[Federal Register Volume 63, Number 137 (Friday, July 17, 1998)]
[Rules and Regulations]
[Pages 38483-38495]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-18987]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300612; FRL-5768-3]
RIN 2070-AB78
Fipronil; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes new tolerances for combined
residues of fipronil, its metabolites MB46136 and MB45950, and its
photodegradate MB46513, in or on rice grain and rice straw. In
pesticide petition (PP) 7F4832, Rhone Poulenc AG, Inc. requested these
tolerances under the Federal Food, Drug and Cosmetic Act (FFDCA), as
amended by the Food Quality Protection Act of 1966 (FQPA).
DATES: This regulation is effective July 17, 1998. Objections and
requests for hearings must be received by EPA on or before September
15, 1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, OPP-300612, must be submitted to: Hearing Clerk
(1900), Environmental Protection Agency, Rm. M3708, 401 M St., SW.,
Washington, DC 20460. Fees accompanying objections and hearing requests
shall be labeled ``Tolerance Petition Fees'' and forwarded to: EPA
Headquarters Accounting Operations Branch, OPP (Tolerance Fees), P.O.
Box 360277M, Pittsburgh, PA 15251. A copy of any objections and hearing
requests filed with the Hearing Clerk identified by the docket control
number, OPP-300612, must also be submitted to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticide Programs, Environmental Protection Agency,
401 M St., SW., Washington, DC 20460. In person, bring a copy of
objections and hearing requests to Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@epa.gov. Copies of objections and hearing
requests must be submitted as an ASCII file avoiding the use of special
characters and any form of encryption. Copies of objections and hearing
requests will also be accepted on disks in WordPerfect 5.1/6.1 file
format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket control
number OPP-300612. No Confidential Business Information (CBI) should be
submitted through e-mail. Electronic copies of objections and hearing
requests on this rule may be filed online at many Federal Depository
Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Ann Sibold, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA, (703) 305-6788, e-mail:
sibold.ann@epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of June 20, 1997 (62
FR 33641) (FRL-5723-7), EPA issued a notice pursuant to section 408 of
the FFDCA, 21 U.S.C. 346a(e), announcing the filing of a pesticide
petition for a tolerance (PP 7F4832) by Rhone Poulenc AG, Inc., P.O.
Box 12014, 2 T.W. Alexander Drive, Research Triangle Park, NC 27709.
This notice included a summary of the petition prepared by Rhone
Poulenc AG, Inc., the registrant. There were 11 comments received in
response to the notice of filing and all supported establishing the
tolerance.
The petition proposed to use a 56% flowable solid (FS) formulation
(Product name: ICON 6.2 FS Insecticide) to treat rice seed to control
the pests rice water weevil and chinch bugs.
The petition further requested that 40 CFR 180.517 be amended by
establishing new tolerances for combined residues of the insecticide
fipronil, its metabolites MB46136 and MB45950, and its photodegradate
MB46513 in or on rice grain at 0.04 parts per million (ppm) and rice
straw at 0.10 ppm. Tolerances for residues of fipronil (expressed as
fipronil and its metabolites MB45950 and MB46136) in or on animal
commodities have recently been established (40 CFR 180.517(a)).
Fipronil is registered in the United States for use on field corn,
on golf course and commercial turf, on pets, and in roach and ant bait
stations.
I. Risk Assessment and Statutory Findings
New section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of the FFDCA defines ``safe'' to mean that ``there is
a reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) requires EPA to give special consideration to
exposure of infants and children to the pesticide chemical residue in
establishing a tolerance and to ``ensure that there is a reasonable
certainty that no harm will result to infants and children from
aggregate
[[Page 38484]]
exposure to the pesticide chemical residue. . . .''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings.
A. Toxicity
1. Threshold and non-threshold effects. For many animal studies, a
dose response relationship can be determined, which provides a dose
that causes adverse effects (threshold effects) and doses causing no-
observed effects (the ``no-observed effect level'' or ``NOEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOEL from
the study with the lowest NOEL by an uncertainty factor (usually 100 or
more) to determine the Reference Dose (RfD). The RfD is a level at or
below which daily aggregate exposure over a lifetime will not pose
appreciable risks to human health. An uncertainty factor (sometimes
called a ``safety factor'') of 100 is commonly used since it is assumed
that people may be up to 10 times more sensitive to pesticides than the
test animals, and that one person or subgroup of the population (such
as infants and children) could be up to 10 times more sensitive to a
pesticide than another. In addition, EPA assesses the potential risks
to infants and children based on the weight of the evidence of the
toxicology studies and determines whether an additional uncertainty
factor is warranted. Thus, an aggregate daily exposure to a pesticide
residue at or below the RfD (expressed as 100% or less of the RfD) is
generally considered acceptable by EPA. EPA generally uses the RfD to
evaluate the chronic risks posed by pesticide exposure. For shorter-
term risks, EPA uses a RfD approach or calculates a margin of exposure
(MOE) by dividing the estimated human exposure into the NOEL from the
appropriate animal study. Commonly, EPA finds MOEs lower than 100 to be
unacceptable. This 100-fold MOE is based on the same rationale as the
100-fold uncertainty factor.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short-term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential-human
carcinogen, different types of risk assessments (e.g., linear low-dose
extrapolations or MOE calculation based on the appropriate NOEL) will
be carried out based on the nature of the carcinogenic response and the
Agency's knowledge of its mode of action.
2. Differences in toxic effect due to exposure duration. The
toxicological effects of a pesticide can vary with different exposure
durations. EPA considers the entire toxicity data base, and based on
the effects seen for different durations and routes of exposure,
determines which risk assessments should be done to assure that the
public is adequately protected from any pesticide-exposure scenario.
Both short and long durations of exposure are always considered.
Typically, risk assessments include ``acute,'' ``short-term,''
``intermediate-term,'' and ``chronic'' risks. These assessments are
defined by the Agency as follows.
Acute risk, by the Agency's definition, results from 1-day
consumption of food and water, and reflects toxicity which could be
expressed following a single-oral exposure to the pesticide residues.
High-end exposure to food and water residues are typically assumed.
Short-term risk results from exposure to the pesticide for a period
of 1-7 days, and therefore overlaps with the acute risk assessment.
Historically, this risk assessment was intended to address primarily
dermal and inhalation exposure which could result, for example, from
residential pesticide applications. However, since enaction of FQPA,
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from
food, water, and residential uses when reliable data are available. In
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all
three sources are not typically added because of the very-low
probability of this occurring in most cases, and because the other
conservative assumptions built into the assessment assure adequate
protection of public health. However, for cases in which high-end
exposure can reasonably be expected from multiple sources (e.g.
frequent and widespread homeowner use in a specific geographical area),
multiple high-end risks will be aggregated and presented as part of the
comprehensive risk assessment/characterization. Since the toxicological
endpoint considered in this assessment reflects exposure over a period
of at least 7 days, an additional degree of conservatism is built into
the assessment; i.e., the risk assessment nominally covers 1-7 days
exposure, and the toxicological endpoint/NOEL is selected to be
adequate for at least 7 days of exposure. (Toxicity results at lower
levels when the dosing duration is increased.)
Intermediate-term risk results from exposure for 7 days to several
months. This assessment is handled in a manner similar to the short-
term risk assessment.
Chronic risk assessment describes risk which could result from
several months to a lifetime of exposure. For this assessment, risks
are aggregated considering average exposure from all sources for
representative population subgroups including infants and children.
B. Aggregate Exposure.
In examining aggregate exposure, section 408 of the FFDCA requires
that EPA take into account available and reliable information
concerning exposure from the pesticide residue in the food in question,
residues in other foods for which there are tolerances, residues in
groundwater or surface water that is consumed as drinking water, and
other non-occupational exposures through pesticide use in gardens,
lawns, or buildings (residential and other indoor uses). Dietary
exposure to residues of a pesticide in a food commodity are estimated
by multiplying the average daily consumption of the food forms of that
commodity by the tolerance level or the anticipated pesticide residue
level. The Theoretical Maximum Residue Contribution (TMRC) is an
estimate of the level of residues consumed daily if each food item
contained pesticide residues equal to the tolerance. In evaluating food
exposures, EPA takes into account varying consumption patterns of major
identifiable subgroups of consumers, including infants and children.
The TMRC is a ``worst case'' estimate since it is based on the
assumptions that food contains pesticide residues at the tolerance
level and that 100% of the crop is treated by pesticides that have
established tolerances. If the TMRC exceeds the RfD or poses a lifetime
cancer risk that is
[[Page 38485]]
greater than approximately one in a million, EPA attempts to derive a
more accurate exposure estimate for the pesticide by evaluating
additional types of information (anticipated residue data and/or
percent of crop treated data) which show, generally, that pesticide
residues in most foods when they are eaten are well below established
tolerances.
II. Aggregate Risk Assessment and Determination of Safety
The toxicology data base for fipronil has previously been
evaluated and was considered adequate to support registration for use
on corn (62 FR 62970) (FRL-5757-4). Since that time, MB46513 has been
identified. It appears to have greater toxicity than the parent,
fipronil. MB46513 is not an animal or plant metabolite. Rather, it
forms when the parent compound fipronil is exposed to sunlight. It is
not present on corn, but is potentially present on rice due to the
foliar application (to germinated rice seed).
Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed
the available scientific data and other relevant information in support
of this action, EPA has sufficient data to assess the hazards of
fipronil and to make a determination on aggregate exposure, consistent
with section 408(b)(2) of the FFDCA, for tolerances for combined
residues of fipronil, its metabolites MB46136 and MB45950, and its
photodegradate MB46513 in or on rice grain at 0.04 ppm and rice straw
at 0.10 ppm.
A. Toxicology Data Base
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by fipronil and its
photodegradate MB46513 are discussed in this unit.
1. Acute studies--i. Technical fipronil. A battery of acceptable
acute toxicity studies place technical fipronil in toxicity Categories
II and III. It is classified as a non-sensitizer.
ii. Icon 6.2 FS (56% fipronil). A battery of acute toxicity studies
submitted for Icon 6.2 FS places it in toxicity categories II and III.
This formulation is classified as a sensitizer.
iii. MB46513. Based on acute oral and acute dermal studies, MB46513
is classified in toxicity category I. No studies were submitted for
acute inhalation, primary eye, primary dermal, and dermal
sensitization.
2. Subchronic toxicity testing. The data base for subchronic
toxicity is considered complete. No additional studies are required at
this time.
i. Fipronil. a. An acceptable subchronic oral toxicity feeding
study in the rat established the lowest observed-effect level (LOEL) to
be 30 ppm for males (1.93 milligram (mg)/kilogram (kg)/day) and females
(2.28 mg/kg/day) based on alterations in serum-protein values and
increased weight of the liver and thyroid. The NOEL was 5 ppm for males
(0.33 mg/kg/day) and females (0.37 mg/kg/day).
b. An acceptable subchronic oral toxicity feeding study in the
mouse established the LOEL at 25 ppm (3.2 and 4.53 mg/kg/day, for males
and females, respectively) based on a possible decreased body-weight
gain. The no-observed adverse-effect level (NOAEL) was 10 ppm (1.27 and
1.72 mg/kg/day, for males and females, respectively). The NOEL is less
than or equal to 1 ppm (0.13 and 0.17 mg/kg/day for males and females,
respectively) based on hepatic hypertrophy at all doses.
c. An acceptable subchronic oral toxicity [capsule] study in the
dog established that the LOEL is 10.0 mg/kg/day for males (based on
clinical signs of toxicity) and 2.0 mg/kg/day for females (based on
clinical signs of toxicity and decreased body-weight gain). The NOEL is
2.0 mg/kg/day for males and 0.5 mg/kg/day for females.
d. An acceptable repeated dose dermal study using the rat found
that the systemic LOEL was 10 mg/kg/day based on decreased body-weight
gain and food consumption; the dermal irritation LOEL is greater than
10.0 mg/kg/day. The systemic NOEL was 5.0 mg/kg/day; the dermal
irritation NOEL was greater than or equal to 10.0 mg/kg/day.
ii. MB46513. a. An acceptable subchronic oral toxicity feeding
study using the rat found that the LOEL was 3 ppm (0.177 and 0.210 mg/
kg/day for males and females, respectively) based on the occurrence of
aggressivity, irritability to touch and increased motor activity in one
male (these signs are also observed in the mouse). The NOEL was 0.5 ppm
(0.029 and 0.035 mg/kg/day for males and females, respectively). The
study demonstrates that the metabolite is more toxic than the parent
chemical fipronil when administered to rats for 90 days.
b. An acceptable subchronic oral toxicity feeding study using the
mouse found that the LOEL is 2 ppm (0.32 mg/kg/day), based on the
aggressive and irritable behavior with increased motor activity in
males. The NOEL is 0.5 ppm (0.08 mg/kg/day).
c. An acceptable subchronic oral toxicity feeding study using the
dog established that the LOEL is 35 ppm (1.05 mg/kg/day), based on
behavioral changes in 2 out of 5 females. The NOEL is 9.5 ppm (0.29 mg/
kg/day).
