Herbicide safety relative to common targets in plants and mammals

Abstract

Most modern herbicides have low mammalian toxicity. One of the reasons for this safety is that the target site for the herbicides is not often present in mammals. There are approximately 20 mechanisms of action that have been elucidated for herbicides. Of these, some do share common target sites with mammals. The mechanisms include formation of free radicals, protoporphyrinogen oxidase (PROTOX), glutamine synthetase (GS) and 4-hydroxyphenylpyruvate dioxygenase (HPPD). PROTOX, HPPD and GS inhibitors have been shown to inhibit these enzymes in both plants and mammals and there are measurable effects in mammalian systems. However, the consequences of inhibiting a common target site in plants can be quite different than in animals. What may be a lethal event in plants, eg inhibition of HPPD, can have a beneficial effect in mammals, eg treatment for tyrosinemia type I. These chemicals also have low mammalian toxicity due to rapid metabolism and/or excretion of the herbicide from mammalian systems.

Herbicide selectivity in alfalfa crops

“…The mechanism of action of these herbicides inhibits the enzyme acetolactate synthase (ALS) in plants, blocking the synthesis of aliphatic side chain amino acids such as valine, leucine and isoleucine. ALS inhibitors are characterized as systemic and can accumulate in the apical meristems, preventing the growth and development of sensitive plants, but visually, phytotoxicity is processed slowly (Shaner, 2003).…”

Potential of agricultural fungicides for antifungal drug discovery

“…One of the exceptions is fluconazole, a fungicide product discovered by the pharmaceutical sector that is now used as a pharmaceutical but also was patented as a chemical with applications in crop production. [29][30][31][32][33][34] Bioavailability is highly important for any bioactive agent. The Lipinski's Rule of Five [35] can be considered as the reference for defining physicochemical and structural parameters for oral drug bioavailability.…”

Herbicides: the Face and the Reverse of the Coin. An in Vitro Approach to the Toxicity of Herbicides in Non-Target Organisms

“…Most modern herbicides have low mammalian toxicity, because research for new herbicides often rejects chemicals affecting metabolic pathways that are shared by mammals. In many cases, the low mammalian toxicity has to do with the fact that these chemicals interfere with biochemical pathways that do not exist in mammals, such as photosynthesis, essential amino acids biosynthesis or chlorophyll biosynthesis (Shaner, 2003). There are about 20 mechanisms of action that have been elucidated for herbicides.…”

“…inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD), can even have a beneficial effect in mammals, e.g. treatment for tyrosinemia type I (Shaner, 2003). Also a common enzyme existing in plants and mammals, e. g. acetyl-CoA carboxilase (ACCase), can be inhibited by the herbicides cyclohexanediones and the aryloxyphenoxypropionates, killing plants, and not affecting ACCase in mammals.…”

“…Also a common enzyme existing in plants and mammals, e. g. acetyl-CoA carboxilase (ACCase), can be inhibited by the herbicides cyclohexanediones and the aryloxyphenoxypropionates, killing plants, and not affecting ACCase in mammals. ACCase plays the same role in the fatty acid biosynthesis of the different organisms, despite vast differences in its regulation and protein structure (Incledon & Hall, 1997;Shaner, 2003). These herbicides suppress de novo synthesis of fatty acids in sensitive species by inhibiting the activity of plastid-associated ACCase.…”