BCPC Congress, November 9 – 11, 2009, Glasgow UK
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Initium® – An Innovative Fungicide
of a New Chemical Class for the Control of Oomycetes
R. Gold*, M. Scherer*, J. Rether*, J. Speakman*, B. Navé*, T. Levy*, R. Storer** & D. Marris**
* BASF SE, Agrocentre, 67117 Limburgerhof, Germany
** BASF plc, Earl Road, Cheadle Hulme, UK
Abstract
Initium is an innovative new fungicide active ingredient under development by BASF. Initium is a mitochondrial respiration inhibitor and belongs to a new class of chemistry, the pyrimidylamines. Initium has been shown in field trials to be a highly selective
and effective fungicide that can be used in preventive spray applications against late blight and downy mildews in a wide range
of speciality crops. It has an excellent toxicological and ecotoxicological profile and is highly suitable for use in integrated crop
management programmes.
Introduction
Late blight and downy mildews are important and devastating diseases of crops world wide. Initium is a fungicide with activity
against these Oomycete pathogens developed by BASF. Since its discovery in 2004 it has undergone detailed evaluation in laboratory tests and in extensive global field testing programmes. This paper describes its chemical and physical properties, mode of
action and biological properties, field performance and safety profile.
Chemical and Physical Properties
Trade name
Initium
Company development code
BAS 650 F
Common name
Ametoctradin
Chemical name (IUPAC)
[1,2,4] Triazolo [1,5-a] pyrimidin-7-amine, 5-ethyl-6-octyl
Molecular formula
C15H25N5
Structural formula
1
Molecular weight
275.4 g/mol
CAS no
865318-97-4
Appearance
crystalline solid
Purity
> 980 g/kg
Melting point
197.7-198.7 °C
Boiling point
Decomposition prior to boiling (234 °C)
Vapour pressure
2.1 x 10-10 Pa at 20 °C
Solubility
(water at 20 °C, pH 7): 0.15 mg/l
Dissociation constant
2.78
Partition coefficient
log P = 4.40
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Toxicological Properties
Trade name
Initium ®
Rat acute oral toxicity
LD50 > 2000 mg/kg bw
Rat acute dermal toxicity
LD50 > 2000 mg/kg bw
Skin irritation
Not irritating
Eye irritation
Not irritating
Genotoxicity
Not genotoxic
Initium displays an excellent toxicological profile. Acute mammalian toxicology studies indicate that Initium is not harmful after
ingestion, dermal exposure or inhalation. It is also not irritating to eyes or skin and is not a sensitizer.
Ecotoxicological Properties
Trade name
Initium
Birds (quail, mallard) acute oral toxicity
NOEC > 2000 mg/kg bw
Birds (quail, mallard) sub acute dietary
NOEC > 5000 mg/kg diet
Birds (quail, mallard) reproduction
NOEL > 1400 mg/kg diet
Earthworms acute toxicity
NOEC > 1000 mg/kg dry soil
Bees contact
LD50 contact > 100 µg per bee
Non-target arthropods field
no effects
Rainbow trout
LC50 > 23.1 mg/l
Daphnia
EC50 > 28.4 mg/l
Sediment dweller (Chironomus sp.)
NOEC 221.6 mg/kg dry sediment
Green algae
EC50 > 100 mg/l
Initium shows an excellent ecotoxicological profile. It is practically non toxic to birds, mammals, honeybees, earthworms and other
soil macro-organisms, or to non-target soil micro-organisms and their ecosystem function. The use of Initium in accordance
with good agricultural practice does not pose any risk to aquatic ecosystems. It is ideal for use in integrated crop management
programmes.
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Laboratory and Glasshouse Results
Mode of action
Initium® is a potent inhibitor of the mitochondrial respiratory chain in target pathogens. More specifically, Initium interferes with
complex III, also called the bc1 complex. Complex III is a membrane protein complex, consisting of 11 subunits in the respiratory chain.
Complex III inhibition
Initium
Pyraclostrobin
Fig. 1. Inhibition of complex III by Initium and pyraclostrobin.
To test complex III activity, mitochondrial particles were
isolated from Pythium ultimum. The turnover of ubiquinon,
Negative control
(non-complex III
inhibitor)
0
added as substrate, was detected photometrically.
20
40
Measurements of complex III activity show strong inhibition
60
80
100
(% inhibition) at 4E-07 M
by Initium and pyraclostrobin.
By inhibiting complex III (Fig. 1), Initium impairs the electron transport in the respiratory chain of the pathogen, thus making it unable to generate the energy required for keeping the organism alive. Research has demonstrated that Initium is not cross-resistant
to phenylamides (e.g. metalaxyl), Qo inhibitors (e.g. strobilurins) and carboxylic acid amides (e.g. dimethomorph) (data not shown).
Biological characterisation
Macroscopically, Initium is a highly effective inhibitor of zoospore formation and release, zoosporangia release, motility and
germination. At very low concentrations (0.05 mg/l), Initium rapidly leads to bursting of zoospores that puts an immediate stop
on the development of infectious stages of the pathogen (Figs. 2, 3).
Untreated
Initium treated
0s
60 s
0s
2s
2h
5h
4s
7s
Fig. 2. Light microscope images of Plasmopara viticola zoospores. The untreated zoospore (left) remains intact and forms a germ tube within 5 hours.
