Glyphosate

Glyphosate is one of the most widely used and controversial herbicides in the world. Known chemically as N-(phosphonomethyl)glycine, it has played a central role in modern agriculture since the 1970s due to its effectiveness against a broad spectrum of weeds. While hailed as a breakthrough in weed management, glyphosate has also been the subject of global debate over its environmental and health effects. This article presents a comprehensive examination of glyphosate, covering its discovery, chemistry, mechanism of action, production, agricultural applications, resistance issues, toxicology, regulatory framework, and its broader implications for sustainable agriculture.

Discovery and Historical Development

Glyphosate was discovered in 1950 by the Swiss chemist Henri Martin while working for the Cilag Chemical Company, though its herbicidal potential went unrecognised at the time. In 1970, John E. Franz, a chemist at Monsanto (now part of Bayer), rediscovered and identified its unique herbicidal properties. Glyphosate was patented by Monsanto and commercially introduced in 1974 under the brand name Roundup.
Its effectiveness as a non-selective, systemic herbicide rapidly made it a cornerstone of weed control in agriculture, forestry, and urban management. The introduction of glyphosate-tolerant genetically modified (GM) crops in the mid-1990s—such as Roundup Ready soybean, maize, and cotton—further expanded its use worldwide.

Chemical Nature and Structure

Chemically, glyphosate is an organophosphorus compound with the molecular formula C₃H₈NO₅P and a molecular weight of 169.07 g mol⁻¹. Structurally, it contains three key functional groups: a carboxylic acid, an amine, and a phosphonic acid. These groups confer water solubility and enable glyphosate to chelate metal ions.
Glyphosate is usually formulated as its isopropylamine, potassium, or ammonium salt to enhance solubility and ease of application. In its pure form, it is a white, odourless crystalline powder that dissolves readily in water but poorly in organic solvents.
Because of its ionic nature, glyphosate binds strongly to soil particles, reducing mobility and leaching potential under most conditions. However, its persistence varies depending on soil composition, microbial activity, and environmental factors.

Mechanism of Action

Glyphosate acts by inhibiting a key enzyme in the shikimate pathway—5-enolpyruvylshikimate-3-phosphate synthase (EPSPS)—which is essential for the synthesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) in plants, fungi, and some bacteria.
When glyphosate blocks this pathway, plants cannot produce these vital amino acids, leading to the accumulation of shikimate and disruption of protein synthesis, cell metabolism, and ultimately, plant death.
The shikimate pathway does not exist in animals or humans, which is one reason glyphosate was initially considered to have low toxicity to non-target organisms. However, subsequent research has raised concerns about indirect effects on gut microbiota and ecological systems.

Production and Formulations

Industrial production of glyphosate involves the reaction of glycine with phosphorus trichloride and other intermediates under controlled conditions. The final product is often neutralised with isopropylamine or other bases to form water-soluble salts.
Commercial formulations typically include surfactants to improve leaf penetration and wetting properties. For example, early Roundup formulations contained polyethoxylated tallow amine (POEA), which enhanced herbicidal action but also increased toxicity to aquatic organisms. Modern formulations use alternative surfactants with improved environmental profiles.

Agricultural and Non-Agricultural Uses

Agricultural ApplicationsGlyphosate is valued for its broad-spectrum herbicidal activity, killing annual and perennial weeds, including grasses, sedges, and broadleaf species. It is primarily used for:

• Pre-plant weed control before sowing crops.
• Post-harvest field preparation to manage weeds before the next planting cycle.
• Pre-emergent and post-emergent spraying in non-selective applications.
• In-crop use in genetically engineered glyphosate-resistant (Roundup Ready) crops such as soybeans, cotton, maize, and canola.

The adoption of glyphosate-resistant crops allowed farmers to simplify weed management, reduce tillage, and increase crop yields while lowering costs and labour.
Non-Agricultural UsesOutside agriculture, glyphosate is used in forestry, gardens, parks, railway embankments, and along roadsides to control unwanted vegetation. It is also used in aquatic environments (in specific low-toxicity formulations) to manage invasive aquatic weeds.

Advantages and Role in Modern Agriculture

The widespread use of glyphosate is attributed to several key advantages:

• Broad-spectrum activity: Effective against a wide range of weeds.
• Systemic action: Translocated throughout the plant, killing both roots and shoots.
• Environmental compatibility: Degrades primarily through microbial action, with minimal bioaccumulation.
• Compatibility with conservation tillage: Enables no-till or reduced-till farming, which conserves soil structure and moisture and reduces erosion.
• Economic efficiency: Provides cost-effective weed management and reduces the need for mechanical weed control.

