Emamectin benzoate 231

1 Emamectin benzoate 231 Emamectin benzoate (247) First draft prepared by T. van der Velde-Koerts, Centre for Substances and Integrated Risk Assessment, National Institute of Public Health and the Environment, The Netherlands EXPLANATION Residue and analytical aspects of Emamectin were considered for the first time by the present Meeting. The toxicological and residue evaluation was scheduled for the 2011 JMPR by the Forty-second Session of the 2010 CCPR (ALINORM 10/33/24). Emamectin is a foliar insecticide derivative of abamectin, which is isolated from fermentation of Streptomyces avermitilis, a naturally occurring soil actinomycete.

2 It acts by stimulating the release of -aminobutyric acid, an inhibitory neurotransmitter, thus causing insect paralysis within hours of ingestion, and subsequent insect death 2 4 days later. It has registered uses in many countries on fruits, vegetables, cereals, tree nuts, oilseeds, herbs and tea. Other related avermectins are abamectin, ivermectin, doramectin and eprinomectin of which abamectin has been evaluated before by JMPR and abamectin and the other avermectins have been evaluated by JECFA. The manufacturer supplied information on identity, metabolism, storage stability, residue analysis, use pattern, residues resulting from supervised trials on pome fruit, stonefruit, grapes, brassica vegetables, fruiting vegetables, leafy vegetables, legume vegetables, cottonseed, fate of residue during processing, and livestock feeding studies.

3 In addition, Japan supplied information on use pattern. IDENTITY Emamectin exists in various forms: as Emamectin (free base), as Emamectin benzoate salt (MK244) and as Emamectin hydrochloride (MK243). Emamectin benzoate exists as the anhydrous and various hydrated forms having different crystal morphologies. The amount of water is nonstoichiometric. [Merck Index]. Experiments described in this evaluation were carried out with various hydrate forms of the Emamectin benzoate salt. Emamectin benzoate (MK-0244) is the common name for (4"R)-4"-deoxy-4"-(methylamino)avermecti n B1 benzoate (MAB1), which is a mixture of 4"R)-4"-deoxy-4"-(methylamino)avermectin B1a benzoate (MAB1a or Emamectin B1a benzoate ) and 4"R)-4"-deoxy-4"-(methylamino)avermectin B1b benzoate (MAB1b or Emamectin B1b benzoate ).

4 The avermectins in Emamectin benzoate are specified as a ratio MAB1a:MAB1b = 90:10 (w/w) and differ by a methylene group at the C26 alkyl substituent: CH2CH3 for MAB1a and CH3 for MAB1b. Emamectin (free base) ISO common name: Emamectin (BSI, E-ISO, ANSI) mixture of > 90% Emamectin B1a and < 10% Emamectin B1b. Chemical name IUPAC: Emamectin : no IUPAC name available Emamectin B1a: (10E,14E,16E,22Z)-(1R,4S,5 S,6S,6 R,8R,12S,13S,20R,21R,24S)-6 -[(S)-sec-butyl]-21,24-dihydroxy-5 ,11,13,22-tetramethyl-2-oxo-(3,7,19-trio xatetracyclo[ , ,24] pentacosa-10,14,16,22-tetraene)-6- spiro-2 -(5 ,6 -dihydro-2 H-pyran)-12-yl 2,6-dideoxy-3- O-methyl-4-O-(2,4,6-232 Emamectin benzoate trideoxy-3-O-methyl-4-methylamino- -L-lyxo-hexapyranosyl)- -L-arabino-hexapyranoside Emamectin B1b.

5 (10E,14E,16E,22Z)-(1R,4S,5 S,6S,6 R,8R,12S,13S,20R, 21R,24S)-21,24-dihydroxy-6 -isopropyl-5 ,11,13,22-tetramethyl-2-oxo-(3,7,19-trio xatetracyclo[ , ,24] pentacosa-10,14,16,22-tetraene)-6- spiro-2 -(5 ,6 -dihydro-2 H-pyran)-12-yl 2,6-dideoxy-3-O-methyl-4-O-(2,4,6-trideo xy-3-O-methyl-4-methylamino- -L-lyxo-hexapyranosyl)- -L-arabino-hexapyranoside CAS: Emamectin : (4 R)-4 -deoxy-4 -(methylamino) avermectin B1 or 4 -deoxy-4 -(methylamino)-(4 R)-avermectin B1 Emamectin B1a: (4''R)-5-O-demethyl-4'' -deoxy-4'' -(methylamino)avermectin A1a or 5- O-demethyl-4 -deoxy-4 -(methylamino)-(4 R)-avermectin A1a Emamectin B1b: (4''R)-5-O-demethyl-25-de(1-methylpropyl )-4''-deoxy-4''-(methylamino)-25-(1-meth ylethyl)-avermectin A1a or 5- O-demethyl-25-de(1-methylpropyl)-4 -deoxy-4 -(methylamino)-25-(1-methylethyl)-(4 R)-avermectinA1a CAS Registry No: Emamectin : 119791-41-2 (formerly 137335-79-6) CIPAC No: Emamectin : 791 Synonyms/trade names: Emamectin : 4''-epi-methylamino-4'' -deoxyavermectin B1 Emamectin B1a.

