Standard Article

You have free access to this content

Fungicides, an Overview

  1. Keith J. Brent

Published Online: 15 APR 2003

DOI: 10.1002/047126363X.agr089

Encyclopedia of Agrochemicals

Encyclopedia of Agrochemicals

How to Cite

Brent, K. J. 2003. Fungicides, an Overview. Encyclopedia of Agrochemicals. .

Author Information

  1. Bristol, England

Publication History

  1. Published Online: 15 APR 2003

1 Origins

  1. Top of page
  2. Origins
  3. Evolution of the Modern Fungicide Armory
  4. Fungicides Today and Tomorrow
  5. Bibliography
  6. Further Reading

The damaging effects of plant diseases have been recognized since time immemorial. There are a number of references to the affliction of crops by blasts, mildews, and the like in the bible and in classical Latin writings, but the recognition that this damage was caused mostly by fungi came very much later. It was in the mid-19th century, through the publications of the Reverend M. J. Berkeley, Anton de Bary, the Tulasne brothers, and other pioneers of plant pathology, that certain fungi became known to be causal agents of crop disease. However, effective methods for preventing or decreasing the damage caused by fungal diseases of crops began to emerge somewhat earlier than this.

Disinfection of wheat seed to protect against bunt disease, which is now known to be caused by the fungus Tilletia caries, was advocated around 1750 by Jethro Tull. The seed was sprinkled with brine (aqueous solution of sodium chloride) and dried with lime. The use of brine is said to have originated from the planting of seed salvaged from a shipwreck. The efficacy of this treatment was soon demonstrated by Mathieu Tillet (1) in field experiments, which were probably the first fungicide trials ever done and were remarkably well conducted. Later, Benedict Prevost found that treatment of bunted seed with copper sulfate gave better control (2). Copper preparations, especially powdered copper carbonate, were used for many years until they were superseded by organomercurials, first reported in 1913 by the company I.G. Farben-Industrie A-G (3). Phenyl- and alkyl-mercury seed treatments proved even more effective than copper treatments against wheat bunt, controlled a broader range of seed-borne diseases of cereals, and were less injurious to the seed. Being cheap as well as efficacious, their use became routine on wheat and barley in many countries and persisted in some of them up to the early 1990s.

Regarding diseases of foliage and fruit, the first fungicide to become widely used was lime-sulfur. This originated in the work and writings of William Forsyth, gardener to King George the Third of Great Britain and Ireland. Having done field trials in Hyde Park in London, he recorded in 1802 that a mixture of sulfur, lime, tobacco, and elder-buds, when applied to fruit trees, suppressed powdery mildew (4). Lime-sulfur and, later, wettable sulfur preparations became increasingly used in Europe and the U.S. during the 19th century. Their first application to grape vines, which became by far the largest crop to be treated with sulfur, was also made in England by a Mr. Tucker of Margate in Kent, after whom the grape powdery mildew (now Uncinula necator) was first named as Oidium Tuckeri. Later, sulfur formulations found disease targets other than powdery mildews, for example apple scab (caused by Venturia inaequalis).

Then came the well-known discovery in ca. 1885 of Bordeaux mixture by Alexis Millardet (5), originating from its application to grape vines in order to deter thieves. Many other fungicide formulations based on copper compounds, notably copper oxychloride and cuprous oxide, were to follow. These gave control of downy mildew of grapes, caused by Plasmopara viticola, potato blight, caused by Phytophthora infestans, and other diseases not controlled by sulfur.

Since these earlier pioneering efforts in disease control, which focused on a few crops in Europe, the enormity of the damage caused by fungi to crops of many kinds throughout the world has become clear. Oerke, from a study of eight major crops, concluded in 1996 that crop disease globally causes a potential yield loss of 17.5%, and that this is reduced to 13.5% through control measures (6). The adoption of hygienic cultural practices, especially crop rotation, and the planting of disease-resistant varieties have decreased or prevented disease-induced losses in many crops, but fungicide application has been over many years, and still remains, the predominant means of crop disease management worldwide. Fortunately, the number, diversity, effectiveness, and safety of agricultural fungicides have all increased greatly, especially over the last three or four decades.

2 Evolution of the Modern Fungicide Armory

  1. Top of page
  2. Origins
  3. Evolution of the Modern Fungicide Armory
  4. Fungicides Today and Tomorrow
  5. Bibliography
  6. Further Reading

The first-invented fungicides, based on sulfur, copper, and mercury, served the farmer well. However, they were not fully effective against certain diseases, especially after infection had occurred, and tended to injure crops so that, in the absence of disease, they sometimes reduced yields or crop quality. There was much scope for other fungicide treatments with improved properties.

In 1934, the discovery of the dithiocarbamate fungicides was reported by Tisdale and Williams (U.S. Patent 1,972,961), working at E. I. du Pont de Nemours and Co., and independently by Martin in England (7). Over the next 10 years, major fungicides such as thiram, zineb, and maneb emerged within this family. The modern relative, mancozeb, is used very widely today in many crops. The dithiocarbamates proved as effective, in some situations more so, and less injurious to crop plants, compared with copper, sulfur, and mercury. However, like these earlier materials, they are surface fungicides. They penetrate little into plants, and so cannot affect established infections, which generally extend well below the plant surface. Moreover, treatments to foliage and fruit have to be repeated at frequent intervals in order to replace losses through weathering and to protect new plant growth.

