13000 Federal Register / Vol. 62, No. 53 / Wednesday, March 19, 1997 / Notices

[PF–720; FRL–5592–6]

BASF Corporation; Pesticide

Tolerance Petition Filing

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice of filing.

SUMMARY: This notice announces the

filing of a pesticide petition proposing

regulations establishing tolerances for

residues of vinclozolin [3-(3,5-dichlorophenyl)-5-methyl-5-vinyl-1,3-

oxazolidine-2,4-dione)] and metabolites

containing the 3.5-dichloroanaline

moiety at 5.0 ppm to control Botrytis

gray mold and Scelertinia white mold

on succulent beans. In conjunction with

this petition, BASF is requesting that

the tolerances for prunes, plums,

tomatoes grapes (excluding grapes

grown for wine production) and raisins

be withdrawn by the Agency. This

notice includes a summary of the

petition that was prepared by the

petitioner, BASF Corporation.

DATES: Comments, identified by the

docket number [PF–720], must be

received on or before April 18, 1997.

ADDRESSES: By mail, submit written

comments to Public Response and

Program Resources Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St. SW.,

Washington, DC 20460. In person, bring

comments to Rm. 1132, CM #2. 1921

Jefferson Davis Highway, Arlington, VA

22202. Comments and data may also be

submitted electronically be sending

electronic mail (e-mail) to: oppdocket@epamail.epa.gov. Electronic

comments must be submitted as an

ASCII file avoiding the use of special

characters and any form of encryption.

Comments and data will also be

accepted on disks in WordPerfect 5.1

file format or in ASCII file format. All

comments and data in electronic form

must be identified by docket control

number [PF–720]. Electronic comments

on this notice may be filed online at

many Federal Depository Libraries.

Additional information on electronic

submissions can be found below this

document.

Information submitted as a comments

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:

Connie Welch, Product Manager (PM)

21, Registration Division, (7505C),

Office of Pesticide Programs,

Environmental Protection Agency, 401

M. St., SW., Washington, DC. Office

location, telephone number and e-mail

address: Rm. 227, CM#2, 1921 Jefferson

Davis Highway, Arlington, VA 703–

305–6226. e-mail: welch.connie

@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: EPA has

received pesticide petition (PP) 9F3762

from BASF Corporation, Agricultural

Products, PO Box 13528, Research

Triangle Park, NC 27709, proposing

pursuant to section 408(d) of the Federal

Food, Drug and Cosmetic Act (FFDCA),

21 U.S.C section 346a (d), to amend 40

CFR part 180 by establishing tolerances

for residues of vinclozolin [3-(3,5-

dichlorophenyl)-5-methyl-5-vinyl-1,3-

oxazolidine-2,4-dione) and metabolites

containing the 3,5-dichloroanaline

moiety when used as a fungicide in or

on raw agricultural commodity

succulent beans at 5.0 ppm. EPA has

determined that the petition contains

data or information 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 these data support granting of

the petition. Additional data may be

needed before EPA rules on the petition.

The proposed analytical method is gas

chromatography using Electron Capture

detection.

As required by section 408(d) of the

FFDCA, as recently amended by the

Food Quality Protection Act, BASF

Corporation included in the petition a

summary of the petition and

authorization for the summary to be

published in the Federal Register in a

notice of receipt of the petition. The

summary represents the views of BASF;

EPA, as mentioned above, is in the

process of evaluating the petition. As

required by section 408(d)(3) EPA is

including the summary as a part of this

notice of filing. EPA may have made

minor edits to the summary for the

purpose of clarity.

I. Petition Summary

A. Plant Metabolism

BASF Corporation notes that

metabolism in plants is understood, the

residues of concern are vinclozolin [3-

(3,5-dichlorophenyl)-5-methyl-5-vinyl1,3-oxazolidine-2,4-dione) and

metabolites containing the 3,5-

dichloroanaline moiety.

B. Analytical Method

The proposed analytical method

involves extraction, hydrolysis,

distillation, partition, and

deriviatization followed by detection of

residues by gc/ecd. An enforcement

method has been published in FDA’s

Pesticide Analytical Methods, Volume

II pg. 876–887.

C. Magnitude of the Residues

Sixteen residue trials were carried out

in 7 succulent bean producing states;

CA, FL, MI, NY, NC, OR, and WI.

Residue in the succulent beans ranged

from 0.38 to 2.40 ppm and averaged

0.83 ppm.

D. Toxicological Profile

1. Acute Toxicity. The acute toxicity

studies place technical vinclozolin in

acute toxicity category IV for acute oral

(LD50 of >15,000 mg/kg), and inhalation

(LD50 of 29.1 mg/l) and acute toxicity

category III for acute dermal (LD50 of

>5,000 mg/kg) , eye (minimal) and

dermal (minimal) irritation and the

technical material is a positive skin

sensitizer.

