April 1948
INDUSTRIAL AND ENGINEERING CHEMISTRY
(158) Ibid., E-636 (1945). (159)Ibid., E-656 (1945). (160) Ibid., E-706 (1946). (161) Roark, R. C., and Keenan, G. L., Ibid., Pub. 22 (1931). (162) Robertson, A., and Rusby, G. L., J . Chem. SOC.,1937,497. and Thompson, M. R., J . Am. Pharm. Assoc., 26, (163) Rosen, H., 631 (1937). (164) Rusicka, L., and Pfeiffer, M., Helv. Chim. Acta, 16, 1208 (1933). (165) Sequeira, J. H., Brit. J . Dermatol. Syphilis, 48,473 (1936). Schechter, M. S., and Haller, H. L., J . Ewn. (166) Siegler, E. H., Entomol., 37,416 (1944). (167) Sievers, A. F., Russell, G. A., Lowman, M. S., Fowler, E. D., Erlanson, C. O., and Little, V. A., U. S. Dept. Agr., Tech. Bull. 595 (1938). (168) Smith, C. R.,U.S. Dept. Agr.Yearbook, 1928,388. (169) Smith, C. R., J.Am. Chem. SOC.,53,277(1931). (170) Ibid., 56, 1561 (1934). (171) Ibid., 57,959 (1935). (172) Smith, C. R.,J . Econ. Entoml., 30,724 (1937). (173) Soloway, S. R., and LaForge, F. B., J . Am. Chem. SOC.,69,979 (1947). (174) Stiudinger, H., and Rusicka, L., Helv. Chim. Acta, 7,177,201, 212,236,245, 377,390,406,442,448 (1924). (175) Sullivan, W. N., Goodhue, L. D., and Fales, J. H., Soap Sanit. Chemicals,16,No.6,121 (1940). (176) Swinale, M.C., and Cooper, J. F., J . Econ. Entomol., 28, 220 (1935).
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(177) Swingle, W. T.,Haller, H. L., Siegler, E. H., and Swingle, M. C., Science, 93,60 (1941). (178) Takei, S., Miyajima, S., and Ono, M., Ber., 65B,1041 (1932). (179) Ibid., 66B, 1826 (1933). (180) Tattersfield, F., Ann. Applied Biol.,18,602 (1931). (181) Tattersfield, F.,and Martin, J. T., J. SOC.Chem. Ind., 56, 77T (1937). (182) Tattersfield, F.,and Martin, J. T., Ann. Applied Bwl., 25,411 (1938). (183) Tischler, N., J . Econ. Entomol., 28,215 (1935). (184) Tonking, H.D., E. African Med. J., 13,7(1936). (185) Uhle, E. C.,and Jacobs, W. A., J. Biol. Chem., 160, 243 (1945). (186) Wadley, F. M., U. S. Dept. Agr., Bur. Entomol. Plant Quarantine, ET-233 (1946). (187) Watson, J. R., and Tissot, A. N., Fla. Agr. Expt. Sta., Bull. 370 (1942). (188) Weed, A., Soap Sanit. Chemicals,14,No.6,133 (1938). (189) Wells, R. W., Bishopp, F. C., and Laake, E. W., J . Econ. Entomol., 15,90 (1922). (190) Wheeler, E.H., Ibid., 38,281 (1945). (191) Wheeler, E.H., and LaPlante, A. A.,'Jr., Ibid., 39,211 (1946). (192) Wilcoxon, E.,Hartsell, A., and Wilcoxon, F., Contrib. Boyce Thompson Inst., 11, 1 (1939). (193) Woke, P. A,, J . AQT.Research, 58,289(1939). (194) Worsley, R. R. Le G., Ann. Applied Biol., 26,650(1939). RECEIVED November 22, 1947.
Inorganic, Insectieides L. B. Norton,
Cornell University, Ithacd, N . Y.
