[Federal Register Volume 69, Number 207 (Wednesday, October 27, 2004)]
[Notices]
[Pages 62680-62688]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-24039]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2004-0273; FRL-7676-1]


BAS 320 I; 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 for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket identification (ID) number OPP-
2004-0273, must be received on or before November 26, 2004.

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: Ann Hanger, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 306-0395; e-mail address: <a href="/cdn-cgi/l/email-protection#c7afa6a9a0a2b5e9a6a9a987a2b7a6e9a0a8b1"><span class="__cf_email__" data-cfemail="e189808f868493cf808f8fa1849180cf868e97">[email protected]</span></a>.

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:
    <bullet> Crop production (NAICS 111)
    <bullet> Animal production (NAICS 112)
    <bullet> Food manufacturing (NAICS 311)
    <bullet> Pesticide manufacturing (NAICS 32532)
    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 ID number OPP-2004-0273. 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 <greek-i>2, 1801 South Bell St., 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

[[Page 62681]]

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.
    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-2004-0273. 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 <a href="/cdn-cgi/l/email-protection#6e011e1e430a010d050b1a2e0b1e0f40090118"><span class="__cf_email__" data-cfemail="87e8f7f7aae3e8e4ece2f3c7e2f7e6a9e0e8f1">[email protected]</span></a>, 
Attention: Docket ID Number OPP-2004-0273. 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-2004-0273.
    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 
<greek-i>2, 1801 South Bell St., Arlington, VA, Attention: Docket ID 
Number OPP-2004-0273. 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

[[Page 62682]]

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.

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: October 19, 2004.
Lois Rossi,
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

Pesticide Petition 4F6839

    EPA has received a pesticide petition (PP 4F6839) from BASF 
Corporation, P.O. 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. 346a(d), to amend 40 CFR part 180 by 
establishing a tolerance for residues of BAS 320 I, a mixture 
comprising 4-{(2E)-2-({[4-(trifluoromethoxy)anilino] carbonyl{time}  
hydrazono)-2-[3-(trifluoromethyl)phenyl]ethyl{time}  benzonitrile and 
4-{(2Z)-2-({[4-(trifluoromethoxy)anilino] carbonyl{time}  hydrazono)-2-
[3-(trifluoromethyl) phenyl]ethyl{time}  benzonitrile in or on the raw 
agricultural commodity tuberous and corm vegetables (crop subgroup 1-C) 
at 0.05 parts per million (ppm), leafy vegetables (crop group 4) at 35 
ppm, head and stem brassica (crop subgroup 5-A) at 5 ppm, leafy 
brassica greens (crop subgroup 5-B) at 25 ppm, fruiting vegetables 
(crop group 8) at 1.0 ppm. EPA has determined that the petition 
contains data or information regarding the elements set forth in 
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. In three plant metabolism studies (cabbage, 
tomato and cotton), the major component of the residue was BAS 320 I 
(E- and Z-isomers). The major degradate was the ketone, M320I04 and an 
oxidized and cyclized metabolite, M320I23, was present in lesser 
amounts. These four compounds were defined as the residues of concern 
and were incorporated into an analytical method. In the confined 
rotational crop studies plant uptake was very limited and the residues 
were a mixture of minor and polar components.
    2. Analytical method. BASF Analytical Method No. 531/0 was 
developed to determine residues of BAS 320 I (E- and Z-Isomer) and its 
metabolites M320I04 and M320I23, the residues of concern in plants, in 
crop matrices. In this method, residues of BAS 320 I are extracted from 
plant matrices with methanol/water (70:30; v/v) and then partitioned 
into dichloromethane. For oily matrices, the residues are extracted 
with a mixture of isohexane/acetonitrile (1:1; v/v). The final 
determination of BAS 320I and its metabolites is performed by LC/MS/MS.
    3. Magnitude of residues. Field trials were carried out in order to 
determine the magnitude of residue in the following crops: Broccoli, 
cabbage, celery, head lettuce, leaf lettuce, mustard greens, pepper 
(bell and non-bell), potato, spinach, and tomato. Field trials were 
conducted in the required regions. Field trials were carried out using 
the maximum label rate, the maximum number of applications and the 
minimum preharvest interval. In addition, processing studies were 
conducted on potatoes and tomatoes to determine the concentration 
factor during normal processing of the raw agricultural commodities. No 
animal feeding studies were conducted.

