Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41835

were observed in the mid-high and

highest dose group test with a slight

progression of severity to the highest

dose group tested; (d) a higher incidence

of splenomegaly was observed only in

the male mice of the highest dose group;

(e) histopathological examinations

revealed an ectopic proliferation of the

mucosal and glandular epithelium in

the submucosal layer of the glandular

stomach in male and female mice in the

highest dose group tested, these changes

were assessed to represent heteroplastic,

ectopic proliferative changes

accompanied by lumen dilatation and

cytological degeneration; (f) a higher

incidence of hyperkeratosis of the

forestomach was observed in both male

and female mice and hyperplasia of the

squamous epithelium of the

forestomach of female male mice was

observed in the highest dose group

tested; (g) vacuolic changes in the

exocrine pancreas of the high dose

female was observed; (h) no increased

incidence of neoplasms occurred at any

dose levels tested in this study.

iv. Carcinogenicity. Prohexadione

calcium was shown to be noncarcinogenic in mice, rats, and dogs.

Therefore, based on the results of the

carcinogenicity studies in mice, rats,

and dogs and the results of genotoxicity

testing, the threshold approach to

regulating prohexadione calcium is

appropriate

5. Animal metabolism. The

metabolism in animals (goats and

poultry) is adequately understood.

6. Endocrine disruption. No specific

tests have been conducted with

prohexadione calcium to determine

whether the chemical may have an

effect in humans that is similar to an

effect produced by a naturally occurring

estrogen or other endocrine effects.

However, there were no significant

findings in other relevant toxicity

studies, i.e., teratology and multigeneration reproductive studies, which

would suggest that prohexadione

calcium produces endocrine related

effects.

C. Aggregate Exposure

1. Dietary exposure. For purposes of

assessing the potential dietary exposure,

K-I has estimated aggregate exposure

based on the Theoretical Maximum

Residue Contribution (TMRC) from the

proposed tolerance for prohexadione

calcium in/on peanut nutmeat at 0.8

ppm. The TMRC is a ‘‘worse case’’

estimate of dietary exposure since it is

assumed that 100% of all crops for

which tolerances are established are

treated and that pesticide residues are

always found at the tolerance levels.

Dietary exposure to residues of

prohexadione calcium in or on food will

be limited to residues on peanut

nutmeat. Peanut hay and meal are fed to

animals; thus exposure of humans to

residues in peanut hay and meal might

result if such residues carry through to

meat, milk, poultry, or eggs. However,

K-I has concluded that there is no

reasonable expectation that measurable

residues of prohexadione calcium will

occur in meat, milk, poultry, or eggs

from this use. There are no other

established U.S. tolerances for

prohexadione calcium, and there are no

currently registered uses for

prohexadione calcium on food or feed

crops in the U.S.

Dietary exposure to residues of

prohexadione calcium from the

proposed tolerances on peanuts would

account for less than 0.14% of the RfD

(0.20 mg/kg/day) for the general

population of the US and all

subpopulation groups. The most highly

exposed group in the subpopulation

groups would be non-nursing infants (<

1 year old), which uses 0.39% of the

RfD.

2. Drinking water. Other potential

sources of exposure to prohexadione

calcium for the general population are

residues in drinking water and exposure

from non-occupational sources.

Exposure to residues of prohexadione

calcium in drinking water is not

anticipated. There is no established

Maximum Concentration Level (MCL) or

Health Advisory Level (HAL) for

prohexadione calcium under the Safe

Drinking Water Act (SDWA).

3. Non-dietary exposure.

Prohexadione calcium is not currently

registered for any nonagricultural use.

The potential for non-occupational

exposure to the general population is

therefore not present.

D. Cumulative Effects

The potential for cumulative effects of

prohexadione calcium and other

substances that have a common

mechanism of toxicity has been

considered. No evidence or information

exists to suggest that toxic effects

produced by prohexadione calcium

would be cumulative with those of any

other chemical compound.

E. Safety Determination

1. U.S. population— Reference dose

(RfD). Using the conservative exposure

assumptions described above and based

on the completeness and the reliability

of the toxicity data, it has estimated that

aggregate exposure to prohexadione

calcium will utilize 0.14% of the RfD for

the U.S. population. K-I concludes that

there is a reasonable certainty that no

harm will result from the aggregate

exposure to residues of prohexadione

calcium, including anticipated dietary

exposure and non-occupational

exposures.

2. Infants and children. Since

developmental and reproductive

toxicity occurs at levels at or above the

levels shown to exhibit parental toxicity

and since these levels are significantly

higher than those used to calculate the

RfD, K-I believes the RfD of 0.20 mg/kg/

day is an appropriate measure of safety

for infants and children.

Using the conservative exposure

assumptions described above, it is

concluded that the portion of the RfD

that will be utilized by aggregate

exposure to residues of prohexadione

calcium resulting from the proposed

tolerances will be less than 0.14% for all

populations of infants and children. The

most highly exposed group in the

subpopulation groups would be nonnursing infants (< 1 year old) which

uses 0.39% of the RfD. Therefore, based

on the completeness and reliability of

the toxicity data and the conservative

exposure assessment, it is concluded

that there is a reasonable certainty that

no harm will result to infants and

children from aggregate exposure to the

residues of prohexadione calcium,

including all anticipated dietary

exposure and all other non-occupational

exposures.

F. International Tolerances

A maximum residue level has not

been established for prohexadione

calcium by the Codex Alimentarius

Commission.

[FR Doc. 98–20768 Filed 8–4–98; 8:45 am]

BILLING CODE 6560–50–F

ENVIRONMENTAL PROTECTION

AGENCY

[PF–818; FRL–6017–1]

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–818, must be

received on or before September 4,

1998.

ADDRESSES: By mail submit written

comments to: Public Information and

Records Integrity Branch, Information

Resources and Services Division
41836 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

(7502C), Office of Pesticides Programs,

Environmental Protection Agency, 401

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

person bring comments to: Rm. 119, 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. 119 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

Sidney Jackson .............. Rm. 268, CM #2, 703–305–7610, e-mail:jackson.sidney@epamail.epa.gov. 1921 Jefferson Davis Hwy, Arlington, VA

Beth Edwards ................ Rm. 206, CM #2, 703–305–5400, e-mail: edwards.beth@epamail.epa.gov. Do.

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–818]

(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

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 (insert docket

number) 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: July 23, 1998.

James Jones,

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. Interregional Research Project 4 (IR4)

PP 6E4667

EPA has received a pesticide petition

(PP 6E4667) from the Interregional

Research Project 4(IR4), 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 residues of

pyridate, 0-(6-chloro-3-phenyl-4-

pyridazinyl)-S-octyl carbonothioate and

its metabolite 6-chloro-3-phenylpyridazine-4-ol (known as SAN 1367),

and conjugates of SAN 1367 in or on the

raw agricultural commodity garbanzo

beans (also known as chick peas) at 0.1

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 support granting of the

petition. Additional data may be needed

before EPA rules on the petition. This

notice contains a summary of the

petitions prepared by Novartis Crop

Protection, Inc. (formerly Sandoz Agro

Inc.), the registrant.

2. Novartis Crop Protection, Inc.

PP 6F4754

EPA has received a pesticide petition

(PP 6F4754) from Novartis Crop

Protection, Inc, 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 residues of pyridate, 0-

(6-chloro-3-phenyl-4-pyridazinyl)-Soctyl carbonothioate and its metabolite

6-chloro-3-phenyl-pyridazine-4-ol

(known as SAN 1367), and conjugates of

SAN 1367 in or on the raw agricultural

commodities head and stem Brassica

Subgroup 5A at 0.3 parts per million

(ppm). (Sidney Jackson)

A. Residue Chemistry

1. Plant metabolism. The metabolism

of pyridate in plants is well understood

based on studies with broccoli, corn,

and peanut. Pyridate is rapidly broken

down by hydrolysis to its major

degradation product, SAN 1367. The

SAN 1367 metabolite is further

conjugated to glucoside and degraded.

