### Page 1 of 14 UNITED STATES ENVIRONMENTAL PROTECTI ON AGENCY

WASHI NGTON, D.C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES 

### MEMORANDUM **Date :**  July 16 , 200 9 **Ingredient: Fluopyram**  . Report of the Residues of Concern Knowledgebase Subcommittee (ROCKS). **PC Code:** 080302 **DP Barcode:** D367115 **Decision No.:** 393949 **Registration No. :**  264 - RNTI ; 432 - RUIL; 264 - RNTT **Petition No.:** 8F7358 **Regulatory Action:** Section 3 Registration **Risk Assessment Type:** NA **Cas e No.:**  NA **T XR No.:**  NA **CAS No.:** 658066 - 35 - 4 **MRID No.:** NA **40 CFR:** 180.xxx **From:** Edward Scollon , ROCKS Executive Secretary

Health Effects Division (HED) (7509P) **Through:** Christine L . Olinger, ROCKS Co - Chair

Mary Ko Manibusan, ROCKS Co - Chair HED (7509P) **To:** Fluopy

ram Risk Assessment Team Risk Assessment Branch III (RAB III) HED (7509P) The ROCKS met on June 4 , 200 9 to discuss the residues of concern for the fungicide fluop yram in food and drinking water. This was a joint meeting between the US EPA, EU (Germany) , and PMRA (Canada) . As such, the residues of concern for risk assessment and tolerance expression for each party are reviewed in this document. Team Members: Leung Chen g , M yron Ottley, Sheila Heal y , Steve Funk , Whang Phang, P aula Deschamp RO C K S Members Attended: Mary Manibusan, Christine Olinger, Rick Loranger, George Kramer, Edward Scollon , Ray Kent , Greg Orrick EFED Attended: Mohammed A. Ruhman , Mah Shamim

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PMRA Attended (via teleconference): Is abelle Pilote, Michael Hone ym an, Minoli Silva EU Attended (via teleconference): Thomas Kuhl, Bernd Stein, Steffen M atezki Material Reviewed:  Summary

of toxicological data and residue chemistry  Summary

of EU residue field trials  Environmental Degradates for Fluopy ram, DP#365542, MA Ruhman, June 1, 2009  DEREK for Windows evaluations for fluop yram, lactame, AE C656948 - 7 - hydroxy, AE C656948 -benzamide , AE C656948 - E - olefine, and AE C656948 - Z - olefine available upon request Committee Recommendation : **Table 1. Summary of Metabolites and**  **Degradates to be included in the Risk Assessment .**  ***** Matrix Residues included in Risk Assessment Residues included in Tolerance Expression Plants Primary Crops fluopyram (fluopyram + benzamide (M25) for legumes and oil seed crops) fluopyram Rotational Crops Livestock Ruminants Fluopyram + benzamide (M25) +7 - OH - fluopyram + ol e fins (E,Z) (M02, M03) F luopyram + benzamide (M25) Poultry Fluopyram + benzamide (M25) + ol e fins (E,Z) (M02, M03) Drinking Water fluopyram Not Applicable * Chemical names and abbreviations can be found in Table 1. 

### ROCKS Recommendation for Tolerance Expression Language Section (a)(1) would be for plants; (a)(2) is for livestock (a) (1) General. Tolerances are establ ished for residues of the fungicide fluopy ram , including its m etabolites and degradates, in or on the commodities in the table. Compliance with the tolerance levels specified below is to be determined by measuring only fluopy

ram ( N - [2 - [3 - chloro - 5 - (trifluoromethyl) - 2 -py ridinyl]ethyl] - 2 - (trifluoromethyl)benzamide ) . (a) (2) General. Tolerances are establ ished for residues of the fungicide fluopy ram , including its metabolites and degradates, in or on the commodities in the table. Compliance with the tolerance levels specified below is to be determined by measuring only the sum of fluopy ram ( N - [2 - [3 - chloro - 5 - (trifluoromethyl) - 2 -py ridinyl]ethyl] - 2 - (trifluoromethyl)benzamide ) and its benzamide metabolite [ 2 - (trifluoromethyl ) -benzamide ] , calculated as the stoichiometric equivalent of fluop yram , in or on the commodity .