B. Toxicological Profile

    1. Acute toxicity. Based on the available acute toxicity data BAS 
320 I and its formulated product do not pose acute toxicity risks.

                                            For Technical BAS 320 I:
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Oral LD50                              Rat                      Lethal dose 50 (LD50 >   Category IV
                                                                 5,000 milligrams/
                                                                 kilogram body weight
                                                                 (mg/kg b.w.)
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[[Page 62683]]

 
Oral LD50                              Mouse                    LD50 > 5,000 mg/kg b.w.  Category IV
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Dermal LD50                            Rat                      LD50 > 5,000 mg/kg b.w.  Category IV
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Inhalation LC50                        Rat                      >5.2 mg/liters (L)       Category IV
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Eye irritation                         Rabbit                   Not irritating           Category IV
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Skin irritation                        Rabbit                   Not irritating           Category IV
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Skin sensitization (Maximization       Guinea pig               Not sensitizing
 test)
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                                      For the BAS 320 00 I SC formulation:
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Oral LD50                              Rat                      LD50> 2,000 mg/kg b.w.   Category III
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Dermal LD50                            Rat                      LD50> 4,000 mg/kg b.w.   Category III
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Inhalation LC50                        Rat                      >5.2 mg/L                Category IV
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Eye irritation                         Rabbit                   Slightly irritating      Category III
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Skin irritation                        Rabbit                   Not irritating           Category IV
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Skin sensitization (Modified Buehler   Guinea pig               Not sensitizing
 Method)
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    2. Genotoxicty. In a battery of three in vitro and two in vivo 
mutagenicity assays consisting of all required end-points (point 
mutation, chromosomal damage, and DNA damage and repair), the weight of 
the evidence for BAS 320 I indicates a lack of potential genotoxicity.
    Specifically, for the battery of three in vitro mutagenicity assays 
with BAS 320 I, no positive responses were observed for increased 
revertant frequencies with and without metabolic activation bacterial 
reverse mutation assay or for increased mutant frequencies with and 
without metabolic activation Hypoxanthine guanine phophoribosyl 
transferase (HGPRT) locus assay. Although there was a positive result 
for a statistically increased number of structurally aberrant 
metaphases in the chromosomes, which indicates clastogenic potential 
under in vitro conditions, this result was only observed without 
metabolic activation cytogenicity study with V79 cells.
    Importantly, the potential biological significance of this apparent 
chromosome damage observed in vitro only without metabolic activation, 
was evaluated in vivo using the mouse micronucleus assay. Testing in 
the in vivo micronucleus study with NMRI mice was conducted at a high 
dose level (2,000 mg/kg b.w.) that demonstrated clinical symptoms of 
toxicity, including piloerection and poor general state, in 5 of 5 
animals. No significant or dose-related increases in chromosomal damage 
were observed in this in vivo test, indicating that BAS 320 I does not 
cause chromosomal aberrations in intact animals.
    Moreover, it has also been recognized by EPA that more weight 
should be placed on in vivo systems than in vitro systems as expressed 
in the Agency's weight of evidence for genotoxic evaluation of a 
chemical included in the ``Guidelines for Mutagenicity Risk 
Assessment'' (Federal Register, September 24, 1986, Vol. 51: 34006-
34012). Thus, the negative in vivo results (non-clastogenicity for 
chromosomal aberrations) observed in the mouse micronucleus assay and 
the rat hepatocytes assay, should override the positive results 
obtained in the in vitro assay only without metabolic activation. 
Furthermore, it has been noted that in vitro systems may simulate 
abnormal physiological conditions from prolonged exposure to a chemical 
in the absence of S-9 metabolic activation (Brusick, D.J. (editor) 
1987. Genotoxicity Produced in Cultured Mammalian Cell Assay by 
Treatment Conditions. Mutation Research, Vol. 189, No.1: 1-69 and 
Sofuni, T. 1993. Japanese Guidelines for Mutagenicity Testing. 
Environmental and Molecular Mutagenesis, Vol. 21, No.1: 2-7). 
Consequently, based on the weight of the evidence presented above, BAS 
320 I does not pose a genotoxic concern.
    3. Reproductive and developmental toxicity. Potential reproductive 
toxicity of BAS 320 I was investigated in a 2-generation reproduction 
toxicity study in Wistar rats by oral gavage administration. 
Originally, the highest dose tested (HDT) by oral gavage was 75 mg/kg 
b.w./day, which induced both excessive maternal toxicity (very high 
incidences of poor general health in females during premating, 
gestation, and lactation; and statistically decreased food consumption, 
body weights, and body weight gain) as well as excessive developmental 
toxicity (statistically impaired pup body weights and body weight 
gain), which altogether resulted in high pup mortality. Consequently, a 
meaningful assessment of the potential reproductive toxicity of the 
test compound at this excessively toxic dose level was not possible. 
Thereafter, for the next two successive parental generations of rats, 
which were originally derived from the parents treated at 75 mg/kg 
b.w./day, the HDT was 50 mg/kg b.w./day.
    Subsequently, the no observable adverse effect level (NOAEL) for 
parental toxicity was 20 mg/kg b.w./day, based on the following effects 
for females at 50 mg/kg b.w./day (HDT for two consecutive generations) 
-

