Document ID: EPA-HQ-OPP-2007-0945-0006
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-11-12T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460      

	OFFICE OF PREVENTION, PESTICIDE

	AND TOXIC SUBSTANCES

	

  SEQ CHAPTER \h \r 1 MEMORANDUM

DATE:  		30-SEP-2008  

SUBJECT:		4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB); Application
for a Section 3 Registration on Mint.  Summary of Analytical Chemistry
and Residue Data.

PC Code:  019201	DP Barcode:  349646

Decision No.:  383254	Registration No.:  71368-5

Petition No.:  7E7257	Regulatory Action:  Section 3 Registration

Risk Assessment Type:  NA	Case No.:  2365

TXR No.:  NA	CAS No.:  94-81-5

MRID No.:  47218701	40 CFR:  180.318

		              									Ver.Apr.08

		          	

FROM:			Sarah J. Levy, Chemist

			Registration Action Branch 1 (RAB1)

			Health Effects Division (HED; 7509P)

		

THROUGH:	George F. Kramer, Ph.D., Senior Chemist

			RAB1/HED (7509P)

				

TO:			Daniel Rosenblatt, Risk Manager 05

			Registration Division (RD; 7505P)

This document was originally prepared under contract by Dynamac
Corporation (2275 Research Blvd, Suite 300; Rockville, MD 20850;
submitted 06-FEB-2008).  The document has been reviewed by the HED and
revised to reflect current Office of Pesticide Programs (OPP)
policies.Executive Summary

4-(4-chloro-2-methylphenoxy)butanoic acid (referred to as MCPB) is a
phenoxybutyric acid herbicide currently registered to Nufarm Americas
Inc., for the control or suppression of Canada thistle and certain other
broadleaf weeds.  The only currently registered food/feed use of MCPB is
on peas.  A tolerance for negligible residues of MCPB has been
established under 40 CFR §180.318(a) for pea at 0.1 ppm (N) and is
currently expressed in terms of MCPB per se.

The Interregional Research Project No. 4 (IR-4), on behalf of the
Agricultural Experiment Station of Washington, has submitted a petition,
PP#7E7257, proposing the establishment of a permanent tolerance for
residues of the herbicide MCPB in/on:

Mint tops (leaves and stems)	0.25 ppm

Concurrently, the petitioner has   SEQ CHAPTER \h \r 1 requested an
amendment of the end-use product, Thistrol® Herbicide (EPA Reg. No.
71368-5), a 2 lb acid equivalent (ae)/gal emulsifiable-concentrate (EC)
formulation of MCPB sodium salt, to include a new use pattern on mint. 
Thistrol® is proposed for a fall application to established mint at up
to 0.5 lb ae/A with a 40-day preharvest interval (PHI); a spring
treatment may also be made at an unspecified rate.  The proposed use
pattern should be revised to specify a maximum seasonal rate.

For purposes of this petition, based on the pea foliage metabolism data
and since mint is a minor crop (low-consumption commodity), the nature
of the residue in primary crops is adequately understood based on a
metabolism study conducted with peas.  The HED Metabolism Committee has
determined that the residues to be regulated for both tolerance and risk
assessment purposes in plant commodities are the free and conjugated
MCPB and MCPA ((4-chloro-2-methylphenoxy)acetic acid).

There are no livestock feedstuffs associated with the proposed use on
mint.  Therefore, no livestock metabolism data are required to support
this petition.  Data pertaining to livestock enforcement method, storage
stability data, or feeding studies are also not required.

The Agency previously requested that a method for the determination of
free and conjugated MCPB and MCPA be developed for enforcement purposes.
 A gas chromatography/mass spectrometry (GC/MS) analytical method
entitled, “An Analytical Method for the Determination of Residues of
MCPB and its Metabolite MCPA in Peas, Vines and Pods” was previously
submitted for plant commodities.  Upon review, the Agency found the
method inadequate and requested the method be revised and new method
validation data be submitted for the revised method.  

Acceptable analytical method and validation data were submitted for
MCPB, MCPA and 2-HMCPA in pea matrices.  These data have been reviewed
by HED and are classified as scientifically acceptable (Memo, T.
Goodlow, 01-JUL-2008; DP#: 330176).  The review of the method and
validation were sent to the Biological and Economic Analysis
Division’s (BEAD’s) Analytical Chemistry Laboratory (ACL) and deemed
adequate for enforcement purposes (e-mail, C. Stafford to D. Vogel,
16-JUN-2008).

For data collection, samples of mint tops (leaves and stems) and oil
were analyzed for residues of free and conjugated MCPB and MCPA using a
GC/MS method similar to that developed for peas.  The lowest level of
method validation (LLMV) for MCPB and MCPA was 0.05 ppm each in/on mint
tops and oil.  The method was adequately validated prior to and in
conjunction with the analysis of field trial samples.

