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teratogenic, or fetus-deforming, properties of the substances, were being compiled, but these results were not immediately made available to biologists outside the government. The data remained—somewhat frustratingly, in the view of some scientists who had been most curious about the effects of herbicides-out of sight, and a number of attempts by biologists who had heard about the teratological study of 2,4,5-T to get at its findings appear to have been thwarted by the authorities involved. Upon being asked to account for the apparent delay in making this information available to biologists, an official of the National Institute of Environmental Health Sciences (another branch of the National Institutes of Health) has declared, with some heat, that the results of the study itself and of a statistical summary of the findings prepared by the Institute were in fact passed on as they were completed to the Commission on Pesticides and Their Relationship to Environmental Health, a scientific group appointed by Secretary of Health, Education, and Welfare Robert Finch and known—after its chairman, Dr. E. M. Mrak, of the University of California—as the Mrak Commission. Dr. Samuel E. Epstein, chief of the Laboratories of Environmental Toxicology and Carcinogenesis at the Children's Cancer Research Foundation in Boston, who was co-chairman of the Mrak Commission panel considering the teratogenic potential of pesticides, tells a different story on the availability of the Bionetics study. He says that he first heard about it in February. At a meeting of his panel in August he asked for a copy of the report. Ten days later, the panel was told that the National Institute of Environmental Health Sciences would be willing to provide a statistical summary but that the group could not have access to the full report on which the summary was based. Dr. Epstein says that the panel eventually got the full report on September 24th "by pulling teeth."

Actually, as far back as February, officials at the National Cancer Institute had known, on the basis of a preliminary written outline from Bionetics, the findings of the Bionetics scientists on the fetus-deforming role of 2,4,5-T. Dr. Richard Bates, the officer of the National Institutes of Health who was in charge of coordinating the Bionetics project, has said that during the same month this information was put into the hands of officials of the Food and Drug Administration, the Department of Agriculture, and the Department of Defense. "We had a meeting with a couple of scientists from Fort Detrick, and we informed them of what we had learned,” Dr. Bates said recently. "I don't know whether they were the right people for us to see. We didn't hear from them again until after the DuBridge announcement at the White House. Then they called up and asked for a copy of the Bionetics report."

At the Department of Agriculture, which Dr. Bates said had been informed in February of the preliminary Bionetics findings, Dr. Tschirley, one of the officials most intimately concerned with the permissible uses of herbicidal compounds, says that he first heard about the report on 2,4,5-T through the DuBridge announcement. At the Food and Drug Administration, where appropriate officials had been informed in February of the teratogenic potential of 2,4,5-T, no new action was taken to safeguard the public against 2,4,5-T in foodstuffs. In fact, it appears that no action at all was taken by the Food and Drug Administration on the matter during the whole of last year. The explanation that F.D.A. officials have offered for this inaction is that they were under instructions to leave the whole question alone at least until December, because the matter was under definitive study by the Mrak Commission-the very group whose members, as it turns out, had such extraordinary difficulty in obtaining the Bionetics data. The Food Toxicology Branch of the F.D.A. did not have access to the full Bionetics report on 2,4,5-T until after Dr. DuBridge issued his statement, at the end of October.

Thus, after the first word went to various agencies about the fetus-deforming potential of 2,4,5-T, and warning lights could have flashed on in every branch of the government and in the headquarters of every company manufacturing or handling it, literally almost nothing was done by the officials charged with protecting the public from exposure to dangerous or potentially dangerous materials-by the officials in the F.D.A., in the Department of Agriculture, and in the Department of Defense. It is conceivable that the Bionetics findings might still be hidden from the public if they had not been pried loose in midsummer through the activities of a group of young law students. The students were members of a team put together by the consumer-protection activist Ralph Nader—and often referred to as Nader's Raiders—to explore the labyrinthine

