[Federal Register Volume 68, Number 31 (Friday, February 14, 2003)]
[Notices]
[Pages 7542-7548]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-3694]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2002-0341; FRL-7289-5]


Boscalid; 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

[[Page 7543]]

regulations for residues of boscalid in or on various food commodities.

DATES: Comments, identified by docket ID number OPP-2002-0341, must be 
received on or before March 17, 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: Richard Keigwin, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305-7618; 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)
    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-2002-0341. 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.
    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,

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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-2002-0341. 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-2002-0341. 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-2002-0341.
    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-2002-0341. 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.

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: February 3, 2003.
Debra Edwards,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of a 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 1F6313

    EPA has received a pesticide petition (1F6313) 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 boscalid, 3-
pyridinecarboxamide, 2-chloro-N-(4'-chloro(1,1'-biphenyl)-2-yl)]] in or 
on the following primary raw agricultural commodities and processed 
commodities: Root vegetables (crop group 1-B) 1.0 parts per million 
(ppm), tuberous and corm vegetables (crop group 1-C) 0.05 ppm, bulb 
vegetables (crop group 3) 3.0 ppm, leafy vegetables (crop group 4) 11.0 
ppm, head and stem brassica (sub crop group 5-A) 3.0 ppm, legume 
vegetables (crop group 6) 2.2 ppm, fruiting vegetables (crop group 8) 
1.0 ppm, cucurbit vegetables (crop group 9) 1.5 ppm, stonefruit (crop 
group 12) 1.7 ppm, berries (crop group 13) 3.5 ppm, tree nuts (crop 
group 14) 0.25 ppm, almond hulls 3.0 ppm, pistachios 0.65 ppm, mint 
30.0 ppm, grapes 3.5 ppm, raisins 8.5 ppm, strawberries 1.2 ppm, peanut 
0.05 ppm, peanut meal 0.15 ppm, peanut oil 0.15 ppm, canola 3.5 ppm, 
sunflower seed 3.5 ppm.
    BASF Corporation also proposes to amend 40 CFR part 180 by 
establishing tolerances for residues of 3-pyridinecarboxamide, 2-
chloro-N-(4'-

