[Federal Register Volume 68, Number 58 (Wednesday, March 26, 2003)]
[Notices]
[Pages 14628-14635]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-7246]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0008; FRL-7289-2]


Vinclozolin; Notice of Filing a Pesticide Petition To Establish a 
Tolerance for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations to make permanent 
the tolerances for residues, and to extend existing tolerances for 
residues of a certain pesticide chemical in or on various food 
commodities.

DATES: Comments, identified by docket ID number OPP- 2003-0008, must be 
received on or before April 25, 2003.

ADDRESSES: Comments may be submitted electronically, by mail, or 
through hand delivery/courier. Follow the detailed instructions as 
provided in Unit I. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Mary L. Waller, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-9354; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
    [sbull] Crop production (NAICS 111)
    [sbull] Animal production (NAICS 112)
    [sbull] Food manufacturing (NAICS 311)
    [sbull] Pesticide manufacturing (NAICS 32532)
    [sbull] Antimicrobial pesticides (NAICS 32561)
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2003-0008. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute. The official public docket is the collection of materials 
that is available for public viewing at the Public Information and 
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The docket telephone number is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.

[[Page 14629]]

    Certain types of information will not be placed in the EPA Dockets. 
Information claimed as CBI and other information whose disclosure is 
restricted by statute, which is not included in the official public 
docket, will not be available for public viewing in EPA's electronic 
public docket. EPA's policy is that copyrighted material will not be 
placed in EPA's electronic public docket but will be available only in 
printed, paper form in the official public docket. To the extent 
feasible, publicly available docket materials will be made available in 
EPA's electronic public docket. When a document is selected from the 
index list in EPA Dockets, the system will identify whether the 
document is available for viewing in EPA's electronic public docket. 
Although not all docket materials may be available electronically, you 
may still access any of the publicly available docket materials through 
the docket facility identified in Unit I.B. EPA intends to work towards 
providing electronic access to all of the publicly available docket 
materials through EPA's electronic public docket.
    For public commenters, it is important to note that EPA's policy is 
that public comments, whether submitted electronically or in paper, 
will be made available for public viewing in EPA's electronic public 
docket as EPA receives them and without change, unless the comment 
contains copyrighted material, CBI, or other information whose 
disclosure is restricted by statute. When EPA identifies a comment 
containing copyrighted material, EPA will provide a reference to that 
material in the version of the comment that is placed in EPA's 
electronic public docket. The entire printed comment, including the 
copyrighted material, will be available in the public docket.
    Public comments submitted on computer disks that are mailed or 
delivered to the docket will be transferred to EPA's electronic public 
docket. Public comments that are mailed or delivered to the docket will 
be scanned and placed in EPA's electronic public docket. Where 
practical, physical objects will be photographed, and the photograph 
will be placed in EPA's electronic public docket along with a brief 
description written by the docket staff.

C. How and To Whom Do I Submit Comments?

    You may submit comments electronically, by mail, or through hand 
delivery/courier. To ensure proper receipt by EPA, identify the 
appropriate docket ID number in the subject line on the first page of 
your comment. Please ensure that your comments are submitted within the 
specified comment period. Comments received after the close of the 
comment period will be marked ``late.'' EPA is not required to consider 
these late comments. If you wish to submit CBI or information that is 
otherwise protected by statute, please follow the instructions in Unit 
I.D. Do not use EPA Dockets or e-mail to submit CBI or information 
protected by statute.
    1. Electronically. If you submit an electronic comment as 
prescribed in this unit, EPA recommends that you include your name, 
mailing address, and an e-mail address or other contact information in 
the body of your comment. Also include this contact information on the 
outside of any disk or CD ROM you submit, and in any cover letter 
accompanying the disk or CD ROM. This ensures that you can be 
identified as the submitter of the comment and allows EPA to contact 
you in case EPA cannot read your comment due to technical difficulties 
or needs further information on the substance of your comment. EPA's 
policy is that EPA will not edit your comment, and any identifying or 
contact information provided in the body of a comment will be included 
as part of the comment that is placed in the official public docket, 
and made available in EPA's electronic public docket. If EPA cannot 
read your comment due to technical difficulties and cannot contact you 
for clarification, EPA may not be able to consider your comment.
    i. EPA Dockets. Your use of EPA's electronic public docket to 
submit comments to EPA electronically is EPA's preferred method for 
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket, and follow the online instructions for submitting comments. 
Once in the system, select ``search,'' and then key in docket ID number 
OPP-2003-0008. The system is an ``anonymous access'' system, which 
means EPA will not know your identity, e-mail address, or other contact 
information unless you provide it in the body of your comment.
    ii. E-mail. Comments may be sent by e-mail to [email protected], 
Attention: Docket ID Number OPP-2003-0008. In contrast to EPA's 
electronic public docket, EPA's e-mail system is not an ``anonymous 
access'' system. If you send an e-mail comment directly to the docket 
without going through EPA's electronic public docket, EPA's e-mail 
system automatically captures your e-mail address. E-mail addresses 
that are automatically captured by EPA's e-mail system are included as 
part of the comment that is placed in the official public docket, and 
made available in EPA's electronic public docket.
    iii. Disk or CD ROM. You may submit comments on a disk or CD ROM 
that you mail to the mailing address identified in Unit I.C.2. These 
electronic submissions will be accepted in WordPerfect or ASCII file 
format. Avoid the use of special characters and any form of encryption.
    2. By mail. Send your comments to: Public Information and Records 
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2003-0008.
    3. By hand delivery or courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Office of Pesticide 
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall 
2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket 
ID Number OPP-2003-0008. Such deliveries are only accepted during the 
docket's normal hours of operation as identified in Unit I.B.1.

