Metconazole; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food, 18008-18012 [05-7064]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 70, Number 67 (Friday, April 8, 2005)]
[Notices]
[Pages 18008-18012]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-7064]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2005-0016; FRL-7703-7]


Metconazole; Notice of Filing a Pesticide Petition to Establish a 
Tolerance for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket identification (ID) number OPP-
2005-0016, must be received on or before May 9, 2005.

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:  Mary Waller, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-9354; e-mail address: waller.mary@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:
     Crop production (NAICS 111)
     Animal production (NAICS 112)
     Food manufacturing (NAICS 311)
     Pesticide manufacturing (NAICS 32532)
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

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

    1. Docket. EPA has established an official public docket for this 
action under docket ID number OPP-2005-0016. 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, 1801 S. Bell St., Arlington, VA. This docket 
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The docket telephone number is (703) 305-
5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at https://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 https://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.1. 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

[[Page 18009]]

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 https://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-2005-0016. 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-2005-0016. 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-2005-0016.
    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, 1801 S. Bell St., Arlington, VA, Attention: Docket ID 
Number OPP-2005-0016. 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.

[[Page 18010]]

List of Subjects

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


    Dated: March 28, 2005.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

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

Kureha Chemical Industry Co., Ltd

PP 9E5052

    EPA has received a pesticide petition (PP 9E5052) from Kureha 
Chemical Industry Co., Ltd, c/o Company Agent, BASF Corporation, P.O. 
Box 13528, Research Triangle Park, NC, 27704-3528 proposing pursuant to 
section 408(d) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. 
346a(d), to amend 40 CFR part 180 by establishing a tolerance for 
residues of metconazole in or on the raw agricultural commodity bananas 
at 0.05 parts per million. EPA has determined that the petition 
contains data or information regarding the elements set forth in 
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated 
the sufficiency of the submitted data at this time or whether the data 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1.Plant metabolism. The qualitative nature of the residues of 
metconazole in bananas is adequately understood. The metabolism of 
metconazole in bananas is characterized by a significant amount 
(greater than 85%) of unchanged parent compound. In addition to the 
parent compound, many other minor residue components (each less than 2% 
of the total recovered radioactivity in the whole fruit) were detected. 
Metconazole is the only residue of toxicological concern in bananas.
    2.Analytical method. A practical analytical method for detecting 
and measuring the level of metconazole residues in whole bananas and 
banana pulp is submitted to EPA with this petition. Quantitation of 
residues of metconazole in bananas is by gas chromatography with a 
nitrogen-phosphorus detector. This independently validated method is 
appropriate for the enforcement purposes of this petition.
    3.Magnitude of residues. Residue field trials were conducted in 
representative countries exporting the commodities of this petition to 
the United States. Twelve field trials were conducted with bagged and 
unbagged bananas, with three sites located in each of four countries, 
Ecuador, Honduras, Costa Rica, and Mexico. The residue values reported 
from these field trials were all less than the proposed tolerance of 
0.05 ppm for whole bananas. No processing study is included with this 
petition as bananas have no processed commodities according to the EPA 
Residue Chemistry Test Guidelines.

