Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 63235

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.

James Jones,

Acting Director, Registration Division, Office

of Pesticide Programs.

Therefore, 40 CFR chapter I is

amended as follows:

PART 180—[AMENDED]

1. The authority citation for part 180

continues to read as follows:

Authority: 21 U.S.C. 346a and 371.

2. Section 180.418 is revised to read

as follows:

§ 180.418 Cypermethrin and an isomer

zeta-cypermethrin; tolerances for residues.

(a) General. (1) Tolerances are

established for residues of the

insecticide cypermethrin (±)alpha

cyano-(3-

phenoxyphenyl)methyl(±)cis,trans3(2,2-dichloroethenyl-2,2-

dimethylcyclopropanecarboxylate in or

on the following commodities:

Commodity Parts per

million

Brassica, head and stem .......... 2.0

Brassica, leafy .......................... 14.0

Cattle, fat .................................. 0.05

Cattle, mbyp .............................. 0.05

Cattle, meat .............................. 0.05

Cottonseed ................................ 0.5

Goats, fat .................................. 0.05

Goats, mbyp ............................. 0.05

Goats, meat .............................. 0.05

Hogs, fat ................................... 0.05

Hogs, mbyp ............................... 0.05

Hogs, meat ............................... 0.05

Horses, fat ................................ 0.05

Horses, mbyp ............................ 0.05

Horses, meat ............................ 0.05

Lettuce, head ............................ 10.0

Milk ............................................ 0.05

Onions, bulb .............................. 0.10

Pecans ...................................... 0.05

Sheep, fat ................................. 0.05

Sheep, mbyp ............................. 0.05

Sheep, meat ............................. 0.05

(2) [Reserved]

(b) Section 18 emergency exemptions.

[Reserved]

(c) Tolerances with regional

registrations. [Reserved]

(d) Indirect or inadvertent residues.

[Reserved]

[FR Doc. 97–30947 Filed 11–25–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Part 180

[OPP–300577; FRL–5754–8]

RIN 2070–AB78

Zeta-Cypermethrin; Pesticide

Tolerance

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes

tolerances for residues of zetacypermethrin in or on cabbage at 2.0

parts per million (ppm); cottonseed at

0.5 ppm; lettuce, head at 10.0 ppm;

onions, bulb at 0.10 ppm; pecans at 0.05

ppm; and the fat, meat, and meat

byproducts (mbyp) of cattle, goats, hogs,

horses, and sheep at 0.05 ppm. It also

removes time limitations for tolerances

for residues of zeta-cypermethrin on the

same commodities that expire on

November 15, 1997. FMC Corporation

requested this tolerance under the

Federal Food, Drug, and Cosmetic Act,

as amended by the Food Quality

Protection Act of 1996.

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–300577,

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–

300577, 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. Follow the

instructions in Unit VI. of this preamble.

No Confidential Business Information

(CBI) should be submitted through email.

FOR FURTHER INFORMATION CONTACT: By

mail: Beth Edwards, 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) 305–5400, e-mail:

edwards.beth@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: On June

15, 1984, EPA established time-limited

tolerances under section 408 of the

Federal Food, Drug, and Cosmetic Act

(FFDCA), 21 U.S.C. 346a(d) and 348 for

residues of cypermethrin on cottonseed;

fat, meat, and mbyp of cattle, goats,

hogs, horses, poultry, and sheep; and

milk (49 FR 24864). As additional crop

tolerances were established, they were

also made time-limited. These

tolerances expire on November 15,

1997. FMC Corporation, on September

15, 1997, requested that the time

limitation for tolerances established for

residues of the insecticide zetacypermethrin in these commodities be

removed based on environmental effects

data that they had submitted as a

condition of the registration. FMC

Corporation also submitted a summary

of its petition as required under the

FFDCA, as amended by the Food

Quality Protection Act (FQPA) of 1996

(Pub. L 104–170).

In the Federal Register of September

25, 1997, (62 FR 50337) (FRL–5748–2),

EPA issued a notice pursuant to section

408 of the FFDCA, 21 U.S.C. 346a(e)

announcing the filing of pesticide

petitions (PP 2F2623, 4F2986, 3F2824,

7F3498, and 4F3011) for tolerances by

FMC Corporation, 1735 Market St.,

Philadelphia, PA 19103. This notice

included a summary of the petition

prepared by FMC Corporation, the

registrant. There were no comments

received in response to the notice of

filing.

The petition requested that 40 CFR

180.418 be amended by removing the

time limitation for tolerances for

residues of the insecticide and

pyrethroid, zeta-cypermethrin in or on

cabbage at 2.0 ppm; cottonseed at 0.5

ppm; lettuce, head at 10.0 ppm; onions,

bulb at 0.10 ppm; and pecans at 0.05

ppm. Animal commodities were not
63236 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

included in the notice of filing but are

being included in this final rule.

The basis for the time-limited

tolerances, that expire November 15,

1997, was given in the October 20, 1993,

Federal Register (58 FR 54094). These

time-limited tolerances were predicated

on the expiration of pesticide product

registrations that were made conditional

due to lack of certain ecological and

environmental effects data. The

rationale for using time-limited

tolerances was to encourage pesticide

manufacturers to comply with the

conditions of registration in a timely

manner. There is no regulatory

requirement to make tolerances timelimited due to the conditional status of

a product registration under the Federal

Insecticide, Fungicide, and Rodenticide

Act (FIFRA), as amended. It is current

EPA policy to no longer establish time

limitations on tolerance(s) with

expiration dates if none of the

conditions of registration have any

bearing on human dietary risk. The

current petition action meets that

condition and thus the expiration dates

associated with specific crop tolerances

are being deleted.

I. Risk Assessment and Statutory

Findings

New section 408(b)(2)(A)(i) of the

FFDCA allows EPA to establish a

tolerance (the legal limit for a pesticide

chemical residue in or on a food) only

if EPA determines that the tolerance is

‘‘safe.’’ Section 408(b)(2)(A)(ii) of the

FFDCA defines ‘‘safe’’ to mean that

‘‘there is a reasonable certainty that no

harm will result from aggregate

exposure to the pesticide chemical

residue, including all anticipated

dietary exposures and all other

exposures for which there is reliable

information.’’ This includes exposure

through drinking water and in

residential settings, but does not include

occupational exposure. Section

408(b)(2)(C) of the FFDCA 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

drinking water) and through exposures

that occur as a result of pesticide use in

residential settings.

