Document ID: EPA-HQ-OPP-2009-0273-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-06-10T04:00Z

EPA Registration Division contact for PP# 9E7546: Laura Nollen, (703)
305-7390

	EPA Registration Division contact for PP# 9F7547: Jennifer Gaines,
(703) 305-5967

Interregional Research Project Number 4 (IR-4) and Makhteshim-Agan of
North American

	Petition Numbers PP# 9E7546, 8E7426

	

EPA has received a pesticide petition, PP # 9E7546, from IR-4, 500
College Road East, Suite 201W, Princeton, NJ 08540,  proposing, pursuant
to section 408(d) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C.
346a(d), to amend 40 CFR 180.598 by establishing a tolerance for
residues of novaluron,
N-[[[3-chloro-4-[1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy]phenyl]amino
]carbonyl]-2,6-difluorobenzamide, in or on vegetable, fruiting, group 8
at 1.1 parts per million (ppm); vegetable, cucurbit, group 9 at 0.25
ppm; berry, low growing, subgroup 13-07G at 0.50 ppm; cocona at 1.1 ppm;
eggplant, African at 1.1 ppm; eggplant, pea at 1.1 ppm; eggplant,
scarlet at 1.1 ppm; goji berry at 1.1 ppm; huckleberry, garden at 1.1
ppm; martynia at 1.1 ppm; naranjilla at 1.1 ppm; okra at 1.1 ppm;
roselle at 1.1 ppm; sunberry at 1.1 ppm; tomato, bush at 1.1 ppm;
tomato, currant at 1.1 ppm; tomato, tree at 1.1 ppm; bean, snap,
succulent  at 0.60 ppm;  bean, dry  at 0.20 ppm; and Swiss chard at 12
ppm. 

In addition, EPA received a pesticide petition, PP # 9F7547, from
Makhteshim-Agan of North America, Inc., 4515 Falls of Neuse Road,
Raleigh, NC 27609 proposing, pursuant to section 408(d) of the Federal
Food, Drug, and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR 180.598
by establishing a tolerance for residues of novaluron,
N-[[[3-chloro-4-[1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy]phenyl]amino
]carbonyl]-2,6-difluorobenzamide, in or on sorghum, grain at 3 ppm;
sorghum, aspirated grain fractions at 25 ppm; sorghum, forage at 6 ppm,
and sorghum, stover at 40 ppm, and the request to increase the
established livestock tolerances for residues of novaluron in or on
poultry, fat to 7.0 ppm; poultry, meat to 0.40 ppm poultry, meat
byproducts to 0.80 ppm; hog, fat to 1.5 ppm; hog, meat to 0.07 ppm; hog,
meat byproducts to 0.15 ppm; and eggs to 1.5 ppm.

Makhteshim-Agan of North America, Inc., 4515 Falls of Neuse Road,
Raleigh, NC 27609, is the manufacturer and basic registrant of
novaluron. Makhteshim-Agan of North America, Inc., prepared and
summarized the following information in support of the subject pesticide
petition for novaluron. EPA has determined that the petition contains
data or information regarding the elements set forth in section
408(d)(2) of the FFDCA. However, EPA has not fully evaluated the
sufficiency of the submitted data at this time or whether the data
supports granting of the petition. Additional data may be needed before
EPA rules on the petition.

A.	Residue Chemistry

1.    Plant Metabolism 

	The qualitative nature of the residue of novaluron in plants is
adequately understood based on acceptable plant metabolism studies
reflecting its uses on apples, cabbage, cotton, and potatoes. These
plant metabolism studies have demonstrated that novaluron does not
metabolize and is non-systemic (does not translocate within the plant).
The results observed in the plant and livestock metabolism studies show
similar metabolic pathways. The residue of concern, which should be
regulated, is the parent compound, novaluron, only. 			

		

2.	Analytical Method

An adequate analytical method, gas chromatography/electron capture
detector (GC/ECD), as published in the Federal Register of April 5, 2006
(Volume 71, Number 65; FRL-7756-8), is available for enforcing
tolerances of novaluron residues in or on Cucurbits, Fruiting
Vegetables, Beans (snap and dry), Low-growing Berries, Swiss Chard and
Grain Sorghum. The method verification trial supports a limit of
quantitation (LOQ) of 0.05 ppm, and the limit of detection (LOD) is
0.005 ppm for the different matrices. The limit of quantitation (LOQ =
0.05 ppm) was taken as the lowest level validated by this method.    

