[Federal Register Volume 65, Number 24 (Friday, February 4, 2000)]
[Notices]
[Pages 5639-5643]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-2484]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-908; FRL-6398-9]


Novartis Crop Protection; Notice of Filing a Pesticide Petition 
To Establish a Tolerance for Certain Pesticide Chemicals 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 
certain pesticide chemicals in or on various food commodities.

DATES:  Comments, identified by docket control number PF-908, must be 
received on or before March 6, 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.

[[Page 5640]]

To ensure proper receipt by EPA, it is imperative that you identify 
docket control number PF-908 in the subject line on the first page of 
your response.

FOR FURTHER INFORMATION CONTACT:  By mail: Cynthia Giles-Parker (PM 
22), Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania 
Ave., NW., Washington, DC 20460; telephone number: (703) 305-7740; and 
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-908. 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 (CM #2), 1921 Jefferson Davis Highway, Arlington, VA, 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
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-908 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, Ariel Rios Bldg., 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, CM #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-908. 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 certain 
pesticide chemicals in or on various food commodities under section 408 
of the Federal Food,

[[Page 5641]]

Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that 
this petition contains 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 
supports 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: January 24, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

9F6004

    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. EPA is publishing the petition summary verbatim without 
editing it in any way. 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.
    EPA has received a pesticide petition (9F6004) from Novartis Crop 
Protection, P.O. Box 18300, Greensboro, NC 27419 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 1,2,3-benzothiadiazole-7-carbothioic acid S-methyl 
ester (acibenzolar-S-methyl) in or on the raw agricultural commodity 
brassica leafy vegetables crop group and bananas at 1.0 and 0.1 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. Novartis believes the metabolism of 
acibenzolar-S-methyl has been well characterized. Only 4.6% and 14.9% 
of the total radioactive residue (TRR) was non-extractable in lettuce 
at the recommended application rate and three times the recommended 
application rate, respectively. Non-extractables were also low in a 
tomato metabolism study; 3.4% and 7.4% in tomatoes and foliage, 
respectively. The metabolism in these crops proceeded via hydrolysis of 
benzo [1,2,3] thiadiazole-7-carbothioic acid S-methyl ester to benzo 
[1,2,3] thiadiazole-7-carboxylic acid (BTCA), followed by conjugation 
as ester, glycoside and/or other plant constituents. The metabolism 
profile supports the use of an analytical enforcement method that 
accounts for acibenzolar-S-methyl and metabolites containing the benzo 
[1,2,3] thiadiazole-7-carboxylic acid (BTCA) moiety.
    2. Analytical method. Novartis Analytical Method AG-671A is a 
practical and valid method for the determination and confirmation of 
CGA-245704 (acibenzolar-S-methyl) in raw agricultural commodities (RAC) 
and processing substrates from the tobacco, leafy (including brassica) 
and fruiting vegetable crop groups at a limit of quantitation (LOQ) of 
0.02 ppm. The method involves extraction, solid phase cleanup of 
samples with analysis by high performance liquid chromotography (HPLC) 
with ultraviolet (UV) detection or confirmatory LC/MS. The validity is 
demonstrated by the acceptable accuracy and precision obtained on 
numerous procedural recovery samples (radiovalidation and field trial 
sample sets), and by the extractability and accountability obtained by 
the analysis of weathered radioactive substrates using Analytical 
Method AG-671A. Novartis Analytical Method REM 172.11 is a practical 
and valid method for the determination and confirmation of CGA-245704 
in RAC of bananas at a LOQ of 0.02 ppm. The method involves hydrolytic 
extraction, partitioning, and solid phase cleanup of samples with 
analysis by two-column HPLC switching with UV detection. The validity 
is demonstrated by the acceptable accuracy and precision obtained on 
numerous procedural recovery samples (banana, tomatoes, cucumbers, and 
milk).
    3. Magnitude of residues. This petition is supported by 17 field 
trials conducted on representative members of the brassica leafy 
vegetable crop groupings. All samples were analyzed for by the total 
residue method (AG-671A) to determine the combined residues of 
acibenzolar-S-methyl and metabolites which contain the benzo [1,2,3] 
thiadiazole-7-carboxylic acid (BTCA) moiety. In brassica leafy 
vegetables, the maximum residues found on representative commodities 
were 0.63 ppm, 0.57 ppm, 0.31 ppm, 0.64 ppm, and 0.80 ppm, for broccoli 
(flower, head and stem), cabbage head (with wrapper leaves), cabbage 
head (without wrapper leaves), cabbage wrapper leaves, and mustard 
greens leaves, respectively. A tolerance of 1.0 ppm for the brassica 
leafy vegetable crop group has been proposed. This petition is 
supported by 14 field trials conducted on bananas. Banana samples were 
analyzed for by the total residue method REM 17.11 to determine the 
combined residues of acibenzolar-S-methyl and metabolites which contain 
the benzo [1,2,3] thiadiazole-7-carboxylic acid (BTCA) moiety. The 
maximum residue found in bananas was 0.08 ppm. A tolerance of 0.1 ppm 
in bananas has been proposed.

