[Federal Register Volume 62, Number 228 (Wednesday, November 26, 1997)]
[Rules and Regulations]
[Pages 62970-62979]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-30949]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300587; FRL-5757-4]
RIN 2070-AB78
Fipronil; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for combined residues
of fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-
[(1R,S)-(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile) and its
metabolites MB 46136 (5-amino-1-[2,6-dichloro-4-
(trifluoromethyl)phenyl]4-[(trifloumethyl) sulfonyl]-1H-pyrazole-3-
carbonitrile) and MB 45950 (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)
phenyl]-4-[(trifluoromethyl)thio]-1H-pyrazole-3-carbonitrile) in or on
field corn grain, stover, and forage; milk fat, (reflecting residues in
whole milk); eggs; poultry fat, meat, and meat byproducts; hog fat,
meat, meat byproducts, and liver; and liver, fat, meat, and meat
byproducts of cattle, goat, horse, and sheep. In petition number 5F4426
Rhone Poulenc AG, Inc. requested this tolerance under the Federal Food,
Drug and Cosmetic Act (FFDCA), as amended by the Food Quality
Protection Act of 1966 (Pub. L. 104-170).
DATES: This regulation is effective November 26, 1997. Objections and
requests for hearings must be received by EPA on or before January 26,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300587], 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-300587], 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. 1132, CM #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@epamail.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-300587]. 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: Marion Johnson, 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:
johnson.marion@epamail.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 5F4426) by Rhone Poulenc AG Company, 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, the registrant. There were no comments received in response to
the notice of filing.
The petition requested that 40 CFR part 180 be amended by
establishing a tolerance 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 MB 46136 (5-amino-1-[2,6-dichloro-4-
(trifluoromethyl)phenyl]-4-[(trifluoromethyl) sulfonyl]-1H-pyrazole-3-
carbonitrile) and MB 45950 (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)
phenyl]-4-[(trifluoromethyl)thio]-1H-pyrazole-3-carbonitrile) in or on
the following items: corn, field, grain -- 0.02 ppm; corn, field,
stover -- 0.30 ppm; corn, field, forage -- 0.15 ppm; Milk, fat
(reflecting 0.05 ppm in whole milk) -- 1.50 ppm; Liver of cattle, goat,
horse and sheep -- 0.10 ppm; eggs -- 0.03 ppm; Fat of cattle, goat,
horse and sheep -- 0.40 ppm; poultry fat -- 0.05 ppm; meat of cattle,
goat, horse and sheep -- 0.04 ppm; poultry meat -- 0.02 ppm; meat
byproducts (except liver) of cattle, goat, horse and sheep -- 0.04 ppm;
poultry meat byproducts -- 0.02 ppm; hog fat -- 0.04 ppm; hog liver --
0.02 ppm; hog meat byproducts (except liver) -- 0.01 ppm; hog meat --
0.01 ppm.
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) 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 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
[[Page 62971]]
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 percent 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 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 hundredfold MOE is based on the same rationale as
the hundredfold 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, FFDCA section 408 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 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.
Percent of crop treated estimates are derived from Federal and
private market survey data. Typically, a range of estimates are
supplied and the upper end of this range is assumed for the exposure
assessment. By using this upper end estimate of percent of crop
[[Page 62972]]
treated, the Agency is reasonably certain that exposure is not
understated for any significant subpopulation group. 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, to pesticide residues. For this
pesticide, the most highly exposed population subgroup (non-nursing
infants <1 year="" old)="" was="" not="" regionally="" based.="" ii.="" aggregate="" risk="" assessment="" and="" determination="" of="" safety="" consistent="" with="" section="" 408(b)(2)(d),="" 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),="" for="" a="" tolerance="" for="" combined="" residues="" of="" fipronil="" (5-amino-1-[2,6-="" dichloro-4-(trifluoromethyl)phenyl]-4-[(1r,s)-="" (trifluoromethyl)sulfinyl]-1h-pyrazole-3-carbonitrile)="" and="" its="" metabolites="" mb="" 46136="" (5-amino-1-[2,6-dichloro-4-="" (trifluoromethyl)phenyl]-4-[(trifluoromethyl)="" sulfonyl]-1h-pyrazole-3-="" carbonitrile)="" and="" mb="" 45950="" (5-amino-1-[2,6-dichloro-4-(trifluoromethyl)="" phenyl]-4-[(trifluoromethyl)thio]-1h-pyrazole-3-carbonitrile)="" in="" or="" on="" the="" following="" items="" at="" the="" following="" levels:="" ------------------------------------------------------------------------="" tolerance="" (in="" parts="" per="" commodity="" million)="" ------------------------------------------------------------------------="" corn,="" field,="" grain........................="" 0.02="" corn,="" field,="" stover.......................="" 0.30="" corn,="" field,="" forage.......................="" 0.15="" eggs......................................="" 0.03="" fat="" of="" cattle,="" goat,="" horse="" and="" sheep......="" 0.40="" hog="" fat...................................="" 0.04="" hog="" liver.................................="" 0.02="" hog="" meat="" byproducts="" (except="" liver)........="" 0.01="" hog="" meat..................................="" 0.01="" liver="" of="" cattle,="" goat,="" horse="" and="" sheep....="" 0.10="" milk,="" fat="" (reflecting="" 0.05="" ppm="" in="" whole="" 1.50="" milk).="" meat="" of="" cattle,="" goat,="" horse="" and="" sheep.....="" 0.04="" meat="" byproducts="" (except="" liver)="" of="" cattle,="" 0.04="" goat,="" horse="" and="" sheep.="" poultry="" fat...............................="" 0.05="" poultry="" meat..............................="" 0.02="" poultry="" meat="" byproducts...................="" 0.02="" ------------------------------------------------------------------------="" epa's="" assessment="" of="" the="" dietary="" exposures="" and="" risks="" associated="" with="" establishing="" the="" tolerance="" follows.