FUNGICIDE FORMULATION AGROBIOLOGY

Following up on the previous article on?Fungicide Mode of Action , this article covers Agrobiological aspects of Insecticide Formulation.

Fungicides are chemicals that are used to control or prevent fungal diseases in crops, plants, and animals. They are widely used in agriculture and horticulture to protect crops from fungal diseases, to improve crop yields, and to maintain the quality and appearance of plants.

Fungicides can be classified into several types based on their mode of action, chemical structure, and selectivity. Formulating fungicides into effective and stable products is a complex process that involves the selection of appropriate active ingredients, adjuvants, and excipients.

In this article, we will discuss the various types of fungicides and their modes of action, and we will explore the factors that are considered when formulating fungicides. We will also discuss the challenges and considerations involved in formulating fungicides for different applications and environments.

An important factor to consider when formulating a fungicide is the solubility of the active ingredient in the fungicide. Fungicides that are highly soluble are generally easier to formulate, as they can be dissolved in a variety of solvents. However, highly soluble fungicides can also be more prone to leaching, which means they can be washed away by rain or irrigation and may not be as effective in protecting the plants.

Overall, the formulation of a fungicide is an important consideration in its effectiveness and safety. Careful consideration of the active ingredient, mode of action, solubility, and other ingredients can help to ensure that the fungicide is properly formulated for the specific needs of the plants and the environment in which they are grown.

Fungicide formulation development options are determined by pathogen biology and active ingredient physical-chemical characteristics, including:

• Fungal biology – true fungi vs. oomycetes
• Active ingredient solubility – hydrophilic or lipophilic
• Active ingredient uptake – contact, systemic or translaminar
• Application timing – protective, curative or eradicative
• Mode of action – spores (protective; respiratory inhibition) or mycelia (curative; ergosterol inhibition)

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Fungal Biology

True fungi (Kingdom Mycota) share several biochemical or structural features, which are the targets of fungicides and may impart specificity i.e., the fungicide kills or inhibits fungi.

The fungicidal target Chitin is a component of fungal and insect cell walls, and ergosterol is a component of fungal cell membranes but is absent in animal and plant cell membranes. Ergosterol is formed in fungi via a multistep ergosterol synthesis pathway – a factor that has important implications for resistance management.

The Oomycetes (Kingdom Protista) are not true fungi but use the same mechanisms and strategies to infect plants. Plant pathologists group then with fungal pathogens. Oomycetes include destructive plant pathogens, including the genus Phytophthora (potato late blight), Pythium (damping off disease) and Peronospora / Pseudoperonospora (Downy Mildews). Instead of chitin, oomycetes cell walls contain cellulose, and ergosterol is not a principal sterol in the Oomycete cell membrane.

Fungicides targeting chitin and ergosterol synthesis are thus generally ineffective against these pathogens. Downy mildews can be confused with unrelated fungal powdery mildews but are insensitive to fungicides able to control powdery mildew.

When spores land on a leaf, they germinate and form a germ tube before forming an appressorium, which serves as an attachment structure at the penetration site.

The penetration hyphae grow through the epidermal cell and intercellular space, first forming primary invading hyphae and then secondary hyphae populating intercellular spaces.

In compatible interactions, primary haustoria form in the mesophyll cells, and within days the formation of secondary haustoria occurs. Two to three weeks after infection, new spores erupt from the leaf – these may be wind or water dispersed and serve as the source of inoculum for new infections.

Fungicide systemicity and activity

With regard to systemicity, fungicides may be classified as contact (non-systemic), translaminar (locally systemic) or systemic.

Preventative or protective (contact) fungicides stop spore germination on the leaf surface to prevent infection. Applied before disease infection, they tend to be more lipophilic as they must remain on the leaf surface to prevent spore germination and penetration.

As contact fungicides tend to be based on older chemistries, they have multisite modes of action (rather than the more specific modes of action of more modern, systemic fungicides. As there is less risk of resistance, there is less need to combine multiple active ingredients, which may be incompatible with each other or with formulation components).

Contact fungicides generally require higher doses than systemic fungicides, and due to their exposure to the environment on the leaf surface, they tend to be less UV- & rainfast, reducing their duration of efficacy to 3-10 days. Contact fungicides thus require more applications than systemic fungicides.