D. How Should I Submit CBI to the Agency?

    Do not submit information that you consider to be CBI 
electronically through EPA's electronic public docket or by e-mail. You 
may claim information that you submit to EPA as CBI by marking any part 
or all of that information as CBI (if you submit CBI on disk or CD ROM, 
mark the outside of the disk or CD ROM as CBI and then identify 
electronically within the disk or CD ROM the specific information that 
is CBI). Information so marked will not be disclosed except in 
accordance with procedures set forth in 40 CFR part 2.
    In addition to one complete version of the comment that includes 
any information claimed as CBI, a copy of the comment that does not 
contain the information claimed as CBI must be submitted for inclusion 
in the public docket and EPA's electronic public docket. If you submit 
the copy that does not contain CBI on disk or CD ROM, mark the outside 
of the disk or CD ROM clearly that it does not contain CBI. Information 
not marked as CBI will be included in the public docket and EPA's 
electronic public docket without prior notice. If you have any 
questions about CBI or the procedures for claiming CBI, please consult 
the person listed under FOR FURTHER INFORMATION CONTACT.

[[Page 14630]]

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
ID number assigned to this action in the subject line on the first page 
of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in FFDCA section 408(d)(2); 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.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.

    Dated: March 18, 2003.
Debra Edwards,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by FFDCA section 408(d)(3). The summary of the petition was 
prepared by the petitioner and represents the view of the petitioner. 
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.

BASF Corporation

PP 1F6278

    EPA has received a pesticide petition (1F6278) from BASF 
Corporation, Agricultural Products, P.O. Box 13528, Research Triangle 
Park, NC 27709-3528 proposing, pursuant to section 408(d) of the FFDCA, 
21 U.S.C. 346a(d), to amend 40 CFR part 180.380 by making permanent the 
tolerances for residues of vinclozolin, 3-(3,5-dichlorophenyl)-5-
ethenyl-5-methyl-2,4-oxazolidinedione and its metabolites containing 
the 3,5-dichloroaniline moiety in or on the raw agricultural 
commodities canola at 1.0 parts per million (ppm); eggs, milk, and the 
meat, fat, and meat byproducts of cattle, goats, hogs, horses, and 
sheep at 0.05 ppm; and in the meat, fat, and meat byproducts of poultry 
at 0.1 ppm. In addition, BASF had proposed extending the existing 
tolerance on succulent beans at 2.0 ppm for an additional 2 years. EPA 
has determined that the petition contains data or information regarding 
the elements set forth in section 408(d)(2) of the FFDCA; however, EPA 
has not fully evaluated the sufficiency of the submitted data at this 
time or whether the data supports granting of the petition. Additional 
data may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. BASF Corporation notes that metabolism in 
plants is understood, the residues of concern are vinclozolin, 3-(3,5-
dichlorophenyl)-5-methyl-5-vinyl-1,3-oxazolidine-2,4-dione) and 
metabolites containing the 3,5-dichloroanaline moiety.
    2. Analytical method. The proposed analytical method involves 
extraction, hydrolysis, distillation, partition, and deriviatization 
followed by detection of residues by gas chromatograph/electron capture 
detector (gc/ecd). An enforcement method has been published in FDA's 
Pesticide Analytical Methods, Volume II pg. 876-887.
    3. Magnitude of residues. Data previously submitted in support of 
the tolerances in canola, succulent beans and meat, milk, poultry, and 
eggs have been reviewed by the Agency and been found adequate to 
support the tolerances requested.

B. Toxicological Profile

    1. Acute toxicity. On July 18, 2000, EPA published in the Federal 
Register (65 FR 44453) (FRL-6594-8), time limited tolerances for 
vinclozolin in canola, succulent beans and meat, milk, poultry and 
eggs. The toxicological profile as reported in that Federal Register is 
repeated in this Notice. A battery of acute toxicity studies placed 
technical vinclozolin in toxicity category IV for acute oral toxicity 
lethal dose (LD)50 of > 10,000 milligrams/kilograms (mg/
kg)), and acute inhalation toxicity (LC50 of 29.1 mg/liter 
(L)); and toxicity category III for acute dermal toxicity 
(LD50 of > 5,000 mg/kg). Technical vinclozolin caused 
minimal eye and dermal irritation and the technical material is 
positive for skin sensitization.
    2. Genotoxicity. Genotoxicity testing showed no evidence of 
mutagenic activity. (For details see the July 18, 2000 Federal Register 
(65 FR 44453)).
    3. Reproductive and developmental toxicity--i. In four 
developmental toxicity studies, vinclozolin was given orally from 
gestational day (gd) 6 through 19 as follows: Study 4--dose levels of 
0, 15, 50, or 150 mg/kg/day; study 5--dose levels of 0, 50, 100, 200 
mg/kg/day; study 6--dose levels of 0, 200, 400 mg/kg/day; and study 8--
dose levels of 0, 600, and 1,000 mg/kg/day. At the gd 20, the fetuses 
were evaluated.
    The developmental toxicity no observed adverse effect level (NOAEL) 
was set at 15 mg/kg/day and the developmental lowest observed adverse 
effect level (LOAEL) was 50 mg/kg/day. The maternal toxicity LOAEL was 
< 600 mg/kg/day.
    ii. A developmental study in rats via dermal exposure for 6 hours/
day on intact skin with dosages of 0, 60, 180, and 360 mg/kg/day 
highest dose tested (HDT) had a developmental NOAEL of 60 mg/kg/day and 
a maternal NOAEL of 60 mg/kg/day.
    iii. A developmental study in rabbits via oral gavage resulted in 
dosages of 0, 20, 80, and 300 mg/kg/day HDT with a developmental NOAEL 
of 300 mg/kg/day and a maternal NOAEL of 300 mg/kg/day.
    iv. 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.
    A two-generation rat 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 a reproductive NOAEL of 4.9 
mg/kg/day and pup effects at 29 mg/kg/day; and with a parental NOAEL of 
4.9 mg/kg/day. (For a detailed discussion of the

