Page 1 of 50 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES February 1, 2006 SUBJECT: Imazalil. Reregistration List B Chemical Number 111901; Case No. 2325 Revised Product and Residue Chemistry Chapters for the HED Risk Assessment. No MRID No. DP Barcode D294373.

FROM: Thurston Morton, Chemist Reregistration Branch 4 Health Effects Division ( 7509C)

and David E. Hrdy, Biologist Reregistration Branch 4 Health Effects Division ( 7509C)

THRU: Susan V. Hummel, Branch Senior Scientist Reregistration Branch 4 Health Effects Division ( 7509C)

TO: Kendra Tyler Special Review Branch Special Review & Reregistration Division ( 7508C)

Attached is the revised Residue Chemistry Chapter for the reregistration eligibility document ( RED). This revision corrects the previous Residue Chemistry Chapter by reassessing the horse, fat tolerance at 0.01 ppm and correcting the commodity definitions. This was originally completed by Dynamac Corporation under supervision of HED. It has undergone secondary review in the branch and has been revised to reflect current Agency policies. Page 2 of 50 Outstanding data required at the present time include: GLN 830.7050, UV/ Visible Absorption, GLN 860.1340, analytical method for imazalil in livestock tissue and , GLN 860.1360, multiresidue method data for imazalil metabolites, GLN 860.1480, residue data resulting from a fumigation application to poultry houses.

cc : Chem F, Chron F, Morton, Hrdy RDI: SVH: 2/ 1/ 06 TM, Thurston Morton, Rm. 816D CM2, 305 6691, mail code 7509C Page 3 of 50 Cl Cl O N N CH 2 IMAZALIL REREGISTRATION ELIGIBILITY DECISION:

PRODUCT CHEMISTRY CONSIDERATIONS PC Code 111901; Case No. 2325 DESCRIPTION OF CHEMICAL Imazalil [ 1( 2( 2,4 dichlorophenyl) 2( 2 propenyloxy) ethyl) 1H imidazole] is a systemic fungicide used for postharvest treatment of citrus fruits and bananas ( foreign use) and for seed treatment of barley and wheat prior to planting.

Empirical Formula: C 14 H 14 Cl 2 N 2 O Molecular Weight: 297.17 CAS Registry No.: 73790 28 0 PC Code: 111901 IDENTIFICATION OF ACTIVE INGREDIENT Imazalil is a yellow or brown crystalline solid with a melting point of 50 C, density of 1.348 x 103 kg/ m3, octanol/ water partition coefficient ( log P ow ) of 3.82, and vapor pressure of 3.6 x 10 4 Pa at 25 C. Imazalil is slightly soluble in water ( 293 ppm at 20 C), and is very soluble in methanol, ethanol, 2 propanol, dimethylbenzene, acetonitrile, N, N dimethylformamide, tetrahydrofuran, 1 methyl 2 pyrrolidinone, 1,2 ethanediol, 1,2 propanediol, and glacial acetic acid (> 500 g/ L at 25 C).

MANUFACTURING USE PRODUCTS A search of the Reference Files System ( REFS) conducted 1/ 22/ 02 identified two imazalil manufacturing use products ( MP) registered under PC Code 111901: the Janssen Pharmaceutic 97.5% technical ( T; EPA Reg. No. 43813 2) and the Makhteshim Agan of North America Inc. ( MANA) 98.5% technical ( T; EPA Reg. No. 11678 55). Both technicals are subject to a reregistration eligibility decision. Page 4 of 50 REGULATORY BACKGROUND The Imazalil Phase 4 Review dated 10/ 19/ 90 by S. Funk determined that additional data were required concerning all product chemistry guidelines except OPPTS 830.1550 ( product identity) for imazalil; the product chemistry data submission for OPPTS 830.1550 was determined to be acceptable for Phase 5 review. Subsequent to the Phase 4 Review, all new product chemistry data have been submitted in support of the reregistration of imazalil.

The current status of the product chemistry data requirements for the imazalil T/ TGAI is presented in the attached data summary table. Refer to this table for a listing of the outstanding product chemistry data requirements.

CONCLUSIONS All pertinent product chemistry data requirements have been satisfied for the Janssen 97.5% T/ TGAI, except that additional data are required concerning UV/ visible absorption ( OPPTS 830.7050). Provided that the registrant submits the data required in the attached data summary table for the imazalil T/ TGAI, and either certifies that the suppliers of beginning materials and the manufacturing process have not changed since the last comprehensive product chemistry review or submits a complete updated product chemistry data package, HED has no objections to the reregistration of imazalil with respect to product chemistry data requirements.

All pertinent product chemistry data requirements have been satisfied for the Makhteshim Agan of North America Inc. ( MANA) 98.5% technical T/ TGAI, except that additional data are required concerning UV/ visible absorption ( OPPTS 830.7050). Provided that the registrant submits the data required in the attached data summary table for the imazalil T/ TGAI, and either certifies that the suppliers of beginning materials and the manufacturing process have not changed since the last comprehensive product chemistry review or submits a complete updated product chemistry data package, HED has no objections to the reregistration of imazalil with respect to product chemistry data requirements. Page 5 of 50 AGENCY MEMORANDA CITED IN THIS DOCUMENT CBRS No( s): 6098 Subject: Dioxin Review for Imazalil From: S. Funk To: Dated: 2/ 23/ 90 MRID( s): 40478201 CBRS No( s): 7014 Subject: Product Chemistry Data Review for Technical Imazalil to Determine the Potential for Halogenated Dibenzo p Dioxin/ Dibenzofuran Formation. Additional Data. I. D. No. 43813 1. Rereg Case No. 2325. From: S. Funk To: K. Davis Dated: 11/ 16/ 90 MRID( s): 41595901 CBRS No( s): 7117 DP Barcode( s): D156801 Subject: Supplement to Phase 3 Registrant Response and Reply to Manufacturing DCI to Evaluate the Potential for Halogenated Dibenzo p dioxin/ Dibenzofuran Formation. Reregistration Case No. 2325 From: S. Funk To: K. Davis Dated: 5/ 10/ 91 MRID( s): 41545101 CBRS No( s): 10342 DP Barcode( s): D181284 Subject: Imazalil. Product Chemistry Data and Stability of 3H Imazalil. From: L. Cheng To: K. Davis Dated: 9/ 25/ 92 MRID( s): 40478201 CBRS No( s): 8845 DP Barcode( s): D170516 Subject: Reregistration of Imazalil. Janssen Pharmaceutica 97.5% T ( EPA Reg. No. 43813 2). From: P. Deschamp To: J. Ellenberger/ B. Briscoe Dated: 10/ 8/ 92 MRID( s): 41606106 and 41889801 Page 6 of 50 CBRS No( s): 11365 DP Barcode( s): D187938 Subject: Reregistration of Imazalil. Janssen Pharmaceutica Product Chemistry Data for their 97.5% T ( EPA Reg. No. 43813 2). List B Case No. 2325. Chemical No. 111901. From: P. Deschamp To: K. Depukat Dated: 3/ 18/ 93 MRID( s): None CBRS No( s): 12010 DP Barcode( s): D192069 Subject: Reregistration of Imazalil. Janssen Pharmaceutical Product Chemistry Data for the 97.5% Technical ( EPA Reg. No. 43813 2). List B Case No. 2325. From: S. Funk To: K. Davis/ K. Depukat Dated: 8/ 12/ 93 MRID( s): 42793800 42793802, and 42403101 CBRS No( s): 12920 DP Barcode( s): D197279 Subject: Imazalil. Case No. 2325. Janssen Pharmaceutical Product Chemistry Data § 61 1 for the 97.5% Technical ( EPA Reg. No. 43813 2). From: L. Cheng To: K. Depukat Dated: 3/ 8/ 94 MRID( s): 43016801 CBRS No( s): 13708 DP Barcode( s): D203270 Subject: Imazalil Reregistration. Janssen's 5/ 5/ 94 Response [ 61 2( b) Data for Product 43813 2] to Agency 4/ 6/ 94 Letter. From: K. Dockter To: K. Davis/ K. Depukat Dated: 7/ 18/ 95 MRID( s): 43223001 DP Barcode( s): D231609 Subject: Product Chemistry Review of Imazalil Technical. From: A. Smith To: J. Stone Dated: 4/ 10/ 97 MRID( s): 44107201 11, 44107218, 44134401, 44134402, 44145401 Page 7 of 50 PRODUCT CHEMISTRY CITATIONS Bibliographic citations include only MRIDs containing data which fulfill data requirements.

References ( cited):

40478201 Goodwine, W. ( 1987) Product Identity and Composition [ Imazalil]: IMZ PC 61. Unpublished study prepared by Janssen Pharmaceutica. 334 p.

41545101 Goodwine, W. ( 1987) Product Identity and Composition: Imazalil: Lab Project Number: IMZ PC 61. Unpublished study prepared by Janssen Pharmaceutica. 8 p.

41595901 Janssen Pharmaceutica ( 1990) 1, 3 Dichlorobenzene Manufacturing Process and Impurities: Supplement: Lab Project Number: IMZ PC 61. Unpublished study. 8 p.

41606106 Crauwils, R.; Dingenen, J. ( 1990) Physical and Chemical Characteristics of Imazalil ( R23979): Fungaflor Technical: Lab Project Number: IMZ PC 63 ( 1). Unpublished study prepared by Janssen Pharmaceutica. 101 p.

41889801 Niusmans, S.; Lauwers, W.; Smet, M. ( 1991) Analysis and Certification of Product Ingredients Fungaflor Technical: Lab Project Number: IMZ PC 62. Unpublished study prepared by Janssen Research Foundation. 75 p.

42403101 Goodwine, W. ( 1987) Supplement to MRID 40478201: Product Identity and Composition, Guideline Series 61: Description of Beginning Materials and Manufacturing Process. Unpublished study prepared by Janssen Pharmaceutica. 7 p.

42793801 Nijsmans, G.; Lauwers, W.; DeSmet, M. ( 1993) Analysis and Certification of Product Ingredients Fungaflor Technical: Lab Project Number: IMZ PC 62: ST BO GC 930323: ST QA 93 8. Unpublished study prepared by Janssen Pharmaceutica. 72 p.

42793802 Crauwels, R.; Van Dingenen, J. ( 1993) Physical and Chemical Characteristics of Imazalil Fungaflor Technical: Lab Project Number: IMZ PC 63: 930409: PC CHAR 93 17. Unpublished study prepared by Janssen Pharmaceutica. 21 p. 43016801 Janssen ( 1993) Supplement to Primary MRID 40478201 and Secondary MRID 41889801: Product Identity and Composition Imazalil: Lab Project Number: IMZ PC 61. Unpublished study. 13 p.

43016801 Janssen ( 1993) Supplement to Primary MRID 40478201 and Secondary MRID 41889801: Product Identity and Composition Imazalil: Lab Project Number: IMZ PC 61. Unpublished study. 13 p.

43223001 Goodwine, W. ( 1994) Product Identity & Composition: Discussion of Impurities: Imazalil: Supplement: Lab Project Number: IMZ PC 61. Unpublished study prepared by Janssen Pharmaceutica. 7 p.

44107201 Morrisey, M. ( 1995) Determination of Identity, Purity, and Stability for Standards Used for Impurity Analysis of Magnate ( Technical): Study Number: HWI6413 115. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107202Registration Department, Makhteshim Chemical Works, LTD. ( 1996) Magnate ( Imazalil Technical) Product Chemistry Data: Study Number: R9236. Unpublished study Submitted by Makhteshim Chemical Works, Ltd. Page 8 of 50 44107203 Morrisey, M. ( 1995) Analysis of Magnate ( Imazalil) Technical and its Impurities: Study Number: HWI6413 116. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107204 Morrisey, M. ( 1996) Color Determination of Imazalil TGAI: Study Number: HWI6413 118. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107205 Morrisey, M. ( 1996) Physical State Determination of Imazalil TGAI: Study Number: HWI6413 119. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107206 Morrisey, M. ( 1996) Odor Determination of Imazalil TGAI: Study Number: HWI6413 120. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107207 Morrisey, M. ( 1995) Series 63 Product Chemistry Determinations of Magnate ( Imazalil) Technical ( Melting Point): Study Number: HWI6413 117A. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107208 Morrisey, M. ( 1995) Series 63 Product Chemistry Determinations of Magnate ( Imazalil) Technical ( Relative Density): Study Number: HWI6413 117B. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107209 Morrisey, M. ( 1995) Series 63 Product Chemistry Determinations of Magnate ( Imazalil) Technical ( Solubility in Organic Solvents): Study Number: HWI6413 117C. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107210 Teeter, D. ( 1996) Dissociation Constant Determinations of Imazalil TGAI: Study Number: HWI6413 123. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107211 Morrisey, M. ( 1996) Octanol/ Water Partition Coefficient Determination of Imazalil TGAI: Study Number: HWI6413 121. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44107218 Hogg, A. ( 1991) Imazalil ( Batch No: 1471 24/ 2) Determination of Vapor Pressure: Study Number: 306/ 59. Unpublished study Submitted by Makhteshim Chemical Works, Ltd.

44134401 August, J. ( 1996) pH Determination of Magnate ( Imazalil) Technical: Study Number: CHW 6413 142. Unpublished study Submitted by Makhteshim Agan of North America, Inc.

