[Federal Register Volume 65, Number 165 (Thursday, August 24, 2000)]
[Notices]
[Pages 51608-51612]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-21673]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-958; FRL-6598-6]


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 control number PF-958, must be 
received on or before September 25, 2000.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-958 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT:  By mail: Jim Tompkins, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; 
telephone number: (703) 308-6379; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be 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:

 
------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                       affected entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    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 the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
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 Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations'' and then look up the entry for this document under the 
``Federal Register--Environmental Documents.'' You can also go directly 
to the Federal Register listings at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-958. The official record 
consists of the documents specifically referenced in this action, any 
public comments received during an applicable comment period, and other 
information related to this action, including any information claimed 
as confidential business information (CBI). This official record 
includes the documents that are physically located in the docket, as 
well as the documents that are referenced in those documents. The 
public version of the official record does not include any information 
claimed as CBI. The public version of the official record, which 
includes printed, paper versions of any electronic comments submitted 
during an applicable comment period, is available for inspection in the 
Public Information and Records Integrity Branch (PIRIB), Rm. 119, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal

[[Page 51609]]

holidays. The PIRIB telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-958 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: ``[email protected],'' or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-958. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
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 version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified 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 
control 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 contain data or information 
regarding the elements set forth in 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 August 11, 2000.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. 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.

American Cyanamid Company

9F5092

    EPA has received a pesticide petition 9F5092 from American Cyanamid 
Company, P.O. Box 400, Princeton, NJ 08543-0400 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 the herbicide ( )-2-4,5-dihydro-4-methyl-4-(1-
methylethyl)-5-oxo-1-H-imidazol-2-yl-5-methyl-3-pyridinecarboxylic acid 
(also known as imazapic), applied as either the free acid or the 
ammonium salt, and its metabolite ( )-2-[4,5-dihydro-4-
methyl-4-(1-methylethyl)-5-oxo-1-H-imidazol-2-yl]-5-hydroxymethyl-3-
pyridinecarboxylic acid, both free and conjugated, in or on the raw 
agricultural commodities grass forage at 35 parts per million (ppm), 
and grass hay at 15 ppm. Tolerances are also proposed for ( 
)-2-4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1-H-
imidazol-2-yl-5-methyl-3-pyridinecarboxylic acid and its free 
hydroxymethyl metabolite alone in milk, meat of cattle, sheep, goats, 
and horses, fat of cattle, sheep, goats, and horses, meat by-products 
(except kidney) of cattle, sheep, goats, and horses at 0.1 ppm and 
kidney of cattle, sheep, goats, and horses at 2.0 ppm. EPA has 
determined that the petition contains data or information regarding the 
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of the residues of 
imazapic in grass is adequately understood. Based on results of a grass 
metabolism study conducted with a representative of this crop group, 
Bermuda grass, residues of concern for tolerance setting purposes in 
grass are parent imazapic and its hydroxymethyl metabolite, both free 
and glucose conjugated.
    2. Analytical method. Practical analytical methods for detecting 
and measuring the residues of concern in grass and animal commodities 
are

[[Page 51610]]

submitted to EPA with this petition. The analytical methods for grass 
commodities, milk, meat, and meat by-products are based on capillary 
electrophoresis with limits of quantitation (LOQ) of 0.5 ppm for grass 
commodities, 0.01 ppm for milk, and 0.05 ppm for meat and meat by-
products. Measurement of imazapic residues in milk fat and tissue fat 
is accomplished by high performance liquid chromatography/positive ion 
electro spray ionization tandem mass spectrometry (LC/MS). The 
validated LOQ of the method is 0.01 ppm for milk fat and 0.05 ppm for 
tissue fat. These independently validated methods are appropriate for 
the enforcement purposes of this petition.
    3. Magnitude of residues. A total of 13 field trials was conducted 
with representative grasses for this crop group at the proposed use 
rate for imazapic on grass. The residue values based on the proposed 
label use pattern and reported from these field trials were all less 
than the proposed tolerances of 35 ppm for grass forage and 15 ppm for 
grass hay. No processing study is included with this petition as 
grasses from pasture and rangeland have no processed commodities 
according to the EPA residue chemistry test guidelines.

