Although phosphorous acids/phosphites (H3PO3) are registered in South Africa for the control of Phytophthora nicotianae and Phytophthora citrophthora in citrus, and Phytophthora. Cinnamomi in avocado crops, the compound is not approved for use in macadamia orchards.
However, The Macadamia understands that out of desperation to control phytophthora infestation, some farmers are applying phosphonates and fosetyl-AI as foliar spray, stem paint or spray, or soil drench to control the disease, regardless of the outstanding approvals.
Experts warn that this means the industry could be in contravention when exporting the crop – particularly to the European Union – and that it is illegal to use the product out of its registration within the South African context.
The Macadamia also understands that applications for registration of products for use on macadamia trees were lodged in 2020 and 2021 and are being reviewed by the Registrar at the Department of Agriculture, Land Reform and Rural Development, in line with the Fertilisers, Farm Feeds, Agricultural Remedies and Stock Remedies Act (Act 36 of 1947).
However, the process can take 10 years or more, which means thousands of farmers who planted more than 10 000ha to macadamias in 2021 and 2022 alone at a cost of about R60 000 per ha are having to watch their trees being decimated by phytophthora, with little or nothing to fight off the threat.
The Macadamia approached the department for comment but none was forthcoming.
Domestic farmers disadvantaged
A macadamia tree showing evidence of phytophthora. It can take anything up to one to three years for the tree to die.
Dr Schalk Schoeman, an independent research expert and Director at Sonbesie Consulting, said while the law (Act 36 of 1947) governing product registration in South Africa was a very good piece of legislation, the slow bureaucratic approval process was putting domestic farmers at a real disadvantage. “In Australia and the United States, for example, these products have been registered for use in macadamia orchards for years already. The slow process of approval here is effectively pulling the competitive rug out from under our farmers’ feet,” he said.
Francois van Deventer, the CPD Technical Lead – Fungicides at Syngenta South Africa, agreed that farmers were in a difficult position. “Unfortunately, by law one cannot make a recommendation on an unregistered (Act 36 of 1947) product, and given the regulatory cost associated with bringing and keeping a new product to market – just one of the aspects to consider – a business case must make sense before a company will make the investment.”
From the discovery and research phase to final commercialisation could take 10 years or more for registration. and the estimated development cost of the active ingredient (discovery to the first commercially available product) is around US$250 million.
A patent is granted for 20 years once an active ingredient is discovered, but then all of the development work still needs to be done. “If the commercial release in the target markets is delayed for some reason, the impact on the potential return on investment is significant,” Van Deventer said.
For generic products with exact active ingredient loading, he added, only a portion of the technical data was required for registration.
“However, the original research and development company remains responsible for maintaining the maximum residue levels or MRLs and registration of the active ingredient efficiency.
“If a company wants to add a target crop or dose that is not on the original label, it has to prove that in efficacy trials and phytotoxicity and residue trials, or anything else applicable to the claim. There are no shortcuts.”
Anthony Maina, Head of Communications at Bayer in Africa, said the reason the Bayer product Alliette® – the first phosphonic acid-based product to come to market – was not registered for use in the domestic macadamia industry was that at the time of its registration, the macadamia hectares in South Africa did not meet the threshold needed to register a new molecule on the crop. He did not respond to whether the current hectares under orchards met the required threshold.
However, Wilbri Vorster, Bayer Crop Science Horticulture Go-to-Market Lead for Africa, said while he could not divulge information of registration processes under way, there were “some products planned for launch within the next one to two years”.
Barry Christie, Group Agriculture Technical Manager at the Green Farms Nut Company, said what was attractive about phosphorous acids/phosphites (H3PO3) was if they were used in low dosages, they galvanised the macadamia tree into using its own defences, whereas in high concentrations, the fungicide would effectively suppress the soil-dwelling pathogen.
Soil-borne pathogen
Phytophthora (P.cinnamomi) – a soil-borne pathogen of Southeast Asian origin – usually attacks the macadamia tree’s feeder roots, or if there is a wound on the bark or branches, the fungus will then develop a “true” canker. The tree can take between one and three years to die, depending on the management of the orchard.
In a paper titled The Occurrence and Impact of Phytophthora on the African Continent authored by Jan Nagel, Marleka Gryzenhout, Bernard Slippers and Michael Wingfield in 2013, a total of 23 species of the pathogen were known on the African continent, 20 of which were known in South Africa.
It is estimated that at least 10% of yield losses and 10% of the annual gross value loss in the domestic industry could be attributed to diseases caused by the pathogen.
In essence, P.cinnamomi invades the tree’s feeder root system, and over successive growing seasons, the tree health continues to decline with a reduction in yield until it dies off completely. Early evidence of the pathogen includes yellowing or wilting leaves, a decreased nut set, and early nut drop, and it spreads easily to younger trees.
Once the pathogen is in the soil, treatment is necessary to remedy the soil. Severely affected trees should be removed so that the soil can be adequately treated to contain the spread of the disease.
A review authored by Professor Elizabeth Dann from Australia’s University of Queensland, Queensland Alliance for Agriculture and Food Innovation, and Professor Adéle McLeod from the Department of Plant Pathology at Stellenbosch University, titled Phosphonic (phosphorous) acid: A long-standing and versatile crop protectant, reveals that phosphonic acid-based fungicides have been used extensively as crop protectants since the late 1970s.
“Discovering that phosphonates are effective against foliar and soil-borne oomycete disease, such as Phytophthora, Pythium and Plasmopara, was a significant breakthrough, especially for soil-borne pathogens that are notoriously difficult to manage,” the review said.
