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Home , Animal testing, Draize test

The End of Animal Testin g? TH E HSU S WORK S WITH SCIENTISTS , GOVERNMENTS , AND CORPORATION S TO PIONEE R METHOD S THA T REPLAC E ANIMA L US EINPRODUCT SAFET Y EVALUATION by ANGELA MOXLEY

A hidden cost lurks behind the sweetener in your morning dict effects in people, and that they are simply too inefficient to coffee, the paint on your living room walls, perhaps even the soap meet the high demand for chemical testing. These changes have you use to wash your hands. spurred a revolution that is moving the field toward tests per - At some point in their development, these products or their formed in computer simulations and modern-day petri dishes— raw ingredients may have been applied to the eyes or skin of live developments that could spell the end of animal use in animals, injected into their bodies, or pumped into their stomachs within two decades. or airways. In tests of potential , subjects are given a In conducting conventional animal tests, says Martin substance every day for two years; other tests involve killing preg - Stephens, HSUS vice president of animal issues, “you nant animals and studying the fetuses. don’t have to know a lot about animals’ biology; you hope that it’s Governments in most developed countries require a battery similar to our own and you just do the test. Whereas now we know of on materials including food additives, drugs and a lot more about human and animal biology, and we can model vaccines, , and many other chemicals. The results may be things in the test tube that we couldn’t necessarily do 50 years ago.” used to ban potential toxins, formulate standards to protect The old methods are “basically using animals as surrogate workers who handle them, warn certain classes of people such as people,” he says. “We can do better.” pregnant women against taking a drug, or create packaging labels to let consumers know what to do if, for example, the product FOR SHAKY SCIENCE splashes into their eyes. In addition to the often severe suffering inflicted during safety tests, But the real-life applications for some tested substances are which are almost always conducted without relief, as trivial as an “improved” laundry detergent, a new eye shadow, or animals used in testing suffer mental and emotional a copycat drug to replace a profitable pharmaceutical whose patent stress from repeated, often rough handling and nearly constant has expired. confinement. No one knows exactly how many animals suffer each year for While , guinea pigs, , birds, and fish are used in toxicity testing, but the annual toll is likely in the millions in the toxicity testing, rats and mice are the mammalian species most fre - U.S. alone. Each test consumes dozens to thousands of animals quently experimented on—yet these rodents are exempted from apiece, says Troy Seidle, Humane Society International director even the modest provisions of the Act, and facili - for research and toxicology; registration of a single re - ties are not required to report how many they use. quires more than 50 experiments and the use of as many as 12,000 Chosen for their small size, high reproduction rate, and animals. relatively docile nature, rats and mice are too often perceived as But recent years have brought a growing recognition among content in a lab setting; many people mistakenly think the need scientists and government officials that the welfare of animals in for a natural environment has been bred out of them, says laboratories matters to the public, that animal tests often don’t pre - Stephens. But several years ago, a film documenting rats taken

humanesociety.org 21 Fear of toxins in products and the environ - get . So what levels should raise ment, combined with the development of alarm? What you find is that at the end of Full-body restraints hold rabbits during the application of a test substance to their eyes—in some cases, for lifesaving substances such as penicillin and the day, there is a gross characterization more than 24 hours following the procedure. the polio vaccine, has led to entrenched where unless results are at one end of the support of among many sci - extreme or the other, you typically don’t entists and government regulators. have high confidence that people are going But numerous prominent failures over to react the same way.” S U S H

the decades have underscored the weak - E Out of 3,000 cancer tests in animals, 53 H T ; Y T

nesses of animal tests. Results can vary from T percent identified the tested substances— E G / Z E

lab to lab and species to species. Seidle H some as common as acetaminophen—as C N A S points out that birth defect studies in rats I carcinogenic, says Thomas Hartung, di - U Q I S : and rabbits failed to detect the develop - P rector of the Center for Alternatives to O T M O

mentally toxic effects of PCBs (industrial R Animal Testing at . F , E G A

compounds widely used in the U.S. until a P Hartung says this figure is likely 10 times E T I S O

1979 ban on their manufacture), for ex - P higher than it would be in humans, probably P O . K ample, while cancer tests have missed the C because rats are much more prone to tumors. O T S O T

hazards of substances such as asbestos, ben - O Animal testing of pharmaceuticals has F E