2. Chronic Toxicity Testing.

a. Chronic feeding Nonrodent. A 1-

year feeding study in dogs fed dosages

of 0, 1.1 , 2.4, 4.9, and 48.7 mg/kg/day

with a No-Observed Adverse-Effect

Level (NOAEL) of 2.4 mg/kg/day based

on the following effects: (1) slight

decrease in hematological and increase

clinical chemistry values in the 48.7

mg/kg/day dose group (highest dose

tested - (HDT)); (2) increased absolute

and/or relative weights for the testes

(male only), adrenals, liver, spleen, and

thyroids in the either the 4.9 or 48.7 mg/

kg/day dose groups; and (3) a doserelated atrophy of the prostate in the 4.9

or 48.7 mg/kg/day dose groups; and (4)

microscopic findings in the adrenal and

testes (males) in the 48.7 mg/kg/day

dose group and liver findings for both

male and female dogs in the 48.7 mg/kg/

day dose groups and in the females in

the 4.9 mg/kg/day dose group, only.

b. Chronic feeding/Oncogenicity -

Rats. A combination of 2 chronic

feeding and one carcinogenicity studies

that were performed separately, resulted

in rats being fed combined dosages of 0,

1.2, 2.4, 7.0, 23, 71, 143, and 221 mg/

kg/day (males) and 0, 1.6, 3.1, 7.0, 23,

71, 180, and 221 mg/kg/day (females)

with a NOAEL of 1.2 mg/kg/day (males)

and 1.6 mg/kg/day (females) based on

the following effects: (1) decreased body

weights in both males and female rat at
Federal Register / Vol. 62, No. 53 / Wednesday, March 19, 1997 / Notices 13001

dose levels ≥23 mg/kg/day dose groups

with a progression of severity to the

upper levels; (2) decreased food

consumption in both males and female

rats at dose levels ≥71 mg/kg/day dose

groups with a progression of severity to

the upper dose levels; (3) cataracts with

associative histopathology at dose levels

≥23 mg/kg/day and lenticular changes at

dose levels ≥7.0 mg/kg/day for male and

female rats; (4) hematological and

clinical chemistry value changes at dose

levels ≥71 mg/kg/day dose groups with

increase of severity at the higher doses

tested; (5) increased absolute and/or

relative weights for adrenals at dose

levels ≥143 mg/kg/day, for the liver at

dose levels ≥71 mg/kg/day, for the testes

at dose levels ≥23 mg/kg/day, and for

the ovaries at dose levels ≥143 mg/kg/

day; (6) microscopic findings were

observed in the liver, adrenal, pancreas,

testes (males), ovaries and uterus

(females) were seen in dose levels of

≥7.0 mg/kg/day with a progression of

severity of histological effects in the

upper dose levels; and (7) an increased

incidence of neoplasms occurred at dose

levels greater than the maximum

tolerated dose (MTD) of 23 mg/kg/day in

the liver, adrenals, pituitary, prostate

(males), uterus (females), and ovaries

(females) at dose levels ≥143 mg/kg/day.

In the testes (males), neoplasms were

seen slightly below the MTD at dose

levels ≥7.0 mg/kg/day due the

antiandrogenic nature of vinclozolin.

3. Oncogenicity - Mice. An

oncogenicity study in mice fed dosages

of 0, 2.1, 20.6, 432, and 1,225 (HDT) mg/

kg/day (males) and 0, 2.8, 28.5, 557, and

1,411 (HDT) mg/kg/day (females) with a

NOAEL of 20.6 mg/kg/day (males) and

28.5 mg/kg/day (females) based on the

following effects: (1) increased mortality

in the highest dose tested (HTD) as

compared to controls; (2) decreased

body weights and significant signs of

clinical toxicity were observed in both

males and female mice at the upper two

dose levels with a progression of

severity; (3) hematological and clinical

chemistry value changes were observed

at the highest dose tested; (4) increased

absolute and/or relative weights for

adrenals and liver were observed at the

upper two dose levels, atrophic seminal

vesicles and coagulation glands with

reduction of the prostate (males) and

atrophic uteri were observed at the

upper two dose levels; (5) microscopic

findings were observed in the liver,

adrenal, testes (males), ovaries and

uterus (females), and related sexual

organs were seen in the upper two dose

levels; (6) an increased incidence of

neoplasms occurred at dose levels

greater than the maximum tolerated

dose (>28.5 mg/kg/day) in the liver of

female mice.

4. Developmental Toxicity Testing

a. Teratology - Rat. A combination of

four developmental studies in rats via

oral gavage resulted in dosages of 0, 15,

50, 100, 150, 200, 400, 600, and 1000

(HDT) mg/kg/day with a development

toxicity NOAEL of 15 mg/kg/day and a

maternal toxicity NOAEL equal to or

greater than 400 mg/kg/day based on the

following: (1) no obvious signs of

maternal toxicity were observed at dose

levels less than or equal to 400 mg/kg/

day; (2) an increased number of fetus

with retarded ossification of thoracic

vertebral bodies at dose levels greater

than or equal to 200 mg/kg/day and

increased number of fetus with soft

tissue variations at dose levels greater

than or equal to 400 mg/kg/day, both

findings are regarded as unspecific

embryo-/fetotoxic effects indicating

transient delays in development but not

indicative of a teratogenic effect; and (3)

a statistical significant decrease or

reduction of the anogenital index (AGI)

in male was observed at levels greater

than or equal to 50 mg/kg/day.