Over the next 30 years, several other types of surface fungicide were introduced. The most important are probably the phthalimides, exemplified by captan, discovered by the Standard Oil Development Company together with Rutgers University (8), which was followed by captafol and folpet. Later chlorothalonil, the only member of its class and still widely used in cereals and other crops, was developed by the Diamond Alkali Company (9).

Systemic fungicides, which would penetrate and move in the treated plants and, hence, might eradicate existing infections and also move into new growth and resist weathering, thus avoiding repeated application, were sought after for many years but proved hard to find. Eventually, in the late 1960s, no less than six different types of systemic fungicide with high levels of effectiveness appeared in rapid succession: benzimidazoles, carboxamides, morpholines, 2-amino-pyrimidines, and organophosphorus and antibiotic rice blast fungicides. The reason for this sudden appearance of all these major systemics is not at all clear. Their chemical and biological properties, places of origin, and discovery processes were diverse. The adoption of in vivo screening tests and increased screening throughputs probably contributed, together with some luck.

A second batch of highly active fungicides, with different degrees of systemicity, emerged in the mid-1970s: dicarboximides, phenylamides, triazoles, and fosetyl-aluminium. After a lull of some 15 years, yet another wave has recently appeared, comprising strobilurins, anilinopyrimidines, and phenylpyrroles.

These modern fungicides have attained new standards of disease control, often at relatively low doses, coupled with relatively low mammalian toxicity. Some of them work against specific targets, for example dicarboximides against Botrytis and Sclerotinia spp. and 2-amino-pyrimidines against powdery mildews. Others have a broad spectrum of action, especially the strobilurins, which are unique in working on all the major classes of plant-pathogenic fungi (oomycetes, ascomycetes, and basidiomycetes). Some are highly xylem-mobile, but others, notably the dicarboximides and strobilurins, have only limited mobility in the treated plant. Phloem mobility, permitting movement out of treated leaves and downward translocation to roots is generally absent but has been observed with fosetyl-aluminium.

The biochemical mechanisms of action are diverse and cannot be described here individually. As a general rule, the surface fungicides (sometimes called protectant fungicides—a misnomer because all systemic fungicides exert a protectant action) have a multiple action, affecting a number of different target enzymes in the target fungus, whereas the systemics affect either a single site or a relatively small number of sites. Thus, the systemics are vulnerable to development of resistance in populations of the target pathogens through single-gene mutations that modify the site of action. In practice, many problems of resistance to almost all classes of systemic fungicides have occurred, whereas most of the surface fungicides have not encountered resistance development after many years of widespread use, often on schedules of many repeated applications.

3 Fungicides Today and Tomorrow

  1. Top of page
  2. Origins
  3. Evolution of the Modern Fungicide Armory
  4. Fungicides Today and Tomorrow
  5. Bibliography
  6. Further Reading

Over 200 fungicides have been introduced into agriculture to date, and, of these, some 140 are in current use. Many of these are described in the articles that follow. The number of formulated products, based on single fungicides or on mixtures of two or more, is several times larger. In 1998, the global sales value of fungicides was of the order of five and a half billion U.S. dollars. While some fungicides have been withdrawn from commercial use for various reasons, the majority of those discovered are still in use. These include Bordeaux mixture and sulfur, whose use is currently increasing because their application is permitted under certain circumstances in organic crop production.

When properly applied at the correct times, fungicides usually perform very well and have an acceptable margin of safety to humans, wild life, and crop plants. However, we still need new fungicides for several reasons. Despite the large total number of fungicides that are available, each particular crop disease typically is well controlled by only two or three marketed fungicides, each with its strengths and limitations. A wider choice of treatment is desirable for many crop diseases. The development of resistant mutants of target pathogens has led to losses of effectiveness, in certain regions and uses, of most of the modern fungicide classes. Further resistance problems seem likely to arise despite the considerable efforts of the agrochemical industry and farm advisory services to promote the use of countermeasures. New types of fungicide can act as effective replacements for these problem situations and also increase the diversity of treatment, which is a mainstay of fungicide resistance management. Certain fungicides, for example, captafol, binapacryl, organomercurials, and ethylenebisdithiocarbamates, have been banned from or restricted in commercial application because of perceived toxicological risks or because manufacturers are not prepared to do additional toxicological or environmental safety evaluations required by regulatory authorities, and further withdrawals for these reasons are likely to occur.

Fortunately, new fungicides with distinctive chemical and biological properties continue to be invented. Fungicides introduced over the past two years or so, or known to be at an advanced development stage, include, among others, famoxadone (Du Pont), quinoxyfen (DowElanco), fenhexamid (Bayer), iprovalicarb (Bayer), and MON6500 (Monsanto), together with several newer strobilurins. MON65500 is unusual in that it controls take-all disease of wheat (caused by Gaeumannomyces graminis var tritici), a root disease unaffected by almost all other fungicides. Fluquinconazole also has reported recently to be effective against take-all.

