[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: <a href="/cdn-cgi/l/email-protection#58372828753c373b333d2c183d283935393134763d2839763f372e"><span class="__cf_email__" data-cfemail="610e11114c050e020a0415210411000c00080d4f0411004f060e17">[email protected]</span></a>. 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: 
<a href="/cdn-cgi/l/email-protection#09636661677a66672764687b606667496c796864686065276c7968276e667f"><span class="__cf_email__" data-cfemail="deb4b1b6b0adb1b0f0b3bfacb7b1b09ebbaebfb3bfb7b2f0bbaebff0b9b1a8">[email protected]</span></a>.

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 F<INF>1</INF> and 
F<INF>2</INF> offspring; decreased litter size in the F<INF>1</INF> and 
F<INF>2</INF> litters; decreased body weights in the F<INF>1</INF> and 
F<INF>2</INF> litters; decrease in the percentage of F<INF>1</INF> 
parental animals mating; reduction in fertility index in F<INF>1</INF> 
parental animals; reduced post-implantation survival and offspring 
postnatal survivability in the F<INF>2</INF> litters; and delay in 
physical development in the F<INF>1</INF> and F<INF>2</INF> 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 <greek-m>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 <greek-m>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 <greek-m>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 
<greek-m>g/plate without S9 activation and up to 500 <greek-m>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 <greek-m>g/ml with and without S9 activation.
    6. Metabolism study. An acceptable metabolism study in the rat 
using <SUP>14</SUP>-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 
Na<SUP>125</SUP>I at a dose level of 1 <greek-m>Ci <SUP>125</SUP>I. 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 <SUP>125</SUP>I 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 <SUP>125</SUP>I incorporated in the thyroid and in the 
blood: thyroid ratios along with elevated levels of <SUP>125</SUP>I 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 <SUP>125</SUP>I in the blood to thyroid weight was reduced. 
The administration of perchlorate produced further reductions in the 
<SUP>125</SUP>I content in the thyroids and in the blood: thyroid 
<SUP>125</SUP>I 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 [<SUP>125</SUP>I] thyroxine at a dosage of 10 
<greek-m>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 <ls-thn-eq> 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  10<SUP>-5</SUP> 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)<SUP>-1</SUP> 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<SUP>-6</SUP> mg/kg/day and exposure for children is 4.9  x  
10<SUP>-6</SUP> 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:
    <a href="/cdn-cgi/l/email-protection#fc938c8cd198939f979988bc998c9d919d9590d2998c9dd29b938a"><span class="__cf_email__" data-cfemail="dab5aaaaf7beb5b9b1bfae9abfaabbb7bbb3b6f4bfaabbf4bdb5ac">[email protected]</span></a>.

    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


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