In a developmental study in rats via

dermal exposure for six hours/day on

intact skin with dosages of 0, 60, 180,

and 360 mg/kg/day (HDT) with a

development toxicity NOAEL of 60 mg/

kg/day and a maternal toxicity NOAEL

of 60 mg/kg/day based on the following:

(1) increased absolute liver weights at

dose levels >180 mg/kg/day; and (2)

decreased anogenital distance and index

at dose levels >180 mg/kg/day.

b. Teratology - Rabbits. A

developmental study in rabbits via oral

gavage resulted in dosages of 0, 20, 80,

and 300 mg/kg/day (HDT) with a

development toxicity NOAEL of 300

mg/kg/day and a maternal toxicity

NOAEL of 300 mg/kg/day based on no

signs of maternal or meaningful fetal

toxicity were observed at any of the

dose levels mentioned.

A second developmental study in

rabbits via oral gavage resulted in

dosages of 0, 50, 200, and 800 mg/kg/

day (HDT) with a development toxicity

NOAEL of 200 mg/kg/day and a

maternal toxicity NOAEL of 50 mg/kg/

day based on the following: (1) severe

maternal toxicity with simultaneous

change in hematological values changes

and high number of abortions at the

HDT; and (2) increased absolute and/or

relative weights for adrenals in the mid

and high dose groups.

5. Reproductive Toxicity Testing

a. Two-Generation Reproduction -

Rat. A two-generation reproduction

study (consisting of two studies: study

A - dose levels of 0, 2.0 and 4.1 mg/kg/

day; study B - dose levels of 0, 4.9, 29

100, and 307 mg/kg/day) with rats fed

dosages of 0, 2.0, 4.1, 4.9, 29, 100, and

307 mg/kg/day with a reproductive

NOAEL of 4.9 mg/kg/day based on

feminization of male and the ability not

to mate at dose levels >100 mg/kg/day

and pup effects at 29 mg/kg/day; and

with a parental NOAEL of 4.9 mg/kg/

day based on general toxicity consistent

with previous rat studies at levels >29

mg/kg/day. Study A was performed to

clarify an equivocal finding of decreased

absolute and relative weight of the

epididymides without any

morphological correlation in the male

FY and FZ generations in Study B.

However, EPA stated ‘‘the effects at the

4.9 mg/kg/day dose level was minimal

and considered sufficiently close to a

NOAEL. The study is acceptable and 4.9

mg/kg/day dose level was considered to

be the No Observed-Effect Level

(NOEL).’’

6. Mutagenicity

A Modified Ames Test (3 studies;

point mutation): Negative; HostMediated Assay (point mutation):

Negative; Mouse Lymphoma Test (point

mutation): Negative; In Vitro CHO Cells

(point mutation): Negative; In Vitro

Cytogentics - CHO Cells (Chromosome

Aberrations): Negative; In Vivo

Dominant Lethal Test - Male NMRI

Mouse (Chromosome

Aberrations):Negative; Rec Assay (2 test;

DNA damage and repair): Negative; In

Vitro UDS Test Using Hepatocyte ( DNA

damage and repair): Negative; In Vivo

SCE Using Chinese Hamster ( DNA

damage and repair): Negative

Based on the data present and weight

of evidence, BASF concludes that

vinclozolin does not pose a mutagenic

hazard to humans.

7. Other Relevant Testing

a. Mechanistic Studies/Mode of

Action - Anti-androgenicity Activity

A series of mechanistic studies were

performed to elucidate and define the

anti-androgenic properties of

vinclozolin. The following conclusions

can be drawn from the in vivo data:

The anti-androgenic effects observed

are not related to an inhibition of

androgen-steroid hormone synthesis.

The anti-androgenic effects are not

related to an inhibition of 5 alphareductase activity.

The anti-androgenic effects are a

result of a competitive binding to the

androgen receptor resulting in an

inactivation of this receptor.

The anti-androgenic effects are

mediated by the hydrolysis metabolite

M1 and probably not by vinclozolin or

the main metabolite, R8.

The anti-androgenic effects are related

to a second hydrolysis metabolite M2

which is a slightly more potent anti-androgen
13002 Federal Register / Vol. 62, No. 53 / Wednesday, March 19, 1997 / Notices

than M1. However M2 concentrations

are very low and the compound may not

contribute much to the in vivo effects.

b. Metabolism - Rat

i. Oral studies. BASF has submitted

results from a number of metabolism

studies using wistar rats. The results of

these studies can be summarized as

follows: vinclozolin is well absorbed

(@85 percent) and intensively

metabolized, the liver playing an

important role (@65 percent of the

radioactivity administered was found in

the bile and no unchanged active

ingredient was excreted in the urine).

