62304 Federal Register / Vol. 62, No. 225 / Friday, November 21, 1997 / Notices

ERP No. F–FHW–E54009–NC, US 117

Corridor Improvement Project, US 13/70

at Goldsboro, north to US 301 in

Wilson, Funding and Section 404

Permit, Wayne and Wilson Counties,

NC.

Summary: EPA continued to favor

Alternative 1, the improvement of the

present road, or Alternative 4, a new

alignment outside the Little River

critical watershed area. EPA is

concerned that this project could

directly or indirectly cause the

degradation of the Little River and

reduce the classified use of this river as

a water supply. EPA would like to see

commitments to long-term maintenance

of measures to minimize the inflow of

pollutants to the river.

ERP No. F–FHW–K50007–CA,

Benicia-Martinez Bridge System Project,

Construction/Reconstruction, Portions

of I–680, I–780 and I–80 Corridors,

Funding, U.S. CGD Bridge Permit and

COE Section 10 and 404 Permits, Contra

Costa and Solano Counties, CA.

Summary: EPA expressed continuing

concerns on the placement of new toll

booths in close proximity to an

industrial facility using hazardous

materials and requested FHWA to

reconsider its decision. EPA also

requested FHWA provide additional

information on a contingency plan to

guide travelers along the highway in the

event of a chemical upset or accidental

releases. EPA asked that the Record of

Decision clarify what level of High

Occupancy Vehicle (HOV) features

would be part of the project, and

strongly recommend that all feasible

efforts to implement one or more

dedicated HOV lanes for both north and

southbound traffic in peak commute

periods be part of the final project.

ERP No. F–NAS–A12041–00, X–33

Advanced Technology Demonstrator

Vehicle Program, Final Design,

Construction and Testing,

Implementation, Approvals and Permits

Issuance, CA, UT and WA.

Summary: EPA had no objection to

proposed action.

ERP No. F–USN–L11031–WA, Puget

Sound Naval Station, Sand Point,

Disposal and Reuse, Implementation,

King County, WA.

Summary: Review of the Final EIS

was not deemed necessary. No formal

comment letter was sent to the

preparing agency.

ERP No. FA–DOE–K03007–CA,

Petroleum Production at Maximum

Efficient Rate, updated Information for

the Sale of Naval Petroleum Reserve No.

1 (NPR–1 also called ‘‘Elk Hills’’)

Amendment for Kern County General

Plan, Elk Hills, Kern County, CA.

Summary: Review of the Final EIS

was not deemed necessary. No formal

comment letter was sent to the

preparing agency.

Dated: November 18, 1997.

B. Katherine Biggs,

Associate Director, NEPA Compliance

Division, Office of Federal Activities.

[FR Doc. 97–30696 Filed 11–20–97; 8:45 am]

BILLING CODE 6560–50–U

ENVIRONMENTAL PROTECTION

AGENCY

[PF–778; FRL–5755–4]

Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: This notice announces the

initial filing of pesticide petitions

proposing the establishment of

regulations for residues of certain

pesticide chemicals in or on various

food commodities.

DATES: Comments, identified by the

docket control number PF–778, must be

received on or before December 22,

1997.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch, Information

Resources and Services Division

(7502C), Office of Pesticides Programs,

Environmental Protection Agency, 401

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

person bring comments to: Rm. 1132,

CM #2, 1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically to: oppdocket@epamail.epa.gov. Follow the

instructions under ‘‘SUPPLEMENTARY

INFORMATION.’’ No confidential

business information should be

submitted through e-mail.

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). CBI should not be submitted

through e-mail. Information marked as

CBI 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 address

given above, from 8:30 a.m. to 4 p.m.,

Monday through Friday, excluding legal

holidays.

FOR FURTHER INFORMATION CONTACT: The

product manager listed in the table

below:

Product Manager Office location/telephone number Address

Joanne Miller (PM 23) ... Rm. 237, CM #2, 703–305–6224, e-mail:miller.joanne@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Kerry Leifer .................... Rm. 4W17, CS #1, 703–308–8811, e-mail: leifer.kerry@epamail.epa.gov. 2800 Crystal Drive, Arlington,

VA

SUPPLEMENTARY INFORMATION: EPA has

received pesticide petitions as follows

proposing the establishment and/or

amendment of regulations for residues

of certain pesticide chemicals in or on

various food commodities under section

408 of the Federal Food, Drug, and

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

EPA has determined that these petitions

contain data or information regarding

the elements set forth in section

408(d)(2); however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data supports granting of the

petition. Additional data may be needed

before EPA rules on the petition.