Formulation development options for contact fungicides include increasing rainfastness and UV stability, improving efficacy (reduced rates) through optimized distribution on the leaf surface.

Curative/eradicant (systemic) fungicides stop early pathogen development inside the plant. Eradicant fungicides are effective at advanced stages of colonization (when symptoms are present).

Applied after infection but before visible symptoms, active ingredients with curative function tend to be less lipophilic as they need to penetrate the leaf and move throughout the plant to target existing infection.

Systemic fungicides are typically effective at lower doses than contact fungicides because they penetrate the plant and are thus more UV- & rainfast, with a duration of efficacy of 14-28d, and require fewer applications. In addition, systemic fungicides may have translaminar activity, allowing them to pass through the leaf from the upper (sprayed) to the lower (unsprayed) surface and to target pathogens on the underside of leaves.

Systemic insecticides are relatively modern, more selective chemistries and tend to have a single-site mode of action. To address resistance issues, they are typically used in combinations with other insecticidal active ingredients, which can introduce compatibility issues that must be addressed by appropriate formulation and adjuvant technologies.

Fungicide systemicity is associated with higher residues (MRLs) and the risk of phytotoxicity through systemic accumulation.

Formulation development options for systemic fungicides include optimizing uptake kinetics to improve efficacy while avoiding phytotoxicity and optimizing formulations for compatibility in tank mixes.

Depending on the formulation choice (EC; SC) and choice of adjuvants, curative activity may be increased (usually at the cost of protective activity) or vice versa.

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Translaminar fungicides (locally systemic), such as QoI or Strobilurin fungicides redistribute the fungicide from the upper, sprayed leaf surface to the lower, unsprayed surface. Some Triazole (protective and early curative) fungicides may also have translaminar activity.

Translaminar movement takes place via the lipophilic leaf surface and lipophilic extra cellular pathways.

By affecting uptake across the cuticle and intracellular or extracellular transport within the plant, adjuvants are an additional factor deciding whether chemical and biochemical active ingredients have apoplastic (extracellular), symplastic (intracellular) or translaminar (from adaxial to abaxial leaf surface) activity.

Fungicide Classes and agrobiological groups

Active ingredient physical-chemical characteristics properties may be obtained through various sources, including the Pesticide Properties Database (University of Hertfordshire) and ePesticide Manual (British Crop Protection Council)

It is possible to identify trends and group the key fungicide modes of action based on our understanding of pathogen biology, active ingredient physical-chemical characteristics and fungicidal systemicity.

Mode of action classes may be grouped into systemic or contact fungicides based on whether they are hydrophilic or lipophilic.

Fungicide active ingredients – predictive models for formulation and adjuvant options

By placing fungicide active ingredients into the predictive Bromilow model based on their lipophilicity (logP) and partition coefficient (pKa), we can determine and visualize pesticide mobility and predict their suitability for contact and systemic activity.

Many common fungicides are clustered around the “low” end of the systemicity scale and are primarily xylem mobile.

For a fungicide to be considered curative, the active ingredient must be systemically translocated within the plant to inhibit (cure) existing fungal hyphal growth within the leaf. Very few fungicides are phloem systemic (FOS-Al; CAR) and truly curative, and these may translocate to leaf tips and meristems, reducing their efficacy and increasing the risk of phytotoxicity.

Protective fungicides are described as having contact action, remaining on the leaf surface where they can protect the plant against the germination of newly landed fungal spores.

The expanded Bromilow model can be used to predict appropriate formulations and adjuvants for specific active ingredients.

For hydrophilic active ingredients, solubilization in the aqueous spray solution in water-based formulations is generally possible, while for lipophilic active ingredients that are soluble in organic solvents such as oil, emulsion formulations or microcapsule formulations are appropriate. If multiple active ingredients are to be mixed, SE, ZW, ZC or ZE can be considered.

