Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations 24941

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 address in

‘‘ADDRESSES’’ at the beginning of this

document.

III. Regulatory Assessment

Requirements

This final rule extends time-limited

tolerances that were previously

extended by EPA 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).

In addition, 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).

Since this extension of existing timelimited tolerances does 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.

IV. 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, EPA

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: April 22, 1998.

James Jones,

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.

§ 180.509 [Amended]

2. In § 180.509, the table in paragraph

(b) is amended by changing the date

‘‘August 1, 1998’’ to read ‘‘2/1/00’’,

wherever it appears.

[FR Doc. 98–11763 Filed 5–5–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Part 180

[OPP–300653; FRL–5788–5]

RIN 2070–AB78

Cymoxanil; Pesticide Tolerance

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

SUMMARY: This regulation establishes a

tolerance for residues of the fungicide,

cymoxanil, 2-cyano-N-

[(ethylamino)carbonyl]-2-

(methoxyimino) acetamide, in or on

potatoes. E.I. DuPont de Nemours &

Company submitted a petition under the

Federal Food, Drug and Cosmetic Act

(FFDCA), as amended by the Food

Quality Protection Act of 1996 (Pub. L.

104–170) requesting this tolerance.

DATES: This regulation is effective May

6, 1998. Objections and requests for

hearings must be received by EPA on or

before July 6, 1998.

ADDRESSES: Written objections and

hearing requests, identified by the

docket control number, [OPP–300653],

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–

300653], must also be submitted to:

Public Information and Records

Integrity Branch, Information Resources

and Services Division (7502C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person, bring

a copy of objections and hearing

requests to Rm. 119, 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–

300653]. 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: Mary Waller, Acting Product

Manager (PM) 21, 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) 308–9354, e-mail:

waller.mary@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: In the

Federal Register of (July 25, 1997, 62 FR

40075)(FRL–5726–4), EPA issued a

notice pursuant to section 408 of the

Federal Food, Drug, and Cosmetic Act

(FFDCA), 21 U.S.C. 346a(e) announcing

the filing of pesticide petition (PP

7F4805) for a tolerance by E.I. DuPont

de Nemours and Company, E. I. DuPont

Agricultural Products, Walker’s Mill,
24942 Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations

Barley Mill Plaza, P.O. Box 80038,

Wilmington, Deleware, 19880–0038.

This notice included a summary of the

petition prepared by E.I. DuPont de

Nemours & Company, the registrant. No

comments were received in response to

the notice of filing.

The petition requested that 40 CFR

180.503 be amended by establishing a

tolerance for residues of the fungicide

cymoxanil, 2-cyano-N-

[(ethylamino)carbonyl]-2-

(methoxyimino) acetamide, in or on

potatoes at 0.05 parts per million (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

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
Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations 24943

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 percent 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

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

(children 1 to 6 years 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 cymoxanil to make a

determination on aggregate exposure,

consistent with section 408(b)(2), for a

tolerance for residues of cymoxanil 2-

cyano-N-[(ethylamino)carbonyl]-2-

(methoxyimino) acetamide in or on

potatoes. EPA’s assessment of the

dietary exposures and risks associated

with establishing this tolerance 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 cymoxanil is

discussed below.

1. Acute toxicity. A battery of acute

toxicity studies resulted in an acute oral

LD50 = 760 milligrams/kilograms (mg/

kg) for males and LD50 =1,200 mg/kg for

females; an acute dermal LD50 > 2,000

mg/kg for both sexes; an acute

inhalation LC50 > 5.06 for both sexes; no

ocular irritation; slight dermal irritation

and a finding that the cymoxanil is not

a dermal sensitizer.

2. Subchronic toxicity. a. A

subchronic oral toxicity/neurotoxicity

study in rats fed cymoxanil at dose

levels of 0, 100, 750, 1,500, or 3,000

ppm (0, 6.54, 47.6, 102, or 224 mg/kg/

day for males, and 0, 8.0, 59.9, 137, or

333 mg/kg/day for females) for

approximately 97 days. A group of 10

rats/sex/dose were evaluated for

subchronic systemic toxicity and a

group of 10 rats/sex/dose underwent

neurobehavioral testing at pre-test, 5, 9,

and 13 weeks. The control and highdose groups were assessed for

neuropathology. The LOEL for

subchronic systemic toxicity is 1,500

ppm based on decreases in body

weights, body weight gains, and food

efficiency in the females, and body

weight decreases and testicular and

epididymal changes in the males. The

no-observed-effect level (NOEL) for

subchronic systemic toxicity is 750

ppm.