Most rodents in labs live alone in shoebox-size cages with nothing to do; experiments may leave them in near G A /

zene, and cigarette smoke, delaying con - S also provided dubious information. Ninety-

constant pain with no relief. B A R K

sumer and worker protection measures by L two percent of drugs that pass the animal E A H C I

decades in some cases. M testing stage are ultimately abandoned, ac -

from a lab and put in an enclosed natural been shown to be distressful. ; R E E V Cancer study results are particularly / cording to a 2004 Food and Drug Adminis - area revealed something different: They im - Animal testing has historically been a H C S I M

problematic, says Stephens. Every day for A tration report. Of these, 60 percent caused mediately began digging burrows, building “health-crisis-driven enterprise,” Stephens L F G N

two years, animals receive the largest dose A adverse effects in human clinical trials that nests, and creating their own society. says. In the 1930s, a toxin in a mascara G F L O

possible that is not immediately sick - W weren’t predicted in animals; the other 40 “There’s a sense that these animals product caused blindness in women : P

O The Way Fo rward: Eye Irritat ion T

ening, a concentration far higher M percent were found to be ineffective in

don’t quite experience the suffering that and one death, leading to the de - O R F ,

E Sixty-five years after it was devised by toxicologist John Draize, a test

than what people would be ex - G people, despite promising results in animals.

other animals can experience. Partly it has velopment of eye irritation tests As many as A P S I remains the standard animal study for measuring eye irritation caused by chemicals H

posed to, he says. “These chem - T “That’s 92 percent of drug candidates

something to do with their small size, and on rabbits. In the 1950s and . K C

O and products. The test substance is put in the rabbit’s eye sac, says Martin Stephens, 12,00 0 icals could be no problem given T down the drain after many years of research, S it has something to do with their stoic de - 1960s, birth defects in babies I / animals die in I Y

N vice president of animal research issues for The HSUS, “and the eyelids are held shut so in realistic doses, but when you A development, and investment,” says Seidle. meanor,” says Stephens, noting that rodents born to pregnant women who the testing of a single V A pesticide B A the substance can get on the cornea and all around the eye.” The eyes are rated for S

overwhelm the body—the liver, C “It’s a tremendously high attrition rate,

have evolved behaviors to hide weaknesses took the drug trig - : T I B

B irritancy as indicated by redness, ulceration, hemorrhaging, cloudiness, or blindness.

the kidney—there can be a kind of A which speaks very poorly of the methods from predators. “They’re not like dogs, who gered new requirements for wide - R ; K

C The rabbits are held for up to 21 days and then killed. indirect toxicity just from that,” he says. O that are currently available. So for many of T

will let you know what’s going on. So it’s spread reproductive toxicity testing in S I / Z

T A leading alternative method uses the corneas of cow eyes left over from the meat Interpretation of the results also poses R the companies, animal testing is just bad for especially sad that these are the animals who animals. And concern about pesticides A W H

C industry. The cow eye test and a similar test using chickens’ eyes have been approved problems, Stephens notes. “Some animals S business. It’s costing them way too much, are used the most in the lab—because they resulted in the creation of a laundry list of A R D

: in the U.S. and Europe as alternative methods for assessing severe eye irritants or cor - E

are going to get cancer just because animals S and in this economic climate they can’t

are the hardest to figure out when they’re in required animal tests in the 1970s and ’80s. U O

M rosive materials, meaning live animals need no longer be used to test for substances ; pain or distress.” E afford it.” M I T

S likely to cause the worst suffering. Negative test results using these methods, however, M Hartung agrees. “I think that people It’s too easy for a researcher to glance A E R D

/ require further tests in rabbits, and no alternative methods have yet been approved for

Rats and mice have N have learned over the last few years that the A

into a cage, see a quiet mouse huddled in I R

complex needs for D

A evaluating milder irritants.

