[Federal Register Volume 68, Number 112 (Wednesday, June 11, 2003)]
[Notices]
[Pages 34950-34955]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-14328]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0194; FRL-7310-4]


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-2003-0194, must be 
received on or before July 11, 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:  Joanne I. Miller, Registration 
Division

[[Page 34951]]

(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW.,Washington, DC 20460; telephone number: 
(703) 305-6224; and 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 categories and entities may include, but are not 
limited to:
    [sbull] Crop production (NAICS 111)
    [sbull] Animal production (NAICS 112)
    [sbull] Food manufacturing (NAICS 311)
    [sbull] Pesticide manufacturing (NAICS 32532)
     This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

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

    1. EPA Docket. EPA has established an official public docket for 
this action under docket ID number OPP-2003-0194. The official public 
docket consists of the documents specifically referenced in this 
action, any public comments received, and other information related to 
this action. Although, a part of the official docket, the public docket 
does not include Confidential Business Information (CBI) or other 
information whose disclosure is restricted by statute. The official 
public docket is the collection of materials that is available for 
public viewing at the Public Information and Records Integrity Branch 
(PIRIB), Rm. 119, Crystal Mall 2, 1921 Jefferson Davis Hwy., 
Arlington, VA. This docket facility is open from 8:30 a.m. to 4 p.m., 
Monday through Friday, excluding legal holidays. The docket telephone 
number is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/.
     An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although, not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.
     Certain types of information will not be placed in the EPA 
dockets. Information claimed as CBI and other information whose 
disclosure is restricted by statute, which is not included in the 
official public docket, will not be available for public viewing in 
EPA's electronic public docket. EPA's policy is that copyrighted 
material will not be placed in EPA's electronic public docket but will 
be available only in printed, paper form in the official public docket. 
To the extent feasible, publicly available docket materials will be 
made available in EPA's electronic public docket. When a document is 
selected from the index list in EPA dockets, the system will identify 
whether the document is available for viewing in EPA's electronic 
public docket. Although, not all docket materials may be available 
electronically, you may still access any of the publicly available 
docket materials through the docket facility identified in Unit I.B. 
EPA intends to work towards providing electronic access to all of the 
publicly available docket materials through EPA's electronic public 
docket.
     For public commenters, it is important to note that EPA's policy 
is that public comments, whether submitted electronically or on 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-2003-0194. The system is an ``anonymous access'' system, which 
means EPA will not

[[Page 34952]]

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-2003-0194. 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-2003-0194.
    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-2003-0194. Such deliveries are only accepted during the 
docket's normal hours of operation as identified in Unit I.B.1.

D. How Should I Submit CBI to the Agency?

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

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

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

II. What Action is the Agency Taking?

     EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in FFDCA section 408(d)(2); however, 
EPA has not fully evaluated the sufficiency of the submitted data at 
this time or whether the data support granting of the petition. 
Additional data may be needed before EPA rules on the petition.

List of Subjects

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

     May 28, 2003.
Debra Edwards,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

     The petitioner's summary of the pesticide petition is printed 
below as required by FFDCA section 408(d)(3). The summary of the 
petition was prepared by BASF Corporation 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 3F6568