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chloro(1,1'-biphenyl)-2-yl) in or on the following raw agricultural and 
processed commodities of rotational crops: Beet root 1.0 ppm, root 
vegetables (crop group 1-B) 1.0 ppm, leaves of root and tuber 
vegetables (crop group 2) 1.0 ppm, head and stem brassica (sub crop 
group 5-A) 3.0 ppm, leafy brassica greens (sub crop group 5-B) 18.0 
ppm, legume vegetables - peas (crop group 6) 2.2 ppm, foliage of legume 
vegetables (crop group 7): forage 1.5 ppm, hay 2.0 ppm, vines 0.05 ppm, 
cucurbit vegetables (crop group 9) 1.5 ppm, cereal grains (crop group 
15) 0.20 ppm, forage fodder and straw of cereal grains (crop group 16) 
forage 2.0 ppm, straw 3.0 ppm, fodder 1.5 ppm, grass forage fodder and 
hay (crop group 17) forage 2.0 ppm, hay 8.0 ppm, straw 0.3 ppm, seed 
0.2 ppm, non-grass animal feeds (crop group 18) forage 1.0 ppm, hay 2.0 
ppm, seed 0.2 ppm, mint 30.0 ppm, cotton seed 0.05 ppm, cotton gin by-
products 0.3 ppm, soybean seed 0.1 ppm, soybean hulls 0.2 ppm, flax 
seed 3.5 ppm, sunflower seed 3.5 ppm, and rice hulls 0.5 ppm.
    BASF Corporation is also proposing to amend 40 CFR part 180 by 
establishing tolerances for the combined residues of 3-
pyridinecarboxamide, 2-chloro-N-(4'-chloro (1,1'-biphenyl)-2-yl and its 
metabolite 2-chloro-N-(4'chloro-5-hydroxy-biphenyl-2-yl)nicotinamide 
expressed in parent equivalents in the following animal commodities: 
Cow milk 0.10 ppm, cow muscle 0.10 ppm, cow fat 0.30 ppm, cow meat by-
products 0.35 ppm, eggs 0.02 ppm, poultry muscle 0.05 ppm, poultry fat 
0.05 ppm, and poultry meat by-products 0.05 ppm.
    EPA has determined that the petition contains data or information 
regarding the elements set forth in section 408(d)(2) of the FFDCA; 
however, EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data support granting of the petition. 
Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. Nature of the residue studies (OPPTS 860.1300) 
were conducted in grapes, lettuce, and beans as representative crops in 
order to characterize the fate of boscalid, also known as BAS 510 F, in 
all crop matrices. In all three crops, the BAS 510 F Residues of 
Concern (ROC) were characterized as parent (BAS 510 F). A confined 
rotational crop study also determined that parent was the residue of 
concern in the representative crops of radish, lettuce, and wheat.
    2. Analytical method. In plants the parent residue is extracted 
using an aqueous organic solvent mixture followed by liquid/liquid 
partitioning and a column cleanup. Quantitation is by gas 
chromatography/mass spectrometry (GC/MS). In livestock the residues are 
extracted with methanol. The extract is treated with enzymes in order 
to release the conjugated glucuronic acid metabolite. The residues are 
then isolated by liquid/liquid partition followed by column 
chromatography. The hydroxylated metabolite is acetylated followed by a 
column cleanup. The parent and acetylated metabolite are quantitated by 
gas chromatography/electron capture detection (GC/ECD).
    3. Magnitude of residues. Field trials were carried out in order to 
determine the magnitude of the residue in the following crops: Almonds, 
beans (dry and succulent), edible peas (dry and succulent), canola, 
carrot, cucurbits, grape, lettuce, leafy vegetables (brassica and non-
brassica), onion (dry bulb and green), peanut, pecan, pepper (bell and 
chili), pistachio, potato, berries (crop group), stonefruit (cherries, 
peaches, plums), strawberry, tomato, mint, and sunflower. Field trials 
were conducted in the United States and Canada in the required regions. 
Field trials were carried out using the maximum label rate, the maximum 
number of applications, and the minimum preharvest interval for each 