2. Analytical method. The proposed

analytical method is ‘‘Method of

analysis of determination of residues of

pyridate and its metabolites CL 9673
Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41837

and conjugated CL 9673 in plant

materials’’, Report No. 758e, March

1992, Agrolinz Agrarchemikalien

Ges.m.b.H. (V/6).

3. Magnitude of residues. Residue

trials have been conducted with

pyridate on the additional crops

requested in the pending petitions. The

proposed tolerances are recommended

at the limit of determination for the

method, which is the maximum

expected residue from the

geographically representative field trial

data.

Pyridate strongly adsorbs to soil and

was shown to be immobile in soil

column leaching studies. Pyridate has a

short half-life, low water solubility, and

low volatility. Due to its solubility and

hydrolysis characteristics, pyridate will

not persist in the environment.

San 1367 is further degraded and

mineralized to volatile CO2 and bound

metabolites. It is susceptible to

photolysis. Column leaching studies

and field dissipation studies indicated

that SAN 1367 tends to degrade faster

than it is translocated below the 0-15 cm

layer. Therefore under typical

agricultural conditions and labeled uses,

leaching of SAN 1367 is not an issue of

concern.

B. Toxicological Profile

Data are summarized below

concerning the mammalian toxicity of

pyridate. According to Novartis’

interpretation of these data, pyridate is

not a carcinogen or a mutagen, has low

oral and dermal toxicity to mammals,

and causes no reproductive or

developmental effects.

1. Acute toxicity. Results of a rat acute

oral study showed a lethal dose LD50 of

4,690 milligram/kilogram (mg/kg) body

weight/day (bwt/day) (5,993 mg/kg in

males and 3,544 mg/kg in females). In

a rat acute dermal study, the LD50 was

shown to be >2,000 mg/kg. A rat acute

inhalation study yielded a LD50 >4.37

mg/milliliter (ml).

Results of a primary eye irritation

study in the rabbit indicated that

pyridate is a mild irritant. A primary

dermal irritation study showed pyridate

to be a moderate skin irritant, whereas,

a dermal sensitization study indicated it

is a sensitizer.

2. Genotoxicity. Pyridate was tested in

the Ames test, mouse micronucleus

assay, chromosome aberration assay

with Chinese hamster ovary cells, the

REC assay, and rat hepatocyte

unscheduled DNA synthesis assay.

Results were negative for mutagenicity

and chromosome aberrations.

3. Reproductive and developmental

toxicity. A developmental toxicity study

in the rat dosed at 0, 55, 165, 400, and

495 milligram/kilograms/day (mg/kg/

day) showed maternal toxicant noobserved effect level (NOEL) of 165 mg/

kg/day, and developmental NOEL >495

mg/kg/day.

A developmental toxicity study in the

rabbit with doses of 0, 150, 300, and 600

mg/kg/day showed a maternal toxicant

NOEL of 300 mg/kg/day and

developmental NOEL >600 mg/kg/day.

Results of a multi-generational

reproduction study with rats dosed at 0,

2.2, 10.8, and 67.5 mg/kg/day showed a

NOEL of 10.8 mg/kg/day for maternal

and developmental toxicity.

4. Subchronic toxicity. Results of a 21-

day dermal study showed a NOEL

>1,000 mg/kg. A 90-day feeding study in

rat dosed at 0, 62.5, 177, and 500 mg/

kg/day showed a NOEL of 62.5 mg/kg/

day. No neuropathological effects were

found. A 90-day feeding study in dogs

with doses of 0, 20, 60 and 200 mg/kg/

day showed a NOEL of 20 mg/kg/day.

Slight degenerative myelopathy in the

peripheral nerves was observed at the

highest dose level (HDL), which is much

higher than the NOEL and the expected

exposure from field use.

5. Chronic toxicity. A 1-year feeding

study in dogs was conducted with doses

of 0, 5, 20 and 60 mg/kg/day for 34-

weeks. After week 34, the doses were

increased to 30, 100, and 150 mg/kg/day

because no toxic effects were evident at

the lower doses. The final results

showed a systemic NOEL of 20 mg/kg/

day.

A lifespan (121 week) chronic/

carcinogenicity study in rats treated

with analytical levels of 0, 2.2, 10.8, and

67.5 mg/kg/day (equivalent to 0, 48,

240, and 1,500 ppm) showed a systemic

NOEL of 10.8 mg/kg/day (240 ppm)

based on body weight depression. No

carcinogenic potential was observed.

In an 18- month carcinogenicity

study, mice were fed doses of 0, 400,

800, 1,600 and 7,000 ppm of pyridate.

In males, dose levels were

approximately 0, 47.7; 97.1; 169.5, and

882.6 mg/kg bwt/day; in females, dose

levels were approximately 0, 54.5,

114.6, 204.3, and 1,044.6 mg/kg bwt/

day. NOEL was 800 ppm (97.1 mg/kg in

males and 114.6 mg/kg in females).

Results showed no evidence of

carcinogenicity.

i. Chronic effects. The Reference Dose

(RfD) has been established based on the

chronic toxicity database. The RfD =

0.11 mg/kg bwt/day based on the NOEL

of 10.8 mg/kg bwt/day from the lifespan

rat oncogenicity study due to body

weight depression in males, and

assuming a safety factor of 100.

ii. Acute effects. Acute dietary

analysis compared the daily dietary

exposure to the lowest NOEL for

subchronic studies. EPA’s current

policy for Tier I analysis uses the

conservation assumption that all

residues are at a high end estimate or

maximum, typically taken as the

tolerance value. Acute dietary

assessment for pyridate was generated

by comparing the ratio of exposure and

the NOEL from the 90-day feeding study

in dogs of 20 mg/kg bwt/day to

determine a margin of exposure (MOE).

The exposure estimate includes all

current and pending tolerances from

Novartis Agro, Inc. and IR-4. MOE of

100 or more are considered acceptable.

For all subgroups evaluated, the MOE is

greater than 140,000.

iii. Carcinogenicity. Existing data

demonstrate that there is no evidence of

carcinogenicity in rats at 1,500 ppm

(67.5 mg/kg/day) or mice at 7,000 ppm

(883 mg/kg bwt/day in males, and

1,044.6 mg/kg bwt/day in females).

These data have been obtained at dosing

in excess of any dietary exposure.

6. Animal metabolism. Pyridate has

been tested in rats, dogs, cattle,goats,

and hens. In every study, pyridate was

hydrolyzed to SAN 1367 and rapidly

excreted, primarily through the urine as

SAN 1367 or its glucoside or

glucuronide conjugates.

Data from bovine metabolism and

feeding studies established that the uses

proposed do not yield secondary

residues in meat and milk above the

limit of detection. Novartis believes that

data from metabolism and feeding

studies in poultry established that at the

maximum expected dietary burden from

crops treated with pyridate will not

result in quantifiable residues above the

limits of the analytical method. Pyridate

and its metabolites are not persistent

and do not accumulate in animal

systems.

7. Metabolite toxicology. Pyridate has

been tested in rats, dogs, cattle, goats,

and hens. In every study, pyridate was

hydrolyzed to SAN 1367 and rapidly

excreted, primarily through the urine as

SAN 1367 or its glucoside or

glucuronide conjugates. Pyridate and its

metabolites are not persistent and do

not accumulate in animal systems.

C. Aggregate Exposure

Based on environmental fate data,

pyridate is not expected to be found in

drinking water. There are no non-crop

uses for pyridate, and no nonoccupational exposure for residential

use. Exposure would be limited to

dietary exposure described below.