     EPA has received a pesticide petition (PP 3F6568) from BASF 
Corporation, P.O. Box 13528, Research Triangle Park, NC 27709 
proposing, pursuant to section 408(d) of the Federal Food, Drug, and 
Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by 
establishing a tolerance for residues of (3-(4,5-dihydro-isoxazol-3-
yl)-4-methanesulfonyl-2-methylphenyl)-(5-hydroxyl-1-methyl-1H-pyrazol-
4-yl)methanone in or on the raw agricultural commodities: Corn, field, 
forage; corn, field, grain; corn, field, stover; corn, pop, grain; 
corn, pop, stover; corn, sweet, forage; corn, sweet, kernal plus cob 
with husks removed; corn, sweet, stover; cattle, kidney; cattle, liver; 
goat, kidney; goat, liver; hog, kidney; hog, liver; horse, kidney; 
horse, liver; sheep, kidney; and sheep, liver at 0.05; 0.01; 0.05; 
0.01; 0.05; 0.05; 0.01; 0.05; 0.02; 0.70; 0.20; 0.70; 0.20; 0.70; 0.20; 
0.70; 0.20; and 0.70 parts per million (ppm), respectively. EPA has 
determined that the petition contains data or information regarding the 
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of BAS 670 H (3-(4,5-dihydro-
isoxazol-3-yl)-4-methanesulfonyl-2-methylphenyl)-(5-hydroxyl-1-methyl-
1H-pyrazol-4-yl)methanone) was determined in corn forage, stover and 
grain using 14C labeled materials applied to young corn 
plants at an exaggerated application rate of 0.134 lb active 
ingredient/acre. BAS 670 H and

[[Page 34953]]

one significant metabolite, M670H05, were found in low levels in the 
plant matrices with the majority of the radioactive residues 
incorporated into natural products. M670H05 resulted from oxidation of 
the carbonyl bridge to a carboxylic acid with concomitant loss and 
breakdown of the pyrazole ring. The significant metabolite M670H05 was 
found in the rat metabolism study.
    2. Analytical method. Suitable independently validated analytical 
methods (for crop and animal matrices) are submitted for detecting and 
measuring BAS 670 H levels in or on food with a limit of detection that 
is satisfactory for enforcing the requested tolerances. Residues are 
first extracted from the matrices by aqueous solvent then cleaned up by 
acid partitioning into organic solvent, then base partitioned, and 
quantified with application to high performance liquid chromatography 
with dual mass selective detectors (LC/MS/MS).
    3. Magnitude of residues. Field studies were conducted at 30 sites 
over 2 years with sites selected to fulfill both EPA and Canadian Pest 
Management Regulatory Agency (PMRA) requirements. The end product, BAS 
670 00H, was applied broadcast over corn plants in two applications at 
25 g active ingredient/ha (0.022 lb a.i./acre) + 75 g a.i./ha (0.067 lb 
a.i./acre) for a total of 100 g a.i./ha (0.089 lb a.i./acre) with the 
final application targeted for 45 days before milk stage. Samples of 
field corn were harvested at the milk stage to cover sweet corn harvest 
timing. All matrices were analyzed for parent and M670H05 with the 
limit of quantitation (LOQ) setting the proposed tolerances. No 
residues were detected above the LOQ in any of the corn RAC samples 
analyzed (fresh corn, forage, grain, and stover). To determine the fate 
of any BAS 670 residues in processed grain, the field study 
incorporated an exaggerated 5x application rate. No residues above LOQ 
were detected in the 5x treated grain samples; therefore, the analyses 
of the grain processed fractions was not required. The cow feeding 
study at three dosing levels show that food tolerances for parent in 
only kidney and liver matrices are necessary (and not for any other 
matrices such as meat, fat, and milk).

