Vanillin

Vanillin is the principal constituent of vanilla at 12 to 95 percent depending on quality. Vanillin occurs as a glycoside in vanilla and is released by enzymatic cleavage on curing. As a substituted phenol it has weak acid activity. Available data indicates it is safe at standard concentrations.

Skin. Non-irritating at 2 percent on 30 volunteers, 20 percent on 29 volunteers and 0.4 percent on 35 dermatitis patients. In 70 contact dermatitis patients at 10 percent no reactions occurred. At 2 or 5 percent on 25 volunteers it was non-sensitizing. Some Peru balsam-sensitive individuals show mild cross-reactivity. Non-phototoxic.

Oral. Acute oral LD50 in rats was 1.4 to 2.8 g/kg and in guinea pigs 1.4 g/kg. Intraperitoneal LD50 was 480 to 1,190 mg/kg depending on species. Subcutaneous LD50 in rats was 1.5 to 2.6 g/kg.

Subchronic and chronic. Rats given 530 mg/kg/day for 4 days showed no liver lesions. Mice fed 3,000 ppm for 91 days showed no adverse effects. At 10,000 ppm mild effects appeared. At 50,000 ppm growth retardation and enlargement of liver, kidneys and spleen occurred. Rats fed 1,000 to 50,000 ppm for up to two years showed no adverse effects at any dose below 50,000 ppm.

Reproductive. In an ex vivo assay, vanillin did not bind to estrogen receptors in female rat uterus tissue.

Mutagenicity. Not mutagenic in multiple Ames tests and rec assays. Antimutagenic in animal cells in vitro and in vivo. Reduced X-ray induced CA in mouse bone marrow and methotrexate-induced CA in hamster lung cells.

Cancer. Intraperitoneal mouse studies with total doses of 3.6 or 18 g/kg over 24 weeks did not increase primary lung tumors. Vanillin inhibited hepatic carcinogenesis in rats and inhibited carcinogenic nitrosamine activation in mouse hepatic and pulmonary microsomes.

Vanillin can be oxidized to vanillic acid or reduced to vanillyl alcohol. In rabbits, 69 percent of an oral dose was excreted as vanillic acid, either free at 44 percent or conjugated at 25 percent. In rats, one study reported 17 percent free and 24 percent conjugated. In humans, 73 percent of vanillic acid was found in urine, with 2 percent of unchanged vanillin.

Vanillin is a potent inhibitor of sulfotransferase enzymes involved in phenolic drug metabolism, and may also induce microsomal drug-metabolizing enzymes.

Synthetic vanillin is produced at very large scale for food and cosmetic flavoring, from guaiacol or lignin. Vanillin shows antimutagenic activity by enhancing recombinational DNA repair.

Vanilla absolute is used in fine fragrance and luxury cosmetics at very low concentrations. IFRA set a 0.5 percent limit for vanillin in leave-on products in 2009 but later withdrew the standard pending data review.