="" 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="" are="" discussed="" below.="" 1.="" acute="" studies.="" i.="" a="" battery="" of="" acceptable="" acute="" toxicity="" studies="" place="" technical="" fipronil="" in="" toxicity="" categories="" ii="" and="" iii.="" it="" is="" classified="" as="" a="" non-sensitizer.="" ii.="" an="" acceptable="" acute="" neurotoxicity="" study="" in="" the="" rat="" using="" technical="" fipronil="" concluded="" the="" following:="" the="" no="" observed="" effect="" level="" (noel)="" was="" 0.5="" mg/kg="" for="" males="" and="" females.="" the="" low="" observed="" effect="" level="" (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.="" 2.="" subchronic="" toxicity="" testing.="" i.="" an="" acceptable="" subchronic="" toxicity="" study="" in="" the="" dog="" using="" technical="" fipronil="" concluded="" the="" following:="" the="" loel="" was="" 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="" was="" 2.0="" mg/="" kg/day="" for="" males="" and="" 0.5="" mg/kg/day="" for="" females.="" ii.="" a="" supplemental="" subchronic="" toxicity="" study="" in="" the="" rat="" using="" technical="" fipronil="" concluded="" the="" following:="" the="" loel="" was="" 30="" ppm="" for="" males="" (1.93="" mg/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).="" iii.="" an="" acceptable="" 21-day="" dermal="" toxicity="" study="" in="" the="" rabbit="" using="" technical="" grade="" fipronil="" concluded="" the="" following:="" the="" systemic="" loel="" was="" 10="" mg/kg/day="" based="" on="" decreased="" body="" weight="" gain="" and="" food="" consumption;="" dermal="" irritation="" loel=""> 10.0 mg/kg/day. The systemic NOEL was 5.0 mg/
kg/day; Dermal irritation NOEL was greater than or equal to 10.0 mg/kg/
day.
3. Chronic toxicity studies. i. An acceptable chronic toxicity
study in the dog using technical fipronil concluded the following: The
LOEL was 2.0 mg/kg/day based on clinical signs of neurotoxicity and
abnormal neurological examinations. The NOEL was 0.2 mg/kg/day.
ii. An acceptable carcinogenicity study in the mouse using
technical fipronil concluded the following: The LOEL was 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 was 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.
iii. An acceptable combined chronic toxicity/carcinogenicity study
in the rat using technical fipronil concluded the following: The LOEL
was 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 was 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).
4. Developmental and reproduction toxicity studies. i. An
acceptable developmental toxicity study in the rat using technical
fipronil concluded the following: 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/kg/day. The developmental toxicity NOEL was 20 mg/
kg/day or higher.
ii. An acceptable developmental toxicity study in the rabbit using
technical fipronil concluded the following: The maternal toxicity LOEL
was less than or equal to 0.1 mg/kg/day based on reduced body weight
gain, reduced food consumption and efficiency. The 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 greater
than or equal to 1.0 mg/kg/day.
iii. An acceptable multigeneration reproduction study in the rat
using technical fipronil concluded the following: 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
[[Page 62973]]
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).
iv. An acceptable developmental neurotoxicity study using technical
fipronil concluded as follows: 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 LOEL was 10 ppm (0.9 mg/kg/day), based on statistically
significant decrease in group mean pup weights during lactation and
significant increase in time of preputial separation in males. The
developmental neurotoxicity LOEL was 10 ppm (0.9 mg/kg/day) based on a
significant increase in mean motor activity counts in females on
Postnatal Day 17. The NOEL for developmental and developmental
neurotoxicity is 0.5 ppm (0.05 mg/kg/day). It is noted that
developmental neurotoxicity occurred in the absence of maternal
toxicity in this study.
5. Mutagenicity studies-- i. Studies conducted with fipronil. a. An
acceptable Salmonella/mammalian activation gene mutation assaying
technical fipronil concluded as follows: fipronil was not mutagenic in
4 strains of S. typhimurium at concentrations up to 500 g/
plate in the presence or absence of S9 activation.
b. An acceptable in vitro gene mutation assay in mammalian cells/
Chinese hamster V79 cells using technical fipronil concluded as
follows: Fipronil was negative for inducing forward gene mutations at
the HGPRT locus in cultured Chinese hamster V79 cells at concentrations
up to 385.65 g/ml both with and without S9 activation.
c. An acceptable in vitro micronucleus assay in the mouse using
technical fipronil concluded as follows: fipronil was not cytotoxic to
the target cell. There was, however, no evidence of a clastogenic or
aneugenic effect at any dose or at any harvest time.
d. An acceptable cytogenic assay in human lymphocytes using
technical fipronil concluded as follows: there was no evidence of a
clastogenic effect when human lymphocytes were exposed in vitro to
fipronil at doses of 75, 150 or 300 g/ml with and without S9
activation.
ii. Studies conducted with fipronil metabolite MB 46136. a. An
acceptable Salmonella/mammalian activation gene mutation assay using
98.7% pure metabolite showed that the fipronil metabolite was not
mutagenic in 4 strains of S. typhimurium at concentrations of up to 200
g/plate without S9 activation and up to 500 g/plate
in the presence of S9 activation.
b. An acceptable cytogenic assay with human lymphocytes using 98.7%
pure metabolite showed that there was no evidence of a clastogenic
effect when human lymphocytes were exposed in vitro to MB 46136 at
doses of 75, 150 or 300 g/ml with and without S9 activation.
6. Metabolism study. An acceptable metabolism study in the rat
using 14-C 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. Distribution data
showed significant amounts of residual radioactivity in carcass, G.I.
tract, liver, adrenals, and abdominal fat at 168 hours post-dose for
all rats in all dose groups. Repeated low oral dosing or a single high
oral dose resulted in an overall decrease in the amount of residual
radioactivity found, but an increase in the amount in abdominal fat,
carcass, and adrenals. 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%.