B. Toxicological Profile

    1. Acute toxicity--i. Oral (rat): (LD)50 = >2,000 
milligrams/kilogram body weight (mg/kg bwt) (male/female) = Category 
III.
    ii. Dermal (rat): (LD)50 = >2,000 mg/kg bwt (male/
female) = Category III.
    iii. Inhalation (rat): (LC)50 = >5.8 milligrams/per 
liter (mg/L) (male/female) = Category IV.
    iv. Primary eye irritation (rabbit): Slightly irritating = Category 
III.
    v. Primary dermal irritation (rabbit): Slightly irritating = 
Category III.
    vi. Dermal sensitization (guinea pig): Not a sensitizer.
    vii. Oral neurotoxicity (rat): NOAEL = 2,000 mg/kg bwt (male/
female).
    2. Genotoxicty. BAS 670 H was tested for its genotoxic potential in 
a battery of five in vitro or in vivo studies covering all required 
end-points (gene mutations, chromosomal and chromosome aberrations, and 
DNA damage and repair). Several batches of BAS 670 H have been tested 
over the time, from early laboratory produced material to current 
manufacturing process material. BAS 670 H did not demonstrate any 
genotoxic effects in vivo. In vitro, either batches tested for 
chromosomal aberrations caused a slight, significant clastogenic effect 
in the presence of S-9 mix, but the in vivo test for the equivalent 
end-point was negative. Three of the four batches tested in the 
bacterial reverse mutation assay were not mutagenic, but, the batch 
with the least purity displayed a weak mutagenic effect at the highest 
dose in Salmonella typhimurium TA98 in the absence of S-9 mix, most 
likely caused by impurities, which are not present in the current 
production batch. Overall, the weight of the evidence is that BAS 670 H 
is not genotoxic.
    3. Reproductive and developmental toxicity. The reproductive and 
developmental toxicity of BAS 670 H was investigated in a 2-generation 
rat reproduction study as well as in rat, mouse and several rabbit 
teratology studies (with different batches of BAS 670 H) and a rat 
developmental neurotoxicity study.
     There were no adverse effects on fertility of both genders and no 
effect on the reproductive performance of males in the two-generation 
study at any dose tested. There was, however, a high litter loss in 
F0 and F1 associated with insufficient maternal 
care at higher dose levels with clear maternal toxicity. General 
parental toxicity included eye and kidney effects, caused by elevated 
tyrosine levels due to hydroxyphenylpyruvate dioxygenase (HPPD) 
inhibition. The same organs were affected in subchronic and chronic 
feeding studies with rats. Pup effects were observed in the 
F1 and F2 generation including perinatal pup 
mortality and impaired body weight gain, the lower body weight effects 
were considered to lead to brain and spleen weight changes and delays 
in preputial separation. As observed in the parental animals, effects 
on eyes and kidneys were observed in the pups. Renal pelvis dilation 
was observed at lower doses, although, there was no overt maternal 
toxicity, significantly elevated tyrosine levels were observed in the 
dams and pups. The no observed adverse effect level (NOAEL) for 
fertility (F0 and F1, both genders) was 4,000 ppm 
(about 450 mg/kg bwt/day); the NOAEL for reproductive performance was 
40 ppm (about 4 mg/kg body weight/day) for the F1 females. 
The NOAEL for general toxicity was 4 ppm (about 0.4 mg/kg bwt/day). The 
NOAEL for developmental toxicity (growth and development of the 
offspring) was 4 ppm (about 0.4 mg/kg body weight/day) for the 
F1 pups, but was lower than 4 ppm for the F2 pups 
due to renal pelvis dilations at all dose levels.
     Developmental neurotoxicity was not observed at any dose in the 
developmental neurotoxicity study. At all dose levels, eye effects due 
to elevated tyrosine levels were found in dams and pups. Additionally, 
there were decreased body weights in the dams at the high and mid dose, 
but there were no indications of adverse effects on reproductive 
performance of the parental females. In pups of both genders, decreased 
preweaning and postweaning body weight gains and body weights were 
observed at the low dose level and above. This is an indicator of a 
retardation of the general physical development, which is considered to 
be responsible for a slight delay of maturation. The NOAEL for 
developmental neurotoxicity was 800 mg/kg bwt/day (highest dose 
tested). There is no NOAEL for the eye lesions and reduced body weight 
gain of the pups. NOAELs for these effects were determined in prenatal 
development studies in rats, rabbits and mice.
     No developmental toxicity was noted in the mouse prenatal 
development study. In the prenatal development study in rats no 
teratogenic effect was observed, but there was maternal toxicity 
together with skeletal variations in the pups. The same skeletal 
variation (i.e. supernumerary ribs) was also found in rabbit prenatal 
development studies. This effect is associated with the family of HPPD 
inhibiting substances. In addition, several rabbits had pups with a 
soft tissue malformation: unilateral kidney agenesis. The NOAEL for the 
skeletal variations and the kidney agenesis was 0.5 mg/kg bwt/day, the 
NOAEL for overt maternal toxicity was 50 mg/kg bwt/day. The 
developmental effects in rabbits occurred at dose-levels below overt 
maternal toxicity; however, measured tyrosine blood levels in the