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Rationale : Drinking W

ater Degradates (US only) Environmental fate studies indicate that the parent fluopy ram is stable under environmental conditions. Reported half - lives range from 89 days in field and aqueous photolysis studies to >1000 days in aerobic/anaerobic water/sediment systems. Fluop yram is mobile in soil and can therefore , be expected to occur in surface water runoff and/or in ground water leachate. Four metabolites were identified in aerobic soil metabolism studies : AE C656948 - 7 - hydroxy, AE C656948 -benzamide , AE C656948 -py ridylcarboxylic acid (PCA) , and lactame . None of the metabolites exceeded 10% of applied nor were any of the metabolites considered more toxic than the parent. AE C656948 - 7 - hydroxy , AE C656948 -benzamide, and AE C65 6948 - PCA , were also tracked in field dissipation studies. AE C656948 - 7 - hydroxy , though structurally similar to the parent, was only found at 1 - 3% of the fluopy ram levels. AE C656948 - PCA (1.2 - 18%) and AE C656948 - benzamide (0.2 - 16.2%) were more abundant but showed rapid declines. Lactame, a proposed metabolite of parent fluopy ram, was present at low levels in the soil system (1.2%) and as a major metabolite in the aqueous photolysis study (13%). Lactame is structurally dissimilar from parent fluop yram but would only be expected to form at significant levels in clear, shallow water . Based upon the low abundance of the metabolites in the soil studies and their rapid dissipation in the field studies , minimal exposure is expected through drinking water. Furthermore, none of the metabolites are considered more toxic than the parent. Therefore, ROCKS concurs with the risk assessment team that the metabolites are not considered of concern. **Residues of Concern for Monitoring**  **(Enforcement) and Risk Assessment**  Primary and Rotational Crops The metabolism in plants is relatively limited . In plant metabolism studies, unchanged parent accounted for >90% of the residues in grapes, beans, and potatoes and 70% of the residue in red bell peppers. While several metab olites were quantified (most <1% TRR) , only AE C656948 - benzamide exceeded 10% TRR in succulent and dry beans ( 52 - 64% ). M easureable quantities of parent and metabolites (AE C656948 -py ridyl - acetic acid (PAA), AE C656948 -py

ridyl - carboxylic acid (PCA) and AE C656948 -benzamide ) were also found in succulent (at full maturity) and dry beans during European field trials. These metabolites were not measured in US field trials. Of the major metabolites, AE C656948 -benzamide, P AA and PCA result from hydrol ys is of the ethylene bridge; AE C656948 -benzamide is a phenyl cleavage product and P PA and PCA are py ridylcleavage products . AE C656948 - methyl - sulfoxide results from the substitution of the chlorine atom in PCA. None of the metabolites, or their conjugates, are expected to be more toxic than the parent fluopy ram. Furthermore, inclusion of both phenyl and py ridylmetabolites as fluopy ram equivalents for either risk assessment or tolerance expression, would overestimate total exposure to fluopy

ram. Parent fluop y

ram b y itself is expected to an adequate measure of misuse in primary

crops. In addition, parent fluopy ram can be measured by some of the FDA

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multiresidue methods (MRM) while the benzami de metabolite does not lend itself to MRM anal ys is . Therefore, ROCKS recommends fluop yram only for tolerance expression. For risk assessment, ROCKS recommends fluopy ram only , except for legumes and oil seeds. For these commodities , ROCKS recommends fluopy ram + AE C656948 -benzamide due to the high levels of the latter in the bean metabolism studies. In confined rotational crop studies, parent fluop yram also accounted for the majority of residue. However, AE C656948 - 7 - hydroxy (up to 39% TRR, plus its conjugate (up to 16% TRR) ) was found in Swiss chard at all rotation intervals, and the methylsulfoxide metabolite was predominant in wheat grain at longer rotation intervals. The latter metabolite was detected up to 0.10 ppm in field rotational wheat trials and the AE C656948 - 7 - hydroxy compound was found only in wheat straw at 0.10 ppm level. AE C656948 - Benzamide (up to 39% TRR) was also present in Swiss chard. Since the AE C656948 - 7 - hydroxy and the benzamide were not significant residue s in the field rotational studies, the ROCKS recommends that the residue of concern be parent onl y. Although the methylsulfoxide was found in wheat grain at higher levels than parent in the EU rotational field studies, there will be target uses of fluopy ram on grains in the US that will drive risks from those crops. International Harmonization The EU and PMRA are in agreement with ROCKS ’ recommended inclusion of fluopy ram onl y for tolerance expression in primary and rotational crops. The US and PMRA are in agre ement to include fluopy