B. Toxicological Profile

    A complete, valid and reliable database of mammalian and genetic 
toxicology studies supports the proposed tolerance for metconazole on 
bananas. Two geometric isomers of metconazole exist, with the 
fungicidal activity being associated primarily with the cis isomer. The 
technical material that is manufactured for use on bananas is a mixture 
of cis and trans isomers in an 85 to 15 ratio (85:15). Toxicology 
studies submitted in support of this petition were conducted on the 
technical material composed of either the 85:15 isomer mixture (AC 
900768) or a more purified (greater than 95%) sample of the cis isomer 
(WL 136184).
    1.Acute toxicity. AC 900768 technical is considered to be slightly 
toxic (Toxicity Category III) to the rat by the oral route of exposure. 
In an acute oral study in rats, the LD50 value of AC 900768 
technical was 727 milligrams per kilogram of body weight (mg/kg b.w.) 
for males and 595 mg/kg b.w. for females. The oral LD50 for 
combined sexes was 660 mg/kg b.w. An oral LD50 study in rats 
conducted with WL 136184 technical also supports the classification of 
metconazole as slightly toxic by the oral route of exposure. The oral 
LD50 values of WL 136184 technical were 1,626 mg/kg b.w. for 
males and 1,312 mg/kg b.w. for females, with an LD50 value 
for combined sexes of 1,459 mg/kg b.w. Since this petition is for an 
import tolerance, anticipated exposure is only via the oral route. As 
such, oral toxicity data sufficiently assess risk of acute exposure.
    2.Genotoxicty. AC 900768 technical (the 85:15 isomer mixture) and 
WL 136184 technical (greater than 95% cis isomer) were tested in an 
extensive battery of in vitro and in vivo genotoxicity assays measuring 
several different endpoints of potential genotoxicity. Collective 
results from these studies indicate that metconazole does not pose a 
genotoxic risk, and therefore, is not likely to be a genotoxic 
carcinogen.
    3.Reproductive and developmental toxicity. Developmental toxicity 
studies in rats conducted with AC 900768 technical and WL 136184 
technical showed no evidence of teratogenic effects in fetuses, and no 
evidence of developmental toxicity in the absence of maternal toxicity. 
Thus, metconazole is neither a selective developmental toxicant nor a 
teratogen in the rat. In the rat developmental toxicity study with AC 
900768 technical, the no-observable-adverse-effect-level (NOAEL) for 
maternal toxicity was 12 mg/kg b.w./day, based on decreased body weight 
gain at 30 mg/kg b.w./day, the next highest dose tested, and the NOAEL 
for developmental toxicity was also 12 mg/kg b.w./day, based on 
decreased fetal body weights and an increased incidence of skeletal 
ossification variations at 30 mg/kg b.w./day. In the rat developmental 
toxicity study conducted with WL 136184 technical, the NOAEL for 
maternal toxicity was 24 mg/kg b.w./day based on decreased body weight 
gain at 60 mg/kg b.w./day, the highest dose tested, and the NOAEL for 
developmental toxicity was also 24 mg/kg b.w./day, based on an increase 
in the total number of resorptions, reductions in fetal body weights 
and an increased incidence of skeletal ossification variations at 60 
mg/kg b.w./day.
    Results from a developmental toxicity study in rabbits with AC 
900768 also indicated no evidence of teratogenicity or developmental 
toxicity in the absence of maternal toxicity. Thus, metconazole 
technical is neither a selective developmental toxicant nor a teratogen 
in the rabbit. In this rabbit developmental study, the NOAEL for 
maternal toxicity was 20 mg/kg b.w./day based on decreased food 
consumption and body weight gain, reductions in hemoglobin, hematocrit 
and corpuscular volume, increases in platelet counts and alkaline 
phosphatase activity, and increased absolute and relative liver weights 
at 40 mg/kg b.w./day (the highest dose tested). The NOAEL for 
developmental toxicity was also 20 mg/kg b.w./day, based on an increase 
in the total number and mean number of resorptions and decreased fetal 
body weight at 40 mg/kg b.w./day.

[[Page 18011]]

