Document ID: EPA-HQ-OPP-2006-0201-0157
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-10-04T04:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

					WASHINGTON, D.C.  20460

OFFICE OF              

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES 

  SEQ CHAPTER \h \r 1 

January 31, 2006

	

MEMORANDUM

	

SUBJECT:		Residue Chemistry Chapter for the Cacodylic Acid and Salts
Reregistration Eligibility Decision (RED) Document.

DP Barcode:  D309106

			PC Codes:  012501, 012502, and 012503

Chemical Class:  Organo Arsenicals

FROM:		P. Yvonne Barnes, Chemist

			Reregistration Branch 2

			Health Effects Division [7509C]

			and

			Bonnie Cropp-Kohlligian, Environmental Scientist

			Reregistration Branch 4

			Health Effects Division [7509C]

THROUGH:	Alan Nielsen, Branch Senior Scientist

		Reregistration Branch II

		Health Effects Division (7509C)

TO:			Diana Locke, Risk Assessor

			Reregistration Branch 2

			Health Effects Division [7509C]

  SEQ CHAPTER \h \r 1 The summary analytical chemistry and residue data
document was originally prepared under contract by Dynamac Corporation,
The Dynamac Building 2275 Research Boulevard Rockville, MD 20850-3268.

Residue Chemistry Chapter for the

Cacodylic Acid and Salts RED Document

	PC Codes 012501, 012502, and 012503

Reregistration Case 2080

	TABLE OF CONTENTS	page

  TOC \f \* MERGEFORMAT \l "1-3"  

INTRODUCTION	1

REGULATORY BACKGROUND	1

SUMMARY OF SCIENCE FINDINGS	2

GLN 860.1200:  Directions for Use	2

GLN 860.1300:  Nature of the Residue - Plants	4

GLN 860.1300:  Nature of the Residue - Animals	4

GLN 860.1340:  Residue Analytical Methods - Plants	6

GLN 860.1340:  Residue Analytical Methods - Animals	7

GLN 860.1360:  Multiresidue Methods	8

GLN 860.1380:  Storage Stability Data - Plants	8

GLN 860.1380:  Storage Stability Data - Animals	8

GLN 860.1500:  Crop Field Trials	9

GLN 860.1520:  Processed Food/Feed	9

GLN 860.1480:  Meat, Milk, Poultry, Eggs	10

GLN 860.1400:  Water, Fish, and Irrigated Crops	13

GLN 860.1460:  Food Handling	13

GLN 860.1850 and 860.1900:  Confined/Field Accumulation in Rotational
Crops	13

TOLERANCE REASSESSMENT SUMMARY	18

Tolerances Listed Under 40 CFR §180.311	18

Tolerances to be Proposed Under 40 CFR §180.311	18

CODEX HARMONIZATION	19

DIETARY EXPOSURE ASSESSMENT	19

CITATIONS	20

 Published References	20

Master Record Identification Numbers (MRIDs)	20



	CACODYLIC ACID AND SALTS

	REREGISTRATION ELIGIBILITY DECISION

	RESIDUE CHEMISTRY CONSIDERATIONS

	PC Codes 012501, 012502, and 012503

Reregistration Case 2080

INTRODUCTION  TC \l1 "INTRODUCTION 

Cacodylic acid (PC Code 012501) and its sodium salt (PC Code 012502) are
non-selective, contact, organoarsenical herbicides.  Since there are
currently no registered products or food/feed uses of the
triethanolamine salt of cacodylic acid (PC Code 012503), this chemical
however will not be discussed further in this document.

The current registered food/feed uses of cacodylic acid and its sodium
salt are as defoliants on cotton.  The Master Label for Cacodylic acid
and its sodium salt is presented in Table A.  MAA Task Force proposes
that all manufacturing-use and end-use products will conform to the
supported master labels for organo arsenicals when finalized. Cacodylic
acid and its sodium salt are also registered for weed control uses on
non-bearing citrus (considered a non-food use), around buildings and
sidewalks, and for lawn renovation.  

REGULATORY BACKGROUND  TC \l1 "REGULATORY BACKGROUND 

The Cacodylic Acid Phase 4 Review was completed 03/11/1991.  A Data
Call-In (DCI) Notice was issued requiring the registrant to submit
several residue chemistry studies for cacodylic acid in order to fulfill
reregistration requirements.  The basic producer, Luxembourg-Pamol, Inc.
has submitted most of the studies requested in the DCI.  All of the
residue chemistry data submitted to-date by the registrant in support of
the reregistration of cacodylic acid and its sodium salt has undergone
Phase 5 Review within HED.  The information contained in this document
summarizes the Residue Chemistry Assessments with respect to the
reregistration of cacodylic acid and its sodium salt.

Tolerances are currently established for residues of the defoliant
cacodylic acid (dimethylarsinic acid), expressed as As2O3, in/on
cottonseed at 2.8 ppm, in kidney and liver of cattle at 1.4 ppm, and in
meat, fat, and meat byproducts (except kidney and liver) of cattle at
0.7 ppm [40 CFR §180.311]. According to 40 CFR §180.3(d)(4), where a
tolerance is established for more than one pesticide containing arsenic
found in or on a raw agricultural commodity, the total amount of such
pesticide shall not exceed the highest established tolerance calculated
as As2O3.

A method for determining residues of cacodylic acid by conversion of
cacodylic acid (as well as other arsenicals) to arsine and detection of
arsine colorimetrically (sensitivity = 0.01 ppm) is published in the
Pesticide Analytical Manual (PAM) Vol. II. for cacodylic acid tolerance
enforcement.  Although the subject method is adequate to determine total
residues of arsenic (not speciation analysis) in/on raw agricultural
commodities from all potential sources of arsenic exposure including
background levels of arsenic, it is not adequate to selectively
determine cacodylic acid residues per se in/on raw agricultural
commodities. It should be noted however, that the requirements for plant
residue analytical methods and ILV to support the reregistration of
cacodylic acid and its sodium salt are currently under review, MRID
459366-01 and MRID 459366-02.  

Based on available cotton metabolism data for cacodylic acid, as well as
published information for arsenicals and plant metabolism data for
monosodium methanearsonate (MSMA) and disodium methanearsonate (DSMA),
the HED Metabolism Committee (HED Metabolism Committee memo, C. Swartz
and B. Cropp-Kohlligian, 01/26/1995) has concluded that the residue of
concern is cacodylic acid per se, which for consistency, will continue
to be expressed as As2O3.  This decision was predicated on the evidence
that little or no demethylation of cacodylic acid is likely to occur
in/on cotton and animal commodities.  Residue analytical methodology
capable of accurately residues quantitation of cacodylic acid per se in
plant and animal tissues for data collection and tolerance enforcement
purposes was also required by the Committee.