b. A subchronic oral study in mice fed

doses of 50, 500, 1,750, 3,500, or 7,000

ppm (average 8.25, 82.4, 294, 566, or

1,306 mg/kg/day, for males; 11.3, 121,

433, 846, or 1,130 mg/kg/day, for

females) for 98 days showed a decrease

in body weight gains in males dosed at

500, 1,750, and 3,500 ppm. An increase

in the absolute liver and spleen weights

was seen in females fed doses of 1,750

and 3,500 ppm. The NOEL was

established at 50 ppm for males and 500

ppm for females; the LOEL was 500

ppm for males and 1,750 ppm for

females.

c. A subchronic oral toxicity study

was conducted in dogs fed doses of 100

or 200 ppm (3 or 5 mg/kg/day) for 13

weeks, or at 250 ppm (5 mg/kg/day) for

2 weeks followed by 500 ppm (11 mg/

kg/day) for 11 weeks. The 250/500 ppm

males had lower epididymal and

testicular weights, and

aspermatogenesis was observed. The

LOEL is 3 mg/kg body weight/day (100

ppm) for dogs based on decreased body

weights and food consumption in

females. The NOEL was not established.

d. In a 28–day dermal toxicity study,

cymoxanil was applied to the shaved

backs of rats for 6 hrs/day at doses of 50,

500, and 1,000 mg/kg/day. There were

no demonstrated effects and no

compound-related histopathology. The

NOEL for systemic toxicity and dermal

irritation was 1,000 mg/kg/day, the

highest dose tested (HDT).

3. Chronic toxicity. a. A combined

chronic/carcinogenicity study was

conducted in rats fed cymoxanil at

doses of 0, 50, 100, 700, or 2,000 ppm

(0, 1.98, 4.08, 30.3, and 90.1 mg/kg/day

for males, and 0, 2.71, 5.36, 38.4, and

126 mg/kg/day for females) for 23

months. A satellite group was included

and terminated at 52 weeks. Because of

poor survival in controls and treated

rats, the study was terminated after 23

months. Survival was 24–45 percent

and 21–40 percent in the male and

female groups, respectively.

Chronic toxicity observed at 126 mg/

kg/day in females included significant

decreases in mean body weight and

body weight gains, a decrease in food

efficiency, and increased incidences of

non-neoplastic lesions in several organ

systems including the lungs, intestines,

and mesenteric lymph nodes. In females

receiving 38.4 mg/kg/day, chronic

toxicity was characterized by increased

incidences of non-neoplastic lesions of

the lungs, liver, sciatic nerve, and eyes

(retinal atrophy). Chronic toxicity in the

males dosed at 30.3 or 90.1 mg/kg/day

included aggressiveness and/or

hyperactivity, decreased mean body

weight and body weight gain, decreased

food efficiency, and increased incidence

of elongate spermatid degeneration and

retinal atrophy. No important effects
24944 Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations

were observed in the low- and low-middose groups. No increases in the

incidences of any neoplasm was

observed in dosed animals. The chronic

LOEL was 30.3 mg/kg/day for males and

38.4 mg/kg/day females based on

histologic changes detected in several

organs of the females and decreased

body weight, body weight gains, and

food efficiency observed in the males

and females. The chronic NOEL is 4.08

mg/kg/day for males and 5.36 mg/kg/

day for females. Under the conditions of

this study, there was no evidence of

carcinogenic potential.

b. A chronic toxicity study was

conducted in dogs fed cymoxanil at

doses of 25, 50, or 100 ppm for females

(0.7, 1.6, or 3.1 mg/kg/day) and 50, 100,

or 200 ppm for males (1.8, 3.0, or 5.7

mg/kg/day) for 52 weeks. The only

effect seen in females in the 100 ppm

treatment group was weight loss during

the first week of the study. No effect was

observed in females in the 25 or 50 ppm

group, or in males in the 50 or 100 ppm

group. The LOEL was 200 ppm for

males, based on depressed weight gains

through week 12 and changes in

hematology and blood chemistry. No

LOEL was established for females. The

NOEL was 100 ppm.

4. Carcinogenicity. a. A combined

chronic/carcinogenicity study,

conducted in rats (described in the

Chronic Toxicity Section, above, Unit

II.A.3.) showed no evidence of

carcinogenic potential.

b. A carcinogenicity study was

conducted in mice fed cymoxanil at

doses of 30, 300, 1,500, and 3,000 ppm

(4.19, 42.0, 216, and 446 mg/kg/day for

males; 5.83, 58.1, 298, and 582 mg/kg/

day for females) for approximately 80

weeks. Two additional groups were

sacrificed at 31–32 days for cell

proliferation and biochemical

evaluation.

Males and females dosed at 300 ppm

and above exhibited alterations in organ

weights and microscopic pathology.

