[Federal Register Volume 60, Number 206 (Wednesday, October 25, 1995)]
[Rules and Regulations]
[Pages 54607-54610]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-26472]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[PP 4F4391/R2180; FRL-4982-8]
RIN 2070-AB78
Pyrithiobac Sodium Salt; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This rule establishes a time-limited tolerance, to expire on
September 30, 1997, for residues of the herbicide pyrithiobac sodium
salt (sodium 2-chloro-6-[(4,6-dimethoxypyrimidin-2-yl)thio]benzoate) in
or on the raw agricultural commodity cottonseed at 0.02 part per
million (ppm). E.I. du Pont de Nemours & Co., Inc., submitted a
petition pursuant to the Federal Food, Drug and Cosmetic Act (FFDCA)
requesting the regulation to establish a maximum permissible level for
residues of the herbicide in or on the commodity.
EFFECTIVE DATE: This regulation becomes effective October 25, 1995.
ADDRESSES: Written objections and hearing requests, identified by the
document control number, [PP4F4391/R2180], may be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests 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 1B2, 1921 Jefferson Davis Hwy., Arlington, VA
22202.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@epamail.epa.gov. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect in 5.1
file format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket number [PP
4F4391/R2180]. No Confidential Business Information (CBI) should be
submitted through e-mail. Electronic copies of objections and hearing
requests on this 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: Theresa A. Stowe, Acting
Product Manager (PM 22), Registration Division (7505C), Office of
Pesticide Programs, Enviromental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location and telephone number: Rm.
[[Page 54608]]
229, CM #2, 1921 Jefferson Davis Hwy., Arlington, VA 22202, (703)-305-
6117; e-mail: stowe.theresa@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA issued a notice published in the Federal
Register of June 15, 1995 (60 FR 31466), which announced that E. I. du
Pont de Nemours Co., Inc., Barley Mill Plaza, Walker's Mill, P.O. Box
80038, Wilmington, DE 19880-0038, had submitted a pesticide petition,
PP 4F4391, to EPA requesting that the Administrator, pursuant to
section 408(d) of the FFDCA (21 U.S.C. 346a(d)), amend 40 CFR part 180
by establishing a regulation to permit residues of pyrithiobac sodium
salt (sodium 2-chloro-6-[(4,6-dimethoxypyrimidin-2-yl)thio]benzoate) in
or on the raw agricultural commodity cottonseed at 0.02 part per
million (ppm).
There were no comments or requests for referral to an advisory
committee received in response to the notice of filing.
The scientific data submitted in the petition and all other
relevant material have been evaluated. The toxicology data considered
in support of the tolerance include the following:
1. A rat acute oral study with a LD50 of 3,300 milligrams
(mg)/kilogram (kg) for males and a LD50 of 3,200 mg/kg for
females.
2. A 90-day rat feeding study with a no-observed-effect level
(NOEL) of 500 ppm (31.8 mg/kg/day for males and 40.5 mg/kg/day for
females) and a lowest-observed-effect level (LOEL) of 7,000 ppm (466 m/
kg/day for males and 58.8 mg/kg/day for females), based on decrease
body weight gains and increased rate of hepatic B-oxidation in males.
3. A 90-day mouse feeding study with a NOEL of 500 ppm (83.1 mg/kg/
day for males and 112 mg/kg/day for females) and a LOEL of 1,500 ppm
(263 mg/kg/day for males and 384 mg/kg/day for females) based on
increased liver weight and an increased incidence of hepatocellular
hypertrophy in males and decreased neutrophil count in females.
4. A 3-month dog feeding study with a NOEL of 5,000 ppm (165 mg/kg/
day) and a LOEL of 20,000 ppm (626 mg/kg/day), based on decrease red
blood cell count, hemoglobin, and hematocrit in females and increased
liver weight in both sexes.
5. A 21-day rat dermal study with a dermal irritation NOEL of 50
mg/kg/day and a dermal irritation LOEL of 500 mg/kg/day based on
increased incidence of erythema and edema, and with a systemic dermal
NOEL of 500 mg/kg/day and a systemic dermal LOEL of 1,200 mg/kg/day
based on body weight gain inhibition.
6. A 90-day rat neurotoxicity screening battery with a systemic
NOEL of 7,000 ppm (466 mg/kg/day for males and 588 mg/kg/day for
females) and a systemic LOEL of 20,000 ppm (1,376 mg/kg/day for males
and 1,609 mg/kg/day for females), based on decreased hind grip strength
and increased foot spay in males, and a neurotoxicity NOEL of 20,000
ppm [highest dose tested (HDT)].