Increases in the percentages excreted in urine and feces were observed
with repeated low oral dosing or a single high dose, while the
percentage found in all tissues combined decreased. There were no
significant sex-related differences in excretion. Major metabolites in
urine included two ring-opened products of the metabolite MB 45897, two
oxidation products (MB 46136 and RPA 200766), and parent chemical (MB
46030). In feces, parent MB 46030 was detected as a significant
fraction of the sample radioactivity as well as the oxidation products
MB 46136 and MB 45950.
7. Special studies. i. A supplemental thyroid function study in the
rat using technical fipronil showed the following: Four groups of 27
male rats per group were administered either methylcellulose (vehicle
control), 10 mg/kg/day fipronil, 200 mg/kg/day propylthiouracil (PTU)
or 50 mg/kg/day Noxyflex for 14 days. On Day 15, each animal received
Na125I at a dose level of 1 Ci 125I. Six
hours later, 9 males per group received either 10 or 25 mg/kg potassium
perchlorate or 0.9% saline solution. 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 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.
ii. A supplemental thyroxine clearance study in the rat using
technical fipronil showed the following: Six groups of six male rats
per group were administered either fipronil (10 mg/kg/day by gavage),
phenobarbital (80 mg/kg/day intraperitoneally) or 0.5% methylcellulose
(vehicle control at 5 ml/kg by gavage) for a duration of either 1 day
or 14 days. Four hours after the final dose of either test substance,
each rat received [125I] thyroxine at a dosage of 10
Ci/kg. 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 1 of treatment.
iii. An acceptable 28-day study in the rat by dietary
administration using 96.2% pure fipronil metabolite RPA 200766 showed
the following: The NOEL was 50 ppm (3.80 mg/kg/day for males and 4.44
mg/kg/day for females). The LOEL was 500 ppm (38.16 mg/kg/day for males
and 43.97 mg/kg/day for females) based on decreased
[[Page 62974]]
hemoglobin values, increased cholesterol values and increased liver
weights in both sexes.
iv. An acceptable 28-Day Study in the rat using technical fipronil
showed that: the LOEL is 25 ppm (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 < 25="" ppm.="" b.="" toxicology="" profile="" the="" toxicology="" endpoints="" and="" dose="" levels="" of="" concern="" have="" been="" identified="" for="" use="" in="" this="" fipronil="" exposure="" and="" risk="" assessment="" as="" set="" forth="" below:="" 1.="" residential="" exposure--i.="" short="" -="" and="" intermediate="" -="" term="" exposure="" (1="" to="" 7="" days).="" a.="" a="" dermal="" absorption="" factor="" is="" set="" at="" less="" than="" 1%="" at="" 24="" hours="" based="" on="" a="" dermal="" absorption="" study.="" b.="" for="" short-="" and="" intermediate-term="" residential="" exposure="" for="" females="" age="" 13+="" years,="" the="" noel="" is="" 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="" in="" the="" 21-day="" dermal="" study.="" in="" the="" supporting="" study="" of="" developmental="" toxicity="" and="" developmental="" neurotoxicity,="" the="" developmental="" noel="" was="" 0.5="" ppm="" (0.05="" mg/kg/day)="" based="" on="" decreased="" mean="" pup="" weights="" during="" lactation="" and="" a="" significant="" increase="" in="" time="" to="" preputial="" separation="" in="" male="" rats="" observed="" at="" the="" developmental="" loel="" of="" 10="" ppm="" (0.9="" mg/kg/day).="" the="" developmental="" neurotoxicity="" loel="" was="" 10="" ppm="" (0.9="" mg/kg/day)="" based="" on="" an="" increase="" in="" mean="" motor="" activity="" counts="" for="" females="" on="" postnatal="" day="" 17.="" it="" should="" be="" noted="" that="" the="" noel="" established="" after="" dermal="" administration="" in="" the="" 21-day="" dermal="" toxicity="" study="" is="" 5="" mg/kg/day.="" when="" the="" co-critical="" study="" noel="" based="" on="" oral="" administration="" in="" the="" developmental="" neurotoxicity="" study,="" 0.05="" mg/kg/day="" is="" corrected="" for="" the="" less="" than="" 1%="" dermal="" absorption,="" exposure="" is="" essentially="" the="" same="" as="" the="" critical="" study="" (5="" mg/kg/day).="" c.="" for="" short-="" and="" intermediate-term="" residential="" exposure="" for="" the="" general="" population,="" including="" infants="" and="" kids,="" the="" noel="" is="" 5.0="" 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="" in="" the="" 21-day="" dermal="" toxicity="" study.="" ii.="" chronic="" or="" residential="" exposure="" (several="" months="" to="" lifetime).="" the="" noel="" is="" 0.5="" ppm,="" 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="" the="" loel="" of="" 1.5="" ppm="" in="" a="" combined="" chronic="" toxicity/carcinogenicity="" study="" in="" the="" rat.="" since="" the="" noel="" identified="" is="" from="" an="" oral="" study,="" a="" dermal="" absorption="" factor="" of="">< 1%="" should="" be="" used="" in="" risk="" calculations.="" 2.="" dietary="" exposure--i.="" acute="" risk="" .="" the="" noel="" is="" 0.5="" mg/kg,="" based="" on="" decreased="" hind="" leg="" splay="" in="" male="" and="" female="" rats="" observed="" at="" loel="5" mg/kg="" in="" the="" acute="" neurotoxicity="" study="" in="" rats.="" ii.="" chronic="" risk.="" the="" rfd="" (reference="" dose)="" for="" fipronil="" is="" 0.0002="" mg/kg/day.="" this="" rfd="" is="" based="" on="" a="" noel="" of="" 0.019="" mg/kg/day="" and="" an="" uncertainty="" factor="" of="" 100;="" the="" noel="" was="" established="" from="" the="" combined="" chronic="" toxicity/carcinogenicity="" study="" in="" rats="" where="" the="" loel="" was="" 1.5="" ppm,="" based="" on="" an="" increased="" incidence="" of="" clinical="" signs="" (seizures="" and="" death)="" and="" alterations="" in="" clinical="" chemistry="" (protein)="" and="" thyroid="" parameters="" (increased="" tsh,="" decreased="" t4).