The determination of radioactivity in

the plasma over a period of seven days

showed that slight accumulation took

place.

ii. Dermal study. In an in vivo dermal

absorption study, male Wistar rats were

dosed with, 14C vinclozolin. Dose levels

of 0.002, 0.02, 0.2, and 2.0 mg/cm2 were

administered to 24 rats per dose level,

applied to a shaved area of approx. 13

cm2 on the back of the rat. Groups of 4

rats were sacrificed at 0.5, 1, 2, 4, 10, or

72 hours following application of the

dose. Urine and feces were collected

during this period. At the end of the

exposure period (10 hours in the case of

the 72 hour treatment group), the skin

site was washed with cotton swabs

moistened with water. A blood sample

was taken prior to sacrifice. The treated

skin along with the GI tract, liver,

kidneys, adrenals, testes, eyes, brain and

carcass were subjected to radioactive

mass balance analysis. Urine from the

bladder was added to the voided

samples. Results of this analysis showed

recoveries of between 81.6–104 percent.

The lowest dose of 0.002 mg/cm2 from

the 10-hour exposure period is

considered to be the most appropriate

dose for use in the occupational risk

assessment, as this dose most closely

approximates the dermal deposition

results obtained in the worker exposure

studies. After the 10–hour exposure the

total percent absorbed at this dose level

was 29.l percent.

Percutaneous absorption of [14C]-

vinclozolin was also assessed in vitro

using rat and human epidermis in flowthrough diffusion cells. The test

substance was applied at two dose

levels, 200 ug/cm2 (high) and 2 ug/cm2

(low), and assessed over 24 hours. A

total of 32 samples (16 rat and 16

human) were used at the high dose

level, and 34 (17 rat and 17 human) at

the low dose level. Samples of human

skin were obtained at postmortem.

Human epidermis was prepared from

full thickness skin by immersion in

water at 60 degrees Celsius for one

minute. Rat epidermis was prepared by

soaking the skin in 2M sodium bromide

for approximately 24 hours. With

respect to the worker exposure relevant

time of eight hours, penetration through

human skin was 16.7 times less at the

high dose tested and 4.2 times less at

the low dose tested than through rat

skin.

E. Threshold Effects

The established Reference Dose (RfD)

for vinclozolin is based on a 2-year

feeding study in rats with a threshold

NOAEL of 1.2 mg/kg/day. Using an

uncertainty factor of 100, the RfD is

calculated to be 0.012 mg/kg/day.

F. Non-Threshold Effects

Vinclozolin is known to be an antiandrogenic agent, thus the consequence

of hormonal imbalance are two-fold; the

primary anti-androgenic effect is a

suppression in androgen target organs

such as epidymides, prostate or seminal

vesicle, whereas stimulation is seen in

organs involved in steroid hormone

synthesis (testes, adrenals, ovaries).

Target organs for hormones must be able

to respond to changes in physiological

levels of hormones, which can fluctuate

significantly as evidenced by the

hormone changes during the female

estrus cycle. It was indeed demonstrated

that changes induced in these organs

were be reversible when hormone levels

return to normal concentrations. It is

only when hormone imbalance

continues over a long time that

irreversible changes occur.

In the case of suppression the affected

organ is forced into a hypofunctional

state. Progressively, the organ becomes

hypotrophic and hypoplastic. With

stimulation on the other hand the initial

changes can be described as

hyperfunction, hypertrophy and

hyperplasia. As mentioned before, it is

only when the hormonal imbalance

continues over a long time that the

ultimate reversible adaptation of the

affected organ (hypoplasia or

hyperplasia) is still not sufficient to

handle the situation and only then an

irreversible transition takes place. In the

case of hormonal suppression atrophy is

the ultimate consequence, in the case of

stimulation, the ultimate consequence

are tumors in the affected organs.

It is thus plausible that at dose levels

which do not result in hypertrophy/

hyperplasia or hypotrophy/hypoplasia

the ultimate consequence of these

adaptive changes, i.e. tumors oratrophy, respectively, cannot occur. For

risk assessment purposes this mode of

action offers the possibility to determine

a threshold for both tumor formation

and atrophy by histopathological

examination of the hyper- or hypofunctional organ. Thus, at dose levels

which do not affect these organs, a

mechanistic NOAEL can be defined and

risk assessment can be carried out using

assessment or safety factors.

The increase in neoplasia observed in

the adrenals, ovaries and uterus were

only seen in female rats at the high dose

levels which was ≥143 mg/kg/day of the

chronic toxicity study and/or

carcinogenicity study. As determined by

BASF and EPA, the 71 mg/kg/day dose

level of the rat chronic/oncogenicity

toxicity study exceeded the criteria for

a MTD. Therefore, based the

physiological status of the animals may

be deteriorated in such a way that low

dose extrapolation of results obtained at

this dose level is not possible. Similarly,

the liver tumors arising in the mouse

oncogenicity at the 1,411 mg/kg/day

dose level in which severe body weight

losses and significant mortality were

observed, clearly exceeding the MTD (as

determined by BASF and EPA - Cancer

Peer Review Document, September,

1996) and is not relevant for risk

assessment purposes.