R ‘’ for what we have been doing

the corner, and move on—especially during burrowing and A M foraging that A But hope is on the horizon. In one recent victory, The HSUS helped ensure that A is not that gold. The limitations are increas - E

the day, when these nocturnal animals are T are denied to S O

C germ-killing cleaning products no longer need to be tested on rabbits’ eyes to deter - them in labs. : ingly obvious,” he says. “Some of the big resting, says Stephens. But to those willing G I P

A mine safety labels in the U.S. “I think E

N companies are running into enormous to pay attention, the signs are there. Dis - I U G

; the Draize eye test is almost history,” Y

T problems. They see it as the toxicology was

tressed rodents may be hunched over with a T E G /

S says Thomas Hartung, director of the

E not always giving them the best advice.”

disheveled appearance, says Seidle. Or they G A M I Center for Alternatives to Animal O

may be highly agitated and hyperactive, D N E

R Testing at Johns Hopkins University, T

L FINDING A BETTER WA Y

exhibiting repetitive behaviors such as A : D

N which formed in 1981 largely in re - U With nearly 300 brands used by 3 billion running in circles or climbing the walls of O R G

K sponse to public outrage over the test. C

A people every day, Procter & Gamble is well-

their shoebox-sized cages. B , E

G “And people are waiting for this— A

L positioned to help drive change in the field.

When the tests are over—after up to L O C nobody likes this assay. We don’t have O two years in some studies—rodents are T The company has spent more than $250 O A rabbit endures H P an answer to all the possible applica - D million over the past 22 years on alterna - an eye irritancy test. A

decapitated by mini-guillotines or have E R P

S tions, but … give it a year or two.”

S tives, reducing its animal usage by 98 per - their necks broken. Many are gassed to U O I V E

R cent in that time, aiding in the development death with , a method that’s P

22 all animals SE PTEMBER | OCTOBER 2009 of 50 alternative methods, and completing journal to reflect on the future of toxicology. more than 400 publications on the topic, Hartung acknowledges the success of says Len Sauers, vice president for product The Way Fo rward: Skin I rritati on and Corrosi on animal advocates in challenging the status safety and regulatory affairs. P&G also Testing for skin irritation and corrosion closely parallels the Draize eye test. quo, and Stephens notes that after decades funds jointly with The HSUS alttox.org , a The test substance is applied to a rabbit’s shaved skin, then removed after four hours. of being shut out of influential decision- website devoted to the advancement of The skin is observed for up to 14 days. making and advisory bodies, animal welfare nonanimal methods, and partners with The Today this test can be fully replaced with what is known as a nonanimal tiered ap - organizations finally have a role in many of HSUS to give financial awards to encourage proach. First, a proven nonanimal test is carried out for skin corrosion, or irreversible them. For one, The HSUS’s international af - alternatives development. tissue destruction. One such test consists of a glass vial capped by an artificial skin-like filiate, HSI, has been a leader in advancing The investment stems from a commit - membrane; when a corrosive substance destroys the barrier, the fluid in the vial changes acceptance of alternatives through the ment to animal welfare and a recognition color or texture. This and other skin model global Organisation for Economic Co-op - that alternatives are often more objective tests have been accepted in the U.S. and eration and Development. “We’re seen as and efficient, Sauers says. For example, a Europe as alternatives to the rabbit test. legitimate players,” Stephens says. “We’re previously standard version of an allergy If a substance is shown to be noncor - not just standing outside the castle, lobbing test involved applying substances to the skin rosive, a second test for milder irritation is stuff over the parapet—we’re engaging on of guinea pigs, observing the effects over a still necessary, for which several high-tech, science policy issues.” month, and then subjectively grading the three-dimensional human skin models response. An alternative test conducted on have been developed. Thanks largely to TOXICITY TESTING mice uses fewer animals and causes less suf - the work of Humane Society International FOR THE 21ST CENTURY fering; researchers measure the proliferation as part of its Hop to It, Europe! campaign to end animal use in skin irritation testing, the In Europe, the push for alternatives has long of a certain cell type, says Mark Lafranconi, EU recently accepted three such models—a victory that “we project, given the testing been driven by cultural views on animal a P&G toxicologist. “So we’re not waiting to requirements for chemicals alone, will probably save upwards of 30,000 rabbits annu - protection, as well as laws such as a 1986 re - see the expression of the ; we’re ally,” says HSI research and toxicology director Troy Seidle. The HSUS anticipates global quirement that nonanimal tests be used seeing a subtle or biochemical change that acceptance of these human skin models within the next year. wherever available and a 2003 EU directive occurs,” he says. “And it becomes much phasing in a ban on animal testing of cos - more objective, much more refined. It also metics products and their raw ingredients. can be conducted in about a third of the animal use. Some of these alternatives use tained in the nonanimal test, prioritizing Even a large-scale EU chemical testing pro - Workers at the Institute for Sciences assess products for eye irritation using cow corneas left over from the meat industry and kept in cubelike chambers—a method preferable to using live animals. After a test substance is applied, time of the original test.” human tissues or animal cell lines grown in the more toxic and common chemicals for gram has pushed corporations and govern - the corneas are measured for opacity; the cloudier the cornea and the more the outermost tissues swell, the greater S V I I the irritation. A second test is performed using dye to measure the effects of irritation on the cornea’s permeability. /