="" iii.="" cancer="" risk.="" fipronil="" has="" been="" classified="" 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.="" the="" rfd="" methodology="" should="" be="" used="" to="" estimate="" human="" risk="" because="" the="" thyroid="" tumors="" appear="" to="" be="" related="" to="" a="" disruption="" in="" the="" thyroid-pituitary="" status.="" there="" was="" no="" apparent="" concern="" for="" mutagenicity="" (no="" mutagenic="" activity).="" b.="" exposures="" and="" risks="" 1.="" from="" food="" and="" feed="" uses.="" in="" today's="" action,="" tolerances="" will="" be="" established="" (40="" cfr="" 180.517)="" in="" or="" on="" a="" variety="" of="" raw="" agricultural="" commodities="" as="" follows:="" ------------------------------------------------------------------------="" tolerance="" (in="" parts="" per="" commodity="" million)="" ------------------------------------------------------------------------="" corn,="" field,="" grain........................="" 0.02="" corn,="" field,="" stover.......................="" 0.30="" corn,="" field,="" forage.......................="" 0.15="" eggs......................................="" 0.03="" fat="" of="" cattle,="" goat,="" horse="" and="" sheep......="" 0.40="" hog="" fat...................................="" 0.04="" hog="" liver.................................="" 0.02="" hog="" meat="" byproducts="" (except="" liver)........="" 0.01="" hog="" meat..................................="" 0.01="" liver="" of="" cattle,="" goat,="" horse="" and="" sheep....="" 0.10="" milk,="" fat="" (reflecting="" 0.05="" ppm="" in="" whole="" 1.50="" milk).="" meat="" of="" cattle,="" goat,="" horse="" and="" sheep.....="" 0.04="" poultry="" fat...............................="" 0.05="" poultry="" meat..............................="" 0.02="" meat="" byproducts="" (except="" liver)="" of="" cattle,="" 0.04="" goat,="" horse="" and="" sheep.="" poultry="" meat="" byproducts...................="" 0.02="" ------------------------------------------------------------------------="" risk="" assessments="" were="" conducted="" by="" epa="" to="" assess="" dietary="" exposures="" and="" risks="" from="" fipronil="" as="" follows:="" i.="" acute="" exposure="" and="" risk.="" acute="" dietary="" risk="" assessments="" are="" performed="" for="" a="" food-use="" pesticide="" if="" a="" toxicological="" study="" has="" indicated="" the="" possibility="" of="" an="" effect="" of="" concern="" occurring="" as="" a="" result="" of="" a="" 1="" day="" or="" single="" exposure.="" the="" acute="" dietary="" exposure="" endpoint="" of="" concern="" for="" fipronil="" is="" neurotoxicological.="" as="" this="" endpoint="" is="" not="" developmental,="" all="" population="" subgroups="" are="" of="" potential="" concern.="" epa="" calculated="" moe="" values="" of="" 277="" for="" the="" u.s.="" population,="" 167="" for="" non-="" nursing="" infants="">< 1="" year="" old)="" and="" 167="" for="" children="" (1-6="" years="" years="" old).="" anticipated="" residues="" were="" used="" for="" milk="" and="" corn="" commodities="" in="" this="" assessment.="" ii.="" chronic="" exposure="" and="" risk.="" chronic="" dietary="" residues="" exposure="" estimates="" (dres)="" for="" fipronil="" were="" calculated="" using="" anticipated="" residues="" derived="" from="" field-trial="" data="" for="" all="" commodities.="" in="" addition,="" an="" anticipated="" market="" share="" of="" 7%="" was="" used="" for="" corn="" grain,="" forage,="" and="" stover.="" the="" proposed="" fipronil="" tolerances="" result="" in="" an="" anticipated="" residue="" contribution="" (arc)="" that="" is="" equivalent="" to="" the="" following="" percents="" of="" the="" rfd:="" u.s.="" population="" (48="" states)...............="" 4.6%="" hispanics.................................="" 5.9%="" non-hispanic="" others.......................="" 5.2%="" non-nursing="" infants="">< 1="" year="" old)........="" 10.1%="" females="" (13+="" years,="" pregnant).............="" 3.2%="" females="" (20+="" years,="" not="" pregnant,="" not="" 3.0%="" nursing).="" females="" (13+="" years,="" nursing)..............="" 4.1%="" children="" (1-6="" years="" old)..................="" 11.1%="" children="" (7-12="" years="" old).................="" 7.4%="" the="" subgroups="" listed="" above="" are:="" (1)="" the="" u.s.="" population="" (48="" states);="" (2)="" infants="" and="" children;="" and,="" (3)="" the="" other="" subgroups="" for="" which="" the="" percentage="" of="" the="" rfd="" occupied="" is="" equal="" to,="" or="" greater="" than,="" that="" occupied="" by="" the="" subgroup="" u.s.="" population="" (48="" states).="" iii.="" percent="" crop="" treated="" and="" anticipated="" residues.="" section="" 408(b)(2)(e)="" 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="" timeframe="" it="" deems="" appropriate.="" section="" 408(b)(2)(f)="" allows="" the="" agency="" to="" use="" data="" on="" the="" actual="" [[page="" 62975]]="" percent="" of="" crop="" treated="" when="" establishing="" a="" tolerance="" only="" where="" the="" agency="" can="" make="" the="" following="" findings:="" a.="" that="" the="" data="" used="" are="" reliable="" and="" provide="" a="" valid="" a="" basis="" for="" showing="" the="" percentage="" of="" food="" derived="" from="" a="" crop="" that="" is="" likely="" to="" contain="" residues.="" b.="" that="" the="" exposure="" estimate="" does="" not="" underestimate="" the="" exposure="" for="" any="" significant="" subpopulation.="" c.="" where="" data="" on="" regional="" pesticide="" use="" and="" food="" consumption="" are="" available,="" that="" the="" exposure="" estimate="" does="" not="" understate="" exposure="" for="" any="" regional="" population.