UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM Date: December 14, 2005 Subject: Formetanate Hydrochloride HED Revised Chemistry Chapter of the RED: Summary of Analytical Chemistry and Residue Data ( Phase 4).

DP Barcode: D324543 PC Code: 097301 From: Danette Drew, Chemist Reregistration Branch 3 Health Effects Division ( 7509C)

Through: Catherine Eiden, Branch Chief Reregistration Branch 3 Health Effects Division ( 7509C)

To: Demson Fuller Reregistration Branch 2 Special Review and Reregistration Branch ( 7509C)

The document " Formetanate Hydrochloride HED Revised Chemistry Chapter of the RED: Summary of Analytical Chemistry and Residue Data, 3/ 27/ 03, D289010" has been revised herein to reflect current Special Local Need ( SLN) registrations.      2    38 Executive Summary Formetanate hydrochloride { m[[( dimethylamino) methylene] amino] phenyl methylcarbamate hydrochloride} is a miticide/ insecticide used on a variety of fruits and alfalfa grown for seed. The 92% wettable powder formulation ( Carzol ® SP) contains formetanate hydrochloride ( HCl) as the sole active ingredient and is registered for foliar or dormant applications using ground or aerial equipment. The registrant is Gowan Company ( transferred from Aventis CropScience, formerly AgrEvo USA Company, on 4/ 30/ 01).

Formetanate HCl was the subject of a Reregistration Standard Guidance Document dated 9/ 83; the Residue Chemistry Chapter of the Guidance Document was completed on 9/ 30/ 82. The Residue Chemistry Chapter of the Formetanate HCl Second Round Review ( SRR) was issued on 5/ 10/ 89. The Residue Chemistry Chapter for the Reregistration Eligibility Decision ( RED) was completed on 4/ 18/ 97 and the resulting preliminary HED Risk Assessment was issued 4/ 6/ 99. Subsequently, a Memorandum of Agreement ( MOA) between the registrant and the EPA was issued ( dated 10/ 14/ 99). This MOA was drawn because the Agency is concerned that formetanate HCl presents dietary, worker, and ecological risks that are not consistent with the FIFRA mandate that pesticides must not pose unreasonable adverse effects.

The MOA stipulated label amendments to lower application rates, increase PHIs ( pre harvest intervals) and limit uses to certain crops in an effort to reduce risks by reducing exposures associated with formetanate HCl. The MOA requirements, for continued use of formetanate HCl on food/ feed crops, as they pertain to residue chemistry, include the following.

( A) Label instructions limiting use to one application of one product containing formetanate hydrochloride per growing season, for all crops.

( B) Label instructions prohibiting use in Florida.

[( C) Label instructions prohibiting use on greenhouse grown ornamental plants.]

( D) Label instruction prohibiting its use on plums and prunes.

( E) Label instructions restricting certain uses as follows:

· Pome fruits ( apples and pears): Pesticide products containing the active ingredient formetanate hydrochloride shall not be applied after bloom. Late season applications may be made to control stink bugs, lygus bugs, and pear rust mites in CA, OR, WA, and ID, upon written approval on a case by case basis by the State agency responsible for enforcement of FIFRA, or authorized by that State agency.

· Peaches and nectarines: Pesticide products containing the active ingredient formetanate hydrochloride shall not be applied after shuck fall.

· Citrus ( oranges, lemons, limes, grapefruit, tangelos and tangerines): Pesticide products containing the active ingredient formetanate hydrochloride shall not be applied after fruit reach one inch in diameter. Pesticide products containing the active ingredient formetanate hydrochloride may be applied to overcropped grapefruits and Valencia oranges above one inch in      3    38 diameter, provided that a preharvest interval (" PHI") of 30 days is observed.

( F) Label instruction requiring a preharvest interval (" PHI") of 21 days for alfalfa ( grown for seed).

( G) Label instructions establishing a maximum application rate of not more than 0.92 pounds of active ingredient per acre on alfalfa grown for seed only.

( H) Label instructions establishing a maximum application rate of not more than 1.15 pounds of active ingredient per acre for all food crops.

( I) Label instructions restricting the replanting of fields after harvest of alfalfa treated with pesticide products containing the active ingredient formetanate hydrochloride, as follows:

Leafy vegetables shall not be planted until 30 days after harvest of treated alfalfa.

Root crops shall not be planted until 120 days after harvest of treated alfalfa.

Small grains and all other crops shall not be planted until 12 months after harvest of treated alfalfa.

The MOA also required that the registrant generate certain data reflecting the new reduced rates and increased PHIs including field trials ( OPPTS 860.1500) for stone fruit, pome fruit, and citrus. A confirmatory orchard crop ( stone or pome fruit) metabolism study was also required. The results of those submissions are summarized in this document. This document updates the previous chemistry chapter ( 4/ 97) and includes only those uses allowed by the MOA.

The nature of the residue of formetanate HCl in livestock and plants has been adequately delineated. Formetanate HCl per se was not identified in the ruminant and poultry metabolism studies. The two cholinesterase inhibiting metabolites ( 3 formamidophenyl methylcarbamate and 3 aminophenyl methylcarbamate) found in milk, liver, and kidney have been determined to be not of significant toxicological concern ( 3/ 15/ 99 Metabolism Assessment Review Committee, MARC, decision). Therefore, no tolerances are required for formetanate HCl and its metabolites for livestock commodities. An adequate method is available for data collection in livestock commodities. This method is similar to Method I of PAM ( Pesticide Analytical Manual) Vol. II. Because tolerances for livestock commodities are not required, the registrant is not required at this time to submit an independent laboratory validation of this method.

The results of the alfalfa, lemon, and orange seedling metabolism studies indicate that the metabolic pathway in plants is similar with resulting metabolites containing the formamidine moiety. Formetanate HCl was the only compound identified in the extractable radioactivity in/ on peaches. The majority of the terminal residue in plants consists mainly of parent compound. The majority of formetanate residues appear on the surface ( peel) of fruit. Parent formetanate HCl is the residue of concern to be included in the tolerance expression and the dietary risk assessment.

An adequate method is available for tolerance enforcement for plant commodities. The gas chromatography/ electron capture detection ( GC/ ECD) Method I is listed in the PAM Vol. II and      4    38 involves hydrolysis of residues to 3 aminophenol and, therefore, determines residues of formetanate HCl and all metabolites convertible to 3 aminophenol.

An adequate method for data collection for plant commodities has been submitted by the registrant. The high performance liquid chromatography ( HPLC) method determines residues of the parent compound formetanate only. An independent laboratory validation ( ILV) of the method was also submitted and found adequate. If the registrant proposes that this be a new enforcement method then the method should be radiovalidated and an Agency method validation should be performed.

Tolerances are established for residues of formetanate hydrochloride per se in or on apple; pear; peach; nectarine; orange; lemon; lime; grapefruit; tangerine; and plum, prune, fresh [ 40CFR 180.276]. According to the MOA, the only food/ feed uses allowed are those on apple, pear, peach, nectarine, orange, lemon, lime, grapefruit, tangelo, tangerine, and alfalfa grown for seed. Formetanate HCl tolerances are reassessed in this document for the permitted food uses ( see Table 6). The tolerances were reassessed based on limited field trial data performed at the reduced rate and increased PHIs. In general the field trial data did not satisfy the requirements for number of field trials ( see " Residue Chemistry Deficiencies" below). At such time as the additional field trials are received and deemed adequate, the reassessed tolerances will be reevaluated.

Residue Chemistry Deficiencies · 860.1300 Nature of the Residue Pending submission of adequate information regarding the use of peach leaves to support the storage stability of peach extract, the requirement for plant metabolism data for formetanate HCl will be fulfilled.

· 860.1500 Crop Field Trials Tolerance reassessment will be reevaluated upon receipt and acceptance of the following outstanding data: Apple: Four additional field trials in Regions 1, 5, and 11 must be conducted ( the trials should include an early and late season application as allowed in the MOA); Pear: Two additional field trials in Regions 10 and 11 must be conducted ( the trials should include an early and late season application as allowed in the MOA); Peach: Three additional field trials in Regions 1 ( or 2), 5, and 10 must be submitted. Nectarine: Details pertaining to the field procedures used in the at harvest study ( i. e., application method and timing, equipment, spray volumes, tank mix adjuvants) and multiple application rates must be provided.; Citrus Fruit: Five additional orange field trials in Regions 6 and 10 must be conducted. An additional lemon trial ( Region 10) and 2 additional grapefruit trials ( Regions 6, 10) are also required.      5    38 Chemical Overview TABLE 1. Test Compound Nomenclature Compound Chemical Structure Common name Formetanate HCl Company experimental name Carzol ®

IUPAC name 3 dimethylaminomethyleneaminophenyl methylcarbamate monohydrochloride CAS name Methanimidamide, N, N dimethyl N [ 3[[( methylamino) carbonyl] oxy] phenyl], monohydrochloride CAS # 23422 53 9 TABLE 2. Physicochemical Properties 1 Parameter Value Melting point/ range 191.2 C pH   2.5 ( 10% solution)

Density 200 450 g/ L Water solubility ( 25 ° C) 82.2 g/ 100mL Solvent solubility ( g/ 100mL at 20 ° C) n hexane < 0.00005 ethylacetate 0.0001 toluene 0.001 acetone 0.007 dichloromethane 0.03 methanol 28.3 Vapor pressure at 25 ° C 1.6 x 10 6 mmHg Dissociation constant ( pKa) 8.0 Octanol/ water partition coefficient ( KOW) < 0.002 UV/ visible absorption spectrum 2   max: Molar Absorbance Absorbance Media Maximum Coefficient Acidic 208 nm 22130 250 nm 16603 Neutral 208 nm 21934 250 nm 16540 Basic 236 nm 23015 Results indicate no significant change in absorption in acidic and neutral media; however, a significant change in the wavelength maximum was observed in basic media.

1 Information collected from a 92% technical product or from D173714, 8/ 26/ 92, W. Smith. 2 Information collected from D270875,11/ 7/ 02, D. Drew.      6    38 860.1200 Directions for Use An OPPIN search conducted on 12/ 14/ 05 identified one formetanate HCl end use product ( EP) registered to Gowan Co. for use on food/ feed crops ( Table 3). There are two Special Local Need ( SLN) registrations under FIFRA Section 24.

HED has examined the registered food/ feed use patterns and reevaluated the available residue chemistry database for adequacy in supporting these use patterns. A comprehensive summary of formetanate HCl food/ feed use patterns, based on the product labels registered to Gowan, is presented in Table 4. The status of reregistration requirements for each guideline topic listed in Table 7 is based on the use patterns registered by the basic producer. 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.

The registered use of formetanate HCl on alfalfa grown for seed in CA, ID, NV, OR, WA and AZ is considered to be a non food use, since these states have established programs designed to prevent diversion of alfalfa forage, hay, seed, and seed screenings ( from treated alfalfa grown for seed) to livestock feed.

Table 3. Formetanate HCl EP with Food/ Feed Uses Registered to Gowan EPA Reg. No. Label Acceptance Date Formulation Product Name 10163 2651 7/ 23/ 02 92% WP Carzol ® SP in Water Soluble Packaging Miticide/ Insecticide 1 Including SLNs AZ030012, ID030016 ( alfalfa for seed [ non food use]) TABLE 4 ( Formerly Table A2) FOOD/ FEED USE PATTERNS SUMMARY FOR Formetanate hydrochloride ( CASE 0091)      7    38 SITE NAME Product/ Site Limitations Application Type ( for any Reg.# at any rate) ( aggregate) Application Timing ( for any Reg.# at any rate) Application Equipment ( for any Reg.# at any rate)

( aggregate) Max. Single Appl.

