Transcript DPX-E2Y45 – Introducing of a Novel Anthranilamide

Altacor™ WG Insecticide
(DPX-E2Y45)
Introducing
a Novel Anthranilic Diamide
Insecticide from DuPont
Daniel W. Sherrod
DuPont Crop Protection
Memphis Market Center
Memphis, TN 38017
DuPont Crop Protection
 Code:
DPX-E2Y45
 Common Name: Chlorantraniliprole (ISO) - RynaxypyrTM
 CAS:
3-Bromo-N-[4-chloro-2-methyl-6[(methylamino)carbonyl]phenyl]-1(3-chloro-2-pyridinyl)-1H-pyrazole-5carboxamide
Br
 Chemical Structure:
H
H3C
N
O
H
N
N
N
Cl
O
Cl
CH 3
 Empirical Formula: C18H14BrCl2N5O2
 Molecular Weight: 483.15 g/mole
N
DuPont Crop Protection
Activates Insect Ryanodine Receptors
200
Rynaxypyr™ EC50 = 40 nM
190
100
140
50
1 min
90
40
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
0
-10
-9
-8
-7
Concentration (log M)
-6
-5
Ca2+ Mobilization Threshold (M)
150
1000
240
50 nM
[Ca2+]i Increase (nM)
1 uM
Rynaxypyr
r2 = 0.91
100
2
r = 0.84
r2 = 0.84
10
1
P. xylostella
S. frugiperda
H. virescens
0.1
0.01
0.001
0.001
0.01
0.1
1
10
Insect LC50 (ppm)
 Rynaxypyr™ and related anthranilic diamides stimulate release
of Ca2+ stores
 Rynaxypyr™ is selective for ryanodine receptors
 Insecticidal activity is highly correlated with Ca2+ store release
100
1000
DuPont Crop Protection
Does Not Impact Commercialized Targets
Targets Below Reflect MoA for > 90% of Commercial Insecticides
Excitatory Neuron
Muscle
OPs
Carbamates
AChE
Glut
ACh
Na+/K+
channels
Pyrethroids
Indoxacarb
GABA
Motor Neuron
Insect Neuromuscular Signaling Pathway
DuPont Crop Protection
What is the Ryanodine Receptor (RyR)?
O
Chiral
O
Ryanodine
Receptor Complex
O
O
O
N
O
O
CAM
RyR
RyR
O
O
Ryanodine
(Natural Plant Toxin)
 Calcium channel
cytosol
lumen
Ca2+
 Regulates release of stored calcium
 Critical for muscle contraction
 Complex includes accessory proteins
 Previously, no synthetic RyR agents known with
insecticidal properties
CAM
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Insect Poisoning Symptoms
Rapidly Affects Skeletal and Cardiac Muscle
 Rapid feeding cessation
 General lethargy
 Partial paralysis
 Regurgitation
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Resistance Management
Baseline Susceptibility
Heliothines
 Australia, Brazil, India, Spain, USA
Spodoptera spp.
 Brazil, Indonesia, Japan, Malaysia, Spain,
Thailand, USA, Vietnam
DuPont Crop Protection
Effects of DPX-E2Y45 in the Environment
Bees
• Negligible risk in field studies
Non-target•
Insects
T1: Negligible toxicity to standard
species (mites, parasitoids) +
Chrysoperla, Orius
• T2 to T4: Safety to predatory larvae of
Coccinellids and Episyrphus
Birds and Mammals
•
Negligible risk
Surface water
Plants
• Negligible risk
• No/low transport
to flowering parts
Soil
• Earthworms: Negligible risk
• Soil Micro: Negligible risk
• Fish: Negligible risk
• Algae: Negligible risk
• Aquatic Inverts:
 High acute toxicity
 Moderate chronic
toxicity
Sediment
• Chironomus: Negligible
to moderate risk
DuPont Crop Protection
Mammalian Toxicity
 E2Y45 exhibits a remarkably favorable toxicity
profile
 Little or no toxicological effects have been
observed following single doses as high as
5000 mg/kg bw and following repeat doses as high
as ~1500 mg/kg bw/day
 The low toxicity of this product combined with low
use rates provide large margins of safety for
consumers and workers
DuPont Crop Protection
E2Y45: Mammalian Toxicology
 Lack of adverse effects for the following endpoints:
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

