Skin irritant effects of esters of phorbol and related polyols

The skin irritant potencies of several naturally occurring and semisynthetic polyfunctional esters based on the tigliane hydrocarbon skeleton were studied using a mouse ear irritancy assay. The compounds used were esters of 12-deoxyphorbol, 12-deoxy-16-hydroxyphorbol, and phorbol. Observations were also made on the time interval between application of these compounds in acetone solution to the mouse ear, and the attainment of maximum response. Structure/activity relationships are discussed and compared with previous observations on the skin irritant potencies of esters based on the closely related daphnane hydrocarbon skeleton. The possible nature of the site of action in the target membrane is also discussed.