Thiocarbamates safener

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. 

The history of another thiocarbamate, butylate, is similar to that of EPTC. Initially marketed without a safener, butylate s propensity for crop injury resulted in some resistance to its use from farmers. When butylate was released with a safener, this combination product became widely accepted. Because EPTC was more volatile than butylate, it tended to be better suited for the cool soils of the northern Com Belt. Butylate, on the other hand, was better adapted to the southern corn-growing region of the Central Plains. 

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. 

R-29 148 exhibits safener activity comparable to R-25 788 when tank-mixed with thiocarbamates. 

Independent of this discovery, in 1982 scientists from the same company were working on a project aimed at preparing novel Acetyl-CoA carboxylase inhibitors, based upon the typical cyclohexanedione structure known for this class. The first targeted compound (2), prepared as shown in Fig. 4.3.1, showed some herbicidal activity and they thus attempted preparation of a phenyl analogue in a similar manner. This led not to the expected product (3), but to the triketone (4). This compound was devoid of herbicidal activity, but (luckily ) in safener screens the compound showed antidotal effects in Soya for thiocarbamate herbicides. A further round of synthesis optimization was undertaken and it was found that the compound (5) with an ortho-chloro substituent showed reasonable herbicidal activity. Furthermore, they noticed that it exhibited the same unique bleaching symptomology observed for leptospermone (1, Fig. 4.3.1) [4]. Further optimiza-... 

Various actions of thiocarbamates on lipid contents, lipid labeling, membrane constituents, and growth regulators have been reported (see Ref. 59). In addition, several antidotes or safeners which increase the tolerance of crop plants to thiocarbamates have been shown to reverse the effects of these herbicides on lipid metabolism. ... 

In summary, thiocarbamates have been shown to specifically affect very long chain fatty acid (and wax/cutin/suberin) synthesis in a variety of plant tissues in vivo. This effect is most likely due to the formation of a more active metabolite (possibly a sulfoxide) and can be reversed by safening agents. It seems probable that effects on fatty acid elongation are important in the mechanism of action of thiocarbamates. 

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