Fig. 1 Structure of pyridalyl R 3,3-Dichloro-2-propenyloxy compound 1 H CF3 (CH2) 3,3-Dichloro-2-propenyloxy compound 2 Lead compound 3 (Insecticidal

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1 Research and Development of a ovel Insecticide pyridalyl Sumitomo Chemical Co., Ltd. Agricultural Chemicals Research Laboratory oriyasu SAKAT obuhito UEDA Crop Protection Division-International Kimitoshi UEDA rganic Synthesis Research Laboratory Sanshiro ATSU Basic Chemicals Research Laboratory Toru HAGA Environmental Health Science Laboratory Takuo FUJISAWA Yoshitaka TIGAHARA Pyridalyl was discovered and has been under worldwide development by Sumitomo Chemical Co., Ltd. It was already registered in some Asian countries in 2004, including Japan. This novel insecticide exerts excellent control against various lepidopterous and thysanopterous pests on cotton and vegetables. any existing insecticide-resistant strains of lepidopterous pests can be adequately controlled by pyridalyl as well as susceptible strains. Since pyridalyl develops quite unique insecticidal symptoms, it is considered that pyridalyl has a different mode of action from any other existing insecticides. Its excellent safety to mammals and various beneficial arthropods would provide us with an important tool in IP (Integrated Pest anagement). 200-

2 Fig. 1 Structure of pyridalyl R 3,3-Dichloro-2-propenyloxy compound 1 H CF3 (CH2) 3,3-Dichloro-2-propenyloxy compound 2 Lead compound 3 (Insecticidal activity) Fig. 2 Discovery of the lead compound

3 CF3 Lead compound 3 R 3 Y Z Linker R pyridalyl Fig. 3 ptimization of the lead compound 3 Table 2 Insecticide pyridalyl cyfluthrin pyrimifos methyl chlorfluazuron Insecticidal activity of pyridalyl against insecticide resistant strain of P. xylostella ass LC0 (mg a.i./litre) resistant strain susceptible strain synthetic pyrethroid organic phosphate benzoyl phenylurea 2.6 > 00 > 40 > Table 1 Scientific name Cnaphalocrosis medinalis Helicoverpa armigera Helicoverpa zea Heliothis virescens amestra brassicae Spodoptera exigua Spodoptera litura Pieris rapae Plutella xylostella Insecticidal activity of pyridalyl against lepidopterous pests Stage* 1 L3 L3 L2 L2 L3 L3 L3 L2 L3 LC0 Test method DAT* 2 (mg a.i./litre) Leaf dip Leaf dip Leaf dip Leaf dip Leaf dip *1 L2 and L3 means 2nd and 3rd instar larva, respectively. *2 Days after treatment 200-

4 ortality (%) Fig. 4 pyridalyl 100ppm chlorfenapyr 0ppm emamectin benzoate ppm Days after treatment Residual activity and rain fastness of pyridalyl Table 3 Scientific name Trichogramma japonicum Chrysoperla carnea Harmonia axyridis rius sauteri Phytoseiulus persimilis Apis mellifera Bombus terrestris Beneficial arthropods not affected by pyridalyl at 100 mg a.i./litre beneficials Egg parasitic wasp of lepidoptera Predatory Chrysopidae Predatory Coleoptera Predatory Hymenoptera Predatory Acarina Pollinator Pollinator *1 L2-3 means 2nd to 3rd instar larvae. Stage* 1 Adult L2-3 L2-3 Adult/ymph Adult Worker Worker Test method Insect dip Direct spray Direct spray o. of larvae/10 plants 100 pyridalyl 100ppm 90 permethrin 100ppm 80 chlorfenapyr 0ppm 70 untreated Fig. Days after treatment Field trial against Diamondback moth, Plutella xylostella on cabbage 200-

5 o. of insects/10 plants o. of Thrips/10 plants o. of Larvae/10 plants Fig. 6 Efficacy against Tobacco cutworm, Spodoptera litura Days after treatment Efficacy against Thrips Days after treatment 0 pyridalyl 100ppm chlorfuruazuron 2ppm untreated pyridalyl 100ppm chlorfuruazuron 2ppm untreated The effect against Pirate bug, rius strigicollis Days after treatment pyridalyl 100ppm chlorfuruazuron 2ppm untreated The efficacy against Tobacco cutworm, Spodoptera litura, and Thrips with effect against the population of Pirate bug, rius strigicollis of pyridalyl µ 10mm A B Development of S. Iitura larvae in the control (A) and sub-lethal symptoms caused by lower dosages of pyridalyl (B, C, D). Each larva was photgraphed 1 to days after treatment (left to right). The larvae in the control group (A) developed normally. B, C and D shows symptoms (circled area) occurring in larvae treated with pyridalyl at 1.6, 6.2 and 2ng, respectively. The larvae treated with 2ng of pyridalyl turned black and died days after treatment (D). Fig. 7 C D The effect of topical application of pyridalyl on Tobacco cutworm, Spodoptera litura 200-

