FILE NAME:   company.wpt   (9/23/2008) (xml)

Fipronil rice grain, Sept 2008	

ATTENTION: 

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

All text in blue font (instructions for preparing the document), should
be removed prior to sending the document to the Federal Register Staff. 
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COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE

(1/1/2005)

EPA Registration Division contact: [John Hebert at 703-308-6249]	

TEMPLATE:

	EPA has received a pesticide petition ([insert petition number]) from
[BASF Corporation ], [P.O. Box 13528, Research Triangle Park , NC 27709]
proposing, pursuant to section 408(d)

 by establishing a tolerance for residues of [mixture comprising
fipronil
(5-amino-1[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-trifluorome
thyl)sulfinyl]-1H-pyrazole-3-carbonitrile)  and its metabolites
5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)
sulfonyl]-1H-pyrazole-3-carbonitrile and
5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)t
hio]-H-pyrazole-3-carbonitrile  and its photodegradate
5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluorom
ethyl)]-1H-pyrazole-3-carbonitrile] in or on the raw agricultural
commodity [rice, grain] at [0.04] parts per million (ppm).  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.

                                      

. [The metabolism of fipronil is adequately understood. Adequate

. [Validated analytical methods are available for detecting and
measuring levels of fipronil and its metabolites in  rice.  The Method
utilizes Capillary Gas Chromatography equipped with a Ni electron
capture detector.  Alternatively, a Liquid Chromatograph with Mass/Mass
Detector (LC/MS/MS) may be used.  The Limit of Quantitation for rice is
0.01 ppm for all analytes. The Limit of Detection is 0.003 for all
analytes.]	

			

. [Field trials were carried out in order to determine the

magnitude of residue in rice.  Field trials were carried out using the
maximum label rate of 100 grams a.i. per hectare applied as treatment
rate in Brazil.  The maximum seed treatment rate was conducted in Brazil
at 500 grams a.i. per 100 kg of seed.  The results demonstrate the any
residue is below 0.01 ppm for all analytes.    I

.  [For technical fipronil :

Oral LD50		Rat	  	LD50 = 97 mg/kg b.w.		category II

(moderately toxic)

Dermal LD50		Rat	  	LD50 > 2000 mg/kg b.w. (HDT)	category III

(slightly toxic)

Dermal LD50		Rabbit	  	LD50 = 354 mg/kg b.w.		category II

(moderately toxic)

Inhalation LC50	Rat	  	LC50 = 0.39 mg/L			category II

(moderately toxic)

Eye Irritation		Rabbit	  	slight irritation			category III

Skin Irritation	Rabbit	  	slight	irritation			category IV

Skin Sensitization 

(Maximization Test)	Guinea pig 	Not sensitizing]

Acute			Rat		NOAEL = 2.5 mg/kg/day

Neurotoxicity				(for general toxicity)]

.  [Fipronil was negative in both in vitro and in vivo assays conducted

.  [Fipronil: The developmental toxicity NOELs in the rat and rabbit
were 20 mg/kg/day (HDT) and 1 mg/kg/day (HDT), respectively. Maternal
toxicity was observed in the rat at the HDT as evidenced by decreased
body weight gain and food efficiency. In the rabbit, the maternal
toxicity NOAEL was less than 0.1 mg/kg/day, based on reduced body weight
gain and food efficiency at all dose levels tested. In a two-generation
rat study, the NOEL for parental (systemic) toxicity was 3 ppm (0.26
mg/kg/day for both sexes combined), based on increased weight of the
thyroid glands and liver in males and females, decreased weight of the
pituitary gland in females, and an increased incidence of follicular
epithelial hypertrophy in females at 30 ppm.  The NOEL for reproductive
toxicity was 30 ppm (2.64 mg/kg/day for both sexes combined), based on
clinical signs of toxicity in pups, decreased litter size, decreased pup
body weights, decreased mating, decreased fertility index, reduced pre-
and postnatal survival, and delays in physical development at 300 ppm
(26.03 and 28.40 mg/kg/day for males and females, respectively). 