3. 	Magnitude of Residues

i.     Cucurbits:  A total of 21 residue field trials have been
conducted with cucumbers, cantaloupe and summer squash during the 2006
season covering the major growing areas in the NAFTA Regions. The
supported use pattern on all cucurbits is a maximum of three foliar
applications at a maximum rate of 12 fl. oz product/A, or 0.08 lb ai/A
at 14-day intervals (for a total seasonal application of 0.24 lb ai/A),
and a pre-harvest interval (PHI) of 1 day. The proposed tolerance for
cucurbits (Group 9) is 0.25 ppm. The crop group tolerance is proposed
because the tolerances for all individual crops are within a factor of
5. Crop-specific details are as follows: 

Cantaloupe: Eight field trials were conducted at the supported use
pattern. Measured novaluron residues on cantaloupe range from below the
limit of detection (LOD, 0.015 ppm) to 0.0933 ppm. The average residue
is 0.0339 ppm, assuming one-half LOD for all residues below the LOD. The
estimated tolerance for cantaloupe is 0.15 ppm using the MRL calculator.

Cucumbers: Six field trials were conducted at the supported use pattern
covering NAFTA Regions 2 (2 trials), III (1 trial), V (2 trials), and VI
(1 trial). Measured novaluron residues on cucumbers were below the limit
of quantitation (LOQ, 0.05 ppm) in all samples. The estimated tolerance
for cucumbers is therefore 0.05 ppm. 

Summer squash: Seven field trials were conducted at the supported use
pattern covering NAFTA Regions 2 (2 trials), III (1 trial), V (1 trial),
VI (1 trial), X (1 trial), and XI (1 trial). Measured novaluron residues
on summer squash range from below the LOD (0.013 ppm) to 0.074 ppm. The
average residue is 0.0327 ppm, assuming one-half LOD for all residues
below the LOD. The estimated tolerance for summer squash is 0.25 ppm
using the MRL calculator.

Fruiting vegetables: A total of 32 residue trials have been conducted
with tomatoes (15 field plus 4 greenhouse trials), bell peppers (9
trials) and non-bell peppers (4 trials) covering the major growing areas
in the NAFTA Regions.  Residue data on these commodities will support
tolerances on Vegetable, fruiting (Group 8), and the commodities cocona,
African eggplant, pea eggplant, scarlet eggplant, goji berry, garden
huckleberry, martynia, naranjilla, okra, roselle, sunberry, bush tomato,
currant tomato, and tree tomato. The supported use pattern on all
fruiting vegetables is a maximum of three foliar applications at a
maximum rate of 12 fl. oz product/A, or 0.08 lb ai/A at 7-day intervals
(for a total seasonal application of 0.24 lb ai/A), and a pre-harvest
interval (PHI) of 1 day. The proposed tolerance for Vegetable, fruiting
is 1.1 ppm. The crop group tolerance is proposed at 1.1 ppm because the
estimated tolerances for all individual crops - tomato, bell pepper, and
non-bell pepper, are within a factor of 5. Crop-specific details are as
follows: 

 

Tomatoes: The current registered tolerance for tomatoes is 1 ppm (40 CFR
180.598, issued on December 10, 2008, Federal Register Volume 73, Number
238). The average residue in field trials is 0.161 ppm.

Bell peppers: Nine field trials were conducted in the U.S. and Canada at
the supported use pattern with Rimon 0.83 EC covering NAFTA Growing
Regions II (1 trial), III (1 trial), V (4 trials), VI (1 trial), and X
(2 trials) during the 2006 season. Measured novaluron residues on Bell
peppers range <0.05 ppm (LOQ) to 0.037 ppm. The average residue is 0.14
ppm, assuming one-half LOQ for all residues below the LOQ. The estimated
tolerance for bell peppers is 0.90 ppm using the MRL calculator.

