Topical absorption and inactivation of cytotoxic anticancer agents in vitro

Cytotoxic anticancer agents may pose carcinogenic or teratogenic risks to personnel who prepare or administer drugs to patients with cancer.

A series of laboratory studies were done to quantify the extent of percutaneous absorption and topical inactivation for various cytotoxic anticancer agents. Topical inactivation of anthracyclines and anthracene DNA intercalating agents was evaluated using Ames bacterial mutagenicity assays and reverse-phase high-performance liquid chromatography measurements.

Drug levels passing through human abdominal skin exposed in vitro for 24 hours to 100 micrograms of daunorubicin, doxorubicin, and melphalan were negligible and typically less than the high-performance liquid chromatography sensitivity limit of 1-5 ng/ml (less than or equal to 0.001% possible absorption). Melphalan powder was recoverable from the air near a mortar and pestle used to crush 14 2-mg tablets manually; beyond 12 inches, no airborne drug was recoverable. A standard (4%) concentration of calcium hypochlorite completely inactivated the anthracyclines daunorubicin and doxorubicin but not mitoxantrone. This agent required treatment at a calcium hypochlorite concentration of 432 milligrams for complete inactivation.

In summary, topical cytotoxic drug absorption is negligible (if it occurs at all). However, mechanical manipulations of oral formulations may present a risk of exposure to airborne drug particles. Concentrated calcium hypochlorite is extremely effective in the the topical inactivation of certain carcinogenic cytotoxic agents.