Rate to a Single Site ( AI unless notedotherwise) InconvertibleLabel ( L) DosagesAlso Present MaxSeaso nalRate ( L) Dosage sAlsoPres ent Max. #

Apps Per Crop Cycle ( cc) and Year ( at any rate) Min Retmt Intv ( days)

( at any rate) PHI/ PGI/ PSIUse Limitations ( at any rate)

( May not apply to all Reg. # s within group)

ALFALFA 21 day( s) preharvest interval. Do not apply through any type of irrigation system. Do not contaminate water, food or feed.

Do not contaminate water, food, or feed by storage or disposal. Do not feed to livestock. Do not graze livestock in treated areas.

Do not graze livestock in treated orchards. Do not graze or feed treated crop to livestock. For terrestrial uses, do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark.

Formulation is contained within water soluble bags. Grown for seed only.

Rotational/ plant back crop restriction.

Geographic allowable: AZ CA ID NV OR WAGeographic disallowable: FL A second application ( post bloom) may be made to control lygus bugs in AZ and ID.

Low volume spray ( concentrate)/ Spray FoliarAircraft/ Ground .92 lb A 1.84 lb/ cc 2/ ccNS NS Low volume spray ( concentrate)/ Spray PrebloomAircraft/ Ground .92 lb A .92 lb/ cc 1/ ccNS NS Geographic disallowable: CA APPLE Do not apply after petal fall. Do not apply through any type of irrigation system. Do not contaminate water, food, or feed by storage or disposal.

Do not graze livestock in treated orchards. For terrestrial uses,

do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark. Formulation is contained within water soluble bags.

[ A second, later season, application may be made to control stink bugs, lygus bugs, and pear rust mites in CA, OR, WA, and ID only after written approval by the State agency responsible for enforcement of FIFRAor authorized by that State agency. ]

Geographic disallowable: FL High volume spray ( dilute)/ Low volume spray ( concentrate) BloomHigh volume ground sprayer/ Low volume sprayer 1.15 lb A 1.15 lb/ cc 2/ ccNS NS High volume spray ( dilute)/ Low volume spray ( concentrate) FoliarHigh volume ground sprayer/ Low volume sprayer 1.15 lb A 1.15 lb/ cc 2/ ccNS NS Spray Petal fall through foliarSprayer 1.15 lb A NS 1/ ccNS NS Geographic allowable: WA Late Season application TABLE 4 ( Formerly Table A2) FOOD/ FEED USE PATTERNS SUMMARY FOR Formetanate hydrochloride ( CASE 0091)      8    38 High volume spray ( dilute)/ Low volume spray ( concentrate) Petal fallHigh volume ground sprayer/ Low volume sprayer 1.15 lb A 1.15 lb/ cc 2/ ccNS NS High volume spray ( dilute)/ Low volume spray ( concentrate) PinkHigh volume ground sprayer/ Low volume sprayer 1.15 lb A 1.15 lb/ cc 2/ ccNS NS High volume spray ( dilute)/ Low volume spray ( concentrate)

PrebloomAircraft/ High volume ground sprayer/ Low volume sprayer .92 lb A 1.15 lb/ cc 2/ ccNS NS ( Geographic disallowable:

CA ,

for campylomma control)

Spray When neededAircraft/ Ground 1.15 lb A NS NSNS NS GRAPEFRUIT Do not apply through any type of irrigation system. Do not contaminate water,

food, or feed by storage or disposal. Do not graze livestock in treated orchards.

For terrestrial uses, do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark. Formulation is contained within water soluble bags. Do not apply after fruit reach a diameter of one inch.

If unharvested grapefruit and Valencia oranges are present from the previous crop, an application may be made to the new crop. A preharvest interval of 30 days must be observed for the unharvested crop. Geographic disallowable: FL High volume spray ( dilute)/ Spray FoliarAircraft/ High volume ground sprayer/ Sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS 30 day( s) preharvest interval.

Geographic allowable: AZ CA TX LEMON Do not apply through any type of irrigation system. Do not contaminate water,

food, or feed by storage or disposal. Do not graze livestock in treated orchards.

For terrestrial uses, do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark. Formulation is contained within water soluble bags. Do not apply after fruit reach a diameter of one inch. Geographic disallowable: FL Broadcast/ High volume spray ( dilute)/ Low volume spray ( concentrate)/ Spray FoliarAircraft/ High volume ground sprayer/ Sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS 60 day( s) preharvest interval.

Geographic allowable: AZ CA TX LIME Do not apply through any type of irrigation system. Do not contaminate water,

food, or feed by storage or disposal. Do not graze livestock in treated orchards.

For terrestrial uses, do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark. Formulation is contained within water soluble bags. Do not apply after fruit reach a diameter of one inch Geographic disallowable: FL Spray FoliarAircraft/ Sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS Geographic allowable: CA TABLE 4 ( Formerly Table A2) FOOD/ FEED USE PATTERNS SUMMARY FOR Formetanate hydrochloride ( CASE 0091)      9    38 NECTARINE Do not apply after petal fall. Do not apply through any type of irrigation system. Do not contaminate water, food, or feed by storage or disposal.

Do not graze livestock in treated orchards. For terrestrial uses,

do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark. Formulation is contained within water soluble bags.

Geographic disallowable: FL High volume spray ( dilute)/ Low volume spray ( concentrate)

BloomAircraft/ High volume ground sprayer/ Low volume sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS High volume spray ( dilute)/ Low volume spray ( concentrate) Petal fallAircraft/ High volume ground sprayer/ Low volume sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS ORANGE Do not apply through any type of irrigation system. Do not contaminate water,

food, or feed by storage or disposal. Do not graze livestock in treated orchards.

For terrestrial uses, do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark. Formulation is contained within water soluble bags. Do not apply after fruit reach a diameter of one inch. If unharvested grapefruit and Valencia oranges are present from the previous crop, an application may be made to the new crop. A preharvest interval of 30 days must be oserved for the unharvested crop. Geographic disallowable: FL High volume spray ( dilute)/ Spray FoliarAircraft/ High volume ground sprayer/ Sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS 30 day( s) preharvest interval.

Geographic allowable: AZ CA TX PEACH Do not apply after petal fall. Do not apply through any type of irrigation system. Do not contaminate water, food, or feed by storage or disposal.

Do not graze livestock in treated orchards. For terrestrial uses,

do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark. Formulation is contained within water soluble bags.

Geographic disallowable: FL High volume spray ( dilute)/ Low volume spray ( concentrate) Petal FallHigh volume ground sprayer/ Low volume sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS PEAR Do not apply after petal fall. Do not apply through any type of irrigation system. Do not contaminate water, food, or feed by storage or disposal.

Do not graze livestock in treated orchards. For terrestrial uses,

do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark. Formulation is contained within water soluble bags.

[ A second, later season, application may be made to control stink bugs, lygus bugs, and pear rust mites in CA, OR, WA, and ID only after written approval by the State agency responsible for enforcement of FIFRAor authorized by that State agency. ]

Geographic disallowable: FL High volume spray ( dilute)/ Low volume spray ( concentrate) FoliarHigh 1.15 lb A 1.15 NSNS NS TABLE 4 ( Formerly Table A2) FOOD/ FEED USE PATTERNS SUMMARY FOR Formetanate hydrochloride ( CASE 0091)      10    38 volume ground sprayer/ Low volume sprayer lb/ cc Spray Petal fall through foliarSprayer 1.15 lb A NS 1/ ccNS NS Spray PostharvestSprayer 1.15 lb A NS 1/ ccNS NS Geographic allowable: WA TABLE 4 ( Formerly Table A2) FOOD/ FEED USE PATTERNS SUMMARY FOR Formetanate hydrochloride ( CASE 0091)

11 Spray When neededGround 1.15 lb A NS NSNS NS TANGELO D o not apply through any type of irrigation system. food, or feed by storage or disposal. Do not gra For terrestrial uses, do not apply directly to wa present or to intertidal areas below the mean high water mark. within water soluble bags. Do not appl inch. Geographic disallowabl Spray FoliarAircraft/ Sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS G TANGERINES Do not apply through any type of irrigation system. food, or feed by storage or disposal. Do not gra For terrestrial uses, do not apply directly to wa present or to intertidal areas below the mean high water mark. within water soluble bags. Do not appl inch. Geographic disallowable: FL High volume spray ( dilute)/ Spray FoliarAircraft/ High volume ground sprayer/ Sprayer 1.15 lb A 1.15 lb/ cc 1/ ccNS NS G Product Number( s) Contained in this Report : 010163 00265 ; AZ030012, ID030016 860.1300 Nature of the Residue  Plants Tolerances are established for residues of formetanate hydrochloride per se in or on apple; pear; peach; nectarine; orange; lemon; lime; grapefruit; tangerine; and plum, prune, fresh [ 40CFR 180.276]. According to the 10/ 99 MOA, the only food/ feed uses allowed are those on apples, pears, peaches, nectarines, oranges, lemons, limes, grapefruit, tangelos, tangerines, and alfalfa grown for seed.

The qualitative nature of the residue in alfalfa is adequately understood; the majority of the terminal residue in alfalfa forage consists mainly of parent compound and related compounds containing the 3 aminophenol moiety.

A lemon study ( MRID 42684605) was deemed inadequate because the test substance was not      12    38 applied foliarly, and therefore the resulting metabolic profile did not take into account metabolites resulting from translocation. In addition, the total radioactive residue ( TRR) was not properly determined in the whole fruit. The lemon metabolism study indicated that parent formetanate was the major residue and metabolites were identified as 3 dimethylaminomethylenaminophenol, 3 formaminophenyl   methyl carbamate ( SN35902), and 3 formaminophenol ( SN38075) ( D189020, C. Swartz, 1/ 3/ 97). The MARC determined that SN35902 and SN38075 were not of toxicological concern as they are 86 and 48 times, respectively, less potent as cholinesterase inhibitors than parent formetanate ( 3/ 15/ 99 MARC).

A literature study on orange seedlings also shows that the metabolic pathway in plants proceeds primarily by hydrolysis to SN35902 ( major metabolite, 11% TRR) and SN38075 and related conjugates. The phenol ( SN38075) is deformylated to 3 aminophenol and acelylated to 3 acetamidophenol ( Roberts, Terry, and David Hudson,( editors). Metabolic Pathways of Agrochemicals, Part 2: Insecticides and Fungicides, Cambridge: The Royal Society of Chemistry, 1999).

Gowan Company submitted a study investigating the metabolism of [ 14C] formetanate hydrochloride in peach as a result of the 10/ 99 MOA ( MRID 45595601). Radiolabeled [ 14C] formetanate HCl, uniformly labeled in the phenyl ring, was applied to two separate branches of a peach tree at rates equivalent to 1.15 lb ai/ A ( 1x rate) and 11.5 lb ai/ A ( 10x rate). Samples of peach leaves were harvested on the day of treatment, and samples of immature and mature fruit were collected from each branch at 33 and 91 days posttreatment, respectively.

TRR were determined in samples of peach leaves and immature peaches by summing radioactivity in the extracts and the nonextractable radioactivity. TRR in mature peaches were determined by combustion/ LSC. Samples of leaves were rinsed with 0.1% HCl to extract radioactivity. Samples of immature peaches were rinsed and then extracted with 0.1% HCl, and samples of mature peaches were extracted with 0.1% HCl. The aqueous extracts of peach leaves ( both treatment rates) and immature and mature peaches ( 10x rate only) were analyzed by HPLC. Peach leaf extracts were also analyzed by thin layer chromatography ( TLC).

Following treatment of a branch of a peach tree with [ 14C] formetanate HCl at 10X rate ( 11.5 lb ai/ A), TRR were 112 187 ppm in/ on peach leaves harvested 0 days posttreatment, 0.014 0.026 ppm in/ on immature peaches harvested 33 days posttreatment, and 0.004 0.008 ppm in/ on mature peaches harvested 91 days posttreatment. Approximately 87 92% of TRR were extractable from peach leaves, and approximately 48 77% of TRR were extractable from immature and mature peaches. Only extracts of peach leaves from this treatment rate were analyzed. Formetanate HCl was identified at 80.2 85.3% TRR; the remainder of the aqueous extractable radioactivity consisted of unknowns, each of which was present at   5.2% TRR.

