title: Dietary intake and risk assessment of phototoxic furocoumarins in humans.
abstract: The question of whether the furocoumarin content of vegetables is sufficient to induce phototoxic skin reactions after ultraviolet irradiation was examined in two experiments with four human volunteers. In a first experiment, 300 g of celery roots (total phototoxic furocoumarin content 28.2 micrograms/g) was ingested. No skin reactions were observed after UVA exposure (1.5-9 J/cm2), and the blood levels of the furocoumarins--psoralen, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP)--were below the analytical detection limit of 2 ng/ml. To investigate the phototoxic effects of a mixture of the two most important furocoumarins in vegetables, after gastro-intestinal uptake, 8-MOP and 5-MOP (15 mg each) were ingested separately in a 50% alcoholic solution. A strong and persistent erythema was induced in three out of the four subjects (UVA dose: 3-25 J/cm2). The blood levels immediately before UVA irradiation varied between 14 and 114 ng/ml (8-MOP), and 17 and 70 ng/ml (5-MOP). In the subject who did not show phototoxicity, the blood levels remained at trace levels (3 ng/ml). Two subjects were also tested with a mixture of 10 mg 8-MOP plus 10 mg 5-MOP; in one subject the mixture induced pigmentation only, while in the other a mild-to-medium erythema was induced. The blood levels of the furocoumarins in the two subjects were similar (12-15 ng/ml for 8-MOP and 5-MOP). It is concluded that in humans the phototoxic threshold dose of furocoumarin mixtures is of the order of 10 mg 8-MOP plus 10 mg 5-MOP, which is equivalent to about 15 mg 8-MOP per person (blood levels of 8-MOP and 5-MOP at 30 min after ingestion of about 10-15 ng/ml each). This phototoxic threshold dose was not reached by the consumption of celery roots and other conventional vegetables under normal dietary habits (experimental intake of 2-8 mg per subject of the potentially phototoxic furocoumarin mixture). However, the safety factor between the possible actual intake of furocoumarins and the phototoxic threshold dose is about 2-10, which is relatively small.
authors.affiliation: Swiss Federal Office of Public Health, Division of Food Science, Bern, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Schlatter
authors.forename: B
authors.initials: B
authors.lastname: Zimmerli
authors.forename: R
authors.initials: R
authors.lastname: Dick
authors.forename: R
authors.initials: R
authors.lastname: Panizzon
authors.forename: C
authors.initials: C
authors.lastname: Schlatter
mesh_terms: D000078223:5-Methoxypsoralen; D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid; D011564:Furocoumarins / Q000097:blood; D006801:Humans; D008297:Male; D008730:Methoxsalen / Q000008:administration & dosage / Q000009:adverse effects*; D010787:Photosensitivity Disorders / Q000097:blood / Q000139:chemically induced*; D012307:Risk Factors; D014466:Ultraviolet Rays / Q000009:adverse effects; D014675:Vegetables
chemical_list: D011564:Furocoumarins; D000078223:5-Methoxypsoralen; D008730:Methoxsalen