The official record for this notice of

filing, as well as the public version, has

been established for this notice of filing

under docket control number [PF–778]

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 record is located

at the address in ‘‘ADDRESSES’’ at the

beginning of this document.

Electronic comments can be sent

directly to EPA at:

opp-docket@epamail.epa.gov
Federal Register / Vol. 62, No. 225 / Friday, November 21, 1997 / Notices 62305

Electronic comments must be

submitted as an ASCII file avoiding the

use of special characters and any form

of encryption. Comment and data will

also be accepted on disks in

Wordperfect 5.1 file format or ASCII file

format. All comments and data in

electronic form must be identified by

the docket number PF-778 and

appropriate petition number. Electronic

comments on notice may be filed online

at many Federal Depository Libraries.

List of Subjects

Environmental protection,

Agricultural commodities, Food

additives, Feed additives, Pesticides and

pests, Reporting and recordkeeping

requirements.

Dated: November 10, 1997

James Jones,

Acting Director, Registration Division, Office

of Pesticide Programs.

Summaries of Petitions

Petitioner summaries of the pesticide

petitions are printed below as required

by section 408(d)(3) of the FFDCA. The

summaries of the petitions were

prepared by the petitioners and

represent the views of the petitioners.

EPA is publishing the petition

summaries verbatim without editing

them in any way. The petition summary

announces the availability of a

description of the analytical methods

available to EPA for the detection and

measurement of the pesticide chemical

residues or an explanation of why no

such method is needed.

1. BASF Corporation

PP 7F4848

EPA has received a pesticide petition

(PP 7F4848) from BASF Corporation,

P.O. Box 13528, Research Triangle Park,

NC 27709-3528 proposing pursuant to

section 408(d) of the Federal Food, Drug

and Cosmetic Act, 21 U.S.C. 346a(d), to

amend 40 CFR part 180 by establishing

tolerances for residues of diflufenzopyr,

(2-[1-[[[(3,5-difluorophenyl)

amino]carbonyl]hydrazono] -ethyl]-3-

pyridinecarboxylic acid), and its

metabolites M1 (8-methylpyrido(2,3-

d)pyridazin-5(6H)-one) and M5 (6-((3,5-

Difluorophenyl-carbamoyl-8-methylpyrido (2,3-d)-5-pyridazinone) all as the

M1 component in or on the raw

agricultural commodities corn grain,

corn forage and corn fodder at 0.05 parts

per million (ppm). EPA has determined

that the petition contains data or

information regarding the elements set

forth in section 408(d)(2) of the FFDCA;

however, EPA has not fully evaluated

the sufficiency of the submitted data at

this time or whether the data supports

granting of the petition. Additional data

may be needed before EPA rules on the

petition.

A. Residue Chemistry

1. Analytical method. The proposed

analytical method involves extraction,

partition, clean-up and detection of

residues by gas chromatography/

nitrogen phosphorous detector (gc/npd).

2. Magnitude of residues. Over 20

residue trials were conducted in 16

states. Residues of diflufenzopyr, M5

and M1 were measured as M1 by gc/

npd. The method of detection had a

limit of detection of 0.01 parts per

million (ppm). Residues ranged from

non detectable (majority) to 0.02 ppm rt

text.

B. Toxicological Profile

1. Acute toxicity. A battery of acute

toxicity tests were conducted which

place diflufenzopyr in acute oral

toxicity category IV, acute dermal

toxicity category IV, acute inhalation

toxicity category IV, primary eye

irritation category III, and primary

dermal irritation category IV.

Diflufenzopyr is not a dermal sensitizer.

Diflufenzopyr is not a neurotoxin in

males and females at 2,000 mg/kg (limit

test).

2. Genotoxicity. Diflufenzopyr was

found to be negative for mutagenicity in

a battery of mutagenicity tests (Ames

Testing, Mouse Lymphoma testing In

vivo micronucleus assay (mouse) and

Unscheduled DNA synthesis).

