Joint Statement from the ACNFP & COT Subgroup on the Conclusion of a Review of a Proposal under “REACH” by the French Agency to classify Cannabidiol (CBD) through all exposure routes

Joint Statement from the Advisory Committee on Novel Foods and Processes (ACNFP) & The Committee on Toxicity (COT) Subgroup on the Conclusion of a Review of a Proposal under “REACH” by the French Agency ANSES to classify Cannabidiol (CBD) through all exposure routes, including food, ad having potential for reproductive toxicity both in utero for unborn children exposed through the placenta, and for infants exposed through breast milk at 150mg/kg bw/day

Executive Summary

The ACNFP/COT Subgroup has the remit to consider and review all relevant data received on CBD or hemp derived products to advise of their safe use. To support and inform the FSA’s risk assessments and consumer advice in this area, the Subgroup was tasked with considering a proposal by the French Agence Nationale chargèe de la Sécurité Sanitire de l’Alimentation, de l’Environment et du Travail (ANSES) to classify CBD as a reproductive toxicant at 150 mg/kg bw/day.

This statement addresses whether the data from the ANSES proposal provides new evidence that challenges the conclusions outlined in the joint ACNFP and COT ‘s provisional Acceptable Daily Intake (ADI) statement from October 2023, in particular for vulnerable groups. The Subgroup was asked to advise the FSA on this issue and whether the current data gaps on reproductive and developmental toxicity were addressed by the new data.

The Subgroup concluded that the studies identified in the ANSES proposal did not provide evidence to support any alteration to the applied uncertainty factors, and the findings from the new studies were consistent with the wider body of evidence considered in the statement of October 2023.

Introduction

The FSA is committed to keeping the provisional ADI for >98% pure CBD under review as new data on CBD safety emerges. Under the Classification, Labelling and Packaging (CLP) provisions for chemicals in the EU, a proposal from ANSES has been made to classify CBD as a substance, through all exposure routes including food, as having potential for reproductive and developmental toxicity at doses of 150 mg/kg bw/day. This included additional information that might inform the provisional ADI and raised questions on whether the information provided addressed the data gaps for reproductive and developmental toxicity identified in the Joint ACNFP/COT statement (2023) on a provisional ADI for 98% or greater purity CBD^(footnote).

In line with the Joint ACNFP and COT Subgroup’s remit, and the FSA commitment, the emergence of the ANSES proposal prompted the need for expert advice on whether the new data had an impact on the provisional ADI (published by FSA in October 2023 establishing a provisional ADI of 10mg/day) equivalent to 0.15 mg/kg body weight for a 70 kg adult^(footnote)) , in which information on reproductive toxicity was a notable data gap.

The Subgroup was commissioned to review the studies within the ANSES proposal, with the objective of providing scientific advice to address the following questions:

• Understand to what extent the data that has been collated by ANSES is consistent with the data used to generate the provisional ADI for CBD of 98% or greater purity.
• Identify whether the data provided any additional information to address the data gap identified on reproductive toxicity in the original statement on the provisional ADI.
• Whether existing uncertainty factors are sufficient to reassure that adverse effects are unlikely at the provisional ADI.

Determine whether the additional information assessed by ANSES identifies any changes to the COT and ACNFP advice that could impact the FSA/FSS’s consumer advice for vulnerable groups.

Methodology

To determine the impact of the new data on the provisional ADI, the Subgroup conducted an initial scoping exercise. The Subgroup concluded that of the sixty-four studies reviewed within the ANSES report, thirteen were considered to be pertinent reproductive studies for further review. These were to be ranked, based on the Klimisch score assigned within the report, as a marker of scientific quality.  

Two further studies of high quality were identified as having already been evaluated as part of the subgroup’s work on CBD, which were now available in published form. As such they were not considered further in this review. The Subgroup was asked to advise on whether the thirteen published works provided any further evidence to address the questions that formed the scope of the review outlined above.

ACNFP and COT Findings

The joint ACNFP and COT Subgroup held a meeting in September 2025, to discuss impact and relevance of the key papers cited by ANSES that were extracted and itemised in the preliminary review.

A key point of consideration identified by the Subgroup was the difference in scope of the ACNFP/COT Subgroup 2023 review and the ANSES systematic review. Whilst the ANSES assessment was hazard-based and focused largely on Hazard Identification as required by the Chemical, Labelling and Packaging (CLP) Regulations for which it was compiled. The ACNFP/COT Subgroup review was primarily risk-based and conducted with the objective of considering the risk to consumers. As such, while the ANSES assessment demonstrates consideration of risk to consumers, the overarching focus by ANSES is on Hazard Identification (in connection with the REACH Regulation in EU).

