Testing for Seeds of Destruction

...Even with their limitations, they are the most reliable method we have of judging whether that new, widely advertised "taste treat" on the grocer's shelf is likely to contain seeds of destruction tomorrow — or thirty years from now...

...Once a chemical has been shown to cause cancer in animals, another controversy begins...

...If no chemical could be banned until human cancers appeared, more and more people might be exposed to a carcinogen during those years...

...In the typical animal experiment for a food additive, fifty mice are fed a diet including the largest amount of the additive that does not produce immediate harmful effects, fifty mice are fed the diet with one-third that amount of additive, and fifty mice (the control group) are fed the same diet without any of the chemical being tested...

...Condensed cigarette smoke does cause tumors in mice when it is applied to the skin...

...But there are only a few chemicals which all the experts see as linked to human cancer...

...On this basis, the EPA concluded that dye manufacturers should be allowed to dump one pound of benzidine a day into a moderately large river...

...A rigorous experiment could detect only those chemicals that cause cancer at a rate greater than one out of 2,000 to 20,000 persons," says Michael F. Jacobson, microbiologist and co-director of the Center for Science in the Public Interest...

...Diethylnitrosamine, an organic chemical, was shown to cause liver cancer in rats three to four months after first exposure...

...There is no threshold...

...In 1970, the Food Protection Committee recommended a dose ten to one thousand times greater than a person might be expected to consume...

...After this test period, all surviving mice are killed and carefully examined for abnormal growth in any tissue — skin, glands, nervous system, respiratory and digestive tracts...

...On the other hand, consumer groups and other scientists attack the animal tests as not being cautious enough...

...Some result in useless data because corners were cut to hold down costs...

...Animal tests are the major criterion for chemical safety because such tests cannot — or should not — be done directly on humans, and the chance contacts between people and chemicals rarely provide enough evidence to establish cause-and-effect relationships...

...Red dye #4 has also been banned...

...by chloroform, an ingredient in many drugs, toothpastes, and cosmetics...

...Carried to their logical conclusion, these considerations of carcinogenesis [cancer production] strike at the very roots of technological advance in food production," says Leon Goldberg, a toxicologist at Albany Medical College...

...The mice are observed for eighty weeks, during which time the researchers examine any that appear unhealthy...

...However, Dr...

...Second, since people may react to a chemical more acutely than test animals do, a high dose could have the same effect on an animal as a lower dose would have on a person...

...But only a few hundred chemicals are tested each year in long-term animal studies, because of the time required and expense...

...The second is that the experimental situation, in which large amounts of a chemical are fed to relatively small numbers of animals, is an unrealistic model for the potential human experience, in which large numbers of people will eat smaller amounts of the substance...

...So far, however, about 90 per cent of the known carcinogens tested have been identified in the new tests as causing DNA changes...

...So far, scientists have been able to test only a small fraction of the chemicals in widespread use...

...Useful as they are, experimental animals are not miniature human beings...

...That amount was divided by 100, the standard "safety factor" used in toxicology to allow for the unknown differences between rats and humans...

...A recent toxicology text concludes that any chemical "reliably and unambiguously" causing tumors in any animal species "would constitute a certain risk for at least a portion of the human species...

...Estrogen, a hormone that has long been known to cause cancer in mice, was used as a drug for thirty years before its carcinogenic effect on people was reported...

...But a committee of cancer experts assembled by the Department of Health, Education, and Welfare stated that no level of exposure to a cancer-causing chemical should be considered safe for man...

...But no one is certain why these natural defenses against cancer sometimes fail...

...Even when researchers obtain clear results in an animal test, can they apply the results to people...

...Those, now normal, bacteria will reproduce and form colonies which appear as white spots on the plate...

...The President's Science Advisory Committee was less certain...

...We have good reason to believe — though it is not yet proved — that some, perhaps most, chemical carcinogens will have definable thresholds...

...This method is so fast and simple that all new compounds could be screened routinely for possible cancer activity...

...Altogether, laboratory tests have produced evidence that some 1,400 substances — Julie Miller writes on developments in biology and chemistry for Science News magazine...

...In April, a University of California biochemist, Bruce N. Ames, received a national award for a screening technique using bacteria as the experimental organism...