[[Page 14631]]

results of these studies see the Federal Register of July 18, 2000 (65 
FR 44453)).
    4. Chronic toxicity--i. A 1-year chronic feeding study in dogs fed 
dosages of 0, 1.1, 2.4, 4.9, and 48.7 mg/kg/day with a NOAEL of 2.4 mg/
kg/day.
    ii. A combination of 2 chronic feeding studies and 1 
carcinogenicity study 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). An increased incidence of 
neoplasms occurred at dose levels greater than the maximum tolerated 
dose (MTD) of greater than or equal to 23 mg/kg/day in the liver, 
adrenal, pituitary, prostate (males), uterus (females), and ovaries 
(females) at dose levels greater than or equal to 143 mg/kg/day. In the 
testes (males), Leydig cell adenomas were seen at the MTD for dose 
levels greater than or equal to 23.0 mg/kg/day due to the anti-
androgenic nature of vinclozolin.
    5. Carcinogenicity. A carcinogenicity 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.
    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. (For a detailed discussion of the results of these studies 
see the Federal Register of July 18, 2000 (65 FR 44453)).

C. Toxicological Endpoints

    EPA determined the following toxicological endpoints as reported in 
the Federal Register Notice of July 18, 2000. That reference provides a 
complete description of the Agency's rationale for the values assigned.
    1. Acute toxicity. EPA selected the NOAEL of 6 mg/kg/day. The 
population subgroup of concern is females (13+) because the endpoint is 
an in utero effect applicable only to females of childbearing age. An 
uncertainty factor (UF) of 100 was used to account for interspecies 
extrapolation and intraspecies variation. On this basis, the acute 
reference dose (aRfD) is 0.06 mg/kg/day. EPA determined that a 10X FQPA 
safety factor is applicable. The acute population adjusted dose (aPAD) 
is 0.006 mg/kg/day. An acute dose and endpoint were not identified for 
other population subgroups.
    2. Chronic toxicity. EPA has established the Reference Dose (RfD) 
for vinclozolin at 0.012 mg/kg/day. This RfD is based on a NOAEL of 1.2 
mg/kg/day from the combined chronic toxicity/carcinogenicity study in 
rats. An UF of 100 was used to account for interspecies extrapolation 
and intraspecies variation. A 10X FQPA safety factor was added 
resulting in a chronic population adjusted dose (cPAD) of 0.0012 mg/kg/
day.
    3. Short- and intermediate-term toxicity. For short- and 
intermediate-term dermal and inhalation toxicity, the NOAEL of 3 mg/kg/
day from a rat developmental toxicity study was selected for the 
population subgroup of concern, females (13+). A dermal absorption 
factor of 25% was used to correct for route-to-route extrapolation 
(oral to dermal exposure) and a default inhalation absorption factor of 
100% was assumed for oral to inhalation exposure. The margin of 
exposure (MOE) for females (13+), infants and children is 1,000X.
    4. Long-term dermal and inhalation toxicity (cancer and non-
cancer). For chronic non-cancer and cancer dermal and inhalation 
toxicity, EPA selected the chronic NOAEL of 1.2 mg/kg/day from the 
combined rat chronic toxicity/carcinogenicity study. The Q1* 
calculated in a low-dose linear extrapolation is 2.9 x 10-1 
(mg/kg/day). A dermal absorption factor of 25% was used to correct for 
route-to-route extrapolation (oral to dermal exposure) and a default 
inhalation absorption factor of 100% was assumed for oral to inhalation 
exposure. The cancer assessment includes not only the adult U.S. 
population but also infants and children as well.
    5. Carcinogenicity. Vinclozolin is classified as a Group C 
carcinogen based on Leydig (interstitial testicular) cell tumors in a 
perinatal rat developmental toxicity study. A non-linear (MOE) approach 
was determined to be appropriate based on a weight-of-the-evidence 
conclusion that tumor induction is via an anti-androgenic mechanism. 
Use of the PAD for overall anti-androgenic effects (0.0012 mg/kg/day) 
is also protective of cancer effects because it is protective of the 
anti-androgenic effects that are, in effect, precursors to tumor 
formation.
    6. Overall anti-androgenic effects. The Agency has determined that 
use of the most sensitive regulatory toxicity endpoint and the highest 
UF would be protective of the anti-androgenic effects on all population 
subgroups caused by vinclozolin including developmental/reproductive 
effects as well as carcinogenic effects. In the case of vinclozolin, 
the most sensitive toxicity endpoint/dose and UF are derived from the 
rat oral chronic/carcinogenicity study, i.e., the NOAEL of 1.2 mg/kg/
day and an UF of 1,000. The PAD of 0.0012 mg/kg/day was used in 
assessment of risks resulting from the anti-androgenic activity of 
vinclozolin.
    7. Endocrine disruption. A series of mechanistic studies (in vivo 
and in vitro) were conducted to define the anti-androgenic properties 
of vinclozolin. The results of these studies showed that vinclozolin 
elicits the anti-androgenic effects by binding to androgen sensitive 
organs.

