62970 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

Commodity Parts per million

Horses, meat ........ 0.5

Milk, fat (reflecting

0.1 ppm in whole

milk) ................... 1.0

Poultry, fat ............. 0.05

Poultry, mbyp ........ 0.05

Poultry, meat ......... 0.05

Sheep, fat ............. 1.0

Sheep, mbyp ......... 0.1

Sheep, meat ......... 0.5

Strawberries .......... 3.0

* * * * *

[FR Doc. 97–30948 Filed 11–25–97; 8:45 am]

BILLING CODE 6560–50–F

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.

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-pyrazole3-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]-1Hpyrazole-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: oppdocket@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]-1Hpyrazole-3-carbonitrile) and its

metabolites MB 46136 (5-amino-1-[2,6-

dichloro-4-(trifluoromethyl)phenyl]-4-

[(trifluoromethyl) sulfonyl]-1Hpyrazole-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
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 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
62972 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

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-pyrazole3-carbonitrile) and its metabolites MB

46136 (5-amino-1-[2,6-dichloro-4-

(trifluoromethyl)phenyl]-4-

[(trifluoromethyl) sulfonyl]-1Hpyrazole-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:

Commodity

Tolerance

(in 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 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 milk).

1.50

Meat of cattle, goat, horse and

sheep.

0.04

Meat byproducts (except liver)

of cattle, goat, horse and

sheep.

0.04

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 nonsensitizer.

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
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 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 postimplantation 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 μg/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 μg/

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 μg/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 μg/plate

without S9 activation and up to 500 μg/

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 μg/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 μCi 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 μCi/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
62974 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

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:

Commodity

Tolerance

(in 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 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 milk).

1.50

Meat of cattle, goat, horse and

sheep.

0.04

Poultry Fat ................................ 0.05

Poultry Meat ............................. 0.02

Meat Byproducts (except liver)

of cattle, goat, horse and

sheep.

0.04

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 nonnursing 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 nursing).3.0%

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
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 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 × 10-5

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 × 10-6

mg/kg/day and exposure for children is

4.9 × 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
62976 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

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 preand/or postnatal exposure with fipronil.

Specifically, in a developmental

neurotoxicity study in rats, the

developmental and developmentalneurotoxicity 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
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 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 intermediateterm 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
62978 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

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-pyrazole3-carbonitrile) and its metabolites MB

46136 (5-amino-1-[2,6-dichloro-4-

(trifluoromethyl)phenyl]-4-

[(trifluoromethyl) sulfonyl]-1Hpyrazole-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:

Commodity

Tolerances

(in 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 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
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 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 § 180.517 to read

as follows:

§ 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]-1Hpyrazole-3-carbonitrile) and its

metabolites 5-amino-1-[2,6-dichloro-4-

(trifluoromethyl)phenyl]-4-

[(trifluoromethyl) sulfonyl]-1Hpyrazole-3-carbonitrile and 5-amino-1-

[2,6-dichloro-4-(trifluoromethyl)

phenyl]-4-[(trifluoromethyl)thio]-1Hpyrazole-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 milk).

1.50

Meat Byproducts (except liver) of

cattle, goat, horse and sheep.

0.04

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

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Part 180

[OPP–300569; FRL–5751–1]

RIN 2070–AB78

Tebufenozide; Pesticide Tolerances for

Emergency Exemptions

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes a

time-limited tolerance for residues of

tebufenozide in or on sugarcane. This

action is in response to EPA’s granting

of an emergency exemption under

section 18 of the Federal Insecticide,

Fungicide, and Rodenticide Act

authorizing use of the pesticide on

sugarcane. This regulation establishes a

maximum permissible level for residues

of tebufenozide in this food commodity

pursuant to section 408(l)(6) of the

Federal Food, Drug, and Cosmetic Act,

as amended by the Food Quality

Protection Act of 1996. The tolerance

will expire and be revoked on December

31, 1998.

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–300569],

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–

300569], 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, Crystal Mall #2,

1921 Jefferson Davis Hwy., Arlington,

VA.

A copy of objections and hearing

requests filed with the Hearing Clerk

may also be submitted electronically by

sending electronic mail (e-mail) to: oppdocket@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–

300569]. No Confidential Business

Information (CBI) should be submitted

through e-mail. Electronic copies of

objections and hearing request on this

rule may be filed online at many Federal

Depository Libraries.

FOR FURTHER INFORMATION CONTACT: By

mail: David Deegan, 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: CM #2,

1921 Jefferson Davis Hwy., Arlington,

VA, (703) 308–9358, e-mail:

deegan.dave@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA, on

its own initiative, pursuant to section

408(e) and (l)(6) of the Federal Food,

Drug, and Cosmetic Act (FFDCA), 21

U.S.C. 346a(e) and (l)(6), is establishing