...Then, only a few weeks later, the FDA reversed its decision and banned the dye...

...It states that no food additive will be permitted in any detectable amount if it has been shown to cause cancer when fed in any amount to any animals or people...

...The body's reaction to two aspirin tablets is totally unlike its reaction to two bottles of aspirin...

...DNA changes resulted from only a few of the substances that had been tested in animals and found not to increase the incidence of cancer...

...Experiments with thousands of animals would take too long and cost too much...

...Federal law now flatly bans food additives shown to cause cancer...

...Chemical reactions, particularly in the liver, may change substances into more or less harmful compounds...

...Controversy surrounds the techniques used to identify cancer-causing food additives Testing for Seeds of Destruction JULIE MILLER "No red dye #2 in the food coloring," read a hastily handwritten announcement taped above the supermarket collage of prepackaged, mass-produced Spice Island gourmet ingredients...

...The scientists assembled by HEW recommended that 20,000 compounds be tested...

...The Food Protection Committee of the National Academy of Sciences defends the use of animal tests with two arguments: First, no significant aspect of cancer has been shown to differ fundamentally between man and experimental animals...

...But whatever the results, they are not always meaningful...

...A cancer-causing agent may occasionally be detected directly from observations of people — a London surgeon determined in 1775 that scrotal skin cancer, common among chimney sweeps, was produced by contact with soot—but such discoveries are rare...

...One thing on which most researchers do agree, however, is that even if there is a threshold for the effects of these chemicals on people, we do not know what that level is...

...The customers had been asking about it—not just the students and the organic gardeners, but also the man in the leisure suit and the grandmother with two turkeys in her cart...

...In a $10 million investigation, Shell had demonstrated that dieldrin caused liver tumors in several strains of mice, even at the lowest doses tested...

...An additive is suspected of causing cancer if there is a significantly higher incidence of tumors among the animals eating the additive than among the control group...

...A chemical that was used in dye manufacturing, 2-napthylamine, causes urinary tract cancer more readily in humans and dogs than it does in mice, rats, or guinea pigs...

...The Shell Company claimed dieldrin was safe because it found no sign of cancer among highly exposed workers at the plant manufacturing the pesticide...

...Hundreds of laboratories have already begun to use this test - Because not all DNA changes cause cancer, the results of these tests may not be equivalent to the results of traditional animal experiments...

...Hundreds of generations of growth have occurred without the cells reverting to a normal state...

...In a perfect experiment, the animal used should treat a chemical the same way the human body does...

...Like radiation, chemicals are thought to cause cancer by creating changes in DNA...

...On this vital point, the experiments have been criticized by both industry and consumer groups...

...For example, the immune system can destroy abnormal cells that arise in the body...

...We believe that the [bacterial] test can play a central role in a long-term program of cancer prevention," wrote Ames and co-worker Joyce McCann...

...In contrast to the law on food additives, the Environmental Protection Agency (EPA) can set standards for cancer-causing chemicals in drinking water...

...They hope that chemicals likely to cause cancer will be identified much more quickly, before a company "puts millions of dollars into development and doesn't want to find out its product is a carcinogen...

...Some scientists argue that people are more likely than laboratory animals to detoxify chemicals, but other researchers take the opposite position, insisting that people may be more susceptible to cancer...

...You'd have to eat pistachio nuts continuously for twenty hours a day to get that much red dye #2," one skeptic complained...

...In some cases, however, there is no threshold...

...a white rat costs about a dollar, while a Rhesus monkey costs more than $100...

...At this rate it will take a lifetime to go through the list — and by then thousands of new chemicals will be in use...

...The first is that a chemical will not necessarily have the same effect on animals as on people...

...Researchers cite two major reasons for testing chemicals in large doses: First, low dosage would require the use of more animals to demonstrate that an incidence of tumors was due to the chemical tested rather than just to chance...

...The test costs only $200 per chemical, and can be completed in three days...

...Furthermore, small rodents can be housed in a limited area, and they have already been extensively studied so that researchers know what types of cancer are likely to occur...

...The test clearly measures genetic changes that occur in only a few of the millions of bacteria exposed to a chemical...

...Toxicologist Samuel S. Epstein of Case Western Reserve University says, "Lower concentration [of cancer-causing chemicals] simply means lower incidence [of cancer...