Affected organs were the testes and

epididymis in males, the

gastrointestinal tract in females, and the

liver in both sexes. Male mice fed 300

ppm exhibited treatment-related

increased frequency of sperm cyst/cystic

dilation, tubular dilation, and increased

lymphoid aggregate. Centrilobular

apoptotic hepatocytes, pigmentcontaining macrophages, and granuloma

were detected in males dosed with 300

ppm. Elevated centrilobular

hepatocellular hypertrophy and

associated significant increases in liver

weight in males dosed with 300 ppm

was considered a pharmacologic

response to cymoxanil. Hyperplastic

gastropathy increased significantly in

300 ppm female mice and cystic

enteropathy of the small intestine

showed a significant positive trend. At

the 1,500 ppm dose, decreases in body

weight, body weight gain, and food

efficiencies were observed in males and

females. In addition to the testicular and

epididymal abnormalities observed at

the lower dose, the 1,500 ppm males

exhibited increased incidence of sperm

granuloma and bilateral oligospermia.

Females at 1,500 ppm exhibited the

microscopic liver abnormalities seen in

males at the lower dose. Cystic

enteropathy was observed in males at

1,500 ppm. At 3,000 ppm, there were

significant reductions in body weight,

body weight gain, food consumption,

and food efficiencies in males and

females. Survival over 18 months was

decreased in the 3,000 ppm females, 57

percent compared to 69 percent in

controls. Early deaths among high-dose

females were attributed to pancreatic

acinar cell necrosis and/or stress,

evidenced by splenal and thymic

atrophy and bone marrow congestion.

The 3,000 ppm females exhibited

increased frequency of pallor, weakness,

and hunching over. Male mice fed 3,000

ppm showed hematological signs of

decreased circulating erythrocyte mass

at the 12–month evaluation. The high

dose also resulted in gross and

microscopic pathology of the liver,

gastrointestinal tract, and testes. Dosing

was considered adequate based on

decreased body weight gains and an

increase in non-neoplastic lesions in

both sexes relative to the controls at the

highest dose level.

The LOEL was 300 ppm, based on

toxicity to the testes and epididymides

in males and toxicity to the

gastrointestinal mucosa in females. The

NOEL was 30 ppm. Under the

conditions of this study, there was no

evidence of a carcinogenic effect.

5. Developmental toxicity. a. A

prenatal developmental toxicity study

was conducted in rats gavaged with

cymoxanil on days 7–16 of gestation at

dose levels of 0, 10, 25, 75, or 150 mg/

kg/day. The maternal LOEL was 25 mg/

kg/day, based upon reduced body

weight, body weight change, and food

consumption. The maternal NOEL was

10 mg/kg/day. The developmental LOEL

was 25 mg/kg/day, based upon a

significant increase in overall

malformations and a generalized doserelated delay in skeletal ossification.

Fetal body weights were significantly

decreased at 75, 150 and 150 mg/kg/day.

Increased early resorptions resulted in

reduced litter sizes. The developmental

NOEL was 10 mg/kg/day.

b. A prenatal developmental toxicity

study was conducted in rabbits gavaged

with cymoxanil on days 6–18 of

gestation at dose levels of 0, 4, 8, or 16

mg/kg/day. There was no evidence of

treatment-related maternal or

developmental toxicity. A maternal and

developmental LOEL was not

determined; the maternal and

developmental NOEL was  ́ 16 mg/kg/

day. When considered along with other

prenatal developmental toxicity studies

in rabbits, this study provides

acceptable information that assists in

determining the overall maternal and

developmental NOEL and LOEL for

cymoxanil in a nonrodent species.

c. A prenatal developmental toxicity

study was conducted in rabbits gavaged

with cymoxanil on days 6–18 of

gestation at dose levels of 8, 16, or 32

mg/kg/day. Uncertainties regarding the

source of the parental rabbits

substantially reduced the confidence

that any observed skeletal effects were

solely related to treatment.

d. A prenatal developmental toxicity

study was conducted in rabbits gavaged

with cymoxanil on days 6–18 of

gestation at dose levels of 0, 1, 4, 8, or

32 mg/kg/day. The females showed

significant posttreatment increases in

body weight gain at 8 and 32 mg/kg/day.

The maternal LOEL was 8 mg/kg/day,

based upon a significant dose-related

rebound in maternal body weight. The

maternal NOEL was 4 mg/kg/day. The

developmental LOEL was 8 mg/kg/day,

based upon an increase in skeletal

malformations of the cervical and

thoracic vertebrae and ribs; and, at 32

mg/kg/day, cleft palate was observed.

The developmental NOEL was 4 mg/kg/

day.

6. Reproductive toxicity. A twogeneration reproduction study was

conducted in rats fed cymoxanil at

doses of 100, 500, or 1,500 ppm

(equivalent to 6.5, 32.1, or 97.9 mg/kg/

day in males and 7.9, 40.6, or 130 mg/

kg/day in females) over two consecutive

generations. No effects of treatment

were observed at 100 ppm. The parental

systemic LOEL was 500 ppm based

upon reduced pre-mating body weight,

body weight gain, and food

consumption for F1 males; and

decreased gestation and lactation body

weight for F1 females. The parental

systemic NOEL was 100 ppm. The

offspring LOEL was 500 ppm based

upon decreased F1 pup viability on

postnatal days 0–4 and on a significant

reduction in F2b pup weight. The

offspring NOEL was 100 ppm.