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Options for systemic fungicides

• Surfactants / wetters - Surfactants allowing spray droplets to spread beyond their initial contact area, providing a greater area of uptake for systemic active ingredients, or a more homogenous distribution on the leaf surface for active ingredients with contact activity. Surfactants with a low HLB (shorter EO chains) are absorbed into the cuticle and increase the fluidity of waxes, increasing the permeance of lipophilic fungicides in the cuticle (possible crop phytotoxicity). Hydrophilic surfactants include oil-in-water emulsifying agents, detergents, and solubilizing agents and are suited for foliar-applied hydrophilic fungicides. Lipophilic surfactants include penetrators (oils) and are suited for foliar-applied lipophilic active ingredients.
• Crop oils and COCs - Crop oils and crop oil concentrates (COCs) enhance spreading and penetration of some (high MW, more lipophilic) systemic and translaminar fungicides. Can induce phytotoxicity.
• Humectants - Enhance the hydration of the cuticle and the permeance of hydrophilic fungicides into the cuticle.
• Formulation - Emulsions tend to be more effective than suspensions; suspension formulations often allow higher loading and are less phytotoxic.

Options for contact fungicides

• Surfactants - wetters Surfactants allowing spray droplets to spread beyond their initial contact area, providing a more homogenous distribution on the leaf surface for active ingredients with contact activity.
• Stickers - increase droplet or particle adherence to the leaf surface and prevent run-off on application and wash-off during heavy rainfall. Spreader-stickers contain surfactants (spreading) and stickers (increase adhesion)
• Crop oils and COCs - enhance spreading of contact fungicides and can improve rainfastness but can lead to leaf penetration and phytotoxicity.
• Formulation - Suspension concentrate formulations are generally retained better than wettable powder formulations.

Optimization for tank-mixed fungicides

The need to incorporate agricultural actives (ais) in high electrolyte systems, such as fertilizers for in-furrow applications or in tank mixes with other fungicides, insecticides, and biostimulants for spray applications, provides a significant challenge to the formulator, including flocculation (precipitation) and the risk of blocked nozzles, phytotoxicity, active ingredient degradation and the inactivation of biologicals.

• Precipitation may occur in high-electrolyte solutions, especially SC formulations. Most non-ionic adjuvants have low cloud points and phase-separate under high-salt conditions; thus, cationic, anionic, or, increasingly, amphoteric surfactants are required. However, these adjuvants are often incompatible with other actives, may be environmentally or plant-toxic, or cause excessive foaming.
• Phytotoxicity may occur when mixing active ingredients, such as cytotoxic sulfur, copper, and captan fungicides mixed with oil-containing products (as they are cytotoxic; leaf penetration can lead to phytotoxicity). Phosphites (phosphorous acids) and copper combinations can be phytotoxic, as copper can become more available and phytotoxic in acidic solutions. Triazole fungicides mixed with non-ionic surfactants or foliar fertilizers can lead to increased uptake, with increased systemic accumulation and phytotoxicity. Antioxidants, herbicide safeners, and the judicious choice of adjuvants can help alleviate the risk of phytotoxicity, while evidence indicates that the co-application of certain insecticides may improve crop compatibility.
• Degradation occurs when fungicidal active ingredients degrade each other in tank mixes, for example, lime in mixes with Captan, Mancozeb, Iprodione (all susceptible to alkaline hydrolysis). Formulation optimization options include the inclusion of alkalizers or acidifiers, and compatibilizer adjuvants (amphoteric surfactants and hydrotropes). Adjuvants, such as combinations of amphoteric surfactants and hydrotropes, that work as compatibilizers allow different active ingredients to be mixed to increase the effectiveness of crop protection formulations. When pH is low, amphoteric surfactants have cationic characteristics and when pH is alkaline have anionic characteristics. Hydrotropes are alternatives to common surfactants and improve the solubility of hydrophobic particles without forming micelles.
• Inactivation of biologicals, such as copper (cytotoxic, antibacterial) with bacterial biofungicides and fungicides, such as triazoles with fungal biofungicides (e.g., Trichoderma) is an issue when tank-mixing, and this inactivation can be alleviated using compatibilizer adjuvants, as well as formulation compartmentalization (SE, OD, CS, inclusion technologies).

Overall, the formulation of a fungicide is an important consideration in its effectiveness and safety. Careful consideration of the active ingredient, mode of action, solubility, and other ingredients can help to ensure that the fungicide is properly formulated for the specific needs of the plants and the environment in which they are grown.

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