...Whatever limits may be set by law or regulation, there can be no effective control until we know which chemicals are likely to cause cancer...

...In contrast, if a chemical that causes DNA changes is added, the genetic defect will be corrected in a few of the millions of bacteria...

...Animals do have some defenses against cancer, and that protection may be effective against only small amounts of genetic damage...

...Old people, adolescents, blacks, vegetarians, suburbanites, sick people, malnourished people—all may eventually eat a chemical being investigated...

...These scientists note that humans have a wider variety of cell types for a chemical to attack...

...Nevertheless, dieldrin was eventually banned by the Environmental Protection Agency...

...The red dye #2 debate is only one in a continuing series of controversies involving chemicals that may or may not cause cancer...

...The damage inflicted by radiation (such as X-rays) on the genetic material DNA, for example, is proportional to the amount of radiation, even at the lowest levels measured...

...Is there any level below which the substance will do no harm...

...As a rule, tests are run eighty weeks for mice, two years for rats, and four to seven years for dogs...

...Typically, poisons show no ill effect below a certain level, called the threshold...

...The long interval between an individual's exposure to a cancer-causing chemical and the appearance of symptoms makes it difficult to pin down the cause of a tumor...

...The President's Science Advisory Committee made no attempt to resolve these sharply conflicting views...

...But the company claimed that the mouse data could not be used to predict the effect in man, since workers exposed to the chemical had not developed tumors...

...Did the experiments prove that red dye #2 causes cancer in rats...

...Even with successful development of alternative tests, however, we will still be relying on rats, mice, and guinea pigs as indicators of food and drug safety for years to come...

...The Food Protection Committee has suggested allowing cancer-causing chemicals to be used at levels that have no harmful effect on the most sensitive species of animal tested...

...Although the association of human lung cancer with smoking has been well-documented, scientists have been unable to find clear evidence of lung tumors in mice and rats in response to tobacco smoke...

...The FDA does not routinely repeat manufacturers' experiments to check the conclusions...

...In identifying substances that cause cancer, scientists have already found some sensitivity differences between experimental animals and humans...

...drugs, food additives, pesticides, industrial chemicals, cosmetics — might cause cancer...

...Benzidine, which is widely used for manufacturing dyes, has been clearly linked to bladder cancer among workers...

...Toxicologists have long been aware of the first objection, which they call the "mouse-to-man" problem...

...Can one predict the straw that will break a healthy camel's back, or does the back begin breaking when the first straw is piled on...

...The agency then calculated, from a study on rats, the amount of benzidine that would result in that level of risk...

...Therefore, experimenters generally use at least two types of animals — most frequently rats and mice, although some tests on dogs, rabbits, guinea pigs, or monkeys are included...

...More significantly, critics have charged that industry scientists deliberately or unconsciously distort their findings to render them more favorable to the companies sponsoring the research...

...A 'no-detectable amount' clause is a refuge in the face of ignorance," the group reported...

...second, all chemicals known to cause cancer in people also cause cancer in one or more experimental animals...

...This lack of consensus reflects disagreement on the techniques and significance of laboratory testing...

...The most serious disputes, however, stem from a more theoretical problem...

...The advantage of using rats and mice as experimental animals is that they are relatively cheap...

...This means that as many as 10,000 to 100,000 Americans could be stung by a 'safe' food additive...

...It is a long, frequently too long, step from the observation of the effects of such provocative and bizarre experiments to those of man's daily diet," says Julius M. Coon, a Jefferson Medical College pharmacologist who headed many of the National Academy of Sciences studies on food safety...

...This method has attracted much interest because, besides being cheaper and faster than animal tests, it can more easily detect chemicals that cause genetic changes only infrequently...

...and by sodium nitrite, a preservative used in bacon and other smoked or preserved meats and fish...

...Red dye #2, the most common food coloring, was used in products ranging from soft drinks to breakfast cereals...

...Emmanuel Farber, director of the Fels Research Institute at Temple University Medical School, testified that workers had been exposed for a maximum of twenty years, while liver cancer may take more than thirty years to develop...

...New tests are also being developed to supplement animal experiments — methods that look directly for changes in the genetic material instead of waiting for tumors to develop...

