Safener for Herbicides

Herbicide safeners (also referred to as herbicide antidotes or protectants) fulfill an important role in crop protection. Safeners are chemicals that protect crop plants from unacceptable injury caused by herbicides. Either by placement on the crop seed or by way of a physiological selectivity mechanism, safeners in commercial use do not negatively impact the weed control of the herbicide. Although many herbicides have been developed for use without a safener, some of the strongest and most broad-spectrum herbicides tend towards border-line crop selectivity, which may completely preclude use in a particular crop or at least limit maximum use rates or the crop varieties that can be safely treated. It is for such situations that safeners have been developed. Several books and reviews of safeners have been written over the past 20 years [1-3]. It is not the intention of this chapter to cover in detail older safeners, but rather to focus on more recently developed commercial safeners as well as some of the older compounds still in wide commercial usage. 

The story of herbicide safeners began in 1947 with an accidental observation by Otto Hoffmann, a researcher in the Gulf Oil Company. On entering his greenhouse on a hot summer afternoon he saw that tomato plants had suffered injury that he presumed was from 2,4-D vapor drift. However, plants treated with 2,4,6-trichlorophenoxyacetic acid showed no symptoms of this injury [4]. Hoffmann recognized the potential use of such an effect and started research into compounds that could protect crops from herbicide injury. 

A fundamental problem for safener discovery and development is to find safeners that do not also antagonize weed control. The fruits of Gulf Oil Company research (reported by Hoffmann in 1969) was 1,8-naphthalic anhydride (NA), which works best as a seed treatment, whereby antagonism of weed control is not an issue. To the authors knowledge just over a dozen further safeners have been commercialized in the years since NA was introduced, although several of the early safeners have since been superseded and/or withdrawn. This subse- 

Modem Crop Protection Compounds. Edited by W. Kramer and U. Sdiirmer Copyright 2007 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31496-6 

To ensure maximum crop safety, safeners that are applied in mixture with the herbicides need to act quicker than the herbicide injury develops. The mechanism of action of safeners has received much scientific attention and will be dealt with in some detail in this chapter (Section 5.3). 

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Chapter 5, entitled Safeners for Herbicides , demonstrates the progress in this research field, bringing out new compounds that create highly competitive products for the farmers out of only partly selective herbicides having a very broad weed spectrum and very low application rates ( the chemical answer to genetically modified herbicide resistant crops ). 

As described for benoxacor, dichlormid also has similar physicochemical properties to those of the herbicide components, allowing for similar plant uptake profiles for good safening potential. Further extensive coverage of dichlormid can be found in Crop Safeners for Herbicides [1]. 

K. Halzios, R. Hoagland (Eds.), Crop Safeners for Herbicide, Academic Press, San Diego 1989. 

M. Barrett, in Crop Safeners for Herbicides Development, Uses and Mechanisms of Action (K. K. Hatzios and R. E. Hoagland, eds.), p. 195, Academic Press, San Diego (1988). 

Modification of the Toxicity of Pesticides with Formulation Additives. Potentially the use of additives to modulate the toxicity of pesticides could lead to a considerable increase in their safety to non-target species, man included. This concept has been well explored and exploited in adding safeners to certain herbicides such as the thiocarbamates. These compounds stimulate defensive metabolic reactions in the crop species but not in weeds This principle has also been applied to vertebrates, but only to a very limited degree. Under some circumstances the thiocarbamate rice herbicide, molinate, may show toxicity to carp in nearby ponds. Based on a knowledge of the safeners that are active in plants, a compound was discovered that, when applied with molinate, acted as an antidote/safener for the carp (20). Little effort, either theoretical or empirical, seems to have gone into developing other such examples. 

Iodosulfuron-methyl-sodium was the first safened sulfonylurea herbicide on the market [17, 18] when introduced in 1999 and has been commercialized by Bayer CropScience for use both in cereals and maize. A safener such as mefen-pyr-diethyl (cf Fig. 2.2.2) is a chemical that, when applied to crop plants, reduces the injury caused by herbicides to an acceptable level. A safener ideally does not... 

Mesosulfuron-methyl (AE F130060) (Table 2.2.11) [19] was the second safened sulfonylurea herbicide for cereal crops to be commercialized. This compound was introduced in 2001 and has been commercialized by Bayer CropScience [20, 21]. Its strength is broad-spectrum post-emergence grass weed control. Mesosulfuron-methyl, at a dose rate of 4.5-15 g-a.i. ha , reliably controls 24 different grass weed species from 12 different families. Among the commercially... 

The use of benoxacor with (S)-metolachlor is particularly necessary under stress conditions for maize. Injury to corn from (S)-metolachlor is greater under cool or wet soil conditions [6-8] where both the availability of the herbicide may be increased and the ability of maize to metabolize metolachlor reduced [9]. Benoxacor and metolachlor have similar chemical properties, influencing there behavior in soil, and this tends to ensure that the safener and herbicide are taken up together, hence providing safening under various weather conditions. 

This compound was recently developed as a safener for the sulfonylurea herbicide foramsulfuron in maize. Metabolism studies revealed that isoxadifen-ethyl also acts by enhancement of foramsulfuron metabolism in maize, while it does not influence the rate of metabolism of this herbicide in susceptible weed species [17, 18]. 

In corn, the catalyst for adoption of preplant incorporated applications was not the introduction of an herbicide, but the introduction of safeners. The thiocarbamate herbicide S-ethyl dipropylthiocarbamate (EPTC) for corn weed control was first used in Illinois as early as 1961 however, the propensity for EPTC to injure com limited its use to 1% or less of the Illinois crop up to 1970 (Table 4.1). Dichlormid, a safener later packaged with EPTC, greatly improved crop safety and resulted in nearly one-quarter of the com acreage being treated with EPTC throughout the Corn Belt by 1976. 

Polyamine safening agents for phenylcarbomoylamine acid herbicides", Japan. Kokai. Tokkyo Koho 78,94,035. January 24, 1977. 

Research on chemical antidotes or safeners has been summarized in several reviews and published symposia (3.-9). Most of the major developments (Table I) have resulted from impirical screening programs by Industry that may have been stimulated by observations of herbicide antagonism in plants (3, 10). However, some of the research on mode of action of antidotes has been directed at finding new ways to protect crop plants from herbicides (3). The research to be discussed in this text, namely the use of subtoxic herbicide pretreatments to improve crop tolerance to selected herbicides, arises in part from research on the mode of action of R-25788 as a selective antidote for EPIC or butylate in corn. 

Gianessi et al. [7] therefore compared the amount of glyphosate that had been used on herbicide tolerant soybeans in 2001 to the amoimt of mixed herbicides that would be required to achieve the same degree of weed control. For each U.S. state, an alternative mix of herbicides was composed for comparison, based on the outcomes of a survey among experts, e.g. a mix of Boimdary (metribuzin s-metolachlor), Flexstar (fome-safen), and Select (clethodim) in Iowa (Table 1). 

Direct-seeded rice does not tolerate pretilachlor in doses required for adequate weed control. The Ciba Geigy AG has discovered and developed a new safening agent, 4,6-dichloro-2-phenyl-pyrimidine (CGA123 407,23), which protects the rice seedling from damage and does not interfere with the herbicidal activity of pretilachlor. 

Foramsulfuron (AE FI30360) [48] is a postemergence sulfonylurea herbicide for the control of major grass species and certain broadleaf weeds in maize (Table 2.2.21). It is applied with the safener isoxadifen-ethyl (AE F122006) (Fig. 2.2.7) and in some products in combination with small quantities iodosulfuron-methyl-sodium [49]. 

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