Phosphorous acid-containing crop protection compounds comprise the metal salts of phosphonic acid and esters of phosphonic acid.
Effective use in native ecosystems
As the first phosphonic acid-based fungicide to come to the market, Alliette® contained aluminium tris (ethyl phosphonate), which is the aluminium salt of ethyl hydrogen. “Subsequently several other formulations were registered as fungicides, mainly potassium phosphonate – as a mixture of potassium hydrogen and dipotassium – and more recently sodium and ammonium phosphonates,” the review says.
Of interest, the compounds are also being used off-label in native ecosystems and forestry, particularly to protect indigenous species susceptible to the disease.
One example is the use of the phosphorous acids/phosphonates to treat Phytophthora (P.cinnamomi) collar rot by scientists at Kirstenbosch Gardens in Cape Town to protect the rare, highly endangered Sorocephalus imbricatus (Thunb.) R.Br. – a shrub in the Proteaceae family.
In the McLeod and Dann review, pure phosphorous acid is described as “white crystalline, hygroscopic solid (flakes), and in aqueous solution exists at equilibrium with its tautomeric form, phosphonic acid H2PO3. The latter is a very stable liquid, though very acidic, so preferred fungicide formulations have been neutralised with metal salts (e.g., potassium hydroxide – KOH) to reduce phytotoxic effects”.
The review confirms that phosphonic acid is “truly ambimobile”, which means it can move both upwards and downwards within the plant. As a result the compound can be applied as foliar sprays: from the ground, from the air, as a soil drench, a trunk spray and by injecting the trunk of the tree.
Timing critical
Night spraying underway in a macadamia orchard in the Mpumalanga area. Experts are warning growers who might be using phsophonates and fosetyl-AI off-label that the practice is illegal
Debbie Matteucci, an independent product development and regulatory specialist, said phosphonic acid moved in accordance with the highest movement of flow by the plant. For example, during flowering or fruiting, high concentrations will end up in the tree canopy, whereas during other growth cycles, the active ingredients will collect in the roots. “This means, depending on the type of disease, the application timing is critical,” she said.
The review describes how quickly the compound moves through a tree – a “trunk-injected” avocado tree showed traces of the compound in its leaves within 24 hours, with accumulation in the roots and the bark several days later.
“It has been 40 years since the release of the first phosphonic acid-based fungicide and it remains highly effective, which shows it is ‘low risk’ for resistance,” the scientists say.
In their review, McLeod and Dann suggest that the research and experts they quote were comfortable that phosphonic acid-based crop protectants would continue as an “extremely valuable tool” for farmers but, they cautioned, extensive research was still under way to assess its efficacy and ideal application in domestic orchards.
What are Phosphonates?
Phosphonates break down in plants to phosphonic acid and their salts (potassium or ammonium), whereas fosetyl-Al breaks down to fosetyl and phosphonic acid. Phosphonic acid, phosphorous acid and phosphite are, in principle, all referring to the same active compound in plants to which fosetyl-Al and phosphonates break down, and which are responsible for controlling Phytophthora diseases.
Timeline:
Francois van Deventer, who is the CPD Technical Lead – Fungicides at Syngenta South Africa, detailed for The Macadamia the estimated timeline for the registration and commercialisation of a product containing a new active ingredient:
- Discovery and Research (two-10 years): This phase involves identifying and developing a new active ingredient, including initial screening, synthesis, and formulation. The timeline can vary widely based on the complexity of the molecule and the need for additional research to understand its efficacy and safety.
- Regulatory Approval (five-10 years): Obtaining regulatory approval for a new crop protection product is a lengthy and costly process. It involves extensive testing for efficacy, environmental impact, and human and animal safety. The timeline can vary based on the region and the specific requirements of regulatory agencies. Usually done simultaneously in all relevant main target markets such as the EU, USA, Latin America and some other regulatory authorities, such as CODEX etc.
- Field Trials and Development (two-five years): Once regulatory approval is obtained, field trials and further development are necessary to optimise application methods, dosages, and product performance under real-world conditions.
- Commercialisation (one-three years): This phase involves scaling up production, establishing distribution channels, and launching the product in the market. This is usually in selected first wave countries. Other countries will follow later. In South Africa this process i.e. the formal registration application after all the field efficacy trials have been conducted, should take two years, but in reality, this timeframe is not readily being met.
It’s important to note that these timelines and costs are general estimates, and actual timelines and expenses can vary widely based on the specific product, regulatory environment, and market conditions. Additionally, the process can be influenced by factors such as technological advancements, changes in regulatory requirements, and unforeseen challenges during development.
Requirements:
For new active ingredient registration in South Africa, the following requirements among others must be submitted for all agricultural remedies, whether new molecules or generic. The only data that is waived for a generic product are studies on the active ingredient and some efficacy and residue data requirements when the product is shown to be equivalent to the original product and claiming uses are already on the original product label.
- Detailed composition and specification of active ingredient
- Certificate of active ingredient manufacturer and product formulation plant
- Analytical method validation and the manufacturing process (known as the 5 batch report)
- Pharmacology and toxicology studies of the active ingredient
- Environmental impact studies of active ingredient
- Pharmacology and toxicology studies of the formulated product
- Environmental impact studies of the formulated product
- Risk assessment reports (effect of exposure on vulnerable groups/children)
- Physical properties and storage stability of formulated product
- GHS rationale and declaration
- Efficacy and phytotoxicity data and reports
- Residue reports for both field and lab data
- Bee toxicity studies for formulated product and active ingredient
