[Federal Register Volume 59, Number 27 (Wednesday, February 9, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-2699]
[[Page Unknown]]
[Federal Register: February 9, 1994]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP-5F3251/P577; FRL-4757-5]
RIN No. 2070-AC18
Pesticide Tolerances for Aluminum Tris(O-Ethylphosphonate)
AGENCY: Environmental Protection Agency (EPA).
ACTION: Proposed rule.
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SUMMARY: This document proposes to establish a tolerance for residues
of the fungicide fosetyl-Al, aluminum tris(O-ethylphosphonate) in or on
dried hops at 45 ppm. This regulation to establish the maximum
permissible level of residue of the fungicide in or on the commodity
was requested in a petition submitted by Rhone-Poulenc Ag Co.
DATES: Comments, identified by the document control number [PP-5F3251/
P577], must be received on or before March 11, 1994.
ADDRESSES: By mail, submit written comments to: Public Docket and
Freedom of Information Section, Field Operations Division (7506C),
Office of Pesticide Programs, Environmental Protection Agency, 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 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. 1128 at
the Virginia address given above, from 8 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Product
Manager (PM) 22, Registration Division (7505C), Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location and telephone number: Rm. 229, CM #2, 1921 Jefferson Davis
Hwy., Arlington, VA 22202, (703)-305-5540.
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of May 24, 1985 (50 FR 21503), which announced that
Rhone-Poulenc Ag Co., P.O. Box 12014, 2 T.W. Alexander Drive, Research
Triangle Park, NC 27709, had submitted a pesticide tolerance petition
(PP 5F3251) and a food/feed additive petition (FAP 5H5468) 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),
establish a tolerance for the fungicide fosetyl-Al, aluminum tris(O-
ethylphosphonate) in or on fresh hops at 10 parts per million (ppm) and
dried hops at 20 ppm, respectively. Subsequently, Rhone-Poulenc
petitioned the Agency to amend the proposed tolerance for dried hops to
increase the tolerance from 20 ppm to 45 ppm. Rhone-Poulenc amended the
proposed tolerance a second time, notice of which appeared in the
Federal Register of January 7, 1994 (59 FR 1017), requesting a section
408 tolerance for fosetyl-Al of 45 ppm in hops instead of separate
tolerances for fresh and dried hops under sections 408 and 409. There
were no comments received in response to the initial notice of filing.
Prior to this action, EPA had not proposed to establish a tolerance
for fosetyl-Al 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 fosetyl-Al 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.'' Elsewhere, the FFDCA lists canning, cooking,
freezing, dehydration, and milling as examples of processing activities
for RACs.
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. EPA requests comments
on this change. To be consistent, EPA is proposing this tolerance as on
dried hops rather than on hops as requested by Rhone-Poulenc.
The data submitted in the petitions and all other relevant material
have been evaluated. The toxciology data considered in support of the
tolerances include:
1. A rat acute oral study with an LD50 of 5.4 grams (g)/
kilogram (kg).
2. A mouse acute oral study with an LD50 of 3.4 gm/kg.
3. A 90-day rat feeding study with a no-observed-effect level
(NOEL) of 5,000 ppm (500 milligrams (mg)/kg/day).
4. A 90-day dog feeding study with a NOEL of 10,000 ppm (250 mg/kg/
day).
5. A 21-day rabbit dermal study with a NOEL of 1.5 g/kg/day (the
highest dose tested (HDT)).
6. A carcinogenicity study in mice with no carcinogenic effects
observed at any dose level under the conditions of the study (the
highest dose tested was 2,857/4,286 mg/kg body weight (bwt)/day).
7. A rat chronic feeding/carcinogenicity study with a NOEL of 8,000
ppm (400 mg/kg/ bwt/day) for systemic effects (carcinogenic effects
observed are discussed below).
8. A 2-year dog feeding study with a NOEL of 10,000 ppm (250 mg/kg
bwt/day) and a lowest-effect-level (LEL) of 20,000 ppm (500 mg/kg bwt/
day) based on slight degenerative effects on the testes.
9. A reproduction study in rats with a NOEL of 300 mg/kg/bwt/day
and an LEL of 600 mg/kg/ bwt/day based on effects on animal weights in
some groups and urinary tract changes in some groups.
10. Teratology studies in rabbits and rats with teratogenic NOELs
of 500 mg/kg/day and 1,000 mg/kg/day, respectively.
11. Ames mutagenicity assays, E. coli phage induction tests,
micronucleus tests in mice, DNA repair tests using E. coli, and
Saccharomyces cervisiae yeast assay that were negative.
As stated in a notice published in the Federal Register of November
2, 1983 (48 FR 50532), carcinogenic effects were noted in the rat
chronic feeding/carcinogenicity study. In this study, Charles River CD
rats were dosed with aluminum tris(O-ethylphosphonate) at levels of 0,
2,000, 8,000, and 40,000/30,000 ppm (0, 100, 400, and 2,000/1,500 mg/kg
bwt/day). The 40,000 ppm dose was reduced to 30,000 ppm after 2 weeks
following observations of staining of the abdominal fur and red
coloration of the urine at 40,000 ppm (2,000 mg/kg bwt/day).
The highest dose level of the chemical tested in the male Charles
River CD-1 rats (2,000/1,500 mg/kg bwt/day) in this study appears to
approximate a maximum tolerated dose (MTD) based on the finding of
urinary bladder hyperplasia at this dose. Similarly, an MTD level
appeared to be satisfied in the female Charles River CD-1 rats at the
high-dose level of 2,000 mg/kg/ bwt/day, during the first 2 weeks of
the carcinogenicity/chronic feeding study, before the dose level was
reduced to 1,500 mg/kg bwt/day.