D. Aggregate Exposure

    For a detailed discussion of the results of these exposure 
calculations see the Federal Register of July 18, 2000 (65 FR 44453).
    1. Dietary exposure. The Agency has previously calculated exposures 
and risks for the canola green beans, meat, milk, poultry and eggs. The 
same calculations should be applied to re-establishing these 
tolerances.
    i. Food--a. acute exposure and risk. Acute dietary risk assessments 
are performed for a food-use pesticide if a toxicological study has 
indicated the possibility of an effect of concern occurring as a result 
of a 1-day or single exposure. The Agency concluded that acute dietary 
exposure estimates for the only population subgroup of concern, females 
(13+), that ``The very conservatively estimated acute dietary risk 
(food only) does not exceed the Agency's level of concern (LOC).''
    b. Chronic exposure and risk. The chronic dietary exposure 
estimates expressed as a percentage of the cPAD (0.0012 mg/kg/day) were 
4% for the U.S. population and 7% for the most highly exposed 
population subgroup, children (1-6 years old). EPA generally has no 
concern for exposures below 100% of the cPAD because the cPAD 
represents the level at or below which daily aggregate dietary exposure 
over a lifetime will not pose appreciable risk to human health. 
Therefore, the chronic dietary risk (food only) does not exceed the 
Agency's LOC.
    ii. For cancer and anti-androgenic risk assessment. EPA believes 
that vinclozolin should be classified as a Group C carcinogen. However, 
due to the relationship between vinclozolin's anti-androgenic 
properties and its carcinogenic effects, the Agency believes protecting 
against the anti-androgenic effects would also be protective against 
potential carcinogenic effects to all population subgroups (including 
infants and children).
    Accordingly, the cPAD will be protective against potential 
carcinogenic effects as well as the developmental/reproductive effects. 
The cPAD already incorporates the full, additional 10x

[[Page 14632]]