    A 2-generation reproductive toxicity study in rats conducted with 
WL 136184 technical (greater than 95% cis isomer) is submitted in 
support of this tolerance petition. The results of the two-generation 
reproduction study with WL 136184 technical are sufficiently 
conservative for evaluating the potential reproductive toxicity of the 
85:15 isomer mixture of metconazole technical. The results from the 
reproductive toxicity study with WL 136184 technical support a NOAEL 
for parental toxicity of 8 mg/kg b.w./day, based on increased ovarian 
weight and increased gestation length at the next highest dose tested 
(32 mg/kg b.w./day). The NOAEL for growth and development of the 
offspring is also 8 mg/kg b.w./day, based on reductions in live litter 
size for F2 litters at 32 mg/kg b.w./day. The NOAEL for 
reproductive performance and fertility was 48 mg/kg b.w./day (the 
highest dose tested).
    Results of the pilot and definitive reproduction studies and 
developmental toxicity studies conducted with AC 900768 technical and/
or WL 136184 technical show no increased sensitivity to developing 
offspring as compared to parental animals, as comparable NOAELs were 
obtained for parental toxicity and growth and development of offspring.
    4.Subchronic toxicity. Short-term (28-day) dietary toxicity studies 
in rats were conducted with AC 900768 and WL 136184 technical 
materials. In the 28-day study with AC 900768, the NOAEL was 100 ppm 
(approximately 9.6 mg/kg b.w./day), based on reductions in body weight, 
body weight gain, food consumption, and hemoglobin concentration for 
males, as well as increased absolute and relative liver weights, and 
increased incidences of hepatic fatty vacuolation and parenchymal 
hypertrophy for males and females at 1,000 ppm (the next highest 
concentration tested). Similar results were observed in the study 
conducted with WL 136184 technical. Based on these results, the NOAEL 
for WL 136184 is 300 ppm (approximately 28.5 mg/kg b.w./day), supported 
by decreased body weights and body weight gains and increased 
incidences of hepatic fatty vacuolation for males and females, 
increased absolute and adjusted liver weights for females, and 
decreased food consumption for males at 1,000 ppm (the next highest 
concentration tested).
    In a 28-day dietary study in dogs conducted with AC 900768 
technical (85:15 isomer mixture), the NOAEL was a dietary concentration 
of 1,000 ppm (approximately 38.6 mg/kg b.w./day), based on decreased 
food consumption, body weight losses, increased alkaline phosphatase 
activity, increased spleen and liver weights, and urinalysis changes 
for males and females, and increased absolute and relative thyroid 
gland weights for females at 7,000 ppm, the highest concentration 
tested.
    Subchronic (90-day) dietary studies in rats were conducted with AC 
900768 technical and WL 136184 technical. In the study conducted with 
AC 900768, the NOAEL was 100 ppm (approximately 6.8 mg/kg b.w./day) 
based on hepatic fatty vacuolation in males at 300 ppm, the next 
highest concentration tested. The NOAEL from the study conducted with 
WL 136184 technical was 450 ppm (approximately 30.9 mg/kg b.w./day) 
based on decreased food consumption, body weights, and body weight 
gains, clinical chemistry changes, increased absolute and adjusted 
liver weights, and histopathological changes in the liver and/or 
stomach for males and females, and decreased red blood cell parameters 
for females at 1,350 ppm, the highest concentration tested.
    In a 90-day dietary study in mice conducted with AC 900768, the 
NOAEL was 30 ppm (approximately 5.5 mg/kg b.w./day), based on increased 
aspartate and alanine aminotransferase activities in males, increased 
absolute and relative weights of the liver and spleen of females, and 
increased incidences of hepatocelluar vacuolation and hypertrophy for 
males and females at 300 ppm, the next highest concentration tested.
    A 90-day dietary study in beagle dogs with AC 900768 technical 
supports a NOAEL of 60 ppm (approximately 2.5 mg/kg b.w./day) based on 
decreased body weight gain and food consumption for females, and a 
slight increase in reticulocyte count for males at 600 ppm, the next 
highest concentration tested.
    5.Chronic toxicity. Findings similar to those observed in the 
short-term subchronic studies were also apparent in the long-term 
dietary toxicity studies conducted in rats, dogs and mice. Long-term 
(104-weeks) administration of AC 900768 (85:15 isomer mixture) to rats 
supported a NOAEL for systemic toxicity of 100 ppm (approximately 4.8 
mg/kg b.w./day), based on increased adjusted liver weight, and 
increased incidences of hepatocellular lipid vacuolation and 
centrilobular hypertrophy at interim sacrifice for males at 300 ppm, 
the next highest concentration tested. In a one-year dietary study in 
beagle dogs, the NOAEL was 300 ppm (approximately 11.1 mg/kg b.w./day), 
based on decreased body weight gain for males during weeks 1 to 13 and 
increased alkaline phosphatase activity for males and females at 1,000 
ppm, the next highest concentration tested.
    In a 104-week carcinogenicity study in rats conducted with AC 
900768, the NOAEL for carcinogenicity was 1,000 ppm (approximately 50 
mg/kg b.w./day), the highest concentration tested. In this study the 
NOAEL for chronic systemic toxicity was 100 ppm (approximately 5.6 mg/
kg b.w./day), based on increased incidences of centrilobular 
hypertrophy and pigment disposition in the liver, and increased 
incidences of cortical vacuolation in the adrenal in males at 300 ppm, 
the next highest concentration tested.
    A 91-week carcinogenicity study in mice with AC 900768 supports a 
NOAEL for non-neoplastic effects of 30 ppm (approximately 4.8 mg/kg 
b.w./day), based on increased white blood cell count for males, 
increased aspartate and alanine aminotransferase activities and 
increased absolute and adjusted liver weight for females, and 
microscopic changes in the liver, spleen and adrenal gland for males 
and females at 300 ppm (the next highest concentration tested). The 
NOAEL for carcinogenicity was 300 ppm (approximately 48.3 mg/kg b.w./
day) based on increased incidences of hepatocellular adenomas in males 
and females and hepatocellular carcinomas in females at 1,000 ppm, the 
highest concentration tested. The increased incidences of hepatic 
adenomas and carcinomas at the highest concentration tested are 
considered to occur through promotional and non-genotoxic secondary 
mechanisms following toxicity and induction of mixed function oxidase 
in mice. Consequently, metconazole is not likely to be oncogenic in 
humans at the insignificant levels of exposure resulting from its use 
as a fungicide.
    AC 900768 technical and WL 136184 technical are not genotoxic 
carcinogens, as supported by a battery of in vitro and in vivo 
mutagenicity tests, which cover all major genetic endpoints.
    6.Animal metabolism. The rat metabolism studies indicate that the 
qualitative nature of the residues of metconazole in animals is 
adequately understood. In studies conducted with radiolabeled AC 900768 
(85:15 isomer mixture) or radiolabeled WL 136184 (greater than 95% cis 
isomer) radioactivity was rapidly eliminated in urine and feces with 48 
hours of dosing. Biliary excretion was shown to be a prominent route of 
elimination. At both high and low doses of AC 900768, male rats 
generally excreted statistically significantly lower amounts of 
radioactivity in the urine, and greater amounts of radioactivity in the 
feces,