44134402 August, J. ( 1996) Stability Determination of Magnate ( Imazalil) Technical: Study Number: CHW 6413 142. Unpublished study Submitted by Makhteshim Agan of North America, Inc. Page 9 of 50 Case No. 2325 Chemical No. 111901 Case Name: Imazalil Registrant: Janssen Pharmaceutics Product( s): 97.5% T ( EPA Reg. No. 43813 2)

PRODUCT CHEMISTRY DATA SUMMARY Guideline Number Requirement Are Data Requirements Fulfilled? 1 MRID Number 2 830.1550 Product identity and composition Y 40478201, 42793800 3, 42793802 3, 43016801 4 830.1600 Description of materials used to produce the product Y 40478201, 41595901 5, 41545101 6, 42403101 3 830.1620 Description of production process Y 40478201, 41595901 5, 41545101 6, 42403101 3 830.1670 Discussion of formation of impurities Y 40478201, 43223001 7 830.1700 Preliminary analysis Y 41889801 830.1750 Certified limits Y 41889801, Letter 2/ 9/ 93 8, 42793800 3 830.1800 Enforcement analytical method Y 41889801, Letter 2/ 9/ 93 8, 42793801 3 830.6302 Color Y 41606106 830.6303 Physical state Y 41606106 830.6304 Odor Y 41606106 830.6313 Stability to normal and elevated temperatures, metals, and metal ions Y 41606106, Letter 2/ 9/ 93 8, 42793802 3 830.7000 pH Y 41606106 830.7050 UV/ Visible absorption N 9 830.7200 Melting point/ melting range Y 41606106 830.7220 Boiling point/ boiling range N/ A 10 830.7300 Density/ relative density/ bulk density Y 41606106 830.7370 Dissociation constants in water Y 41606106 830.7550 Partition coefficient ( n octanol/ water), shake flask method Y 41606106 830.7840 Water solubility: column elution method; shake flask method Y 41606106, Letter 2/ 9/ 93 8, 42793802 3 830.7950 Vapor pressure Y 41606106 1 Y = Yes; N = No; N/ A = Not Applicable.

2 The bolded reference was evaluated in the Imazalil Phase 4 Review, 10/ 19/ 90, S. Funk and was subsequently reviewed under CBRS No. 6098, 2/ 23/ 90, S. Funk, and CBRS No. 10342, D181384, 9/ 25/ 92 L. Cheng ( for OPPTS 830.1600 and 1620 only); underlined references were reviewed under CBRS No. 8845, D170516, 10/ 8/ 92, P. Deschamp; and all other references were reviewed as noted. Page 10 of 50 3 CBRS No. 12010, D192069, 8/ 12/ 93, S. Funk.

4 CBRS No. 12920, D197279, 3/ 8/ 94, L. Cheng.

5 CBRS No. 7014, 11/ 16/ 90, S. Funk.

6 CBRS No. 7117, D156801, 5/ 10/ 91, S. Funk.

7 CBRS No. 13708, D203270, 7/ 18/ 95, K. Dockter.

8 CBRS No. 11365, D187938, 3/ 18/ 93, P. Deschamp.

9 The OPPTS Series 830, Product Properties Test Guidelines require data pertaining to UV/ visible absorption for the PAI.

10 Data are not required because the TGAI is a solid at room temperature. Page 11 of 50 Case No. 2325 Chemical No. 111901 Case Name: Imazalil Registrant: Makhteshim Agan of North America Inc. ( MANA) Product( s): 98.5% T ( EPA Reg. No. 11678 55)

PRODUCT CHEMISTRY DATA SUMMARY Guideline Number Requirement Are Data Requirements Fulfilled? 1 MRID Number 830.1550 Product identity and composition Y 4410702 2 830.1600 Description of materials used to produce the product Y 4410702 2 830.1620 Description of production process Y 4410702 2 830.1670 Discussion of formation of impurities Y 4410702 2 830.1700 Preliminary analysis Y 4410703 2 830.1750 Certified limits Y 4410703 2 830.1800 Enforcement analytical method Y 4410703 2 830.6302 Color Y 4410704 2 830.6303 Physical state Y 44107205 2 830.6304 Odor Y 44107206 2 830.6313 Stability to normal and elevated temperatures, metals, and metal ions Y 44134402 2 830.7000 pH Y 44134401 2 830.7050 UV/ Visible absorption N3 830.7200 Melting point/ melting range Y 44107207 2 830.7220 Boiling point/ boiling range N/ A 4 830.7300 Density/ relative density/ bulk density Y 44107208 2 830.7370 Dissociation constants in water Y 44107210 2 830.7550 Partition coefficient ( n octanol/ water), shake flask method Y 44107211 2 830.7840 Water solubility: column elution method; shake flask method Y 44145401 2 830.7950 Vapor pressure Y 44107218 2 1 Y = Yes; N = No; N/ A = Not Applicable. 2 D231609, 4/ 10/ 97, A. Smith. 3 The OPPTS Series 830, Product Properties Test Guidelines require data pertaining to UV/ visible absorption for the PAI. 4 Data are not required because the TGAI is a solid at room temperature. Page 12 of 50 IMAZALIL REREGISTRATION ELIGIBILITY DECISION RESIDUE CHEMISTRY CONSIDERATIONS PC Code No. 111901; Case 2325 TABLE OF CONTENTS page INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 REGULATORY BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 SUMMARY OF SCIENCE FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 GLN 860.1200: Directions for Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 GLN 860.1300: Nature of the Residue  Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 GLN 860.1300: Nature of the Residue  Livestock . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 GLN 860.1340: Residue Analytical Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 GLN 860.1360: Multiresidue Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 GLN 860.1380: Storage Stability Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 GLN 860.1400: Water, Fish, and Irrigated Crops . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 GLN 860.1460: Food Handling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 GLN 860.1480: Meat, Milk, Poultry, Eggs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 GLN 860.1500: Crop Field Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 GLN 860.1520: Processed Food/ Feed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 GLN 860.1850 and 860.1900: Confined/ Field Accumulation in Rotational Crops . . . . 27 TOLERANCE REASSESSMENT SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Tolerances Established Under 40 CFR § 180.413 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Tolerances To Be Proposed Under 40 CFR § 180.413 . . . . . . . . . . . . . . . . . . . . . . . . . 34 Tolerances Established Under 40 CFR § 180.413( b) . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Pending Tolerance Petitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 CODEX HARMONIZATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 AGENCY MEMORANDA RELEVANT TO REREGISTRATION . . . . . . . . . . . . . . . . . . . . 38 MASTER RECORD IDENTIFICATION NUMBERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Page 13 of 50 IMAZALIL REREGISTRATION ELIGIBILITY DECISION RESIDUE CHEMISTRY CONSIDERATIONS PC Code No. 111901; Case 2325 INTRODUCTION Imazalil [ 1( 2( 2,4 dichlorophenyl) 2( 2 propenyloxy) ethyl) 1H imidazole] is a systemic fungicide registered for postharvest treatment of citrus fruits and bananas ( foreign use) and for seed treatment of barley and wheat prior to planting. Imazalil's end use products are marketed by Janssen Pharmaceutica in the United States under the trade names Fecundal ® and Fungaflor ® , and by Makhteshim Agan of North America Inc. as Magnate ® , all of which are emulsifiable concentrate ( EC) formulations. Fungaflor ® and Magnate ® are also formulated as a soluble powder ( SP) for use on bananas imported into the United States from Colombia, Costa Rica, Ecuador, Guatemala, Honduras, and Mexico. The reregistration of imazalil is being supported by Janssen Pharmaceutica, and by Makhteshim Agan of North America Inc. ( MANA).

REGULATORY BACKGROUND The Imazalil Phase 4 Review of 10/ 19/ 90 and the subsequent Imazalil Data Call In ( DCI) Notice of 12/ 31/ 90 summarized the status of available residue chemistry data for the reregistration of imazalil. The Phase 4 Review identified several data deficiencies including plant and livestock metabolism, residue analytical methods, storage stability, and magnitude of the residue in plants and livestock. Several studies have been submitted and evaluated in response to the Imazalil DCI. This document presents an overall and up to date Residue Chemistry Science Assessment with respect to the reregistration of imazalil.

The established tolerances for plant commodities [ 40 CFR § 180.413( a)] are expressed in terms of the combined residues of imazalil and its metabolite R014821 [ 1( 2,4 dichlorophenyl) 2( 1Himidazole 1 yl) 1 ethanol]. Plant commodity tolerances range from 0.05 ppm ( barley grain, cottonseed, and wheat grain) to 10 ppm ( citrus fruits). Tolerances are also established for the combined residues of imazalil and R014821 in citrus oil and citrus dried pulp, each at 25 ppm. The established tolerances for livestock commodities [ 40 CFR § 180.413( b)] are expressed in terms of the combined residues of imazalil and its metabolites R014821 and R042243 [ 3[ 1( 2,4 dichlorophenyl) 2( 1H imidazole 1 yl) ethoxyl] 1,2 propanediol]. Animal commodity tolerances range from 0.01 ppm ( milk and fat, meat, and meat byproducts of cattle, goats, hogs, horses, and sheep) to 0.50 ppm ( liver of cattle, goats, hogs, horses, and sheep). No tolerances are established for eggs or poultry tissues. Adequate GC/ ECD methods are listed in the Pesticide Analytical Manual ( PAM), Vol. II for enforcement of imazalil tolerances, as currently expressed. Codex Page 14 of 50 MRLs for residues of imazalil in/ on plant commodities are currently defined in terms of imazalil per se, and as such are not compatible with U. S. tolerances.

SUMMARY OF SCIENCE FINDINGS GLN 860.1200: Directions for Use According to a REFS search, conducted on 1/ 22/ 2002, there are three active end use products ( see Table A1) registered to Janssen Pharmaceutica and Makhteshim Agan of North America Inc. ( MANA) which contain the active ingredient imazalil which is registered for use on domestically grown food/ feed crops ( i. e., citrus fruits, barley, and wheat). There are additional imazalil enduse products registered for use on imported bananas grown in Costa Rica, Colombia, Ecuador, Guatemala, Honduras, and Mexico. HED has examined translated imazalil foreign labels ( Fungaflor ® 75 SP labels) supplied by Janssen Pharmaceutica. The foreign uses were found to be adequate for the purpose of assessing whether or not the submitted banana field trial data reflect the maximum imazalil residues of concern likely to occur in/ on bananas.

Table A1. Imazalil End Use Products with Food/ Feed Uses Registered to Janssen Pharmaceutica and to Makhteshim Agan of North America Inc.

EPA Reg. No. Label Acceptance Date Formulation Product Name 43813 6 9/ 9/ 85 44.6% ( 4.17 lb/ gal) EC Fungaflor ® 500 EC 43813 14 8/ 7/ 95 9.5% ( 0.84 lb/ gal) EC Fecundal ® 100 EC 66222 20 8/ 23/ 01 44.5% EC Magnate ® 500 EC The above labels specify a re entry interval of 48 hours. There are no rotational crop restrictions specified on the labels. A review of the imazalil labels and supporting residue data suggest those label amendments are required to specify the number of applications for some registered crops. The 9.5% EC ( EPA Reg. No. 43813 14) formulation should be amended to specify a maximum of one seed treatment prior to planting of fields with seed treated barley and wheat. When end use product DCIs are developed ( e. g., at issuance of the RED), RD should require that all end use product labels ( e. g., MAI labels, SLNs, and products subject to the generic data exemption) be amended such that they are consistent with the basic producer labels.

A comprehensive summary of imazalil food/ feed use patterns, based on the product labels registered to Janssen Pharmaceutica and Makhteshim Agan of North America Inc. ( MANA), is presented in Table A2. A tabular summary of the residue chemistry science assessments for the reregistration of imazalil is presented in Table B. The status of reregistration requirements for each guideline topic listed in Table B is based on the use patterns registered by the basic producers, Janssen Pharmaceutica and Makhteshim Agan of North America Inc. ( MANA). This chapter does not include uses registered to other registrants, such as the poultry hatchery use registered to Schering Plough ( EPA Reg. No. 773 55 and 773 56) for which no residue data are available. Page 15 of 50 Table A2. Food/ Feed Use Patterns on EP Labels Subject to Reregistration for Imazalil ( Case 2325).

Site Application Timing Application Type Application Equipment Formulation [ EPA Reg. No.] Maximum Single Application Rate Maximum Number of Applications Per Season Maximum Seasonal Rate Preharvest Interval, Days Use Directions and Limitations Bananas ( Imported)

Post harvest treatment Spray, fog, dip, or drench Fungaflor ® 75 SP ( no U. S. registration) 0.07% of product in water or 525 ppm ai 1 ( Implied) 525 ppm ai ( Implied) 0 1 The labels recommend that " crowns and fruit need to be wetted carefully and thoroughly."

According to information provided by Janssen Pharmaceutica, spray, fog, dip, or drench application should be made for 3 to 25 seconds.

Barley and Wheat Seed treatment Mechanical slurry or misttype of seed treatment equipment 9.5% ( 0.84 lb/ gal) EC [ 43813 14] 1.5 fl. oz of product/ 100 lbs of seed( cwt)

or 0.01 lb ai/ cwt ( equivalent to 100 ppm; mg ai/ kg seed) Not specified ( NS) NS NS Treated seeds should be adequately dyed, and any dye added to treated seeds must be cleared for use under 40 CFR § 180.1001. Treated seeds should not be used for food, feed, or oil purposes. The grazing or feeding of livestock on treated areas for six weeks after planting is prohibited.

