Federal Register / Vol. 60, No. 55 / Wednesday, March 22, 1995 / Proposed Rules 15113

* * * * *

[FR Doc. 95–6933 Filed 3–21–95; 8:45 am]

BILLING CODE 6560–50–F

40 CFR Parts 180, 185, and 186

[FAP 4H5683/P600; FRL–4935–1]

RIN 2070–AC18

Hexazinone; Pesticide Tolerances and

Food/Feed Additive Regulations

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Proposed rule.

SUMMARY: This document proposes to

amend the current tolerance for residues

of the herbicide hexazinone (3-

cyclohexyl-6-(dimethylamino)-1-

methyl-1,3,5-triazine-2,4(1H,3H)-dione

and its metabolites (calculated as

hexazinone) in or on sugarcane at 0.2

part per million (ppm) by revoking the

current tolerance and reestablishing the

same tolerance with regional

registration and tolerance as described

by 40 CFR 180.1(n). EPA also proposes

to establish food and feed additive

regulations for residues of hexazinone

and its metabolites (calculated as

hexazinone) in sugarcane molasses at

0.5 ppm. E. I. du Pont de Nemours &

Co., Inc., requested these proposed

regulations.

DATES: Written comments, identified by

the document control number [FAP

4H5683/P600], must be received on or

before April 21, 1995.

ADDRESSES: By mail, submit written

comments to: Public Response Section,

Field Operations Division (7506C),

Office of Pesticide Programs,

Environmental Protection Agency, 401

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

person, bring comments to: Rm. 1132,

CM #2, 1921 Jefferson Davis Hwy.,

Arlington, VA 22202.

Information submitted as a comment

concerning this document 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 comment 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. All written

comments will be available for public

inspection in Rm. 1132 at the Virginia

address given above, from 8 a.m. to 4

p.m., Monday through Friday, excluding

legal holidays.

FOR FURTHER INFORMATION CONTACT: By

mail: Joanne I. Miller, Product Manager

(PM) 23, Registration Division (7505C),

Environmental Protection Agency, 401

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

Office location and telephone number:

Rm. 237, CM #2, 1921 Jefferson Davis

Hwy., Arlington, VA 22202, (703–305–

7830).

SUPPLEMENTARY INFORMATION: E.I. du

Pont de Nemours & Co., Inc., has

requested a regional registration for the

use of hexazinone end-use pesticide

products for the use site, sugarcane. The

company proposed that the use-site

exclude the State of Florida, because the

product is not efficacious in muck soils

at dosages that would be economically

viable to growers. The company has

stated that the rate needed for weed

control in the typically high organic soil

of Florida used for the culture of

sugarcane would exceed the maximum

labelled dosage. In addition, the

company also stated that the high rates

would not be economically viable

considering other less expensive, lower

application rate products. Based on the

information submitted, the company has

proposed a geographically limited

registration for use of hexazinone in

sugarcane. In this case, the company

contends that there is little likelihood

for the use of hexazinone in the State of

Florida and that its residue data are

representative of all sugarcane-growing

areas of the United States.

Published information on acres of

sugarcane grown in the State of Florida

on other than organic soils (Spodosols,

Entisols, Mollisols) was 11.1% of a total

of 464,191 acres in 1993 (Sugar Y

Azucar 89:(1): 39–44). EPA has no data

on potential residues of hexazinone

when used in the culture of sugarcane

commodities from studies with

sugarcane cultured in the State of

Florida. Residue chemistry data from a

Florida study are required to allow the

unrestricted use of hexazinone in the

culture of sugarcane.

EPA issued a notice, published in the

Federal Register of July 13, 1994 (59 FR

35179), which announced that E.I. Du

Pont de Nemours & Co., Inc., had

submitted food additive petition (FAP)

4H5683 to EPA requesting that the

Administrator, pursuant to section 409

of the Federal Food, Drug and Cosmetic

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

40 CFR parts 185 and 186 by

establishing tolerances for residues of

the herbicide hexazinone (3-cyclohexyl6-dimethylamino)-1-methyl-1,3,5-

triazine-2,4-(1H,3H)-dione) in or on

sugarcane molasses at 5.0 ppm and

sugarcane bagasse at 0.5 ppm.

