[Federal Register Volume 61, Number 244 (Wednesday, December 18, 1996)]
[Notices]
[Pages 66658-66661]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-32091]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-682; FRL-5576-9]


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 imazapyr (AC 243997) [2-
[4,5-dihydro-4-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-
pyridinecarboxylic acid], applied as the acid or ammonium salt, in or 
on field corn. This summary was prepared by the petitioner.
DATES: Comments, identified by the docket number [PF-682], must be 
received on or before, January 17, 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, DC20460. In person, bring comments to RM 1132, CM #2, 1921 
Jefferson Davis Highway, Arlington, VA 22202. 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.
    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 4:00 p.m., Monday through 
Friday, excluding legal holidays.
    Comments and data may also be submitted electronically by sending 
electronic mail (e-mail) to: [email protected]. 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 5.1 file format or ASCII file format. 
All comments and data in electronic form must be identified by the 
docket number [PF-682]. No 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 J. Taylor, Product 
Manager (PM) 23, Registration Division, (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 401 M St., SW., Washington, 
DC 20460. Office location and telephone number: Rm. 241, CM #2, 1921 
Jefferson Davis Highway, Arlington, VA 22202, 703-305-6027, e-mail: 
[email protected].
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition (PP 
6F4641) from American Cyanamid Company, P.O. Box 400, Princeton, NJ 
08543, proposing pursuant to section 408(d) of the Federal Food, Drug 
and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by 
establishing a tolerance for residues of the herbicide imazapyr in or 
on the raw agricultural commodities field corn grain, fodder, and 
forage each at 0.05 ppm. The proposed analytical method is Capillary 
Electrophoresis Method 2657. 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 for Imazapyr on Field Corn

     On November 9, 1995, American Cyanamid Company petitioned the EPA 
for a permanent tolerance for the residues of imazapyr on or in field 
corn grain, forage, and fodder. Imazapyr is currently registered for 
weed control in non-crop sites. This is the first registration 
application for a food use in the United States. Section 408(b)(2)(A) 
of the amended Federal Food, Drug, and Cosmetic Act allows the 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 the EPA to support the establishment, 
under section 408(b)(2)(D) of the amended FFDCA, of a tolerance for 
imazapyr on field corn.

A. Residue Chemistry

    1.  Plant metabolism.  The qualitative nature of the residues of 
imazapyr in corn is adequately understood. In corn forage, fodder and 
grain samples, the only significant component is parent compound. A 
modified processing study, utilizing corn treated at exaggerated rates, 
indicates that the low levels of residue in grain did not concentrate 
in corn oil and concentrated only slightly ( 1.2x) in corn 
meal.
    2. Analytical method.  A practical analytical method (Capillary 
Electrophoresis Method 2657) for detecting and measuring levels of 
imazapyr in corn has been submitted to

[[Page 66659]]

EPA. This method is appropriate for enforcement purposes.
    3. Magnitude of residues. In field corn residue studies conducted 
at a slightly exaggerated use rate, no residues were detected at levels 
above 0.05 ppm (the limit of quantitation for the analytical method). 
These field studies clearly support the proposed tolerance of 0.05 ppm.

B. Toxicological Profile

    A complete battery of mammalian toxicology studies supports the 
tolerance for imazapyr on field corn. The database is complete, valid 
and reliable, and all studies have been accepted by EPA and found to 
meet EPA requirements.
    1.  Acute toxicity. Imazapyr technical is relatively non-toxic via 
the oral route of exposure, and only slightly toxic via the dermal and 
inhalation routes of exposure.

------------------------------------------------------------------------
                                                                        
------------------------------------------------------------------------
Acute oral toxicity in rats...............  LD50 > 5,000 mg/kg          
Acute dermal toxicity in rabbits..........  LD50 > 2,000 mg/kg          
Acute inhalation toxicity in rats.........  LC50 > 1.3 mg/l             
Primary eye irritation in rabbits.........  Irreversible irritation     
Primary dermal irritation in rabbits......  Slightly irritating         
Dermal sensitization in guinea pigs.......  Non-sensitizer              
------------------------------------------------------------------------

    2.  Genotoxicity. Imazapyr has shown no genotoxic activity in in 
vitro tests, indicating that this compound is not a mutagen.

------------------------------------------------------------------------
                                                                        
------------------------------------------------------------------------
Ames......................................  Non-mutagenic               
Chromosomal aberrations...................  Non-genotoxic               
Mammalian gene mutation (CHO/HGPRT).......  Non-mutagenic               
Unscheduled DNA synthesis.................  Non-genotoxic               
------------------------------------------------------------------------

    3.  Reproductive and developmental toxicity.  Results indicate that 
imazapyr is not a reproductive toxicant, a developmental toxicant, or a 
teratogen.