7. Neurotoxicity. a. The neurotoxicity

portion of the subchronic/neurotoxicity

study in rats demonstrated no effects on

the functional observation battery or on

motor activity after 5, 9, and 13 weeks

of dietary doses of cymoxanil at 0, 100,
Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations 24945

750, 1,500, or 3,000 ppm (0, 6.54, 47.6,

102, or 224 mg/kg/day for males, and 0,

8.0, 59.9, 137, or 333 mg/kg/day for

females) for 97 days. There were no

treatment-related gross or microscopic

findings detected in the nervous system

or skeletal muscles. Grip strength and

foot splay measurements were

decreased (non-significantly) in males at

224 mg/kg/day in the 13–week

subchronic neurotoxicity study in rats,

although these findings occurred in

conjunction with decreased body

weight. A LOEL for neurobehavioral and

neuropathic effects was not established.

The NOEL for neurotoxicity was 3,000

ppm.

b. In the combined chronic toxicity/

carcinogenicity study in rats, increased

incidence of sciatic nerve axon/myelin

degeneration was observed in females

fed cymoxanil at doses of 38.4 and 126

mg/kg/day for 104 weeks. Also,

increased incidence and severity of

retinal atrophy was observed in males at

30.3 and 90.1 mg/kg/day as well as in

females at 38.4 and 126 mg/kg/day.

These two findings demonstrated a

dose-related effect. In addition, clinical

observations of hyperactivity and

aggressiveness were reported in males at

700 and 2,000 ppm (30.3 and 90.1 mg/

kg/day).

c. In the carcinogenicity study in

mice, absolute brain weight was

decreased in both sexes at 1,500 and

3,000 ppm (216/298 mg/kg/day and

446/582 mg/kg/day for males/females,

respectively).

d. No evidence of developmental

anomalies of the fetal nervous system

were observed in the prenatal

developmental toxicity studies in either

rats, or rabbits, at maternally toxic oral

doses up to 25 and 32 mg/kg/day,

respectively. In addition, there was no

evidence of behavioral or neurological

effects on the offspring in the twogeneration reproduction study in rats.

e. There were no major data gaps for

the assessment of potential

neurotoxicological effects due to

cymoxanil. However, following a

weight-of-the evidence review of the

database, which suggested that

neuropathological lesions, changes in

brain weight, axon/myelin degeneration,

and retinal atrophy could result from

long-term exposure to cymoxanil, the

Agency will require a confirmatory

developmental neurotoxicity study in

rats.

8. Mutagenicity. Mutagenicity studies

with cymoxanil included gene mutation

assays in bacterial and mammalian

cells, a mouse micronucleus assay and

an in vivo/in vitro unscheduled DNA

synthesis (UDS) assay in rats. These

studies did not demonstrate

mutagenicity. An in vitro unscheduled

DNA synthesis assay-primary rat

hepatocytes was positive from 5–500 μg/

mL and cytotoxicity was seen at

concentrations of  ́ 500 μg/mL. A

chromosome aberrations in human

lymphocytes assay was also positive at

100 - 1,500 μg/mL, positive at 1,250 and

1,500 μg/mL -S9, and 850–1,500 μg/mL

+S9.

9. Metabolism. A metabolism study

was conducted by gavaging rats with

single doses of radiolabeled cymoxanil

at 2.5 or 120 mg/kg, or as a single dose

(2.5 mg/kg) following a 14–day

pretreatment with unlabeled cymoxanil

(2.5 mg/kg/day). Radiolabeled

cymoxanil was readily absorbed through

the intestinal tract. Maximum plasma

concentrations were attained within 3–

5 hours of dosing, then declined

steadily. Dose rate and pretreatment did

not appear to affect absorption.

Elimination was not dependent on sex

or dosing regimen; occurring

predominantly in the urine (63.8–74.8

percent), during the first 24 hours (58–

66 percent). Fecal excretion accounted

for 15.7–23.6 percent of the dose, and

radioactivity in the tissues and carcasses

accounted for <1 percent of the dose at

sacrifice for all three dosing regimens. A

pilot study indicated that approximately

3 percent of the dose would be expected

to be respired as 14CO2.

For each dosing regimen, there was

also no difference between male and

female rats in the distribution of

radioactivity in tissues. No

accumulation of radioactivity was

observed over time in any tissues.

However, in comparison, concentrations

of radioactivity were highest in liver

and kidney and lowest in brain tissue at

96 hours post-dosing sacrifice.

