[Federal Register Volume 68, Number 215 (Thursday, November 6, 2003)]
[Notices]
[Pages 62798-62807]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-27955]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0208; FRL-7321-1]


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 regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket ID number OPP-2003-0208, must be 
received on or before December 8, 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: Cynthia Giles-Parker, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-7740; 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 Code 111)
    [sbull] Animal Production (NAICS Code 112)
    [sbull] Food Manufacturing (NAICS Code 311)
    [sbull] Pesticide Manufacturing (NAICS Code 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-2003-0208. 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

[[Page 62799]]

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, EPA may not be able to consider your comment.
    i. EPA Dockets. Your use of EPA's electronic public docket to 
submit comments to EPA electronically is EPA's preferred method for 
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket, and follow the online instructions for submitting comments. 
Once in the system, select ``search,'' and then key in docket ID number 
OPP-2003-0208. The system is an`` anonymous access'' system, which 
means EPA will not know your identity, e-mail address, or other contact 
information unless you provide it in the body of your comment.
    ii. E-mail. Comments may be sent by e-mail to [email protected], 
Attention: Docket ID Number OPP-2003-0208. In contrast to EPA's 
electronic public docket, EPA's e-mail system is not an ``anonymous 
access'' system. If you send an e-mail comment directly to the docket 
without going through EPA's electronic public docket, EPA's e-mail 
system automatically captures your e-mail address. E-mail addresses 
that are automatically captured by EPA's e-mail system are included as 
part of the comment that is placed in the official public docket, and 
made available in EPA's electronic public docket.
    iii. Disk or CD ROM. You may submit comments on a disk or CD ROM 
that you mail to the mailing address identified in Unit I.C.2. These 
electronic submissions will be accepted in WordPerfect or ASCII file 
format. Avoid the use of special characters and any form of encryption.
    2. By mail. Send your comments to: Public Information and Records 
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2003-0208.
    3. By hand delivery or courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Office of Pesticide 
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall 
2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket 
ID Number OPP-2003-0208. 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

[[Page 62800]]

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:October 23, 2003.
Debra Edwards,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by FFDCA section 408(d)(3). The summary of the petition was 
prepared by the petitioner and represents the view of the petitioner. 
The petition summary announces the availability of a description of the 
analytical methods available to EPA for the detection and measurement 
of the pesticide chemical residues or an explanation of why no such 
method is needed.

BASF Corporation

PP 2F6434 and 3F6580

    EPA has received pesticide petitions (PP 2F6434 and 3F6580) from 
BASF Corporation, Research Triangle Park, NC, 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 tolerances for 
residues of Boscalid (3-pyridinecarboxamide, 2-chloro-N-(4'-
chloro(1,1'-biphenyl)-2-yl) in or on the following raw agricultural and 
processed commodities: pome fruit at 3.0 ppm; apple pomace at 20.0 ppm 
and hops at 35.0 ppm, and soybean aspirated grain fraction at 2.5 ppm. 
EPA has determined that the petitions contain 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.
    These individual summaries are printed below as they were received 
from the petitioner.

PP 2F6434

A. Residue Chemistry

    1. Plant metabolism. Nature of the residue studies (OPPTS 
Harmonized Guidline 860.1300) were conducted in grapes, lettuce and 
beans as representative crops in order to characterize the fate of 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 clean up. Quantitation is by gas 
chromatography using 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 clean-up. The parent and acetylated metabolite are 
quantitated by gas chromatography with electron capture detection.
    3. Magnitude of the residues. Field trials were carried out in 
order to determine the magnitude of the residue in the apples, pears 
and hops. Field trials were conducted in the United States 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, a processing study 
was conducted on apples to determine concentration factors during 
normal processing of the raw agricultural commodity into the processed 
commodities.