Seed treatment Mechanical slurry or misttype of seed treatment equipment 44.5%

EC [ 66222 20] 0.34 fl. oz of product/ 100 lbs of seed( cwt) Not specified ( NS) NS NS Treated seeds should be adequately dyed, and any dye added to treated seeds must be cleared for use under 40 CFR § 180.1001. Treated seeds should not be used for food, feed, or oil purposes. The grazing or feeding of livestock on treated areas for six weeks after planting is prohibited.

Citrus Fruits Post harvest treatment Dips, wash tanks, and drenches 44.6% ( 4.17 lb/ gal) EC [ 43813 6]

and 44.5%

EC [ 66222 20] 19.2 fl. oz of product/ 100 gal water or 750 ppm ai 2 4000ppm ai Not applicable ( NA) Application should be made in dips, wash tanks,

and drenchers. Length of dip time should not exceed 2 minutes.

Post harvest treatment Wax 25.5 fl. oz of product/ 100 gal water or 1000 ppm ai 2 ( Should not exceed 4000 ppm total) * or*

1 application of 4000ppm in wax 4000ppm ai NA Application should be made to freshly cleaned fruits immediately prior to waxing.

Post harvest treatment Spray brush 25.5 fl. oz of product/ 100 gal water or 1000 ppm ai 2 4000ppm ai NA Application should be made after washing and prior to wax application.

Post harvest treatment Foamer 51.0 fl. oz of product/ 100 gal water or 2000 ppm ai 2 4000ppm ai NA Application should be made as a ready to use foam detergent using a mechanical foamer. Page 16 of 50 Cl Cl O N N CH 2 1 A 0 day PHI has been established for Costa Rica, Guatemala, Honduras, and Mexico; however, pre harvest foliar application of imazalil is not registered for use on bananas at this time.

GLN 860.1300: Nature of the Residue  Plants The reregistration requirements for plant metabolism are fulfilled. Acceptable metabolism studies, reflecting post harvest treatment of imazalil on bananas and oranges as well as seed treatment of imazalil on wheat, were conducted. In all studies, the parent was the predominant residue identified in/ on whole bananas ( 69 82% of the total radioactive residues or TRR), banana pulps ( 68 82% TRR), orange fruits ( 75% TRR), wheat forage ( 24% TRR), and wheat straw ( 17% TRR). The total radioactivity in wheat grain, grown from wheat seeds treated with [ 14C] imazalil at 5x the maximum label rate, was # 0.004 ppm and were not further characterized. The metabolite R014821 was identified as a minor component in/ on banana, whole and pulp (< 5% TRR), orange fruits ( 3 6% TRR), wheat forage ( 8% TRR), and wheat straw ( 4% TRR). Several additional metabolites containing the 2,4 dichlorophenyl group were identified in analyzed commodities but they were detected at relatively low (# 5% TRR) levels. The established tolerances for plant commodities are currently expressed in terms of the combined residues of imazalil and its metabolite R014821. HED concludes that the existing tolerance expression for plant commodities is appropriate for the purpose of reregistration. The chemical structures and chemical names of these regulated compounds are depicted in Figure A.

Figure A. Chemical Names and Structures of Imazalil Residues of Concern in Plant Commodities.

Compound Chemical Structure Common Name: Imazalil Janssen Research Code: R023979 Chemical Name: 1[ 2( 2,4 dichlorophenyl) 2( 2 propenyloxy) ethyl] 1H imidazole Compound Chemical Structure Page 17 of 50 Cl Cl OH N N Common Name: Despropenyl imazalil; ethanol metabolite Metabolite Designation( s): R014821; FK411 Chemical Name: 1[ 2,4 dichlorophenyl) 2( 1H imidazole 1 yl] 1 ethanol GLN 860.1300: Nature of the Residue  Livestock The reregistration requirements for livestock metabolism are fulfilled based on acceptable goat and poultry metabolism studies. These studies indicate that imazalil is extensively metabolized in goat and hen. Only six common metabolites ( out of about twenty identified) were found in both goat and hen. Radioactive residue levels in hen eggs and tissues were < 0.01 ppm ( except 0.028 ppm in liver) when the exaggerated dose was taken into consideration. When normalized to the expected dietary burden, residue levels in the goat ranged from 0.015 ppm to 3.3 ppm in milk and tissues. The results of these studies were presented to the HED Metabolism Committee ( L. Cheng, 8/ 30/ 94), and members of the Committee were asked whether the current tolerance expression for livestock commodities should remain unchanged or whether separate tolerance expressions should be set for ruminant and poultry, and which metabolites should require regulation in each case.

The Committee concluded that ( L. Cheng, 8/ 30/ 94), in the absence of information to the contrary, any metabolite containing the 2,4 dichlorophenyl moiety is of toxicological concern, and must be included in the dietary risk assessment. The Committee also concluded that HED should define a list of metabolites containing this moiety which should be analyzed in livestock feeding studies and explicitly included in the tolerance expression. These metabolites together with the parent compound should serve as marker compounds which should, using the metabolite ratios found in the metabolism studies, be used to determine residue values for dietary risk assessment. It would be assumed that only metabolites identified in the metabolism study as having the 2,4 dichlorophenyl moiety constitute the residue to be included in risk assessment.

The registrant is now pursuing the development of a new GC/ ECD method capable of quantifying residues of imazalil and appropriate marker compounds that account for a high percentage of the total toxic residues in livestock commodities; see " Residue Analytical Methods" section. The marker compounds in milk and ruminant tissues are imazalil, FK772, and FK284 which collectively represent the following percentages of the total toxic residues, as determined by the ruminant metabolism studies: 21% in milk, 72% in muscle, 71% in kidney, 44% in liver, and 33% Page 18 of 50 in fat. The marker compounds in eggs and poultry tissues are imazalil, FK858, and FK326 or FK259 which collectively represent the following percentages of the total toxic residues, as determined by the poultry metabolism studies: 69% in eggs, 45% in liver, 52% in fat, and 100% in muscle. The chemical names and structures of imazalil and marker metabolites in livestock commodities are depicted in Figures B ( milk and ruminant tissues) and C ( eggs and poultry tissues). Page 19 of 50 Cl Cl O N N CH 2 Cl Cl O N H N OH OH O O Cl Cl OH N H N O O Figure B. Chemical Names and Structures of Imazalil and Marker Metabolites In Milk and Ruminant Tissues.

Compound Chemical Structure Common Name: Imazalil Janssen Research Code: R023979 Chemical Name: 1[ 2( 2,4 dichlorophenyl) 2( 2 propenyloxy) ethyl] 1H imidazole Metabolite Designation in Goat Metabolism Study: FK772 Janssen Research Code: R061000 Chemical Name: 3[ 2( 2,4 dichlorophenyl) 2( 2,3 dihydroxypropoxy) ethyl] 2,4 imidazolidinedione Metabolite Designation in Goat Metabolism Study: FK284 Janssen Research Code: R042449 or R043449 Chemical Names: 3( 2( 2,4 dichlorophenyl) 2( hydroxy) 2,4 imidazolidinedione or 1[ 2( 2,4 dichlorophenyl) 2 hydroxyethyl] 2,4 imidazolidinedione Page 20 of 50 ( continued next page) Cl Cl O N N CH 2 Cl Cl O N N OH OH Cl Cl OH NH N H 2 O Figure C. Chemical Names and Structures of Imazalil and Marker Metabolites In Eggs and Poultry Tissues.

Compound Chemical Structure Common Name: Imazalil Janssen Research Code: R023979 Chemical Name: 1[ 2( 2,4 dichlorophenyl) 2( 2 propenyloxy) ethyl] 1H imidazole Metabolite Designation in Poultry Metabolism Study: FK858 Janssen Research Code: R042639 or bishydroxylated imazalil Chemical Names: 3[ 1( 2,4 dichlorophenyl) 2( 1H imidazole 1 yl) ethoxy] 1,2 propanediol or 1[ 2( 2,4 dichlorophenyl) 2( 2,3 dihydroxypropoxy) ethyl] 1H imidazole Metabolite Designation in Poultry Metabolism Study: FK326 Janssen Research Code: R044085 Chemical Name: ( ± )  N[ 2( 2,4 dichlorophenyl) 2 hydroxyethyl] urea Figure C ( continued).

Compound Chemical Structure Page 21 of 50 Cl Cl OH N H 2 Metabolite Designation in Poultry Metabolism Study: FK259 Janssen Research Code: R018238 Chemical Name: 1( 2,4 dichlorophenyl) 2 aminoethanol GLN 860.1340: Residue Analytical Methods An adequate residue analytical method is available for determining the total toxic residues of imazalil in/ on plant commodities but not in livestock commodities.

Method for determination of residues in/ on plant commodities: The Pesticide Analytical Manual ( PAM) Volume II lists a GC/ ECD method, designated as Method I, for the quantitation of residues of imazalil and its metabolite R014821 in/ on bananas, citrus fruits, cottonseed, and small grains. Briefly, residues are extracted from plant samples with heptane: isoamyl alcohol ( 95: 5, v: v), partitioned into 0.1 N H 2 SO 4 , and re extracted from alkaline solution into heptane: isoamyl alcohol ( 95: 5, v: v). The extract is evaporated to dryness, and N, O bis( trimethylsilyl) acetamide is added to convert the metabolite to the trimethylsilyl derivative. Imazalil and the derivatized metabolite are determined separately by GC with electron capture detection from a single injection of the derivative solution. The limits of detection range from 0.01 0.05 ppm, depending on the plant matrix. Plant commodity samples collected from studies pertaining to magnitude of the residues in plant were analyzed for residues of imazalil and its metabolite R014821 using this PAM Volume II method or its modification; in these field studies, method recoveries obtained from concurrent analyses of treated samples were acceptable. This enforcement method has been adequately radio validated using samples from the banana metabolism study.

Methods for determination of residues in livestock commodities: The PAM Volume II also lists a GC/ ECD method, designated as Method II, for the quantitation of residues of imazalil and the metabolites R014821 and R042243. The limits of detection range from 0.01 to 0.05 ppm, depending on the specific matrix. Method II also involves the conversion of the metabolites to the trimethylsilyl derivatives and separate determination of imazalil and the derivatized metabolites. It should be noted that this method is not a precise measure of the total toxic imazalil residues in meat, milk, poultry, and eggs, as determined by the results of livestock metabolism studies. Page 22 of 50 Because of the recommended changes in tolerance expression, a new enforcement method capable of determining imazalil and any metabolite containing the 2,4 dichlorophenyl group in livestock commodities is required. To accomplish this, HED suggested that the registrant develop an enforcement method capable of measuring all compounds containing the 2,4 dichlorophenyl group using a method which converts these residues to a common moiety. Alternatively, the registrant was given the option of developing an enforcement method for a set of marker compounds that account for a high percentage of the total toxic residues in ruminant and poultry.

Attempts by the registrant to develop a common moiety method, based on the oxidation of imazalil and five of its metabolites to 2,4 dichlorobenzoic acid, were unsuccessful due to extraction inefficiency and method recovery variability. The registrant is now pursuing the development of a new GC/ ECD method capable of quantitating residues of imazalil and the appropriate marker metabolites. Preliminary validation data indicate that the proposed GC/ ECD method is adequate for collecting data on residues of imazalil, FK772, and FK284 in milk and ruminant tissues, provided fortified control samples are analyzed concurrently with each set of treated samples to assure that acceptable method recoveries are being achieved for each analysis; independent laboratory validation must be conducted prior to the method being sent to the Agency for validation as an enforcement method. This method was used in the analysis of samples collected from a recently reviewed ruminant feeding study.

For the purpose of reregistration, the registrant must continue to develop/ validate enforcement method( s) for a set of marker compounds that account for a high percentage of the total toxic residues in ruminant and poultry. HED will correct residues to account for the total toxic residue for the purpose of tolerance reassessment as well as for dietary risk exposure assessment.

GLN 860.1360: Multiresidue Methods The 2/ 97 FDA PESTDATA database ( PAM Volume I, Appendix) indicates that the parent imazalil is completely recovered (> 80%) using Multiresidue Methods Section 302 ( Luke Method; Protocol D) but is not recovered using Multiresidue Methods Sections 303 ( Mills, Onley, and Gaither; Protocol E, nonfatty) and 304 ( Mills, fatty food).

Multiresidue methods data have not been submitted for imazalil metabolites that warrant inclusion in the tolerance expression. To fully satisfy reregistration requirements, the following metabolites must be tested through FDA's multiresidue protocols: ( I) metabolite R014821; ( ii) marker metabolites in milk and ruminant tissues ( FK772 and FK284); and ( iii) marker metabolites in eggs and poultry tissues ( FK858, and FK326 or FK259). The registrant is required to follow the directions for the protocols found in PAM Volume I, Appendix II starting with the decision tree for multiresidue methods testing and the accompanying guidance found in the suggestions for producing quality data; i. e. decisions on what protocols to follow and proper application of methods. If the decision tree indicates that recovery is likely, the registrant should consult the data development section of the proper protocols and follow the guidance offered precisely to generate quality data. Page 23 of 50 GLN 860.1380: Storage Stability Data The reregistration requirements for storage stability data are satisfied. Adequate storage stability data for plant and livestock commodities have been submitted and evaluated.