Acibenzolar-S-methyl (Novartis) has attracted special attention because it acts against a very wide range of plant diseases but does not directly affect the growth or metabolism of the causal organisms. It is known to act by stimulating systemic activated resistance (SAR) in the treated plant. The well-established compound probenazole, which for some years has been the leading treatment for rice blast in Japan, is thought to act in a similar way. Pathogen resistance to probenazole has not developed, and such stability of performance may well be a general feature of SAR-inducing compounds.

Thus fungicide invention continues very actively, despite the many mergers between agrochemical companies and consequent reduction in number of research centers and despite the ever-increasing standards of disease control and regulatory requirements with regard to margins of safety to the environment and human health. Discovery still depends largely on high-throughput screening of candidate chemicals, now aided by target-enzyme tests, combinatorial chemistry, and computer modelling. However, the fully rational design of molecules that fit all the needs of a successful practical fungicide (biological activity, stability, environmental safety, crop safety, ease of manufacture, etc.) has yet to be achieved. It is debatable whether the current pace of discovery can be maintained, especially because demand has plateaued or even declined in some areas. One critical factor, at present hard to assess, will be the extent to which plant varieties with improved, long-lasting disease resistance will emerge through genetic engineering and reduce the need for fungicide applications. Use of biological control agents in crop disease management has achieved little significance up to now but may well increase in the future, particularly as seed treatments or in glass-house or produce-storage environments.

Complementary to the inventive effort is the need for further research into the most cost-effective and safe ways of using fungicides. At present, large quantities are wasted through inefficient application, inappropriate timing, or unnecessarily large doses. Computer-based decision-support systems are under development, and research continues on precision delivery systems designed to place pesticides where they are needed in the crop. Both of these approaches may help to optimize fungicide treatments. The need for integration of fungicide applications with other crop management components, such as crop rotation, sowing date, choice of crop variety, fertilizer use, and soil cultivation, is increasingly recognized and researched. The integrated approach requires larger inputs of knowledge and observation by farmers and advisers and depends greatly upon their having a very good understanding of the nature and properties of the fungicides that are available to them.

Bibliography

  1. Top of page
  2. Origins
  3. Evolution of the Modern Fungicide Armory
  4. Fungicides Today and Tomorrow
  5. Bibliography
  6. Further Reading
  • 1
    M. Tillet, Dissertation sur la cause qui corrumpt et noicit les grains de blé dans les epis et sur les moyens de prevenir ces accidens, Bordeaux, 1755.
  • 2
    B. Prevost, Memoire sur la cause immediate de la Carie ou Charbon des blés et de plusieurs autres maladies des plantes et sur les preservatifs de la Carie, Montauban, 1807.
  • 3
    E. Riehm, Mitt. Kaiserlich. Biol. Anst. fur Land- u Forstwirtschaft 14: 89 (1913).
  • 4
    W. Forsyth, A Treatise on the Culture and Management of Fruit Trees, Nichols, London, 1802.
  • 5
    P. M. A. Millardet, Traitment du Mildiou par le Melange de Sulphate de Cuivre et de Chaux. J. Agric. Prat. 49: 513805 (1885).
  • 6
    E.-C. Oerke, in H. Lyr, P. E. Russell, and H. D. Sisler, eds., Modern Fungicides and Antifungal Compounds, Intercept, Andover, MA, 1996, pp. 1724.
  • 7
    H. Martin, J. South Eastern Agric. Coll. 33: 3841 (1934).
  • 8
    A. R. Kittleson, Science 115: 8486 (1952).
  • 9
    N. J. Turner et al., Contrib. Boyce Thompson Inst. 22: 303306 (1964).

Further Reading

  1. Top of page
  2. Origins
  3. Evolution of the Modern Fungicide Armory
  4. Fungicides Today and Tomorrow
  5. Bibliography
  6. Further Reading
  • Anonymous, C. D. S. Tomlin, ed., The Pesticide Manual, 12th ed., British Crop Protection Council, Farnham, 2000. (This gives information on the chemical and biological properties, uses, and toxicology of all fungicides and other pesticides in commercial use worldwide.)
  • Brent, K. J., Pathways to success in fungicide research and technology, in H. Lyr, P. E. Russell, and H. D. Sisler, eds., Modern Fungicides and Antifungal Compounds, Intercept, Andover, MA, 1996, pp. 315.
  • Brent, K. J., Fungicide Resistance in Crop Pathogens: How Can It Be Managed? FRAC Monograph No. 1, Global Crop Protection Federation, Brussels, 1995.
  • Brent, K. J. and Hollomon, D. W., Fungicide Resistance: The Assessment of Risk, FRAC Monograph No. 2, Global Crop Protection Federation, Brussels, 1998.
  • Large, E. C., The Advance of the Fungi, Jonathan Cape, London, 1940.