April 1948
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INDUSTRIAL AND ENGINEERING CHEMISTRY
Even after sizable investments in research, many products fail to reach a retail market. Such development costs seem unjustifiably high and thus appear to be an excessive mark-up on the finished products, which do reach a market. The development of a new agricultural chemical is often a discouraging process. The men in industrial research laboratories are qualified to make all types of chemicals within the facilities of their respective laboratories. These chemicals would be only shelf stock unless they could be used in some manner. A research project usually starts with a selected number of chemicals from laboratory stocks. These chemicals must first be screened for their biological applications, either through facilities owned by the company or through outside research organizations equipped and staffed to run biological tests. Many companies find that screening can be done by an outside organization at less expense than in their own laboratory. The Crop Protection Institute aids manufacturers by furnishing biological data at a reasonable cost. The work of the institute is typical of that carried on in many of the large industrial laboratories and can be used as an example to illustrate screening. For effective *use on plants or animals an agricultural chemical must kill the insect or destroy the fungus without harm to the host. This is a basic requirement for which many screening tests have been developed. The field of agricultural chemistry is still too new for chemists to be able to predict whether this or that chemical will react biologically. The only satisfactory method of determination is to try the chemical through a series of biological screens, which, in one way or another, may indicate if the chemical has any biological value. Laboratories differ in their selection of test animals and plants. In all cases a large stock of testing cultures must be maintained for the tests to run smoothly. For insect testing, houseflies, mosquitocs, bed bugs, roaches, ticks, grain insects, carpet beetles, clothes moths, Mexican bean beetles, Southern armyworms, milkweed bugs, and aphids are in common usage. For Elant testing, beans and tomatoes are in most common use; many other plants are needed ior special tests. A full biological screen will include ten or more different techniques. Most chemicals are rather specific. Thus a chemical that will ki!l houseflies may be of little value against aphids or leaf feeding insects. Another chemical may. be of no value as an insecticide yet be an excellent mildew-proofer, fungicide, or weed killer. A chemical that shows value in screening tests is further eval&ted for range of usefulness, and dosage level, and
is formulated for application, as a gas, aerosol, wet spray, or dust. Testing and retesting is time-consuming and expensive, but if acceptable after screening, the new product must then be put through a long series of laboratory and field teats. Many field tests will be in competition with similar products from other manufacturers. After the development work is done, management must be sold on the advisability of investing in the necessary manufacturing equipment to make the product. This is generally not too difficult because management is fully aware of the value of its research program and ready to make a product which will be of credit to the company. The finished product can now be turned over to the sales organization which in turn must become thoroughly familiar with the product before it can be sold and properly serviced. In the postwar period the public is extremely pest control conscious. Sales of products for pest control boomed during the war and are still a t very high levels. Furthermore, the market for new and better insecticides and fungicides seems unlimited. For as each new agricultural chemical is developed, new uses are found for i t without seriously disturbing the sales of older, competitive materials. The development of D D T has stimulated research with organic chemicals in many agricultural fields. As a result organic chemicals that have many new uses in agriculture are appearing on the market. Selective poisoning is becoming a fine art; chemicals are used in previously unheard of applications-for example, killing soil-infesting insects, sterilizing soil from weed seeds, weeding crops by spray or dusting, destroying unwanted vegetation, protecting forest areas and products, preventing insect breeding, destroying internal parasites in animals, and a host of other new uses. The balance between nature and living plants and animals is extremely narrow. A slight chemical adjustment one way or the other will result in major shifts of this biological balance. Economically the objective is control of the disturbing factor without injury to the major crop, and one of the most promising methods of control is through the field of chemistry and its application to agriculture. Chemicals are coming from the laboratories faster than they can be tested biologically. Screen tests are almost constantly indicating some promising chemical. From this research will come new methods for the future control or eradication of many insects. RECEIVED November 22, 1947.
Fungicides in Food Production
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James G . Horsfall Connecticut Agricultural Experiment Station, New Haven, Con-.