Plant commodities: Several storage stability studies have been submitted and evaluated. These studies showed that residues of imazalil and its metabolite R014821 are stable under frozen storage conditions in/ on: ( I) bananas for up to 38 weeks; ( ii) citrus fruits and their processed commodities for up to 34 weeks; and ( iii) wheat grain and forage for up to 24 weeks. These storage stability data are adequate to validate the storage intervals and conditions of samples collected from respective field and processing studies. It should be noted that HED previously concluded that residues of imazalil and its metabolite R014821 can decline significantly in/ on wheat straw ( 30 40%) over relatively short ( 12 24 weeks) periods of time. However, reanalysis of treated wheat grain and straw samples collected during field trials indicate that residues are stable in these wheat RACs for at least 300 days.

Livestock commodities: Storage stability data, submitted in support of the goat metabolism study, are adequate and indicate that radioactive residues of imazalil in the aqueous extracts of milk, liver, and kidney are stable under frozen storage conditions for up to 15 months. No storage stability data were submitted in support of the hen metabolism study; however, analysis of egg and tissue samples collected from the hen metabolism study were completed within six months of sampling. Samples collected from the ruminant feeding studies were stored frozen for 30 days prior to residue analysis.

GLN 860.1400: Water, Fish, and Irrigated Crops Imazalil is presently not registered for direct use on water and aquatic food and feed crops; therefore, no residue chemistry data are required under these guideline topics.

GLN 860.1460: Food Handling Imazalil is presently not registered for use in food handling establishments; therefore, no residue chemistry data are required under this guideline topic.

GLN 860.1480: Meat, Milk, Poultry, Eggs Ruminants: The reregistration requirements for data depicting the magnitude of imazalil residues of concern in milk and tissues of ruminants are fulfilled. An acceptable ruminant feeding study has been submitted and the maximum theoretical dietary intake of imazalil derived from existing or proposed tolerances has been calculated. As determined by HED, the beef and dairy cattle diets consisting of citrus pulp, wheat straw, wheat grain, and wheat forage would result in burdens of about 6.7 ppm and 4.7 ppm in the diets of dairy cattle and beef cattle, respectively. Page 24 of 50 In the ruminant feeding study, dairy cows were fed imazalil placed into gelatin capsules and administered by balling gun twice daily for 28 consecutive days at feeding levels of 33 ppm, 99 ppm, and 330 ppm. At the feeding level of 33 ppm, the maximum combined residues of imazalil and the marker metabolites FK772 and FK284 were 0.054 ppm in milk, 0.050 ppm in muscle, 0.956 ppm in liver, 0.155 ppm in kidney, and 0.026 ppm in fat. Presently the dietary burden does not contain wet apple pomace as the previous chemistry chapter did. The Chemistry files indicate the apple tolerance petition was withdrawn by the registrant. The 33 ppm feeding level is now 5x and 7x the dairy and beef cattle dietary burden, respectively. The reassessed tolerances for livestock commodities are presented in Table C.

Hogs: Secondary residues of imazalil in hog fall under CFR 180.6 ( a)( 3), since there is no reasonable expectation of finite residues. There is no reasonable expectation of residues because guidance does not support hogs feeding on citrus dried, pulp and therefore tolerances are recommended to be revoked.

Maximum residues of imazalil in the diet of dairy cattle Feed Item Proposed Tolerance ( ppm) % Dry Matter % Livestock Diet Dietary Burden ( ppm)

protein source ( soybeans) na na 20 0 citrus pulp, dried 25 91 20 5.5 wheat forage 0.5 25 60 1.2 TOTAL 100 6.7 Maximum residues of imazalil in the diet of beef cattle Feed Item Proposed Tolerance ( ppm) % Dry Matter % Livestock Diet Dietary Burden ( ppm)

citrus pulp, dried 25 91 15 4.1 protein source ( soybeans) na na 20 0 wheat forage 0.5 25 20 0.4 wheat straw 0.5 88 30 0.18 wheat grain 0.05 89 15 0.01 TOTAL 100 4.7 Page 25 of 50 Residues of Imazalil and its Metabolites in Raw Milk from Cows Fed Imazalil for 28 Days.

Imazalil Feeding Concentration ( ppm) Milk Sampling Day Imazalil Range ( ppm) FK772 ref. B FK284 ref. C Total Residue Range ( ppm)

330 ppm ( 49x) 1 0.010 0.029 0.013 0.020 0.017 0.063 0.040 0.112 3 0.092 0.158 0.021 0.031 0.166 0.209 0.279 0.298 7 0.067 0.078 0.041 0.055 0.134 0.180 0.242 0.313 15 0.042 0.057 0.033 0.049 0.092 0.167 0.167 0.273 22 0.025 0.028 0.026 0.030 0.086 0.127 0.137 0.185 28 0.002 0.016 0.017 0.020 0.053 0.084 0.072 0.120 99 ppm ( 15x) 1 0.003 0.012 0.002 0.004 0.002 0.008 0.007 0.024 3 0.011 0.031 0.011 0.013 0.024 0.049 0.046 0.093 7 0.013 0.021 0.016 0.017 0.030 0.033 0.059 0.071 13 0.007 0.009 0.006 0.008 0.020 0.032 0.033 0.049 20 0.006 0.007 0.011 0.017 0.010 0.017 0.027 0.041 28 0.000 0.005 0.015 0.021 0.013 0.028 0.028 0.054 33 ppm ( 5x) 1 0.011 0.015 0.002 0.003 0.000 0.001 0.013 0.019 3 0.008 0.013 0.007 0.010 0.000 0.001 0.015 0.024 7 0.007 0.017 0.002 0.005 0.004 0.007 0.013 0.029 14 0.006 0.010 0.002 0.004 0.001 0.006 0.009 0.020 21 0.005 0.007 0.007 0.008 0.003 0.005 0.015 0.020 28 0.005 0.016 0.002 0.021 0.008 0.017 0.015 0.054 Residues of Imazalil and its Metabolites in Ruminant Tissues from Cows Fed Imazalil for 28 Days.

Imazalil Feeding Concentration ( ppm) Tissue Imazalil Range ( ppm) Ref. B ( FK 772) Ref. C ( FK284) Total Residue Range ( ppm)

330 ppm ( 70x) Muscle 0.003 0.023 0.015 0.071 0.074 0.105 0.092 0.199 Liver 7.534 12.253 0.622 0.895 0.816 1.535 8.972 14.683 Kidney 0.606 1.453 0.633 1.298 0.355 1.076 1.594 3.827 Fat 0.067 0.224 0.032 0.043 0.014 0.083 0.113 0.350 Imazalil Feeding Concentration ( ppm) Tissue Imazalil Range ( ppm) Ref. B ( FK 772) Ref. C ( FK284) Total Residue Range ( ppm)

Page 26 of 50 99 ppm ( 21x) Muscle 0.000 0.017 0.005 0.017 0.017 0.043 0.022 0.077 Liver 1.380 2.759 0.164 0.514 0.165 0.440 1.709 3.713 Kidney 0.153 0.271 0.191 0.285 0.038 0.072 0.382 0.628 Fat 0.004 0.014 0.004 0.032 0.002 0.021 0.010 0.067 33 ppm ( 7x) Muscle 0.001 0.014 0.002 0.014 0.000 0.022 0.003 0.050 Liver 0.142 0.506 0.072 0.229 0.107 0.221 0.321 0.956 Kidney 0.006 0.035 0.055 0.090 0.000 0.030 0.061 0.155 Fat 0.000 0.014 0.000 0.007 0.000 0.005 0.000 0.026 Poultry: HED has made a determination to not require tolerances for imazalil residues of concern in eggs and poultry tissues since there is no reasonable expectation of finite residues [ 40 CFR § 180.6( a)( 3)]. This determination is based on a review of a poultry feeding study( DP barcode D254805, D. Hrdy, 1/ 19/ 00.) However, a determination of tolerances resulting from a fumigation application has not yet been made and remains a data gap ( see 773 EUP R, memo of 8/ 12/ 85, A. Reiter and S. Hummel).

GLN 860.1500: Crop Field Trials The reregistration requirements for data depicting the magnitude of imazalil and its metabolite R014821 in/ on the following raw agricultural commodities ( RACs) are fulfilled: bananas, barley grain, barley straw, citrus fruits, wheat grain, wheat forage, and wheat straw. Except for the grains of barley and wheat, the available crop field trials reflecting use of registered formulations at 1x the maximum label rate showed finite residues of imazalil and its metabolite R014821 in/ on the RACs of crops for which registration exists.

The Agency has updated the list of raw agricultural and processed commodities and feedstuffs derived from crops ( Table 1, OPPTS GLN 860.1000). Table 1 now lists hay as a RAC of barley, and barley forage was removed as a RAC. No data for barley hay have been submitted. However, the available data for barley forage and straw will be translated to barley hay.

Table 1 also lists wheat hay as a RAC of wheat, and no data for wheat hay have been submitted. The available data for wheat forage and straw will be translated to wheat hay. Residue data for wheat aspirated grain fractions are not required because imazalil's registered use on wheat is limited to seed treatment, which typically does not trigger data requirement for aspirated grain fractions. ( continued; footnotes follow) Page 27 of 50 There are no registered uses of imazalil on cottonseed for which a tolerance is established. To date, no registrants have committed to support imazalil use on cottonseed. Unless, Janssen Pharmaceutica or other registrants submit supporting residue data, HED will recommend for tolerance revocation.

GLN 860.1520: Processed Food/ Feed The reregistration requirements for studies pertaining to the magnitude of the residue in the processed commodities of citrus fruits are fulfilled. Acceptable citrus processing studies, reflecting post harvest treatments and conducted according to commercial practice, were separately conducted on grapefruit, oranges, and lemons. Citrus fruits were treated with imazalil in a wax formulation at 1x and 2x the maximum registered label rates. The studies showed that residues of imazalil and its metabolite R014821 do not concentrate in juice; the combined residues reduced by  90% in citrus juice. However, residues of imazalil and its metabolite R014821 do concentrate in dried pulp and oil. In dried pulp, the maximum average concentration factor of total residues in oranges was 2.5x; the overall average concentration factor of total residues for the three citrus crops was 1.7x. In oil, the average concentration of total residues was 3.3x in lemon, 15.0x in grapefruit, and 28.0x in oranges; the overall average concentration factor in oil for the three citrus crops was 16.0x. Refer to " Tolerance Reassessment Summary" section for recommendations with respect to the need for tolerances as a result of concentration of residues in citrus processed commodities.

HED has earlier concluded that barley and wheat grain processing studies are not required. This determination was based on the theoretical concentration factors for barley and wheat grain processed commodities ( 1.2 9x), the apparent residues < LOQ from the use of exaggerated application rates ( 6.3x and 10x), and the use pattern ( seed treatment), which is unlikely to result in surface residues on the grain. The combined residues of imazalil and its metabolite R014821 in/ on barley and wheat processed commodities are not likely to exceed the reassessed tolerances for barley and wheat grains.

GLN 860.1850 and 860.1900: Confined/ Field Accumulation in Rotational Crops Confined and/ or field accumulation studies are not required because the use of imazalil on annual crops ( represented by barley and wheat) eligible for reregistration is limited to seed treatment prior to crop planting. Furthermore, the available plant metabolism data indicate that the total radioactivity in wheat grain, grown from wheat seeds treated with [ 14C] imazalil at 5x the maximum label rate, was # 0.004 ppm. HED does not anticipate uptake of imazalil residues of concern in/ on rotational crops when registered formulations of imazalil are applied to primary crops according to the maximum registered use patterns. No specific rotational crop restrictions should be imposed at this time.

Table B. Residue Chemistry Science Assessments for Reregistration of Imazalil. Table B ( continued).