The registrant submitted GC/MS residue analytical method descriptions
and validation data for the determination of cacodylic acid per se in/on
raw agricultural commodities.  These methods have been deemed acceptable
(with corrections to test sample results for low method recoveries) for
data collection purposes but are deemed unacceptable, in their current
form, for tolerance enforcement purposes.

SUMMARY OF FINDINGS  TC \l1 "SUMMARY OF SCIENCE FINDINGS 

GLN 860.1200:  Directions for Use  TC \l2 "GLN 860.1200:  Directions for
Use 

The only currently registered food/feed uses of cacodylic acid and its
sodium salt are as defoliants on cotton.  Cacodylic acid and its sodium
salt are also registered for uses on non-bearing citrus with a
restriction limiting application to crops which will not bear fruit
within one year (12 months) of application; hence, the non-bearing
citrus uses are consider non-food uses.

According to a the MAA Task Force the master labels indicate the use
patterns, type and timing of application, application limitations,
maximum application rate, maximum applications per-crop, and pre-grazing
interval. There are no Special Local Needs registrations for use of
cacodylic acid and its sodium salt. A summary of the food/feed use
sites, patterns, and restrictions subject to reregistration for
cacodylic acid and its sodium salt is provided in Table A.

Luxembourg-Pamol, Inc. has submitted the residue chemistry data in
support of the reregistration of cacodylic acid and its sodium salt. 
The food/feed use sites, patterns, and restrictions that will be
specified on their labels (specified in the Table) are consistent with
the food/feed use sites, patterns, and restrictions for cacodylic acid
and its sodium salt prescribed by the Agency, herein.

The maximum use patterns for cacodylic acid and its sodium salt as
prescribed by the Agency, herein, are based primarily on the use
patterns supported by the available residue chemistry data and
secondarily on the use patterns which the registrants wishes to support.
 A tabular summary of the residue chemistry science assessment for the
reregistration of cacodylic acid and its sodium salt is presented in
Table B.  The conclusions listed in Table B regarding the reregistration
eligibility of cacodylic acid and its sodium salt are predicated on the
use sites, patterns, and restrictions prescribed by the Agency and
summarized in Table A.

When end-use product DCIs are developed (e.g., at issuance of the RED),
the Registration Division (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 food/feed
use sites, patterns, and restrictions specified in Table A and that all
end-use product labels registered for use on non-bearing citrus or other
orchard crops be amended, as necessary, to restrict applications to
crops which will not bear fruit within one year of application.

GLN 860.1300:  Nature of the Residue - Plants  TC \l2 "GLN 860.1300: 
Nature of the Residue - Plants 

The requirements for plant metabolism data to support the reregistration
of cacodylic acid and its sodium salt are fulfilled.  An acceptable
metabolism study depicting the qualitative nature of the residue in
cotton has been submitted and has undergone a Phase 5 review within HED.
 No additional plant metabolism data are required to support the
reregistration of cacodylic acid and its sodium salt.

A cotton metabolism study was conducted at approximately 3.6x the
maximum supported use rate, using [14C] Cacodylic acid.  The average
total radioactive residue level in/on cotton leaf samples was 9.94 ppm. 
The average total radioactive residue level in delinted cottonseed
samples was 0.01 ppm.  The delinted cottonseed sample bearing the
highest radioactive residue level (0.05 ppm) was subjected to solvent
extraction (water, methanol, and hexane) followed by acid and base
hydrolysis.  Cottonseed aqueous extracts contained 68% of the total
radioactive residues (0.03 ppm).  Each of the other cottonseed extracts
(methanol, hexane, 0.1 N hydrochloric acid, and 0.1 N sodium hydroxide)
contained less than 7% of the total radioactive residues (<0.01 ppm). 
Bound residues accounted for 20% of the total radioactive residues (0.01
ppm).  HPLC analyses of the aqueous cottonseed sample extract indicated
that the major radioactive residue was parent (0.02 ppm).  Thin layer
chromatography analysis of the hexane extract (oil fraction) of the
cottonseed sample (7% total radioactive residues; <0.01 ppm) indicated
that the parent compound was present in the extract.  

The Agency determined that it is appropriate to translate data from the
[14C] Cacodylic acid cotton metabolism study to satisfy plant metabolism
data requirements for the sodium salt of cacodylic acid.

Based on the available cotton metabolism data for cacodylic acid, as
well as published information for arsenicals and plant metabolism data
for monosodium methanearsonate (MSMA) and disodium methanearsonate
(DSMA), the HED Metabolism Committee (HED Metabolism Committee memo, C.
Swartz and B. Cropp-Kohlligian, 01/26/1995) concluded that the residue
of concern (i.e., that which is of toxicological concern and requires
regulation) associated with the use of cacodylic acid is cacodylic acid
per se, which, for consistency, will continue to be expressed as As2O3. 
This decision was predicated on the evidence that little or no
demethylation of cacodylic acid is likely to occur in/on cotton
commodities.  Only residues of cacodylic acid per se are expected to be
incurred in/on cotton commodities resulting from treatment of cotton
with cacodylic acid.

GLN 860.1300:  Nature of the Residue - Animals  TC \l2 "GLN 860.1300: 
Nature of the Residue - Animals 

The requirements for animal metabolism data to support the
reregistration of cacodylic acid and its sodium salt are fulfilled. 
Acceptable metabolism studies depicting the qualitative nature of the
residues in ruminants and poultry have been submitted and have undergone
a Phase 5 review within HED.  No additional animal metabolism data are
required to support the reregistration of cacodylic acid and its sodium
salt.

In a ruminant metabolism study, lactating goats were orally dosed with
[14C] Cacodylic acid at a dietary level of 52 ppm for 3 days.  The
feeding level represents 4.7x the maximum theoretical dietary burden of
11 ppm to beef and dairy cattle (see GLN 860.1480:  Meat, Milk, Poultry,
and Eggs).  Radioactive residues in edible tissues (liver, kidney,
muscle, and fat) accounted for approximately 0.7% to 1.3% of the
administered radioactivity.  Radioactive residues in milk did not
account for any measurable percentage (<0.1%) of the administered dose. 
Radioactive residue levels were lower in milk (0.036 ppm to 0.092 ppm)
than in edible tissues except fat and did not increase significantly
throughout the dosing period.  Levels of radioactive residues in edible
tissues were highest in liver (0.677 ppm and 0.900 ppm) and lowest in
fat (0.031 ppm and 0.054 ppm).  Radioactive residues in edible ruminant
tissues and milk were adequately characterized/identified.  Mild acid
hydrolysis of edible tissues released 81% to 97% of the total
radioactive residue which was identified as cacodylic acid.  Organic
solvent extraction of whole milk and mild acid hydrolysis of skim milk
released a total of 85% of the total radioactive residues from milk. 
Cacodylic acid accounted for the majority of residues found in milk (64%
of the total radioactive residues; 0.023 ppm), with only trace amounts
(<0.01 ppm) of unidentified metabolites.