[[Page 62684]]

increased incidences of poor general health in females during 
premating, gestation, and lactation; 3 of 25 dams with complete litter 
losses; and statistically significantly reduced body weights during 
premating, gestation, and lactation.
    The NOAEL for offspring/pup toxicity was 20 mg/kg b.w./day, based 
on a slight increased incidence of pup mortality at 50 mg/kg b.w./day. 
Whereas the NOAEL for fertility in this study was 50 mg/kg b.w./day 
(HDT for two generations), the NOAEL for reproductive performance was 
considered to be 20 mg/kg b.w./day, based on 3 of 25 dams with complete 
litter losses, of which 2 of these 3 dams had indications of poor 
nursing for their first generation of pups. It is noteworthy that 
because most of the pup mortality was due to poor nursing in only 2 of 
25 dams, this finding may be considered to be incidental. Importantly, 
no comparable impairment of reproductive performance occurred for the 
succeeding parental generation treated by oral gavage administration at 
50 mg/kg b.w./day.
    In a developmental (teratology) toxicity study in the Wistar rat, 
the results indicated that the NOAEL for maternal toxicity was 40 mg/kg 
b.w./day, based on statistically decreased food consumption and body 
weight gains at 120 mg/kg b.w./day (HDT). The NOAEL for fetal 
(prenatal)/developmental toxicity was 120 mg/kg b.w./day (HDT). In 
addition, there were no indications of any teratogenic effects in the 
rat fetuses at 120 mg/kg b.w./day (HDT). Therefore, BAS 320 I is 
considered to be neither a developmental toxicant nor a teratogenic 
agent in the rat.
    In a developmental (teratology) toxicity study in the Himalayan 
rabbit, the results indicated that the NOAEL for maternal toxicity was 
100 mg/kg b.w./day, based on several clinical symptoms of toxicity 
(including ataxia and poor general state) occurring in 4 of 25 does at 
300 mg/kg b.w./day, for which 2 of these 4 does had abortions prior to 
being sacrificed early, with a third doe at 300 mg/kg b.w./day being 
sacrificed moribund. Similarly, the NOAEL for fetal (prenatal)/
developmental toxicity was 100 mg/kg b.w./day, based on slightly 
decreased mean fetal body weights as well as an increased rate for a 
certain skeletal variation, namely incomplete ossification of 
sternabrae. Because developmental toxicity was only observed at dose 
levels that were maternally toxic, BAS 320 I is not selectively toxic 
to the fetal rabbit.
    Lastly, in this rabbit developmental toxicity study, there were no 
indications of any teratogenic effects in the rabbit fetuses at 300 mg/
kg b.w./day (HDT). Therefore, BAS 320 I is not teratogenic in the 
rabbit.
    4. Subchronic toxicity. In the Sprague-Dawley rat, treatment by 
oral gavage with BAS 320 I for a subchronic duration (90-day timepoint 
in the chronic toxicity/carcinogenicity study) resulted in reduced food 
consumption and/or decreased mean body weight and/or body weight gains 
in males and females at 300 mg/kg b.w./day and in increased incidences 
of hepatocellular centrilobular hypertrophy in the livers of males at 
300 mg/kg b.w./day. Under the conditions of the study, the NOAEL for 
oral administration of BAS 320 I for 90 days was 60 mg/kg b.w./day.
    In the beagle dog, treatment by oral gavage with BAS 320 I for a 
subchronic duration (90-day timepoint in the chronic toxicity study) 
resulted in reduced body weight gain and/or decreased food consumption 
in several dogs at 30 mg/kg b.w./day and slightly decreased mean cell 
hemoglobin concentration (MCHC) at 30 mg/kg b.w./day. Under the 
conditions of the study, the NOAEL for oral administration of BAS 320 I 
for 90 days was 12 mg/kg b.w./day.
    Lastly, in a subchronic (90-day) dermal toxicity study conducted 