( continued; footnotes follow) Page 28 of 50 GLN: Data Requirements Current Tolerances, ppm [ 40 CFR] Must Additional Data Be Submitted? References 1 860.1200: Directions for Use Not applicable ( N/ A) Yes 2 See Tables A1 and A2 860.1300: Plant Metabolism N/ A No 00027532, 00087542, 00087543, 00096418, 00157188, 42012006 3, 42012007 3, 42012008 4, 42012009 4, 42403102 5, 42626901 6, 43308401 7, 43965701 8, 92072019, 92072020, 92072035, 92072036, 92072037 860.1300: Livestock Metabolism N/ A No 00027533, 00084644, 42012005 3, 42454801 9, 42454802 9, 42593602 9, 42838201 10, 4294940111, 43076101 12, 92072021, 92072038 860.1340: Residue Analytical Methods  Plant commodities N/ A No 00109269, 00127900, 42454803 13, 42454804 13, 42454805 13, 42626902 6, 44532901 14, 92072022, 92072023  Livestock commodities N/ A Yes 15 00109269, 44337701 16, 44455601 17, 92072024 860.1360: Multiresidue Methods N/ A Yes 18 FDA PESTDATA database ( PAM Volume I, Appendix)

860.1380: Storage Stability Data  Plant/ processed commodities N/ A No 00157189, 42626903 6, 42643301 19, 4275530120 , 92072025  Livestock commodities N/ A No 42838201 10 860.1500: Crop Field Trials Citrus Fruits Group 10.0 [ § 180.413( a)] No 40509402, 40509403, 92072027, 92072030 21, 92072040 21 Cereal Grains Group  Barley, grain 0.05 [ § 180.413( a)] No 00127900, 00150020, 00157190, 42852001 22, 92072026, 92072042  Wheat, grain and aspirated grain fractions 0.05 [ § 180.413( a)] No 23 00127900, 00157190, 42852002 22, 42868101 22, 43285001 24, 92072029, 920722041 Fodder, Forage, Hay, and Straw of Cereal Grains Group Table B ( continued). GLN: Data Requirements Current Tolerances, ppm [ 40 CFR] Must Additional Data Be Submitted? References 1 Page 29 of 50 1. Bolded references were evaluated in the Imazalil Phase 4 Review ( S. Funk, 10/ 19/ 90). All other references were reviewed as noted.  Barley, hay and straw 0.5, forage and straw [ § 180.413( a)] No 25 00127900, 00150020, 00157190, 42852001 22, 92072026, 92072042  Wheat, forage, hay, and straw 0.5, forage and straw [ § 180.413( a)] No 26 00127900, 00157190, 42852002 22, 42868101 22, 43285001 24, 92072029, 920722041 Miscellaneous Commodities  Bananas 3.0, whole; 0.2, pulp [ § 180.413( a)] No 42058701 27, 42710501 28  Cotton, seed and gin byproducts 0.05, cottonseed [ § 180.413( a)] No 29 00127900, 92072028, 92072039 860.1520: Processed Food/ Feed  Barley 0.05, grain [ § 180.413( a)] No 30  Citrus 10.0, citrus fruits [ § 180.413( a)]; 25.0, citrus oil [ § 185.3650]; 25.0, citrus dried pulp [ § 186.3650] No 40509403, 42348301 31, 42405501 31, 42454806 32, 92072040 21  Wheat 0.05, grain [ § 180.413( a)] No 30 860.1480: Meat, Milk, Poultry, Eggs  Milk and the Fat, Meat, and Meat Byproducts of Cattle, Goats, Hogs, Horses, and Sheep 0.01, milk, fat, meat, mbyp; 0.5, liver [ § 180.413( b)] No 00079192, 00079193, 00109269, 44568301 33  Eggs and the Fat, Meat, and Meat Byproducts of Poultry § 180.6( a) 3 Yes34 860.1400: Water, Fish, and Irrigated Crops N/ A N/ A 860.1460: Food Handling N/ A N/ A 860.1850: Confined Rotational Crops N/ A No 860.1900: Field Rotational Crops None established No Table B ( continued).

Page 30 of 50 2. The 9.5% EC ( EPA Reg. No. 43813 14) formulation of imazalil should be amended to specify a maximum of one seed treatment prior to planting of fields with seed treated barley and wheat. 3. DP Barcode D171401, 2/ 4/ 92, L. Cheng.

4. DP Barcode D198235, 5/ 3/ 94, L. Cheng.

5. DP Barcode D181284, 9/ 25/ 92, L. Cheng.

6. DP Barcode D187506, 1/ 10/ 94, L. Cheng.

7. DP Barcode D205954, 9/ 22/ 94, L. Cheng.

8. DP Barcode D224876, 6/ 12/ 96, L. Cheng.

9. DP Barcodes D182706 and D186541, 2/ 17/ 93, J. Abbotts.

10. DP Barcode D193375, 8/ 17/ 93, J. Abbotts.

11. DP Barcode D195726, 11/ 17/ 93, S. Funk.

12. DP Barcode D198599, 7/ 14/ 94, L. Cheng.

13. DP Barcode D182707, 6/ 24/ 93, S. Funk.

14. DP Barcode 245510, 1/ 19/ 00, D. Hrdy.

15. Because of the recommended changes in tolerance expression, a new enforcement method capable of determining imazalil and any metabolite containing the 2,4 dichlorophenyl group in livestock commodities is required. The registrant must continue to develop/ validate enforcement method( s) for a set of marker compounds that account for a high percentage of the total toxic residues in ruminant. HED will correct residues to account for the total toxic residue for the purpose of tolerance reassessment as well as for assessing dietary risk exposure.

16. DP Barcode D238452, 1/ 20/ 99, S. Piper.

17. DP Barcode D242498 ( currently under secondary review at HED).

18. The following metabolites must be tested through FDA's multiresidue protocols: ( I) metabolite R014821; ( ii) marker metabolites in milk and ruminant tissues ( FK772 and FK284). The registrant is required to follow the directions for the protocols found in PAM Volume I, Appendix II starting with the decision tree for multiresidue methods testing and the accompanying guidance found in the suggestions for producing quality data; i. e. decisions on what protocols to follow and proper application of methods. If the decision tree indicates that recovery is likely, the registrant should consult the data development section of the proper protocols and follow the guidance offered precisely to generate quality data.

19. DP Barcode D187775, 3/ 2/ 93, S. Funk.

20. DP Barcode D191318, 11/ 18/ 93, D. Miller.

21. DP Barcode D220386, 5/ 8/ 96, S. Funk. Table B ( continued).

Page 31 of 50 22. DP Barcode D194151, 12/ 21/ 93, S. Funk. 23. Adequate residue data have been submitted for wheat grain. Residue data for wheat aspirated grain fractions are not required because imazalil's registered use on wheat is limited to seed treatment.

24. DP Barcode D205092, 1/ 20/ 95, L. Cheng.

25. Adequate residue data have been submitted for barley straw. Table 1 of OPPTS GLN 860.1000 now lists hay as a RAC of barley, but forage was removed from the list. No data for barley hay have been submitted. The available data for barley forage and straw will be translated to barley hay.

26. Adequate residue data have been submitted for wheat forage and straw. Table 1 of OPPTS GLN 860.1000 now lists hay as a RAC of wheat, and no data for wheat hay have been submitted. The available data for wheat forage and straw will be translated to wheat hay.

27. DP Barcode D170886, 8/ 13/ 92, A. Aikens.

28. DP Barcode D189963, 7/ 14/ 94, L. Cheng.

29. There are no registered uses of imazalil on cottonseed for which a tolerance is established. To date, no registrants have committed to support imazalil use on cottonseed. Unless Janssen Pharmaceutica or other registrants submit supporting residue data, HED will recommend for tolerance revocation.

30. The requirements for barley and wheat processing studies are waived based on the theoretical concentration factors for barley and wheat grain processed commodities ( 1.2 9x), on apparent residues < LOQ from the use of exaggerated application rates ( 6.3x and 10x), and on the use pattern ( seed treatment), which is unlikely to result in surface residues on the grain. The combined residues of imazalil and its metabolite R014821 in/ on barley and wheat processed commodities are not likely to exceed the reassessed tolerance of barley and wheat grains.

31. DP Barcode D181319, 9/ 3/ 92, S. Funk.

32. DP Barcode D182575, 2/ 17/ 93, S. Funk.

33. DP Barcode D244510, 1/ 22/ 99, S. Piper.

34. A determination of tolerances resulting from a fumigation application has not yet been made. Residue data for this use remains a data gap ( see 773 EUP R, memo of 8/ 12/ 85, A. Reiter and S. Hummel). Page 32 of 50 TOLERANCE REASSESSMENT SUMMARY Tolerances for residues in/ on plant commodities are established under 40 CFR § 180.413( a). They are currently expressed in terms of the combined residues of imazalil [ 1( 2( 2,4 dichlorophenyl) 2( 2 propenyloxy) ethyl) 1H imidazole] and its metabolite R014821 [ 1( 2,4 dichlorophenyl) 2 ( 1H imidazole 1 yl) 1 ethanol]. The qualitative nature of the residue in plants is adequately understood. HED has determined that the current tolerance expression for plant commodities is appropriate.

Tolerances for residues in livestock commodities are established under 40 CFR § 180.413( b). They are currently expressed in terms of the combined residues of imazalil and its metabolites R014821 and R042243 [ 3[ 1( 2,4 dichlorophenyl) 2( 1H imidazole 1 yl) ethoxyl] 1,2 propanediol]. The qualitative nature of the residue in livestock is adequately understood. The HED Metabolism Committee concluded that, in the absence of information to the contrary, any metabolite containing the 2,4 dichlorophenyl moiety is of toxicological concern and must be included in the conduct of the dietary risk assessment but a list of marker metabolites in addition to imazalil should be defined for inclusion in the tolerance expression ( L. Cheng, 8/ 30/ 94).

The tolerance expression for livestock commodities listed under 40 CFR § 180.413( b) should be amended to regulate imazalil, 3[ 2( 2,4 dichlorophenyl) 2( 2,3 dihydroxypropoxy) ethyl] 2,4 imidazolidinedione ( FK772), and 3[ 2( 2,4 dichlorophenyl) 2( hydroxy)] 2,4 imidazolidinedione ( FK284). Because of issues related to residue analytical methods, HED hereby defines a list of marker metabolites representing the 2,4 dichlorophenyl group moiety. For dietary assessment, the total toxic residues will be adjusted using the ratios of imazalil and the marker metabolites that were found in the livestock metabolism studies. The marker compounds in milk and ruminant tissues are imazalil, FK772, and FK284; these marker compounds collectively represent the following percentages of the total toxic residues, as determined by the ruminant metabolism studies: 21% in milk, 72% in muscle, 71% in kidney, 44% in liver, and 33% in fat. The chemical names and structures of these marker metabolites are depicted in Figure B.

A summary of imazalil tolerance reassessments is presented in Table C. The reassessments of tolerances for some commodities are contingent upon the implementation of the requested label revision. Page 33 of 50 Tolerances Established Under 40 CFR § 180.413( a)

Sufficient field trial data reflecting the maximum label use pattern are available to reassess the established tolerances for the following RACs as defined: bananas ( whole); bananas ( pulp); barley, forage; barley, grain; barley straw; citrus fruits ( POST H); wheat, forage; wheat, grain; and wheat, straw.

The established tolerances listed under 40 CFR § 180.413( a) are reassessed at the same levels except those listed for the grains of barley and wheat. Higher tolerances are required for barley and wheat grains, from 0.05 ppm to 0.1 ppm, to reflect the sensitivity of the data collection method and to account for apparent residues in/ on control grain samples.

Acceptable citrus processing studies, reflecting postharvest treatments, have been submitted and evaluated. The data from these studies showed that residues of imazalil and its metabolite R014821 do not concentrate in juice but do concentrate in oil. In oil, the average concentration of total residues was 3.3x in lemon, 15.0x in grapefruit, and 28.0x in oranges; the overall average concentration factor in oil for the three citrus crops was 16.0x. These processing data suggest that a tolerance for juice is not needed, and that the established tolerance of 25 ppm for citrus oil is too low. The maximum combined residues of imazalil and its metabolite R014821 expected in citrus oil, based on the HAFT residue for oranges ( 6.68 ppm) and the maximum average concentration factor for oranges ( 28.0x) would be 187 ppm. The reassessed tolerance for citrus oil is, therefore, 200 ppm.

The available citrus processing studies reflecting postharvest treatments showed that residues of imazalil and its metabolite R014821 concentrated marginally in dried pulp. The maximum average concentration factor of total residues in orange dried pulp was 2.5x; the overall average concentration factor of total residues in citrus dried pulp was 1.7x. These processing data suggest that the established tolerance of 25 ppm for dried pulp is adequate. The maximum combined residues of imazalil and its metabolite R014821 expected in citrus dried pulp, based on the HAFT residue for oranges ( 6.68 ppm) and the maximum average concentration factor for oranges ( 2.5x) would be 16.7 ppm.

The reregistration requirements for barley and wheat grain processing studies have been waived. Therefore, tolerances for the processed commodities of barley and wheat are not required.

The established tolerance for banana pulp should be revoked since it is the Agency policy to establish a tolerance on the whole commodity ( including peel after removing and discarding crown tissue and stalk). The available data on banana pulp may be used for the purpose of dietary risk assessment.

The established tolerance for cottonseed should be revoked because there are no registered uses of imazalil on cottonseed, and no registrants have committed to support imazalil use on cotton. Page 34 of 50 Tolerances To Be Proposed Under 40 CFR § 180.413( a)

Tolerances for barley hay and wheat hay must be proposed. The available data for barley forage and straw will be translated to barley hay. The available data for wheat forage and straw will be translated to wheat hay. A tolerance of 0.5 ppm is recommended for both barley and wheat hay.

Tolerances Established Under 40 CFR § 180.413( b)

An acceptable ruminant feeding study has been submitted and evaluated. At the feeding level of 33 ppm, the maximum combined residues of imazalil and the marker metabolites ( FK772 and FK284) were 0.054 ppm in milk, 0.050 ppm in muscle, 0.956 ppm in liver, 0.155 ppm in kidney, and 0.026 ppm in fat.

The reassessed tolerances are 0.02 ppm for milk, 0.02 ppm for muscle of cattle, goats, horses, and sheep; 0.01 ppm for fat of cattle, goats, horses, and sheep; 0.20 ppm for mbyp ( meat by products) of cattle, goats, horses, and sheep; and 0.20 ppm for liver of cattle, goats, horses, and sheep.

A poultry feeding study was required to determine whether tolerances would be required for imazalil residues of concern in eggs and poultry tissues. There is no reasonable expectation of finite residues [ 40 CFR § 180.6( a)( 3)]. However, a determination of tolerances resulting from a fumigation application has not yet been made and remains a data gap ( see 773 EUP R, memo of 8/ 12/ 85, A. Reiter and S. Hummel.)

