Document ID: EPA-HQ-OPP-2006-0880-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-11-22T05:00Z

FILE NAME:   company.wpt   (7/1/2004)

ATTENTION: All commodity terms must comply with the Food and Feed
Commodity Vocabulary database (http://www.epa.gov/pesticides/foodfeed/).

COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE

(7/1/2004)

EPA Registration Division contact: [insert name and telephone number
with area code]	

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[Insert petition number]

Summary of Petitions

	EPA has received a pesticide petition ([insert petition number]) from
Interregional Research Project Number 4 (IR-4), 681 U.S. Highway #1
South, North Brunswick, NJ 08902-3390 proposing, pursuant to section
408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C.
346a(d), to amend 40 CFR part 180 to establish an exemption from the
requirement of a tolerance for foramsulfuron, 
2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-4-(for
maylamino)-N,N-dimethylbenzamide (CAS #173159-57-4) in or on the raw
agricultural commodities popcorn and sweet corn. 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 metabolism of foramsulfuron in corn has been
investigated and is understood. Two primary routes of degradation occur
for foramsulfuron. One pathway involves the hydrolysis of the
sulfonylurea bridge, resulting in AE F153745 (4-formylamino-N,
N-dimethyl-2-sulfamoylbenzamide) and AE F092944 (2
amino-4,6-dimethoxypyrimidine). Foramsulfuron also hydrolyzes at the
formamide moiety on the phenyl ring to produce AE F130619 (4
amino-2-[3-(4,6-dimethoxypyrimidin-2-yl)ureidosulfonyl]-N,N-dimethylbenz
amide). All these metabolites are subjected to further degradation
leading to the formation of highly polar, water soluble components. The
two metabolites resulting from cleavage of the sulfonylurea bridge,
namely AE F153745 and AE F092944 were found in the extractable residue
of the forage and stover. Only traces of AE F130619 (from hydrolysis of
the formamide moiety) were found also in the forage and stover. The
major metabolite detected in plants (AE F153745) was also identified in
the rat and livestock metabolism studies.

	2. Analytical method.  Since foramsulfuron and its metabolic degradates
are not of toxicological concern, analytical methods are not applicable.

3. Magnitude of residues. Since foramsulfuron and its metabolic
degradates are not of toxicological concern, and this petition is a
request for an exemption from a tolerance, the magnitude of residues is
not applicable.   

B. Toxicological Profile

	1. Acute toxicity.  Foramsulfuron has been shown to have very low acute
toxicity to mammals irrespective of the route of exposure. 
Foramsulfuron was not toxic orally (LD50 greater than 5,000 mg/kg),
dermally (LD50 > 2,000 mg/kg) or by inhalation (LC50 > 5.04 mg/L.  It
was mildly irritating to the eyes and neither a skin irritant nor a skin
sensitizer.  Based on these results, foramsulfuron would be classified
as EPA Category III for dermal toxicity and eye irritation, and EPA
Category IV for skin irritation, oral and inhalation toxicity.  

	2. Genotoxicity.  Foramsulfuron is not mutagenic or genotoxic. 
Foramsulfuron was negative in a battery of tests which examined gene
mutation in bacteria and mammalian cells, chromosome damage in vitro and
in vivo and DNA damage in mammalian cells in vivo. 

	3. Reproductive and developmental toxicity.  Foramsulfuron was tested
in rats and rabbits for developmental toxicity (teratogenicity).  In
rabbits, foramsulfuron produced no developmental toxicity at up to 500
mg/kg/d (highest dose tested), despite maternal toxicity (reduced
maternal body weight gain and food consumption).  No maternal or
developmental toxicity was seen in rats at the highest doses tested (the
international limit dose of 1,000 mg/kg/d).  In a two generation rat
reproduction study at doses up to 1082 mg/kg/d, no treatment related
effects were observed, including no effects on reproductive parameters
(fertility, mating, gestation, parturition, litter size sex ratios),
parental toxicity, neonatal toxicity or on markers of endocrine function
(oestrous cycling, balanopreputial separation, vaginal opening,
spermatogenetic function and capacity). Therefore, foramsulfuron is
neither a developmental nor a reproductive toxicant.  

 

	4. Subchronic toxicity.  Foramsulfuron was not toxic in subchronic
dietary  studies in rats, mice or dogs.  There were no treatment-related
effects and no mortality in rats consuming up to 1,677 mg of
foramsulfuron/kg body weight/day for 90 days.    

In a 90 day feeding study in mice, at dietary concentrations of
foramsulfuron up to 6,400 ppm (1002 - 1178 mg/kg/d males and females,
respectively), there were no treatment related deaths or effects. 

In a 90-day study in beagle dogs, at dietary concentrations of
foramsulfuron up to 1,000 mg/kg/d (the international limit dose), there
were no treatment-related clinical signs or mortalities. 