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


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
Acute oral, dermal and inhalation toxicity
Skin and eye irritation; skin sensitization
Genotoxicity in vitro and in vivo
Subacute and subchronic toxicity in rats, mice, and dogs
Reproductive and developmental toxicity
Neurotoxicity
Immunotoxicity
Chronic toxicity after 1 year in dogs
Chronic toxicity after 1 and 2 years in rats
Oncogenicity after 2 years in rats and 18 months in mice
DuPont Crop Protection
Rynaxypyr™ Exhibits Insect
Receptor Selectivity
Insect Receptor:
Mammalian Receptor:
Single isoform
RyR1 – “skeletal”
Cell Line
PC12
C2C12
IMR32
120
Source
Rat
Mouse
Human
RyR2 – “cardiac”
RyR3 – “non-specific”
Expressed Isoforms
RyR2 & RyR1
RyR1 & RyR3
Not Defined
Insect
Normalized Response
(% of max)
Periplaneta
Drosophila
100
Heliothis
80
Mammalian
60
C2C12
EC50 = 14 m
PC12
EC50 > 100 m
IMR32 EC50 > 100 m
350 to >3000X
Selectivity
40
20
0
-9.0
-8.0
-7.0
-6.0
-5.0
RynaxypyrTM Concentration (log M)
-4.0
DuPont Crop Protection
Selectivity to Beneficial Arthropods
ORDER
Neuroptera
FAMILY
Chrysopidae
SPECIES
RATE (g ai/Ha)
Chrysoperla carnea
25-100
Mallada signatus
30-60
Coleoptera
Coccinellidae
Hippodamia sp.
25
Hippodamia variegatta
30
Harmonia axyridis
50-100
Hemiptera
Nabidae
Nabis kimbergii
30
Anthrocoridae
Orius insidiosus
50
Anthocoris nemoralis
60
Geocoris punctipes
50
Lygaeidae
Acari
Phytoseiidae
Amblyseius herbicolus
100
Euseius citrifolius
100
Iphiseiodes zulugai
100
Typhlodromus occidentalis
50-100
Hymenoptera
Trichogrammatidae
Trichogramma pretiosum
60
Trichogramma chilonis
33
Braconidae
Bracon hebetor
50
Dolichogidea tasmanica
30-60
Encyrtidae
Ageniaspis citricola
50
Aphelinidae
Aphelinus mali
30-60
█ no impact, (0-30% mortality); (Ratings according to IOBC/ WPRS Working Group,
Hassan et al. 1988).
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Pest Spectrum – Lepidoptera
 Noctuidae
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Heliothines (bollworms, budworms), Earias spp. (bollworms)
Spodoptera spp. (armyworms), Agrotis (cutworms)
Pseudoplusia, Trichoplusia (loopers)
Alabama argillaceae (leaf worms)
 Tortricidae
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Argytotaenia, Choristoneura (leafrollers)
Carposina,Cydia,Grapholita (fruit moths), Lobesia (berry moths)
 Crambidae
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Chilo (stem borers), Ostrinia (corn borers)
Hellula (cabbage worms)
Lerodea (leaf folders)
Leucinodes, Neoleucinodes (fruit borers)
 Gelechiidae, Pieridae, Plutellidae



Anarsia (twig borers), Tuta, Keiferia (pin worms)
Pieris (whites, sulfur)
Plutella xylostella (diamondback moth)
 Gracillariidae