These benefits have made glyphosate indispensable in modern agricultural systems and integral to high-yield crop production.

Weed Resistance and Agronomic Challenges

Continuous and intensive use of glyphosate has led to the emergence of glyphosate-resistant weed species. Resistance develops through genetic mutations in the EPSPS enzyme or through metabolic and physiological adaptations in plants.
Over 40 weed species worldwide have evolved resistance, including Amaranthus palmeri (Palmer amaranth), Conyza canadensis (Canadian fleabane), and Lolium rigidum (annual ryegrass).
To manage resistance, integrated weed management strategies are recommended, such as:

• Crop rotation and diversification.
• Alternating herbicides with different modes of action.
• Using mechanical and cultural weed control methods.
• Applying herbicide mixtures judiciously.

The rise of resistance has renewed interest in developing new herbicides and genetically engineered crops with multiple herbicide tolerance traits.

Toxicology and Health Considerations

Acute ToxicityGlyphosate is classified as low in acute toxicity for mammals, with an oral LD₅₀ value exceeding 5,000 mg/kg in rats. However, surfactants in commercial formulations may increase toxicity. Exposure can cause mild symptoms such as skin or eye irritation, nausea, and respiratory discomfort when inhaled as spray mist.
Chronic ExposureThe most contentious debate regarding glyphosate concerns its potential carcinogenicity and long-term health effects. In 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as “probably carcinogenic to humans (Group 2A),” based on limited evidence in humans and sufficient evidence in experimental animals.
Other regulatory agencies, including the European Food Safety Authority (EFSA), the U.S. Environmental Protection Agency (EPA), and Health Canada, have concluded that glyphosate is unlikely to pose a carcinogenic risk under normal exposure conditions.
Apart from cancer risk, glyphosate exposure has been studied for potential links to endocrine disruption, reproductive toxicity, and effects on gut microbiota. Results remain inconclusive, with ongoing scientific debate and litigation in several countries.
Human Exposure PathwaysHumans may be exposed to glyphosate through:

• Occupational handling and spraying.
• Residues in food or water, though typically below regulatory limits.
• Environmental drift from sprayed fields.

Proper protective equipment, adherence to label instructions, and safe handling procedures significantly minimise risk.

Environmental Fate and Ecological Impact

Degradation and MobilityGlyphosate binds strongly to soil minerals such as iron and aluminium oxides, which limits leaching into groundwater. It is primarily degraded by soil microorganisms into aminomethylphosphonic acid (AMPA) and eventually into carbon dioxide, water, and phosphate. Its half-life in soil ranges from a few days to several months depending on conditions.
Impact on Non-target OrganismsWhile glyphosate itself has low toxicity to mammals, birds, and fish, its surfactant-containing formulations can be harmful to aquatic life. Concerns also exist about its effects on soil microbes, pollinators, and biodiversity, particularly through habitat alteration from intensive weed eradication.
There is also evidence suggesting that widespread glyphosate use may indirectly affect nutrient cycling, soil health, and symbiotic fungi critical to plant growth.

Regulation and Global Status

Glyphosate is approved for use in over 150 countries, but its regulatory status varies widely due to health and environmental concerns.

• European Union: The EU has repeatedly reviewed glyphosate’s approval; while it remains authorised, several member states have imposed restrictions or announced phase-outs.
• United States: The EPA maintains that glyphosate poses no unreasonable risk when used according to label directions.
• Other Regions: Countries such as Sri Lanka, Thailand, and Mexico have implemented partial or total bans, citing precautionary principles.

Regulatory agencies continually review new evidence, balancing agricultural benefits against potential risks.

Emerging Alternatives and Sustainable Practices

To reduce dependency on glyphosate, researchers and farmers are exploring alternative weed control strategies:

• Mechanical weeding and precision agriculture technologies.
• Bioherbicides derived from natural microorganisms and plant extracts.
• Crop rotations and cover cropping to suppress weed growth naturally.
• Integrated weed management (IWM) combining chemical, biological, and cultural practices.

The development of next-generation herbicides with novel mechanisms and improved safety profiles is an active area of research.