------------------------------------------------------------------------
                                                                        
------------------------------------------------------------------------
Teratology in rats........................  NOEL (maternal) = 300 mg/kg/
                                             day                        
                                            NOEL (developmental) = 1,000
                                             mg/kg/day*                 
Teratology in rabbits.....................  NOEL (maternal) = 400 mg/kg/
                                             day*                       
                                            NOEL (developmental) = 400  
                                             mg/kg/day*                 
2-Generation reproduction in rats.........  NOEL (parental reproductive)
                                             = 10,000 ppm* (
                                             800 mg/kg/day in males)    
                                             ( 980 mg/kg/day
                                             in females)                
------------------------------------------------------------------------
* Highest dose tested.                                                  

    4.  Subchronic toxicity.  No treatment-related adverse effects were 
noted in subchronic toxicity studies at the highest doses tested.

------------------------------------------------------------------------
                                                                        
------------------------------------------------------------------------
13-Week oral feeding in rats..............  NOEL  20,000 ppm*
                                             ( 1,740 mg/kg/ 
                                             day)                       
21-Day dermal in rabbits..................  NOEL = 400 mg/kg/day*       
------------------------------------------------------------------------
* Highest dose tested.                                                  

    5.  Chronic toxicity. The EPA Carcinogenicity Peer Review 
Committee, on April 26, 1995, assigned imazapyr to Group E for 
carcinogenic potential since there is ``no evidence of carcinogenicity 
in at least two adequate animal tests in different species. ``No 
treatment related effects were observed, and no increase in tumors was 
observed at any dose level.

------------------------------------------------------------------------
                                                                        
------------------------------------------------------------------------
1-Year chronic toxicity in dogs...........  NOEL = 10,000 ppm*          
                                             ( 250 mg/kg/   
                                             day)                       
18-Month chronic toxicity & oncogenicity    NOEL = 10,000 ppm*          
 in mice.                                    ( 1500 mg/kg/  
                                             day)                       
24-Month chronic toxicity & oncogenicity    NOEL = 10,000 ppm*          
 in rats.                                    ( 500 mg/kg/day
                                             in males) ( 640
                                             mg/kg/day in females)      
------------------------------------------------------------------------
* Highest dose tested                                                   

    6. Animal metabolism. The qualitative nature of the residues of 
imazapyr in animals is adequately understood. Based on metabolism 
studies with goats, hens and rats, there is no reasonable expectation 
that measurable imazapyr-related residues will occur in meat, milk, 
poultry or eggs from the proposed use.
    7. Metabolite toxicology.  No significant metabolites were detected 
in plant or animal metabolism studies. Therefore, toxicology studies 
with metabolites are not required.
    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 imazapyr would be associated with endocrine 
effects.

C. Aggregate Exposure

    1. Dietary exposure-- i.  Food. The Theoretical Maximum Residue 
Concentrations (TMRC) of imazapyr on or in field corn are:
      0.000070 mg/kg b.w./day for the general U.S. population
      0.000142 mg/kg b.w./day for non-nursing infants
      0.000165 mg/kg b.w./day for children 1 to 6 years of age
      0.000123 mg/kg b.w./day for children 7 to 12 years of 
age.
    These values are calculated from the proposed 0.05 ppm tolerance of 
imazapyr on corn using a ``worse case'' estimate of dietary exposure. 
This conservative estimate assumes that 100 percent of all field corn 
is treated with imazapyr and that the residues of imazapyr on corn are 
at the tolerance level (0.05 ppm). In reality, field trials with 
sampling at least 30 days after treatment resulted in no residues above 
the analytical method limit of quantitation (0.05 ppm).
    Dietary exposure to residues of imazapyr in or on food will be 
limited to residues on corn. Field corn grain, forage, fodder and 
milled byproducts could be fed to animals. However, there is no 
reasonable expectation that measurable residues of imazapyr will occur 
in meat, milk, poultry or eggs from the proposed use. There are no 
other established tolerances for imazapyr, and there are no other 
registered uses for imazapyr on food or feed crops in the United 
States.
    With a Reference Dose (RfD) of 2.50 mg/kg b.w./day, the dietary 
exposure for this proposed use will utilize only 0.0028 percent of the 
RfD for the general U.S. population.
    ii. Drinking water. There is no available information about 
imazapyr exposure via levels in drinking water. Imazapyr has been 
registered for non-crop uses for 12 years and there are no confirmed 
findings in either ground or surface water from these uses. Low initial 
soil residue levels due to low application rates (0.014 lb. ae/acre) 
contribute to the minimal risk of exposure to imazapyr in drinking 
water from this use.