Novartis Agro has no information that

would indicate that pyridate would

have a mechanism of toxicity common

to any other registered pesticide.
41838 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

1. Dietary exposure—food. Pyridate is

registered for use in corn, peanut, and

cabbage. The pending petitions add the

use in grain sorghum, collards, and the

stem and head Brassica subgroup. The

potential dietary exposure of the

population to residues of pyridate or its

metabolites is calculated based on

Theoretical Maximum Residue

Contribution (TMRC) for all crops with

pyridate use. The TMRC is a worst case

estimate of dietary exposure since it

assumes that 100% of all crops for

which tolerances are established are

treated with pyridate, and that pesticide

residues are present at the tolerance

levels. Novartis maintains that this

method of calculation result in an

overestimation of the exposure and is

considered conservative. Dietary

exposure is not expected in meat, milk,

poultry, or eggs, based on cow and hen

feeding studies, animal metabolism

studies, and the fact the residue studies

indicate that residues are not present in

crops fed to animals above the limit of

detection.

2. Drinking water. Drinking water is

not expected to be a means of exposure

to pyridate. Environmental studies

indicate that pyridate binds to the soil

and is rapidly hydrolyzed into its

metabolites. The metabolites are then

photolyzed and further degraded and

finally mineralized to CO2. Leaching

studies and lysimeter studies indicate

that under typical agricultural

conditions, neither pyridate nor its

metabolites were detected below 30 cm.

Groundwater monitoring studies

conducted in Europe have not

confirmed any detection of pyridate or

metabolites. Therefore significant

movement of pyridate is not likely and

is not a considerable factor in assessing

human health risk.

3. Non-dietary exposure. There are no

registered uses for pyridate on

residential or recreational turf.

Therefore, non-dietary exposure of

pyridate is not likely and not a factor in

assessing human health risk.

D. Cumulative Effects

Pyridate belongs to the pyridazine

group of herbicidal compounds and has

a unique mode of action in plants.

Novartis does not have data to indicate

a common mechanism of toxicity to

other compounds in humans. Therefore,

Novartis concludes that cumulative

effects from common mechanisms of

action are unlikely.

E. Safety Determination

1. U.S. population. The RfD is

calculated to be 0.11 mg/kg bwt/day.

The estimates of exposure are based on

conservative assumptions that all crops

with a tolerance for pyridate are treated

and that all residues found are at the

maximum or tolerance level. The

dietary exposure to the U.S. population

for the current uses plus the garbanzo

beans and Brassica uses is estimated at

most to be 0.000019 mg/kg/day, which

is 0.017% of the RfD. Therefore Novartis

concludes that there is reasonable

certainty of no harm from aggregate

exposure of residues of pyridate or its

metabolites including all dietary and

other non-occupational exposures.

2. Infants and children. Pyridate is

not a reproductive or developmental

toxicant. Therefore no specific effects on

infants and children are expected. Based

on the weight of evidence of the toxicity

studies, Novartis concludes that an

additional safety factor is not warranted.

Using the same assumptions as above,

the exposure to infants and children is

presented as a percent of RfD. The

dietary exposure for the current uses

plus the garbanzo beans and Brassica

uses for non-nursing infants is estimated

at 0.000045 mg/kg/day, which is

0.041% of the RfD. For children age 1-

6, the estimated exposure is 0.000057

mg/kg/day, 0.052% of the RfD, and

exposure to children age 7-12 is

estimated to be 0.000044 mg/kg/day,

which is 0.040% of the RfD. Therefore,

Novartis concludes that there is

reasonable certainty of no harm from

aggregate exposure of residues of

pyridate or its metabolites including all

dietary and other non-occupational

exposures.

F. International Tolerances

No international tolerances have been

established by CODEX Alimentarius

Commission (Sidney Jackson).

3. Valent U.S.A. Company

PP 7F3485, 1F3949, 6F4648

EPA has received a request from

Valent U.S.A. Company, 1333 North

California Boulevard, Suite 600, Walnut

Creek, CA 94596-8025 proposing

pursuant to section 408(d) of the Federal

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

346a(d), to amend 40 CFR 180.466 by

establishing tolerances for residues of

fenpropathrin, alpha-cyano-3-

phenoxybenzyl 2,2,3,3-

tetramethylcyclopropanecarboxylate, in

or on the raw agricultural commodities

pome fruit (crop group 11) and grapes

at 5.0 ppm, head and stem brassica

(crop group 5A) at 3.0 ppm, citrus fruit

(crop group 10) at 2.0 ppm, melons

(crop group 9A) at 0.5 ppm, and in the

processed products citrus oil at 50 ppm,

raisins at 10 ppm, and dried citrus pulp

at 4.0 ppm. The tolerances were first

proposed in response to pesticide

petitions PP 7F3485, 1F3949, and

6F4648. EPA has determined that the

request 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.

Background Information and Use Profile

Fenpropathrin is the active ingredient

in DANITOL 2.4 EC Spray (EPA Reg.

No. 59639-35) and TAME 2.4 EC Spray

(EPA Reg. No. 59639-77). To support

DANITOL use, tolerances have been

established on cottonseed; cottonseed

oil; meat, meat byproducts, and fat of

cattle, goats, hogs, horses, sheep and

poultry; eggs; milkfat; peanuts; peanut

hay; strawberries; and tomatoes. A time

limited tolerance on red currants has

been established to support a Section 18

in the state of Washington with an

expiration date of December 31, 1998.

The pending tolerances that are the

subject of this notice of filing are on

grapes and on the crop groups pome

fruits (11), citrus (10), head and stem

brassica (5A), and melons (9A), with

associated processing products citrus

oil, raisins, and dried citrus pulp.

Fenpropathrin is a pyrethroid

insecticide with broad spectrum activity

on insects and mites. When formulated

as the product DANITOL 2.4 EC Spray

the product is registered for agricultural

use on outdoor terrestrial food crops. A

separate fenpropathrin product, TAME

2.4 EC Spray, is registered for

commercial, professional non-food use

on indoor and outdoor ornamental and

nursery stock. There are no uses

registered for professional indoor pest

control, termite prevention, homeowner

use, or turf application.

The products are applied as dilute

emulsions in water directly to plants to

control harmful insects and mites. In

agriculture, depending on the crop and

pest, the use rates vary from 0.15 to 0.4

pounds of active ingredient per acre (lb.

ai./a), with a maximum total use on all

crops of 0.8 lb. ai./a per season. Preharvest intervals (phi) range from 21-

days on cotton to 1-day on citrus. Plant

metabolism studies have shown that the

plant and animal residues are best

defined as parent fenpropathrin.

Because of the mode of application and

short phi, finite residues of

fenpropathrin are often found on treated

agricultural commodities requiring

tolerances above the 0.01 ppm limit of

quantitation of the residue analytical

methodology. However, analyses of RAC

samples from plants treated at the
Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41839

maximum application rates, and

minimum retreatment intervals and phi

demonstrate that anticipated residues

are much below tolerance levels. In

addition, it has been demonstrated that

fenpropathrin is not plant systemic and

that residues occur only on plant parts

that have been directly treated.

A. Residue Chemistry

Summary. An extensive plant and

animal metabolism data base

demonstrates that the appropriate

definition of aged fenpropathrin residue

is parent. Ruminant and poultry

metabolism followed by feeding studies

have shown that the ratios of residues

in feed to secondary residues in animal

products are very low in most

commodities, with higher (but still

relatively low) ratios in body fat and

milk fat. This section will describe

metabolism and field residue data

supporting the establishment of

tolerances for residues of fenpropathrin

in or on the raw agricultural

commodities pome fruit (crop group 11)

and grapes at 5.0 ppm, head and stem

brassica (crop group 5A) at 3.0 ppm,

citrus fruit (crop group 10) at 2.0 ppm,

melons (crop group 9A) at 0.5 ppm, and

in the processed products citrus oil at

50 ppm, raisins at 10 ppm, and dried

citrus pulp at 4.0 ppm The approved

analytical method is capillary gas-liquid

chromatography with flame ionization

detection.