safety factor for the protection of infants and children (i.e., it is 
derived from the NOAEL of 1.2 mg/kg/day with an MOE of 1,000 - 10x for 
intraspecies extrapolation; 10x for interspecies variation; and 10x for 
FQPA). Since this approach (using the cPAD) would be more protective 
than the proposed POD for cancer risk assessment of 3 mg/kg/day, and 
includes an additional 10x factor for the protection of infants and 
children, a separate non-linear risk assessment for cancer is not 
necessary.
    Exposure estimates expressed as a percentage of the anti-androgenic 
PAD (0.0012 mg/kg/day) were 4% for the general U.S. population and 7% 
for the most highly exposed population subgroup, children (1-6 years 
old). In addition, as a point of comparison, the MOE was calculated to 
be 75,000 for the general U.S. population and 38,000 for children (1-6 
years old).
    2. Drinking water. In general, available monitoring data are of 
limited use because metabolite concentration measurements were not 
performed. For both surface water and ground water, the sum of 
vinclozolin and its principal metabolites, assumed to degrade 
completely to 3,5-dichloroaniline (here-in-after referred to as 3,5-
DCA), have been used to assess the cancer risk associated with 3,5-DCA 
whereas vinclozolin per se has been used for the vinclozolin risk 
assessments.
    In the absence of reliable, available monitoring data, EPA uses 
models to calculate the estimated environmental concentrations (EECs) 
of pesticides in ground water and surface water. However, EPA does not 
use these model estimates to quantify risk. Currently, EPA uses 
drinking water level of concerns (DWLOCs) as a surrogate to capture 
risk associated with exposure to pesticides in drinking water. A DWLOC 
represents the concentration of a pesticide in drinking water that 
would be acceptable as an upper limit in light of total aggregate 
exposure to that pesticide from food, water, and residential uses (if 
any). A DWLOC will vary depending on the residue level in foods, the 
toxicity endpoint and the drinking water consumption patterns and body 
weights for specific population subgroups. The calculated DWLOC is 
compared to the model estimate (EEC), and if the model estimates are 
below the DWLOC, the risks are not considered to be of concern.
    For estimating ground water concentrations of vinclozolin and 3,5-
DCA, EPA used the Screening Concentration in Ground Water (SCI-GROW) 
model. Using SCI-GROW, the acute and chronic ground water EEC of 
vinclozolin per se is 0.53 parts per billion (ppb), and the acute and 
chronic ground water EEC of 3,5-DCA is 2.65 ppb.
    For estimating surface water concentrations of vinclozolin and 3,5-
DCA, EPA used tier II models, Pesticide Root Zone Model (PRZM) 3.12 and 
Exposure Analysis Modeling System (EXAMS) 2.975. The acute (peak) 
surface water EEC for vinclozolin is 5.68 ppb and for 3,5-DCA is 26 
ppb. The chronic (annual mean) surface water EEC for vinclozolin is 
0.165 ppb and for 3,5-DCA is 3.12 ppb.
    i. Acute exposure and risk. For the population subgroup of concern, 
females (13+), the DWLOCs for vinclozolin per se at the various 
percentiles of exposure are as follows: 0 ppb at the 99.9th percentile; 
4 ppb at the 99.85th percentile; 30 ppb at the 99.8th percentile; 47 
ppb at the 99.75th percentile; 80 ppb at the 99.6th percentile; and 92 
at the 99.5th percentile. At all but the very highest percentiles of 
exposure (99.85th and above), the DWLOC for vinclozolin per se is 
higher than the EEC of 5.68 ppb in surface water and 0.53 ppb in ground 
water. Given the level of refinement in the vinclozolin exposure 
estimate, using the highest percentiles of exposure in estimating risk 
would unreasonably overstate risk. Therefore, there is reasonable 
certainty that exposure to vinclozolin per se in drinking water will 
result in no harm.
    ii. Chronic exposure and risk. The following chronic DWLOCs were 
calculated for vinclozolin per se: General U.S. population, 41 ppb; 
females (13+) 35 ppb; and children (1-6 years old), 11 ppb. The lowest 
DWLOC of 11 ppb for children 1-6 years old is higher than the EEC of 
0.165 ppb in surface water and 0.53 ppb in ground water. Therefore, 
there is reasonable certainty that exposure to vinclozolin in drinking 
water will result in no harm.
    3. Non-dietary exposure. From non-dietary exposure. There are no 
vinclozolin pesticide products registered for use by homeowners. 
Therefore, there is no potential for homeowner handler exposure to 
vinclozolin pesticide products. Vinclozolin can, however, be 
occupationally used in a manner that may lead to post-application 
exposures to the general population, in particular, golfers playing on 
treated golf courses and homeowners and their families coming into 
contact with or playing on sod which was previously treated on a sod 
farm. A chemical-specific turf exposure study was used to measure human 
exposure as well as residue dissipation over time.
    All residential exposures are considered to be short-/intermediate-
term duration (i.e., 1 day to 1 week and 1 week to several months, 
respectively), and the same endpoint applies to both durations of 
exposure. As the endpoints selected are from oral toxicity studies 
(NOAEL of 3 mg/kg/day for females (13+)) and NOAEL of 5 mg/kg/day for 
infants and children, route-to-route exposure was corrected by applying 
a 25% dermal absorption factor and a 100% default inhalation absorption 
factor was assumed. A 100% safety factor was used and a 10X FQPA safety 
factor was added raising the Agency's LOC to 1,000.
    Post-application risks to the general population were considered 
for golfers following treatment of greens, tees, and fairways. Adult 
golfer exposures, women (13+), were less than the Agency's LOC even on 
the day of application (MOE = 1,700). Given the magnitude of the MOE 
for adult women golfers, the Agency does not believe that the risks to 
child golfers would exceed the Agency LOC either because the skin 
surface area/body weight ratio of the typical child golfer is similar 
to that of adults (within 15%). Therefore, the MOE for a child golfer 
is only slightly less than the MOE for adult golfers.
    Since the risk assessment published in the Federal Register, of 
July 18, 2000 (65 FR 44453) establishing the tolerances in canola, BASF 
has established a 24 day preharvest interval for the harvest of turf 
for transplant into residential settings. The MOE calculated under this 
scenario is 1,100 which is below the Agency's LOC.

E. Cumulative Effects

    Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) requires that, when considering 
whether to establish, modify, or revoke a tolerance, the Agency 
consider ``available information'' concerning the cumulative effects of 
a particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.''
    Vinclozolin, procymidone, and iprodione are members of the imide 
group of the dicarboximide class of fungicides. Each of these three 
pesticides can metabolize to 3,5-DCA. FQPA requires EPA to estimate 
cumulative risk from consumption of food and water containing 3,5-DCA 
derived from vinclozolin, iprodione, and procymidone.
    1. Acute exposure and risk. EPA has certain evidence that these 
compounds induce similar toxic effects but has not

[[Page 14633]]