The study demonstrated a significantly elevated incidence of
urinary bladder tumors (adenomas and carcinomas combined) at the
highest dose level tested (2,000/1,500 mg/kg) in male Charles River CD-
1 rats. The tumors were mainly seen in surviving males at the time of
terminal sacrifice. The original pathological diagnosis of these tumors
was independently confirmed by another consulting pathologist, who also
reported an elevated incidence of urinary bladder hyperplasia in high-
dose male rats. No increase in incidence of urinary bladder tumors was
observed in female rats.
In 1986, the Health Effects Division Peer Review Committee for
Carcinogenicity of the Office of Pesticide Programs concluded that the
available data provided limited evidence of the carcinogenicity of
fosetyl-Al in male rats and classified the pesticide as a Category C
carcinogen (possible human carcinogen with limited evidence of
carcinogenicity in animals) in accordance with proposed Agency
guidelines, published in the Federal Register of November 23, 1984 (49
FR 46294). The Health Effects Division Peer Review Committee for
Carcinogenicity determined that a quantitative risk assessment was not
appropriate for the following reasons:
1. The carcinogenic response observed with this chemical was
confined solely to the high-dose males at one site (urinary bladder) in
rats.
2. The tumor response was primarily due to an increase in benign
tumors.
3. The tumors were seen only in surviving animals at the time of
terminal sacrifice.
4. The carcinogenic effects were observed only at unusually high
doses which exceed the commonly used limit dose of 1,000 mg/kg/day
recommended as an upper-limiting dose for bioassays.
5. The chemical was not carcinogenic when administered in the diet
to Charles River CD-1 mice at dose levels ranging from 2,500 to 30,000
ppm (357 to 4,286 mg/kg bwt/day).
6. Fosetyl-Al was not mutagenic in eight well conducted genotoxic
assays.
In 1993, the Health Effects Division Peer Review Committee (PRC)
for Carcinogenicity revisited the carcinogenicity classification of
fosetyl-Al owing to a recent 90-day feeding study of fosetyl-Al in rats
that showed a strong association between the presence of uroliths in
the urinary bladder and the incidence of urinary bladder tumors in
treated rats. The PRC concluded that fosetyl-Al is not amenable to
classification using the current Agency cancer guidelines. Based on a
mechanistic evaluation of the only tumors seen, those that occurred at
exceptionally high doses in the bladder of male rats, it appears that
humans are not likely to be exposed to doses of fosetyl-Al that produce
the urinary tract toxicity that precedes and seems to lead to the tumor
response in rats. In particular, anticipated human dietary and
occupational exposures to fosetyl-Al are far below the NOEL in rats for
the apparent urinary tract tumor precursors (stone formation and
attendant epithelial irritation). These effects are produced in rats at
extremely high doses, under conditions not anticipated to occur outside
of the experimental laboratory. The PRC concludes that pesticidal use
of fosetyl-Al is unlikely to pose a carcinogenic hazard to humans.
Therefore, the standard risk assessment approach of using the Reference
Dose (RfD) based on systemic toxicity was applied to fosetyl-Al.
Using a 100-fold safety factor and the NOEL of 250 mg/kg bwt/day
determined by the most sensitive species from the 2-year dog feeding
study, the RfD is 3.0 mg/kg bwt/day. The theoretical maximum residue
contribution (TMRC) from the established and proposed tolerances is
0.0453 mg/kg bwt/day and utilizes 1.5 percent of the RfD for the
overall U.S. population. The exposure of the most highly exposed
subgroup in the population did not utilize a significantly greater
amount of the RfD. Previous tolerances have been established for
fosetyl-Al, aluminum tris(O-ethylphosphonate), in asparagus, avocadoes,
brassica vegetable crop group, caneberries, citrus, cucurbit vegetables
group, dry bulb onions, fresh ginseng root, leafy vegetables crop
group, pineapples, pineapple forage and fodder, and strawberries.
The metabolism of aluminum tris(O-ethylphosphonate) in plants is
adequately understood. There is no reasonable expectation of secondary
residues occurring in milk, eggs, and meat of livestock or poultry as a
result of this use on hops.
An adequate analytical method, gas-liquid chromatography, is
available for enforcement purposes. Because of the long lead time from
establishing these tolerances to publication of the enforcement
methodology in the Pesticide Analytical Manual, Vol. II, the analytical
methodology is being made available in the interim to anyone interested
in pesticide enforcement when requested from: Calvin Furlow, Public
Information Branch, Field Operations Division (7506C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location and telephone number: Rm. 242, CM
#2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703)-305-4432.
The pesticide is considered useful for the purposes for which the
tolerances are sought. 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 5F3251/P577]. 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 establshing 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 26, 1994.
Stephen L. Johnson,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, it is proposed that 40 CFR part 180 be amended as
follows:
PART 180--[AMENDED]-
1. In part 180:
a. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 346a and 371.
b. In Sec. 180.415, by amending paragraph (a) by alphabetically
inserting the raw agricultural commodity dried hops, to read as
follows:
Sec. 180.415 Aluminum tris(O-ethylphosphonate); tolerances for
residues.
(a) * * *
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Parts per
Commodity million
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Hops, dried................................................ 45
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* * * * *
[FR Doc. 94-2699 Filed 2-8-94; 8:45 am]
BILLING CODE 6560-50-F