Non-bell peppers: Four field trials were conducted with Rimon 0.83 EC at
the supported use pattern covering NAFTA Growing Regions III (1 trial),
V (1 trial), VI (1 trial), and X (1 trial) during the 2006 season.
Measured novaluron residues on non-bell peppers range from <LOQ (0.05
ppm) to 0.36 ppm. The average residue is 0.15 ppm, assuming one-half LOQ
for all residues below the LOQ. The estimated tolerance for non-bell
peppers is 1.1 ppm using the MRL calculator. 

iii. 	Beans, snap, succulent: The proposed tolerance for Beans, snap,
succulent is 0.60 ppm based on the MRL calculator. Fourteen field trials
were conducted with Rimon 0.83 EC in snap beans at the supported use
pattern of three applications at a maximum rate of 12 fl. oz product/A,
or 0.08 lb ai/A at 7-day intervals (for a total seasonal rate of 0.24 lb
ai/A), and a PHI of 3 days covering NAFTA Growing Regions I (1 trial),
II (4 trials), III (2 trials), V (5 trials), and XI (1 trial) during the
2006 season. Measured novaluron residues on snap beans range from <0.05
ppm (LOQ) to 0.46 ppm. The average residue is 0.18 ppm, assuming
one-half LOQ for all residues below the LOQ. 

iiii.  Beans, dry: The proposed tolerance for Beans, dry, is 0.20 ppm
based on the MRL calculator. Thirteen field trials were conducted with
Rimon 0.83 EC in dry beans at the supported use pattern of three
applications at a maximum rate of 12 fl. oz product/A, or 0.08 lb ai/A
at 7-day intervals (for a total seasonal rate of 0.24 lb ai/A), and a
PHI of 1 day covering NAFTA Growing Regions I (1 trial), V (5 trials),
VII (2 trials), VIII (1 trial), IX (1 trial), X (1 trial), and XI (1
trial) during the 2007 season. Measured novaluron residues on dry beans
range from <0.05 ppm (LOQ) to 0.36 ppm. The average residue is 0.044
ppm, assuming one-half LOQ for all residues below the LOQ. 

iiiii. 	Low growing berries: The proposed tolerance for low growing
berries (Subgroup #13-07G) is 0.50 ppm based on the MRL calculator. Ten
field trials were conducted with Rimon 0.83 EC in strawberries at the
supported use pattern of three foliar applications at a maximum rate of
12 fl. oz product/A, or 0.08 lb ai/A at 7-day intervals (for a total
seasonal rate of 0.24 lb ai/A), and a PHI of 1 day covering NAFTA
Growing Regions I (1 trial), II (1 trial), III (1 trial), V (3 trials),
X (3 trials), and XII (1 trial) during the 2007 season. Measured
novaluron residues in the trials range from <0.05 ppm (LOQ) to 0.287
ppm, with an average residue of 0.14 ppm. 

iiiiii. Swiss chard: The proposed tolerance for Swiss chard is 12 ppm
based on the MRL calculator. Three field trials were conducted with
Rimon 0.83 EC in Swiss chard at the supported use pattern of three
foliar applications at a maximum rate of 12 fl. oz product/A, or 0.08 lb
ai/A at 7-day intervals (for a total seasonal rate of 0.24 lb ai/A), and
a PHI of 1 day covering NAFTA Growing Regions VI (1 trial), and X (2
trials) during the 2007 season. Measured novaluron residues in the
trials range from 2.2 ppm to 6.6 ppm, with an average residue of 4.2
ppm. 

iiiiiii. Sorghum, grain: The proposed tolerances for grain sorghum
commodities are 3 ppm (grain), 25 ppm (aspirated grain fractions), 6 ppm
(forage) and 40 ppm (stover) based on the MRL calculator. Twelve field
trials were conducted with Rimon 0.83 EC in sorghum at the supported use
pattern of three foliar applications at a maximum rate of 12 fl. oz
product/A, or 0.08 lb ai/A at 7-14-day intervals (for a total seasonal
rate of 0.234 lb ai/A), and PHIs for the grain and stover of 14 days and
for forage of 7 days covering NAFTA Growing Regions II (1 trial), IV (1
trial), V (3 trials), VI (2 trials), VII (2 trials), and VIII (3 trials)
during the 2007 season. Measured novaluron residues from these trials
range from 0.68 ppm to  1.69 ppm in grain, 0.73 ppm to 4.2 ppm in
forage, and when corrected for appropriate moisture content, 5.6 ppm to
27.3 ppm in stover. Because the proposed use is on grain sorghum only,
no residues in sorghum syrup are needed because the syrup is not
produced from the grain sorghum plant. 