with BAS 320 I technical in Wistar rats, the results support a NOAEL of 
100 mg/kg b.w./day, based on decreased food consumption (females) and 
decreased body weight change in males and females at 300 mg/kg b.w./
day, the next HDT.
    5. Chronic toxicity. In the Sprague-Dawley rat, treatment by oral 
gavage with BAS 320 I for a 2-year chronic duration resulted in dose-
related increased incidences of hepatocellular centrilobular 
hypertrophy in the livers of males and females at 60 mg/kg b.w./day and 
at 300/200 mg/kg b.w./day and hepatocellular basophilic alteration in 
males at 60 and 300 mg/kg b.w./day. (Note: Beginning the first day of 
Week 3, the dose level of the high-dose females was lowered from 300 to 
200 mg/kg b.w./day, due to an adverse effect of -71% decreased body 
weight gain as compared to controls.)
    Therefore, the NOAEL for systemic toxicity following oral 
administration of BAS 320 I for 24 months to Sprague-Dawley rats was 30 
mg/kg b.w./day for males and females. Importantly, treatment with BAS 
320 I to rats for 2 years resulted in no test substance-related 
neoplastic findings, and therefore, the NOAEL for oncogenicity was 300/
200 mg/kg b.w./day (HDT).
    In the CD-1 mouse, treatment by oral gavage with BAS 320 I for an 
18-month chronic duration resulted in a treatment-related increased 
incidence of increased brown pigment in the spleens of male and female 
animals administered 1,000 mg/kg b.w./day (HDT), as compared to 
controls. Under the conditions of the study, the NOAEL for systemic 
toxicity following oral administration of BAS 320 I for 18 months to 
CD-1 mice was 250 mg/kg b.w./day (the next HDT) for males and females. 
Importantly, treatment with BAS 320 I to mice for 18 months resulted in 
no test substance-related neoplastic findings, and therefore, the NOAEL 
for oncogenicity was 1,000 mg/kg b.w./day (HDT).
    In the beagle dog, treatment via gelatin capsules with BAS 320 I 
for a 12-month chronic duration resulted in reduced body weight gain 
and/or decreased food consumption in several dogs at 30 mg/kg b.w./day 
and slightly decreased mean MCHC at 30 mg/kg b.w./day. Under the 
conditions of the study, the NOAEL for oral administration of BAS 320 I 
for 12 months was 12 mg/kg b.w./day.
    i. Threshold effect. For estimated chronic exposure, the 
calculation of the chronic reference dose (chronic RfD) is based on the 
results of the chronic toxicity studies in the rat, mouse, and dog, and 
the two-generation reproduction study in the rat. For BAS 320 I, the 
lowest NOAEL for chronic toxic effects is 12 mg/kg b.w./day from the 
12-month dog study. A safety factor of 100 is applied to the NOAEL of 
12 mg/kg b.w./day, which results in a chronic RfD of 0.12 mg/kg b.w./
day.
    ii. Non threshold effect. Since there were no test substance-
related neoplastic findings following long-term treatment with BAS 320 
I to mice for 18 months or to rats for 24 months, the NOAEL for 
oncogenicity in both studies was established at the respective HDT. 
Therefore, BAS 320 I should be classified as ``not likely to be a human 
carcinogen.''
    6. Animal metabolism. In the rat and goat metabolism studies, the 
majority of the dose was rapidly excreted in the feces. The low levels 
that were absorbed were distributed throughout various tissues. BAS 320 
I was the major component of the extractable residues in all tissues 
and milk and is the only residue of concern. Metabolism of BAS 320 I 
occurs by hydroxylation and conjugation on either of the phenyl rings 
or at the ethylene bridge and are the major routes of detoxification. 
Cleavage of the semicarbazide bond to yield M320I04 also occurs, 
usually with accompanying conjugation. The only residue of concern is 
BAS 320 I.

