with any definitive long-term 2,4,5-T studies. It is very reasonable to assume that as long as 2,4-D will, under dry conditions such as you find in Idaho, have harmful effects on crops a year or more after use that 2,4,5-T would also.

Senator HART. Doctor, thank you very much. It was a helpful paper.

The signal a few moments ago indicated another roll being called in the Senate. I apologize to Dr. Kotin, but we will have to take another recess, and I will be back just as soon as I can get on the roll.

(Recess.)

Senator HART. The Committee will be in order.

Our concluding witness on this first day of hearing is the Director of the National Institute of Environmental Health Sciences, Dr. Paul Kotin.

STATEMENT OF DR. PAUL KOTIN, DIRECTOR, NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

Dr. KOTIN. Mr. Chairman, I am privileged to be here today engaging in the practice of one of my most pleasant responsibilities-that of discussing the programs and plans of the National Institute of Environmental Health Sciences of which I am Director. Our Institute is a newcomer in the executive branch; we have been in existence since 1966, achieving the status of National Institute of Environmental Health Sciences only in January 1969.

This activity started as a small segment of the Department of Health, Education, and Welfare's effort in environmental health in response to recommendations made by several public advisory committees during the late 1950's and early 1960's. These committees starting with one chaired in 1958 by Dr. Stanhope Bayne-Jones and concluding with one headed in 1965 by Dr. Detlev W. Bronk-repeatedly emphasized the necessity of establishing within the Public Health Service an organization dedicated to performing fundamental research into the real and potential effects of human health wrought by a rapidly changing environment.

The decision of the Surgon General in 1966 that this research program be located within the National Institutes of Health-that Federal agency responsible for building the Nation's base of fundamental biomedical, health-related research-made clear the mission envisioned for our program. That mission was and is:

First, to determine the magnitude and significance of the hazard to man's health from long-term exposures to low-level concentrations of chemical, physical, and biological agents in the environment; and second, to elucidate the underlying mechanisms of adverse response with the hope that principles and generalizations would be identified to provide a scientific base for criteria upon which control agencies could set standards for protective and preventive measures.

During the present (1970) fiscal year, Congress and the President have authorized $17,730,000 to be expended in the conduct of this program.

Since you may be familiar with other programs of the National Institutes of Health, I would like to take just a moment to point out

to you some ways in which we are similar to other parts of NIH and some ways in which we differ. I might preface this by saying that we are similar to other NIH research components in more ways that we are different.

Like the other research institutes of NIH, our mission reflects two very important principles of operation: (1) We are in business primarily to add to the fundamental knowledge and understanding of environmental agents which as biomedical hazards immediately or ultimately affect human health.

In other words, we are concerned about the what and how of health effects first and foremost in human beings. That we must also understand that what and how of the complex constituents of our environment in order to perform the primary task is obvious.

Nevertheless, it is the results in humans which is of overriding concern to us. (2) The responsibility for taking direct action to control or eliminate the hazards which we must identify resides in other components of HEW.

I hasten to emphasize that we do not consider our job done until our findings are made available to the appropriate components of Government. To accomplish this, we maintain effective, close, and continuing relationships with the Environmental Health Service, the Food and Drug Administration, the Department of Interior, the Department of Agriculture, the Federal Trade Commission, and other agencies with control responsibilities.

The reasons for the distinction between fundamental research and control powers are, I think, important. First, the urgency in the need for control measures requires research directed to answering today's questions with today's techniques.

There is, however, an equally, or perhaps more, important need for research directed to questions having long-range implications extending for decades and perhaps even generations into the future. It is in response to this need that our Institute's program is designed.

While techniques frequently used in attacking these two sets of questions are similar, the orientation and end points stand in sharp contrast.

Second, freedom from control activities permits us to devote our total effort to research.

Third, control activities are performed by experts in an environment in which the guidelines for operation are completely dedicated to this responsibility.

Fourth, our relationship with industries, communities, and individuals is one based exclusively on scientific grounds rather than one of regulation, monitoring, and enforcing.

Finally, our inputs to control agencies are objective and provide an impartial basis for the very real practical considerations which must be faced in formulating and inaugurating control measures.

As noted, the fruits of our work are promptly forwarded to appropriate Government agencies for use in the pursuit of their mison with virtual simultaneous publication in professional journals rater than in the popular press.

This practice assures that our findings are subject to the scrutiny

and critical review of other researchers who have an opportunity to question our methods and conclusions by usual stringent standards.

I hope that the preceding discussion has placed the National Institute of Environmental Health Sciences in perspective for you.

I would now like briefly to tell you in somewhat greater detail some of the things we are doing, why we are doing them, and how we come to be involved in the resolution of the problem which is the subject of these hearings.

Speaking quite broadly, the NIEHS program attempts to employ a wide spectrum of scientific disciplines and bring them to bear on real and potential human health problems resulting from:

1. Changes in the makeup of the environment in consequence of technological progress and industrialization;

2. Changes in the size and characteristics of the population; and 3. Changes in the character of interactions between these two. In order to best understand the significance of changes in the makeup of the environment, we employ the disciplines of analytical and synthetic chemistry, pharmacology, and of biophysics.

In order to better understand our changing population and the subtle interactions of new and changing environments on people, we employ the sciences of epidemiology, biometry, pathology, and toxicology.

In order to establish the mode and mechanisms of interactions, we employ all categorical divisions of scientific inquiry with special emphasis on comparative biology to assure maximum relevance of research data to man.

These varied resources and methods have so far been brought to bear in programs studying the potential health hazards of:

Natural products including fungal contaminants of food; fibers and polymer dusts, asbestos and fiberglas; alpha radiation; trace metals (such as lead) and their compounds; hydrocarbons and their reaction products; tobacco smoke; and pesticides and pesticide synergists (including herbicides).

