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avermectin (Agri-Mek, Affirm) Time-limited Tolerance 9/95

[Federal Register: September 13, 1995 (Volume 60, Number 177)]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4E4419/P626; FRL-4970-8]
RIN 2070-AC
Avermectin B1 and its Delta-8,9 Isomer
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: EPA proposes to establish time-limited tolerances for the combined 
residues of the insecticide avermectin B1 and its delta-8,9-isomer in or on 
the raw agricultural commodities dried hops and cattle fat. The proposed 
regulation to establish maximum permissible levels for residues of the 
insecticide was requested in a petition submitted by the Interregional 
Research Project No. 4 (IR-4). The time-limited tolerances for dried hops and 
cattle fat would expire on April 30, 1996.

DATES: Comments, identified by the document control number [PP 4E4419/P626], 
must be received on or before October 13, 1995.

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 comments to: Rm. 1132, CM #2, 1921 Jefferson Davis 
Hwy., Arlington, VA 22202. Comments and data may also be submitted to OPP by 
sending electronic mail (e-mail) to:
                  opp-docket@epamail.epa.gov
    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 4E4419/P626]. Electronic comments on this proposed rule may be filed 
online at many Federal Depository Libraries. Additional information on 
electronic submissions can be found in the "SUPPLEMENTAL INFORMATION" section 
of this document.
    Information submitted as a comment concerning this document may be claimed 
confidential by marking any part or all of that information as "Confidential 
Business Information." CBI should not be submitted through e-mail. Information 
marked as CBI 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 4:30 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Hoyt L. Jamerson, Registration 
Division (7505W), Office of Pesticide Programs, Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460. Office location and telephone 
number: Sixth Floor, Crystal Station #1, 2800 Jefferson Davis Hwy., Arlington, 
VA 22202, (703)-308-8783; e-mail: jamerson.hoyt@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: The Interregional Research Project No. 4 (IR-4), 
New Jersey Agricultural Experiment Station, P.O. Box 231, Rutgers University, 
New Brunswick, NJ 08903, has submitted pesticide petition (PP) 4E4419 to EPA 
on behalf of the Idaho, Oregon, and Washington Hop Commissions, and the Hop 
Growers of America. This petition requests that the Administrator, pursuant to 
section 408(e) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 
346a(e), amend 40 CFR 180.449 by establishing time-limited tolerances for the 
combined residues of the insecticide avermectin B1 [a mixture of avermectins 
containing greater than or equal to 80 percent avermectin B1a (5-O-demethyl 
avermectin A1a and less than or equal to 20 percent avermectin B1b (5-O-
demethyl-25-de(1-methylpropyl)-25-(1-methylethyl) avermectin A1a)] and its 
delta-8,9-isomer in or on the raw agricultural commodities dried hops at 0.5 
part per million (ppm) and cattle fat at 0.015 ppm.
    The scientific data submitted in the petition and other relevant material 
have been evaluated. The toxicological data considered in support of the 
proposed tolerances include:
    1. A 1-year feeding study with dogs fed diets containing 0.25, 0.50, or 
1.0 milligram (mg)/kilogram (kg)/day with a no-observed-effect level (NOEL) of 
0.25 mg/kg/day. A high incidence of mydriasis (excessive dilation of the pupil 
of the eye) was observed in male and female dogs at the 0.50-mg/kg/day dose 
level.
    2. A 2-year chronic toxicity/carcinogenicity study with rats fed diets 
containing 0, 0.75, 1.5, or 2.0 mg/kg/day with a systemic NOEL of 1.5 
mg/kg/day. Tremors were observed in male and female rats fed diets containing 
2.0 mg/kg/day. No carcinogenic effects were observed under the conditions of 
the study.
    3. A chronic toxicity/carcinogenicity study in mice fed diets containing 
0, 2.0, 4.0, or 8.0 mg/kg/day for 94 weeks with a systemic NOEL of 4 mg/kg/day 
based on increased mortality, dermatitis, and extramedullary hematopoiesis in 
the spleen of males, and body weight loss in females at the 8.0 mg/kg/day dose 
level.
