[Federal Register Volume 60, Number 128 (Wednesday, July 5, 1995)]
[Rules and Regulations]
[Pages 34871-34874]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-16428]
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40 CFR Part 180
40 CFR Part 180
[PP 1F4025/R2148; FRL-4963-3]
RIN 2070-AB78
Pesticide Tolerance for O-[2-(1,1-Dimethylethyl)-5-Pyrimidinyl]
O-Ethyl-O-(1-Methylethyl) Phosphorothioate
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes a time-limited tolerance for residues of
the insecticide O-[2-(1,1-dimethylethyl)-5-pyrimidinyl] O-ethyl-O-(1-
methylethyl) phosphorothioate in or on the raw agricultural
commodities, corn, sweet (K+CWHR); corn, grain, field, and pop; corn,
forage and fodder, field, pop, and sweet at 0.01 part per million
(ppm). The Agricultural Division of Miles, Inc., requested in a
petition submitted pursuant to the Federal Food, Drug and Cosmetic Act
(FFDCA) this regulation to establish a maximum permissible level for
residues of the insecticide.
EFFECTIVE DATE: This regulation becomes effective July 5, 1995.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP 1F4025/R2148], may be submitted to:
Hearing Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M
St., SW., Washington, DC 20460. 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. A copy of any objections and hearing requests
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 (7506C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. In person, bring copy of objections and hearing requests to
Rm. 1132, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202.
Comments and data may also be submitted electronically 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 in 5.1 file format or ASCII file
format. All comments and data in electronic form must be identified by
the docket number [1F4025/R2148]. 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 in
this document.
FOR FURTHER INFORMATION CONTACT: By mail: Robert A. Forrest, Product
Manager (PM) 14, Registration Division (7505C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St., SW., Washington,
DC 20460. Office location and telephone number: Rm. 219, CM #2, 1921
Jefferson Davis Hwy., Arlington, VA 22202, (703)-305-6600; e-mail:
forrest.robert@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA issued a notice, published in the
Federal Register of April 5, 1995 (60 FR 17355), which announced that
Miles, Inc., Agriculture Division, 8400 Hawthorn Road, P.O. Box 4913,
Kansas City, MO 64120, had submitted a pesticide petition, PP 1F4025,
to EPA requesting that the Administrator, pursuant to section 408(d) of
the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d),
establish a tolerance for residues of the insecticide ``phostebupirim''
(O-[2-(1,1-dimethylethyl)-5-pyrimidinyl] O-ethyl-O-(1-methylethyl)
phosphorothioate) in or on the raw agricultural commodities corn,
fresh; corn, grain, field and pop; and corn, forage and fodder, field,
pop, and sweet at 0.01 part per million (ppm). (Because the name
``phostebupirim'' was not accepted as the common name, no further
reference to this name will be made.) For consistency, the raw
agricultural commodity, corn, fresh is expressed as corn, sweet
(K+CWHR).
There were no comments received in response to the notice. The
scientific data submitted in the petition and other relevant material
have been evaluated. The toxicological data considered in support of
the tolerance include:
1. Several acute toxicological studies placing the technical grade
of the insecticide in toxicity category I.
2. A 3-week subacute rabbit dermal study with a no-observed-effect
level (NOEL) of 0.3 milligram/kilogram/day (mg/kg/day) for
cholinesterase inhibition effects. Levels tested were 0.3, 1.0, and 3.0
mg/kg/day.
3. A subchronic (86 days) rat-feeding study with a NOEL for
cholinesterase effects of 4.0 ppm and a systemic NOEL of 12.0 ppm.
Levels tested were 2.0, 4.0, 12.0, and 36.0 ppm. (0.1, 0.2, 0.6, and
1.8 mg/kg/day, respectively).
4. An acute delayed neurotoxicity study in hens in which a dosage
of 10 mg/kg was administered by gavage with no delayed neurotoxicity
effects observed under conditions of the study.
5. A 1-year dog-feeding study with a NOEL of 0.02 mg/kg/day.
Plasma, red blood cell, and brain cholinesterase inhibition effects
were observed at the 5.0 ppm (0.125 mg/kg) dose level. No systemic
effects were observed under the conditions of the study. Levels tested
were 0.2, 0.7, and 5.0 ppm. (0.005, 0.018, and 0.125 mg/kg/day,
respectively).
6. The following three studies fulfill the rat chronic/oncogenicity
study requirement.
a. A 2-year rat-feeding carcinogenicity study with a NOEL of 1.0
ppm for cholinesterase inhibition and 5.0 ppm for systemic effects. The
study was negative for carcinogenic effects under the conditions of the
study. Systemic effects observed at the 25-ppm dose level consisted of
a decrease in body weight gain for first 6 months (males); soft stools;
and poor general conditions, salivation, and tremors (females). Levels
tested were 1.0 ppm, 5.0 ppm, and 25.0 ppm. (0.05, 0.25, and 1.25 mg/
kg/day, respectively).