3. Reproductive and developmental

toxicity—i. Developmental toxicity (rat).

Sprague-Dawley rats were dosed with 0,

100, 300 and 1,000 mg/kg/day

diflufenzopyr in the diet from days 6

through 15 of gestation. The maternal no

observed adverse effect level (NOAEL)

was determined to be 300 mg/kg/day

and the maternal lowest effect level

(LEL) was determined to be 1,000 mg/

kg/day based on reduced body weight

gain, and reduced absolute and relative

feed consumption during the dosing

period. The developmental NOAEL was

determined to be 300 mg/kg/day and the

developmental LEL was determined to

be 1,000 mg/kg/day based on reduced

fetal body weight and reversible delays

in sternal and caudal vertebral

ossification.

ii. Developmental toxicity (rabbit).

New Zealand white rabbits were dosed

with 0, 30, 100, and 300 mg/kg/day

diflufenzopyr in the diet from days 6

through 19 of gestation. The maternal

NOEL was determined to be 30 mg/kg/

day and the maternal LEL was

determined to be 100 mg/kg/day based

on increased incidence of abnormal

feces and weight loss for the entire

dosage period. The developmental

NOEL was determined to be 100 mg/kg/

day and the developmental LEL was

determined to be 300 mg/kg/day based

on increased incidences of

supernumerary thoracic ribs, a variation

in fetal ossification that commonly

occurs at maternally toxic dosages. Only

at the 300 dose level deaths and

abortions were accompanied by gastric

trichobezoars. Diflufenzopyr was not

teratogenic to rabbit fetuses even at the

higher of two dosages (100 and 300 mg/

kg/day) that were toxic to the does.

iii. Reproductive toxicity testing. In a

2-Generation Reproduction study,

Wistar rats were dosed with 0, 500,

2,000 and 8,000 ppm diflufenzopyr in

the diet. The parental: systemic NOAEL/

reproductive-developmental NOEL was

determined to be 2,000 ppm in both

sexes (averaging 600 mg/kg/day in

females during gestation). The parental

LEL was determined to be 8,000 ppm

(averaging 2,500 mg/kg/day in females

during gestation) based on weight gain

deficits in males and females during

premating and pregnancy phases. The

developmental NOEL was determined to

be 2,000 ppm (averaging 400 mg/kg/day

in dams during lactation) and the LEL

determined to be 8,000 ppm (averaging

1,500 mg/kg/day in dams during

lactation) based on slightly lower live

birth (93%) and viability (90%) indices.

4. Subchronic toxicity— i. 21-Day

dermal (rabbit). Rabbits were repeatedly

dosed with diflufenzopyr at 0, 100, 300

and 1,000 mg/kg/day for 21 days. The

NOAEL for systemic toxicity and dermal

irritation was determined to be 1,000

mg/kg/day.

ii. 90-Day rodent (rat). Wistar rats

were dosed with diflufenzopyr at 0,

1,000, 5,000, 10,000 and 20,000 ppm in

the diet for 90 days. The NOEL was

determined to be 5,000 ppm (350 mg/

kg/day) for males and 430 mg/kg/day in

females. The LEL was determined to be

10,000 ppm (720 mg/kg/day) for males

and 890 mg/kg/day in females based on

reduced body weight gains, impaired

food utilization; disturbances in

hematology values in males, clinical

chemistry values in both sexes, values

for urinalysis in females; with

histopathology seen in both sexes as

increased foamy macrophages in the

lungs.

iii. 90-Day mouse. CD-1 mice were

dosed with diflufenzopyr at 0, 350,

1,750, 3,500 and 7,000 ppm in the diet

for 13 weeks. The NOEL was

determined to be 7,000 ppm (1,225 mg/

kg/day) in males and (1,605 mg/kg/day)

in females as no clear toxic effects were

observed.

iv. 90-Day non-rodent (dog). Beagle

dogs were dosed with diflufenzopyr at
62306 Federal Register / Vol. 62, No. 225 / Friday, November 21, 1997 / Notices