Following treatment of a branch of a peach tree with [ 14C] formetanate HCl at 11.5 lb ai/ A, TRR were 594 1130 ppm in/ on peach leaves harvested 0 days posttreatment, 0.170 0.233 ppm in/ on immature peaches harvested 33 days posttreatment, and 0.033 0.110 ppm in/ on mature peaches harvested 91 days posttreatment. Approximately 93 95% of TRR were extractable from peach leaves, and approximately 72 76% of TRR were extractable from immature and mature peaches. Formetanate HCl was the only compound identified in the extractable radioactivity, at 86.4 89.4% TRR ( 514 1000 ppm) in/ on peach leaves, 49% TRR ( 0.115 ppm) in/ on immature peaches, and 47% TRR ( 0.052 ppm) in/ on mature peaches. The remainder of the aqueous extractable radioactivity consisted of unknowns, each of which was present at   7.4% TRR.

This study did not attempt to extract or determine organic activity or bound residues; only an      13    38 aqueous HCl extraction was performed, yielding 72% ( 0.079 ppm) TRR on mature peaches. The remaining 0.031 ppm ( 28%) TRR were labeled as " nonextractable." Nonetheless, the majority of the TRR in/ on peaches are identified as parent and the unknowns are less than 0.008 ppm. Also, the results of the alfalfa, lemon, and orange seedling studies indicate that the metabolic pathway in plants is similar with resulting metabolites containing the formamidine moiety. Based on that information and that the enforcement method is a common moiety method ( all metabolites converted to 3 aminophenol), additional data on the metabolism of formetanate residues on peaches are not required at this time; however, the peach study is inadequate to satisfy data requirements for a plant metabolism study with peach because additional data are required pertaining to storage stability. The registrant should provide supporting chromatographic evidence for their statement that a day 0 leaf extract was found to be stable for 13 months, and justification for use of a day 0 leaf extract to support the storage of an extract of peach fruit for up to 9 months prior to analysis.

Pending submission of adequate information regarding the use peach leaves to support the storage stability of peach extract, the requirement for plant metabolism data for formetanate HCl will be fulfilled.

860.1300 Nature of the Residue  Livestock The reregistration data requirement for livestock metabolism is fulfilled. Acceptable studies depicting the qualitative nature of the residue in ruminants and poultry have been submitted. Formetanate hydrochloride per se was not identified in the metabolism studies. The two cholinesterase inhibiting metabolites ( 3 formamidophenyl methylcarbamate and 3 aminophenyl methylcarbamate) found in milk, liver, and kidney have been determined to be not of significant toxicological concern. Therefore, no tolerances are required for formetanate hydrochloride and its metabolites for livestock commodities ( 3/ 15/ 99 MARC).

860.1340 Residue Analytical Methods Adequate methods are available for data collection and tolerance enforcement for plant commodities. A GC/ ECD method ( Method I) is listed in the PAM Vol. II for the enforcement of formetanate hydrochloride tolerances in fruits. This method involves hydrolysis of residues to 3 aminophenol and, therefore, determines residues of formetanate and all metabolites convertible to 3 aminophenol. Methods A and A( 1) are two TLC colorimetric methods deemed adequate for data collection for the respective purposes of formetanate hydrochloride residue confirmation and determination of formetanate hydrochloride hydrolysis products.

An adequate method for data collection for plant commodities has been submitted by the registrant. The HPLC method determines residues of the parent formetanate only. An ILV of the method was also submittted and found adequate. If the registrant proposes that this be a new enforcement method, the method should be radiovalidated and an Agency method validation should be performed.

An adequate method is available for data collection in livestock commodities. This method is similar to Method I of PAM Vol. II, but includes an additional acid hydrolysis step to release bound residues. Because tolerances for livestock commodities are not required, the registrant is not required at this time to submit an ILV of this method.      14    38 860.1360 Multiresidue Methods The January 1994 FDA PESTDATA database ( PAM Volume I, Appendix I, 10/ 99 update) has no information pertaining to the recovery of formetanate HCl through multiresidue methods ( MRMs). The registrant attempted to conduct methods trials with formetanate HCl ( Protocols A through E) but these submissions did not provide information regarding recoveries via FDA's MRMs. This is not a deficiency as water soluble formetanate HCl would not be expected to extract efficiently via FDA's MRMs.

860.1380 Storage Stability The reregistration requirements for storage stability data are fulfilled. The available storage stability data indicate that formetanate residues are generally stable in frozen apples and stone fruits for up to 33 months, and in frozen citrus fruits for up to 2 years. Residues of the metabolite 3 formamidophenyl N methylcarbamate declined after storage intervals of 9 to 33 months. This metabolite is considered not of significant toxicological concern. Storage stability data support the storage intervals used in the field trial studies.

860.1400 Water, Fish, and Irrigated Crops Formetanate hydrochloride is not presently registered for direct use on water and aquatic food and feed crops; therefore, no residue chemistry data are required under this guideline topic.

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

860.1480 Meat, Milk, Poultry, and Eggs Adequate livestock feeding studies have been submitted to the Agency. The reregistration requirements for magnitude of the residue in meat, milk, poultry, and eggs are fulfilled.

Milk and the fat, meat, and meat byproducts of cattle, goats, hogs, horses, and sheep: The maximum theoretical dietary burdens of formetanate HCl to beef and dairy cattle are 1.5 ppm and 0.75 ppm, respectively, based on a diet consisting of wet apple pomace ( 40% and 20%, respectively, of the diet). An adequate dairy cattle feeding study has been submitted; the study reflected dosing with formetanate HCl ~ 20, 60, and 200 ppm for 28 31 days. These dosing levels represent 13X, 40X, and 130X the maximum theoretical dietary burden to beef cattle and 27X, 80X, and 270X the maximum theoretical dietary burden to dairy cattle.

No detectable residues of parent formetanate were observed in milk, fat, muscle, kidney, and liver. The two cholinesterase inhibiting metabolites ( 3 formamidophenyl methylcarbamate [ SN 35902] and 3 aminophenyl methylcarbamate [ SN 38075]) found in dairy milk, liver, and kidney have been determined to be not of significant toxicological concern as a result of an in vitro study. The study found that these metabolites were 86 and 48 times less potent as cholinesterase inhibitors than parent formetanate. These findings, along with the fact that these two metabolites      15    38 are found in rats and thus their toxicity is assessed when the parent compound is assessed, indicate that the tolerance expression does not need to include these metabolites ( J. Doherty, 12/ 10/ 98, DP: D249197; MARC Decisions 1/ 12/ 99, D252123 and 3/ 15/ 99, D254395). Therefore, no tolerances are required for formetanate hydrochloride and its metabolites for milk and the fat, meat, and meat byproducts of cattle, goats, horses, and sheep ( 40CFR 180.6( a)( 3)).

A 2/ 19/ 97 HED metabolism committee decision determined that for purposes of risk assessment, only the potentially cholinesterase inhibiting metabolites ( 3 formamidophenyl methylcarbamate and 3 aminophenyl methylcarbamate) should be considered for livestock commodities. These metabolites were found in dairy milk, liver, and kidney at combined levels of 0.012 ppm, 0.018 ppm, and 0.055 ppm, respectively, using a 100x feeding rate. Since these two metabolites have been determined as not of significant toxicological concern, milk and the fat, meat, and meat byproducts of cattle, goats, horses, and sheep do not need to be included in the dietary risk assessment for formetanate HCl.

Fat, meat, and meat byproducts of hogs: No tolerances are required for the fat, meat, and meat byproducts of hogs because there are no registered uses of formetanate hydrochloride on any swine feed item.

Eggs and the fat, meat, and meat byproducts of poultry: Currently, there are no registered uses of formetanate hydrochloride on any poultry feed item, and there are no registered direct animal treatments of formetanate hydrochloride to poultry; therefore, no residue chemistry data are required for poultry commodities.

860.1500 Crop Field Trials Tolerances are established for residues of formetanate hydrochloride per se in or on apple; pear; peach; nectarine; orange; lemon; lime; grapefruit; tangerine; and plum, prune, fresh [ 40CFR 180.276]. According to the 10/ 99 MOA, the only food/ feed uses allowed are those on apple, pear, peach, nectarine, orange, lemon, lime, grapefruit, tangelo, tangerine, and alfalfa grown for seed.

Limited residue data are available to support uses on apple, pear, peach, nectarine orange, lemon, lime, grapefruit, tangelo and tangerine at the MOA maximum application rate of 1.15 lb a. i./ A. The registrant submitted field trial studies at the new reduced rate for apple, pear, peach, nectarine, orange, grapefruit and lemon. The number of trials for these studies were determined to be inadequate.

Field trial data are no longer required for alfalfa commodities since the use on alfalfa grown for seed in CA, ID, NV, OR, WA and AZ is considered to be a non food use.

Table 5. Summary of Residues from the Crop Field Trials with Formetanate HCl Formetanate only ( HPLC method) Residues ( ppm) Formetanate and Metabolites ( GC/ ECD common moeity method) Residues ( ppm) Crop Matrix App. Rate ( lb ai/ A) PHI ( days)

Mean HAFT Min. Max. Mean HAFT Min. Max.

Pear and Apple ( label rate = 1.15 lb ai/ A lb ai/ A total application rate, not to be applied after petal fall1)

Pear 1.15 ~ 120 0.015 < 0.030 < 0.030 < 0.030 0.010 < 0.020 < 0.020 < 0.020 Apple 1.15 ~ 120 0.015 < 0.030 < 0.030 < 0.030 0.014 < 0.022 < 0.020 0.024      16    38 Apple 2.30 14 0.38 0.38 0.34 0.43 0.26 0.26 0.24 0.28 Peach and Nectarine ( label rate = 1.15 lb ai/ A lb ai/ A total application rate, not to be applied after shuck fall)

Peach 1.15 57 124 0.015 < 0.030 < 0.030 < 0.030 0.010 < 0.020 < 0.020 < 0.020 Nectarine 0.9 1.12 87 116 0.05 < 0.10 < 0.10 < 0.10 0.056 0.25 < 0.020 0.29 Citrus2 ( label rate = 1.15 lb ai/ A lb ai/ A total application rate, not to be applied to fruit > 1" in diameter) 3 Grapefruit 1.15 215 0.015 < 0.030 < 0.030 < 0.030 0.010 < 0.020 < 0.020 < 0.020 Grapefruit ( overcrop) 1.15 42 0.060 0.060 0.061 0.059 0.042 0.042 0.031 0.054 Grapefruit ( overcrop) 1.15 30 0.054 0.054 0.048 0.060 0.070 0.070 0.058 0.081 Lemon 1.15 207 0.015 < 0.030 < 0.030 < 0.030 0.010 < 0.020 < 0.020 < 0.020 Lemon ( overcrop) 1.15 42 0.46 0.46 0.44 0.48 0.50 0.50 0.47 0.54 Lemon ( overcrop) 1.15 30 0.98 0.98 0.87 1.1 0.98 0.98 0.95 1.1 Orange 1.15 269 0.015 < 0.030 < 0.030 < 0.030 0.016 0.022 < 0.020 0.023 Orange ( overcrop) 1.15 42 0.20 0.20 0.19 0.20 0.31 0.31 0.42 0.20 Orange ( overcrop) 1.15 30 0.28 0.28 0.23 0.34 0.45 0.45 0.40 0.50 1 One additional late season application may be made pears and apples to control stink bugs, lygus bugs, and pear rust mites in CA, OR, WA, and ID, upon written approval on a case by case basis by the State agency responsible for enforcement of FIFRA, or authorized by that State agency. No PHI is specified but a 16 day REI ( re entry interval) applies to hand harvesting fruit. 2 may be applied to oranges, lemons, limes, grapefruit, tangelos, tangerines. 3 May be applied to overcropped grapefruit and Valencia oranges > 1" provided a 30 day PHI is observed. May be applied to lemons > 1" provided a 60 day PHI is observed.