[[Page 62685]]

    7. Metabolite toxicology. Toxicity of the metabolites of BAS 320 I 
with potential exposure to humans was concurrently evaluated during 
toxicity testing of the parent except for the metabolite M320I23 that 
was not observed in the rat metabolism study. The Z-isomer (M320I02) of 
BAS 320 I was evaluated in additional toxicity tests to confirm no 
differences between the minor Z-isomer component and BAS 320 I 
technical with a 9 to 1 E-isomer to Z-isomer ratio, respectively. The 
results show no toxicological concerns:
    i. Toxicity studies with the metabolite M320I23.
    <bullet> Acute toxicity study with metabolite M 320I023
    <bullet> The metabolite M 320I023 of BAS 320 I technical 
demonstrates low acute toxicity via the oral route of exposure in the 
rat.
    <bullet> Oral LD<INF>50</INF> > 2,000 mg/kg b.w. (category III).
    ii. Subchronic toxicity study with metabolite M 320I023.
    In the Sprague-Dawley rat, treatment by oral gavage with metabolite 
M 320I023 of BAS 320 I technical for a subchronic (90-day) duration 
resulted in systemic toxicity effects of increased relative liver 
weights (females) and increased incidences of liver hepatocellular 
centrilobular hypertrophy in males and females at 1,000 mg/kg b.w./day 
(HDT), as compared to controls. Under the conditions of the study, the 
NOAEL for oral administration of the metabolite M 320I023 of BAS 320 I 
for 90 days was 200 mg/kg b.w./day (next HDT) in males and females.
    iii. Mutagenicity/Genotoxicity studies with metabolite M 320I023.
    In a battery of three in vitro and one in vivo mutagenicity assays 
consisting of all required end-points (point mutation, chromosomal 
damage, and DNA damage and repair), the weight of the evidence for the 
metabolite M 320I023 (parent ketone) of BAS 320 I technical indicates a 
lack of potential genotoxicity.
    Specifically, for the battery of three in vitro mutagenicity assays 
with metabolite M 320I023 of BAS 320 I technical, no positive responses 
were observed for increased revertant frequencies with and without 
metabolic activation bacterial reverse mutation assay or for increased 
mutant frequencies with and without metabolic activation HGPRT locus 
assay. Although there was a positive result for a statistically 
increased number of structurally aberrant metaphases in the 
chromosomes, which indicates clastogenic potential under in vitro 
conditions, this result was only observed with metabolic activation 
cytogenicity study with V79 cells.
    Importantly, the potential biological significance of this apparent 
chromosome damage observed in vitro only with metabolic activation, was 
evaluated in vivo using the mouse micronucleus assay. Testing in this 
in vivo micronucleus study with NMRI mice was conducted at a high dose 
level (2,000 mg/kg b.w.), that demonstrated no clinical symptoms of 
toxicity but which represents the limit dose for this assay. No 
significant or dose-related increases in in vivo chromosomal damage 
were observed, indicating that the metabolite M 320I023 of BAS 320 I 
technical does not cause chromosomal aberrations in intact animals.
    Moreover, it has also been recognized by U.S. EPA that more weight 
should be placed on in vivo systems than in vitro systems as expressed 
in the Agency's weight of evidence for genotoxic evaluation of a 
chemical included in the ``Guidelines for Mutagenicity Risk 
Assessment'' ( Federal Register, September 24, 1986, Vol. 51: 34006-
34012). Thus, the negative in vivo results (non-clastogenicity for 
chromosomal aberrations) observed in the mouse micronucleus assay 
should override the positive results obtained in the in vitro assay 
only with metabolic activation. Furthermore, it has been noted that in 
vitro systems may simulate abnormal physiological conditions (Brusick, 
D.J. (editor) 1987. Genotoxicity Produced in Cultured Mammalian Cell 
Assay by Treatment Conditions. Mutation Research, Vol. 189, No.1: 1-
69). Additionally, it has been reported in the literature that S-9 
metabolic activation does not often have adequate cofactors for 
activating detoxifying mechanisms found in the whole animal system 
Ashby, J. 1983. The Unique Role of Rodents in The Detection of Possible 
Human Carcinogens and Mutagens. Mutation Research, Vol. 115: 117-213 
Galloway, S.M. 1994. Chromosome Aberrations Induced In Vitro: 
Mechanisms. Delayed Expression, and Intriguing Questions. Environmental 
and Molecular Mutagenesis, Vol. 23, Supplement 24: 44-53. Consequently, 
based on the weight of the evidence presented above, the metabolite M 
320I023 of BAS 320 I technical does not pose a genotoxic concern.
    Therefore, as indicated from the results of the mammalian toxicity 
studies as well as the mutagenicity assays, metabolite M 320I023 of BAS 
320 I does not demonstrate more adverse toxicity when compared to the 
BAS 320 I.
    iv. Toxicity studies with the Z-Isomer of technical BAS 320 I.
    <bullet> Acute toxicity study with Z-Isomer. The Z-isomer of BAS 
320 I technical demonstrates low acute toxicity via the oral route of 
exposure in the rat.
    <bullet> Oral LD<INF>50</INF> > 5,000 mg/kg b.w. (category IV).
    v. Subchronic toxicity study with Z-Isomer. In the Sprague-Dawley 
rat, treatment by oral gavage with the Z-isomer of BAS 320 I for a 
subchronic (90-day) duration resulted in impaired body weight gain only 
in females at the mid-dose (300 mg/kg b.w./day) and the high-dose 
(1,000 mg/kg b.w./day), as compared to controls. Several microscopic 
changes were observed in female animals at these two dose levels, but 
all morphologic changes were regarded to be indirect effects of the 
impaired body weight gain. Under the conditions of the study, the NOAEL 
for oral administration of the Z-isomer of BAS 320 I for 90 days was 
1,000 mg/kg b.w./day (HDT) in males and 100 mg/kg b.w./day (lowest dose 
tested) in females.
    vi. Mutagenicity/Genotoxicity study with Z-Isomer. In an in vitro 
mutagenicity assay with the Z-isomer of BAS 320 I, there were no 
positive responses observed for increased revertant frequencies with 
and without metabolic activation bacterial reverse mutation assay.
    Therefore, as indicated from the results of the mammalian toxicity 
studies as well as the mutagenicity assay, the minor isomer of BAS 320 
I, namely the Z isomer, does not demonstrate more adverse toxicity when 
compared to BAS 320 I. 8. Endocrine disruption. Data from the 
reproduction / developmental toxicity and short- and long-term repeated 
dose toxicity studies with BAS 320 I in the rat, rabbit, mouse, or dog, 
do not suggest any endocrine disruption activity. This information is 
based on the absence of any treatment-related effects from the 
histopathological examination of reproductive organs as well as a low 
level of concern for possible effects on fertility, reproductive 
performance, or any other aspect of reproductive function, or on growth 
and development of the offspring.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. Assessments were conducted to 
evaluate the potential risk due to acute and chronic dietary exposure 
of the U.S. population to residues of BAS 320 I. This insecticide and 
its metabolites (M320I04, M320I23) were expressed as the parent 
compound (BAS 320 I). The dietary analysis was conducted on all 
proposed crops which include potatoes, sweet potatoes, yams, leafy 
greens subgroup, leaf petioles subgroup, head &

