By M.M. Hargraves, MD
Summary: In this thoughtful speech before the National Wildlife Federation, a Mayo Clinic physician presents his opinion on the causal effects of farming chemicals on human health. Citing numerous cases studies from twenty-five years of clinical practice, Dr. Hargraves presents a strong correlation of pesticide exposure with specific illnesses. While Hargraves concedes that “no one is capable of speaking with authority about exact causal relationships of pesticides and human health,” he maintains that “the vast majority of patients suffering from the blood…and lymphoid diseases have a significant history of exposure to the various hydrocarbons which in turn includes most of the pesticides of today.” Original source unknown, 1959. Lee Foundation for Nutritional Research reprint 105.
Chemical Pesticides and Conservation Problems
Presented as part of panel discussion before the 23rd annual convention of the National Wildlife Federation, Sheraton-McAlpin Hotel, New York, February 27, 1959.
Although I accepted this assignment quite willingly, it was not without many misgivings, I assure you. I realize that what I have to say today will be accepted as coming from someone speaking with authority, and yet I fully realize that no one is capable of speaking with authority about exact causal relationships of pesticides and human health.
For this and other reasons, I should like it to be understood at the onset that I am not speaking as a representative of the Mayo Clinic nor of my associates who practice medicine there. I am expressing my own personal opinion and no other. As an individual who has had considerable experience in the conservation field, a passing knowledge of farm and industrial practices, and twenty-five years in the practice of medicine, during which time I have seen people from all walks of life and from all parts of the country, I feel that I may have some advantage in correlating various aspects of the overall problem of pesticides in forming my opinions. However, such opinions do not necessarily make me an authority.
The “problem” of pesticides has generated considerable heat in the last few years, and this largely stems from the unknown effect, as yet, on human, animal, aquatic, and other biological values. The difficulty has arisen largely because each of us is viewing the “problem” from his own particular sphere of personal interest and specialized knowledge. This understandable situation has given rise to widely divergent views that have never been correlated with the views of those working in different [other] spheres and having different experience.
Actually, I doubt that any of us is completely aware of the real magnitude of the problem, particularly when we use the term pesticide. The shorter Oxford English Dictionary defines pest as, first, “any deadly epidemic disease or pestilence” or, second, “anything or person that is noxious, destructive, or troublesome.” It is of interest that the term pesticide is not yet included in this all-inclusive dictionary printed twenty-five years ago, and the term therefore must be of recent origin.
Since the suffix “-cide” means to cut or to kill, the term pesticide could be of the magnitude of your interpretation of what constitutes a pest. I believe that the present concept of a pesticide, however, is a lethal agent employed to destroy noxious insects and plants. Since the term noxious is also subject to individual interpretation, the problem grows in complexity. When one also realizes that the as yet relatively nonspecific pesticides in use today cannot discriminate between noxious and beneficial, the problem is further compounded. It is of little wonder that it becomes heated when the judgment of the one applying the pesticide must also be questioned as to his ability to so discriminate.
Before proceeding further, I believe that a scrutiny of the objectives of pesticide use is in order. Simply stated, perhaps we could agree that our objective in pesticide use is that of providing a more abundant and fuller life for the majority of involved people by controlling and altering the environment of our habitat. Here, of course, there will be a wide divergence of opinion as to what constitutes a more abundant and fuller life. However, I doubt that even in a group of this sort—dedicated as it is to the preservation of desirable natural environmental values—that there are many who would exchange their present-day living standard for that of their prehistoric, cave-dwelling ancestor. The problem of future change then becomes relative, as to both the means to be employed and the ends to be achieved.
However, the past is an accomplished fact, and everything that our ancestors did that was considered an advancement to the more abundant life was accomplished by the use of newly developed tools to alter the environment of their habitat. An often neglected or unrecognized corollary of this statement is that our ancestors were able to adjust to these environmental changes of their habitat. Conversely, and it would seem obvious without saying it, those who could not adjust perished and did not transmit their hereditary make-up to that of the surviving population. In other words this was the survival of those best fitted to adjust to the new environment of the habitat. That fact is still true today and is, of necessity, the crux of my thesis. If, then, you will agree with me that there are certain inherent risks in manipulating our habitat environment by means of new tools, I believe that we could summarize those risks associated with pesticide use as follows:
1. There is a loss of certain existing environmental values and ecological relationships, which are displaced by the resulting new ones, and only time and readjustment will prove which we may need for survival.