workings of the Food and Drug Administration. In the course of their investigations, one of the law students, a young woman named Anita Johnson, happend to see a copy of the preliminary report on the Bionetics findings that had been passed on to the F.D.A. in February, and its observations seemed quite disturbing to her. Miss Johnson wrote a report to Nader, and in September she showed a copy of the report to a friend who was a biology student at Harvard. In early October, Miss Johnson's friend, in a conversation with Professor Matthew Meselson, mentioned Miss Johnson's report on the preliminary Bionetics findings. This was the first that Dr. Meselson had heard of the existence of the Bionetics study. A few days previously, he had received a call from a scientist friend of his asking whether Dr. Meselson had heard of certain stories, originating with South Vietnamese journalists and other South Vietnamese, of an unusual incidence of birth defects in South Vietnam, which were alleged to be connected with defoliation operations there.

A few days later, after his friend sent him further information, Dr. Meselson decided to obtain a copy of the Bionetics report, and he called up an acquaintance in a government agency and asked for it. He was told that the report was “confidential and classified," and inaccessible to outsiders. Actually, in addition to the preliminary report there were now in existence the full Bionetics report and a statistical summary prepa red by the National Institute of Environmental Health Sciences, and, by nagging various Washington friends, Dr. Meselson obtained bootlegged copies of the two latest reports. What he read seemed to him to have such serious implications that he got in touch wih acquaintances in the White House and also with someone in the Army to alert them to the problems of 2,4,5-T, in the hope that some new restrictions would be placed on its use. According to Dr. Meselson, the White House people apparently didn't know until that moment that the reports on the adverse effecs of 2,4,5-T even existed. (Around that time, according to a member of Nader's Raiders, “a tremendous lid was put on this thing” within government agencies, and on the subject of the Bionetics work and 2,4,5-T “people in government whom we'd been talking to freely for years just shut up and wouldn't say a word.") While Dr. Meselson awaited word on the matter, a colleague of his informed the press about the findings of the Bionetics report. Very shortly thereafter, Dr. DuBridge made his public announcement of the proposed restrictions on the use 2,4,5-T.

In certain respects, the DuBridge announcement is a curious document. In its approach to the facts about 2,4,5-T that were set forth in the Bionetics report, it reflects considerable sensitivity to the political and international issues that lie behind the widespread use of this powerful herbicide for civilian and military purposes, and the words in which it describes the reasons for restricting its use appear to have been very carefully chosen:

"The actions to control the use of the chemical were taken as a result of findings from a laboratory study conducted by Bionetics Research Laboratories which indicated that offspring of mice and rats given relatively large oral doses of the herbicide during early stages of pregnancy showed a higher than expected number of deformities.

“Although it seems improbable that any person could receive harmful amounts of this chemical from any of the existing uses of 2,4,5-T, and while the relationships of these effects in laboratory animals to effects in man are not entirely clear at this time, the actions taken will assure safety of the public while further evidence is being sought."

These actions, according to the statement, included decisions that the Department of Agriculture would cancel manufacturers' registrations of 2,4,5-T for use on food crops, effective at the beginning of 1970, "unless by that time the Food and Drug Administration has found a basis for establishing a safe legal tolerance in and on foods," and that the Departments of Agriculture and the Interior, in their own programs, would stop the use of 2,4,5-T in populated areas and in all other areas where residues of the substance could reach man. As for military Uses of 2,4,5-T, the statement said, “The chemical is effective in defoliating trees and shrubs and its use in South Vietnam has resulted in reducing greatly the number of ambushes, thus saving lives.” However, the statement continued, "the Department of Defense will [henceforth) restrict the use of 2,4,5-T to areas remote from the population."