APPLE , PEAR According to the 10/ 99 MOA, the specific requirements for continued use of formetanate hydrochloride on apples and pears include label revision to specify that the pesticide shall not be applied after bloom ( petal fall) along with a maximum application rate of not more than 1.15 lb ai/ A ( 1.25 lb Carzol ® SP) for all food crops. One additional late season application may be made to control stink bugs, lygus bugs, and pear rust mites in CA, OR, WA, and ID, upon written approval on a case by case basis by the State agency responsible for enforcement of FIFRA, or authorized by that State agency.

Prior to the submission of the apple and pear studies ( MRIDs 45485001 and 45485002), HED reviewed a protocol for the conduct of apple, pear , peach, orange, lemon and grapefruit field trials ( DP Barcode D263912, 3/ 15/ 00, D. Drew). In the submitted protocol, the registrant proposed to conduct three pear field trials and four apple field trials each reflecting one application rate ( at a reduced rate of 1.15 lb ai/ A) and an approximate PHI of 70 170 days to coincide with petal fall. According to the registrant, the number of planned field trials is based on EPA Draft Science Policy # 6040 " Guidance for the Conduct of Bridging Studies for Use in Acute Dietary Probabilistic Risk Assessment." In its review of submitted protocol, HED recognized that the number of planned pear and apple field trials is in accordance with the cited Policy # 6040; however, the application scenario ( only one rate) for the planned studies would be as per OPPTS 860.1500 guidelines and not Policy # 6040. [ Note: the draft Science Policy # 6040 has since been      17    38 incorporated into the final Science Policy paper # 6063, " Guidance for Refining Anticipated Residue Estimates for Use in Acute Dietary Probabilistic Risk Assessment", dated June 15, 2000.] The registrant was informed that as per Policy # 6040, a minimum of three different application rates for each site would be necessary in order to compare or " bridge" results and calculate the relationship between the original maximum application rate ( 3.68 lb ai/ A) that was the basis for the established apple and pear tolerance and the proposed lower rate.

Therefore, in order to satisfy reregistration requirements, HED's protocol review recommended two options: Option A ( bridging studies as per Policy # 6040) or Option B ( crop field trials as per 860.1500). For Option A, the registrant was informed that they need not perform pear bridging trials as long as the apple bridging trials and resulting data are deemed adequate. The recommendation to translate apple bridging data to pears is based on the identical use patterns of these crops as per 10/ 14/ 99 MOA. For Option B, a total of eight apple field trials should be conducted at the registrant proposed application rate in Regions 1, 5 and 11, and a total of four pear field trials should be conducted at the registrant proposed application rate in Regions 10 and 11. The 860.1500 guidelines recommend a total of 16 apple and 8 pear field trials. The reduced number of trials recommended by HED takes into consideration the expectation of nondetectable residues and the reflection of regions representing the greatest formetanate HCl use per crop. All trials should reflect Good Laboratory Practice ( GLP) and follow applicable recommendations in OPPTS 860.1500, Test Guidelines for Crop Field Trials. A late season application timing should be included and should coincide with the growing period which would typically be vulnerable to late season infestations of stink bugs, lygus bugs, and pear rust mites on pome fruit. If resulting data are inadequate to support the new application rate and PHIs, then additional trials may be required.

Apple ( MRID 45485002)

In the current study ( MRID 45485002), a total of four apple field trials were conducted in NY ( 1 trial), MI ( 1 trial), and WA ( 2 trials). In three test sites ( MI, NY, and WA), a representative 92% SC formulation of formetanate HCl was applied once at petal fall as a broadcast spray at 1.15 lb ai/ A ( 1x the maximum rate recommended rate by the 10/ 14/ 99 MOA). In another WA trial location, the same test formulation was applied twice, at petal fall and again at crop maturity at 1.15 lb ai/ A per application ( 2x); this portion of the study was conducted in order to generate residue decline data but may also be used to determine residues resulting from a late season application ( using the 14 day PHI data to reflect the required 16 day re entry interval for harvesting). Samples of mature apple fruits were harvested from the 1x treatment plots at 107 134 days posttreatment. Fruit samples were also collected from the 2x plots at 0, 4, 7, 14, 21, 28, and 35 days following the last treatment. Two analytical methods were used to determine residues in/ on collected samples. One method ( HPLC/ UV) measured only parent formetanate and the other method ( GC/ ECD) is a common moiety method, slightly modified from PAM Volume II, which measured parent and several metabolites convertible to 3 aminophenol. These methods are adequate for data collection based on acceptable concurrent method recovery data. Residues of parent formetanate, as determined by HPLC/ UV, were nondetectable (< 0.03 ppm) in/ on 1x treated apples. As determined by GC/ ECD, residues of formetanate plus metabolites ( measured as 3 aminophenol) ranged from nondetectable (< 0.02 ppm) to 0.024 ppm in/ on 1xtreated samples.

Residues of parent formetanate in/ on 2x treated apples, as determined by HPLC/ UV, were 0.70 0.79 ppm at 0 day PHI, 0.34 0.43 ppm at 14 day PHI, and 0.28 0.32 ppm at 35 day PHI.      18    38 The submitted residue data for apples are not acceptable to support the terms of the 10/ 14/ 99 MOA between the Agency and the registrant. The number of sites and geographic representation for conducting bridging studies on apples was adequate for Option A ( bridging studies per EPA Science Policy # 6040, draft version 7/ 29/ 99); however, the application scenario ( only one application rate) was not in accordance with Option A requirements. Application rates were adequate for Option B ( 860.1500 field trials) but the number of field trials were not adequate.

If the registrant intends to conduct bridging studies for apples in accordance with Option A ( Science Policy # 6040), then additional field trials that reflect the guidance as outlined above should be conducted in Regions 1 and 5/ 11; the required study should include the requirement for multiple application rates and ensuring that all application rates used in the bridging study result in quantifiable residues.

Alternatively, if the registrant intends to conduct apple field trials in accordance with Option B ( OPPTS 860.1500), then at least four additional field trials in Regions 1, 5, and 11 must be conducted ( the trials should include an early and late season application as allowed in the MOA).

Pear ( MRID 45485001)

Three pear field trials were conducted in CA( 1 trial) and WA( 2 trials). In two test sites ( CA and WA), a representative 92% SC formulation of formetanate HCl was applied once at petal fall as a foliar airblast spray at 1.15 lb ai/ A ( 1x). In another WA test location, the same test formulation was applied twice, at petal fall ( 3.78 lb ai/ A) and again at crop maturity ( 1.15 lb ai/ A) for a total application of 4.93 lb ai/ A (~ 4.3x); this portion of the study was conducted in order to generate residue decline data. Samples of mature pear fruits were harvested from the 1x treatment plots at 118 121 days posttreatment. Fruit samples were also collected from the 4.3x plots at 0, 4, 8, 14, 21, 28, and 35 days following the last treatment. Two analytical methods were used to determine residues in/ on collected samples. One method ( HPLC/ UV) measured only parent formetanate and the other method ( GC/ ECD) is a common moiety method, slightly modified from PAM Volume II, which measured parent and several metabolites. These methods are adequate for data collection based on acceptable concurrent method recovery data.

Residues of parent formetanate, as determined by HPLC/ UV, were nondetectable (< 0.03 ppm) in/ on 1x treated pears. As determined by GC/ ECD, residues of formetanate plus metabolites ( measured as 3 aminophenol) were also nondetectable (< 0.02 ppm) in/ on 1x treated samples.

The submitted residue data for pears are not acceptable to support the terms of the 10/ 14/ 99 MOA between the Agency and the registrant. The number of sites and geographic representation for conducting bridging studies on pears was adequate for Option A ( bridging studies per Science Policy # 6040); however, the application scenario ( only one application rate) was not in accordance with Option A requirements. Application rates were adequate for Option B ( 860.1500 field trials) but the number of field trials were not adequate.

If the registrant intends to conduct bridging studies for pears in accordance with Option A, then additional side by side field trials in Regions 10 and 11 must be conducted. It should be noted that since the tolerance setting formetanate HCl use pattern on apples and pears is identical, as are the new proposed use patterns, and since the wide geographic representation proposed for apples includes a late season application in the primary pear growing region, it would be reasonable to translate the apple bridging data to pears. Therefore, the registrant need not perform pear bridging studies provided the apple bridging studies and resulting data are deemed adequate.      19    38 Alternatively, if the registrant intends to conduct pear field trials in accordance with Option B ( 860.1500), then at least two additional field trials in Regions 10 and 11 must be conducted ( the trials should include an early and late season application as allowed in the MOA).

PEACH , NECTARINE According to the 10/ 14/ 99 MOA, the specific requirements for continued use of formetanate hydrochloride on peaches and nectarines include label revisions to specify that the pesticide shall not be applied after shuck fall along with a maximum application rate of not more than 1.15 lb ai/ A for all food crops.

In the submitted field trial protocol, the registrant proposed to conduct three peach field trials reflecting one application rate ( at a reduced rate of 1.15 lb ai/ A). According to the registrant, the number of planned field trials is based on EPA Science Policy # 6040 " Guidance for the Conduct of Bridging Studies for Use in Acute Dietary Probabilistic Risk Assessment." In its review of submitted protocol, HED recognized that the number of planned peach field trials is in accordance with the cited Policy # 6040; however, the application scenario ( only one rate) for the planned study would be as per OPPTS 860.1500 guidelines and not Policy # 6040. The registrant was informed that as per Policy # 6040, a minimum of three different application rates for each site would be necessary in order to compare or " bridge" results and calculate the relationship between the original maximum application rate that was the basis for establishing the peach tolerance and the proposed lower rate. For Option A, the registrant was informed that they need not perform nectarine bridging trials as long as the peach bridging trials and resulting data are deemed adequate. The recommendation to translate peach bridging data to nectarines is based on the identical use patterns of these crops as per 10/ 14/ 99 MOA.

For Option B, a total of 6 peach field trials should be conducted at the registrant proposed application rate in Regions 1, 5 and 11, and a total of 4 nectarine field trials should be conducted at the registrant proposed application rate in Regions 10 and 11. The 860.1500 guidelines recommend a total of 12 peach and 8 nectarine field trials. The reduced number of trials recommended by HED takes into consideration the expectation of nondetectable residues and the reflection of regions representing the greatest formetanate HCl use per crop. All trials should reflect GLP and follow applicable recommendations in OPPTS 860.1500.

Peach ( MRID 45485003)

Three peach field trials were conducted in SC( 1 trial), MI( 1 trial), and CA( 1 trial). In each test site, a representative 92% SC formulation of formetanate HCl was applied once at petal fall as a broadcast spray at 1.15 lb ai/ A. Samples of mature peach fruits were harvested at 57 124 days posttreatment. Two analytical methods were used to determine residues in/ on collected samples. One method ( HPLC/ UV) measured only parent formetanate and the other method ( GC/ ECD) is a common moiety method, slightly modified from PAM Volume II, which measured parent and several metabolites convertible to 3 aminophenol. These methods are adequate for data collection based on acceptable concurrent method recovery data.

Residues of parent formetanate, as determined by HPLC/ UV, were nondetectable (< 0.03 ppm) in/ on treated peaches. As determined by GC/ ECD, residues of formetanate plus metabolites ( measured as 3 aminophenol) were also nondetectable (< 0.02 ppm) in/ on treated samples.      20    38 The submitted residue data for peaches are not acceptable to support the terms of the 10/ 14/ 99 MOA between the Agency and the registrant. The number of sites and geographic representation for conducting bridging studies on peaches was adequate for Option A; however, the application scenario ( only one application rate) was not in accordance with Option A requirements. Application rates were adequate for Option B but the number of field trials were not adequate.