3. Chronic toxicity studies. The data base for chronic toxicity is
considered complete. No additional studies are required at this time.
i. An acceptable chronic feeding study in the rat using fipronil
found that the LOEL is 1.5 ppm for males (0.059 mg/kg/day) and females
(0.078 mg/kg/day) based on an increased incidence of clinical signs and
alterations in clinical chemistry and thyroid parameters. The NOEL is
0.5 ppm for males (0.019 mg/kg/day) and females (0.025 mg/kg/day). The
study demonstrated that fipronil is carcinogenic to rats at doses of
300 ppm in males (12.68 mg/kg/day) and females (16.75 mg/kg/day).
ii. An acceptable chronic oral toxicity [capsule] study in the dog
using fipronil established a LOEL at 2.0 mg/kg/day based on clinical
signs of neurotoxicity and abnormal neurological examinations. The NOEL
is 0.2 mg/kg/day.
4. Carcinogenicity studies. The data base for carcinogenicity is
considered complete. No additional studies are required at this time.
i. The results of a carcinogenicity study in the rat using fipronil
is described in Unit II.A.3.i of this preamble.
ii. A acceptable carcinogenicity [feeding] study in the mouse using
fipronil found that the LOEL is 10 ppm (1.181 mg/kg/day for males and
1.230 mg/kg/day for females) based on decreased body-weight gain,
decreased food conversion efficiency (males), increased liver weights
and increased incidence of hepatic histopathological changes. The NOEL
is 0.5 ppm (0.055 mg/kg/day for males and 0.063 mg/kg/day for females).
The study demonstrated that fipronil is not carcinogenic to CD-1 mice
when administered at doses of 30 ppm.
5. Developmental toxicity studies. The data base for developmental
toxicity is considered complete. No additional studies are required at
this time.
i. Fipronil. a. An acceptable prenatal developmental study in the
rat found that the maternal toxicity LOEL was 20 mg/kg/day based on
reduced body-weight gain, increased water consumption, reduced food
consumption, and reduced food efficiency. The maternal toxicity NOEL
was 4 mg/kg/day. The developmental toxicity LOEL was greater than 20
mg/
[[Page 38486]]
kg/day. Developmental toxicity NOEL was 20 mg/kg/day or higher.
b. An acceptable prenatal developmental study in the rabbit found
that the maternal toxicity LOEL was 0.1 mg/kg/day or lower, based on
reduced body-weight gain, reduced food consumption and efficiency.
Maternal toxicity NOEL was less than 0.1 mg/kg/day. The developmental
toxicity LOEL was greater than 1.0 mg/kg/day. The developmental
toxicity NOEL was 1.0 mg/kg/day or higher.
ii. MB46513. An acceptable prenatal developmental study using the
rat found that the maternal toxicity LOEL was 2.5 mg/kg/day and the
NOEL was 1.0 mg/kg/day based an increase in clinical signs of toxicity
(reduced body-weight gain, food consumption and food efficiency). The
Developmental Toxicity LOEL was 2.5 mg/kg/day and the NOEL was 1.0 mg/
kg/day based on the slight increase in fetal and litter incidence of
reduced ossification of several bones.
6. Reproduction toxicity studies. The data base for reproductive
toxicity is considered complete. No additional studies are required at
this time.
An acceptable two-generation reproduction study in the rat using
fipronil concluded that the LOEL for parental (systemic) toxicity was
30 ppm (2.54 mg/kg/day for males and 2.74 mg/kg/day for females) 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 the
females. The NOEL for parental (systemic) toxicity was 3 ppm (0.25 mg/
kg/day for males and 0.27 mg/kg/day for females).
The LOEL for reproductive toxicity was 300 ppm (26.03 mg/kg/day for
males and 28.40 mg/kg/day for females) based on clinical signs of
toxicity in the F1 and F2 offspring; decreased
litter size in the F1 and F2 litters; decreased
body weights in the F1 and F2 litters; decrease
in the percentage of F1 parental animals mating; reduction
in fertility index in F1 parental animals; reduced post-
implantation survival and offspring postnatal survivability in the F2
litters; and delay in physical development in the F1 and
F2 offspring. The NOEL for reproductive toxicity was 30 ppm
(2.54 mg/kg/day for males and 2.74 mg/kg/day for females).
7. Neurotoxicity. The data base for neurotoxicity is considered
complete. No additional studies are required at this time.
i. Fipronil. a.An acceptable acute neurotoxicity study in the rat
concluded the following: The NOEL was 0.5 mg/kg for males and females.
The LOEL was 5.0 mg/kg for males and females based on decreased hind-
leg splay at the 7 hour post-treatment evaluation in males and females.
b. An acceptable acute neurotoxicity study in the rat concluded
that the NOEL was 2.5 mg/kg. The LOEL is 7.5 mg/kg, based on decreased
body-weight gains, food consumption and feed efficiency in females,
decreased hindlimb splay in males (at 7-hours post test) and decreased
grooming in females (14-days post test).
c. An acceptable subchronic neurotoxicity screening battery in the
rat concluded the LOEL was 150 ppm (8.89 mg/kg/day, males; 10.8 mg/kg/
day, females) based on the results of the functional observational
battery (FOB); the NOEL was 5.0 ppm (0.301 mg/kg/day, males; 0.351 mg/
kg/day, females).
d. In a developmental neurotoxicity study, fipronil was
administered to 30 female rats/group in the diet at dose levels of 0,
0.5, 10, or 200 ppm (0.05, 0.90, or 15 mg/kg/day, respectively) from
gestation day 6 to lactation day 10. This study found that the maternal
LOEL was 200 ppm (15 mg/kg/day), based on decreased body weight, body-
weight gain, and food consumption. The maternal NOEL was 10 ppm (0.90
mg/kg/day). The developmental toxicity LOEL is 10 ppm (0.9 mg/kg/day),
based on a marginal but statistically significant decrease in group
mean pup weights during lactation and significant increase in time of
preputial separation in males. The NOEL for developmental toxicity is
0.5 ppm (0.05 mg/kg/day). The developmental neurotoxicity LOEL is 200
ppm (15 mg/kg/day) based on: Decreased auditory startle response;
reduced swimming direction scores, group mean angle measurements, and
water ``Y'' maze times trails; and decreased absolute-brain weights.
The NOEL for developmental neurotoxicity is 10 ppm (0.90 mg/kg/day).
It is noted that developmental toxicity occurred at a dose lower
than the maternal-toxicity NOEL in this study. However, EPA did not
consider this to indicate increased susceptibility to infants and
children. See Unit II.F.1.ii.d of this preamble for a detailed
discussion of this point.
ii. MB46513. An acceptable acute neurotoxicity study in the rat
concluded that the neurobehavioral LOEL for rats is 12 mg/kg based on
decreases in body-weight gains and food consumption for males and
females during the week following treatment, significant decreases in
locomotor activity 6-hours post dosing for both males and females,
decreases in hind-limb splay and rectal temperature at 6-hours post
dose in males and females, decreases in the proportion of high-dose
males with an immediate righting reflex on days 7 and 14. Decreased
forelimb grip strength in males on day 7 and increased forelimb grip
strength in high-dose females at 6-hours post dosing was possibly
related to the treatment, because there were also slight increases in
forelimb grip strength in high-dose males at 6 hours and slight
decreases in forelimb grip strength in high dose females at 7 days and
in high-dose males and females at 14 days.. The NOEL is 2 mg/kg.
8. Mutagenicity. The available studies indicate that fipronil and
MB46513 are not mutagenic in bacteria and are not clastogenic in vitro
or in vivo up to doses that showed clear test material interaction with
the target cells. Based on these considerations, EPA concluded that
there is no concern for mutagenicity. The submitted test battery for
both compounds satisfy the new mutagenicity initial testing battery
guidelines. No further studies are required at this time.
i. Fipronil. a. An acceptable gene mutation/bacteria test using
salmonella typhimurium concluded that fipronil was not mutagenic.
b. An acceptable in vitro gene mutation assay in mammalian cells/
Chinese hamster V79 cells concluded as follows: Fipronil was negative
for inducing forward gene mutations at the HGPRT locus in cultured
Chinese hamster V79 cells.
c. An acceptable cytogenetic in vivo micronucleus assay in the
mouse concluded as follows: There was no evidence of a clastogenic or
aneugenic effect at any dose or at any harvest time.
d. An acceptable cytogenetic assay in human lymphocytes concluded
as follows: There was no evidence of a clastogenic effect when human
lymphocytes were exposed in vitro to fipronil.
ii. MB46513. a. An acceptable gene mutation/bacteria test using
salmonella typhimurium showed that there was no evidence of a mutagenic
response at any dose.
b. An acceptable gene mutation/in vitro assay in mammalian cells
considering the HPRT locus in Chinese Hamster Ovary (CHO) cells showed
that MB46513 did not induce forward mutations at the HPRT locus in CHO
cells at any dose level tested.
c. An acceptable cytogenetics/in vivo mouse bone marrow
micronucleus assay showed that there was no significant increase in the
frequency of MPCEs in bone marrow after any MB46513 treatment time;
therefore, the test article is considered negative in this micronucleus
assay.
9. Metabolism study. The data base for metabolism is considered to
be
[[Page 38487]]
complete. No additional studies are required at this time.
i. Fipronil. An acceptable metabolism study in the rat using 14-C
labeled and unlabeled fipronil showed the following: With oral dosing,
the rate and extent of absorption appeared similar among all dose
groups, but may have been decreased at the high dose. There were no
significant sex-related differences in excretion. Feces appeared to be
the major route of excretion for fipronil derived radioactivity, where
45-75% of an administered dose was excreted. Excretion in urine was
between 5-25%. Major metabolites in urine included two ring-opened
products of the metabolite MB45897, two oxidation products (MB46136 and
RPA200766), and the parent chemical. In feces, the parent was detected
as a significant fraction of the sample radioactivity as well as the
oxidation product MB46136 and MB45950. Since MB46513 is not an animal
metabolite but a photodegradate, it was not found in this study.
ii. MB46513. In a acceptable rat metabolism study, 14C
labeled MB46513 was administered to rats by gavage as a single dose or
as a single dose following a 14-day pretreatment with unlabeled
MB46513. Unchanged MB46513 in urine accounted for less than 0.1% of the
dose. Fecal excretion of unchanged MB46513 is the principal pathway for
elimination of MB46513 from rats. The high levels of radioactivity in
fat compared to blood and the prolonged elimination half-life indicate
that there is a potential for bioaccumulation of MB46513 in fatty
tissues.
10. Dermal absorption--i. Fipronil. An acceptable study using the
rat found that the quantity of fipronil absorbed was less than 1% at
all doses. The system was saturated at 3.88 mg/cm2. The
dermal absorption rat was calculated to be less than 1% at 24 hours.
ii. MB46513. An acceptable study in the rat using [14C]
labeled MB46513 found that after 24 hours of exposure, dermal
absorption of MB46513 was minimal. For all dose groups, the majority of
the dose was not absorbed (90.2-102.3%), and only trace amounts (equal
to or less than 0.1%) of radioactivity were excreted in the urine and
feces. There was 2.35% adhered to the skin and absorbed at the 10 hour
time point with the lowest dose applied (0.006 mg/cm2).
11. Special studies--i. Fipronil. a. A supplemental thyroid
function study in the rat showed the following: The treatment with
fipronil or Noxyflex appeared to result in stimulation of the thyroid
glands as evidenced by increased accumulation of 125I in the
thyroid glands and by increases in the ratios of radioactive
distribution between the blood and thyroid. These changes were
accompanied by increases in thyroid weight. Treatment with
propylthiouracil (PTU) produced decreases in the amount of
125I incorporated in the thyroid and in the blood: Thyroid
ratios along with elevated levels of 125I in the blood.