1. Plant metabolism. The plant

metabolism of fenpropathrin has been

studied in five different crop plant

species: cotton, apple, tomato, cabbage,

and bean. Radiocarbon labeling has

been in the cyclopropyl ring of the acid,

in the aryl rings of the alcohol, and in

the nitrile of fenpropathrin, a

cyanohydrin ester. The permutations of

radiocarbon label position and plant

species yield a total of 17 separate,

reviewed studies. Each of the studies

involved foliar treatment of the plants

under either greenhouse or field

conditions and, while the actual

treatment conditions and times to

harvest and analyses varied from study

to study, the results of the many studies

are remarkably consistent. The total

toxic residue is best defined as parent,

fenpropathrin.

Fenpropathrin remains associated

with the site of application and only

traces are found in seeds (e.g., bean or

cotton) or in other parts of the plant not

directly exposed to the application.

Much of the parent residue can be

removed from the plant material with a

mild hexane/acetone or hexane rinse,

demonstrating that the residue is

located on or near the outside surface of

the plant material. The primary

metabolic pathway for fenpropathrin in

plants is similar to that in mammals.

There are no qualitatively unique plant

metabolites; the primary aglycones are

identical in both plants and animals.

2. Analytical method. Adequate

analytical methodology is available to

detect and quantify fenpropathrin (and

its metabolites) at residue levels in

numerous matrices. The methods use

solvent extraction and partition and/or

column chromatography clean-up steps,

followed by separation and quantitation

using capillary column gas-liquid

chromatography with flame ionization

detection. The extraction efficiency has

been validated using radiocarbon

samples from the plant and animal

metabolism studies. The enforcement

methods have been validated at

independent laboratories, and by EPA.

The limit of quantitation for

fenpropathrin in raw agricultural

commodity samples is 0.01 ppm.

3. Magnitude of residues—i. Pome

fruit (Crop Group 11). The proposed

section 408 tolerance for fenpropathrin

in/on Pome Fruit (Crop Group 11) is 5.0

ppm. The proposed tolerance will

permit finite residues of fenpropathrin

on pome fruit -- apple, pear, oriental

pear, crabapple, and related fruits -- as

a result of application of DANITOL 2.4

EC Spray to orchards. The field residue

data to support a fenpropathrin

tolerance on the pome fruit crop

grouping includes data on apples from

26 sites and pears from 18 sites

providing data from 44 sites across the

U.S. The mean residue from all samples

is 1.83 ppm. In the subset of samples

that exactly fit the proposed use pattern

the average residue is 0.83 ppm (n = 16,

σn -1 = 0.55 ppm) with a maximum

value of 1.8 ppm.

ii. Apples. The residue data base from

apples that supports the proposed crop

group tolerance includes all samples

from field residue studies that were

treated two or more times at 0.4 lb. ai./

a with a 14-day phi. These experiments

were performed over 5- years at 26 sites

in 10 states. There were 38 separate

treatments yielding 73 separate, treated

samples for analysis. The average

residue was 2.15 ppm (n = 73,σn -1 =

1.37 ppm). These data do not include

supporting information at higher or

lower rates, and harvested at different

phi. In the 38-treatment data base there

are only four treatments with only two

applications that are completely

consistent with the proposed use

pattern that is limited to a maximum

single application rate of 0.4 lb. ai./a, a

seasonal maximum of 0.8 lb. ai./a, and

a 14 phi. The highest average residue

(HAR) found in these crop field trials for

fenpropathrin on apples was 1.13 ppm.

The average residue was 0.77 ppm (n =

8, σn -1 = 0.40). Data obtained by

separate analyses of peelings and pulp

demonstrated that the bulk of

fenpropathrin residues were located on

the peeling of the apples.

Five apple processing studies were

performed. These studies demonstrated

that fenpropathrin residues did not

concentrate in apple juice

(concentration factor all <<1, average =

0.06), but did concentrate in wet

pomace (average concentration factor =

3.05). No additional tolerance for the

processed product wet apple pomace is

needed because the HAR times the

average concentration factor for wet

pomace is less than the proposed

tolerance of 5 ppm (1.13 ppm x 3.05 =

3.45 ppm).

iii. Pears. The residue data base from

pears that supports the proposed crop

group tolerance includes all samples

from field residue studies that were

treated two or more times at 0.4 lb. ai./

a with a 14-day phi. These experiments

were performed over 4-years at 18 sites

in 5 states. There were 30 separate

treatments yielding 60 separate, treated

samples for analysis. The average

residue was 1.44 ppm (n = 60, σn -1 =

1.01). This does not include supporting

information at higher or lower rates, and

harvested at different phi. In the 30-

treatment data base there are only four

treatments with only 2 applications that

are completely consistent with the

proposed use pattern, which is the same

as in apples, and is limited to a

maximum single application rate of 0.4

lb. ai./a, a seasonal maximum of 0.8 lb.

ai./a, and a 14-day phi. The HAR found

in these crop field trials for

fenpropathrin on pears was 1.8 ppm.

The average residue was 0.88 ppm (n =

8, σn -1 = 0.69).

iv. Grapes. The proposed section 408

tolerance for fenpropathrin on grapes is

5 ppm. The residue data base that

supports the tolerance includes all

samples from field residue studies that

were treated 4- times at 0.2 lb. ai./a with

a 21-day phi. Excluded from the

calculation of the tolerance, and the

chronic and acute exposure analyses is

data from one site that were

demonstrated to be outliers (The

analytical determinations were very

high, more than six sigma above the

mean of the other determinations).

These experiments were performed over

4-years at 14 sites in 4 states. There

were 14 separate treatments yielding 28

separate, treated samples for analysis.

The average residue was 1.06 ppm (n =

28, σn -1 = 0.71). This does not include

supporting information at higher or

lower rates, different numbers of

applications, or different phi. The HAR
41840 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

found in crop field trials for

fenpropathrin on grapes was 3.1 ppm.

Four processing studies yielding

raisins and juice, and 5 additional

studies yielding grape juice only (total

of 9), were performed. These studies

demonstrated that fenpropathrin

residues were greatly reduced in grape

juice (concentration factor all <<1,

average = 0.06), but did concentrate in

raisins (average concentration factor =

1.76). An additional tolerance for the

processed product raisins is needed

because the HAR times the average

concentration factor for raisins is greater

than the proposed tolerance of 5 ppm

(3.1 ppm x 1.76 = 5.55 ppm). A Section

408 tolerance for fenpropathrin on

raisins of 10 ppm is proposed.

v. Citrus. The proposed Section 408

tolerance for fenpropathrin on citrus

fruit (Crop Group 10) is 2 ppm. The

residue data base from citrus that

supports the tolerance includes all

samples from field residue studies that

were completely consistent with the

proposed use pattern of 2 applications

at 0.4 lb. ai./a with a 1-day phi. In

oranges, the experiments were

performed over 5-years at 13 sites in 4

states. There were 13 separate

treatments yielding 24 separate, treated

samples for analysis. The average

residue in oranges was 0.39 ppm (n =

24, σn -1 = 0.35 ppm). In grapefruit, the

experiments were performed in a single

year at 7 sites in 3 states. There were 7

separate treatments yielding 14 separate,

treated samples for analysis. The

average residue in grapefruit was 0.29

ppm (n = 14, σn -1 = 0.13 ppm). In

lemons, the experiments were

performed in a single year at 3 sites in

2 states. There were 3 separate

treatments yielding 6 separate, treated

samples for analysis. The average

residue in lemons was 0.52 ppm (n = 6,

σn -1 = 0.06 ppm).

For the overall crop grouping citrus

fruits the average residue was 0.37 ppm

(n = 44, σn -1 = 0.28 ppm). The HAR

found in all citrus crop field trials

meeting the proposed use pattern for

fenpropathrin on citrus was 1.2 ppm.