Additionally, vinclozolin is not a

genotoxic agent and mechanistic studies

have shown the increased incidence of

liver tumors in male rat and female mice

is a result of liver tumor promoting

properties of the test substance.

Vinclozolin is not an initiator of the

carcinogenic event. Based on the

available data, the mechanism of

promotion is the induction of liver cell

proliferation of the test substance. The

data available also indicate that dose

levels which do not induce liver toxicity

also do not induce cell proliferation nor

enhance the carcinogenic process.

Therefore, BASF concludes that a

threshold for liver carcinogenicity can

be defined to be at least 143 mg/kg/day

in the rat and at least 557 mg/kg/day in

the mouse.

Concerning the testicular tumors

(Leydig cell tumors), results of the longterm studies with vinclozolin

demonstrate that hormone-related

carcinogenesis was only observed in

rats, and with the exception of Leydig

cell tumors only at dose levels which

exceeded the MTD criteria. The

relevance of Leydig cell tumors to men

should be seen in the light that this is

a very rare human tumor and that the

precursor change (i.e. Leydig cell

hyperplasia) has not been observed in

patients treated with flutamide. In

addition, the toxicology of cimitidine, a

H2-receptor antagonist with antiandrogenic properties resulting in a size

reduction and atrophy of the prostate

and seminal vesicles in chronic rat

studies. Moreover, an increase in benign

Leydig cell tumors, and a decrease in
Federal Register / Vol. 62, No. 53 / Wednesday, March 19, 1997 / Notices 13003

pituitary and mammary tumor

incidence were noted; hence a toxicity

potential not unlike that of vinclozolin

is evident. Despite the fact that over 30

million patients have been treated with

cimitidine, this therapeutic agent has

been demonstrated to be extremely safe,

clearly indicating that the rat Leydig cell

tumors have very little relevance for

humans. A similar conclusion is drawn

by other investigators ‘‘Leydig cell

tumors of the rat have limited

significance because of the fundamental

differences in testicular control

mechanisms.’’ It is therefore concluded

that the observed neoplastic changes do

not pose a relevant hazard to humans.

EPA in the September, 1996, Cancer

Peer Review Document, came to the

same basic conclusion that the Leydig

cell tumors are a very uncommon tumor

type in humans which implies the

threshold dose for humans would be

greater than for rats. EPA based this

conclusion on the work performed by

Dr. C. Capen (Professor Charles C.

Capen, Leydig Cell Tumors: Pathology,

Physiology, and Mechanistic

Considerations in Rats, The Toxicology

Forum, 1994 Annual Summer Meeting,

p. 110).

In the EPA Carcinogenicity Peer

Review Document of September 1996,

the Agency stated ‘‘[T]his classification

of Group B2 was based on statistically

significant increases in multiple tumor

types in male Wistar rats and ovarian

tumors in female Wistar rats at a dose

which was excessive. The MOE

approach was chosen because the

tumors were benign at dose levels

which were considered to be excessive,

and there was little concern for

mutagencity of vinclozolin. Mechanistic

data for the Leydig cell tumors also

provided further support for the use of

the MOE approach.’’ It is BASF’s

understanding that EPA has performed

another Cancer Peer Review in January,

1997. This rereview is based the

pathology peer review performed by Dr.

Charles Capen (Professor of Pathology at

The Ohio State University) concerning

the criteria used in diagnosing the

ovarian and prostate tumors seem in the

chronic/oncogenicity rat study for

vinclozolin and the report of the FIFRA

Scientific Advisory Panel (SAP)

concerning vinclozolin. The data

generated by Dr. Capen were also

presented to the SAP by BASF and are

a bases for the conclusions drawn by the

Panel. BASF is awaiting the result of

this second Cancer Peer Review.

To further support the conclusion

stated above, the most recent meeting of

the FIFRA SAP concluded the

following: (Proceeding of the October,

1996, meeting were issued in December,

1996)

‘‘[B]ased on these data (as presented by

BASF Corporation and EPA), it is far from

established that vinclozolin is carcinogenic

to the rat. It is not ruled out, however. In

addition, there is little concern for

mutagenicity as expressed by the Agency

reviews...

‘‘[B]ased on (1), we would consider the

possibility that vinclozolin is a carcinogen in

rats or mice, but the evidence for this is not

compelling. The Panel believes that the

classification of vinclozolin using the new

guidelines would be ‘‘not likely to be a

carcinogenic hazard to humans...’’

‘‘[T]he most appropriate method of risk

quantification is on a non-linear model, MOE

approach based on a NOEL for nonneoplastic effects...’’

Therefore both the Agency and the

SAP have agreed that vinclozolin

should be regulated as a threshold

chemical using the standard margin of

exposure approach, BASF concurs with

those opinions.