All this sounds eminently fair and sensible, but whether it represents a candid exposition of the facts about 2,4,5-T and the Bionetics report is debatable. The White House statement that the Bionetics findings "indicated that offspring of mice and rats given relatively large oral doses of the herbicide during early stages of pregnancy showed a higher than expected number of deformities" is, in the words of one eminent biologist who has studied the Bionetics data, “an understatement.” He went on to say that “if the effects on experimental animals are applicable to people it's a very sad and serious situation.” The actual Bionetics report described 2,4,5-T as producing "sufficiently prominent effects of seriously hazardous nature" in controlled experiments with pregnant mice to lead the authors "to categorize [it] as probably dangerous." The report also found 2,4-D “potentially dangerous but needing further study." As for 2,4,.-T, the report noted that, with the exception of very small subcutaneous dosages, “all dosages, routes, and strains resulted in increased incidence of abnormal fetuses" after its administration. The abnormalities in the fetuses included lack of eyes, faulty eyes, cystic kidneys, cleft palates, and enlarged livers. The Bionetics report went on to report on further experimental applications of 2,4,5-T to another species :


"Because of the potential importance of the findings in mice, an additional study was carried out in rats of the Sprague-Dawley strain. Using dosages of 21.5 and 46.4 mg/kg (that is, dosages scaled to represent 21.5 and 46.4 milligrams of 2,4,5-T per kilogram of the experimental animal's body weight] suspended in 50 per cent honey and given by the oral route on the 6th through 15th days of gestation, we observed excessive fetal mortality (almost 80 per cent) and a high incidence of abnormalities in the survivors. When the beginning of administration was delayed until the 10th day, fetal mortality was somewhat less but still quite high even when dosage was reduced to 4.6 mg/kg. The incidence of abnormal fetuses was threefold that in controls even with the smallest dosage and shortest period used.

"It seems inescapable that 2,4,5-T is teratogenic in this strain of rats when given orally at the dosage schedules used here."

Considering the fetus-deforming effects of the lowest oral dosage of 2,4,5-T used in the Bionetics work on rats—to say nothing of the excessive fetal mortality—the White House statement that "relatively large oral doses of the herbicide . . . showed a higher than expected number of deformities" is hardly an accurate description of the results of the study. In fact, the statistical tables presented as part of the Bionetics report showed that at the lowest oral dosage of 2,4,5-T given to pregnant rats between the tenth and fifteenth days of gestaltion thirty-nine per cent of the fetuses produced were abnormal, or three times the figure for control animals. At what could without much question be described as "relatively large oral doses” of the herbicide-dosages of 21.5 and 16.4 inilligrams per kilogram of body weight of rats, for example the percentage of abnormal fetuses was ninety and a hundred per cent, respectively, or a good bit higher than one would be likely to deduce from the phrase "a higher than expected number of deformities." The assertion that "it seems improbable that any person could receive harmful amounts of this chemical from any of the existing uses of 2,4,5-T" also appears to be worth examining, for this is precisely what many biologists are most worried about in relation to 2,4,5-T and allied substances.

It seems fair, before going further, to quote a cautionary note in the DuBridge statement: “The study involved relatively small numbers of laboratory rats and mice. More extensive studies are needed and will be undertaken. At best it is difficult to extrapolate results obtained with laboratory animals to mansensitivity to a given compound may be different in a man than in animal species. ..." It would be difficult to get a biologist to disagree with these seemingly sound generalities. However, the first part of the statement does imply, at least to a layman, that the number of experimental animals used in the Bionetics study had been considerably smaller than the numbers used to test commercial compounds other than 2,4,5-T before they are approved by agencies such as the Food and Drug Administration and the Department of Agriculture. In this connection, the curious layman could reasonably begin with the recommendations, in 1963, of the President's Science Advisory Committee on the rise of pesticides, which proposed that companies putting out pesticides should be required from then on to demonstrate the safety of their products by means of toxicity studies on two generations of at least two warm-blooded mammalian species. Subsequently, the F.D.A. set up new testing requirements, based on these recommendations, for companies producing pesticides. However, according to Dr. Joseph McLaughlin, of the Food Toxicology Branch of the F.D.A., the organization actually requires applicants for permission to sell pesticides to present the results of tests on only one species (usually, in practice, the rat). According to Dr. McLaughlin, the average number of experimental animals used in studies of pesticides is between eighty and a hundred and sixty, including animals used as controls but excluding litters produced. The Bionetics studies of 2,4,5-T used both mice and rats, and their total number was, in fact, greater, not less, than this average. Including controls but excluding litters, the total number of animals used in the 2,4,5-T studies was two hundred and twenty-five. Analysis of the results by the National Institute of Environmental Health Sciences found them statistically “significant," and this is the real purpose of such a study: it is meant to act as a coarse screen to shake out of the data the larger lumps of bad news. Such a study is usually incapable of shaking out anything smaller; another kind of study is needed to do that.