Through its work with P&G and other a test tube or computer models that map testing, and eliminating redundant or need - R ments to invest in nonanimal tests, says E

R These precise assessments replace the subjective on rabbits, where researchers visually determine the E B L I

corporations, The HSUS is advancing alter - cellular structures and processes. Other less testing requirements. H Stephens. level of irritation and assign a score. N O S I L

native methods based on the “Three Rs” ap - strategies involve conducting tests on ani - The HSUS is pressing government L A : T H G

proach of replacing, reducing, and refining mals only when negative results are ob - agencies and politicians on both sides of the I R ; S U

Atlantic to become more accepting of S H E H T /

animal-free alternatives in regulatory pro - Y E / 50 Percent

L The Way Forward: I R E L

grams for drugs, pesticides, and other chem - L E H C I One of the most notorious animal experiments, the Lethal lethal poisoning remains the objective. Furthermore, for pesticides icals—a tough task in a sometimes hostile M : T F E

L Dose 50 Percent or “LD 50 ” test involves giving animals a substance and each of their raw ingredients, authorities in the U.S. and environment, says Seidle. “You have to con - E L D D I through force-feeding, inhalation, and/or skin applications and other countries require acute toxicity studies to be carried out vince government regulators that Door No. M D N A

P measuring the amount that kills half the test subjects. Rats, mice, by all three methods. Humane Society International research

2 is just as good, if not better than, Door No. O T , E G

A and rabbits are mostly used as surrogates for humans, while tests and toxicology director Troy Seidle is working with progressive

1 that they’ve been using for decades—in P E T I S

O on fish and birds are carried out to examine potential hazards to corporate and government scientists in Europe to challenge some cases for most of their careers—and P P O . S populations. such testing requirements “in the hopes of sparing tens of U

often can’t be bothered changing.” Advocates S H E H

T LD 50 -type studies have evolved since their creation in 1927 thousands of animals each year from one of the cruelest fates must also persuade authorities to accept / Y E L I R and are today referred to more generally as “acute toxicity” studies. imaginable,” he says. E

methods validated in other countries so that L L E H C I Thomas Hartung, director of the Center for Alternatives to Animal Alternative methods are also being developed; one promising

multinational companies don’t have to M ; ! W

O Testing at Johns Hopkins University, notes that the test “is dramat - approach uses death of cells in a test tube as a starting point for

follow a maze of regulations. N N O I

T ically losing importance.” Test group sizes have been reduced from predicting the dose that kills half the animals. Martin Stephens, A

In spite of the red tape, progress is T I O L P

X 150 in the 1970s to 40 or fewer today. In some parts of the world, HSUS vice president of animal research issues, hopes these alter -

being made, however incrementally. To E L A M I such as the U.K., regulators now accept nonlethal signs of toxicity natives will eventually be supplanted by wholly cell-based date, nearly 50 alternative tests have been N A P O

T instead of death. methods, as well as the use of emerging technology to examine S

declared scientifically valid. Acceptance of : P

Toxicology at the National Institutes of Health Chemical Genomics Center revolves around assessing compounds using O T But this modest animal welfare refinement has been imple - what causes toxicity in humans and predict “what would be the alternative techniques is becoming main - M trays with tiny cell-filled wells. Robots can perform thousands of tests in an afternoon. Experiments are conducted at O R F ,

several dosage levels and examine multiple cell effects to ensure precision and accuracy, says Sunita Shukla, a post - E mented only for force-feeding tests; for inhalation and skin studies, lethal dose in a person in a much more sophisticated way.” stream, says Hartung, as evidenced by his G A

doctoral fellow whose position is funded in part through an alternatives award from The HSUS and Procter & Gamble. P S I H

