6 hours, there are no significant concerns of accumulation (Millar et al., 2018).
The ADME data provides context for interpreting the toxicological data. It is noted that the bioavailability of CBD is typically low but can be affected by food matrices. The food context for CBD could therefore impact on CBD bioavailability. It was noted that the potential for CBD to accumulate in the body has not been examined based on the data supplied. This has been taken into account in considering the assessment factors to account for uncertainty in setting the provisional ADI.
2.9. Nutritional Information
The FSA and FSS sought clarification of the potential for the presence of antinutritional factors from the preparation. It was noted that hemp can contain a range of substances that could impact the digestion and absorption of nutrients from the diet. These include phytic acid (which can negatively affect the bioavailability of dietary and endogenous minerals and proteins), tannins (which can interrupt the absorption of iron), trypsin inhibitors (which can affect protein digestion), and saponins (which at larger quantities cause gastric irritation and increase the permeability of the intestine).
The product is highly purified as indicated in the information on the composition. There are no substances present that would be expected to impact the digestion or absorption of nutrients from the diet.
The data on nutritional composition confirm that CBD has no caloric or nutritional value. The application is not intending that CBD replace another food in the diet. Consumption of the novel food at the proposed use levels is not expected to be nutritionally disadvantageous for consumers.
2.10. Toxicological Information
Toxicological studies on CBD were performed by the applicant to support the safety assessment of the novel food. The respective study reports are unpublished and claimed as confidential and proprietary data. They were considered essential in the assessment of the safety of the novel food and were reviewed by the ACNFP. How data on systemic toxicity was managed and interpreted in the context of the provisional ADI is explained in the sub-chronic toxicology section below (section 2.10.2).
2.10.1. Genotoxicity
In vitro genotoxicity testing of CBD was conducted under Good Laboratory Practice (GLP) conditions and utilised the following OECD guidelines: in vitro bacterial reverse mutation test (OECD TG 471) and in vitro mammalian cell micronucleus test (OECD TG 487). This approach is recommended by the UK Committee on Mutagenicity and is also the basis of guidance on the preparation and submission of an application for authorisation of a novel food in the context of assimilated Regulation (EU) 2015/2283.
The in vitro bacterial reverse mutation test demonstrated that this CBD ingredient was non-mutagenic, in the absence or presence of metabolic activation. In addition, the in vitro mammalian cell micronucleus test demonstrated that CBD was non-clastogenic and non-aneugenic in the absence and presence of metabolic activation.
The results from these in vitro studies support the conclusion that the novel food (>98% pure CBD) is not genotoxic. This is consistent with the view of the Committee on Mutagenicity in reviewing CBD generically as a substance from evidence available in the public domain (Committee on Mutagenicity; MUT/MIN/2020/1, 2020).
2.10.2. Sub-chronic toxicology study
A Joint Subgroup of the ACNFP and COT was formed to address a series of questions in relation to the safety of CBD, cannabinoids and hemp-derived ingredients.
The applicant provided a Repeated Dose 13-week Oral Toxicity Study in Rodents [(Labcorp, study number 8462626)], which was conducted under GLP conditions and to OECD Test Guideline 408. In this 90-day study, male and female rats were dosed once a day with 0 (corn oil), 15, 30, or 60 mg/kg bw/day CBD by oral gavage at a dose volume of 5 mL/kg bw. The control group (0 mg/kg bw/day) and high-dose group (60 mg/kg bw/day) both contained 15 male and 15 female rats, and dose groups 15 and 30 mg/kg bw/day both contained 10 male and 10 female rats. Of the control group and high-dose group, 5 males and 5 females were allocated to the recovery period and retained not dosed for 4-weeks.
The applicant concluded a NOAEL of 60 mg/kg bw/day; the Subgroup reviewed the data and concluded a NOAEL from the study of 30 mg/kg bw/day, based on liver enlargement and histopathological changes in the adrenal. The Subgroup considered the critical effect on the liver to be the NOAEL and thus a point of departure (POD) of 30 mg/kg was confirmed by the Subgroup.
The Subgroup reviewed the data and concluded the effects seen at 30 mg/kg bw/day were minimal but not adverse; however the effects seen at 60 mg/kg bw/day are potentially adverse. As such the Subgroup considered that the NOAEL for the study be 30 mg/kg bw/day. A review of the study by the Subgroup supported the conclusion that it was of sufficient quality to support the safety of the novel food.
In addition to the data submitted by the applicant there is a body of evidence on the effect of 98% or greater CBD. In order to take account of all pertinent data and to put the individual assessment in the context of the totality of relevant evidence for the active substance, the data from this application was compared to the wider body of evidence.
A weight of evidence approach allowed the Subgroup to identify a provisional ADI for CBD ingredients of >98% purity of 0.15 mg/kg bw/day or 10 mg per day for a 70 kg healthy adult (Joint position paper from the ACNFP and COT; FSA consumer advice published in October 2023). This value was identified to be protective of the most sensitive known effects in the liver and thyroid parameters and included consideration of data gaps and uncertainties.
The dataset includes several studies where highly purified CBD has been tested. Given the low level of contaminants, it is reasonable to consider that these represent the effect of CBD as a substance and are therefore relevant to other novel foods with similar compositions.
