MCW-25-chloro-2-(3,4,4-trifluoro-but-3-ene-1-sulfonyl)-thiazole

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ClO O

A New Proprietary Nematocide A New Proprietary Nematocide from Makhteshim Chemical Worksfrom Makhteshim Chemical Works

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Chemistry

3

Proprietary Molecule

Preliminary data available on:•Toxicology•Mode of Action•Spectrum of Activity

Global development project begun in 2008

Joint OECD Review – North America, South America, Western Europe, Japan

Global registrations expected 2013-2014

4

Efficacy and Operational Use

Formulations:–1.5% Granular–Emulsifiable Concentrate (EC 48%)–Slow release formulations (25 CS) under development for

drench / drip application.Crops:– Fruiting Vegetables – Cucurbits– Potatoes, Tobacco, Bananas

Nematode Targets:Meloidogyne spp., Rhadopholus spp., Pratylencus spp.

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Activity of MCW2 against Meloidogyne javanica

Chart 1. shoot fresh weight tomato plants grown in soil not inoculated (A) and inoculated with Meloidogyne javonica (B). Diagram C shows the severity of infection of tomato roots on a scale of 0-5.

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MCW-2

cadusafos

femamiphos

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cadusafos

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NoM.javanica

InoculatedM.javanica

Severity of Infection

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Acts as a true nematocide - kills nematodes thru contact with the product.This is a significant difference in comparison with all other non-fumigant

nematocides (P-ester, carbamates) which only inactivate nematodes as long as the active ingredient is present.

High level of efficacy against root-knot nematodes (Meloidogyne spp.)– Good residual activity– Clear dose response– Less variable than standards– New mode of action

Good crop safety after soil incorporation Root systemicNo insecticidal effects

MCW2 in Crop Protection

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Nematocidal activity of MCW2 against Meloidogyne javanica

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concentration (mg/l)

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cadusafos

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Cahrt 2. % of paralyzed larva of Meloidogyne javonica after exposure to nematocides for 24h(A), 48h(B). And 24h after wash by water (C).

24 HrExposure

48 HrExposure

24 HrAfter Wash

Suggested GAP

480 EC: •Pre application 1.5 – 2 kg. a.i per ha. •Post application (depend on residues results and efficacy trials) 1 – 1.5 kg. a.i. per ha.•Crops – Vegetables, Potatoes, Flowers, Bananas and others.

GR 1.5%•Pre application 2 – 2.5 kg. a.i. per ha. Mainly for the Japanese market.•Crops - Vegetables, Potatoes, Flowers

Plan to finalize in 2008.

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Acute ToxicologyToxicology:

Acute oral, rat LD50 >500 mg/kgDermal, rat LD50 >4000 mg/kgInhalation, rat LC50 >5058 mg/m3 airSubchronic feeding, rat NOAEL 4.3 mg/kg

Mutagenicity Negative in pilot testsDevelopmental Tox No prohibitive results in pilot

studies (rats, rabbits)

Eye irritation (rabbit) No irritant effect to the eyeSkin irritation (rabbit) No irritant effect to the skin

Skin sensitization (MT in guinea pigs) + Sensitizer

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Efate & Ecotox

Ecotoxicology:No prohibitive findings regarding beneficial and non-target organisms (no insecticidal activity).

Environmental Fate:Moderate soil degradation and soil absorption.Low leaching potential expected.

Nematocide Products Comparison

Trade Name MCW2 Nemathorin Namacur Temik Videte

Active ingredient

fosthiazate fenamiphos aldicarb oxamyl

Chemical class

fluoroalkenyle Organophosphate

Organophosphate

carbamate carbamate

US registration

ISK BIOSCIENCES CORPORATION

BAYER CORP

BAYER CROPSCIENCE LP (Cancelled in Europe on 7/21/05)

E. I. Du Pont

Acute oral tox(LD50)