0, 1,500, 10,000, and 30,000 ppm in the

diet for 13 weeks. The NOEL was

determined to be 1,500 ppm (58 mg/kg/

day) in males and (59 mg/kg/day) in

females. The LEL was determined to be

10,000 ppm (403 mg/kg/day) in males

and (424 mg/kg/day) in females based

on histopathological disturbances seen

as erythreoid hyperplasia in the bone

marrow and extramedullary

hemopoiesis in the liver of a few dogs

and hemosiderin deposits in Kupffer

cells in 1 female dog.

v. 90-Day neurotoxicity (rat). Rats

were dosed with diflufenzopyr at 0, 25,

75, and 1,000 mg/kg/day in the diet for

13 weeks. At the 1,000 mg/kg/day

treatment there was associated weight

gain and impaired efficiency of food

utilization. Therefore the no adverse

effect level was set at 75 mg/kg/day. The

NOAEL for subchronic neurotoxicity

was determined to be 1,000 mg/kg/day

based on the absence of changes

indicative of neurotoxicity.

5. Chronic toxicity—i. 1-Year nonrodent (dog). Beagle dogs were dosed

with diflufenzopyr at 0, 750, 7,500 and

15,000 ppm in the diet for one year. The

NOEL was determined to be 750 ppm

(26 mg/kg/day) in males and (28 mg/kg/

day) in females. The LOAEL was 7,500

ppm (299 mg/kg/day) in males and (301

mg/kg/day) in females. This is based on

an erythropoietic response in bone

marrow and increased hemosiderin

deposits in spleen, liver and kidneys.

Peripheral hematology investigations

revealed mild to moderate

reticulocytosis at the 7,500 and 15,000

ppm dose levels, in the absence of any

signs of anemia. The erythropoietic

response of bone marrow is thought to

compensate probable toxic effects to

erythrocytes. Because of a similarity of

NOEL levels from this dog study and the

rat chronic/oncogenicity study a

suggested risk assessment reference

dose (Rfd) is calculated by using 25 as

a Noel level with a 100 fold safety factor

ending with 0.25 mg/kg/day.

ii. Combined rodent chronic toxicity/

oncogenicity (rat). Wistar rats were fed

0, 500, 1,500, 5,000 and 10,000 ppm

diflufenzopyr in the diet for 104 weeks.

The NOEL was determined to be 500

ppm (22 mg/kg/day) in males and (29

mg/kg/day) in females. The NOAEL was

determined to be 1,500 ppm (69 mg/kg/

day) in males and (93 mg/kg/day) in

females based on reduced body weight

gains of 8 % in males and 7% in

females. The LEL was determined to be

5,000 ppm (235 mg/kg/day ) in males

and(323 mg/kg/day) in females based on

9% reduced weight gain in females and

11% in males plus males showed lower

triglyceride and higher phosphate

levels. Diflufenzopyr was not

carcinogenic under the conditions of the

test.

iii. Oncogenicity in the rodent

(mouse). CD-1 mice were fed 0, 700,

3,500 and 7,000 ppm diflufenzopyr in

the diet for 78 weeks. The NOAEL was

determined to be 7,000 ppm (1037 mg/

kg/day) in males and (1,004 mg/kg/day)

in females. There were no changes or

histopathological findings attributed to

the dietary inclusion of test material in

the 52 (interim) or 78 (terminal) week

animals. Diflufenzopyr was not

carcinogenic under the conditions of the

test.

C. Aggregate Exposure

1. Dietary exposure. The potential

aggregate dietary exposure is based on

the Theoretical Maximum Residue

Contribution (TMRC) from the

tolerances for all crops on which

diflufenzopyr is to be applied. The

TMRC from the proposed use of

diflufenzopyr of corn at the tolerance

level of 0.05 ppm is 0.173168 ug/kg/day,

and utilizes 0.069 percent of the RfD for

the overall U.S. population. The

exposure of the most highly exposed

subgroup in the population, nonnursing infants, is 0.195424 ug/kg/day,

and utilizes 0.078 percent of the RfD.

2. Drinking water. Based on the

studies submitted to EPA for assessment

of environmental risk, BASF does not

anticipate exposure to residues of

diflufenzopyr in drinking water. There

is no established maximum

concentration level for residues of

diflufenzopyr in drinking water under

the Safe Drinking Water Act.

