FR Doc 03-27955

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[Federal Register: November 6, 2003 (Volume 68, Number 215)]
[Notices]
[Page 62798-62807]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06no03-49]

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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: giles-parker.cynthia@epa.gov.

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 opp-docket@epa.gov,
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

[[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

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.

[[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]

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