A. Toxicity

1. Threshold and non-threshold

effects. For many animal studies, a dose

response relationship can be

determined, which provides a dose that

causes adverse effects (threshold effects)

and doses causing no-observed effects

(the ‘‘no-observed effect level’’ or

‘‘NOEL’’).

Once a study has been evaluated and

the observed effects have been

determined to be threshold effects, EPA

generally divides the NOEL from the

study with the lowest NOEL by an

uncertainty factor (usually 100 or more)

to determine the Reference Dose (RfD).

The RfD is a level at or below which

daily aggregate exposure over a lifetime

will not pose appreciable risks to

human health. An uncertainty factor

(sometimes called a ‘‘safety factor’’) of

100 is commonly used since it is

assumed that people may be up to 10

times more sensitive to pesticides than

the test animals, and that one person or

subgroup of the population (such as

infants and children) could be up to 10

times more sensitive to a pesticide than

another. In addition, EPA assesses the

potential risks to infants and children

based on the weight of the evidence of

the toxicology studies and determines

whether an additional uncertainty factor

is warranted. Thus, an aggregate daily

exposure to a pesticide residue at or

below the RfD (expressed as 100% or

less of the RfD) is generally considered

acceptable by EPA. EPA generally uses

the RfD to evaluate the chronic risks

posed by pesticide exposure. For shorter

term risks, EPA calculates a margin of

exposure (MOE) by dividing the

estimated human exposure into the

NOEL from the appropriate animal

study. Commonly, EPA finds MOEs

lower than 100 to be unacceptable. This

100-fold MOE is based on the same

rationale as the 100-fold uncertainty

factor.

Lifetime feeding studies in two

species of laboratory animals are

conducted to screen pesticides for

cancer effects. When evidence of

increased cancer is noted in these

studies, the Agency conducts a weight

of the evidence review of all relevant

toxicological data including short-term

and mutagenicity studies and structure

activity relationship. Once a pesticide

has been classified as a potential human

carcinogen, different types of risk

assessments (e.g., linear low-dose

extrapolations or MOE calculation based

on the appropriate NOEL) will be

carried out based on the nature of the

carcinogenic response and the Agency’s

knowledge of its mode of action.

2. Differences in toxic effect due to

exposure duration. The toxicological

effects of a pesticide can vary with

different exposure durations. EPA

considers the entire toxicity data base,

and based on the effects seen for

different durations and routes of

exposure, determines which risk

assessments should be done to assure

that the public is adequately protected

from any pesticide exposure scenario.

Both short and long durations of

exposure are always considered.

Typically, risk assessments include

‘‘acute,’’ ‘‘short-term,’’ ‘‘intermediateterm,’’ 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 singleoral 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,
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 63237

and the toxicological endpoint/NOEL is

selected to be adequate for at least 7

days of exposure. (Toxicity results at

lower levels when the dosing duration

is increased.)

Intermediate-term risk results from

exposure for 7 days to several months.

This assessment is handled in a manner

similar to the short-term risk

assessment.

Chronic risk assessment describes risk

which could result from several months

to a lifetime of exposure. For this

assessment, risks are aggregated

considering average exposure from all

sources for representative population

subgroups including infants and

children.

B. Aggregate Exposure

In examining aggregate exposure,

section 408 of the FFDCA requires that

EPA take into account available and

reliable information concerning

exposure from the pesticide residue in

the food in question, residues in other

foods for which there are tolerances,

residues in ground water 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.

II. Aggregate Risk Assessment and

Determination of Safety

Consistent with section 408(b)(2)(D)

of the FFDCA, EPA has reviewed the

available scientific data and other

relevant information in support of this

action, EPA has sufficient data to assess

the hazards of zeta-cypermethrin and to

make a determination on aggregate

exposure, consistent with section

408(b)(2) of the FFDCA, for residues of

zeta-cypermethrin in or on cabbage at

2.0 ppm; cottonseed at 0.5 ppm; lettuce,

head at 10.0 ppm; onions, bulb at 0.10

ppm; pecans at 0.05 ppm; and the fat,

meat, and mbyp of cattle, goats, hogs,

horses, and sheep at 0.05 ppm. EPA’s

assessment of the dietary exposures and

risks associated with establishing the

tolerances follows.

A. Toxicological Profile

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 zetacypermethrin are discussed in this unit.

1. Acute toxicity studies with

technical zeta-cypermethrin: oral LD50

in the rat is 134.4 milligram (mg)/

kilogram (kg) for males and 86.0 mg/kg

for females—Toxicity Category II.

2. Acute toxicity studies with

cypermethrin bridged to zetacypermethrin: dermal LD50 > 2460 mg/

kg in rabbits and LD50 > 4920 in rats—

Toxicity Category III; inhalation (LC50

2.5 mg/liter (L) for females and > 2.5

mg/L in males—Toxicity Category III;

primary eye irritation— not irritating—

Toxicity Category IV; primary dermal

irritation, primary irritation score (PIS)

0.71 —Toxicity Category IV; dermal

sensitization—moderate sensitizer in

two studies, negative in other studies;

delayed type neurotoxicity in hens—no

evidence of delayed type neurotoxicity

in hens at dose levels of 0, 2,500, 5,000,

or 10,000 mg/kg; neurotoxicity screen in

rats—NOEL and lowest-observed effect

level (LOEL) established as < 20 mg/

kg—at 20 mg/kg decreased motor

activity and gait abnormalities.

3. In a 90-day feeding study, rats were

dosed at 0, 10, 50, 150, 250, 500, or 900

ppm (0, 0.6, 2.7, 8.4, 13.8, 28.2, or 55.7

mg/kg/day for males and 0, 0.6, 3.3, 9.6,

16.3, 32.2, or 65.2 mg/kg/day for

females). The NOEL is 250 ppm (13.9

mg/kg/day) and the LOEL is 500 ppm

(28.2 mg/kg/day) based on decreases in

bodyweight and bodyweight gains and

food consumption at 28.2 mg/kg/day

and above and deaths; clinical signs of

neurotoxicity; decreases in erythrocyte

and leukocyte counts, hemoglobin, and

hematocrit, and increases in blood urea

nitrogen (BUN) at 55.7 mg/kg/day.

4. The 21-day dermal, subchronic oral

study in the dog and the 21-day

inhalation studies are bridged from

cypermethrin.

