A broader view on deriving a reference dose for THC traces in foods

Area of Science:

• Food Safety
• Toxicology
• Pharmacology

Background:

• The European Food Safety Authority (EFSA) established an Acute Reference Dose (ARfD) of 1 µg/kg bw/day for delta-9-tetrahydrocannabinol (THC).
• This ARfD was based on potential acute health risks from industrial hemp food products.
• The scientific basis for EFSA's 2015 opinion, including the selection of a Point of Departure and the absence of a No Observed Adverse Effect Level (NOAEL), requires critical review.

Purpose of the Study:

• To critically review the scientific basis for EFSA's recommended ARfD for THC.
• To reconsider the risk assessment for deriving an ARfD for THC.
• To establish a revised, evidence-based ARfD for THC in food products.

Main Methods:

• Review of pharmacokinetic and pharmacodynamic studies.
• Analysis of forensic data from healthy human cohorts.
• Identification of Lowest Observed Adverse Effect Level (LOAEL) and derivation of a No Observed Adverse Effect Level (NOAEL) for THC.
• Application of uncertainty factors for deriving a tolerable upper intake level.

Main Results:

• A higher LOAEL for THC's effects on the central nervous system was identified compared to EFSA's 2015 assessment.
• A NOAEL was derived, indicating a threshold for psychomotor function impairment only after oral THC intake exceeding 2.5 mg.
• This 2.5 mg dose corresponds to mean THC blood serum levels below 2 ng/mL, within the forensic threshold for impairment (2-5 ng/mL).

Conclusions:

• A NOAEL of 2 x 2.5 mg THC per day (taken ≥6 hours apart) is proposed for healthy adults.
• This leads to a revised tolerable upper intake level (or 'daily dose of no concern') of 7 µg/kg bw/day.
• The most conservative estimate for a daily ARfD is 3.5 µg/kg bw/day, with other justifiable estimates up to 14 µg/kg bw/day.