crop or crop group. In addition, processing studies were conducted on 
the following crops to determine concentration factors during normal 
processing of the raw agricultural commodity into the processed 
commodities: Canola, grape, peanut, plum, tomato, sunflower, and mint. 
Magnitude of the residue studies were also carried out in dairy cows 
and hens. Tier III field rotational crop studies were conducted to 
support rotational crop tolerances for beet roots, beet tops, cotton, 
foliage of legume vegetables, soybeans, cereals, grass and non-grass 
animal feeds. Processing studies were conducted on soybeans and rice to 
determine concentration factors.

B. Toxicological Profile

    1. Acute toxicity. Based on available acute toxicity data BAS 510 F 
and its formulated products do not pose acute toxicity risks. The acute 
toxicity studies place technical BAS 510 F in toxicity category IV for 
acute oral; category III for acute dermal and category IV for acute 
inhalation. BAS 510 F is category IV for both eye and skin irritation, 
and it is not a dermal sensitizer. Two formulated end use products are 
proposed, a Water Dispersible Granule (WG) termed BAS 510 02 F 
containing 70% BAS 510 F and a Water Dispersible Granule (WG) termed 
BAS 516 02 F containing a 2:1 mixture of BAS 510 F and BAS 500 F. BAS 
510 02 F has an acute oral toxicity category of III, acute dermal of 
III, acute inhalation of IV, eye irritation of III, skin irritation of 
IV, and is not a dermal sensitizer. BAS 516 02 F has an acute oral 
toxicity category of III, acute dermal of III, acute inhalation of IV, 
eye irritation of III, skin irritation of IV, and is not a dermal 
sensitizer.
    2. Genotoxicity. Ames Test (one study; point mutation): Negative; 
In Vitro CHO/HGPRT Locus Mammalian Cell Mutation Assay (one study; 
point mutation): Negative; In Vitro V79 Cell Cytogenetic Assay (one 
study; chromosome damage): Negative; In Vivo Mouse Micronucleus (one 
study; chromosome damage): Negative; In Vitro Rat Hepatocyte (one 
study; DNA damage and repair): Negative. BAS 510 F has been tested in a 
total of five genetic toxicology assays consisting of in vitro and in 
vivo studies. It can be stated that BAS 510 F did not show any 
mutagenic, clastogenic or other genotoxic activity when tested under 
the conditions of the studies mentioned above. Therefore, BAS 510 F 
does not pose a genotoxic hazard to humans.
    3. Reproductive and developmental toxicity. The reproductive and 
developmental toxicity of BAS 510 F was investigated in a 2-generation 
rat reproduction study as well as in rat and rabbit teratology studies.
    There were no adverse effects on reproduction in the 2-generation 
study at any dose tested. Pup effects were observed, with parental 
toxicity, at the highest dose tested only. In both parental 
generations, reduced food consumption and reduced body weight (bwt) 
gain were observed at 10,000 ppm. Both absolute and relative liver 
weights were increased 21% in F1 generation parental females at the 
high dose of 10,000 ppm only. Hepatocellular centrilobular hypertrophy 
(usually slight) was observed in many animals of both sexes in both the 
F0 and F1 generations at 1,000 ppm, and in all animals of both sexes at 
10,000 ppm. Additionally, some of the parental male rats at 10,000 ppm, 
in both generations, displayed centrilobular liver cell degeneration. 
Developmental toxicity was seen at 1,000 ppm in the form of decreased 
pup weights in the F2 males, and at 10,000 ppm in the form of decreased 
pup weight for both males and females of both the F1 and F2 
generations. The parental systemic and developmental toxicity no 
observed adverse effect levels (NOAEL) are both 100 ppm (12 milligrams/
kilogram/day (mg/kg/day).