In a subchronic toxicity study, dogs

were dosed at 0, 5, 50, 500, or 1,500

ppm (corresponding to 0, 125, 1.25,

12.5, and 37.5 mg/kg/day) for 13 weeks.

The LOEL is 1,500 ppm (37.5 mg/kg/

day, based on clinical signs indicating

neurotoxicity). The NOEL is 500 ppm

(12.5 mg/kg/day).

In a 21-day dermal toxicity study,

rabbits were dosed at 2, 20, or 200 mg/

kg/day with daily applications for 3

weeks for a total of 15 applications.

Five/sex/group were abraded prior to

application of the test material. The

LOEL is 200 mg/kg/day based on liver

effects. The NOEL is 20 mg/kg/day.

In a 21-day subchronic inhalation

toxicity study, rats were dosed by nose

only exposure at concentrations of 0,

0.01, 0.05, or 0.25 mg/L for 6 hours per

day, 5 days per week for a total of 15

exposures. Additional satellite groups of

five/sex were included for recovery

assessment and analysis of

cypermethrin in the brain. The LOEL is

0.05 mg/L based mainly on bodyweight

decrease. The NOEL is 0.01 mg/L.

5. The chronic/oncogenicity studies

are bridged from cypermethrin.

In a chronic toxicity study, dogs were

dosed at 0, 1, 5, or 15 mg/kg/day for 52

weeks. The LOEL is 5 mg/kg/day based

on gastrointestinal effects. The NOEL is

1 mg/kg/day.

In a carcinogenicity study, mice were

dosed at control-1, control-2, 100, 400,

and 1,600 ppm (corresponding to 0, 0,

14, 57, or 229 mg/kg/day) for 97 weeks

for males and 101 weeks for females.

The LOEL is 400 ppm (57 mg/kg/day)

based on liver weight. The NOEL is 100

ppm (14 mg/kg/day). This study was

determined to be positive for induction

of benign alveologenic neoplasms.

Adequacy of dosing for carcinogenicity

is based upon typically 9% decreases in

males and 12% in females in the first

months of the study.

In a chronic toxicity/carcinogenicity

study, rats were dosed at control-1,

control-2, 20, 150, or 1,500 ppm

(corresponding to 0, 0, 1, 7.5, or 75 mg/

kg/day) for 2 years. Satellite groups of

12/sex were sacrificed after 1 year of

dosing. The LOEL is 1,500 ppm (75 mg/

kg/day) based on bodyweight. The

NOEL is 150 ppm (7.5 mg/kg/day).

Cypermethrin was not considered to be
63238 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

oncogenic in this study. A possible

association with increased testicular

interstitial tumors was not considered

definite.

6. Zeta-cypermethrin was tested in a

developmental toxicity study in rats at

the following dose levels: 0, 5, 12, 25,

or 35 mg/kg/day. Groups of 25 females

were administered the test chemical by

gavage on gestation days 6 through 15

in a volume of 5 milliliter (ml)/kg

bodyweight. No developmental toxicity

was observed at any dose level. The

maternal NOEL is 12.5 mg/kg and the

maternal LOEL is 25 mg/kg based on

decreases in bodyweight and

bodyweight gain and food consumption

and clinical signs of toxicity,

particularly neurotoxicity. The

developmental NOEL is 35 mg/kg/day

highest dose tested (HDT). The LOEL

was not established.

7. The developmental toxicity study

in the rabbit is bridged from

cypermethrin.

In a developmental toxicity study,

rabbits were dosed at 0 (empty capsule),

0 (capsule plus corn oil), 3, 10, or 30

mg/kg/day on days 6 to 18 inclusive of

gestation. There were no effects of any

kind reported on the does. The maternal

LOEL is > 30 mg/kg/day. The maternal

NOEL is > 30 mg/kg/day. There were no

treatment related effects on either the

skeletal or visceral structures reported.

The developmental LOEL is > 30 mg/kg/

day. The developmental NOEL is > 30

mg/kg/day.

In a developmental toxicity study,

rabbits were dosed at 0, 100, 450, or 700

mg/kg/day from days 7 through 19 of

gestation. The does were sacrificed on

day 29 of gestation. The maternal LOEL

is 450 mg/kg/day, based on bodyweight

gain. The maternal NOEL is 100 mg/kg/

day. There were no indications of

developmental toxicity. The NOEL and

LOEL for developmental toxicity is >

700 mg/kg/day.

8. Zeta-cypermethrin was tested in a

two-generation reproduction study in

groups of 30 male and 30 female rats at

the following dose levels: 0, 7.5, 25, 100,

375, or 750 ppm (0, 0.5, 1.8, 7, 27, or

45 mg/kg/day). The parental and

reproductive NOELs are 7 mg/kg/day

and LOELs are 27 mg/kg/day based on

decreased parental and pup weight,

particularly during lactation, clinical

signs of toxicity, and death at 45 mg/kg/

day.

9. Zeta-cypermethrin was tested in a

reverse mutation assay in salmonella

typhimurium strains TA1535, TA1537,

TA100, TA1538, and TA98 at 0, 100,

333, 1,000, 3,333, 5,000, or 10,000

microgram (©g)/plate. It gave a very

weak positive response (two-fold

increase in revertants/plate) in strain

TA100 at 10,000 ©g/plate without S–9

activation in two-separate experiments.

Doses of 3,333 and 5,000 ©g/plate gave

1.5 and 1.6-fold increases in revertants/

plate, respectively. Strains TA98,

TA1535, TA1537, and TA1538 treated

in the presence and absence of

mammalian S–9 activation were not

affected. Zeta-cypermethrin is therefore

considered a possible weak mutagen

under the conditions of the assay.

10. Zeta-cypermethrin was tested in

an in vitro mammalian cell gene

mutation assay in Chinese hamster

ovary (CHO) cells (CHO–K1–BH4,

subclone D1) at the following dose

levels: 0, 1, 10, 25, 50, 100, 400, 700, or

1,000 ©g/ml, both in the absence and

presence of S–9 activation. No evidence

of increased forward mutation rate at

the hypoxanthine guanine

phosphoribose transferase (HGPRT)

locus was observed at any dose tested

under the conditions of these assays.

The solubility limit of the test

compound in culture media was

approximately 100 ©g/ml.