If the registrant intends to conduct bridging studies for peaches in accordance with Option A, then additional side by side field trials in Regions 2, 5, and 10 must be conducted.

Alternatively, if the registrant intends to conduct peach field trials in accordance with Option B ( 860.1500), then results from three additional field trials in Regions 1 ( or 2), 5, and 10 must be submitted.

Nectarines ( MRID 45071301)

The registrant submitted the results of a formetanate HCL at harvest study on nectarines ( MRID 45071301). In this study, nectarine samples were collected from California growers who had treated the crops early in the season near the required lower application rate of 1.15 lb ai/ A ( as determined by grower's pesticide application records). Sixteen nectarine trials were conducted in CA ( Region 10). In 13 trials, nectarines were harvested 87 116 days following a single application of " Carzol 90SP" at 0.9 1.125 lb ai/ A. In 3 trials, nectarines were harvested 77 87 days following the last of two applications at 0.99 1.125 lb ai/ A. It is unclear from the study report if the application rates listed for the trials receiving two applications represent a single or total application rate. Details pertaining to the field procedures used in the study ( i. e., application method and timing, equipment, spray volumes, tank mix adjuvants) were not provided.

It is not clear what end product was used in the trials. The only currently registered formetanate HCL end product is a 92% SC formulation Carzol ® SP, EPA Reg. No. 10163 265. The study reports that the test substance and reference compound used was Carzol ® SP, 92%, EPA Reg. No. 45639 163 [ now 10163 265]. However, trial summary tables ( from grower's records) report that applications were made using " Carzol 90 SP" applied as 1.25 lb product / A, or 1.125 lb ai/ A. Calculations of active ingredient applied appear based on a 90% product. There are no 90% products registered. The EPA registration number for the end product used in the trials was not reported.

Two analytical methods were used to determine residues in/ on collected samples. One method ( HPLC/ UV) measured only parent formetanate and the other method ( GC/ ECD) is a common moiety method, slightly modified from PAM Volume II, which measured parent and several metabolites. These methods are adequate for data collection based on acceptable concurrent method recovery data.

Residues in/ on samples of nectarines harvested 87 116 days following a single application of the SC formulation at 0.9 1.125 lb ai/ A were: ( i) nondetectable (< 0.10 ppm) as determined by HPLC/ UV, ( ii) from nondetectable (< 0.02 ppm) to 0.26 ppm as determined by GC/ ECD with an RTX 5 column, and ( iii) from nondetectable (< 0.02 ppm) to 0.29 ppm as determined by GC/ ECD with a DB 1701 column.

Residues in/ on samples of nectarines harvested 77 87 days following the last of two applications of the SC formulation at 0.99 1.125 lb ai/ A were: ( i) nondetectable (< 0.10 ppm) as determined by HPLC/ UV; ( ii) nondetectable (< 0.02 ppm) to 0.49 ppm as determined by GC/ ECD with an RTX 5      21    38 column, and ( iii) nondetectable (< 0.02 ppm) to 0.53 ppm as determined by GC/ ECD with a DB 1701 column.

The submitted nectarine field trial data are deemed inadequate because details pertaining to the field procedures used in the study ( i. e., application method and timing, equipment, spray volumes, tank mix adjuvants) and specific multiple application rates were not provided.

CITRUS ( use limited to oranges, lemons, limes, grapefruit, tangelos, tangerines)

According to the 10/ 14/ 99 MOA, the specific requirements for continued use of formetanate hydrochloride on citrus fruit ( limited to oranges, lemons, limes, grapefruit, tangelos, and tangerines) include label revisions to specify that the pesticide shall not be applied after fruit reaches one inch in diameter along with a maximum application rate of not more than 1.15 lb ai/ A for all food crops. Formetanate HCl may be applied to overcropped ( both mature and immature fruit on tree at time of treatment) grapefruits and Valencia oranges above one inch in diameter, provided that a preharvest interval ( PHI) of 30 days is observed.

In the submitted protocol, the registrant proposed to conduct one orange ( region 10), one lemon ( region 10), and one grapefruit ( region 6) field trial reflecting one application rate ( at a reduced rate of 1.15 lb ai/ A) when fruit is   1 inch in diameter. For overcropped grapefruit and Valencia oranges, fruit that was mature at application will be harvested at 30 days PHI and fruit that was   1 inch in diameter will be harvested at maturity. According to the registrant, the number of planned field trials is based on EPA Science Policy # 6040 for bridging studies. In its review of the submitted protocol, HED recognized that the number of citrus field trials is in accordance with the cited Policy # 6040; however, the application scenario ( only one rate) for the planned study would be as per OPPTS 860.1500 guidelines and not Policy # 6040. The registrant was informed that as per Policy # 6040, a minimum of three rates for each site would be necessary in order to compare or " bridge" results and calculate the relationship between the original maximum application rate ( 4.6 lb ai/ A) that was the basis for establishing the citrus fruit tolerances and the proposed lower rate.

For Option B, a total of three grapefruit field trials ( region 10) should be conducted at the registrant proposed application rate. A total of two trials ( region 10) should be conducted for lemons and six trails ( regions 6 and 10) should be conducted for oranges. The 860.1500 guidelines recommend a total of 6 grapefruit, 5 lemon, and 12 orange filed trials. The reduced number of trials recommended by HED takes into consideration that formetanate HCl use is prohibited in FL, the expectation of nondetectable residues, and the reflection of regions representing the greatest formetanate HCl use per crop. All trials should reflect GLP and follow applicable recommendations in OPPTS 860.1500, Test Guidelines for Crop Field Trials. If resulting data are inadequate to support the new application rate and PHIs, then additional trials may be required.

In the current study ( MRID 45798901), a total of three field trials were conducted, one grapefruit trial in Texas ( region 6), one lemon trial in Arizona ( region 10), and one orange trial in California ( region 10). In the trials a representative 92% SC formulation of formetanate HCl was applied once by foliar airblast at 1.15 lba. i/ A. Applications were made to grapefruit at 1" new crop fruit ( 72 BBCH 1), to lemons at 73 BBCH, and to oranges when fruit was ~ 40% of final size ( 74 BBCH). Applications were made when previous crop ( mature) fruit was present. Samples ( 2 per trial) were collected at crop maturity ( 207 269 days after last treatment [ DALA]). One method ( HPLC/ UV) measured only parent formetanate and the other method ( GC/ ECD) is a common moiety method, slightly modified from PAM Volume II, which measured parent and metabolites      22    38 convertible to 3 aminophenol. These methods are adequate for data collection based on acceptable concurrent method recovery data.

Residues of parent formetanate, as determined by HPLC/ UV, were nondetectable (< 0.03 ppm) in/ on 1x treated citrus ( immature fruit treated at 1.15 lb ai/ a and harvested at maturity, 207 269 days PHI). As determined by GC/ ECD, residues of formetanate plus metabolites were nondetectable (< 0.02 ppm) on all 1x treated samples except for one orange sample at 0.023 ppm.

Samples of the ( old) mature crop ( grapefruit, lemon, and oranges) present at the time of treatment were also collected at 0, 7, 14, 21, 30, and 42 days after application; this portion of the study was conducted in order to generate residue decline data but can also serve to determine residues on ( old) mature fruit at the 30 day and 60 day PHI.

Grapefruit and Valencia oranges that were mature at the time of treatment were collected at a 30 day PHI and had average residues of parent formetanate at 0.054 ppm and 0.28 ppm, respectively, and had residues of formetanate plus metabolites at 0.070 ppm and 0.45 ppm, respectively. Mature treated lemons collected at a 30 day PHI had average residues of parent formetanate and formetanate plus metabolites at 0.98 ppm.

Grapefruit and Valencia oranges that were mature at the time of treatment were collected at a 42 day PHI and had average residues of parent formetanate at 0.060 ppm and 0.20 ppm, respectively, and had residues of formetanate plus metabolites at 0.042 ppm and 0.31 ppm, respectively. Mature treated lemons collected at a 42 day PHI had average residues of parent formetanate at 0.46 ppm and formetanate plus metabolites at 0.50 ppm.

The submitted citrus field trial data are deemed inadequate to support reregistration requirements because the conducted study was not in full accordance with either Option A ( bridging studies) or Option B ( crop field trials). If the registrant intends to conduct bridging studies for citrus in accordance with Option A, then field trials should be conducted in Regions 6 and 10; the required study should include the requirement for multiple ( side by side) application rates and ensuring that all application rates used in the bridging study result in quantifiable residues.

Alternatively, if the registrant intends to conduct citrus field trials in accordance with Option B, then 5 additional orange field trials in Regions 6 and 10 must be conducted. An additional lemon trial ( region 10) and 2 additional grapefruit trials ( Regions 6, 10) are also required.

860.1520 Processed Food and Feed Adequate apple and citrus processing studies are available for tolerance reassessment in processed commodities. Residues of formetanate HCl do not concentrate in apple juice ( 0.3x), orange juice ( 0.1x), orange oil ( 0.1x) or dried citrus pulp ( 0.8x). Apple processing data demonstrate that a tolerance must be proposed for residues in wet apple pomace. Based on a HAFT residue value of 0.38 ppm from the apple field trials ( 2 applications, one late season, for a total of 2.3 lb ai/ A; 14 day PHI) and an average concentration factor of 4X from four processing studies, a tolerance of 1.5 ppm would be appropriate for residues in apple, wet pomace.

1 BBCH is a standardized system for identifying plant growth stages phenologically. For citrus, BBCH growth stage Code 72 is defined as green fruit surrounded by sepal crown. BBCH 73 is defined as when some fruits slightly yellow; beginning of physiological fruit drop. BBCH 74 is when fruit is about 40% of final size      23    38 860.1850 Confined Accumulation in Rotational Crops and 860.1900 Field Accumulation in Rotational Crops Since there is a registered use on alfalfa grown for seed, a crop which can be rotated, residue data for rotational crops is required. The reregistration data requirements for accumulation in rotational crops are tentatively fulfilled ( D213962, C. Swartz, 10/ 10/ 95). The MOA requires that the registrant amend labels to specify the following: Leafy vegetables shall not be planted until 30 days after harvest of treated alfalfa.. Root crops shall not be planted until 120 days after harvest of treated alfalfa. Small grains and all other crops shall not be planted until 12 months after harvest of treated alfalfa. The existing EP label ( 10163 265) does contain the required rotational crop restrictions. ( However, associated SLN AZ030012 instructions for use on alfalfa grown for seed do not specify plant back intervals.)

860.1550 Proposed Tolerances The tolerances listed in 40 CFR § 180.276 are expressed in terms of formetanate hydrochloride { m [[( dimethylamino) methylene]  amino] phenyl methylcarbamate hydrochloride} and are summarized in Table 6 below. Tolerances were reassessed based on results of either the HPLC method ( parent formetanate) or the GC/ ECD enforcement method ( formetanate plus metabolites), whichever resulted in the higher residues.

The established 3 ppm tolerance for residues of formetanate HCl in apple and pear may be reduced to 0.50 ppm based on the new residue data for apples where formetanate HCl was applied at the maximum rate and included a late season application ( total 2.3 lb a. i/ A and 14 day PHI).

The available data for nectarine and peach indicate the established tolerances ( 4 ppm and 5 ppm, respectively) may be reduced to 0.40 ppm. Nectarine data were translated to peach data for tolerance reassessment. Even though there were no detectable residues (< 0.03) in the peach trials, only two trials were performed. Since there were a significant number of detectable residues in nectarines at the new rate of 1.15 lb ai/ A, it cannot automatically be assumed that there would be no detects in peaches without an adequate number of peach samples tested.

Based on the 30 day PHI residue data for mature treated oranges, grapefruit and lemons ( 1.15 lb a. i/ A), the tolerances for grapefruit and orange may be reassessed at 1.5 ppm. The highest residue from the lemon, grapefruit, and orange trials on mature fruit at a 30 day PHI was used to reassess the tolerance for formetanate HCl on grapefruit and orange.

