2010 JMPR Monograph Feb 24 2011 - Food and Agriculture ...

1 Thiamethoxam 1787 THIAMETHOXAM (245) The first draft was prepared by Mr. Denis Hamilton Primary Industries and Fisheries Australia EXPLANATION Thiamethoxam is a nicotinoid compound with broad-spectrum insecticidal properties. It is registered for use on numerous crops in many countries against sucking and chewing insects in vegetables, ornamentals, field crops, deciduous fruits, citrus, cotton and rice. It possesses contact and stomach activity. Its systemic properties has resulted in its use against foliar feeding insects via seed treatment, soil application, through irrigation systems, or applied to the trunks of trees. It is also registered for direct foliar application.

2 The compound was evaluated as a new compound by the 2010 jmpr for both residues and toxicology. The Meeting received information on physical and chemical properties, animal and plant metabolism, environmental fate, analytical methods, storage stability, use patterns, processing, farm animal feedingand supervised residue trials. IDENTITY Thiamethoxam is a nicotinoid compound with broad-spectrum insecticidal properties. ISO common name thiamethoxam Chemical name IUPAC (EZ)-3-(2-chloro-1,3-thiazol-5-ylmethyl) -5-methyl-1,3,5-oxadiazinan-4-ylidene(ni tro)amine CAS 3-[(2-chloro-5-thiazolyl)methyl]tetrahyd ro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4 -imine CAS Number 153719-23-4 CIPAC Number 637 Synonyms for active substance: CGA 293343 Molecular formula C8H10 ClN5O3S Molecular mass Structural formula NONNSNClNO2 Thiamethoxam isomers Thiamethoxam is described as an EZ mixture.

3 It is generally believed that the activation energy for the E Z interconversion for the C = N bond is low and that an equilibrium mixture is rapidly established at ambient temperature. NNHNSHNClNCH3 OOCGA 3227041788 Thiamethoxam The situation is similar for metabolite CGA 322704. In this case the E form is likely to be favoured in the equilibrium mixture because of possible formation of a hydrogen bond from the secondary amine to the nitro group. The E form of CGA 322704 is equivalent to the compound clothianidin. PHYSICAL AND CHEMICAL PROPERTIES Pure active ingredient: Thiamethoxam Property ResultRef Description (purity ) Slightly cream, fine crystalline powder, odourless 35446 Melting point, melting range (purity ) C 35441 Vapour pressure (purity ), OECD 104 10-9 Pa at 20 C 10-9 Pa at 25 C.

4 Measurements at to 121 C 35445 Water solubility (purity ) at 25 C, OECD 105 g/L (pure water, no buffer, measured pH of aqueous phase ) 35444 Octanol/water partition coefficient (purity ) at 25 C, OECD 107 log Pow = (pure water, no buffer, measured pH of aqueous phase ) 36610 Hydrolysis rate (purity ) [14C-oxadiazin label] pH 9, 25 C: 30 days test; = days ABR-97013 Hydrolysis rate (purity ) [14C-thiazol label] pH 1, 60 C: 96% remained after 5 days test pH 5, 60 C: 99% remained after 5 days test pH 7, 60 C: 5 days test; = 8 daysABR-96106 Photolysis rate, xenon arc at 410 w/m2 for 12 hours/day, 25 C, 10 mg/L in pH 5 buffer (purity > ) [14C-thiazol label] = days ABR-98091 Dissociation constant in water (purity ), OECD 112 no dissociation within pH range 2 to 12 38123 The hydrolysis of CGA 322704, an important metabolite and hydrolysis product of thiamethoxam was investigated by Ulbrich (1999, 98UL03).

5 CGA 322704 Hydrolysis rate (radiochemical purity ) [14C-thiazol label]. Starting concentration: 5 mg/L. pH , sterile, dark, 20 C: no decline after 31 days test pH , sterile, dark, 20 C: no decline after 31 days test pH , sterile, dark, 20 C: no decline after 31 days test pH , sterile, dark, 20 C: no decline after 31 days test. 98UL03 Technical material: Thiamethoxam Property Result Ref Description (purity ) Off-white, fine powder, odourless 58210 Solubility in organic solvents (purity ) at 25 C Acetone 48 g/L; dichloromethane 110 g/L; ethyl acetate g/L; hexane < 1 mg/L; methanol 13 g/L; octanol 620 mg/L; toluene 680 mg/L 58212 Hydrolysis rate (purity ) [14C-oxadiazin label] pH 1, 60 C: 96% remained after 5 days test pH 5, 60 C: 101% remained after 5 days test pH 7, 25 C: 96% remained after 30 days test pH 9, 40 C: 96 hours test, = 28 hours ABR-97013 Hydrolysis rate (purity ) [14C-oxadiazin label] pH 7, 40 C: 87% remained after 30 days test pH 7, 60 C: 20 days test; = 17 days ABR-97013 Hydrolysis rate (purity ) [14C-thiazol label] pH 5, 25 C: 100% remained after 30 days test pH 9, 25 C: 30 days test; = 100 hours ABR-96106 Hydrolysis rate (purity ) [14C-thiazol label] pH 7, 60 C: 30 days test; = 12 days pH 9, 40 C: 30 days test; = 26 hours pH 9, 60 C: 17 days test.