These overall citrus data only include

data from samples that are consistent

with the proposed use pattern, and do

not include supporting information at

higher or lower rates, and harvested at

different phi. Data obtained by separate

analyses of peelings and pulp from

oranges demonstrated that the bulk of

fenpropathrin residues were located on

the peeling, exterior, of the oranges.

There are two processing studies

performed in citrus (oranges) with

processing to juice, dried citrus pulp,

and citrus oil. The studies demonstrated

that fenpropathrin did not concentrate

in juice (concentration factor all <<1),

but did concentrate in dried citrus pulp

(average concentration factor = 2.6), and

in citrus oil (average concentration

factor = 40.5). Thus it can be calculated

from the HAR that residues of 3.12 ppm

(1.2 x 2.6) could occur in dried citrus

pulp and 48.6 ppm (1.2 x 40.5) could

occur in citrus oil. Since residues could

be present in the not ‘‘ready to eat’’

commodities at levels (3.12, 48.6 ppm)

appreciably higher than the proposed

RAC tolerance of 2 ppm, tolerances are

being proposed. After rounding, the

proposed tolerances are 4.0 ppm for

dried citrus pulp, and 50.0 ppm for

citrus oil.

vi. Melons (Cantaloupe). The

proposed Section 408 tolerance for

fenpropathrin in/on melons (crop group

9A) is 0.5 ppm. The field residue data

that support this proposal come from 10

locations in 7 states. At these ten

locations there was a total of 14 separate

trials, yielding 36 separate, treated

samples for analysis. Samples from

treatments that were consistent with the

proposed maximum use pattern -- 0.2 lb.

ai./a, 4 applications, 7-day spray

interval, 7-day pre-harvest interval --

gave 20 separate samples for analysis.

The mean of the 20 determinations is

0.175 ppm (n = 20, σn-1 = 0.077 ppm)

and a maximum value of 0.31 ppm.

Separate analyses of pulp and rind

demonstrated that the bulk of the

residues were present on the rind.

vii. Head and Stem Brassica. A

proposed Section 408 tolerance of 3.0

ppm is proposed for fenpropathrin in/

on Head and stem brassica (crop group

5A) -- cabbage, cauliflower, broccoli,

brussels sprouts, and related non-leafy

brassica. The field residue data to

support a fenpropathrin tolerance on the

crop grouping head and stem brassica

includes data on broccoli from 7

sitesand cabbage from six sites

providing data from 13 sites across the

U.S. Samples from trials that were

consistent with the proposed maximum

use pattern for the crop group -- the first

application at 0.2 lb. ai./a and 2

additional applications at 0.3 lb. ai./a (a

total application of 0.8 lb. ai./a), 7-day

spray interval, 7-day pre-harvest

interval -- gave a mean residue of 0.62

ppm(n = 26, σn-1 = 0.69) with a

maximum value of 2.8 ppm.

viii. Broccoli. Field residue data come

from 7 locations in 4 states. At these

locations there were a total of 8 separate

trials yielding 28 separate, treated

samples for analysis. Samples from

trials that were consistent with the

proposed maximum use pattern gave 14

separate samples for analysis. The mean

of the 14 determinations is 0.369 ppm

(n = 14, σn-1 = 0.157 ppm)and a

maximum value of 0.58 ppm.

ix. Cabbage. Field residue data come

from 6 locations in 6 states. At these six

locations there was a total of 7 separate

trials yielding 26 separate, treated

samples for analysis. Trials that were

consistent with the proposed maximum

use pattern gave 12 separate samples for

analysis. The mean of the

determinations is 0.92 ppm (n = 12, σn1 = 0.93 ppm) and a maximum value of

2.8 ppm. Analyses of cabbage heads

with wrapper leaves removed

demonstrated that the bulk of the

residue was on the exterior of the

cabbages with a mean residue of 0.04

ppm (n = 12, σn-1 = 0.05 ppm) and a

maximum value of 0.19 ppm.

x. Secondary residues. Residues in

animal feed may transfer to animal

products, meat, milk, and eggs, used in

human food. The existing tolerances on

meat and meat by-products of cattle,

goats, hogs, horses and sheep at 0.1

ppm, fat of cattle, goats, hogs, horses

and sheep at 1.0 ppm, milk fat

(reflecting 0.08 ppm in whole milk) at

2.0 ppm, and poultry meat, fat, meat byproducts and eggs at 0.05 ppm are,

adequate to allow the addition of the

proposed uses. Both chronic and acute

dietary assessments show very low

residue contribution from secondary

residues in animal products to all

population sub-groups.

B. Toxicological Profile

Summary. The existing registrations

and tolerances of fenpropathrin are

supported at EPA by a complete

toxicology data base. Toxicity endpoints

of concern have been identified by the

Agency’s Health Effects Division,

Hazard Identification Assessment

Review Committee (Meeting July 17,

1997; Revised Memorandum November

14, 1997). The identified endpoints are

an acute dietary of 6.0 mg/kg/day

(systemic) and a chronic dietary of 2.5

mg/kg/day (RfD = 0.025 mg/kg/day, UF

= 100). No endpoints of concern were

identified by the Committee for

occupational or residential, dermal or

inhalation exposures of any duration.

Further, in the Revised Memorandum of

November 14, 1997, the Committee

concluded that an additional safety

factor, beyond 100 was not needed to

account for special sensitivity of infants

and children to fenpropathrin. In a

separate action, fenpropathrin has been

evaluated for carcinogenicity by the

HED RfD/Peer Review Committee. In a

Memorandum from Dr. G. Z. Ghali to

Mr. G. La Rocca dated March 18, 1993,

it was concluded that in valid studies

with adequate doses that the compound

‘‘did not alter the spontaneous tumor
Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41841

profile in both rats and mice’’.

Fenpropathrin was classified as Group

E.

1. Acute toxicity. Oral LD50 in the rat

is 54.0 milligram/kilogram (mg/kg) for

males and 48.5 mg/kg for females -

Toxicity Category I; dermal LD50 is

1,600 mg/kg for males and 870 mg/kg

for females - Category II; acute

inhalation (impossible to generate

sufficient test article vapor or aerosol to

elicit toxicity) - Category IV; primary

eye irritation (no corneal involvement,

mild iris and conjunctival irritation) -

Category III; and primary dermal

irritation (no irritation) - Category IV.

Fenpropathrin is not a sensitizer.

2. Genotoxicity. Studies on gene

mutation and other genotoxic effects:

An Ames Assay was negative for

Salmonella TA98, TA100, TA1535,

TA1537, and TA1538; and E coli

WP2uvrA (trp-) with or without

metabolic activation. Sister

Chromosome Exchange in CHO-K1 Cells

- there were no increases in sister

chromatid exchanges seen in the CHOK1 cells treated with S-33206 or the

DMSO vehicle. Cytogenetics in vitro

(CHO/CA) - negative for chromosome

aberrations (CA) in Chinese hamster

ovary (CHO) cells exposed in vitro to

toxic doses ( > 30 nanogram) without

activation; and to limit of solubility

(1,000 nanogram) with activation. In

Vitro Assay in Mammalian Cells -

equivocal results - of no concern. DNA

Damage/Repair in Bacillus subtilis - not

mutagenic or showing evidence of DNA

damage at > 5,000 nanogram/paper disk.

3. Reproductive and developmental

toxicity. In a developmental toxicity

study in rats, pregnant female rats were

dosed by gavage on gestation days 6-15

at 0 (corn oil control) 0.4, 1.5, 2.0, 3.0,

6.0, or 10.0 mg/kg/day. The maternal no

observed adverse effect level (NOAEL)

is 6 mg/kg/day; maternal LEL is 10 mg/

kg/day based on death, moribundity,

ataxia, sensitivity to external stimuli,

spastic jumping, tremors, prostration,

convulsions, hunched posture, squinted

eyes, chromodacryorrhea, and

lacrimation; developmental NOAEL is >

10 mg/kg/day.