11. Zeta-cypermethrin was tested in

an in vivo rat bone marrow

chromosomal aberration assay. Groups

of 15 male and 15 female SpragueDawley rats were administered single

doses by gavage with 0, 31.25, 62.5, or

125 mg/kg zeta-cypermethrin in corn

oil. Five rats/sex were sacrificed at 6,

18, and 30 hours-post dosing.

Cyclophosphamide was used as the

positive control (60 mg/kg). No evidence

of structural chromosomal aberrations

was demonstrated at either 6, 18, or 30

hours-post dosing.

12. Zeta-cypermethrin was tested in

an unscheduled deoxyribonucleic acid

(DNA) synthesis assay in male Fischer

344 rat primary hepatocyte cells. The

dose levels tested were 0, 14, 45, 140,

450, 1,400, or 4,500 ©g/ml. No

unscheduled DNA synthesis was

observed at any dose level up to 4,500

©g/ml in the primary hepatocyte

cultures under the conditions of the

assay. Minimal cytotoxicity was

observed at the highest doses.

Incomplete solubility of the test

compound in culture media was

observed, particularly at the higher

doses. The positive control gave clear

positive responses. The study is

acceptable for regulatory purposes.

13. The metabolism studies are

bridged from cypermethrin.

Several studies with both rats, dogs,

and mice are available to support the

requirement for metabolism in

mammals. Some of these studies assess

individual cis- and trans-radiolabeled

isomers and other studies assess the

metabolism of cypermethrin with the

label in either the cyclopropyl of the

phenoxybenzyl ring. In general the

following has been demonstrated from

these studies:

Cypermethrin is readily absorbed

from the gastrointestinal tract and

extensively metabolized. It is mostly

excreted in the urine and contains

several characterized metabolites

derived from conjugation of the

hydrolysis products of the parent

compound following cleavage of the

esteratic linkage site. The following

three executive summaries describe the

metabolism of cypermethrin in rats.

First study—First group. Six/sex rats,

Wistar strain rats, were dosed with a

single dose 0.61 mg/animal of labeled

cis-cypermethrin isomers in 0.5 ml of

corn oil. The rats were individually

housed in metabolism cages and their

urine and fecal matter collected daily

until sacrifice. Two rats of each sex

were sacrificed after 24 and 72 hours

and after 8 days. Samples of the blood

and selected tissues were assessed for

radioactivity content.

Second group. Three/sex rats were

dosed with 0.615 mg/animal of labeled

trans-cypermethrin in 0.8 ml of corn oil.

In addition to the urine and fecal

collections, expired air was also

collected from one male and one female.

Total recovery was from 97.2% to

100.5%. About 70% of cis- and 80% of

trans-cypermethrin was excreted in 24

hours. Essentially all was excreted in 8

days. Most of the label was excreted in

the urine (> 53%) with less in the feces

and (< 20%) for the trans (males and

females) and cis (males only) groups

and < 1% in the air for all groups. A sex

difference with respect to excretion in

the urine from the cis-isomer was noted

for females since about equal amounts

(35%) were found in both the urine and

feces. Several urinary and fecal

metabolites were tentatively

characterized.

Second study. One group of three/sex

Wistar strain rats was dosed with a

single-oral dose (approximately 1.3 mg/

kg) of 14C-cyclopropyl labeled

cypermethrin in corn oil (0.8 ml). The

rats were then placed in glass

metabolism cages and their urine and

feces were collected. Special

metabolism cages for trapping any

radioactivity expired through their

respiratory system were used for one

male and one female rat. The rats were

sacrificed after 3 days and their blood

and selected tissues were assessed for

radioactivity, 85.5% for males and

97.2% for females of 14C was excreted

in 72 hours. The urine (55.8% for males

and 69.4% for females) was the major

route of excretion with the feces

containing the balance. The air

contained only 0.1% or less. Tissue
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 63239

retention was highest in the skin (1.2%)

and liver (0.74% for males but only

0.18% for females) and fat (0.57 to

0.66%).

Third study. In a series of nine

different studies, labeled cypermethrin

(1 mg/kg or less) in corn oil or separated

cis- or trans-cypermethrin isomers were

given by gavage to single or groups of

two or three Wistar strain rats. Their

urine and in some cases fecal matter

was collected at various intervals such

as 18 hours to 3 days. In another set of

experiments, labeled cypermethrin was

administered to rats that were fitted

with bile duct cannalulas and their bile

collected for 4-5 hours while the rat was

under anesthesia. Cis- and trans-14Ccyclopropyl labeled cypermethrin was

demonstrated to form glucuronide

conjugations of cis- and trans-acids and

hydroxyacids. Only 1.6% or less of the

total dose is excreted in the bile. Most

of the cypermethrin in the feces was

unmetabolized. The glucuronide

conjugates in the urine were found to be

unstable and subject to hydrolysis.

14. Acute delayed type neurotoxicityhens. Cypermethrin was tested in the

hen following a protocol similar to the

series 81–7 guideline. The dose levels

tested were 0, 2,500, 5,000, and 10,000

mg/kg but there was no indication of the

delayed type neurotoxicity noted.

15. Acute neurotoxicity screen-rats.

There are two acute neurotoxicity

studies with cypermethrin.

First study. Rats were dosed with

cypermethrin at dose levels of 0, 20, 60,

or 120/100 mg/kg. The rats displayed

gait, muscle effects, and

choreoathetosis. Motor activity was

decreased for all dose groups for males

(estimated 45%, 66%, and 85% for the

20, 60, and 100 mg/kg dose group

respectively) and gait abnormalities

were present in the low-dose group.

Body temperature was increased about 1

°C in the low-dose male group but

decreased for the higher groups. Some

10 other parameters were affected at 60

mg/kg and/or above. These included:

Salivation, urination, arousal, abnormal

motor movement, forelimb, or hindlimb

grip strength, landing foot splay, touch

response, and tail pinch response. The

LOEL and NOELs for neurotoxicity are

< 20 mg/kg. At 20 mg/kg decreased

motor activity and gait abnormalities

resulted.

