Draize test



The Draize Test is an animal test devised in 1944 by Food and Drug Administration (FDA) toxicologist John H. Draize and coworkers. Initially for testing cosmetics, the procedure today typically involves applying 0.5 ml or 0.5 g of a test substance to an animal's eye or skin for four hours then observing the results for up to 14 days, for signs of erythema and edema in the skin test, and redness, swelling, discharge, ulceration, hemorrhaging, cloudiness, or blindness in the eyes. The test subject is commonly an albino rabbit. According to the National Anti-Vivisection Society, after the test, the animals are killed.

The tests are controversial, considered by some to be an example of animal cruelty, as well as unscientific because of the differences between rabbit and human eyes, and because of the subjective nature of the visual evaluations. In 1971, toxicologists Carrol Weil and Robert Scala of Carnegie Mellon University distributed three test substances for comparative analysis to 24 different university and state laboratories. The laboratories returned significantly different evaluations, from non-irritating to severely irritating, for the same substances (Weil and Scala 1971). The study predates the implementation in 1981 of the modern Draize protocol. A 2004 study by the U.S. Scientific Advisory Committee on Alternative Toxicological Methods reported that, using the modern Draize skin test, the "underprediction of an irritant as a mild irritant ranged from 10.3% to 38.7%, an irritant as a non-irritant ... from 0% to 0.01%, [and] a mild irritant as a nonirritant ... from 3.7% to 5.5%." (pdf).

The FDA considers the test to play an important role in safety determination for regulated products, stating "to date, no single test, or battery of tests, has been accepted by the scientific community as a replacement [for] ... the Draize test" Moreover, chemicals are currently not Draize tested on animals if they have already shown adverse effects in vitro, thereby reducing the number and severity of tests carried out.

Due to its controversial nature, the use of the Draize test in the U.S. and Europe has declined in recent years and is sometimes modified so that anaesthetics are administered and lower doses of the test substances used. According to MSPCA-Angell, the second oldest humane society in the United States: "Animal use for eye irritancy tests has fallen by an estimated 85 to 90 percent as computer use for storing and exchanging information has increased ..." 

Background
John Henry Draize (1900–1992) obtained a BSc in chemistry then a PhD in pharmacology, studying hyperthyroidism. He then joined the University of Wyoming and investigated plants poisonous to cattle, other livestock, and people. The U.S. Army recruited Draize in 1935 to investigate the effects of mustard gas and other chemical agents.

In 1938, after a number of reports of coal tar in mascara leading to blindness, The U.S. Congress passed the Federal Food, Drug, and Cosmetic Act, placing cosmetics under regulatory control (Wilhelmus 2001). The following year Draize joined the FDA, and was soon promoted to head of the Dermal and Ocular Toxicity Branch where he was charged with developing methods for testing the side effects of cosmetic products. This work culminated in a report by Draize, his laboratory assistant, Geoffrey Woodard, and division chief, Herbert Calvery, describing how to assess acute, intermediate, and chronic exposure to cosmetics by applying compounds to the skin, penis, and eyes of rabbits (Draize et al 1944).

Following this report, the techniques were used by the FDA to evaluate the safety of substances such as insecticides and sunscreens and later adopted to screen many other compounds. By Draize's retirement in 1963, and despite never having personally attached his name to any technique, irritancy procedures were commonly known as "the Draize test" (Kay and Calandra 1962). To distinguish the target organ, the tests are now often referred to as "the Draize eye test" and "the Draize skin test".

Draize's 1944 paper is one of the most cited publications in toxicology, with more than one journal citation per week during the last quarter of the 20th century. He received the tenth medal from the American Society of Cosmetic Chemists for his work (Wilhelmus 2001).

However, by the 1960s and 1970s, Draize's technique was coming under criticism from animal rights activists, initially by Peter Singer then under a campaign driven by Henry Spira. Such protests are widely credited with encouraging cosmetics companies to replace the Draize eye test with in vitro methods, and in some cases, to discontinue animal testing altogether (Holden 1989). Consequently, the number of rabbits used for the Draize eye test fell by over 87% during the 1980s (Holden 1988).