T h e ionic nature of the inorganic insecticides results in easier penetration through the gut wall than through the integument of the insect, in the retention of toxicity of an ion in different combinations, and in high stability. The absorption of a toxic ion occurs mainly from solution, so that the potential toxicity of an ion is modified by its solubility from its compounds in the digestive juices of insects. A limited number of elements form compounds sufficiently toxic for practical insecticidal use. The arsenites are more toxic to insects than the arsenates but less suitable for use on plants because of greater solubility and plant injury. Similar considerations of solubility and phytotoxicity apply to the fluorine compounds, which rival the arsenicals in versatility. The importance of insect kill through the physical action of chemically inert materials such as mineral diluents and carriers has only recently been fully recognized.
C
OMPARATIVELY little work has been done in the past few years on the inorganic insecticides because the extremely rapid development i n the organic field has concentrated interest sharply i n t h a t direction. Consequently the present paper is designed as a review of the most significant properties and problems of the inorganic materials, based on work most of which is not new. The organic insecticides have displaced the inorganic i n many applications, but there are numerous situations in which the inorganic are still t o be preferred because of superior effectiveness, safety t o foliage, lack of high toxicity t o parasites and predators of the insect pest, or more fully understood pharmacological properties. The inorganic insecticides differ sharply from the organic in several particulars. Many of these differences arise from the largely ionic and relatively simple composition of the inorganic compounds. The insect integument is less permeable t o water and ions than t o organic and other poorly ionized compounds. Good lipoid solubility appears t o favor penetration of this barrier and to increase the rate and extent of contact action of organic compounds (11 ) . Acidification of the highly ionized sodium
arsenite i n solution to give the poorly ionized arsenious acid increases the penetration of arsenic into mosquito pupae (9). Similar results have been obtained with other compounds. On the other hand, portions of the digestive tract are more permeable to ions and simpler molecules, so t h a t the inorganic materials are easily absorbed from solution. Although there is some overlapping, i t is consequently found that most organic insecticides function best i n contact with the outer parts of the insect, whereas most of the inorganic are best as stomach poisons, absorbed through the gut wall after ingestion. A second conkquence of the ionic nature of the inorganic toxicants is that the effect depends chiefly on the concentration of the one toxic ion in solution (33) and little on its original state of combination. In practice the different compounds of the same ion may show considerable differences in effectiveness because of inadequate solubility, incomplete dissociation, additional toxicity furnished by accompanying ions, or possibly the formation of complex ions (18). This situation contrasts sharply with the behavior of the organic compounds where no single group ensures toxicity and where slight changes in any group may destroy the toxicity of the whole compound. A third characteristic of the ionic inorganic toxicants is their stability. The toxic ions go through most reactions unchanged and the essential element conferring toxicity will usually still show at least some effect even after a drastic change in its state of combination within a n ion. The inorganic materiaIs are usually stable t o air, sunlight, and high temperatures, and are seldom volatile. They are, however, subject to hydrolysis and solution i n water and t o precipitation of the toxic ion as compounds too insoluble for absorption into the insect system. ION SOLUBILITY
The solubility of the toxic ion is frequently the limiting facto1 i n the effectiveness of its compounds. Absorption of the ion both by insects and by plants occurs chiefly from water solution. If the ion is rendered completely insoluble, i t can pass through the insect without absorption and cause only possible mechanical injury. The solubility in pure water is seldom a reliable criterion
