Document ID: EPA-HQ-OPP-2008-0769-0010
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-12-09T05:00Z

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C.  20460

OFFICE OF              

PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES 

MEMORANDUM

DATE:  	31-JAN-2008

SUBJECT:	PP#2F06430.  Novaluron on Cotton, Pome Fruits, and Potato. 
Review of Amendment Dated 21-JUN-2006 Submitted in Response to HED’s
Memoranda of 22-MAR-2004.  Submission of Requested Poultry Feeding
Study.  MRID#: 46870601.  DP#: 336897.  Chemical#: 124002.  Decision#:
368928.  40 CFR 180.598.

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:		John Hebert/Kable Davis, RM 07

Registration Division (RD) (7505P)

In conjunction with PP#2F06430, the Agency established the following
permanent tolerances for residues of novaluron
(N-[[[3-chloro-4-[1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy]phenyl]
amino]carbonyl]-2,6-difluorobenzamide) per se:

Fruit, pome, group 11	2.0 ppm

Apple, wet pomace	8.0 ppm

Cotton, undelinted seed	0.6 ppm

Cotton, gin by-products	30 ppm

Vegetables, tuberous and corm, subgroup 1C	0.05 ppm

Cattle#, meat	0.60 ppm

Cattle#, meat byproducts, except liver and kidney	0.60 ppm

Cattle#, fat	11 ppm

Cattle#, liver	1.0 ppm

Cattle#, kidney	1.0 ppm

Hog, meat	0.01 ppm

Hog, meat byproducts	0.01 ppm

Hog, fat	0.05 ppm

Milk	1.0 ppm

Milk, fat	20 ppm

Poultry, meat	0.03 ppm

Poultry, mbyp	0.04 ppm

Poultry, fat	0.40 ppm

Eggs	0.05 ppm

# Cattle, goat, horse, and sheep

Registration of Rimon( 10 EC (emulsifiable concentrate; EPA Reg. No.
66222-35) was conditional upon the submission of additional residue
chemistry data (Memo, G. Kramer, 22-MAR-2004; DP#: 285474).  The current
amendment addresses residue chemistry deficiencies identified in HED's
previous review (Memo, G. Kramer, 22-MAR-2004; DP#: 285474).  Note that
several of the deficiencies related to this petition were addressed in
the following memorandum:  G. Kramer, 10-MAY-2005; DP#: 315890.

Executive Summary of Chemistry Deficiencies

• Submission of an interference study and/or confirmatory method.

• Submission of additional storage stability data for the poultry
feeding study.

Note to RD:  The appropriate chemical name for novaluron is
“N-[[[3-chloro-4-[1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy]phenyl]am
ino]carbonyl]-2,6-difluorobenzamide.”  HED recommends that 40 CFR
180.598 should be amended accordingly.

RECOMMENDATIONS

HED continues to recommend for a conditional registration of Rimon(,
pending submission of an interference study and/or confirmatory method
and additional storage stability data for the poultry feeding study. 
Based on the submitted feeding study, the existing egg tolerance should
be increased to 0.07 ppm.

CONCLUSIONS

OPPTS 860.1340 Residue Analytical Methods - Plants

An interference study is still required to determine whether other
pesticides registered on the same commodities interfere with the
determination of novaluron; an interference study may be waived if a
specific single-analyte confirmatory method is submitted.

860.1480 Meat, Milk, Poultry, and Eggs

HED requests additional storage stability data for the poultry feeding
study.

DETAILED CONSIDERATIONS

Deficiency - OPPTS 860.1340 Residue Analytical Methods - Plants (from
Memo, G. Kramer, 22-MAR-2004; DP#: 285474)

The proposed plant enforcement methods, GC/ECD and HPLC/UV, need to pass
a PMV by ACL/BEAD before the methods can be deemed adequate for
tolerance enforcement.  In addition, the petitioner is required to
submit radiovalidation and interference studies.  Radiovalidation of the
GC/ECD and HPLC/UV methods is required, using radiolabeled samples from
the plant metabolism studies, in order to determine whether the methods
adequately extract aged (weathered) residues of novaluron.  An
interference study is required to determine whether other pesticides
registered on the same commodities interfere with the determination of
novaluron; an interference study may be waived if a specific
single-analyte confirmatory method is submitted.

Petitioner's Response:  The petitioner submitted acceptable plant and
livestock radiovalidation studies (MRID#s 45638304 and 46714901; See
Memo, S. Levy, 23-AUG-2006; DP#: 325183).  The radiovalidation data
support the analytical methods as enforcement methods.  

HED's Conclusion:  The Analytical Chemistry Branch (ACB) has
successfully completed the petition method validation (PMV) (Memo, S.
Levy, 15-SEP-2004; DP#: 306998).  However, an interference study and/or
confirmatory method have not been submitted.  This deficiency remains
partially resolved.

