Hexadecane-induced hyperkeratinization of guinea pig skin. III. Cutaneous penetration of topically applied hexadecane-1-C-14.

The C-14 content of epidermis, dermis, subdermal muscle and certain other tissues was determined 48 hours following topical application of hexadecane-1-C-14 to the skin of guinea pigs. The effect of simultaneous application of U.S.P. heavy mineral oil, n-docosane, and heptane as well as hexadecane pre-treatment on the extent of penetration of hexadecane-1-C-14 was also measured. Large amounts of C-14 were found in the epidermis whereas relatively little accumulated in the dermis and underlying tissues. Each of the carrier vehicles reduced the amount of C-14 in the epidermis; whereas, docosane and mineral oil, but not heptane, reduced the amount of C-14 in the dermis and subdermal muscle. This correlated with the ability of heavy mineral oil and docosane, but not heptane, to decrease the dermatoxic effects of hexadecane. Pre-treatment of the skin with hexadecane 48 hours prior to application of hexadecane-1-C-14, if anything, increased the amount of the C-14 in the epidermis; however, pre-treatment with mineral oil:hexadecane reduced the amount of epidermal and dermal C-14 from a subsequent application of mineral oil:hexadecane-1-C-14. The results support the proposal that heavy mineral oil and alkanes with a chain length of over 20 carbon atoms reduce the dermatoxic effect of hexadecane by interfering with its penetration to the site of action. This site would appear to be either the deeper layers of epidermis or possibly the dermis. The increased uptake of hexadecane-C-14 by the epidermis following pretreatment with hexadecane provides a possible explanation for the more severe response seen with multiple hexadecane applications as opposed to a single application of the same amount of material.