In a poultry metabolism study, laying hens were orally dosed with [14C]
Cacodylic acid at a dietary level of 60 ppm for 3 days.  The feeding
level represents 300x the maximum theoretical dietary burden of 0.2 ppm
to poultry (see GLN 860.1480:  Meat, Milk, Poultry, and Eggs). 
Radioactive residues in tissue and egg samples accounted for
approximately 3% of the administered radioactivity.  Radioactive residue
levels in egg yolks and egg whites increased throughout the 3-day dosing
period to maximums of 0.237 ppm and 0.471 ppm, respectively.  Data do
not indicate whether residues in egg fractions (yolks and whites)
plateaued by the end of the study.  Radioactive residue levels in edible
poultry tissues (liver, muscle, and fat) were highest in liver (0.273
ppm) and lowest in fat (0.018 ppm).  Radioactive residues in edible
poultry tissues and eggs were adequately characterized/identified.  Mild
acid hydrolysis released the majority of the radioactive residues (79%
to100% of the total radioactive residues) from egg fractions (yolks and
whites) and edible poultry tissues (liver, muscle, and fat).  HPLC
analyses of acid hydrolysates of egg fractions and edible poultry
tissues identified cacodylic acid as the major residue (75% to 98% of
the total radioactive residues).

Based on the available ruminant and poultry metabolism data for
cacodylic acid, as well as published information for arsenicals and
animal metabolism data for monosodium methanearsonate (MSMA) and
disodium methanearsonate (DSMA), the HED Metabolism Committee (HED
Metabolism Committee memo, C. Swartz and B. Cropp-Kohlligian, 1/26/95)
concluded that the residue of concern (i.e. that which is of
toxicological concern and requires regulation) associated with the use
of cacodylic acid is cacodylic acid per se, which, for consistency, will
continue to be expressed as As2O3.  This decision was predicated on the
evidence that little or no demethylation of cacodylic acid is likely to
occur in/on animal commodities.  Only residues of cacodylic acid per se
are expected to be incurred in animal commodities resulting from oral
exposure by livestock to feed stuffs derived from cotton commodities
treated with cacodylic acid. 

Available Published Information Concerning Animal Metabolism:  The
weight of evidence indicates that the methylation of arsenic which is
believed to occur in animals is a true detoxicating process.  Data have
demonstrated that organic as well as inorganic arsenic is methylated in
animals to form monomethyl arsonates and/or dimethyl arsonates.  Lakso
and Peoples (1975) found that about half of the arsenic found in the
urine of cows and dogs exposed to high levels of inorganic arsenic
(trivalent and pentavalent) were methylated derivatives.  Tam et. al.
(1978) determined that when monomethyl arsonates and dimethyl arsonates
have been found in the dog, dimethyl arsonate is more abundant. 
Therefore, given the ubiquity and abundance of arsenic in nature and the
probable mechanism of detoxicating arsenic in animals, dimethyl
arsonates are probably quite common in man and nature at finite
background levels.

GLN 860.1340:  Residue Analytical Methods - Plants  TC \l2 "GLN
860.1340:  Residue Analytical Methods - Plants 

The requirements for plant residue analytical methods to support the
reregistration of cacodylic acid and its sodium salt are not fulfilled. 
The registrant has proposed a GC/MS method which, in its current form,
is deemed unacceptable for enforcement purposes due to low method
recoveries obtained from samples “freshly” fortified with cacodylic
acid at levels equivalent to the reassessed tolerance levels for
residues of cacodylic acid per se in/on undelinted cottonseed and cotton
gin by-products.  Since the proposed GC/MS method, which selectively
quantitates residues of cacodylic acid per se, is considered superior to
the colorimetric method currently listed in the Pesticide Analytical
Manual (PAM), Vol. II, which quantitates residues of total arsenic (but
not speciation analysis) from all sources of arsenic exposure including
background levels, the Agency will conduct a “paper” review of the
method, possibly recommending minor modifications to the method to
improve method recoveries, and perform a method validation of the
“modified” GC/MS method.  An independent method validation of the
proposed GC/MS method will not be required at this time; however, the
registrants must radiovalidate the proposed GC/MS method using samples
from the cotton metabolism study and provide specificity/interference
data considering arsenic compounds other than cacodylic acid (including
but not limited to MSMA and DSMA).

Currently, the Pesticide Analytical Manual (PAM), Vol. II, lists a
colorimetric method for determination of residues of cacodylic acid
in/on raw agricultural commodities for enforcement of tolerances for
residues of cacodylic acid.  In brief, the method involves digestion of
the sample with strong acid and conversion of all arsenic residues to
arsine.  The method has a sensitivity of 0.01 ppm. A radiovalidated
residue analytical method capable of selectively/accurately quantitating
residues of cacodylic acid per se in/on undelinted cottonseed and cotton
gin byproducts for the purposes of tolerance enforcement is required. 
Without such a method to distinguish residues of cacodylic acid per se
from other arsenical compounds, tolerances (existing or required) for
residues of cacodylic acid per se in/on undelinted cottonseed and cotton
gin by-products would be practically unenforceable.

The registrant has submitted a GC/MS method for the determination of
cacodylic acid residues in/on undelinted cottonseed, cotton gin
byproducts, and cotton processed commodities.  In brief, cacodylic acid
residues are extracted from samples with water and derivatized using
methyl thioglycolate under acidic conditions.  The derivatized analogs
are partitioned into hexane and analyzed by GC/MS.  The reported limits
of quantitation for cacodylic acid residues in/on undelinted cottonseed
and cotton gin byproducts are 0.05 ppm and 1.0 ppm, respectively. 
Limits of detection (LOD) have not been reported.

Although the subject GC/MS method, with corrections for low method
recoveries, has been deemed acceptable for collecting data from
submitted cotton/cottonseed magnitude of the residue studies, it is not,
in its current form, adequate for enforcement purposes due to low method
recoveries obtained from samples “freshly” fortified with cacodylic
acid at levels equivalent to the reassessed tolerance levels for
residues of cacodylic acid per se in/on undelinted cottonseed and cotton
gin by-products.  The method recoveries of cacodylic acid per se from
“freshly” fortified samples of undelinted cottonseed and cotton gin
byproducts using this method at lower fortification levels (0.05 ppm to
0.5 ppm for undelinted cottonseed and 0.05 ppm to 1 ppm for cotton gin
byproducts) were generally within the acceptable 70% -120% range;
however method recoveries of cacodylic acid per se at the higher
fortification levels (2 ppm to 3 ppm for undelinted cottonseed and 2 ppm
to 61 ppm for cotton gin by-products) were generally below the
acceptable 70% -120% range (average recovery of 62% at 2 ppm to 3 ppm
for undelinted cottonseed and 53% to 62% average recovery at 2 ppm to 61
ppm for cotton gin byproducts).