ram onl y for risk assessment, except f or legumes and o il seeds, which include parent fluop yram + AE C656948 -benzamide. The EU recommends inclusion of f luopy ram + AE C656948 -benzamide + AE C656948 - 7 - hydroxy + AE C656948 - 7 - hydroxy conjugates , AE C656948 - 7 - OH - GA and AE C656948 - 8 - OH - GA , for risk assessment. AE C656948 - 7 - OH - GA and AE C656948 - 8 - OH - GA are glucos yl ated conjugates of AE C656948 - 7 - hydroxy . At this meeting, the EU explained that they tend to include all quantifiable residues in dietary risk assessment, as opposed to US policy of including only

those c ompounds which pose potential risk greater to or equal the parent chemical . ROCKS determined these additional metabolites were not of concern. The additional metabolites are not expected to be more toxic than the parent compound . DEREK for Windows anal ysis of fluopy ram, AE C656948 -benzamide, AE C656948 - 7 - hydroxy , and AE C656948 E - and Z - olefines did not indicate any alerts. However, the lack of alerts for fluopy ram indicates that DEREK may be of limited use for this chemical . There are minimal toxicity concerns for the conjugates as these are likel y to b e more soluble in water, which would enhance in vivo clearance. The residue levels of these metabolites are low relative to the parent fluopy ram . Refer to Table 2 for a comparison of residues of concer n between the US, PM RA, and the EU recommended residues of concern . Livestock Commodities The metabolism in livestock is more extensive than was found in plant studies . The major residues identified at varyingsampling intervals include parent, AE C6569 48 -benzamide, AE C656948 - 7 - hydroxy, and AE C656948 E - and Z - olefines. In the egg and poultry metabolism studies, AE C656948 -benzamide (up to 99% TRR) accounted for the majority of residue in egg, muscle, fat, and liver. Parent fluop yram (18 %) was found in eggs and AE C656948 - olefines ( 14 % ) in the liver . Similarly in the goat, AE C656948 -benzamide accounted for the majority of

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residue (up to 99% TRR) in milk, muscle, fat, liver, and kidney . Fluopy ram (46%), AE C656948 - 7 - hydroxy (22%), and AE C656948 - ol efines (33%) were found at l ower levels in milk, muscle, and fat. The phenyl metabolite, AE C656948 -benzamide , was a major metabolite in both plant and livestock metabolism studies. However, the p yridyl metabolites, AE C656948 - py ridyl - acetic acid (PAA) and AE C656948 -py ridyl - carboxyl ic acid (PCA) , were not present in the livestock studies. While the fate of the p yridyl portion of the molecule is unknown , ROCKS determined tolerance expression and risk assessment decisions could be made without fully eluci dating the livestock metabolic pathway . Calculating the benzamide residues in terms of parent equivalents would likely account for the unknown py ridylmetabolites. Feeding studies confirmed the rapid transformation of parent fluopy ram; AE C656948 -benzami de was the onl y major residue in edible poultry matrices while fluopy

ram, AE C656948 -benzamide and AE C656948 - olefines were measured in the milk and meat of dairy cattle. In the cattle study, the levels of benzamide metabolite were significantly higher than the parent in many samples. Therefore, ROCKS recommends fluopy ram + AE C656948 -benzamide for tolerance enforcement in ruminant and poultry commodities ; fluopy ram + AE C656948 -benzamide + AE C656948 - 7 - hydroxy fluopy ram + AE C656948 E - and Z - olefines fo r risk assessments in ruminant commodities; and fluopy ram + AE C656948 -benzamide + AE C656948 E - and Z olefines for risk assessment in poultry . EU/Canada The US, EU, and Canada are in agreement on parent fluopy ram + AE C656948 -benzamide for purposes of to lerance enforcement in livestock. The US, EU , and Canada are also in agreement regarding which compounds to include for risk asse ss ment of poultry commodities. However, consistent with their decisions for plants, the EU has proposed the inclusion of the conjugated metabolites, AE C656948 - 7 - OH - GA and AE C656948 - 8 - OH - GA , for risk assessments in ruminants. Attachment s: Chemical Names and Structures Attachment 1

