Measurement of Bioavailability: Measuring Absorption Through Skin In Vivo in Rats and Humans

Stephen V. Bounds1, David R. Hawkins1

1 Huntingdon Life Science, Huntingdon
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 5.2
DOI:  10.1002/0471140856.tx0502s00
Online Posting Date:  May, 2001
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Absorption through the skin is a route of exposure to a wide variety of therapeutic and/or environmental compounds. In vivo assays are advantageous in that they retain intact epidermal and dermal structures and thus reflect a more normal situation. The test compound is applied to the skin in a protected area for a specified period of time. At the end of the incubation, skin, tissues, and excreta are assessed for the presence of the test compound. The assay can also be performed with volatile compounds. When performed using laboratory animals, it is possible to assess the distribution of the compound throughout the body. If human volunteers are studied such analysis is limited to the skin, blood, and excreta.

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Table of Contents

  • Basic Protocol 1: Measurement of Dermal Absorption in the Rat
  • Alternate Protocol 1: Measurement of Absorption of Volatile Compounds
  • Basic Protocol 2: Measurement of Dermal Absorption in Human Volunteers
  • Commentary
  • Figures
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Basic Protocol 1: Measurement of Dermal Absorption in the Rat

  • Radiolabeled test compound (labeled with 14C or 3H) at >98% purity
  • Adult male rats, 8 to 12 weeks old, 225 to 250 g (at least four per data point)
  • Solvents such as acetone or methanol
  • Oxidizer
  • Sodium hydroxide
  • Triton X‐405
  • Animal clippers
  • Spacer: saddle (silicon rubber) or O‐ring (Teflon, or nonabsorbent rubber)
  • Adhesive (cyanoacrylate: e.g., Superglue)
  • Gauze (metal mesh or plastic) to fit above spacer
  • Application device, e.g., syringe or calibrated pipet (Gilson or equivalent)
  • Metabolism cages (Jencons)
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Literature Cited

Literature Cited
   Hayes, W.J. 1983. Ethical considerations involving studies of pesticides and other xenobiotics in man. In IUPAC Pesticide Chemistry: Human Welfare and Environment, Vol. 3. Mode of Action, Metabolism & Toxicology (J. Miyamoto and P.C. Kearney, eds.) pp. 387‐394. Pergamon Press, London.
   Susten, A.S., Dames, B.L., and Nieneier, R.W. 1986. In vivo percutaneous absorption studies of volatile solvents in hairless mice. I. Description of a Skin‐Depot. J. Appl. Toxicol. 6:43‐46.
   Wester, R.C. and Noonan, P.K. 1980. Relevance of animal models for percutaneous absorption. Int. J. Pharmaceutics 7:99‐110.
   Wester, R.C., Sedik, L., Melendres, J., Logan, F., Maibach, H.I., and Russell, I. 1993 Percutaneous absorption of diazinon in humans. Fd. Chem. Toxicol. 31:569‐572.
   Wester, R.C., Bucks, D.A.W., and Maibach, H.I. 1994. Human in vivo percutaneous absorption of pyrethrin and piperonyl butoxide. Fd. Chem. Toxicol. 32:51‐53.
   Wilks, M.F. and Woollen, B.H. 1994. Human volunteer studies with non‐pharmaceutical chemicals: Metabolism and pharmacokinetic studies. Hum. Exp. Toxicol. 13:383‐392.
   Winter, S.M. and Sipes, I.G. 1993. The disposition of acrylic acid in the male Sprague‐Dawley rat following oral or topical administration. Fd. Chem. Toxicol. 31:615‐621.
Key References
   Anonymous. 1993. Subdivision F. Hazard Evaluation—Humans and Domestic Animals: Proposed New Guideline Section 85‐3. Dermal Absorption Studies of Pesticides. Fed Regist. 58202‐54350.
   Declaration of Helsinki, 1983 (revised version, October 1983). In Good Clinical Practice in Europe (M.E. Allen, ed.) pp. 73‐76. Rostrum, Romford, U.K.
   Environmental Protection Agency (EPA). 1993. Dermal Exposure Assessment: Principles and Application. EPA Report No. EPA/600/8‐92/022B. U.S. Department of Commerce, Washington, D.C.
   Organisation for Economic Co‐operation and Development (OECD) Environmental Health and Safety Division. Proposal for Two New Guidelines on Percutaneous Absorption. OECD Environmental Health and Safety Division Discussion Document, ref. ENV/EHS/HK/ mc/94.103. OECD, Paris.
   U.K. Department of Health. 1984. Notes of Guidance on the Administration of Radioactive Substances for Purposes of Diagnosis, Treatment or Research. Administration of Radioactive Substances Advisory Committee, Enclosure HN 84 5. U.K. Department of Health, London, U.K.
   World Medical Association. 1982. Proposed International Guidelines for Biochemical Research Involving Human Subjects. World Health Organization, Geneva.
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