ENVIRONMENTAL PROTECTION AGENCY

DEPARTMENT OF THE TREASURY

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[PP 4E4349/P582; FRL-4865-5]

RIN No. 2070-AC18

Pesticide Tolerance for Amitraz

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: This document proposes to establish a time-limited tolerance

for residues of the insecticide/miticide amitraz (N'-[2,4-

dimethylphenyl]-N-[[(2,4-dimethylphenyl)-imino]methyl]-N-

methylmethanimidamide) and its metabolites N-(2,4-dimethylphenyl)-N-

methyl formamide and N-(2,4-dimethylphenyl)-N-methylmethanimidamide

(both calculated as the parent) in or on dried hops at 75 ppm, with an

expiration date of 2 years after the beginning date of a final rule.

Nor-Am Chemical Co. submitted a petition to EPA to establish the

maximum permissible levels of residues of the insecticide/miticide in

or on the commodity.

DATES: Comments, identified by the document control number [PP 4E4349/

P582], must be received on or before June 16, 1994.

ADDRESSES: Comments may be submitted to: Public Docket and Freedom of

Information Section, Field Operations Division (7506C), Office of

Pesticide Programs, 401 M St., SW., Washington, DC 20460. In person,

bring comments to: Rm. 1128, CM #2, 1921 Jefferson Davis Hwy.,

Arlington, VA 22202.

Information submitted as a comment concerning this document may be

claimed confidential by marking any part or all of that information

``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. 1128 at

the address given above, from 8 a.m. to 4 p.m., Monday through Friday,

excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: By mail: Dennis H. Edwards, Jr.,

Product Manager (PM) 19, Registration Division (7505C), Environmental

Protection Agency, 401 M St., SW., Washington, DC 20460. Office

location and telephone number: Rm. 207, CM #2, 1921 Jefferson Davis

Hwy., Arlington, VA 22202, (703)-305-6386.

SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the

Federal Register of December 13, 1991 (56 FR 65080), which announced

that Nor-Am Chemical Co., Little Falls Centre One, 2711 Centerville

Rd., Wilmington, DE, 19808, had submitted a food additive petition (FAP

2H5618) to EPA requesting that the Administrator, pursuant to sections

408(d) and 409 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21

U.S.C. 346a(d), 348, establish a tolerance for the insecticide/miticide

amitraz (N'[2,4-dimethylphenyl]-N-[[(2,4-dimethylphenyl)imino]methyl]-

N-methyl-methanimidamide) and its metabolites N-(2,4-dimethylphenyl)-N-

methyl formamide and N-(2,4-dimethylphenyl)-N-methylmethanimidamide

(both calculated as the parent compound) in or on imported dried hops

at 75 ppm. There were no comments received in response to the initial

notice of filing.

Prior to this proposal, EPA had not proposed to establish a

tolerance for amitraz on hops because dried hops have been considered a

processed food requiring a section 409 tolerance and EPA was concerned

that a section 409 tolerance for amitraz might be prohibited by section

409's Delaney anti-cancer clause. Recently, EPA reclassified dried hops

as a raw agricultural commodity. Tolerances for raw agricultural

commodities are set under section 408 of the FFDCA, which contains no

Delaney clause.

EPA has been considering for some time whether dried hops are

properly classified as a processed food. The FFDCA defines a RAC as

``food in its raw or natural state, including all fruits that are

washed, colored, or otherwise treated in their unpeeled natural form

prior to marketing,'' 21 U.S.C. 321 (r). Elsewhere the FFDCA lists

canning, cooking, freezing, dehydration, and milling as examples of

processing activities for RACs (21 U.S.C. 342(a)(2)).

Hops are a unique commodity, used almost exclusively as a flavoring

agent for beer. Harvested in a fresh form (green hops), they are

immediately dried in kilns. This on-farm drying is necessary to prevent

spoilage and always occurs prior to the shipment of the dried hops to

beer manufacturers. While the drying of hops is, in the most general

sense, a form of dehydration, both EPA and FDA have traditionally

treated many forms of dried or partially dried food as RACs, e.g.,

peanuts and grains. Both domestic and international hops growers have

asserted that dried hops should be considered a RAC because the drying

process takes place immediately upon harvest, before the hops leave the

farm or enter commerce, i.e., ``prior to marketing.''