B. Toxicological Profile

    1. Acute toxicity. Imazapic technical is considered to be nontoxic 
(toxicity category IV) to the rat by the oral route of exposure. In an 
acute oral toxicity study in rats, the LD50 value of 
imazapic technical was greater than 5,000 milligrams/kilograms body 
weight (mg/kg bwt) for males and females. The results from an acute 
dermal toxicity study in rabbits indicate that imazapic is slightly 
toxic (toxicity category III) to rabbits by the dermal route of 
exposure. The dermal LD50 value of imazapic technical was 
greater than 2,000 mg/kg bwt for both male and female rabbits. Imazapic 
technical is considered to be nontoxic (toxicity category IV) to the 
rat by the respiratory route of exposure. The 4-hour LC50 
value was greater than 5.52 mg/L (analytical) for both males and 
females. Imazapic technical was shown to be non-irritating to rabbit 
skin (toxicity category IV) and minimally irritating to the rabbit eye 
(toxicity category III). Based on the results of a dermal sensitization 
study, imazapic technical is not considered a sensitizer in guinea 
pigs.
    2. Genotoxicty. Imazapic technical was tested in a battery of four 
in vitro and one in vivo genotoxicity assays measuring several 
different endpoints of potential genotoxicity. Collective results from 
these studies indicate that imazapic does not pose a mutagenic or 
genotoxic risk.
    3. Reproductive and developmental toxicity. The developmental 
toxicity study in Sprague Dawley rats conducted with imazapic technical 
showed no evidence of teratogenic effects in fetuses and no evidence of 
developmental toxicity. Thus, imazapic is neither a developmental 
toxicant nor a teratogen in the rat. In the rat developmental toxicity 
study with imazapic technical, the no observed adverse effect level 
(NOAEL) for maternal toxicity and developmental toxicity was 1,000 mg/
kg bwt/day, the highest dose tested.
    Results from a developmental toxicity study in New Zealand White 
rabbits with imazapic technical also indicated no evidence of 
teratogenicity or developmental toxicity. Thus, imazapic technical is 
neither a developmental toxicant nor a teratogen in the rabbit. In the 
rabbit developmental toxicity study, the NOAEL for maternal toxicity 
was 350 mg/kg bwt/day, based on decreased food consumption and body 
weight gain at 500 mg/kg bwt/day, the next highest dose tested. The 
NOAEL for developmental toxicity was determined by EPA to be 500 mg/kg 
bwt/day; the excessive mortality in dams at 700 mg/kg bwt/day (the 
highest dose tested) resulted in too few fetuses that were available 
for evaluation.
    The results from the two-generation reproduction toxicity study in 
rats with imazapic technical support a NOAEL for parental toxicity of 
20,000 ppm (or approximately 1,344 mg/kg bwt/day, calculated from food 
consumption data), the highest concentration tested. The NOAEL for 
growth and development of the offspring is also 20,000 ppm, or 1,344 
mg/kg bwt/day. Results from the reproduction study and the 
developmental toxicity studies conducted with imazapic technical show 
no increased sensitivity to developing offspring as compared to 
parental animals, because the NOAELs for growth and development of 
offspring were equal to or greater than the NOAELs for parental 
toxicity.
    4. Subchronic toxicity. A short-term (21-day) dermal toxicity study 
in rabbits was conducted with imazapic technical. No dermal irritation 
or abnormal clinical signs were observed at dose levels up to and 
including 1,000 mg/kg bwt/day (highest dose tested), supporting a NOAEL 
for dermal irritation and systemic toxicity of 1,000 mg/kg bwt/day. In 
a subchronic (13-week) dietary toxicity study in rats with imazapic 
technical, no signs of systemic toxicity were noted, supporting a NOAEL 
of 20,000 ppm (or approximately 1,625 mg/kg bwt/day, calculated from 
food consumption data), the highest concentration tested. The 
requirement for a subchronic dietary toxicity study in non-rodents is 
satisfied by the one-year dietary toxicity study in dogs.
    5. Chronic toxicity. A one-year dietary toxicity study was 
conducted with imazapic technical in Beagle dogs at dietary 
concentrations of 0, 5,000, 20,000, and 40,000 ppm. In this study, the 
NOAEL for systemic toxicity was less than 5,000 ppm or approximately 
158 mg/kg bwt/day (137 mg/kg bwt/day for males and 180 mg/kg bwt/day 
for females), calculated from food consumption data, based on a slight 
skeletal myopathy, characterized by degeneration/necrosis of single 
fibers (minimal severity) and lymphocyte/macrophage infiltration in 
skeletal muscle, in males and females, and slightly decreased serum 
creatinine in females at 5,000 ppm (lowest concentration tested).
    The skeletal myopathy observed at 5,000 ppm was considered of 
minimal toxicological significance because the limited presence and the 
minimal severity of skeletal myopathy was evident in only a few fibers 
out of hundreds evaluated per section per animal. Further, these focal 
myopathies of minimal severity were not consistently diagnosed in all 
skeletal muscles sites examined per dog (i.e., vastus and abdominal 
muscles, diaphragm and esophagus). Moreover, no clinical observations 
indicative of muscle dysfunction were noted in any animal in the study. 
Finally, although the skeletal myopathy noted at 40,000 ppm (highest 
concentration tested) was associated with increases in creatine kinase, 
aspartate aminotransferase and lactate dehydrogenase, no statistically 
or biologically significant increases in these serum enzymes were noted 
during the study period for animals in the 5,000 ppm group. As such, 
the minimal myopathy diagnosed microscopically at 5,000 ppm was not 
considered to impair or adversely affect the functional capacity of the 
affected skeletal muscles.
    In a 2-year chronic dietary oncogenicity and toxicity study in rats 
conducted with imazapic technical, the NOAEL for oncogenicity and 
chronic systemic toxicity was 20,000 ppm (approximately 1,133 mg/kg 
bwt/day, calculated from food consumption data), the highest 
concentration tested. An 18-month chronic dietary oncogenicity and 
toxicity study in mice with imazapic technical supports a NOAEL for 
oncogenicity and for chronic systemic toxicity of 7,000 ppm (or 
approximately 1,288 mg/kg bwt/day, calculated from