    4. A two-generation reproduction study in rats fed diets containing 0, 
0.06, 0.12, or 0.40 mg/kg/day with a NOEL of 0.12 mg/kg/day. The lowest-
observed-effect level (LOEL) was established at 0.40 mg/kg/day based on 
increased retinal folds in weanlings, increased dead pups at birth, decreased 
viability indices, decreased lactation indices, and decreased pup body 
weights.
    5. A developmental toxicity study with rats given gavage doses of 0, 0.4, 
0.8, or 1.6 mg/kg/day with no developmental toxicity observed under the 
conditions of the study.
    6. A developmental toxicity study with mice given gavage doses at 0, 0.1, 
0.2, 0.4, or 0.8 mg/kg/day. The LOEL for developmental toxicity (cleft palate) 
was established at 0.4 mg/kg/day.
    7. A developmental toxicity study with rabbits given gavage doses with 
NOEL's for developmental and maternal toxicity at 1.0 mg/kg/day. The LOEL for 
developmental toxicity was established at 2.0 mg/kg/day based on cleft palate, 
clubbed foot, and delayed ossification.
    8. Avermectin B1 tested negative for mutagenic effects in the Ames assay, 
V-79 mammalian cell assay, structural chromosomal aberration assay (in vitro 
in Chinese hamster ovary cells), and in vivo bone marrow cytogenic study in 
male mice. Avermectin B1 produced an increase in single strand DNA breaks in a 
rat in vitro hepatocyte mutagenicity study. However, no mutagenic effects were 
observed when the assay was carried out in vivo at 10.6 mg/kg.
    Toxicity studies reviewed for the delta-8,9-isomer of avermectin B1 
include:
    9. A developmental toxicity study in rats given gavage doses of 0, 0.25, 
0.50, and 1.0 mg/kg/day with no developmental toxicity observed under the 
conditions of the study.
    10. A mouse developmental toxicity study with a NOEL of 0.06 mg/kg/day 
based on developmental toxicity (cleft palate) at the 0.10 mg/kg/day dose 
level.
    11. A one-generation reproduction study with rats fed diets containing 0, 
0.06, 0.12, or 0.40 mg/kg/day with a NOEL for reproductive effects at 0.40 
mg/kg/day. There were no reproductive effects observed under the conditions of 
the study.
    12. An Ames mutagencity study was negative in the presence of S-9 
activation.
    Dietary risk assessements for avermectin indicate that there is minimal 
risk from established tolerances and the proposed tolerances for dried hops 
and cattle fat. Dietary risk assessments were conducted using the Reference 
Dose (RfD) to assess chronic exposure and risk and the Margin of Exposure 
(MOE) for acute toxicity.
    The RfD is calculated at 0.0004 mg/kg/day, based on a NOEL of 0.12 
mg/kg/of body weight/day from the two-generation reproduction study in the rat 
and an uncertainty factor of 300. The anticipated residue contribution (ARC) 
from existing tolerances and the proposed tolerances for dried hops and cattle 
fat utilizes 6 percent of the RfD for the general population and 21 percent of 
the RfD for nonnursing infants (less than 1-year old).
    The MOE is a measure of how closely the high-end acute dietary exposure 
comes to the NOEL from the toxicity endpoint of concern. For avermectin the 
MOE was calculated as a ratio of the NOEL (0.06 mg/kg/day) from the mouse 
developmental toxicity study to dietary exposure, as estimated for the 
population subgroup at greatest risk (females of child-bearing age). The MOE 
for females of childbearing age is greater than 100 for high-end exposure. 
Acute dietary MOE's of of less than 100 are generally of concern to EPA.
    The nature of the residue in or on hops is adequately understood. The 
enforcement method, which was developed by the registrant, Merck Research 
Laboratories, has been validated by an independent laboratory. The enforcement 
method will be submitted to the Food and Drug Administration for publication 
in the Pesticide Analytical Manual, Volume II (PAM II), when EPA's Analytical 
Chemistry Laboratory has successfully completed its own validation of the 
enforcement method. The analytical method is being made available, in the 
interim, to anyone with an interest in pesticide enforcement when requested 
from: Calvin Furlow, Public Response and Program Resources Branch, Field 
Operations Divisions (7506C), Office of Pesticide Programs, Environmental 
Protections Agency, 401 M St., SW., Washington, DC 20460. Office location and 