Pending Tolerance Petitions PP# 4F3096: Janssen Pharmaceutica had originally proposed in a petition, FAP 4H5434, the establishment of tolerances for residues of imazalil and its metabolite R014821 [ 1( 2,4 dichlorophenyl) 2( 1H imidazole 1 yl) 1 ethanol] in/ on the pome fruit group at 7.0 ppm and in wet/ dry apple pomace at 30 ppm. The petitioner subsequently withdrew FAP 4H5434 and revised PP# 4F3096, for the establishment of a tolerance on pear at 10 ppm. Following review of the proposed uses and residue data, HED recommended for the establishment of a tolerance on pear at 10 ppm ( DP Barcode D197176, 6/ 2/ 94, M. I. Rodriguez). Janssen Pharmaceutica proposed in a separate petition, PP# 7F3530, for tolerances on melons ( excluding watermelon) by post harvest application and sweet corn by seed treatment. Page 35 of 50 Table C. Tolerance Reassessment Summary for Imazalil.

Commodity Current Tolerance, ppm Reassessed Tolerance, ppm Comment [ Correct Commodity Definition]

Tolerances Established Under 40 CFR § 180.413( a)

Bananas ( Whole) 3.00 3.0 The tolerance for banana pulp should be revoked because it is the Agency policy to establish a tolerance on the whole commodity ( including peel after removing and discarding crown tissue and stalk). The available data on banana pulp may be used for the purpose of dietary risk assessment. Bananas ( Pulp) 0.20 Revoke Barley, forage 0.5 Revoke This RAC has been deleted from Table 1 of OPPTS GLN 860.1000.

Barley, grain 0.05 0.1 A higher tolerance is needed to reflect the sensitivity of the data collection method and to account for apparent residues in/ on control grain samples.

Barley, straw 0.5 0.5 Citrus fruit ( POST H) 10.0 10.0 Citrus oil 25.0 200 Citrus pulp ( dried) 25.0 25 Cottonseed 0.05 Revoke The tolerance should be revoked because there are no registered uses of imazalil on cottonseed, and no registrants have committed to support imazalil use on cottonseed.

Wheat, forage 0.5 0.5 Wheat, grain 0.05 0.1 A higher tolerance is needed to reflect the sensitivity of the data collection method and to account for apparent residues in/ on control grain samples.

Wheat, straw 0.5 0.5 Tolerances To Be Proposed Under 40 CFR § 180.413( a)

Barley, hay None established 0.5 The available data for barley forage and straw will be translated to barley hay.

Wheat, hay None established 0.5 The available data for wheat forage and straw will be translated to wheat hay.

Tolerances Established Under 40 CFR § 180.413( b)

Cattle, fat 0.01 0.01 Cattle, liver 0.50 0.20 Cattle, meat 0.01 0.02 Cattle, mbyp 0.01 0.20 Cattle, meat byproducts Goats, fat 0.01 0.01 Goat, fat Goats, liver 0.50 0.20 Goat, liver Goats, meat 0.01 0.02 Goat, meat Goats, mbyp 0.01 0.20 Goat, meat byproducts Hogs, fat 0.01 Revoke § 180.6( a) 3 Hogs, liver 0.50 Revoke § 180.6( a) 3 Hogs, meat 0.01 Revoke § 180.6( a) 3 Hogs, mbyp 0.01 Revoke § 180.6( a) 3 Horses, fat 0.01 0.01 Horse, fat Horses, liver 0.50 0.20 Horse, liver Horses, meat 0.01 0.02 Horse, meat Commodity Current Tolerance, ppm Reassessed Tolerance, ppm Comment [ Correct Commodity Definition]

Page 36 of 50 Horses, mbyp 0.01 0.20 Horse, meat byproducts Milk 0.01 0.02 Sheep, fat 0.01 0.01 Sheep, liver 0.50 0.20 Sheep, meat 0.01 0.02 Sheep, mbyp 0.01 0.20 Sheep, meat byproducts However, a determination of tolerances resulting from a fumigation application has not yet been made and remains a data gap ( see 773 EUP R, memo of 8/ 12/ 85, A. Reiter and S. Hummel). Page 37 of 50 CODEX HARMONIZATION The Codex Alimentarius Commission has established several maximum residue limits ( MRLs) for imazalil in/ on various raw agricultural commodities. The Codex MRLs are expressed in terms of imazalil per se. The Codex MRLs and the U. S. tolerances are incompatible with respect to tolerance expression. The U. S. tolerances for plant commodities are in expressed terms of the combined residues of imazalil and its metabolite R014821. The expression of U. S. tolerances for livestock commodities will be amended to include imazalil, marker metabolite FK772, and marker metabolite FK284. Both Codex and U. S. have established MRLs/ tolerances for bananas, citrus fruits, and wheat grain, forage, hay, and straw. However, the residue levels are not in harmony presumably because of differences in good agricultural practices. A numerical comparison of the Codex MRLs and the corresponding reassessed U. S. tolerances is presented in Table D.

Table D. Codex MRLs for Imazalil and applicable U. S. tolerances.

Codex Reassessed U. S. Tolerance ( ppm) Recommendation and Comments Commodity ( As Defined) MRL ( mg/ kg) Step Banana 2 Po a CXL 3.0 Citrus fruits 5 Po CXL 10.0 Cucumber 0.5 CXL No U. S. registration.

Gherkin 0.5 CXL No U. S. registration.

Melons, except watermelon 2 CXL No U. S. registration.

Persimmon, Japanese 2 Po CXL No U. S. registration.

Pome fruits 5 Po CXL No U. S. registration.

Potato 5 Po b CXL No U. S. registration.

Raspberries, Red, Black 2 CXL No U. S. registration.

Strawberry 2 CXL No U. S. registration.

Wheat 0.01(*) c CXL 0.1 for grain Wheat straw and fodder, Dry 0.1 CXL 0.5 for forage, hay, and straw a Po = Postharvest treatment of the commodity. b Washed before analysis. c Asterisk designates MRL set at the limit of quantitation. Page 38 of 50 AGENCY MEMORANDA RELEVANT TO REREGISTRATION DP Barcode: None Subject: Imazalil. DEB Phase 4 Review. From: S. Funk To: K. Davis Dated: 10/ 18/ 90 MRID: None DP Barcode: D164394 Subject: Protocol for Determination of the Nature of the Residue in Ruminants for Imazalil. From: S. Funk To: K. Davis Dated: 7/ 2/ 91 MRID: None DP Barcode: D165032 Subject: Protocols for the Citrus Processing and Winter Wheat Field Trials for Imazalil. From: S. Funk To: K. Davis Date: 7/ 16/ 91 MRID( s): None DP Barcode: D168504 Subject: Reregistration of Imazalil. Janssen Pharmaceutica 90 Day Response to Phase 4 DCI. From: S. Funk To: K. Davis Dated: 12/ 3/ 91 MRID: None DP Barcode: D168495 Subject: Response to Registrant's Concerns/ Questions Arising from the Imazalil Phase 4 Reregistration DCI. From: B. Cropp Kohlligian To: B. Briscoe Dated: 1/ 28/ 92 MRID: None DP Barcode: D171401 Subject: ID# 111901 43813. Imazalil. Response to Phase IV Review. From: L. Cheng To: K. Davis Dated: 2/ 4/ 92 MRID: 42012005 through 42012009 DP Barcode: D173008 Subject: Reregistration of Imazalil. Protocol for Nature of the Residue in Wheat. From: S. Funk To: K. Davis Date: 2/ 25/ 92 MRID( S): None Page 39 of 50 DP Barcode: D179225 Subject: Reregistration of Imazalil. Poultry Metabolism Protocol. From: S. Funk To: K. Davis Dated: 8/ 6/ 92 MRID: None DP Barcode D170886 Subject: Imazalil Reregistration. Magnitude of the Residue  Post Harvest Treatment of Bananas ( Foreign). Guideline 171 4k ( Magnitude of the Residue  Crop Field Trial). From: A. Aikens To: B. Briscoe and K. Davis Date: 8/ 13/ 92 MRID: 42058701 DP Barcode: D181319 Subject: Imazalil: FIFRA 6( a)( 2) Data and Reregistration. Processing Studies for Citrus: Preliminary Findings. From: S. Funk To: K. Davis Dated: 9/ 3/ 92 MRID: 42348301 and 42405501 DP Barcode: D179225 Subject: Reregistration of Imazalil. Poultry Metabolism Protocol. Addendum to Memorandum of 8/ 6/ 92. From: S. Funk To: K. Davis Dated: 9/ 24/ 92 MRID: None DP Barcode: D181284 Subject: Imazalil. Product Chemistry Data and Stability of 3H Imazalil. From: L. Cheng To: K. Davis Dated: 9/ 25/ 92 MRID: 42403101 and 42403102 DP Barcode: None Subject: Non concurrence on Draft FR Notice. PP# 5F3250. Imazalil on Forage and Hay of Wheat and Barley. From: R. Cook To: C. Giles Parker Date: 1/ 7/ 93 MRID( s): None DP Barcodes: D182706 and D186541 Subject: Imazalil, Reregistration. Nature of the Residue in Ruminant and Analytical Methods for Plants. From: J. Abbotts To: K. Depukat Dated: 2/ 17/ 93 MRID: 42454801 through 42454804, and 42593602 Page 40 of 50 DP Barcode: D182575 Subject: Imazalil. Citrus processing Studies. From: S. Funk To: K. Davis Dated: 2/ 17/ 93 MRID: 42454806 DP Barcode: D187775 Subject: Imazalil: Citrus and Citrus Processed Commodities Storage Stability. From: S. Funk To: K. Depukat Date: 3/ 2/ 93 MRID( s): 42643301 DP Barcode: D189000 Subject: Imazalil: ( 1) Wheat Processing Waiver Request; ( 2) Poultry Metabolism Protocol Change. From: S. Funk To: K. Davis and K. Depukat Date: 4/ 6/ 93 MRID( s): None DP Barcode: None Subject: Meeting with Janssen Pharmaceutica, 4/ 28/ 93, on Imazalil Metabolism in Goat. From: J. Abbotts To: K. Depukat Dated: 4/ 30/ 93 MRID: None DP Barcode: D182707 Subject: Imazalil ( List B; Case 2325; Chemical 111901): Analytical Method for the Determination of Imazalil and R14821 in/ on Bananas, Citrus, and Citrus Processed Commodities. Research Method and Enforcement Method Comparison. From: S. Funk To: K. Depukat and K. Davis Dated: 6/ 24/ 93 MRID( s): 42454803 through 42454805 DP Barcode: D193375 Subject: Imazalil, Reregistration. Nature of the Residue in Ruminant, Supplemental Data. From: J. Abbotts To: K. Depukat Dated: 8/ 17/ 93 MRID: 42838201 DP Barcode: D194053 Subject: FAP# 3H5680. Reregistration of Imazalil. Petition for a Revised Tolerance for Banana Pulp ( PP# 8E2100). Petition for a Revised Food Additive Tolerance for Citrus Oil. From: S. Funk To: C. Giles Parker, J. Stone, K. Davis, and K. Depukat Dated: 11/ 3/ 93 MRID: None Page 41 of 50 DP Barcode: D195726 Subject: Imazalil ( List B, Chemical 111901, Case 2325). Nature of the Residue in Poultry ( Preliminary). From: S. Funk To: K. Davis and K. Depukat Date: 11/ 17/ 93 MRID: 42949401 DP Barcode: D191318 Subject: Imazalil. Storage stability in Wheat ( Grain, Forage, and Straw). From: D. Miller To: K. Depukat Date: 11/ 18/ 93 MRID: 42755301 DP Barcode: D194151 Subject: Reregistration of Imazalil ( List B, Chemical 111901, Case 2325). Magnitude of the Residue in Wheat and Barley ( 171 4( k)) and in Processed Commodities of Wheat and Barley ( 171 4( l)). From: S. Funk To: K. Davis and K. Depukat Dated: 12/ 21/ 93 MRID: 42852001, 42852002, and 42868101 DP Barcode: D187506 Subject: Imazalil. Case No. 2325. Registrant's Response to Reregistration. From: L. Cheng To: K. Depukat Dated: 1/ 10/ 94 MRID: 42626901 through 42626903 DP Barcode: D198235 Subject: Imazalil. Case 2325. Phase IV Review of Orange and Banana Metabolism Studies. From: L. Cheng To: K. Depukat Dated: 5/ 3/ 94 MRIDs: 42012008 and 42012009 DP Barcode: D197176 Subject: PP4F3096: Imazalil ( Fungaflor 500 EC) in/ on Pears. Amendment Dated 11/ 22/ 93. From: M. I. Rodriguez To: C. Giles Parker, J. Stone, and A. Kocialski Dated: 6/ 2/ 94 MRID: None DP Barcode: D189963 Subject: Imazalil. Case 2325. Registrant's Response to Magnitude of the Residue in/ on Bananas. From: L. Cheng To: K. Depukat Dated: 7/ 14/ 94 MRID: 42710501 Page 42 of 50 DP Barcode: D198599 Subject: Imazalil. Case No. 2325. Nature of the Residue in Laying Hen. From: L. Cheng To: K. Depukat Dated: 7/ 14/ 94 MRID: 43076101 DP Barcode: None Subject: Imazalil. Hen and Ruminant Metabolism Studies. To be Presented to the HED Metabolism Committee on August 8, 1994. From: L. Cheng To: HED Metabolism Committee Dated: 8/ 4/ 94 MRID: None DP Barcode: None Subject: Imazalil. Laying Hen and Lactating Goat Metabolism. The Metabolism Committee Meeting Held on August 18, 1994. From: L. Cheng To: The HED Metabolism Committee Dated: 8/ 30/ 94 MRID( s): None DP Barcode: D205954 Subject: Imazalil. Case No. 2325. Supplemental Data to Orange Metabolism Study. From: L. Cheng To: K. Depukat Dated: 9/ 22/ 94 MRID: 43308401 DP Barcode: None Subject: Imazalil. Case No. 2325. Residues to be Measured in the Animal Feeding Studies. From: L. Cheng To: K. Depukat Dated: 11/ 1/ 94 MRID( s): None DP Barcode: D206723 Subject: Imazalil. Case No. 2325. Rebuttal to Geographic Representation for Postharvest Use: Bananas. From: L. Cheng To: K. Depukat Dated: 11/ 29/ 94 MRID: None DP Barcode: D209996 Subject: Imazalil. Case No. 2325. Metabolism on Banana  Postharvest Treatment. Review of Protocol. From: L. Cheng To: K. Depukat Dated: 1/ 3/ 95 MRID: None Page 43 of 50 DP Barcode: D205092 Subject: Imazalil. Case No. 2325. Magnitude of Residue in Winter Wheat Forage, Straw and Grain Grown From Treated Seed. From: L. Cheng To: K. Depukat Dated: 1/ 20/ 95 MRID: 43285001 DP Barcode: D215063 Subject: Imazalil  Application of DES Proviso to Existing Feed Additive Tolerances From: G. Kramer To: Chemistry Branch Files Dated: 5/ 12/ 95 MRID: None DP Barcode: D214575 Subject: Imazalil. Case No. 2325. Residue Analytical Method for the Animal Feeding Studies. From: L. Cheng To: K. Depukat Dated: 6/ 8/ 95 MRID( s): None DP Barcode: D220386 Subject: Imazalil ( Chemical 111901, Case 2325, List B): Citrus Oil Food Additive Tolerance. From: S. Funk To: N. Nazmi and W. Hazel Dated: 5/ 8/ 96 MRIDs: 92072030 and 92072040 DP Barcode: D224876 Subject: Imazalil. Case 2325. Metabolism on Bananas From Post Harvest Treatment. From: L. Cheng To: P. Deschamp Dated: 6/ 12/ 96 MRID( s): 43965701 DP Barcode: D239118 Subject: Imazalil ( Chemical 111901, Case 2325, List B). GLN 860.1480. Protocol for a Ruminant Feeding Study. From: S. Funk To: D. Monos and W. Waldrop Dated: 10/ 30/ 97 MRID: None DP Barcode: D247703 Subject: Imazalil ( 111901), Registrant response to Poultry Feeding Study. From: S. Piper To: K. Farwell Dated: 9/ 18/ 98 MRID: None Page 44 of 50 DP Barcode: D238452 Subject: Imazalil ( Chemical 111901, Case 2325, List B). Analytical Method  Ruminants From: S. Piper To: M. Metzger Dated: 1/ 20/ 99 MRID: 44337701 DP Barcode: D245510 Subject: Imazalil ( Chemical 111901, Case 2325, List B). Janssen Pharmaceutica. GLN 860.1480. Ruminant Feeding Study. From: S. Piper To: M. Metzger Dated: 1/ 22/ 99 MRID: 44568301 DP Barcode: D242498 Subject: Method Validation for a Proposed Enforcement Method  Animal Commodities. From: David E. Hrdy, Biologist To: Susan V. Hummel, Branch Senior Scientist Dated: 1/ 19/ 00 MRID: 44455601 DP Barcode: D244510 Subject: Radiovalidation of PAM Vol. II Method Using Samples From Banana Metabolism Study. From: David E. Hrdy, Biologist To: Susan V. Hummel, Branch Senior Scientist Dated: 1/ 19/ 00 MRID: 44532901 MASTER RECORD IDENTIFICATION NUMBERS References Used To Support Reregistration 00027532 Meuldermans, W.; Swijsen, E.; Hendricks, E.; et al. ( 1979) The Metabolic Fate of Imazalil on Oranges. ( Unpublished study received Mar 5, 1980 under AZ 79/ 5; prepared by Janssen Pharmaceutica, submitted by state of Arizona for Janssen R & D, Inc., New Brunswick, N. J.; CDL: 241950 B)