B.	 Toxicological Profile

	1.   	Acute Toxicity

In an acute oral toxicity study in rats, novaluron had an LD50 >5,000
mg/kg.  A dermal toxicity study in rats resulted in an LD50 greater than
2,000 mg/kg.  The LC50 for acute inhalation in rats was greater than
5.15 mg/l.  In rabbits, novaluron is not a skin irritant, but it is a
mild eye irritant.  Novaluron is not a sensitizer in guinea pigs.

		2.	  Genotoxicity

The mutagenic potential of Novaluron was investigated in several in vivo
and in vitro studies.  Results in two Ames assays, an in vivo mouse
micronucleus assay, an in vitro unscheduled DNA synthesis (UDS) assay,
an in vitro cell mutation assay, and an in vitro human lymphocyte
clastogenicity test were negative.  Novaluron is therefore considered to
have no potential to induce mutagenicity.

		3.    Reproductive and Developmental Toxicity

	i.   A two generation rat reproduction study was conducted with dose
levels of 1,000, 4,000, and 12,000 ppm (74.2, 297.5, 894.9 mg/kg/day,
and 84, 336.7, 1,009.8 mg/kg/day for males and females, respectively). 
Maternal and offspring toxicity was evidenced by increased absolute and
relative spleen weights, whereas reproductive toxicity was observed only
in males at 297.5 mg/kg/day (LOAEL) based on decreased epididymal sperm
counts and increased age at preputial separation in the F1 generation.
The no observed adverse effect level (NOAEL) in males was 1,000 ppm
(74.2 mg/kg/day) and in females it was $12,000 ppm (1,009.8 mg/kg/day).

	ii.   Teratology studies were conducted in the rat and rabbit.  No
treatment-related mortalities were observed in either study.  No effect
on survival, development or growth of fetuses was noted in either
species in either study.  No maternal or developmental toxicity was
observed up to and including the limit dose of 1,000 mg/kg/day (NOAEL).
These two studies demonstrate that novaluron was not teratogenic in
either rats or rabbits. 

		4.	Subchronic Toxicity

Rats, mice and dogs all show the same toxicologic response.  Generally, 
 novaluron induces small increases in methemoglobin; red cells are   
sequestered; and, compensatory hematopoiesis occurs.  The severity of
these changes is well within the physiological capacity of the animals
and is judged   not adverse.

Rats treated topically with novaluron in a 28-day study at 0, 75, 400
and 1,000 mg/kg/day did not show signs of systemic toxicity.  Small
treatment-related increases in methemoglobin were seen in both sexes at
1,000 mg/kg/day and in females at 400 mg/kg/day.  The highest
methemoglobin value seen in females was 1.28% compared with 0.86% in
controls.  Organ weights, macroscopic and microscopic examination of
organs and tissues did not reveal any treatment-related changes.

	

Two 13-week rat studies were conducted.  In one study, doses were
administered at 50, 100, 200, 400 ppm (3.52, 6.93, 13.83, 27.77
mg/kg/day and 4.38, 8.64, 17.54 and 34.39 mg/kg/day for males and
females, respectively). The LOAELs from the combined results were 27.77
mg/kg/day in males based on increased occurrence of extramedullary
hematopoiesis and hemosiderosis in spleen; and 8.64 mg/kg/day in females
based on reduction in hemoglobin, hematocrit and RBC count; increased
occurrence of extramedullary hematopoiesis and hemosiderosis in spleen
and liver.  The NOAEL was determined to be 4.38 mg/kg/day.  

A 13-week mouse study was conducted with dose levels of 30, 100, 1,000,
10,000 ppm (4.2, 12.8, 135.9, 1,391.9 and 4.7, 15.2, 135.6, 1,493.1
mg/kg/day, for males and females, respectively).  The NOAEL was
determined to be 100 ppm (12.8 and 15.2 mg/kg/day, male and females,
respectively).  The LOAEL was 1,000 ppm (135.9 and 135.6 mg/kg/day,
males and females, respectively) based on increased body weight gain,
low erythrocyte counts, and secondary splenic changes.  There were no
clinical treatment-related signs noted.