2. There is an acquired responsibility to maintain constant surveillance or policing protection of the resulting environment, since the introduction of the pesticide must now be a constant operating check in the new ecological balance established by its use.
3. There is a health hazard to existing individuals in the habitat, both from the effect of actual personal contact with the agent and from the need for habitat readjustment.
Actually, because of the ecological implications of each of these three risks, they can scarcely be separated, even for discussion’s sake. However, I will attempt to enlarge upon risk number three, that is, the health hazards, or the jeopardy to survival, experienced by the individual member of a population subjected to pesticide exposure.
Before any such effort can be made, it is necessary to attempt to clarify or define many terms or circumstances relating to cause and effect. I hope by this course to bring as much of the picture into focus as possible and avoid, as best we can, the half truths that can enter such a controversial discussion. There are enough half truths as it is even when we marshal all of the scientific evidence that we have available, and half truths can lead to individual panic and mass hysteria. There is need to avoid supplying any more ammunition than possible to the ever present paranoid but still mentally compensated crank who is back of many of the hysterical crusades that periodically emerge in every period of civilization. While such an individual may serve a purpose, he can still cloud an issue in need of solution for the common good.
Because I believe that the following concepts are either based on established facts or clinical evidence hard to deny, I present them for your consideration.
1. Pesticidal agents may be of many types, such as the inorganic elements of arsenic, lead, sulfur, and mercury, or the various plant glucosides, such as strychnine, curare, and digitalis, or bacterial by-products, such as dicoumarin. The toxicological effects of these agents are well known and will not be discussed. The pesticide of today’s discussion is the hydrocarbon, both aliphatic and aromatic, and its modified chloro-, bromo-, and nitro- forms, as well as the saturated, unsaturated, and cyclic chain compounds. In fact, the multitude of possible chemical combinations is almost beyond imagination, and the pesticides of the future potentially would seem to hold promise of great specificity of action, putting tremendous power of selective destruction in the hands of the user.
2. It may come as a surprise to many of you to find out that petroleum and the petroleum distillates are the most commonly used as well as the oldest pesticides of the day. While petroleum, asphalt, and tar have been used for centuries, it was only about 100 years ago that kerosene, or “coal-oil,” was combined with soap, as an emulsifying agent, and used as a pesticide, especially for the control of the various mites, scales, and other pests that damage fruit trees, shrubs, and bushes.
The implications of this statement are tremendous from a medical point of view, since this categorically puts our gasolines, fuel oils, cleaning fluids, lubricants, solvents, and a multitude of other petroleum agents into the class of pesticides whether we like it or not. Consequently, when we begin to look to “pesticides” and their effect on human health, you can see that we are surrounded by potential hazards, and it is difficult to differentiate between the multiple exposures as to which might be responsible for any particular pathologic state.
3. The problem of multiple exposures is inherent in petroleum and its distillation products. It was shown by careful distillation of a single sample from one oil well that more than two hundred different hydrocarbons were present in that sample. It is further recognized that no two oil fields yield a product of the same composition and that many crude oils are rich in the aromatic hydrocarbons, that is, the benzol series notorious for producing blood dyscrasias such as aplastic anemia, leukemia, and the lymphomas.
The problem is further complicated by today’s refinery change over to thermal cracking and reforming and, more recently, to catalytic cracking and reforming, which tremendously increases the percentage of aromatic, cyclic, and unsaturated compounds. This gives us our high-octane fuels, fuel oils, solvents, thinners, and multiple basic compounds for a rapidly expanding petrochemical industry to purify and fabricate into innumerable new products, which contribute to today’s more “abundant life.”
