Animal Models of Skin Toxicity

Stephen R. Kaufman, M.D.

Animal models to determine dermatological toxicity of consumer products are scientifically inadequate. It is dangerous to put significant confidence in the animal tests, because the animal data and the human experience correlate poorly. The most reliable data has been and remains that which is obtained from human volunteers and from careful and thorough reporting of adverse reactions experienced by consumers.

There are two main areas of skin toxicity testing-irritancy and sensitization (allergic potential). Animal testing in irritancy is notoriously unreliable. Marks notes several fundamental differences in the structure of human and animal skin. He states, “These variations between species could well influence the results of testing for irritancy.”1

This certainly appears to be the case. Kligman writes:

Many substances that are completely benign for human skin will produce gross and microscopic damage in animals ... Furthermore, animal skin lacks the capacity to differentiate among substances which in human testing cover a range from very mild to moderately irritating.2

Philips et al, found that the ranking of irritants in animals is very different from that of man.3 Thus, Kligman summarizes:

As regards the great majority of materials that humans apply to the integument (skin) for cleansing, beautifying, and correcting surface abnormalities, it is safe to conclude that animal models are not reliable for predicting which of these may pose a hazard.2

There are several different tests for sensitization, all of which suffer fundamental scientific difficulties. Bronaugh and Mailback object to the Draize sensitization test as “...not sufficiently sensitive to identify the allergenic potential of many contact allergens.”4 Use of the complete Freund’s adjuvant (CFA) is more sensitive, but “...guinea pig tests that use CFA are so sensitive that they may identify as contact allergens materials whose allergenicity is trivial from a practical standpoint.”5

The guinea pig maximization test (GPMT) is considered by many toxicologists to be a superior test, but it too has difficulties. The protocol calls for intradermal injection of CFA alone and with 10% sodium lauryl sulfate. Thus, the exposure of lab animals is very different from the kind of contact humans have with potential sensitizers. Bronaugh and Mailback write, “The GPMT is an excellent procedure for identification of contact allergens, but it is far less adequate for predictive purposes for finished products.”4 While this test is fairly reliable for certain chemicals, it is less helpful in determining risk of sensitization to the products with which people actually come in contact.

For years, toxicologists have attempted to develop reliable animal models of dermal toxicity. However, it appears that basic differences between the skin of people and animals have confounded their efforts. Fortunately, new in vitro techniques offer hope for improved dermal toxicity testing. For example, the SkintemTM test determines the ability of a substance to penetrate a macromolecular barrier matrix. It demonstrated 100% sensitivity and 90% specificity compared to Draize test results for 42 cosmetic and pharmaceutical products, acids and bases, and industrial chemicals.6 While further validation testing is needed, these results are encouraging.

In vitro tests hold promise to determine severe irritants, but human volunteers have been and remain the most reliable subjects to determine if a cosmetic or household product causes mild or moderate skin irritation. Indeed, regardless of the animal data, dermatologists often tell patients to try a new lotion on their wrists for a few days before facial or general body application. Elder concludes, “No information is more valuable for the determination of a human health hazard than medically documented human experience.”7


1. Marks R: Testing for cutaneous toxicity, in Balls M, Riddell RJ, Worden AN (eds): Animals and Alternatives in Toxicity Testing. London, Academic Press, 1983, pp 313-327.

2. Kligman, AM: Assessment of mild irritants, in Frost P, Horwitz SN (eds): Principles of Cosmetics for the Dermatologist. St. Louis, Mosby, 1982, pp 265-273.

3. Philips L: A comparison of rabbit and human skin response to certain irritants. Toxicol Appl Pharmacol 1972;21:369-382.

4. Bronaugh RI, Maibach HI: Reactions to cosmetics and tests to identify problemproducts, in Frost P, Horwitz SN (eds): Principles of Cosmetics for the Dermatologist. St. Louis, Mosby, 1982.

5. Maguire HC, Cipriano D: Allergic contact dermatitis in laboratory animals, in Drill VA, Lazar P (eds): Cutaneous Toxicity. New York, Raven Press, 1984, pp 55 62.

6. Gordon VC, Kelly CP, Bergman HC: Skintex, an in vitro method for determining dermal irritation. Presented at the Society of Toxicology 28th Annual Meeting, Atlanta, February 27, 1989.

7. Elder, RI: CIR: an experiment in industrial self-regulation. Cosmetic Technology. 1979;1:30.