Peak plasma concentrations for the

low and high dose groups were attained

within 3–5 hours of dosing, and both

dose groups had similar elimination

half-lives from plasma, suggesting that

the metabolic process was not saturated

by the high dose. In addition, there was

a fortyfold difference in the area under

the curve for plasma from the low and

high dose groups, approximating the 48-

fold difference in the dose levels.

The metabolite profile in urine and

feces was similar between sexes and

among dose groups. In the urine, the

majority of the radioactivity (36.7–55

percent of the dose) was free and/or

conjugated [14C]glycine, and 2-cyano-2-

methoxyiminoacetic acid (IN-W3595)

(6.5–33 percent of the dose) was also

found. Intact [14C]cymoxanil was not

detected. In the feces, trace levels (<1

percent of the dose) of [14C]cymoxanil

and IN-W3595 were detected, but the

majority of radioactivity was the free

and conjugated [14C]glycine (8.5–13.1

percent of the dose). The data indicate

that the principal pathway for the

elimination of cymoxanil from rats is

via renal elimination.

Based on the data, the proposed

metabolic pathway involves hydrolysis

of cymoxanil to IN-W3595, which is

then degraded to glycine. Subsequently,

glycine is incorporated into natural

constituents or further metabolized.

10. Other toxicological

considerations. The submitted

mutagenicity test battery satisfied the

new mutagenicity initial testing battery

guidelines and the available studies

indicate that cymoxanil is not

mutagenic in bacterial or cultured

mammalian cells. There is, however,

confirmed evidence of clastogenic

activity and UDS induction in vitro. In

contrast, cymoxanil was neither

clastogenic nor aneurogenic in mouse

bone marrow cells and did not induce

a genotoxic response in rat somatic or

germinal cells. Accordingly, the

negative results from the mouse bone

marrow micronucleus assay support the

lack of carcinogenic effect in the rat and

mouse long-term feeding study.

Similarity of clinical signs were

observed in the micronucleus and in

vivo UDS assay, but the confidence in

the negative findings of the in vivo UDS

assay was not high because of a failure

to demonstrate that test material

reached either target tissue. It was

concluded that the test may have been

inadequate because of the short interval

between dosing and cell harvest.

Therefore, the Agency will be requiring

that a supplemental rat dominant lethal

assay be conducted to determine if any

effects are noted which are associated

with genetic damage to male germinal

cells.

B. Toxicological Endpoints

1. Acute toxicity-females 13+. To

assess acute dietary exposure, the

Agency used a NOEL of 4 mg/kg/day

from prenatal developmental toxicity

studies in rabbits based on an increase

in skeletal malformations of the cervical

and thoracic vertebrae and ribs at 8 mg/

kg/day. EPA determined that the 10x

factor to account for enhanced

sensitivity of infants and children

(required by FQPA) should be reduced

to 3x. An MOE of 300 is required for the

acute dietary assessment to protect the

sub-population of concern, ‘‘Females

13+,’’ due to neuropathological lesions

seen in the chronic toxicity study in rats

and the need for an additional

developmental neurotoxicity study.

Acute toxicity-general population. An

acute dose and endpoint was not

selected for the general population and
24946 Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations

the sub-population including ‘‘infants

and children’’ because there were no

observable effects in oral toxicology

studies, and no maternal toxicity in the

developmental toxicity studies in rats or

rabbits attributable to a single dose.

2. Short- and intermediate-term

residential toxicity. The Agency

determined that this dose and endpoint

was not applicable for risk assessment

because no dermal or systemic toxicity

was seen in a 28 day dermal toxicity

study, at the limit dose.

3. Chronic residential toxicity. Based

on the use pattern, chronic dermal

exposure is not anticipated and longterm dermal risk assessment is not

required.

4. Chronic dietary toxicity. An RfD of

0.013 mg/kg/day was established based

on a chronic feeding study in rats with

a NOEL of 4.08 mg/kg/day and an

uncertainty factor of 300.

5. Carcinogenicity. Based on the lack

of evidence of carcinogenicity in mice

and rats, EPA has classified cymoxanil

as a ‘‘not likely’’ human carcinogen,

according to EPA’s Proposed Guidelines

for Carcinogen Risk Assessment (April

10, 1996).

C. Exposures and Risks

1. From food and feed uses. Timelimited tolerances of 0.05 ppm have

been established in the 40 CFR

180.503(b) for residues of cymoxanil in

or on potatoes and tomatoes under

section 18 of FIFRA. In today’s action,

a tolerance will be established for

residues of cymoxanil in or on potatoes

at 0.05 ppm under section 3 of FIFRA

in 40 CFR 180.503(a) and the section 18

tolerance for potatoes will be removed.

