**Forty Years with Glyphosate**

#### András Székács and Béla Darvas

*Department of Ecotoxicology and Environmental Analysis, Plant Protection Institute, Hungarian Academy of Sciences Hungary* 

#### **1. Introduction**

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of a plenary address at the conference of North American Fuzzy Information

If one were to pick the most notified pesticide of the turn of the millennium, the choice would most likely be glyphosate. Although DDT remains to be the all-time star in the Hall of Fame of pesticides, the second most admitted pesticide active ingredient must be the phosphonomethylglycine type compound of Monsanto Company, glyphosate.

Indeed, the two boasted pesticides show certain similarities in their history of discovery and fate. Both were synthesised first several decades prior to the discovery of their pesticide action. DDT and glyphosate were first described as chemical compounds 65 and 21 years before their discovery as pesticides, respectively. Both fulfilled extensive market need, therefore, both burst into mass application right after the discovery of their insecticide/herbicide activity. They both were, to some extent, connected to wars: a great part of the use of DDT was (and remains to be) hygienic, particularly after Word War II, but also the Vietnam War; while glyphosate plays an eminent role in the "drug war" (Plan Colombia) as a defoliant of marijuana fields in Mexico and South America. And last, not least, ecologically unfavourable characteristics of both was applauded as advantageous: the persistence of DDT had been seen initially as a benefit of long lasting activity, and the zwitterionic structure and consequent outstanding water solubility of glyphosate, unusual among pesticides, also used to be praised, before the environmental or ecotoxicological disadvantages of these characteristics were understood.

Yet there are marked differences as well between these two prominent pesticide active ingredients. Meanwhile the career of DDT lasted a little over three decades until becoming banned (mostly) worldwide, the history of glyphosate has gone beyond that by now, since the discovery of its herbicidal action (Baird et al., 1971). And while DDT is the only Nobel prize laureate pesticide, glyphosate was the "first billion dollar product" of the pesticide industry (Franz et al., 1997). Moreover, meanwhile the course of DDT was rather simple: rapid rise into mass utlilisation, discovery of environmental persistence, development of pest resistance, loss of efficacy, and subsequent ban; the history of glyphosate is far more diverse: its business success progressed uncumbered, receiving two major boosts. First, the patent protection of glyphosate preparations was renewed in the US in 1991 for another decade on the basis of application advantages due to formulation novelties, and second, its sales were further strengthened outside Europe with the spread of glyphosate-tolerant (GT) genetically modified (GM) crops. This market success has been limited significantly neither

Forty Years with Glyphosate 249

facilities have been suspended being limited by the market demand. Extended use of GT plants in the Word would help on this problem, even if Europe is hesitant to allow commercial cultivation of this kind of GM plants. The overall situation has led to continously decreasing glyphosate prices on the Word market, and has significant effects on

Glyphosate is a phosphonomethyl derivative of the amino acid glycine. It is an amphoteric chemical substance containing a basic secondary amino function in the middle of the molecule and monobasic (carboxylic) and dibasic (phosphonic) acidic sites at both ends (Fig. 1). Containing both hydrogen cation (H+) donor (acidic) and acceptor (basic) functional groups, it can form cationic and anionic sites within the small molecule, the dissociation constants (pKa) of these three functional groups are 10.9, 5.9 and 2.3, and therefore, similarly to amino acids, glyphosate can form a zwitterionic structure (Knuuttila & Knuuttila, 1979). This is reflected in excellent water solubility (11.6 g/l at 25 oC). Consequently, its lipophilicity is very low (logP < -3.2 at 20 oC, pH 2-5), and is insoluble in organic solvents e.g., ethanol, acetone or xylene (Tomlin, 2000). To further increase its already good water solubility it is often formulated in form of its ammonium, isopropylammonium, potassium, sodium or trimethylsulphonium (trimesium) salts. The order of water solubility is glyphosate << ammonium salt < sodium salt < potassium salt < isopropylammonium salt < trimesium salt, the solubility of the trimesium

> N H

Fig. 1. The chemical structure of *N*-(phosphonomethyl)glycine, glyphosate, containing a basic function (amine) in the middle of the molecule and two acidic moieties (carboxylic and

It has been known since the early seventies that glyphosate acts by inhibiting aromatic amino acid biosynthesis in plants (Jaworski, 1972; Amrhein et al., 1980), and elaborate research has revealed that the responsible mechanism is blocking a key step in the so-called shikimate pathway (Herman & Weaver, 1999), responsible for the synthesis of aromatic amino acids and critical plant metabolites. Glyphosate exerts this effect by inhibiting the activity of the enzyme 5-enolpyruvyl shikimate 3-phosphate synthase (EPSPS) catalyzing the transformation of phosphoenol pyruvate (PEP) to shikimate-3-phosphate (S3P) (Amrhein et al., 1980). This metabolic pathway exists in plants, fungi, and bacteria, but not in animals (Kishore & Shah 1988). Although higher order living organisms lack this metabolic route, therefore, are not expected to be directly affected by this herbicide, the environmental consequences of the widespread use of glyphosate have been reported (Cox,

Being an amino acid (glycine) derivative itself, glyphosate inhibits the formation of the main intermediate, by binding as an analogue of the substrate PEP to its catalytic site on the enzyme. The inhibition of this catabolic pathway blocks the synthesis of triptophan, phenylalanine and tyrosine, and in consequence, the synthesis of proteins. The lack of the

P

OH <sup>O</sup>

OH

salt being two orders of magnitude higher than that of glyphosate.

HO

O

dispread of GT plants.

**2.2 Mode of action** 

phosphonic acids) at both ends.

2000; Santillo et al., 1989).

by the recognition of the water-polluting feature of the parent compound, nor by the emerging weed resistance worldwide.

It is not a simple task to predict whether glyphosate continues to rise in the near future, or its application will be abating. To facilitate better assessment of these two possibilities, the present work attempts to provide a summary of the utility and the environmental health problems of glyphosate applications.