4. When we speak of a pesticide, we seldom refer to a single, pure compound, such as DDT, chlordane, lindane, dieldrin, 2-4-D, or others. The next time that you look at an insecticidal aerosol or a can of fly spray, I suggest that you read the label. You will find not only does it contain 2 to 5 percent of one or more of the chlorinated hydrocarbons, but these are suspended in 10 to 14 percent of “petroleum distillate,” together with some suspending or dispersing agent. In the can of bulk spray, the “petroleum distillate” may [constitute] 99+ percent, with a repellent such as pyrethrins added.
It is possible that the aromatic, cyclic, and unsaturated hydrocarbons of the “vehicle” may be more important as toxic agents when inhaled by the human bystander than the DDT or other agent that is being suspected of mischief. We forget, for example, that in the so-called “gypsy moth program,” one pound of DDT is suspended in one gallon of petroleum distillate (lightly glossed over as “one gallon of light oil”), to which is added one quart of xylene, which is dimethylbenzene.
5. In spite of toxicological work with animals, it is still entirely possible that aromatic hydrocarbons such as commercial xylene, when added to pesticidal mixtures, may be potent cytotoxic agents to the hypersensitive human who inhales them.
6. When dealing with poisons of any sort, most of us think in quantitative terms for any given substance. For example, the physician prescribes an accepted quantitative dose of drug to this patient and expects to get a result about in proportion to the mass or quantity given; the toxicologist determines the quantity of a poison that will kill 50 percent or 70 percent or 95 percent of a test animal or insect [population] and expresses his results as LD50, LD70 or LD95; the layman thinks quantitatively when he says “there was enough there to kill a horse.”
Such quantitative arguments are continually being used to reassure the public regarding the safety of pesticides, and toxicological experiments on animals (including human volunteers) are also being used as a yardstick for such measurement of safety. Such quantitative reassurance is of small comfort to the hypersensitive individual who reacts qualitatively and dies in spite of the reassurance.
7. In the human race, there is undoubtedly a more heterogeneous mixture of protoplasmic characteristics than in any other species. Certainly no two of us react alike to an emotional disturbance, and I am sure there is as much variation in our protoplasmic reaction to noxious agents. If this were not true, there would be little need for a physician, because it is the susceptible individual who “catches cold,” contracts pneumonia, or gets poliomyelitis, rheumatic fever, acute nephritis, hay fever and asthma, poison ivy, arteriosclerosis, heart disease, high blood pressure, and ulcers, to name a few. I might add that since modern medicine, in its broad sense, is saving more and more of these susceptible individuals from an early death, we can expect an increasing number of them in our expanding population, since their protoplasmic variations will be transmitted to their offspring.
In my opinion it is this susceptible or hypersensitive individual who runs the greatest risk of reacting adversely to the various hydrocarbons used as pesticides. It has long been known that chronic intoxication by benzol will produce aplastic anemia, leukemia, or lymphomas in certain susceptible individuals while not doing so in their exposed associates. In medicine practically every new drug that appears is first tried on 100 or 500 patients [to show there are no] severe “side effects.” However, by the time thousands or hundreds of thousands of patients have used it, reports begin to appear of susceptible individuals developing severe side effects such as liver damage, hemorrhagic disease, bone marrow failure, or other conditions that may end fatally. In fact, there is hardly a drug that does not have to be used without assuming a calculated risk, and in my opinion the same thing must be said of the pesticides.
8. With many noxious agents, intermittent exposures or exposures repeated after variable lapses of time may permit the susceptible individual to develop a marked degree of sensitivity, so that the next exposure may precipitate a disastrous consequence. Our periodic spray program would be an ideal mechanism to precipitate such a disaster.
9. Multiple exposures complicate our problem tremendously. Not only do our pesticides come mixed in a commercial form for more effective killing power, but we are also supplied in our environment each individual ingredient, to eat and inhale and do our own internal mixing. Reputedly, we ingest a goodly amount of chlorinated hydrocarbon in our food and store it in our body fat. Consider, then, the possibilities of inhaling very significant quantities of the fat solvents while working with gasolines, fuel oils, dry-cleaning agents, paint and varnish vehicles and thinners, solvents in the rubber and metal industries, and vapors of gasoline and diesel motors that constitute a major portion of city smells and smog, and perhaps the problem takes on a new complexion as well as greater complexity.
