Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Several animal studies were available for skin sensitization with Vanillin. Amongs of them, four were of reliability 2; One of them was selected as key study and had reliability 2 (Hazleton, 1992), and the others were selected as supporting studies with reliability 2 (Basketter, 2001; Gad, 1986; Wang, 1987).

The key study was a maximization test, and the summary is the following:

In a dermal sensitization study (Hazleton, 1992) with Vanilline cristallisée (purity unknown) in ethanol, young adult Dunkin-Hartley guinea pigs (10/sex) were tested using the method of Maximization. The doses tested for induction and challenge phases were: 35% (intradermal induction), 73% (epicutaneous induction and challenge)
Signs of irritation were noted during the induction.
The macroscopic examinations did not reveal any lesion of delayed hypersensitivity in the 20 treated animals. No cutaneous abnormality was noted in the 20 guinea pigs examined in the control group.
From the result obtained under the experimental conditions employed, vanillin did not provoke any reaction of cutaneous sensitization in the animals examined.

Two other studies were a LLNA and a MEST tests. In the first one (Basketter et al., 2001), CBA/Ca mice (4 females) were testing with Vanillin in acetone/olive oil (4:1 v/v), using the method of Local Lymph Node Assay (LLNA) at doses of 0, 2.5, 5, 10, 25 and 50%. During the study no positive lymphoproliferative response were observed at all doses tested. In this study, Vanillin was not a dermal sensitizer.

In the study of Gad et al (1986) CF-1 female mice were tested in a Mouse Ear Swelling Test (MEST) with Vanillin (purity unknown).All mice were topically dose with 100 µl of Vanillin in solvent (50%) or solvent alone (controls) applied to the center of the shaved region. The application was allowed to dry before the animal was returned to its cage. Tape stripping and topical application of the appropriate solution to the stomach were repeated for 3 additional consecutive days. Seven days after the final topical application to the stomach, 20 µl of Vanillin in solution (50%) was applied to the left ear of each animal (test and control) and 20 µl of the solvent was applied to the right ear. At both 24 an 48 hours after this challenge, animals were lightly anesthetized with ether and the thicknesses of both ears were measured. Vanillin presented a percentage of swelling of 4%. In these conditions Vanillin could be considered as negative in MEST, and Vanillin was not sensitizing in this test.

The study of Wang et al (1987) investigated the skin irritation and sensitizing potential of chemicals in manufacture of Vanillin, using specific process with urotropine. In this study, male and female albino guinea pig were tested with Vanillinat 10or 100% using a modified Buehler test and at 100 % using a patch test. No signs of irritation were noted. In Buehler test the induction was done by topical application (occlusive) at 10% with Vanillin in petrolatum for 24 -hour application, 3 times in 2 weeks on napes of 10 animals. The challenge was done 2 weeks after final induction by topical application (occlusive) with 100% Vanillin on left flanks. No signs of sensitization were observed. A cross-reactivity was done with other substances and did not revealed cross-sensitization. Based on these results, Vanillin was neither irritant nor sensitizer.

Five other studies were not taken into account, because they had reliability 3 or 4, due to lack of details of the study, to permit to consider them for the assessment.

Three Human data with validity 2 confirmed the results obtained in animal studies. These studies were Patch tests on Humans (Hausen, 2001; Francalanci, 2000; Wang, 1987).

In the study of Hausen (2001), occlusive patch of 5% of Vanillin were applied for 24h to 102 volunteers already positive to BalsamPeru. Vanillin gave negative results on patients already sensitized with Balsam of Peru.

In the study of Francalanci (2000), 54 patients who presented eczematous lesions on the lips probably due to toothpastes, received occlusive patch test with 10% of Vanillin for two days. 1/54 patient react positively to Vanillin, it is not sufficient to consider Vanillin as sensitizing.

In the study of Wang (1987), Vanillin was tested with other substance of urotropine process for the manufacturing of the Vanillin. 0/45 patients had positive results, so Vanillin was not sensitizing in this patch test study

See section 7.10.4 for more details.

All the results available indicated that Vanillin was not a sensitizer.According to classification criteria of EC regulation 1272/2008 Vanillin should not be classified for sensitisation.

Migrated from Short description of key information:
Vanilline is not sensitizing based on studies on animals and humans.

Justification for classification or non-classification