The submitted magnitude of the residue data for mint tops are adequate
pending revised Sections B.  The conducted trials reflect the proposed
PHI but the application rates were 1.5-2x the maximum proposed single
application rate.  There are adequate storage stability data to validate
the storage conditions and durations of samples collected from the field
trials.  Label revisions are requested to specify a maximum seasonal
rate.  The field trial data for mint were entered into the spreadsheet
(Guidance for Setting Pesticide Tolerances Based on Field Trial Data
SOP) to determine an appropriate tolerance level for mint top.

An adequate processing study was conducted on mint.  The study showed
that the combined residues of MCPB and MCPA did not concentrate in mint
oil; therefore, a tolerance for mint oil is not required.

A satisfactory confined accumulation in rotational crops study following
application of MCPB is requested before the appropriate PBIs and the
need for a limited field rotational crop study can be determined.  HED
recommends further that the confined rotational crop study monitor for
both MCPB and MCPA.  

Analytical standards for MCPB and MCPA are currently available in the
EPA National Pesticide Standards Repository.

  SEQ CHAPTER \h \r 1 Regulatory Recommendations and Residue Chemistry
Deficiencies

Pending submission of a revised Section B (see requirements under
860.1200) and a revised Section F (see requirements under 860.1550),
there are no residue chemistry issues that would preclude granting a
conditional registration for use of the MCPB herbicide on mint or the
establishment of permanent tolerances for the combined residues of free
and conjugated MCPB and MCPA as follows:

Peppermint, tops	0.20 ppm

Spearmint, tops	0.20 ppm

Note to RD:  The current tolerance established under 40 CFR §180.318 is
for residues of 4-(2-methyl-4-chlorophenoxy)butyric acid) [MCPB] per se
in/on peas at 0.1 ppm.  The tolerance expression should be revised in
accordance with recommendations from the HED Metabolism Committee
decision (08-JUN-1995) and the HED Chapter of the RED (Memo, E. Méndez,
04-AUG-2005; DP#: 314047)).  The residues of concern for both tolerance
enforcement and risk assessment purposes are MCPB and MCPA, free and
conjugated.  The preferred chemical names for MCPB and MCPA are
4-(4-chloro-2-methylphenoxy)butanoic acid and
(4-chloro-2-methylphenoxy)acetic acid, respectively.

A human-health risk assessment is forthcoming in a separate document.

860.1200  Directions for Use

•	The petitioner should submit a revised Section B to specify a
maximum seasonal use rate for mint.  The submitted crop field trial data
will support a maximum total application rate of 1.8 lb ae/A, with a
single fall application at up to 1 lb ae/A and a subsequent spring
application at up to 0.8 lb ae/A.  In addition, the label should be
revised to specify minimum ground and aerial spray volumes.  Appropriate
plant-back intervals (PBIs) will be determined following the review of
an acceptable MCPB confined rotational crop study; however, until that
time, a revised Section B should be submitted to specify that rotation
should be limited to crops from which MCPB or MCPA use is registered.

860.1550  Proposed Tolerances

•	The petitioner should submit a revised Section F to reflect the
residues of concern and to reflect correct commodity definition and
tolerance levels as reflected in Table 7.

860.1800  Confined Accumulation in Rotational Crops

•	A satisfactory confined accumulation in rotational crops study
following application of MCPB is requested before the appropriate PBIs
and the need for a limited field rotational crop study can be
determined.  HED recommends further that the confined rotational crop
study monitor for both MCPB and MCPA. 

Background

MCPB is a selective herbicide used postemergence as a broadcast foliar
application to control broad-leaved annual and perennial weeds (Canada
thistle).  The end-use products are sodium salts; the only registered
food use is on peas.  The chemical structure and nomenclature of MCPB
and its metabolite MCPA are presented in Table 1.  The physiochemical
properties of the technical grade of MCPB are presented in Table. 2.



  SEQ CHAPTER \h \r 1 Table 1.		MCPB Nomenclature.

Chemical structure	

Common name	MCPB

IUPAC name	4-(4-chloro-o-tolyloxy)butyric acid

CAS name	4-(4-chloro-2-methylphenoxy)butanoic acid

CAS registry number	94-81-5

End-use product (EP)	2 lb ae/gal EC sodium salt formulation (Thistrol®
Herbicide; EPA Reg. No. 71368-5)

Chemical structure of 

MCPA metabolite	

(4-chloro-2-methylphenoxy)acetic acid

Table 2. 	Physicochemical Properties of MCPB.

