[Federal Register Volume 65, Number 188 (Wednesday, September 27, 2000)]
[Notices]
[Pages 58074-58078]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-24680]


-----------------------------------------------------------------------

ENVIRONMENTAL PROTECTION AGENCY

[PF-976; FRL-6744-6]


Notice of Filing a Pesticide Petition to Establish a Tolerance 
for a Certain Pesticide Chemical in or on Food

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: This notice announces the initial filing of a pesticide 
petition proposing the establishment of regulations for residues of a 
certain pesticide chemical in or on various food commodities.

DATES: Comments, identified by docket control number PF-976, must be 
received on or before October 27, 2000.

ADDRESSES: Comments may be submitted by mail, electronically, or in 
person. Please follow the detailed instructions for each method as 
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure 
proper receipt by EPA, it is imperative that you identify docket 
control number PF-976 in the subject line on the first page of your 
response.

FOR FURTHER INFORMATION CONTACT: By mail: James Tompkins, Registration 
Division (7505W), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; 
telephone number: (703) 305-5697; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural 
producer, food manufacturer or pesticide manufacturer. Potentially 
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                      affected  entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------

    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in the table could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether or not this action might apply to certain entities. If you have 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How Can I Get Additional Information, Including Copies of this 
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this 
document, and certain other related documents that might be available 
electronically, from the EPA Internet Home Page at http://www.epa.gov/. 
To access this document, on the Home Page select ``Laws and 
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the 
entry for this document under the ``Federal Register--Environmental 
Documents.'' You can also go directly to the Federal Register listings 
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for 
this action under docket control number PF-976. The official record 
consists of the

[[Page 58075]]

documents specifically referenced in this action, any public comments 
received during an applicable comment period, and other information 
related to this action, including any information claimed as 
confidential business information (CBI). This official record includes 
the documents that are physically located in the docket, as well as the 
documents that are referenced in those documents. The public version of 
the official record does not include any information claimed as CBI. 
The public version of the official record, which includes printed, 
paper versions of any electronic comments submitted during an 
applicable comment period, is available for inspection in the Public 
Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 
#2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 a.m. to 4 
p.m., Monday through Friday, excluding legal holidays. The PIRIB 
telephone number is (703) 305-5805.

C. How and to Whom Do I Submit Comments?

    You may submit comments through the mail, in person, or 
electronically. To ensure proper receipt by EPA, it is imperative that 
you identify docket control number PF-976 in the subject line on the 
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records 
Integrity Branch (PIRIB), Information Resources and Services Division 
(7502C), Office of Pesticide Programs (OPP), Environmental Protection 
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public 
Information and Records Integrity Branch (PIRIB), Information Resources 
and Services Division (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The 
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by 
e-mail to: [email protected], or you can submit a computer disk as 
described above. Do not submit any information electronically that you 
consider to be CBI. Avoid the use of special characters and any form of 
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be 
identified by docket control number PF-976. Electronic comments may 
also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

    Do not submit any information electronically that you consider to 
be CBI. You may claim information that you submit to EPA in response to 
this document as CBI by marking any part or all of that information as 
CBI. Information so marked will not be disclosed except in accordance 
with procedures set forth in 40 CFR part 2. In addition to one complete 
version of the comment that includes any information claimed as CBI, a 
copy of the comment that does not contain the information claimed as 
CBI must be submitted for inclusion in the public version of the 
official record. Information not marked confidential will be included 
in the public version of the official record without prior notice. If 
you have any questions about CBI or the procedures for claiming CBI, 
please consult the person identified under FOR FURTHER INFORMATION 
CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

    You may find the following suggestions helpful for preparing your 
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used 
that support your views.
    4. If you estimate potential burden or costs, explain how you 
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this 
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket 
control number assigned to this action in the subject line on the first 
page of your response. You may also provide the name, date, and Federal 
Register citation.