="" in="" addition="" the="" agency="" must="" provide="" for="" periodic="" evaluation="" of="" any="" estimates="" used.="" the="" percent="" of="" crop="" treated="" estimates="" for="" fipronil="" were="" derived="" from="" federal="" and="" market="" survey="" data.="" 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="" 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.="" such="" evaluation="" will="" likely="" be="" conducted="" no="" sooner="" than="" 5="" years="" after="" date="" of="" issuance="" of="" this="" tolerance.="" further,="" as="" required="" by="" the="" fqpa,="" epa="" will="" issue="" a="" data="" call-in="" under="" section="" 408(f)="" to="" all="" fipronil="" registrants="" for="" data="" on="" anticipated="" residues,="" to="" be="" submitted="" no="" later="" than="" 5="" years="" from="" the="" date="" of="" issuance="" of="" this="" tolerance.="" 2.="" from="" drinking="" water.="" epa="" does="" not="" have="" monitoring="" data="" available="" to="" perform="" a="" quantitative="" drinking="" water="" risk="" assessment="" for="" fipronil="" at="" this="" time.="" epa="" estimated="" ground="" and="" surface="" water="" exposure="" using="" the="" generic="" expected="" environmental="" concentration="" (geneec)="" model,="" a="" screening="" level="" model="" for="" determining="" concentrations="" of="" pesticides="" in="" surface="" water.="" geneec="" uses="" the="" soil/water="" partition="" coefficient,="" hydrolysis="" half="" life,="" and="" maximum="" label="" rate="" to="" estimate="" surface="" water="" concentration.="" in="" addition,="" the="" model="" contains="" a="" number="" of="" conservative="" underlying="" assumptions.="" therefore,="" the="" drinking="" water="" concentrations="" derived="" from="" geneec="" for="" surface="" water="" are="" likely="" to="" be="" overestimated.="" as="" fipronil="" is="" relatively="" immobile="" in="" soil,="" residues="" in="" groundwater="" are="" expected="" to="" be="" less="" than="" those="" in="" surface="" water.="" i.="" acute="" exposure="" and="" risk.="" the="" exposure="" estimate="" for="" surface="" water="" is="" 247="" ppt="" (peak="" concentration).="" based="" on="" an="" acute="" noel="" of="" 0.5="" mg/kg/="" day="" and="" water="" consumption="" of="" 1="" l/d="" for="" a="" 10="" kg="" child,="" the="" worst-case="" estimates="" of="" residues="" in="" drinking="" water="" (247="" ppt)="" result="" in="" a="" child="" exposure="" of="" 2.5="" x="">-5 mg/kg/day. This exposure value
corresponds to a MOE of 20,000 for the most highly exposed subgroup for
acute exposure (children 1-6 years old). As this value exceeds 100,
fipronil residues in surface drinking water do not pose an acute risk.
ii. Chronic exposure and risk. The exposure estimate for surface
water is 48.8 ppt (54-day average). Based on a RfD of 0.0002 (mg/kg/
day)-1 and water consumption of 2 L/d for a 70 kg adult
(male) and of 1 L/d for a 10 kg child (1-6 years old), the worst-case
estimates of residues in drinking water (48.8 parts per trillion (ppt))
result in the following exposures: Adult exposure is 1.4 x
10-6 mg/kg/day and exposure for children is 4.9 x
10-6 mg/kg/day. These exposure values correspond to 0.7% of
the RfD for adult males and 2.4% of the RfD for children (1-6 years
old).
3. From non-dietary exposure. Fipronil is currently registered for
use on the following residential non-food sites: ant and cockroach bait
traps ranging from 0.01 to 0.05% active ingredient; and flea and tick
control products for dogs and cats, including a pump spray (0.29% RTU
(ready to use) and a 9.7% RTU spot treatment in which a premeasured
small amount is applied between the pet's shoulder blades. The flea and
tick spray use is expected to result in the highest exposure of
fipronil products. Based on the high MOE's resulting from these uses
(see below), the application of small amounts between the pet's
shoulder blades was not addressed. This use is expected to result in
much lower exposure based on lower duration and a considerably smaller
area being treated. Exposure from the use of fipronil in self contained
bait stations is also expected to result in lower exposures since there
is no contact with the pesticide.
i. Acute exposure and risk. For incidental non-dietary (acute)
exposures, the endpoint selected for acute dietary (oral) assessments
is used. The NOEL is 0.5 mg/kg/day. The MOE for a child/hand-to-mouth
exposure after petting a wet or recently treated pet is 5,000 to 8,000.
ii. Chronic exposure and risk. Fipronil is reportedly strongly
bound to the skin and does not come off the dog once dry. Therefore,
the use of fipronil products in residential situations is not expected
to result in chronic exposures. It should be noted that an exposure
study assessing exposures resulting from the pet uses will be submitted
in the fall of 1997. The risk assessment may be refined at that time.
iii. Short- and intermediate-term exposure and risk. Label
directions on pet care products state that applications of fipronil are
expected to occur several times per year in residential settings,
resulting in acute and short- and intermediate-term exposures. The
endpoint selected for short and intermediate-term non-occupational
exposure assessments is based on the results of a 21-day dermal
toxicity study. The systemic toxicity NOEL is 5.0 mg/kg/day. The MOE
for applicators of the 0.29% ready-to-use formulation on dogs and cats
is 50,000. The MOE for a child/dermal contact with a wet or recently
treated pet is 1,000 to 2,000.
iv. 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) 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
[[Page 62976]]
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 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.
D. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. For the most highly exposed subgroup (children 1-6
years old), the calculated MOE value is 160 (the reciprocal of the sum
of the reciprocal food, residential and water MOEs). (The MOE is 167
for food, 5,000 for residential (oral) and 20,000 for water). This
aggregate MOE does not exceed the HED's level of concern for acute
dietary exposure.
2. Chronic risk. Based on the available data and assumptions for
dietary/water/residential exposure and risk estimates, the population
group estimated to be most highly exposed is children (1-6 years old)
with a risk estimate from combined sources equaling 13.5% of the RfD
(11.1% dietary + 2.4% water). As previously noted, no chronic
residential exposure is anticipated. EPA generally has no concern for
exposures below 100% of the RfD because the RfD represents the level at
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health. EPA concludes that there is
a reasonable certainty that no harm will result from aggregate exposure
to fipronil residues.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure should take into account chronic dietary food and
water (considered to be a background exposure level) plus indoor and
outdoor residential exposure. However, the short and intermediate term
end points for fipronil are based on dermal exposure, and chronic
endpoints are based on dietary exposure. The two exposure scenarios use
different toxicological end points, and thus are not comparable in
toxicological terms. At the present time, EPA does not know how to
aggregate dermal and oral exposures for this chemical. For this reason,
EPA has not developed a short and intermediate term risk assessment for
fipronil. Further, as indicated above, when viewed independently,
neither oral nor dermal exposure posed a risk of concern.
E. Aggregate Cancer Risk for U.S. Population
Based on the Cancer Peer Review Committee recommendation that the
RfD approach be used to quantify carcinogenicity, a quantitative
dietary cancer risk assessment was not performed. Dietary risk concerns
due to long-term consumption of fipronil residues are adequately
addressed by the chronic exposure analysis using the RfD.
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.
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. The developmental neurotoxicity study provided
further information about the acute and chronic neurotoxic effects
during prenatal and postnatal development.
FFDCA section 408 provides that EPA shall apply an additional
tenfold 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.
2. FQPA considerations. EPA has evaluated the chemical fipronil for
FQPA considerations. The following discussion represents the
information EPA considered.
i. Developmental toxicity studies. 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 by 40 CFR part 158.
ii. Reproductive toxicity study. An acceptable two-generation
reproduction study in rats has been submitted to the Agency, meeting
basic data requirements, as defined for a food-use chemical by 40 CFR
part 158.
iii. Developmental neurotoxicity study. An acceptable developmental
neurotoxicity study was conducted with fipronil and reviewed by the
Agency.
iv. Pre- and post-natal sensitivity. There are no data gaps for the
assessment of the effects of fipronil on developing animals following
in utero and/or early postnatal exposure.
v. Conclusion. The available data contained evidence of increased
sensitivity of rats to alterations in functional development following
pre- and/or postnatal exposure with fipronil. Specifically, in a
developmental neurotoxicity study in rats, the developmental and
developmental-neurotoxicity NOEL of 0.5 ppm (0.05 mg/kg/day) was lower
than the maternal toxicity NOEL of 10 ppm (0.9 mg/kg/day). In the
offspring, decreased pup weights, increased time of preputial
separation in males, and increased
[[Page 62977]]
motor activity counts in female pups were observed at the developmental
LOEL of 10 ppm (0.9 mg/kg/day), while maternal toxicity (decreased body
weight, body weight gain, and food consumption) was observed at the
maternal LOEL of 200 ppm (15 mg/kg/day).
Previously conducted studies with fipronil did not identify any
issues of increased sensitivity in the fetuses or pups following pre-
and/or postnatal exposure. In the prenatal developmental toxicity study
in rats, there was no evidence of developmental toxicity at the highest
doses tested (20 mg/kg/day). Maternal toxicity (decreased body weight
gain, food consumption and/or water consumption) was observed at this
dose (20 mg/kg/day) with the maternal NOEL established at 4 mg/kg/day.