Parameter	Value	Reference

Melting point/range	101.5-103.0ºC	RD Memorandum; 

H. Podall, 08-MAR-2002; DP# 279212

pH	5.6 (1% w/v)

	Density	1.26 g/mL at 20ºC

	Water solubility at 20ºC	60.4 mg/L (purified water)

29.9 mg/L in pH 4 buffer

3.83 mg/L in pH 7 buffer

>250 g/L in pH 10 buffer

	Solvent solubility at 20ºC	n-heptane			0.414 g/L

xylene			37.6 g/L

methylene chloride		69.9 g/L

n-octanol			71.6 g/L

ethyl acetate		144 g/L

methanol & acetone	>250 g/L

	Vapor pressure 	4 x 10-7 torr at 25ºC

	Dissociation constant, pKa	4.6 at 20ºC

	Octanol/water partition coefficient, Log(KOW)	pH 4	3.45

pH 7	1.33

pH 10	-0.21

	UV/visible absorption spectrum						dm/

solvent 		conc.	max	  A       (mol/cm)

water/MeOH	20.78	229	0.881	9700

		103.9	280	0.797	1750

			286sh	0.697	1530

Acid/MeOH	20.78	229	0.888	9770

		103.9	280	0.799	1760

			287sh	0.697	1530

Base/MeOH	20.78	229	0.871	9590

		103.9	280	0.800	1760

			287sh	0.695	1530

	

860.1200  Directions for Use

The petitioner has submitted an undated draft label for the 2 lb ae/gal
EC formulation (Thistrol® Herbicide; EPA Reg. No. 71368-5) of MCPB
sodium salt.  A summary of the proposed use pattern for mint is detailed
in Table 3.

Table 3.     Summary of Directions for Use of MCPB.

Applic. Timing, Type, and Equip.	Formulation

[EPA Reg. No.]	Applic. Rate 

(lb ae/A)	Max. No. Applic. per Season	Max. Seasonal Applic. Rate

(lb ae/A)	PHI

(days)

Mint

Early Postemergence;

Ground or aerial	2 lb ae/gal EC

[71368-5]	0.25-0.5	Not specified

(NS)	NS	40

	Use Directions and Limitations:  For control of winter annual weeds, a
fall application at 0.25-0.5 lb ae/A may be applied.  A single spring
application works best for field bindweed suppression.  Application may
be made alone or as a tank mix with other herbicides.  Do not use this
product if minor mint injury is unacceptable.  PBIs for rotational crops
are not specified.

Conclusions.  The proposed use directions are incomplete to allow
evaluation of the residue data relative to the proposed use on mint.  A
revised Section B should be submitted to specify a maximum seasonal rate
for mint.  The submitted crop field trial data will support a maximum
total application rate of 1.8 lb ae/A, with a single fall application at
up to 1 lb ae/A and a subsequent spring application at up to 0.8 lb
ae/A.  In addition, the label should be revised to specify minimum
ground and aerial spray volumes.  The need for PBIs will be determined
following the review of an outstanding MCPB confined rotational crop
study; however, until that time, a revised Section B should be submitted
to specify that rotation can only occur to a MCPB or MCPA registered
crop.

860.1300 Nature of the Residue - Plants

HED Memo:  S. Funk, 20-JUN-1995; DP#s: 196282 and 207498

For purposes of this petition, based on the pea foliage metabolism data
and since mint is a minor crop (low-consumption commodity), the nature
of the residue in primary crops is adequately understood based on a
metabolism study conducted on peas.  MCPB is metabolized to MCPA, and
the latter is hydroxylated to 6-chloro-2-hydroxymethylphenoxy acetic
acid.  The HED Metabolism Committee (08-JUN-1995) determined that the
residues to be regulated for both tolerance and risk assessment purposes
in plant commodities are the free and conjugated MCPB and MCPA.

NOTE to RD:  The current tolerance established under 40 CFR §180.318 is
for residues of MCPB per se in/on peas at 0.1 ppm.  The tolerance
expression should be revised in accordance with these recommendations
(the HED Metabolism Committee decision and the HED Chapter of the
Reregistration Eligibility Decision Document (RED) (Memo, E. Méndez,
04-AUG-2005; DP#: 314047)).

860.1300 Nature of the Residue - Livestock

There are no livestock feedstuffs associated with the proposed use on
mint.  Therefore, data requirements for livestock metabolism are not
relevant to this tolerance petition.

860.1340 Residue Analytical Methods

Tolerance enforcement methods

HED Memo:  S. Funk, 23-MAY-1996; DP#: 224170

HED Memo:  T. Goodlow, 01-JUL-2008; DP#: 330176

The Pesticide Analytical Manual (PAM) Vol. II lists PAM Vol. I, Section
222 Method A for chlorophenoxy acids in nonfatty foods.  A limit of
quantitation (LOQ) is not specified.  For enforcement of tolerances for
MCPA, PAM Vol. II lists PAM Vol. I, Sections 221.1, 421, and 422.  A LOQ
is not specified.  HED notes that Section 221.1 has now become Section
402 (GC method for acids and phenols) and Sections 421 and 422
(thin-layer chromatography (TLC) methods) no longer exist.  The Residue
Chemistry Chapter of the Registration Standard for MCPA, dated
31-AUG-1981, noted that the PAM Vol. I method is adequate for
enforcement of tolerances for residues of MCPA in livestock commodities
as-is but recommended that the method be modified with a hydrolysis step
for enforcement of MCPA tolerances for plant commodities.