“We’re not just here to pump out data,” she says. “We’re here to get data that’s meaningful for the toxicology world.” recent invitation from a leading science T

24 all animals SE PTEMBER | OCTOBER 2009 humanesociety.org 25 In the nonanimal skin irritation test developed by Massachusetts-based MatTek Corporation, test substances are applied to tiny pieces of MatTek’s EpiDerm™ human skin-like tissue for an hour. After the substances are removed, the tissues are incubated for 42 hours before being mixed with a special chemical. When the mixture’s color intensity is measured in a spectrophotometer, dark purple indicates the test substance will not be irritating to human skin.

A government alternatives center was approving nonanimal tests. And although A Vision and a Strategy calls for limiting established in 1991 as the cornerstone of a California, New Jersey, and New York have animal testing to situations where new well-funded strategic approach in Europe. By passed laws requiring the use of available alternatives are not yet ideal—and predicts comparison, it wasn’t until 1997 that the U.S. alternatives, no such federal law exists. that such targeted animal testing will even- government—long considered underfunded But recent developments have vaulted tually diminish. Early last year, three federal and scattered in its Three Rs efforts—estab- the U.S. to the forefront of the field. In 2004, agencies signed an agreement to cooperate lished an alternatives agency, which has since the Chemical Genomics Center at the Na- in the research, development, and validation been criticized for sluggish movement on tional Institutes of Health began applying a of the new strategy. technology borrowed from the pharmaceu- Stephens, who served on the com- tical industry to the testing of compounds. mittee that produced the report, estimates Using high-speed automated robots that the effort will require an investment of Cruelty-Free and, instead of animals, cells and isolated $2 billion over 10 years. For its part, The Shopping molecular targets, the technique turns tradi- HSUS is lobbying for federal funding, tional toxicology on its head. Rather than encouraging conversation through forums Many companies conduct animal observing effects in animals and trying to such as alttox.org, and pushing scientists, testing on , personal care, extrapolate the results to people, the tech- regulators, and industry to work together. and household products to satisfy nology attempts to uncover the processes in “Some people will say, ‘This is a generation safety requirements, though it is not the human body that lead to toxicity and to away; talk to us when you’re finished,’” specifically mandated for these ma- pinpoint the chemicals that trigger them. Stephens says. “But we’re trying to en- terials in the U.S. The HSUS is a The shift is expected to not only drastically courage the development of pilot programs founding member of the Coalition reduce animal testing but produce results that will demonstrate pieces of the ap- for Consumer Information on Cos- that will better serve public health and safety. proach, so that people won’t be so daunted metics, which maintains a list of Center director Dr. Chris Austin says by the prospect of the approach having to products where no animal testing the new science will enable researchers to conquer the whole field at once.” was used in any phase of develop- rapidly assess tens of thousands of com- Austin notes that the Tox 21 project has ment by the company or its labora- pounds, an impossible outcome with ani- enjoined groups that have not always seen tories or suppliers. mal testing. But the project is exploring eye-to-eye on the issue of animal use in tox- uncharted territory, he notes, and scientists icity testing:“We are working very closely to- TO FIND OUT which products must prove that results obtained in cells gether to meet a common goal in a very M

are on the list—identified on their O C . K

are relevant to those that occur in the cooperative, respectful, collegial way,” he E T T

packaging by the CCIC’s leaping A M ,

entire body. says.“Whenever you have groups of human K E T

bunny logo—and to order a free T A

A 2007 report commissioned by the beings who have seen themselves as adver- M D

pocket-sized shopping guide, N A ,

Environmental Protection Agency formal- saries … working together for a common M O C visit leapingbunny.org. . E V

ized the new approach as the way of the goal, for the common good, that ought to be O J , E V O future. Toxicity Testing in the 21st Century: celebrated. That’s what this represents.” J

26 allanimals SEPTEMBER | OCTOBER 2009