Thus, the DuBridge statement seems to give rise to this question : If the Bionetics study, based on the effects of 2,4,5-T on two hundred and twenty-five experimental animals of two species, appears to be less than conclusive, on the ground that “the study involved relatively small numbers of laboratory rats and mice," what is one to think of the adequacy of the tests that the manufacturers of pesticides make? If, as the DuBridge statement says, “at best it is difficult to extrapolate results obtained with laboratory animals to man," what is one to say of the protection that the government affords the consumer when the results of tests of pesticidal substances on perhaps a hundred and twenty rats are officially extrapolated to justify the use of the substances by a population of two hundred million people not to mention one to two million unborn babies being carried in their mothers' wombs?

The very coarseness of the screen used in all these tests—that is, the relatively small number of animals involved—means that the bad news that shows up in the data has to be taken with particular seriousness, because lesser effects tend not to be demonstrable at all. The inadequacy of the scale on which animal tests with, for instance, pesticides are currently being made in this country to gain F.D.A. approval is further indictated by the fact that a fetus-deforming effect that might show up if a thousand test animals were used is almost never picked up, since the studies are not conducted on that scale; yet if the material being tested turned out to have the same effect, quantitatively, on human beings, this would mean that it would cause between three and four thousand malformed babies to be produced each year. The teratogenic effects of 2,4,5-T on experimental animals used by the Bionetics people, however, were not on the order of one in a thousand. Even in the case of the lowest oral dose given rats, they were on the order of one in three.

Again, it fair to say that what is applicable to rats in such tests may not be applicable to human beings. But it is also fair to say that studies involving rats are conducted not for the welfare of the rat kingdom but for the ultimate protection of human beings. In the opinion of Dr. Epstein, the fact that the 2,4,5-T used in the Bionetics study produced teratogenic effects in both mice and rats underlines the seriousness of the study's implications. In the opinion of Dr. McLaughlin, this is even further underlined by another circumstance that the rat, as a test animal, tends to be relatively resistant to tetratogenic effects of chemicals. For example, in the late nineteen-fifties, when thalidomide, that disastrously teratogenic compound, was being tested on rats in oral dosages ranging from low to very high, no discernible fetus-deforming effects were produced. And Dr. McLaughlin says that as far as thalidomide tests on rabbits were concerned, "You could give thalidomide to rabbits in oral doses at between fifty and two hundred times the comparable human level to show any comparable teratogenic effects.” In babies born to women who took thalidomide, whether in small or large dosages and whether in single or multiple dosages, between the sixth and seventh weeks of pregnancy, the rate of deformation was estimated to be one in ten.

Because of the relatively coarse testing screen through which compounds like pesticidesmand food additives as well—are sifted before they are approved for general or specialized use in this country, the Food and Drug Administration theoretically maintains a policy of stipulating, as a safety factor, that the maximum amount of such a substance allowable in the human diet range from one two-thousandth to one one-hundredth of the highest dosage level of the substance that produces no harmful effects in experimental animals. (In the case of pesticides, the World Health Organization takes a more conservative view,

considering one two-thousandth of the "no-effect" level in animal studies to be a reasonable safety level for human exposure.) According to the standards of safety established by F.D.A. policy, then, no human being anywhere should ever have been exposed to 2,4,5-T, because in the Bionetics study of rats every dosage level produced deformed fetuses. A “no-effect" level was never achieved.