The Agency previously requested that a method for the determination of
MCPB and MCPA be developed for enforcement purposes.  In response, a
GC/MS analytical method entitled, “An Analytical Method for the
Determination of Residues of MCPB and its Metabolite MCPA in Peas, Vines
and Pods” was submitted for plant commodities.  In the review of the
method, no additional work was requested concerning radiovalidation,
provided extensive changes were not made to the extraction and
hydrolysis steps, but the Agency recommended that the method be modified
to provide increased precision at the current tolerance of 0.1 ppm for
peas, that analyte qualitative identification and quantitation
procedures be revised, and that a new validation data (cold study) be
submitted after the improvements are made.  After acceptable method
validation of the revised method, an ILV should also be conducted.

Analytical method and validation data were submitted for MCPB, MCPA and
2-HMCPA in pea matrices.  These data have been reviewed by HED and are
classified as scientifically acceptable (Memo, T. Goodlow, 01-JUL-2008;
DP#: 330176).  The review of the method and validation were sent to the
Biological and Economic Analysis Division’s (BEAD’s) Analytical
Chemistry Laboratory (ACL) and deemed adequate for enforcement purposes
(e-mail, C. Stafford to D. Vogel, 16-JUN-2008).

Data-collection method

In the mint field trial and processing studies, samples of mint tops and
oil were analyzed for residues of MCPB and MCPA using the GC/MS method
entitled, “Gas Chromatographic/Mass Spectrometric Method for Analysis
of Chlorophenoxy Acid Herbicides:  MCPB and MCPA in Peas” with minor
modifications.  For mint tops, modifications included a reduced sample
size and estimating the speed of centrifugation since the tachometer on
the centrifuge was inoperative.  For mint oil, modifications included
devising a different extraction scheme to accommodate both MCPB and an
oil matrix (use of acetone and acetone/water was not compatible for the
oily matrix), reduced sample size, centrifugation not needed, and the
partitioning step changed to accommodate an oily matrix.  This method is
similar to the method previously developed for the analysis of MCPB and
MCPA in peas (Memo, S. Funk, 23-MAY-1996; DP#: 224170).

For mint tops, homogenized samples were sequentially extracted with
acetone and acetone/water (1:1, v:v), centrifuged, and the supernatants
combined.  The extract was acidified with concentrated hydrochloric acid
and partitioned with petroleum ether.  The aqueous layer was
repartitioned two more times with petroleum ether.  The combined
petroleum ether fractions were evaporated to dryness and derivatized
with diazomethane.  Hexane was added, the sample was rotary evaporated
just to dryness, and additional hexane was added prior to Florisil
column cleanup, using 5% ethyl acetate/hexane to elute residues.  The
eluate was analyzed by GC/MS.  For mint tops, the following ions are
monitored for MCPB:  m/z 141 and 242 (quantitation) and MCPA:  m/z 214
(quantitation) and 216.  The calculated LOQ and limit of detection (LOD)
for MCPB, were 0.012 and 0.004 ppm for mint tops.  The calculated LOQ
and LOD for MCPA, were 0.009 and 0.003 ppm for mint tops.  The LLMV for
both MCPB and MCPA was 0.05 ppm for mint tops.

Mint oil samples were dissolved in hexane and extracted with 0.01N
sodium hydroxide containing sodium chloride or sodium sulfate.  The
aqueous layer was acidified with concentrated hydrochloric acid and
partitioned into dichloromethane/hexane.  The dichloromethane/hexane
fraction was dried through anhydrous sodium sulfate.  The aqueous layer
was repartitioned two more times with dichloromethane/hexane.  The
combined organic fractions were evaporated to dryness and derivatized
with diazomethane.  Hexane was added to the sample, rotary evaporated
just to dryness, and additional hexane added prior to Florisil column
cleanup, using 5% ethyl acetate/hexane to elute residues.  The resulting
eluate was concentrated and residues redissolved in 0.1% corn oil in
hexane for GC/MS analysis.  For mint oil, the following ions are
monitored for MCPB:  m/z 242 and MCPA:  m/z 214 and 216.  The calculated
LOQ and limit of detection LOD for MCPB were 0.044 and 0.015 ppm for
mint oil; the calculated LOQ and LOD for MCPA were 0.039 and 0.013 ppm. 
The LLMV for both MCPB and MCPA was 0.05 ppm for mint oil.

The method was adequately validated prior to and in conjunction with the
analysis of field trial samples, using samples of untreated mint tops
fortified with MCPB and MCPA at 0.05-0.20 ppm each and oil fortified
with MCPB and MCPA at 0.05-0.10 ppm each.