In the prenatal developmental toxicity study in rabbits, there was also
no evidence of developmental toxicity at the highest doses tested (1.0
mg/kg/day). Maternal toxicity (decreased body weight gain, food
consumption and/or water consumption) was observed at this same dose
(1.0 mg/kg/day) and lower, with the maternal NOEL established at < 0.1="" mg/kg/day.="" additionally,="" in="" the="" two-generation="" reproduction="" study="" in="" rats,="" offspring="" toxicity="" was="" observed="" only="" in="" the="" presence="" of="" parental="" toxicity.="" the="" offspring="" noel="" was="" 30="" ppm="" (2.54-2.74="" mg/kg/day),="" based="" upon="" clinical="" signs="" of="" toxicity,="" decreased="" litter="" size,="" decreased="" body="" weights,="" decreased="" pre-="" and="" postnatal="" survival,="" and="" delays="" in="" physical="" development="" at="" the="" loel="" of="" 300="" ppm="" (26.0-28.4="" mg/kg/day).="" in="" the="" parental="" animals,="" reproductive="" toxicity="" (reductions="" in="" mating="" and="" fertility)="" was="" also="" observed="" at="" the="" 30="" ppm="" dietary="" level.="" the="" systemic="" noel="" for="" the="" parental="" animals="" was="" 3="" ppm="" (0.25-0.27="" mg/kg/day),="" based="" upon="" increased="" weight="" of="" the="" thyroid="" gland="" and="" liver="" in="" both="" sexes,="" decreased="" weight="" of="" the="" pituitary="" gland="" in="" the="" females,="" and="" increased="" incidence="" of="" thyroid="" follicular="" epithelial="" hypertrophy="" in="" the="" females="" at="" the="" loel="" of="" 30="" ppm.="" in="" considering="" whether="" additional="" uncertainty="" factors="" were="" needed="" to="" protect="" children,="" epa="" noted="" that="" the="" developmental="" neurotoxicity="" noel="" of="" 0.05="" mg/kg/day,="" when="" adjusted="" for="" 1%="" dermal="" absorption,="" yields="" an="" equivalent="" noel="" of="" 5="" mg/kg/day,="" the="" value="" established="" as="" the="" systemic="" noel="" in="" the="" 21-day="" dermal="" study="" in="" rabbits.="" this="" value="" was="" selected="" for="" use="" in="" the="" short="" term="" and="" intermediate="" risk="" assessment="" calculations="" for="" fipronil.="" the="" noel="" used="" for="" the="" rfd="" calculation="" was="" 0.019="" mg/kg/day="" from="" the="" combined="" chronic="" toxicity-carcinogenicity="" study="" in="" the="" rat,="" a="" value="" that="" is="" even="" lower="" than="" the="" noel="" used="" for="" short-="" and="" intermediate-term="" exposure.="" therefore,="" it="" was="" concluded="" that="" the="" risk="" assessment="" calculations="" as="" defined,="" will="" provide="" adequate="" protection="" for="" sensitive="" subpopulations,="" including="" infants="" and="" children.="" the="" committee="" determined="" that="" the="" third="" uncertainty="" factor="" in="" the="" risk="" assessment="" of="" fipronil,="" under="" the="" provisions="" of="" the="" fqpa="" mandate="" to="" ensure="" the="" protection="" of="" infants="" and="" children,="" was="" not="" warranted="" for="" chronic="" or="" less="" than="" life="" time="" exposure="" and="" could="" be="" removed.="" epa="" believes="" that="" reliable="" data="" support="" using="" the="" hundredfold="" margin/factor,="" rather="" than="" the="" thousandfold="" margin/factor,="" when="" epa="" has="" a="" complete="" data="" base="" under="" existing="" guidelines,="" and="" when="" the="" severity="" of="" the="" effect="" in="" infants="" or="" children,="" the="" potency="" or="" unusual="" toxic="" properties="" of="" a="" compound,="" or="" the="" quality="" of="" the="" exposure="" data="" do="" not="" raise="" concerns="" regarding="" the="" adequacy="" of="" the="" tenfold="" margin/factor.="" for="" the="" reasons="" outlined="" above,="" epa="" has="" determined="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" to="" infants="" and="" children="" from="" aggregate="" exposure="" to="" residues="" of="" fipronil="" following="" its="" use="" on="" field="" corn="" and="" other="" uses="" registered="" to="" date.="" iii.="" other="" considerations="" a.="" endocrine="" disrupter="" effects="" epa="" is="" required="" to="" develop="" a="" screening="" program="" to="" determine="" whether="" certain="" substances="" (including="" all="" pesticides="" and="" inert="" ingredients)="" ``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="" ingredient="" and="" end="" use="" products="" for="" endocrine="" disrupter="" effects.="" b.="" metabolism="" in="" plants="" and="" animals="" epa="" considers="" the="" nature="" of="" the="" residue="" in="" corn="" to="" be="" understood.="" fipronil="" is="" metabolized="" by:="" (1)="" hydrolysis="" to="" the="" amide="" (rpa="" 200766)="" with="" further="" hydrolysis="" to="" the="" carboxylic="" acid="" (rpa="" 200761)="" or="" (2)="" oxidation="" to="" the="" sulfone="" mb="" 46136.="" the="" epa="" metabolism="" committee="" has="" concluded="" that="" the="" residues="" of="" concern="" for="" the="" tolerance="" expression="" and="" dietary="" risk="" assessment="" in="" corn="" and="" animal="" racs="" are="" fipronil,="" mb="" 46136,="" and="" mb="" 45950.="" c.="" analytical="" enforcement="" methodology="" analytical="" methodology="" suitable="" for="" the="" enforcement="" of="" the="" proposed="" tolerance="" is="" available.="" for="" corn="" racs,="" the="" registrant="" has="" submitted="" a="" proposed="" analytical="" enforcement="" method="" which="" measures="" the="" parent="" and="" its="" metabolites="" (mb="" 45950,="" and="" mb="" 46136)="" in="" a="" single="" chromatographic="" separation="" using="" gc="" with="" ecd.="" the="" limit="" of="" quantitation="" (loq)="" for="" each="" compound="" is="" 0.01="" ppm="" in="" grain="" and="" 0.02="" ppm="" in="" forage="" and="" fodder.="" this="" method="" has="" undergone="" a="" successful="" petition="" method="" validation="" (pmv).="" for="" animal="" racs,="" the="" registrant="" has="" submitted="" a="" proposed="" analytical="" enforcement="" method="" which="" measures="" the="" parent="" and="" its="" metabolites="" (mb="" 45950="" and="" mb="" 46136)="" in="" a="" single="" chromatographic="" separation="" using="" gc="" with="" ecd.="" the="" loq="" of="" cattle,="" goat,="" horse="" and="" sheep="" for="" each="" compound="" is="">< 0.02="" ppm.="" this="" method="" has="" also="" undergone="" a="" successful="" pmv.="" d.="" magnitude="" of="" residues="" as="" a="" result="" of="" this="" use,="" residues="" of="" fipronil="" are="" not="" expected="" to="" exceed="" the="" following="" levels:="" corn,="" field,="" grain.........................................="" 0.02="" ppm="" corn,="" field,="" stover........................................