However, the weights of the thyroids from these animals were increased
by over 2.5 fold compared to the controls and therefore, the ratio of
125I in the blood to thyroid weight was reduced. The
administration of perchlorate produced further reductions in the
125I content in the thyroids and in the blood: Thyroid
125I radioactivity ratio. There was no evidence of an
inhibition of iodide incorporation by either fipronil or noxyflex.
b. A supplemental thyroxine clearance study in the rat using
technical fipronil showed the following: Fipronil had no effect on
mortality or other ante mortem parameters. Phenobarbital-treated
animals were observed to have collapsed posture, lethargy and shallow
breathing on the first day of treatment. There was no effect of
fipronil on clearance after 1 day of treatment. However, after 14 days,
there was a decrease in terminal half life (52% of control level) and
increases in clearance and volume of distribution (261% and 137% of
control level, respectively). The effects seen with phenobarbital
treatment were similar, although quantitatively not as severe and were
evident on day one of treatment.
c. An acceptable 28-day dietary study in the rat concluded that the
LOEL is 25 ppm or lower (3.4 mg/kg/day in males; 3.5 mg/kg/day in
females), based on clinical laboratory changes, increased absolute
liver weights in females and histopathological alterations in the
thyroid glands. The NOEL is less than 25 ppm.
ii. MB46513. An acceptable 28-day dietary range-finding study in
the rat measured thyroid hormone levels as well as standard study
parameters. It found that the LOEL is 30 ppm (2.20 and 2.32 mg/kg/day
for males and females, respectively), based on clinical signs including
piloerection, curling up and thin appearance; and decreased body
weights in both sexes. The NOEL is 3 ppm (0.23 and 0.24 mg/kg/day for
males and females, respectively).
B. Toxicology Endpoints
The toxicology endpoints for fipronil and MB46513 are presented in
this unit.
1. Fipronil--i. RfD. The RfD for fipronil is 0.0002 mg/kg/day using
a NOEL of 0.019 mg/kg/day (0.5 ppm) established from a combined chronic
toxicity/carcinogenicity study in rats and an uncertainty factor of
100. The LOEL=1.5 ppm (male (M): 0.059 mg/kg/day; female (F): 0.078 mg/
kg/day), based on an increased incidence of clinical signs (seizures
and death) and alterations in clinical chemistry (protein) and thyroid
parameters.
ii. Carcinogenic classification and risk quantification. EPA has
classified this chemical as a Group C--Possible Human Carcinogen, based
on increases in thyroid follicular-cell tumors in both sexes of the
rat, which were statistically significant by both pair-wise and trend
analyses. EPA has used the RfD methodology to estimate human risk
because the thyroid tumors are due to a disruption in the thyroid-
pituitary status. There was no apparent concern for mutagenicity.
iii. Dermal absorption. The percent absorbed was less than 1% at 24
hours based on a dermal absorption study.
iv. Other toxicological endpoints--a. Acute dietary (1 day). In an
acute neurotoxicity study in rats the NOEL was 2.5 mg/kg/day based on
decreased body-weight gains, food consumption and feed efficiency in
females, and decreased hind-limb splay in males at 7-hours post dosing
at 7.5 mg/kg/day LOEL. Although a developmental neurotoxicity study
with the parent compound fipronil had a lower NOEL, EPA determined that
the effects from that study are not attributable to a single exposure
(dose) and therefore are not appropriate for acute dietary-risk
assessments.
b. Short- and intermediate-term residential (dermal). In a 21-day
dermal study the NOEL was 5 mg/kg/day based on decreased body-weight
gain and food consumption in male and female rabbits observed at the
LOEL of 10 mg/kg/day. The dermal NOEL is supported by the oral NOEL of
0.05 mg/kg/day established in a developmental neurotoxicity study when
used in conjunction with a dermal absorption factor of 1%. This yields
an equivalent-dermal dose of 5 mg/kg/day.
c. Chronic residential (non-cancer). In a combined chronic
toxicity/carcinogenicity study in the rat, the NOEL is 0.5 ppm (M:
0.019 mg/kg/day; F: 0.025 mg/kg/day), based on an increased incidence
of clinical signs (seizures and death) and alterations in clinical
chemistry (protein) and thyroid parameters (increased TSH, decreased
T4) at 1.5 ppm (M: 0.059 mg/kg/day; F: 0.078 mg/kg/day). Since the NOEL
identified is from an oral study, a
[[Page 38488]]
dermal absorption factor of less than 1% was used in risk calculations.
(This study/dose was also used to establish the chronic RfD).
2. MB46513--i. RfD. There is no long-term (chronic or
carcinogenicity) studies are available for MB46513. However, the
toxicity profile of MB46513 indicate this material to be approximately
10 times more potent than the parent compound when the NOELs/LOELs are
compared (with the exception of the acute toxicity tests). See table 1
in this preamble.
Table 1.--A Comparison of Toxicities of Photodegradate MB46513 and
Fipronil
------------------------------------------------------------------------
Photodegradate
Study MB46513 Fipronil
------------------------------------------------------------------------
Acute Oral...................... LD50= 16 mg/kg LD50= 92 mg/kg
Acute Neurotoxicity............. NOEL/LOEL= 2/12 mg/ NOEL/LOEL= 2.5/7.5
kg mg/kg
NOEL/LOEL= 0.5/5.0
mg/kg
28-Day Oral--Rat................ NOEL/LOEL= 0.23/ NOEL/LOEL= 3.4 mg/
2.2 mg/kg/day kg/day lowest
dose tested (LDT)
90-Day Oral--Mouse.............. NOEL/LOEL= 0.08/ NOEL/LOEL= 1.7/
0.32 mg/kg/day 3.2 mg/kg/day
90-Day Oral--Rat................ NOEL/LOEL= 0.029/ NOEL= 0.33/1.9 mg/
0.18 mg/kg/day kg/day
Developmental--Rat.............. Maternal NOEL/ Maternal NOEL/
LOEL= 1/2.5 mg/kg/ LOEL= 4/20 mg/kg/
day day
Developmental NOEL/ Developmental NOEL/
LOEL= 1/2.5 mg/kg/ LOEL= 20 mg/kg/
day day highest dose
tested (HDT)
------------------------------------------------------------------------
As shown in table 1 of this preamble, the 28-day and 90-day
subchronic oral studies and oral developmental studies consistently
demonstrated an approximately 10-fold greater potency of MB46513 as
compared to the parent compound, fipronil. In the acute oral tests, the
difference between the LD50 values for MB46513 and fipronil
is not considered significant due to the insensitivities inherent in
this test.
EPA concluded that there is sufficient experimental evidence to
warrant the application of a 10-fold Potency Adjustment Factor (PAF) to
the chronic NOEL for the parent compound to calculate a chronic NOEL
for MB46513 in the absence of test data on the chemical. An adjusted
NOEL was established at 0.0019 mg/kg/day for MB46513.
An Uncertainty Factor (UF) of 100 was applied to account for inter
(10 x)-and intra-(10x) species variation.
ii. Carcinogenic classification and risk quantification. No
carcinogenicity studies are available with MB46513. Fipronil, the
parent compound, was classified as a Group C Carcinogen (Possible Human
Carcinogen). This classification is based on increased incidence of
thyroid follicular-cell tumors in rats. EPA used the RfD methodology
for the quantification of human risk because the thyroid tumors are
related to a disruption in the thyroid-pituitary status and there was
no apparent concern for mutagenicity or available information from
structurally related analogs. EPA has no reason to believe MB46513 is
more carcinogenic than the parent. EPA determined that it was
appropriate to use the RfD methodology to quantify chronic risk for
MB46513. The NOEL used for the chronic RfD has been adjusted by the PAF
to account for the fact that MB46513 is about 10 times more toxic than
the parent (except for acute toxicity).
iii. Dermal absorption. The percent absorbed is estimated at
approximately 2% at 10 hours based on a dermal absorption study with
MB46513.
iv. Other toxicological endpoints--a. Acute dietary. The NOEL is 2
mg/kg in an acute neurotoxicity study in rats (with MB46513) based on
significant decreases in locomotor activity in both sexes during the
first 30 minutes as well as decreases in hind-limb splay and rectal
temperature in both sexes at 6-hours post dosing at 12 mg/kg/day LOEL.
Effects were seen on the day of treatment after a single-oral exposure
(dose) and thus is appropriate for this risk assessment. For reasons
noted in Unit II.B.1.iv of this preamble, EPA did not use a
developmental neurotoxicity study with the parent compound fipronil for
this risk assessment.
b. Short- and intermediate-term dermal exposure (1 to 7 days) (1
week to several months). The adjusted dose of 0.5 mg/kg/day was derived
by dividing the study NOEL of 5 mg/kg/day by the PAF of 10 (5/10= 0.5
mg/kg/day). The LOEL was based on decreases in body-weight gain and
food consumption. The dose and endpoint from the 21-day dermal study
with the parent compound was used for the following reasons:
(1) A 21-dermal toxicity study with MB46513 is not available.