6 H H H X X=halogen, s, Ts, etc. pyridalyl Fig. 8 Synthetic routes to pyridalyl Table 4 IS ame Code umber Chemical ame (IUPAC) Trade ame CAS R olecular Formula olecular Weight Physical Form dor Density elting Point Vapor Pressure Solubility Physical and chemical properties of pyridalyl pyridalyl S ,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[- (trifluoromethyl)-2-pyridyloxy]propyl ether Pleo C18 H14 4 F Liquid (20 C) dorless (20 C) 1.44 g/cc (20 C) < 17 C Pa (2 C) Water : 0.1 ppb (20 C) rganic solvents: soluble in most Table Storage conditions Ambient temperature 40 C 4 C Table 6 Stability of pyridalyl technical grade Storage period 6 months 12 months 18 months 24 months 36 months 1 month 2 months 3 months 1 week 2 weeks Remaining content (%) Physical and chemical properties of Pleo flowable Items Typical value (ethods) Appearance Whitish viscous liquid (Visual observation) Density 1.0 g/cc (CIPAC T3.3.2) ph 6.2 (Electric ph meter, without dilution) Viscosity 1070 mpa S (Brookfield viscometer, Spindle o.2, 6 rpm, 2 C) Suspensibility 98 % (CIPAC T41, 1000 times, 20 C, 1 min) Stability Physical and chemical properties after storage at ambient temperature for 4 years were very stable 200-

7 1 2 Table 7 Compound pyridalyl Pleo flowable (10% pyridalyl formulation) Acute toxicity studies with pyridalyl and Pleo flowable Administration route ral Dermal Inhalation a) ral Dermal a) LC0 (mg/m 3 ), 4 hours inhalation from nose LD0 (mg/kg) Rat (SD) ale Female >000 >000 >000 >000 >2010 >2010 >2000 >2000 >2000 >2000 γ Table 8 utagenicity studies with pyridalyl Study Test System Study Condition Result Reverse mutation (Ames test) In vitro gene mutation In vitro chromosomal aberration icronucleus In vivo/in vitro unscheduled DA synthesis S.typhimurium : TA100, TA98, TA13, TA137 E.coli : WP2uvrA Chinese hamster ovary cells (CH-K1-BH4) Chinese hamster lung cells (CHL/IU) ouse (CD-1), males/group Rat (SD), 3 males/group S9mix : 9.77 ~ 313µg/plate +S9mix : 39.1 ~ 120µg/plate S9mix : 9.4 ~ 300µg/mL +S9mix : 2.0 ~ 10.0µg/mL S9mix : 20 ~ 120µg/mL +S9mix : 1 ~ 2µg/mL 00, 1000, 2000mg/kg (single oral administration), 24hr (all doses) & 48h (2000mg/kg) 00, 1000, 2000mg/kg (single oral administration), 2 ~ 4hr & 1 ~ 16hr egative egative Weakly positive (+S9mix) egative egative 200-

8 Table 9 Short term, long term and carcinogenicity studies with pyridalyl Species Administration period Administration route Dose AEL Dog (Beagle) Dog (Beagle) Rat (SD) Rat (SD) ouse (CD-1) 13 weeks 2 weeks 13 weeks 104 weeks 78 weeks ral (capsule) ral (capsule) ral (dietary) ral (dietary) ral (dietary) 10, 100, 1000 (300)mg/kg/day 1.,, 20, 80mg/kg/day 100, 1000, 2000ppm 30, 100, 00, 1000ppm 1, 0, 1000, 200ppm 10mg/kg/day 20mg/kg/day ale:.6mg/kg/day (100ppm), Female: 6.4mg/kg/day (100ppm) ale: 3.40mg/kg/day (100ppm), Female: 4.10mg/kg/day (100ppm) ale:.04mg/kg/day (0ppm), Female: 4.78mg/kg/day (0ppm) Table 10 Developmental and reproductive toxicity studies with pyridalyl Study Species Administration period Administration route Dose AEL Developmental Toxicity Developmental Toxicity 2-Generation Reproductive Toxicity Rat (SD) Rabbit (JW) Rat (SD) rganogenesis (GD 6-19) rganogenesis (GD 6-27) 10 weeks pre-mating, 2 weeks mating, 3 weeks gestation and 3 weeks lactation (P and F1), weeks (F2) ral (gavage) ral (gavage) ral (dietary) 10, 0, 20 mg/kg/day 1, 0, 10 mg/kg/day 40, 200, 1000ppm o teratogenicity P: 10mg/kg/day F1: 20mg/kg/day o teratogenicity P: 0mg/kg/day F1: 0mg/kg/day P: 40ppm (ale: 3.10mg/kg/day) (Female: 3.37mg/kg/day) F1: 40ppm Reproduction: 40ppm 200-

9 β α α S CH3 H H H Conjugate U S U malonic acid C2 H S-1812-DP-e S-1812-DP U H 3,3-dichloro-2 P S U U 3,3-dichloro-2 U -propenoic acid -propenol P H H C2 U S-1812-Ph-CH2CH pyridalyl S HPH C2 H H H U S-1812-PYP S-1812-Py-H DCH U Conjugate H S U H C2 H Conjugate S U HTFP HPD U H C2 U Conjugate H H CH3 CH3 -ethyl-htfp -ethyl-hpd S-1812-DHQ : ammal P : Plant S : Soil U : Photolysis ain pathways are circled. Fig. 9 Proposed metabolic and degradation pathways of pyridalyl 200-

10 µ µ 200-

11 2 Table 11 Species Carp Alga 1) Daphnia magna Bobwhite quail Summary results of toxicity tests on nontarget organisms Study Acute Acute Acute Acute 1)Selenastrum capricornutum Results 96hrLC0 > 10 mg/l 72hrEC0 > 10 mg/l 48hrEC0 = 3.8 µg/l LD0 > 220 mg/kg 200-

12 PRFILE 200-

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