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of the availability of the ion to the insect or to t,he plant,. The solvent and reactive characteristics of the water on plant surfaces are modified by dissolved exudates, carbon dioxide, and other products of the vital processes of the plant ( 2 2 ) . The digestive juices of insects contain buffer systems, salts, colloids, and products derived from food which may react with the toxic compound and affect the quantity of toxic ion rendered soluble (2, 8, 18, 28). Fulmek (6) found that the toxicity of a series of metallic arsenites and arsenates to several species of insects showed little relation to their solubility in water, but was closely correlated with their solubility in a buffer solut,ion of p H 9 similar t o that in the gut of the silk worm. Swingle (27) showed t'hat the decomposition of the arsenicals depended both on the pH and on the anions, particularly t,he phosphates, found in the digestive juices. Markos and Campbell ( I S ) found rvide differences in the susceptibility t o calcium arsenate of armyivorms fed on different host plants. Those fed on the highly acid rhubarb were far more sus'ceptible. The composition and properties of the digestive juice vary widely not only in different insect species, but. also in different parts of the gut of t,he same insect (31). These variations go far in explaining many otherwise anomalous differences in t,he effectiveness of t,he inorganic insecticides under practical conditions. TOXICITY TO PLANTS AND ANIMALS
One of t,he greatest drawbacks in the use ,of the inorganic insecticides is their almost universal toxicity to other forms of life, both animal and plant. Shepard (2.4) records lethal doses of arsenic trioxide from 4.3 to 110 mg. per kg. of body weight for insects, 1.7 to 167 for warm-blooded animals, and a measurable effect on transpiration of oats in water cultures containing 1 p.p.m. of arsenic t.rioxide. Toxicity to animals has prevented the use on food plants and ot,her products of some otherwise good insecticides, and has led to legal restrictions on the permissible residues of lead, arsenic, and fluorine. I n spite of extensive study of the residue problem, no method has been found t o eliminate toxic residues except reduction of the quantity of insecticide applied or earlier application, substitution of other materials for part of the season, or mechanical or chemical removal after harvest. The toxicity to plants has been a major fact,or requiring detailed study of the chemistry of the inorganic insecticides t o be used on food plants. The margin of safety between control of the insect and injury to the plant is often so narrow that small differences i n composition, concentration, formulation, or physical properties may be decisive in permitting the use of a material for a specific purpose, Interaction of the insecticide with ot,her ingredients of a spray or dust, or even with the dissolved compounds in hard water, may render a material either less effective in insect control or more injurious to the plant. The term compatibility has been used widely to designate the absence of chemical interaction, Roark (33) has suggested the t'erm suitability as preferable for practical use because some pairs of compounds may undergo a chemical reaction and therefore be chemically inconipatible, yet the reaction may not render the mixture unsuit'able for use. A good example of incompatibilit'y but suitability is the widely used combination of lead arsenate and lime-sulfur which can be used for some purposes in spite of rather extensive interaction. In general, successful inorganic insecticides show a margin of safety widened by a far greater solubility in t'he insect digestive juice than in the usual spray mixture of the water on plant surfaces. The data on t,his point are far from complete, but are consistent where available.
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TOXIC ELEMENTS
A very limited number of elements form ions sufficiently toxic to be practical as insecticides. Except for borderline cases and untested materials, the list would include mercury, boron, thallium, arsenic, antimony, selenium, and fluorine. Sulfur as the
c H E M Is T R Y
Vol. 40, No. 4
