The second most frequent ADR trigger (84 clock-stopped issues across 44 opinions) and the hardest to recover from: 29% of assessments end inadequate — the highest rate of any section. Missing or flawed toxicological studies are the single most common cause of unfavorable opinions. The 90-day subchronic study and the genotoxicity battery are the most critical requirements.
The specific issues EFSA most frequently flags in this section. Each of these has caused a clock stop in at least one published case.
Tiered approach: Tier I — genotoxicity battery (bacterial reverse mutation + in vitro mammalian cell test); Tier II — 90-day subchronic study in rodents (OECD TG 408); Tier III — reproductive/developmental toxicity and chronic studies if indicated. All studies GLP-compliant, conducted on material representative of the final commercial product. Clear NOAEL derivation with margin of exposure calculation. For fermentation-derived products: genotoxicity testing on both the final product and the culture supernatant. Human tolerance or clinical safety data where available.
Real findings from EFSA panel opinions. Each quote is verbatim from a published assessment.
“No reproductive and developmental toxicity studies with α-tocopherol-containing oil suspensions of lycopene extracted from B. trispora have been performed.”
“In consideration of these equivocal results and taking into account the trend of increased micronucleated cells observed, the applicant was requested to repeat the in vitro micronucleus study, using cytochalasin B.”
“Applying a default uncertainty factor of 200 to the NOAEL, the Panel considers that the margins of exposure (i.e. 55 in adolescents and 19 in infants) between the intake of the NF at the proposed use and use levels and the identified NOAEL are insufficient.”
“Given the limitations of the human study provided (e.g. small number of subjects, short duration, low dose, limited safety endpoints) and the absence of history of safe use of the NF and/or its source, EFSA requested a 90‑day subchronic toxicity study.”
How this section plays out differently depending on your novel food type.
Full genotoxicity battery + subchronic study almost always required. Chronic study may be needed depending on intended use level and population exposure. Human clinical data often specifically requested.
Human safety data at proposed doses is a known data gap per EFSA’s 2021 statement. Long-term effects remain unresolved.
Genotoxicity testing on the culture supernatant is a critical and frequently missed requirement. EFSA has developed specific guidance for microorganism-derived products.
Human studies on infant populations specifically relevant given the target consumer group.
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