GLN 860.1340:  Residue Analytical Methods - Animals

Tolerances for residues of cacodylic acid in animal commodities
resulting from ingestion of feed stuffs derived from raw agricultural
commodities treated with cacodylic acid will not be required/retained
(see GLN 860.1480:  Meat, Milk, Poultry, and Eggs); therefore, no
additional animal residue analytical methods data are required to
support the reregistration of cacodylic acid and its sodium salt.

The registrant submitted a GC/MS method for determining residues of
cacodylic acid in animal commodities.  In brief, cacodylic acid residues
in tissues, eggs and cream are extracted from samples with water and
acetonitrile, centrifuged, and filtered (3x).  The residues are then
concentrated by rotary evaporation, partitioned with dichloromethane for
clean-up, and derivatized using methyl thioglycolate under acidic
conditions.  The derivatized cacodylic acid analogs are then partitioned
into hexane and analyzed by GC/MS.  For analysis of whole and skim milk,
samples are acidified with concentrated hydrochloric acid, centrifuged,
and cacodylic acid residues in the supernatant are derivatized and
determined using the same procedures.

Although the subject GC/MS method, with corrections to test sample
results for low method recoveries derived from radiovalidation data, has
been deemed acceptable for collecting data from submitted animal feeding
studies, it would not be adequate for enforcement purposes due to low
radiovalidation method recoveries indicating the possibility that
“weathered” residues of cacodylic acid are not adequately recovered
from animal tissues using this method.

GLN 860.1360:  Multiresidue Methods  TC \l2 "GLN 860.1360:  Multiresidue
Methods 

Multiresidue method testing data to support the reregistration of
cacodylic acid and its sodium salt are not required.  No data pertaining
to the testing of cacodylic acid through the FDA multiresidue methods
have been submitted.  The 06/1999 PESTRAK database (PAM, Vol. I,
Appendix I) does not contain any information for cacodylic acid.  Having
considered the decision tree for PAM, Vol. I, Appendix II, Paragraph
(d)(1) and accompanying guidance found in the suggestions for producing
quality data, it is deemed unlikely that residues of cacodylic acid per
se will be adequately recovered using any of the existing multiresidue
method protocols.

GLN 860.1380:  Storage Stability Data - Plants  TC \l2 "GLN 860.1380: 
Storage Stability Data - Plants 

The requirements for plant storage stability data to support the
reregistration of cacodylic acid and its sodium salt are fulfilled.  No
additional plant storage stability data are required to support the
reregistration of cacodylic acid and its sodium salt.

The available data indicate that cacodylic acid residues are stable at
-30 °C to -10 °C in undelinted cottonseed, oil and meal for ~8 months,
cotton gin byproducts for ~10 months, and cottonseed hulls for ~11
months.   

GLN 860.1380:  Storage Stability Data - Animals

The available egg, poultry muscle, and poultry liver storage stability
data submitted in conjunction with the ruminant and poultry feeding
studies are considered unreliable as the GC/MS method used in the
storage stability study does not appear to adequately extract
“weathered” residues of cacodylic acid from animal commodities. 
However, additional storage stability data will not be required to
support the ruminant and poultry feeding studies since test sample
results from the feeding studies have been corrected for radiovalidation
method recoveries.  Test samples from the poultry metabolism study used
to radiovalidate the GC/MS method were in storage (frozen) for up to 3
years prior to radiovalidation analyses; hence, correction of test
sample results from the ruminant and poultry feeding study for
radiovalidation method recoveries will also compensate for any possible
decline in cacodylic acid residue levels due to storage.  Furthermore,
data from the poultry and ruminant metabolism studies indicate that
cacodylic acid residues are relatively stable in animal tissues. 
Residues of cacodylic acid accounted for >97% of the total radioactive
residues in poultry muscle, fat, liver and egg yolk samples after ~40
days of storage at -20 °C, and for 81% - 97% of the total radioactive
residues in goat liver, kidney, fat, and muscle after 11 months of
storage at -20 °C.

GLN 860.1500:  Crop Field Trials  TC \l2 "GLN 860.1500:  Crop Field
Trials 

Provided that all registrants amend end-use product labels, as
necessary, to specify a maximum application rate of 0.6 lb
a.i./A/application and 0.6 lb a.i./A/season for cotton and a minimum PHI
of 7 days, the requirements for cotton field trial data to support the
reregistration of cacodylic acid and its sodium salt are fulfilled. 
Based on available cotton field trial data the currently established
tolerance of 2.8 ppm for residues of cacodylic acid in/on cottonseed,
expressed as As2O3, should be increased to 3 ppm and a tolerance of 40
ppm for residues of cacodylic acid in/on cotton gin byproducts,
expressed as As2O3, should be established.  No additional crop field
trial data are required to support the reregistration of cacodylic acid
and its sodium salt.

The submitted cotton field trial data, corrected for low “fresh”
method recoveries, indicate that the maximum residues of cacodylic acid
per se in/on undelinted cottonseed and cotton gin byproducts resulting
from the maximum supported use rate of cacodylic acid on cotton are 4.3
ppm and 51 ppm, respectively.  The highest average field trial (HAFT)
values for residues of cacodylic acid per se in/on undelinted cottonseed
and cotton gin byproducts are 4.2 ppm and 45 ppm, respectively.  The
average values for residues of cacodylic acid per se in/on undelinted
cottonseed and cotton gin byproducts are 0.8 ppm and 21 ppm,
respectively.

The submitted cotton field trial data indicate that 4.3 ppm and 51 ppm
would be appropriate tolerance levels for residues of cacodylic acid per
se in/on undelinted cottonseed and cotton gin byproducts, respectively. 
These residue levels would be equivalent to 3 ppm and 37 ppm of
cacodylic acid expressed as As2O3, respectively, based on a conversion
factor of 0.7168 (2 mols of cacodylic acid (molecular weight of 137.99)
to make 1 mol of As2.O3 (molecular weight 197.82)).  Therefore, the
currently established tolerance of 2.8 ppm for residues of cacodylic
acid in/on cottonseed, expressed as As2O3, should be increased to 3 ppm
and a tolerance of 40 ppm for residues of cacodylic acid in/on cotton
gin byproducts, expressed as As2O3, should be established.

