[Federal Register Volume 61, Number 249 (Thursday, December 26, 1996)]
[Notices]
[Pages 68036-68039]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-32796]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-680; FRL-5576-7]
American Cyanamid Company; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
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SUMMARY: This notice is a summary of a pesticide petition proposing the
establishment of a regulation for residues of AC 299263
[()-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-
imidazol-2-yl]-5-(methoxymethyl)-3-pyridinecarboxylic acid] in or on
soybean seed.
DATES: Comments, identified by the docket number [PF-680], must be
received on or before, January 27, 1997.
ADDRESSES: By mail, submit written comments 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 comments to Rm. 1132, CM #2,
1921 Jefferson Davis Highway, Arlington, VA. Comments and data may also
be submitted electronically by sending electronic mail (e-mail) to:
opp-docket@epamail.epa.gov. Electronic comments on this notice may be
filed online at many Federal Depository Libraries. Additional
information on electronic submissions can be found below in Unit II. of
this document.
Information submitted as comments concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI 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. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: Robert Taylor, Product Manager (PM)
25, Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location, telephone number, and e-mail address: Rm. 241, CM #2,
1921 Jefferson Davis Highway, Arlington, VA, Telephone: 703-305-6027,
e-mail: taylor.robert@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP)
6F4649 from American Cyanamid Company, P.O. Box 400, Princeton, NJ
08543-0400, proposing pursuant to section 408(d) of the Federal Food,
Drug, and Cosmetic Act (FDDCA), 21 U.S.C. section 346a(d), to amend 40
CFR
[[Page 68037]]
part 180 by establishing a tolerance for residues of the herbicide AC
299263 in or on the raw agricultural commodity soybean seed at 0.1 ppm.
The proposed analytical method is HPLC Method M2248.01.
Pursuant to section 408(d)(2)(A)(i) of the FFDCA, as amended,
American Cyanamid Company has submitted the following summary of
information, data, and arguments in support of their pesticide
petition. This summary was prepared by American Cyanamid Company and
EPA has not fully evaluated the merits of the petition.
EPA edited the summary to clarify that the conclusions and
arguments were the petitioner's and not necessarily EPA's and to remove
certain extraneous material.
I. Petition Summary
On November 30, 1995, American Cyanamid Company petitioned the EPA,
under pesticide petition (PP) 6F4649, for a permanent tolerance of 0.1
ppm for the residues of AC 299263 on soybean seed.
Section 408(b)(2)(A) of the amended FFDCA allows EPA to establish a
tolerance only if the Administrator determines that there is a
``reasonable certainty that no harm will result from the aggregate
exposure to the pesticide chemical residue, including all anticipated
dietary exposures and all other exposures for which there is reliable
information.''
All of the studies required for the proposed use pattern have been
completed and submitted to EPA for review. The available information
indicates there is a reasonable certainty that no harm will result from
various types of exposure.
The following is a summary of the information submitted to EPA to
support the establishment, under section 408(b)(2)(D) of the amended
FFDCA, of a tolerance for AC 299263 on soybean seed.
A. Residue Chemistry
1. Plant metabolism. The qualitative nature of the residues of AC
299263 in soybeans is adequately understood. Parent compound is the
only residue of concern. The requirement for a processing study was
waived by EPA based on the results of field trials at rates up to 5x
the maximum label rate. In these trials, there was no measurable
residue of AC 299263 in soybean seed above the validated sensitivity of
the method (0.05 ppm). In addition, results from the plant metabolism
study showed no detectable residues of AC 299263 in oil obtained from
soybean seed which had been treated at an exaggerated use rate.
2. Analytical method. A practical analytical method (HPLC Method
M2248.01) for detecting and measuring levels of AC 299263 in soybean
seed has been submitted to EPA. This method is appropriate for
enforcement purposes.
3. Magnitude of residues. No apparent residues of AC 299263 were
observed in soybean seed at or above 0.05 ppm (the limit of
quantitation for the analytical method). These field studies, conducted
at 1-5x the highest intended label use rate, clearly support the
proposed tolerance of 0.1 ppm.
B. Toxicological Profile
A complete battery of mammalian toxicity studies supports the
tolerance for AC 299263 on soybean seed. The data base is complete,
valid and reliable, and all studies have been submitted to EPA for
review.
1. Acute toxicity. Based on EPA criteria, AC 299263 technical
material is relatively non-toxic via the oral and inhalation routes of
exposure (Category IV), and is only slightly toxic (Category III) via
dermal exposure.