Furthermore, the objectives of the ACNFP/COT Subgroup statement and the ANSES review were different. The ACNFP/COT Subgroup acknowledged, as indicated in its original review in 2023, the evidence from the studies in the ANSES review suggesting possible effects on development and reproduction occurred at doses of CBD significantly higher than the provisional ADI.

The ACNFP/COT Subgroup did not identify any significant findings that contradicted the literature previously reviewed. Subgroup members considered that the reproductive and developmental toxicity methodology was not consistent. Notably, the low sample sizes, lack of full reproductive cycle observation, dosages and mode of exposure used in many of the studies, reduces the applicability of the evidence in a risk assessment context. The studies continue to suggest areas of uncertainty and where further work would be beneficial but did not challenge the current UK provisional ADI and associated advice.

The additional animal study data included impacts of prenatal CBD exposure on behaviour and development, which the Subgroup were able to consider in the context of infant development. The use of detailed behavioural assessments (ultrasonic vocalizations and motor skills tests) and exploration of epigenetic changes (DNA methylation) resulting from prenatal CBD exposure provided members with a nuanced view of how CBD exposure might affect developmental milestones in a sex-dependent manner and a molecular basis for observed behavioural changes.

How CBD affects both sensory processing (pain sensitivity) and cognitive function, as well as underlying neurobiological mechanisms (neuronal excitability) were also considered. The integration of both functional assessments (echocardiography) and molecular analyses (qPCR, RNA-seq), offered members a robust investigation into the long-term effects of prenatal CBD exposure on cardiac health.

The possible impacts on development and the lack of robust data in this area had been previously noted as part of the provisional ADI and were considered as areas that should remain under review. However, no evidence was presented at doses similar to the provisional ADI of 10mg/day  and this is a potential issue and uncertainty in the assessment, which was included as part of the generation of the uncertainty factors for the UK statement. The Subgroup is of the view that there is still uncertainty about the effects of CBD on reproduction and hence caution on the use of CBD by vulnerable groups is appropriate.

In the absence of sufficient reliability or robust statistical power in some cases, the ANSES systematic review did not resolve existing uncertainties and data gaps. Notably the impact of CBD on total body burden, neurodevelopmental and behavioural changes were data gaps that were previously identified and not addressed sufficiently enough by the new data. Members agreed that these should be closely monitored to ensure that the scale of impact is not larger than that accounted for by the uncertainty factors. These were considered in reviewing the applicability of the current 300-fold uncertainty factor applied in the establishment of a provisional acceptable daily intake of CBD in foods in 2023^(footnote).

While the findings from the studies cited by ANSES reinforced the need for data to address these uncertainties in the longer term, the studies did not extensively explore these areas and members agreed that the uncertainties remain unaddressed.  In light of this, the Subgroup agreed that consideration of the current gaps still supported the use of an additional uncertainty factor of 3 (in addition to the “standard” uncertainty factor of 100). The applied factor still covers the uncertainties sufficiently to support safe use of CBD at exposures up to the provisional ADI. Advice for vulnerable groups including pregnant and lactating women and other specifically identified vulnerable groups including those taking medication and the immunosuppressed not to consume CBD still remains. 

Conclusion

Following review, the opinion of the ACNFP/COT Subgroup was that none of the new datasets or extra published works resolved any of the uncertainties that were identified when the provisional ADI was established.

The Subgroup considers that the current 300-fold uncertainty factor should remain and provides sufficient reassurance in the light of remaining uncertainties relating to reproductive toxicity. However, the remaining critical data gaps and uncertainties mean that the FSA’s application of a careful approach, which states CBD should not be consumed by pregnant or breastfeeding women, children, prospective parents trying for a baby, by people taking medication and those who are immunosuppressed, still stands. There is no new evidence that would justify a change in this position and, as such, these groups should continue to be regarded as potentially vulnerable groups.

The Subgroup affirms that the aforementioned caveats, vulnerabilities and the issue of total body burden, support the 2023 recommendations from the ACNFP/COT Subgroup and the resulting FSA consumer guidance, irrespective of the results presented within the ANSES proposal.

Therefore, it was the Subgroup’s view that the provisional ADI should remain unchanged, alongside existing advice that underpins FSA 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, prospective parents trying for a baby, and those who are immunosuppressed are advised against consumption of CBD due to remaining data gaps and residual uncertainties concerning the safety of CBD for these groups of consumers.