In a developmental neurotoxicity study in the rat, the NOAEL for
maternal toxicity was 10 ppm (0.91 mg/kg/day), based on decreased body
weights and body weight gain at 200 ppm (HDT; 15 mg/kg/day).
Considerable maternal toxicity at the HDT prevented adequate
neurotoxicity evaluation of pups at this dose level. There was no
evidence of neurotoxicity at 10 ppm (0.91 mg/kg/day), which was the
NOAEL for developmental neurotoxicity. The NOAEL for general
developmental toxicity was 0.5 ppm (0.05 mg/kg/day), based on systemic
effects consisting of decreases in pup weights during lactation and
increases in time of preputial separation in males at 10 ppm.]

	

[Fipronil:   The NOAEL for systemic toxicity in rat was 5 ppm (0.35
mg/kg/day for both sexes combined), based on alterations in serum
protein values and

increased weight of the liver and thyroid at 30 ppm (1.93 and 2.28
mg/kg/day for males and females, respectively). The NOAELs in the dog
were 2 and 0.5 mg/kg/day for male and female, respectively, based on
clinical signs of toxicity in males at 10 mg/kg/day and clinical signs
of toxicity and decreased body weight gain in females at 2 mg/kg/day. 
The NOAEL for mice was 10 ppm (1.27 and 1.72 mg/kg/day for males and
females, respectively), based on a possible decreased body weight gain
at 25 ppm (3.2 and 4.53 mg/kg/day for males and females, respectively).
A repeated dose dermal study in the rabbit had a systemic NOAEL of 5
mg/kg/day, based on decreased body weight gain and food consumption at
10 mg/kg/day, and a dermal irritation NOEL of 10.0 mg/kg/day (HDT).

. [Fipronil:    The NOAEL for systemic toxicity in a one-year feeding

. [The metabolism of fipronil is adequately understood.

. [MB46513 photodegradate

Acute Oral Toxicity:

 Oral LD50		Rat		LD50 = 16 mg/kg b.w.		category I

(highly toxic)

Dermal LD50		Rabbit		LD50 > 2000 mg/kg b.w. (HDT)	category III 

(slightly toxic)

Acute Neurotoxicity: The NOEL was 2 mg/kg, based on decreases in body
weight gain and food consumption in males and females during the week
following treatment, decreases in locomotor activity, hind-limb splay
and rectal temperature 6-hr post dosing in males and females, and
decreases in the proportion of males with an immediate righting reflex
on days 7 and 14, at 12 mg/kg/day. 

In a rat developmental toxicity study, the NOEL was 1 mg/kg/day, based
on the slight increase in fetal and litter incidence of reduced
ossification of several bones at 2.5 mg/kg/day.

Subchronic Toxicity: The NOAEL in the rat was 3 ppm (0.18 and 0.21
mg/kg/day in males and females, respectively), based on clinical signs
of toxicity in both sexes and decreased body weight and body weight gain
in males at 10 ppm. The NOEL for the mouse was 0.5 ppm (0.08 mg/kg/day),
based on the aggressive and irritable behavior with increased motor
activity in males at 2 ppm. The NOEL for the dog was 9.5 ppm (0.29
mg/kg/day), based on behavioral changes in females at 35 ppm (1.05
mg/kg/day).

The rat chronic/carcinogenicity study was negative for carcinogenicity. 
The LOAEL for females was 0.5 ppm (0.032 mg/kg/day), based on clinical
signs of toxicity.  There was no NOEL established. For males, the NOAEL
was 2 ppm (0.098 mg/kg/day), based on clinical signs of toxicity, and
stomach and lung histopathology at 10 ppm (0.497 mg/kg/day). No thyroid
effects are observed in any of the rat, mouse or dog studies with MB
46513, supporting the conclusion that there is no concern for cancer due
to exposure to MB 46513.]