It was considered whether the wider data and therefore the provisional ADI for CBD of 98% or greater purity was relevant to the review of this novel food. It was considered appropriate, on the basis that the test substance used in the study to support the novel food was 98% pure and the compositional data was consistent with a highly purified CBD. The contaminants present were not suggestive of a significant impact on the toxicology. The point of departure in the form of a NOAEL from the study submitted to support safety of this novel food once corrected for CBD content, is consistent with the range of the points of departure used to develop the provisional ADI (ACNFP and COT, 2023). The NOAEL was also based on the same effect – impacts on the liver. The uncertainty factors identified in the provisional ADI would also apply to the applicant’s submitted study (Labcorp, study number 8462626 unpublished) for the same reasons as identified in the provisional ADI statement. It was, therefore, considered scientifically appropriate to apply the provisional ADI of 0.15 mg/kg bw/day or 10 mg/day as identified in the joint statement of the ACNFP and COT on ≥98% pure forms of CBD to the novel food in this application.
2.11. Allergenicity
This CBD isolate comprises >98% CBD and the production process for CBD does not introduce any risk of allergenic potential. As a chemical entity the potential for IgE mediated food allergy is unlikely.
Given that CBD as a substance is not considered allergenic, the allergenicity assessment considered whether the other 2% of the novel foods’ composition was likely to be allergenic or elicit food allergic reactions. It was noted that none of the raw materials or processing aids used in the production process are derived from or contain any of the allergenic food ingredients specified under assimilated Regulation (EU) No 1169/2011 on the provision of food information to consumers. This suggests that the potential to elicit reactions in those sensitive to those foods is unlikely.
The novel food is unlikely to trigger allergic reactions in the target population under the proposed conditions of use.
3. Discussion
The novel food is a CBD isolate ingredient from industrial hemp containing >98% CBD, produced using a multi-step manufacturing process.
This CBD isolate is intended to be used as a food ingredient in food supplements for adults, excluding pregnant and lactating women, and other specifically identified vulnerable groups at a defined intake for each product type of up to 10 mg CBD per day; it is not intended to replace any food.
In October 2023, the Joint ACNFP and COT Subgroup identified a provisional acceptable daily intake (ADI) of 10 mg per day (0.15 mg/kg bw/day) for CBD products containing 98% CBD or above, such as the novel food discussed in this assessment. A weight of evidence approach was used to arrive at a provisional ADI of 10 mg/day (0.15 mg/kg bw/day). The most sensitive human health effects, which this provisional ADI protects against, are seen consistently in the liver and thyroid in a number of studies using ≥98% pure CBD. This value also takes account of the lack of human-based long-term evidence or evidence regarding potentially vulnerable groups.
Based upon the dossier of evidence provided by the applicant, the safety of the novel food was reviewed and evidence to reach a conclusion on safety provided. The evidence presented by the applicant was then compared to the wider data set on CBD, and the evidence presented is consistent with evidence presented to support the development of a provisional ADI of 10 mg/day for CBD of 98% purity or above. As such it is appropriate to apply the provisional ADI to this novel food.
This is subject to the existing advice to consumers that pregnant and breastfeeding women, and people taking any prescription medication, should avoid the consumption of CBD. Consumers on regular medications should seek advice from a medical professional before using any type of CBD food product. In addition, children and prospective parents trying for a baby are advised against consumption of CBD, as are those who are immunosuppressed, due to remaining data gaps and residual uncertainties concerning the safety of CBD for these groups of consumers. These contraindications would also apply to this novel food.
The maximum safe exposure for healthy adults of 70 kg as identified in the provisional ADI is 10 mg per day from all food sources. If the inclusion level of this CBD isolate leads to an intake per individual serving of each product type of 10 mg/day, multiple intakes of food products containing CBD on the same day should be avoided to support minimising exposure to below the provisional ADI.
4. Conclusions
The FSA and FSS have undertaken the assessment of CBD isolate and both concluded that the novel food is safe under the proposed conditions of use and does not pose a safety risk to human health. The anticipated intake levels and the proposed use was not considered to be nutritionally disadvantageous.
These conclusions were supported by the information in the novel food dossier submitted by the applicant plus the supplementary information and could not have been reached without the following data claimed as proprietary by the applicant:
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annexes to the dossier which relate to the identity of the novel food, the production process, stability, methods of analysis, particle size analysis and toxicology;
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in vitro bacterial reverse mutation test [(Labcorp study number 8462622)], in vitro mammalian cell micronucleus test [(Labcorp study number 8242623)] and 13-weeks repeat dose feeding study [(Labcorp study number 8462626)].
Abbreviations
Acknowledgements
With thanks to the members of the ACNFP during the course of the assessment who were; Dr Camilla Alexander White, Dr Anton Alldrick, Dr Kimon Andreas Karatzas, Ms Alison Austin, Dr Mark Berry, Professor George Bassel, Dr Christine Bosch, Professor Dimitris Charalampopoulos, Dr Cathrina Edwards, Professor Susan Fairweather-Tait, Professor Paul Fraser, Dr Hamid Ghoddusi, Dr Andy Greenfield, Professor Wendy Harwood, Professor Huw D. Jones, Dr Ray Kemp, Dr Elizabeth Lund, Professor Harry J. McArdle, Rebecca McKenzie, Professor Clare Mills, Dr Antonio Peña-Fernández, Dr Lesley Stanley, Professor Hans Verhagen, Dr Maureen Wakefield, and Professor Bruce Whitelaw.
To note, interests were received from members of the ACNFP: Dr Alldrick declared a potential interest relating to his previous employment; this was considered a potential conflict and as a result he was not present for discussions of CBD by the Committee. Emeritus Prof Harry McArdle declared an interest from his work with EFSA’s novel food Committee in considering data requirements for CBD. While not seen as a conflict, to avoid Prof McArdle being subject to information that would influence his EFSA work, it was agreed that he would not be present in discussions for CBD by the ACNFP but could supply comments for consideration by the Committee upon review of the minutes.