II. What Action is the Agency Taking?

    EPA has received a pesticide petition as follows proposing the 
establishment and/or amendment of regulations for residues of a certain 
pesticide chemical in or on various food commodities under section 408 
of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. 
EPA has determined that this petition contains data or information 
regarding the elements set forth in section 408(d)(2); however, EPA has 
not fully evaluated the sufficiency of the submitted data at this time 
or whether the data support granting of the petition. Additional data 
may be needed before EPA rules on the petition.

List of Subjects

    Environmental protection, Agricultural commodities, Feed additives, 
Food additives, Pesticides and pests, Reporting and recordkeeping 
requirements.


    Dated: September 19, 2000.
  James Jones,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by section 408(d)(3) of the FFDCA. The summary of the 
petition was prepared by the petitioner and represent the view of the 
petitioner. EPA is publishing the petition summary verbatim without 
editing it in any way. The petition summary announces the availability 
of a description of the analytical methods available to EPA for the 
detection and measurement of the pesticide chemical residues or an 
explanation of why no such method is needed.

American Cyanamid Company

0F6186

    EPA has received a pesticide petition (0F6186) from American 
Cyanamid Company, P.O. Box 400, Princeton, NJ. 08543-0400 proposing, 
pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 
CFR part 180 by establishing a tolerance for residues of herbicide 
imazethapyr, 2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-
imidazol-2-yl]-5-ethyl-3-pyridine-carboxylic acid) as its free acid or 
its ammonium salt (calculated as the acid), and its metabolite 2-[4,5-
dihydro-4-methyl-4-(1- methylethyl-5- oxo-1H-imidazol-2-yl]-5-(1-
hydroxyethyl)-3-pyridinecarboxylic acid both free and conjugated in or 
on the raw agricultural commodities(RAC) rice grain at 0.5 parts per 
million (ppm) and rice straw at 0.3 ppm and in or on crayfish at 0.1 
ppm. EPA has determined that the petition contains data or information 
regarding the elements set forth in section 408(d)(2) of the FFDCA; 
however, EPA has not fully evaluated the sufficiency of the submitted 
data at this time or whether the data support granting of the petition. 
Additional data may be needed before EPA rules on the petition.

[[Page 58076]]

A. Residue Chemistry

    1. Plant metabolism. The qualitative nature of the residues of 
imazethapyr in rice is adequately understood. Based on studies 
conducted on soybean, edible forage legumes, and corn, parent 
imazethapyr, and common metabolites CL 288511 and CL 182704 are the 
only residues of concern for tolerance setting purposes.
    2. Analytical method. Practical analytical methods for detecting 
and measuring imazethapyr residues of concern in rice, its processed 
commodities, and crayfish are submitted to EPA with this petition. The 
analytical method for rice commodities, grain, and straw is based on 
capillary electrophoresis with limits of quantitation (LOQ) of 0.05 
ppm. Measurement of imazethapyr residues in polished rice, hull, and 
bran are accomplished by liquid chromatography/atmospheric pressure 
ionization-electrospray (API/ES) mass spectrometry (LC/MS). The 
validated LOQ of the method is 0.025 ppm. A CZE-methodology is also 
submitted for the determination of imazethapyr in crayfish with limits 
of quantitation of 50 parts per billion (ppb). These independently 
validated methods are appropriate for the enforcement purposes of this 
petition.
    3. Magnitude of residues. A total of nineteen field trials were 
conducted with imazethapyr and its metabolites on rice in 1997 and 1998 
at several different use rates and timing intervals to represent the 
use patterns which would result in the highest residue. In these 
trials, residues of parent compound AC 263499 in grain and straw were 
less than the limit of quantitation (0.05 ppm). The hydroxy metabolite, 
CL 288511 was detected in grain samples at a maximum value of 0.085 
ppm. All straw samples analyzed for CL 288511 residues were less than 
the limit of quantitation (0.05 ppm). The glucose conjugate, CL 182704 
was detected at a maximum value of 0.11 ppm in grain. All straw samples 
analyzed for CL 182704 residues were less than the limit of 
quantitation (0.05 ppm). The RAC samples were also processed into 
polished rice, hull, and bran. Results from these studies support the 
proposed tolerances of 0.5 ppm for rice grain and 0.3 ppm for rice 
straw. Based on the chemical nature of imazethapyr, results from a fish 
bioaccumulation study and further studies conducted on a surrogate 
chemical, imazapyr (CL 243997), there is no reasonable expectation of 
finite residues of imazethapyr in crayfish. However, the registrant is 
proposing a tolerance in or on crayfish at 0.1 ppm.