[[Page 34954]]

dams were substantially elevated at these dose levels. Elevated 
tyrosine levels are known to cause kidney toxicity.
    4. Subchronic toxicity. The subchronic toxicity of BAS 670 H was 
investigated in 90-day feeding studies in rats, mice and dogs, and in a 
28-day dermal administration study in rats. Several supplemental short-
term mechanistic studies in rats and mice were performed to elucidate 
the mode of action. Generally, very mild toxicity was observed in mice 
and dogs at high doses. In a combined neurotoxicity 90-day feeding 
study in rats, no signs of neurotoxicity were observed. Effects were 
seen in the pancreas, eye, kidney, liver, and thyroid gland. The target 
organs are identical with those in the chronic feeding studies with 
rats.
     Two modes of action have been elucidated for BAS 670 H by short-
term mechanistic studies, one leading to effects on eyes, kidney and 
liver, and a second leading to effects at the thyroid: BAS 670 H causes 
elevated tyrosine levels by HPPD inhibition accounting for effects on 
eye, liver and kidney. The mouse is the accepted model for this 
tyrosine level elevations, and a NOAEL of 1.2 mg/kg bwt/day was 
established for tyrosine elevation in mice. Other mechanistic studies 
demonstrated an impairment of pituitary-thyroid hormone levels by 
enhancing the hepatic clearance of thyroid hormones. The NOAEL for 
interference with thyroid hormones was 0.4 mg/kg bwt/day. The NOAEL for 
effects on the exocrine pancreas in rats was 1.1 mg/kg/bwt/day. Similar 
effects were seen in the 28-day dermal study with rats; the NOAEL was 
100 mg/kg bwt/day.
    5. Chronic toxicity. The chronic toxicity and oncogenicity studies 
with BAS 670 H include two 12-month feeding studies with dogs, an 18-
month mouse feeding study, a 12-month rat chronic feeding study and a 
24-month rat oncogenicity study. In the chronic dog study, mild 
reductions of the body weight were observed at high doses. The NOAEL 
was 100 ppm (2.9 and 3.1 mg/kg bwt/day in males and females 
respectively).
     In the 18-month chronic feeding study in mice, increased liver 
weights were seen at high doses. The NOAEL was 80 ppm (19 and 26 mg/kg 
bwt/day in males and females respectively). BAS 670 H was not 
carcinogenic to mice. In the chronic feeding studies in rats, the main 
target organs were eye, liver, kidney, thyroid gland, and pancreas. The 
same organs were affected in the subchronic studies. Short-term 
mechanistic studies demonstrated that BAS 670 H causes elevated 
tyrosine levels by HPPD inhibition accounting for effects on the eye, 
liver and kidney. The mouse is the accepted model for this tyrosine 
level elevation, and a NOAEL of 1.2 mg/kg bwt/day was established for 
tyrosine elevation in mice. The NOAEL for effects on the exocrine 
pancreas in rats 6 ppm in both genders (0.4 and 0.5 mg/kg bwt/day in 
males and females respectively). At the end of the 24-month 
oncogenicity study, there was a slight but significant increase in 
benign thyroid adenomas in both genders. The thyroid was the only organ 
affected and the increase of the adenomas was significant only at the 
highest dose tested, while considerable general toxicity was already 
seen at 20-times lower doses. The mechanism of thyroid tumor formation 
by BAS 670 H was thoroughly investigated in short-term mechanistic 
studies. An enhanced hepatic clearance of thyroid hormones impairs 
pituitary-thyroid hormone levels leading to hypertrophy, hyperplasia 
and ultimately neoplasia. There is general agreement, that this 
mechanism is well understood in rodents and is of minor relevance to 
humans. A clear NOAEL of 0.4 mg/kg bwt/day was demonstrated for effects 
on thyroid hormone levels. A threshold (non-linear) cancer assessment 
is proposed and a cancer classification as ``not likely to be a human 
carcinogen.''
    6. Animal metabolism. In the rat metabolism studies, the majority 
of the residue was excreted within 48 hours from both males and 
females. In all matrices investigated unchanged parent is the main 
component. Degradation starts with hydroxylation of the oxazole ring. 
The identified metabolites from both pyrazole ring label and phenyl 
ring label studies are reported. Goat and hen metabolism studies were 
conducted with feeding levels of about 10 ppm. In the goat, the 
majority of the applied dose was excreted. Non-metabolized BAS 670H was 
the major radioactive residue, and M670H02, formed from hydroxylation 
at the 4-position of the isoxazole ring, was the only significant 
metabolite formed. In poultry BAS 670 F was also rapidly excreted. 
Residues in liver consisted mainly of BAS 670H, and the only 
significant metabolite in poultry was again M670H02. The significant 
metabolite M670H02 was found in the rat metabolism study.
    7. Metabolite toxicology. Toxicity of the metabolites of BAS 670 H 
with potential exposure to humans was concurrently evaluated during 
toxicity testing of the parent, because both plant and animal 
metabolites are formed during the course of toxicity testing. Both 
plant and animal metabolites are considered not of toxicological 
concern. Some testing was conducted on the anaerobic aquatic 
metabolite, 670M10. The results as given below show no toxicological 
concern:
    [sbull] Bacterial reverse mutation test (Ames): No effect = 
negative.
    [sbull] Mammalian somatic cell gene mutation test (MNT): No effect 
= negative.
    [sbull] Cytogenetic study in vivo (mouse HPRT): No effect = 
negative.
    [sbull] 28-Day feeding study (rat): NOAEL 1,197 mg/kg bwt/day and 
1,304 mg/kg bwt/day (male and female, respectively).
    8. Endocrine disruption. BAS 670 H has been shown to alter thyroid 
hormone levels in rats as also observed with other 4-
hydroxyphenylpyruvate dioxygenase enzyme inhibitor active ingredients. 
However, there have been no effects noted on sexual or other hormones 
in numerous subchronic and chronic toxicity studies with multiple 
species.