Second study. Rats were dosed with

cypermethrin in corn oil as control, 30,

100, or 200 mg/kg. The rats were

assessed at pretest, 4 hours after

treatment and on days 7 and 14 for

Functional Observational Battery (FOB)

and motor activity. After day 14, five/

sex were prepared for

neurohistopathology. At 100 mg/kg,

ataxia (two males and two females) and

related conditions (staggered or

impaired gait, decreased activity,

splayed hindlimbs, and limp condition)

and decreased motor activity (49%, p <

0.001 for males and 33%, p < 0.01 for

females) resulted. In addition, some

females had salivation, lacrimation and/

or soiled fur. At 200 mg/kg, deaths

resulted (one male and two females) as

well as several other parameters being

affected. The LEL is 100 mg/kg based

primarily on ataxia and related

conditions. The NOEL is 30 mg/kg.

The first study in Unit II. A.15. of this

preamble is considered to define the

neurotoxicity to cypermethrin because

responses were noted at lower-dose

levels. The second study used a variable

and large dose of corn oil and a different

strain of rat.

16. Subchronic neurotoxicity screen

in rats. Rats were dosed with

cypermethrin as control, 500, 1,300 or

1,700 ppm (31, 77, or 102 for males and

37, 95, or 121 for females mg/kg/day) for

90 days in a subchronic neurotoxicity

study. At 1,300 ppm, females displayed

ataxia (1/10), splayed hindlimbs (5/16),

impaired gait (4/10), and decreased

feces (4/10) as well as decreased

bodyweight gain (∼41%). Males had

only decreased bodyweight gain (∼27%)

and increased landing foot splay. At

1,700 ppm, males showed ataxia (8/10)

and additional related symptoms and

females had decreased motor activity

(∼27%). The LEL is 1,300 ppm (77 mg/

kg/day) based on several effects. The

NOEL is 500 ppm (31 mg/kg/day).

Because the studies in Units II. A.15.

and 16. of this preamble are screens,

neurotoxicity studies will be required

under a special Data Call-In (DCI) letter

pursuant to section 3(c)(2)(B) of FIFRA.

Although these data are lacking, EPA

has sufficient toxicity data base to

support these tolerances and these

additional studies are not expected to

significantly change its risk assessment.

B. Toxicological Endpoints

1. Acute toxicity. For acute dietary

risk assessment, EPA recommends use

of a NOEL of 0.5 mg/kg/day based on

the NOEL of 1.0 mg/kg/day from the

cypermethrin chronic toxicity study in

dogs and a correction factor of two to

account for the differences in the

percentage of the biologically active

isomer. The LOEL of this study of 5.0

mg/kg/day was based on gastrointestinal

disturbances observed in the first week

of the study.

2. Short- and intermediate-term

toxicity. For short- and intermediateterm MOE’s, EPA recommends use of a

NOEL of 2.5 mg/kg/day based on

neurotoxic signs in dogs starting at week

1. The inhalation NOEL is 5.0 with a

correction factor of 2. Dermal absorption

rate was 25%. A dermal absorption rate

of 25% was recommended based on the

weight-of-the-evidence available for

structurally related pyrethroids.

3. Chronic toxicity. EPA has

established the RfD for zetacypermethrin at 0.005 mg/kg/day. This

RfD is based on gastrointestinal

disturbances in dogs with an

uncertainty factor of 200 to account for

differences in percent biologically active

isomers in enriched product.

Since insufficient data on zetacypermethrin are available to establish

an RfD, the data from cypermethrin

were used in establishing an RfD for

zeta-cypermethrin. The NOELs from the

cypermethrin studies were divided by 2

as a correction factor, assuming the

worst case that the biologically active

isomers are the ones which carry most

of the toxicity. The following paragraph

summarizes the decision logic for

establishing the RfD for zetacypermethrin from the cypermethrin

data base.

In general, the most sensitive species

for the 10 synthetic pyrethroids appears

to be the dog. For zeta-cypermethrin the

Agency does not have any toxicity data

on the dog that can be compared with

the dog studies conducted with

cypermethrin. In addition, the Agency

also does not have any chronic studies

on zeta-cypermethrin that can be

compared with those conducted with

cypermethrin. Therefore, although a

comparison of the LEL’s from the zetacypermethrin studies with the

corresponding LEL’s from the

cypermethrin studies does not show a

pronounced difference in toxicity, for

risk assessment purposes, the Agency

has decided to use the toxicity

endpoints from cypermethrin with a

two-fold correction factor to account for

the differences in the percentages of the

more biologically active isomers in the

enriched technical product (zetacypermethrin). This would also apply to

the inhalation endpoint because the

Agency has no inhalation studies with

zeta-cypermethrin. The Agency is

making a conservative assumption that

most of the toxicity for cypermethrin

will be from the four more biologically

active isomers of zeta-cypermethrin.

Based on previous documentation, the

Agency is assuming that the percentages

of the isomers are approximately as

follows:

Cypermethrin, eight isomers with

percentage compositions ranging from

11–14% and zeta-cypermethrin, eight

isomers with four insecticidally less

active ones at a concentration of 1%

each. The remaining four isomers, two
63240 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

of which are regarded as being the most

insecticidally active, will be present at

a concentration of 24% each.

4. Carcinogenicity. No carcinogenicity

studies are available for zetacypermethrin. Using its Guidelines for

Carcinogen Risk Assessment published

September 24, 1986 (51 FR 33992) the

Carcinogenicity Peer Review Committee

(CPRC) has classified cypermethrin as a

weak Group C (possible human

carcinogen) based on the increased

incidence in lung adenomas in female

CD-1 mice, but did not recommend

assignment of a cancer potency factor

(Q*1) for a linear quantitative cancer

risk assessment. An RfD approach was

recommended for human risk

assessment purposes. It is assumed that

zeta-cypermethrin would also test

positively for lung adenomas in female

CD-1 mice.

C. Exposures and Risks

1. From food and feed uses.

Tolerances have been established (40

CFR 180.418) for the residues of zetacypermethrin in or on a variety of raw

agricultural commodities. Tolerances

range from 0.05 ppm in animal

commodities to 10.0 ppm in head

lettuce. Registered uses include cabbage,

cotton, head lettuce, onions, and

pecans. Risk assessments were

conducted by EPA to assess dietary

exposures and risks from zetacypermethrin 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 assessment used

Monte Carlo modeling incorporating

anticipated residues and percent crop

treated refinements. The acute dietary

MOE at the 99.9th percentile for the

overall U.S. population is 126. The MOE

at the 99.9th percentile for children 1–

6 years of age is 105. EPA concludes

that there is a reasonable certainty of no

harm for MOEs of 100 or greater.

