[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: 
[email protected]. 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: [email protected].

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:
    [email protected]


    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