In general, fungicides differ from insecticides in that they are protective in action rather than direct. Specifications for the ideal fungicide, theories of the mechanism of killing fungi, and the performance of new organic fungicides are discussed. ARMERS for generations have known the need for fungiF c i d e s . The famous epidemic of late blight and rot of tomatoes in 1946 emphasized this need to home gardeners as well. Chemicals for many fungus diseases are reasonably satisfactory, but other diseases run unchecked for lack of suitable materials. The purpose of this paper is t o report on the useful chemicals, both new and old.
Three facts are essential to an understanding of fungicidal action (2): (1) The use of fungicides is generally preventive. In very few cases can fungicides be used to eliminate infections already begun. I n food production, fungicides are used to protect foliage, fruit, seeds, and roots against damage, during both productionand marketing. (2) Fungus diseases run rampant chiefly during wet weather. (3) As far as is known, a chemical must be in solution before it will kill a fungus. These three circumstances establish a pattern for fungicides, irrespective of their composition, that is an optimum compromise between the factors concerned. RESISTANCE TO WEATHER.Because practical difficulties prevent the application of chemicals during the infective rains, it is
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necessary to apply them in dry weather. The chemical must have the capacity to cling to the treated tissue during the bright dry weather preceding the rains, and then be able to hang on despite severe buffeting by wind and water during the storms. Therefore, as a prerequisite, the chemical must be exceedingly stable to light, air, and water in the presence of foreign dust and dirt. POTENCY TO FUNGI.The qualifications of insolubility and stability are not so difficult to find among organic and inorganic chemicals. However, at the same time, the chemical must be sufficiently unstable and soluble to penetrate and attack the living parts of the fungal cell. NONPOTENCY TO THE HOST. If, after careful search among the possibilities, a stable-unstable, and soluble-insoluble compound mere found, there would then be the requirement of nonpotency to the host. The chemical should kill one type of plant protoplasm (the fungus) without simultaneously killing another type of protoplasm (the host). Until about 150 years ago, when copper and mercury fungicides became known, sulfur was the only pesticide used in agriculture. During the past ten years greater advances have been made in the development of new fungicides than in a11 the previous years. MECHARISMS OF KILLING FUNGI
Sulfur ‘and copper fungicides are sufficiently insoluble and stable to resist sun, wind, and rain, yet are soluble enough to penetrate a fungal spore and kill it. There are two major theories to account for this effect: The oligodynamic theory and the suicide theory (6). The first theory envisages a situation where a sublethal dose of the chemical exists in a solubility equilibrium in the drop of water. The spore absorbs the soluble material which is then replaced from the reservoir of insoluble material, Eventually the spore takes up enough toxicant to killit. Despite considerable evidence in support of it, the oligodynamic theory is probably of minor importance. The second theory postulates that as the spore begins to germinate, it excretes substances into the drop of water around it. The excretory products dissolve the toxicant, presumably by the formation of a water-soluble salt. This salt then diffuses into the spore and kills it. Thus the spore accomplishes its own destruction. I n practice both mechanisms probably operate. I n the case of insoluble copper protectants, like basic copper sulfate, it has been assumed that organic acids, especially amino acids, are the active solubilizers. I n the case of elemental sulfur, the proponents of the suicide theory (6) are somewhat less specific. All they know is that hydrogen sulfide is liberated from elemental sulfur by living tissue. Hydrogen sulfide can be shown to be highly toxic to fungal tissue. Therefore, the spore kills itself by causing the liberation of toxic hydrogen sulfide from the sulfur. Knowledge of what goes on inside the cell is limited; there are three explanations regarding the action of copper: the popular theory, that the heavy metal coagulates the protoplasm so that it can no longer operate normally; another, that the copper interferes with the energy-releasing systems of the cell; and further, that it need not penetrate the cell, but operates as the oxide formed by hydrolysis, and the oxide acts to overcatalyze oxidation. I n the case of sulfur, i t has been proposed recently that the hydrogen sulfide acts as a metal precipitant (1). It precipitates the metals in the cell that are essential to its life processes. It may also overload the -SH component of some of the oxidationreduction systems in the cell. NEW ORGANIC FUNGICIDES