[[Page 7546]]

    No teratogenic effects were noted in either the rat or rabbit 
developmental studies. In the rat study, evidence of maternal or 
developmental toxicity was not observed at any dose (highest dose 
tested of 1,000 mg/kg/day). Neither a maternal nor developmental lowest 
observed adverse effect level (LOAEL) were found since the highest dose 
tested was the NOAEL in both studies. In the rabbit teratology study, 
maternal toxicity observed at the mid dose of 300 mg/kg bwt consisted 
of discolored/reduced feces in one dam and an abortion in one dam. This 
finding is not necessarily indicative of a definitive test substance 
related adverse effect. The dam which displayed the fecal alterations 
and abortion also displayed decreased body weight and body weight gain 
- compared to the group mean - during gestation. These decreases 
occurred even prior to compound administration. Food consumption was 
also dramatically decreased in this dam compared to the other animals 
in the group. Every day from gestation day (GD) 1 - 12, this dam had 
food consumption values, which were less than half the mean for the 
group (compound administration began on GD 7). From GD 13 to 26 (when 
the animal aborted and was sacrificed) this dam ate essentially nothing 
(food consumption during this time period was <= 1.5 grams/day). These 
decreases in body weight, body weight gain, and food consumption, prior 
to compound administration, all indicate an animal in poor health and 
this poor state of health, rather than compound exposure, was likely 
the reason for the fecal alterations and abortion.
    At the high dose of 1,000 mg/kg bwt a maternal body weight gain 
decrease compared to controls of 81% was observed during the treatment 
period. Reduced food consumption, reduced body weight and abortions in 
three dams, were also seen at 1,000 mg/kg/day. Evidence of 
developmental toxicity was not seen at any dose tested.
    Developmental neurotoxicity (DNT) was not observed at any dose in 
the developmental neurotoxicity study. No maternal toxic effects were 
noted at any dose in this study. No developmental toxicity was seen at 
the low dose of 12 mg/kg/day (100 ppm). Reduced body weights and body 
weight gains were seen at 118 mg/kg/day (1,000 ppm) during postnatal 
day (PND) 1-4. Reduced body weights and body weight gains were seen at 
1,183 mg/kg/day (10,000 ppm) as well as decreased absolute pup brain 
weight at day 11 post partum (p.p.) (both sexes) and decreased brain 
length (males only) at day 11 p.p. The reduced pup brain weights and 
decreased brain length go hand-in-hand and both are due to the 
decreased pup weights seen at this dose. In this respect, it should be 
noted that pup brain weights relative to body weight at p.p. 11 were 
not significantly different from controls at this dose.
    Though no maternal toxicity was seen in this study, other studies 
using similar doses of BAS 510 resulted in maternal toxicity. A dose of 
118 mg/kg/day in female rats of the same strain in the multi-generation 
study, resulted in an increased incidence of hepatic centrilobular 
hypertrophy a parameter which could not have been detected in the DNT 
study as liver histopathology on parental animals was not performed in 
the DNT study.
    4. Subchronic toxicity. The subchronic toxicity of BAS 510 F was 
investigated in 90-day feeding studies with rats, mice and dogs, and in 
a 28-day dermal administration study in rats. A 90-day neurotoxicity 
study in rats was also performed. Generally, mild toxicity was 
observed. At high dose levels (doses above the LOAELs) in feeding 
studies, all three species displayed alterations in various clinical 
chemistry parameters. These clinical chemistry alterations were likely 
secondary to general toxicity. Statistically significant increased 
absolute and relative thyroid weights were observed in male rats only 
at doses at and above the LOAEL. Increased absolute and relative liver 
weights were observed in both sexes at doses above the LOAEL in rats 
and dogs. Increased absolute and relative liver weights were seen in 
both sexes of the mouse at lower doses. However, the increases in liver 
weights at these lower doses in the mouse were not deemed to be 
compound related due to the unusually low concurrent control liver 
weight values. At doses above the LOAELs, liver weight increases were 
supported by histopathology alterations in the rat and mouse, but not 
in the dog. Overall, only mild toxicity was observed in oral subchronic 
testing.
    In the 28-day repeat dose dermal study, no systemic effects were 
noted up to the highest dose tested of 1,000 mg/kg/day.
    In a 90-day rat neurotoxicity study, there was no mortality, signs 
of clinical toxicity, adverse effects on food consumption or body 
weight, at any dose level in either sex. No signs of neurotoxicity were 
observed during clinical observations, functional observation 
batteries, motor activity measurements of neuropathology. Therefore, 
there were no selective neurotoxic effects. Adverse effects were not 
seen even at the highest dose level tested. A LOAEL was not found and 
the NOAEL is the highest tested of 15,000 ppm (1,050 mg/kg/day in 
males; 1,272 mg/kg/day in females).
    5.Chronic toxicity. Based on review of the available data, the 
Reference Dose (RfD) for BAS 510 F will be based on a 24-month feeding 
study in rats with a threshold no observed effect level (NOEL) of 5 mg/
kg/day. Using an uncertainty factor of 100, the RfD is calculated to be 
0.05 mg/kg/day. The following are summaries of chronic toxicity studies 
submitted to EPA. The chronic toxicity/oncogenicity studies with BAS 
510 F include a 12-month feeding study with Beagle dogs, an 18-month 
B63CF1 mouse feeding study, a 24-month Wistar rat chronic feeding study 
and a 24-month Wistar rat oncogenicity study.
    At the highest dose tested in dogs, effects observed consisted 
primarily of increased liver and thyroid weights and some serum 
clinical chemistry changes. The NOAEL was 800 ppm (21.8 mg/kg bwt 
males; 22.1 mg/kg bwt females).
    Decreased body weights were seen in males in the mouse chronic 
study at doses of 400 ppm and above. Decreased female body weight was 
seen at doses of 2,000 ppm and above. The target organ in this study 
was the liver. In both the rat chronic and oncogenicity studies, the 
highest dose tested of 15,000 ppm exceeded a maximum tolerated dose 
(MTD) and was discontinued after 17 months. Effects observed at the 
next highest dose of 2,500 ppm primarily centered around the thyroid 
and liver.
    Overall, mild toxicity was observed with chronic exposure to BAS 
510 F. No evidence of treatment-induced oncogenicity was observed in 
the mouse or dog studies. A slight increase in thyroid follicular cell 
adenomas was seen in both sexes at the high dose when the data from 
both rat bioassays are combined.
    A mode of action (MOA) for the thyroid follicular cell adenomas has 
been proposed. This MOA is based on the EPA publication ``Assessment of 
Thyroid Follicular Cell Tumors,'' March 1998, EPA/630/R-97/002. This 
document describes the criteria, which must be met in order for a 
compound to be considered under the MOA described in that publication. 
BASF Corporation believes that BAS 510 F has met the cited criteria.
    Threshold effects. Based on a review of the available chronic 
toxicity data, BASF believes EPA will establish the Reference Dose 
(RfD) for BAS 510 F at 0.05 mg/kg/day. This RfD for BAS 510 F is based 
on the 2-year chronic and 2-year oncogenicity studies in rats with a 
threshold average NOAEL of 5 mg/kg/