B. Toxicological Profile

    A complete, valid and reliable data base of mammalian and genetic 
toxicology studies support the proposed tolerances for imazethapyr. 
This data base was previously reviewed by the EPA in support of the 
tolerance petition and registration of imazethapyr on soybeans, legume 
vegetables, corn, alfalfa, and peanuts.
    1. Acute toxicity. Imazethapyr technical is considered to be 
nontoxic (toxicity category IV) to the rat by the oral route of 
exposure. In an acute oral toxicity study in rats, the LD50 
value of imazethapyr technical was greater than 5,000 milligrams/
kilograms (mg/kg) bwt for males and females. The results from an acute 
dermal toxicity study in rabbits indicate that imazethapyr is slightly 
toxic (toxicity category III) to rabbits by the dermal route of 
exposure. The dermal LD50 value of imazethapyr technical was 
greater than 2,000 mg/kg bwt for both male and female rabbits. 
Imazethapyr technical is considered to be non-toxic (toxicity category 
IV) to the rat by the respiratory route of exposure. The 4-hour 
LC50 value was greater than 3.27 mg/L (analytical) and 
greater than 4.21 mg/L (gravimetric) for both males and females. 
Imazethapyr technical was shown to be non-irritating to rabbit skin 
(toxicity category IV) and mildly irritating to the rabbit eye 
(toxicity category III). Based on the results of a dermal sensitization 
study (Buehler), imazethapyr technical is not considered a sensitizer 
in guinea pigs.
    2. Genotoxicty. Imazethapyr technical was tested in a battery of 
four in vitro and one in vivo genotoxicity assays measuring several 
different endpoints of potential genotoxicity. Collective results from 
these studies indicate that imazethapyr does not pose a mutagenic or 
genotoxic risk.
    3. Reproductive and developmental toxicity. The developmental 
toxicity study in Sprague Dawley rats conducted with imazethapyr 
technical showed no evidence of developmental toxicity or teratogenic 
effects in fetuses. Thus, imazethapyr is neither a developmental 
toxicant nor a teratogen in the rat. The no observed adverse effect 
level (NOAEL) for maternal toxicity was 375 mg/kg bwt/day, based on 
clinical signs of toxicity in the dams (e.g. excessive salivation) at 
1,125 mg/kg bwt/day. Imazethapyr technical did not exhibit 
developmental toxicity or teratogenic effects at maternal dosages up to 
and including 1,125 mg/kg bwt/day, the highest dose tested (HDT). 
Results from a developmental toxicity study in New Zealand white 
rabbits with imazethapyr technical also indicated no evidence of 
developmental toxicity or teratogenicity. Thus, imazethapyr technical 
is neither a developmental toxicant nor a teratogen in the rabbit. The 
NOAEL for maternal toxicity was 300 mg/kg bwt/day, based on decreased 
food consumption and bwt gain, abortion, gastric ulceration, and death 
at 1,000 mg/kg bwt/day, the next HDT. The NOAEL for developmental 
toxicity and teratogenic effects was determined to be >1,000 mg/kg bwt/
day based on no developmental toxicity or fetal malformations 
associated with the administration of all doses. The results from the 
2-generation reproduction toxicity study in rats with imazethapyr 
technical support a NOAEL for reproductive toxicity of 10,000 ppm 
(equivalent to 800 mg/kg bwt/day). The NOAEL for non-reproductive 
parameters (i.e. decreased weanling bwts) is 5,000 ppm.
    4. Subchronic toxicity. A short-term (21-day) dermal toxicity study 
in rabbits was conducted with imazethapyr technical. No dermal 
irritation or abnormal clinical signs were observed at dose levels up 
to and including 1,000 mg/kg bwt/day ( HDT), supporting a NOAEL for 
dermal irritation and systemic toxicity of 1,000 mg/kg bwt/day. In a 
subchronic (13-week) dietary toxicity study in rats with imazethapyr 
technical, no signs of systemic toxicity were noted, supporting a NOAEL 
of 10,000 ppm the highest concentration tested (HCT) (equivalent to 820 
mg/kg bwt/day). In a subchronic (13-week) dietary toxicity study in 
dogs with imazethapyr technical, no signs of systemic toxicity were 
noted, supporting a NOAEL of 10,000 ppm (equivalent to 250 mg/kg bwt/
day), the HCT.
    5. Chronic toxicity. A 1-year dietary toxicity study was conducted 
with imazethapyr technical in Beagle dogs at dietary concentrations of 
0, 1,000, 5,000, and 10,000 ppm. In this study, the NOAEL for systemic 
toxicity was 1,000 ppm (equivalent to 25 mg/kg bwt/day), based on 
slight anemia, i.e., decreased red cell parameters observed at 5,000 
and 10,000 ppm concentrations. No treatment-related histopathological 
lesions were observed at any dietary concentration, including the HCT 
(10,000 ppm).
    In a 2-year chronic dietary oncogenicity and toxicity study in rats 
conducted with imazethapyr technical, the NOAEL for oncogenicity, and 
chronic systemic toxicity was 10,000 ppm (equivalent to 500 mg/kg bwt/
day), the HCT. An 1-month chronic dietary oncogenicity and toxicity 
study in mice with imazethapyr technical support, a