3. Non-dietary exposure. BASF has

not estimated non-occupational

exposure for diflufenzopyr since the

only pending registration for

diflufenzopyr is limited to commercial

crop production use. Diflufenzopyr

products are not labeled for any

residential uses therefore, eliminating

the potential for residential exposure.

The potential for non-occupational

exposure to the general population is

considered to be insignificant.

D. Cumulative Effects

BASF also considered the potential

for cumulative effects of diflufenzopyr

and other substances that have a

common mechanism of toxicity. BASF

has concluded that consideration of a

common mechanism of toxicity is not

appropriate at this time since there is no

indication that toxic effects produced by

diflufenzopyr would be cumulative with

those of any other chemical compounds.

Semicarbazone chemistry is new and

diflufenzopyr has a novel mode of

action compared to currently registered

active ingredients.

E. Safety Determination

1. U.S. population. Dietary and

occupational exposure will be the major

routes of exposure to the U.S.

population and ample margins of safety

have been demonstrated for both

situations. The TMRC from the

proposed tolerance of 0.05 ppm is

0.173168 ug/kg/day and utilizes 0.0692

percent of the RfD for the overall U.S

population. The MOEs for occupational

exposure are greater than 7,000. Based

on the completeness and reliability of

the toxicity data and the conservative

exposure assessments, there is a

reasonable certainty that no harm will

result from the aggregate exposure of

residues of diflufenzopyr including all

anticipated dietary exposure and all

other non-occupational exposures.

2. Infants and children. Dietary

exposure of the most highly exposed

subgroup in the population, nonnursing infants, is 0.195424 ug/kg/day.

This accounts for only 0.078 percent of

the RfD. There are no residential uses of

diflufenzopyr and contamination of

drinking water is extremely unlikely.

All chronic, lifespan and

multigenerational bioassays in

mammals plus tests in aquatic

organisms and wildlife failed to reveal

any endocrine effects. Based on the

completeness and reliability of the

toxicity data and the conservative

exposure assessment, there is a

reasonable certainty that no harm will

result to infants and children from the

aggregate exposure of residues of

diflufenzopyr including all anticipated

dietary exposure and all other nonoccupational exposures.

F. International Tolerances

A maximum residue level has not

been established for diflufenzopyr by

the Codex Alimentarius Commission.

2. Novartis Crop Protection, Inc.

PP 7E3489

EPA has received a pesticide petition

(PP 7E3489) from Novartis Crop

Protection, Inc. (formerly Ciba Crop

Protection), P.O. Box 18300,

Greensboro, NC 27419. proposing

pursuant to section 408(d) of the Federal

Food, Drug and Cosmetic Act, 21 U.S.C.

346a(d), to amend 40 CFR part 180 by

establishing a tolerance for combined

residues of 4-(dichloroacetyl)-3,4-

dihydro-3-methyl-2H-1,4-benzoxazine

(benoxacor) when used as an inert

ingredient (safener) in pesticide

formulations containing metolachlor in

or on raw agricultural commodities for

which tolerances have been established

for metolachlor. The proposed

analytical method is capillary gas
Federal Register / Vol. 62, No. 225 / Friday, November 21, 1997 / Notices 62307

chromatography using Nitrogen/

Phosphorous (N/P) detection. EPA has

determined that the petition contains

data or information regarding the

elements set forth in section 408(d)(2) of

the FFDCA; however, EPA has not fully

evaluated the sufficiency of the

submitted data at this time or whether

the data supports granting of the

petition. Additional data may be needed

before EPA rules on the petition.

A. Residue Chemistry

1. Plant/Animal metabolism. Novartis

Crop Protection, Inc. (Novartis) notes

that the metabolism in plants and

animals (goat, hen, and rat) is well

understood. Identified metabolic

pathways are similar in plants and

animals.

2. Analytical method. Novartis

Analytical Method AG536(C) is

available and involves extraction,

filtering, dilution, partitioning, and

cleanup. Samples are then analyzed by

capillary gas chromatography using

Nitrogen/Phosphorous (N/P) detection.

The limit of quantitation (LOQ) is 0.01

ppm.

3. Magnitude of residues. More than

30 residue trials were conducted in 19

states on a variety of agricultural crops

[corn (field and sweet); soybeans,

potatoes, green beans, radishes,

sorghum, peanuts, head lettuce, peas].