Risk assessments were conducted by

EPA to assess dietary exposures and

risks from cymoxanil as follows:

a. Acute exposure and risk. Acute

dietary risk assessments are performed

for a food-use pesticide if a toxicological

study indicates an effect of concern may

occur as a result of a 1–day or single

exposure. For the subpopulation of

concern, females 13+, the estimated

acute MOE of 5,000 demonstrates no

acute dietary concern.

b. Chronic exposure and risk. The

chronic dietary risk analysis used the

RfD of 0.013 mg/kg/day. Chronic dietary

exposure estimates utilized tolerance

level residues on potatoes and tomatoes

and assumed 100 percent of the crops

were treated. The risk assessment

resulted in use of <1 percent of the RfD

for the general population, including

infants (< 1 year old), and < 2 percent

of the RfD for children (1–6 or 7–12

years old).

2. From drinking water. No

monitoring data are currently available

to perform a quantitative drinking water

risk assessment. Cymoxanil appears to

be mobile in soils, although its rapid

environmental dissipation precludes

extensive leaching. Cymoxanil was not

detected below 0–15 cm of soil.

Degradates of cymoxanil are mobile, but

short-lived, and are not expected to pose

a threat to ground water.

EPA estimated 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. Surface water

estimates derived from GENEEC

assumed 7 applications of 0.12 lbs.

active ingredient/acre would be applied.

The model indicated that cymoxanil in

surface water could reach 4.13 parts per

billion (ppb) (peak concentration) and

0.19 ppb (average 56 day concentration

).

a. Acute exposure and risk. EPA

calculated drinking water levels of

concern (DWLOC) for acute exposure by

using the acute toxicity endpoint. The

acute dietary food exposure (from the

DRES analysis) was subtracted from the

ratio of the acute NOEL (used for acute

dietary assessments) to the ‘‘acceptable’’

MOE for aggregate exposure to obtain

the acceptable acute exposure to

cymoxail in drinking water.

EPA has calculated DWLOCs for acute

exposure to cymoxanil in drinking

water for females (13+ years old) to be

380 ppb. The maximum estimated

concentrations of cymoxanil in surface

and ground water are below EPA’s

levels of concern for cymoxanil in

drinking water as a contribution to acute

aggregate exposure. Therefore, EPA

concludes with reasonable certainty that

residues of cymoxanil in drinking water

do not contribute significantly to the

aggregate acute human health risk.

b. Chronic exposure and risk. Chronic

(non-cancer), drinking water levels of

concern are 450 ppb for the U.S.

population and 130 ppb for children (1–

6 years old). The estimated average

concentrations of cymoxanil in surface

and ground water are less than EPA’s

levels of concern for cymoxanil in

drinking water as a contribution to

chronic aggregate exposure. Therefore,

EPA concludes with reasonable

certainty that residues of cymoxanil in

drinking water do not contribute

significantly to the aggregate chronic

human health risk.

3. From non-dietary exposure.

Cymoxanil is not registered for use on

residential non-food sites. Therefore, no

non-occupational, non-dietary exposure

and risk are expected.

4. Cumulative exposure to substances

with common mechanism of toxicity.

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

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
Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations 24947

case common mechanism of activity

will be assumed).

At this time, EPA does not have

available data to determine whether

cymoxanil has a common mechanism of

toxicity with other substances or how to

include this pesticide in a cumulative

risk assessment. Cymoxanil is

structurally related to metazachlor,

dimethenamid and amiphos. Of these

pesticides, only dimethenamid is

currently registered for use in the

United States. Unlike other pesticides

for which EPA has followed a

cumulative risk approach based on a

common mechanism of toxicity,

cymoxanil 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 cymoxanil has a common

mechanism of toxicity with other

substances and that structurally-related

chemicals will not have common toxic

metabolites to cymoxanil.

D. Aggregate Risks and Determination of

Safety for U.S. Population

1. Acute risk. The MOE for the acute

dietary (food only) risk assessment for

the population subgroup of concern,

females 13+ years, was estimated at

5,000. This risk estimate does not

exceed the Agency’s level of concern.

EPA has calculated drinking water

levels of concern (DWLOCs) for acute

exposure to cymoxanil in drinking

water for females (13+ years old) to be

380 ppb. Chronic (non-cancer), drinking

water levels of concern are 450 ppb for

the U.S. population and 130 ppb for

children (1–6 years old). Therefore, EPA

concludes with reasonable certainty that

the potential risks from aggregate acute

exposure (food & water) would not

exceed the Agency’s level of concern.

2. Chronic risk. Using the TMRC

exposure assumptions described above,

EPA has concluded that aggregate

exposure to cymoxanil from food will

utilize <1 percent of the RfD. The

estimated average concentrations of

cymoxanil in surface and ground water

are less than EPA’s levels of concern for

cymoxanil in drinking water as a

contribution to chronic aggregate

exposure. Therefore, EPA concludes

with reasonable certainty that residues

of cymoxanil in drinking water do not

contribute significantly to the potential

aggregate chronic human health risk at

the present time, considering the

present uses and those proposed in this

action.