(2) There is low potential for risk from dermal exposure due to
minimal dermal absorption as indicated for both the parent (< 1%)="" and="" the="" mb46513="" (2%)="" materials.="" (3)="" the="" developmental/developmental="" neurotoxicity="" noel="" of="" 0.05="" mg/="" kg/day="" for="" fipronil="" (established="" in="" the="" developmental="" neurotoxicity="" study),="" adjusted="" for="" 1%="" dermal="" absorption="" (da),="" results="" in="" a="" comparable="" dermal="" dose="" of="" 5="" mg/kg/day="" (i.e.,="" 0.05="" mg/kg/day="" '="" 1%="" da="5" mg/kg/day)="" which="" essentially="" is="" the="" same="" as="" the="" noel="" for="" fipronil="" in="" the="" 21-day="" dermal="" toxicity="" study.="" residential="" exposure="" to="" mb46513="" is="" not="" expected="" while="" spraying="" or="" handling="" a="" recently="" treated="" pet="" as="" these="" are="" brief="" periods="" usually="" occurring="" indoors,="" and="" mb46513="" forms="" upon="" exposure="" to="" sunlight.="" post-="" application="" exposure="" to="" the="" degradate="" is="" also="" not="" expected="" due="" to="" the="" products="" reportedly="" strong="" affinity="" to="" the="" sebum="" and="" epidermis="" of="" pets.="" c.="" chronic="" dermal="" exposure="" (several="" months="" to="" lifetime).="" based="" on="" the="" current="" use="" pattern="" for="" mb46513="" (i.e.,="" 1="" application/year="" at="" planting),="" long-term="" exposure="" via="" the="" dermal="" route="" is="" not="" expected.="" residential="" exposures="" are="" not="" chronic="" in="" nature="" as="" label="" uses="" for="" pets="" indicate="" treatment="" every="" 1="" to="" 3="" months.="" d.="" recommendation="" for="" aggregate="" exposure="" risk="" assessments.="" an="" aggregate="" systemic="" (oral)="" and="" dermal="" exposure-risk="" assessment="" is="" not="" appropriate="" due="" to="" differences="" in="" the="" toxicity="" endpoints="" observed="" between="" the="" oral="" (neurotoxicity="" and="" alterations="" in="" clinical="" chemistry="" and="" thyroid="" parameters)="" and="" dermal="" (decreases="" in="" body-weight="" gain="" and="" food="" consumption)="" routes.="" an="" aggregate="" oral="" and="" inhalation="" risk="" assessment="" is="" not="" required="" due="" to="" the="" lack="" of="" exposure="" potential="" via="" the="" inhalation="" route="" based="" on="" the="" current="" use="" pattern.="" c.="" exposures="" and="" risks="" 1.="" from="" food="" and="" feed="" uses.="" tolerances="" have="" been="" established="" (40="" cfr="" 180.517)="" for="" the="" combined="" residues="" of="" fipronil="" in="" or="" on="" on="" corn,="" eggs,="" meat,="" milk,="" and="" poultry.="" risk="" assessments="" were="" conducted="" by="" epa="" to="" assess="" dietary="" exposures="" and="" risks="" from="" fipronil="" and="" mb46513="" as="" follows:="" i.="" acute="" dietary="" risk.="" an="" acute="" dietary="" risk="" assessment="" is="" required="" for="" fipronil="" and="" its="" metabolites="" and="" degradate.="" the="" noel="" of="" 2.5="" mg/kg="" was="" selected="" as="" the="" endpoint="" to="" be="" used="" for="" fipronil,="" mb46136,="" mb45950,="" and="" mb46513.="" since="" mb46513="" does="" not="" appear="" to="" be="" significantly="" more="" acutely="" toxic="" than="" the="" parent,="" it="" was="" incorporated="" into="" the="" acute="" dietary="" risk="" evaluation="" system="" (dres)="" run="" for="" rice.="" if="" further="" refinements="" in="" the="" acute="" dietary="" risk="" assessment="" are="" required="" in="" the="" future,="" a="" separate="" dres="" run="" for="" mb46513="" only="" will="" be="" performed.="" [[page="" 38489]]="" table="" 2.--acute="" risk="" for="" fipronil,="" its="" metabolites,="" and="" degradate="" ----------------------------------------------------------------------------------------------------------------="" exposure="" (mg/kg/="" subgroup="" rfd="" (mg/kg/day)="" level="" of="" concern="" day)="" percent="" of="" rfd="" ----------------------------------------------------------------------------------------------------------------="" general="" u.s.="" population.........="" 0.025="" 100%="" rfd="" 0.0018="" 7="" infants="">< 1="" year)..............="" 0.025="" 100%="" rfd="" 0.003="" 12="" children="" (1-6="" years)............="" 0.025="" 100%="" rfd="" 0.003="" 12="" females="" (13+="" years).............="" 0.025="" 100%="" rfd="" 0.0012="" 5="" males="" (13+="" years)...............="" 0.025="" 100%="" rfd="" 0.0014="" 6="" ----------------------------------------------------------------------------------------------------------------="" epa="" does="" not="" consider="" the="" acute="" dietary="" risks="" to="" exceed="" the="" level="" of="" concern.="" ii.="" chronic="" dietary="" risk.="" a="" chronic="" dietary="" risk="" assessment="" is="" required="" for="" fipronil,="" mb46136,="" and="" mb45950.="" the="" rfd="" used="" for="" the="" chronic="" dietary="" analysis="" for="" parent="" fipronil="" and="" 2="" metabolites="" is="" 0.0002="" mg/kg/day.="" the="" rfd="" used="" for="" mb46513="" is="" 0.00002="" mg/kg/day.="" the="" analysis="" evaluates="" individual="" food="" consumption="" as="" reported="" by="" respondents="" in="" the="" united="" states="" department="" of="" agriculture="" (usda)="" 1977-="" 78="" nationwide="" food="" consumption="" survey="" (nfcs)="" and="" accumulates="" exposure="" to="" the="" chemical="" for="" each="" commodity.="" chronic="" dres="" for="" fipronil,="" mb46136,="" mb45950,="" and="" mb46513="" are="" summarized="" in="" table="" 3="" of="" this="" preamble.="" the="" dres="" analysis="" utilized="" the="" anticipated="" residues="" calculated="" from="" field-trial="" data="" for="" all="" animal,="" corn,="" and="" rice="" commodities.="" the="" proposed="" fipronil="" uses="" result="" in="" an="" anticipated="" residue="" contribution="" (arc)="" that="" is="" equivalent="" to="" the="" following="" percent="" of="" the="" rfd:="" table="" 3.--chronic="" dietary="" risk="" ----------------------------------------------------------------------------------------------------------------="" fipronil,="" mb46136,="" and="" subgroups="" mb45950="" photodegradate="" mb46513="" total="" ----------------------------------------------------------------------------------------------------------------="" u.s.="" population="" (48="" states)..........="" 4.8%="" 1.7%="" 6.5%="" hispanics............................="" 6.2%="" 2.9%="" 8.1%="" non-hispanic="" others..................="" 5.8%="" 3.9%="" 9.7%="" nursing="" infants="">< 1="" year="" old).......="" 2.8%="" 2.3%="" 5.1%="" non-nursing="" infants="">< 1="" year="" old)...="" 11.2%="" 5.5%="" 16.7%="" females="" (13+="" years,="" pregnant)........="" 3.3%="" 1.2%="" 4.5%="" females="" (13+="" years,="" nursing).........="" 4.2%="" 1.6%="" 5.8%="" children="" (1-6="" years="" old).............="" 11.4%="" 3.8%="" 15.2%="" children="" (7-12="" years="" old)............="" 7.6%="" 2.3%="" 9.9%="" females="" (20+="" years,="" not="" pregnant,="" not="" 3.0%="" 1.2%="" 4.2%="" nursing).="" ----------------------------------------------------------------------------------------------------------------="" epa="" does="" not="" consider="" the="" chronic="" dietary="" risk="" to="" exceed="" the="" level="" of="" concern.="" anticipated="" residues.="" section="" 408(b)(2)(e)="" of="" the="" ffdca="" authorizes="" epa="" to="" consider="" available="" data="" and="" information="" on="" the="" anticipated="" residue="" levels="" of="" pesticide="" residues="" in="" food="" and="" the="" actual="" levels="" of="" pesticide="" chemicals="" that="" have="" been="" measured="" in="" food.="" if="" epa="" relies="" on="" such="" information,="" epa="" must="" require="" that="" data="" be="" provided="" 5="" years="" after="" the="" tolerance="" is="" established,="" modified,="" or="" left="" in="" effect,="" demonstrating="" that="" the="" levels="" in="" food="" are="" not="" above="" the="" levels="" anticipated.="" following="" the="" initial="" data="" submission,="" epa="" is="" authorized="" to="" require="" similar="" data="" on="" a="" time="" frame="" it="" deems="" appropriate.="" percent="" crop="" treated.="" section="" 408(b)(2)(f)="" of="" the="" ffdca="" states="" that="" the="" agency="" may="" use="" data="" on="" the="" actual="" percent="" of="" food="" treated="" for="" assessing="" chronic="" dietary="" risk="" onl="" if="" the="" agency="" can="" make="" the="" following="" findings:="" (1)="" that="" the="" data="" used="" are="" reliable="" and="" provide="" a="" valid="" basis="" to="" show="" what="" percentage="" of="" the="" food="" derived="" from="" such="" crop="" is="" likely="" to="" contain="" such="" pesticide="" residue.="" (2)="" that="" the="" exposure="" estimate="" does="" not="" underestimate="" exposue="" for="" any="" significant="" subpopulation="" group.="" (3)="" if="" data="" are="" available="" on="" pesticide="" use="" and="" food="" consumption="" in="" a="" particular="" area,="" the="" exposure="" estimate="" does="" not="" understate="" exposue="" for="" the="" population="" in="" such="" area.="" in="" addition,="" the="" agency="" must="" provide="" for="" periodic="" evaluation="" of="" any="" estimates="" used.="" to="" provide="" for="" the="" periodic="" evaluation="" of="" the="" estimate="" of="" percent="" crop="" treated="" as="" required="" by="" the="" section="" 408="" (b)(2)(f)="" of="" the="" ffdca,="" epa="" may="" require="" registrants="" to="" submit="" data="" on="" percent="" crop="" treated.="" anticipated="" residues,="" based="" on="" average="" field="" trial="" values,="" and="" percent="" crop="" treated="" information="" were="" used="" to="" estimate="" dietary="" risk="" for="" the="" chronic="" dietary="" risk="" assessment.="" for="" the="" acute="" dietary="" risk="" assessment,="" anticipated="" residues="" in="" blended="" commodities="" (such="" as="" corn="" and="" rice="" processed="" commodities)="" were="" used,="" without="" the="" adjustment="" for="" percent="" crop="" treated.="" however,="" tolerance="" level="" residues="" were="" used="" for="" fat;="" meat="" by-products;="" meat="" of="" cattle,="" goats,="" hogs,="" horses,="" sheep,="" and="" poultry;="" and="" eggs.="" since="" milk="" is="" a="" blended="" commodity,="" an="" anticipated="" residue="" value="" was="" used.="" as="" required="" by="" the="" fqpa,="" epa="" will="" issue="" a="" data="" call-in="" under="" section="" 408(f)="" of="" the="" ffdca="" to="" all="" fipronil="" registrants="" for="" data="" on="" anticipated="" residues,="" to="" be="" submitted="" no="" later="" than="" 5="" years="" from="" the="" date="" of="" issuance="" of="" these="" tolerances.="" the="" percent="" of="" crop="" treated="" estimates="" for="" fipronil="" and="" mb46513="" were="" based="" on="" an="" estimate="" of="" percent="" crop="" treated="" by="" existing="" products="" used="" to="" control="" rice="" water="" weevil="" and="" chinch="" bugs.="" in="" addition,="" as="" set="" forth="" in="" 62="" fr="" 62970,="" market="" share="" estimates="" were="" used="" for="" corn.="" they="" were="" based="" on="" an="" estimate="" of="" percent="" crop="" treated="" by="" other="" insecticides="" to="" control="" corn="" rootworm,="" wireworm,="" and="" corn="" borer.="" epa="" considers="" these="" data="" reliable.="" a="" range="" of="" estimates="" are="" supplied="" by="" this="" data="" and="" the="" upper="" end="" of="" this="" range="" was="" used="" for="" the="" exposure="" assessment.="" by="" using="" this="" upper="" end="" estimate="" of="" percent="" crop="" treated,="" the="" agency="" is="" reasonably="" certain="" that="" exposure="" is="" not="" underestimated="" for="" any="" significant="" subpopulation.="" further,="" regional="" consumption="" information="" is="" taken="" into="" account="" through="" epa's="" computer-based="" model="" for="" evaluating="" the="" exposure="" of="" significant="" subpopulations="" including="" several="" regional="" groups.="" review="" of="" this="" regional="" [[page="" 38490]]="" data="" allows="" the="" agency="" to="" be="" reasonably="" certain="" that="" no="" regional="" population="" is="" exposed="" to="" residue="" levels="" higher="" than="" those="" estimated="" by="" the="" agency.