Deficiency - OPPTS 860.1480 Meat, Milk, Poultry, and Eggs (from Memo,
G. Kramer, 22-MAR-2004; DP#: 285474)

The petitioner has requested a waiver for the conduct of a poultry
feeding study.  Based on the maximum residues observed in the poultry
metabolism study, quantifiable residues would be expected in a feeding
study.  HED thus requested that the petitioner submit a poultry feeding
study.

Petitioner's Response:  A protocol for the requested poultry feeding
study was submitted by the petitioner and reviewed by HED (Memo, G.
Kramer, 05-MAY-2005; DP#: 315891).  The petitioner submitted a poultry
feeding study (MRID#: 46870601) that was adequate to demonstrate the
magnitude of novaluron residues in poultry commodities.  However, sample
storage intervals were not reported.

HED's Conclusion:  HED previously recommended for the following poultry
tolerances based on the results of a poultry metabolism study:  fat -
0.40 ppm; meat byproducts - 0.04 ppm; meat - 0.03 ppm; egg – 0.05 ppm
(Memo, S. Levy, 22-MAR-2004; DP#: 285474).  The levels of novaluron in
the poultry metabolism study were normalized to 1x and then multiplied
by a factor of 10x to account for the longer duration of a feeding
study.

Cotton is the only poultry feed item associated with the registered uses
of novaluron.  The reasonably balanced diet (RBD) of novaluron to
poultry is presented in Table 1.  This poultry dietary burden was
calculated using the registered tolerance level for cotton, undelinted
seed (0.60 ppm).

Table 1.  Poultry Dietary Burden.

Feedstuff (Type)	Tolerance (ppm)	%Dry Matter1	%Diet1	Dietary Burden2
(ppm)

cottonseed meal (PC)	0.60	89	20	0.12

Total dietary burden	0.12

1  Table 1 (OPPTS Guideline 860.1000).

2  Dietary Burden = [tolerance/% DM (cattle)] x %diet).  Poultry diets
are not corrected for %dry matter.

Poultry feeding study

46870601.der.wpd

Four groups of twelve laying hens each were dosed with novaluron at 0,
0.12, 0.36, and 1.2 ppm in the feed for 56/57 consecutive days. 
Following withdrawal of the test diet after 56/57 days, three satellite
groups of 12 birds each were returned to the control diet for 14, 42, or
70 days, to measure the kinetics of depuration.  Composite egg samples
were collected on Days -1, 3, 7, 9, 15, 19, 23, 27, 30, 33, 37, 40, 44,
47, 51, and 54 for all four groups.  Additional composite egg sampling
was conducted on Days 1, 5, and 12 for the 1.2 ppm group (Group 4). 
Hens were sacrificed within 24 hours after the treatment, and composite
samples of muscle, liver, kidney, skin (with attached fat), and
abdominal fat were collected.  The maximum dose tested thus appears to
be 10X the dietary burden.

Samples were analyzed for residues of novaluron per se using a liquid
chromatography with mass-spectrometric detection (LC/MSD) method.  The
method was validated with the analysis of egg and tissue samples
fortified at 0.01-1.0 ppm.  Concurrent method recoveries were also
analyzed for egg and tissue samples fortified at 0.01-3.0 ppm.  The
validated limit of quantitation (LOQ) was 0.01 ppm in chicken egg and
tissues.  The limit of detection (LOD) was 0.5 ng/mL (equivalent to
0.0025 ppm in all matrix types).  The maximum residues of novaluron in
eggs and tissues are listed below in Table 2.

Table 2.  Results of a Poultry Feeding Study with Novaluron.

Matrix	

Maximum Residue Levels (ppm) by Feeding Level*

	

0.12 (ppm)	

0.36 (ppm)	

1.2 (ppm)

Eggs, Day 7	0.020	0.092	0.246

Eggs, Day 27	0.045	0.179	0.542

Eggs, Day 54	0.063	0.181	0.702

Muscle	0.014	0.031	0.160

Liver	0.034	0.096	0.364

Kidney	0.039	0.089	0.368

Skin + Attached fat	0.161	0.462	1.842

Abdominal fat	0.323	0.988	3.011

Conclusions:  Based on the feeding study and the current MTDBs, HED
concludes that the currently-established tolerance levels are
sufficient; with the exception of eggs.  The egg tolerance should be
increased to 0.07 ppm.

  

The poultry feeding study will be classified as scientifically
acceptable, pending submission of additional storage stability
information.  Sample storage intervals for poultry commodities were not
reported, nor was it demonstrated that the storage interval for the
residue samples was less than 1 month.  Storage stability data for
novaluron residues should be submitted that support the storage
conditions and intervals of poultry egg and poultry skin/fat, muscle,
liver, kidney, and abdominal fat tissue samples used in this study or
the petitioner should demonstrate that the storage interval for the
residue samples was less than one month.  When the requested data and
information has been submitted, HED will reassess the adequacy of the
recommended livestock commodity tolerances.  This deficiency is
partially resolved.

ATTACHMENT

46870601.der.doc

RDI: G. Kramer (31-JAN-2008), RAB1 Chemists (30-JAN-2008)

S. Levy:S-10953:PM#1:(703)305-0783:7509P:RAB1

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