There were no detectable residues of

benoxacor at the limit of quantitation

(LOQ) of 0.01 ppm (many samples were

analyzed at an LOQ of 0.005 ppm and

no residues were detected) in any raw

agricultural commodity or processed

commodity. No transfer of residue to

animals is expected through their diet.

Benoxacor is stable for a minimum of 12

months at temperatures down to -15°C.

B. Toxicological Profile

1. Acute toxicity. A rat acute oral

study with an LD50 > 5,000 mg/kg, a

rabbit acute dermal study with an LD50

> 2,010 mg/kg, a rat inhalation study

with an LC50 > 2,000 mg/liter, a primary

eye irritation study in the rabbit

showing moderate eye irritation, a

primary dermal irritation study in the

rabbit showing benoxacor is not a skin

irritant, and a skin sensitization study

which showed benoxacor to be a skin

sensitizer in the Guinea pig. Results of

a dermal absorption study show a

maximum of 55.7% of benoxacor is

absorbed by the rat following a 24 hour

dermal exposure. Benoxacor was

applied to the shaved skin of 5 male and

5 female New Zealand white rabbits at

dose levels of 0, 1,500, or 1,010 mg/kg

for at least 22 consecutive days. This

study showed benoxacor is not dermally

toxic at doses greater than the limit dose

of 1,000 mg/kg/day.

2. Genotoxicty. Benoxacor did not

induce point mutations in vitro at limit

(cytotoxic) concentrations in a

Salmonella/mammalian microsome test

or show any mutagenic activity in the

Chinese hamster V79 mammalian point

mutation test and is neither clastogenic

nor aneugenic in the Chinese hamster at

doses up to the limit dose of 5,000 mg/

kg. Benoxacor did not induce

unscheduled DNA synthesis in isolated

rat hepatocytes at cytotoxic

concentrations up to 20 micrograms/ml.

3. Reproductive and developmental

toxicity. A 2-generation reproduction

study in the rat at approximate doses of

0, 0.5, 2.5, 25 or 50 mg/kg/day. No

effects on fertility, reproductive

performance or development were seen

in the rat at a maximally-tolerated dose

of 50 mg/kg/day. Treatment related

effects on body weight at feeding levels

of > 25 mg/kg/day were accompanied by

marginally reduced food intake only in

the high dose group. The parental NOEL

ranged from 3.4 to 4.8 mg/kg/day while

the developmental NOEL was

approximately 10-fold greater. A

developmental toxicity study in the rat

at doses of 0, 1, 100, or 400 mg/kg/day

by gavage with maternal and

developmental NOEL’s of 1 and 100 mg/

kg/day, respectively. Maternal, embryo,

and fetal toxicity were observed at doses

> 100 mg/kg/day. A developmental

toxicity study in the rabbit at doses of

0, 0.5, 2.5, 12.5 or 62.5 mg/kg/day.

Slight evidence of maternal and fetal

toxicity was observed at 62.5 mg/kg/

day. The maternal and developmental

NOEL’s were 12.5 mg/kg/day.

4. Subchronic toxicity. Six groups of

15 male and 15 female Sprague Dawley

rats were fed benoxacor at dietary

concentrations of approximately 0, 0.5,

5, 15, 50 or 300 mg/kg/day for 13 weeks.

The liver (pigmentation, karyomegaly,

cytomegaly, bile duct proliferation,

portal mononuclear cell infiltration) and

stomach (pyloric gland degeneration

and necrosis) were identified as target

organs in the 300 mg/kg/day group.

Based on a significant depression of

body weight gain at 50 and 300 mg/kg/

day as well as hematology, clinical

chemistry and pathology findings, the

NOEL was determined to be 15 mg/kg/

day.

A 90-day feeding study in the dog at

approximate doses of 0, 0.25, 1, 5, 50,

150, or 400 mg/kg/day. Liver, kidney,

stomach, and thymus were identified as

target organs. The NOEL was 50 mg/kg/

day. The maximum tolerated dose was

exceeded at > 150 mg/kg/day.