[[Page 51611]]

food consumption data), the highest concentration tested.
    The EPA has classified imazapic as a group E carcinogen (evidence 
of non-carcinogenicity for humans) based on the absence of treatment-
related tumors in acceptable carcinogenicity studies in both rats and 
mice.
    6. Animal metabolism. The rat and goat metabolism studies indicate 
that the qualitative nature of the residues of imazapic in animals is 
adequately understood. In the rat metabolism study conducted with radio 
labeled AC 263222 (imazapic technical) no detectable radioactivity was 
excreted via expired air. In both the rat and goat metabolism studies, 
urinary excretion was the primary elimination route with 95% and 81.7% 
of the radioactivity, respectively, excreted in the urine. The major 
component in the urine from both studies was the unchanged parent 
compound.
    There was no significant bioaccumulation of radioactivity in the 
tissues from the rat metabolism study. In the goat metabolism study, 
blood and tissue samples taken following sacrifice at approximately 23 
hours after the last dose contained less than 0.01% of the administered 
radioactivity, and the entire milk sample contained less than 0.03% of 
the administered radioactivity. As with the residues in other samples 
from the rat and goat metabolism studies, the major residue in the goat 
tissue and milk samples was parent compound. A hen metabolism study is 
not required, because grasses from pasture or rangelands are not used 
as significant feedstuff for poultry according to the EPA residue 
chemistry test guidelines.
    7. Metabolite toxicology. Metabolism studies in grass and peanuts 
indicate that the only significant metabolite is the hydroxymethyl 
metabolite of imazapic, both free and glucose conjugated. The 
hydroxymethyl metabolite has also been identified in minor quantities 
in the rat metabolism study and in a previously submitted goat 
metabolism study. No additional toxicologically significant metabolites 
were detected in any of the plant or animal metabolism studies.
    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 imazapic on the endocrine 
system.

