Initium® – An Innovative Fungicide - BASF Crop Protection

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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 fi eld 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 profi le 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 fi eld testing programmes. This paper describes its chemical and physical properties, mode of
action and biological properties, fi eld performance and safety profi le.
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 C 15 H 25 N 5
Structural formula
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 coeffi cient 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 profi le. 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 fi eld 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 profi le. 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 specifi cally, 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.
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,
added as substrate, was detected photometrically.
Measurements of complex III activity show strong inhibition
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).
0 s 60 s
2 h 5 h
Complex III inhibition
Fig. 2. Light microscope images of Plasmopara viticola zoospores. The untreated zoospore (left) remains intact and forms a germ tube within 5 hours.
Initium
Pyraclostrobin
Negative control
(non-complex III
inhibitor)
The Initium-treated zoospore (right) ruptures within 5 seconds and cytoplasm leakes from the spore.
0 20 40 60 80 100
Untreated Initium treated
(% inhibition) at 4E-07 M
0 s 2 s
4 s 7 s

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Untreated zoospore
5 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.
Ruptured zoospore after Initium ® treatment
Initium has a high affi nity for the waxy layer of the leaf epidermis and through adsorption forms a stable protective fi lm against
fungal attack (Fig. 4). Initium exhibits very good rainfastness, however, under the infl uence of moisture such as dew, a small but
effective portion of the active ingredient is gradually redistributed from the fi lm leading to an increase in protection.
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
2 µm
Methods and Materials
The fi eld 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.
3 µm
Fig. 4. Scanning electron microscopy image of Initium spray deposit on a
tomato leaf. The particles of the active ingredient are bound to the surface
like a fi lm.

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Table 1. Activity spectrum of Initium ®
Disease Pathogen
Grape downy mildew Plasmopara viticola
Potato late blight
Tomato late blight
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)
Treatment 1 Dose Mean % index of attack and statistics 2
g a.i./ha Leaves Clusters
Initium 300 11 B 3 C
Cyazofamid 100 10 B 5 B
Untreated – 60 A 75 A
Number of trials 28 28
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)
Treatment 1 Dose Mean % index of attack Statistics²
g a.i./ha Leaves
Initium 300 11 C
Fluazinam 200 16 B
Untreated – 78 A
Number of trials
Phytophthora infestans
Downy mildew in cucurbits Pseudoperonospora cubensis
Downy mildew in lettuce Bremia lactucae
Downy mildews and late
blight in vegetables
Other Peronospora &
Phytophthora species
Depending on target disease, Initium will be used at 200 to 300 g active ingredient per hectare.
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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
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 confi rmed fi eld resistance (e.g. phenylamides, Qo inhibitors or
carboxylic acid amides). To ensure the long-term effi cacy 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 fi eld.
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 profi le 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.
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