– Plant and Livestock Metabolites and Degradates Attachment 2

– Drinking Water Degradates

### Page 6 of 14 Ta ble 2. Summary

of Metabolites and Degradates to be included in the Risk Assessment and Tolerance Expressions. Matrix US EU Canada RA TOL RA TOL RA TOL Plants Primary Crop Fluopyram (Fluopyram + benzamide for legumes and oil seed crops) Fluopyram Fluop yram + benzamide (M25) + 7 - OH - fluopyram (M08) + 7 - OH - Glc (M11) + 7 - OH - Glc MA(M12) Fluopyram Fluopyram + (Fluopyram + benzamide for legumes and oil seed crops) Fluopyram

Rotational Crop Fluopyram

(Fluopyram + benzamide for legumes and oil seed crops) Fluopy ram Fluopyram +

benzamide (M25) + 7 - OH - fluopyram (M08) + 7 - OH - Glc (M11) + 7 - OH - Glc MA(M12) Fluopyram Fluopyram (Fluopyram + benzamide for legumes and oil seed crops) Fluopyram

Livestock Ruminant Fluopyram + benzamide + 7 - OH fluopyram + olefins (E, Z) F luopyram +

benzamide Fluopyram +

benzamide + 7 - OH fluopyram (M08)+ olefins (E, Z) + 7 - OH - CA(M09) + 7 - OH - GA (M20b) Fluopyram +

benzamide Fluopyram +

benzamide + 7 - OH fluopyram + olefins (E, Z) Fluopyram +

benzamide Poultry Fluopyram +

benzamide + olefins (E, Z) Fluopyram +

benzamide Fluopyram +

benzamide + olefins (E, Z) Fluopyram +

benzamide Fluopyram +

benzamide + olefins (E, Z) Fluopyram +

benzamide Drinking Water Fluopyram Not Applicable Not Applicable Not Applicable Not Applicable Not Applicable l

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Attachment 1: Plant and Livestock Metabolites and Degradates C ommon and/or Code Name Chemical Name Structure fluopyram; AE C656948 N - [2 - [3 - chloro - 5 - (trifluoromethyl) - 2 - pyridinyl]ethyl] - 2 - (trifluoromethyl)benzamide N H O N

Cl C F 3 C F 3

AE C656948 -N - oxide; M 01 N - {2 - [3 - chloro - 1 - oxido - 5 - (trifluoromethyl) pyridin - 2 - yl]ethyl} - 2 - (trifluoromethyl)benzamide N H O N +

Cl C F 3 C F 3 O AE C656948 - E - olefine; BCS AA10627; M02 N - {(E) - 2 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] ethenyl} - 2 - (trifluoromethyl)benzami de N H O N

Cl C F 3 C F 3

AE C656 948 - Z - olefine; BCS AA10650; M03 N - {(Z) - 2 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] ethenyl} - 2 - (trifluoromethyl)benzamide N H O

N Cl

C F 3 C F 3

AE C656 948 -phenol - glc; M06 N O N

Cl C F 3 C F 3

O H O H O H O O H O

AE C656948 -phenol - GA ; M07 N H O N

Cl C F 3 C F 3

O O H O H O H O O H O

AE C656948 - 7 -hydroxy; BCS AA10065; M08 N - {2 - [3 - chloro - 5 - (trifluoromethyl)pyridin 2 - yl] - 2 - hydroxyethyl} - 2 - (trifluoromethyl) benzamide O H N H O N

Cl C F 3 C F 3

AE C656948 - 7 - OH - GA; M09 1 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] - 2 - {[2 - (trifluoromethyl) - benzoyl]amino}ethyl beta -D glucopyranos iduronic acid O O H O H O H O O H N H O N

Cl C F 3 C F 3

O

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C ommon and/or Code Name Chemical Name Structure AE C656948 - 7 - OH - SA; M10 1 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] - 2 - ({[2 - (trifluoromethyl)phenyl] - carbonyl}amino)ethyl hydrogen sulfate O N H O N