B. Toxicological Profile

    1. Acute toxicity. The risk from acute dietary exposure to 
acibenzolar-S-methyl is considered to be very low. CGA-245704 and the 
formulated 50 WG product have low orders of acute toxicity by the oral, 
dermal and inhalation exposure routes. Results from acute studies all 
fall within toxicity rating categories of III or IV. CGA-245704 
technical has a low order of acute toxicity, is only slightly 
irritating to skin and eyes, but may cause sensitization by skin 
contact. An LD50 of greater than 5,000 milligrams/kilograms 
(mg/kg) was observed for the acute oral toxicity study in rats. The 
lowest no observed adverse effect level (NOAEL) in a short-term 
exposure scenario, identified as 50 mg/kg in the rabbit and rat 
teratology studies, is 10-fold higher than the chronic NOAEL. Based on 
worst case assumptions, the chronic exposure assessments (see below) 
did not result in any margin of exposure (MOE) less than 3,330 for even 
the most impacted population subgroup. Novartis believes the MOE is 
greater than 100 for any population subgroups; EPA considers MOEs of 
100 or more as satisfactory. The following are results from the acute 
toxicity tests conducted on the technical material:
    i. Rat oral LD50 > 5,000 mg/kg/bwt male/female (M/F) 
toxicity Category IV.
    ii. Rat dermal LD50 > 2,000 mg/kg/bwt (M/F) toxicity 
Category III.
    iii. Acute inhalation LC50 > 5,000 mg/L (M/F) toxicity 
Category IV.
    iv. Rabbit eye irritation: Minimally irritating--toxicity Category 
III.
    v. Rabbit dermal irritation: Slightly irritating--toxicity Category 
IV.
    vi. Dermal sensitization: Sensitizer.
    2. Genotoxicty. CGA-245704 technical was not mutagenic or 
clastogenic and did not provoke unscheduled DNA

[[Page 5642]]