In a 28-day repeated dose dermal toxicity study in rats, foramsulfuron
produced no treatment-related effects at doses up to 1,000 mg/kg/d. 

	5. Chronic toxicity.  In rats, dietary administration of up to 20000
ppm of foramsulfuron (equivalent to 976 and 1305 mg/kg/d for males and
females, respectively) for 2 years, produced no evidence of toxicity or
oncogenicity.

Similarly in mice, no oncogenic activity was found after dietary
treatment with up to 8000 ppm (equating to 1115 and 1358 mg/kg/day in
males and females, respectively) for 18 months, which was slightly in
excess of the international limit dose.

EPA classified foramsulfuron as having "no evidence of carcinogenicity".
 

The lowest chronic no effect level (NOEL) was 849 mg/kg/d in the rat
chronic/oncogenicity study. Given the absence of any carcinogenicity,
significant genotoxicity, reproduction toxicity, developmental toxicity
or any other special hazard potential, and taking into consideration the
low toxicity profile, poor absorption and rapid excretion (predominantly
of parent compound), a safety factor of 100 is considered appropriate.
Therefore the proposed Reference Dose (RfD) is 8.5 mg/kg body
weight/day.

	6. Animal metabolism.  The qualitative nature of the residues of
foramsulfuron and its metabolite AE F153745 in animals is adequately
understood.  Based on metabolism studies with cows, hens and rats, there
is no reasonable expectation that measurable foramsulfuron-related
residues will occur in meat, milk, poultry or eggs from the proposed
uses.   

	7. Metabolite toxicology.  No toxicologically significant metabolites
were detected in plant or animal metabolism studies.  Therefore, no
metabolites need to be regulated.

	8. Endocrine disruption.  No special studies have been conducted to
investigate the potential of foramsulfuron to induce estrogenic or other
endocrine effects.  However, no evidence of estrogenic or other
endocrine effects have been noted in any of the standard toxicology
studies that have been conducted with this product and there is no
reason to suspect that any such effects would be likely. 

C. Aggregate Exposure

	1. Dietary exposure.   

	i. Food.  Residues of foramsulfuron and its metabolic degradates are
not of toxicological concern. Therefore, dietary exposure through he
food is not a concern.

	ii. Drinking water. Residues of foramsulfuron and its metabolic
degradates are not of toxicological concern. Therefore, dietary exposure
through water is not a concern.

	2. Non-dietary exposure.  Exposure to foramsulfuron for the
mixer/loader/ground boom/aerial applicator was calculated using the
Pesticide Handlers Exposure Database (PHED). It was assumed that the
product would be applied to a maximum of 50 hectares per day (125 A/day)
by ground boom applicator and 140 hectares per day (350 A/day) by aerial
applicator at a maximum use rate of 45 grams a.i./ha. Normal work attire
consisting of long-sleeved shirt, long pants, and protective gloves was
assumed in the PHED assessment. Margins of exposure (MOEs) for a 70 kg
operator were calculated utilizing a dermal NOEL of 1,000 mg/kg body
weight/day from the rat dermal toxicity study and an inhalation NOEL of
50 mg/kg body weight/day based on an oral administration, developmental
toxicity study in the rabbit.  There were no signs of developmental
toxicity in the rabbit developmental toxicity study. The combined MOE
(inhalation plus dermal) for foramsulfuron was 126,000 for a ground
operator undertaking mixing, loading and spraying. For aerial
application where the mixer/loader was assumed to be a different
operator from the pilot combined MOEs were 60,400 for the mixer/loader
and 1,425,000 for the pilot. The results indicate that large margins of
safety exist for the proposed use of foramsulfuron.

The timing of foramsulfuron application to corn is such that field
reentry shortly after spraying is atypical. Therefore estimations of
worker reentry exposure were not considered necessary. 

D. Cumulative Effects

	There is no available data at this time to determine whether
foramsulfuron has a common mechanism of toxicity with other substances
or how to include this pesticide in a cumulative risk assessment. 
Therefore a cumulative assessment was not done for this chemical.  

E. Safety Determination

	1. U.S. population.  Because foramsulfuron and its degradates are not
of toxicological concern and there is low exposure to foramsulfuron and
its degradates, this exemption from the  requirement of a tolerance in
or on popcorn and sweet corn will not pose a dietary risk under
reasonably foreseeable circumstances.

	2. Infants and children. Since a dietary risk assessment was not
conducted for foramsulfuron due to its low toxicity, a safety factor for
infants and children is not applicable to the determination of the risk
due to exposure of infants and children to foramsulfuron.

F. International Tolerances

	There are no Codex Alimentarius Commission (CODEX) maximum residue
levels (MRLs) established for residues of foramsulfuron. 

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