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 wettable granule (WG) termed BAS 510 02 F containing 70% 
BAS 510 F and a wettable 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 category III, acute 
inhalation of category IV, eye irritation of category III, skin 
irritation of category IV, and is not a dermal sensitizer. BAS 516 02 F 
has an acute oral toxicity category of III, acute dermal of category 
III, acute inhalation of category IV, eye irritation of category III, 
skin irritation of category IV, and is not a dermal sensitizer.

[[Page 62801]]

    2. Genotoxicity. Ames Test (1 Study; point mutation): Negative; In 
Vitro CHO/HGPRT Locus Mammalian Cell Mutation Assay (1 Study; point 
mutation): Negative; In Vitro V79 Cell Cytogenetic Assay (1 Study; 
Chromosome Damage): Negative; In Vivo Mouse Micronucleus (1 Study; 
Chromosome Damage): Negative; In Vitro Rat Hepatocyte (1 Study; DNA 
damage and repair): Negative. BAS 510 F has been tested in a total of 5 
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 two-
generation rat reproduction study as well as in rat and rabbit 
teratology studies.
    There were no adverse effects on reproduction in the two-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 bodyweight 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 NOAEL's are both 100 ppm 
(12 mg/kg/day).
    No teratogenic effects were noted in either the rat or rabbit 
developmental studies. In the rat study, evidence of maternal or 
developmental toxicity were not observed at any dose (highest dose 
tested of 1,000 mg/kg/day). Neither a maternal nor developmental 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 milligrams/kilogram of body weight (mg/kg bw) 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 less than or equal to 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 bw 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 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 post natal 
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 multigeneration study, 
resulted in an increased incidence of hepatic centrilobular hypertrophy 
- a parameter which could not have been detected in the developmental 
neurotoxicity (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, or 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

[[Page 62802]]

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 bw males; 
22.1 mg/kg bw 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.
    6. Threshold effects. Based on a review of the available chronic 
toxicity data, BASF believes EPA will establish the 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 NOEL of 5 mg/kg/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 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 ademonas at the high 
dose in both sexes in the rat. A threshold-based MOA 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 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, 1 - 
2 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.
    7. Animal metabolism. In the rat, the predominat 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 metabolized 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. In 
hens and goats the residues of concern were determined to be parent, 
the hydroxylated metabolite M510 F01 (2-chloro-N-(4'chloro-5-hydroxy-
biphenyl-2-yl)nicotinamide), and the glucuronic acid of the metabolite 
M510 F02.
    8. Metabolite toxicology. No additional studies were required for 
metabolite toxicology.
    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 to include the proposed uses of apples and 
hops. The dietary exposure included prior tolerances for beet root, 
root vegetables, tuberous and corm vegetables, bulb vegetables, leafy 
vegetables, head and stem brassica, leafy brassica greens, legume 
vegetables, fruiting vegetables, cucurbit vegetables, stonefruit, 
berries, tree nuts, pistachios, cereal grains, mint, grapes, raisins, 
strawberries, peanut, peanut meal, peanut oil, cotton seed, soybean 
seed, canola, flax seed and sunflower seed in addition to the new 
tolerances for apples and hops. 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. The one exception to the use of defaults 
was for the apple processing, where an average calculated processing 
factor of 0.09 was used for apple juice. For apple juice concentrate, 
the juice factor of 0.09 was adjusted by the ratio of the default 
concentrate (3.9) and default juice (1.3) processing factors, which led 
to an estimated processing factor of 0.27 for apple juice concentrate. 
Even with these worst-case assumptions, it was determined that the 
Theoretical Maximum Residue Contribution (TMRC) was only 34.0% of the 
reference dose for the U.S. population and 77.1% 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 non-
nursing infants <1 year old. For dietary exposure estimation, 100% crop 
treated and tolerance values for residues were used. The resulting 
acute exposure prediction for non-nursing infants (the highest exposed 
age-related subpopulation) resulted in an acceptable 10.6% 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 and surface water levels 
were determined using SCIGROW and FIRST models, respectively. The 
drinking water level of concerns (DWLOCs) for chronic exposure are 
obtained by subtracting the chronic dietary food. This is outlined in 
the following table.

