3-Cyclohexene-1-methanol, α,4-dimethyl-α-(4-methyl-3-penten-1-yl)-

Endpoint summary

Description of key information

Skin irritation (OECD 404, GLP): not irritating (BASF 1989; 18H0646/882254)
Eye irritation (OECD 404, GLP): not irritating (BASF 1989; 11H0646/882255)

Additional information

Skin irritation

In the key in vitro study, i.e. EpiDerm™ Corrosivity test, (-) alpha-Bisabolol (nat. roh), a main component (stereoisomer) of the registered substance racemic alpha-Bisabolol, was found to be non corrosive under the chosen testing conditions (BASF 2001; 61H0588/002196). The mean viability of the test substance treated tissues determined after 3 minutes and 1 hour was 105% and 124% of the negative control, respectively. For the assessment of the irritating potential an in vivo key study according to OECD 404 and GLP is available. Here, (-)-αlpha-Bisabolol has been dermally applied undiluted (semiocclusive) to 3 Vienna White rabbits for 4 hours (BASF 1989; 18H0646/882254). The mean scores (24, 48, 72 hours) were 1.0, 0.3, 1.7 for erythema and 0, 0, 0.3 for edema for each animal respectively. All findings were fully reversible within 7 days.

In a supporting study, not according to current guidelines, 6 New Zealand White rabbits have been treated dermally with undiluted (+/-)-αlpha-Bisabolol for 24 hours under occlusive dressing (BASF 1979, 79/65). Mean scores (25h, 72h incl. all animals) were 0.3 for erythema and 0.3 for edema, respectively.

Several other studies using alpha-Bisabolol at lower concentrations in human patch tests and animal tests did not indicate evident skin irritation properties.

Overall, based on the available data, racemic (+/-)-αlpha-Bisabolol is considered to be not irritating to skin.

 

Eye irritation

As key in vitro study, a Chorioallantois Membrane in vitro corrosion test (HET-CAM) is available to evaluate the potential of the test substance to induce ocular damage (BASF 2001; 60H0588/002197). The stereoisomer (-) alpha-Bisabolol (nat. roh; undiluted and 10% in olive oil) as a main component of the registered substance racemic alpha-Bisabolol was applied to the chorioallantois membrane (3 eggs per test concentration). The time until appearance of effects was measured. Time until the presence of hemorrhagia, lysis, and coagulation was determined to be 301 seconds after application. Accordingly, the irritation index was 0 for both the undiluted test substance and the 10% solution. Overall, Bisabolol nat. roh was determined to be non-corrosive under the conditions of this in vitro test and does not imply the risk of serious damage to the eye.

For the assessment of the eye irritation potential, an in vivo key study according to OECD 405 and GLP is available. Here, (-)-alpha-Bisabolol has been applied undiluted to the conjunctival sac of the right eyelid of 3 Vienna White rabbits (BASF 1989; 11H0646/882255). The mean scores (24, 48, 72 hours) were 1.0, 1.3, 1.3 for conjunctival redness of each animal respectively and findings fully reversed within 72 hours. Mean scores for corneal opacity, iritis and chemosis were 0 for all animals assessed.

In an eye irritation study not according to current guidelines, a single application of 0.1 mL of unchanged (+/-)-alpha-Bisabolol into the right eye of 6 New Zealand White rabbits was performed (BASF 1979; 79/65). A mean irritation score (24h, 48h, 72h; all animals) of 1 was determined for corneal opacity. This effect was fully reversible within 4 days. The mean scores for iritis, conjunctival redness and chemosis (mean 24h, 48h, 72h; all animals) were 0.8, 1 and 1.8, respectively. These effects were not fully reversible within the 7 days observation time. Restriction of the performed test is that the observation time was not 21 days as required according to OECD 405. Accordingly, it can not be verified whether the effects were completely resolved within 21 days. Under the test conditions chosen, an irritating potential of the test substance to the eye cannot be fully excluded, however, less than 4/6 animals reached the relevant threshold for classification according to the CLP criteria.

Overall, based on the available data, racemic (+/-)-αlpha-Bisabolol is considered to be not irritating to eyes.

Justification for classification or non-classification

The present data on skin and eye irritation do not fulfill the criteria laid down in 67/548/EEC and regulation (EU) 1272/2008, and therefore, a non-classification is warranted.