A 90-day feeding study in CD-1 mice

at dietary concentrations of

approximately 0, 6.25, 62.5, 250, or 750

mg/kg/day for 90 days. Effects on

survival, clinical signs, body weight,

food consumption, the hematological

system, and liver and kidney were seen

at 750 mg/kg/day and to a lesser extent

at 250 mg/kg/day. The NOEL was 62.5

mg/kg/day.

5. Chronic toxicity. A 52-week feeding

study in the dog at doses of 0, 1, 5, 40,

or 80 mg/kg. Liver and kidney were

identified as target organs and the NOEL

was established at 5 mg/kg.

An 18-month oncogenicity study in

the mouse at approximate doses of 0,

1.4, 4.2, 84, or 168 mg/kg/day with a

NOEL of 4.2 mg/kg/day for both chronic

toxicity and tumors. Target organs were

the liver and forestomach. A

carcinogenic response was noted in the

forestomach and is likely to be linked to

a non-genotoxic mode of action

involving direct irritation to the

epithelial lining of the forestomach and

limiting ridge between the nonglandular and glandular stomach.

A 24-month chronic feeding and

oncogenicity study in the rat at

approximate doses of 0, 0.5, 2.5, 25, or

50 mg/kg/day. Liver and forestomach

were identified as target organs. A

carcinogenic response was seen in the

forestomach and is likely linked to a

non-genotoxic mode of action involving

direct irritation to the epithelial lining

of the forestomach and the limiting

ridge. The NOEL for tumors was 25 mg/

kg/day and the NOEL for chronic

toxicity was 0.5 mg/kg/day.

Based on the available chronic

toxicity data, EPA has established the

RfD for benoxacor at 0.004 mg/kg/day.

This RfD is based on the 2 year feeding

study in rats with a NOEL of 0.4 mg/kg/

day and an uncertainty factor of 100.

The uncertainty factor of 100 was

applied to account for inter-species

extrapolation (10) and intra-species

variability (10).

Using the Guidelines for Carcinogenic

Risk Assessment published September

24, 1986 (51 FR 33992), Novartis

believes the Agency will classify

benoxacor as a Group C carcinogen

(possible human carcinogen) based on

findings of a carcinogenicity effect in

the non-glandular stomach of both rats

and mice. Because this carcinogenic

response was only observed at high

doses in the non-glandular stomach of

the rodent, an anatomical structure not

found in humans, it is likely this

response occurred via a non-genotoxic,

threshold based mechanism. Novartis

believes exposure to benoxacor should

be regulated using a margin of exposure

approach where the carcinogenic NOEL

established in the most sensitive

species, the mouse, was 4.2 mg/kg/day.
62308 Federal Register / Vol. 62, No. 225 / Friday, November 21, 1997 / Notices

C. Aggregate Exposure

1. Dietary exposure— Food. For

purposes of assessing the potential

dietary exposure under the proposed

tolerances, Novartis has estimated

aggregate exposure based on the

theoretical maximum residue

contribution (TMRC) from the

benoxacor tolerance of 0.01 ppm in or

on raw agricultural commodities for

which tolerances have been established

for metolachlor. In conducting this

exposure assessment, Novartis has made

very conservative assumptions--100% of

all raw agricultural products for which

tolerances have been established for

metolachlor will contain benoxacor

residues and those residues would be at

the level of the tolerance (0.01 ppm)

which result in an overestimate of

human exposure.

2. Drinking water. Although

benoxacor is mobile and hydrolyzes

slowly at low pHs, it rapidly degrades

in the soil (half-life of 49 days under

aerobic conditions and 70 days

anaerobically). Based on this data,

Novartis does not anticipate exposure to

residues of benoxacor in drinking water.

This is supported by extensive

experience with metolachlor, where in

large scale ground water monitoring

studies, metolachlor has been detected

in less than 4% of the samples with the

typical value being 1 ppb or less. Since

benoxacor is formulated as a 1 to 30

ratio with metolachlor, (maximum of 0.2

pounds benoxacor per acre) the

presence of benoxacor in groundwater is

highly unlikely. The EPA has not

established a Maximum Concentration

Level for residues of benoxacor in

drinking water.

3. Non-dietary exposure. Novartis has

evaluated the estimated nonoccupational exposure to benoxacor and

based on its low use rate concludes that

the potential for non-occupational

exposure to the general population is

unlikely except for the potential

residues in food crops discussed above.