[[Page 7547]]

day for males and females. Using an uncertainty factor of 100, the RfD 
is calculated to be 0.05 mg/kg/day. Based on the acute toxicity data, 
BASF believes that BAS 510 F does not pose any acute dietary risks.
    BAS 510 F was shown to be non-carcinogenic in mice and dogs. There 
was a slight increase in thyroid follicular cell adenomas at the high 
dose in both sexes in the rat. A threshold-based mode of action for 
these tumors based on the EPA publication ``Assessment of Thyroid 
Follicular Cell Tumors'' (EPA/630/R-97/002, March, 1998) has been 
proposed. BASF believes the data to support this proposed mode of 
action are strong, and that the thyroid tumors seen in the rat 
following BAS 510 F exposure have a threshold. In addition, a battery 
of genotoxicity studies demonstrated that BAS 510 F has no genotoxic or 
clastogenic potential. Therefore, BASF believes that the threshold 
approach to regulating BAS 510 F is appropriate. Also, it should be 
noted that, while the Agency has in the past considered tumors of this 
type to be potential human carcinogens, the European Union has 
published a policy which considers these tumor types, when they occur 
at low incidence rates in the rat, to not be relevant to man. The 
publication: ``European Commission, European Chemicals Bureau, ECBI/49/
99 Add. 1 Rev. 2; Draft Summary Record, Commission Group of Specialized 
Experts in the Fields of Carcinogenicity, Mutagenicity and 
Reprotoxicity, Meeting at Arona, 12 September 1999.'' Therefore, BASF 
believes that these tumors are not likely relevant to humans and, if 
these tumors are to be considered relevant to humans, the threshold 
approach to cancer risk assessment is appropriate.
    6. Animal metabolism. In the rat, the predominant route of 
excretion of BAS 510 F is fecal with urinary excretion being minor. The 
half-life of BAS 510 F is less than 24 hours. Saturation of absorption 
appears to be occurring at the high dose level. BAS 510 F is rapidly 
and intensively metabolised to a large number of biotransformation 
products. The hydroxylation of the diphenyl moiety was the 
quantitatively most important pathway. Second most important was the 
substitution of the Cl of the 2-chloropyridine part against SH by 
conjugation with glutathione. No major differences were observed with 
regard to label, sex, and dose level. In hens and goats the residues of 
concern were determined to be parent, the hydroxylated metabolite 
M510F01 (2-chloro-N-(4'chloro-5-hydroxy-biphenyl-2-yl)nicotinamide), 
and the glucuronic acid of the metabolite M510F02.
    7. Metabolite toxicology. No additional studies were required for 
metabolite toxicology.
    8. Endocrine disruption. No specific tests have been conducted with 
BAS 510 F to determine whether the chemical may have an effect in 
humans that is similar to an effect produced by a naturally occurring 
estrogen or other endocrine effects. However, there were no significant 
findings in other relevant toxicity studies (i.e., subchronic and 
chronic toxicity, teratology and multi-generation reproductive studies) 
which would suggest that BAS 510 F produces endocrine-related effects.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. A chronic dietary exposure analysis 
was conducted for BAS 510 F including crops which are target uses as 
well as inadvertent residues in rotational crops. The analysis assumed 
100% of the crops were treated, default processing factors (even though 
much lower experimentally-derived processing factors are available), 
and used the tolerance value for residues. Even with these worst-case 
assumptions, it was determined that the Theoretical Maximum Residue 
Contribution (TMRC) was only 30.1% of the RfD dose for the U.S. 
population and 62.5% for children 1-6 years (the highest exposed age-
related subpopulation). Based on the toxicology results, an acute 
dietary risk assessment for BAS 510 F is most likely not required, but 
if so only for children 1-6 years. For dietary exposure estimation, 
100% crop treated and tolerance values for residues were used. The 
resulting acute exposure prediction for children 1-6 years (the highest 
exposed age-related subpopulation) resulted in an acceptable 8.8% of 
the acute reference dose at the 95th percentile. If a more realistic 
scenario were used assuming percent crop treated and the range of 
residues, a much lower exposure would be obtained.
    ii. Drinking water. Estimates of ground water and surface water 
levels were determined using Screening Concentrations in Ground Water 
(SCI-GROW) and First Index Reservoir Screening Tools (FIRST) models, 
respectively. Using SCI-GROW to estimate chronic exposure to BAS 510 F 
from drinking water, drinking water consumption utilizes 0.15% of the 
RfD for the U.S. population and 0.044% for children ages 1-6. Using 
FIRST to estimate chronic exposure to BAS 510 F from drinking water, 
drinking water consumption utilizes 0.08% of the RfD for the U.S. 
population and 0.24% of the RfD for children ages 1-6.
    2. Non-dietary exposure. BAS 510 F is not currently planned for 
residential uses. Thus, residential exposure is not aggregated into the 
risk assessment.