="" to="" provide="" for="" the="" periodic="" evaluation="" of="" these="" estimates="" of="" percent="" crop="" treated="" and="" to="" meet="" the="" requirement="" for="" data="" on="" anticipated="" residues,="" epa="" may="" require="" fipronil="" registrants="" to="" submit="" data="" on="" percent="" crop="" treated.="" 2.="" dietary="" exposure="" (drinking="" water="" source).="" epa="" does="" not="" have="" monitoring="" data="" available="" to="" perform="" a="" quantitative="" drinking="" water="" risk="" assessment="" for="" fipronil="" at="" this="" time.="" using="" environmental="" fate="" data,="" epa="" developed="" ground="" and="" surface="" water="" exposure="" estimates="" for="" use="" on="" corn="" and="" rice.="" i.="" ground="" water="" (tiered="" assessment).="" the="" environmental="" fate="" data="" for="" fipronil="" indicate="" a="" moderate="" to="" high="" persistence="" and="" relatively="" low="" mobility="" in="" terrestrial="" environments.="" based="" on="" the="" sci-gro="" model,="" acute="" drinking="" water="" concentrations="" in="" shallow="" ground="" water="" on="" highly="" vulnerable="" sites="" are="" not="" likely="" to="" exceed="" the="" values="" set="" forth="" in="" tables="" 4-7="" of="" this="" preamble:="" table="" 4.--estimated="" ground="" water="" residues="" of="" fipronil="" and="" its="" metabolites="" ------------------------------------------------------------------------="" corn="" parts="" per="" billion="" (ppb)="" rice="" (ppb)="" ------------------------------------------------------------------------="" fipronil........................="" 0.055="" 0.00804="" mb46136.........................="" 0.001="" 0.00038="" mb45950.........................="" 0.00036="" 0.000685="" ------------------------------------------------------------------------="" total:......................="" 0.05636="" 0.009105="" ------------------------------------------------------------------------="" table="" 5.--estimated="" ground="" water="" residues="" of="" photodegradate="" mb46513="" ------------------------------------------------------------------------="" corn="" (ppb)="" rice="" (ppb)="" ------------------------------------------------------------------------="" photodegradate="" mb46513..........="" 0.00026="" 0.004138="" ------------------------------------------------------------------------="" chronic="" concentrations="" are="" not="" expected="" to="" be="" higher="" than="" acute="" values.="" highly="" vulnerable="" sites="" are="" those="" with="" low-organic="" matter,="" coarse="" textured="" soils="" (e.g.,="" sands="" and="" loamy="" sands)="" and="" shallow-ground="" water.="" the="" fate="" data="" for="" fipronil="" and="" its="" degradates="" indicate="" a="" higher="" potential="" mobility="" on="" coarse-textured="" soils="" (sand="" or="" loamy="" sands).="" ii.="" surface="" water="" (tiered="" assessment).="" based="" on="" the="" environmental="" fate="" assessment,="" fipronil,="" mb46513,="" mb46136,="" and="" mb45950="" can="" potentially="" move="" into="" surface="" waters.="" since="" fipronil="" is="" used="" as="" an="" in-="" furrow="" application="" on="" field="" corn,="" the="" runoff="" potential="" of="" fipronil="" residues="" is="" expected="" to="" be="" lower="" than="" for="" unincorporated="" surface="" application="" techniques.="" since="" photodegradation="" is="" a="" major="" route="" of="" degradation="" for="" fipronil,="" its="" dissipation="" is="" expected="" to="" be="" dependent="" on="" physical="" components="" of="" the="" water="" (i.e.="" sediment="" loading)="" which="" affect="" sunlight="" penetration.="" the="" maximum="" fipronil="" concentration="" for="" acute="" (peak="" concentration)="" and="" chronic="" (56-day="" average="" )="" based="" on="" the="" tier="" 1="" geneec="" surface="" water="" modeling="" is="" shown="" in="" the="" table="" 6="" of="" this="" preamble:="" table="" 6.--surface="" water="" concentrations="" for="" fipronil="" and="" its="" metabolites="" based="" on="" geneec="" modeling="" ----------------------------------------------------------------------------------------------------------------="" corn="" rice="" -------------------------------------------------------------------------------="" acute="" peak="" estimated="" environmental="" chronic="" 56-day="" eec="" acute="" peak="" eec="" chronic="" 56-day="" eec="" concentration="" (ppb)="" (ppb)="" (eec)="" ----------------------------------------------------------------------------------------------------------------="" fipronil........................="" 2.05="" 0.78="" 1.45="" 0.40="" mb46136.........................="" 0.168="" 0.062="" 0.061="" 0.004="" mb45950.........................="" 0.039="" 0.019="" 0.1296="" 0.013="" ----------------------------------------------------------------------------------------------------------------="" total.......................="" 2.257="" 0.861="" 1.6406="" 0.417="" ----------------------------------------------------------------------------------------------------------------="" table="" 7.--surface="" water="" concentrations="" for="" photodegradate="" mb46513="" based="" on="" geneec="" modeling="" ----------------------------------------------------------------------------------------------------------------="" corn="" rice="" -------------------------------------------------------------------------------="" acute="" peak="" eec="" chronic="" 56-day="" eec="" acute="" peak="" eec="" chronic="" 56-day="" eec="" (ppb)="" (ppb)="" ----------------------------------------------------------------------------------------------------------------="" photodegradate="" mb46513..........="" 0.014="" 0.009="" 0.359="" 0.066="" ----------------------------------------------------------------------------------------------------------------="" iii.="" drinking="" water="" risk="" (acute="" and="" chronic).="" to="" calculate="" the="" drinking="" water="" level="" of="" concern="" (dwloc)="" for="" acute="" exposure="" relative="" to="" an="" acute="" toxicity="" endpoint,="" the="" acute="" dietary="" food="" exposure="" (from="" the="" dres="" analysis)="" was="" subtracted="" from="" acute="" rfd="" to="" obtain="" the="" acute="" exposure="" to="" fipronil="" (plus="" mb45950="" and="" mb46136)="" in="" drinking="" water.="" to="" calculate="" the="" dwloc="" for="" chronic="" (non-cancer,="" cancer)="" exposure="" relative="" to="" a="" chronic="" toxicity="" endpoint,="" the="" chronic="" dietary="" food="" exposure="" (from="" dres)="" was="" subtracted="" from="" the="" chronic="" rfd="" to="" obtain="" the="" acceptable="" chronic="" (non-cancer)="" exposure="" to="" fipronil,="" mb45950,="" and="" mb46136="" in="" drinking="" water.="" dwlocs="" were="" then="" calculated="" using="" default="" body="" weights="" and="" drinking="" water="" consumption="" figures.="" a.="" acute="" risk.="" epa="" has="" calculated="" dwlocs="" for="" acute="" exposure="" to="" fipronil,="" mb45950,="" mb46136,="" and="" mb46513="" in="" surface="" and="" ground="" water="" for="" the="" u.s.="" population="" and="" children="" (1-6="" yrs="" ).="" they="" are="" 810="" and="" 220="" ppb,="" respectively.="" b.="" chronic="" risk.="" for="" chronic="" (non-cancer)="" exposure="" to="" fipronil="" (plus="" mb45950="" and="" mb46136)="" in="" surface="" and="" ground="" water,="" the="" drinking="" water="" levels="" of="" concern="" are="" 6.67="" and="" 1.77="" ppb="" for="" u.s.="" population="" and="" children="" (1-6="" years="" old),="" respectively.="" c.="" maximum="" and="" average="" concentrations.="" estimated="" maximum="" concentrations="" of="" fipronil,="" mb45950,="" mb46136,="" and="" mb46513="" in="" surface="" and="" ground="" water="" are="" 2.271="" and="" 0.05662="" ppb="" (with="" 0.00026="" ppb="" from="" mb46513="" included),="" respectively.="" the="" estimated="" average="" concentration="" of="" fipronil,="" mb45950,="" and="" mb46136="" in="" surface="" water="" is="" 0.861="" ppb.="" chronic="" concentrations="" in="" ground="" water="" are="" not="" expected="" to="" be="" higher="" than="" the="" acute="" concentrations.="" for="" the="" purposes="" of="" the="" screening-level="" assessment,="" the="" maximum="" and="" average="" concentrations="" in="" [[page="" 38491]]="" ground="" water="" are="" not="" believed="" to="" vary="" significantly.="" the="" maximum="" estimated="" concentrations="" of="" fipronil,="" mb45950,="" and="" mb46136="" in="" surface="" and="" ground="" water="" are="" less="" than="" epa's="" levels="" of="" concern="" for="" fipronil,="" mb45950,="" and="" mb46136="" in="" drinking="" water="" as="" a="" contribution="" to="" acute="" aggregate="" exposure.="" the="" estimated="" average="" concentrations="" of="" fipronil,="" mb45950,="" and="" mb46136="" in="" surface="" and="" ground="" water="" are="" less="" than="" epa's="" levels="" of="" concern="" for="" fipronil,="" mb45950,="" and="" mb46136="" in="" drinking="" water="" as="" a="" contribution="" to="" chronic="" aggregate="" exposure.="" therefore,="" taking="" into="" account="" the="" present="" uses="" and="" uses="" proposed="" in="" this="" action,="" epa="" concludes="" with="" reasonable="" certainty="" that="" residues="" of="" fipronil,="" mb45950,="" and="" mb46136="" in="" drinking="" water="" (when="" considered="" along="" with="" other="" sources="" of="" exposure="" for="" which="" epa="" has="" reliable="" data)="" would="" not="" result="" in="" unacceptable="" levels="" of="" aggregate="" human="" health="" risk="" at="" this="" time.="" d.="" mb46513="" (chronic="" only).="" for="" chronic="" (non-cancer)="" exposure="" to="" mb46513="" in="" surface="" and="" ground="" water,="" the="" drinking="" water="" levels="" of="" concern="" are="" 0.69="" and="" 0.19="" ppb="" for="" u.s.="" population,="" children="" (non-="" nursing="" infants,="">< 1="" year="" old),="" respectively.="" to="" calculate="" the="" dwloc="" for="" chronic="" (non-cancer,="" cancer)="" exposure="" relative="" to="" a="" chronic="" toxicity="" endpoint,="" the="" chronic="" dietary="" food="" exposure="" (from="" dres)="" was="" subtracted="" from="" the="" rfd="" to="" obtain="" the="" acceptable="" chronic="" (non-cancer)="" exposure="" to="" mb46513="" in="" drinking="" water.="" dwlocs="" were="" then="" calculated="" using="" default="" body="" weights="" and="" drinking="" water="" consumption="" figures.="" estimated="" maximum="" concentrations="" of="" mb46513="" in="" ground="" water="" is="" 0.00026="" ppb.="" the="" estimated="" average="" concentration="" of="" mb46513="" in="" surface="" water="" is="" 0.009="" ppb.="" chronic="" concentrations="" in="" ground="" water="" are="" not="" expected="" to="" be="" higher="" than="" the="" acute="" concentrations.="" for="" the="" purposes="" of="" the="" screening-level="" assessment,="" the="" maximum="" and="" average="" concentrations="" in="" ground="" water="" are="" not="" believed="" to="" vary="" significantly.="" the="" estimated="" average="" concentrations="" of="" mb46513="" in="" surface="" and="" ground="" water="" are="" less="" than="" epa's="" levels="" of="" concern="" for="" mb46513="" in="" drinking="" water="" as="" a="" contribution="" to="" chronic="" aggregate="" exposure.="" therefore,="" taking="" into="" account="" the="" present="" uses="" and="" uses="" proposed="" in="" this="" action,="" epa="" concludes="" with="" reasonable="" certainty="" that="" residues="" of="" mb46513="" in="" drinking="" water="" (when="" considered="" along="" with="" other="" sources="" of="" exposure="" for="" which="" epa="" has="" reliable="" data)="" would="" not="" result="" in="" unacceptable="" levels="" of="" aggregate="" human="" health="" risk="" at="" this="" time.="" 3.="" from="" non-dietary="" exposure.="" the="" residential="" uses="" of="" fipronil="" include="" the="" use="" of="" ant="" and="" cockroach="" bait="" traps="" ranging="" from="" 0.01="" to="" 0.05="" percent="" active="" ingredient.="" in="" addition,="" three="" fipronil="" products="" are="" registered="" to="" control="" fleas="" and="" ticks="" on="" dogs="" and="" cats.="" these="" products="" are="" applied="" to="" the="" fur="" of="" the="" animal="" as="" a="" ready-to-use="" pump="" spray="" or="" as="" a="" ready-to-use,="" pour-on,="" spot="" treatment="" made="" along="" the="" back="" of="" the="" animal="" between="" the="" shoulder="" blades.="" i.="" ant="" and="" roach="" baits.="" exposure="" from="" the="" use="" of="" fipronil="" in="" self="" contained="" bait="" stations="" is="" expected="" to="" result="" in="" low="" exposures="" since="" there="" is="" no="" contact="" with="" the="" pesticide.