="" 0.30="" ppm="" corn,="" field,="" forage........................................="" 0.15="" ppm="" secondary="" residues="" in="" animal="" commodities="" from="" this="" proposed="" use="" on="" corn="" are="" not="" expected="" to="" exceed="" the="" following="" levels:="" eggs.......................................................="" 0.03="" ppm="" fat="" of="" cattle,="" goat,="" horse="" and="" sheep.......................="" 0.40="" ppm="" hog="" fat....................................................="" 0.04="" ppm="" hog="" liver..................................................="" 0.02="" ppm="" hog="" meat="" byproducts="" (except="" liver).........................="" 0.01="" ppm="" hog="" meat...................................................="" 0.01="" ppm="" milk,="" fat="" (reflecting="" 0.05="" ppm="" in="" whole="" milk)..............="" 1.50="" ppm="" liver="" of="" cattle,="" goat,="" horse="" and="" sheep.....................="" 0.10="" ppm="" meat="" byproducts="" (except="" liver)="" of="" cattle,="" goat,="" horse="" and="" sheep.....................................................="" 0.04="" ppm="" meat="" of="" cattle,="" goat,="" horse="" and="" sheep......................="" 0.04="" ppm="" poultry="" fat................................................="" 0.05="" ppm="" poultry="" meat...............................................="" 0.02="" ppm="" poultry="" meat="" byproducts....................................="" 0.02="" ppm="" e.="" international="" residue="" limits="" there="" are="" no="" codex,="" canadian,="" or="" mexican="" mrls="" established="" for="" fipronil="" [[page="" 62978]]="" in/on="" corn="" and="" animal="" racs.="" therefore,="" no="" compatibility="" problems="" exist.="" f.="" rotational="" crop="" restrictions="" the="" rotational="" crop="" restrictions="" specified="" on="" the="" labels="" (1="" month="" for="" leafy="" vegetables,="" 5="" months="" for="" root="" crops,="" 12="" months="" for="" small="" grains="" and="" all="" other="" crops)="" are="" supported="" by="" the="" results="" of="" the="" confined="" rotational="" crop="" study.="" iv.="" conclusion="" therefore,="" the="" tolerance="" is="" 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="" mb="" 46136="" (5-amino-1-[2,6-="" dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)="" sulfonyl]-1h-="" pyrazole-3-carbonitrile)="" and="" mb="" 45950="" (5-amino-1-[2,6-dichloro-4-="" (trifluoromethyl)="" phenyl]-4-[(trifluoromethyl)thio]-1h-pyrazole-3-="" carbonitrile)="" in="" or="" on="" the="" following="" items="" at="" the="" levels="" specified:="" ------------------------------------------------------------------------="" tolerances="" (in="" parts="" commodity="" per="" million)="" ------------------------------------------------------------------------="" corn,="" field,="" grain.........................................="" 0.02="" corn,="" field,="" stover........................................="" 0.30="" corn,="" field,="" forage........................................="" 0.15="" eggs.......................................................="" 0.03="" fat="" of="" cattle,="" goat,="" horse="" and="" sheep.......................="" 0.40="" hog="" fat....................................................="" 0.04="" hog="" liver..................................................="" 0.02="" hog="" meat="" byproducts="" (except="" liver).........................="" 0.01="" hog="" meat...................................................="" 0.01="" liver="" of="" cattle,="" goat,="" horse="" and="" sheep.....................="" 0.10="" meat="" byproducts="" (except="" liver)="" of="" cattle,="" goat,="" horse="" and="" sheep.....................................................="" 0.04="" meat="" of="" cattle,="" goat,="" horse="" and="" sheep......................="" 0.04="" milk,="" fat="" (reflecting="" 0.05="" ppm="" in="" whole="" milk)..............="" 1.50="" poultry="" fat................................................="" 0.05="" poultry="" meat...............................................="" 0.02="" poultry="" meat="" byproducts....................................="" 0.02="" ------------------------------------------------------------------------="" 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="" january="" 26,="" 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(i).="" 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="" confidential="" business="" information="" (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="" and="" electronic="" submissions="" epa="" has="" established="" a="" record="" for="" this="" rulemaking="" under="" docket="" control="" number="" [opp-300587]="" (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="" 1132="" 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="" highway,="" 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 a tolerance 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, 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
[[Page 62979]]
408(d), such as the tolerance 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 Advocacy of the Small Business
Administration.
VIII. Submission to Congress and the General Accounting Office
Under 5 U.S.C. 801(a)(1)(A), as added by the Small Business
Regulatory Enforcement Fairness Act of 1996, the Agency has submitted 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 General Accounting Office prior to publication of this rule in
today's Federal Register. This 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: November 14, 1997.
Stephen L. Johnson,
Acting Director, 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. By adding a new Sec. 180.517 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 in or on the
following items at the levels specified:
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
Corn, field, grain........................ 0.02
Corn, field, stover....................... 0.30
Corn, field, forage....................... 0.15
Eggs...................................... 0.03
Fat of cattle, goat, horse and sheep...... 0.40
Hog Fat................................... 0.04
Hog Liver................................. 0.02
Hog Meat.................................. 0.01
Hog Meat Byproducts (except liver)........ 0.01
Liver of cattle, goat, horse and sheep.... 0.10
Milk, fat (reflecting 0.05 ppm in whole 1.50
milk).
Meat Byproducts (except liver) of cattle, 0.04
goat, horse and sheep.
Meat of cattle, goat, horse and sheep..... 0.04
Poultry Fat............................... 0.05
Poultry Meat.............................. 0.02
Poultry Meat Byproducts................... 0.02
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 97-30949 Filed 11-25-97; 8:45 am]
BILLING CODE 6560-50-F
