[Federal Register Volume 59, Number 122 (Monday, June 27, 1994)]
[Unknown Section]
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From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-15567]


[[Page Unknown]]

[Federal Register: June 27, 1994]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 799

[OPPTS-42134E; FRL-4874-1]
Rin 2070-AC27

 

Proposed Revocation of Final Multi-substance Rule for the Testing 
of Neurotoxicity

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Environmental Protection Agency is proposing to revoke the 
Multi-Substance Rule for the Testing of Neurotoxicity at 40 CFR 
799.5050, promulgated under section 4 of the Toxic Substances Control 
Act (``TSCA''), at 58 FR 40262, July 27, 1993. On October 8, 1993, the 
Chemical Manufacturers Association (CMA) and the manufacturers and 
processors of these substances filed suit seeking review of the rule in 
the 5th Circuit Court of Appeals. EPA is proposing to revoke this rule 
as part of a settlement agreement reached with the manufacturers of 
these chemicals, who have agreed to perform certain neurotoxicity and 
pharmacokinetics testing on 7 of the 10 chemicals subject to the final 
test rule, subject to execution of enforceable consent agreements 
(``ECA'') containing these studies. Elsewhere in this Federal Register, 
EPA is announcing an administrative stay of the final rule pending 
final action on this proposed revocation.
DATES: Written comments on the proposed revocation of the test rule 
must be received on or before July 27, 1994.

ADDRESSES: Submit written comments identified by the document control 
number, OPPTS-42134E, in triplicate to: TSCA Public Docket Office 
(7407), Rm. NE B607, Office of Pollution Prevention and Toxics, 
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. 
A public version of the administrative record supporting this action, 
with any confidential business information deleted, is available for 
inspection at the above address from 12 noon to 4:00 p.m. Monday 
through Friday, except legal holidays.

FOR FURTHER INFORMATION CONTACT: Catherine Roman, Chemical Control 
Division, (7405), Office of Pollution Prevention and Toxics, 401 M St., 
SW., Washington, DC 20460, (202) 260-8155.
SUPPLEMENTARY INFORMATION: The Environmental Protection Agency is 
proposing to revoke the Multi-Substance Rule for the Testing of 
Neurotoxicity at 40 CFR 799.5050, promulgated under section 4 of the 
Toxic Substances Control Act (``TSCA''), at 58 FR 40262, July 27, 1993. 
On October 8, 1993, the Chemical Manufacturers Association (CMA) and 
the manufacturers and processors of these substances filed suit seeking 
review of the rule in the 5th Circuit Court of Appeals. The 
manufacturers of 7 of the 10 chemicals subject to the final test rule 
have agreed, subject to certain conditions set forth in the settlement 
agreement (Ref. 3), to conduct a set of neurotoxicity and 
pharmacokinetics testing under enforceable consent agreements 
(``ECA''). If ECA negotiations are successful, EPA believes that the 
previously issued final test rule would no longer be needed. EPA 
believes that, under a negotiated ECA, neurotoxicity and 
pharmacokinetics testing would be conducted and results made publicly 
available more quickly, and EPA resources used more effectively, than 
if EPA continued to litigate the merits of the final test rule.
    The final test rule was published on July 27, 1993 (58 FR 40262), 
and requires manufacturers and processors of 10 substances to conduct 
testing for neurotoxicity. It is anticipated that the following seven 
substances would be tested pursuant to ECAs: acetone (CAS No. 67-64-1), 
technical grade n-amyl acetate (CAS No. 628-63-7), n-butyl acetate (CAS 
No. 123-86-4), ethyl acetate (CAS No. 141-78-6), isobutyl alcohol (CAS 
No. 78-83-1), methyl isobutyl ketone (CAS No. 108-10-1), and 
tetrahydrofuran (CAS No. 109-99-9). Testing is currently underway for 
n-butyl acetate and isobutyl alcohol. Pharmacokinetics testing would be 
conducted on butyl acetate to determine if its test results for 
neurotoxicity can be used to assess the neurotoxicity of its 
metabolite, 1-butanol. EPA does not anticipate entering into an ECA for 
1-butanol (CAS No. 71-36-3), diethyl ether (CAS No. 60-29-7), or 2-
ethoxyethanol (CAS No. 110-80-5), three other substances for which 
testing is required under the final test rule.
    Elsewhere in this Federal Register, EPA is soliciting interested 
parties for participation in or monitoring of ECA negotiations. The 
settlement agreement signed by EPA and the parties to the lawsuit in 
April 1994 will be the starting point for the ECA negotiations.

