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

Endpoint summary

Additional information

No key studies are available for the assessment of the toxicokinetics, metabolism and distribution of racemic (+/-) alpha-Bisabolol.

Based on its physicochemical properties, i.e. small molecular weight, moderate LogPow and low to moderate water solubility at room temperature (MW=222.37, Log Kow = 4.8; Water solubility = 28 mg/L), (+/-) alpha-Bisabolol is considered to become readily bioavailable via the dermal and oral route. On the basis of an expected low vapour pressure at room temperature (Vapour pressure = 95 Pa at 109°C), the exposure of (+/-) alpha-Bisabolol via inhalation as a vapour is low. Systemic toxicity signs have been observed in rats after repeated oral dosing of (-) alpha-Bisabolol above the limit dose, indicating bioavailability via the oral route. In this study, urinalysis revealed a positive ketone body reaction. No clinco-chemical parameters indicated any impairment of the lipid metabolism, therefore, alpha-Bisabolol is assumed to be metabolized and excreted as ketone bodies via the urine. 

In a dermal penetation study in mice reported in literature using the stereoisomer (-) alpha - Bisabolol, i.e. a main component of racemic (+/-) alpha - Bisabolol, evident dermal absorption has been observed ( Hahn B., Hölzl J., 1987). The radiolabeled test substance was prepared by biochemical incorporation of [14C] acetate into the molecule. The test substance was applied to the skin of nude mice of the NMRI strain, either with Arlatone or with acetone. The mice were sacrificed at 1, 3 and 5 hours after application and radioactivity was measured in samples of skin, fat and muscle tissues. After 1 hour, 80% of the applied radioactivity remained on and in the skin at the application site. By 3 hours radioactivity at the exposure site decreased to 57%. Five hours after topical application, approx. 50% of the applied dose was detected in or on the skin. 14C-alpha Bisabolol was also detected in both fatty and muscular tissues of the neck. Ninety percent of this radioactivity was analysed as intact test substance. In order to demonstrate the distribution of the test substance in the skin, a part of this tissue was cut into horizontal slices by a cryotome. Autoradiograms of these sliced were produced. Densitometric measurement showed that there was a fast penetration of the test substance into the skin. Five hours after the topical application, the test substance was displaced from outermost to innermost areas.

Pretreatment of epidermis from abdominal human cadaver skin with a 1:1 alpha-Bisabolol:propylenglycol mixture increased the permeability of 5-fluorouracil and triamcinolone acetonide by 17- and 73-fold, respectively (Andersen 1999). A 5.4-fold increase in the permeability of 5-FU was observed after pretreatment with alpha-Bisabolol alone.

Overall, a good bioavailability via the oral and dermal route is to be considered for (+/-) alpha-Bisabolol.

 

References  (not included as endpoint study record)  

Andersen 1999; Thirty-ninth report of the Cosmetic Ingredient Review Expert Panel; Int J Toxicol; Vol 18, Suppl 3.