Sugarcane bagasse is not currently

considered a food or a feed commodity

by EPA; therefore, the requested

tolerance is not proposed to be

established in this document.

There were no comments received in

response to the notice of filing. The

scientific data submitted with the

petition and other relevant material

have been evaluated. The toxicological

and residue chemistry data considered

in support of the proposed actions

include the following:

1. Plant and animal metabolism

studies.

2. Enforcement methodology for

determining residues.

3. A 90-day feeding study with rats,

with a NOEL of 50 mg/kg/day and an

LEL of 150 mg/kg/day with the effect

being decreased body weights in both

sexes.

4. A 90-day feeding study with dogs,

with a NOEL of 25 mg/kg/day, increase

alkaline phosphatase, decreased

albumin/globulin, and increased

absolute and relative liver weights in

both sexes.

5. A 21-day dermal study in rabbits,

with a NOEL of 1,000 mg/kg/day, the

highest dose tested (HDT).

6. A 12-month chronic feeding study

with dogs, with a NOEL of 5.0 mg/kg/

day and a lowest effect level (LEL) of

37.5 mg/kg/day with thinness in one

male dog, increased alkaline

phosphatase in males, decrease albumin

and increased golbulin in males, pale

kidneys in one female, and increased

incidence of hepatocellular vacuolation

in males, and cytoplasmic inclusions

and pigmented Kupffer cells in the

livers of females.

7. A 24-month carcinogenicity study

in mice that was equivocal for

adenomas/carcinomas, with no

statistical significance in pair-wise

comparison between control and dosed

animals; systemic NOEL of 30 mg/kg/

day and systemic LEL of 375 mg/kg/day.

8. A developmental toxicity study

with rats, with a maternal NOEL of 100

mg/kg/day and maternal LEL of 400 mg/

kg/day; a developmental NOEL of 100

mg/kg/day and developmental LEL of

400 mg/kg/day (decreased fetal body

weight, increased incidence of fetuses

with no kidney papilla, and increased

incidence of fetus with unossified

sternebrae).

9. A developmental toxicity study in

rabbits, with a maternal NOEL of 50 mg/

kg/day and a maternal LEL of 125 mg/

kg/day (decreased body weight gains,

increased resorptions and increased

clinical signs); and with a

developmental NOEL of 50 mg/kg/day

and a developmental LEL of 125 mg/kg/

day (decreased body weight and delayed

ossifications of extremities).
15114 Federal Register / Vol. 60, No. 55 / Wednesday, March 22, 1995 / Proposed Rules

10. A two-generation reproductive

study with rats with a reproductive

NOEL of 10 mg/kg/day and an LEL of

100 mg/kg/day and an LEL of 100 mg/

kg/day (decreased pup weight in F1, F2a,

and F2b litters) and decreased pup

survival at 250 mg/kg/day in F2b litters;

systemic NOEL of 10 mg/kg/day and

LEL of 100 mg/kg/day (decreased body

weight and body weight gains).

11. A chronic feeding/carcinogenicity

study in rats with a negative

carcinogenic potential and a systemic

NOEL of 10 mg/kg/day and an LEL of

50 mg/kg/day (decreased food efficiency

and weight gains in females).

12. A gene mutation assay with

Salmonella strains TA1535, TA1537,

TA1538, TA100, and TA98 with and

without S–9 activation, negative.

13. A gene mutation (in vitro) CHO/

HGPRT assay at cytotoxic doses (13.9

mM, without S–9 and 9.9 mM with S–

9 activation), negative.

