[Federal Register Volume 59, Number 206 (Wednesday, October 26, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-26468]
[[Page Unknown]]
[Federal Register: October 26, 1994]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 8F3689/R2081; FRL-4912-8]
RIN 2070-AB78
Pesticide Tolerances for Aluminum Tris(O-Ethylphosphonate)
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of the
fungicide fosetyl-Al, aluminum tris(O-ethylphosphonate), in or on pome
fruit at 10 parts per million (ppm). This regulation to establish the
maximum permissible level of residues of the fungicide in or on this
commodity was requested in petitions submitted by Rhone-Poulenc Ag Co.
DATES: This regulation becomes effective October 26, 1994.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 8F3689/R2081], may be submitted to:
Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M
St., Washington, DC 20460. A copy of any objections and hearing request
filed with the Hearing Clerk should be identified by the document
control number and submitted to: Public Response and Program Resources
Branch, Field Operations Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington
DC 20450. In person, bring copy of objections and hearing request to:
Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, 1921
Jefferson Davis Hwy., Arlington, VA 22202. Fees accompanying objections
shall be labeled ``Tolerance Petition Fees'' and forwarded to: EPA
Headquarters Accounting Operations Branch, OPP (Tolerance Fees), P.O.
Box 360277M, Pittsburgh, PA 15251.
FOR FURTHER INFORMATION CONTACT: By mail: Cynthia Giles-Parker, Product
Manager (PM) 22, Registration Division, 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 October 20, 1988 (53 FR 41238), 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 8F3689), and a food/feed additive petition (FAP 8H5567) 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 pome fruit at 10 ppm and pome fruit
juice and pome fruit pomace (wet and dry) at 12 ppm, respectively.
Subsequently, the Agency reviewed an apple-processing study and
concluded that section 409 tolerances for pome fruit juice and pome
fruit pomace were unnecessary, and the food/feed additive petition was
withdrawn.
EPA issued a notice, published in the Federal Register of August 3,
1994 (59 FR 39568), which announced that EPA was reissuing the
pesticide petition (PP 8F3689) for the fungicide, aluminum tris(O-
ethylphosphonate), in or on pome fruit at 10 ppm. EPA reissued the
petition because more than 5 years had passed since the first notice of
filing.
There were no comments or requests for referral to an advisory
committee received in response to these notices of filing.
The data submitted in the petitions and all other relevant material
have been evaluated. The toxicology 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 a slight degenerative effects on the testes.
9. A reproduction study in rats with a NOEL of 300 mg/kg bwt/day
and a 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 the 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 due to a recent 90-day feeding study of fosetyl-Al in rats
which 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
0.058818 mg/kg bwt/day and utilizes 2 percent of the RfD for the
overall U. S. population. For exposure of the most highly exposed
subgroup in the population, nonnursing infants, the TMRC is 0.130051
mg/kg bwt/day and utilizes 4 percent 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, dried hops, 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 pome fruit. Based on an apple-processing study, a
concentration of fosetyl-Al into process fractions did not occur and
food/feed additive tolerances are not needed in conjunction with these
uses on pome fruit.
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 information and data considered,
the Agency concludes that the establishment of the tolerances will
protect the public health. Therefore, the tolerances are established as
set forth below.
Any person adversely affected by this regulation may, within 30
days after publication of this document in the Federal Register, file
written objections and/or request a hearing with the Hearing Clerk, at
the address given above (40 CFR 178.20). A copy of the objections and/
or hearing requests filed with the Hearing Clerk should be submitted to
the OPP docket for this rulemaking. The objections submitted must
specify the provisions of the regulation deemed objectionable and the
grounds for the objections (40 CFR 178.25). Each objection must be
accompanied by the fees provided by 40 CFR 180.33(i). If a hearing is
requested, the objections must include a statement of the factual
issue(s) on which a hearing is requested, and the requestor's
contentions on each such issue, and a summary of the evidence relied
upon by the objection (40 CFR 178.27). A request for a hearing will be
granted if the Administrator determines that the material submitted
shows the following: there is a genuine and substantial issue of fact;
there is a reasonable possibility that available evidence identified by
the requestor would, if established, resolve on or more of such issues
in favor of the requestor, taking into account uncontested claims or
facts to the contrary; and resolution of the factual issue(s) in the
manner sought by the requestor would be adequate to justify the action
requested (40 CFR 178.32).
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: September 30, 1994.
Daniel M. Barolo,
Director, Office of Pesticide Programs.
Therefore, 40 CFR part 180 is 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. 180.415, by amending paragraph (a) in the table therein
by adding and alphabetically inserting the following entry, 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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Pome fruit................................................. 10
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* * * * *
[FR Doc. 94-26468 Filed 10-25-94; 8:45 am]
BILLING CODE 6560-50-F