Cl C F 3 C F 3

S O

O O H

AE C 656948 - 7 -hydroxy - glc; M11 N - [2 - [3 - chloro - 5 - (trifluoromethyl)pyridin 2 - yl] - 2 - (beta -D - glucopyranosyloxy)ethyl] - 2 - (trifluoromethyl) benzamide O O H O H O H O O H N H O N

Cl C F 3 C F 3

AE C656948 - 7 -hydroxy - glc - MA; M12 1 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] - 2 - {[2 - (trifluoromethyl) - benzoyl]amino}ethyl 6 - O - (carboxyacetyl) -beta -D - glucopyranoside O O H O H O H O N H O N

Cl C F 3 C F 3

O O O H O AE C656948 - 8 -hydroxy; M18 N - {2 - [3 - chl oro - 5 - (trifluoromethyl)pyridin 2 - yl] - 1 - hydroxyethyl} - 2 - (trifluoromethyl) benzamide N H O N

Cl C F 3 C F 3 O H

AE C656948 - 8 -hydroxy - glc - MA; M19 1 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] - 1 - {[2 - (trifluoromethyl) - benzoyl]amino}ethyl 6 - O - (carboxyacetyl) -beta -D - glucopyranoside O O H O H O H O O O O H O

N H O N

Cl C F 3 C F 3

AE C656948 - 8 - OH - GA; M20 2 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] - 1 - {[2 - (trifluoromethyl) - benzoyl]amino}ethyl beta -D glucopyranosiduronic acid O H O H O H O O H

O O

N H O N

Cl C F 3 C F 3

AE C656948 - di - OH - GA; M21 O H O H N H O N

Cl C F 3 C F 3

O H

O H O H O O H O O

- H 2 O AE C656948 -hydroxy - glyc - gluc ; M22 N H O N

Cl C F 3 C F 3

glyc = glycoside

gluc = glucuronic acid glyc - gluc

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C ommon and/or Code Name Chemical Name Structure AE C656948 -benzamid e; AE F148815; BCS - AA 10014; M25 2 - (trifluoromethyl) -benzamide N H 2 O C F 3

AE C656948 -benzamide - SA ; M31 N H 2 O C F 3 O S O O H O

AE C656948 -benzoic acid; M33 2 - (trifluoromethyl) -benzoic acid O H O C F 3

AE C656948 -hydroxyethyl - glc; M35 2 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl]ethyl beta -D - glucopyranoside O H O H O H O O H O N Cl C F 3

AE C 656948 -hydroxyethyl - di - glc; M36 2 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl]ethyl 6 - O -beta -D - glucopyranosyl -beta D - glucopyranoside O O H O H O H O

O H

O

O H O H O H O N

Cl C F 3 AE C656948 -hydroxyethyl - GA; M37 2 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl]ethyl beta -D - gluco py

ranosiduronic acid O O H O H O H O O H

N

Cl O C F 3 AE C656948 -pyridyl - acetic acid (PAA); M40 [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl]acetic acid N Cl C F 3 O H O AE C656948 - PAA - glycoside ; M42 N Cl C F 3 O O g l yc

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C ommon and/or Code Name Chemical Name Structure AE C656948 -pyridyl - carboxylic acid (PCA); M43 3 - chloro - 5 - (trifluoromethyl)pyridine - 2 - carboxylic ac id O H N Cl C F 3

O AE C656948 - methyl - sulfoxide; M45 3 - (methylsulfinyl) - 5 - (trifluoromethyl) pyridine - 2 - carboxylic acid C F 3 N S

O O H O C H 3

AE C656948 - enol - GA; M04 O O H O H O H O O H O N O N

Cl C F 3 C F 3

AE C656948 - 7 - OH -phenol; M13 N H O N

Cl C F 3 C F 3 O H O H AE C656948 - 7 - OH -phenol - GA; M14 N H O N

Cl C F 3 C F 3 O H O O H O H O H O O H O

AE C656948 - 7 - OH -phenol - SA; M 15 N H O N

Cl C F 3 C F 3 O H O S O O H O AE C656948 - 7 - OH - methyl - sulfone; M16 O H N H O N