In a developmental toxicity study in

rabbits, pregnant female New Zealand

rabbits were dosed by gavage on

gestation days 7 through 19 at 0, 4, 12,

or 36 mg/kg/day. Maternal NOEL is 4

mg/kg/day; maternal LEL is 12 mg/kg/

day based on grooming, anorexia,

flicking of the forepaws; developmental

NOEL is > 36 mg/kg/day (HDT).

A 3-generation reproduction study

was performed in rats. Rats were dosed

with fenpropathrin at concentrations of

0, 40, 120, or 360 ppm (0, 3.0, 8.9, or

26.9 mg/kg/day in males; 0, 3.4, 10.1, or

32.0 mg/kg/day in females,

respectively). Parents (male/female):

Systemic NOEL = 40 ppm (3.0/3.4 mg/

kg/day). Systemic LEL = 120 ppm (8.9/

10.1 mg/kg/day) based on body tremors

with spasmodic muscle twitches,

increased sensitivity and maternal

lethality; reproductive NOEL = 120 ppm

(8.9/10.1 mg/kg/day). Reproductive LEL

= 360 ppm (26.9/32.0 mg/kg/day) based

on decrease mean F1B pup weight,

increased F2B loss. Pups (male/female):

Developmental NOEL = 40 ppm (3.0/3.4

mg/kg/day). Developmental LEL = 120

ppm (8.9/10.1 mg/kg/day) based on

body tremors, increased mortality.

4. Subchronic toxicity. In a

subchronic oral toxicity study, rats were

dosed at concentrations of 0, 3, 30, 100,

300, or 600 ppm in the diet. The lowest

effect level (LEL) is 600 ppm (30 mg/kg/

day) based on body weight (bwt)

reduction (female), body tremors, and

increased brain (female) and kidney

(male) weights. The NOEL is 300 ppm

(15 mg/kg/day).

In a subchronic oral toxicity study,

dogs were dosed at concentrations of 0,

250, 500, or 1,000 ppm in the diet. A

1,000 ppm dog was sacrificed moribund

during the third week after having

tremors and showing other signs of

poisoning caused by the test article.

Because of this death, the dose for this

group was reduced to 750 ppm for the

remainder of the study. The LOEL is 250

ppm (7.25 mg/kg/day) based on signs of

GI tract disturbance. There was no

NOEL -- note dog chronic, below)

In a 21-day dermal toxicity study,

rabbits were dosed 5-days/week for 3

weeks on abraded or unabraded skin at

doses of 0, 500, 1,200, or 3,000 mg/kg/

day. There were no dose-related effects

on bwt, food consumption, clinical

pathology, gross pathology, or organ

weights. Trace or mild inflammatory

cell infiltration was seen in the intact

and abraded skin in all groups,

including controls, and was attributed

to the test article. The systemic NOEL is

> 3,000 mg/kg/day. Local irritation only.

Although a 21-day dermal toxicity

study in rabbits is available the Agency

has determined that rats are the most

sensitive species to ascertain the dermal

toxicity potential of pyrethroid

insecticides. Although these data are

lacking, EPA has sufficient toxicity data

to support these tolerances and these

additional studies are not expected to

significantly change the risk assessment.

5. Chronic toxicity. In a 1-year feeding

study, dogs were dosed at 0, 100, 250,

or 750 ppm in the diet. The systemic

LEL is 250 ppm (6.25 mg/kg/day) based

on tremors in all dogs. The neurologic

NOEL is 100 ppm (2.5 mg/kg/day); the

systemic NOEL is 100 ppm (2.5 mg/kg/

day).

In a chronic feeding/carcinogenicity

study, rats were dosed at 0, 50, 150, 450,

or 600 ppm in the diet (0, 1.93, 5.71,

17.06, or 22.80 mg/kg/day in males, and

0, 2.43, 7.23, 19.45, or 23.98 mg/kg/day

in females). There was no evidence of

carcinogenicity at any dose up to and

including 600 ppm. The systemic NOEL

(male) is 450 ppm (17.06 mg/kg/day).

The systemic NOEL (female) is 150 ppm

(7.23 mg/kg/day). Systemic LEL (male)

is 600 ppm highest dose tested (HDT)

based on increased mortality, body

tremors, increased pituitary, kidney,

and adrenal weights. The systemic LEL

(female) is 450 ppm (19.45 mg/kg/day)

based on increased mortality and body

tremors.

In a chronic feeding/carcinogenicity

study, mice were dosed at 0, 40, 150, or

600 ppm in the feed (0, 3.9, 13.7, or 56.0

mg/kg/day in males, and 0, 4.2, 16.2, or

65.2 mg/kg/day in females). Mortality

was highest during the final quarter of

the study, but the incidence was similar

in all dosed and control groups. No

other indications of toxicity or

carcinogenicity were seen. The systemic

NOEL is ≤ 600 ppm (HDT; male/female,

56.0/65.2 mg/kg/day). text.

6. Animal metabolism. In a

metabolism study in rats, animals were

dosed with radiolabelled fenpropathrin

radiolabelled in either the alcohol or

acid portion of the molecule. Rats

received 14 daily oral low-doses of 2.5

mg/kg/day of unlabelled fenpropathrin

followed by a 15th dose of either the

alcohol or acid radiolabelled

fenpropathrin. Groups of rats received a

single dose of either of the 2

radiolabelled test articles at 2.5 mg/kg or

25 mg/kg. No clinical signs were seen in

any rats.

The major biotransformations

included oxidation at the methyl group

of the acid moiety, hydroxylation at the

4’-position of the alcohol moiety,

cleavage of the ester linkage, and

conjugation with sulfuric acid or

glucuronic acid.

Four metabolites were found in the

urine of rats dosed with alcohol labeled

fenpropathrin. The major metabolites

were the sulfate conjugate of 3-(4’-

hydroxyphenoxy)benzoic acid and 3-

phenoxybenzoic acid (22-44% and 3-9%

of the administered dose, respectively).

The major urinary metabolites of the

acid-labeled fenpropathrin were TMPAglucuronic acid and TMPA-CH2OH (11-

26% and 6-10% of the administered

dose, respectively). None of the parent

chemical was found in urine.

The major elimination products in the

feces included the parent chemical (13-

34% of the administered dose) and four
41842 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

metabolites. The fecal metabolites (and

the percentage of administered dose)

included CH2OH-fenpropathrin (9

20%), 4’-OH-fenpropathrin (4-11%),

COOH-fenpropathrin (2-7%), and 4’-

OH-CH2OH-fenpropathrin (2-7%).

There are no qualitatively unique

plant metabolites . The primary

aglycones are identical in both plants

and animals; the only difference is in

the nature of the conjugating moieties

employed.

The metabolism and potential toxicity

of the small amounts of terminal plant

metabolites have been tested on

mammals. Glucoside conjugates of 3-

phenoxy-benzyl alcohol and 3-

phenoxybenzoic acid, administered

orally to rats, were absorbed as the

corresponding aglycones following

cleavage of the glycoside linkage in the

gut. The free or reconjugated aglycones

were rapidly and completely eliminated

by normal metabolic pathways. The

glucose conjugates of 3-phenoxybenzyl

alcohol and 3-phenoxy-benzoic acid are

less toxic to mice than the

corresponding aglycones.

7. Endocrine disruption. No special

studies to investigate the potential for

estrogenic or other endocrine effects of

fenpropathrin have been performed.

However, as summarized above, a large

and detailed toxicology data base exists

for the compound including studies

acceptable to the Agency in all required

categories. These studies include

evaluations of reproduction and

reproductive toxicity and detailed

pathology and histology of endocrine

organs following repeated or long term

exposure. These studies are considered

capable of revealing endocrine effects

and no such effects were observed.