E. Aggregate Cancer Risk for U.S.

Population

EPA has classified cymoxanil as a

‘‘not likely’’ human carcinogen, based

on the lack of evidence of

carcinogenicity in mice and rats, and

therefore has a reasonable certainty that

no harm will result from exposure to

residues of cymoxanil.

F. Aggregate Risks and Determination of

Safety for Infants and Children

Safety factor for infants and children

- in general. In assessing the potential

for additional sensitivity of infants and

children to residues of cymoxanil, 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 maternal pesticide

exposure during gestation.

Reproduction studies provide

information relating to effects from

exposure to the pesticide on the

reproductive capability of mating

animals and data on systemic toxicity.

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 uncertainty

factor (usually 100 for combined interand 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.

The Agency determined that for

cymoxanil, the 10x factor for the

protection of infants and children (as

required by FQPA) should be reduced to

3x, based on the following weight of the

evidence considerations: (1) No

increased sensitivity in fetuses as

compared to maternal animals was

observed following in utero exposures

in developmental studies in rats and

rabbits; (2) no increased sensitivity in

pups when compared to adults was seen

in the two-generation reproduction

study in rats; (3) the toxicology data

base is complete except for the

requirement to submit a developmental

neurotoxicity study; and (4) no frank

neurotoxicity was seen in the 90–day

neurotoxicity study. The Agency has

determined that a MOE of 300 is

required because of the observance of

neuropathological lesions in the chronic

toxicity study in rats and the need for

a developmental neurotoxicity study.

III. Other Considerations

A. 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.

B. Metabolism in Plants and Animals

Plants. Based on a metabolism study

on potatoes, the nature of the residue is

adequately understood. Only the parent

cymoxanil compound is of regulatory

concern.

Animals. Based on a metabolism

study in lactating goats, the nature of

the residue in animals is adequately

understood. Only the parent cymoxanil

compound is of regulatory concern.

C. Analytical Enforcement Methodology

An adequate enforcement method,

AMR 3705–95, is available to enforce

the tolerance on potatoes. Quantitation

is by HPLC/UV. These methods have

been submitted for publication in PAM

I. The methods are available to anyone

who is interested in pesticide residue

enforcement from: Calvin Furlow,

Information Resources and Services

Division (7502C), Office of Pesticide

Programs, Environmental Protection

Agency, 401 M St., SW., Washington,

DC 20460. Office location and telephone

number: Crystal Mall #2, Rm 101FF,

1921 Jefferson Davis Hwy., Arlington,

VA (703) 305–5229.

D. Magnitude of Residues

Residues of cymoxanil resulting from

the proposed use will not exceed 0.05

ppm in potatoes. The tolerance on

potatoes is for the raw agricultural

commodity as defined in 40 CFR

180.1(j)(1). For risk assessment

purposes, it was concluded that
24948 Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations

residues resulting from the proposed

use will not exceed 0.05 ppm in

potatoes.

E. International Residue Limits

There are no Codex or Canadian

residue limits established for cymoxanil

on potatoes but a Mexican maximum

residue limit (MRL) of 0.05 ppm is

established for potatoes. Therefore, no

compatibility problems exist for the

proposed tolerance on potatoes.

F. Rotational Crop Restrictions

The confined rotational crop studies

provided adequate results to conclude

that a 30–day plant back interval is

sufficient for all crops.

IV. Conclusion

Therefore, the tolerance is established

for residues of cymoxanil, 2-cyano-N-

[(ethylamino)carbonyl]-2-

(methoxyimino) acetamide, in or on the

raw agricultural commodity, potatoes, at

0.05 ppm.

V. Objections and Hearing Requests

The new FFDCA section 408(g)

provides essentially the same process

for persons to ‘‘object’’ to a tolerance

regulation issued by EPA under new

section 408(e) and (l)(6) as was provided

in the old section 408 and in section

409. However, the period for filing

objections is 60 days, rather than 30

days. EPA currently has procedural

regulations which govern the

submission of objections and hearing

requests. These regulations will require

some modification to reflect the new

law. However, until those modifications

can be made, EPA will continue to use

those procedural regulations with

appropriate adjustments to reflect the

new law.

Any person may, by July 6, 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 EPA docket for this

rule making. 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 Docket and Electronic

Submissions

EPA has established a record for this

rulemaking under docket control

number [OPP–300653] (including any

comments and data submitted

electronically). A public version of this

record, including printed, paper

versions of electronic comments, which

does not include any information

claimed as CBI, is available for

inspection from 8:30 a.m. to 4 p.m.,

Monday through Friday, excluding legal

holidays. The public record is located in

Room 119 of the Public Information and

Records Integrity Branch, Information

Resources and Services Division

(7502C), Office of Pesticide Programs,

Environmental Protection Agency,

Crystal Mall #2, 1921 Jefferson Davis

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

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 was published on May

4, 1981 (46 FR 24950) and was provided

to the Chief Counsel for Advocacy of the

Small Business Administration.