element, or as lime-sulfur, has insecticidal uses but is used more often as a fungicide; it needs a supplementary material for adequate insect control. Mercury, t,hallium, and selenium are too toxic to warm-blooded animals for general use on food plants. Selenium has the interesting property of being absorbed from the soil by some plants; the selenate and sulfate ions apparently are somewhat int>erchangeable. This propert,y has been utilized for the control of aphids and red spider mites on ornamental plants (1, 1.5). This is one of the few known cases of successful insect control by a material introduced into the plant. Boron in the form of borax has been used on household insects, but is not widely applicable. Antimony has been used as tartar emetic (potassium antimonyl tartrate). I t shows considerable toxicity to some insect,s but its use is restricted. Arsenic and fluorine compounds are by far the most generally applicable of the inorganic materials for use on plants. Their importance and t.he large amount of information on tgeir characteristics merit separate discussion. ARSENICALS
Arsenic is toxic to insect,s in both the trivalent and pentavalent states. The arsenites are more toxic t o most, insect species (24) t'han the arsenates, but not t o all ( 1 4 ) . Fulmek (6) found that the arsenites of copper, magnesium, calcium, zinc, lead, and iron were each more toxic than the corresponding arsenates to the insects tested. Tests of this type are always complicated by differences in solubility as well as the potential toxicity of t,he ion in question. As already noted, Fulmek found the solubility of t,he arsenic in an alkaline buffer correlated with the toxicity. The usually greater solubility of t.he arsenites would be expcct,ed to enhance the greater inherent toxicity of the arsenite ion. The greater solubility and toxicity of the arsenites ran be fully utilized in poison baits and other applications where phyt,otoxicity is not a factor. Here the more soluble arsenic trioxide and sodium arsenite can be used, as well as the convenient Paris green (copper acetoarsenit,e). The latter compound was formerly used on plants, but it has been almost completely supplanted by the safer arsenat'es. Dearborn (3) found that an extensive series of fatty acids formed double copper salt,s with copper arsenite analogous to Paris green. Some of these compounds appeared to have some advantages over the acetate both in t,oxicity and in physical properties. Other arsenit,es have been studied, but none have competed seriouslv mit,h the arsenates for use on plants. The greater safety and versatility of the arsenates have resulted in their almost complete displacement of the arsenit,es for use on plants, in spite of their inferior toxicity t o insects. Most of the metals form extensive series of arsenates of varying acidity and basicity (12, i7, 19, 20, 25). This characteristic gives a greater choice of properties, but makes the preparation of a reproducible material more difficult. blost of these compounds exist only in the solid stmate,and the majority in each series can exist, only in equilibrium with a solut,ion of quite different, ratios of the component ions. Consequently, thei- dissolve differentially in water and inost solutions with hydrolysis and alteration of the solid compound. Only a few of them have a true solubility except' in narrow ranges of solution composition. The amount of arsenic rendered soluble is very dependent upon the p H and ionic composit,ion of the solution in contact, Tvith them. High p H values shift the equilibrium toward more basic solid compounds, wit'h consequent, liberation of soluble arsenic. Low pH values tend t o dissolve the cations preferent,ially and give more acidic solid compounds. If carried far enough, this may also eventually lead to more soluble arsenate ion. Most of the apparent, anomalies in the behavior of the different metallic arsenates can be traced to variations in the type of compounds present, t,he ranges of st,ability of corresponding types, and the digestive juices of the insects concerned. Dilead arsenate, the most versatile of the arsenates, can be prepared in substantially pure form. It is stable in slightly acid solution with very little soluble arsenic formed. Being acidic, i t is extensively hydrolyzed in alkaline solution. Ginsburg ( 7 ) investigated its formation of water-soluble arsenic in .the presence of a number of salts likely t o be found in hard water. Alkalinity always appeared to cause breakdown as well as precipitants for lead. Chlorides were very active, presumably because of the formation of a n insoluble lead chloroarsenate having a composition analogous to a basic arsenate and release of the remainder of the arsenic in soluble form. Basic lead arsenate can be used on very susceptible foliage since it is subject t o little hydrolysis under normal conditions and does not release soluble arsenic with chlorides such as those resulting from spray near the coasts.