C. Aggregate Exposure

    1. Dietary exposure. The potential dietary exposure to imazapic has 
been calculated from the proposed tolerances for use on grasses and 
from the previously established tolerance for peanuts. These very 
conservative chronic dietary exposure estimates used the tolerance 
value for peanuts and the proposed tolerance values for meat and milk. 
In addition, these estimates assume that 100% of the peanut crop and 
all meat and milk contain imazapic residues.
    i. Food. Using the assumptions discussed above, the theoretical 
maximum residue concentration (TMRC) values of imazapic were calculated 
for the U.S. general population and subgroups. Based on the peanut 
tolerance and the proposed tolerances for meat and milk, the TMRC 
values for each group are 0.000778 mg/kg bwt/day for the general U.S. 
population; 0.001257 mg/kg bwt/day for all infants; 0.001524 mg/kg bwt/
day for non-nursing infants; 0.002878 mg/kg bwt/day for children 1 to 6 
years of age, and 0.001430 mg/kg bwt/day for children 7 to 12 years of 
age. Potential exposure to residues of imazapic in food will be 
restricted to intake of peanuts, peanut butter, peanut oil, meat, meat 
byproducts, and milk.
    ii. Drinking water. As a screening-level assessment for aggregate 
exposure, the U.S. EPA evaluates a drinking water level of comparison 
(DWLOC), which is the maximum concentration of a chemical in drinking 
water that would be acceptable in light of total aggregate exposure to 
that chemical. Based on the chronic reference dose (RfD) of 0.5 mg/kg 
bwt/day and the EPA's default factors for body weight and drinking 
water consumption, the DWLOCs have been calculated to assess the 
potential dietary exposure from residues of imazapic in water. For the 
adult population, the chronic DWLOC was 17,473 and for children the 
DWLOC was estimated to be 4,971 parts per billion (ppb).
    Chronic drinking water exposure analyses were calculated using EPA 
models for Screening Concentration in Groundwater (SCI-GROW) for ground 
water and Generic Expected Environmental Concentration (GENEEC) for 
surface water. The calculated peak GENEEC value is 5.58 ppb and the 
SCI-GROW value is 0.56 ppb. For the U.S. adult population, the 
estimated exposures of imazapic residues in surface water and ground 
water are approximately 0.03% and 0.003%, respectively, of the DWLOC. 
The estimated exposures of children to imazapic residues in surface 
water and ground water are approximately 0.1% and 0.01%, respectively, 
of the DWLOC. Therefore, the exposures to drinking water from imazapic 
use are negligible.
    2. Non-dietary exposure. Imazapic products are not currently 
registered or requested to be registered for residential or urban use; 
therefore, the estimate of residential exposure is not relevant to this 
tolerance petition.

D. Cumulative Effects

    Imazapic is a member of the imidazolinone class of herbicides. 
Other compounds of this class are registered for use in the U.S. 
However, the herbicidal activity of the imidazolinones is due to the 
inhibition of acetohydroxy acid synthase (AHAS), an enzyme only found 
in plants. AHAS is part of the biosynthetic pathway leading to the 
formation of branched chain amino acids. Animals lack AHAS and this 
biosynthetic pathway. This lack of AHAS contributes to the low toxicity 
of the imidazolinone compounds in animals. We are aware of no 
information to indicate or suggest that imazapic has any toxic effects 
on mammals that would be cumulative with those of any other chemical. 
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 RfD represents the level at or below which 
daily aggregate exposure over a lifetime will not pose appreciable 
risks to human health. Results from the 1-year chronic dietary toxicity 
study in dogs supports the lowest observed effect level (LOAEL) of 
5,000 ppm, equivalent to approximately 137 mg/kg bwt/day for males. The 
EPA applied an uncertainty or safety factor of 300 to the LOAEL based 
on a safety factor of 100 to account for interspecies extrapolation and 
intraspecies variability, and an additional factor of 3 to account for 
the lack of a NOAEL in the chronic dog study. Applying a safety factor 
of 300 to this LOAEL of 137 mg/kg bwt/day results in the RfD of 0.50 
mg/kg bwt/day. The chronic dietary exposure of 0.00078 mg/kg bwt/day 
for the general U.S. population will utilize only 0.2% of the RfD of 
0.5 mg/kg bwt/day. EPA generally has no concern for exposures below 
100% of the RfD. Due to the low toxicity of imazapic, an acute exposure 
dietary risk assessment is not warranted. The complete and reliable 
toxicity data base, the low toxicity of the molecule, and the 
conservative chronic dietary exposure assumptions support the

[[Page 51612]]

conclusion that there is a ``reasonable certainty of no harm'' from the 
proposed use of imazapic on grasses and the currently registered crop, 
peanuts.
    2. Infants and children. The conservative dietary exposure 
estimates previously presented will utilize 0.3% of the RfD for all 
infants, for the non-nursing infant group, and for children ages 7 to 
12. The chronic dietary exposures for children 1 to 6 years of age, the 
most highly exposed subgroup, will utilize only 0.6% of the RfD. 
Results from the two-generation reproduction study in rats and the 
developmental toxicity studies in rabbits and rats indicate no 
increased sensitivity to developing offspring when compared to parental 
toxicity. These results also indicate that imazapic is neither a 
developmental toxicant nor a teratogen in either the rat or rabbit. 
Therefore, an additional safety factor is not warranted, and the RfD of 
0.5 mg/kg bwt/day, which utilizes a 300-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 imazapic from use on grasses.

[FR Doc. 00-21673 Filed 8-23-00; 8:45 am]
BILLING CODE 6560-50-F