GLN 860.1520:  Processed Food/Feed  TC \l2 "GLN 860.1520:  Processed
Food/Feed 

The requirements for cottonseed processing data to support the
reregistration of cacodylic acid and its sodium salt are fulfilled.  No
tolerances for residues of cacodylic acid in the processed commodities
of cottonseed are required.  No additional processing data are required
to support the reregistration of cacodylic acid and its sodium salt.

The available cottonseed processing data indicate that residues of
cacodylic acid do not concentrate in hulls, meal, or refined oil. 
Residues of cacodylic acid in the processed commodities were less than
the residues in the raw agricultural commodity, with average reduction
factors of 0.7x, <0.2x, and <0.2x for cottonseed hulls, meal, and
refined oil, respectively.

GLN 860.1480:  Meat, Milk, Poultry, Eggs  TC \l2 "GLN 860.1480:  Meat,
Milk, Poultry, Eggs 

The requirements for meat/milk/poultry/egg magnitude of the residue data
to support the reregistration of cacodylic acid and its sodium salt are
fulfilled.  No additional meat/milk/poultry/egg magnitude of the residue
data are required to support the reregistration of cacodylic acid and
its sodium salt.

No additional tolerances for residues of cacodylic acid in animal
tissues resulting from the ingestion of feed stuffs derived from raw
agricultural commodities treated with cacodylic acid at the maximum
supported use rates are required.  Moreover, since background residue
levels of cacodylic acid found in milk and tissues of cattle may
substantially exceed those resulting from the ingestion of feed stuffs
derived from raw agricultural commodities treated with cacodylic acid at
the maximum supported use rates, tolerances for residues of cacodylic
acid in milk and beef tissues are not practically enforceable. 
Therefore, currently established tolerances for residues of the
defoliant cacodylic acid (dimethylarsinic acid), expressed as As2O3, and
in kidney and liver of cattle at 1.4 ppm, and in meat, fat, and meat
byproducts (except kidney and liver) of cattle at 0.7 ppm should be
revoked.

  

NOTE:  Although tolerances for residues of cacodylic acid in milk and
tissues of cattle are not being required/retained due to potential
background levels of cacodylic acid, estimates for secondary residues of
cacodylic acid incurred in milk and animal tissues (except poultry and
swine) resulting from ingestion of feed stuffs derived from raw
agricultural commodities treated with cacodylic acid should be included
in dietary exposure/risk estimates.

Dietary Burden Calculations:  Using the available residue chemistry data
for animal feed stuffs derived from raw agricultural commodities treated
with cacodylic acid, the maximum theoretical dietary burden for beef and
dairy cattle is 11 ppm.  For poultry and swine, the maximum theoretical
dietary burdens are 0.2 and 0.1 ppm, respectively.

Calculation of maximum theoretical dietary burdens for livestock.

Commodity	

% Dry Matter a	

% Diet a	

Maximum Residue Estimate (ppm)	

Dietary Contribution (ppm) b

Beef and Dairy Cattle

Cotton, undelinted seed	88	25	4.2c	1.2

Cotton gin byproducts	90	20	45c	10

Cotton, meal	89	15	0.8d	0.1e

Cotton, hulls	90	20	3.0d	0.7e

MAXIMUM THEORETICAL DIETARY BURDEN	11

Poultry

Cotton, meal	Not Applicable	20	0.8d 	0.2

MAXIMUM THEORETICAL DIETARY BURDEN	0.2

Swine

Cotton, meal	Not Applicable	15	0.8d 	0.1

MAXIMUM THEORETICAL DIETARY BURDEN	0.1

a	Table 1, OPPTS GLN 860.1000.

b	Contribution = [maximum residue estimate/ %DM (if cattle)] X  % diet).

c	Highest Average Field Trial (HAFT) value, expressed as cacodylic acid
equivalents, based on available cotton field trial data.

d  	Available cottonseed processing data indicate that residues of
cacodylic acid are reduced by factors of ca. 0.2x and 0.7x in meal and
hulls, respectively.  Based on these reduction factors and the Highest
Average Field Trial (HAFT) value of residues of cacodylic acid in/on
undelinted cottonseed (4.2 ppm), residue levels of cacodylic acid are
estimated at 0.8 ppm and 3.0 ppm in/on cottonseed meal and hulls,
respectively.

e	Not included in Maximum Theoretical Dietary Burden calculation.

For poultry and egg:  Provided that all registrants amend end-use
product labels, as necessary, to specify a maximum application rate of
0.6 lb a.i./A/application and 0.6 lb a.i./A/season for cotton and a
minimum PHI of 7 days, the available poultry metabolism and magnitude of
the residue data demonstrate that there is no reasonable expectation of
finite residues of cacodylic acid in egg and poultry tissues from the
feed stuffs derived from raw agricultural commodities treated with
cacodylic acid (40 CFR § 180.6(a)(3)).  Therefore, no tolerances for
residues of cacodylic acid in egg and poultry are required due to the
feed stuffs derived from raw agricultural commodities treated with
cacodylic acid.

For swine:  Provided that all registrants amend end-use product labels,
as necessary, to specify a maximum application rate of 0.6 lb
a.i./A/application and 0.6 lb a.i./A/season for cotton and a minimum PHI
of 7 days, the available animal metabolism and magnitude of the residue
data demonstrate that there is no reasonable expectation of finite
residues of cacodylic acid in tissues of swine from the feed stuffs
derived from raw agricultural commodities treated with cacodylic acid
(40 CFR § 180.6(a)(3)).  Therefore, no tolerances for residues of
cacodylic acid in swine are required due to the feed stuffs derived from
raw agricultural commodities treated with cacodylic acid.

For milk and meat:  Provided that all registrants amend end-use product
labels, as necessary, to specify a maximum application rate of 0.6 lb
a.i./A/application and 0.6 lb a.i./A/season for cotton and a minimum PHI
of 7 days, the available ruminant metabolism and magnitude of the
residue data demonstrate that finite residues of cacodylic acid are
likely to be incurred in milk, beef muscle, beef fat, beef liver, and
beef kidney from the feed stuffs derived from raw agricultural
commodities treated with cacodylic acid (40 CFR § 180.6(a)(1)).  Based
on the ruminant magnitude of the residue data, corrected for low
radiovalidation method recoveries, the maximum residues of cacodylic
acid per se resulting from the maximum theoretical dietary burden of
cacodylic acid to beef and dairy cattle (11 ppm) are estimated at 0.003
ppm in milk, 0.011 ppm in beef muscle, 0.019 ppm in beef fat, 0.110 ppm
in beef liver, and 0.236 ppm in beef kidney.  [Note: The maximum residue
estimate for residues of cacodylic acid per se in milk (0.003 ppm) is
below the GC/MS method validated limit of quantitation (0.01 ppm).]   
These residue values would be equivalent to 0.007 ppm in whole milk
(using LOQ of 0.01 ppm), 0.008 ppm in muscle, 0.014 ppm in fat, 0.079
ppm in liver, and 0.169 ppm in kidney, respectively, expressed as As2O3,
based on a conversion factor of 0.7168 (2 mols of cacodylic acid
(molecular weight of 137.99) to make 1 mol of As2.O3 (molecular weight
197.82)).