synthesis when tested thoroughly in a battery of standard in vivo, and 
in vitro independent assays, using both eukaryotes and prokaryotes, and 
with or without metabolic activation. These tests are summarized below:
    i. Microbial/Microsome Mutagenicity Assay: Non-mutagenic.
    ii. Mammalian Cell Chinese Hampster Ovary (CHO) Mutagenicity Assay: 
Non-mutagenic; Non-clastogenic.
    iii. Chinese Hampster (CH) Bone marrow: Non-clastogenic; negative 
for chromosome aberrations.
    iv. Mouse Micronucleus Test: Non-clastogenic; negative for 
chromosome aberrations.
    v. DNA Damage and Repair Rat hepatocyte: Negative.
    3. Reproductive and developmental toxicity. Acibenzolar-S-methyl is 
not a teratogenic hazard except at, or close to, the maximum tolerated 
dose. In the rat multigeneration study, CGA-245704 (acibenzolar-S-
methyl) technical had no effect on rat reproductive parameters 
including gonadal function, estrus cycles, mating behavior, conception, 
parturition, lactation, weaning, and sex organ histopathology. At 4,000 
ppm, parental body weights (bwt) were reduced. This demonstrated by the 
results of the following studies:
    i. Rat oral teratology--Maternal NOAEL of 200 mg/kg based on 
embryotoxicity and teratogenic effects; fetal NOAEL of 50 mg/kg.
    ii. Rabbit oral teratology study--Maternal NOAEL of 50 mg/kg based 
on maternal toxicity and slightly delayed ossification; fetal NOAEL of 
300 mg/kg based on changes in bwt.
    iii. Rat 2-generation reproduction study--NOAEL of 25 mg/kg based 
on weight development in adults at 4,000 ppm and pups during lactation 
at 2,000 ppm and above. No adverse effects on reproduction or 
fertility.
    4. Subchronic toxicity. No signs of neurotoxicity were noted with 
CGA-245704 in both acute and subchronic studies even at the highest 
dose levels of 800 mg/kg and 8,000 ppm, respectively. The evaluated 
parameters included functional observation battery, motor activity 
measurement and neurohistopathologic assessment. These tests are 
summarized below:
    i. Rat 28-day dermal study--NOAEL of 1,000 mg/kg/day.
    ii. Dog 90-day feeding study--NOAEL of 10 mg based on reduced bwt 
gain at 50 mg/kg/day.
    iii. Mouse 90-day feeding--NOAEL of  30 mg/kg based on reduced bwt 
development at 1,000 ppm and above.
    iv. Rat 90-day feeding study--NOAEL of 25 mg/kg based on 
inappetence and reduced bwt development at higher dose levels (4,000, 
and 8,000 ppm).
    5. Chronic toxicity. Based on the available chronic toxicity data, 
Novartis Crop Protection, Inc. believes the Reference Dose (RfD) for 
acibenzolar-S-methyl is 0.05 mg/kg/day. Acibenzolar-S-methyl is not 
oncogenic in rats or mice and is not likely to be carcinogenic in 
humans. No carcinogenic activity was detected in mice and rats at the 
Maximum Tolerated Dose (MTD). There was no evidence of carcinogenicity 
in an 18-month feeding study in mice and a 24-month feeding study in 
rats. Dosage levels in both the mouse and the rat studies were adequate 
for identifying a cancer risk. Novartis believes acibenzolar-S-methyl 
should be classified as a ``Not Likely'' carcinogen based on the lack 
of carcinogenicity in rats and mice.
    6. Animal metabolism. Metabolism proceeded primarily via hydrolysis 
to form the corresponding carboxylic acid (BTCA) which was subsequently 
conjugated with several amino acids including glycine, lysine and 
ornithine. Elimination was rapid in all cases. Oxidation of the 
aromatic ring of the acid was a very minor pathway observed in goats. 
The metabolic fate of CGA-245704 in plants paralleled that observed in 
animals. The major metabolite in all test systems was the same 
hydrolysis product BTCA. Thus, the metabolism profile supports the use 
of an analytical enforcement method that accounts principally for 
parent and BTCA.
    7. Metabolite toxicology. In short-term toxicity studies in rats, 
CGA-210007 was found to be of, at most, equal or less toxicity than the 
parent compound. As with parent CGA-245704, the subchronic NOAEL for 
CGA-210007 was 100 mg/kg bwt.
    8. Endocrine disruption. Acibenzolar-S-methyl does not belong to a 
class of chemicals known or suspected of having adverse effects on the 
endocrine system. Developmental toxicity studies in rats and rabbits 
and a reproduction study in rats gave no indication that acibenzolar-S-
methyl might have any effects on endocrine function related to 
development and reproduction. Acibenzolar-S-methyl is not a teratogenic 
hazard except at, or close to, the maximum tolerated dose. The chronic 
studies also showed no evidence of a long-term effect related to the 
endocrine system.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. For the purposes of assessing the 
potential dietary exposure under the proposed tolerances, Novartis has 
estimated aggregate from the previously requested tolerances for the 
raw agricultural commodities: leafy vegetables (excluding spinach) at 
0.25 ppm; spinach at 1.0 ppm; and fruiting vegetables at 1.0 ppm (PP 
8F4974); and the requested tolerances for brassica leafy vegetables at 
1.0 ppm and bananas at 0.1 ppm (PP 9F6004). Maximum expected chronic 
exposure to CGA-245704 in the diets of the most sensitive sub-
population, children (1-6 years), was calculated to be 0.5% of the RfD. 
For the U.S. population (48 contiguous States) chronic exposure was 
0.3% of the RfD. Acute dietary exposure is also minimal. Exposure to 
the most sensitive sub-population, children (1-6 years), was 2.17% of 
the acute RfD (aRfD). Acute exposure to the U.S. population was 1.2% of 
the aRfD. Dietary exposure analyses for CGA-245704 (and CGA-210007) 
were conducted using anticipated residues generated from field trials 
conducted at the maximum use rate and minimum pre-harvest interval 
(PHI). In addition, actual dietary exposure would be much less than the 
estimates made herein since significant residue reduction often takes 
place in commerce and during food preparation and cooking. Projected 
market share was included on all commodities except bananas. One 
hundred percent market share was assumed for bananas. These results 
(minimal exposure) show more than a reasonable certainty of no harm.
    ii. Drinking water. The potential for exposure to CGA-245704 
through drinking water (surface or ground water) is slight due to the 
minimal level of this chemical anticipated to reach these bodies of 
water. This expectation is based on the rapid degradation of CGA-245704 
and the recommended low use rates that will further restrict the amount 
of chemical available for leaching or run-off. A Maximum Contaminant 
Level Goal (MCLG) of 350 parts per billion (ppb) has been calculated 
for CGA-245704. This calculated safe exposure value is substantially 
above the levels that are likely to be found in the environment under 
proposed conditions of use.
    2. Non-dietary exposure. Novartis believes that the potential for 
non-occupational exposure to the general public is unlikely except for 
potential residues in food crops discussed above. The proposed uses for 
acibenzolar-S-methyl are for agricultural crops and the product is not 
used residentially in or around the home.