6 4''-epi-(methylamino)-4''deoxy-avermecti n B1a Emamectin B1b: 4''-epi-(methylamino)-4''deoxy-avermecti n B1b Emamectin benzoate 233 Structural formula: Molecular formula: Emamectin B1a: C49H75NO13 Emamectin B1b: C48H73NO13 Molecular weight: Emamectin B1a: Emamectin B1b: Emamectin benzoate (anhydrous form) ISO common name: Emamectin benzoate mixture of > 90% Emamectin B1a benzoate and < 10% Emamectin B1b benzoate . 234 Emamectin benzoate Chemical name: IUPAC: Emamectin benzoate : no IUPAC name available Emamectin B1a benzoate : (10E,14E,16E,22Z)-(1R,4S,5 S,6S,6 R,8R,12S,13S,20R,21R,24S)-6 -[(S)-sec-butyl]-21,24-dihydroxy-5 ,11,13,22-tetramethyl-2-oxo-(3,7,19-trio xatetracyclo[ , ,24] pentacosa-10,14,16,22-tetraene)-6- spiro-2 -(5 ,6 -dihydro-2 H-pyran)-12-yl 2,6-dideoxy-3-O-methyl-4-O-(2,4,6-trideo xy-3-O-methyl-4-methylamino- -L-lyxo-hexapyranosyl)- -L-arabino-hexapyranoside benzoate Emamectin B1b benzoate .

7 (10E,14E,16E,22Z)-(1R,4S,5 S,6S,6 R,8R,12S,13S,20R,21R,24S)-21,24-dihydrox y-6 -isopropyl-5 ,11,13,22-tetramethyl-2-oxo-(3,7,19-trio xatetracyclo[ , ,24] pentacosa-10,14,16,22-tetraene)-6- spiro-2 -(5 ,6 -dihydro-2 H-pyran)-12-yl 2,6-dideoxy-3-O-methyl-4-O-(2,4,6-trideo xy-3-O-methyl-4-methylamino- -L-lyxo-hexapyranosyl)- -L-arabino-hexapyranoside benzoate CAS: Emamectin benzoate : (4 R)-4 -deoxy-4 -(methylamino) avermectin B1 benzoate or 4 -deoxy-4 -(methylamino)-(4 R)-avermectin B1 benzoate Emamectin B1a benzoate : (4''R)-5-O-demethyl-4'' -deoxy-4'' -(methylamino)avermectin A1a benzoate or 5- O-demethyl-4 -deoxy-4 -(methylamino)-(4 R)-avermectin A1a benzoate Emamectin B1b benzoate : (4''R)-5-O-demethyl-25-de(1-methylpropyl )-4''-deoxy-4''-(methylamino)-25-(1-meth ylethyl)-avermectin A1a benzoate or 5- O-demethyl-25-de(1-methylpropyl)-4 -deoxy-4 -(methylamino)-25-(1-methylethyl)-(4 R)-avermectinA1a benzoate CAS Registry No: Emamectin benzoate : 155569-91-8 Emamectin B1a benzoate : 138511-97-4 Emamectin B1b benzoate : 138511-98-5 CIPAC No: - Synonyms/trade names: Emamectin benzoate .

8 4''-deoxy-4''-epi-N-methylaminoavermecti n B1 benzoate 4''-epi-methylamino-4'' -deoxyavermectin B1 benzoate MK244 Emamectin B1a benzoate : 4''-epi-(methylamino)-4''deoxy-avermecti n B1a benzoate NOA 426007 Emamectin B1b benzoate : 4''-epi-(methylamino)-4''deoxy-avermecti n B1b benzoate NOA 422390 Emamectin benzoate 235 Structural formula: OONHOOOOHOHOOOOHHORHHHOOHO R = CH2CH3 for Emamectin B1a benzoate R = CH3 for Emamectin B1b benzoate Molecular formula: Emamectin B1a benzoate : C56H81NO15 or Emamectin B1b benzoate : C55H79NO15 or Molecular weight: Emamectin B1a benzoate : Emamectin B1b benzoate : Spectra The structural formula for MK244, batch AMS 921/2, was confirmed by 1H-NMR, 13C-NMR, IR, UV-VIS and MS [Oggenfuss, 1999, MK244/0175] Physical and chemical properties for Emamectin benzoate Pure active ingredient Emamectin benzoate : minimum purity 950 g/kg.

9 The content of the Emamectin B1a and B1b according to the manufacturer is: min. 900 g/kg Emamectin B1a benzoate and max. 70 g/kg Emamectin B1b benzoate . A technical substance with a high purity ( w/w) was used for the determination of the physico-chemical properties. Since the technical material contains a little amount of water ( w/w), the material was named Emamectin benzoate hemihydrate by the manufacturer. No data were submitted for the Emamectin B1a benzoate and Emamectin B1b benzoate variants. Parameter Result References Guidelines/method Appearance white solid at 25 C Emamectin benzoate hydrate form, purity w/w, MAB1a MAB1b , water % unknown [Das, 2000, MK244/0216, Syngenta 2011c] visual Vapour pressure a mean 4 10-6 2 10-6 Pa (n = 3; 1 stdev) at C: Emamectin benzoate hydrate form, batch L-656,748-052S002 purity w/w; MAB1a MAB1b , water [McCauley, 1992, MK244/0047, Syngenta 2011c] EEC A4.

10 OECD 104 gas saturation method Melting point b 141 146 C (2 C/min, under nitrogen) 142 147 C (2 C/min, under ambient air) 140 145 C (1 C/min, under nitrogen) Emamectin benzoate hydrate form, batch L-656,748-052S002 purity w/w; MAB1a MAB1b [McCauley, 1992, MK244/0047, Syngenta 2011c] EEC A1; OECD 102; differential scanning calorimetry (DSC) 236 Emamectin benzoate Parameter Result References Guidelines/method , water Octanol/water partition coefficient c,d At pH (NaAc-HAc) buffer: (n = 2 3; 1 stdev) At pH (KH2PO4-NaOH buffer: (n = 2 3; 1 stdev) At pH (Na2B4O7-H))