Therefore, the acute dietary risk

assessment for zeta-cypermethrin

indicates a reasonable certainty of no

harm.

ii. Chronic exposure and risk. The RfD

used for the chronic dietary analysis is

0.005 mg/kg/day based on a NOEL of 1.0

mg/kg/day from the cypermethrin

chronic dog study and an uncertainty

factor of 200 (used to account for the

differences in the percentage of the

biologically active isomer). The

endpoint effect of concern was based on

gastrointestinal disturbances observed

in the first week of the study at the

LOEL of 5.0 mg/kg/day. The chronic

dietary exposure assessment used

anticipated residues, monitoring data,

and percent of crop treated information

. The chronic dietary exposure estimate

for the overall U.S. population was

calculated to be 0.000018 mg/kg/day

(0.4% RfD utilized) and for children 1–

6 years was calculated to be 0.00027

mg/kg/day (0.5% RfD utilized).

EPA notes that the acute dietary risk

assessments used Monte Carlo modeling

(in accordance with Tier 3 of EPA June

1996 ‘‘Acute Dietary Exposure

Assessment’’ guidance document)

incorporating anticipated residues and

percent of crop treated refinements. The

chronic dietary risk assessments used

anticipated residues and percent crop

treated information.

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 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 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 zeta-cypermethrin 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 meet

the requirement for data on anticipated

residues, EPA will issue a DCI notice

pursuant to FFDCA section 408(f)

requiring submission of data on

anticipated residues in conjunction with

approval of the registration under the

FIFRA.

2. From drinking water. Laboratory

and field data have demonstrated that

cypermethrin is immobile in soil and

will not leach into ground water.

Estimates of zeta-cypermethrin drinking

water concentrations were generated

with the PRZM1 and EXAMS computer

models. Based on these analyses, the

contribution of water to the dietary risk

estimate is negligible. Therefore, EPA

concludes that together these data

indicate that residues are not expected

to occur in drinking water.

i. Acute exposure and risk. The acute

drinking water exposure and risk

estimates are 0.000126 mg/kg/day (MOE

of 3,982) and 0.000242 mg/kg/day (MOE

of 2,069) for the overall U.S. population

and non-nursing infants < 1 year old,

respectively.

ii. Chronic exposure and risk. The

chronic drinking water exposure and

risk estimates are 0.000005 mg/kg/day

(0.1% of RfD utilized) and 0.000021 mg/

kg/day (0.4% of RfD utilized) for the

overall U.S. population and non-nursing

infants < 1 year old, respectively.

3. From non-occupational non-dietary

exposure. Zeta-cypermethrin is

registered for agricultural crop

applications only; therefore, no nonoccupational, non-dietary exposure is

expected.

4. Cumulative exposure to substances

with common mechanism of toxicity.

Section 408(b)(2)(D)(v) of the FFDCA

requires that, when considering whether

to establish, modify, or revoke a

tolerance, the Agency consider

‘‘available information’’ concerning the

cumulative effects of a particular

pesticide’s residues and ‘‘other

substances that have a common

mechanism of toxicity.’’ The Agency

believes that ‘‘available information’’ in

this context might include not only

toxicity, chemistry, and exposure data,

but also scientific policies and

methodologies for understanding

common mechanisms of toxicity and

conducting cumulative risk

assessments. For most pesticides,

although the Agency has some

information in its files that may turn out

to be helpful in eventually determining

whether a pesticide shares a common
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 63241

mechanism of toxicity with any other

substances, EPA does not at this time

have the methodologies to resolve the

complex scientific issues concerning

common mechanism of toxicity in a

meaningful way. EPA has begun a pilot

process to study this issue further

through the examination of particular

classes of pesticides. The Agency hopes

that the results of this pilot process will

increase the Agency’s scientific

understanding of this question such that

EPA will be able to develop and apply

scientific principles for better

determining which chemicals have a

common mechanism of toxicity and

evaluating the cumulative effects of

such chemicals. The Agency anticipates,

however, that even as its understanding

of the science of common mechanisms

increases, decisions on specific classes

of chemicals will be heavily dependent

on chemical specific data, much of

which may not be presently available.

Although at present the Agency does

not know how to apply the information

in its files concerning common

mechanism issues to most risk

assessments, there are pesticides as to

which the common mechanism issues

can be resolved. These pesticides

include pesticides that are

toxicologically dissimilar to existing

chemical substances (in which case the

Agency can conclude that it is unlikely

that a pesticide shares a common

mechanism of activity with other

substances) and pesticides that produce

a common toxic metabolite (in which

case common mechanism of activity

will be assumed).

Four members of the insecticide class

pyrethroids produce a common

metabolite known as DCVA (3-(2,2-

dichloroethenyl)-2,2-

dimethylcyclopropane carboxylic acid).

These insecticides are cyfluthrin,

cypermethrin, zeta-cypermethrin, and

permethrin. Although the residues of

DCVA can be estimated, no toxicology

data on the compound per se are

available to directly conduct a hazard

evaluation and thereby establish an

appropriate endpoint for use in a joint

risk assessment. To date, for the purpose

of assessing the risk of the parent

compound, the toxicity of the DCVA has

been assumed to be equivalent to the

parent compound. However, due to the

markedly different toxicological profiles

of cyfluthrin, cypermethrin, zetacypermethrin, and permethrin, EPA

does not believe that it would be

appropriate to cumulate DCVA residues

from these pesticides, or DCVA residues

from one of these pesticides with the

parent of another of these pesticides, in

conducting the risk assessment for these

pesticides.

Accordingly, EPA does not have, at

this time, available data to determine

whether zeta-cypermethrin has a

common mechanism of toxicity with

other substances or how to include this

pesticide in a cumulative risk

assessment. For the purposes of this

tolerance action, therefore, EPA has not

assumed that zeta-cypermethrin has a

common mechanism of toxicity with

other substances.

D. Aggregate Risks and Determination of

Safety for U.S. Population

1. Acute risk. The acute aggregate risk

assessment takes into account exposure

from food and water. The MOE

calculated at the 99.9th percentile for

the overall U.S. population is 122. The

Agency has no cause for concern if total

acute exposure calculated for the 99.9th

percentile yields a MOE of 100 or larger.

Therefore, the Agency has no acute

aggregate concern due to exposure to

zeta-cypermethrin through food and

drinking water.