C. Aggregate Exposure

1. Dietary exposure. Toxicity

endpoints of concern have been

identified by the Agency’s Health

Effects Division, Hazard Identification

Assessment Review Committee (July 17,

1997). The identified endpoints are a

Chronic Dietary of 2.5 mg/kg/day (RfD

= 0.025 mg/kg/day, UF = 100) and an

Acute Dietary of 6.0 mg/kg/day

(systemic). Thus, both chronic and acute

dietary exposure and risk analyses are

necessary.

2. Food. Chronic and acute dietary

exposure analyses were performed for

fenpropathrin using anticipated

residues and accounting for proportion

of the crop treated. The crops included

in the analyses are the raw agricultural

commodities cottonseed, currants,

peanuts, strawberries, tomatoes, pome

fruits, citrus, grapes, head and stem

brassica, and melons; processed

products from these crops; and the

resulting secondary residues in meat,

milk, and eggs. A report along with a

supplemental report of these exposure/

risk analyses has been submitted to the

Agency including a detailed description

of the methodology and assumptions

used.

Chronic dietary exposure was

calculated for the U.S. population and

26 population subgroups. The results

from several representative subgroups

are listed below. Chronic dietary

exposure was at or below 1.7 % of the

reference dose with grapes and apples

the commodities contributing the most

to chronic exposure. Generally

speaking, the Agency has no cause for

concern if total residue contribution for

published and proposed tolerances is

less than 100% of the RfD.

SUMMARY OF CHRONIC DIETARY

(FOOD) EXPOSURES TO

FENPROPATHRIN RESIDUES

Population Subgroup

Exposure(mg/kg

bw/day)

Percent

ofRfD

Total U.S. Population (all seasons) 0.000165 0.7

Females (13+/

Nursing) 0.000285 1.1

Non-Hispanic

other than B/

W 0.000246 1.0

Children (1-6

Years) 0.000435 1.7

All Infants (<1

Year Old) 0.000193 0.8

Non-Nursing Infants (<1 Year

Old) 0.000127 0.5

Nursing Infants

(<1 Year Old) 0.000351 1.4

Acute dietary exposure was

calculated for the U.S. population,

Females (13+/Pregnant/Not Nursing),

and five children subgroups. The subpopulation, Females (13+/Pregnant/Not

Nursing), was included because the

toxicity endpoint for acute dietary

exposure identified by the Agency is

based on clinical signs of toxicity in the

dams from the rat developmental

toxicity study. The calculated exposures

and margins of exposure (MOE) for the

higher exposed proportions of the

subgroups are listed below. In all cases,

margins of exposure exceed onehundred.

CALCULATED ACUTE DIETARY EXPOSURES TO FENPROPATHRIN RESIDUES IN FOOD (PER-CAPITA DAYS)

Population Subgroup

99th Percentile 99.9th Percentile

Exposure(mg/kg

bw/day)

MOE

Exposure(mg/kg

bw/day)

MOE

U.S. Polulation .................................................................................................................. 0.003296 1,821 0.010173 590

Females (13+/Pregnant/NotNursing) ................................................................................ 0.002737 2192 0.005595 1072

Children 1-6 ...................................................................................................................... 0.008461 709 0.020678 290

Children 7-12 .................................................................................................................... 0.005322 1,127 0.012195 492

All Infants .......................................................................................................................... 0.002963 2,025 0.029691 202

Nursing Infants (<1) .......................................................................................................... 0.007142 840 0.050337 119

Non-Nursing Infants (<1) .................................................................................................. 0.001874 3,202 0.004863 1,234

It should be noted that the numbers

of individuals in the dietary survey of

some population subgroups is small.

These ‘‘under represented’’ subgroups

are weighted to account for their

proportions in the total U.S. Population

and in various geographic and ethnic

subpopulations. If in these under

represented subgroups there are

individuals with unusual dietary

consumption patterns anomalous Monti

Carlo selected diets will occur at the

lower probability exposures (e.g. 99th

and 99.9th percentiles) often times

leading to unrealistically high

calculated exposures. Such is the case

for Nursing Infants (<1). Two of these

babies were reported to be fed raw

grapes. In one case, one nursing infant

was reported to consume 310 grams of

raw grapes in a single day. This is a very

unusual diet for any infant. Because of

this dietary anomaly, and the weighting

factor for this population subgroup, the
Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices 41843

MOE for nursing infants approaches

100.

3. Drinking water. Since

fenpropathrin is applied outdoors to

growing agricultural crops, the potential

exists for fenpropathrin or its

metabolites to reach ground or surface

water that may be used for drinking

water. Because of the physical

properties of fenpropathrin, the Agency

has determined that it is unlikely that

fenpropathrin or its metabolites can

leach to potable groundwater.

To further quantify potential exposure

from drinking water, surface water

concentrations for fenpropathrin were

estimated using GENEEC 1.2. The

average 56-day concentration predicted

in the simulated pond water was 0.22

ppb. The residence time of

fenpropathrin in surface water has been

measured and is short. In pond studies,

fenpropathrin half-lives in the water

column were less than 1.5 days, thus

this 56-day modeled half-life probably

considerably overestimates any real

surface water concentration. Using

standard assumptions about bwt and

water consumption, the chronic

exposure from this drinking water

would be 6.3 x 10-6 and 2.2 x 10 -5 mg/

kg bw/day for adults and children,

respectively; less than 0.09 % of the RfD

for children. Based on this worse case

analysis, the contribution of water to the

dietary risk is negligible.

4. Non-dietary exposure.

Fenpropathrin, as the product TAME

2.4 EC Spray, is registered for

professional non-food use both indoors

and outdoors on ornamentals and nonbearing nursery fruit trees.

Fenpropathrin has no animal health,

homeowner, turf, termite, indoor pest

control, or industrial uses. Quantitative

information concerning human

exposure from this ornamental use is

not available, but exposure to the

general public from this use of

fenpropathrin is expected to be

minimal. It is important to note that no

endpoints of concern were identified by

the Health Effects Division, Hazard

Identification Assessment Review

Committee for occupational or

residential, dermal or inhalation

exposures of any duration. Thus, no risk

assessment is needed.

D. Cumulative Effects

Section 408(b)(2)(D)(v) requires that

the Agency must consider ‘‘available

information’’ concerning the cumulative

effects of a particular pesticide’s

residues and ‘‘other substances that

have a common mechanism of toxicity.’’

Available information in this context

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.

There are numerous other pesticidal

compounds, pyrethroids and natural

pyrethrins, that are structurally related

to fenpropathrin and may have similar

effects on animals. In consideration of

potential cumulative effects of

fenpropathrin and other substances that

may have a common mechanism of

toxicity, there are currently no available

data or other reliable information

indicating that any toxic effects

produced by fenpropathrin would be

cumulative with those of other chemical

compounds. Thus, only the potential

risks of fenpropathrin have been

considered in this assessment of

aggregate exposure and effects.

Valent will submit information for

EPA to consider concerning potential

cumulative effects of fenpropathrin

consistent with the schedule established

by EPA at 62 FR 42020 (August 4, 1997)

and other EPA publications pursuant to

the Food Quality Protection Act.

E. Safety Determination

The Food Quality Protection Act of

1996 introduces a new standard of

safety, a reasonable certainty of no

harm. To make this determination, at

this time the Agency should consider

only the incremental risk of

fenpropathrin in its exposure

assessment. Since the potential chronic

and acute exposures to fenpropathrin

are small (<< 100 % of RfD, MOE ≤ 100)

the provisions of the FQPA of 1996 will

not be violated.