I. Background

    On July 27, 1993 (58 FR 40262) EPA issued a test rule under TSCA 
section 4 that required manufacturers and processors of ten substances 
to conduct testing for neurotoxicity (Ref. 1). The required testing was 
the same for all 10 substances and included acute and subchronic 
functional observational battery and motor activity, and subchronic 
neuropathology and schedule-controlled operant behavior. These 10 
substances are listed below: 

------------------------------------------------------------------------
            Chemical name                            CAS No.            
------------------------------------------------------------------------
acetone                                                   67-64-1       
n-amyl acetate, technical grade                          628-63-7       
1-butanol                                                 71-36-3       
n-butyl acetate                                          123-86-4       
diethyl ether                                             60-29-7       
2-ethoxyethanol                                          110-80-5       
ethyl acetate                                            141-78-6       
isobutyl alcohol                                          78-83-1       
methyl isobutyl ketone                                   108-10-1       
tetrahydrofuran                                          109-99-9       
------------------------------------------------------------------------

    The manufacturers of these substances petitioned for review of the 
final rule under TSCA section 19 in the Fifth Circuit Court of Appeals 
(Ref. 2). Subsequent to the filing of this challenge to the rule, EPA, 
the Chemical Manufacturers Association (``CMA''), and authorized 
representatives of all parties challenging the rule, entered into 
settlement negotiations to resolve the lawsuit.
    As a result of these settlement discussions, CMA and the other 
parties to the lawsuit have agreed, subject to certain conditions set 
forth in the settlement agreement (Ref. 3), to conduct neurotoxicity 
and pharmacokinetics testing of seven chemical substances under 
negotiated ECAs, to be implemented by an order issued by EPA under TSCA 
section 4. Testing on two of the chemicals subject to the final rule, 
n-butyl acetate and isobutyl alcohol, is already underway. It is CMA's 
stated intent that such testing continue on schedule during the 
pendency of this proceeding (Ref. 3).
    In turn, EPA has agreed to propose to withdraw the final test rule. 
EPA is aware that the settlement agreement contemplates a reduced set 
of testing on fewer chemicals than the testing regimen required by the 
final rule. Although EPA believes that the rulemaking record contains 
substantial evidence to support the testing requirements in the final 
rule, EPA has decided not to proceed with the litigation at this time. 
EPA believes that the uncertain outcome of the court's decision is 
outweighed by the benefits of allowing testing to proceed immediately. 
EPA believes that the settlement agreement is in the public interest as 
it will allow testing to proceed on an expedited basis, without the 
uncertainties of protracted litigation. EPA notes that although CMA's 
lawsuit has been dismissed without prejudice by the 5th Circuit Court 
of Appeals, in response to a joint motion for a stay, it can be 
reinstated by either party upon filing of a letter with the court (Ref. 
21). This Notice will allow all interested parties an opportunity to 
evaluate and comment on EPA's proposed revocation of the final rule and 
decision to pursue an ECA as the mechanism for achieving testing.

II. Testing Program

    The testing program required for all 10 substances by the final 
test rule includes the following tests conducted according to the 
designated TSCA test guidelines:

------------------------------------------------------------------------
                                                                 TSCA   
                            Test                               guideline
------------------------------------------------------------------------
Functional observational battery, acute and subchronic......  Sec. 798.6
                                                                050     
Motor activity, acute and subchronic........................  Sec. 798.6
                                                                200     
Neuropathology, subchronic..................................  Sec. 798.6
                                                                400     
Schedule-controlled operant behavior (SCOB), subchronic.....  Sec. 798.6
                                                               500      
------------------------------------------------------------------------