G. Aggregate Exposure

1. Dietary exposure. For the purpose

of assessing the potential chronic

dietary exposure, BASF has estimated

aggregate exposure based on Theoretical

Maximum Residue Contribution

(TMRC) for all exisiting tolerances and

registered uses of vinclozolin including

the proposed tolerance of vinclozolin on

succulent beans at 5.0 ppm. In this

analysis tolerance levels were used for

all crops except stonefruit were used. In

the case of stonefruit, anticipated

residues based on the available residue

data. Where reliable data were available

and acceptable to the Agency percent

crop treated was also used. This

analysis revealed that for the general

U.S. population and children - ages 1-

6 (the most sensitive sub-population),

vinclozolin treated crops utilized 25

percent and 45 percent, respectively, of

the RfD (0.012 /kg/day). BASF estimates

that withdrawal of the tolerances in

prunes, plums, tomatoes, grapes (except

those grown for wine production) and

raisins will reduce the percent RfD

consumed by at least one-third;

reducing the percent RfD consumed in

children - ages 1-6 from 45 percent to

30 percent and for the general

population from 25 percent to 16

percent. BASF is currently analyzing the

available monitoring data for

vinclozolin residues to determine the

actual exposure to vinclozolin residues.

Preliminary analysis indicates that no

sub-population in the United States is

exposed to over 1 percent of the RfD.

EPA has expressed concern for acute

dietary risk in the draft RED for the

subgroup population -women of

childbearing age (13 years and older)

due to the hormonal effects of

vinclozolin.

In response to this concern, BASF

requested that Technical Assessment

Systems, Inc. (TAS), conduct an acute

dietary analysis for vinclozolin that

used the current consumption data and

exposure models capable of calculating

a real world estimates of potential

exposure to residues in food.

The acute exposure analysis, utilized

the principles of Tier 1 and Tier 3

analyzes presented to the FIFRA

Science Advisory Panel in September,

1995, and subsequently implemented by

OPP/EPA. Using appropriate

methodology, available residue

distribution data, and percent crop

treated information it was determined

the margin of exposure to the most

sensitive sub-population exceeded 100

(the value generally accepted by the

Agency as sufficient) at the very

conservative 99.9th percentile of the

population; when all crops having

tolerances; plus succulent beans and

cranberries were included in the

analysis. When prunes, plums tomatoes,

grapes (excluding those grown for wine

production) and raisins were removed

from the analysis, the margin of

exposure at the 99.9th percentile was

determined to be 425 for women of

childbearing age.

2. ‘‘Other’’ Exposure. Other potential

sources of potential exposure to

vinclozolin for the general population to

residues of vinclozolin are residues in

drinking water and exposure from nonoccupational sources. For drinking

water, based on the available

environmental fate data, BASF does not

anticipate routine exposure to residues

of vinclozolin in drinking water. There

is no established Maximum

Concentration Level (MCL) or Health

Advisory Level (HAL) for vinclozolin

under the Safe Drinking Water Act

(SDWA).

For non-occupational exposure,

vinclozolin is included in a number of

formulations used for professional

treatment of golf-courses and turf.

Posting and notification procedures

ensure that there is no exposure to the

general public either during or

following treatment.

BASF has a flowable formulation

containing vinclozolin which is

available to the homeowner for use on

residential lawns. Treatment rates (1.0

oz a.i./1,000 sq. ft.) and the number of

treatments allowed per year are low.

BASF believes that this minor use will

not impact significantly on the aggregate

exposure to vinclozolin since this use

represents less than 0.5 percent of total

vinclozolin use.
13004 Federal Register / Vol. 62, No. 53 / Wednesday, March 19, 1997 / Notices

Additionally, for the homeowner

handler and homeowner

postapplication, EPA has estimated

these non-occupational exposure for

vinclozolin in the draft Registration

Eligibility Document issued to BASF on

February 2, 1996. EPA stated the

following:

a. ‘‘The MOE’s for homeowners

handlers were greater than 100 for both

the low-pressure hand-held sprayer and

backpack sprayer assuming long-sleeve

shirt, long pants, shoes, and socks are

worn. All homeowner handlers were

assumed not be exposed seven days or

more in a 90-day period and, the shortterm endpoint is used in determining

the MOE’s. The Application rate for

homeowners was assumed to be five

gallons of dilute spray per day.’’

b. In a simmilar analysis for

postapplication exposure for

homeowners a margin of exposure

greater than 100 was calculated based

on a worst case analysis using

strawberry data as a surrogate.

Therefore, based on the completeness

and reliability of the toxicity data, and

the assessment discussed above, BASF

concludes that there is a reasonable

certainty that no harm will result from

aggregate exposure to residues of

vinclozolin, including all anticipated

dietary exposure.

H. Cumulative Exposure

BASF has considered the potential for

cumulative effects of vinclozolin and

other substances that have a common

mechanism of toxicity. BASF is aware of

two other substance active ingredients

which are structurally similar,

iprodione and procymidone. However,

BASF believes that consideration of a

common mechanism of toxicity is not

appropriate at this time. This

conclusion was similarly drawn by

Rhone-Poulenc the manufacturer of

iprodione in a recent Notice of Filing for

that compound.