NOTE:  A residue analytical method capable of selectively/accurately
quantitating residues of cacodylic acid in milk and animal tissues for
the purposes of tolerance enforcement is not currently available. 
Without such a method to distinguish residues of cacodylic acid from
other arsenicals, tolerances (existing or required) for residues of
cacodylic acid in milk and tissues of cattle would be practically
unenforceable.

Available Published Information Concerning Background Residue Levels of
Arsenic in Animal Tissues:  As previously discussed (see GLN 860.1300: 
Nature of the Residue - Animals), the weight of evidence indicates that
little or no demethylation of arsenicals is likely to occur in animals. 
Moreover, methylation of arsenicals has been demonstrated to be a true
detoxicating process in animals.  Organic as well as inorganic forms of
arsenic are methylated in animals to potentially significant levels of
dimethyl arsonate.  Studies have found that about half of the arsenic
found in the urine of animals exposed to high levels of inorganic
arsenic (trivalent and pentavalent) are methylated derivatives. Given
the ubiquity and abundance of arsenic in the environment and the
potential for methylation of arsenicals in animals, residues of dimethyl
arsonate are probably quite common in animals as finite background
levels.

lk (1 detect out of 18 results; 6% with detectable residues (≥0.01
ppm)), 0.018 ppm in beef steak (5 detects out of 18 results; 28% with
detectable residues (≥0.01 ppm)), and 0.036 ppm in beef liver (7
detects out of 18 results; 39% with detectable residues (≥0.01 ppm)). 

 Other sources have found total residues of arsenic, expressed as As2O3,
as high as 0.05 ppm in milk (Woolson, 1974) and as high as 1.3 ppm in
beef (Schroeder and Balassa, 1966).  Since arsenic (inorganic and
organic) has been demonstrated to be methylated in cows as a
detoxicating process, a substantial portion of these total arsenic
residues found in milk and meat as background levels are likely to be
monomethyl arsonates and/or dimethyl arsonates, with dimethyl arsonate
the more abundant.  Hence, if only a fraction of the highest background
residues of arsenic (expressed as As2O3) found in milk and meat (0.05
ppm and 1.3 ppm, respectively) are actually metabolized to residues of
cacodylic acid, these background levels of cacodylic acid would
substantially exceed the maximum residue levels of cacodylic acid
(expressed as As2O3) estimated to be incurred in whole milk and beef
tissues (0.007 ppm and 0.169 ppm, respectively) from the maximum
theoretical dietary burden to beef and dairy cattle for residues of
cacodylic acid.

GLN 860.1400:  Water, Fish, and Irrigated Crops  TC \l2 "GLN 860.1400: 
Water, Fish, and Irrigated Crops 

Cacodylic acid is presently not registered for direct use on water and
aquatic food and feed crops; therefore, no residue chemistry data are
required under this topic.

GLN 860.1460:  Food Handling  TC \l2 "GLN 860.1460:  Food Handling 

Cacodylic acid is presently not registered for use in food-handling
establishments; therefore, no residue chemistry data are required under
this topic.

GLN 860.1850 and 860.1900:  Confined/Field Accumulation in Rotational
Crops  TC \l2 "GLN 860.1850 and 860.1900:  Confined/Field Accumulation
in Rotational Crops 

The requirement for confined rotational crops data to support the
reregistration of cacodylic acid and its sodium salt is fulfilled. 
Based on an adequate confined rotational crop study, plantback intervals
for rotational crops are not required on end-use product labels. 
Limited field rotational crop studies and tolerances for cacodylic acid
residues of concern in rotational crop commodities are not required.



Table A.	Maximum Use Patterns and Restrictions Supported Under the
Reregistration Process for Cacodylic 

		Acid and Sodium Salts (Case 2080).

**Master Label supported by the Luxembourg-Pamol, Incorporated

	MAATF/051209-323 dated December 09, 2005



Table A. Continued	 Maximum Use Patterns, and Restrictions Supported
Under the

				 Reregistration Process for Cacodylic Acid and Sodium Salts (Case
2080)

**Master Label supported by the Luxembourg-Pamol, Incorporated

	MAATF/051209-323 dated December 09, 2005

Table B.   Residue Chemistry Assessments for Reregistration of Cacodylic
Acid.

GLN:  Data Requirements	Current Tolerances, ppm [40 CFR §180.311]	Must
Additional Data Be Submitted?	References 

860.1200:  Directions for Use	Not applicable	Yes 	See Table A

860.1300:  Plant Metabolism	Not applicable	No	42886601 

860.1300:  Animal Metabolism	Not applicable	No 	42975001, 43059901 

860.1340:  Residue Analytical Methods

 -	Plant commodities	Not applicable	Yes 	44325801 

 -	Animal commodities	Not applicable	No 4	44415202 

860.1360:  Multiresidue Methods	Not applicable	No 

	860.1380:  Storage Stability Data

	 -	Plant commodities	Not applicable	No	443200018, 44325802 8

 -	Animal commodities	Not applicable	No 4	44415202 9

860.1500:  Crop Field Trials

	 -	Cotton, seed and gin byproducts	2.8, seed	No	44325801 8

860.1520:  Processed Food/Feed

 -	Cottonseed	None	No	44087401 

860.1480:  Meat, Milk, Poultry, Eggs

 -	Milk and the Fat, Meat, and Meat Byproducts of Cattle, Goats, Hogs,
Horses, and Sheep	0.7, fat, meat, and meat byproducts (except kidney and
liver) of cattle;

1.4, kidney and liver of cattle	No 4	44415203 9

 -	Eggs and the Fat, Meat, and Meat Byproducts of Poultry

	None	No 4	44415201 9

860.1400:  Water, Fish, and Irrigated

  ADVANCE \x 50 Crops	Not applicable	No

	860.1460:  Food Handling	Not applicable	No

	860.1850:  Confined Rotational Crops	None	No	43091101 

860.1900:  Field Rotational Crops	None	No

	



TOLERANCE REASSESSMENT SUMMARY  TC \l1 "TOLERANCE REASSESSMENT SUMMARY 

Tolerances for residues of cacodylic acid in/on plant and animal
commodities (40 CFR §180.311) are currently expressed in terms of
As2O3.  The HED Metabolism Committee (HED Metabolism Committee memo, C.
Swartz and B. Cropp-Kohlligian, 01/26/1995) has determined that the
tolerance expression is appropriate.  A summary of cacodylic acid
tolerance reassessments is presented in Table C.