    In the above tests, the test substance is to be administered to 
rats by the inhalation route of exposure in either a single exposure 
(acute) or repeated exposures over a 90-day period (subchronic). In 
both acute and subchronic studies, the test substance is to be 
administered to several groups of experimental animals, one exposure 
concentration being used per group. The animals are then to be observed 
under carefully standardized conditions with sufficient frequency to 
ensure the detection of behavioral and/or neurologic abnormalities over 
the range of exposures and also to determine the exposure level which 
results in no neurotoxic effect, i.e. no observed adverse effect level 
(NOAEL). The non-invasive functional observational battery is designed 
to detect gross functional deficits in young adult animals resulting 
from exposure to the administered chemical. The non-invasive motor 
activity test is designed to examine changes in the level and pattern 
of the animals' physical movement. These deficits and changes are also 
to be evaluated in the context of changes in other organ systems. The 
test for neuropathology is designed to detect and characterize 
morphologic changes in the tissue of the nervous system. The nervous 
system tissues are to be examined grossly and microscopically, 
beginning with tissues from animals in the highest dose group and 
proceeding to lower dose groups until a no observed adverse effect 
level (NOAEL) is determined. The non-invasive schedule-controlled 
operant behavior (SCOB) test is intended to evaluate the effects of 
repeated exposure to a chemical on performance of a learned behavior by 
measuring the rate and pattern of responding in relationship to the 
schedule of reinforcement.
    In 1991 EPA updated its guidelines for neurotoxicity testing. The 
1991 guidelines incorporate the functional observational battery, motor 
activity, and neuropathology into a single guideline entitled 
``Neurotoxicity Screening Battery.'' The SCOB test guideline remains a 
separate guideline. The 1991 guidelines evaluate the same endpoints as 
the older guidelines and also provide for greater flexibility in the 
conduct of the testing.
    In September 1993, CMA requested, on behalf of its member companies 
subject to the testing requirements of the final rule, that EPA permit 
testing to be conducted according to the 1991 guidelines instead of the 
guidelines specified in the final test rule (Ref. 4). EPA agreed to 
this modification (Ref. 5). CMA also requested modifications of the 
test guidelines (Refs. 10, 14, 18 and 20) and modifications of the 
deadlines for submitting the test results (Refs. 10, 12, and 15). EPA 
granted most of these requests (Refs. 11, 13, 16, 17, and 19). The 
settlement agreement contemplates the retention of all modifications to 
the final rule's testing requirements in the anticipated ECAs.
    The settlement agreement contemplates the execution of ECAs to 
conduct neurotoxicity and pharmacokinetics testing of the following 7 
chemical substances: 

------------------------------------------------------------------------
             Substance                              Tests               
------------------------------------------------------------------------
acetone............................  SCOB (subchronic)                  
n-amyl acetate, technical grade....  Screening battery (acute and       
                                      subchronic)                       
n-butyl acetate....................  Screening battery (acute and       
                                      subchronic)                       
                                     SCOB (subchronic)                  
                                     Pharmacokinetics/metabolism        
ethyl acetate......................  Screening battery (acute and       
                                      subchronic)                       
                                     SCOB (subchronic)                  
isobutyl alcohol...................  Screening battery (acute and       
                                      subchronic)                       
                                     SCOB (subchronic)                  
methyl isobutyl ketone.............  SCOB (subchronic)                  
tetrahydrofuran....................  Screening battery (acute and       
                                      subchronic)                       
------------------------------------------------------------------------