yet determined whether or not these compounds modulate androgens by a 
common mechanism of toxicity. In fact, there is evidence that iprodione 
does not share a common mechanism of toxicity as it disrupts the 
endocrine system by inhibiting androgen synthesis rather than competing 
for the androgen receptor as vinclozolin does. In addition, these three 
chemicals do not have any known metabolites/degradates in common with 
the possible exception of 3,5-DCA which is structurally and 
toxicologically different from the parent compounds and unlikely to be 
an androgen receptor antagonist.
    EPA has, at this time, some data which suggests that vinclozolin 
and procymidone have a common mechanism of toxicity. An article 
published in Toxicology & Industrial Health (Vol. 15, ISS 1-2, 1999, 
pg. 80-93) which reports the findings by Dr. Earl Gray, National Health 
and Environmental Effects Research Laboratory, U.S. EPA, Research 
Triangle Park, NC, suggests that procymidone alters sexual 
differentiation in the male rat by acting as an androgen-receptor 
antagonist in vivo and in vitro. The Agency has yet to make a 
conclusion as to whether these data are sufficient to evaluate whether 
vinclozolin and procymidone have a common mechanism of toxicity.
    Even if it is assumed that vinclozolin and procymidone share a 
common mechanism of toxicity, a finding of reasonable certainty of no 
harm for vinclozolin can be made because any cumulative risk resulting 
from adding procymidone residues in wine to vinclozolin exposure is 
unlikely to differ significantly from the risk of vinclozolin alone. 
This conclusion is based on a number of factors. The exposure 
assessment for vinclozolin estimates that vinclozolin exposure through 
wine grapes contributes < 2% of the total vinclozolin exposure. The 
percent of imported wine grapes that are treated with procymidone is 
similar to that of vinclozolin (estimated 10% of wine grapes treated 
with vinclozolin and 9.4% of wine grapes treated with procymidone), and 
therefore, the exposure pattern for these chemicals is similar. In 
addition, the exposure estimates conservatively assume that all wine 
bearing vinclozolin residues also contain procymidone residues. In all 
likelihood, wine grapes would be treated with either vinclozolin or 
procymidone but not both chemicals. Vinclozolin exposure and 
procymidone exposure through wine grapes would each add < 2% to the 
``cumulative exposure.'' As noted above, the acute food-only risk of 
vinclozolin is 83% of the aPAD at the 99.8th percentile of exposure, 
and the acute ground water EEC of 0.53 ppb and the acute surface water 
EEC of 5.68 ppb are lower than the drinking water DWLOC which is 30 ppb 
at the 99.8th percentile of exposure. There is ultimately enough room 
in the risk cup to accommodate vinclozolin and procymidone risk, even, 
if in the future, EPA does determine that procymidone and vinclozolin 
share a common mechanism of toxicity.
    2. Carcinogenic exposure and risk. Since 3,5-DCA is not a 
registered pesticide, there is no FIFRA toxicology data base for this 
compound. In previous risk assessments, EPA has used the Q1* 
for p-chloroaniline (PCA) to assess the carcinogenicity (only 
toxicological endpoint identified for 3,5-DCA) for other structurally 
related chloroanilines. EPA's approach on chloroanilines is to consider 
chloroaniline metabolites to be toxicologically equivalent to PCA 
unless there is sufficient evidence that the metabolite is not 
carcinogenic. A Q1* of 6.38 x 10-2 (mg/kg/day) 
has been calculated for p-chloroaniline based on the spleen sarcoma 
rate in male rats from a National Toxicology Program bioassay.
    Exposure to 3,5-DCA was evaluated from the following sources: 
Residues of vinclozolin- and iprodione-derived 3,5-DCA in food and 
wine, residues of procymidone-derived 3,5-DCA in imported wine, and 
3,5-DCA residues in water from domestic agricultural uses of iprodione 
and vinclozolin. There are no U.S. registrations for procymidone. 
Therefore, an evaluation of exposure to procymidone-derived 3,5-DCA in 
water is not appropriate.
    3. Food risk--i. From vinclozolin-derived 3,5-DCA residues. Cancer 
risks were 2.6 x 10-7 for all crops, excluding strawberries 
and stone fruits. BASF notes that the last day for legal use of 
vinclozolin in either strawberries or stonefruit was January 2000. In 
effect neither commodity has been treated with vinclozolin since the 
1999 use season. In addition, the last day for legal use of vinclozolin 
on onions and raspberries was December 15, 2001. As a result the 
theoretical cancer risk calculated is an overestimation and these risks 
do not exceed the Agency's LOC.
    ii. From iprodione-derived 3,5-DCA residues. As stated in the July 
1998 Iprodione RED fact sheet, the cancer risk associated with 3,5-DCA 
derived from iprodione was 6 x 10-9. This risk does not 
exceed the Agency's LOC.
    iii. From procymidone-derived 3,5-DCA residues. The cancer risk 
associated with 3,5-DCA in imported wine produced from grapes treated 
with procymidone was estimated to be 3.7 x 10-7. This risk 
does not exceed the Agency's LOC.
    4. Drinking water risk--i. From vinclozolin derived 3,5-DCA. Since 
the use on onions has been eliminated, the carcinogenic DWLOC for 3,5-
DCA (based on the commodities currently available for consumption) has 
been calculated to range from 0.46 ppb to 1.6 ppb. Using Tier II PRZM/
EXAMS, the modeled EECs are 0.64 ppb for lettuce and 0.34 ppb for 
canola. The use site which represents the highest modeled exposure in 
drinking water is golf courses. Application to golf course turf is 
currently permitted on grass mowed at 1 inch or less. Using the Tier I 
generic expected environmental concentration (GENEEC) model, the Agency 
has calculated a chronic EEC of 0.29 ppb based on application to tees 
and greens and a chronic EEC of 2.33 ppb assuming application to tees, 
greens, and fairways. These EECs were the result of refinements to the 
GENEEC model. These refinements included the incorporation of an 87 
percent crop area factor as well as the percentage of the golf course 
that actually receives pesticide treatment, bringing the resulting PCA 
factor down to 17%. It was assumed that tees and greens comprise 2.8% 
of the acreage of a golf course. When fairways are included, an 
additional 16.7% of the golf course is treated. The EEC of 2.33 ppb 
exceeds the DWLOC. In evaluating whether this EEC indicated a risk of 
concern EPA considered the following factors:
    ii. The drinking water assessment on turf is based on GENEEC, a 
screening-level Tier I model. At present, PRZM-EXAMS, the Tier II 
model, does not have the appropriate parameters to accurately model 
turf runoff. Although GENEEC is not an ideal tool for use in drinking 
water risk assessments, it can provide high-end estimates of the 
concentrations that might be found in a confined pond of one hectare. 
Drinking water from surface water sources does not typically come from 
this type of scenario, but rather from bodies of water that are 
substantially larger than such ponds and from diverse watersheds. 
Unlike a confined pond, there is always some flow (in a river) or turn 
over (in a lake or reservoir) resulting in an over-estimation of the 
persistence of the chemicals near the drinking water utility intakes. 
Although a PCA of 17% was used to refine the model, the Agency 
recognizes that there are still uncertainties in the accuracy of the 
model to represent drinking water concentrations.