[[Page 62686]]

stem brassica subroup, leafy brassica greens subgroup, and fruiting 
vegetables except cucurbits.
    Secondary residues from meat, milk, and eggs were not included in 
this assessment since the proposed crops are only considered for human 
consumption with the exception of processed potato commodities being 
potentially utilized in animal feed. Animal feeding studies were not 
required on potatoes based on results of residues of BAS 320 I and its 
metabolites (M320I04 and M320I23) in unwashed potatoes. Following an 
application rate 18 times the proposed seasonal rate, residues in 
potatoes were at or below the limit of quantitation (LOQ) and thus the 
proposed tolerance level was set at the LOQ and no feeding studies were 
needed.
    The acute and chronic dietary exposure estimates were based on the 
proposed tolerance values, 100 percent crop treated values, 
concentration/processing factors and consumption data from the USDA 
Continuing Survey of Food Intake by Individuals (CSFII 1994 - 1996, 
1998) and the EPA Food Commodity Ingredient Database (FCID) using 
Exponent's Dietary Exposure Evaluation Module (DEEM-FCID) software. 
Result exposure estimates were compared against the BAS 320 I acute 
Population Adjusted Dose (aPAD) and chronic Population Adjusted Dose 
(cPAD) of 20 mg/kg b.w./day and 0.12 mg/kg b.w./day, respectively. 
Exposure estimates for the BAS 320 I acute dietary assessment were well 
under 100% of the aPAD at the 99.9\th\ percentile (see table below). 
The overall U.S. population and the highest exposed subpopulation (all 
infants) used only 1.16% and 3.26% of the aPAD, respectively. 
Additional refinements including the use of anticipated residues and 
predicted percent crop treated would further reduce the acute exposure 
estimates.