[[Page 18012]]

 compared to females. The pattern of metabolites detected was similar 
at high and low doses, and little or no parent compound was found in 
the feces or urine. Five days following oral dosing of AC 900768 at the 
higher level, low levels of radioactivity were detected in the majority 
of tissues analyzed; however higher concentrations of radioactivity 
were found in the adrenal glands, gastro-intestinal tract and liver. A 
comparison of radioactivity levels in the adrenal glands following oral 
administration of low and high doses indicates that uptake in the 
adrenal may be saturable. No differences in tissue levels were noted 
between males and females. Hen and goat metabolism studies are not 
required, because bananas are not used as significant feedstuff for 
poultry or cattle.
    7.Metabolite toxicology. The metabolite CL 382390 was identified in 
the banana metabolism study at levels of less than 0.02 ppm or less 
than 2% of the total radioactive residue in whole bananas. This 
specific monohydroxylated metabolite was not confirmed in the rat 
metabolism studies; however, other monohydroxylated metabolites, 
including its stereo isomer were identified. In addition, CL 382390 was 
shown to have a low order of acute toxicity via the oral route with an 
LD50 value of greater than 5,000 mg/kg b.w. Another 
metabolite not identified in the rat metabolism studies, 
triazolylalanine, was found in the triazole-3,5-14C CL 900768 treated 
banana at less than 0.02 ppm or less than 2% of the total radioactive 
residue in whole bananas. Triazolylalanine has been shown to have a low 
order of acute toxicity by the oral route with an oral LD50 
value of greater than 5,000 mg/kg [WHO/FAO Joint Meeting on Pesticide 
Residues (JMPR) review, 1989]. Thus, the parent metconazole is 
considered to be the only toxicologically significant residue in 
bananas.
    8.Endocrine disruption. Collective organ weight data and 
histopathological findings from the two-generation rat reproductive 
study, as well as from the subchronic and chronic toxicity studies in 
three different animal species, demonstrate no apparent estrogenic 
effects or treatment-related effects of metconazole on the endocrine 
system.