[[Page 58077]]

NOAEL for oncogenicity of 10,000 ppm, the HCT (equivalent to 1,500 mg/
kg bwt/day), and a NOAEL for chronic systemic toxicity of 5,000 ppm 
(equivalent to 750 mg/kg bwt/day), based on decreased bwt gain in both 
sexes). The EPA has classified imazethapyr as a Group E carcinogen 
(evidence of non-carcinogenicity for humans) based on the absence of 
treatment-related tumors in acceptable carcinogenicity studies in both 
rats, and mice.
    6. Animal metabolism. The rat, goat, and hen metabolism studies 
indicate that the qualitative nature of the residues of imazethapyr in 
animals is adequately understood. In 3 rat metabolism studies conducted 
with radio-labeled imazethapyr technical the major route of elimination 
of the herbicide was through rapid excretion in urine and to a much 
lesser extent in feces. In the first study, almost 100% of the 
administered material was recovered in excreta within 96 hours (89-95% 
in urine, 6-11% in feces). The major residue in urine and feces was 
parent compound. Approximately 2% of the dose was metabolized and 
excreted as the -hydroxyethyl derivative of imazethapyr. In 
the second study, the test material was rapidly and completely 
eliminated unchanged in the urine within 72 hours of dosing. After 24 
hours, 92.1% of radio-activity was excreted in the urine with 4.67% in 
the feces. There was no significant bioaccumulation of radio-activity 
in the tissues from this rat metabolism study (< 0.01 ppm after 24 
hours). In the third study, 4 groups treated with radio-labeled 
imazethapyr readily excreted >95% of the test material in the urine and 
feces within 48 hours. A high percentage (97-99%) of the test material 
was excreted in the urine as unchanged parent, the remainder as the 
-hydroxyethyl derivative of imazethapyr. For all 3 studies, 
the major route of elimination of the herbicide in rats was through 
rapid excretion of unchanged parent compound in urine. It is clear that 
imazethapyr and its related residues do not accumulate in tissues and 
organs.
    In the goat metabolism study, parent 14C-imazethapyr was 
dosed to lactating goats at 0.25 ppm and 1.25 ppm. Results showed 
14C-residues of <0.01 ppm in milk, and <0.05 ppm in leg 
muscle, loin muscle, blood, fat, liver, and kidney. Laying hens dosed 
at 0.5 ppm and 2.5 ppm with 14C-imazethapyr showed 
14C-residues of <0.05 ppm in eggs and all tissues (blood, 
muscle, skin/fat, liver, and kidney).
    Additional animal metabolism studies have been conducted with CL 
288511 (main metabolite in treated crops fed to livestock) in both 
laying hens and lactating goats. These studies have been repeated to 
support subsequent use extensions on crops used as livestock feed items 
which would theoretically result in a higher dosing of imazethapyr-
derived residues to livestock ( i.e., corn, alfalfa). In these studies, 
lactating goats dosed at 42 ppm of 14C-CL 288511 showed 
14C-residues of <0.01 ppm in milk, leg muscle, loin muscle, 
and omental fat. 14C-residues in blood were mostly <0.01 ppm 
but reached 0.01 ppm on 2 of the treatment days. 14C-residue 
levels in the liver, and kidney were 0.02 and 0.09 ppm, respectively. 
Laying hens dosed at 10.2 ppm of 14C-imazethapyr showed 
14C-residues of <0.01 ppm in eggs and all tissues (blood, 
muscle, skin/fat, liver, and kidney). 14C-imazethapyr or 
14C-CL 288511 ingested by either laying hens or lactating 
goats was excreted within 48 hours of dosing. These studies indicate 
that parent imazethapyr and CL 288511-related residues do not 
accumulate in milk or edible tissues of the ruminant.
    7. Metabolite toxicology. Metabolism studies in soybean, peanut, 
corn, and alfalfa indicate that the only significant metabolites are 
the -hydroxyethyl derivative of imazethapyr, CL 288511 and its 
glucose conjugate CL 182704. The -hydroxyethyl metabolite has 
also been identified in minor quantities in the previously submitted 
rat metabolism studies and in goat and hen metabolism studies. No 
additional toxicologically significant metabolites were detected in any 
of the plant or animal metabolism studies.
    8. Endocrine disruption. Collective organ weight data and 
histopathological findings from the 2-generation rat reproductive 
study, as well as from the subchronic and chronic toxicity studies in 3 
different animal species demonstrate no apparent estrogenic effects or 
treatment-related effects of imazethapyr on the endocrine system.