14. A structural chromosome

aberration (mammalian cells in culture)

cytogenetic assay in Chinese hamster

ovary cells with CHO chromosomal

aberrations with and without S–9

metabolic activation, positive.

15. A structural chromosome

aberration (mammalian cells in culture)

cytogenetic assay in rat bone marrow,

negative.

16. An unscheduled DNA synthesis

study with rats at doses of 1 × 105 to 30

mM, negative.

17. A rat metabolism study with a

single dose, resulted in 97% of

radioactivity excreted within 7 days (20

percent in feces and 77 percent in

urine); the major metabolites were

demethylated hydroxylated compounds.

As part of EPA’s evaluation of

potential human health risks,

hexazinone has been the subject of two

Peer Reviews by the Office of Pesticides’

Carcinogenicity Peer Review

Committee. The first Peer Review, dated

October 10, 1991, indicated that based

on the weight of evidence, hexazinone

was classified as a Group C carcinogen,

possible human carcinogen. The

committee recommended that for the

purposes of risk characterization, the

EPA reference dose (RfD) approach

should be used for quantification of

human risk.

E. I. du Pont de Nemours & Co.

questioned the finding of the first Peer

Review and presented a reevaluation of

the mouse carcinogenic study based on

contemporary diagnostic nomenclature

of the pathology of the neoplasium

found. The pathologist classified the

hepatocellular carcinomas and

hyperplastic nodules as either

hepatocellular carcinoma,

hepatocellular adenoma, or a focus of

cellular alteration (nonneoplastic). The

Peer Review findings were based on a

pathological diagnosis that classified all

hyperplastic nodules as tumors/

adenomas.

A second Peer Review dated May 11,

1994, was conducted based on the

reclassification of the pathology. Based

on another weight-of-evidence

evaluation the Carcinogenicity Peer

Review Committee determined that

hexazinone should be recategorized as a

Group D, not classifiable as to human

carcinogenicity. That is, the evidence is

inadequate and cannot be interpreted as

showing either the presence or absence

of a carcinogenic effect. Based on this

conclusion, EPA determines that

hexazinone does not induce cancer

within the meaning of the Delaney

Clause.

The Peer Review Committee

considered the following facts regarding

the toxicology data on hexazinone in a

weight-of-evidence determination of

carcinogenic potential:

1. Based on the registrant’s

submission of reevaluated liver sections,

hexazinone feed in the diet of CD-1

male and female mice was not

associated with any pairwise

statistically significant increases in

adenomas, carcinomas, or combined

adenomas/carcinomas, when the

controls were compared to the treated

groups. Female mice had a statistically

significant dose-related trend (P = 0.014)

for combined hepatocellular adenoma/

carcinoma, but the pairwise comparison

of the high-dose group to control was

not statistically significant. The

incidence of combined hepatocellular

adenomas/carcinomas (9%) in females

at the highest dose exceeded the range

of these tumors in historical controls (0-

5%).

Male mice had a statistically

significant increasing dose-related trend

in foci of cellular alteration in the liver

and also a significant increase (p =

0.004) in these nonneoplastic lesions in

the pairwise comparison of the highest

dose and the controls. The HDT,

although very high, was not considered

by the Committee to have been

excessive for assessing the carcinogenic

potential of hexazinone in mice.

2. Hexazinone fed in the diet to male

and female Spragus-Dawley rats at doses

up to 125 mg/kg/day was not associated

with statistically significant increases of

any neoplasms in either sex.

The dosing in this study was

considered to be marginally adequate

based on the lack of significant toxicity

and enhanced survival.

3. Hexazinone was mutagenic both

with and without S-9 activation in an in

vivo assay for chromosomal aberrations

in Chinese hamster ovary cells (almost

at the level of a positive control without

activation). The response in a Chinese

hamster ovary (CHO) gene mutation

assay with activation was equivocal.

Hexazinone was negative in the

Salmonella assay, in an in vivo

cytogenetic assay, and in a UDS assay.