[[Page 34872]]
b. A 6-month cholinesterase study in rats with a NOEL of 0.3 ppm
(0.02 mg/kg) for erythrocyte cholinesterase inhibition. There were no
apparent systemic effects observed under conditions of the study. The
levels tested were 0.3, 1.0, and 3.0 ppm. (0.015, 0.05, and 0.15 mg/kg/
day, respectively).
c. A 12-month sacrifice study in rats administered 0 or 25 ppm
(1.25 mg/kg/day) in which a decrease in body weight gain, an increase
in food consumption, and an inhibition of brain cholinesterase activity
were observed.
7. The following two studies fulfill the mouse chronic/oncogenicity
study.
a. A 2-year mouse carcinogenicity study which was negative for
carcinogenic effects under the conditions of the study. The
cholinesterase NOEL was 1.0 ppm (0.52 mg/kg/day for males and 0.58 mg/
kg/day for females) for erythrocyte, plasma and brain. Levels tested
were 1.0 ppm, 9.0 ppm, and 80.0 ppm.
b. A 12-month mouse cholinesterase study with a NOEL for
cholinesterase inhibition of 0.3 ppm in males (0.13 mg/kg/day) and less
than 0.3 ppm in females (0.16 mg/kg/day). The lowest-observed-effect
level (LOEL) in males was 1.0 ppm (0.43 mg/kg/day) and in females, 0.3
ppm (0.16 mg/kg/day). The NOEL for systemic effects was 3.0 ppm (1.23
and 1.63 mg/kg/day in males and females, respectively). Levels tested
were 0.3, 1.0, and 3.0 ppm.
8. A two-generation reproduction study in rats with a developmental
NOEL of 5.0 ppm (approximately 0.25 mg/kg). A decrease in fertility
indices and an increase in number of dead pups were observed at the
25.0-ppm dose level. There were no teratogenic effects observed under
conditions of the study. The maternal NOEL for cholinesterase and
systemic effects was 5.0 ppm. Tremors, decreased body weight gain, and
cholinesterase inhibition were observed at the 25.0-dose level. Levels
tested were 1.0 ppm, 5.0 ppm, and 25.0 ppm.
9. A rat developmental study with no developmental effects observed
under conditions of the study. The maternal NOEL was 0.50 mg/kg. At the
0.75-mg/kg dose level, mortality and a decrease in body weight gain as
well as food consumption during days 11 to 16 of the gestation; and
inhibition of plasma, erythrocyte, and brain cholinesterase was
observed. Levels tested were 0.25, 0.50, and 0.75 mg/kg.
10. A rabbit developmental study with an NOEL of 0.1 mg/kg for
developmental effects (fetotoxicity). At the 0.3 mg/kg-dose, there was
a decreased number of live fetuses/litter, a higher number of
resorptions per group, and a greater number of litters with at least
one resorption. Erythrocyte cholinesterase inhibition was also observed
at the 0.3-mg/kg dose level. The test material was administered by
gavage at doses of 0.03, 0.1, and 0.3 mg/kg.
11. Several mutagenicity studies in which the insecticide showed no
evidence of mutagenic effects. These studies included gene mutation in
cultured Chinese Hamster ovary cells (CHO/HGPRT); salmonella plate
assays; in vivo micronucleus assay in mice; sister chromatid exchange
assay in Chinese hamster ovary cells; unscheduled DNA synthesis assay
in primary rat hepatocytes; and mitotic recombination.
12. A rat metabolism study demonstrated that the insecticide was
readily absorbed, distributed, metabolized, and excreted and that
bioaccumulation and retention of the compound and/or its metabolites
are low in rats. In vivo and in vitro metabolism studies indicate that
the insecticide is metabolized by mixed function oxidases to O-[2-(1,1-
dimethylethyl)-5-pyrimidinyl] O-ethyl-O-(1-methylethyl)
phosphorothioate (OMAT), an oxygen analog, which is rapidly hydrolyzed
to 2-(1,1-dimethylethyl)-5-hydroxypyrimidine (TPHP) and excreted as the
glucuronide conjugate of TBHP, a major metabolite representing 60 to 74
percent of the administered radioactivity.
The reference dose (RfD) is established at 0.0002 mg/kg/day based
on a NOEL of 0.02 mg/kg/day from the 2-year dog feeding study and an
uncertainty factor of 100. The Theoretical Maximum Residue Contribution
(TMRC) from the current action is estimated at .000006 mg/kg of body
weight/day and utilizes 2.887 percent of the RfD for the U.S.
population. There are no other tolerances established for this
chemical.