Conclusions:  The GC/MS method is adequate as a data-collection method
for the determination of MCPB and MCPA in mint tops and oil; the method
is similar to the proposed GC/MS enforcement method.  Acceptable
analytical method and validation data were submitted for MCPB, MCPA and
2-HMCPA in pea matrices.  These data have been reviewed by HED and are
classified as scientifically acceptable (Memo, T. Goodlow, 01-JUL-2008;
DP#: 330176). The review of the method and validation were sent to
BEAD’s ACL and deemed adequate for enforcement purposes (e-mail, C.
Stafford to D. Vogel, 16-JUN-2008).

860.1360 MRMs

No MRM testing data were submitted with this petition.  The FDA PESTDATA
database (dated JUN-2005) indicates that MCPB is completely recovered
using multiresidue method Section 402 E1 and Section 402 E2, but a small
recovery (4-13%) using multiresidue method Section 402.  Recovery of
MCPA is variable (60-131%) using multiresidue method Section 402 (method
for acids and phenols).  The database did not include any information
for any of the other test methods.  Use of MRMs for purposes of MCPB
tolerance enforcement is not adequate, as there is no hydrolysis step to
release conjugated residues.

860.1380 Storage Stability

DER Reference List:	47218701.de1.doc

			47218701.de2.doc

The storage durations and conditions of samples from the crop field
trial and processing studies submitted to support this petition are
presented in Table 4.

Table 4.		Summary of Storage Conditions and Durations of Samples from
Crop Field Trial and Processing Studies.

Matrix 	Storage Temperature

 (°C)	Actual Storage Duration	Interval of Demonstrated 

Storage Stability

Mint tops 	<-20	43-80 days (1.4-2.6 months)	109 days

Mint oil	<-20	70-86 days (2.3-2.8 months)	91 days

To demonstrate the stability of residues in/on mint tops and oil, a
freezer storage stability study was conducted concurrently with the mint
field trial and processing studies.  Control samples of mint tops and
oil were fortified with MCPB and MCPA, each at 0.10 ppm and placed in
frozen storage.  After 109 (mint tops) or 91 (mint oil) days of frozen
storage, triplicate stored samples were analyzed along with a control
sample and three freshly fortified samples.  

Conclusions:  Residues of MCPB and MCPA were determined stable in/on
mint tops and oil stored frozen for up to 3.6 and 3 months,
respectively.  These data support the frozen storage conditions and
durations of samples from the submitted mint field trial and processing
studies.

860.1480 Meat, Milk, Poultry, and Eggs

There are no livestock feedstuffs associated with the proposed use on
mint.  Therefore, data requirements pertaining to meat, milk, poultry,
and eggs are not relevant to this tolerance petition.

860.1500 Crop Field Trials

DER Reference List:	47218701.de1.doc

Five   SEQ CHAPTER \h \r 1 mint field trials were conducted in the U.S.
during the 2002 growing season in Zones 5 (WI; 2 trials) and 11 (WA; 3
trials).  At each trial location, two broadcast applications of the 2 lb
ae/gal EC sodium salt formulation of MCPB were made.  The first
application was made at 0.961-1.042 lb ae/A (~2x) in the fall when mint
was dormant.  The second application was made at 0.745-0.789 lb ae/A
(~1.5x) in the spring 191-220 days after the first application, for a
total rate of 1.71-1.81 lb ae/A (~1.8x).  Applications were made in
~25-34 gal/A using ground equipment, without an adjuvant.    SEQ CHAPTER
\h \r 1 Samples of mint tops (leaves & stems) were collected 38-40 days
following the second (last) application.

Samples of mint tops were analyzed for residues of free and conjugated
MCPB and MCPA using the GC/MS method entitled, “Gas
Chromatographic/Mass Spectrometric Method for Analysis of Chlorophenoxy
Acid Herbicides:  MCPB and MCPA in Peas” with minor modifications. 
This method is similar to the method previously developed for the
analysis of free and conjugated MCPB and MCPA in peas (Memo, S. Funk,
23-MAY-1996; DP#: 224170).  The method was adequately validated prior to
and in conjunction with the analysis of field trial samples.  The LLMV
for both MCPB and MCPA was 0.05 ppm in mint.  The calculated LOQ and LOD
for MCPB, were 0.012 and 0.004 ppm for mint tops.  The calculated LOQ
and LOD for MCPA, were 0.009 and 0.003 ppm for mint tops.  Mint samples
were stored frozen up to 2.6 months prior to analysis; adequate
concurrent storage stability data are available to support sample
storage conditions and durations.

The results of the mint trials are summarized below in Table 5.  Maximum
individual residues of MCPB and MCPA were 0.13 ppm and <0.05 ppm,
respectively, in/on mint tops harvested 38-40 days following treatment
with the 2 lb ae/gal EC for a total rate of 1.71-1.81 lb ae/A.  Maximum
combined MCPB and MCPA residues were <0.18 ppm in/on mint tops.

Table 5.	Summary of Residue Data from Mint Field Trials with MCPB.

