[Federal Register Volume 61, Number 21 (Wednesday, January 31, 1996)]
[Proposed Rules]
[Pages 3363-3365]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-1917]



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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180

[PP 0E3853/P640; FRL-4993-6]
RIN 2070-AC18


Pesticide Tolerance for Hexaconazole

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: EPA proposes to establish a time-limited tolerance, to expire 
on (3) years after the signature date of the final rule), for residues 
of the fungicide hexaconazole, [alpha-butyl-alpha-(2,4-dichloro-
phenyl)-1H-1,2,4-triazole-1-ethanol)], in or on the imported raw 
agricultural commodity bananas at 0.1 part per million (ppm). Zeneca 
Agrochemicals Products (Zeneca) petitioned for this regulation to 
establish a maximum permissible level for residues of the fungicide.

DATES: Comments, identified by the document control number [PP 0E3853/
P488], must be received on or before March 1, 1996.

ADDRESSES: By mail, submit written comments to: Public Response and 
Program Resources Branch, Field Operations Division (7506C), Office of 
Pesticide Programs, Environmental Protection Agency, 401 M St., SW., 
Washington, DC 20460. In person, bring a copy of the comments to Rm. 
1132, CM #2, 1921 Jefferson Davis Highway., Arlington, VA 22202.
    Information submitted as a comment concerning this notice may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). Information so marked will 
not be disclosed except in accordance with procedures set forth in 40 
CFR part 2. A copy of the comment that does not contain CBI must be 
submitted for inclusion in the public record. Information not marked 
confidential may be disclosed publicly by EPA without prior notice. All 
written comments will be available for public inspection in Rm. 1132 at 
the address given above, from 8 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.
    Comments and data may also be submitted electronically by sending 
electronic mail (e-mail) to: [email protected]. Electronic 
comments must be submitted as an ASCII file avoiding the use of special 
characters and any form of encryption. Comments and data will also be 
accepted on disks in WordPerfect 5.1 file format or ASCII file format. 
All comments and data in electronic form must be identified by the 
docket number, ``[PP 0E3853/P640].'' No Confidential Business 
Information (CBI) should be submitted through e-mail. Electronic 
comments on this proposed rule may be filed online at many Federal 
Depository Libraries. Additional information on electronic submissions 
can be found below.

FOR FURTHER INFORMATION CONTACT: By mail: Connie B. Welch, Product 
Manager (PM) 21, Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location and telephone number: Rm. 227, CM #2, 1921 
Jefferson Davis Highway., Arlington, VA 22202, (703) 305-6900, e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION: EPA is proposing to establish a time-limited 
tolerance for residues of the fungicide hexaconazole, [(alpha-butyl-
alpha-(2,4-dichlorophenyl)-1H-1,2,4-triazole-1-ethanol)], in or on the 
raw agricultural commodity bananas at 0.1 part per million (ppm). The 
proposed regulation to establish a maximum permissible level of the 
fungicide pursuant to section 408(e) of the Federal Food, Drug, and 
Cosmetic Act (FFDCA), 21 U.S.C. 346a, by amending 40 CFR part 180 to 
include this commodity was requested in a petition (0E3853) submitted 
by Zeneca, New Murphy Road, Concord Pike, Wilmington, DE 19897. The 
scientific data submitted in the petition and other relevant material 
have been evaluated. The toxicological data 

