altacor™ wg insecticide (dpx-e2y45) introducing a novel anthranilic diamide insecticide from...

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 ProtectionDuPont 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-5-carboxamide

Chemical Structure:

NH

NH

O

O

NN

N

Br

Cl

Cl

CH3

CH3

Empirical Formula: C18H14BrCl2N5O2

Molecular Weight: 483.15 g/mole


Activates Insect Ryanodine Receptors

40

90

140

190

240

17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37

1 min

50 n

M

40

90

140

190

240

17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37

1 min

50 n

M

1 min

50 n

M1 uM

Rynaxypyr

Concentration (log M)

[Ca2+

] iI n

c rea

se (

nM)

0

50

100

150

200

-10 -9 -8 -7 -6 -5

Rynaxypyr™ EC50 = 40 nMr2 = 0.84

r2 = 0.91r2 = 0.84

0.001

0.01

0.1

1

10

100

1000

0.001 0.01 0.1 1 10 100 1000

P. xylostella

S. frugiperda

H. virescens

Insect LC50 (ppm)

Ca2+

Mob

iliza

tion

Thr

esho

ld (

M)

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


Does Not Impact Commercialized Targets

Targets Below Reflect MoA for > 90% of Commercial Insecticides

ACh

Excitatory Neuron

Motor Neuron

Muscle

GABA

Glut

AChE

Na+/K+

channels

M

M

OPsCarbamates

Mitochondrial

InsecticidesNeonicotinoids

Spinosad

PyrethroidsIndoxacarb

Cyclodienes

Fipro

nil

Insect Neuromuscular Signaling Pathway


What is the Ryanodine Receptor (RyR)?

Calcium channel

Regulates release of stored calcium

Critical for muscle contraction

Complex includes accessory proteins

Previously, no synthetic RyR agents known with insecticidal properties

Ca2+

FKBPFKBP

Triad

in

Junctin

lumen

cytosol

CAM CAM

RyanodineReceptor Complex

CSQ

RyR RyR

O

O

O

O

O

O

O

O

O

N

Chiral

O

O

O

O

O

O

O

O

O

N

Chiral

Ryanodine(Natural Plant Toxin)


Rapidly Affects Skeletal and Cardiac Muscle

Rapid feeding cessation

General lethargy

Partial paralysis

Regurgitation

Insect Poisoning Symptoms


Resistance ManagementBaseline Susceptibility

Heliothines Australia, Brazil, India, Spain, USA

Spodoptera spp. Brazil, Indonesia, Japan, Malaysia, Spain,

Thailand, USA, Vietnam


Effects of DPX-E2Y45 in the Environment

Soil

Surface water

Birds and Mammals• Negligible risk

Bees • Negligible risk in field studies

• 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

Non-target Insects

• T1: Negligible toxicity to standard species (mites, parasitoids) + Chrysoperla, Orius

• T2 to T4: Safety to predatory larvae of Coccinellids and Episyrphus

Plants

• Negligible risk• No/low transport

to flowering parts


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


E2Y45: Mammalian Toxicology Lack of adverse effects for the following endpoints:

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


350 to >3000XSelectivity

Rynaxypyr™ Exhibits Insect Receptor Selectivity

Insect Receptor: Single isoform

Mammalian Receptor: RyR1 – “skeletal” RyR2 – “cardiac” RyR3 – “non-specific”

Cell Line Source Expressed IsoformsPC12 Rat RyR2 & RyR1

C2C12 Mouse RyR1 & RyR3IMR32 Human Not Defined

No

rmal

ized

Res

po

nse

(% o

f m

ax)

RynaxypyrTM Concentration (log M)

0

20

40

60

80

100

120

-9.0 -8.0 -7.0 -6.0 -5.0 -4.0

InsectPeriplaneta

Drosophila

Heliothis

MammalianC2C12 EC50 = 14 m

PC12 EC50 > 100 m

IMR32 EC50 > 100 m


ORDER FAMILY SPECIES RATE (g ai/Ha)

Neuroptera Chrysopidae 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

Lygaeidae Geocoris punctipes 50

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).

Selectivity to Beneficial Arthropods


Noctuidae Heliothines (bollworms, budworms), Earias spp. (bollworms) Spodoptera spp. (armyworms), Agrotis (cutworms) Pseudoplusia, Trichoplusia (loopers) Alabama argillaceae (leaf worms)

Tortricidae Argytotaenia, Choristoneura (leafrollers) Carposina,Cydia,Grapholita (fruit moths), Lobesia (berry moths)

Crambidae 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)

Pest Spectrum – Lepidoptera


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


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 Rynaxypyr™

Biological Attributes

of A Novel Anthranilic Diamide Insecticide in a

New Class of Potent and Selective Ryanodine Receptor

Agonists


RynaxypyrTM acts very fast! In this experiment, RynaxypyrTM was signifincalty faster to stop S. exigua larval feeding than Emamectin Benzoate and Methoxyfenozide

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

RynaxypyrTM 20SC 167 50 1.85 ± 0.3 7 a 5 - 9 -

Emamectin Benzoate 5WG 40 12 3.92 ± 1.0 170 b 125 - 219 24x

Methoxyfenozide 2F 467 140 4.45 ± 1.0 885 c 620 - 1134 126x

ET50 Ratio(minutes)

ET50

(minutes) COMPOUND

RATE (g ai/ha)

SLOPE ± SERATE (ppm)

ET50 CI95%

(minutes)