Commodity	Total Applic. Rate

(lb ae/A) 	PHI (days)	Analyte	Residue Levels (ppm)1

n	Min.	Max.	HAFT2	Median	Mean	Std. 

Dev.

Proposed use pattern = Fall and spring applications may be made with
fall treatment at 0.25-0.5 lb ae/A.  Spring application and total
application rates not specified.  The proposed PHI is 40 days.

Mint tops	1.71-1.81	38-40	MCPB	10	<0.05	0.13	0.12	0.08	0.08	0.03

	MCPA	10	<0.05	<0.05	<0.05	0.05	0.05	--

	Total3	10	<0.10	<0.18	<0.17	0.13	0.13	0.03

1  The LLMV (0.05 ppm) was used for any results reported as <LLMV.

2  HAFT = Highest-Average Field Trial.

3  Total combined MCPB and MCPA residues.

Conclusions.  The submitted residue data for mint tops are adequate. 
The number and locations of crop field trials are in accordance with
OPPTS Guideline 860.1500, and the appropriate samples were collected at
the proposed PHI, following a fall application made at up to 2x the
maximum proposed application rate and subsequent spring application made
at up to 1.5x the maximum proposed application rate.  A residue decline
trial was not conducted, but none is requested because of the dormant
and early season applications, and long PHI.

The residue data for mint tops were entered into the Agency’s
tolerance spreadsheet as specified by the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data SOP to determine appropriate
tolerance levels; see Attachment 2.  The recommended tolerance level was
adjusted by 1.5x, because of the exaggerated application rate. 
Therefore, the recommended tolerance level for MCPB (including MCPA)
in/on peppermint, tops and spearmint, tops is 0.20 ppm (based on 0.18
ppm = 0.27 ppm/1.5).

860.1520 Processed Food and Feed

DER Reference List:	47218701.de2.doc

HED Memo:  S. Funk, 23-MAY-1996; DP#: 224170

IR-4 has submitted   SEQ CHAPTER \h \r 1 a processing study with MCPB on
mint.  Samples used for processing were generated from two mint field
trials conducted in WA and WI during the 2002 growing season.  Mint tops
(leaves and stems) were harvested 38 or 40 days following the last of
two broadcast applications of the 2 lb ae/gal EC sodium salt formulation
of MPCB for a total rate of 1.74-1.80 lb ae/A (~1x the nominal field
trial rate).  The collected mint top samples were distilled into mint
oil.

Samples of mint tops and oil were analyzed for residues of free and
conjugated MCPB and MCPA using the GC/MS method entitled, “Gas
Chromatographic/Mass Spectrometric Method for Analysis of Chlorophenoxy
Acid Herbicides:  MCPB and MCPA in Peas” with minor modifications. 
This method is similar to the method previously developed for the
analysis of MCPB and MCPA in peas (Memo, S. Funk, 23-MAY-1996; DP#:
224170).  The method was adequately validated prior to and in
conjunction with the analysis of mint tops and oil samples.  The LLMV
for both MCPB and MCPA was 0.05 ppm in mint tops and oil.  Samples of
mint tops and oil were stored frozen for up to 2.6-2.8 months prior to
analysis; adequate concurrent storage stability data are available to
support sample storage conditions and durations.

Samples of treated mint tops (raw agricultural commodity (RAC)) bore
average MCPB residues of 0.086 and 0.107 ppm.  Following distillation,
residues of MCPB were nonquantifiable (<0.05 ppm) in mint oil, reducing
0.5-0.6x.  Residues of MCPA were below the LLMV (<0.05 ppm) in/on both
treated mint tops and mint oil, therefore processing factors for MCPA
could not be calculated.

Combined residues of MCPB and MCPA do not appear to concentrate
(0.6x-0.7x processing factors) in mint oil distilled from treated mint
tops bearing quantifiable residues of MCPB; see Table 6.  The observed
processing factors are less than the theoretical concentration factor of
333x for mint oil (based on separation into components; OPPTS 860.1520,
Table 3).

  SEQ CHAPTER \h \r 1 Table 6.	   Summary of Processing Factors for
MCPB.

RAC	Processed 

Commodity	Processing Factor

MCPB	MCPA	Total 

Mint tops	oil	0.5x, 0.6x	Not calculated (both RAC and oil <LLMV)	0.6x,
0.7x

Conclusions.  The available mint processing studies are adequate. 
Following distillation, combined residues of MCPB and MCPA reduced on
average by 0.7x in mint oil.  A separate tolerance is not required for
residues in/on mint oil.

  SEQ CHAPTER \h \r 1 860.1650 Submittal of Analytical Reference
Standards

Analytical standards for MCPB and MCPA are currently available in the
EPA National Pesticide Standards Repository with an expiration date of
8/23/09 for MCPB and 8/1/09 for MCPA (personal communication with Dallas
Wright, ACB, 1/2/08 and 1/9/08).  Analytical reference standards of MCPB
and MCPA must be replenished as requested by the Repository.  The
reference standards should be sent to the Analytical Chemistry Lab,
which is located at Fort Meade, to the attention of either Theresa Cole
or Frederic Siegelman at the following address:

	USEPA

	National Pesticide Standards Repository/Analytical Chemistry Branch/OPP

	701 Mapes Road

	Fort George G. Meade, MD  20755-5350

(Note that the mail will be returned if the extended zip code is not
used.)