Acute oral toxicity in rats: LD50 > 5,000 mg/kg
Acute dermal toxicity in rabbits: LD50 > 4,000 mg/kg
Acute inhalation toxicity in rats: LC50 > 6.3 mg/l (analytical)
Primary eye irritation in rabbits: Slightly to moderately
irritating
Primary dermal irritation in rabbits: Non-irritating to slightly
irritating
Dermal sensitization in guinea pigs: Non-sensitizer
2. Genotoxicity. The results from a battery of three in vitro and
one in vivo genetic toxicity tests with AC 299263 show that this
compound is not mutagenic or genotoxic.
Gene mutation - Ames: Negative
In vitro structural chromosomal aberration assay: Negative
In vitro CHO/HGPRT assay: Negative
In vivo micronucleus aberration assay: Negative
3. Reproductive and developmental toxicity. Results of these
studies indicate that AC 299263 is not a reproductive toxicant, a
developmental toxicant, or a teratogen.
Teratology in rats: NOEL (maternal) = 500 mg/kg/day NOEL (fetal/
developmental) = 1000 mg/kg/day*
Teratology in rabbits: NOEL (maternal) = 300 mg/kg/day NOEL (fetal/
developmental) = 900 mg/kg/day*
Two-Generation reproduction in rats: NOEL (parental and
reproductive) = 20,000 ppm* ( 1639 mg/kg/day)
* highest concentration tested
4. Subchronic toxicity. No treatment-related adverse effects were
noted in subchronic toxicity studies at the highest doses tested.
28-Day dermal in rats: NOEL = 1000 mg/kg/day*
13-Week oral feeding in rats: NOEL = 20,000 ppm* ( 1661
mg/kg/day)
90-Day oral feeding in dogs: NOEL = 40,000 ppm* ( 1368
mg/kg/day)
* highest concentration tested
5. Chronic toxicity. The low order of mammalian toxicity of AC
299263 technical is also evident from the chronic dietary toxicity
studies. These studies showed no increased mortalities or clinical
signs of toxicity attributed to AC 299263 treatment. There was no gross
or microscopic evidence of treatment-related lesions or carcinogenicity
in the three chronic studies conducted in dogs, mice, or rats.
1-Year chronic toxicity in dogs: NOEL = 40,000 ppm* (
1,165 mg/kg/day)
18-Month chronic toxicity and carcinogenicity in mice: NOEL = 7,000
ppm* ( 1201 mg/kg/day)
24-Month chronic toxicity and carcinogenicity in rats: NOEL =
20,000 ppm* ( 1,167 mg/kg/day)
* highest concentration tested
6. Animal metabolism. The qualitative nature of the residues of AC
299263 in animals is adequately understood. Based on metabolism studies
with goats, hens and rats, there is no reasonable expectation that
measurable AC 299263-related residues will occur in meat, milk, poultry
or eggs from the proposed use.
7. Metabolite toxicology. No toxicologically significant
metabolites were detected in plant or animal metabolism studies.
Therefore, no metabolites are required to be regulated.
8. Endocrine effects. Collective organ weights and
histopathological findings from the two-generation rat reproductive
study, as well as from the subchronic and chronic toxicity studies in
two or more animal species, demonstrate no apparent estrogenic effects
or effects on the endocrine system. There is no information available
which suggests that AC 299263 would be associated with endocrine
effects.
C. Aggregate Exposure
1. Dietary exposure.-- (i) Food. The Theoretical Maximum Residue
Concentrations (TMRC) of AC 299263 on or in soybean seed are:
0.000036 mg/kg b.w./day for the general U.S. population
0.000252 mg/kg b.w./day for non-nursing infants
0.000064 mg/kg b.w./day for children 1 to 6 years of age
0.000050 mg/kg b.w./day for children 7 to 12 years of age
[[Page 68038]]
These TMRC values are calculated from the proposed 0.1 ppm
tolerance of AC 299263 on soybean seed using a ``worse case'' estimate
of dietary exposure. This conservative estimate assumes that 100
percent of all soybeans are treated with AC 299263 and that the
residues of AC 299263 on soybean seed are at the tolerance level (0.1
ppm). In fact, no apparent residues were observed in soybean seed at or
above the 0.05 ppm limit of quantitation of the residue method.
There are no other established tolerances for AC 299263, and there
are no other registered uses for AC 299263 on food or feed crops.
(ii) Drinking water. There is no available information about AC
299263 exposures via levels in drinking water. Studies verify that the
use of AC 299263 in soybeans, at the proposed application rate of 0.04
lb. ai/acre, has a low potential for ground water contamination.
Results from field dissipation studies showed rapid initial degradation
of AC 299263 in soil, and additional studies indicate that AC 299263 is
resistant to desorption with time. Furthermore, AC 299263 soil
metabolites suggest a ``moderate to strong'' soil binding potential.