4. Hexazinone is structurally, but not

chemically (lacks aromaticity), related

to the 2-triazines, which are usually

associated with mammary gland tumors

in Sprague-Dawley rats (the same strain

used in the hexazinone study).

Phenobarbital was considered to be a

closer analog, both structurally and

chemically, but unlike hexazinone,

phenobarbital has no known

genotoxicity. Hexazinone may also be

viewed as a pyrimidine analog, a

property which is thought to be

predictive of carcinogenicity.

The Reference Dose (RfD) is

established at 0.05 mg/kg/day, based on

a NOEL of 5.0 mg/kg/day in the 12-

month dog-feeding study and an

uncertainty factor of 100. The

Anticipated Residue Contribution (ARC)

from the current actions is estimated at

7.4 × 10-5 mg/kg of body weight/day for

the general population and utilizes less

than 15% of the RfD for the U.S.

population. The ARC for the most

exposed subgroups is 2.0 × 10¥2 mg/kg/

body weight/day for nonnursing infants

(less than 1 year old) and 1.0 × 10¥2 mg/

kg/body weight/day for children (1 to 6

years old), or 40.0 and 20.0 percent of

the RfD, respectively. No appreciable

risk is expected from chronic dietary

intake because the RfD is not exceeded

for either the general population or any

subgroup.

The nature of the residue is

adequately understood for establishing

these tolerances.

An adequate analytical method, gas

chromatography with a nitrogenphosphorus detector, is available for

enforcement purposes.

The pesticide is considered useful for

the purpose for which these tolerances

are sought, and these tolerances will

limit dietary exposure to this pesticidal

chemical. There are currently no actions

pending against the registration of this

chemical.

Based on the information and data

considered, the Agency has determined

that the tolerances and food/feed

additive regulations established by

amending 40 CFR parts 180, 185, and

186 would protect the public health.

Therefore, it is proposed that the

tolerances and food/feed additive

regulations be established as set forth

below.

Any person who has registered or

submitted an application for registration
Federal Register / Vol. 60, No. 55 / Wednesday, March 22, 1995 / Proposed Rules 15115

of a pesticide, under the Federal

Insecticide, Fungicide, and Rodenticide

Act (FIFRA) as amended, which

contains any of the ingredients listed

herein, may request within 30 days after

publication of this document in the

Federal Register that this rulemaking

proposal be referred to an Advisory

Committee in accordance with section

408(e) of the FFDCA.

Interested persons are invited to

submit written comments on the

proposed regulation. Comments must

bear a notation indicating the document

control number, [FAP 4H5683/P600].

All written comments filed in response

to this petition will be available in the

Public Response and Program Resources

Branch, at the address given above from

8 a.m. to 4 p.m., Monday through

Friday, except legal holidays.

Under Executive Order 12866 (58 FR

51735, Oct. 4, 1993), the Agency must

determine whether the regulatory action

is ‘‘significant’’ and therefore subject to

all the requirements of the Executive

Order (i.e., Regulatory Impact Analysis,

review by the Office of Management and

Budget (OMB)). Under section 3(f), the

order defines ‘‘significant’’ as those

actions likely to lead to a rule (1) having

an annual effect on the economy of $100

million or more, or adversely and

materially affecting a sector of the

economy, productivity, competition,

jobs, the environment, public health or

safety, or State, local or tribal

governments or communities (also

known as ‘‘economically significant’’);

(2) creating serious inconsistency or

otherwise interfering with an action

taken or planned by another agency; (3)

materially altering the budgetary

impacts of entitlement, grants, user fees,

or loan programs; or (4) raising novel

legal or policy issues arising out of legal

mandates, the President’s priorities, or

the principles set forth in this Executive

Order.

Pursuant to the terms of this

Executive Order, EPA has determined

that this rule is not ‘‘significant’’ and is

therefore not subject to OMB review.