To make a reasonable guess about the general safety of 2,4,5-T for human beings, as the material has been used up to now, the most appropriate population area to observe is probably not the relatively healthy and well-fed United States, where human beings are perhaps better equipped to withstand the assault of toxic substances, but South Vietnam, where great numbers of civilians are halfstarved, ravaged by disease, and racked by the innumerable horrors of war. In considering any potentially harmful effects of 2,4,5-T on human beings in Vietnam, some attempt has to be made to estimate the amount of 2,4,5-T to which people, and particularly pregnant women, may have been exposed as a result of the repeated defolioation operations. To do so, a comparison of known rates of application of 2,4,5-T in the United States and in Vietnam is in order. In this country, according to Dr. Tschirley, the average recommended application of 2,4,5-T in aerial spraying for woody-plant control is between three-quarters of a pound and a pound per acre. There are about five manufacturers of 2,4,5-T in this country, of which the Dow Chemical Company is one of the biggest. One of Dow Chemical's best-sellers in the 2,4,5-T line is Esteron 245 Concentrate, and the cautionary notes that a drum of Esterone bears on its label are hardly reassuring to anyone lulled by prior allegations that 2,4,5-T is a substance of low toxicity:

Avoid Contact with Eyes, Skin, and Clothing

Keep out of the reach of children Under the word “WARNING” are a number of instructions concerning safe use of the material, and these include, presumably for good reason, the following admonition:

Do not contaminate irrigation ditches or water used for domestic purposes." Then comes a "notice':

"Seller makes no warranty of any kind, express or implied, concerning the use of this product. Buyer assumes all risk of use or handling, whether in accordance with directions or not."

The concentration of Esteron recommended—subject to all these warnings, cantions, and disclaimers—for aerial spraying in the United States varies with the type of vegetation to be sprayed, but probably a fair average would be threequarters to one pound acid equivalent of the raw 2.4.15-T per acre. In Vietnam, however, the concentration of 2.4..5-T for each acre sprayed has been far higher. In Agent Orange, the concentrations of 2,4,15-T have a veraged thirteen times the recommended concentrations used in the United States. The principal route through which quantities of 2,4,5-T might be expected to enter the human system in Vietnam is through drinking water, and in the areas sprayed most drinking water comes either from rainwater cisterns fed from house roofs or from very shallow wells. It has been calculated that, taking into account the average amount of 2,4,55-T in Agent Orange sprayed per acre in Vietnam by the military, and assuming a one-inch rainfall (which is quite common in South Vietnam) after a spraying, a forty-kilo (about eighty-eight-pound) Vietnamese woman drinking two litres (about 1.8 quarts) of contaminated water a day could very well be absorbing into her system a hundred and twenty milligrams, or about one twohundred-and-fiftieth of an ounce, of 2,4,5-T a day; that is, a daily oral dosage of three milligrams of 2.4.5-T per kilo of body weight. Thus, if a Vietnamese woman who was exposed to Agent Orange was pregnant, she might very well be absorbing into her system a percentage of 2,4..5-T only slightly less than the percentage that deformed one out of every three fetises of the pregnant experimental rats. To pursue further the question of exposure of Vietnamese to 2,4.5-T concentrations in relation to concentrations officially considered safe for Americans, an advisory subcommittee to the Secretary of the Interior, in setting up guidelines for maximum safe contamination of surface water by pesticides and allied substances some time ago, recommended a concentration of one-tenth of a milligram of 2,4,5-T in one litre of drinking water as the maximum safe concentration. Thus, a pregnant Vietnamese woman who ingested a hundred and twenty milligrams of 2,4,5-T in two litres of water a day would be exposed to 2.4.5-T at six hundred times the concentration officially considered safe for Americans.

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