...The official turnaround reflected confusion among scientists about the interpretation of laboratory research...

...The assumption is that the effect of the chemical on at least one type of animal tested will resemble the effect on man...

...In recent months, animal tests have pointed to dangers posed by the insecticide kepone...

...Its 1970 report concluded, "Our scientific knowledge for the interpretation of results of such animal tests in terms of potential [human] harm is still most primitive...

...Toxicologists estimate cancer development takes at least one-eighth the average life span of an animal...

...Animal tests have been attacked with two major arguments...

...If a chemical that causes no genetic changes is added to the plate, no bacteria will grow...

...On the one hand, manufacturers (as well as some scientists) charge that the tests are too cautious, resulting in the condemnation of chemicals that will not actually harm people...

...Human cancers resulting from exposure to vinyl chloride were not found until two-and-a-half years after liver tumors had been reported in mice...

...A chemical's effect on the body may vary among types of animals or even among individuals...

...Most testing of food and drugs is done by the companies that market or plan to market a product or by laboratories that the companies hire...

...Bacteria, fruit flies, and human skin cells grown in the laboratory are used in these new procedures...

...Its safety had been questioned for twenty years, but late last December the U.S...

...Some experiments are inconclusive because they were poorly planned...

...If so, was the dye likely to cause cancer in people...

...Experiments with rodents have the additional advantage of providing results more rapidly than tests with larger animals...

...Often, however, this simply cannot be determined...

...The tests are then often repeated, using a different experimental animal...

...The debate over whether red dye #2 should be banned from foods had been in the news for weeks...

...The EPA decided in 1974 that it would be an acceptable risk for the general public if one person in a million developed cancer from benzidine in water...

...The Shell Company invoked this argument to defend the safety of the pesticide dieldrin, contending that people might detoxify the chemical although mice do not...

...in monkeys, the results came after one to three years...

...To overcome, in part, the "bacteria-to-man" problem, Ames adds a mixture of broken cells from rat or human liver...

...Food and Drug Administration (FDA) had finally announced that the dye was safe...

...After chemicals damage a cell, that cell must grow and divide, producing more abnormal cells, until a tumor eventually appears...

...The dispute over the interpretation of laboratory findings covers basic principles of safety testing, and thus involves high stakes for the food, drug, and chemical industries...

...Besides the "mouse-to-man" dispute, the main objection to current animal studies is the high dosage of chemicals used in tests...

...These cell components can toxify and detoxify chemicals as the mammal would have done...

...different species often vary in their ability to "toxify" or "detoxify" chemicals...

...The classical example of human chemical sensitivity did not involve cancer but birth defects: In the thalidomide disaster of 1961, that drug turned out to be sixty times more effective in causing defects in human infants than in mice...

...Even among people, a common problem with drugs is that some patients react with extreme sensitivity, showing the same effects that most people suffer only after receiving much larger doses...

...The Toxic Substances Act allows the administrator of the EPA to demand testing of new chemicals, or of new uses of old chemicals, before they are put on the market If animal tests for carcinogenesis are required, manufacture of a new chemical could be delayed for years...

...But again, what happens to bacteria may not happen to humans...

...The evidence for genetic change observed in the Ames test is the correction of a genetic defect Millions of bacteria with a specific genetic defect are spread on a plate of medium where they cannot grow, but where normal bacteria could multiply freely...

...When cancer cells reproduce, they pass on the DNA change that converted them from normal cells into cells that grow without restraint...

...The tests take several years and can cost more than $100,000...

...A new law, signed by President Ford on October 12, should increase the amount of testing of chemicals...

...The birth defect incidence in humans was also 100 times that of rats, 200 times that of dogs, and 700 times that of hamsters...

...The Delaney Clause of the 1958 Food Additives Amendment is probably the most specific, inflexible safety ruling on the books...

...Because the alteration of the genetic material is permanent, many small DNA changes, which accumulate over a person's lifetime, may lead to a cancerous state...

...Varying human reactions are also cited in defense of animal tests...

...Some cancer researchers believe genetic damage, even by low levels of carcinogens, will eventually result in cancer...

...For example, some kinds of animals absorb and store a chemical that would pass right through another species...