For several years Gerhard Zbinden, a leading world toxicologist, has condemned one of the most common tests used to check the safety of cosmetics, pesticides, and other products. The LD-50 test is a ``wasteful endeavor,'' he wrote back in 1973. And he has repeatedly said that ``the value determined in animals rarely bears a meaningful relation with the lethal dose in man.'' The LD-50 (Lethal Dose 50 percent) method involves force-feeding chemical substances to a group of 40 to 200 animals until half of them die.
Partly because of the criticism by Dr. Zbinden and others, the United States Food and Drug Administration discourages use of the LD-50. But the test continues to be a mainstay, especially in the pesticide industry.
In fact, while the FDA's ``red book'' of testing guidelines tells companies that the LD-50 is not recommended, the following pages give an explanation of how to perform the test. The agency is working to change this, says Gary Flamm, director at the FDA's Office of Toxicological Sciences. In the meantime, however, other regulatory agencies continue to accept LD-50 results from research labs.
No one opposes the need to test products before they get into the hands, on the skin, or in the eyes of American consumers - or their children. What is fiercely debated, however, is the use of live animals.
Outspoken animal welfare and animal rights groups have long campaigned to curb or stop live-animal testing, but almost all cosmetics, toiletries, household items, and pesticides still must go through live-animal acute toxicology tests before they hit the shelves.
While the news media periodically report instances of abuse and excessive waste in university and medical laboratories, companies have had little incentive to respond to the resulting flashes of public displeasure.
Now, however, some companies are finding permanent alternatives to live-animal testing. A large number have been able to decrease the number of animals required for acute toxicology research, which studies the potential effect chemicals and poisons have on human beings.
In response to the public's plea to use fewer animals, a few companies have cracked down on irresponsible and excessive testing by demanding that their laboratories demonstrate ``very good reasons why they need to do a test,'' says Gavin Anderson, who analyzes and oversees the funding of the Colgate-Palmolive Company's testing and research into alternative methods.
Many companies have already made what appears to be a sincere attempt to stem dependence on LD-50. Recent surveys done by animal rights coalitions indicate that over the past five years the number of animals used in the LD-50 test has declined 75 percent.
Another procedure, known as the up/down test, has now been accepted by the American Society for Tests of Materials. It is a modified LD-50, which uses as few as five animals per test. The Procter & Gamble Company has been a leader in making the switch to the up/down method, and it reports that since it stopped using LD-50, its use of animals for consumer product safety testing has dropped 61 percent.
Still, for various reasons, P&G and other companies claim they cannot eliminate animal testing altogether. They say that they would like to, but that for now they have no choice. Other government regulatory agencies continue to demand results from the industry's standby tests: the LD-50, Draize eye, and Draize skin tests.
The Draize tests involve putting substances like cosmetics and cleansers into rabbits' eyes and on their exposed skin to test for inflammation and injury.
Even some animal welfare groups acknowledge that eliminating all animal testing will require a lot more research and time. ``All knowledge has a price tag on it,'' says John Mcardle, scientific director at the New England Anti-Vivisection Society. While the FDA does not specify how companies are to meet its safety requirements, its ``red book'' on testing so far indicates that only these and other live-animal tests are adequate.
Animal-test estimates vary
Estimates of the number of animals used each year in laboratory tests vary widely. The Institute for Laboratory Animal Resources puts the number at 20 million, while various scientific reports suggest it could be as high as 200 million. Toxicology research makes up about 20 percent of the total.
The Cosmetic, Toiletries and Fragrance Association, the trade group for an industry that has faced the harshest criticism, has made the largest contributions to the Johns Hopkins Center for Alternatives to Animal Testing, in Baltimore, which is the only such research effort under way.
Procter & Gamble has been pushing to phase out the two Draize tests by using both clinical studies in human subjects and modified skin irritation tests that use fewer animals.
Scientists say advances in other alternatives such as tests using egg membranes, cell and tissue cultures, and computer models show the tremendous potential, even if so far limited, for mimicking existing live-animal tests. The CAM (chorioallantoic membrane) test, which involves testing chemical substances on undeveloped chick embryos to measure irritation, shows promise as a complete alternative.