10. In view of these multiple exposures, there is the very good possibility—and probability—that many of these agents may have synergistic effects, that is, one greatly enhances the effect of another. For example, in the Merck Index one finds that piperine “has been used to impart pungent taste to brandy. (It is a) useful insecticide: Harvill, Hartzell, Arthur…have shown that piperine is more toxic to house flies than pyrethrum and that a mixture of 0.05 percent piperine and 0.01 percent pyrethrins is more toxic than 0.10 percent pyrethrins.”
There is considerable experimental evidence showing that some agents have the ability to block protective mechanisms in the mammalian body, permitting a second agent to destroy the animal during this refractory state. I believe that such mechanisms are probably in operation when the pesticides impair human health.
In presenting this partial list of factors that have to be taken into account when one talks about the “health hazards of pesticides,” I trust that I have shed some light on the problem and not simply confused it more. It seems to me that both opponents and proponents of pesticide use must be tempered by the responsibility that such complexity conveys.
[Though] one cannot categorically give exact causal relationships of pesticides and health at the moment, it must be remembered that there is always a beginning with every new or novel experience, when observation and circumstantial evidence must be used in making decisions for action and for opening up areas for research. So far as the pesticides are concerned, we in medicine are largely at the observation and circumstantial evidence stage. I often envy the entomologist, who can raise hundreds or millions of insects for controlled experimental laboratory investigation, while I struggle with successive patients, each with his own individual protoplasmic variations, piecing together a story of multiple exposures in an uncontrolled environment and trying to come up with a causal relationship of pesticides and disease states. It is little wonder that I get irritated when he writes and asks what experimental evidence I have to substantiate my beliefs.Since I am still in the observation stage, I should like to present a few thumbnail sketches of typical case histories that I feel contain considerable circumstantial evidence.
A man came to the Mayo Clinic because of a severe toxic pruritus, which he had had for a period of about four years. Numerous medications had been used, but none had seemed to be of any help. Lymph node biopsy finally revealed Hodgkin’s granuloma, and his skin complaint was that of an associated toxic pruritus. It was determined that at the onset of his illness the patient was engaged in a research project at one of the large United States government experimental farms, working on the nutrition of hogs. The hogs developed a severe dermatitis during the experiment, and the patient had repeatedly and intensively sprayed these animals with an aqueous solution of lindane.
A farmer with acute, fatal aplastic anemia had used an insecticidal powder consisting of “75 percent naphthalene” and its analogues to “scrub” into the backs of his cattle and to put into the nests and litter of his large chicken house throughout the winter.
A farmwife [used] insecticide powder containing “25 percent benzene hexachloride and its isomers” (actually hexachlorocyclohexane, not a benzol product) to kill flies and insects about the kitchen, back porch, outside toilet, and other areas. [She] “could sweep up the flies by the dustpanful.” [She developed] leukemic reticuloendotheliosis, with marked bone marrow invasion and depression of all peripheral blood elements.
A ten-year-old boy developed acute leukemia shortly after using an entire “bug bomb” “fighting bees” (wasps) in a closed garage.
A business executive [went on a] three-week “pack trip” into the mountains from September to October. The tents were sprayed with insecticides in the evening. Examination in December revealed: severe suppression of all blood elements; liver dysfunction (14 percent BSP [bromsulphthalein] dye retention); and “disturbed” hyperplastic bone marrows, consisting largely of leukoblasts and early erythroid cells. Sixteen months later [he is] slowly improving.
A banker from a small town in the Midwest was found to have chronic myelogenous leukemia. His major interest outside of the bank was a 200-head herd of registered beef cattle, which he continuously cared for [and] fitted for showing with petroleum distillate containing 40 percent chlordane.