6 = hours ABR-96106 Hydrolysis rate (purity ) [14C-thiazol label] pH 7, 25 C: 98% remained after 30 days test pH 7, 40 C: 30 days test; = 70 days ABR-96106 Thiamethoxam 1789 Property ResultRef Photolysis rate, xenon arc at 410 w/m2 for 12 hours/day, 25 C, 10 mg/L in pH 5 buffer (purity ) [14C-oxadiazin label] = days ABR-97023 NONNSOClHONHNSNClNO2 NHClSNNHONO2 ThiamethoxamNONNSNClNO2 NHNHNSNClNO2NH2 NSClNOA 404617 CGA 309335 CGA 322704 CGA 355190 Figure 1 Products of thiamethoxam hydrolysis were identified by Lowery (1997, ABR-97013) and Clark (1998, ABR-96106). CGA 309335, CGA 355190 and NOA 404617 were the major products of hydrolysis.

7 CGA 322704 was a minor product. NONNSOClThiamethoxamNONNSNClNO2 NHNHNSNClNO2 NONNSNHClNONHNHNHNHNSOClNHNH2 ONHNONHONHNONHOOH+ COS+CNHO isocyanic acidCGA 322704methylureaCGA 353968 CGA 355190 NOA 407475 CGA 353042 Figure 2 Products of thiamethoxam photolysis were identified by Sparrow (1997, ABR-97023) and Schwartz (1998, ABR-98091). FORMULATIONS The main formulation types are: Code Description Examples FS flowable concentrate for seed treatment 350 g/L, 600 g/L FS flowable concentrate for seed treatment (includes mefenoxam and fludioxonil) 258 g/L, 336 g/L 1790 Thiamethoxam Code Description Examples GR granule (includes pyroquilon) 80 g/kg SC suspension concentrate 240 g/L SC suspension concentrate (includes azoxystrobin) 65 g/L SG water soluble granule 750 g/kg SL soluble concentrate 240 g/L WG water dispersible granule 100 g/kg, 250 g/kg, 300 g/kg, 400 g/kg ZC a mixed formulation of CS and SC (includes lambda-cyhalothrin)

8 141 g/L A number of products are registered that contain thiamethoxam and another active ingredient, viz., azoxystrobin, fludioxonil, pyroquilon, lambda-cyhalothrin, lufenuron and cyproconazole. METABOLISM AND ENVIRONMENTAL FATE Metabolism and environmental fate studies used thiamethoxam 14C labelled in the guanidine position or in position-2 the thiazole ring. NONNSNClNO2* [14C-oxadiazin-4]thiamethoxam = [14C-guanidine]thiamethoxam NONNSNClNO2* [14C-thiazol]thiamethoxam Structures, names and codes for metabolites are summarised below. Five possibilities for describing each metabolite are: a simple name, which could be a common name, a simplified systematic name, an abbreviation or a pseudo-common name ( hydroxy-cypermethrin) the systematic chemical name it may be too cumbersome for use in discussion and tables the CAS number CAS numbers are not available for many metabolites the company code number, CGA 322704 serial numbers, , metab 1, metab 2, etc.

9 In this evaluation, metabolites are described by the company code number where available or a metabolite serial number used in the metabolite studies. It should be noted that metabolite serial numbers are not necessarily consistent between studies, metabolites 4U, 8U and 13U are the same compound. 1-methyl-3-nitroguanidine Systematic: N-nitro-N'-methylguanidine CAS number: 4245-76-5 Code: NOA 405217 Code: MNG (clothianidin evaluation) NHNO2 NHN 1-methylguanidine Systematic: N-methylguanidine Code: CGA 382191 Code: MG (clothianidin evaluation) NH2 NHNH Thiamethoxam 1791 CGA 265307 Systematic: N-(2-chlorothiazol-5-ylmethyl)-N'-nitrog uanidine CAS number: 135018-15-4 Code: CGA 265307 Code: TZNG (clothianidin evaluation) NHNHNSNO2 NHCl CGA 282149 Systematic: 3,6-dihydro-3-methyl-N-nitro-2H-1,3,5-ox adiazin-4-amine CAS number: 153719-38-1 Code: CGA 282149 NHONNO2N CGA 309335: Systematic: (2-chlorothiazol-5-yl)-methylamine CAS number: 120740-08-1 Code.

10 CGA 309335 NH2 NSCl CGA 322704 Systematic: N-(2-chlorothiazol-5-ylmethyl)-N'-methyl -N"-nitroguanidine CAS number: 131748-59-9 Code: CGA 322704 Note17 NHNHNSNClNO2 CGA 322704-NO-glucoside Hydroxylamine glucoside of CGA 322704 NHNNSNClNO2 OOHCH2 OHOHHOO CGA 340575 Systematic: 3,6-dihydro-N-nitro-2H-1,3,5-oxadiazin-4 -amine CAS number: 123019-22-7 Code: CGA 340575 NHONNO2NH CGA 349208 Systematic: 2-chloro-5-thiazolemethanol CAS number: 145015-15-2 Code: CGA 349208 CH2 OHNSCl CGA 353042 Systematic: 3,6-dihydro-3-methyl-2H-1,3,5-oxadiazin- 4-amine Code: CGA 353042 NONHNH CGA 353968 Systematic: 1-(2-chlorothiazol-5-ylmethyl)-3-methylu rea Code: CGA 353968 Code: TZMU (clothianidin evaluation) NHNHNSOCl CGA 355190 Systematic: 3-(2-chlorothiazol-5-ylmethyl)-5-methyl- [1,3,5]oxadiazinan-4-one Code: CGA 355190 NONNSOCl CGA 359683 Systematic: 2-chlorothiazole-5-carboxylic acid CAS number: 101012-12-8 Code: CGA 359683 Code: CTCA (clothianidin evaluation) COOHNSCl 17 Note that clothianidin is the E isomer of CGA 322704 ([C(E)]-N-[(2-chloro-5-thiazolyl)methyl] -N'-methyl-N"-nitroguanidine), CAS number 210880-92-5 (formerly 205510-53-8) (Wood, 2010 ).