860.1850/1900 Confined/Field Accumulation in Rotational Crops

HED Memo:  F. Fort, 09-MAR-2004; DP#: 197125

HED Memo:  F. Fort, 12-MAR-2008; DP#: 305068

Previously, the MCPB Task Force had submitted a request for a waiver of
the requirements for a confined accumulation in rotational crops study
for MCPB, based on the fact that MCPB has a very short half-life and
that MCPB soil residues would have gone through a minimum of 5
half-lives prior to planting another crop (3-4 months for peas). 
Residues of MCPA, a degradation product of MCPB, would be more likely to
be present then residues of MCPB.  The MCPB Task Force suggested that
EPA, therefore, rely on the MCPA rotational crop study.

The Agency agreed that MCPA would more likely be found in soil and that
this requirement may be satisfied with a confined accumulation in
rotational crops study with MCPA since this compound is the major
metabolite for MCPB.  However, the study that the registrant referred to
was found to be deficient (Memo, F. Fort, 09-MAR-2004; DP#: 197125).  In
their waiver request, the MCPB Task Force stated that EPA’s primary
reason for not accepting the previous study (MRID 40961301) was that a
maximum rate of 0.75 lb ae/A was used, whereas labels included rates of
up to 10.75 lb ae/A.  The MCPB Task Force stated that all the labels
have either  been changed or are in the process of being changed so that
no more than 0.75 lb ae/A will be registered.  Thus, EPA’s objection
will no longer apply.  HED recommended that if the registrant decreases
the maximum use rate for MCPA to no more than 0.75 lb ae/A, HED has no
reservations with granting the waiver request (Memo, F. Fort,
12-MAR-2008; DP#: 305068).

The submitted MCPB mint crop field trial data support a maximum total
application rate of 1.8 lb ae/A, with a single fall application at up to
1 lb ae/A and a subsequent spring application at up to 0.8 lb ae/A. 
Because this application rate is significantly higher than the
conditions HED recommended for previously (Memo, F. Fort, 12-MAR-2008;
DP#: 305068) when granting the MCPA confined rotational crop data
waiver, HED recommends that the MCPB Task Force submit a MCPB confined
rotational crop study.  HED recommends further that the confined
rotational crop study monitor for both MCPB and MCPA.  

The need for field rotational crop studies and/or rotational crop
restrictions will be determined following the review of the outstanding
MCPB confined rotational crop study.  Until an acceptable study is
submitted, rotation should be limited to crops from which MCPA and MCPB
use is registered.

860.1550 Proposed Tolerances

IR-4 has proposed a tolerance expression in terms of the residues of
MCPB.  Currently, a permanent tolerance is established for residues of
MCPB per se in/on pea at 0.1 ppm (N) [40 CFR §180.318(a)].  The HED
Metabolism Committee (08-JUN-1995) has determined that the residues to
be regulated for both tolerance and risk assessment purposes in plant
commodities are free and conjugated MCPB and MCPA.  The petitioner is
requested to submit a revised Section F to specify the tolerance
expression in terms of the combined residues of MCPB and MCPA (free and
conjugated).

No tolerances are established for livestock commodities and livestock
tolerances are not addressed in this petition as the proposed use does
not include any new uses on crops having livestock feedstuffs.  SEQ
CHAPTER \h \r 1 

Adequate field trial data are available to set a tolerance on mint tops;
the available data suggest that the proposed tolerance for mint leaves
is too high.  Based on the mint processing study, residues of MCPB and
MCPA do not appear to concentrate in oil; therefore, a separate
tolerance is not required for mint oil.

The tolerance proposed by the petitioner along with the HED’s
recommended tolerance are listed below in Table 7.    SEQ CHAPTER \h \r
1 The recommended tolerance level for mint tops (leaves and stems) in
the current petition was determined using recent Agency Guidance
(Guidance for Setting Pesticide Tolerances Based on Field Trial Data
SOP) and maximum likelihood estimation to impute censored values.  The
residue data used for the tolerance calculations and the supporting
spreadsheet outputs are presented in Attachment 2.

  SEQ CHAPTER \h \r 1 There are no established or proposed Codex,
Canadian, or Mexican maximum residue limits (MRLs) for MCPB.

Table 7.    Tolerance Summary for MCPB.

Commodity	Proposed Tolerance (ppm)	Recommended Tolerance (ppm)	Comments;

Correct Commodity Definition

Mint tops (leaves and stems)	0.251	0.202	Separate tolerances should be
established for Peppermint, tops and Spearmint, tops

1   The petitioner indicated that the proposed tolerance is based on the
MRL Calculator.  In those cases where no detectable residues were found
(LLMV = 0.05 ppm), a value of 0.025 ppm was used by the petitioner to
calculate the MRL.