VIII. Submission to Congress and the

General Accounting Office

The Congressional Review Act, 5

U.S.C. 801 et seq., as added by the Small

Business Regulatory Enforcement

Fairness Act of 1996, generally provides

that before a rule may take effect, the

agency promulgating the rule must

submit a rule report, which includes a
Federal Register / Vol. 63, No. 87 /Wednesday, May 6, 1998 /Rules and Regulations 24949

copy of the rule, to each House of the

Congress and to the Comptroller General

of the United States. EPA will submit a

report containing this rule and other

required information to the U.S. Senate,

the U.S. House of Representatives, and

the Comptroller General of the United

States prior to publication of the rule in

the Federal Register. This rule is not a

‘‘major rule’’ as defined by 5 U.S.C.

804(2).

List of Subjects in 40 CFR Part 180

Environmental protection,

Administrative practice and procedure,

Agricultural commodities, Pesticides

and pests, Reporting and recordkeeping

requirements.

Dated: April 22, 1998.

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. Section 180.503 is amended by

adding text to paragraph (a) to read as

follows and by removing the entry for

‘‘potatoes’’ in paragraph (b) .

§ 180.503 Cymoxanil; tolerances for

residues.

(a) General . A tolerance is established

for residues of the fungicide, cymoxanil,

2-cyano-N-[(ethylamino)carbonyl]-2-

(methoxyimino) acetamide, in or on the

following food commodity.

Commodity Parts per million

Potatoes ............................... 0.05

* * * * *

[FR Doc. 98–11764 Filed 5–5–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

40 CFR Part 180

[OPP–300654; FRL–5789–3]

RIN 2070–AB78

Peroxyacetic Acid; Exemption From

the Requirement of a Tolerance

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Final rule.

SUMMARY: This document establishes an

exemption from the requirement of a

tolerance for residues of the

antimicrobial pesticide peroxyacetic

acid up to 100 ppm, in or on raw

agricultural commodities, in processed

commodities, when such residues result

from the use of peroxyacetic acid as an

antimicrobial agent on fruits, tree nuts,

cereal grains, herbs, and spices. Ecolab,

Inc. requested this exemption under the

Federal Food, Drug, and Cosmetic Act,

as amended by the Food Quality

Protection Act of 1996 (Pub. L. 104–

170).

DATES: This regulation is effective May

6, 1998. Objections and requests for

hearings must be received by EPA on or

before July 6, 1998.

ADDRESSES: Written objections and

hearing requests, identified by the

docket control number, [OPP–300654],

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–

300654], must also be submitted to:

Public Information and Records

Integrity Branch, Information Resources

and Services Division (7502C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person, bring

a copy of objections and hearing

requests to Rm. 119, 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–

300654]. 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: Marshall Swindell, Product

Manager 33, Antimicrobials Division

(7510W), Office of Pesticide Programs,

Environmental Protection Agency, 401

M St., SW., Washington, DC 20460.

Office location, telephone number, and

e-mail address: 2800 Crystal Drive, 6th

Floor, Arlington, VA, 22202, 703–308–

6341, e-mail:

swindell.marshall@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: In the

Federal Register of January 14, 1998 (63

FR 2232) (FRL–5759–6), EPA, issued a

notice pursuant to section 408 of the

Federal Food, Drug, and Cosmetic Act

(FFDCA), 21 U.S.C. 346a(e) announcing

the filing of a pesticide petition (PP)

7F4808 for tolerance by Ecolab, Inc., 370

Wabasha Street, St. Paul, MN 55102.

This notice included a summary of the

petition prepared by Ecolab, Inc., the

registrant. There were no comments

received in response to the notice of

filing.

Subsequently, the proposed tolerance

exemption was amended to delete meat,

meat by-products, poultry, milk, and

eggs. This was done because at the low

proposed use concentrations, no

residues of toxicological concern are

expected on any animal feeds that may

be exposed to peroxyacetic acid.

Therefore, no residues of toxicological

concern are anticipated either in

animals that may consume these feeds,

or in associated animal by-products.

In addition, the proposed tolerance

exemption was amended to include a

maximum residue limit of 100 ppm for

peroxyacetic acid. This limitation was

added because of Agency concerns that

a high use concentration could result in

measurable residues of peroxyacetic

acid. Residue data will be needed to

increase or remove this limitation.

I. Risk Assessment and Statutory

Findings

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

FFDCA allows EPA to establish a

tolerance or an exemption from the

requirement of a tolerance (the legal

limit for a pesticide chemical residue in

or on a food) only if EPA determines

that the tolerance or exemption from the

requirement of a 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