Bergapten In Citrus Extracts Poses Phototoxic Skin Risk, EFSA Confirms

Citrus Phototoxicity: Bergapten, Furocoumarins, and Skin Risk

A 2021 European Food Safety Authority (EFSA) opinion confirmed that bitter orange extract containing 5-methoxypsoralen (bergapten) is a skin irritant, sensitiser, and potential phototoxic agent. This assessment highlights a critical concern for perfumers and formulators using citrus-derived ingredients. Furocoumarins, phototoxic compounds prevalent in many citrus oils, necessitate careful understanding and management to mitigate skin risks.

Dietary Intake of Furocoumarins Raises Skin Cancer Risk

A 2020 study conducted by researchers from Brown University, Harvard, and the University of Connecticut analyzed data from 58,466 women and 48,311 men across two long-term US cohort studies. Published in the Journal of Investigative Dermatology, the study found that participants with the highest dietary intake of furocoumarins—primarily from citrus fruits like oranges, grapefruit, and lemons—had a 38% greater risk of developing squamous cell carcinoma compared to those with the lowest intake.

The study used food frequency questionnaires and a database of furocoumarin concentrations in foods to quantify intake. It adjusted for established risk factors such as UV exposure, sun sensitivity, and geographic location. The findings suggest a systemic mechanism: furocoumarins consumed and absorbed into the bloodstream are activated by UV light, leading to cellular DNA damage. This biochemical mechanism applies equally to furocoumarins applied directly to the skin in fragrant products.

How Furocoumarins Damage Skin Cells Under Light

Bergapten and psoralen are planar, tricyclic aromatic molecules capable of intercalating between DNA base pairs. Upon absorption of UVA radiation (320-400 nm), these molecules become excited and form covalent cross-links between DNA strands, inhibiting DNA replication and cell division.

This process results in cell death, inflammation, and phototoxic responses such as severe erythema, blistering, and hyperpigmentation resembling burns. Chronic DNA damage from this mechanism can contribute to mutagenesis and carcinogenesis, as evidenced by the 2020 cohort study. The phototoxic effect depends on furocoumarin concentration, UV dose, and individual skin sensitivity. Notably, EFSA also identified bitter orange extract as a skin sensitiser, adding to its hazard profile.

EFSA’s Assessment Reflects Broad Regulatory Caution

EFSA’s Feed Additives Panel evaluated bitter orange extract for animal feed safety, concluding it is safe only at limited concentrations (102 to 400 mg/kg, depending on the species). For dogs, cats, and ornamental fish, EFSA could not establish safety due to insufficient data.

More relevant for fragrance formulation were EFSA’s hazard classifications: irritant to skin, eyes, and respiratory tract; skin sensitiser; and phototoxic due to bergapten content. This multi-hazard profile underscores why the International Fragrance Association (IFRA) maintains strict standards limiting furocoumarins, particularly bergapten, in cosmetic products. The EFSA opinion highlights the need for careful evaluation even in non-cosmetic applications involving skin contact.

Practical Guidance for Perfumers and Formulators

Managing furocoumarin risk begins with ingredient selection. Many citrus essential oils, especially cold-pressed oils like bergamot, lime, and bitter orange, contain significant levels of bergapten. Industry practice often employs bergapten-free distillates, where furocoumarins are removed through a second distillation process, ensuring compliance with IFRA Standards.

Formulators must verify IFRA Certificates of Conformity for all citrus ingredients to ensure bergapten limits are met. For leave-on products applied to sun-exposed skin areas—such as perfumes, creams, and lotions—the limits are most stringent. The 2020 cohort study suggests that systemic exposure from high dietary intake may also contribute to risk, though dermal application from cosmetics typically delivers a more localized dose.

Clear product labeling is essential. While phototoxicity is not an allergic reaction, warning consumers to avoid sun exposure on areas where citrus-rich fragrances are applied is a responsible measure, particularly for products using natural citrus extracts with non-standardized compositions. This aligns with broader transparency needs for products designed for sensitive populations.

In summary, the phototoxicity of citrus furocoumarins like bergapten is a well-documented chemical risk supported by recent epidemiological and regulatory assessments. Perfumers and formulators can effectively manage this risk by using processed, compliant ingredients, adhering to IFRA Standards, and providing appropriate user guidance, ensuring the safe use of citrus in fragrance applications.

Sources:
https://pubmed.ncbi.nlm.nih.gov/34335921/
https://pubmed.ncbi.nlm.nih.gov/32221600/
https://pubmed.ncbi.nlm.nih.gov/11511848/