S e w organic fungicides have been developed partly by method but mostly by guess. An outstanding instance of the former is tetrachlorobenzoquinone; its value as a fungicide was dis-
Vol. 40, No. 4
covered by a rubber chemist (7). It is now used commercially (as a seed protectant, not as a foliage protectant) on thousands of bushels of legume seeds, such as peas, to prevent the growth of rot-producing fungi in the soil. Tetraohlorobenzoquinone is an example of specificity, a characteristic that will often present a problem to entomologists and farmers. The compound is too photochemically active to succeed on foliage. It must be used below ground where it will be in the dark. The fungicidal action of sulfur has been extended by means of organic compounds, especially dithiocarbamates (8). The use of organic sulfur compounds in plant pathology preceded their use in animal pathology but sulfone compounds have not proved effective in plant pathology. Three types of dithiocarbamate compounds have reached the stage of commercial adoption: (1) Tetramethylthiuram disulfide is used primarily for turf diseases, although i t gives satisfactory control of diseases of agricultural crops. (2) The use of metal salts of dithiocarbamic acid-for example, ferric dimethyldithiocarbamate-as foliage protectants particularly on fruit crops is increasing; ferric dimethyldithiocarbamate is used, to the extent of manufacturing capacity, on fruit crops, especially on apples for the scab disease; and zinc dimethyldithiocarbamate is used on vegetables, especially tomatoes for anthracnose and early blight. (3) Metal salts of bisdithiocarbamic acid are the most recent arrival in the field of the dithiocarbamates (1). Sodium ethylenebisdithiocarbamate in a mixture with D D T and a small amount of zinc sulfate and lime has gone far toward capturing the potato market from Bordeaux mixture. This feat was considered impossible as late as 1943. Recently zinc ethylenebisdithiocarbamate has partially replaced t h e sodium salt plus zinc sulfate and lime. Quaternary ammonium compounds have been tested as foliage protectants, but they generally are too susceptible to loss b y weathering. About the only practical material so far developed for the protectant field is phenyl mercuric triethanolammonium lactate ( 4 ) . This material bids fair to invade the apple scab field, and already seems established in the field of turf diseases. 1-Hydroxy-2-trichIoroethy1 bis-2-chloroethyl phosphite ( 3 ) and certain glyoxalidine derivatives, such as 2-heptadecylglyoxalidirie (Q),have shown good preliminary promise. The success of these two groups remains to be demonstrated. TWO NEW TRENDS
I n the past, research emphasis on developing new fungicides has been directed at finding fungus killers. Recent research indicates that the prevention of reproduction may be of significance. If the fungus cannot reproduce itself it cannot induce any great amount of damage. Chemotherapy, or the treatment of plants from the inside out, rather than from the outside in, offers distinct promise. Although it has not been investigated extensively on food crops, it may provide a means of combating the dread Dutch elm disease. The chemical that is being tested on a practical scale a t t h e moment is 8-hydroxyquinoline benzoate. LITERATURE CITED
(1) Barratt, R. W., and Horsfall, J. G., Conn. Agr. Expt. Station. BUZZ.508, 1-51 (1947).
Horsfall, J. G., “Fungicides and Their Action,” Waltham, Mass., Chronica Botanica Co., 1945. (3) Horsfall, J. G., and Barratt, R. W., Phytopathology, 37, 10 (1947) (4) Howard. F. L.. and Sorrel], M. B., Ibid.,33, 1114 (1943). ( 5 ) McCallan, S.E. A., and Wilooxon, F., Contrib. Bogce T h o m p s o n Inst., 3, 13-38 (1931). ( 6 ) Swingle, W. T., U . S. Dept. Agr., Div. Vegetable Physiol. and Pathol., Bull. 9 , 1-37 (1896). (7) ter Horst, W.T. (to U. S. Rubber C o . ) , U. S.Patent 2,349,771 (May 23, 1944). (8) Tisdale, W. H., and Williams, I., U. S.Patent 1,972,961 (1934). (9) Wellman, R. H., and McCallan, S. E. A., Contrib. Boyce Thompson Inst., 14, 151-60 (1946) (2)
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RECEIVED hTovember 22, 1947.