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.'' BAS 510 F is a foliar fungicide 
chemically belonging to the carboxin class of fungicides. BAS 510 F 
acts in the fungal cell by inhibiting of mitochondrial respiration 
through inhibition of the succinate-ubiquinone oxidase reductase system 
in Complex II of the mitochondrial electron transport chain. BAS 510 F 
shares this mode of action with only one other currently registered 
U.S. pesticide carboxin. EPA is currently developing methodology to 
perform cumulative risk assessments. At this time, there is no 
available data to determine whether BAS 510 F has a common mechanism of 
toxicity with other substances or how to include this pesticide in a 
cumulative risk assessment. Unlike other pesticides for which EPA has 
followed a cumulative risk approach based on a common mechanism of 
toxicity, BAS 510 F does not appear to produce a toxic metabolite 
produced by other substances.

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 that aggregate exposure to BAS 
510 F will utilize 30.2% of the RfD for the US population. For the 
highest exposed age-related subpopulation (children 1-6 years), the 
maximum aggregate exposure is predicted to be 62.8% of the reference 
dose. BASF concludes that there is a reasonable certainty that no harm 
will result from the aggregate exposure to residues of BAS 510 F, 
including anticipated dietary and drinking water exposures and non-
occupational exposures.
    2. Developmental toxicity in the rat. A developmental study was 
conducted via oral gavage in rats with dosages of 0, 100, 300, and 
1,000 mg/kg bwt/day with a maternal and developmental no observed 
adverse effect level (NOAEL) of 1,000 mg/kg. No evidence of 
developmental toxicity was observed up to the highest dose tested.
    3. Developmental toxicity in the rabbit. A developmental study was

[[Page 7548]]

conducted via oral gavage in rabbits with dosages of 0, 100, 300, and 
1,000 mg/kg bwt/day. The NOAEL for maternal toxicity was 100 mg/kg bwt/
day and was 1,000 mg/kg/day for developmental toxicity. As noted above 
this NOAEL is based on fecal alterations and an abortion in a single 
dam at the next highest dose of 300 mg/kg/day. The dam which displayed 
the fecal alterations and abortion also displayed decreased body 
weight, body weight gain and food consumption - compared to the group 
mean - during gestation. These decreases occurred even prior to 
compound administration. These decreases in body weight, body weight 
gain, and food consumption, prior to compound administration, all 
indicate an animal in poor health and this poor state of health, rather 
than compound exposure, was likely the reason for the fecal alterations 
and abortion. No teratogenic effects were observed at any dose level.
    4. Reproductive toxicity. A 2-generation reproduction study in rats 
was conducted with dosages of 0, 12, 118, and 1,183 mg/kg bwt/day. No 
impairment of reproductive function was noted at any dose. The parental 
and developmental NOAEL are both 12 mg/kg/day. Mild effects in both the 
parents and pups were noted at 118 mg/kg/day and consisted of an 
increased incidence of hepatic centrilobular hypertrophy in parents 
and, in the pups, slightly decreased body weight and body weight gain 
(7%) in F2 generation only, and only in males. At 1,183 mg/kg/day 
paternal effects included decreased body weights and food consumption, 
increased liver weights and increased incidence of hepatic 
centrilobular hypertrophy and degeneration. Pup effects at this dose 
were an increase in pup mortality in the F2 only and a decreased body 
weight in F1 and F2.
    5. Reference dose. In all reproductive studies, the NOAELs for 
developmental effects were either equal to or higher than those for the 
parents. Therefore, BAS 510 F shows no selective toxicity for the 
young. In addition, there were no direct neurotoxicity effects noted in 
either the acute or subchronic neurotoxicity studies.
    Based on these results, no additional safety factors to protect 
children are warranted. Since the reproductive studies NOAELs are 
higher than the RfD calculated from the chronic rat study, BASF 
believes the RfD of 0.05 mg/kg/day is also appropriate to measure 
safety for infants and children. Therefore, the chronic population 
adjusted dose is also 0.05 mg/kg bwt/day.

F. International Tolerances

    A maximum residue level has not been established for BAS 510 F in 
any crop by the Codex Alimentarius Commission.

[FR Doc. 03-3694 Filed 2-13-03; 8:45 am]
BILLING CODE 6560-50-S