[[Page 62803]]



     Percentages of Reference Dose for Chronic Exposure to BAS 510 F
------------------------------------------------------------------------
                                                    U.S.
                                                 Population  Children 1-
                                                 (% of RfD)    6 (% of
-----------------------------------------------------------------RfD)---
Chronic dietary exposure                               34.0         77.1
------------------------------------------------------------------------
Remainder of RfD available for water (%)               66.0         22.9
 (Drinking Water Level of Concern)
------------------------------------------------------------------------
SCIGROW ground water estimation\1\                    0.015        0.044
------------------------------------------------------------------------
FIRST surface water estimation1                        0.08         0.24
------------------------------------------------------------------------
Total of RfD used by diet and water                    34.1        77.4
------------------------------------------------------------------------
\1\ Used highest values predicted from the model for all agricultural
  uses; assumes 2L/day and 60 kg for adult; 1L/day and 10 kg for child

    Overall, using worst-case parameters the predicted aggregate 
exposure by all potential routes for both adults and children is less 
than the chronic reference dose.
    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 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.
    The 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 34.1% of the RfD for the U.S. population. For the 
highest exposed age-related subpopulation (children 1-6 years), the 
maximum aggregate exposure is predicted to be 77.4% 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. Infants and children--i. 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 bw/day with a maternal and developmental 
No-Adverse-Effect Level (NOAEL) of 1,000 mg/kg. No evidence of 
developmental toxicity was observed up to the highest dose tested.
    ii. Developmental toxicity in the rabbit. A developmental study was 
conducted via oral gavage in rabbits with dosages of 0, 100, 300 and 
1,000 mg/kg bw/day. The NOAEL for maternal toxicity was 100 mg/kg bw/
day and was 1,000 mg/kg/day for developmental toxicity. As noted above 
in section B.3. (Reproductive and developmental toxicity), 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.
    iii. Reproductive toxicity. A two-generation reproduction study in 
rats was conducted with dosages of 0, 12, 118, and 1,183 mg/kg bw/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.
    iv. Reference dose. In all reproductive studies, the NOAEL's 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 NOAEL's are 
higher than the RfD calculated from the chronic rat study, BASF 
believes the Reference Dose of 0.05 mg/kg/day is also appropriate to 
measure safety for infants and children. Therefore, the chronic 
Population Adjusted Dose (cPAD) is also 0.05 mg/kg bw/day.

F. International Tolerances

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

PP 3F6580

A. Residue Chemistry

    1. Plant metabolism. Nature of the residue studies (OPPTS 
Harmonized

[[Page 62804]]

Guideline 860.1300) were conducted in grapes, lettuce and beans as 
representative crops in order to characterize the fate of Boscalid (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 clean up. Quantitation is by GC/MS. 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 clean-up. The parent and 
acetylated metabolite are quantitated by GC/ECD.
    3. Magnitude of the residues. Field trials were carried out in 
order to determine the magnitude of the residue in soybean and soybean 
aspirated grain fraction. 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. In addition, a processing study 
was conducted on the soybean to determine concentration factors. Tier 
III field rotational crop studies were conducted to support rotational 
crop tolerances for soybean.