Two 13-week dog studies were conducted.   One study resulted in an NOAEL
of 100 mg/kg/day and a LOAEL of 300 mg/kg/day based on low erythrocyte
counts and secondary splenic and liver changes.  No clinical
treatment-related signs were noted.  Another study, was conducted using
only one dose level of 10 mg/kg/day.  There were no clinical or
histopathological treatment-related signs and the NOEL was determined to
be 10 mg/kg/day.

		5.	Chronic Toxicity

	i.    Chronic toxicity and oncogenicity was evaluated in the rat, mouse
and dog.  The rat chronic toxicity and oncogenicity was conducted with
dose levels of 25, 700, 20,000 ppm (1.1, 30.6, 884.2 and 1.4, 39.5,
1,113.5 mg/kg/day for males and females, respectively).  The LOAEL in
male and female rats was 30.6 and 39.5 mg/kg/day, respectively, based on
evidence of erythrocyte damage and turnover resulting in a regenerative
anemia in both sexes. The corresponding NOAEL was 25 ppm (1.1 and 1.4
mg/kg/day for male and female rats, respectively). There was no evidence
of carcinogenicity in this study.  A mouse chronic toxicity study was
conducted with dose levels of 30, 450, 7,000 ppm (3.6, 53.4, 800.0 and
4.3, 63.3, 913.4 mg/kg/day for males and females, respectively).  The
LOAEL in male and female mice was 53.4 and 63.3 mg/kg/day, respectively,
based on erythrocyte turnover due to hemoglobin oxidation and resulting
in a compensated anemia. The corresponding NOAEL was 30 ppm (3.6 and 4.3
mg/kg/day for male and female mice, respectively). There was also no
evidence of carcinogenicity in this study.  Chronic toxicity was
investigated in dogs using dose levels of 10, 100, 1,000 mg/kg/day.  The
NOAEL of 100 mg/kg/day was based on methemoglobin.

		ii.  	The chronic reference dose (cRfD) of 0.011 mg/kg/day has been
established on the basis of the chronic carcinogenicity study in rats.
An uncertainty factor (UF) of 100 was applied to the NOAEL of 1.1
mg/kg/day for male rats deriving to the cRfD. 

 		iii. 	 In accordance with the EPA Draft Guidelines for Carcinogen
Risk Assessment (July 1999), novaluron is classified as not likely to be
carcinogenic to humans due to results of oncogenicity studies that show
no evidence of carcinogenicity in rats and mice.  

		6.	Animal Metabolism

Metabolism studies in rats and goats were conducted with the parent
material labeled in both the difluorophenyl and chlorophenyl moieties.
Rats absorb little novaluron when it is administered orally.  More than
90% of the dietary administered [chlorophenyl 14C(U)] novaluron is
recovered in the feces.  When the diflurophenyl ring of the molecule is
labeled, the recovered 14C activity in the feces is lower but still
above 75%.  The difference is thought to reflect intestinal metabolism
by microbial flora and the higher absorption of the diflurophenyl
metabolites.

The parent molecule as well as its degradates are absorbed from the
gastrointestinal tract.  All parent material is metabolized either upon
initial entry into the systemic circulation or, if sequestered to the
fat, upon its depuration back to the systemic circulation.  There is no
intact novaluron found in the urine. Novaluron=s high octanol-water
partition coefficient is responsible for its preferential movement to
fat.  The half-life in fat calculated from the rat metabolism study is
approximately 55 hours.

Two groups of metabolites are formed after oral administration of
novaluron.  One group is typified by the aniline metabolite
3-chloro-4-(1,1,2-trifluoro-2-trifluoromethoxyethoxy) aniline, referred
to as 3-TFA.  The other group of metabolites is typified by
2,6-difluorobenzoic acid is from the diflurophenyl moiety of the
molecule.  Nearly all the metabolites are formed at a level of 1% or
less of the applied dose.  They are rapidly excreted.

The metabolism in goats and hens mimics that seen in rats.