Tolerances Listed Under 40 CFR §180.311  TC \l2 "Tolerances Listed
Under 40 CFR §180.311 :

Sufficient residue chemistry data are available to reassess the adequacy
of the currently established tolerance for residues of cacodylic acid
in/on cottonseed.  Based on available cotton field trial data, the
currently established tolerance of 2.8 ppm for residues of cacodylic
acid in/on cottonseed, expressed as As2O3, should be increased to 3 ppm,
and the correct commodity definition is undelinted cottonseed.

Sufficient residue chemistry data are available to reassess the
currently established tolerances for residues of cacodylic acid in
cattle tissues.  Since background residue levels of cacodylic acid found
in beef tissues and milk may substantially exceed those incurred from
the maximum theoretical dietary burden from ingestion of feed stuffs
derived from raw agricultural commodities treated with cacodylic acid at
the maximum supported use rates, tolerances for residues of cacodylic
acid in beef tissues and milk are not practically enforceable. 
Therefore, currently established tolerances for residues of the
defoliant cacodylic acid (dimethylarsinic acid), expressed as As2O3, in
kidney and liver of cattle at 1.4 ppm, and in meat, fat, and meat
byproducts (except kidney and liver) of cattle at 0.7 ppm should be
revoked.

Tolerances to be Proposed Under 40 CFR §180.311  TC \l2 "Tolerances to
be Proposed Under 40 CFR §180.311 :

As a result of a September 1995 Agency revision to the residue chemistry
test guidelines, the currently recognized raw agricultural commodities
of cotton are the undelinted seed and cotton gin byproducts.  Therefore,
a tolerance must be proposed for residues of cacodylic acid in/on cotton
gin byproducts.  Sufficient field trial data are available to determine
an appropriate tolerance for residues of cacodylic acid in/on cotton gin
by-products.  Based on available cotton field trial data, a tolerance of
40 ppm for residues of cacodylic acid in/on cotton gin byproducts,
expressed as As2O3, should be established.



Table C.   Tolerance Reassessment Summary for Cacodylic Acid.

Commodity	Established Tolerance, ppm	Reassessed Tolerance, ppm	Comments

[Correct Commodity Definition]

	Tolerances Listed Under 40 CFR §180.311

Cattle, fat	0.7	Revoke	Background residue levels of cacodylic acid found
in beef tissues and milk may substantially exceed those resulting from
the maximum theoretical burdens to beef and dairy cattle through
ingestion of feed stuffs derived from raw agricultural commodities
treated with cacodylic acid at the maximum supported use rates.  Hence,
tolerances for residues of cacodylic acid in beef tissues are not
practically enforceable.

Cattle, kidney	1.4

Cattle, liver	1.4

Cattle, mbyp (except kidney and liver)	0.7

Cattle, meat	0.7

Cottonseed	2.8	3	[Cotton, undelinted seed]

Tolerances To Be Proposed Under 40 CFR §180.311

Cotton, ginned byproducts	–	40

	

CODEX HARMONIZATION  TC \l1 "CODEX HARMONIZATION 

There are no established Codex MRLs for cacodylic acid.  Therefore,
issues of Codex harmonization do not exist.

DIETARY EXPOSURE ASSESSMENT  TC \l1 "DIETARY EXPOSURE ASSESSMENT 

No monitoring data for residues of cacodylic acid per se are available
from FDA and USDA.  The available monitoring data on total arsenic (as
As2O3) from the FDA Total Diet Study (Market Baskets 91-3 through 97-1)
are limited for the food/food-forms of concern here and are likely to
significantly overestimate dietary exposure from cacodylic acid
resulting from the supported use rates of cacodylic acid since they
include residues of arsenic from all potential sources including
background.  Hence, all anticipated residue estimates should be based on
available residue chemistry data for cacodylic acid incorporating
percent of crop treated as appropriate.  Anticipated residue estimates
should be provided for cotton commodities as well as milk and tissues of
cattle.  Anticipated residue estimates for cattle tissues may be
translated to other animal tissues as appropriate.  [NOTE:  The
available animal metabolism and magnitude of the residue data
demonstrate that there is no reasonable expectation of finite residues
of cacodylic acid in tissues of poultry and swine from the feed stuffs
derived from raw agricultural commodities treated with cacodylic acid
(40 CFR § 180.6(a)(3)).]

CITATIONS

Published References

1.     Hood, R.D. Cacodylic Acid:  Agricultural Uses, Biologic Effects,
and Environmental Fate.  Veterans Administration Monograph, 1985.

2.     Lakso, J.U., and S.A. Peoples.  “Methylation of Inorganic
Arsenic by Mammals.”

	J. Agric. Food Chem.  23:674-76, (1975).

3.     National Academy of Sciences.  1977.  Arsenic, Medical and
Biological Effects of Environmental Pollutants.  Washington, National
Academy of Science.

4.     Schroeder, H.A., and Balassa, J.B.  “Abnormal Trace Elements in
Man: Arsenic.”  

	J. Chronic Diseases  19:85-106, (1966).

5.     Tam, G.K.H., et.al.  “Separation of Arsenic Metabolites in Dog
Plasma and Urine Following Intravenous Injection of 74As.”  Anal.
Biochem.  896:505-11, (1978).

6.     Woolson, E.A.  “Arsenical Pesticides.”  A Symposium Sponsored
by the Division	Pesticide Chemistry at the 168th Meeting of the American
Chemical Society in Atlantic City, New Jersey, September 9, 1974. 
Washington, American Chemical Society. 

Master Record Identification Numbers (MRIDs)

42886601 O'Neal, S. (1993) Metabolic Fate and Distribution of (carbon
14) Cacodylic Acid in Cotton: Lab Project Number: 618: 1502. Unpublished
study prepared by PTRL East, Inc. 95 p. 

42975001 Krautter, G. (1993) The Metabolism of (carbon 14)-Cacodylic
Acid in Lactating Goats Following Oral Administration for 3 Consecutive
Days: Lab Project Number: 615: 1548. Unpublished study prepared by PTRL
East, Inc. 176 p. 

43059901 Krautter, G. (1993) The Metabolism of (carbon-14)-Cacodylic
Acid in Laying Hens Following Oral Administration for 3 Consecutive
Days: Lab Project Number: 616: 1569. Unpublished study prepared by PTRL
East, Inc. 146 p.