C. Aggregate Exposure

    1. Dietary exposure. A chronic population adjusted dose (cPAD) of 
0.00044 mg/kg/day is proposed. This cPAD is based on a lowest observed 
adverse effect level (LOAEL) of 0.4 mg/kg/day for pup renal pelvis 
dilation in the 2-generation rat reproduction study with an extra 3X 
uncertainty factor for using the LOAEL (rather than a NOAEL) plus a 3X 
Food Quality Protection Act (FQPA) factor on top of the standard 100X 
uncertainty factor. So the total uncertainty factor is 900 (3 x 3 x 
100), and the cPAD is calculated as 0.4/900 = 0.00044.
     An acute dietary population adjusted dose (aPAD) is proposed as 
0.0013 mg/kg/day. This aPAD is based upon a NOAEL of 0.4 mg/kg/day 
obtained in the rat thyroid hormone study and a 3X FQPA uncertainty 
factor on top of the standard 100 (0.4/300 = 0.0013).
     BAS 670 H has been shown to be non-carcinogenic in mice, but was 
associated with an increase in thyroid follicular cell tumors at high 
doses in the rat. These tumors have been shown to develop by a non-
genotoxic mode of action, in fact they were the consequence of induced 
changes of thyroid hormone levels. Therefore BAS 670 H should be 
classified as ``not likely to be a human carcinogen.''
    i. Food. Exposure estimates were compared against the cPAD and aPAD 
of 0.0013 mg/kg bwt/day and 0.004 mg/kg bwt/day, respectively. Results 
of the chronic dietary exposure assessments demonstrated that even with 
the worst-case assumptions (residues at tolerance level and 100% crop 
treated), the estimated chronic dietary exposure was