Benoxacor is used only on agricultural

crops and is not used in or around the

home.

D. Cumulative Effects

Novartis also considered the potential

for cumulative effects of benoxacor and

other substances that have a common

mechanism of toxicity. Novartis

concluded that consideration of a

common mechanism of toxicity is not

appropriate at this time. Novartis does

not have any reliable information to

indicate that toxic effects seen at high

doses of benoxacor (generalized liver

toxicity, nephrotoxicity and the

occurrence of forestomach tumors in an

organ not present in humans) would be

cumulative with those of any other

chemical compounds; thus Novartis is

considering only the potential risks of

benoxacor in its aggregate exposure

assessment.

E. Safety Determination

1. U.S. population. Using the

conservative exposure assumptions

described above and based on the

completeness and reliability of the

toxicity data base for benoxacor,

Novartis has calculated that aggregate

exposure to benoxacor will utilize 4.7%

of the RfD for the U.S. population based

on chronic toxicity endpoints and only

0.4% based on a margin of exposure

assessment and a carcinogenic NOEL of

4.2 mg/kg/day. EPA generally has no

concern for exposures below 100

percent 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. Novartis concludes

that there is a reasonable certainty that

no harm will result from aggregate

exposure to benoxacor residues.

2. Infants and children. Using the

same conservative exposure

assumptions used for the determination

in the general population, Novartis has

concluded that the percent of the RfD

that will be utilized by aggregate

exposure to residues of benoxacor is

5.3% for nursing infants less than 1 year

old, 20.2% for non-nursing infants,

11.9% for children 1-6 years old and

7.7% for children 7-12 years old. These

worst case estimates are likely at least

4 times greater than actual values when

considering that benoxacor residues

have not been detected at the limit of

quantitation of 0.005 ppm (tolerance is

0.01 ppm) and using a more realistic

market share of 50% rather than the

conservative 100%. Therefore, based on

the completeness and reliability of the

toxicity data base and the conservative

exposure assessment, Novartis

concludes that there is a reasonable

certainty that no harm will result to

infants and children from aggregate

exposure to benoxacor residues.

F. International Tolerances

A maximum residue level has not

been established for benoxacor by the

Codex Alimentarius Commission.

[FR Doc. 97–30659 Filed 11–20–97; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[FRL–5925–9]

Availability of Draft Document on

Information for States on Developing

Affordability Criteria for Drinking Water

AGENCY: Environmental Protection

Agency.

ACTION: Notice of document availability.

SUMMARY: The Environmental Protection

Agency is making available for public

comment a draft document entitled

Information for States on Developing

Affordability Criteria for Drinking

Water. The Safe Drinking Water Act

Amendments of 1996 require the

Agency to publish information to assist

states in developing affordability

criteria. To meet the statutory schedule,

this information must be published by

February 6, 1998. The draft document

being made available today was

developed by a diverse working group

of stakeholders under the auspices of

the National Drinking Water Advisory

Council (NDWAC). The full NDWAC

reviewed this draft and recommended it

to EPA as a draft to be made available

for public comment. EPA invites

interested members of the public to

submit comments on the draft

document. EPA will consider public

comments and publish a final document

by the February 6, 1998, statutory

deadline.

DATES: Submit comments on or before

December 31, 1997.

ADDRESSES: Address all comments

concerning this draft document to Peter

E. Shanaghan, Small Systems

Coordinator, Office of Ground Water

and Drinking Water, Mail Code 4606,

401 M Street SW., Washington, DC

20460.

FOR FURTHER INFORMATION CONTACT:

Peter E. Shanaghan, 202–260–5813 or

shanaghan.peter@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: A copy of

the draft document may be obtained by

calling the Safe Drinking Water Hotline

at 1–800–426–4791. The hotline

operates Monday through Friday, 9:00

a.m.–5:30 p.m. (EST). The document

may also be downloaded from EPA’s

homepage, http://www.epa.gov/

OGWDW.

Elizabeth Fellows,

Acting Director, Office of Ground Water and

Drinking Water.

[FR Doc. 97–30660 Filed 11–20–97; 8:45 am]

BILLING CODE 6560–50–M