1. U.S. population—i Chronic

exposure. Using the dietary exposure

assessment procedures described above

for fenpropathrin, calculated chronic

dietary exposure resulting from residue

exposure from existing and proposed

uses of fenpropathrin is minimal. The

estimated chronic dietary exposure from

food for the overall U.S. population and

many non-child/infant subgroups is 1.1

[Females (13+/Nursing), 0.000285 mg/kg

bw/day] to 0.4 % of the RfD. Addition

of the small but worse case potential

chronic exposure from drinking water

(calculated above) increases exposure by

only 6.3 x 10-6 mg/kg bw/day, and the

maximum occupancy of the RfD from

1.14 % to 1.16 %. Generally, the Agency

has no cause for concern if total residue

contribution is less than 100 % of the

RfD. It can be concluded that there is a

reasonable certainty that no harm will

result to the overall U.S. Population and

many non-child/infant subgroups from

aggregate, chronic exposure to

fenpropathrin residues.

ii. Acute. The potential acute

exposure from food to the U.S.

population and various non-child/infant

population subgroups (shown above)

provide MOE values greatly exceeding

100. Addition of the worse case, but

very small ‘‘background’’ dietary

exposure from water is not sufficient to

change the MOE values significantly

(see table below). In a conservative

policy, the Agency has no cause for

concern if total acute exposure

calculated for the 99.9th percentile

yields a MOE of 100 or larger. It can be

concluded that there is a reasonable

certainty that no harm will result to the

overall U.S. Population and many nonchild/infant subgroups from aggregate,

acute exposure to fenpropathrin

residues.

AGGREGATE U.S.POULATION ACUTE

DIETARY EXPOSURE

Source of Exposure

Exposure(mg/

kgbw/day)

99.9th Percentile Margin

ofExposure

Chronic Water ... 0.000006 -

99.9th Percentile

Acute Exposure -- Food ... 0.010173 589.8

99.9th Percentile

Aggregate

Acute Exposure Food +

Water ............. 0.010179 589.4

2. Infants and children. Safety Factor

for Infants and Children: In assessing

the potential for additional sensitivity of

infants and children to residues of

fenpropathrin, FFDCA section 408

provides that EPA shall apply an

additional margin of safety, up to tenfold, for added protection for infants

and children in the case of threshold

effects unless EPA determines that a

different margin of safety will be safe for

infants and children.

The toxicological data base for

evaluating pre- and post-natal toxicity

for fenpropathrin is complete with

respect to current data requirements.

There are no special pre- or post-natal

toxicity concerns for infants and

children, based on the results of the rat

and rabbit developmental toxicity

studies or the 3-generation reproductive

toxicity study in rats. EPA HED Hazard
41844 Federal Register / Vol. 63, No. 150 /Wednesday, August 5, 1998 / Notices

ID Committee (Revised Memorandum,

November 14,1997) has concluded that

reliable data support use of the standard

100-fold uncertainty factor and that an

additional uncertainty factor is not

needed for fenpropathrin to be further

protective of infants and children.

3. Chronic risk. Using the

conservative exposure assumptions

described above, the percentage of the

RfD that will be utilized by dietary (food

only) exposure to residues of

fenpropathrin ranges from 0.5 % for

Non-Nursing Infants (<1 year old), up to

1.7 % for Children (1 - 6 years).

Addingthe worse case potential

incremental exposure to infants and

children from fenpropathrin in drinking

water ( 2.2 x 10 -5 mg/kg bw/day) to the

chronic dietary exposure from food

(0.000435 mg/kg bw/day) does not

materially increase the aggregate,

chronic dietary exposure and only

increases the occupancy of the RfD by

0.09% to 1.8 % for Children (1 - 6

years). EPA generally has no concern for

exposures below 100% of the RfD

because the RfD represents the level at

or below which daily aggregate dietary

exposure over a lifetime will not pose

appreciable risks to human health. It

can be concluded that there is a

reasonable certainty that no harm will

result to infants and children from

aggregate, chronic exposure to

fenpropathrin residues.

4. Acute. The potential acute

exposure from food to the various child

and infant population subgroups

(shown above) provide MOE values

exceeding 100. Addition of the worse

case, but very small ‘‘background’’

dietary exposure from water (2.2 x 10 -5

mg/kg bw/day) is not sufficient to

change the MOE values significantly

(see table below). In a conservative

policy, the Agency has no cause for

concern if total acute exposure

calculated for the 99.9th percentile

yields a MOE of 100 or larger. It can be

concluded that there is a reasonable

certainty that no harm will result to

infants and children from aggregate,

acute exposure to fenpropathrin

residues.

AGGREGATE NURSING INFANTS (> 1

YEAR) ACUTE DIETARY EXPOSURE

Source of Exposure

Exposure

(mg/kg bw/

day)

99.9th Percentile Margin of Exposure

Chronic Water ... 0.000022 -

99.9th Percentile

Acute Exposure - Food .... 0.050337 119.2

99.9th Percentile

Aggregate

Acute Exposure Food +

Water ............. 0.050359 119.1

F. Safety Determination Summary

Aggregate acute or chronic dietary

exposure to various sub-populations of

children and adults demonstrate

acceptable risk. Aggregate chronic

dietary exposures to fenpropathrin

occupy considerably less than 100% of

the RfD, and all aggregate acute dietary

MOE values exceed 100. Chronic and

acute dietary risk to children from

fenpropathrin should not be of concern.

Further, fenpropathrin has no other

uses, such as animal health, indoor pest

control, homeowner use or turf

applications, that could lead to unique,

enhanced exposures to vulnerable subgroups of the population. It can be

concluded that there is a reasonable

certainty that no harm will result to the

U.S. Population or to any sub-group of

the U.S. population, including infants

and children, from aggregate chronic or

aggregate acute exposures to

fenpropathrin residues resulting from

approved and pending uses.

G. International Tolerances

Codex Maximum Residue Limits

186 -- FENPROPATHRIN

Main uses -- 8 -- INSECTISCIDE/

ACARACIDE

JMPR -- 83

ADI -- 0.03 mg/jg body weight (1993)

RESIDUE -- Fenpropathrin (fat soluble)

Commodity

Code Name MRL (mg/

kg) Step JMPR CCPR

MM 0812 ............................................................................... Cattle meat 0.5 (fat) 6 93 ....................

ML 0812 ................................................................................ Cattle milk 0.1 F 6 93 ....................

MO 0812 ............................................................................... Cattle, Edible offal of 0.05 CXL (1995)

SO 0691 ................................................................................ Cotton seed 1 CXL (1995)

OC 0691 ............................................................................... Cotton seed oil, Crude 3 CXL .................... (1995)

VO 0440 ................................................................................ Egg plant 0.2 6 93 ....................

PE 0112 ................................................................................ Eggs 0.01 (*) CXL .................... (1995)

VC 0425 ................................................................................ Gherkin 0.2 CXL D (1995)

FB 0269 ................................................................................ Grapes 5 6 93 ....................

VO 0445 ................................................................................ Peppers, Sweet 1 CXL .................... (1995)

FP 0009 ................................................................................ Pome fruits 5 CXL .................... (1995)

PM 0110 ............................................................................... Poultry meat 0.02 (fat) CXL .................... (1995)

PO 0111 ................................................................................ Poultry, Edible offal of 0.01 (*) CXL .................... (1995)

V0 0448 ................................................................................ Tomato 1 CXL .................... (1995)

There are small differences between

the Section 408 tolerances and the

Codex MRL values for secondary

residues in animal products. These

minor differences are mainly caused by

differences in the methods used to

calculate animal feed dietary exposure.

The only substantial difference between

the US tolerance and the Codex MRL

value is for tomatoes. The JMPR

reviewer required that the MRL exceed

the highest field residue value rounded

up to unit value. The EPA reviewer

agreed with Valent that one set of field

residue samples was possibly

compromised by the presence of a high

rate processing treatment nearby. High

outliers were ignored, and the tolerance

was set at 0.6 ppm. (Beth Edwards)

[FR Doc. 98–20769 Filed 8–4–98; 8:45 am]

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