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 02F 
containing 70% BAS 510 F and a Water Dispersible Granule (WG) termed 
BAS 516 02F containing a 2:1 mixture of BAS 510 F and BAS 500F. BAS 510 
02F 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 02F 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 (1 Study; point mutation): Negative; In 
Vitro CHO/HGPRT Locus Mammalian Cell Mutation Assay (1 Study; point 
mutation): Negative; In Vitro V79 Cell Cytogenetic Assay (1 Study; 
Chromosome Damage): Negative; In Vivo Mouse Micronucleus (1 Study; 
Chromosome Damage): Negative; In Vitro Rat Hepatocyte (1 Study; DNA 
damage and repair): Negative. BAS 510 F has been tested in a total of 5 
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 two-
generation rat reproduction study as well as in rat and rabbit 
teratology studies.
    There were no adverse effects on reproduction in the two-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 bodyweight 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 NOAEL's are both 100 ppm 
(12 mg/kg/day).
    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 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 bw 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 1 to 12, this dam had food consumption values, which were 
less than half the mean for the group (compound administration began on 
day GD 7) From gestation day 13 to 26 (when the animal aborted and was 
sacrificed) this dam ate essentially nothing (food consumption during 
this time period was less than or equal to 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 bw 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 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 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 
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 F resulted in maternal toxicity. A dose 
of 118 mg/kg/day in female rats of the same strain in the

[[Page 62805]]

multigeneration 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, or 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, or 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-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 bw males; 
22.1 mg/kg bw 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 2000 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.
    6. 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 NOEL of 5 mg/kg/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 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 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, 1 - 2 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.
    7. 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 metabolized 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 M510 F01 (2-chloro-N-(4'chloro-5-
hydroxy-biphenyl-2-yl)nicotinamide), and the glucuronic acid of the 
metabolite M510 F02.
    8. Metabolite toxicology. No additional studies were required for 
metabolite toxicology.
    9. 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

[[Page 62806]]

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 reference 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 and surface water levels 
were determined using SCIGROW and FIRST models, respectively. The 
drinking water level of concerns (DWLOCs) for chronic exposure is 
obtained by subtracting the chronic dietary food. This is outlined in 
the following table.

     Percentages of Reference Dose for Chronic Exposure to BAS 510 F
------------------------------------------------------------------------
                                     U.S. Population    Children 1-6 (%
                                        (% of RfD)          of RfD)
------------------------------------------------------------------------
Chronic dietary exposure                         30.1               62.5
------------------------------------------------------------------------
Remainder of RfD available for                   69.9               37.5
 water (%) (Drinking Water Level
 of Concern)
------------------------------------------------------------------------
SCIGROW ground water estimation\1\             0.015%             0.044%
------------------------------------------------------------------------
FIRST surface water estimation\1\               0.08%              0.24%
------------------------------------------------------------------------
Total of RfD used by diet and                   30.2%             62.8%
 water
------------------------------------------------------------------------
\1\ Used highest values predicted from the model for all agricultural
  uses; assumes 2L/day and 60 kg for adult; 1L/day and 10 kg for child

    Overall, using worst-case parameters the predicted aggregate 
exposure by all potential routes for both adults and children is less 
than the chronic reference dose.
    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 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.
    The 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 U.S. 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. Infants and children--i. 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 bw/day with a maternal and developmental 
No-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 
conducted via oral gavage in rabbits with dosages of 0, 100, 300 and 
1,000 mg/kg bw/day. The NOAEL for maternal toxicity was 100 mg/kg bw/
day and was 1,000 mg/kg/day for developmental toxicity. As noted above 
in section 3.0, 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.
    i. Reproductive toxicity. A two-generation reproduction study in 
rats was conducted with dosages of 0, 12, 118, and 1,183 mg/kg bw/day. 
No

[[Page 62807]]

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 
decreased body weight in F1 and F2.
    ii. Reference dose. In all reproductive studies, the NOAEL's 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 NOAEL's are 
higher than the RfD calculated from the chronic rat study, BASF 
believes the Reference Dose of 0.05 mg/kg/day is also appropriate to 
measure safety for infants and children. Therefore, the chronic 
Population Adjusted Dose (cPAD) is also 0.05 mg/kg bw/day.

F. International Tolerances

    A maximum residue level (MRL) has not been established for BAS 510 
F in any crop by the Codex Alimentarius Commission.
[FR Doc. 03-27955 Filed 11-5-03; 8:45 am]
BILLING CODE 6560-50-P