    Compared with the final rule, the above testing program represents 
a retention of the full set of tests for three chemicals (n-butyl 
acetate, ethyl acetate, and isobutyl acetate), a reduction in tests for 
four chemicals (acetone, n-amyl acetate, methyl isobutyl ketone, and 
tetrahydrofuran), and an elimination of testing for three chemicals (1-
butanol, diethyl ether, and 2-ethoxyethanol). It is anticipated, 
however, that the pharmacokinetics/metabolism test of n-butyl acetate 
may indicate that the separate testing of 1-butanol may not be 
necessary, and because of this 1-butanol manufacturers have agreed to 
share in the cost of n-butyl acetate testing. The evaluation of the 
pharmacokinetics and metabolic fate of butyl acetate will be performed 
in a study of its in vivo hydrolysis to 1-butanol. If the conversion of 
butyl acetate to 1-butanol is sufficiently rapid and complete, EPA may 
determine that the neurotoxic effects of 1-butanol can be predicted 
from the results of butyl acetate testing. If this is not the case, EPA 
may consider reproposing separate testing of 1-butanol.
    The anticipated testing programs for acetone and methyl isobutyl 
ketone (MIBK) include only the SCOB; the neurotoxicity screening 
battery for these two substances would be eliminated. EPA agreed to 
this change for the following reasons: The body of available toxicity 
data on both chemicals is considerable, and the available studies, 
which might, at some level, have shown the types of functional and 
morphologic effects which would be detected by the screening battery, 
do not indicate such effects. Furthermore, the SCOB test, as a test of 
performance dependent on learning and memory, evaluates a very 
different endpoint than those evaluated by the available toxicity 
studies. The SCOB may detect effects not seen in existing studies and 
represents a greater data gap for these chemicals. In the case of 
acetone, there is an additional reason for retaining the subchronic 
SCOB in the testing program. The acute SCOB test of acetone by Glowa 
and Dews was positive (Ref. 6), and EPA believes this positive finding 
bears further investigation in a repeated-dose test. For these reasons, 
EPA believes that this testing would represent a reasonable compromise 
which could avoid protracted litigation while still developing relevant 
data necessary to determine the neurotoxicity of these two chemical 
substances.
    MIBK is currently listed as a hazardous air pollutant (HAP) under 
the Clean Air Act (CAA). EPA is considering initiating a TSCA section 4 
testing program for several CAA HAPs, including MIBK. If neurotoxicity 
testing of MIBK is proposed under this HAPs testing effort, EPA 
believes that a delay of MIBK testing under the anticipated ECA would 
be warranted. The delay, which would remain in effect pending the 
promulgation of the future HAPs test rule, would allow EPA and the MIBK 
test sponsors to coordinate testing efforts under the consent order and 
the future test rule to achieve the most efficient use of testing 
resources.
    For both MIBK and acetone, EPA reserves the right to initiate 
future rulemaking or consent agreements if data from the SCOB tests, 
other section 4 test programs, or any additional new information 
indicate the need for such a step.
    The anticipated testing programs for n-amyl acetate and 
tetrahydrofuran would include only the neurotoxicity screening battery; 
the SCOB tests would be eliminated. Given the limited nature of 
neurotoxicity testing on these chemicals, EPA believes that, at this 
time, the screening battery tests alone would represent an appropriate 
set of tests on these chemicals. Another factor influencing EPA's 
decision is that n-amyl acetate had the lowest production volume and 
lowest estimated exposure of all 10 substances in the final test rule. 
For these reasons, EPA believes that this testing would represent a 
reasonable compromise which could avoid protracted litigation while 
still developing relevant data necessary to determine the neurotoxicity 
of these two chemical substances. EPA, however, reserves the right to 
initiate future rulemaking or consent agreements if new information or 
the data developed from the screening battery tests of n-amyl acetate 
and tetrahydrofuran indicate a need for such a step.
    The decision to propose to revoke all testing requirements for 
diethyl ether and 2-ethoxyethanol (2-EE) is primarily based on the 
estimated potential exposure to these substances. Diethyl ether has the 
second lowest production volume of the 10 substances in the test rule, 
which should directly influence potential exposure. A second 
consideration was that the available toxicity data on diethyl ether 
includes several human studies and more behavioral studies than were 
available on the other 9 substances.
    In the case of 2-ethoxyethanol, EPA anticipates a reduction in the 
potential exposure estimated by the proposed and final rules. The 
environmental release of 2-ethoxyethanol has been confirmed to be on 
the decline by Toxic Release Inventory (TRI) data recently made 
available for the years 1990, 1991, and 1992 (Ref. 9). It is the only 
substance in the final test rule for which current information 
indicates that there is no consumer exposure, i.e. the producers of 2-
EE who are parties to the settlement agreement have represented to EPA 
that there are no current consumer uses of the chemical (Ref. 3). To 
monitor the possible reemergence of any consumer uses of 2-
ethoxyethanol, in the near future EPA intends to propose and promulgate 
a Significant New Use Rule (``SNUR'') under TSCA section 5(a)(2) to 
require notification to EPA 90 days prior to the manufacture, import, 
or processing of 2-EE for use in a consumer product. The parties to the 
agreement have agreed not to oppose such a rule (Ref. 3). Concerning 
occupational exposure to 2-ethoxyethanol, EPA believes that if the 
recently proposed OSHA health standard for 2-ethoxyethanol (58 FR 
15526, March 23, 1993) becomes effective it should reduce the 
likelihood of occupational exposure (Ref. 7). OSHA's regulatory agenda 
schedules this health standard to be finalized as soon as April 1995 
(Ref. 8). Should the implementation of the OSHA health standard be 
significantly delayed because of a legal challenge or if the consumer 
use of 2-ethoxyethanol reemerges, EPA may feel compelled to reconsider 
proposing testing at that time. As stated earlier, EPA reserves the 
right to initiate future rulemaking or consent agreements on these two 
substances if it appears warranted at that time.