Congress indicated in its most recent appropriations bill for EPA

that it believes that EPA's treatment of dried hops as a processed food

was a misinterpretation of the statute. That bill, Public Law 103-124,

which was signed by President Clinton on October 28, 1993, prohibits

EPA from using funds for any regulatory activity under FFDCA or FIFRA

resulting from the classification of hops as a processed food. In the

Congressional report that accompanied the bill, the Appropriations

Committee explained that this limitation on spending was directed at

barring EPA from acting on what Congress believes is an erroneous

interpretation of the term RAC as it applies to dried hops, S. Rep.

103-137, 103d Cong., 1st Sess. 121 (1993). In consideration of these

factors, EPA revised its guidelines to change the classification of

dried hops from a processed commodity to a RAC.

The data submitted in the petition and all other relevant material

have been evaluated. The toxicology data considered in support of the

tolerance include:

1. A 2-year rat feeding/carcinogenicity study which was negative

for carcinogenic effects under the conditions of the study and which

had a NOEL of 50 ppm (2.5 mg/kg/bwt) for noncarcinogenic effects.

2. A three-generation rat reproduction study with a NOEL of 15 ppm

(1.5 mg/kg/bwt); rat and rabbit teratology studies which were negative

at doses up to 12 mg/kg/bwt and 25 mg/kg/bwt, respectively.

3. A 2-year mouse carcinogenicity study which demonstrated an

increase in the incidence of hepatocellular tumors in female mice.

4. A 2-year dog feeding study with a NOEL of 0.25 mg/kg/bwt which

demonstrated increased blood glucose and slight hypothermia after

dosing at the 1.0 mg/kg/bwt dose. The reference dose (RfD), based on

the 2-year dog feeding study with a NOEL of 0.25 mg/kg/bwt and a 100-

fold uncertainty factor, is calculated to be 0.0025 mg/kg of body

weight/day.

The 2-year mouse carcinogenicity study which showed an increase in

the incidence of hepatocellular tumors in female mice was referred to

the Agency's Carcinogen Assessment Group (CAG) for evaluation. CAG

(1986) concluded that amitraz should be classified as a possible human

carcinogen, Group C. This classification is based on the Agency's

``Guidelines for Carcinogen Risk Assessment'' published in the Federal

Register of September 24, 1986 (51 FR 33992). In its evaluation, CAG

considered the following information:

1. The positive carcinogenic effects were found in only one

species, the mouse.

2. Tumors were discovered mostly in animals at the scheduled

terminal sacrifice.

3. The rat was negative for carcinogenic effects at doses as high

as 200 ppm.

4. There is no positive epidemiological carcinogenicity data for

amitraz.

On February 12, 1986, the Federal Insecticide, Fungicide and

Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) completed a

review of the data base for the Group C classification of amitraz. The

SAP concluded that the weight-of-the-evidence was inadequate to clearly

categorize amitraz. Amitraz has also been determined to be negative in

the gene mutation, host-mediated, and dominant-lethal test systems.

Studies such as the Ames bacterial test, a mouse lymphoma assay, and an

unscheduled DNA synthesis in human embryonic cells have been conducted

with amitraz, also with negative results. For these reasons, the SAP

disagreed with the Agency classification and recommended that amitraz

be classified as a Group D carcinogen (not classifiable as to human

carcinogenicity).

Despite the SAP's recommendation, the Agency continued to regulate

amitraz as a Group C carcinogen, without quantification of the risk. In

late 1990, however, the Agency decided to reexamine the weight-of-the-

evidence regarding the carcinogenic potential of amitraz. The ``C''

classification was reaffirmed, but quantification of potential human

cancer risk, using a low-dose extrapolation model (Q*1), was

recommended. This decision was based on the fact that amitraz was

associated with the induction of multisite benign and malignant tumors

in different strains of male and female mice. Some of these tumors

(hepatocellular tumors) are considered relatively uncommon in female

B6C3F1 mice.