2   HED notes that the recommended tolerance level is based on the MRL
Calculator.  In those cases where no quantifiable residues were found
(total combined MCPB and MCPA LLMV = 0.10 ppm), maximum likelihood
estimation (MLE) procedures were needed to impute censored values. 
Furthermore, the recommended tolerance level was divided by 1.5x,
because of the exaggerated application rate.  The unrounded tolerance
value and the appropriate rounding rule was applied to the revised
tolerance calculation.  Therefore, the recommended tolerance level for
MCPB (including MCPA) in/on peppermint, tops and spearmint, tops is 0.20
ppm (based on 0.18 ppm = 0.27 ppm/1.5).

  SEQ CHAPTER \h \r 1 Attachments

Attachment 1:  International Residue Limit Status (IRLS) Sheet.

Attachment 2:  Tolerance Assessment Calculations.

Template Version September 2005

cc:  M. Metzger (RRB1)

RDI: G.F. Kramer (30-SEP-2008), RAB1 Chemists (26-MAR-2008)

S. Levy: S-10953: PY1: (703)305-0783: 7509P: RAB1

Attachment 1:  International Residue Limit Status (IRLS) Sheet.

INTERNATIONAL RESIDUE LIMIT STATUS

Chemical Name: 4-(2-methyl-4-chlorophenoxy) butyric acid	Common Name:

MCPB	X Proposed tolerance

 Reevaluated tolerance

 Other	Date: 31-DEC-2007

Codex Status (Maximum Residue Limits)	U. S. Tolerances

X No Codex proposal step 6 or above

 No Codex proposal step 6 or above for the crops requested	Petition
Number:  PP#7E7257

DP#:  343743

Other Identifier:  

Residue definition (step 8/CXL): N/A	Reviewer/Branch:  S. Levy/RAB1

	Residue definition:  MCPB [4-(2-methyl-4-chlorophenoxy) butyric acid]

Crop (s)	MRL (mg/kg)	Crop(s) 	Tolerance (ppm)

Mint tops (leaves and stems)	0.25

Li業獴映牯䌠湡摡ݡ楌業獴映牯䴠硥捩ݯ堇丠⁯楌業獴

 No Limits for the crops requested	X No Limits

 No Limits for the crops requested

Residue definition:  N/A

	Residue definition:  N/A

Crop(s)	MRL (mg/kg)	Crop(s)	MRL (mg/kg)

	Notes/Special Instructions:  S.Funk, 01/02/2008.

Attachment 2:  Tolerance Assessment Calculations.

The dataset used to establish a tolerance for MCPB on mint tops
consisted of field trial data representing application rates of
1.71-1.81 lb ae/A (two broadcast applications, the first at 0.961-1.042
lb ae/A followed by a second at 0.745-0.789 lb ae/A) with a 38- to
40-day PHI.  As specified by the Guidance for Setting Pesticide
Tolerances Based on Field Trial Data SOP, the field trial PHIs are
within 25% of the minimum label PHI, but the field trial application
rates were 1.5-2x the maximum label application rate.  The residue
values used to calculate the tolerance are provided in Table I-1. 
Because 4 of 10 field trial sample results were below the combined LLMV
(<0.10 ppm), MLE procedures were needed to impute censored values. 

The MCPB-mint tops dataset was entered into the tolerance spreadsheet. 
Visual inspection of the lognormal probability plot (Figure I-1)
provided in the spreadsheet indicates that the dataset is reasonably
lognormal.  The result from the approximate Shapiro-Francia test
statistic (Figure I-2) confirmed that the assumption of lognormality
should not be rejected.

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:on.  Therefore, the recommended tolerance level for MCPB (including
MCPA) in/on peppermint, tops and spearmint, tops is 0.20 ppm (based on
0.18 ppm = 0.27 ppm/1.5).

Table I-1.	Residue data used to calculate tolerance for MCPB on mint
tops.

Regulator:	EPA

Chemical:	MCPB

Crop:	Mint tops (MLE)

PHI:	38-40 Days

App. Rate:	1.706-1.807 lb ae/A

Submitter:	IR-4

MRID Citation:	MRID 47218701

	Combined Residues of MCPB and MCPA (ppm)

	0.120

	0.151

	0.068

	0.079

	0.086

	0.093

	0.145

	0.169

	0.150

	0.184

Figure I-   SEQ Figure_II- \* ARABIC  1 .  Lognormal probability plot of
MCPB field trial data for mint tops.

Figure I- 2.   Tolerance spreadsheet summary of MCPB field trial data
for mint tops.

Page   PAGE  1  of   NUMPAGES  18 

MCPB	Summary of Analytical Chemistry and Residue Data	DP#:  349646