2. Chronic risk. Using the Anticipated

Residue Contribution (ARC) exposure

assumptions, EPA has concluded that

aggregate exposure to zeta-cypermethrin

from food and water will utilize 0.5% of

the RfD for the U.S. population. The

major identifiable subgroup with the

highest-aggregate exposure is children,

ages 1–6 years old, discussed in Unit II.

F. of this preamble. 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 zeta-cypermethrin residues.

3. Short- and intermediate-term risk.

Short- and intermediate-term aggregate

exposure takes into account chronic

dietary food and water (considered to be

a background exposure level) plus

indoor and outdoor residential

exposure. Based on zeta-cypermethrin

not being registered for residential nonfood sites, EPA concludes that the

aggregate short- and intermediate-term

risks do not exceed levels of concern

(MOE less than 100), and that there is

reasonable certainty that no harm will

result from aggregate exposure to zetacypermethrin residues.

E. Aggregate Cancer Risk for U.S.

Population

No carcinogenicity studies are

available for zeta-cypermethrin.

However, cypermethrin has been

classified as a weak Group C carcinogen

with no Q*1 based on the increased

incidence in lung adenomas in female

CD-1 mice. Based on the

recommendation that the RfD approach

be used, a quantitative dietary cancer

risk assessment was not performed.

Dietary risk concerns due to long-term

consumption of cypermethrin are

adequately addressed by the DRES

chronic exposure analysis using the

RfD. For the U.S. population, less than

1% of the RfD is occupied by aggregate

chronic food and water exposure.

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 zetacypermethrin, EPA considered data

from developmental toxicity studies in

the rat and rabbit and a two-generation

reproduction study in the rat. The

developmental toxicity studies are

designed to evaluate adverse effects on

the developing organism resulting from

pesticide exposure during prenatal

development to one or both parents.

Reproduction studies provide

information relating to effects from

exposure to the pesticide on the

reproductive capability of mating

animals and data on systemic toxicity.

Section 408 of the FFDCA provides

that EPA shall apply an additional 10-

fold margin of safety for infants and

children in the case of threshold effects

to account for pre-and post-natal

toxicity and the completeness of the

data base 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 interand intra-species variability) and not the

additional 10-fold MOE/uncertainty

factor when EPA has a complete data

base under existing guidelines and

when the severity of the effect in infants

or children or the potency or unusual

toxic properties of a compound do not

raise concerns regarding the adequacy of

the standard MOE/safety factor.

ii. Developmental toxicity studies. In

a prenatal developmental toxicity study

in rats, there was no evidence of

developmental toxicity at the HDT (35

mg/kg/day). Maternal toxicity (ataxia,

urine and feces stained fur, decreased

bodyweight gain and food consumption)

was observed at the maternal LOEL (25

mg/kg/day), and the maternal NOEL was

established at 12.5 mg/kg/day. In
63242 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

addition, an acceptable prenatal

developmental toxicity study in rabbits

conducted with cypermethrin was

submitted.

iii. Reproductive toxicity study. In the

two-generation reproduction study in

rats, offspring toxicity (decreased pup

weight gain during lactation) was

observed at the same treatment level

which resulted in parental systemic

toxicity (NOEL = 100 ppm or 27 mg/kg/

day; LOEL = 375 ppm or 45 mg/kg/day).

iv. Pre- and post-natal sensitivity.

There is no evidence of additional

sensitivity to young rats following preor post-natal exposure to zetacypermethrin.

v. Conclusion. The data base related

to pre- and post-natal sensitivity is

complete. Based on the information in

Unit II. F. of this preamble, EPA

concludes that reliable data support use

of the standard 100-fold uncertainty

factor, and that an additional

uncertainty factor is not needed to

protect the safety of infants and

children.

2. Acute risk. The acute aggregate risk

assessment takes into account exposure

from food and water. The MOE

calculated at the 99.9th percentile for

children age 1–6 is 102. The Agency has

no cause for concern if total acute

exposure calculated for the 99.9th

percentile yields an MOE of 100 or

larger. Therefore, the Agency has no

acute aggregate concern due to exposure

to zeta-cypermethrin through food and

drinking water.

3. Chronic risk. Using conservative

exposure assumptions, EPA has

concluded that aggregate exposure to

zeta-cypermethrin from food and water

will utilize 0.6% of the RfD for children,

ages 1–6 years old. 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 to

infants and children from aggregate

exposure to zeta-cypermethrin residues.

4. Short- or intermediate-term risk.

Based on zeta-cypermethrin not being

registered for residential non-food sites,

EPA concludes that the aggregate shortand intermediate-term risks do not

exceed levels of concern, and that there

is reasonable certainty that no harm will

result.

5. Special docket. The complete acute

and chronic exposure analyses

(including dietary, non-dietary, drinking

water, and residential exposure, and

analysis of exposure to infants and

children) used for risk assessment

purposes can be found in the Special

Docket for the FQPA under the title

‘‘Risk Assessment for Extension of

Tolerances for Synthetic Pyrethroids.’’

Further explanation regarding EPA’s

decision regarding the additional safety

factor can also be found in the Special

Docket.

G. Endocrine Disrupter Effects

EPA is required to develop a

screening program to determine whether

certain substances (including all

pesticides and inerts) ‘‘may have an

effect in humans that is similar to an

effect produced by a naturally occurring

estrogen, or such other endocrine

effect....’’ The Agency is currently

working with interested stakeholders,

including other government agencies,

public interest groups, industry, and

research scientists in developing a

screening and testing program and a

priority setting scheme to implement

this program. Congress has allowed 3

years from the passage of FQPA (August

3, 1999) to implement this program. At

that time, EPA may require further

testing of this active ingredient and end

use products for endocrine disrupter

effects.

III. Other Considerations

A. Metabolism In Plants and Animals

The metabolites found in plants and

livestock also are formed in the rat. It

was concluded that 3-phenoxybenzoic

acid (PBA) and its conjugates are not of

concern based on toxicology data for

PBA. In the absence of toxicology data,

the cis- and trans-isomers of DCVA are

considered to be of comparable toxicity

to the parent. In light of Codex

Maximum Residue Limits (MRLs)

including only the parent compound,

the parent being recoverable by the

Food and Drug Administration (FDA)

multi-residue Methods I and II, and the

DCVA is not likely to be measured by

these methods, it was concluded that

tolerances should be set in terms of

cypermethrin only. Crop field trials

should continue to include analyses for

residues of cis- and trans-DCVA.