Data: P. Marçon & G. Hannig, Delaware, USA


DuPont RynaxypyrTM

Exceptional Crop Protection

RynaxypyrTM

50 GAH

Methoxyfenozide 140 GAH

E. Benzoate12 GAH

UTC

Photos: P. Marçon, Delaware, USA


DuPont RynaxypyrTM

High Insecticidal Potency

RynaxypyrTM is one order of magnitude more potent against Cydia pomonella, when compared to commonly used commercial standards

Comparative Insecticidal Potency of RynaxypyrTM vs. Commercial Standards against Cydia pomonella neonate larvae (exposure by Ingestion)

RynaxypyrTM 20SC 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)

Cydia pomonellaneonate larvae

LC90 (CI95%) (ppm)

Species Compound LC50 (CI95%) (ppm)

Reps

Data: J. L. Rison et. al., Nambsheim, France


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

* Eggs treated with RynaxypyrTM

Intoxicated Neonate attempting to get out of the egg

Dead Neonate does not complete eclosion

* Anticarsia gemmatalis eggs

DuPont RynaxypyrTM Ovi-Larvicidal Activity

Photos: M. Lima, São Paulo, Brazil


COTTON – RESCUE APPLICATION Heliothine populations were allowed to hatch and

develop into populations ranging in age up to 3-6 day old larvae prior to application. Key learning's center on the 3 to 5 and 6 to 8 DAT evaluations to determine the knockdown effects of E2Y45 on an established population of Heliothines.

Evaluations at 3 to 5 DAT had significant terminal damage with all treatments due to the delay in application. E2Y45 at 0.066 and 0.088 lb ai/ac resulted in similar protection with a significant reduction in terminal damage observed by 6 to 8 DAT.

Reduction in square damage ranged from 85% to 90% for all rates of E2Y45 at 6 to 8 DAT. Overall, less terminal, square, and boll damage was observed with E2Y versus Tracer when used in a rescue situation.


COTTON – RESCUE APPLICATION

Yields of lint/ac with E2Y at 0.066 and 0.088 lb ai/ac (2 trials) were 210 to 290 lbs greater than Tracer and 520 to 600 lbs greater than the UTC.

This data supports excellent knockdown control with E2Y45 at the 0.066 and 0.088 lb ai/ac rates.


COTTON – RESIDUAL CONTROL

3 - 4 DAT : E2Y45 at rates of 0.066 and 0.088 lb ai/ac were equal in performance and provided good to excellent insect control and damage reduction ratings. Efficacy was slightly lower with the 0.044 lbai/ac rate of E2Y45 which performed similar to the standard, Tracer.

7 DAT: control of live larvae in the terminals and squares was excellent with E2Y45 at 0.088 lb ai/ac. Reduction in terminal and square damage was similar with all rates of E2Y45 at 7 DAT. Overall, E2Y45 performance exceeded that of Tracer at this evaluation period.


COTTON – RESIDUAL CONTROL

10-11 DAT: E2Y45 at 0.088 lb ai/ac continued to provide good control of terminal larvae (83%) and excellent control of square larvae (93%). Control of square larvae was similar between the 0.088 and 0.066 lbai/ac rates with both exceeding 0.044 lbai/ac. Reduction in terminal and square damage was similar with all rates of E2Y45 at 7 DAT. Overall, E2Y45 performance exceeded that of Tracer at this evaluation period.

14-17 DAT: E2Y45 at 0.088 lb ai/ac provided the highest level of insect control and fruit protection. Overall performance declined with the 0.066 and 0.044 lbai/ac rates of E2Y45. Tracer performance dropped significantly.


COTTON – HELIOTHINE CONTROL E2Y45 at 0.044 lbai/ac provides insect control and plant protection equivalent to, to slightly better than Tracer. At 0.044 lbaia/c, the residual control seems greater than Tracer and a trend is present for better yields.

Limited data is available comparing E2Y45 at 0.066 lbai/ac to Tracer (3 trials). Data supports better performance versus Tracer at this rate.

E2Y45 at 0.088 lbai/ac provides significantly greater insect control, plant protection and offers longer residual when compared to Tracer at 0.067 lbai/ac. In nine trials with direct comparisons, the average yield increase with this rate is 57% which is 17% greater than Tracer’s average.


COTTON – HELIOTHINE CONTROL

When compared to BG II, 0.088 lbai/ac of E2Y45 provides equivalent insect control and fruit protection and has averaged 8% more yield versus BG II.

Limited data collected in 2004 for the 0.066 lbai/ac rate of E2Y45 (1-2 data points per evaluation) supported insect control and damage ratings slightly less than BG II. The 0.044 lbai/ac rate of E2Y45 did not provide control equivalent to BG II.


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


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 RynaxypyrTM

In a nutshell ….


• Stanley Royal• Sue Rick• Glenn Hammes• J. Dan Smith• Dickie Edmund• Eric Castner• Charlie Grymes• Danny Tamayo• Hugo Ramirez• Wayne Steele• C. Steve Williams

Acknowledgments

• Fred Marmor• Paula Marcon• Clifton Brister• Jay Ellis• Dennis Goldsberry


THANK YOU!

altacor™ wg insecticide (dpx-e2y45) introducing a novel anthranilic diamide insecticide from...

Documents

dupont crop protection

negligible toxicity

dupont crop protection

negligible risk algae

negligible risk fish

dupont daniel

pathway slide

vietnam slide