	

.  [Data from the reproduction / developmental toxicity and short- and
long-term repeated dose toxicity studies with fipronil in the rat,
rabbit, mouse, or dog, do not suggest any endocrine disruption activity.
 This information is based on the absence of any treatment-related
effects from the histopathological examination of reproductive organs as
well as the absence of possible effects on fertility, reproductive
performance, or any other aspect of reproductive function, or on growth
and development of the offspring. Evidence of offspring toxicity was
observed only in the presence of significant parental toxicity. Fipronil
disrupts the thyroid-pituitary axis. However, mechanistic studies have
demonstrated that fipronil decreases thyroid hormone levels in long-term
studies via increased clearance, rather than a direct effect on the
thyroid. Concerns related to long-term exposure of fipronil are
addressed in human risk estimates, as the chronic RfD (0.0002 mg/kg/day)
is based on endpoints that include thyroid hormone related effects in
rats.]		

	

.  [Acute Dietary Exposure Assessment

The acute population adjusted dose (aPAD) used was 0.025 mg/kg bw/day. 
The dietary exposure includes both food and water.  The acute water
concentration was 2.654 ppb (ug/L).   This water value is the highest
modeled water concentration and is related to the onion seed use.  The
maximum fipronil acute dietary exposure from food and water is 25 %
aPAD.  The results of the acute dietary assessment are presented in
Table 1.

Table 1.  Fipronil Acute Dietary Analysis for Food and Water Conducted
by the US EPA for all Existing and New Uses.  

 

Subgroups	

Exposure at 95th Percentile  (mg/kg bw/day)	

% aPADa

US Population	0.002345	9.4

All infants (< 1 year)	0.003215	12.9

Children 1-2	0.006195	24.8

Children 3-5	0.004412	17.6

Children 6-12	0.002878	11.5

Youth 13-19	0.001811	7.2

Adults 20-49	0.001343	5.4

Adults 50+ yrs	0.0011	4.4

Females 13 - 49 yrs	0.00128	5.1





a The aPAD = 0.025 mg/kg bw/day.

Chronic Dietary Exposure Assessment

The chronic population adjusted dose (cPAD) used was 0.0002 mg/kg
bw/day.  The dietary exposure includes both food and water.  The chronic
water concentration was 0.318 ppb (ug/L).   This water value is the
highest modeled water concentration and is related to the onion seed
use.  The maximum fipronil chronic dietary exposure from food and water
is 96%.   .  The results of the chronic dietary assessment are presented
in Table 2.  

Table 2 Fipronil Chronic  Dietary Analysis for Food and Water Conducted
by the US EPA for all Existing and New Uses. 

Subgroups	

Chronic Exposure  (mg/kg bw/day)	

% aPADa

US Population	0.000096	48.0

All infants (< 1 year)	0.000126	63.0

Children 1-2	0.000192	96.0

Children 3-5	0.000186	93.0

Children 6-12	0.00013	65.0

Youth 13-19	0.000098	49.0

Adults 20-49	0.000079	39.5

Adults 50+ yrs	0.00008	40.0

Females 13 - 49 yrs	0.000074	37.0





 ADVANCE \d6 



. [The drinking water values used for the dietary exposure analysis were
from the US EPA assessment (June 19, 2007. PC code 129121, DP Barcode
322415, 319940, 328892).  The highest modeled water concentrations are
from the use on onion seeds.  The acute water concentration is 2.654 ppb
(ug/L) and the chronic water concentration is 0.317 ppb (ug/L).  

Acute Aggregate Exposure and Risk (Food and water)

The acute aggregate risk associated with the existing and new fipronil
uses does not exceed a level of concern.  The estimated exposure at the
95th percentile uses < 25% of the aPAD (Table 1).   

Short- and Intermediate Term Aggregate Exposure and Risk (Food, Water
and Residential Exposure)

Short- and intermediate-term aggregate exposure takes into account
residential exposure plus chronic exposure from food and water.  

The US EPA determined that short-term exposure was greatest from the pet
use of fipronil.  Therefore, the US EPA conducted a short-term aggregate
risk assessment using children (1-2 years old) with the combined dermal
and oral exposures from pet use.  Since the level of concern for oral
and dermal are different, the Aggregate Risk Index (ARI) method was used
to evaluate short-term aggregate risk. An ARI greater than one indicate
an acceptable level of risk.  Adult short-term post-application is
considered negligible and an short-term aggregate risk for adults was
not conducted.  The ARI for children 1-2 years old was 1.5 and,
therefore, short-term aggregate risk estimates do not exceed the level
of concern.