Based on the 42 day PHI residue data for mature treated oranges, grapefruit and lemons ( 1.15 lb a. i/ A), the tolerances for lemon ( 60 day PHI required) may be reassessed at 0.60 ppm. The highest residue from the lemon, grapefruit, and orange trials on mature fruit at a 42 day PHI was used to reassess the tolerance for formetanate HCl on lemon.

Tolerances for residues of formetanate HCl on lime, tangerine and tangelo ( fruit that are not overcropped) may be reduced to 0.03 ppm [ LOQ] based on 207 day PHI residue data for lemons.

Tolerances for residues of formetanate HCl in plums, prune, fresh should be revoked as use on      24    38 plums is no longer permitted.

Apple processing data demonstrate that a tolerance must be proposed for residues in apple, wet pomace. Based on a HAFT residue value of 0.38 ppm from the apple field trials ( 2 applications, one of them late season, for a total of 2.3 lb ai/ A; 14 day PHI) and an average concentration factor of 4X from four processing studies, a tolerance of 1.5 ppm would be appropriate for residues of formetanate HCl in apple, wet pomace.

The reassessed tolerances for formetanate HCl residues are based on new field trials ( apple, pear, peach, nectarine, orange, grapefruit, lemon) submitted in response to the 10/ 99 MOA. While those field trials generally reflect the new maximum rate and minimum PHIs, the number of field trials were insufficient. When the additional required field trials are submitted, the tolerance reassessment will be reevaluated.

No maximum residue limits ( MRLs) for formetanate HCl have been established by Codex for any agricultural commodity. Therefore, no compatibility questions exist with respect to U. S. tolerances.

Table 6. Tolerance Reassessment Summary for Formetanate Hydrochloride Commodity Current Tolerance ( ppm) Tolerance Reassessment ( ppm) 1 Comment/ [ Correct Commodity Definition]

Tolerances Listed Under 40 CFR § 180.276 Apple 3 0.50 Pear 3 0.50 Grapefruit 4 1.5 Lemon 4 0.60 Lime 4 0.03 Oranges 4 1.5 [ orange]

Tangerine 4 0.03 Nectarine 4 0.40 Peach 5 0.40 Plum, prune, fresh 2 revoke no longer a registered use Tolerances To Be Proposed Under 40 CFR § 180.276 Apple, wet pomace None 1.5 Tangelo None 0.03 1 Reassessed tolerances are based on insufficient field trial data . When additional acceptable field trial data are received, the tolerance reassessment will be reevaluated.      25    38 Table. 7. Formetanate Hydrochloride Data Requirements GLN: Data Requirements Current Tolerances, ppm [ 40 CFR] Must Additional Data Be Submitted? References i 860.1200: Directions for Use N/ A = Not Applicable No See Tables 3 and 4.

860.1300: Plant Metabolism N/ A Yes ii 00077703, 00077711, 40280501, 42684605 iii, 455956012 860.1300: Livestock Metabolism N/ A No 00164328, 00164329, 42664414 42664417 iv, 43329001 v, 43329002 5 860.1340: Residue Analytical Methods  Plant commodities N/ A No 00029161, 00035917, 40411802  Livestock commodities N/ A No 40557601 860.1360: Multiresidue Methods N/ A No 42664406 vi, 42983201 vii 860.1380: Storage Stability Data N/ A No viii 00077702, 40411803, 42664407 4, 42664408 4, 42723601 4, 43329003 5, 43384401 43384405 ix, 43610401 43610403 x 860.1500: Crop Field Trials Citrus Fruits ( Citrus spp., Fortunella spp.) Group  Grapefruit 4 [ 180.276] Yes17 00077665, 00077702, 41708501 xi, 41708502 11, 41708505 11,4579890117      26    38 GLN: Data Requirements Current Tolerances, ppm [ 40 CFR] Must Additional Data Be Submitted? References i  Lemon 4 [ 180.276] Yes17 00077702, 4170850211, 41708505 11,4579890117  Lime 4 [ 180.276] Yes17 00077702 xii, 4579890117  Orange 4 [ 180.276] Yes17 00073455, 00077665, 00077702, 41708501 11, 41708503 11,41708504 11, 4579890117  Tangelo None Yes17 00077768, 4579890117  Tangerine 4 [ 180.276] Yes17 00077768, 4579890117 Pome Fruits Group  Apple 3 [ 180.276] Yes18 00077702, 00077710, 45485002 18  Pear 3 [ 180.276] Yes18 00077710, 45485001 18 Stone Fruits Group  Nectarine 4 [ 180.276] Yes19 00077762, 40411803, 42664410 4, 4507130119  Peach 5 [ 180.276] Yes18 00077762, 40411803, 45485003 18  Plum 2 [ 180.276] No 00077762 Non Grass Animal Feeds  Alfalfa seed, forage, and hay None established No xiii 40534301 860.1520: Processed Food/ Feed  Apple None established No 00077721      27    38 GLN: Data Requirements Current Tolerances, ppm [ 40 CFR] Must Additional Data Be Submitted? References i  Citrus None Established No 00073455, 00077665, 00077702  Plum None Established No 00077762 860.1480: Meat, Milk, Poultry, Eggs  Milk and the Fat, Meat, and Meat Byproducts of Cattle, Goats, Hogs, Horses, and Sheep None established No 41299601 41299603 xiv  Eggs and the Fat, Meat, and Meat Byproducts of Poultry None established No xv 860.1400: Water, Fish, and Irrigated Crops None established N/ A 860.1460: Food Handling None established N/ A 860.1850: Confined Rotational Crops N/ A No21 43170401 xvi, 43583101xvii 860.1900: Field Rotational Crops None established No 20 1 Bolded references were reviewed in the Residue Chemistry Chapter of the Formetanate HCl Second Round Review ( SRR) dated 5/ 10/ 89. Unbolded references were reviewed in the Residue Chemistry Chapter of the Formetanate Reregistration Standard dated 9/ 30/ 82. All other references were reviewed as noted.

ii. DP Barcode D281044, 2/ 10/ 03, D. Drew. The registrant must provide supporting chromatographic evidence for their statement that a Day 0 leaf extract was found to be stable for 13 months, and justification for use of a Day 0 leaf extract to support the storage of an extract of peach fruit for up to 9 months prior to analysis.

iii. CBRS No. 11518, DP Barcode D189020, 1/ 7/ 97, C. Swartz.

iv. CBRS No. 11729, DP Barcode D190256, 5/ 18/ 94, C. Swartz.

v. CBRS No. 14240, DP Barcode D206806, 2/ 10/ 97, C. Swartz.

vi. Forwarded to FDA for review ( memo dated 5/ 21/ 93 from L. Edwards to H. Hundley).      28    38 vii. Forwarded to FDA for review ( CBRS No. 12806, DP Barcode D196721, 11/ 22/ 93, L. Edwards).

viii. Residues of the metabolite 3 formamidophenyl N methylcarbamate declined after storage intervals of 9 33 months. Additional data pertaining to this metabolite will not be required at this time, as that metabolite has been determined to be not of significant toxicological concern.

ix. CBRS No. 14534, DP Barcode D208231, 2/ 11/ 97, C. Swartz.

x. CBRS No. 15469, DP Barcode D214581, 9/ 19/ 95, C. Swartz.

xi. CB No. 7522, 3/ 11/ 91, F. Toghrol.

xii. CBRS No. 12887, DP Barcode D197102, 2/ 4/ 97, C. Swartz.

xiii. The use on alfalfa grown for seed in CA, ID, NV, OR, WA and AZ is considered to be a nonfood use, since these states have established programs designed to prevent diversion of alfalfa forage, hay, seed, and seed screenings ( from treated alfalfa grown for seed) to livestock feed. No data and no tolerances for residues in alfalfa commodities are required.

xiv. CB Nos. 6127, 6128, and 6129, 4/ 18/ 90, R. Perfetti.

xv. Currently there are no registered uses of formetanate HCl on any poultry feed items and there are no direct livestock treatments of formetanate HCl to poultry; therefore, a poultry feeding study and tolerances for residues in poultry commodities are not required.

xvi. CBRS No. 13459, DP Barcode D201138, 5/ 2/ 94, C. Swartz.

17. DP Barcode 286406, 1/ 15/ 03, D. Drew. Five additional orange field trials in Regions 6 and 10 must be conducted. An additional lemon trial ( region 10) and 2 additional grapefruit trials ( Regions 6, 10) are also required.

18. DP Barcode D278011, 1/ 8/ 03, D. Drew. Apples: at least four additional field trials in Regions 1, 5, and 11 must be conducted ( the trials should include an early and late season application as allowed in the MOA; Pears: at least two additional field trials in Regions 10 and 11 must be conducted ( the trials should include an early and late season application as allowed in the MOA); Peaches: three additional field trials in Regions 1 ( or 2), 5, and 10 must be submitted.

19. DP Barcode D265072, 2/ 10/ 03, D. Drew. Details pertaining to the field procedures used in the study ( i. e., application method and timing, equipment, spray volumes, tank mix adjuvants) and multiple application rates must be provided.