EPA has not established a Maximum Concentration Level for AC 299263
in drinking water under the Safe Drinking Water Act, because it is
unlikely to be found in ground water. Because of the very low level of
mammalian toxicity of parent AC 299263 and its two major soil
metabolites, there is no health risk to humans from exposure to parent
or soil metabolites in ground water. A Lifetime Health Advisory level
for AC 299263 in drinking water calculated by EPA procedures would be
81.55 mg/liter, assuming a 20% relative contribution from water.
There is a reasonable certainty that no harm will result from
dietary exposure to AC 299263, because dietary exposure to residues on
food will use only a small fraction of the Reference Dose (including
exposure of sensitive populations), and exposure through drinking water
is expected to be insignificant.
2. Non-dietary exposure. There is no available information
quantifying non-dietary exposure to AC 299263. However, based on the
physical and chemical characteristics of the compound, the proposed use
pattern and available information concerning its environmental fate,
non-dietary exposure is expected to be negligible.
D. Cumulative Effects
AC 299263 belongs to the imidazolinone class of compounds. The
herbicidal activity of the imidazolinones is due to the inhibition of
acetohydroxy acid synthase (AHAS), an enzyme only found in plants. AHAS
is part of the biosynthetic pathway leading to the formation of
branched chain amino acids. Animals lack AHAS and this biosynthetic
pathway. This lack of AHAS contributes to the extremely low toxicity of
AC 299263 in mammals. Although other registered imidazolinones have a
similar herbicidal mode of action, there is no information available to
suggest that these compounds exhibit a similar toxicity profile in the
mammalian system. Since AC 299263 is relatively non-toxic, cumulative
effects of residues of AC 299263 and other compounds are not
anticipated.
E. Safety Determination
1. U.S. population. Based on a RfD of 11.65 mg/kg b.w./day,
supported by a NOEL of 40,000 ppm or 1165 mg/kg b.w./day from the 1-
year dog study and a safety (uncertainty) factor of 100, the ``worse
case'' estimate of chronic dietary exposure of AC 299263 in soybean
seed will utilize approximately 0.0003 percent of the RfD for the
general U.S. population. EPA generally has no concern for exposures
below 100 percent of the RfD because the RfD represents the level at or
below which daily aggregate dietary exposure over a lifetime will not
pose appreciable risks to human health. The complete and reliable
toxicity data and the conservative chronic exposure assumptions support
the conclusion that there is a ``reasonable certainty of no harm'' from
aggregate exposure to AC 299263 residues.
2. Infants and children. The conservative estimates, as described
above, indicate that dietary exposure of AC 299263 on soybeans will
utilize approximately 0.002 percent of the RfD for non-nursing infants,
approximately 0.0006 percent of the RfD for children ages 1 to 6, and
approximately 0.0004 percent of the RfD for children ages 7 to 12.
No developmental, reproductive, or fetotoxic effects were noted at
the highest doses of AC 299263 tested in guideline studies. The only
maternal effects in the rat and rabbit teratology studies were
decreased body weights, body weight gains, and absolute and relative
feed consumption in the higher dose groups of each study.
Based on the current toxicological data requirements, the data base
relative to pre-and post-natal effects for children is complete, valid,
and reliable. Results from the teratology studies and the two-
generation reproduction study, which support NOELs for fetal/
developmental effects or reproductive/offspring effects, respectively,
equivalent to the highest concentrations tested, suggest that there is
no additional sensitivity of infants and children to residues of AC
299263. Therefore, an additional safety (uncertainty) factor is not
warranted, and the RfD of 11.65 mg/kg b.w./day, which utilizes a 100-
fold safety factor, is appropriate to assure a reasonable certainty of
no harm to infants and children.
F. International Tolerances
There is no Codex maximum residue level established for residues of
AC 299263 on soybean seed.
II. Administrative Matters
Interested persons are invited to submit comments on this notice of
filing. Comments must bear a notation indicating the document control
number, [PF-680]. All written comments filed in response to this
petition will be available in the Public Response and Program Resources
Branch, at the address give above from 8:30 a.m. to 4 p.m., Monday
through Friday, except legal holidays.
A record has been established for this notice under docket number
[PF-680] including comments and data 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 8:30 a.m.
to 4 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 #2,
1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments can be sent directly to EPA at:
opp-docket@epamail.epa.gov
Electronic comments must be submitted as 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 all comments 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 comments
submitted directly in writing. The official rulemaking record is the
paper record maintained at the address
[[Page 68039]]
in ``ADDRESSES'' at the beginning of this document.
List of Subjects
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: December 17, 1996.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 96-32796 Filed 12-24-96; 8:45 am]
BILLING CODE 6560-50-F