The Agency prepared a dietary risk assessment for amitraz in

support of the cotton tolerances recently established (58 FR 14314;

Mar. 17, 1993). The resulting dietary risk was calculated to be 2.5 X

10-6 (for the cottonseed/eggs/poultry use, plus pears, cattle,

swine and honey/beeswax). New assessments, using more accurate usage

information for cotton, pears, swine, and the honey (beehive) use, have

since lowered the overall risk to 1.7 X 10-6. The addition of the

use on hops will add 1.2 X 10-6 to this risk, assuming exposure

over a lifetime of 70 years. However, as this is a 2-year tolerance,

the actual risk is much lower.

The tolerance established would be for 2 years, with an expiration

date of 2 years after the beginning date of a final rule. The Agency

expects additional residue data to be submitted, as well as further

information on usage and sales of amitraz overseas, which may enable

EPA to refine and reevaluate the risk at the end of the 2-year period.

At this time, no residue data has been submitted for the U.S., and

there are no U.S. registrations for the use of amitraz on hops. The

Agency will not consider any applications for registration of amitraz

to be used on hops in the U.S., nor will EPA consider any special local

needs registrations (FIFRA section 24c) for amitraz.

The anticipated residue contribution (ARC) for this chemical from

published tolerances utilizes 1.4% of the RfD. The proposed tolerance

will contribute 0.000025 mg/kg/bwt/day to the human diet utilizing an

additional 1% of the RfD. This results in a total utilization of 2.4%

of the RfD.

The OPP Reference Dose Committee (RfD) recently reviewed the

toxicity data base for amitraz. In doing so, the Committee indicated

that based on evidence of some developmental toxicity at relatively low

dose levels in the rabbit developmental toxicity study, an acute

dietary risk assessment was appropriate. A Margin of Exposure (MOE) for

females aged 13 and above (the population subgroup of concern for

developmental toxicity) was calculated by comparing the NOEL of 5.0 mg/

kg bwt/day from the rabbit study to the calculated high-end exposure of

0.05 mg/kg bwt/day. The calculated MOE in this case is exactly 100;

generally, the Agency is not concerned unless the MOE is less than 100.

The analysis assumes uniform distribution of amitraz in the commodity

supply and that residues are present at tolerance level for the

published uses in addition to hops. The Agency considers this to be

extremely unlikely.

The nature of the residue in plants and livestock is adequately

understood. The analytical method is a common moiety method which

converts amitraz and its two metabolites to 2,4-dimethylaniline.

Determination of the residues is by gas chromatography using 63Ni

electron detection. There are currently no actions pending against

continued registration of this chemical.

Based on the above information considered by the Agency, 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 FIFRA, as amended, which contains

any of the ingredients listed herein, may request within 30 days after

publication of this document in the Federal Register that this

rulemaking proposal be referred to an Advisory Committee in accordance

with FFDCA section 408(e).

Interested persons are invited to submit written comments on the

proposed regulation. Comments must bear a notation indicating the

document control number, [PP 4E4349/P582]. All written comments filed

in response to this petition will be available in the Public Docket and

Freedom of Information Section, at the address given above from 8 a.m.

to 4 p.m., Monday through Friday, except legal holidays.

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, Recording and

recordkeeping requirements.

Dated: May 9, 1994.

Stephen L. Johnson,

Acting Director, Registration Division, Office of Pesticide Programs.

Therefore, it is proposed that chapter I of title 40 Code of

Federal Regulations 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. 180.287, by amending the table therein by adding and

alphabetically inserting the raw agricultural commodity dried hops, to

read as follows:

Sec. 180.287 Amitraz; tolerances for residues.

* * * * *

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Parts per

Commodity million

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Hops, dried\1\............................................. 75

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\1\Tolerance expires (date 2 years after beginning date of final rule).

[FR Doc. 94-12102 Filed 5-13-94; 2:31 pm]

BILLING CODE 6560-50-F