[[Page 14634]]

    iii. The GENEEC model uses the 56-day average of pesticide 
concentrations immediately after an event (application of pesticide). 
This short time-period may not adequately characterize a person's 
average daily exposure over a year, even more so, over a life time of 
70 years.
    iv. The GENEEC model assumes that once in every 10 years the EEC 
will be exceeded. For the other 9 out of 10 years the level of residue 
in drinking water is likely to be below the EEC with at least one half 
of the years falling significantly below by a factor of 5 to 10. 
Therefore, a person may be exposed to the EEC once in every 10 years or 
a total of 7 times during a lifetime of 70 years. The Agency believes 
the potential for such a lifetime exposure is minimal.
    v. Iprodione 3,5-DCA. As stated in the RED, the DWLOC for 3,5-DCA 
derived from domestic uses of iprodione was estimated to be 0.55 ppb. 
The 3,5-DCA EEC in surface water associated with the use of iprodione 
alone was estimated to be 0.45 ppb. Thus, the iprodione derived 3,5-DCA 
carcinogenic DWLOC is not exceeded.
    vi. From procymidone 3,5-DCA. There is no drinking water exposure 
because procymidone is not registered for use in the United States.
    The cumulative, food-only cancer risk associated with 3,5-DCA 
derived from all three of these imide fungicides is 6.3 x 
10-7 when stone fruit and strawberries are excluded from 
consideration. There is uncertainty in the above risk estimates in that 
a surrogate Q1* is being used for 3,5-DCA. However, due to 
the structural similarities of 3,5-DCA and p-chloroaniline (PCA), EPA 
believes that for 3,5-DCA, the use of the PCA Q1* represents 
an upper-bound estimate.
    The 3,5-DCA DWLOC from all three imide fungicides and those 
currently registered vinclozolin uses which are not being supported 
after this use season ranges from 0.26 ppb to 1.4 ppb. The estimated 
concentration of 3,5-DCA in water from applications of iprodione (1998 
iprodione RED) is 0.45 ppb and falls within the range of the aggregated 
DWLOC cited above. The estimated concentration of 3,5-DCA in water from 
applications of vinclozolin is estimated to range from 0.29 ppb to 2.33 
ppb.
    As already stated, this range could potentially present a risk of 
concern based on the model, however, based on how the model estimates 
residue concentrations for cancer assessment, it is unlikely that a 
cancer risk of concern is present.