Cl C F 3 C F 3

S O 2 C H 3 AE C656948 - 7 - OH - hydroxy - phenol SA; M17 N H O N

Cl C F 3 C F 3 O H O S O O H O

O H AE C656948 - methoxy - di - OH - GA; M23 N H O N

Cl C F 3 C F 3 C H 3 O O H glucuronic acid AE C656948 -benzoyl - serine; M24 N - acetyl - O - [2 - (trifluoromethyl)benzoyl] - serine O O N

H C H 3 C F 3

O

H O O

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C ommon and/or Code Name Chemical Name Structure AE C656948 -hydroxy -benzamide; M26 N H 2 O C F 3

O H AE C656948 -benzamide - OH - GA; M27 N H 2 O C F 3

O H O H O H O O H O O

AE C 656948 -benzamide - cysteine ; M28 O C F 3 N H 2 S N H C H 3 O H O O AE C 656948 - BA - methyl - sulfoxide; M29 N H 2 O C F 3

S O C H 3

AE C656948 - BA - methyl - sulfone; M30 N H 2 O C F 3

S O O C H 3 AE C656948 -benzamide -N,O - GA; M32 1 - O - {[2 - (trifluoromethyl) - benzoyl]amino} -beta -D - glucopyranuronic acid O O H O H O H O O H N H

O O C F 3

AE C656948 - ethyl - diol; M38 1 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] ethane - 1,2 - diol O H N Cl C F 3

O H

AE C656948 - ethyl - diol - GA; M39 O H N Cl C F 3

O H O H O H O H O O H O O - H 2 O

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C ommon and/or Code Name Chemical Name Structure AE C656948 -hydroxy - PAA; M41 [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl](hydroxy)acetic acid O H O O H N Cl C F 3

AE C656 948 -pyridyl - methyl - cystein; M44 N - acetyl - S- {[3 - chloro - 5 - (trifluoromethyl) pyridin - 2 - yl]methyl}cysteine N H C H 3 O H

O O N C F 3

Cl S

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Attachment 2: Fluopy

ram and Its Major Environmental Degradates. **Code Name/ Synonym**  **Chemical Name Chemical Structure**  **PARENT** fluopyram; AE C656948 **CAS:** N - [2 - [3 - chloro - 5 - (trifluoromethyl) - 2 - pyridinyl]ethyl] - 2 - (trifluoromethyl)benzamide **CAS -**  **no: Formula:**  C 17 H 17 ClF 4N4 O 5 S **MW :**  500.86 g/mol N H O N

Cl C F 3 C F 3

**ME TABOLITES**  AE C656948 - 7 -hydroxy; BCS - AA10065; M08 N - {2 - [3 - chloro - 5 - (trifluoromethyl)pyridin - 2 - yl] - 2 -hydroxyethyl} - 2 - (trifluoromethyl)benzamide **Formula:** C 16 H 11 ClF 6N 2 O 2 **MW :**  412.72 g/mol O H N H O N

Cl C F 3 C F 3

Lactame 2,9 -bis(trifluromethyl) - 6,7 - dihydropyridol[2,3 - e][2]benza zocin - 8(5 H

) - one **Formula:** C 16 H 10 F 6N 2 O **MW :**  360.26 g/mol N C F 3 N H O F 3 C

### Page 14 of 14 AE C656948 -benzamide; AE F148815; BCS AA10014; M25 2 - (trifluoromethyl)benzamide **Formula:** C 8 H 6 F 3 NO **MW :**  189.14 g/mol 

# N H 2 

# O C F 3

AE C656948 -pyridyl carboxylic acid (PCA); M43 3 - chloro - 5 - (trifluoromethyl)pyridine - 2 - carboxylic acid **Formula:** C 7 H 3 ClF 3 NO 2 **MW :**  225.26 g/mol 

### O H N Cl C F 3



### O AE C656948 - methyl sulfoxide; M45 3 - (methylsulfinyl) - 5 - (trifluoromethyl) pyridine - 2 - carboxylic acid **Formula:** C 8 H 6 F 3 NO 3 S **MW :**  253.20 g/mol 

### C F 3 

### N S

O O H O C H 3