00027533 Meuldermans, W.; Swijsen, E.; Hendricks, E.; et al. ( 1979) Plasma and Milk Levels, Distribution, Excretion and Biotransformation of Imazalil after Repeated Administration to a Lactating Goat. ( Unpublished study received Mar 5, 1980 under AZ 79/ 5; prepared by Janssen Pharmaceutica, submitted by state of Arizona for Janssen R & D, Inc., New Brunswick, N. J.; CDL: 241950 C)

00079192 Meuldermans, W.; Woestenborghs, R.; Michielsen, L.; et al. ( 1981) Residue Levels of Imazalil and Two of Its Basic Metabolites in Cows following Repeated Oral Dosing at Three Dose Levels: R 23 979/ 24. ( Unpublished study received Jun 25, 1981 under 43818 1; prepared by Janssen Pharmaceutica N. V., Belgium, submitted by Edmar Cleaning Corp., Long Island City, N. Y.; CDL: 245310 E)

00079193 Meuldermans, W.; Woestenborghs, R.; Michielsen, L.; et al. ( 1981) Milk Levels of Imazalil and Two of Its Basic Metabolites in Lactating Cows following Repeated Oral Dosing of Three Dose Levels: R 23 979/ 23. ( Unpublished Page 45 of 50 study received Jun 25, 1981 under 43818 1; prepared by Janssen Pharmaceutical N. V., Belgium, submitted by Edmar Cleaning Corp., Long Island City, N. Y.; CDL: 245310 F)

00084644 Meuldermans, W.; Swysen, E.; Hendrickx, J.; et al. ( 1981) Plasma and Milk Levels, Distribution, Excretion and Biotransformation of Imazalil after Repeated Administration to a Lactating Goat: Addendum 1: Levels of Tritiated Water in the Various Tissues, and Further Data on the Metabolite Pattern in Liver: Serial No. R 23 979/ 14 Add. 1. ( Unpublished study received Oct 8, 1981 under 43813 1; prepared by Janssen Pharmaceutica, Belgium, sub 00087541 Janssen R & D, Incorporated ( 1981) [ Residue of Imazalil on Bananas]. ( Unpublished study received Dec 3, 1981 under 8E2100; CDL: 070508 A)

00087542 Meuldermans, W.; Hurkmans, R.; Hendrickx, J.; et al. ( 1980) The Metabolic Fate of Imazalil on Banana Plants: Serial No. R 23 979/ 21. ( Unpublished study received Dec 3, 1981 under 8E2100; prepared by Janssen Pharmaceutica, Belgium, submitted by Janssen R & D, Inc., New Brunswick, N. J.; CDL: 070508 B)

00087543 Meuldermans, W.; Hurkmans, R.; Buedts, J.; et al. ( 1981) The Metabolic Fate of Imazalil on Banana Plants. Addendum 1: Translocation into Sleeved Bunches: Serial No. R 23 979/ 25. ( Unpublished study received Dec 3, 1981 under 8E2100; prepared by Janssen Pharmaceutica, Belgium, submitted by Janssen R & D, Inc., New Brunswick, N. J.; CDL: 070508 C)

00096418 Vonk, J. W. ( 1977) The Fate of Imazalil in Barley Plants Grown from Treated Seed: Report of Project 2. ( Unpublished study received Feb 24, 1982 under 43813 1; prepared by Organisch Chemisch Instituut TNO, The Netherlands, submitted by Janssen R & D, Inc., New Brunswick, N. J.; CDL: 070702 C)

00109269 Goodwine, W. ( 1982) Letter sent to H. Jacoby dated Jul 27, 1982: Imazalil Citrus. ( Unpublished study received Jul 27, 1982 under 43813 1; submitted by Janssen R & D, Inc., New Brunswick, NJ; CDL: 071009 A)

00127900 Janssen R & D, Inc. ( 1983) [ Residues of Imazalil]. ( Compilation; unpublished study received Apr 28, 1983 under 43813 3; CDL: 071574 B)

00150020 Woestenborghs, R. ( 1985) Imazalil Residue in Wheat and Barley . Unpublished compilation prepared by Janssen Pharmaceutica. 44 p.

00157188 Janssen Research Products Information Service ( 1985) Residue and Analytical Methodology of Imazalil in Apples and Pears . Unpublished compilation. 172 p.

00157189 Van Leemput, L.; Swysen, E.; Woestenborghs, R.; et al. ( 1986) The Stability of Imazalil derived Residue on Oat Forage and Wheat Straw under Various Storage Conditions: Serial No. R 23979/ L17. Unpublished study prepared by Janssen Research Products Information Service. 25 p.

00157190 Van Leemput, L. ( 1986) Letter sent to P. Ruelene dated Feb 4, 1986: Imazalil related residues in forage, grain and straw samples grown from treated seeds: Samples collected in summer and winter of 1985. Prepared by Janssen Research Products Information Service. 151 p.

40509402 Leigh, W. ( 1987) Residues of Imazalil and Metabolite T 824 on Citrus Fruits Following Postharvest Application: Proj. ID X1 1988. Unpublished study prepared by Pent A Vate, Inc. 34 p.

40509403 Leigh, W. ( 1988) Residues of Imazalil and Metabolite T 824 on Citrus Fruits and Citrus Juice following Postharvest Application: Proj. ID X2 1988. Unpublished study prepared by Pent A Vate, Inc., Biological Testing and Research Laboratory. 22 p. Page 46 of 50 42012005 Van Leemput, L. ( 1991) Phase 3 Summary: Excretion, Metabolism and Tissue Depletion of [ 14 Carbon] Enilconazole (. . .) After Repeated Oral Dosing in Broiler Chickens: Lab Project Number: R23979/ 47: V5388. Unpublished study prepared by Janssen Pharmaceutical Foundation. 13 p.

42012006 Van Leemput, L. ( 1990) Revised Phase 3 Summary of Reformat with MRID 00027532 and Related MRID 00084643: The Metabolic Fate of Imazalil on Oranges: Lab Project No. R23979/ 18: 393. Unpublished study prepared by Janssen Pharmaceutica N. V. 12 p.

42012007 Van Leemput, L. ( 1990) Revised Phase 3 Summary of Reformat with MRID 00087542 and Related MRID 00087543: The Metabolic Fate of Imazalil on Banana Plants: Lab Project No. R23979/ 21: 379. Unpublished study prepared by Janssen Pharmaceutica N. V. 13 p.

42012008 Reulens, P. ( 1990) Revised Phase 3 Reformat of MRID 00027532: The Metabolic Fate of Imazalil on Oranges: Lab Project No. R23979/ 18: 393. Unpublished study prepared by Janssen Pharmaceutica N. V. 7 p.

42012009 Garnier, A. ( 1990) Revised Phase 3 Reformat of MRID 00087542 & Related MRID 00087543: The Metabolic Fate of Imazalil on Banana Plants: Lab Project No. R 23979/ 21: 379. Unpublished study prepared by Janssen Pharmaceutica N. V. 52 p.

42058701 Garnier, A. ( 1991) Analysis of Imazalil Derived Residues in Bananas: Lab Project Number: AGR3. Unpublished study prepared by Janssen Pharmaceutica N. V. 777 p.

42348301 Goodwine, W. ( 1992) Magnitude of Residue: Imazalil and Metabolite ( R14821) in Processing Fractions of Lemons, Oranges, and Grapefruits Resulting from Postharvest Treatment with Fungaflor 500 EC Raw Data Summary: Lab Project Number: AGR8. Unpublished study prepared by Janssen Pharmaceutica. 23 p.

42403102 Ruelens, P.; Garnier, A. ( 1992) Supplement to MRIDs 42012008 and 42012009: Response to Deficiencies Noted in EPA Correspondence Dated April 2, 1992: Lab Project Number: R23979/ FK1347. Unpublished study prepared by Janssen Pharmaceutica. 62 p.

42405501 Goodwine, W. ( 1992) Magnitude of Residue: Imazalil and Metabolite R14821 in Processing Fractions of Lemons, Oranges, and Grapefruits Resulting From Postharvest Treatment with Fungaflor 500 EC Survey of Imazalil and R14821 Residues in Citrus Oils: Lab Project Number: AGR8. Unpublished study prepared by PENT A Vate, Inc. 5 p.

42454801 Van Dijk, A. ( 1992) ( Carbon 14) Imazalil: Distribution, Degradation, Metabolism and Excretion After Repeated Oral Administration to a Lactating Goat: Lab Project Number: 296662: R23979/ FK1206. Unpublished study prepared by RCC Umweltchemie AG. 328 p.

42454802 Mannens, G. ( 1992) A Study on Milk and Tissue Metabolite of Imazalil in Lactating Goat After Repeated Oral Administration at 10 mg/ kg/ Day: Lab Project Number: R 23979/ FK1346. Unpublished study prepared by Janssen Research Foundation. 55 p.

42454803 Ligtvoet, T. ( 1992) A Validated Gas Chromatographic Method for the Determination of Total Regulable Residues of Imazalil on Bananas: Lab Project Number: AGR 16: 56. Unpublished study prepared by Janssen Research foundation. 66 p.