[[Page 34955]]

less than 12.5% of the cPAD for the total U.S. population and all the 
subpopulations. The greatest exposure occurred in infants and children. 
Exposure estimates for the acute dietary assessment were well under 
100% of the acute population adjusted dose (aPAD) at the 
99th percentile. The overall U.S. population and the highest 
exposed subpopulation (infants <1 year) utilized only 5.3% and less 
than 21%, respectively.
    ii. Drinking water. There are no established maximum contaminant 
levels or health advisory levels for residues of BAS 670 H or its 
metabolites in drinking water. A tier 1 drinking water modeling 
assessment for BAS 670 H using the FIRST model (for surface water) and 
SCI-GROW (for ground water) produced estimated maximum concentrations 
of 0.22 parts per billion (ppb) (chronic) for surface water and 0.20 
ppb for ground water. These estimated concentrations are less than a 
worst case calculated acceptable level of 3.95 ppb children chronic 
drinking water levels of concern (DWLOC) for residues in drinking water 
based on chronic aggregate exposure. Therefore, taking into account all 
uses and exposures one concludes, with reasonable certainty that 
residues of BAS 670 H in drinking water will not result in unacceptable 
levels of aggregate human health risk at this time.
    2. Non-dietary exposure. There are no registered or proposed 
residential uses for BAS 670 H.

D. Cumulative Effects

     At this time, there is no available information to indicate that 
BAS 670 H or its metabolites have a common mechanism of toxicity with 
other substances. Therefore, there is no reason to include this 
pesticide or its metabolites in a cumulative risk assessment. For the 
purposes of this tolerance action, EPA has not assumed that BAS 670 H 
and its metabolites have a common mechanism of toxicity with other 
substances.

E. Safety Determination

    1. U.S. population. Aggregate exposure to the overall U.S. 
population utilized only 8.7% of the aPAD and 12.7% of the cPAD, 
respectively. Therefore, no harm to the overall U.S. population would 
result from the use of BAS 670 H on field, sweet, or pop corn.
    2. Infants and children. There is a complete toxicity base for BAS 
670 H and exposure data are complete or are estimated based on data 
that reasonably accounts for potential exposures. Taking into account 
the completeness of the data base, BASF Corporation concludes that the 
FQPA safety factor should be retained but reduced to 3X. This is based 
on the occurrence of kidney malformations in rabbits and skeletal 
variations in rabbits and rats, all occurring at doses, which caused 
either maternal tyrosine elevations or other evidence of maternal 
toxicity. The full toxicological data base that has been developed for 
BAS 670 H includes many additional mechanistic studies, revealing 
consistency and the mode of action of these effects. The kidney was a 
target organ in all repeated dose studies and these effects were caused 
by elevated tyrosine levels due to inhibition of the HPPD enzyme. Using 
the standard worst case exposure assumptions (residues at tolerance 
level and 100% crop treated), aggregate exposure to BAS 670 H from food 
and water will utilize 33% and less than 24% of the aPAD and cPAD, 
respectively for infants and children. EPA generally has no concern for 
exposures below 100% of the PAD because it represents the level at or 
below which daily aggregate exposure over a lifetime will not pose 
appreciable risks to human health. BASF Corporation concludes that 
there is a reasonable certainty that no harm will result to infants or 
children from aggregate exposure to BAS 670 H residues with the 
approval of this tolerance petition.

F. International Tolerances

     No maximum residue levels (MRLs) have been established for BAS 670 
H by the CODEX Alimentarius Commission or in Mexico.
[FR Doc. 03-14328 Filed 6-10-03; 8:45 am]
BILLING CODE 6560-50-S