7. A 78-week dietary carcinogenicity study in mice with a NOEL of
1,500 ppm [217 mg/kg/day (males) and 319 mg/kg/day (females)] and a
LOEL of 5,000 ppm [745 mg/kg/day (males) and 1,101 m/kg/day (females)]
based on decreased body weight/gain in both sexes, treatment related
increase in the incidence of foci/focus of hepatocellular alternation
in males, and increased incidence of glomerulonephropathy [murine] in
both sexes, and an increased incidence of infarct in the kidney and
keratopathy of the eyes in 1.43 mg/kg/day and a LOEL of 28.6 mg/kg/day
(males) and 92.9 mg/kg/day (females) based on hepatocellular
enlargement and a greater incidence and severity of hepatocellular
vacuolation. There was evidence of carcinogenicity based on significant
differences in the pair-wise comparisons of the liver tumors in the 150
and 1,500 dose groups (but not at the high dose of 5,000 ppm). The
carcinogenic effects observed are discussed below.
8. A 24-month rat chronic feeding/carcinogenicity study with a
systemic NOEL of 1,500 ppm (58.7 mg/kg/day) for males and 5,000 ppm
(278 mg/kg/day) for females and a systemic LOEL of 5,000 ppm (200 mg/
kg/day) for males and 1,500 ppm (918 mg/kg/day) for females based on
decreases in body weight, body weight gains and food efficiency in
females, increased incidence of eye lesions in males and females, mild
changes in hematology and urinalysis in both sexes, clinical signs
suggestive of urinary tract dysfunction in males and females, increased
incidence of focal cystic degeneration in the liver and renal tubular
adenomas and adenocarcinomas in males, increased rate of hepatic
peroxisomal B-oxidation in males and an increased incidence of
inflammatory, degenerative, and neoplastic microscopic lesions in the
kidney in females. There was evidence of carcinogenicity based on the
increasing trend in kidney tubular combined adenoma/carcinoma in male
rats and an increasing trend in kidney tubular bilateral and/or
unilateral adenomas in females. The carcinogenic effects observed are
discussed further below.
9. A 1-year dog chronic feeding study with a NOEL of 5,000 ppm (143
mg/kg/day for males and 166 mg/kg/day for females) and a LOEL of 20,000
ppm (580 mg/kg/day for males and 647 mg/kg/day for females) based on
decreases in body weight gain and increased liver weight.
10. A two generation reproduction study in rats with a maternal
NOEL of 1,500 ppm (103 mg/kg/day) and a maternal LOEL of 7,500 ppm (508
mg/kg/day ppm), based on decreased body weight/gain and food efficacy.
The reproductive and offspring NOEL is 7,500 ppm (508 mg/kg/day) and
the reproductive and offspring LOEL is 20,000 ppm (1,551 mg/kg/day),
based on decreased pup body weight.
11. A developmental toxicity study in rabbits with a maternal and
developmental NOEL of 300 mg/kg and a maternal LOEL of 1,000 mg/kg
based on deaths, decreased body weight gain and feed consumption,
increased incidence of clinical signs, and an increase in early
resorptions and a developmental LOEL of 1,000 mg/kg, based on decreased
fetal body weight gain.
12. A developmental toxicity study in rats with a maternal NOEL 200
mg/kg and a maternal LOEL of 600 mg/kg due to increased incidence of
salivation. The developmental NOEL is 600 mg/kg and the developmental
LOEL is 1,800 mg/kg based on the increased incidence of skeletal
variations .
13. No evidence of gene mutation was observed in a test for
induction of forward mutations at the HGPRT locus in Chinese hamster
ovary cells. No evidence was observed for inducing reverse gene
mutation in two independent assays with Salmonella typhimurium with and
without mammalian metabolic activation. Pyrithiobac-sodium was negative
for the induction of micronuclei in the bone marrow cells of mice, and
negative for induction of unscheduled DNA synthesis in rat primary
hepatocytes. Pyrithiobac-sodium was positive for inducing chromosome
aberrations assay in human lymphocytes.
14. A rat metabolism study showed that radiolabeled pyrithiobac-
sodium is excreted in urine and feces with greater than 90 percent
being eliminated within 48 hours. A sex difference was observed in the
excretion and biotransformation. Females excreted a greater amount of
the radiolabel in the urine than males following all dosing regimens,
with a corresponding lower amount being eliminated in the feces
compared to the males.