="" ii.="" pet="" care.="" for="" purposes="" of="" setting="" a="" tolerance,="" an="" aggregate="" short-term="" and="" intermediate-term="" systemic="" (oral)="" and="" dermal="" exposure="" risk="" assessment="" which="" includes="" the="" pet="" care="" products="" is="" not="" appropriate="" due="" to="" differences="" in="" the="" toxicity="" endpoints="" observed="" between="" the="" oral="" (neurotoxicity="" and="" alterations="" in="" clinical="" chemistry="" and="" thyroid="" parameters)="" and="" dermal="" (decreases="" in="" body-weight="" gain="" and="" food="" consumption)="" routes.="" further,="" though="" fipronil="" is="" currently="" registered="" for="" residential="" uses,="" no="" chronic="" residential="" exposure="" is="" anticipated.="" 4.="" cumulative="" exposure="" to="" substances="" with="" common="" mechanism="" of="" toxicity.="" fipronil="" is="" structurally="" similar="" to="" other="" members="" of="" the="" pyrazole="" class="" of="" pesticides="" (i.e.,="" tebufenpyrad,="" pyrazolynate,="" benzofenap,="" etc.).="" further,="" other="" pesticides="" may="" have="" common="" toxicity="" endpoints="" with="" fipronil.="" section="" 408(b)(2)(d)(v)="" of="" the="" ffdca="" 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.''="" the="" agency="" believes="" that="" ``available="" information''="" in="" this="" context="" might="" include="" not="" only="" toxicity,="" chemistry,="" and="" exposure="" data,="" but="" also="" scientific="" policies="" and="" methodologies="" for="" understanding="" common="" mechanisms="" of="" toxicity="" and="" conducting="" cumulative="" risk="" assessments.="" for="" most="" pesticides,="" although="" the="" agency="" has="" some="" information="" in="" its="" files="" that="" may="" turn="" out="" to="" be="" helpful="" in="" eventually="" determining="" whether="" a="" pesticide="" shares="" a="" common="" mechanism="" of="" toxicity="" with="" any="" other="" substances,="" epa="" does="" not="" at="" this="" time="" have="" the="" methodologies="" to="" resolve="" the="" complex="" scientific="" issues="" concerning="" common="" mechanism="" of="" toxicity="" in="" a="" meaningful="" way.="" epa="" has="" begun="" a="" pilot="" process="" to="" study="" this="" issue="" further="" through="" the="" examination="" of="" particular="" classes="" of="" pesticides.="" the="" agency="" hopes="" that="" the="" results="" of="" this="" pilot="" process="" will="" increase="" the="" agency's="" scientific="" understanding="" of="" this="" question="" such="" that="" epa="" will="" be="" able="" to="" develop="" and="" apply="" scientific="" principles="" for="" better="" determining="" which="" chemicals="" have="" a="" common="" mechanism="" of="" toxicity="" and="" evaluating="" the="" cumulative="" effects="" of="" such="" chemicals.="" the="" agency="" anticipates,="" however,="" that="" even="" as="" its="" understanding="" of="" the="" science="" of="" common="" mechanisms="" increases,="" decisions="" on="" specific="" classes="" of="" chemicals="" will="" be="" heavily="" dependent="" on="" chemical="" specific="" data,="" much="" of="" which="" may="" not="" be="" presently="" available.="" although="" at="" present="" the="" agency="" does="" not="" know="" how="" to="" apply="" the="" information="" in="" its="" files="" concerning="" common="" mechanism="" issues="" to="" most="" risk="" assessments,="" there="" are="" pesticides="" as="" to="" which="" the="" common="" mechanism="" issues="" can="" be="" resolved.="" these="" pesticides="" include="" pesticides="" that="" are="" toxicologically="" dissimilar="" to="" existing="" chemical="" substances="" (in="" which="" case="" the="" agency="" can="" conclude="" that="" it="" is="" unlikely="" that="" a="" pesticide="" shares="" a="" common="" mechanism="" of="" activity="" with="" other="" substances)="" and="" pesticides="" that="" produce="" a="" common="" toxic="" metabolite="" (in="" which="" case="" common="" mechanism="" of="" activity="" will="" be="" assumed).="" epa="" does="" not="" have,="" at="" this="" time,="" available="" data="" to="" determine="" whether="" fipronil="" has="" a="" common="" mechanism="" of="" toxicity="" with="" other="" substances="" or="" how="" to="" include="" this="" pesticide="" in="" a="" cumulative="" risk="" assessment.="" unlike="" other="" pesticides="" for="" which="" epa="" has="" followed="" a="" cumulative="" risk="" approach="" based="" on="" a="" common="" mechanism="" of="" toxicity,="" fipronil="" does="" not="" appear="" to="" produce="" a="" toxic="" metabolite="" produced="" by="" other="" substances.="" for="" the="" purposes="" of="" this="" tolerance="" action,="" therefore,="" epa="" has="" not="" assumed="" that="" fipronil="" has="" a="" common="" mechanism="" of="" toxicity="" with="" other="" substances.="" 5.="" endocrine="" disruption.="" epa="" is="" required="" to="" develop="" a="" screening="" program="" to="" determine="" whether="" certain="" substances="" (including="" all="" pesticides="" and="" inerts)="" ``may="" have="" an="" effect="" in="" humans="" that="" is="" similar="" to="" an="" effect="" produced="" by="" a="" naturally="" occurring="" estrogen,="" or="" such="" other="" endocrine="" effect...''.="" the="" agency="" is="" currently="" working="" with="" interested="" stakeholders,="" including="" other="" government="" agencies,="" public="" interest="" groups,="" industry,="" and="" research="" scientists="" in="" developing="" a="" screening="" and="" testing="" program="" and="" a="" priority="" setting="" scheme="" to="" implement="" this="" program.="" congress="" has="" allowed="" 3="" years="" from="" the="" passage="" of="" fqpa="" (august="" 3,="" 1999)="" to="" implement="" this="" program.="" at="" that="" time,="" epa="" may="" require="" further="" testing="" of="" this="" active="" [[page="" 38492]]="" ingredient="" and="" end="" use="" products="" for="" endocrine="" disrupter="" effects.="" d.="" aggregate="" risks="" and="" determination="" of="" safety="" for="" u.s.="" population="" 1.="" acute="" aggregate="" exposure="" and="" risk.="" using="" refined="" exposure="" assumptions="" (anticipated="" residues="" for="" blended="" commodities),="" a="" high-end="" exposure="" estimate="" (food="" only)="" was="" calculated="" for="" these="" subgroups:="" females="" 13+="" years,="" for="" the="" general="" u.s.="" population,="" infants="">< 1="" year),="" children="" (1-6="" years),="" and="" males="" 13+.="" these="" risk="" estimates="" are="" the="" same="" as="" those="" displayed="" in="" table="" 2="" of="" this="" preamble.="" the="" maximum="" estimated="" concentrations="" of="" fipronil="" in="" surface="" and="" ground="" water="" are="" less="" than="" epa's="" levels="" of="" concern="" for="" fipronil="" in="" drinking="" water="" as="" a="" contribution="" to="" acute="" aggregate="" exposure.="" 2.="" short-="" and="" intermediate-term="" aggregate="" exposure="" and="" risk.="" an="" aggregate="" systemic="" (oral)="" and="" dermal="" exposure="" risk="" assessment="" is="" not="" appropriate="" due="" to="" differences="" in="" the="" toxicity="" endpoints="" observed="" between="" the="" oral="" (neurotoxicity="" and="" alterations="" in="" clinical="" chemistry="" and="" thyroid="" parameters)="" and="" dermal="" (decreases="" in="" body-weight="" gain="" and="" food="" consumption)="" routes.="" 3.="" chronic="" aggregate="" exposure="" and="" risk.="" chronic="" dietary="" exposure="" estimates="" for="" fipronil,="" mb46136,="" mb45950,="" and="" mb46513="" utilized="" anticipated="" residues="" and="" a="" projected="" market="" share="" and="" are="" thus="" highly="" refined.="" for="" the="" u.s.="" population,="" 6.5%="" of="" the="" rfd="" is="" occupied="" by="" dietary="" (food)="" exposure.="" though="" fipronil="" is="" currently="" registered="" for="" residential="" uses,="" no="" chronic="" residential="" exposure="" is="" anticipated.="" the="" estimated="" average="" concentrations="" of="" fipronil="" in="" surface="" and="" ground="" water="" are="" less="" than="" epa's="" levels="" of="" concern="" for="" fipronil="" in="" drinking="" water="" as="" a="" contribution="" to="" chronic="" aggregate="" exposure.="" 4.="" aggregate="" cancer="" risk="" for="" u.s.="" population.="" for="" fipronil="" plus="" mb46136="" and="" mb45950,="" epa="" finds="" that="" the="" dietary="" risk="" concerns="" due="" to="" long-term="" consumption="" of="" fipronil="" residues="" are="" adequately="" addressed="" by="" the="" dres="" chronic="" exposure="" analysis="" using="" the="" rfd.="" for="" mb46513,="" epa="" finds="" that="" the="" dietary="" risk="" concerns="" due="" to="" long-term="" consumption="" of="" mb46513="" residues="" are="" adequately="" addressed="" by="" the="" dres="" chronic="" exposure="" analysis="" using="" the="" rfd.="" 5.="" safety="" finding.="" based="" on="" unit="" ii.c.="" of="" this="" preamble,="" epa="" concludes="" that="" there="" is="" a="" reasonable="" certainty="" of="" no="" harm="" from="" aggregate="" exposure="" to="" fipronil.="" f.="" aggregate="" risks="" and="" determination="" of="" safety="" for="" infants="" and="" children="" 1.="" safety="" factor="" for="" infants="" and="" children--i.="" in="" general.="" in="" assessing="" the="" potential="" for="" additional="" sensitivity="" of="" infants="" and="" children="" to="" residues="" of="" fipronil,="" epa="" considered="" data="" from="" developmental="" toxicity="" studies="" in="" the="" rat="" and="" rabbit,="" a="" two-generation="" reproduction="" study="" in="" the="" rat,="" and="" a="" developmental="" neurotoxicity="" study="" in="" the="" rat.="" the="" developmental="" toxicity="" studies="" are="" designed="" to="" evaluate="" adverse="" effects="" on="" the="" developing="" organism="" resulting="" from="" pesticide="" exposure="" during="" prenatal="" development="" to="" one="" or="" both="" parents.="" reproduction="" studies="" provide="" information="" relating="" to="" effects="" from="" exposure="" to="" the="" pesticide="" on="" the="" reproductive="" capability="" of="" mating="" animals="" and="" data="" on="" systemic="" toxicity.="" growth,="" survival="" and="" general="" toxicity="" are="" evaluated="" for="" two="" generations="" of="" offspring.="" developmental="" neurotoxicity="" studies="" are="" designed="" to="" evaluate="" adverse="" effects="" on="" the="" nervous="" system="" of="" the="" developing="" organism="" resulting="" from="" pesticide="" exposure="" of="" the="" pregnant="" and="" nursing="" mother="" during="" several="" critical="" stages="" of="" prenatal="" and="" postnatal="" development.="" section="" 408="" of="" the="" ffdca="" provides="" that="" epa="" shall="" apply="" an="" additional="" 10-fold="" margin="" of="" safety="" for="" infants="" and="" children="" in="" the="" case="" of="" threshold="" effects="" to="" account="" for="" pre-and="" post-natal="" toxicity="" and="" the="" completeness="" of="" the="" database="" unless="" epa="" determines="" that="" a="" different="" margin="" of="" safety="" will="" be="" safe="" for="" infants="" and="" children.="" margins="" of="" safety="" are="" incorporated="" into="" epa="" risk="" assessments="" either="" directly="" through="" use="" of="" a="" moe="" analysis="" or="" through="" using="" uncertainty="" (safety)="" factors="" in="" calculating="" a="" dose="" level="" that="" poses="" no="" appreciable="" risk="" to="" humans.="" epa="" believes="" that="" reliable="" data="" support="" using="" the="" standard="" moe="" and="" uncertainty="" factor="" (usually="" 100="" for="" combined="" inter-="" and="" intra-species="" variability))="" and="" not="" the="" additional="" tenfold="" moe/="" uncertainty="" factor="" when="" epa="" has="" a="" complete="" data="" base="" under="" existing="" guidelines="" and="" when="" the="" severity="" of="" the="" effect="" in="" infants="" or="" children="" or="" the="" potency="" or="" unusual="" toxic="" properties="" of="" a="" compound="" do="" not="" raise="" concerns="" regarding="" the="" adequacy="" of="" the="" standard="" moe/safety="" factor.="" ii.="" data="" on="" susceptibility--a.="" neurotoxicity.="" fipronil="" has="" demonstrated="" neurotoxicity="" in="" the="" acute="" and="" subchronic="" rat="" neurotoxicity="" studies="" as="" well="" as="" in="" the="" rat="" chronic/oncogenicity="" and="" chronic="" dog="" studies.