III. Proposed Revocation of Final Test Rule and Issues for Comment

    Based upon the reasons stated above, EPA is proposing to revoke the 
final Multi-Substance Rule for the Testing of Neurotoxicity (40 CFR 
799.5050). The decision to allow manufacturers of these substances to 
conduct neurotoxicity and pharmacokinetics testing under ECAs should 
allow for the most timely development and public availability of data 
to assess the potential neurotoxicity of these compounds. While EPA 
acknowledges that the testing that may be conducted under ECAs may not 
be as extensive as that required by the final test rule, EPA believes 
that use of the ECA process will result in the fastest development of 
data. Testing and data development will proceed without the potentially 
lengthy delay of testing pending resolution of costly litigation on the 
merits of the final test rule.

IV. Rulemaking Record

    EPA has established a record for this proposed revocation under 
docket no. OPPTS-42134E. This record contains the information EPA 
considered in reaching the settlement agreement and the following 
information:

A. Supporting Documentation

    (1) Federal Register notices pertaining to this proposed rule 
consisting of:
    (a) Notice of proposed multi-substance rule for the testing of 
neurotoxicity (56 FR 9105, March 4, 1991).
    (b) Notice of final multi-substance rule for the testing of 
neurotoxicity (58 FR 40262, July 27, 1994).
    (2) Communications consisting of:
    (a) Written letters.
    (b) Contact reports of telephone conversations.
    (c) Meeting summaries.

B. References

    (1) Final multi-substance rule for the testing of neurotoxicity 
(58 FR 40262, July 27, 1993).
    (2) Chemical Manufacturers Association (CMA). Petition for 
Review. Filed with United States Court of Appeals for the Fifth 
Circuit. (October 8, 1993).
    (3) United States Court of Appeals for the Fifth Circuit. 
Settlement Agreement between Environmental Protection Agency (USEPA) 
and petitioners. No. 93-5381. (April 28, 1994).
    (4) CMA. Letter from Gordon Strickland to Michael Stahl, Office 
of Compliance Monitoring, Office of Pollution Prevention and Toxics 
(OPPT), USEPA, Washington, DC. (September 16, 1993).
    (5) USEPA. Letter from Charles Auer, Chemical Control Division 
(CCD), OPPT to Gordon Strickland, CMA, Washington, DC. (September 
21, 1993).
    (6) Glowa, J.R. and Dews, P.B. ``Behavioral toxicology of 
volatile organic solvents. IV. Comparisons of the rate-decreasing 
effects of acetone, ethylacetate, methyl ethyl ketone, toluene, and 
carbon disulfide on schedule-controlled behavior of mice.'' Journal 
of the American College of Toxicology. 6:461-469. (1987).
    (7) Occupational Safety and Health Administration (OSHA). 
Proposed rule: ``Occupational exposure to 2-methoxyethanol, 2-
ethoxyethanol and their acetates (Glycol ethers).'' 58 FR 15526 
(March 23, 1993).
    (8) OSHA. Regulatory Agenda. ``Glycol ethers: 2-methoxyethanol, 
2-ethoxyethanol, and their acetates.'' 59 FR 20647. (April 25, 
1994).
    (9) USEPA. Toxic Release Inventory (TRI). Total annual 
environmental releases of 2-ethoxyethanol for the years 1987 through 
1992. TRI printouts. (May 6, 1994).
    (10) CMA. Letter from Barbara Francis to Charles Auer, CCD, 
OPPT, USEPA. (September 30, 1993).
    (11) USEPA. Letter from Charles Auer, CCD, OPPT to Barbara 
Francis, CMA. (October 18, 1993).
    (12) CMA. Letter from Gordon Strickland to Michael Stahl, OCM, 
OPPT, USEPA. (October 26, 1993).
    (13) USEPA. Letter from Charles Auer, CCD, OPPT to Gordon 
Strickland, CMA. (November 4, 1993).
    (14) CMA. Letter from Barbara Francis to Charles Auer, CCD, 
OPPT, USEPA. (November 5, 1993).
    (15) Latham Watkins, Counselors for CMA. Application for Stay or 
modification of acetone testing. (November 5, 1993).
    (16) USEPA. Letter from Charles Auer, CCD, OPPT to Barbara 
Francis, CMA. (November 9, 1993).
    (17) USEPA. Letter from Charles Auer, CCD, OPPT to William 
Rawson, CMA. (November 17, 1993).
    (18) CMA. Letter from Barbara Francis to Charles Auer, CCD, 
OPPT, USEPA. (March 17, 1994).
    (19) USEPA. Letter from Charles Auer, CCD, OPPT to Barbara 
Francis, CMA. (April 12, 1994).
    (20) CMA. Letter from Barbara Francis, CMA, to Charles Auer, 
CCD, OPPT, USEPA. (June 17, 1994).
    (21) United States Court of Appeals for the Fifth Circuit. 
Dismissal of petitioners appeal against EPA. No. 93-5381. (May 13, 
1994).
    The public record for this rulemaking is available for inspection 
in the TSCA Nonconfidential Information Center (also known as the TSCA 
Public Docket Office), Rm. NE B607, 401 M St., SW., Washington, DC from 
12 noon to 4:00 p.m., Monday through Friday, except legal holidays.