Pursuant to the requirements of the

Regulatory Flexibility Act (Pub. L. 96–

354, 94 Stat. 1164, 5 U.S.C. 601–612),

the Administrator has determined that

regulations establishing new tolerances

or raising tolerance levels or

establishing exemptions from tolerance

requirements do not have a significant

economic impact on a substantial

number of small entities. A certification

statement to this effect was published in

the Federal Register of May 4, 1981 (46

FR 24950).

List of Subjects in 40 CFR Parts 180,

185, 186

Administrative practice and

procedure, Agricultural commodities,

Food additives, Feed additives,

Pesticides and pests, Processed foods,

Reporting and recordkeeping

requirements.

Dated: March 9, 1995.

Daniel M. Barolo,

Director, Office of Pesticide Programs.

Therefore, it is proposed that 40 CFR

parts 180, 185, and 186 be amended as

follows:

PART 180—[AMENDED]

1. In part 180:

a. The authority citation for part 180

continues to read as follows:

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

b. In § 180.396, the existing text is

designated as paragraph (a), and the

table therein is amended by removing

the entry for sugarcane, and new

paragraph (b) is added, to read as

follows:

§ 180.396 Hexazinone; tolerances for

residues.

(a) * * *

(b) A tolerance with regional

registration, as defined in § 180.1(n) and

which excludes use of hexazinone on

sugarcane in Florida, is established for

combined residues of the herbicide

hexazinone (3-cyclohexyl-6-

(dimethylamino)-1-methyl-1,3,5-

triazine-2,4(1H,3H)-dione) and its

metabolites (calculated as hexazinone)

in or on the following raw agricultural

commodity:

Commodity Parts per

million

Sugarcane ................................. 0.2

PART 185—[AMENDED]

2. In part 185:

a. The authority citation for part 185

continues to read as follows:

Authority: 21 U.S.C. 346a and 348.

b. By adding new § 185.3575, to read

as follows:

§ 185.3575 Hexazinone; tolerances for

residues.

A food additive tolerance with

regional registration, as defined in

§ 180.1(n) and which excludes use of

hexazinone on sugarcane in Florida, is

established for combined residues of the

herbicide hexazinone (3-cyclohexyl-6-

(dimethylamino)-1-methyl-1,3,5-

triazine-2,4(1H,3H)-dione) and its

metabolites (calculated as hexazinone)

in or on the following commodity:

Commodity Parts per

million

Sugarcane, molasses ............... 0.5

PART 186—[AMENDED]

3. In part 186:

a. The authority citation for part 186

continues to read as follows:

Authority: 21 U.S.C. 348.

b. By adding new § 186.3575, to read

as follows:

§ 186.3575 Hexazinone; tolerances for

residues.

A feed additive tolerance with

regional registration, as defined in

§ 180.1(n) and which excludes use of

hexazinone on sugarcane in Florida, is

established for combined residues of the

herbicide hexazinone (3-cyclohexyl-6-

(dimethylamino)-1-methyl-1,3,5-

triazine-2,4(1H,3H)-dione and its

metabolites (calculated hexazinone) in

or on the following feed commodity:

Commodity Parts per

million

Sugarcane, molasses ............... 0.5

[FR Doc. 95–6931 Filed 3–21–95; 8:45 am]

BILLING CODE 6560–50–F

DEPARTMENT OF TRANSPORTATION

Coast Guard

46 CFR Parts 4 and 5

[CGD 95–023]

Marine Safety Investigation Process

Review

AGENCY: Coast Guard, DOT.

ACTION: Notice and request for

comments.

SUMMARY: The Coast Guard conducts

marine casualty investigations to

determine the causes of casualties. The

findings of an investigation may lead to

proceedings for the suspension or

revocation of a merchant mariner’s

license, certificate of registry, or

document, the assessment of a civil

penalty, or to criminal prosecution. The

Coast Guard is reviewing its marine

safety investigation process to identify

possible improvements, and is seeking

input from the public.