C. Aggregate Exposure

    1. Dietary exposure. The potential dietary exposure to imazethapyr 
has been calculated from the proposed tolerance for use on rice and 
previously established tolerances for peanuts, legume vegetables, 
soybeans, alfalfa, endive, lettuce, and corn. This very conservative 
chronic dietary exposure estimate used the proposed tolerance of 0.5 
ppm for rice, and tolerance values of 0.1 ppm for peanuts, 0.1 ppm for 
legume vegetables, 0.1 ppm for soybeans, 3.0 ppm for alfalfa, 0.1 ppm 
for endive (escarole), 0.1 ppm for lettuce, and 0.1 ppm for corn. In 
addition, these estimates assume that 100% of these crops contain 
imazethapyr residues.
    i. Food. Potential exposure to residues of imazethapyr in food will 
be restricted to intake of rice, peanuts, legume vegetables, soybeans, 
alfalfa (sprouts), endive, lettuce, and corn. Using the assumptions 
discussed above, the theoretical maximum residue concentration (TMRC) 
values of imazethapyr were calculated for the U.S. general population 
and subgroups. Based on the tolerances given above, the TMRC values for 
each group are:
     0.000419 mg/kg bwt/day for the general U.S. population.
     0.001104 mg/kg bwt/day for all infants (<1-year).
     0.001298 mg/kg bwt/day for non-nursing infants.
     0.000870 mg/kg bwt/day for children 1 to 6 years of age.
     0.000610 mg/kg bwt/day for children 7 to 12 years of age.
    The TMRC values indicate that non-nursing infants are the most 
highly exposed population subgroup.
    ii. Drinking water. As a screening-level assessment for aggregate 
exposure, the U.S. EPA evaluates a drinking water level of comparison 
(DWLOC), which is the maximum concentration of a chemical in drinking 
water that would be acceptable in light of total aggregate exposure to 
that chemical. In 1990, the EPA set the reference dose (RfD) for 
imazethapyr at 0.25 mg/kg bwt/day, based on the NOAEL from the 1-year 
dietary toxicity study in dogs of 25 mg/kg bwt/day and a 100-fold 
uncertainty factor. Based on the chronic RfD of 0.25 mg/kg bwt/day and 
the EPA's default factors for bwt and drinking water consumption, the 
DWLOCs have been calculated to assess the potential dietary exposure 
from residues of imazethapyr in water. For the adult population the 
chronic DWLOC was 8,735 ppb and for children the DWLOC was estimated to 
be 2,491 ppb.
    Chronic drinking water exposure analyses were calculated for 
imazethapyr using EPA screening models screening concentration in 
ground water ((SCI-GROW) for ground water and (generic expected 
environmental concentration) (GENEEC) for surface water). The SCI-GROW 
value is 16.54 ppb and the calculated peak GENEEC value is 5.96 ppb by 
aerial application. For the U.S. adult population, the estimated 
exposures of imazethapyr residues in groundwater and surface water are 
approximately 0.19% and 0.07%, respectively, of the DWLOC. The 
estimated exposures of children to imazethapyr residues in ground water 
and surface water are approximately 0.66%, and 0.24%,