Pro-testing description of the test
According to the British Research Defence Society, a group representing 5,000 animal researchers and institutions in the UK, the Draize eye test is now a "very mild test," in which small amounts of substances are used and are washed out of the eye at the first sign of irritation. The UK Home Office has published guidance and minimum severity protocols for the procedure. 

In a letter on January 12, 2006 to the science journal Nature, written to refute an article saying that the Draize test had not changed much since the 1940's, Nobel prize winner Professor Sir Andrew Huxley described the test as follows: "A substance expected from its chemical nature to be seriously painful must not be tested in this way; the test is permissible only if the substance has already been shown not to cause pain when applied to skin, and in vitro pre-screening tests are recommended, such as a test on an isolated and perfused eye. Permission to carry out the test on several animals is given only if the test has been performed on a single animal and a period of 24 hours has been allowed for injury to become evident." 

Anti-vivisectionist description of the test
According to the American National Anti-Vivisectionist Society, the Draize eye irritancy test and the Draize skin irritancy test cause "extreme discomfort and pain" to the animals involved.

In the Draize test for eye irritancy, according to the society's website, solutions of products are applied directly into the animals' eyes, which can cause "intense burning, itching and pain." Clips are placed on the rabbits' eyelids to hold them open during the test period, which can last several days, during which time the rabbits are placed in restraining stocks. The chemicals often leave the eyes "ulcerated and bleeding."

In the Draize test for skin irritancy, the test substances are applied to skin that is shaved and abraded (several layers of skin are removed with sticky tape), then covered with plastic sheeting. The test solutions may cause "intense pain, burning and itching." 

Alleged differences between rabbit and human eyes


Dr. Kirk Wilhelmus, professor in the Department of Ophthalmology at Baylor College of Medicine, conducted a comprehensive review of the Draize eye test in 2001. He reported that the anatomy and biochemistry of the rabbit eye is not the same as that of the human eye, and that the low tear production, blink frequency, and differences in ocular surface area indicate that testing substances on rabbits might not predict the effects on humans. However, he noted "that eyes of rabbits are generally more susceptible to irritating substances than the eyes of humans" making them a conservative model of the human eye. Wilhelmus concluded "The Draize eye test ... has assuredly prevented harm" to humans, but predicts it will be "supplanted as in vitro and clinical alternatives emerge for assessing irritancy of the ocular surface" (Wilhelmus 2001).

Ophthalmologist and antivivisectionist Stephen R. Kaufman writes: "As a Chief Resident, I have three years of experience at Bellevue Hospital (an Eye Trauma Center), where I have treated scores of toxic eye injuries in the emergency room. I have never used Draize data to assist the care of a patient... I know of no case in which another ophthalmologist found Draize data useful." He argues that rabbits are used because they have large eyes, are easy to handle, and are inexpensive. But he points to what he says are significant differences between rabbits' eyes and human eyes:


 * The rabbit epithelial (surface) layer is 10 times more permeable to hydrophilic solutes than the human eye.
 * Bowman's membrane (the next layer) is six times thicker in man.
 * The rabbit's threshold of pain in the eye is much higher than that of humans, so irritating substances are not washed away as readily.
 * Rabbits have a less efficient tearing system than humans.
 * Unlike people, rabbits have a nictitating (winking) membrane (third eyelid), which has an unclear effect on elimination of foreign materials.
 * Humans develop corneal epithelial vacuoles in response to some toxic substances, but rabbits do not.
 * The rabbit mean corneal thickness is .37 mm, while that of man is .51 mm.
 * Rabbits are more susceptible to damage (alkaline) materials, because the pH of their aqueous humor is .82 compared to .71-.73 for man.
 * The cornea represents 25% of the rabbit eye surface area, but only 7% of the surface area in man.

Due to these differences and the widespread concern at the use of animals, industry and regulatory bodies responsible for public health are actively developing animal free tests to reduce the requirement for Draize testing. However, a recent review in the journal Alternatives To Laboratory Animals concluded, "despite extensive efforts ... there is still no in vitro method that is fully validated as a regulatory replacement" (Curren and Harbell 2002).