April 1948
I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
A s might be expected from these same properties, i t shows considerably less toxicity t o insects than the dilead arsenate (%$). Much attention has been given t o correctives intended t o minimize the formation of water-soluble arsenic from lead and other arsenicals on plant surfaces. Lime, Bordeaux mixture, and zinc, aluminum, and iron salts are among the materials showing this effect. The mechanism is open t o some question, but is at least in part a precipitation or adsorption of the arsenic released from t h e arsenical by solution or hydrolysis. Such a mechanism should lead t o more extensive hydrolysis eventually, with the formation of more basic compounds which would be safer, but less toxic. With lime, the effect may be only temporary because of its neutralization by carbonation. Nevertheless correctives have been sufficientlysuccessful for wide use. ?he physical properties of lead arsenate have received much attention. Improvements in the particle shape and size have made the material more easily suspended in water and more adherent t o foliage. The effect of these factors on toxicity is not entirely clear (4, 26). Surface active materials have been added to improve distribution on the plant surfaces and various oils and other sticking agents t o increase adherence. The most spectacular of these stickers has been oil emulsified in such a way t h a t i t preferentially wets the lead arsenate at the moment of spraying or impact on the plant surface (9Q). This dynamite spray permits the building up of extremely high deposits t o control heavy insect infestations. Such variations in formulation have often succeeded where a simple lead arsenate suspension would not give satisfactory results. Acid calcium arsenate, unlike the corresponding lead arsenate, yields far too much soluble arsenic for use on foliage. A more basic material is used, prepared with a n excess of lime. Unfortunately, this process gives a heterogeneous mixture of several calcium arsenates which varies wide1 in composition with the details of preparation ( 1 6 , 17, 19, 2Oy. The amount of watersoluble arsenic does not give a reliable indication of the composition nor of the safety t o plants because of t h e temporary safening action of the excess lime (61). A safer product can be made by autoclaving or preparing in such a way as t o decrease the proportion of acidic compounds present in the mixture. However as in the lead arsenate series, the use of too basic a compound may lower the toxicity t o insects. The arsenates of other metals, such as manganese and magnesium, have been used, generally as mixtures of the more basic compounds. Basic copper arsenate can be made in pure form with a uniform particle size, and has had some use (30, 38). Numerous other metallic arsenates have been tried, uoually with only moderate success. FLUORINE
Some of the fluorine compounds are capable of competing with the arsenicals in insect control. Sodium fluoride and fluosilicate can be used in baits and other applications remote from food products, but are too injurious for direct use on plants. The problem is similar to t h a t with the arsenicals-to obtain s o h bility in the insect but not on the plant. This problem has been met probably most successfully by cryolite which furnishes little soluble fluoriine under field conditions but appears capable of releasing the soluble fluorine under the conditions found in the insect gut. Barium fluosilicate, which hydrolyzes under alkaline conditions to give soluble fluoride, has also proved useful. Most of the constituents of hard water dr, not seem t o be highly detrimental to these fluorine compounds, but lime and other calcium compounds lower their toxicity, forming calcium fluoride which has a low toxicity because of extreme insolubility. The fluorine compounds have not been used as widely as the arsenicals partly because their properties were not as well worked out, and partly because they raised a toxic residue problem comparable t o t h a t of the arsenicals. PHYSICAL TOXICITY
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Frankenfeld (5) has discussed the toxic effects of finely divided chemically inert mineral materials on insects in stored products. Similar effects have been noted with these materials as dust deposits on plants where both desiccation of the insect and increased penetration of the toxicant may beoperative ( I O ) . Asmany of these same materials are increasing in prominence as carriers and diluents for organic toxicants used in the field, this physical action is of special interest. It may go far toward explaining the superiority of certain formulations; the dependence of the desiccating effect on temperature and humidity may account for some of the discrepancies in effectiveness of the same formulations under different weather conditions.