[[Page 58078]]

respectively, of the DWLOC. Therefore, the exposures to drinking water 
from imazethapyr use are negligible.
    2. Non-dietary exposure. Imazethapyr products are notcurrently 
registered or requested to be registered for residential use; therefore 
the estimate of residential exposure is not relevant to this tolerance 
petition.

D. Cumulative Effects

    Imazethapyr is a member of the imidazolinone class of herbicides. 
Other compounds of this class are registered for use in the United 
States. 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 imazethapyr has any toxic 
effects on mammals that would be cumulative with those of any other 
chemical. Therefore, for the purposes of this tolerance petition no 
assumption has been made with regard to cumulative exposure with other 
compounds having a common mode of action.

E. Safety Determination

    1. U.S. population. The RfD represents the level at or below which 
daily aggregate exposure over a lifetime will not pose appreciable 
risks to human health. In 990, the EPA set the RfD for imazethapyr at 
0.25 mg/kg bwt/day, based on the NOAEL from the 1-year dietary toxicity 
study in dogs of 25 mg/kg bwt/day and a 100-fold uncertainty factor. 
The chronic dietary exposure of 0.000419 mg/kg bwt/day for the general 
U.S. population will utilize only 0.2% of the RfD of 0.25 mg/kg bwt/
day. EPA generally has no concern for exposures below 100% of the RfD. 
Due to the low toxicity of imazethapyr, an acute exposure dietary risk 
assessment is not warranted. The complete and reliable toxicity data 
base, the low toxicity of the active ingredient, and the results of the 
chronic dietary exposure risk assessment, support the conclusion that 
there is a ``reasonable certainty of no harm'' from the proposed use of 
imazethapyr on imidazolinone tolerant rice. Furthermore, these factors 
support the proposed tolerance on rice.
    2. Infants and children. The conservative dietary exposure 
estimates of all registered uses including the proposed tolerance for 
rice show exposures of 0.001104, 0.000440, 0.000870, and 0.000610 mg/kg 
bwt/day which will utilize 0.4, 0.2, 0.3, and 0.2% of the RfD for all 
infants (<1 year), nursing infants, children 1-6 years, and children 7-
12 years, respectively. The chronic dietary exposures for non-nursing 
infants, the most highly exposed subgroup, will utilize only 0.5% of 
the RfD. Results from the 2-generation reproduction study in rats and 
the developmental toxicity studies in rabbits and rats indicate no 
increased sensitivity to developing offspring when compared to parental 
toxicity. These results also indicate that imazethapyr is neither a 
developmental toxicant nor a teratogen in either the rat or rabbit. 
Therefore, an additional safety factor is not warranted, and the RfD of 
0.25 mg/kg bwt/day, which utilizes a 100-fold safety factor is 
appropriate to ensure a reasonable certainty of no harm to infants and 
children.

F. International Tolerances

    There are no Codex maximum residue levels established or proposed 
for residues of imazethapyr on rice.
[FR Doc. 00-24680 Filed 9-26-00; 8:45 am]
BILLING CODE 6560-50-S