Topical absorption and inactivation of cytotoxic anticancer agents in vitro

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. Cytotoxic anticancer agents may pose carcinogenic or teratogenic risks to personnel who prepare or administer drugs to patients with cancer. Methods. 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. Results. Drug levels passing through human abdominal skin exposed in vitro for 24 hours to 100 μg of daunorubicin, doxorubicin, and melphalan were negligible and typically less than the high-performance liquid chromatography sensitivity limit of 1-5 ng/ml (≤ 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 g/l for complete inactivation. Conclusions. 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 topical inactivation of certain carcinogenic cytotoxic agents.

Original languageEnglish (US)
Pages (from-to)983-987
Number of pages5
JournalCancer
Volume70
Issue number4 SUPPL.
StatePublished - 1992

Fingerprint

Cytotoxins
Antineoplastic Agents
Daunorubicin
Melphalan
Pharmaceutical Preparations
Anthracyclines
Doxorubicin
High Pressure Liquid Chromatography
Intercalating Agents
Skin Absorption
Mitoxantrone
Reverse-Phase Chromatography
Powders
Tablets
Air
In Vitro Techniques
Skin
DNA
calcium hypochlorite
Neoplasms

Keywords

  • anthracyclines
  • handling
  • hazards
  • hypochlorite
  • melphalan
  • mutagens
  • skin toxicity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Topical absorption and inactivation of cytotoxic anticancer agents in vitro. / Dorr, Robert T; Alberts, David S.

In: Cancer, Vol. 70, No. 4 SUPPL., 1992, p. 983-987.

Research output: Contribution to journalArticle

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abstract = "Background. Cytotoxic anticancer agents may pose carcinogenic or teratogenic risks to personnel who prepare or administer drugs to patients with cancer. Methods. 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. Results. Drug levels passing through human abdominal skin exposed in vitro for 24 hours to 100 μg of daunorubicin, doxorubicin, and melphalan were negligible and typically less than the high-performance liquid chromatography sensitivity limit of 1-5 ng/ml (≤ 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 g/l for complete inactivation. Conclusions. 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 topical inactivation of certain carcinogenic cytotoxic agents.",
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