Phyllonorycter, Phyllocnistis (leafminers)
DuPont Crop Protection
Formulations
 20 SC
 200 g/L suspension concentrate
 1.667 lb ai/gal suspension concentrate
 CoragenTM
 35 WG
 35% water dispersible granule
 AltacorTM
 Formulation Studies
 Excellent compatibility with other insecticides/fungicides
 Excellent spray tank clean-out properties
 Excellent mixing and handling characteristics
DuPont Crop Protection
Product Attributes
 Excellent plant protection on a broad spectrum
of Lepidoptera and other key pest species,
effective at low rates of application
 Long-lasting protection and rainfast
 Excellent fit in IPM & IRM programs
 Controls insecticide-resistant strains
 Low toxicity to wildlife such as birds, fish, and
mammals
DuPont Crop Protection
DuPont Rynaxypyr™
Biological Attributes
of A Novel Anthranilic Diamide Insecticide in a
New Class of Potent and Selective Ryanodine Receptor Agonists
DuPont Crop Protection
DuPont RynaxypyrTM
Rapid Feeding Cessation
Time to feeding cessation (minutes) of S. exigua 3rd instar larvae
exposed to dry insecticide residues on treated tomato leaves
COMPOUND
RynaxypyrTM 20SC
Emamectin Benzoate 5WG
Methoxyfenozide 2F
RATE
(ppm)
RATE
SLOPE ± SE
(g ai/ha)
ET 50
(minutes)
167
50
1.85 ± 0.3
7a
40
467
12
140
3.92 ± 1.0
4.45 ± 1.0
170 b
885 c
ET 50 CI95%
(minutes)
5-9
125 - 219
620 - 1134
ET 50 Ratio
(minutes)
24x
126x
 RynaxypyrTM acts very fast! In this experiment, RynaxypyrTM
was signifincalty faster to stop S. exigua larval feeding than
Emamectin Benzoate and Methoxyfenozide
Data: P. Marçon & G. Hannig, Delaware, USA
DuPont Crop Protection
DuPont RynaxypyrTM
Exceptional Crop Protection
RynaxypyrTM
50 GAH
E. Benzoate
12 GAH
Methoxyfenozide
140 GAH
Photos: P. Marçon, Delaware, USA
UTC
DuPont Crop Protection
DuPont RynaxypyrTM
High Insecticidal Potency
Comparative Insecticidal Potency of RynaxypyrTM vs. Commercial Standards
against Cydia pomonella neonate larvae (exposure by Ingestion)
LC50 (CI95%)
(ppm)
LC90 (CI95%)
(ppm)
4
0.4 (0.3-0.6)
3.1 (2.3-4.7)
RynaxypyrTM 35WG
3
0.4 (0.3-0.6)
3.7 (2.4-7.1)
Azinphos-methyl 50WP
3
3.9 (2.7-5.1)
28.7 (19.9-49.2)
Methoxyfenozide 240SC
2
3.3 (0.2-3.8)
313 (NA)
Species
Compound
Cydia pomonella
neonate larvae
RynaxypyrTM 20SC
Reps
 RynaxypyrTM is one order of magnitude more potent against
Cydia pomonella, when compared to commonly used
commercial standards
Data: J. L. Rison et. al., Nambsheim, France
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DuPont RynaxypyrTM
Ovi-Larvicidal Activity
* Anticarsia gemmatalis eggs
* Eggs treated with RynaxypyrTM
Intoxicated Neonate attempting to get out of the egg
Dead Neonate does not complete eclosion
 RynaxypyrTM has excellent ovi-larvicidal activity
 RynaxypyrTM is a potent larvicide and will control neonates as
they ingest the corion to eclode from the egg
Photos: M. Lima, São Paulo, Brazil
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DuPont RynaxypyrTM
Rainfastness and Residual Activity
RynaxypyrTM shows robust rainfastness and
residual activity, characteristics which are
explained by fundamental biological attributes:

Potent insecticidal activity

Translaminar movement

Rapid feeding cessation

Exceptional crop protection
DuPont Crop Protection
DuPont RynaxypyrTM
In a nutshell ….
 Favorable Toxicological and
Eco-toxicological profile
 Effective and Long-lasting
 Crop and Yield protection
 Broad Spectrum
 Novel mode of action
 Excellent crop safety
 Soft on beneficial arthropods
 Excellent fit into IPM and IRM
Programs
DuPont Crop Protection
Acknowledgments
• Stanley Royal
• Sue Rick
• Glenn Hammes
• J. Dan Smith
• Dickie Edmund
• Eric Castner
• Charlie Grymes
• Danny Tamayo
• Hugo Ramirez
• Wayne Steele
• C. Steve Williams
• Fred Marmor
•
•
•
•
Paula Marcon
Clifton Brister
Jay Ellis
Dennis Goldsberry
DuPont Crop Protection
THANK YOU!