	7.     Metabolite Toxicology

   

Makhteshim-Agan of North America Inc., has determined that there are no
metabolites of toxicological concern and therefore, no metabolites need
to be included in the tolerance expression and require regulation. For
drinking water assessment the soil degradates, chlorophenyl urea and
chloroaniline will be included besides the parent, novaluron. 

	

8.    Endocrine Disruption

   	

No special studies investigating potential estrogenic or other endocrine
effects of novaluron have been conducted.  However, inspection of
in-life data from toxicology studies does not indicate that novaluron is
an endocrine disruptor.  Specifically, endocrine organ weights (e.g.,
thyroid, testes, ovaries, pituitary from the two-generation study) were
not adversely affected by novaluron.  Milestones of sexual development
were not affected by novaluron; and, reproduction was not adversely
affected.  Based on these observations, there is no evidence to suggest
that novaluron has an adverse effect on the endocrine system. 

C.   Aggregate Exposure

	1.	Dietary Exposure

Tolerances have been established (40 CFR 180.598) for the residues of
novaluron, in or on the following raw agricultural commodities: Apple,
wet pomace at 8.0; Brassica, head and stem, subgroup 5A at 0.5 ppm;
cattle, fat at 11 ppm; cattle, fat at 11 ppm; cattle, kidney at 1.0 ppm;
cattle, liver at 1.0 ppm; cattle, meat at 0.60 ppm; cattle, meat
byproducts, except liver and kidney at 0.60 ppm; cotton, gin byproducts
at 30 ppm; cotton, undelinted seed at 0.60 ppm; egg at 0.05 ppm; fruit,
pome, group 11 at 2.0 ppm; goat, fat at 11 ppm; goat, kidney at 1.0 ppm;
goat, liver at 1.0 ppm; goat, meat at 0.60 ppm; goat, meat byproducts
except liver and kidney at 0.60 ppm; hog, fat at 0.05 ppm; hog, meat at
0.01 ppm; hog, meat byproducts at 0.01 ppm; horse, fat at 11 ppm; horse,
kidney at 1.0 ppm; horse, liver at 1.0 ppm; horse, meat at 0.60 ppm;
horse, meat byproducts, except liver and kidney at 0.60 ppm; milk at 1.0
ppm; milk, fat at 20 ppm; poultry, fat at 0.40 ppm; poultry, meat at
0.03 ppm; poultry, meat byproducts at 0.04 ppm; sheep, fat at 11 ppm;
sheep, kidney at 1.0 ppm; sheep, liver at 1.0 ppm; sheep, meat at 0.60
ppm; sheep, meat byproducts, except liver and kidney at 0.60 ppm,
sugarcane, cane at 0.50 ppm, tomato at 1.0 ppm, and vegetables, tuberous
and corn, subgroup 1C at 0.05 ppm.

This Notice of Filing includes exposure assessments for potential
residues of novaluron in or on vegetables, cucurbit (Group 9);
vegetables, fruiting (Group 8); the commodities cocona, African
eggplant, pea eggplant, scarlet eggplant, goji berry, garden
huckleberry, martynia, naranjilla, okra, roselle, sunberry, bush tomato,
currant tomato, and tree tomato; beans, snap, succulent; beans, dry; low
growing berries (Subgroup 13-07G); Swiss chard, and sorghum, grain and
forage. EPA is presently reviewing the IR-4 petitions PP# 8E7425 and PP#
8E7426 concerning the pending tolerances of novaluron on bushberries;
brassica, leafy greens (Subgroup 5B); turnip greens; and stone fruit
(Group 12), which are also included in this dietary exposure assessment.
The assessment is based on average residues from field trials (except
cottonseed, for which tolerances were used), DEEM default processing
factors and percent crop treated assumptions from previous assessments
for pending and registered crops. 

		i. 	Food

		a.   Acute Dietary Exposure. No toxicological endpoint attributable to
a single exposure was identified in the available toxicology studies,
including the rat and rabbit developmental studies.  Therefore, the
acute aggregate risk is negligible.