43091101 O'Neal, S. (1994) A Confined Rotational Crop Study with
(carbon-14)-Cacodylic Acid Using Carrots (Daucus carota), Lettuce
(Lactuca sativa) and Barley (Hordeum vulgare): Lab Project Number: 507:
1534.  Unpublished study prepared by Pan-Agricultural Labs., Inc.; PTRL
East, Inc.; Pharmacology & Toxicology Research Lab.  223 p.

44087401 Leppert, B. (1996) Magnitude of Cacodylic Acid Residues in
Cotton, A Processing Study: Final Report: Lab Project Number: 6293-142:
SARS-95-1 1: CHW 6293-142. Unpublished study prepared by Stewart
Agricultural Research Services, Inc. and Corning Hazleton, Inc. 508 p. 

44320001 Leppert, B. (1996) Supplement to "Magnitude of Cacodylic Acid
Residues in Cotton, A Processing Study": Lab Project Number: SARS-95-11:
6293-142: CHW 6293-142. Unpublished study prepared Hazleton, Inc. 173 p.

44325801 Leppert, B. (1996) Magnitude of Cacodylic Acid Residues in
Cotton: Final Report: Lab Project Number: SARS-95-10: 6293-141:
SARS-95-CA-IOB. Unpublished study prepared by Stewart Agricultural
Research Services, Inc. 408 p. 

44325802 Leppert, B. (1996) Supplemental to Magnitude of Cacodylic Acid
Residues in Cotton: Supplement to Final Report: Lab Project Number:
6293-141: SARS-95-10: CHW 6293-141. Unpublished study prepared by
Stewart Agricultural Research Services, Inc. and Corning Hazleton, Inc.
168 p. 

44415201 Keller, G.; Peterson, K. (1997) Magnitude of the Residues of
Cacodylic Acid and Methylarsonic Acid in Edible Tissues and Eggs of
Laying Hens: Final Report: Lab Project Number: 6314-105: CHW 6314-105.
Unpublished study prepared by Coming Hazleton Inc. 409 p. 

44415202 Keller, G.; Peterson, K. (1997) Validation of the Method for
the Determination of Cacodylic Acid and Methylarsonic Acid Using Eggs
and Tissues from a Laying Hen Metabolism Study: Final Report: Lab
Project Number: CHW 6314-108: 6314-108: CHW 6314-105. Unpublished study
prepared by Coming Hazleton Inc.90 p. {OPPTS 860.1340}

44415203 Keller, G.; Peterson, K. (1997) Magnitude of the Residues of
Cacodylic Acid and Methylarsonic Acid in Edible Tissues and Milk of
Lactating Dairy Cows: Final Report: Lab Project Number: CHW 6314-106:
6314-106. Unpublished study prepared by Corning Hazleton Inc. 351 p. 

 PAGE   2 

 PAGE   3 

References have undergone a Phase 5 Review within HED as noted.

Registrants must amend all end-use product labels of cacodylic acid and
its sodium salt registered for use on cotton, as necessary, to conform
to the Agency’s prescribed maximum use patterns and restrictions
specified in Table A.  Registrants must amend all end-use products
labels of cacodylic acid and its sodium salt registered for use on
non-bearing citrus, as necessary, to restrict applications to crops
which will not bear fruit within one year of application.

DP Barcode D194647, 11/15/95, B. Cropp-Kohlligian.

The requirements for animal metabolism, storage stability, and
meat/milk/poultry/egg magnitude of the residue data to support the
reregistration of cacodylic acid and its sodium salt are fulfilled.  No
additional animal metabolism, storage stability, and
meat/milk/poultry/egg magnitude of the residue data are required to
support the reregistration of cacodylic acid and its sodium salt.  Since
background residue levels of cacodylic acid found in beef tissues and
milk may substantially exceed those resulting from the ingestion of feed
stuffs derived from  raw agricultural commodities treated with cacodylic
acid at the maximum supported use rates, tolerances for residues of
cacodylic acid in beef tissues and milk are not practically enforceable.
 Therefore, currently established tolerances for residues of the
defoliant cacodylic acid (dimethylarsinic acid), expressed as As2O3, in
kidney and liver of cattle at 1.4 ppm, and in meat, fat, and meat
byproducts (except kidney and liver) of cattle at 0.7 ppm should be
revoked.

Since tolerances for residues of cacodylic acid in animal commodities
will not be required/retained, no additional animal residue analytical
method data are required to support the reregistration of cacodylic acid
and its sodium salt. 

DP Barcode D196657, 7/24/96, B. Cropp-Kohlligian.

DP Barcode D198198, 7/15/96, B. Cropp-Kohlligian.

The requirements for plant residue analytical methods to support the
reregistration of cacodylic acid and its sodium salt are not fulfilled. 
The registrant has proposed a GC/MS method which, in its current form,
is deemed unacceptable for enforcement purposes due to low method
recoveries obtained from samples “freshly” fortified with cacodylic
acid at levels equivalent to the reassessed tolerance levels for
residues of cacodylic acid per se in/on undelinted cottonseed and cotton
gin by-products.  Since the proposed GC/MS method, which selectively
quantitates residues of cacodylic acid per se, is considered superior to
the colorimetric method currently listed in the Pesticide Analytical
Manual (PAM), Vol. II, which quantitates residues of total arsenic (but
not speciation analysis) from all sources of arsenic exposure including
background levels, the Agency will conduct a “paper” review of the
method, possibly recommending minor modifications to the method to
improve method recoveries, and perform a method validation of the
“modified” GC/MS method.  An independent method validation of the
proposed GC/MS method will not be required at this time; however, the
registrants must radiovalidate the proposed GC/MS method using samples
from the cotton metabolism study and provide specificity/interference
data considering arsenic compounds other than cacodylic acid (including
but not limited to MSMA and DSMA).

DP Barcodes D240407 and D240412, 02/14/00, B. Cropp-Kohlligian.

DP Barcodes D242954 and D245341, 02/14/00, B. Cropp-Kohlligian.

 

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ta to support the reregistration of cacodylic acid and its salts are not
required.  No data pertaining to the testing of cacodylic acid through
the FDA multiresidue methods has been submitted.  The 06/1999 PESTRAK
database (PAM, Vol. I, Appendix I) does not contain any information for
cacodylic acid.  Having considered the decision tree for PAM, Vol. I,
Appendix II, Paragraph (d)(1) and accompanying guidance found in the
suggestions for producing quality data, it is deemed unlikely that
residues of cacodylic acid per se will be adequately recovered using any
of the existing multiresidue method protocols.

DP Barcodes D229203 and D229837, 03/18/97, B. Cropp-Kohlligian.

DP Barcode D198883, 07/3/96, B. Cropp-Kohlligian.