A building contractor with fatal acute leukemia, when inspecting his housing development each day, would commonly “varnish a door for exercise” (using a petroleum distillate) before returning to his office.
A farmer admitted to the Mayo Clinic with an acute leukemia [had] spent a great deal of time during the preceding winter refinishing his furniture [using] a varnish remover containing “less than 49 percent benzol plus paint and varnish.”
A factory inspector who developed thrombotic thrombocytopenic purpura after a period of painting and decorating his house [experienced a] seemingly complete recovery after several weeks of steroid therapy and multiple transfusions. [He then experienced a] fatal relapse one year later, after again painting in his house and garage (in spite of previous advice against it) as well as vacationing in a small, closed tent heated by a gasoline lantern and stove because of inclement weather.
A carpenter [was] admitted in July 1958 [with] acute leukemia of the myelocytic type. [He] expired one month later. In his work he set a lot of Formica and tile using an adhesive, and he washed the excess adhesive off with gasoline after the job of setting was complete. He had had two “big jobs” with Formica the year before, with a great deal of gasoline exposure. In February 1958 he had another such exposure, followed by “the flu,” from which he never recovered. [This was] undoubtedly the onset of his leukemic symptoms, which progressed until his death in August.
A sales executive [was diagnosed with] acute leukemia. The patient actually was a paint chemist and manufacturer for the first seventeen years after getting out of college. Following this experience, he was the sales manager for another paint company. His illness began with redecoration of his own home—work done intermittently [with] some of his plant employees; [they] painted outside in good weather and inside in bad weather (with the house closed). Following this, he developed the present illness, which brought him to the Mayo Clinic. A diagnosis of acute leukemia was established; 6-mercaptopurine induced a very nice remission. He went to Florida to rest and recuperate and did well until the city began to fog the streets and neighborhood with insecticides for mosquito and fly control. The patient returned to the Mayo Clinic with an acute exacerbation of his disease and died after several weeks of supportive treatment with multiple transfusions, steroids, and 6-mercaptopurine therapy.
A housewife—the patient abhorred spiders—in mid-August used an insecticide aerosol sprayer (containing DDT and petroleum distillates) to very thoroughly spray her entire basement, under the stairs, in the fruit cupboards, and in all protected areas. She got nauseated and quite ill at the end of this period of spraying but recovered satisfactorily within the next few days. In September she repeated the performance on two occasions; she got ill on each occasion and began to develop fever, joint pains, and malaise [and then] acute phlebitis in the left leg. [She was] hospitalized on my service [with] splenomegaly [and the] blood picture of an acute myeloblastic leukemia. She died within the ensuing month.
A lawyer was admitted with an acute aplastic anemia. In the preceding few years, [he] had been exposed to considerable “fly spray,” but just preceding the present illness, the patient inhaled high concentrations of an insecticidal mixture consisting of 4 percent chlordane in 96 percent petroleum distillates as a “cure” for an upper respiratory infection. With supportive care and avoidance of further exposure, the patient seems to have made a complete recovery.
A Puerto Rican patient had multiple abdominal masses, causing partial bowel obstruction. Biopsy of the supraclavicular nodes revealed a lymphoblastic lymphosarcoma, for which he received treatment. Exposure history: Most of his life he had slept under the protecting cover of a mosquito netting tent; then, three years ago, the mosquito netting tent was displaced by a chlorinated hydrocarbon-petroleum distillate spray; several times a week, the bedroom was sprayed and closed for a period of time before the patient retired. After three years of this exposure, he appeared at the Mayo Clinic with his lymphoma.
A thirty-three-year-old farmwife was referred to the clinic with essentially a pure erythrocyte aplasia. No exposure history to common farm or household agents was obtained. However, it was finally determined that in her music room, where she played and practiced her piano for variable times each day, there was a lindane “fumigator” to keep the room free of moths, flies, and mosquitoes. This gadget is a recent addition to American life, in which a small container is electrically heated to vaporize lindane crystals into the air of the room. The patient had been inhaling these fumes intermittently for about a year.