telephone number: Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 
22202 (703)-305-5937.
    Any secondary residues will be covered by existing tolerances for meat, 
meat byproducts, and milk and the proposed tolerance for cattle fat at 0.015 
ppm. The established tolerances for meat, meat byproducts, and milk will 
expire on April 30, 1996, which coincides with conditional registrations for 
use of avermectin on cotton and citrus. (See the Federal Registers of August 
3, 1994 (59 FR 39505) and September 30, 1994 (59 FR 49825), for additional 
information regarding the conditional registrations for cotton and citrus.) 
The proposed tolerance for cattle fat will expire on April 30, 1996, which 
also coincides with the expiration date for time-limited tolerances for meat, 
meat byproducts, and milk. EPA intends to make a decision on the registrations 
for cotton and citrus prior to April 30, 1996. If full registration is issued, 
the time-limited restrictions will be removed from the avermectin tolerances 
for meat, meat byproducts, cattle fat, and milk.
    EPA is establishing the tolerance for dried hops with an expiration date 
of April 30, 1996, to allow IR-4 time to submit additional residue data in 
support of a permanent tolerance for dried hops, and to allow EPA additional 
time to evaluate the enforcement method for dried hops. A permanent tolerance 
for dried hops must also await establishment of permanent tolerances for meat, 
meat byproducts, cattle fat, and milk.
    There are currently no actions pending against the continued registration 
of this chemical.
    Based on the information and data considered, the Agency has determined 
that the tolerance established by amending 40 CFR part 180 would protect the 
public health. Therefore, it is proposed that the tolerance be established as 
set forth below.
    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.
    Interested persons are invited to submit written comments on the proposed 
regulation. Comments must bear a notation indicating the document control 
number, [PP 4E4359/P626]. Electronic comments can be sent directly to EPA at:
                       opp-Docket@epamail.epa.gov
    Electronic comments must be submitted as an ASCII file avoiding the use of 
special characters and any form of encryption.
    A record has been established for this rulemaking under docket number [PP 
4E4419/P626] (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.
    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.
    Under Executive Order 12866 (58 FR 51735, Oct. 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.
    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: August 30, 1995.


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. In Sec. 180.449, by amending paragraph (a) in the table therein by 
adding and alphabetically inserting listings for cattle fat and dried hops and 
by amending paragraph (b) by revising the introductory text, to read as 
follows:

Sec. 180.449   Avermectin B1 and its delta-8,9-isomer; tolerances for 
residues.

    (a) *  *  *

------------------------------------------------------------------------
                                                 Parts per    Expiration
Commodity                                         million        date   
------------------------------------------------------------------------
                                                                        
Cattle, fat...................................     0.015          Do.
                                                                     
                  *        *        *        *     *                 
Hops, dried...................................     0.5            Do.
                  *        *        *        *     *                 
                                                                     
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    (b) A tolerance is established for the combined residues of the 
insecticide avermectin B1 [a mixture of avermectins containing greater than or 
equal to 80 percent avermectin B1a (5-O-demethyl avermectin A1a) and greater 
than or equal to 20 percent avermectin B1b (5-O-demethyl-25-de(1-methylpropyl) 
-25-(1-methylethyl) avermectin A1a)] and its delta-8,9-isomer in or on the 
following commodities:
* * * * *