[[Page 54609]]
The Health Effects Division Carcinogenicity Peer Review Committee
has concluded that the available data provide limited evidence of the
carcinogenicity of pyrithiobac sodium salt in mice and rats and has
classified pyrithiobac sodium salt as a Group C (possible human
carcinogen with limited evidence of carcinogenicity in animals) in
accordance with Agency guidelines, published in the Federal Register in
1986 (51 FR 33992, Sept. 24, 1986) and recommended that for the purpose
of risk characterization a low-dose extrapolation model should be
applied to the experimental animal tumor data for quantification for
human risk (Q1*). This decision was based on liver adenomas,
carcinomas and combined adenoma/carcinomas in the male mouse and rare
kidney tubular adenomas, carcinomas and combined adenoma/carcinomas in
male rat. The unit risk, Q1* (mg/kg/day)-1, of pyrithiobac-
sodium is 1.05 x 10-3 (mg/kg/day)-1 in human equivalents
based on male kidney tumors.
Based on assumption that 100% of the crop is treated with
pyrithiobac- sodium, the upper-bound limit of the dietary carcinogenic
risk is calculated in the range of 1 incidence in a billion (1.0 x
10-9).
Processing studies for cotton have shown that pyrithiobac-sodium
does not concentrate in cottonseed processed commodities. Therefore,
food/feed additive tolerances are not needed in conjunction with these
uses.
Using the NOEL of 58.7 mg/kg/day from the most sensitive species in
the rat chronic feeding study with a 100-fold safety factor, the
Reference Dose (RfD) for systemic effects is 0.58 mg/kg/day. The
theoretical maximum residue contribution (TMRC) from the established
and proposed tolerances is 0.000001 mg/kg/day and utilizes less than 1
percent of the RfD for the overall U.S. population. For exposure of the
most highly exposed subgroup in the population, children aged 1 through
6 years of age, the TMRC is 0.000001 mg/kg/day, which is still less
than 1 percent of the RfD.
The metabolism of pyrithiobac-sodium in plants is adequately
understood. Due to the following chemistry data gap, Magnitude of
Residue Data for cotton gin byproducts [GLN 171-4], EPA believes it is
inappropriate to establish permanent tolerances for the uses of
pyrithiobac-sodium at this time. However, since the pesticide labeling
accepted under the Federal Insecticide Fungicide and Rodenticide Act
(FIFRA), as amended, bears a restriction against feeding cotton gin
byproducts from treated fields to livestock, EPA believes that the
existing data support time-limited tolerances to September 30, 1997.
The nature of the residue in plants is adequately understood for
the purposes of these time-limited tolerances. An analytical method,
high- pressure 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 II). 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 any one 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 Hwy., Arlington, VA 22202, (703-305-5232).
There is no reasonable expectation that secondary residues will
occur in milk, eggs or meat of livestock and poultry since, due to the
label restriction against feeding cotton gin byproducts from treated
fields to livestock, there are no livestock feed items associated with
this action. The pesticide is considered useful for the purpose for
which the tolerance is sought.
Based on the information and data considered, the Agency has
determined that the amending of 40 CFR part 180 will be safe.
Therefore, the regulation 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 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 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 a 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 4F4391/R2180) (including any 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 Rm. 1132 of the Public
Response and Program Resources Branch, Field Operations Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
Crystal Mall 1B2, 1921 Jefferson Davis Highway, Arlington, VA.
Written objections and hearing requests, identified by the document
control number [PP 4F4391/R2180], 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:
[email protected]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, Oct. 4, 1993), the Agency
must determine whether the regulatory action is ``significant'' and
therefore subject to review by the Office of Management and Budget
(OMB) and the requirements of the Executive Order. Under section 3(f),
[[Page 54610]]
the order defines a ``significant regulatory action'' as an action that
is likely to result in 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 referred to 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 the rights and obligations of recipients
thereof; 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 the 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: September 29, 1995.
Penelope A. Fenner-Crisp,
Deputy Director, Office of Pesticide Programs.
Therefore, title 40 of the Code of Federal Regulations is amended
in part 180 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. 180.487, to read as follows:
Sec. 180.487 Pyrithiobac sodium salt (sodium 2-chloro-6-[(4,6-
dimethoxypyrimidin-2-yl)thio]benzoate); tolerances for residues.
A time-limited tolerance is established for residues of the
herbicide pyrithiobac sodium salt (sodium 2-chloro-6-[(4,6-
dimethoxypyrimidin-2-yl)thio]benzoate) in or on the following raw
agricultural commodity:
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Parts per Expiration
Commodity million date
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Cottonseed.................................... 0.02 Sept. 30,
1997.
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[FR Doc. 95-26472 Filed 10-24-95; 8:45 am]
BILLING CODE 6560-50-F