F. Safety Determination

    1. U.S. population--i. Acute risk. The acute dietary (food only) 
risk does not exceed the Agency's LOC at the percentiles of exposure up 
to the 99.8th percentile. Using anticipated residues, PCT data, and 
PICT data, the population subgroup of concern, females (13+) utilized 
83% of the dietary (food only) aPAD at the 99.8th percentile of 
exposure. For drinking water, the EEC of 5.68 ppb in surface water and 
the EEC of 0.53 in ground water did not exceed the DWLOC of 30 ppb at 
the 99.8th percentile of exposure.
    ii. Chronic risk. Using the exposure assumptions described above, 
aggregate dietary exposure to the U.S. population will use 4% of the 
cPAD and exposure to the most highly exposed population subgroup, 
children (1-6 year old) will use 7% of the cPAD. The chronic DWLOCs for 
vinclozolin were 41 ppb for the general U.S. population and 35 ppb for 
the most highly exposed population subgroup, women (13+). The chronic 
DWLOCs were higher than the chronic EEC of 0.53 ppb in ground water and 
0.165 ppb in surface water. EPA generally has no concern for exposures 
below 100% of the cPAD because the cPAD represents the level at or 
below which daily aggregate dietary exposure over a lifetime will not 
pose appreciable risks to human health.
    2. Short- and intermediate-term risk. Short- and intermediate-term 
aggregate exposure takes into account chronic dietary food and water 
(considered to be a background exposure level) plus indoor and outdoor 
residential exposure. All residential exposures are considered to be 
short- and intermediate-term duration and since the same endpoint 
applies to both durations of exposures, the dermal and inhalation 
exposures must be aggregated together with the food and water exposures 
for each population subgroup of concern, females (13+) and infants and 
children. Since the risk assessment published in the Federal Register 
of July 18, 2000 (65 FR 44453), establishing the tolerances in canola, 
BASF has established a 24-day preharvest interval for the harvest of 
turf for transplant into residential settings. The MOE calculated under 
this scenario is 1,100 which is below the Agency's LOC.
    3. Aggregate cancer risk for U.S. population. Because the overall 
anti-androgenic effects are a prerequisite for hyperplasia and tumor 
formation, and are considered to be protective of the potential 
carcinogenic outcome of exposure to the anti-androgenic vinclozolin and 
its metabolites, the overall anti-androgenic aggregate risk which are 
identical to the chronic aggregate risk. The chronic aggregate risks 
are presented. The chronic (non-cancer) aggregate risk was below the 
Agency's LOC for food and drinking water sources of exposure. Chronic 
food-source risks were less than or equal to 7% of the cPAD when stone 
fruit and strawberries are excluded (uses have been canceled). EECs 
were compared to the chronic DWLOCs. The chronic EEC for residues of 
vinclozolin per se in ground water (0.53 ppb) was below the chronic 
DWLOCs for water consumption by adults (41 ppb for the general U.S. 
population and 35 ppb for females (13+)) and by children (11 ppb).
    Cancer risks from vinclozolin derived 3,5-DCA were 2.6 x 
10-7 for all crops, excluding strawberries and stone fruits. 
This risk does not exceed the Agency's LOC. The 3,5-DCA DWLOC from all 
three imide fungicides (including canola, succulent beans, onions, and 
raspberries) ranges from 0.26 ppb to 1.4 ppb. It should be noted that 
vinclozolin is no longer used in onions and raspberries. The 3,5-DCA 
EEC resulting from iprodione use is 0.45 ppb and falls with the range 
of the aggregated DWLOC cited above. The 3,5-DCA EEC resulting from 
vinclozolin use is estimated to range from 0.29 ppb to 2.33 ppb. As 
already stated, this range could potentially present a risk of concern 
based on the model, however, based on how the model estimates residue 
concentrations for cancer assessment, it is unlikely that a cancer risk 
of concern is present.
    4. Determination of safety. Based on these risk assessments, there 
is a reasonable certainty that no harm will result from aggregate 
exposure to vinclozolin residues.
    5. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of vinclozolin, EPA 
considered data from developmental toxicity studies in the rat and 
rabbit and a 2-generation reproduction study in the rat. The 
developmental toxicity studies are designed to evaluate adverse effects 
on the developing organism resulting from maternal pesticide exposure 
during gestation.
    Reproduction studies provide information relating to effects from 
exposure to the pesticide on the reproductive capability of mating 
animals and data on systemic toxicity.
    FFDCA section 408 provides that EPA shall apply an additional 
tenfold margin of safety for infants and children in the case of 
threshold effects to account for prenatal and postnatal toxicity and 
the completeness of the data base unless EPA determines that a 
different margin of safety will be safe for infants and children.

[[Page 14635]]

    6. Prenatal and postnatal sensitivity. The rationale for retaining 
the 10X FQPA safety factor is explained below:
    i. There is evidence of increased susceptibility of offspring 
following in utero exposure to vinclozolin in the prenatal 
developmental toxicity study in rats.
    ii. A developmental neurotoxicity study in rats with an expanded 
protocol is required for vinclozolin as a result of concern for the 
anti-androgenic properties of vinclozolin and its metabolites.

G. Conclusion

    Based on the developmental and reproductive data for vinclozolin, 
EPA determined that an additional 10X safety factor for the protection 
of infants and children (as required by FQPA) should be retained.
    1. Acute risk. No study with vinclozolin indicated that acute 
exposure to vinclozolin is likely to cause an adverse effect of concern 
on infants or children or the general public with the exception of the 
in utero effects on the developing fetus. Risks to the fetus are 
estimated by examining exposure to women of child-bearing age.
    2. Chronic risk. Using the exposure assumptions described in this 
unit, it is concluded that aggregate exposure to vinclozolin from food 
will utilize 7% of the cPAD for infants and children. EPA generally has 
no concern for exposures below 100% of the cPAD because the cPAD 
represents the level at or below which daily aggregate dietary exposure 
over a lifetime will not pose appreciable risks to human health. Since 
the EEC's for residues of vinclozolin per se are lower than the chronic 
DWLOC's, aggregate exposure will not exceed 100% of the cPAD.
    3. Short- or intermediate-term risk. The MOE is greater than or 
equal to 1,010 for aggregate risks to infants and children resulting 
from use of vinclozolin. Therefore, the risks do not exceed the 
Agency's LOC.
    4. Determination of safety. Based on these risk assessments, there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to vinclozolin residues.

H. International Tolerances

    CODEX maximum residue limits (MRLs) for residues of vinclozolin and 
its metabolites containing the 3,5-DCA moiety have been established in 
common bean at 2 ppm, rape seed at 1 ppm (no limit for canola), cattle 
meat and milk at 0.5 ppm, and chicken meat and eggs at 0.05 ppm. No 
Canadian or Mexican tolerances have been established for vinclozolin 
residues in succulent beans, rape, canola, meat, milk, poultry, or 
eggs.
    The CODEX MRLs for canola (rapeseed), cattle meat, cattle milk, and 
poultry eggs are in harmony with the proposed tolerances associated 
with this petition. The chicken meat MRL (0.05 ppm) is not in harmony 
with the proposed tolerance in poultry meat (0.1 ppm) due to recovery 
discrepancies with the analytical method.
[FR Doc. 03-7246 Filed 3-25-03; 8:45 am]
BILLING CODE 6560-50-S