20. CBRS No. 15403, DP Barcode D213962, 10/ 5/ 95, C. Swartz.

21. Since there is a registered use on alfalfa grown for seed, a crop which can be rotated, residue data for rotational crops are required. The reregistration data requirements for accumulation in rotational crops are tentatively fulfilled. The 10/ 99 MOA requires that the registrant amend labels to specify the following: Leafy vegetables shall not be planted until 30 days after harvest of treated alfalfa. Root crops shall not be planted until 120 days after harvest of treated alfalfa. Small grains and all other crops shall not be planted until 12 months after harvest of treated alfalfa.      29    38 AGENCY MEMORANDA RELEVANT TO REREGISTRATION CB Nos.: 6127, 6128, and 6129 Subject: Nor Am Chemical Co. Response to the Formetanate Hydrochloride Reregistration Standard: Ruminant Feeding Studies. From: R. Perfetti To: R. Engler and L. Rossi Dated: 4/ 18/ 90 MRID( s): 41299601 41299603 CB No.: 7522 Subject: Formetanate Hydrochloride ( Carzol ® SP) in or on Citrus. Amendment to the Registration of Carzol SP ( EPA Reg. No. 45639 74) to Change the Application Intervals from 30 Days to 14 Days in CA and AZ. From: F. Toghrol To: D. Edward/ C. Andreasen Dated: 3/ 11/ 91 MRID( s): 41708501 41708505 CB No.: None DP Barcode: None Subject: Formetanate. HCl through FDA Multi Residue Protocols A through E. List A, Case # 0091. From: L. Edwards To: H. Hundley Dated: 5/ 21/ 93 MRID( s): 42664406 CBRS No.: 12806 DP Barcode: D196721 Subject: Reregistration of Formetanate. HCl. Multi Residue Testing Data of Formetanate. List A Case No. 0091. From: L. Edwards To: L. Schnaubelt/ S. Jennings Dated: 11/ 22/ 93 MRID( s): 42983201      30    38 CBRS No.: 13459 DP Barcode: D201138 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Confined Rotational Crop Study. From: C. Swartz To: L. Schnaubelt/ S. Jennings Dated: 5/ 2/ 94 MRID( s): 43170401 CBRS No.: 11729 DP Barcode: D190256 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Nature of the Residue in Ruminants and Poultry; Residue Analytical Methods; Storage Stability; Magnitude of the Residue in Nectarines. From: C. Swartz To: L. Schnaubelt Dated: 5/ 18/ 94 MRID( s): 42664406, 42664407, 42664408, 42664410, 42664414 42664417, and 42723601 CBRS No.: 17066 DP Barcode: D224582 Subject: Formetanate HCl ( List A, Case No. 0091). Anticipated Residues for Chronic Non Cancer Dietary Exposure Assessment. Gowan Company. Chemical No: 097301 From: D. Hrdy To: W. Hazel Dated: 8/ 26/ 96 MRID( s): None CBTS No.: 13795 DP Barcode: D203797 Subject: PP# 4F4357. Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Petition for Tolerances in/ on Alfalfa Forage and Hay. From: C. Swartz To: D. Edwards Dated: 9/ 19/ 95 MRID( s): None CBRS No.: 15469 DP Barcode: D214581 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Guideline 171 4( e): Storage Stability Data in Apples, Citrus and Stone Fruit. From: C. Swartz To: L. Schnaubelt/ S. Jennings Dated: 9/ 19/ 95 MRID( s): 43610401, 43610402, and 43610403 CBRS No.: 15403 DP Barcode: D213962 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Submission to Upgrade the Confined Rotational Crop Study. From: C. Swartz To: L. Schnaubelt/ S. Jennings      31    38 Dated: 10/ 5/ 95 MRID( s): 43583101 CBRS No.: 11518 DP Barcode: D189020 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Citrus Metabolism Study. From: C. Swartz To: W. Hazel Dated: 1/ 7/ 97 MRID( s): 42684605 CBRS No.: 12887 DP Barcode: D197102 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Nor Am's Submission to Support Use of Formetanate Hydrochloride on Limes. From: C. Swartz To: C. Scheltema Dated: 2/ 4/ 97 MRID( s): None CBRS No.: 14240 DP Barcode: D206806 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Registrant Submission to Upgrade Animal Metabolism and Storage Stability Studies. From: C. Swartz To: W. Hazel Dated: 2/ 10/ 97 MRID( s): 43329001, 43329002, and 43329003 CBRS No.: 14534 DP Barcode: D208231 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Registrant Submission of Storage Intervals Incurred During Citrus Residues Studies. From: C. Swartz To: C. Scheltema Dated: 2/ 11/ 97 MRID( s): 43384401 through 43384405 CBRS No.: None DP Barcode: None Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Issues to be presented at the 2/ 19/ 97 meeting of the HED Metabolism Committee. From: C. Swartz To: HED Metabolism Committee Dated: 2/ 19/ 97 MRID( s): None CBRS No.: 13544 DP Barcode: D201901 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Registrant Submission to Supplement Animal Metabolism Studies.      32    38 From: C. Swartz To: C. Scheltema Dated: 2/ 27/ 97 MRID( s): 43090000, 43090001, 43179901, and 43144701 CBRS No.: None DP Barcode: None Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Outcome of the 2/ 19/ 97 meeting of the HED Metabolism Committee. From: C. Swartz To: HED Metabolism Committee Dated: 4/ 15/ 97 MRID( s): None CBRS No.: 17752 DP Barcode: D233099 Subject: Formetanate hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. HED RED: Product and Residue Chemistry Chapters. From: C. Swartz To: R. Perfetti Dated: 4/ 18/ 97 MRID( s): None DP Barcode: D234261 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Response to Review of Citrus Metabolism Study. From: D. Drew To: M. Goodis Dated: 12/ 2/ 98 MRID( s): None DP Barcode: D250747 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Magnitude of the Residue on Oranges, Analytical Method for Determining Residues on Oranges. From: D. Drew To: M. Goodis Dated: 12/ 10/ 98 MRID( s): 44674002, 44674003 DP Barcode: D263912 Subject: Formetanate HCL: Review of Residue Chemistry Proposals Received from Registrant as Required in the 10/ 14/ 99 Memorandum of Agreement. Chemical 097301. From: D. Drew To: D. Fuller Dated: 3/ 15/ 2000 MRID( s): None DP Barcode: D281044 Subject: Formetanate Hydrochloride. List A Reregistration Case No.

0091/ Chemical ID No. 097301 Metabolism of [ U 14C phenyl] Formetanate Hydrochloride in Peaches. From: D. Drew To: D. Fuller      33    38 Dated: 2/ 10/ 03 MRID( s): None DP Barcode: D278011 Subject: Formetanate HCL: Crop Field Trials Pears, Apples, Peaches. Case no. 0091/ PC Code 097301. From: D. Drew To: D. Fuller Dated: 1/ 8/ 2003 MRID( s): 45485001, 45485002, 45485003 DP Barcode: D286406 Subject: Formetanate HCL: Crop Field Trials Citrus. Case no. 0091/ PC Code 097301. From: D. Drew To: D. Fuller Dated: 1/ 15/ 2003 MRID( s): 45798901 DP Barcode: D265072 Subject: Formetanate HCL: Review of Field Trial residue Data on Nectarines Submitted by Aventis CropScience. Case no. 0091/ PC Code 097301. From: D. Drew To: D. Fuller Dated: 2/ 10/ 2003 MRID( s): 45485001, 45485002, 45485001 DP Barcode: D250747 Subject: Formetanate Hydrochloride. List A Reregistration Case No. 0091/ Chemical ID No. 097301. Magnitude of the Residue on Oranges, Analytical Method for Determining Residues on Oranges. From: D. Drew To: M. Goodis Dated: 12/ 10/ 98 MRID( s): 44674002, 44674003 MASTER RECORD IDENTIFICATION NUMBERS 00029161 Nor Am Agricultural Products, Incorporated ( 1969) 332/ 30: Colorimetric Determination of Formetanate HCl. ( Nor Am EP 332) in Plant Material: ( Schering 36 056/ 5 Revised). Method dated May 22, 1969. ( Unpublished study received May 22, 1980 under OE2363; submitted by Interregional Research Project No. 4, New Brunswick, N. J.; CDL: 099438 B)

00035917 Jenny, N. A. ( 1969) Gas Chromatographic Residue Determination of Formetanate HC1 ( Nor Am Carzol) in Plant Material: Report 332/ 41. Method dated Nov 7, 1969. ( Unpublished study received Feb 1, 1973 under 3F1351; submitted by Nor Am Agricultural Products, Inc., Naperville, Ill.; CDL: 096476 F)

00073455 Morton Chemical Company ( 1968) [ Residues of Formetanate on Oranges, Grapefruit and Lemons]. ( Compilation; unpublished study received Nov 29, 1968 under 9G0746; CDL: 091290 E)

00077665 Nor Am Agricultural Products, Incorporated ( 1975) Residues of Formetanate Hydrochloride in Citrus Treated with Carzol SP by Air. Includes method 332/ 30 dated May 22, 1969. ( Compilation; unpublished study received Mar 12, 1975 under 2139 99; CDL: 110595 A)

00077702 Nor Am Agricultural Products, Incorporated ( 1970) [ Residue Data on Carzol SP in      34    38 Citrus Fruits]. ( Compilation; unpublished study received Apr 12, 1970 under 0F0961; CDL: 091643 D)

00077703 Knowles, C. O.; Sen Gupta, A. K. ( 1970) Metabolism of Formetanate Acaricide by Orange Seedlings. ( Unpublished study received Apr 12, 1970 under 0F0961; prepared by Univ. of Missouri, Dept. of Entomology, submitted by Nor Am Agricultural Products, Inc., Naperville, Ill.; CDL: 091643 E)

00077710 Nor Am Agricultural Products, Incorporated ( 1970) Formetanate Hydrochloride Residues in Apples and Pears: The Results of Tests on the Amount of Residue Remaining, Including a Description of the Analytical Method Used. ( Compilation; unpublished study received on unknown date under 0F0989; CDL: 091703 B)

00077711 Schering AG ( 1969) The Fate of Formetanate Hydrochloride Residues on Apples: 2nd Report 1969 on Formetanate Residues. ( Unpublished study received Apr 12, 1970 under 0F0961; submitted by Nor Am Agricultural Products, Inc., Naperville, Ill.; CDL: 091643 L)

00077721 Nor Am Agricultural Products, Incorporated ( 1973) Residues of Formetanate Hydrochloride in Apple Products. ( Compilation; unpublished study, including letter dated Oct 8, 1973 from M. Lambert to Edward Gross, received Apr 25, 1973 under 3H5029; CDL: 221762 F)

00077762 Nor Am Agricultural Products, Incorporated ( 1971) Formetanate Hydrochloride: Results of Tests on the Amount of Residue Remaining: Peaches, Plums, Prunes, Nectarines, Grapes. ( Compilation; unpublished study received Aug 14, 1972 under 2F1238; CDL: 091095 A)

00077768 Nor Am Agricultural Products, Incorporated ( 1971) [ Formetanate Hydrochloride Residues in Grapes and Tangerines]. ( Compilation; unpublished study received Apr 13, 1971 under 1F1141; CDL: 090928 A)

00164328 Campbell, J.; Needham, D. ( 1986) Metabolism and Residues of Formetanate Hydrochloride in Laying Hens: Proj. ID. No. METAB/ 86/ 36. Unpublished study prepared by Schering Agrochemicals Ltd. 24 p.

00164329 Campbell, J.; Needham, D. ( 1986) Excretion and Tissue Residues of Formetanate Hydrochloride in a Lactating Goat: Proj. ID. No. METAB/ 86/ 28. Unpublished study prepared by Schering Agrochemicals Ltd. 24 p.

40280501 Celorio, J. ( 1986) M15 Formetanate HCl: Fate of Formetanate Hydrochloride in Alfalfa ( Medicago sativa L.): Laboratory Project ID: UPSR 30/ 86 PA 36 056.81/ 12. Unpublished study prepared by Schering AG. 45 p.

40411802 R155/ Formetanate HCl: GLC Method of Analysis for Major Formetanate Derived Residues in Nectarines ( 10 970 1/ 87): Laboratory Project ID UPSR 32/ 87 PA 10 970.5/ 11. Unpublished study prepared by Schering AG. 28 p.

40411803 Scheuermann, H. ( 1987) R156 Formetanate HCl: Residues of Formetanate X HCl and Major Metabolites in Stone Fruits Following Foliar Application of CARZOL ( 92 SP) in the USA 1985 and 1986 ( 10 970 11/ 87): Laboratory Project ID UPSR 36/ 87 PA 10 970.6/ 11. Unpublished study prepared by Schering AG. 43 p.

40534301 Scheuermann, H. ( 1988) R157 Formetanate: Residue Decline of Formetanate x HCl and Major Metabolites in Alfalfa Following Foliar Application of Carzol ( 90SP) in the USA 1985 ( 10970 III/ 87): Laboratory Project ID UPSR 50/ 87. Unpublished study prepared by Schering AG, Germany. 52 p.

40557601 Manley, J.; Snowdon, P. ( 1988) R154 Formetanate: Analytical Method for the      35    38 Determination of Residues of Formetanate and Major Metabolites Hydrolysing to 3 Aminophenol in Animal Tissues, Milk and Eggs by Gas Chromatography: Laboratory Project ID RESID/ 87/ 82. Unpublished study prepared by Schering Agrochemicals Limited, England. 38 p.

41299601 Roberts, N.; Cameron, D.; Emerson, E. ( 1988) R163A Formetanate Hydrochloride: Residues in Milk & Tissues of Dairy Cows Animal Phase: Lab Project Number RESID/ 88/ 44; FSB 275/ 861445; 101/ 05/ 001. Unpublished study prepared by Huntingdon Research Centre. 23 p.

41299602 Snowdon, P.; Manley, J. ( 1989) R163 Formetanate derived Residues Containing the 3 Aminophenol Moiety in the Tissues and Milk of Cattle following a 28 Day Feeding Study in the UK, 1986: Lab Project Number RESID/ 88/ 44; 101/ 05/ 001. Unpublished study prepared by Schering Agrochemicals Ltd. 43 p. 41299603 Manley, J.; Snowdon, P. ( 1989) C49 Formetanate: Analytical Method for the Determination of Dietary Concentrations of Formetanate Hydrochloride in Maize Oil by High Performance Liquid Chromatography: Lab Project Number RESID/ 88/ 46; 101/ 01/ 002. Unpublished study prepared by Schering Agrochemicals Ltd. 20 p.