Colgate-Palmolive is possibly the only company now using the CAM test, says Colgate's Mr. Anderson. While it is not yet a total replacement for live-animal testing, he says, ``within a short time we expect to see some concrete validation that the CAM can be used as a complete substitute.''
`Cruelty free' cosmetics
About 100 companies have already begun selling ``cruelty free'' (no live-animal testing involved) cosmetics and shampoos, as well as leatherless shoes and handbags. But hundreds of others have had great difficulty moving away from live-animal tests. The pesticide and cosmetic industries have also begun following the lead of drug companies, which use computers to do most or all of their ``prescreening'' of compounds, says Frankie Trull, president of the Foundation for Biomedical Research, in Washington.
Kurt Enslein, president of Health Designs Inc. in Rochester, N.Y., developed and is marketing a computer toxicity model for the LD-50 as well as both Draize tests. So far, Mr. Enslein says, five federal agencies have bought Health Designs' Topkat software, and ``orders are coming from several major companies.''
``We are now talking about it with some smaller cosmetic companies as well,'' he says.
But even Enslein has doubts about the ability to eliminate live-animal testing completely. ``I don't think there's a replacement for animals,'' he says. ``Animals have repair processes that in vitro [test-tube] methods don't have, and often react in totally unexpected ways.''
Animal tests hard to mimic
Though the industry is ``on the fringes of new technology,'' it has yet to mimic what animal testing can do, says Keith Booman, technical director at the Soap and Detergent Association. The technology has a long way to go, he says.
Toxicology is a relatively young, immature science. John Frazier, associate director at the Johns Hopkins Alternatives Center, says, ``we still don't know what in vitro systems tell us.''
One of the problems Dr. Booman's industry faces is that many of the products are alkaline, which contributes to eye toxicity. ``In alternative tests, alkalinity doesn't show up as a toxic response,'' he says.
And Robert Giovacchini, vice-president of product integrity at the Gillette Company in Boston, says the only replacement test that has come close - the CAM test - has only a 65 to 75 percent predictability rate.
Part of the reason for the skepticism toward alternatives, says Dr. Mcardle at the New England Anti-Vivisection Society, is that ``there's a false sense of security with animal testing.'' The society funds research to look for alternatives to live-animal testing. Existing methods using animals are relatively crude and imprecise, he says.
``If the animal tests were 100 percent predictive, I don't think people would be talking about getting rid of them,'' says a longtime animal rights activist, Annette Pickett, who is on the board of the Anti-Vivisection Society.
``You've got the inertia of tradition of 60-year-old tests as well, and no big counterincentive,'' says Henry Spira, who coordinates the efforts of animal welfare organizations and has worked with several companies. And bringing about change in an area that is already poorly and inconsistently regulated is very difficult, he says.
``To switch from a test that has historical precedent to one that doesn't makes the agent who decided to do it very vulnerable,'' adds Dr. Flamm at the FDA.
Some foreign markets, like Japan, still require the LD-50. And of the more than 60,000 industrial compounds that exist, fewer than 3,000 have been tested, Mcardle reports. With those that are tested, there is often a great deal of needless repetition and duplication. Very few companies say they have data banks to collect the results of tests already completed, and almost none share test results with competing companies.
`New and improved'; more tests
Each time a product is ``new and improved,'' says Flamm, it has to go through the whole range of tests all over again, even if the change is incrementally small. For example, anything meant for people with sensitive skin must by definition be tested.
Animal protection groups contend that very few companies are actively supporting research efforts into alternatives to live-animal testing, even though non-animal tests are much cheaper and more efficient. Indeed, only about 10 major companies contribute substantially to the Johns Hopkins Alternatives Center. But even this amounts to only about $25,000 to $35,000 from each company a year. ``There are a lot of things we could do if we had the resources,'' says Dr. Frazier, the associate director.
Some companies have been accused by anti-vivisection groups of pitching small amounts of money at alternative projects without being sincerely committed.
``But if a company hopes to survive a [product liability suit], they have to be able to show they tested everything and this was an event that could not have been predicted,'' Flamm explains.
``The soap and detergent companies do a tremendous amount of testing [with animals] because they know that little kids will swallow it and get it in their eyes,'' Flamm says.