[[Page 66660]]

    EPA has not established a Maximum Concentration Level for residues 
of imazapyr in drinking water under the Safe Drinking Water Act, 
because imazapyr is unlikely to be found in groundwater.The low level 
of mammalian toxicity further supports the lack of real risk of 
imazapyr to humans. A Lifetime Health Advisory level for imazapyr in 
drinking water calculated by EPA procedures would be 17.5 mg/liter, 
assuming a 20 percent relative contribution from water. There is a 
reasonable certainty that no harm will result from dietary exposure to 
imazapyr, 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 imazapyr. However, based on 
physical and chemical characteristics of the compound, the use 
patterns, and available information concerning its environmental fate, 
non-dietary exposure is expected to be negligible.
    Currently, registrations for imazapyr limit use to non-crop sites. 
Labeled use sites for one group of imazapyr products include railroad, 
utility, pipeline, and highway rights-of-way, utility plant sites, 
petroleum tank farms, pumping installations, fence rows, storage areas, 
non-irrigation ditchbanks, under asphalt, under pond liners, wildlife 
management areas, forestry site preparation, and other non-crop areas. 
Imazapyr products for the above uses are clearly not intended for use 
in residential or recreational areas that have a high potential of 
exposure for the general population. The labels state that these 
imazapyr products are not for use on lawns, walks, driveways, tennis 
courts or similar areas.
    Other imazapyr products are labeled as plant growth regulators for 
applications to limited care-low maintenance areas, such as roadsides, 
airports, fairgrounds, and golf course roughs, and to limited wear 
areas such as industrial, institutional, and cemetery grounds. These 
low rate uses entail minimal exposure potential for the general 
population. The product labeling does not allow use on turf that is 
being grown for sale or other commercial use, such as sod.
    There are imazapyr products marketed for residential use. These 
total vegetation control products are used for spot treatments or bare 
ground applications. These products are to be applied only where no 
plant growth is desired and are not to be used on lawns. Therefore, 
even for the limited residential uses, the potential for exposure is 
minimal.

D. Cumulative effects

    Imazapyr belongs to the imidazolinone class of compounds. Other 
compounds in this class are registered herbicides. However, the 
herbicidal activity of the imidazolinones is due to the inhibition of 
acetohydroxyacid 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 low toxicity of the 
imidazolinone compounds in animals. We are aware of no information to 
indicate or suggest that imazapyr has any toxic effects on mammals that 
would be cumulative with those of any other chemical.

E. Safety Determination

    1.  U.S. population.  The RfD of 2.50 mg/kg b.w./day, supported by 
a NOEL of 10,000 ppm or 250 mg/kg b.w./day from the 1-year dog study 
and a safety (uncertainty) factor of 100, is the ``worst case'' 
estimate of chronic dietary exposure of imazapyr in corn. This proposed 
application will utilize only 0.0028 percent of the RfD for the general 
U.S. population. EPA generally has no concern for exposures below 100 
percent of the RfD which 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, 
indicating low potential mammalian toxicity, and the conservative 
chronic exposure assumptions support the conclusion that there is a 
``reasonable certainty of no harm'' from aggregate exposure to imazapyr 
residues.
    2.  Infants and children.  The conservative estimates for dietary 
exposure to imazapyr from food, as described above in Unit C of this 
notice of filing, indicate that exposure of imazapyr on corn will 
utilize approximately 0.0057 percent of the RfD for non-nursing 
infants, approximately 0.0066 percent for the RfD for children 1 to 6 
years of age, and approximately 0.0049 percent of the RfD for children 
seven to 12 years of age.
    Furthermore, no developmental, reproductive or fetotoxic effects 
were noted at the highest doses of imazapyr tested. The only maternal 
effect in the rat teratology study was increased salivation in the 
highest dose group. The NOEL used to calculate the RfD for the general 
U.S. population is 250 mg/kg b.w./day derived from the 1-year chronic 
toxicity study in dogs. That NOEL is lower than the developmental NOELs 
for the teratology studies in rabbits and rats (1.6 and 4x, 
respectively), as well as lower than the NOEL for the two-generation 
reproduction study in male and female rats (3.2 to 3.9x).
    The EPA has found the database relative to pre-and post-natal 
effects for children to be complete, valid and reliable. There were no 
effects observed in the offspring in the developmental studies in rats 
and rabbits. In the reproduction study, the lack of any pup effects 
observed at 10,000 ppm (the highest dose tested) in their growth and 
development from parturition through adulthood, suggests that there is 
no additional sensitivity for infants and children. Therefore, an 
additional safety (uncertainty) factor is not warranted and the RfD of 
2.50 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 are no Codex maximum residue levels established for residues 
of imazapyr on field corn grain, fodder or forage.

II. Administrative Matters

     Interested persons are invited to submit comments on the notice of 
filing. Comments must bear a notation indicating the document control 
number, [PF-682]. All written comments filed in response to this 
petition will be available in the Public Response and Program Resources 
Branch, at the address given above from 8:30 a.m. to 4:00 p.m., Monday 
through Friday, except legal holidays.
    A record has been established for this notice under docket number 
[PF-682] 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 4:00 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.
    Electronic comments can be sent directly to EPA at:
    opp=D[email protected].



[[Page 66661]]


    Electronic comments 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 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 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 11, 1996.

Stephen L. Johnson,

Director, Registration Division, Office of Pesticide Programs.

[FR Doc. 96-32091 Filed 12-17-96; 8:45 am]
BILLING CODE 6560-50-F