="" b.="" developmental="" toxicity.="" there="" are="" acceptable="" rat="" and="" rabbit="" developmental="" toxicity="" studies="" with="" fipronil.="" there="" is="" no="" evidence="" of="" developmental="" toxicity="" in="" either="" study.="" epa="" also="" considered="" a="" developmental="" study="" conducted="" for="" mb46513.="" in="" that="" study,="" pregnant="" rats="" received="" oral="" administration="" of="" mb46513="" (99.2%).="" for="" maternal="" toxicity,="" the="" noel="" was="" 1.0="" mg/kg/day="" and="" the="" loel="" was="" 2.5="" mg/kg/day="" based="" on="" an="" increase="" in="" clinical="" signs="" of="" toxicity="" (hair="" loss)="" and="" on="" reduced="" body-="" weight="" gain,="" food="" consumption,="" and="" food="" efficiency.="" for="" developmental="" toxicity,="" the="" noel="" was="" 1.0="" mg/kg/day="" and="" the="" loel="" was="" 2.5="" mg/kg/day="" based="" on="" a="" slight="" increase="" in="" fetal="" and="" litter="" incidence="" of="" reduced="" ossification="" of="" several="" bones="" (hyoid,="" 5th/6th="" sternebrae,="" 1st="" thoracic="" vertebral="" body,="" pubic="" bone,="" and="" one="" or="" two="" metatarsi).="" most="" of="" the="" reduced="" ossification="" is="" weak="" evidence="" of="" a="" developmental="" effect.="" although="" the="" minor="" decrement="" in="" fetal="" weight="" at="" 2.5="" mg/kg/day="" has="" questionable="" biological="" relevance,="" the="" decrement="" is="" supported="" by="" the="" delayed="" ossification.="" c.="" reproductive="" toxicity.="" there="" is="" an="" acceptable="" two-generation="" reproduction="" study="" in="" the="" rat="" with="" fipronil.="" toxicity="" to="" the="" offspring="" (clinical="" signs="" of="" toxicity,="" decreased="" litter="" size,="" decreased="" body="" weights,="" decreased="" pre-="" and="" postnatal="" survival,="" and="" delays="" in="" physical="" development.)="" occurred="" only="" at="" levels="" where="" there="" was="" maternal="" toxicity="" (including="" maternal="" mortality).="" d.="" developmental="" neurotoxicity.="" in="" an="" acceptable="" study="" with="" fipronil,="" developmental="" neurotoxicity="" (behavioral="" changes="" and="" decreased="" absolute="" brain="" weights)="" was="" seen="" only="" at="" levels="" where="" there="" was="" maternal="" toxicity="" (decreased="" body="" weight,="" body-weight="" gain="" and="" food="" consumption).="" however,="" developmental="" toxicity="" (including="" marginal="" but="" statistically="" significant="" decrease="" in="" group="" mean="" pup="" weights="" during="" lactation,="" and="" significant="" increase="" in="" time="" of="" preputial="" separation="" in="" males)="" was="" seen="" at="" levels="" below="" levels="" of="" maternal="" toxicity.="" e.="" adequacy="" of="" data.="" an="" acceptable="" two-generation="" reproduction="" study="" in="" rats="" and="" acceptable="" prenatal="" developmental="" toxicity="" studies="" in="" rats="" and="" rabbits="" have="" been="" submitted="" to="" the="" agency,="" meeting="" basic="" data="" requirements,="" as="" defined="" for="" a="" food-use="" chemical.="" in="" addition,="" an="" acceptable="" developmental="" neurotoxicity="" study="" was="" conducted="" with="" fipronil="" and="" reviewed="" by="" the="" agency.="" further,="" epa="" has="" a="" developmental="" toxicity="" study="" for="" mb46513.="" where="" specific="" data="" on="" mb46513="" are="" not="" available,="" the="" toxicity="" of="" the="" photodegradate="" can="" be="" reliably="" estimated="" by="" comparing="" the="" fipronil="" and="" mb46513="" data="" bases="" and="" taking="" into="" consideration="" the="" paf.="" therefore,="" additional="" data="" on="" mb46513="" are="" not="" required="" at="" this="" time.="" there="" are="" no="" data="" [[page="" 38493]]="" gaps="" for="" the="" assessment="" of="" the="" effects="" of="" fipronil="" on="" developing="" animals="" following="" in="" utero="" and/or="" early="" postnatal="" exposure.="" f.="" determination="" of="" susceptibility.="" although="" there="" is="" no="" evidence="" of="" enhanced="" pre="" or="" post="" natal="" susceptibility="" in="" infants="" and="" children="" in="" the="" developmental="" and="" reproduction="" studies="" for="" fipronil="" and="" mb46513,="" the="" developmental="" neurotoxicity="" study="" for="" fipronil="" identified="" a="" developmental="" noel="" (0.05="" mg/kg/day)="" which="" is="" less="" than="" the="" maternal="" noel="" of="" 0.9="" mg/kg/day="" indicating="" an="" apparent="" susceptibility="" issue.="" however,="" epa="" determined="" that="" the="" evidence="" regarding="" susceptibility="" was="" not="" convincing="" due="" to="" the="" equivocal="" nature="" of="" the="" findings.="" of="" principal="" importance="" were="" the="" following="" conclusions:="" (1)="" the="" effects="" observed="" in="" the="" offspring="" at="" the="" loel="" of="" 0.9="" mg/kg/="" day,="" although="" statistically="" significant,="" were="" marginal="" and="" appeared="" to="" define="" a="" threshold="" response="" level="" for="" this="" study.="" (2)="" the="" body="" weight="" findings="" of="" this="" study="" are="" not="" supported="" by="" results="" of="" the="" two-generation="" reproduction="" study="" in="" rats="" at="" similar="" treatment="" levels.="" epa="" concluded="" that="" the="" apparent="" increased="" susceptibility="" in="" the="" developmental="" neurotoxicity="" study="" was="" not="" supported="" by="" the="" overall="" weight-of-the-evidence="" (including="" no="" evidence="" for="" increased="" susceptibility="" in="" the="" developmental="" and="" reproduction="" studies)="" from="" the="" fipronil="" data="" base.="" iii.="" determination="" of="" the="" fqpa="" safety="" factor.="" there="" is="" a="" complete="" toxicity="" data="" base="" for="" fipronil="" and="" exposure="" data="" is="" complete="" or="" is="" estimated="" based="" on="" data="" that="" reasonably="" accounts="" for="" potential="" exposures.="" further,="" as="" discussed="" in="" unit="" ii.f.1.f="" of="" this="" preamble,="" epa="" has="" concluded="" that="" the="" studies="" do="" not="" show="" that="" there="" is="" an="" increased="" susceptibility="" for="" developmental="" effects.="" accordingly,="" epa="" believes="" reliable="" data="" are="" available="" to="" remove="" the="" additional="" 10-fold="" safety="" factor="" for="" the="" protection="" of="" infants="" and="" children.="" 2.="" acute="" risk.="" the="" total="" dietary="" (food="" only)="" percents="" of="" the="" acute="" rfd="" for="" these="" population="" subgroups="" females="" 13+="" years,="" for="" the="" general="" u.s.="" population,="" infants="">< 1="" year),="" children="" (1-6="" years),="" and="" males="" 13+="" ranged="" from="" 6-12%.="" this="" calculation="" was="" based="" on="" an="" acute="" neurotoxicity="" study="" noel="" in="" rats="" of="" 2.5="" mg/kg/day="" for="" fipronil="" and="" 2.0="" mg/kg/day="" for="" mb46513.="" despite="" the="" potential="" for="" exposure="" to="" fipronil="" in="" drinking="" water,="" epa="" does="" not="" expect="" the="" acute="" aggregate="" exposure="" to="" exceed="" epa's="" level="" of="" concern.="" the="" small="" percent="" of="" the="" acute="" dietary="" rfd="" calculated="" for="" females="" 13+="" years="" old="" provides="" assurance="" that="" there="" is="" a="" reasonable="" certainty="" of="" no="" harm="" for="" both="" females="" 13+="" years="" and="" the="" pre-natal="" development="" of="" infants.="" 3.="" chronic="" risk.="" epa="" has="" concluded="" that="" the="" percentage="" of="" the="" rfd="" that="" will="" be="" utilized="" by="" chronic="" dietary="" (food="" only)="" exposure="" to="" residues="" of="" fipronil="" ranges="" from="" 5.1%="" for="" nursing="" infants="" less="" than="" 1="" year="" old,="" up="" to="" 16.7%="" for="" non-nursing="" infants="" less="" than="" 1="" year="" old.="" despite="" the="" potential="" for="" exposure="" to="" fipronil="" in="" drinking="" water,="" epa="" does="" not="" expect="" the="" chronic="" aggregate="" exposure="" to="" exceed="" 100%="" of="" the="" rfd.="" there="" are="" uses="" of="" fipronil="" that="" result="" in="" residential="" exposure,="" but="" is="" not="" expected="" to="" result="" in="" chronic="" exposure.="" epa="" concludes="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" to="" infants="" and="" children="" from="" acute,="" short-="" and="" intermediate-term,="" or="" chronic="" aggregate="" exposure="" to="" fipronil="" residues.="" that="" data="" call-in="" [will]="" require="" such="" data="" to="" be="" submitted="" every="" 5="" years="" as="" long="" as="" the="" tolerances="" remain="" in="" force.="" iii.="" other="" considerations="" a.="" metabolism="" in="" plants="" and="" animals="" 1.="" rhone="" poulenc="" ag,="" inc.="" has="" submitted="" data="" from="" a="" study="" investigating="" the="" metabolism="" of="" fipronil="" in="" rice.="" the="" qualitative="" nature="" of="" the="" residue="" in="" rice="" is="" adequately="" understood="" based="" on="" this="" metabolism="" study.="" fipronil="" was="" detected="" in="" all="" rice="" commodities.="" mb46513="" was="" also="" detected="" in="" all="" commodities.="" mb45950="" and="" mb46136,="" among="" other="" metabolites,="" were="" also="" identified.="" epa="" determined="" that="" the="" fipronil="" residues="" of="" concern="" for="" the="" tolerance="" expression="" and="" dietary="" risk="" assessment="" in="" plants="" animals="" are="" the="" parent="" and="" its="" metabolites="" mb46136="" and="" mb45950="" and="" photodegradate="" mb46513.="" the="" agency,="" therefore,="" has="" determined="" that="" the="" residues="" of="" concern="" for="" the="" proposed="" tolerances="" are="" fipronil,="" mb45950,="" mb46136,="" and="" mb46513.="" 2.="" residues="" in="" eggs,="" meat,="" milk,="" and="" poultry.="" rice="" bran,="" grain,="" hulls,="" and="" straws="" are="" animal="" feed="" items.="" i.="" fipronil.="" the="" maximum="" theoretical="" dietary="" burden="" of="" fipronil="" to="" beef="" and="" dairy="" cattle,="" based="" on="" the="" required="" tolerances="" of="" 0.04="" ppm="" for="" rice="" and="" 0.10="" ppm="" for="" rice="" straw,="" is="" 0.04="" ppm.="" the="" maximum="" theoretical="" dietary="" burden="" of="" fipronil="" to="" poultry,="" based="" on="" the="" proposed="" tolerances="" of="" 0.04="" ppm="" for="" rice="" and="" 0.10="" ppm="" for="" rice="" straw,="" is="" 0.04="" ppm.="" acceptable="" cow="" and="" poultry="" feeding="" studies="" were="" submitted="" and="" reviewed="" in="" conjunction="" with="" the="" pesticide="" petition="" for="" corn.="" based="" on="" these="" studies,="" the="" agency="" has="" already="" established="" appropriate="" tolerance="" levels="" for="" fipronil="" residues="" in/on="" animal="" commodities.="" ii.="" mb46513.="" based="" on="" low="" potential="" for="" residues="" in="" eggs,="" meat,="" and="" milk,="" epa="" will="" not="" require="" animal="" feeding="" studies="" to="" be="" conducted="" with="" mb46513.="" b.="" analytical="" enforcement="" methodology="" 1.="" plants.="" in="" conjunction="" with="" the="" cotton="" petition,="" gas="" chromatography/electron="" capture="" detector="" (gc/ecd)="" method="" ec-95-303="" has="" been="" proposed="" for="" enforcement="" of="" tolerances="" for="" residues="" of="" fipronil="" and="" its="" metabolites="" mb45950,="" mb46136,="" and="" photodegradate="" mb46513,="" and="" rpa200766="" in/on="" plant="" commodities.="" the="" gc="" methods="" used="" for="" the="" analyses="" of="" samples="" collected="" from="" the="" rice="" crop="" field="" trials="" and="" processing="" study="" analyze="" for="" each="" compound="" separately="" and="" are="" adequate="" for="" collection="" of="" residue="" data.="" adequate="" method="" validation="" and="" concurrent="" method="" recovery="" have="" been="" submitted="" for="" these="" methods.="" these="" methods="" are="" similar="" to="" the="" gc="" method="" proposed="" for="" cottonseed="" which="" has="" undergone="" a="" successful="" pesticide="" method="" validation="" (pmv).="" the="" registrant="" has="" been="" notified="" that="" all="" directions="" pertaining="" to="" rpa200766="" should="" also="" be="" removed="" as="" this="" metabolite="" has="" been="" determined="" to="" not="" be="" of="" regulatory="" concern.="" 2.