The TMRC for children, aged 1 to 6 years old, and nonnursing
infants (the subgroups most highly exposed) utilizes 7.0 percent of the
RfD for each subgroup.
An acute dietary exposure analysis utilizing the NOEL of 0.3 mg/kg/
day from the rabbit developmental study as the toxicological endpoint
was conducted. The subpopulation of particular concern (females 13+
years) has a Margin of Exposure (MOE) of 1,667 and therefore has a
negligible acute risk for developmental toxicity from the establishment
of these tolerances. The acute dietary analysis estimates the
distribution of single-day exposures for the overall population and
certain subgroups, and the MOE, calculated as the ratio of the NOEL to
the exposure, is a measure of how close the high-end exposure comes to
the NOEL.
The nature of the residue in plants and animals is adequately
understood. An adequate analytical method, gas-liquid chromatography,
is available for enforcement purposes.
The enforcement methodology has been submitted to the Food and Drug
Administration for publication in the Pesticide Analytical Manual, Vol.
II (PAM). Because of the long lead time for publication of the method
in PAM II, the analytical methodology is being made available in the
interim to anyone interested in pesticide enforcement when requested
from: Calvin Furlow, Public Response and Program Resources 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. 1132, CM #2, 1921 Jefferson
Davis Highway, Arlington, VA 22202, (703)-305-5232.
There is no reasonable expectation that secondary residues will
occur in milk, eggs, or the meat, fat and meat byproducts (mbyp) of
livestock or poultry as a result of this action.
Desirable data lacking include acute and subchronic rat
neurotoxicity studies which are recent data requirements for
cholinesterase-inhibiting pesticides. The gross cholinesterase
inhibitory properties of the insecticide have been characterized in the
available studies; however, additional characterization of the
neurotoxic/neuropathological potential of the insecticide in mammals
(rodents) is necessary. These studies have since been received by the
Agency and are currently in review.
Because of the lack of the mammalian neurotoxicity studies and the
need to be consistent with the conditional registration being issued in
conjunction with this regulation, the Agency is limiting the period of
time that the regulation is to be in effect. Because the conditional
registration being issued is for a combination product consisting of
two active ingredients with the insecticide, cyfluthrin, as the second
active ingredient, a regulation establishing time-limited tolerances
for the use of cyfluthrin on corn is also being issued concurrently
with this regulation. Upon evaluation of the rat neurotoxicity studies
and receipt and evaluation of the other data/information required as
conditions of the registration, the Agency will reassess the tolerances
and registration and, if appropriate, will issue permanent
[[Page 34873]]
tolerances and an unconditional registration for the use of these
insecticides on corn.
There are currently no actions pending against the registration of
this chemical.
Elsewhere in this issue of the Federal Register, the Agency is
concurrently issuing a notice of conditional registration for the use
of this new chemical on corn and a rule establishing a time-limited
tolerance for residues of the insecticide, cyfluthrin, in/on corn
commodities.
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 tolerance is 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 to the regulation and may also request a hearing on
those objections. Objections and hearing requests must be filed 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 fee prescribed 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, the
requestor's contentions on such issues, and a summary of any evidence
relied upon by the objector (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 genuine and substantial issue
of fact; there is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one 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).
A record has been established for this rulemaking under docket
number [PP 1F4025/R2148] (including objections and hearing requests
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.
Written objections and hearing requests, identified by the document
control number [PP 1F4025/R2148], may be submitted to the Hearing Clerk
(1900), Environmental Protection Agency, Rm. 3708, 401 M St., SW.,
Washington, DC 20460.
A copy of electronic objections and hearing requests filed with the
Hearing Clerk can be sent directly to EPA at:
opp-Docket@epamail.epa.gov
A copy of electronic objections and hearing requests filed with the
Hearing Clerk 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 any objections and hearing requests 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 objections and hearing requests 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, 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.
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: June 23, 1995.
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. By adding new Sec. 180.483, to read as follows:
Sec. 180.483 O-[2-(1,1-Dimethylethyl)-5-pyrimidinyl] O-ethyl-O-(1-
methylethyl) phosphorothioate; tolerances for residues.
Time-limited tolerances are established for residues of the
insecticide O-[2-(1,1-dimethylethyl)-5-pyrimidinyl] O-ethyl-O-(1-
methylethyl) phosphorothioate in or on the following raw agricultural
commodities:
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Parts per Expiration
Commodity million date
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Corn, forage and fodder, field, pop, and sweet 0.01 July 6,
1999.
Corn, grain, field and pop.................... 0.01 Do.
[[Page 34874]]
Corn, sweet (K+CWHR).......................... 0.01 Do.
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[FR Doc. 95-16428 Filed 7-3-95; 8:45 am]
BILLING CODE 6560-50-F