42454804 Woestenborghs, R. ( 1992) A Gas Liquid Chromatographic Method for Determining Total Regulable Residues of Imazalil in Citrus Fruit and Process Fractions: Method Validation and Comparison of the Research Method ( Using Internal Standard) with the Enforcement Method (' External Standard' Method): Lab Project Number: R 23979/ AGR 18. Unpublished study prepared by Janssen Research Foundation. 78 p. Page 47 of 50 42454805 Ligtvoet, T. ( 1992) A Gas Chromatographic Method for the Determination of Total Regulable Residues of Imazalil in Bananas: Lab Project Number: 54. Unpublished study prepared by Janssen Pharmaceutica. 30 p.

42454806 Goodwine, W. ( 1992) Imazalil and R14821 Residue Levels in Processing Fractions of Lemon, Oranges and Grapefruits Resulting from Postharvest Treatment with Fungaflor 500 EC: Lab Project Number: AGR8. Unpublished study prepared by Florida Dept. of Citrus, University of Florida and other. 689 p.

42593602 Van Dijk, A. ( 1992) Supplement 2 to MRID 42454801: ( Carbon14) Imazalil, Distribution, Degradation, Metabolism and Excretion after Repeated Oral Administration to a Lactating Goat: Lab Project Nos. 296662: R23979/ FK1206. Unpublished study prepared by R C C Umweltchemie Ag. 21 p.

42626901 O'Connor, J. ( 1992) Imazalil: Distribution and Metabolism in Spring Wheat: Final Report: Lab Project Number: 92/ 1046: JST/ 003/ IMAZALIL: 92/ JST003/ 1046. Unpublished study prepared by Life Science Research Limited. 166 p.

42626902 Ligtvoet, T. ( 1992) A Validated Gas Chromatographic Method for the Determination of Imazalil related Residues in Wheat and Barley ( Grain, Forage, and Straw): Final Report: Lab Project Number: 58. Unpublished study prepared by Janssen Research Foundation. 78 p.

42626903 Garnier, A. ( 1992) Storage Stability of Imazalil derived Residues in Bananas: Lab Project Number: AGR4. Unpublished study prepared by Janssen Research Foundation. 317 p.

42643301 Woestenborghs, R. ( 1993) Storage Stability of Imazalil Derived Residues in Citrus Fruit and Citrus by Products: Lab Project Number: R 23979/ AGR 7. Unpublished study prepared by Janssen Research Foundation. 201 p.

42710501 Garnier, A. ( 1991) Analysis of Imazalil Derived Residues in Bananas: Supplemental submission: Lab Project Number: AGR3. Unpublished study prepared by Janssen Pharmaceutica. 85 p.

42755301 Garnier, A. ( 1993) Storage Stability of Imazalil Derived Residues in Wheat: Final Report: Lab Project Number: AGR10. Unpublished study prepared by Plant Protection Division, Janssen Research Foundation. 285 p.

42838201 Mannens, G. ( 1992) Distribution, Degradation, Metabolism & Excretion After Repeated Oral Administration of ( carbon 14) Imazalil to a Lactating Goat: Supplement 1 to Final Report: Lab Project Number: R 23979/ FK1346. Unpublished study prepared by Janssen Research Foundation. 16 p.

42852001 Helmer, D. ( 1993) Magnitude of Residue: Imazalil and metabolite ( R14821) in Spring Barley Forage, Straw and Grain Grown from Imazalil Treated Seed: Lab Project Number: AGR12: AGR13: 920226. Unpublished study prepared by Janssen Pharmaceutica and Gustafson Research and Development Center. 214 p.

42852002 Helmer, D. ( 1993) Magnitude of Residue: Imazalil and metabolite ( R14821) in Spring Barley Forage, Straw and Grain Grown from Imazalil Treated Seed: Lab Project Number: AGR13: 922105: 922409. Unpublished study prepared by Janssen Pharmaceutica and Gustafson Research and Development Center. 248 p.

42868101 Helmer, D. ( 1993) Magnitude of Residue: Imazalil and Metabolite ( R14821) in Winter Wheat Forage, Straw and Grain Grown from Imazalil Treated Seed: Lab Project Number: AGR9: 91846. Unpublished study prepared by Gustafson Research and Development Center. 391 p.

42949401 Van Leemput, L. ( 1993) Imazalil: Distribution, Metabolism ( Nature of the Residue) and Excretion Study in the Laying Hen: Interim Report: Lab Project Number: 6116B: INTERIM 6116B. Unpublished study prepared by Life Science Research Ltd. 35 p. Page 48 of 50 43076101 Hallifax, D. ( 1993) IMAZALIL: Distribution, Metabolism ( Nature of the Residue) and Excretion Study in the Laying Hen: Final Report: Lab Project Number: JST/ 006: 93/ JST06/ 0615. Unpublished study prepared by Pharmaco LSR Ltd. 274 p.

43285001 Helmer, D. ( 1994) Magnitude of Residue: Imazalil and Metabolite ( R14821) in Winter Wheat Forage, Straw and Grain Grown from Imazalil Treated Seed: Lab Project Number: AGR30. Unpublished study prepared by Janssen Pharmaceutica in cooperation with Gustafson Research and Development Center and Diamond AgResearch. 365 p.

43308401 Van Leemput, L. ( 1994) Supplement to MRID 42012008: The Metabolic Fate of Imazalil on Oranges: Lab Project Number: R23979/ 18. Unpublished study prepared by Janssen Pharmaceutica. 13 p.

43965701 Mannens, G. ( 1996) Nature of Residue of Imazalil After Post Harvest Treatment of Bananas: Final Report: Lab Project Number: R023979/ FK1941: 736A: 736B. Unpublished study prepared by Janssen Research Plant Protection Dept. 111 p.

44051701 van Dijk, A. ( 1996) Feasibility of a Total Residue Method for Imazalil: Lab Project Number: 619481: AG 517. Unpublished study prepared by RCC Umweltchemie AG. 95 p.

44337701 van Dijk, A. ( 1997) Feasibility of Simultaneous Quantification of Imazalil and Relevant Metabolites in Milk and Organs/ Tissues ( Liver, Kidney, Muscle) of Ruminants: ( Final Report): Lab Project Number: 627581. Unpublished study prepared by RCC Umweltchemie Ag. 126 p.

44455601 van Dijk, A. ( 1997) Validation of Analytical Method for Simultaneous Determination of Residues of Imazalil and Two Relevant Metabolites in Ruminant Tissues and Milk: Lab Project Number: 651554. Unpublished study prepared by RCC Umweltchemie Ag. 242 p.

44532901 Remmerie, B. ( 1998) Validation of the Residue Analysis Method for Imazalil: Comparison of the Results obtained by Radio HPLC Analysis with Results from the GC ECD Method as Described in the Pesticide Analytical Manual ( PAM): Final Report: Lab Project Number: R023979/ FK2429. Unpublished study prepared by Janssen Research Foundation. 57 p.

44568301 van Dijk, A. ( 1998) Ruminant Feeding Study: Residues of Imazalil in Milk and Edible Tissues of Cattle: Lab Project Number: 663186. Unpublished study prepared by RCC Umweltchemie AG. 403 p.

92072019 Van Leemput, L. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00087542 and Related MRIDs 00087543. The Metabolic Fate of Imazalil on Banana Plants: Report No. R23979/ 21, Rec # 379. Prepared by Janssen Pharmaceutica. 10 p.

92072020 Van Leemput, L. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00027532. The Metabolic Fate of Imazalil on Oranges: Report No. R23979/ 18, Rec # 393. Prepared by Janssen Pharmaceutica. 10 p.

92072021 Meuldermans, W. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00027533 and Related MRIDs 00084644. Plasma and Milk Levels, Distribution, Excretion and Biotransformation of Imazalil after Repeated Administration to a Lactating Goat: Report No. R23979/ 14, Rec # 380. Prepared by Janssen Pharmaceutica. 8 p.

92072022 Woestenborghs, R. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00109269. A Gas liquid Chromatographic Method for Determining Total Regulable Residues of Imazalil in Citrus Fruit and Citrus By Products: Report Nos. R23979/ 30, Rec #' s 395 and 396. Prepared by Janssen Pharmaceutica. 10 p.

92072023 Woestenborghs, R. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00127900. Gas liquid Chromatographic Method for Determining [ sic] Total Regulable Residues of Imazalil in Seeds, Foliage and Straw from Page 49 of 50 Cereals and Cotton: Report Nos. R23979/ 39 and R23979/ 40, Rec #' s 378 and 377. Prepared by Janssen Pharmaceutica. 8 p.

92072024 Woestenborghs, R. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00109269. Electron Capture GC for Imazalil and Two Metabolites in Bovine Tissues and Milk: Report Nos. R23979/ 31 and R23979/ 32 Rec #' s 386 and 387. Prepared by Janssen Pharmaceutica. 11 p.

92072025 Van Leemput, L. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00157189. The Stability of Imazalil derived Residue on Oat Forage and Wheat Straw under Various Storage Conditions: Report No. R23979/ L19 Rec # 376. Prepared by Janssen Pharmaceutica. 8 p.

92072026 Helmer, D. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00127900 and Related MRIDs 00150020, 00157190. Determinations of Imazalil and T 824 Residue in Barley Forage, Straw and Grain Grown from Imazalil Treated Seed: Report No. 79/ 84, Rec # 374. Prepared by Janssen Pharmaceutica. 11 p.

92072027 Helmer, D. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 40509402 and Related MRIDs 40509403. Residues of Imazalil and Metabolite T 824 on Citrus Fruits following Postharvest Application: Report No. X1, 1988, Rec # 405. Prepared by PENT A VATE, INC. 17 p.

92072028 Helmer, D. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00127900. Determinations of Imazalil and T 824 Residue in Cotton Seed and Foliage Grown from Imazalil Treated Seed: Report No. R23979/ 39, Rec # 378. Prepared by Janssen Pharmaceutica. 8 p.

92072029 Helmer, D. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00127900 and Related MRIDs 00157190, 00150020. Determinations of Imazalil and T 824 Residue in Wheat Forage, Straw and Grain Grown from Imazalil Treated Seed: Report No. 860204, Rec # 375. Prepared by Janssen Pharmaceutica. 10 p.

92072030 Helmer, D. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 40509403. Residues of Imazalil and Metabolite T 824 on Processed Citrus Fruits following Postharvest Application: Report No. X1, Rec. # 405. Prepared by PENT A VATE, INC. 8 p.

92072035 Goodwine, W. ( 1990) Janssen Pharmaceutic Phase 3 Summary of MRID 00157188. On the Fate of Imazalil on Golden Delicious Apples during a Controlled Atmosphere Storage for Up to Seven Months: Report No. R23979/ L9, Rec # 400. Prepared by Janssen Pharmaceutica. 7 p.

92072036 Garnier, A. ( 1990) Janssen Pharmaceutic Phase 3 Reformat of MRID 00087542 and Related MRIDs 00087543. The Metabolic Fate of Imazalil on Banana Plants: Report No. R23979/ 21, Rec # 379. Prepared by Janssen Pharmaceutica. 36 p.

92072037 Ruelens, P. ( 1990) Janssen Pharmaceutic Phase 3 Reformat of MRID 00027532. The Metabolic Fate of Imazalil on Oranges: Report No. R23979/ 18, Rec # 393. Prepared by Janssen Pharmaceutica. 51 p.

92072038 Garnier, A. ( 1990) Janssen Pharmaceutic Phase 3 Reformat of MRID 00027533 and Related MRIDs 00084644. Plasma and Milk Levels, Distribution, Excretion and Biotransformation of Imazalil after Repeated Administration to a Lactating Goat: Report No. R23979/ 14, Rec # 380. Prepared by Janssen Pharmaceutica. 78 p.

92072039 Woestenborghs, R.; Van Leemput, L. ( 1990) Janssen Pharmaceutic Phase 3 Reformat of MRID 00127900. Determinations of Imazalil and T 824 Residue in Cotton Seed and Foliage Grown from Imazalil Treated Seed: Report No. R23979/ 39 Rec # 378. Prepared by Janssen Pharmaceutica N. V. 18 p. Page 50 of 50 92072040 Leigh, W. ( 1990) Janssen Pharmaceutic Phase 3 Reformat of MRID 40509402 and Related MRIDs 40509403. Residues of Imazalil and Metabolite T 824 on Citrus Fruits Following Postharvest Application: Report No. X1, 1988, Rec # 405. Prepared by Janssen Pharmaceutica. 137 p.

92072041 Helmer, D.; Goodwine, W. ( 1990) Janssen Pharmaceutic Phase 3 Reformat of MRID 00157900 and Related MRIDs 00127900, 00157190. Determinations of Imazalil and T 824 Residue in Wheat Forage, Straw and Grain Grown from Imazalil Treated Seed: Report No. 860204, Rec # 375. Prepared by Janssen Pharmaceutica, N. V. 148 p.

92072042 Helmer, D.; Goodwine, W. ( 1990) Janssen Pharmaceutic Phase 3 Reformat of MRID 00127900 and Related MRIDs 00157190, 00150026. Determinations of Imazalil and T 824 Residue in Barley Forage, Straw and Grain Grown from Imazalil Treated Seed: Report No. 79/ 84, Rec. # 374. Prepared by Janssen Pharmaceutica N. V. 146 p.