A physician came to the clinic because of severe jaundice and anemia, which proved to be an acute hemolytic anemia with associated liver damage. His exposure history is interesting. He operates a convalescent rest home that became infested with roaches about mid-December of 1956. The patient attempted to rectify the situation by using aerosol insecticide spray, and he used approximately one “bug bomb” per week, working in all parts of the building—about the pipes, mopboards, bottoms of closets, and other secluded areas of this twenty-two-room sanitorium. Boxes of supplies coming to the sanitorium were also sprayed to prevent any new infestations. The doctor did all of this work himself and continued for approximately eight or nine weeks, progressively becoming more ill until he became so anemic that he collapsed and had to be hospitalized. He has since made a complete recovery and seems to show no ill effect from his near fatal experience.
[A patient spent] eleven years as pilot of crop-dusting planes, using numerous chlorinated hydrocarbons in aqueous solution. [The patent was] worried about exposures; examination revealed early liver dysfunction, with 12 percent dye retention (BSP).A businessman who runs a cotton gin and a contract crop-dusting agency—he buys insecticides by the truckload and contracts pilots and planes to dust for his customers, the planes loading near his warehouse—had depressed bone marrow for several years.
A fifty-five year old MD, his office in an old building, had a roach problem. He used a 25 percent DDT concentrate suspended in a solvent containing “a high proportion of methylated naphthalene” (he “found it to be no more irritating than kerosene”) plus an emulsifier of unknown nature. He diluted it in water and used it as a spray, working most of a Sunday, spraying his basement and all secluded areas. Within a short time, he began to bruise and bleed. Blood studies revealed severe marrow depression; he received twenty-five blood transfusions in the next three and a half months, [followed by] thirty-four more transfusions in the next critical two months, plus treatment with steroid. [It has been a] slow recovery, and a year later [he is] still not back to normal.
I believe that this representative type of case history, of which I have a large number, will illustrate what I mean. In fact, I believe that the vast majority of patients suffering from the blood dysorasias and lymphoid diseases have a significant history of exposure to the various hydrocarbons that in turn include most of the pesticides of today. A careful medical history will almost invariably establish such a relationship.
By Dr. M.M. Hargraves, the Mayo Clinic, Rochester, Minnesota. Original source unknown.
[Excerpt from Journal of the American Medical Association:]Hens, Eggs, and Fungicide-Treated and Fumigated Grains
Tetramethylthiuram disulfide (TMTD), or Arasan, is widely used as a fungicide in the treatment of commercial seed corn. Ethylene dibromide (EDB), or Dowfume EB-5, is widely used to fumigate grains stored in commercial elevators and farm granaries for the control of weevils. In 1955 it was reported that feeding corn treated with TMTD to laying hens resulted in the production of soft-shelled and misshapen eggs. Workers in Israel reported that grains fumigated with EDB, when fed to laying hens as part of their ration, resulted in a gradual diminution in egg size and, in extreme cases, to complete cessation of egg production.
During 1957 an egg producer in South Carolina, maintaining flocks totaling up to 10,000 birds, complained of a diminution in egg size and number after feeding oats as part of the laying hens’ ration. The oats had been treated with the grains fumigant EDB. The birds laid numerous so-called “pee-wee” (less than 18 ounces per dozen) and small (less than 21 ounces per dozen) eggs. The egg size improved when the fumigated oats were withheld but did not return to normal. Feeding trials (revealed that) corn containing tetramethylthiuram disulfide (TMTD) fed to laying hens may have disastrous effect on egg production, even when such grains are heavily diluted with nontreated corn.
By B.W. Bierer, VMD, and C.L. Vickers, DVM. From “The Effect on Egg Size and Production of Fungicide-Treated and Fumigated Grains Fed to Hens,” Journal of the American Veterinary Medical Association, May 15, 1959. Reprinted from J.A.M.A., August 29, 1959, p. 2159. Excerpt and preceding article reprinted as a single publication, Reprint 105, by the Lee Foundation for Nutritional Research, 1959.
Reprint No. 105
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