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CONCLUSION
Further advances in the knowledge of the inorganic insecticides are likely t o take several directions. The effect of the inert materials requires S u c h exploration, A more complete knowledge of the chemistry of complex systems such as the arsenates would almost certainly lead to more effective and safer materials. Further knowledge of the physical properties and supplements would improve toxicity, deposit, adherence, etc. It is possible t h a t more complex ions or further salts of the known toxic elements might be found more effective. Elements not so far considered for use because of cost or rarity might prove practical in the future. Intensive work along most of these lines is unlikely in the near future because the residue problem would still remain, and the recent rapid development of outstandingly effective organic insecticides raises the question whether even the discovery of a greatly improved inorganic insecticide would be of sufficient use t o justify the time spent in its development. The inorganic insecticides are still more effective in certain cases than any of the organjcs yet developed, but it is impossible a t present to predict their future. LITERATURE CITED
(1) Blauvelt, W. E., Florists Emchange Hort. Trade World, 105, No. 17, p. 16 (1945). (2) Campbell, F. C., and Lukens, C., J . Econ. Entomol., 24, 88-94 (1931). (3) Dearborn, F. E., I b i d . , 28,710-14 (1935); 29,445-9 (1936); 30, * 140-3, 958-62 (1937). (4) Dickinson, B. C., and Witman, E. D., Ibid., 37,43-6 (1944). (5) Frankenfeld, J. C., presented at Symposium on Insecticides in Food Production, 112th Meeting A.C.S., New York, N. Y. (6) Fulmek, L., Fortschr. Landw., 4, 209-12 (1929). (7) Ginsburg, J. M., J. Agr. Research, 60, 199-205 (1940). (8) Hastings, E., and Pepper, J. H., J. Econ. Entomol., 36, 857-64 (1943). (9) Hoskins, W. M., Ibid., 25,1212-24 (1932). (10) Hunt, C. R., Ibid., 40,215-19 (1947). (11) Lauger, P., Pulver, R., Montigel, C., Wiesmann, R., and Wlld, H., “Mechanism of Intoxication of DDT Insecticides in Insects and Warm-blooded Animals,” Geigy Go., 1946. (12) McDonnell, C. C., and Smith, C. M., J. Am. Chem. SOC.,38, 2027-38,2366-9 (1916); 39,937-43 (1917). (13) Markos, B. G., and Campbell, F. L., J. Econ. Entomol., 36, 662-5 (1943). (14) Middlekauff, W. W., and Hansberry, R., Ibid., 34, 625-30 (1941). (15) Morris, V. H., Neiswander, C. R., and Sayre, H. D., Plant Physi ~ l . 16, , 197-202 (1941). (16) Nelson, 0.A,, J. Econ. Entomol., 32, 370-2 (1939). (17) Nelson, 0. A., and Haring, M. M., J. Am. Chem. SOC.,59, 221623 (1937). (18) Norton, L. B., and Hansberry,,R., J . Econ. Entomol., 34, 431-7 (1941). (19) Pearce, G. W., and Avens, A. W., J . Am. Chem. SOC.,59, 1258-61 (1937). (20) Pearce, G. W., and Norton, L. B., Ibid., 58, 1104-8 (1936). (21) Pearce, G. W., Norton, L. B., and Chapman, P. J., N. Y . A g r . Expt. Sta. Tech. Bull. 234 (1935). (22) Potts, S. F., J . Econ. Entomol., 23,469-70 (1930). (23) Roark, R. C., Ibid., 37, 302 (1944). (24) Shepard, H. H., “Chemistry and Toxicology of Insecticides,” Minneapolis, Burgess Publishing Co. (1939). (25) Smith, C. M., J . Am. Chem. SOC.,42,259-65 (1920). (26) Smith, C . M., and Goodhue, L. D., IND. ENQ.CHEM.,34, 490-3 (1942). (27) Swingle, H. S., Ala. Agr. Expt. Sta., 46th Ann. R e p t . , 1934, pp. 26-7. (28) Tietz, H. M., J . Econ. Entomol., 17, 471-7 (1924). (29) Washington State College, Emtension Bull. 232 (1938). (30) Waters, H. A., Witman, E. D., and DeLong, D. M., J . Econ. Entomol., 32, 144-6 (1939). (31) Wigglesworth, V. B., “Principles of Insect Physiology,” London, Methuen, 1938. (32) Witman, E. D., Waters, H. A., and Almy, E. F., J. Econ. Entomol., 32, 142-4 (1939). (33) Yeager, J. F., and Munson, S.C., Science. 100, 501-3 (1944). RECEIVED November 22, 1947