	

b.   Chronic Dietary Exposure.  A chronic dietary risk assessment was
conducted using the Dietary Exposure Evaluation Model (DEEM) software
with the Food Commodity Intake Database (DEEM-FCIDTM Version 2.16),
which incorporates consumption data derived from the 1994 - 1998 USDA
Continuing Surveys of Food Intake by Individuals (CSFII). The assessment
included all uses (existing, pending and proposed), assuming provided
percent crop treated estimates at market maturity. A dietary exposure
assessment conducted with the assumption of 100% crop treated is quite
conservative, even when average residues from field trials are assumed.
In order to produce a more accurate estimate of exposures, a refined
assessment using best estimates of the percent crop treated at market
maturity for all registered, pending and proposed commodities has been
conducted assuming the following percent crop treated estimates at
market maturity: cucurbits (18%), fruiting vegetables (14%), low growing
berries (12%), dry beans (16%), snap beans (12%), Swiss chard (15%),
grain sorghum (10%), stone fruit (20%), bushberries (15%), leafy
brassica vegetables (20%), turnip greens (15%), apples (30%), pears
(50%), head and stem brassica (30%), tuberous and corm vegetables (18%),
cotton (12%) and sugarcane (28%). In addition, the assessment is based
on average residues from field trials, average field residues,
anticipated residues for meat and milk products with the exception for
cotton seed commodities and poultry, for which tolerance-level residues
were assumed. An empirical processing factor of 3.39 was calculated
using data from a processing trial for dried plums.  Otherwise, all DEEM
default processing factors were used for juices, dried fruit, etc. among
stone fruit and bushberries.

Anticipated residues in animal tissues (i.e., meat and milk) were
calculated using standard methodology based on recent guidance for
calculating the maximum reasonably balanced diets (MRBD). Average
residues in animal feed items were used in all calculations, with the
exception of cotton seed commodities (seed, meal, hulls), for which the
tolerance (0.6 ppm) was used. Dietary burdens for beef and dairy cattle
are similar to those previously estimated by the Agency, but dietary
burdens for hog and poultry with the addition of grain sorghum translate
into higher anticipated residues in these livestock commodities.
Therefore, the established livestock tolerances for residues of
novaluron need to increase by 7- to 30-fold, i.e. in or on poultry, fat
to 7.0 ppm; poultry, meat to 0.4 ppm poultry, meat byproducts to 0.8
ppm; hog, fat to 1.5 ppm; hog, meat to 0.07 ppm; hog, meat byproducts to
0.15 ppm; and eggs to 1.5 ppm. 

The appropriate cRfD value for novaluron is 0.011 mg/kg/day, based upon
the NOAEL of 1.1 mg/kg/day from the chronic carcinogenicity study in
rats, and an UF of 100. The chronic dietary exposures account for 5.2%
to 28.1% of the cPAD. The most highly exposed subpopulation, children
aged 1-2 years old, has an estimated total novaluron exposure of
0.003092 mg/kg/day, equal to 28.1% of the cPAD. The estimated novaluron
exposure for the general U.S. population (0.000861 mg/kg/day) is
equivalent to 7.8% of the cPAD. 

c.   Novaluron was classified as “not likely to be carcinogenic to
humans.''. Therefore, a quantitative cancer risk assessment was not
conducted. 

	

ii.     Drinking Water

		a. 	  Acute Exposure. Since no acute dietary endpoint was determined,
Makhteshim-Agan of North America, Inc., concludes there is reasonable
certainty of no harm from acute drinking water exposure.

   

b.   Chronic Exposure. There are no monitoring data for novaluron to
complete a comprehensive risk assessment for novaluron in drinking
water. Therefore, the Pesticide Root Zone Model/Exposure Analysis
Modeling System (PRZM/EXAMS, Tier 2 model) was used for the
concentration of novaluron (parent) in surface water, the Food Quality
Protection Act (FQPA) Index Reservoir Screening Tool (FIRST, Tier I
model) was used to estimate surface water concentrations of the
chlorophenyl urea and chloroaniline degradates.  For “Screening
Concentrations In Ground Water” the SCI-GROW model was used, assuming
that novaluron may reach the surface or the ground water via the parent
compound or via its degradates. The modeling represents upper-bound
estimates based on the environmental characteristics and associated
modeling parameters, which are designed to provide conservative, health
protective, high-end estimates of water concentrations, which will not
likely be exceeded. Chronic estimates for the terminal degradate,
chloroaniline, represent the worst case, assuming 100% conversion of the
parent compound. Based on the use of novaluron on apples (highest
application rate, total of 0.96 lb ai/A per season), the calculated EECs
of novaluron derived from these models are 2.61 parts per billion (ppb)
for surface water and 0.009 ppb for ground water. The proposed uses
considered in this assessment all have total annual application rates of
0.24 lb ai/A, which is four times lower than the maximum use on apples.
As reported in the October 20, 2006, Federal Register Notice granting a
Section 18 registration for sugarcane, the highest estimated drinking
water residue by the Agency is 2.61 ppb chloroaniline (novaluron
degradate), which is also being used for this assessment. The chronic
dietary exposure assessment includes as the worst case the annual
average concentration of 2.61 ppb in surface water.