The Agency has previously noted

both structural and toxicological

similarities between iprodione,

procymidone, and vinclozolin. BASF

believes that there are clear differences

in both the type and magnitude of

effects observed after exposure to

vinclozolin when contrasted with

iprodione. BASF believes that there is

no reliable data to indicate cumulative

effects should be considered in

reference to iprodione. As to

procymidone, BASF is unaware of any

conclusive data that would indicate a

common mode of action with

procymidone. It should also be noted

that procymidone’s tolerances are

limited to grapes grown for wine

production outside the United States.

I. Determination of Safety for U.S.

Population

Reference Dose (RfD): Using the

exposure assumptions described above

and the completeness and the reliability

of the toxicity data, BASF has estimated

that aggregate exposure to vinclozolin

will utilize less than 16 percent of the

RfD for the US population. EPA

generally has no concern for exposure

below 100 percent of the RfD. Therefore,

based on the completeness and

reliability of the toxicity data, and the

exposure assessment discussed above,

BASF concludes that there is a

reasonable certainty that no harm will

result from aggregate exposure to

residues of vinclozolin, including all

anticipated dietary exposure and all

other non-occupational exposures.

J. Determination of Safety for Infants

and Children

Reference Dose: Based on the

completeness of vinclozolin’s

toxicological database and the risk

assessment information cited above

BASF believes the RfD used to assess

safety to children should be the same as

that for the general population, 0.012

mg/kg/day. BASF concluded that the

most sensitive child population group is

that of children ages 1 to 6. BASF has

calculated that the exposure to this

group to be <30 percent of the RfD for

all uses including that proposed in this

document. Therefore, based on the

completeness and reliability of the

toxicity data, and the exposure

assessment discussed above, BASF

concludes that there is a reasonable

certainty that no harm will result to

infants and children from aggregate

exposure to residues of vinclozolin,

including all anticipated dietary

exposure and all other non-occupational

exposures.

K. Other Considerations

The qualitative nature of the residues

in plants is adequately understood.

Residues of the parent molecule, and

metabolites containing the 3,5-

dichloroaniline moiety are the only

residues of concern. There is a practical

analytical method for detecting and

measuring levels of vinclozolin in or on

food with a limit of detection that

allows monitoring of food with residues

at or above the levels set in these

tolerances. There has been no need to

establish meat, milk, poultry or egg

tolerances as the crops including

succulent beans on which vinclozolin is

used do not represent animal feed items.

L. International Tolerances

A maximum residue level for

succulent beans has not been

established for vinclozolin by the Codex

Alimentarius Commission.

M. Conclusions

BASF Corporation believes that the

proposed use of vinclozolin on snap

beans would not pose a significant risk

to human health, including that of

infants and children, and is in

compliance with the requirements of the

Food Quality Protection Act of 1996.

Moreover, BASF believes that the

proposed tolerance for vinclozolin on

snap beans should be established.

II. Public Record

Interested persons are invited to

submit comments on this notice of

filing. Comments must bear a notation

indicating the docket control number,

[PF–720]. All written comments filed in

response to this petition will be

available in the Public Response and

Program Resources Branch, at the

address given above from 8:30 a.m. to 4

p.m., Monday through Friday, except

legal holidays.

A record has been established for this

notice under docket control number

[PF–720] 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 public

record is located in Rm. 1132 of the

Public Response and Program Resources

Branch, Field Operations Division

(7506C), Office of Pesticide Programs,

Environmental Protection Agency,

Crystal Mall #2, 1921 Jefferson Davis

Highway, Arlington, VA.

Electronic comments can be sent

directly to EPA at:

opp-docket@epamail.epa.gov

Electronic comments must be

submitted as ASCII file avoiding the use

of special characters and any form of

encryption.

The official record for this notice, as

well as the public version, as described

above will be kept in paper form.

Accordingly, EPA will transfer all

comments received electronically into

printed, paper form as they are received

and will place the paper copies in the

official record which will also include

all comments submitted directly in

writing. The official record is the paper

record maintained at the address in

‘‘ADDRESSES’’ at the beginning of this

document.

Authority: 21 U.S.C. 346a.
Federal Register / Vol. 62, No. 53 / Wednesday, March 19, 1997 / Notices 13005

List of Subjects

Environmental protection,

Administrative practice and procedure,

Agricultural commodities, Pesticides

and pests, Reporting and recordkeeping.

Dated: March 10, 1997.

Stephen L. Johnson,

Director, Registration Division, Office of

Pesticide Programs.

[FR Doc. 97–6909 Filed 3–18–97; 8:45 am]

BILLING CODE 6560–50–F

[OPP–181037; FRL 5593–8]

Dimethomorph; Receipt of Application

for Emergency Exemption, Solicitation

of Public Comment

AGENCY: Environmental Protection

Agency (EPA).

ACTION: Notice.