="" animals.="" a="" method="" for="" the="" determination="" of="" residues="" of="" fipronil,="" mb45950,="" and="" mb46136="" in="" animal="" commodities="" was="" previously="" reviewed="" in="" conjunction="" with="" a="" petition="" for="" corn="" and="" animal="" raw="" agricultural="" commodities="" (racs),="" and="" has="" undergone="" a="" successful="" pmv.="" 3.="" multiresidue="" methods.="" a="" report="" on="" multiresidue="" testing="" of="" fipronil,="" mb45950,="" and="" mb46136="" has="" been="" received="" and="" forwarded="" to="" the="" food="" and="" drug="" administration="" (fda).="" acceptable="" recoveries="" of="" fipronil,="" mb45950,="" and="" mb46136="" were="" obtained="" in="" corn="" grain.="" a="" report="" on="" multiresidue="" testing="" of="" mb46513="" has="" been="" received="" and="" forwarded="" to="" fda.="" acceptable="" recoveries="" of="" mb46513="" were="" obtained="" in="" corn="" forage="" and="" cottonseed.="" c.="" magnitude="" of="" residues="" 1.="" plants.="" the="" submitted="" data="" indicate="" that="" the="" combined="" residues="" of="" fipronil,="" mb45950,="" mb46136,="" and="" mb46513="" will="" not="" exceed="" the="" proposed="" tolerance="" for="" rice="" straw="" (0.10="" ppm),="" or="" the="" proposed="" tolerance="" for="" rice="" grain="" (0.04="" ppm)="" in/on="" samples="" harvested="" at="" maturity="" following="" either="" a="" preplant="" incorporated="" (ppi)="" broadcast="" application="" of="" the="" 80%="" water="" dispersable="" granular="" (wdg)="" formulation="" or="" seed="" treatment="" with="" a="" 10%="" liquid="" formulation="" at="" about="" 0.05="" lb="" active="" ingredient="" (ai)/acre="" (a)="" (1="" x="" the="" proposed="" maximum="" rate).="" [[page="" 38494]]="" based="" on="" the="" highest="" residue="" value="" obtained="" from="" samples="" harvested="" following="" the="" proposed="" ppi="" or="" seed="" treatments="" at="" the="" proposed="" maximum="" use="" rate,="" the="" proposed="" tolerance="" level="" of="" 0.10="" ppm="" for="" rice="" straw="" is="" appropriate.="" no="" residues="" of="" fipronil="" or="" mb46136,="" mb45950,="" or="" mb46513="" were="" detected="" in="" rice="" grain,="" so="" the="" proposed="" tolerance="" level="" for="" rice="" grain="" at="" the="" combined="" limits="" of="" quantitation="" for="" fipronil,="" mb46136,="" mb45950,="" and="" mb46513="" (0.04="" ppm)="" is="" appropriate.="" 2.="" processed="" food/feed.="" rhone="" poulenc="" ag,="" inc.="" submitted="" data="" depicting="" the="" potential="" for="" concentration="" of="" fipronil="" residues="" in="" the="" processed="" commodities="" of="" rice.="" the="" submitted="" rice="" processing="" data="" are="" adequate.="" the="" data="" indicate="" that="" total="" residues="" of="" fipronil,="" mb45950,="" mb46136,="" and="" mb46513,="" and="" rpa200766="" are="" less="" than="" the="" limit="" of="" quantitation="" (loq)="" (0.01="" ppm)="" in/on="" rice="" grain="" harvested="" at="" maturity="" following="" ppi="" broadcast="" application="" of="" the="" 80%="" because="" treatment="" at="" 5-6="" x="" the="" label="" application="" rate="" did="" not="" result="" in="" quantifiable="" levels="" of="" fipronil="" residues="" of="" concern="" in="" rice="" grain,="" all="" further="" requirements="" for="" the="" processing="" study="" are="" waived,="" and="" no="" tolerances="" are="" required="" for="" the="" processed="" commodities="" of="" rice.="" as="" a="" result="" of="" this="" use,="" residues="" of="" fipronil="" are="" not="" expected="" to="" exceed="" the="" proposed="" or="" existing="" tolerances.="" d.="" international="" residue="" limits="" there="" are="" no="" codex,="" canadian,="" or="" mexican="" mrls="" established="" for="" fipronil="" in/on="" rice="" racs.="" therefore,="" no="" compatibility="" problems="" exist.="" e.="" rotational="" crop="" restrictions="" an="" acceptable="" confined="" rotational="" crop="" study="" with="" grain,="" grain="" sorghum,="" lettuce,="" radishes,="" and="" wheat="" was="" submitted="" and="" reviewed="" in="" conjunction="" with="" the="" corn="" petition.="" the="" rotational="" crop="" restrictions="" specified="" on="" the="" labels="" (1="" month="" for="" leafy="" vegetables,="" 5="" months="" for="" root="" crops,="" and="" 12="" months="" for="" small="" grains="" and="" all="" other="" crops)="" are="" supported="" by="" the="" results="" of="" the="" confined="" rotational="" crop="" study.="" iv.="" conclusion="" therefore,="" the="" tolerances="" established="" at="" 40="" cfr="" 180.517="" are="" amended="" to="" include="" combined="" residues="" of="" the="" insecticide="" fipronil,="" mb46136,="" mb45950,="" and="" mb46513="" in="" or="" on="" rice="" grain="" at="" 0.04="" ppm="" and="" rice="" straw="" at="" 0.10="" ppm.="" v.="" objections="" and="" hearing="" requests.="" the="" new="" ffdca="" section="" 408(g)="" provides="" essentially="" the="" same="" process="" for="" persons="" to="" ``object''="" to="" a="" tolerance="" regulation="" issued="" by="" epa="" under="" new="" section="" 408(e)="" and="" (l)(6)="" as="" was="" provided="" in="" the="" old="" section="" 408="" and="" in="" section="" 409.="" however,="" the="" period="" for="" filing="" objections="" is="" 60="" days,="" rather="" than="" 30="" days.="" epa="" currently="" has="" procedural="" regulations="" which="" govern="" the="" submission="" of="" objections="" and="" hearing="" requests.="" these="" regulations="" will="" require="" some="" modification="" to="" reflect="" the="" new="" law.="" however,="" until="" those="" modifications="" can="" be="" made,="" epa="" will="" continue="" to="" use="" those="" procedural="" regulations="" with="" appropriate="" adjustments="" to="" reflect="" the="" new="" law.="" any="" person="" may,="" by="" september="" 15,="" 1998,="" file="" written="" objections="" to="" any="" aspect="" of="" this="" regulation="" and="" may="" also="" request="" a="" hearing="" on="" those="" objections.="" objections="" and="" hearing="" requests="" must="" be="" filed="" with="" the="" hearing="" clerk,="" at="" the="" address="" given="" above="" (40="" cfr="" 178.20).="" a="" copy="" of="" the="" objections="" and/or="" hearing="" requests="" filed="" with="" the="" hearing="" clerk="" should="" be="" submitted="" to="" the="" opp="" docket="" for="" this="" rulemaking.="" the="" objections="" submitted="" must="" specify="" the="" provisions="" of="" the="" regulation="" deemed="" objectionable="" and="" the="" grounds="" for="" the="" objections="" (40="" cfr="" 178.25).="" each="" objection="" must="" be="" accompanied="" by="" the="" fee="" prescribed="" by="" 40="" cfr="" 180.33.="" if="" a="" hearing="" is="" requested,="" the="" objections="" must="" include="" a="" statement="" of="" the="" factual="" issues="" on="" which="" a="" hearing="" is="" requested,="" the="" requestor's="" contentions="" on="" such="" issues,="" and="" a="" summary="" of="" any="" evidence="" relied="" upon="" by="" the="" requestor="" (40="" cfr="" 178.27).="" a="" request="" for="" a="" hearing="" will="" be="" granted="" if="" the="" administrator="" determines="" that="" the="" material="" submitted="" shows="" the="" following:="" there="" is="" genuine="" and="" substantial="" issue="" of="" fact;="" there="" is="" a="" reasonable="" possibility="" that="" available="" evidence="" identified="" by="" the="" requestor="" would,="" if="" established,="" resolve="" one="" or="" more="" of="" such="" issues="" in="" favor="" of="" the="" requestor,="" taking="" into="" account="" uncontested="" claims="" or="" facts="" to="" the="" contrary;="" and="" resolution="" of="" the="" factual="" issues="" in="" the="" manner="" sought="" by="" the="" requestor="" would="" be="" adequate="" to="" justify="" the="" action="" requested="" (40="" cfr="" 178.32).="" information="" submitted="" in="" connection="" with="" an="" objection="" or="" hearing="" request="" may="" be="" claimed="" confidential="" by="" marking="" any="" part="" or="" all="" of="" that="" information="" as="" cbi.="" information="" so="" marked="" will="" not="" be="" disclosed="" except="" in="" accordance="" with="" procedures="" set="" forth="" in="" 40="" cfr="" part="" 2.="" a="" copy="" of="" the="" information="" that="" does="" not="" contain="" cbi="" must="" be="" submitted="" for="" inclusion="" in="" the="" public="" record.="" information="" not="" marked="" confidential="" may="" be="" disclosed="" publicly="" by="" epa="" without="" prior="" notice.="" vi.="" public="" record="" epa="" has="" established="" a="" record="" for="" this="" rulemaking="" under="" docket="" control="" number="" opp-300612="" (including="" any="" comments="" and="" data="" submitted="" electronically).="" a="" public="" version="" of="" this="" record,="" including="" printed,="" paper="" versions="" of="" electronic="" comments,="" which="" does="" not="" include="" any="" information="" claimed="" as="" cbi,="" is="" available="" for="" inspection="" from="" 8:30="" a.m.="" to="" 4="" p.m.,="" monday="" through="" friday,="" excluding="" legal="" holidays.="" the="" public="" record="" is="" located="" in="" room="" 119="" of="" the="" public="" information="" and="" records="" integrity="" branch,="" information="" resources="" and="" services="" division="" (7502c),="" office="" of="" pesticide="" programs,="" environmental="" protection="" agency,="" crystal="" mall="">2, 1921 Jefferson Davis Hwy., Arlington, VA.
Electronic comments may be sent directly to EPA at:
opp-docket@epamail.epa.gov.
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in ADDRESSES at the beginning of this document.
VII. Regulatory Assessment Requirements
This final rule establishes tolerances under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). This final rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does
it require any prior consultation as specified by Executive Order
12875, entitled Enhancing the Intergovernmental Partnership (58 FR
58093, October 28, 1993), or special considerations as required by
Executive Order 12898, entitled Federal Actions to Address
Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16,
[[Page 38495]]
1994), or require OMB review in accordance with Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
Safety Risks (62 FR 19885, April 23, 1997).
In addition, since these tolerances and exemptions that are
established on the basis of a petition under FFDCA section 408(d), such
as the tolerances in this final rule, do not require the issuance of a
proposed rule, the requirements of the Regulatory Flexibility Act (RFA)
(5 U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency has
previously assessed whether establishing tolerances, exemptions from
tolerances, raising tolerance levels or expanding exemptions might
adversely impact small entities and concluded, as a generic matter,
that there is no adverse economic impact. The factual basis for the
Agency's generic certification for tolerance actions published on May
4, 1981 (46 FR 24950) and was provided to the Chief Counsel for
Advocacy of the Small Business Administration.
VIII. Submission to Congress and the General Accounting Office
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. This rule is not a
``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: July 2, 1998.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
2. In Sec. 180.517 by revising the introductory text of paragraph
(a) and adding the following entries to the table in paragraph (a) to
read as follows:
Sec. 180.517 Fipronil; tolerances for residues.
(a) General. Therefore, tolerances are established for combined
residues of the insecticide fipronil (5-amino-1-[2,6-dichloro-4-
(trifluoromethyl)phenyl]-4-[(1R,S)-(trifluoromethyl)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)thio]-1H-pyrazole-3-carbonitrile and its
photodegradate 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl]-4-
[(1R,S)-(trifluoromethyl)]-1H-pyrazole-3-carbonitrile in or on the
following items at the levels specified:
------------------------------------------------------------------------
Commodity Parts per million (ppm)
------------------------------------------------------------------------
* * * * *
Rice grain................................ 0.04
Rice straw................................ 0.10
------------------------------------------------------------------------
* * * * *
[FR Doc. 98-18987 Filed 7-16-98; 8:45 am]
BILLING CODE 6560-50-F