D. Cumulative Effects

    Consideration of a common mechanism of toxicity is not appropriate

[[Page 5643]]

at this time since there is no information to indicate that toxic 
effects produced by acibenzolar-S-methyl would be cumulative with those 
of any other chemicals. Acibenzolar-S-methyl is a plant activator and 
no other compounds in this class are registered in the United States. 
Consequently, Novartis is considering only the potential exposure to 
acibenzolar-S-methyl in its aggregate risk assessment.

E. Safety Determination

    1. U.S. population. For the U.S. population (48 contiguous States) 
chronic exposure was 0.3% of the RfD. Acute dietary exposure is also 
minimal. Acute exposure to the U.S. population was 1.2% of the aRfD. 
EPA usually has no concern for exposures below 100% of the RfD because 
the RfD represents the level at or below which daily aggregate dietary 
exposure over a lifetime will not pose appreciable risks to human 
health. Novartis concludes that there is a reasonable certainty that no 
harm will result from aggregate exposure to acibenzolar-S-methyl 
residues.
    2. Infants and children. Embryotoxicity and fetotoxicity were 
apparent at maternally toxic doses of CGA-245704 technical in rats and 
rabbits. The lowest NOAEL for this effect was established in the 2-
generation reproduction study at 25 mg/kg (200 ppm).
    Maximum expected chronic exposure to CGA-245704 in the diets of the 
most sensitive sub-population, children (1-6 years), was calculated to 
be 0.5% of the RfD. Acute dietary exposure is also minimal. Exposure to 
the most sensitive sub-population, children (1-6 years), was 2.17% of 
the aRfD.
    Additionally, CGA-245704 is not a reproductive toxin. Some signs of 
teratogenicity were found at, or close to, maternally toxic doses. No 
neurotoxic effects or oncogenic activity has been observed with CGA-
245704. From these available toxicology data, no special susceptibility 
of infants or children is anticipated.
    Dietary exposure analyses for CGA-245704 (and CGA-210007) were 
conducted using anticipated residues generated from field trials 
conducted at the maximum use rate and minimum pre-harvest interval 
(PHI). In addition, actual dietary exposure would be much less than the 
estimates made herein since significant residue reduction often takes 
place in commerce and during food preparation and cooking. Projected 
market share was included on all commodities except bananas. One 
hundred percent market share was assumed for bananas. These results 
(minimal exposure) show more than a reasonable certainty of no harm.

  Acute Dietary Exposure for the U.S. Population and the Most Sensitive
             Population Sub-Groups at the 99.9th Percentile
------------------------------------------------------------------------
           Population Sub-group                  % aRfD (Diet Only)
------------------------------------------------------------------------
U.S. Population - 48 contiguous states -    1.20%
 all seasons.
All infants (1 year)......................  1.54%
Nursing infants (1year)...................  0.41%
Non-nursing infants (1 year)..............  1.80%
Children (1-6 years)......................  2.17%
Children (7-12)...........................  1.37%
------------------------------------------------------------------------

    Exposure to residues of CGA-245704 and CGA-210007 in consumed food 
is minimal. Both chronic and acute exposure estimates demonstrate the 
use of CGA-245704 on crops results in more than a reasonable certainty 
of no harm. The results herein are conservative since field trial 
residues utilized in these assessments were generated under maximum 
label use rates and minimum pre-harvest intervals.

F. International Tolerances

    Codex maximum residue levels (MRLs) have not been established for 
residues of CGA-245704 in or on raw agricultural commodities from the 
fruiting vegetable and leafy vegetable crop groups. Maximum residue 
levels of 0.1 ppm have been established for CGA-245704 on wheat in 
Switzerland and Hungary. Proposed CODEX MRLs of 1.0 ppm on tomatoes and 
0.1 ppm on bananas, cereals, wheat, spring barley, and rice have been 
proposed (Japan).
[FR Doc. 00-2484 Filed 2-3-00; 8:45 am]
BILLING CODE 6560-50-F