Between 500 and 1,000 mg/kg

73 mg/kg (M)51-64 mg/kg (F)(Category II)1

2.7 mg/kg (M)3.0 mg/kg (F)(Category I)2

0.8 mg/kg3

(Category I)5.4 mg/kg 5

(Category I)

Acute dermal(LD50)

> 4,000 mg/kg 2396 mg/kg( M)861 mg/kg( F)1

(Category II)

225 mg/kg (M)178.8 mg/kg (F)2

(Category I)

20 mg/kg/day, water5 mg/kg, propylene glycol3

(Category I)

2960 mg/kg5

(Category III)

Acute Inhalation(LC50)

LC50>5,058 mg/L

0.83 mg/L(M)0.56 mg/L(F)1

(Category III)

LC50 = >0.1 mg/L2

(Category II)

LC50 < 0.007 mg/L3

(Category I)

0.12-0.17 mg/L5

(Category II)

Irritation Non irritant eye and skin

Mildly eye irritating; non-skin irritating 1

Mildly eye irritating; non-skin irritating 2

No irritation at lethal dose 3

Mildly eye irritating; non-skin irritating 4

Dermal sensitization

Positive Positive1 Negative2 Negative 3 Negative4

Others New ai ; no RED

IRED IRED is scheduled 3/2007

IRED 20001 EPA Fosthiazate RED Fact Sheet (2004) 2 EPA Fenamiphos IRED (2002) 3 EPA aldicarb HED and EFED Chapter (2006)4 EPA oxmyl IRED (2000) 5 Extoxnet oxmyl

Ecotoxicity

Trade NameMCW2* Nemathorin 1 Namacur 2 Temik 3 Videte 4

Active ingredient

fosthiazate fenamiphos aldicarb oxamyl

Chemical class fluoroalkenyle

Organophosphate

Organophosphate

carbamate carbamate

Birds Non toxic Highly toxic Highly toxic Very highly toxic

Acutely toxic

Freshwater fish Low Non toxic Highly toxic (also its degradates)

Very highly to moderately toxic

Toxic

FreshwaterInvertebrates

Moderate Acutely highly toxic

Highly toxic(also its degradates)

Highly toxic Highly toxic

Honey bee Not toxic Highly toxic (acute basis)

Highly toxic Highly toxic Moderately to high toxic

Wild mammals n.a. n.a. Highly toxic Very highly toxic

Acutely toxic

Earthworms Non toxic Highly toxic Highly toxic

Bioaccumulation10

low moderately low low* Bayer BYI 1921 Early Development Nematocide

Nematocide Products Comparison, cont.

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Major Global Markets and Current Major Products that MCW2 could replace (Preliminary information)

USA - ALDICARB, CHLOROPICRIN, DICHLOROPROPENE, ETHOPROPHOS, FENAMIPHOS, OXAMYL, METAM SODIUM, CADUSAFOS, FOSTHIAZATE, METHYL BROMIDE

Canada - The Canadian Pest Management Regulatory Agency (PMRA) has extended the use of American Vanguard's granular organophosphate insecticides, Thimet 15G (phorate) and Counter 15G (terbufos), until 2012. The extended phase-outs are necessary because of the lack of alternative products to control wireworms (Agriotes spp) in potatoes and sugar beet, respectively, the PMRA points out.

Japan - CADUSAFOS, Oxamyl, Carbosulfan, Pyraclofos enfuracarb, Fosthiazate, Dazomet

Brazil - ALDICARB, CADUSAFOS, CARBOFURAN, DAZOMET, TERBUFOS

Europe – 1,3- DICHLOROPROPENE, ALDICARB, METAM SODIUM, CADUSAFOS, FENAMIPHOS, FOSTHIAZATE, METHYL BROMIDE

Africa – As above

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Regulatory Plan and actions

Regulatory study program underway

OECD review planned and coordinated

Discussions held with regulatory bodies:–EPA, Ireland, Japan, Canada, Brazil

Will present to the OECD Joint Review Committee in Paris (Nov 6th)

First Global registrations anticipated in 2013-2014