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Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Additional information:

Skin sensitization

Divergent results have been obtained by testing alpha-Bisabolol for its skin sensitizing properties.

LLNA:

In the chosen key study, i.e. a LLNA acc. to OECD 429 and GLP, (+/-) alpha-Bisabolol (Dragosantol® 100; purity 95.2%) has been applied to 4 CBA mice per group at 0% (vehicle only) 10%, 25% and 50% in acetone/olive oil (Symrise 2010; C97160). In this study, the stimulation index was determined to be 1.9, 4.0 and 7.9 at 10%, 25% and 50%, respectively. The EC3 value calculated was 17.9%. Neither clinical signs (including dermal irritation) on the ears of the animals nor systemic findings were observed during thestudy period. Based on the chosen testing conditions,(+/-) alpha-Bisabolol was found to be a skin sensitizer.

 

Maximization Test:
In support, a guinea pig maximization test acc. to OECD 406 and GLP is available (Scantox 1998; 01517). For induction, 5% alpha-Bisabolol nat. (purity 98.7%) in peanut oil has been injected intradermally and applied dermally undiluted (occlusive) for 48 hours one week later. After a 14 day resting period, animals were challenged with undiluted alpha-Bisabolol nat. for 24 hours (occlusive) or with the vehicle alone on the anterior or posterior right flank, respectively. After the challenge treatment with alpha-Bisabolol nat. slight erythema (grade 1) was observed in 1 control group animal and in several treatment group animals. In addition, 9/20 animals of the treatment group showed moderate skin reactions (grade 2) after 48 hours and 13/20 animals showed consistent skin reactions at the 24 and 48 hour timepoints. No skin reactions were observed after challenge application of the vehicle only.

A rechallenge has been performed one week after the challenge in the same manner, but with a test article concentration of 25%. No animal of the control group showed any skin reactions. In contrast, 1/20 test group animals showed moderate skin reactions (grade 2) after 48 hours, 2/20 animals showed consistent skin reactions at 24 and 48 hours. No skin reactions were observed after challenge application of the vehicle only.

Notably, at both challenges, there was a suggestion of a greater degree of reaction at the later scoring point, which is consistent with the reactions being allergic rather than irritant in nature. Under the chosen testing conditions, it has been concluded that alpha-Bisabolol nat was generative of provoking a delayed contact hypersensitivity as 9 out of 20 animals were sensitized.

Buehler Test:

In a Buehler test acc. to OECD 406 and GLP, (+/-)-alpha-Bisabolol rac. (purity 86.6%) has been applied undiluted weekly 3 times for 6 hours (occlusive) for induction (BASF 1999; 32H0480/982180). After a 14 day resting period, animals werechallenged with 50% (+/-)-alpha-Bisabolol rac. in Lutrol E 400 DAB for 6 hours (occlusive) or with the vehicle alone on the anterior or posterior right flank, respectively. After the challenge treatment with 50% (+/-)-alpha-Bisabolol rac. no skin reactions were observed in the treatment group (0/20 animals) or control group (0/10 animals). In conclusion, the results of this study show that (+/-)-alpha-Bisabotol rac. does not have a sensitizing effect on the skin of the guinea pig in the BUEHLER Test under the test conditions chosen.

In a Freund complete adjuvant test, taken from literature with limited documentation, (-)-alpha-Bisabolol has been applied intracutaneously at a concentration of 1% into the nape of the neck of Pirbright-Hartley guinea pigs on days 1, 5, 9, 13, 17, and 21 for induction (Hausen 1984). At 10-12 days after the last induction, 1% (-)-alpha-bisabolol in FCA/saline (1:1), was topically applied for challenge. No skin reactions have been reported in any test animal at any reading. 

 

Human tests:

In a HRIPT, 107 subjects have been treated with 9 repeated dermal applications (occlusive, 24 hours respectively) of 10% (estimated:5600 µg/cm2) of (+/-)-alpha-Bisabolol (Dragosantol 100, purity 95.2%; same batch used as in key study) in DEP/EtOH (3:1) for induction (Symrise 2010; C10-3860.01). After a recovery of 14 days after the last induction treatment, a single challenge application was made according to the induction procedure and skin reactions were scored 24h and 72h post-application. No skin reactions were recorded after challenge in any subject. Therefore (+/-)-alpha-Bisabolol (Dragosantol 100) at a concentration of 10% (5600 µg/cm2) did not indicate a potential for dermal irritation or allergic contact sensitization under the chosen testing conditions.

In a human maximization test from secondary source with limited documentation, repeated dermal application of chamomile oil (4% in petrolatum) under occlusion was performed for five alternate-day 48 hour periods to 25 male subjects (Kligmann 1973). Patch test sites were pretreated for 24 hours with 5% aqueous sodium lauryl sulfate under occlusion. Following a ten-day rest period, a challenge patch was applied to a fresh site for 48 hours under occlusion (pretreated for 1 hour with 10% aqueous sodium lauryl sulfate under occlusion). No skin senstitization reactions were observed under the chosen testing conditions.

Taken together, in the available human tests and the Bühler test in guinea pigs, no skin sensitizing potential was observed for alpha-Bisabolol or Chamomile oil. However, it is not possible to exclude the possibility that alpha-Bisabolol displays some potential for skin sensitisation. This conclusion is based on the positive results of the LLNA performed with Dragosantol 100 with an analytical purity of 95.2% and a GPMT performed with Bisabolol alpha nat., with a purity of 98.7 %. Therefore racemic (+/-)-alpha-Bisabolol is considered to be a skin sensitizer.


Migrated from Short description of key information:
Skin sensitization:
LLNA (acc. OECD 429, GLP): skin sensitizer (Symrise 2010; C97160)

Respiratory sensitisation

Endpoint conclusion
Additional information:

No data available.

Justification for classification or non-classification

The present data on dermal sensitization fulfill the criteria laid down in 67/548/EEC and regulation (EU) 1272/2008, and therefore, a classification with R43 and "Skin sensitisation" (Category 1B) is warranted.

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