41708501 J. Moede. ( 1988). R165 FORMETANATE: Residues of formetanate x + HCl and major metabolites in citrus following application of CARZOL 92 SP in the USA 1988. Laboratory Study No. UPSR 89/ 88. Unpublished study conducted by Schering AG, Berlin, Germany and submitted by Nor Am ( Wilmington, DE). 133 p.

41708502 A. Wrede Rucker. ( 1990). R176 FORMETANATE HCL: Residues of formetanate x HCl and major metabolites in citrus following application of CARZOL 92 SP in the USA 1989. Laboratory Study No. UPSR 6/ 90. Unpublished study conducted by Schering AG, Berlin, Germany and submitted by Nor Am ( Wilmington, DE). 41 p.

41708503 A. Wrede Rucker. ( 1990). R177 FORMETANATE HCL: Residues of formetanate x HCl and major metabolites in oranges following application of CARZOL SP 92 in the USA 1989. Laboratory Study No. UPSR 7/ 90. Unpublished study conducted by Schering AG, Berlin, Germany and submitted by Nor Am ( Wilmington, DE). 37 p.

41708504 A. Wrede Rucker. ( 1990). R178 FORMETANATE HCL: Residues of formetanate x HCl and major metabolites in oranges following application of CARZOL 92 SP in the USA 1989. Laboratory Study No. UPSR 8/ 90. Unpublished study conducted by Schering Agrochemicals Limited, Essex, England and submitted by Nor Am ( Wilmington, DE). 38 p.

41708505 A. Wrede Rucker. ( 1990). R179 FORMETANATE HCL: Residues of formetanate x HCl and major metabolites in citrus following application of CARZOL 92 SP in the USA 1989. Laboratory Study No. UPSR 11/ 90. Unpublished study conducted by Schering Agrochemicals Limited, Essex, England and submitted by Nor Am ( Wilmington, DE). 48 p.

42664406 Bowman, M. ( 1992) Testing of Formetanate HCl ( R187) through U. S. FDA Multiresidue Methods: U. S. A., 1992: Lab Project Number: MCB NOR AM/ MR 5: Y 92R 03. Unpublished study prepared by M. C. Bowman & Associates. 76 p.

42664407 Wrede Rucker, A. ( 1992) Stability of Formetanate X HCl and its Metabolite ZK 10 714 during Deep Freeze Storage in Peaches: Interim Report: ( R191 Formetanate HCl): Lab Project Number: U/ R 43/ 92: 020906: PF R 92 029. Unpublished study prepared by Schering AG. 27 p.

42664408 Wrede Rucker, A. ( 1992) Stability of Formetanate HCl and its Metabolite ZK 10 714 during Deep Freeze Storage in Apples: Interim Report: ( R191 Formetanate HCl): Lab Project Number: U/ R/ 45/ 92: 020907. Unpublished study prepared by Schering AG. 27 p.

42664410 Brady, S. ( 1992) At harvest Formetanate derived Residues in or on Nectarines following Treatment with Carzol SP ( Aerial and Ground) at Maximum Use Rates: USA, 1991: Lab      36    38 Project Number: Y 91R 01. Unpublished study prepared by NOR AM Chemical Co. 42 p.

42664414 Reynolds, C. ( 1993) The Nature of the Residues of Formetanate HCl in the Edible Tissues and Milk of a Cow following Oral Administration for 7 days at a Dose Equivalent of 30 ppm in the Diet: Lab Project Number: TOX 92/ 197 76: 020910: T0X 91044. Unpublished study prepared by Schering Agrochemical Ltd. 170 p.

42664415 O'Boyle, F. ( 1993) The Nature of Residues of Formetanate HCl in the Edible Tissues of the Laying Hen following Oral Administration for 14 days at a Dose Equivalent to 10 ppm in the Diet: Lab Project Number: TOX 91045A: 020910: TOX/ 92/ 197 77. Unpublished study prepared by Schering Agrochemical Ltd. 109 p.

42664416 Little, E. ( 1992) Absorption, Distribution and Excretion following Multiple Oral Administration to the Dairy Cow: ( carbon 14) Formetanate HCl: Lab Project Number: 7294 194/ 68: TOX 91044: TOX/ 92/ 197 73. Unpublished study prepared by Hazleton UK and Schering Agrochemicals Ltd. 59 p.

42664417 Reynolds, C. ( 1992) The Excretion and Distribution of Formetanate HCl and its Metabolites in the Laying Hen following Daily Oral Administration at a Dose Rate Equivalent to 10 ppm in the Diet: Lab Project Number: TOX 92/ 197 74: 020911: TOX 91045. Unpublished study prepared by Schering Agrochemical Ltd. 27 p.

42684605 Downey, S. ( 1993) Metabolism of ( carbon 14) Formetanate in Lemons: Lab Project Number: 504Y. Unpublished study prepared by Nor Am Chemical Co. 52 p.

42723601 Scheuermann, H. ( 1990) Stability of Formetanate X HCl in Alfalfa during Deep Freeze Storage: Lab Project Number: UPSR 56/ 90: 4010. Unpublished study prepared by Schering AG. 20 p.

42983201 Williams, L. ( 1993) Testing of Formetanate. HCl Through Protocol A of US FDA Multiresidue Methods: Lab Project Number: Y 92R 08. Unpublished study prepared by NORAM Chemical Co. 26 p.

43170401 Smith, S. ( 1994) Uptake of ( carbon 14) Formetanate Residues in Soil by Rotational Crops under Confined Conditions: Lab Project Number: 503Y. Unpublished study prepared by Nor Am Chemical Co. 167 p.

43329001 Reynolds, C. ( 1994) The Nature of Residues of Formetanate HCl in the Edible Tissues and Milk of a Cow Following Oral Administration for 7 Days at a Dose Equivalent of 30 ppm in the Diet: M19 Addendum 1: Lab Project Number: TOX/ 92/ 197/ 76. Unpublished study prepared by Schering Agrochemicals Ltd. 99 p.

43329002 O'Boyle, F. ( 1994) The Nature of Residues of Formetanate HCl in the Edible Tissues of the Laying Hen Following Oral Administration for 14 Days at a Dose Equivalent to 10 ppm in the Diet: M20 Addendum 1: Lab Project Number: TOX/ 92/ 197/ 77. Unpublished study prepared by Schering Agrochemicals Ltd. 69 p.

43329003 Czochor, L. ( 1994) Response to EPA Review of Formetanate Hydrochloride Storage Stability Data Base. Unpublished study prepared by AgrEvo USA Co. 17 p.

43384401 Wrede, A. ( 1994) Formetanate HCl R165 Addendum to Report: Residues of Formetanate x HCl and Major Metabolites in Citrus Following Application of CARZOL 92 SP in the USA 1988: Lab Project Number: UPSR 89/ 88: PF R88056. Unpublished study prepared by Schering AG and Hoechst Schering AgrEvo GmbH. 13 p.

43384402 Wrede, A. ( 1994) Formetanate HCl R176 Addendum to Report: Residues of Formetanate x HCl and Major Metabolites in Citrus Following Application of CARZOL 92 SP in      37    38 the USA 1989: Lab Project Number: UPSR/ 6/ 90: PF/ R89010. Unpublished study prepared by Schering AG and Hoechst Schering AgrEvo GmbH. 13 p.

43384403 Wrede, A. ( 1994) Formetanate HCl R177 Addendum to Report: Residues of Formetanate x HCl and Major Metabolites in Oranges Following Application of CARZOL 92 SP in the USA 1989: Lab Project Number: UPSR 7/ 90: PF R90003. Unpublished study prepared by Schering AG and Hoechst Schering AgrEvo GmbH. 12 p.

43384404 Wrede, A. ( 1994) Formetanate HCl R178 Addendum to Report: Residues of Formetanate x HCl and Major Metabolites in Oranges Following Application of CARZOL 92 SP in the USA 1989: Lab Project Number: UPSR 8/ 90: PF R90006. Unpublished study prepared by Schering AG and Hoechst Schering AgrEvo GmbH. 12 43384405 Wrede, A. ( 1994) Formetanate HCl R179 Addendum to Report: Project Number: UPSR 11/ 90: PF R90007. Unpublished study prepared by Schering AG and Hoechst Schering AgrEvo GmbH. 13 p.

43583101 Smith, S.; Meyer, B. ( 1994) Uptake of Residues of ( Carbon 14) Formetanate Residues in Soil by Rotational Crops Under Confined Conditions: Addendum 1 to Report: Lab Project Number: 503Y. Unpublished study prepared by AgrEvo USA Co. 95 p.

43610401 Wrede, A. ( 1995) Stability of Formetanate x HCl and Its Metabolite ZK 10714 During Deep Freeze Storage of 33 Months in Apples: Lab Project Number: PF R 92061: R216: R/ V41/ 94.3/ 16. Unpublished study prepared by Hoechst Schering AgrEvo GmbH. 75 p.

43610402 Wrede, A. ( 1995) Stability of Formetanate x HCl and Its Metabolite ZK 10714 During Deep Freeze Storage of 33 Months in Stonefruit: Lab Project Number: PF R 92029: R217: U/ R 43/ 92 PA 10 970.3/ 16. Unpublished study prepared by Hoechst Schering AgrEvo GmbH. 74 p.

43610403 Wrede, A. ( 1995) Stability of Formetanate x HCl and Its Metabolite ZK 10714 During Deep Freeze Storage of 2 Years in Citrus Peel and Citrus Flesh: Lab Project Number: PF R 92030: R218: R/ V 40/ 94 PA 10 970.3/ 16. Unpublished study prepared by Hoechst Schering AgrEvo GmbH. 87 p.

45071301 Singer, S. ( 2000) Magnitude of Formetanate Hydrochloride Derived Residues in or on Nectarines Raw Agricultural Commodities Resulting from Applications of CARZOL, USA, 1999: Lab Project Number: Y99R001: R10 01: R10 02. Unpublished study prepared by Aventis CropScience. 146 p. { OPPTS 860.1500}

45595601 Rupprecht, J. ( 2001) Metabolism of ( U( Carbon14 phenyl) Formetanate Hydrochloride in Peaches: Lab Project Number: 511Y: B003583: Y00E511. Unpublished study prepared by Aventis Cropscience. 53 p. { OPPTS 860.1300}

45485001 Gough, S. ( 2001) Magnitude of the Residue of Formetanate Hydrochloride in Pears After One or Two Applications of CARZOL, USA, 2000: Final Study Report: Lab Project Number: YOOR002: BOO3162: XENOO 10. Unpublished study prepared by Aventis CropScience, Xenos Laboratories, Inc. and ABC Laboratories, Inc. 187 p. { OPPTS 860.1500}

45485002 Gough, S. ( 2001) Magnitude of the Residue of Formetanate Hydrochloride in Apples After One or Two Applications of CARZOL, USA, 2000: Final Study Report: Lab Project Number: Y 95R 02: 43802: YEN00 09. Unpublished study prepared by Aventis CropScience, Xenos Laboratories, Inc. and ABC Laboratories, Inc. 195 p. { OPPTS 860.1500}

45485003 Gough, S. ( 2001) Magnitude of the Residue of Formetanate Hydrochloride in Peaches After One Applications of CARZOL, USA, 2000: Final Study: Lab Project Number: YOOR003: BOO31653: XENOO 19. Unpublished study prepared by Aventis CropScience, Xenos Laboratories, Inc. and ABC Laboratories, Inc. 177 p. { OPPTS 860.1500}      38    38 45798901 Gough, S. ( 2002) Magnitude of the Residue of Formetanate Hydrochloride in Citrus After One Application of CARZOL, USA, 2000: Final Study Report: Lab Project Number: Y00R004: B003164: R0601. Unpublished study prepared by Aventis CropScience and Enviro Test Laboratories. 265 p. { OPPTS 860.1500}

cc:: D. Drew, List File RDI: RRB3 Chemists ( 3/ 24/ 03); C. Eiden ( 3/ 24/ 03); ChemSAC ( 3/ 26/ 03)