Table 3.  Short-term Aggregate Risk for Fipronil.  

Pop.	Food + Water	Oral from pet use	Dermal from pet use	ARI Aggregate

Children 1-2 yrs	LOAEL	EXP	LOC	MOE	LOAEL	LOC	MOE	NOAEL	LOC	MOE



0.1	0.00019	300	520	0.1	300	3300	5	100	5000	1.5

 

Chronic Aggregate Exposure and Risk (food and water)

The chronic aggregate risk associated with the existing and new fipronil
uses does not exceed a level of concern.  The estimated exposure uses
96% of the cPAD (Table 2).    ADVANCE \d6 	]

. [The residential exposure for fipronil products was assessed by the US
EPA in the cotton risk evaluation in 2001.  

Pet Products:

The residential exposure for the Frontline® pet products was assessed. 
The residential exposure for the Frontline® pet products was determined
based on the following submitted studies: 1)  Dermal and Inhalation
Exposure of Commercial Pet Groomers During the Application of
Frontline® Spray Treatment (MRID #44433302), 2) Dermal Exposure of
Commercial Pet Groomers During the Application of Frontline® and Top
Spot® (MRID 44433303), and four studies examining the dislodgeable
residues of fipronil following the spray and spot treatment application
to dogs and cats (MRID 44433301 – 09).  Based on these studies, HED
determined the dermal and inhalation exposure for residential
applicators were 3.0 x 10-3 mg/kg bw/day and 1.78 x 10-6 mg/kg bw/day,
respectively.  The non-dietary, oral (hand to mouth) was estimated to be
no greater than 3.0 x 10-5 mg/kg bw/day1.  The post-application dermal
exposure for toddlers was estimated to be 1.0 x 10-3 mg/kg bw/day1.  The
MOEs for all exposure scenarios evaluated were greater than 1500. 

Fire Ant Products:

The applicator exposure was determined using the “Draft Standard
Operating Procedures for Residential Exposure” (December 18, 1997). 
The greatest homeowner applicator exposure was calculated from the
application of the granular product with a drop spreader.  The average
daily dose for dermal and inhalation exposure were 6.0 x 10-4 mg/kg
bw/day and 1.3 x 10-6 mg/kg bw/day, respectively.  The MOEs for all
exposure scenarios were > 8000.  

Post-application from the fire ant granular products can occur from
dermal exposure and by children ingestion of granules from treated soil
and/or ingestion of treated soil.  Based on a submitted dislodgeable
foliar residue study (MRID 44506901), HED concluded that fipronil cannot
be dislodged from treated turf and post-application exposure from turf
will not occur.  HED calculated the children exposure from the ingestion
of granules in the treated area to be 2.8 x 10-3 mg/kg bw/day which
resulted in a MOE of 890.  The post-application children exposure from
ingestion of treated soil was calculated to be 1.2 x 10-6 mg/kg bw/day
which resulted in a MOE of 83,000. 

	[Section 408(b)(2)(D)(v) requires that, when considering whether to
establish, modify, or revoke a tolerance, the Agency consider available
information concerning the cumulative effects of a particular
pesticide's residues and other substances that have a common mechanism
of toxicity.

 

. [Based on this risk assessment, BASF concludes that there is a
reasonable certainty that no harm will result to the general population
from the aggregate

	[The following Maximum residue levels (MRLs) have been established  by
the Codex

Alimentarius Commission (CODEX) for fipronil residues  on   the
following plant commodities: Banana, 0.005 mg/kg; Barley 0.002 mg/kg;
Cabbage, Head, 0.02 mg/kg; Flowerhead brassicas, 0.02 mg/kg; Maize 0.01
mg/kg; Maize fodder 0.1 mg/kg; Maize forage 0.1; Oats 0.002, mg/kg;
Potato 0.02 mg/kg; Rice 0.01 mg/kg; Rice, straw and fodder, dry, 0.2
mg/kg; Rye 0.002 mg/kg; Sugar beet 0.2 mg/kg; Sugar beet leaves or tops,
0.2 mg/kg; Sunflower seed, 0.002 mg/kg; Triticale, 0.002 mg/kg; Wheat
0.002 mg/kg. 

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