SUMMARY: EPA has received a specific

exemption request from the Florida

Department of Agriculture and

Consumer Services (hereafter referred to

as the ‘‘Applicant’’) to use the pesticide

dimethomorph (CAS 110488–70–5) to

treat up to 7,250 acres of tobacco to

control metalaxyl-resistant blue

mold.The Applicant proposes the use of

a new (unregistered) chemical;

therefore, in accordance with 40 CFR

166.24, EPA is soliciting public

comment before making the decision

whether or not to grant the exemption.

DATES: Comments must be received on

or before April 3, 1997.

ADDRESSES: Three copies of written

comments, bearing the identification

notation ‘‘OPP–181037,’’ should be

submitted by mail to: Public Response

and Program Resource Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, 401 M St., SW.,

Washington, DC 20460. In person, bring

comments to: Rm. 1132, Crystal Mall #2,

1921 Jefferson Davis Highway,

Arlington, VA.

Comments and data may also be

submitted electronically by sending

electronic mail (e-mail) to: oppdocket@epamail.epa.gov. Electronic

comments must be submitted as an

ASCII file avoiding the use of special

characters and any form of encryption.

Comments and data will also be

accepted on disks in WordPerfect in 5.1

file format or ASCII file format. All

comments and data in electronic form

must be identified by the docket number

[OPP–181037]. No Confidential

Business Information (CBI) should be

submitted through e-mail. Electronic

comments on this proposed rule may be

filed online at many Federal Depository

Libraries. Additional information on

electronic submissions can be found

below in this document.

Information submitted in any

comment concerning this notice may be

claimed confidential by marking any

part or all of that information as CBI.

Information so marked will not be

disclosed except in accordance with

procedures set forth in 40 CFR part 2.

A copy of the comment that does not

contain CBI must be provided by the

submitter for inclusion in the public

record. Information not marked

confidential may be disclosed publicly

by EPA without prior notice. All written

comments filed pursuant to this notice

will be available for public inspection in

Rm. 1132, Crystal Mall No. 2, 1921

Jefferson Davis Highway, Arlington, VA,

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

through Friday, except legal holidays.

FOR FURTHER INFORMATION CONTACT: By

mail: Libby Pemberton, Registration

Division (7505W), Office of Pesticide

Programs, Environmental Protection

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

DC 20460. Office location, telephone

number and e-mail: Floor 6, Crystal

Station #1, 2800 Jefferson Davis

Highway, Arlington, VA, (703) 308–

8326; e-mail:

pemberton.libby@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: Pursuant

to section 18 of the Federal Insecticide,

Fungicide, and Rodenticide Act (FIFRA)

(7 U.S.C. 136p), the Administrator may,

at her discretion, exempt a state agency

from any registration provision of

FIFRA if she determines that emergency

conditions exist which require such

exemption. The Applicant has requested

the Administrator to issue a specific

exemption for the use of dimethomorph

on tobacco to control blue mold.

Information in accordance with 40 CFR

part 166 was submitted as part of this

request.

In 1995 and 1996 a national epidemic

of tobacco blue mold, caused by

metalaxyl-resistant strains of the

pathogen, occurred. Resistant strains are

becoming more widely disseminated, a

situation which is exacerbated with a

protracted wet weather pattern.

Previously, blue mold was controlled

primarily by treatment with metalaxyl,

with significant assistance from ferbam

and mancozeb. A very high level of

control was possible with these

materials until metalaxyl-resistant

strains appeared. Labeled pesticides

made under ideal spray conditions but

high disease pressure do not provide

acceptable economic levels of control.

The Applicant states that presently,

there are no fungicides registered in the

U.S. that will provide adequate control

of the metalaxyl-resistant strains of blue

mold. The Applicant states that

dimethomorph has been shown to be

effective against these strains of blue

mold. Dimethomorph holds current

registrations throughout many European

countries. The Applicant estimates that

losses in 1997 could be greater than $7

million without use of dimethomorph.

Under appropriate conditions, it is

possible that this disease could develop

to epidemic proportions, causing major

changes and losses to the U.S. tobacco

industry.

The Applicant proposes to apply

dimethomorph at a maximum rate of

0.225 lbs. a.i. (2.5 lbs. of product) per

acre, by ground with a maximum of 5

applications per crop, to a maximum of

7,250 acres of tobacco.

This notice does not constitute a

decision by EPA on the application. The

regulations governing section 18 require

publication of a notice of receipt of an

application for a specific exemption

proposing use of a new chemical (i.e.,

an active ingredient not contained in

any currently registered pesticide). Such

notice provides for opportunity for

public comment on the application.

Accordingly, interested persons may

submit written views on this subject to

the Field Operations Division at the

address above.

A record has been established for this

notice under docket number [OPP–

181037] (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 public record is located in Room

1132 of the Public Response and

Program Resources Branch, Field

Operations Division (7506C), Office of

Pesticide Programs, Environmental

Protection Agency, Crystal Mall #2,

1921 Jefferson Davis Highway,

Arlington, VA.

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.

The official record for this notice, as

well as the public version, as described

above will be kept in paper form.

Accordingly, EPA will transfer all

comments received electronically into

printed, paper form as they are received

and will place the paper copies in the