[[Page 3364]]
considered in support of the proposed tolerance include the following:
    1. In a 2-year feeding study in rats, hexaconazole was tested at 
10, 100 and 1,000 ppm (equivalent to 0.47, 4.7 and 47 mg/kg/day in 
females and 0.61, 6.1 and 61 mg/kg/day in males). The no-observed-
effect level (NOEL) was established at 100 ppm (equivalent to 0.61 and 
0.47 mg/kg/day in males and females, respectively) for body weight gain 
reduction and liver pathology (centrilobular fatty changes and 
hypertrophy).
    2. A 1-year dog feeding study using doses of 2, 10 and 50 mg/kg/
day, tested hexaconazole in male and female Beagle dogs. The chemical 
was administered in gelatin capsules. The NOEL was established at 2 mg/
kg/day based upon fatty infiltration of the liver and increased liver 
weight.
    3. In a developmental toxicity study, hexaconazole was tested at 
2.5, 25 and 250 mg/kg/day in Wistar rats. The NOEL/LOEL for maternal 
toxicity were considered to be 25 and 250 mg/kg/day based upon reduced 
body weight gain. The LOEL for developmental toxicity was established 
at 25 mg/kg/day based upon delayed skeletal ossification and increased 
incidence of the 14th rib (bilateral). The NOEL for developmental 
toxicity was found to be 2.5 mg/kg/day.
    In two developmental toxicity studies involving New Zealand White 
rabbits, hexaconazole was tested at 25, 50 and 100 mg/kg/day. The NOEL/
LOEL for maternal toxicity were established at 50 and 100 mg/kg/day 
based upon reduced maternal body weight gain. The NOEL/LOEL for 
developmental toxicity were considered to be 25 and 50 mg/kg/day based 
upon decreased mean fetal body weight.
    The Agency is requiring an occupational exposure risk assessment 
based on the NOEL of 2.5 mg/kg/day demonstrated in the developmental 
toxicity study in rats, as well as, an acute dietary exposure study in 
rats.
    4. In a 2-generation reproduction study in Wistar rats, the 
chemical was tested at 20, 100 and 1,000 ppm (equivalent to 1, 5 and 50 
mg/kg/day). On the basis of abnormal liver pathology, a systemic NOEL 
was set at 20 ppm. The NOEL/LOEL for reproductive toxicity were 
established at 100 and 1,000 ppm based upon decreased weight gain and 
survival in pups. Reproductive toxicity of hexaconazole was considered 
minimal.
    5. From a 2-year carcinogenicity study in Wistar rats, hexaconazole 
was classified as a Group C (possible Human) carcinogen with a Q1* 
of 0.023 mg/kg/day based on testicular Leydig cell tumors. This 
classification was recommended based upon a statistically significant 
increase in benign Leydig cell tumors, with a positive dose-related 
trend in rats. Moreover, the Leydig cell tumor is an uncommon tumor in 
this strain of rats, and occurred at an accelerated rate and at a dose 
level below what would be considered an adequate level to determine the 
carcinogenic potential of hexaconazole. There was also some indication 
of marginal increases in liver cell tumors in mice. The classification 
was further supported by structural similarity of hexaconazole to other 
triazole pesticides known for their potential as liver carcinogens in 
mice.
    6. The Reference Dose (RfD) value for use in dietary exposure 
analysis was 0.02 mg/kg body weight(bwt)/day, basis of a NOEL of 2 mg/
kg bwt/day and an uncertainty factor of 100. This NOEL was derived from 
a 1-year feeding study in dogs that showed increased liver weight 
accompanied by fatty infiltration of the liver observed at 10 mg/kg/
day.
    7. A chronic dietary exposure analysis for use of hexaconazole in/
on imported bananas was performed to estimate the Theoretical Maximum 
Residue Contribution (TMRC) for the general population and 22 
population subgroups. Results show the TMRC and %RfD for the U.S. 
population is 0.023 g/kg/day and 0.11% for the RfD, 
respectively. The highest exposed subgroup is non-nursing infants (<1 
year old) for which TMRC and %RfD are 0.108 g/kg/day and 
0.45%, respectively.
    The Agency concluded from this analysis that chronic dietary risk 
is not a concern.
    8. From cancer risk assessment, the upper-bound carcinogenic risk 
from food uses of hexaconazole for the general U.S. population as 
calculated using the following equation:

    Upper Bound Cancer Risk = Dietary Exposure (TMRC)  x  Q1*

Based on a Q1* of 0.023 (mg/kg/day)-1 the upper bound cancer 
risk was calculated to be 5.3  x  10-7, contributed by the upper 
bound excess lifetime carcinogenic risk appears to be below the range 
that the Agency generally considers to be negligible.
    9. Mutagenicity assays including an Ames test, an invitro 
cytogenetics assay in human lymphocytes, an assay for unscheduled DNA 
synthesis in rat hepatocytes, and a micronucleus assay in mice were 
conducted on this chemical. The results of these tests produced no 
evidence of mutagenicity due to hexaconazole.
    Acute toxicity testing is not required for import tolerances and 
those data are not presented here.
    The nature of the residue in bananas is adequately understood. The 
residue to be regulated is parent hexaconazole. Based on the residue 
data submitted which reflected application to bagged bananas (the 
typical agricultural practice in the countries of origin), residue 
levels in bananas treated with hexaconazole are not likely to exceed 
the requested 0.1 ppm tolerance. However, the Agency's current practice 
is to review data on unbagged bananas as well as bagged bananas to 
insure that a worst case scenario is examined. Therefore, the 
petitioner is required to conduct at least four residue trials on 
unbagged bananas. Ample time is provided for completion of these trials 
over the duration of this proposed time-limited tolerance.
    Adequate analytical methodology is available for enforcement. Prior 
to their publication in the Pesticide Analytical Manual, Vol. II, the 
enforcement methodology is being made available in the interim to 
anyone who is interested in pesticide enforcement when requested from: 
Calvin Furlow, Public Information Branch, Field Operations Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
401 M St., SW., Washington, DC 20460. Office location and telephone 
number: Rm 1128C, CM #2, 1921 Jefferson Davis Highway, Arlington, VA 
22202, (703) 305-5232.
    The pesticide is considered useful for the purpose for which the 
tolerance is sought. Based on the information and data considered, the 
Agency has determined that the tolerance established by amending 40 CFR 
part 180 will protect the public health. Therefore, the tolerances are 
established as set forth below. By way of public reminder, this notice 
also reiterates the registrant's responsibility under section 6(a)(2) 
of FIFRA, to submit additional factual information regarding adverse 
effects on the environment and to human health by these pesticides.

Public Docket

    Any person who has registered or submitted an application for 
registration of a pesticide, under the Federal Insecticide, Fungicide, 
and Rodenticide Act (FIFRA) as amended, which contains any of the 
ingredients listed herein, may request within 30 days after publication 
of this notice in the Federal Register that this rulemaking proposal be 
referred to an Advisory Committee in accordance with section 408(e) of 
the FFDCA.

[[Page 3365]]

    Interested persons are invited to submit written comments on the 
proposed regulation. A record has been established for this rulemaking 
under docket number [PP 0E3853/P640] (including comments and data 
submitted electronically as described below). A public version of this 
record, including printed, paper versions of electronic comments, which 
does not include any information claimed as CBI, is available for 
inspection from 8 a.m. to 4:30 p.m., Monday through Friday, excluding 
legal holidays. The public record is located in Room 1132 of the Public 
Response and Program Resources Branch, Field Operations Division 
(7506C), Office of Pesticide Programs, Environmental Protection Agency, 
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Electronic comments can be sent directly to EPA at:

    opp-D[email protected]

    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption.
    The official record for this rulemaking, as well as the public 
version, as described above will be kept in paper form. Accordingly, 
EPA will transfer all comments received electronically into printed, 
paper form as they are received and will place the paper copies in the 
official rulemaking record which will also include all comments 
submitted directly in writing. The official rulemaking record is the 
paper record maintained at the address in ``ADDRESSES'' at the 
beginning of this document.

Administrative 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, 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 entitlement, 
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 Executive Order, EPA has determined 
that this rule is not ``significant'' and is therefore not subject to 
OMB review.

B. Regulatory Flexibility Act

    Pursuant to the requirements of the Regulatory Flexibility Act 
(Pub. L. 96-354, 94 Stat. 1164, 5 U.S.C. 601-612), the Administrator 
has determined that regulations establishing new tolerances or raising 
tolerance levels or establishing exemptions from tolerance requirements 
do not have a significant economic impact on a substantial number of 
small entities. A certification statement to this effect was published 
in the Federal Register of May 4, 1981 (46 FR 24950).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: January 17, 1996.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs
    Therefore, it is proposed that 40 CFR part 180 be amended as 
follows:

PART 180--[AMENDED]

    1. The authority citation for part 180 continues to read as 
follows:

    Authority: 21 U.S.C. 346a and 371.

    2. By adding new Sec. 180.488, to read as follows:


Sec. 180.488   Hexaconazole; tolerance for residues.

    A tolerance is established for residues of the fungicide 
hexaconazole, [alpha-butyl-alpha-(2,4-dichloro-phenyl)-1H-1,2,4-
triazole-1-ethanol)], in or on the imported raw agricultural commodity 
bananas at 0.1 part per million. This tolerance will expire on [ 3 
years after the signature date of the final rule]. There are no U.S. 
registrations as of January 31, 1996 for use on bananas.
[FR Doc. 96-1917 Filed 1-30-96; 8:45 am]
BILLING CODE 6560-50-F