             Acute dietary exposure estimates for BAS 320 I
------------------------------------------------------------------------
                                   Exposure Estimate
      Population Subgroups         (mg/kg b.w./day)        %aPAD\1\
------------------------------------------------------------------------
U.S. population                   0.231788            1.16
---------------------------------
All infants                       0.651674            3.26
---------------------------------
1-2 years                         0.607989            3.04
---------------------------------
3-5 years                         0.424105            2.12
---------------------------------
1-6 years                         0.444105            2.22
---------------------------------
6-12 years                        0.269403            1.35
---------------------------------
13-19 years                       0.153397            0.77
---------------------------------
Females 13-49 years               0.212264            1.06
---------------------------------
Adults 20-49 years                0.210816            1.05
---------------------------------
Males 20+ years                   0.190737            0.95
---------------------------------
Adults 50+ years                  0.183849            0.92
------------------------------------------------------------------------
\1\ 99.9th percentile

    Results of the chronic dietary assessments are listed in the table 
below. The estimated chronic dietary exposure was less than 14.5% of 
the cPAD for all subpopulations. Additional refinements such as the use 
of anticipated residues and predicted percent crop treated would 
further reduce the estimated chronic dietary exposure.

            Chronic dietary exposure estimates for BAS 320 I
------------------------------------------------------------------------
                                   Exposure Estimate
      Population subgroups         (mg/kg b.w./day)          %cPAD
------------------------------------------------------------------------
U.S. population                   0.014905            12.4
---------------------------------
All infants                       0.007363            6.1
---------------------------------
1-2 years                         0.016032            13.4
---------------------------------
3-5 years                         0.016745            14.0
---------------------------------
1-6 years                         0.016241            13.5
---------------------------------
6-12 years                        0.014179            11.8
---------------------------------
13-19 years                       0.012417            10.3
---------------------------------
Females 13-49 years               0.015466            12.9
---------------------------------
Adults 20-49 years                0.015226            12.7
---------------------------------
Males 20+ years                   0.014347            12.0
---------------------------------
Adults 50+ years                  0.015557            13.0
------------------------------------------------------------------------

    ii. Drinking water. Drinking water level of comparison (DWLOC) 
calculation and comparison to surface water and ground water 
estimations are given in the tables below. The expected environmental 
concentrations (EEC) for both ground water and surface water are well 
below the allowable level.

                               Estimated acute drinking water values for BAS 320 I
----------------------------------------------------------------------------------------------------------------
                                  Adult Males (20-49  Adult Females (13-     Children (1-6    Children (birth to
           DWLOC acute                  years)             49 years)            years)              1 year)
----------------------------------------------------------------------------------------------------------------
DWLOC acute ([mu]g/L)             696138.8            596355.81           197403.28           196273.27
---------------------------------
                                                      DEC's
----------------------------------------------------------------------------------------------------------------
PRZM/EXAMS (BASF)                 0.85                0.85                0.85                0.85
Surface water ([mu]g/L).........
---------------------------------
Sci-Grow (BASF)                   0.006               0.006               0.006               0.006
Ground water ([mu]g/L)..........
----------------------------------------------------------------------------------------------------------------


                              Estimated chronic drinking water values for BAS 320 I
----------------------------------------------------------------------------------------------------------------
                                  Adult Males (20-49  Adult Females (13-     Children (1-6    Children (birth to
          DWLOC chronic                 years)             49 years)            years)              1 year)
----------------------------------------------------------------------------------------------------------------
DWLOC chronic ([mu]g/L)           3904.9150           3329.5500           1101.1200           1156.8500
---------------------------------

[[Page 62687]]

 
                                                      DEC's
----------------------------------------------------------------------------------------------------------------
PRZM/EXAMS (BASF)                 0.04                0.04                0.04                0.04
Surface water ([mu]g/L).........
---------------------------------
Sci-Grow (BASF)                   0.006               0.006               0.006               0.006
Ground water ([mu]g/L)..........
----------------------------------------------------------------------------------------------------------------

    iii. Aggregate exposure (Diet + Water). The acute and chronic 
aggregate exposure of BAS 320 I residues is summarized in the table 
below.