In all of these studies we are concerned with the effects of longterm exposures to low levels of concentration because these are the usual characteristics of exposure during life in the environment we have created for ourselves.

Effects are likely to be gradual in appearance, and most commonly the result of interactions of numberous agents combining in additive, synergistic, or antagonistic manners.

To dissect these complexities we must identify interactions at all levels from the intracellular organelle to the whole organism.

Our goals include determinations of threshold for response, effects of repetitive exposures, effects of storage of the agents in living organisms, and the roles of such host factors as age, sex, antecedent or concurrent illness, nutrition, behavioral characteristics, and genetic make-up.

It may seem that our approach is somewhat complex, but it must be so in order to resolve the complex problems wrought by the changes in our environment intrinsic to technological progress.

We have attempted, in the process of establishing the program of the Institute during the past 3 years, to maintain a measure of flexibility amid this essential complexity to provide for response to

unanticipated problems. Our current efforts in response to concern over the widening use of herbicides is in a way a case in point.

You are aware, I am now certain, that the recently completed study which revealed information about the toxicity of the herbicide 2.4.5-T. in fact, was initiated by the National Cancer Institute in 1963.

As indicated earlier, our Institute was not in existence at that time. However, I was the scientific director for etiology in the Cancer Institute at that time, and along with members then and now on my staff played a leading role in the initiation of the research contract with Bionetics Research Laboratories, Inc., which yielded the information under discussion.

Very briefly, that study was undertaken primarily to identify any potential carcinogenic (cancer causing) or teratogenic (birth defect causing) agents in a wide variety of pesticides and allied compounds in commercial use.

We also anticipated that the study would provide data on which to develop improvements in our methods for identifying carcinogenic agents and hopefully identify any correlations that might exist between the carcinogenic and teratogenic capabilities of single specific compounds.

Pesticides were selected for inclusion in the study on either of two bases; First, a projection of the potential extent of their use in terms of their utility in the community; and; second, a judgment as to potential carcinogenicity by virtue of chemical structure or metabolic fate.

In consequence, some 86 pesticidal products-including insecticides, fungicides, and herbicides were subjected to controlled, longterm studies on mice. As had been intended from the start, the study continued through the 1960's.

In the interim, the then Division of Environmental Health Sciences was established, and I was asked to become its first director. In agreeing, I was granted approval to take with me one or two key staff members scientists, as it happened-who had also been associated with the Bionetics contract.

Since intensive programing and developmental responsibilities faced my staff and me during the first years of our Institute, we were quite satisfied to leave the management of the Bionetics pestieide study in the able hands of our successors in the Cancer Institute, Furthermore, it should be recalled that the one major basis for the study was quite clearly related to the mission of the Cancer Institute, the identification of cancer-causing agents in the environ

ment,

Upon completion of the study in early 1969, the Cancer Institute released the results of the study. The results of the teratogenic studes were released to the Mrak Commission immediately as they became available. The popular press took intense interest in the findings reported, and pressures developed for more complete informahon on several of the pesticides included in the study.

The herbicide 2.4.5 T came under special scrutiny because its use ially widespread, particularly in military operations in Vietord that the Bionetics study had shown this chemical com

pound as "causing significantly more deformities than expected" was especially alarming in some quarters.

Dr. Endicott, then director of National Cancer Institute, requested that NIEHS staff familiar with the study in question, and also familiar with teratogenicity and pesticide chemistry generally, be assigned to data analysis and interpretation. NIEHS assumed sole responsibility for the statistical analysis of the very large volume of

data.

During the early stages of the now public discussion, it was pointed out by the Dow Chemical Co., a major supplier of 2,4,5-T, that the materials used in the Bionetics study were significantly different than those which had been supplied by Dow since 1965.

It is certainly true that the 2,4,5-T used in the study contained significantly larger amounts of an impurity, dioxin. This impurity is highly toxic and its presence occurs incidental to minor alterations in the reaction conditions during the manufacture of 2,4,5-T.

Dow Chemical Co. scientists contended that it was the dioxin derivative rather than the 2,4,5-T which had caused the deformities in test animals. A sample of the original 2,4,5-T used in the Bionetics study was analyzed and was found to contain 30 parts per million of this dioxin compound.

In consequence, it became necessary to restudy the situation to see whether the virtually no-longer-existing impurity in 2,4,5-T could be held responsible for the adverse effects.

In order to verify the possible role of dioxin, NIEHS brought its available resources to bear and undertook an accelerated program of research.

Pure 2,4,5-T-and by pure, I mean that which is now in the marketplace with a dioxin concentration of less than one tenth of a part per million-has been made available to us and recently we received the dioxin in pure state so that experiments can be repeated with the pure material, as well as with a combination of the two ingredients.

These studies are now underway. As indicated in prior discussions with the subcommittee staff, the results of this research are not yet complete. At such time as they are, in the very near future, we will be pleased to supply them to this committee.

I would be happy at this time to answer any questions of the committee regarding the mission of NIEHS or the circumstances leading to our current study of 2,4,5-T.

Senator HART. Thank you, Doctor. It was thoughtless of me-I should have suggested, since you commented on having a sore throat before, that you not read the statement, but merely put it into the record.

But I think as long as you were able to get through it, it helps all of us to hear it, rather than waiting for the printed record.

On this business of the study, do you know when the National Cancer Institute received its first data from Bionetics suggesting that 2,4,5-T was teratogenic?

Dr. KOTIN. I can't tell you offhand, but I would be very happy to get it for the record, sir.

(The information was subsequently received for the record :)

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