The Initium-treated zoospore (right) ruptures within 5 seconds and cytoplasm leakes from the spore.
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Ruptured zoospore after Initium ® treatment
Untreated zoospore
5 µm
3 µm
Fig. 3. Low temperature scanning electron microscopy images of Plasmopara viticola zoospores. Whereas the untreated zoospore (left) is intact and turgid,
the Initium-treated zoospore (right) is ruptured and cytoplasm (shown in colour) leakes from the spore.
Initium has a high affinity for the waxy layer of the leaf epidermis and through adsorption forms a stable protective film against
fungal attack (Fig. 4). Initium exhibits very good rainfastness, however, under the influence of moisture such as dew, a small but
effective portion of the active ingredient is gradually redistributed from the film leading to an increase in protection.
Fig. 4. Scanning electron microscopy image of Initium spray deposit on a
2 µm
tomato leaf. The particles of the active ingredient are bound to the surface
like a film.
Less than 10% of the applied active ingredient is taken up by the leaves after 1-7 days (data not shown). The majority of the active
ingredient remains on the leaf surface where it is absorbed on/in the epicuticular wax layer. The vapour phase activity is minimal.
These characteristics indicate that Initium is a non-systemic fungicide.
Field Results
Methods and Materials
The field trials were laid out in randomised blocks with 4 replications. The size of the blocks varied from 10 to 200 m².
All trials were sprayed at the beginning of attack, either using special small plot tractor spray equipment or a knapsack sprayer.
Treatments were applied in 150-1500 litres water/ha. A visual assessment of the % infected leaves, clusters or plants was made
for the plot as a whole. Growth stages are described for crops according to the BBCH scale (BBCH Monograph, 2001).
Crop safety
Initium is characterised by excellent crop safety. At the recommended rates, no crop injury has been observed over several years
in a broad variety of crops.
Spectrum of activity
Initium controls all major Oomycete diseases, e.g. downy mildew caused by Plasmopara viticola in grapes, late blight caused by
Phytophthora infestans in potatoes and tomatoes, and a broad range of downy mildews and late blights in vegetables (e.g. cucurbits, brassicas, onions, and lettuce) a shown in Table 1.
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Table 1. Activity spectrum of Initium ®
Disease
Pathogen
Grape downy mildew
Plasmopara viticola
Potato late blight
Phytophthora infestans
Tomato late blight
Downy mildew in cucurbits
Pseudoperonospora cubensis
Downy mildew in lettuce
Bremia lactucae
Downy mildews and late
Other Peronospora &
blight in vegetables
Phytophthora species
Grape vines
Initium is an excellent tool to control grape downy mildew caused by Plasmopara viticola on leaves and clusters.
The particularly strong protection of grape clusters was demonstrated in numerous trials in Europe (Table 2).
Table 2. Control of Plasmopara viticola in grapes in France, Italy, Hungary,
Germany, Greece, Spain and Portugal in 2006 – 2008 (orthogonal summary)
Treatment1
Dose
g a.i./ha
Mean % index of attack and statistics 2
Leaves
Clusters
Initium
300
11 B
3 C
Cyazofamid
100
10 B
5 B
–
60 A
75 A
28
28
Untreated
Number of trials
1
5-9 applications at BBCH 19-81
using a 10-15 day spray intervals.
Orthogonal ave. of 28 trials.
2
Statistical analysis: SNK-Test
1
3-7 applications at BBCH 19-85
Potatoes
Initium also displayed excellent potato late blight control in trials performed in several countries.
Table 3. Control of Phytophthora infestans in potatoes
in Spain, Germany, Brazil and Taiwan in 2004 – 2005 (orthogonal summary)
Treatment1
Dose
g a.i./ha
Mean % index of attack
Leaves
Statistics²
Initium
300
11
C
Fluazinam
200
16
B
Untreated
–
78
A
Number of trials
8
Depending on target disease, Initium will be used at 200 to 300 g active ingredient per hectare.
5
following a 5-11 day spray interval.
Ave. of 8 trials.
2
Statistical analysis: SNK-Test
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Resistance Management
Initium® is not cross-resistant to Oomycete fungicide classes with confirmed field resistance (e.g. phenylamides, Qo inhibitors or
carboxylic acid amides). To ensure the long-term efficacy of Initium it will only be available in ready formulations combined with
other fungicidal active ingredients of a different mode of action.
Initium shows the best performance when it is applied as a protectant spray before disease is established in the crop. Selection
pressure for resistance is also lower through preventative applications, compared to a curative or eradicant approach, because
the pathogen population is lower at disease onset than when it is already established in the field.
Therefore, Initium should be applied in a preventative manner following the recommendations on the product label.
Conclusions
Initium is a highly active preventive fungicide from a new chemical class for use against Oomycete diseases. It has an excellent
toxicological and ecotoxicological profile and is suitable for use in a range of speciality crops in integrated crop management
programmes. BASF plans worldwide registrations for Initium. Initium will be marketed in ready-mixtures with other Oomycete
active compounds to complement the spectrum of activity and to reduce selection pressure for resistance.
Acknowledgements
The authors would like to thank all colleagues who have contributed to the development of Initium.
References
BBCH Monograph (2001) 2nd edition, edited by U. Meier, published at www.bba.de/veroeff/bbch.
® = Registered trademark of BASF.
© Copyright BASF. All rights reserved.
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