		2.	Non-Dietary Exposure

	Presently and in the future, novaluron is not considered for
residential uses. Novaluron is not registered for use on any sites that
would result in residential exposure. The term “residential exposure''
refers to non-occupational, non-dietary exposure (e.g., for lawn and
garden pest control, indoor pest control, termiticides, and flea and
tick control on pets). Therefore, there is no non-dietary exposure
(acute, short-term, intermediate-term or chronic).

   

D.	Cumulative Effects

To Makhteshim-Agan of North America’s Inc., knowledge, there are
currently no available data or other reliable information indicating
that any toxic effects produced by novaluron would be cumulative with
those of other chemical compounds; thus only the potential risks of
novaluron have been considered in this assessment of its aggregate
exposure.

	

E.	 Safety Determination

   	1.     U.S. Population

No acute aggregate risk assessment was conducted because there is no
toxicological endpoint attributable to a single exposure.  Short- and
intermediate-term aggregate risk assessments were not performed because
of no current or future residential uses. No cancer aggregate risk
assessment was conducted because novaluron has not been shown to be
carcinogenic.  Therefore, only a chronic aggregate risk assessment was
performed based on potential exposure from food and drinking water,
considering all existing and proposed uses.  The chronic exposure of the
U.S. population utilizes 7.8% of the cRfD, and the most sensitive
population subgroup (children 1 to 2 years old) utilizes 28.1% of the
cRfD.  In view of these assessments, Makhteshim-Agan of North America
Inc., concludes that there is reasonable certainty that no harm will
result from the proposed uses of novaluron.		

		2.	 Infants and Children

Section 408 of FFDCA provides that EPA may apply an additional safety
factor for infants and children to account for prenatal and postnatal
toxicity and the completeness of the database. The toxicology database
for novaluron is complete including acceptable data from rat and rabbit
developmental toxicity studies and a two generation rat reproduction
study that have been used to assess the potential for increased
sensitivity of infants and children. The data provided no quantitative
or qualitative evidence of increased susceptibility of rats or rabbits
to in utero and/or postnatal exposure to novaluron. In addition there is
no concern for developmental neurotoxicity resulting from exposure to
novaluron, and a developmental neurotoxicity study is not required.
Therefore, the Agency determined in its recent review to reduce the FQPA
Safety Factor to 1X (Federal Register of June 2, 2004; 69 FR 31013;
FRL-7359-2). Thus, the chronic population adjusted dose (cPAD) is
considered 0.011 mg/kg/day. The DEEM analysis regarding the aggregate
chronic exposure calculations utilizes less than 28.1% of the cPAD for
the most sensitive subgroup, children 1 to 2 years old. Therefore,
Makhteshim-Agan of North America Inc., concludes that there is
reasonable certainty that no harm will result to infants and children
from aggregate exposure to novaluron residues.

	

F.	International Residue Limits

At present, no Canadian, Mexican, or CODEX maximum residue limits (MRLs)
are established for novaluron on cucurbits, fruiting vegetables, the
commodities cocona, African eggplant, pea eggplant, scarlet eggplant,
goji berry, garden huckleberry, martynia, naranjilla, okra, roselle,
sunberry, bush tomato, currant tomato, and tree tomato; beans (dry),
beans (snap, succulent), low growing berries, Swiss chard and sorghum. 
Therefore, international harmonization is not an issue at this time. The
only established CODEX MRLs are for apples (3 ppm), pears (3 ppm) and
potatoes (0.01 ppm).

 

 

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