B. Analytical Enforcement Methodology

Adequate enforcement methodology

Gas Chromatography/Electron Capture

Detector (GC/ECD) is available in

Pesticide Analytical Method II (PAM II)

as Method I to enforce the tolerance

expression.

C. Magnitude of Residues

Residue data from field trials and the

FDA monitoring program (1992–1995)

and the PDP monitoring program (1994)

were used to estimate chronic dietary

exposure. For the chronic analyses,

mean residues from FDA monitoring

were used for lettuce and onions (dry

bulb). Residue field trial data were used

for broccoli, cabbage, cotton, green

onions, mustard greens, and pecans.

For acute dietary exposure analysis,

field trial residue data, along with

percent of crop treated data, were used

in the Monte Carlo analysis.

D. International Residue Limits

Codex MRLs for cypermethrin have

been established which are in harmony

with the U.S. tolerances for meat and

mbyp of cattle, goats, hogs, horses, and

sheep (0.05 ppm); milk (0.05 ppm); and

onions, bulb (0.10 ppm).

Codex MRLs have been established

which exceed the U.S. tolerances for

meat (fat basis) of cattle, goats, hogs,

horses, and sheep (0.2 vs. 0.05 ppm).

Codex MRLs have been established

which are below their U.S. counterparts

for cabbage (brassica vegetables) (1.0 vs.

2.0 ppm) and lettuce, head (2.0 vs. 10.0

ppm).

No Canadian MRLs have been

established for residues of

cypermethrin.

Mexico has established a tolerance for

residues of cypermethrin on cottonseed

(0.5 ppm) which is in harmony with the

U.S. tolerance.

As indicated in this unit, there are

differences between the FFDCA section

408 tolerances and the Codex MRL

values for specific commodities. These

differences could be caused by

differences in methods to establish

tolerances, calculations of animal feed

dietary exposure, and as a result of

different agricultural practices. EPA will

specifically address these differences

when the pesticides are reregistered and

the tolerances made permanent.

IV. Conclusion

Therefore, the tolerances are

established for residues of zetacypermethrin (s-cyano(3-

phenoxyphenyl) methyl (±) cis, trans 3-

(2,2-dichloroethenyl)-2,2-

dimethylcyclopropanecarboxylate) in or

on cabbage at 2.0 ppm; cottonseed at 0.5

ppm; lettuce, head at 10.0 ppm; onions,

bulb at 0.10 ppm; pecans at 0.05 ppm;

and fat, meat, and mbyp of cattle, goats,

hogs, horses, and sheep at 0.05 ppm.

V. Objections and Hearing Requests

The new section 408(g) of the FFDCA

provides essentially the same process

for persons to ‘‘object’’ to a tolerance

regulation issued by EPA under new

section 408(e) and (l)(6) of the FFDCA

as was provided in the old section 408

and in section 409 of the FFDCA.

However, the period for filing objections

is 60 days, rather than 30 days. EPA

currently has procedural regulations
Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations 63243

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

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

The official record for this

rulemaking, as well as the public

version, has been established for this

rulemaking under docket control

number OPP–300577 (including

comments and data submitted

electronically as described below). 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 official rulemaking record

is the paper record maintained at the

Virginia address in ‘‘ADDRESSES’’ at

the beginning of this document.

Electronic comments may be sent

directly to EPA at:

opp-docket@epamail.epa.gov.

Electronic objections and hearing

requests must be submitted as an ASCII

file avoiding the use of special

characters and any form of encryption.

Objections and hearing requests will

also be accepted on disks in

WordPerfect 5.1/6.1 or ASCII file

format. All copies of objections and

hearing requests in electronic form must

be identified by the docket control

number, OPP–300577. No 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.

VII. Regulatory Assessment

Requirements

This final rule establishes tolerances

under section 408(d) of the FFDCA 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 FR7 629, 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 section 408(d)

of the FFDCA, such as the tolerances in

this final rule, do not require the

issuance of a proposed rule, the

requirements of the Regulatory

Flexibility Act (RFA) (5 U.S.C. 601 et

seq.) do not apply. Nevertheless, the

Agency has previously assessed whether

establishing tolerances, exemptions

from tolerances, raising tolerance levels

or expanding exemptions might

adversely impact small entities and

concluded, as a generic matter, that

there is no adverse economic impact.

The factual basis for the Agency’s

generic certification for tolerance

actions published on May 4, 1981 (46

FR 24950) and was provided to the

Chief Counsel for Advocacy of the Small

Business Administration.

VIII. Submission to Congress and the

General Accounting Office

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.

James Jones,

Acting Director, Registration Division, Office

of Pesticide Programs.

Therefore, 40 CFR chapter I is

amended as follows:

PART 180—[AMENDED]

1. The authority citation for part 180

continues to read as follows:

Authority: 21 U.S.C. 346a and 371.

2. Section 180.418 is amended by

adding a new paragraph (a)(2) to read as

follows:

§ 180.418 Cypermethrin and an isomer

zeta-cypermethrin; tolerances for residues.

(a) * * *

(2) Tolerances are established for

residues of the insecticide zetacypermethrin (s-cyano(3-

phenoxyphenyl) methyl (±) cis, trans 3-

(2,2-dichloroethenyl)-2,2-

dimethylcyclopropanecarboxylate) in or

on the following commodities:
63244 Federal Register / Vol. 62, No. 228 / Wednesday, November 26, 1997 / Rules and Regulations

Commodity Parts per million

Cabbage ............... 2.0

Cattle, fat .............. 0.05

Cattle, mbyp .......... 0.05

Cattle, meat .......... 0.05

Cottonseed ............ 0.5

Goats, fat .............. 0.05

Goats, mbyp ......... 0.05

Goats, meat .......... 0.05

Hogs, fat ............... 0.05

Hogs, mbyp ........... 0.05

Hogs, meat ........... 0.05

Horses, fat ............ 0.05

Horses, mbyp ........ 0.05

Horses, meat ........ 0.05

Lettuce, head ........ 10.0

Milk ........................ 0.05

Onions, bulb .......... 0.10

Pecans .................. 0.05

Sheep, fat ............. 0.05

Sheep, mbyp ......... 0.05

Sheep, meat ......... 0.05

* * * * *

[FR Doc. 97–30938 Filed 11–25–97; 8:45 am]

BILLING CODE 6560–50–F