V. Regulatory Assessment Requirements

A. Executive Order 12866

    Under Executive Order 12866 (58 FR 51735, October 4, 1993), the 
Agency must determine whether the regulatory action is ``significant'' 
and therefore subject to all the requirements of the Executive Order 
(i.e., Regulatory Impact Analysis and review by the Office of 
Management and Budget (OMB)). Under section 3(f), the order defines 
``significant'' as those actions likely to lead to a rule (1) having an 
annual effect on the economy of $100 million or more, or adversely and 
materially affecting a sector of the economy, productivity, 
competition, jobs, the environment, public health or safety, or State, 
local, or tribal governments or communities (also known as 
``economically significant''); (2) creating serious inconsistency or 
otherwise interfering with an action taken or planned by another 
agency; (3) materially altering the budgetary impacts of entitlements, 
grants, user fees, or loan programs; or (4) raising novel legal or 
policy issues arising out of legal mandates, the President's 
priorities, or the principles set forth in this Executive Order. 
Pursuant to the terms of this order, EPA has determined that this rule 
would not be ``significant.''

B. Regulatory Flexibility Act

    Under the Regulatory Flexibility Act, 5 U.S.C. 601 et seq., EPA is 
certifying that revocation of this test rule would not have a 
significant impact on a substantial number of small businesses because 
only the 28 manufacturers who sign the anticipated ECAs will be 
responsible for conducting and paying for the testing. None of these 
manufacturers are small businesses.

C. Paperwork Reduction Act

    There are no information collection requirements associated with 
this proposed revocation covered under the provisions of the Paperwork 
Reduction Act of 1980, 44 U.S.C. 3501 et seq.

List of Subjects in 40 CFR Part 799

    Chemicals, Chemical export, Environmental protection, Hazardous 
substances, Health effects, Laboratories, Reporting and recordkeeping 
requirements, Testing.

    Dated: June 18, 1994.

Lynn R. Goldman,
Assistant Administrator for Prevention, Pesticides and Toxic 
Substances.

    Therefore, 40 CFR, chapter I, subchapter R, part 799 is proposed to 
be amended as follows:

PART 799--[AMENDED]

    1. The authority citation for part 799 would continue to read as 
follows:
    Authority: 15 U.S.C. 2603, 2611, 2625.

Sec. 799.5050  [Removed]

    2. By removing Sec. 799.5050.

[FR Doc. 94-15567 Filed 6-24-94; 8:45 am]
BILLING CODE 6560-50-F