                     Estimated aggregate exposure of BAS 320 I residues from food and water
----------------------------------------------------------------------------------------------------------------
                                                         Children (1-6                          Females (13-49
            Exposure              Infants (0-1 year)        years)           Males (20-49           years)
--------------------------------------------------------------------------------years)--------------------------
                                                     FOOD\1\
----------------------------------------------------------------------------------------------------------------
Acute exposure (mg/kg b.w./day)   0.651674            0.444105            0.190737            0.212264
---------------------------------
Chronic Exposure (mg/kg b.w./     0.007363            0.016241            0.014347            0.015466
 day)
%aPAD                             3.26                2.22                0.95                1.06
%cPAD                             6.14                13.5                12.0                12.9
---------------------------------
                                                      WATER
----------------------------------------------------------------------------------------------------------------
Acute exposure (mg/kg b.w./day)   0.000085            0.000057            0.000024            0.000027
---------------------------------
Chronic exposure (mg/kg b.w./     0.00000400          0.000003            0.000001            0.000001
 day)
%aPAD                             0.0004              0.0003              0.0001              0.0001
%cPAD                             0.0033              0.0022              0.0010              0.0011
---------------------------------
                                                    AGGREGATE
----------------------------------------------------------------------------------------------------------------
Acute exposure (mg/kg b.w./day)   0.651759            0.444162            0.190761            0.212291
---------------------------------
Chronic exposure (mg/kg b.w./     0.007367            0.016244            0.014348            0.015467
 day)
%aPAD                             3.26                2.22                0.95                1.06
%cPAD                             6.14                13.5                12.0                12.9
----------------------------------------------------------------------------------------------------------------
\1\ 99.9th percentile

    These results indicate the aggregate exposure of BAS 320 I from 
potential residues in food and water, will not exceed the U.S. EPA's 
level of concern (100% of PAD). The percent acute and chronic PAD were 
< 4 and 14% for all subpopulations, respectively. Overall, considering 
a ``worst-case'' scenario, we can conclude with reasonable certainty 
that no harm will occur from either acute or chronic aggregate exposure 
of BAS 320 I residues from the proposed uses.

D. Cumulative Effects

    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.''
    The EPA is currently developing methodology to perform cumulative 
risk assessments. At this time, there is no available data to determine 
whether BAS 320 I has a common mechanism of toxicity with other 
substances or how to include this pesticide in a cumulative risk 
assessment

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions 
described above and based on the completeness and the reliability of 
the toxicity data, BASF has estimated the aggregate exposure to BAS 320 
I will utilize less than 2% and 14% of the aPAD and cPAD for the U.S. 
population, respectively. For the highest exposed age-related 
subpopulation the maximum aggregate exposure is predicted to be less 
than 3.5% of the aPAD (infants) and 15% of the cPAD (3-5 years).
    2. Infants and children. All subpopulations based on age were 
considered. Infants and children remained below 3.5 and 15% of the 
aggregate aPAD and cPAD for food and water, respectively. BASF, 
considering a worst-case situation, concludes with reasonable certainty 
that no harm will result to infants or children from aggregate exposure 
to BAS 320 I residues.
    No additional FQPA safety factor(s) are considered to be 
appropriate for BAS 320 I, for the following reasons: There is a 
complete toxicity database for BAS 320 I and the exposure data are 
complete or are estimated based on data that reasonably accounts for 
potential exposures. There is no evidence of susceptibility following 
in utero exposure to rats and there is a low level of concern for any 
uncertainties in the developmental toxicity study in rabbits or the 2-
generation reproduction study,

[[Page 62688]]

after establishing toxicity endpoints and traditional uncertainty 
factors to be used in the risk assessment. Based on these data and 
conclusions, a FQPA safety factor of 1X appears to be appropriate for 
BAS 320 I.

F. International Tolerances

    No Maximum residue levels (MRLs) have been established for BAS 320 
I by the Codex Alimentarius Commision (CODEX) or in Canada and Mexico.
[FR Doc. 04-24039 Filed 10-26-04; 8:45 am]
BILLING CODE 6560-50-S


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