C. Aggregate Exposure

    1.Dietary exposure. The potential dietary exposure to metconazole 
has been calculated from the proposed tolerance for bananas. The very 
conservative chronic dietary exposure estimates for this crop assumes 
that 100 percent of all bananas were treated with metconazole and that 
all treated bananas contain metconazole residues at the tolerance level 
of 0.05 ppm.
    2.Food. Using the assumptions discussed above, the Theoretical 
Maximum Residue Concentration (TMRC) values of metconazole were 
calculated for the U.S. general population and subgroups. Based on the 
proposed tolerance, the TMRC values for each group are:
     0.0000142 mg/kg b.w./day for the general population;
     0.0000461 mg/kg b.w./day for all infants;
     0.0000473 mg/kg b.w./day for non-nursing infants;
     0.0000407 mg/kg b.w./day for children 1 to 6 years of age; 
and
     0.0000156 mg/kg b.w./day for children 7 to 12 years of 
age.
    Potential exposure to residues of metconazole in food will be 
restricted to intake of bananas, dried bananas, and banana nectar.
    3.Drinking water. The tolerance proposed in this petition is for a 
raw agricultural commodity imported into the United States. There are 
no approved uses for metconazole in the United States; therefore, the 
potential exposure to metconazole in drinking water is not relevant to 
this petition.
    4.Non-dietary exposure. This petition is for a tolerance on an 
imported commodity. There is no approved use of metconazole in the 
United States. and none is being sought; therefore, the potential for 
non-dietary exposure to metconazole is not pertinent to this petition.

D. Cumulative Effects

    Metconazole is a member of the triazole class of fungicides. Other 
members of this class are registered for use in the United States. 
Although metconazole and other triazoles may have similar fungicidal 
modes of action, there are no available data to determine whether 
metconazole has a common mechanism of mammalian toxicity with other 
triazoles or information on how to include this pesticide in a 
cumulative risk assessment. Therefore, for the purposes of this 
tolerance petition no assumption has been made with regard to 
cumulative exposure with other compounds having a common mode of 
action.

E. Safety Determination

    1.U.S. population. The Reference Dose (RfD) represents the level at 
or below which daily aggregate exposure over a lifetime will not pose 
appreciable risks to human health. The chronic toxicity studies in rats 
and mice are the most appropriate studies to assess chronic dietary 
risk. These studies support a NOAEL of 4.8 mg/kg b.w./day, as the most 
sensitive dose for the estimation of the RfD for metconazole in humans. 
Based on the presence of a complete database for reproductive and 
developmental toxicity, and in the absence of teratogenicity or 
selective developmental toxicity, the use of a 100-fold safety factor 
is warranted for this compound. Applying a safety factor of 100 to this 
NOAEL results in the RfD of 0.048 mg/kg b.w./day. The chronic dietary 
exposure of 0.0000142 mg/kg b.w./day for the general U.S. population 
will utilize only 0.03% of the RfD of 0.048 mg/kg b.w./day. EPA 
generally has no concern for exposures below 100% of the RfD. The 
complete and reliable toxicity data and the conservative chronic 
dietary exposure assumptions support the conclusion that there is a 
``reasonable certainty of no harm'' from potential dietary exposure to 
residues of metconazole in bananas.
    2.Infants and children. The conservative dietary exposure estimates 
previously presented will utilize 0.1 percent of the RfD for all 
infants and as well as for the non-nursing infant group, which is the 
most highly exposed population subgroup. The chronic dietary exposures 
for children 1 to 6 years of age will utilize only 0.08% of the RfD, 
while for children ages 7 to 12 the estimated exposure will utilize 
only 0.03% of the RfD. Results from the two-generation reproduction 
study in rats with WL 136184 (greater than 95% cis isomer) and the 
developmental toxicity studies with AC 900768 in rats and rabbits 
indicate no increased sensitivity to developing offspring when compared 
to parental toxicity. For both the rat and rabbit developmental 
toxicity studies, embryotoxicity was only observed at maternally toxic 
doses. These results indicate that metconazole is neither a selective 
developmental toxicant nor a teratogen in either the rat or rabbit. 
Therefore, an additional safety factor is not warranted, and the RfD of 
0.048 mg/kg b.w./day, which utilizes a 100-fold safety factor is 
appropriate to ensure a reasonable certainty of no harm to infants and 
children.

F. International Tolerances

    There are no Codex maximum residue levels established or proposed 
for residues of metconazole in bananas.

[FR Doc. 05-7064 Filed 4-7-05; 8:45 am]
BILLING CODE 6560-50-S